Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Volume 13 Issue 5
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Petsuksiri, Janjira;Jaishuen, Atthapon;Pattaranutaporn, Pittayapoom;Chansilpa, Yaowalak 1713
Advanced imaging approaches (computed tomography, CT; magnetic resonance imaging, MRI;$^{18}F$ -fluorodeoxyglucose positron emission tomography, FDG PET) have increased roles in cervical cancer staging and management. The recent FIGO (International Federation of Gynecology and Obstetrics) recommendations encouraged applications to assess the clinical extension of tumors rather than relying on clinical examinations and traditional non-cross sectional investigations. MRI appears to be better than CT for primary tumors and adjacent soft tissue involvement in the pelvis. FDG-PET/CT has increased in usage with a particular benefit for whole body evaluation of tumor metabolic activity. The potential benefits of advanced imaging are assisting selection of treatment based upon actual disease extent, to adequately treat a tumor with minimal normal tissue complications, and to predict the treatment outcomes. Furthermore, sophisticated external radiation treatment and brachytherapy absolutely require advanced imaging for target localization and radiation dose calculation. -
Sakthivel, K.M.;Prabhu, V. Vinod;Guruvayoorappan, C. 1719
The Wiskott-Aldrich Syndrome Protein family Verprolin - homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy. -
Objective: To summarize and evaluate various urinary markers for early detection, diagnosis and follow-up of human bladder cancer. Methods: A MEDLINE and PUBMED search of the latest literature on urinary markers for bladder cancer was performed. We reviewed these published reports and made a critical analysis. Results: Most urinary markers tend to be less specific than cytology, yielding more false-positive results, but demonstrating an advantage in terms of sensitivity, especially for detecting low grade, superficial tumors. Some tumor markers appear to be good candidates for early detection, diagnosis, and follow-up of human bladder cancer. Conclusion: A number of urinary markers are currently available that appear to be a applicable for clinical detection, diagnosis, and follow-up of bladder cancer. However, further studies are required to determine their accuracy and widespread applicability.
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Patel, Jayendra B.;Patel, Kinjal D.;Patel, Shruti R.;Shah, Franky D.;Shukla, Shilin N.;Patel, Prabhudas S. 1727
Regardless of advances in treatment modalities with the invention of newer therapies, breast cancer remains a major health problem with respect to its diagnosis, treatment and management. This female malignancy with its tremendous heterogeneous nature is linked to high incidence and mortality rates, especially in developing region of the world. It is the malignancy composed of distinct biological subtypes with diverse clinical, pathological, molecular and genetic features as well as different therapeutic responsiveness and outcomes. This inconsistency can be partially overcome by finding novel molecular markers with biological significance. In recent years, newer technologies help us to indentify distinct biomarkers and increase our understanding of the molecular basis of breast cancer. However, certain issues need to be resolved that limit the application of gene expression profiling to current clinical practice. Despite the complex nature of gene expression patterns of cDNAs in microarrays, there are some innovative regulatory molecules and functional pathways that allow us to predict breast cancer behavior in the clinic and provide new targets for breast cancer treatment. This review describes the landscape of different molecular markers with particular spotlight on vitamin D signaling pathway and apoptotic specific protein of p53 (ASPP) family members in breast cancer. -
Babu, Spoorthy N.;Chetal, Gaurav;Kumar, Sudhir 1737
Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine which plays roles in inflammation, immune responses and cancer development. It assists macrophages in carrying out functions like phagocytosis, adherence and motility. Of late, MIF is implicated in almost all stages of neoplasia and expression is a feature of most types of cancer. The presence of MIF in almost all tumors and all stages of cancer makes it an interesting candidate for cancer therapy. This review explores the roles of MIF in neoplasia. -
Pourshahidi, Sara;Fakhri, Farnaz;Ebrahimi, Hooman;Fakhraei, Bahareh;Alipour, Abbas;Ghapanchi, Janan;Farjadian, Shirin 1745
Oral lichen planus is a premalignant chronic inflammatory mucosal disorder with unknown etiology. It is a multifactorial disease and in addition to genetic background, infections, stress, drug reactions are suggested as risk factors. Helicobacter pylori which is involved in development of many gastrointestinal lesions may also be implicated in oral lichen planus induction. This is of clear importance for cancer prevention and the present study was performed to determine any association between H. pylori infection and oral lichen planus in southwestern Iran. Anti H. pylori IgG levels were determined in 41 patients and 82 sex-age matched controls. The results showed no association between H. pylori infection and oral lichen planus (51% in patients vs. 66% in control). or any of its clinical presentations. -
Li, Xin;Wang, Yang;Li, Xing-Wang;Liu, Bao-Cheng;Zhao, Qing-Zhu;Li, Wei-Dong;Chen, Shi-Qing;Huang, Xiao-Ye;Yang, Feng-Ping;Wang, Quan;Wang, Jin-Fen;Xiao, Yan-Zeng;Xu, Yi-Feng;Feng, Guo-Yin;Peng, Zhi-Hai;He, Lin;He, Guang 1749
Colorectal cancer (CRC), now the third most common cancer across the world, is known to aggregate in families. USP7 is a very important protein with an important role in regulating the p53 pathway, which is critical for genomic stability and tumor suppression. We here genotyped eight SNPs within the USP7 gene and conducted a case-control study in 312 CRC patients and 270 healthy subjects in the Chinese Han population. No significant associations were found for any single SNP and CRC risk. Our data eliminate USP7 as a potential candidate gene towards for CRC in the Han Chinese population. -
Promthet, Supannee;Wiangnon, Surapon;Senarak, Wiporn;Saranrittichai, Kesinee;Vatanasapt, Patravoot;Kamsa-ard, Supot;Wongphuthorn, Prasert;Kasinpila, Chananya;Moore, Malcolm Anthony 1753
This was a survey research conducted in Northestern Thailand during 2009-2010 and designed to evaluate the success of a health education program by comparing levels of health knowledge in the community before and after the launching of a Multi-professional Intervention and Training for Ongoing Volunteer-based Community Health Programme. The survey questionnaire included items about demographic characteristics and health knowledge. The participants were 1,015 members of various communities, who were randomly selected to be included in the survey before launching the intervention, and 1,030 members of the same communities randomly selected to be included in the survey after the intervention was completed. The demographic characteristics of both groups were similar. Overall knowledge and knowledge of all the diseases, except lung and cervical cancer, were significantly higher after the intervention. In conclusion, a Volunteer-based Community Health Programme has advantages for areas where the numbers of health personnel are limited. The use of trained community health volunteers may be one of the best sustainable alternative means for the transfer of health knowledge. -
Hafeez, S.;Ahmed, A.;Rashid, Asif Z.;Kayani, Mahmood Akhtar 1757
Breast cancer is a major cause of death in women worldwide. Mammary tissue expressing xenobiotic metabolizing enzymes metabolically activate or detoxify potential genotoxic breast carcinogens. Deregulation of these xenobiotic metabolizing enzymes is considered to be a major contributory factor to breast cancer. The present study is focused on the expression of the xenobiotic metabolizing gene, CYP1A1, in breast cancer and its possible relationships with different risk factors. Twenty five tumors and twenty five control breast tissue samples were collected from patients undergoing planned surgery or biopsy from different hospitals. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western-blotting were used to investigate the expression of CYP1A1 in breast cancer control and disease samples. mRNA expression of CYP1A1 was down-regulated in 40% of breast tumor samples. Down-regulation was also observed at the protein level. Significnat relations were noted with marital status and tumour grade but not histopathological type. In conclusion, CYP1A1 protein expression was markedly reduced in tumor breast tissues samples as compared to paired control tissue samples. -
Wang, Zhen-Hua;Gao, Qin-Yan;Fang, Jing-Yuan 1761
Background: The appropriate interval between negative colonoscopy screenings is uncertain, but the numbers of advanced neoplasms 10 years after a negative result are generally low. We aimed to evaluate the cost-effectiveness of colorectal neoplasm screening and management based on repeat screening colonoscopy every 10 years or single colonoscopy, compared with no screening in the general population. Methods and materials: A state-transition Markov model simulated 100,000 individuals aged 50-80 years accepting repeat screening colonoscopy every 10 years or single colonoscopy, offered to every subject. Colorectal adenomas found during colonoscopy were removed by polypectomy, and the subjects were followed with surveillance every three years. For subjects with a normal result, colonoscopy was resumed within ten years in the repeat screening strategy. In single screening strategy, screening process was terminated. Direct costs such as screening tests, cancer treatment and costs of complications were included. Indirect costs were excluded from the model. The incremental cost-effectiveness ratio was used to evaluate the cost-effectiveness of the different screening strategies. Results: Assuming a first-time compliance rate of 90%, repeat screening colonoscopy and single colonoscopy can reduce the incidence of colorectal cancer by 65.8% and 67.2% respectively. The incremental cost-effectiveness ratio for single colonoscopy (49 Renminbi Yuan [RMB]) was much lower than that for repeat screening colonoscopy (474 RMB). Single colonoscopy was a more cost-effective strategy, which was not sensitive to the compliance rate of colonoscopy and the cost of advanced colorectal cancer. Conclusion: Single colonoscopy is suggested to be the more cost-effective strategy for screening and management of colorectal neoplasms and may be recommended in China clinical practice. -
Background: The Asia Pacific consensus for colorectal cancer (CRC) recommends that screening programs should begin by the age of 50. However, there have been reports about increasing incidence of CRC at a younger age (i.e. early-onset CRC). Little is known about the features of early-onset CRC in the Vietnamese population. Aim: To describe the clinical, endoscopic and pathological characteristics of early-onset CRC in Vietnamese. Method: A prospective, cross-sectional study was conducted at the University Medical Center from March 2009 to March 2011. All patients with definite pathological diagnosis of CRC were recruited. The early-onset CRC group were analyzed in comparison with the late-onset (i.e.
${\geq}$ 50-year-old) CRC group. Results: The rate of early-onset CRC was 28% (112/400) with a male-to-female ratio of 1.3. Some 22.3% (25/112) of the patients only experienced abdominal pain and/or change in bowel habit without alarming symptoms, 42.9% (48/112) considering their symptoms intermittent. The rate of familial history of CRC in early-onset group was significantly higher that of the late-onset group (21.4% versus 7.6%, p<0.001). The distribution of CRC lesions in rectum, distal and proximal colon were 51.8% (58/112), 26.8% (30/112) and 21.4% (24/112), respectively; which was not different from that in the late-onset group (${\chi}2$ , p = 0.29). The rates for poorly differentiated tumors were also not significantly different between the two groups: 12.4% (14/112) versus 8.3% (24/288) (${\chi}2$ , p = 0.25). Conclusion: A high proportion of CRC in Viet Nam appear at an earlier age than that recommended for screening by the Asia Pacific consensus. Family history was a risk factor of early-onset CRC. Diagnosis of early-onset CRC needs more attention because of the lack of alarming symptoms and their intermittent patterns as described by the patients. -
Ye, J.Z.;Miao, Z.G.;Wu, F.X.;Zhao, Y.N.;Ye, H.H.;Li, L.Q. 1771
The impact of anatomic resection (AR) as compared to non-anatomic resection (NAR) for hepatocellular carcinoma (HCC) as a factor for preventing intra-hepatic and local recurrence after the initial surgical procedure remains controversial. A systematic review and meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990 to 2010 in PubMed and Medline, Cochrane Library, Embase, and Science Citation Index were therefore performed. Intra-hepatic recurrence, including early and late, and local recurrence were considered as primary outcomes. As secondary outcomes, 5 year survival and 5 year disease-free survival were considered. Pooled effects were calculated utilizing either fixed effects or random effects models. Eleven non-randomized studies including 1,576 patients were identified and analyzed, with 810 patients in the AR group and 766 in the NAR group. Patients in the AR group were characterized by lower prevalence of cirrhosis, more favorable hepatic function, and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group. Anatomic resection significantly reduced the risks of local recurrence and achieved a better 5 years disease-free survival. Also, anatomic resection was marginally effective for decreasing the early intra-hepatic recurrence. However, it was not advantageous in preventing late intra-hepatic recurrence compared with non-anatomic resection. No differences were found between AR and NAR with respect to postoperative morbidity, mortality, and hospitalization. Anatomic resection can be recommended as superior to non-anatomic resection in terms of reducing the risks of local recurrence, early intra-hepatic recurrence and achieving a better 5 year disease-free survival in HCC patients. -
Mansour-Ghanaei, Fariborz;Joukar, Farahnaz;Baghaei, Seyed Mohammad;Yousefi-Mashhoor, Mahmood;Naghipour, Mohammad Reza;Sanaei, Omid;Naghdipour, Misa;Shafighnia, Shora;Atrkar-Roushan, Zahra 1779
Background & Objectives: In patients with gastric cancer, the most frequently reported family history of cancer also involves the stomach. The aim of this study was to assess the presence of gastric precancerous lesions in first-degree relatives of patients with gastric cancer and to compare the obtained results with those of individuals with no such family history. Methods: Between 2007 and 2009, 503 consecutive persons more than 30 years old were enrolled in the study covering siblings, parents or children of patients with confirmed adenocarcinoma of stomach. The control group was made up of 592 patients who were synchronously undergoing upper gastrointestinal endoscopy for evaluation of dyspepsia without gastric cancer or any family history. All subjects were endoscopically examined. Results: The overall prevalence of Helicobacter pylori was 77.7% in the cancer relatives and in 75.7% in the control group. Chronic gastritis was found in 90.4% vs. 81.1% (P<0.001). Regarding histological findings, 37(7.4%) of the study group had atrophy vs. 12(1.7%) in the control group (P<0.001), while no difference was observed for intestinal metaplasia (20.3%vs. 21.6%, P=0.58). Dysplasia were shown in 4% of cancer relatives but only 0.4% of the control group (P<0.001). There was no gender specificity. Conclusions: Findings of our study point to great importance of screening in relatives of gastric cancer patients in Iran. -
Objectives: To analyze esophageal cancer incidence and pathological data of Zhongshan in China in 1970-2007, and to provide scientific information for its prevention and control. Methods: From Zhongshan Cancer Registry esophageal cancer incident and pathological data were obtained. Pathological proportions and trends were calculated and analyzed. Results: Although there was a continuously and obviously increasing trend for male incidence rates in 1970-2007 in Zhongshan, squamous cell carcinoma (SCC) and adenocarcinoma (AD) incident proportions during 1990-2007 remained relatively stable. Moreover, SCC was the major pathological type, accounting for 70.6 percent of all new cases, while AD were relatively few and accounted for only 2.66 percent throughout the period. Conclusion: The male esophageal cancer incident pattern in Zhongshan in 1970-2007 was quite different from most other domestic areas. The data suggest that etiological analysis should be enhanced for improved control in Zhongshan.
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Xiang, Bin;Mi, Yuan-Yuan;Li, Teng-Fei;Liu, Peng-Fei 1787
Objective: The p53 tumor suppressor pathway plays an important role in gastric cancer (GC) development. Auto-regulatory feedback control of p53 expression is critical to maintaining proper tumor suppressor function. So far, several studies between p53 Arg72Pro polymorphism and GC have generated controversial and inconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 19 publications. Eligible studies were identified by searching the Pubmed database. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess any link. Results: Overall, a significant association was detected between the p53 Arg72Pro polymorphism and GC risk (Pro-allele vs. Arg-allele: OR = 1.05, 95%CI = 1.01-1.08; Pro/Pro vs. Arg/Arg: OR = 1.13, 95%CI = 1.04-1.22). Moreover, on stratified analysis by race, significantly increased risk was found for Asian populations (Pro-allele vs. Arg-allele: OR = 1.06, 95%CI = 1.02-1.10; Pro/Pro vs. Arg/Arg: OR = 1.16, 95%CI = 1.07-1.26; Pro/Pro+Pro/Arg vs. Arg/Arg: OR = 1.58, 95%CI = 1.09-2.27). Conclusions: Our study provided evidence that the p53 72Pro allele may increase GC risk in Asians. Future studies with larger sample size are warranted to further confirm this association in more detail. -
Meng, Ling-Xin;Chi, Yu-Hua;Wang, Xiang-Xu;Ding, Zhao-Jun;Fei, Li-Cong;Zhang, Hong;Mou, Ling;Cui, Wen;Xue, Ying-Jie 1793
Objective: To analyze the capacity of neurotrophic artemin to promote the motility and invasiveness of MIA PaCa-2 pancreatic cancer cells. Methods: MIA PaCa-2 was cultured in vitro and studied using transwell chambers for motility and invasiveness on treatment with different concentrations of aArtemin or its receptor$GFR{\alpha}3$ were also determined. Expression of matrix metalloproteinase-2 (MMP-2) and epithelial cadherin (E-cadherin) was quantified using RT-PCR and Western blotting. Results: MIA PaCa-2 pancreatic cancer cell motility and invasiveness was significantly increased with artemin and its receptor$GFR{\alpha}3$ with dose dependence (P<0.01). MMP-2 production was also significantly increased (t = 6.35, t = 7.32), while E-cadherin was significantly lowered (t = 4.27, t = 5.61) (P <0.01). Conclusion: Artemin and its receptor$GFR{\alpha}3$ can promote pancreatic cancer cell motility and invasiveness and contribute to aggressive behavior. The mechanism may be related to increased expression of MMP-2 molecule and down-regulation of E-cadherin expression. -
He, Shan-Yang;Xu, Lin;Niu, Gang;Ke, Pei-Qi;Feng, Miao-Miao;Shen, Hong-Wei 1799
Objective: We aimed to analyze the association between excision repair cross-complementing rodent repair deficiency complementation group 1 (XRCC1) and ovarian cancer risk. Methods: We performed a hospital-based case-control study with 155 cases and 313 controls in China. All Chinese cases with newly diagnosed primary ovarian cancer between May 2005 to May 2010 in our hospital were invited to participate within 2 months of diagnosis. Controls were randomly selected from people who requested general health examinations in the same hospital during the same period. SNPs in EXCC1, ERCC1 C8092A and ERCC1 T19007C, were analyzed by PCR-RFLP method. Results: We observed a non-significantly increased risk of ovarian cancer among individuals with ERCC1 8092TT compared with those with the 8092CC genotype (adjusted OR=1.55, 95% CI%=0.74-2.97). Moreover, 19007TT genotype carriers also showed a non-significant increased risk of ovarian cancer over those with the 19007CC genotype (adjusted OR=1.78, 95% CI%=0.91-3.64). Conclusion: Our firstly investigation of links between polymorphisms in the ERCC1 gene and the risk of ovarian cancer in Chinese population demonstrated no significant association. Further large sample studies in Chinese populations are needed. -
Cheng, Zhe;Wang, Wei;Song, Yong-Na;Kang, Yan;Xia, Jie 1803
This study aimed to investigate the effects of Ser/Cys polymorphism in hOGG1 gene, Arg/Pro polymorphism in p53 gene, smoking and their interactions on the development of lung cancer. Ser/Cys polymorphism in hOGG1 and Arg/Pro polymorphism in p53 among 124 patients with lung cancer and 128 normal people were detected using PCR-RFLP. At the same time, smoking status was investigated between the two groups. Logistic regression was used to estimate the effects of Ser/Cys polymorphism and Arg/Pro polymorphisms, smoking and their interactions on the development of lung cancer. ORs (95% CI) of smoking, hOGG1 Cys/Cys and p53 Pro/Pro genotypes were 2.34 (1.41-3.88), 2.12 (1.03-4.39), and 2.12 (1.15-3.94), respectively. The interaction model of smoking and Cys/Cys was super-multiplicative or multiplicative, and the OR (95% CI) for their interaction item was 1.67 (0.36 -7.78). The interaction model of smoking and Pro/Pro was super-multiplicative with an OR (95%CI) of their interaction item of 5.03 (1.26-20.1). The interaction model of Pro/Pro and Cys/Cys was multiplicative and the OR (95%CI) of their interaction item was 0.99 (0.19-5.28). Smoking, hOGG1 Cys/Cys, p53 Pro/Pro and their interactions may be the important factors leading to the development of lung cancer. -
Hu, Kong-Wang;Chen, Fei-Hu;Ge, Jin-Fang;Cao, Li-Yu;Li, Hao 1809
Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses,${\alpha}$ ,${\beta}$ and${\gamma}$ . At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa,$RAR{\beta}$ ,$RAR{\gamma}$ , RXRa,$RXR{\beta}$ ,$RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa,$RAR{\beta}$ ,$RAR{\gamma}$ and$RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower$RAR{\beta}$ ,$RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and$RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer. -
Shaikh, Rizwana B.;Haque, Noor Mohammad Abdul;Al Mohsen, Hassan Abdul Hadi Khalil;Al Mohsen, Ali Abdul Hadi Khalil;Humadi, Marwa Haitham Khalaf;Al Mubarak, Zainab Zaki;Mathew, Elsheba;Al Sharbatti, Shatha 1819
Background: In the United Arab Emirates (UAE) tobacco use is rampant. A less reported, yet widely used form of smoking native to UAE is midwakh or dhokha. The aim of the study is to assess the acute effects of smoking dokha (Arabian pipe) on the cardiovascular and respiratory systems among male university students in the UAE. Method: A quasi-experimental study was conducted among 97 male volunteers aged more than 17 years. Blood pressure, heart rate and respiratory rate of each participant, were measured before and immediately after smoking. A self administered questionnaire was used to collect personal details and data about smoking pattern. Results: Mean increases in systolic blood pressures ($12{\pm}1$ mmHg), heart rates ($20{\pm}2$ bpm) and respiratory rates ($4{\pm}1$ breaths/min) were observed (p < 0.001). A mean decrease in diastolic blood pressures ($1{\pm}1$ mmHg) was observed (p = 0.483). Conclusion: Smoking dokha has a significant acute effect on systolic blood pressure, heart rate and respiratory rate. Anti smoking campaigns must address the ill effects of this form of smoking. Results from the study warrant further research into this method of smoking which is becoming more popular. -
Huang, Wei-Yi;Chen, Dong-Hui;Ning, Li;Wang, Li-Wei 1823
The gene encoding the Nin one binding (NOB1) protein which plays an essential role in protein degradation has been investigated for possible tumor promoting functions. The present study was focused on NOB1 as a possible therapeutic target for breast cancer treatment. Lentivirus mediated NOB1 siRNA transfection was used to silence the NOB1 gene in two established breast cancer cell lines, MCF-7 and MDA-MB-231, successful transfection being confirmed by fluorescence imaging. NOB1 deletion caused significant decline in cell proliferation was observed in both cell lines as investigated by MTT assay. Furthermore the number and size of the colonies formed were also significantly reduced in the absence of NOB1. Moreover NOB1 gene knockdown arrested the cell cycle and inhibited cell cycle related protein expression. Collectively these results indicate that NOB1 plays an essential role in breast cancer cell proliferation and its gene expression could be a therapeutic target. -
Yavari, Parvin;Abadi, Alireza;Amanpour, Farzaneh;Bajdik, Chris 1829
Background: The generalized gamma distribution statistics constitute an extensive family that contains nearly all of the most commonly used distributions including the exponential, Weibull and log normal. A saturated version of the model allows covariates having effects through all the parameters of survival time distribution. Accelerated failure-time models assume that only one parameter of the distribution depends on the covariates. Methods: We fitted both the conventional GG model and the saturated form for each of its members including the Weibull and lognormal distribution; and compared them using likelihood ratios. To compare the selected parameter distribution with log logistic distribution which is a famous distribution in survival analysis that is not included in generalized gamma family, we used the Akaike information criterion (AIC; r=l(b)-2p). All models were fitted using data for 369 women age 50 years or more, diagnosed with stage IV breast cancer in BC during 1990-1999 and followed to 2010. Results: In both conventional and saturated parametric models, the lognormal was the best candidate among the GG family members; also, the lognormal fitted better than log-logistic distribution. By the conventional GG model, the variables "surgery", "radiotherapy", "hormone therapy", "erposneg" and interaction between "hormone therapy" and "erposneg" are significant. In the AFT model, we estimated the relative time for these variables. By the saturated GG model, similar significant variables are selected. Estimating the relative times in different percentiles of extended model illustrate the pattern in which the relative survival time change during the time. Conclusions: The advantage of using the generalized gamma distribution is that it facilitates estimating a model with improved fit over the standard Weibull or lognormal distributions. Alternatively, the generalized F family of distributions might be considered, of which the generalized gamma distribution is a member and also includes the commonly used log-logistic distribution. -
Darehdori, Ahmad Shabanizadeh;Dastjerdi, Mehdi Nikbakht;Dahim, Hajar;Slahshoor, Mohammadreza;Babazadeh, Zahra;Taghavi, Mohammad Mohsen;Taghipour, Zahra;Gaafarineveh, Hamidreza 1833
Objective: Promoter methylation, which can be regulated by MTHFR activity, is associated with silencing of genes. In this study we evaluated the methylation status (type) of the BRCA2 promoter in ovarian cancer patients carrying different genotypes of the MTHFR gene (A or C polymorphisms at position 1298). Methods: The methylation type of the BRCA2 promoter was evaluated using bisulfate-modified DNA in methylation-specific PCR and the MTHFRa1278c polymorphism was assessed by PCR-RFLP. Results: Analysis of the BRCA2 promoter methylation type of cases showed that 7 out of 60 cases (11.7%) were methylated while the remaining 53 (88.3%) were unmethylated. In methylated cases, one out of the 7 cases had a CC genotype and the remaining 6 methylated cases had an AC genotype. The AA genotype was absent. In unmethylated cases, 34, 18, and one out of these had AC, AA and CC genotype, respectively. Conclusion: There was no significant relationship between the methylation types of the BRCA2 promoter in different genotypes of MTHFRa1298c polymorphism in ovarian cancer; p=0.255. There was no significant relation between the methylation types of the BRCA2 promoter in different genotypes of the MTHFRa1298c polymorphism in ovarian cancer. -
Inal, Ali;Kaplan, M. Ali;Kucukoner, Mehmet;Urakcl, Zuhat;Karakus, Abdullah;Islkdogan, Abdurrahman 1837
Background: In spite of the fact that platinum-based doublets are considered the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC), no elderly-specific platinum based prospective phase III regimen has been explored. The aim of this retrospective singlecenter study was to evaluate the efficacy and side effects of cisplatin-based therapy specifically for the elderly. Methods: Patients receiving platinum-based treatment were divided into three groups. In the first group (GC), Gemcitabine was administrated at 1000$mg/m^2$ on days 1, 8 and cisplatin was added at 75$mg/m^2$ on day 1. In the second group (DC), 75$mg/m^2$ docetaxel and cisplatin were administered on day 1. The third group (PC) received 175 mg of paclitaxel and 75 mg of cisplatin on day 1. These treatments were repeated every three weeks. Result: GC arm had 36, the DC arm 42 and the PC arm 29 patients. Grade III-IV thrombocytopenia was higher in the GC arm (21.2% received GC, 2.8% received DC, and 3.8% received PC), while sensory neuropathy was lower in patients with GC arm (3.0%, 22.2%, and 23.1% received GC, DC and PC, respectively). There were no statistically significant difference in the response rates among the three groups (p>0.05). The median Progression-free survival (PFS) was 5.0 months and the median Overall survival (OS) in each group was 7.1, 7.4 and 7.1 months, respectively (p>0.05). Conclusion: The response rate, median PFS and OS were similar among the three treatment arms. Grade III-IV thrombocytopenia was higher in the GC arm, while the GC regimen was more favorable than the other cisplatin-based treatmetns with regard to sensory neuropathy. -
Inal, Ali;Ciltas, Aydin;Yildiz, Ramazan;Berk, Veli;Kos, F. Tugba;Dane, Faysal;Unek, Ilkay Tugba;Colak, Dilsen;Ozdemir, Nuriye Yildirim;Buyukberber, Suleyman;Gumus, Mahmut;Ozkan, Metin;Isikdogan, Abdurrahman 1841
Background: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy has limited impact on overall survival (OS) so that eligible patients should be selected carefully. The aim of this study was to analyze prognostic factors for survival in Turkish advanced pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving gemcitabine (Gem) alone or gemcitabine plus cisplatin (GemCis). Methods: This retrospective evaluation was performed for patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and who received gemcitabine between December 2005 and August 2011. Twenty-seven potential prognostic variables were chosen for univariate and multivariate analyses to identify prognostic factors associated with survival. Results: Among the 27 variables in univariate analysis, three were identified to have prognostic significance: sex (p = 0.04), peritoneal dissemination (p =0.02) and serum creatinine level (p=0.05). Multivariate analysis by Cox proportional hazard model showed only peritoneal dissemination to be an independent prognostic factor for survival. Conclusion: In conclusion, peritoneal metastasis was identified as an important prognostic factor in metastatic pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving Gem or GemCis. The findings should facilitate pretreatment prediction of survival and can be used for selecting patients for treatment. -
Yu, Yong-Jiang;Li, Yu-Min;Hou, Xu-Dong;Guo, Chao;Cao, Nong;Jiao, Zuo-Yi 1845
Objective: Tissue factor (TF) is expressed abnormally in certain types of tumor cells, closely related to invasion and metastasis. The aim of this study was to construct a human gastric cancer cell line SGC7901 stably-transfected with human TF, and observe effects on oxaliplatin-dependent inhibition of invasion and the apoptosis induction. Methods: The target gene TF was obtained from human placenta by nested PCR and introduced into the human gastric cell line SGC7901 through transfection mediated by lipofectamine. Stably-transfected cells were screened using G418. Examples successfully transfected with TF-pcDNA3 recombinant (experimental group), and empty vector pcDNA3 (control group) were incubated with oxaliplatin. Transwell chambers were used to show change in invasive ability. Caspase-3 activity was detected using a colorimetric method and annexin-V/PI double-staining was applied to detect apoptosis. Results: We generated the human gastric cancer cell line SGC7901/TF successfully, expressing TF stably and efficiently. Compared with the control group, invasion increased, whereas caspase-3 activity and apoptosis rate were decreased in the experimental group. Conclusion: TF can enhance the invasive capacity of gastric cancer cells in vitro. Its increased expression may reduce invasion inhibition and apoptosis-inducing effects of oxaliplatin and therefore may warrant targeting for improved chemotherapy. -
Allem, Jon-Patrick;Ayers, John W.;Unger, Jennifer B.;Irvin, Veronica L.;Hofstetter, C. Richard;Hovell, Melbourne F. 1851
Immigration to a nation with a stronger anti-smoking environment has been hypothesized to make smoking less common. However, little is known about how environments influence risk of smoking across the lifecourse. Research suggested a linear decline in smoking over the lifecourse but these associations, in fact, might not be linear. This study assessed the possible nonlinear associations between age and smoking and examined how these associations differed by environment through comparing Koreans in Seoul, South Korea and Korean Americans in California, United States. Data were drawn from population based telephone surveys of Korean adults in Seoul (N=500) and California (N=2,830) from 2001-2002. Locally weighted scatterplot smoothing (lowess) was used to approximate the association between age and smoking with multivariable spline logistic regressions, including adjustment for confounds used to draw population inferences. Smoking differed across the lifecourse between Korean and Korean American men. The association between age and smoking peaked around 35 years among Korean and Korean American men. From 18 to 35 the probability of smoking was 57% higher (95%CI, 40 to 71) among Korean men versus 8% (95%CI, 3 to 19) higher among Korean American men. A similar difference in age after 35, from 40 to 57 years of age, was associated with a 2% (95%CI, 0 to 10) and 20% (95%CI, 16 to 25) lower probability of smoking among Korean and Korean American men. A nonlinear pattern was also observed among Korean American women. Social role transitions provide plausible explanations for the decline in smoking after 35. Investigators should be mindful of nonlinearities in age when attempting to understand tobacco use. -
To assess the impact of household income and economic recession on participation in CRC screening, we estimated annual participating proportions from 2007 to 2009 for different CRC screening modalities according to household income levels. A total of 8,042 subjects were derived from the fourth Korean National Health and Nutrition Examination Survey (KNHANES IV). Multivariate logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for CRC screening with household income quartiles by gender in each year. People were less likely to attend a high-cost CRC screening such as a sigmoidoscopy or colonoscopy independent of the income quartile during the economic recession. Income disparities for participating in opportunistic cancer screening appear to have existed among both males and females during the three years (2007-2009), but were most distinctive in 2009. An increase in mortality of CRC can therefore be expected due to late detection in periods of economic crisis. Accordingly, the government should expand the coverage of CRC screening to prevent excess deaths by reducing related direct and indirect costs during the economic recession.
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Chen, Li-Kun;Liang, Ying;Yang, Qun-Ying;Xu, Fei;Zhou, Ning-Ning;Xu, Guang-Chuan;Liu, Guo-Zhen;Wei, Wei-Dong 1863
Background: Maintenance chemotherapy is one strategy pursued in recent years with intent to break through the chemotherapy plateau for advanced non-small cell lung cancer (NSCLC). However, given the toxicity, platinum-based combinations are rarely given for this purpose. We carried out the present prospective study of triplet platinum-based combination sequential chemotherapy in advanced NSCLC to investigate if patients could tolerate and benefit from such intensive treatment. Methods: From Dec 2003 to Dec 2007, 190 stage IIIB and IV NSCLC patients in Sun yat-sen University sequentially received the 3 platinum-based combination (TP-NP-GP) treatment (T: paclitaxol175$mg/m^2$ d1; N: vinorelbine25$mg/m^2$ d1 and 8; G: gemcitabine1$g/m^2$ d1 and 8; P: cisplatin20$mg/m^2$ d1-5; repeated every 3 weeks). Patients were followed up to at least 3 years to obtain survival data. Treatment toxicities and the quality of life (QOL) were assessed during the whole treatment. Results: There were 187 patients evaluable. The TP, NP and GP response rates with sequential use were 42.8% (80/187), 41.1% (65/158) and 28.8% (21/73) respectively. Median survival time was 18.2 months and the 1, 2 and 3 year overall survival (OS) rates were 78.7%, 38.5% and 21.3%. Patients receiving > 6 cycles of chemotherapy had significantly longer OS and TTP (MST 25.3 vs. 14.5 months, TTP 15.1 vs. 9.1 months). The QOL on the whole for the patients was improved after chemotherapy. Conclusions: The sequential chemotherapy strategy with triplet platinum-based combination regimens can improve the survival outcome and the quality of life of advanced non-small cell lung cancer patients. -
Yehya, Ashwaq Hamid;Yusoff, Narazah Mohd;Khalid, Imran A.;Mahsin, Hakimah;Razali, Ruzzieatul Akma;Azlina, Fatimah;Mohammed, Kamil Sheikh;Ali, Syed A. 1869
Background: To assess the diagnostic potential of tumor-associated high molecular weight DNA in stool samples of 32 colorectal cancer (CRC) patients compared to 32 healthy Malaysian volunteers by means of polymerase chain reaction (PCR). Methods: Stool DNA was isolated and tumor-associated high molecular weight DNA (1.476 kb fragment including exons 6-9 of the p53 gene) was amplified using PCR and visualized on ethidium bromide-stained agarose gels. Results: Out of 32 CRC patients, 18 were positive for the presence of high molecular weight DNA as compared to none of the healthy individuals, resulting in an overall sensitivity of 56.3% with 100% specificity. Out of 32 patients, 23 had tumor on the left side and 9 on the right side, 16 and 2 being respectively positive. This showed that high molecular weight DNA was significantly (p = 0.022) more detectable in patients with left side tumor (69.6% vs 22.2%). Out of 32 patients, 22 had tumors larger than 1.0 cm, 18 of these (81.8%) being positive for long DNA as compared to not a single patient with tumor size smaller than 1.0 cm (p <0.001). Conclusion: We detected CRC-related high molecular weight p53 DNA in stool samples of CRC patients with an overall sensitivity of 56.3% with 100% specificity, with a strong tumor size dependence. -
Gong, Ping;Huang, Xin-En;Chen, Chuan-Ying;Liu, Jian-Hong;Meng, Ai-Feng;Feng, Ji-Feng 1873
Objective: To compare the complications of peripherally inserted central catheters (PICC) by a modified Seldinger technique under ultrasound guidance or the conventional (peel-away cannula) technique. Methods: From February to December of 2010, cancer patients who received PICC at the Department of Chemotherapy in Jiangsu Cancer Hospital were recruited into this study, and designated UPICC if their PICC lines were inserted under ultrasound guidance, otherwise CPICC if were performed by peel-away cannula technique. The rates of successful placement, hemorrhage around the insertion area, phlebitis, comfort of the insertion arm, infection and thrombus related to catheterization were analyzed and compared on days 1, 5 and 6 after PICC and thereafter. Results: A total of 180 cancer patients were recruited, 90 in each group. The rates of successful catheter placement between two groups differed with statistical significance (P <0.05), favoring UPICC. More phlebitis and finger swelling were detected in the CPICC group (P <0.05). From day 6 to the date the catheter was removed and thereafter, more venous thrombosis and a higher rate of discomfort of insertion arms were also observed in the CPICC group. Conclusion: Compared with CPICC, UPICC could improve the rate of successful insertion, reduce catheter related complications and increase comfort of the involved arm, thus deserving to be further investigated in randomized clinical studies. -
Hong, Ri;Shen, Min-He;Xie, Xiao-Hong;Ruan, Shan-Ming 1877
Breast cancer metastasis is the most common cause of cancer-related death in women. Thus, seeking targets of breast tumor cells is an attractive goal towards improving clinical treatment. The present study showed that CCL18 from tumor-associated macrophages could promote breast cancer metastasis via PITPNM3. In addition, we found that pachymic acid (PA) could dose-dependently inhibit migration and invasion of MDA-MB-231cells, with or without rCCL18 stimulation. Furthermore, evidence was obtained that PA could suppress the phosphorylation of PITPNM3 and the combination of CCL18 and PITPNM3. Therefore, we speculate that PA could inhibit breast cancer metastasis via PITPNM3. -
Kadivar, Maryam;Mafi, Negar;Joulaee, Azadeh;Shamshiri, Ahmad;Hosseini, Niloufar 1881
Breast cancer is a heterogeneous disease that is affected by ethnicity of patients. According to hormone receptor status and gene expression profiling, breast cancers are classified into four molecular subtypes, each showing distinct clinical behavior. Lack of sufficient data on molecular subtypes of breast cancer in Iran, prompted us to investigate the prevalence and the clinicopathological features of each subtype among Iranian women. A total of 428 women diagnosed with breast cancer from 2002 to 2011 were included and categorized into four molecular subtypes using immunohistochemistry. Prevalence of each subtype and its association with patients' demographics and tumor characteristics, such as size, grade, lymph-node involvement and vascular invasion, were investigated using Chi-square, analysis of variance and multivariate logistic regression. Luminal A was the most common molecular subtype (63.8%) followed by Luminal B (8.4%), basal-like (15.9%) and HER-2 (11.9%). Basal-like and HER-2 subtypes were mostly of higher grades while luminal A tumors were more of grade 1 (P<0.001). Vascular invasion was more prevalent in HER-2 subtype, and HER-2 positive tumors were significantly associated with vascular invasion (P=0.013). Using muti-variate analysis, tumor size greater than 5 cm and vascular invasion were significant predictors of 3 or more nodal metastases. Breast cancer was most commonly diagnosed in women around 50 years of age and the majority of patients had lymph node metastasis at the time of diagnosis. This points to the necessity for devising an efficient screening program for breast cancer in Iran. Further, prospective surveys are suggested to evaluate prognosis of different subtypes in Iranian patients. -
Zheng, Shan;Song, Qing-Kun;Zhao, Lin;Huang, Rong;Sun, Li;Li, Jing;Fan, Jin-Hu;Zhang, Bao-Ning;Yang, Hong-Jian;Xu, Feng;Zhang, Bin;Qiao, You-Lin 1887
The aim of this study was to detail characteristics of mammary Paget's disease (PD) representing the whole population in China. A total of 4211 female breast cancer inpatients at seven tertiary hospitals from seven representative geographical regions of China were collected randomly during 1999 to 2008. Data for demography, risk factors, diagnostic imaging test, physical examination and pathologic characters were surveyed and biomarker status was tested by immunohistochemistry. The differences of demography and risk factors between PD with breast cancer and other lesions were compared using Chi-square test or t-test, with attention to physical examination and pathological characters. The percentage of PD was 1.6% (68/4211) in all breast cancers. The mean age at diagnosis was 48.1, and 63.2% (43/68) patients were premenopausal. There is no difference in demography and risk factors between PD with breast cancer and other breast cancer (P > 0.05). The main pattern of PD in physical exam and pathologic pattern were patients presenting with a palpable mass in breast (65/68, 95.6%) and PD with underlying invasive cancer (82.4%, 56/68) respectively. The rate of multifocal disease was 7.4% (5/68). PD with invasive breast cancer showed larger tumor size, more multifocal disease, lower ER and PR expression and higher HER2 overexpression than those in other invasive breast cancer (P < 0.05). These results suggested that PD in China is a concomitant disease of breast cancer, and that PD with underlying invasive cancer has more multiple foci and more aggressive behavior compared with other breast invasive cancer. We address the urgent needs for establishing diagnostic and therapeutic guidelines for mammary PD in China. -
Background and Aims: Liver cancer is a major health problem in low-resource countries. Approximately 55% of all liver cancer occurs in China. Hebei Province is one of the important covering nearly 6% of the population of China. The aim of this paper was to explore liver cancer mortality trends during past 30 years, and provide basic information on prevention strategies. Methods: Hebei was covered covered all the three national surveys during 1973-1975, 1990-1992, and 2004-2005 and one provincial survey during 1984-1986. Subjects included all cases dying from liver cancer in Hebei Province. Liver cancer mortality trend and geographic differences across cities and counties were analyzed. Results: There were 82,878 deaths in Hebei Province during 2004-2005 with an average mortality rate was 600.9/10,000, and an age-adjusted rate of 552.3/10,000. Those dying of cancer were 18,424 cases, accounting for 22.2% of all deaths, second only to cerebrovascular disease as a cause of death. Cancer mortality was 133.6/100,000 (age-adjusted rate was 119.2/100,000). Liver cancer ranked fourth in this survey with a mortality rate of 21.0/100,000, 28.4/100,000 in males and 13.35/10,000 in females, accounting for 15.7%, 17.1% and 13.4% of the total number of cancer deaths and in males and females, respectively. The sex ratio was 2.13. Since the 1970s, liver cancer deaths of Hebei province have been increasing slightly. The crude mortality rates in the four surveys were 11.3, 16.0, 17.4, 21.0 per 100,000, respectively, with age-adjusted rates fluctuating during the past 30 years, but the trend also being upwards. There is a tendency for the mortality rates to be higher in coastal than mountain areas, and is relative lower in the plain area, with crude mortality rates of 25.3, 22.1, and 19.1 per 100,000, respectively. There were no notable differences in cride data between urban and rural, but the age-adjusted mortality rate in rural was much higher. Conclusion: Our study indicated that the mortality of liver cancer in Hebei Province is lower than the national average level. There is a slightly increase trend, especially in some counties. Liver cancer is a major health problem and it is necessary to further promote prevention strategies in Hebei province.
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Li, Jian-Yi;Zhang, Yang;Zhang, Wen-Hai;Jia, Shi;Kang, Ye;Zhu, Xiao-Yu 1901
Background: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Methods: Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT-PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. Results: The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Conclusions: Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins. -
Akbari, Mohammad Esmaeil;Haghighatkhah, Hamidreza;Shafiee, Mohammad;Akbari, Atieh;Bahmanpoor, Mitra;Khayamzadeh, Maryam 1907
Background: Breast cancer is the most prevalent cancer and the fifth cause of cancer death in Iranian women. Early detection and treatment are important for appropriate management of this disease. Mammography and ultrasonography are used for screening and evaluation of symptomatic cases and the main diagnostic test for breast cancer is pathological. In this study we evaluated mammography and ultrasonography as diagnostic tools. Methods: In this cross-sectional study 384 mammography and ultrasonography reports for 255 women were assessed, divided into benign and malignant groups. Suspected cases were referred for pathology evaluation. The radiologic and pathologic reports were compared and also comparison was performed based on age groups (more and less than 50 years old), history of breastfeeding and gravidity. Statistical analysis was performed by SPSS. Results: The mean ages of malignant and benign cases were$49{\pm}11.6$ and$43{\pm}11.2$ years, respectively. Sensitivity and specificity for mammography were 73% and 45%, respectively. Sensitivity and specificity for ultrasonography were 69% and 49%, respectively. There were statistical differences between specificity of mammography in patients based on factors such as history of gravidity, breastfeeding and sensitivity in patients equal or more than 50 years old and less. Conclusion: Factors affecting different results in mammography and ultrasonography reports were classified into three groups, consisting of skill, experience and training of medical staff, and setting of instruments. It is recommended that health managers in developing countries pay attention the quality of setting and man power more than current status. Policy-makers and managers must establish guidelines regarding breast imaging in Iran. -
Aim: New technologies for the early detection of pancreatic cancer (PC) are urgently needed. The aim of the present study was to screen for the potential protein biomarkers in serum using proteomic fingerprint technology. Methods: Magnetic beads combined with surface-enhanced laser desorption/ionization (SELDI) TOF MS were used to profile and compare the protein spectra of serum samples from 85 patients with pancreatic cancer, 50 patients with acute-on-chronic pancreatitis and 98 healthy blood donors. Proteomic patterns associated with pancreatic cancer were identified with Biomarker Patterns Software. Results: A total of 37 differential m/z peaks were identified that were related to PC (P < 0.01). A tree model of biomarkers was constructed with the software based on the three biomarkers (7762 Da, 8560 Da, 11654 Da), this showing excellent separation between pancreatic cancer and non-cancer., with a sensitivity of 93.3% and a specificity of 95.6%. Blind test data showed a sensitivity of 88% and a specificity of 91.4%. Conclusions: The results suggested that serum biomarkers for pancreatic cancer can be detected using SELDI-TOF-MS combined with magnetic beads. Application of combined biomarkers may provide a powerful and reliable diagnostic method for pancreatic cancer with a high sensitivity and specificity.
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Fang, Wei-Jia;Zheng, Yi;Wu, Li-Ming;Ke, Qing-Hong;Shen, Hong;Yuan, Ying;Zheng, Shu-Sen 1917
Background: Colorectal cancer is one of the leading causes of mortality worldwide. Genome wide analysis studies have identified sequence mutations causing loss-of-function that are associated with disease occurrence and severity. Epigenetic modifications, such DNA methylation, have also been implicated in many cancers but have yet to be examined in the East Asian population of colorectal cancer patients. Methods: Biopsies of tumors and matched non-cancerous tissue types were obtained and genomic DNA was isolated and subjected to the bisulphite conversion method for comparative DNA methylation analysis on the Illumina Infinium HumanMethylation27 BeadChip. Results: Totals of 258 and 74 genes were found to be hyper- and hypo-methylated as compared to the individual's matched control tissue. Interestingly, three genes that exhibited hypermethylation in their promoter regions, CMTM2, ECRG4, and SH3GL3, were shown to be significantly associated with colorectal cancer in previous studies. Using heatmap cluster analysis, eight hypermethylated and 10 hypomethylated genes were identified as significantly differentially methylated genes in the tumour tissues. Conclusions: Genome-wide methylation profiling facilitates rapid and simultaneous analysis of cancerous cells which may help to identify methylation markers with high sensitivity and specificity for diagnosis and prognosis. Our results show the promise of the microarray technology in identification of potential methylation biomarkers for colorectal cancers. -
Background: Studies investigating the association between 2R/3R polymorphisms in the thymidylate synthase 5'-untranslated enhanced region (TYMS 5'-UTR) and gastric cancer risk have generated conflicting results. Thus, a meta-analysis was performed to summarize the data on any association. Methods: Pubmed, Embase, and CNKI databases were searched for all available studies. The strength of association between TYMS 5'-UTR 2R/3R polymorphism and gastric cancer risk was estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Results: Six individual case-control studies with a total of 1, 472 cases and 1, 895 controls were included into this meta-analysis. Analyses of total six relevant studies showed that there was no obvious association between the TYMS 5'-UTR 2R/3R polymorphism and gastric cancer risk. Subgroup analyses based on ethnicity showed 2R of TYMS 5'-UTR 2R/3R contributes to gastric cancer risk in the Asian population (
$OR_{Homozygote\;model}$ = 1.71, 95%CI 1.19-2.46, P = 0.004;$OR_{Recessive\;genetic\;model}$ = 1.70, 95%CI 1.18-2.43, P = 0.004). However, the association in Caucasian populations was uncertain due to the limited studies. Conclusions: Our meta-analysis suggests that 2R of TYMS 5'-UTR 2R/3R contributes to gastric cancer risk in the Asian population, while this association in Caucasians populations needs further study. -
Tammasakchai, Achiraya;Reungpatthanaphong, Sareeya;Chaiyasut, Chaiyavat;Rattanachitthawat, Sirichet;Suwannalert, Prasit 1929
Oxidative stress has been proposed to be involved in colorectal cancer development. Many dark pigments of plants have potent oxidative stress preventive properties. In this study, unpolished Thai rice was assessed for antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. Red strain unpolished Thai rice was also administered to rats exposed to azoxymethane (AOM) for induction of aberrant crypt foci (ACF). Serum malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) were investigated for cellular oxidative stress and serum antioxidants, respectively. Red pigment unpolished Thai rice demonstrated high antioxidant activity and was found to significantly and dose dependently decrease the total density and crypt multiplicity of ACF. Consumption of Thai rice further resulted in high serum antioxidant activity and low MDA cellular oxidative stress. Interestingly, the density of ACF was strongly related to MDA at r = 0.964, while it was inversely related with FRAP antioxidants (r = -0.915, p < 0.001). The results of this study suggest that the consumption of red strain of unpolished Thai rice may exert potentially beneficial effects on colorectal cancer through decrease in the level of oxidative stress. -
Durnali, Ayse;Tokluoglu, Saadet;Ozdemir, Nuriye;Inanc, Mevlude;Alkis, Necati;Zengin, Nurullah;Sonmez, Ozlem Uysal;Kucukoner, Mehmet;Anatolian Society of Medical Oncology (ASMO), Anatolian Society of Medical Oncology (ASMO) 1935
Introduction: Uterine sarcomas are a group of heterogenous and rare malignancies of the female genital tract and there is a lack of consensus on prognostic factors and optimal treatment. Objective and Methodology: To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatment outcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers from November 2000 to October 2010. Results: Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignant mixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. According to the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4% were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months (95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively. Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%, 78%, 49.4% respectively. Multivariate analysis showed that age${\geq}60$ years and high grade tumor were significantly associated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapy and radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade, adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS. Conclusion: Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS were found to be age and grade. -
Ferronika, Paranita;Triningsih, F.X. Ediati;Ghozali, Ahmad;Moeljono, Abraham;Rahmayanti, Siti;Shadrina, Arifah Nur;Naim, Awang Emir;Wudexi, Ivan;Arnurisa, Alfa Monica;Nanwani, Sandeep Tarman;Harijadi, Ahmad 1943
Introduction: Prostate cancer in Indonesia is the$3^{rd}$ ranking cancer among males and the$5^{th}$ rank for their cancer mortality. Prognostic markers that can identify aggressive prostate cancer in early stages and help select appropriate therapy to finally reduce the mortality are therefore urgently needed. It has been suggested that stem cells in the prostate gland have a role in initiation, progression, and metastasis of cancer, although controversy continues to exist. Maintenance of normal stem cell or reserve cell populations in several epithelia including prostate has been shown to be regulated by p63 and alteration of p63 expression is considered to have an oncogenic role in prostate cancer. We hypothesize that the expression of cytoplasmic aberrance of p63 is associated with high ALDH1A1 expression as a cancer stem cell marker, thus leading to progression of prostate cancer. Methods: Using a cross-sectional study during two years (2009-2010), a total of 79 paraffin embedded tissues of benign prostatic hyperplasia, PIN prostatic intraepithelial neoplasia, low and high Gleason score prostate cancer were investigated using immunohistochemistry. Associations between cytoplasmic p63 and ALDH1A1, as well as with pathological diagnosis, were analyzed by Chi-Square test using SPSS 15.0. Links of both markers with cell proliferation rate (KI-67) and apoptotic rate (cleaved caspase 3) were also analyzed by Kruskal-Wallis test. Results: The mean age of patient at the diagnosis is 70.0 years. Cytoplasmic aberrance of p63 was associated with ALDH1A1 expression (p<0.001) and both were found to have significant relationships with pathological diagnosis (including Gleason score), (p=0.006 and p<0.001 respectively). Moreover, it was also found that higher levels of cytoplasmic p63 were significantly associated with the frequency of proliferating cells and cells undergoing apoptosis in prostate cancers (p=0.001 and p=0.016 respectively). Conclusion: p63 cytoplasmic aberrance is associated with high ALDH1A1 expression. These components are suggested to have an important role in prostate cancer progression and may be used as molecular markers. -
Zhou, Ping;Huang, Wei;Chu, Xing;Du, Liang-Feng;Li, Jian-Ping;Zhang, Chun 1949
Objective: The aim of this meta-analysis is to evaluate associations between LTA-252 A>G and breast cancer (BC). Methods: Electronic searches of several databases were conducted for all online publications. A total of 7 studies involving 4,625 BC patients and 4,373 controls were identified. Results: This meta-analysis showed no significant association between the LTA-252 A>G polymorphism and BC in overall or Caucasian populations. However, a positive association was found limited to Asian populations. Conclusion: Although there was no significant association found between the LTA-252 A>G polymorphism and BC overall, a positive association was found in Asian populations. -
Accuracy of Frozen Sections for Intraoperative Diagnosis of Complex Atypical Endometrial HyperplasiaTuran, Taner;Karadag, Burak;Karabuk, Emine;Tulunay, Gokhan;Ozgul, Nejat;Gultekin, Murat;Boran, Nurettin;Isikdogan, Zuhal;Kose, Mehmet Faruk 1953
Objective: The purpose of this study was to correlate the histological diagnosis made during intraoperative frozen section (FS) examination of hysterectomy samples with complex atypical endometrial hyperplasia (CAEH) diagnosed with definitive paraffin block histology. Methods: FS pathology results of 125 patients with a preoperative biopsy showing CAEH were compared retrospectively with paraffin block pathology findings. Results: Paraffin block results were consistent with FS in 78 of 125 patients (62.4%). The FS sensitivity and specificity of detecting cancer were 81.1% and 97.9%, with negative and positive predictive values of 76.7%, and 98.4%, respectively. Paraffin block results were reported as endometrial cancer in 77 of 125 (61.6%) patients. Final pathology was endometrial cancer in 45.3% patients diagnosed at our center and 76.9% for patients who had their diagnosis at other clinics (p=0.018). Paraffin block results were consistent with FS in 62.4% of all cases Consistence was 98.4% in patients who had endometrial cancer in FS. Conclusion: FS does not exclude the possibility of endometrial cancer in patients with the preoperative diagnosis of CAEH. In addition, sufficient endometrial sampling is important for an accurate diagnosis. -
Brassesco, Maria S.;Pezuk, Julia A.;Morales, Andressa G.;De Oliveira, Jaqueline C.;Valera, Elvis T.;Da Silva, Glenda N.;De Oliveira, Harley F.;Scrideli, Carlos A.;Umezawa, Kazuo;Tone, Luiz G. 1957
Bladder cancer is a common malignancy worldwide. Despite the increased use of cisplatin-based combination therapy, the outcomes for patients with advanced disease remain poor. Recently, altered activation of the PI3K/Akt/mTOR pathway has been associated with reduced patient survival and advanced stage of bladder cancer, making its upstream or downstream components attractive targets for therapeutic intervention. In the present study, we showed that treatment with DTCM-glutaramide, a piperidine that targets PDK1, results in reduced proliferation, diminished cell migration and G1 arrest in 5637 and T24 bladder carcinoma cells. Conversely, no apoptosis, necrosis or autophagy were detected after treatment, suggesting that reduced cell numbers in vitro are a result of diminished proliferation rather than cell death. Furthermore previous exposure to 10${\mu}g/ml$ DTCM-glutarimide sensitized both cell lines to ionizing radiation. Although more studies are needed to corroborate our findings, our results indicate that PDK1 may be useful as a therapeutic target to prevent progression and abnormal tissue dissemination of urothelial carcinomas. -
Wu, Qiao;He, Xiao-Dong;Yu, Lan;Liu, Wei;Tao, Lian-Yuan 1963
Objectives: Recent data show that the metabolic syndrome may play a role in several cancers, but the etiology for biliary tract cancer is incompletely defined. The present aim was to evaluate risk factors for biliary tract cancer in China. Methods: A case-control study in which cases were biliary tract cancer patients referred to Peking Union Medical College Hospital (PUMCH). Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of PUMCH. Data on the metabolic syndrome, liver diseases, family history, and history of diabetes and hypertension were collected by retrospective review of the patients' records and health examination reports or by interview. Results: A total of 281 patients (102 intrahepatic cholangiocarcinoma (ICC), 86 extrahepatic cholangiocarcinoma (ECC) and 93 gallbladder carcinoma (GC)) and 835 age- and sex-matched controls were enrolled.$HBsAg^+/anti-HBc^+$ (P=0.002), history of diabetes (P=0.000), cholelithiasis (P=0.000), TC (P=0.003), and HDL (P=0.000) were significantly related to ICC. Cholelithiasis (P=0.000), Tri (P=0.001), LDL (P=0.000), diabetes (P=0.000), Apo A (P=0.000) and Apo B (P=0.012) were significantly associated with ECC. Diabetes (P=0.017), cholelithiasis (P=0.000) and Apo A (P=0.000) were strongly inversely correlated with GC. Conclusion: Cholelithiasis, HBV infection and metabolic symptoms may be potential risk factors for the development of biliary tract cancer. -
Shi, Yong-Hua;Chen, Rui;Talafu, Tuokan;Nijiati, Rehemu;Lalai, Suzuke 1971
Overexpression of several aquaporins (AQPs) has been reported in different types of human cancer but their role in carcinogenesis, for example in the cervix, have yet to be clearly defined. In this study, expression of AQPs in cervical carcinomawas investigated by real-time PCR, immunofluorescent and immunohistochemical assays and evaluated for correlations with clinicopathologic variables. AQP1, 3, 8 exhibited differential expression in cervical carcinoma, corresponding CIN and mild cervicitis. AQP1 was predominantly localized in the microvascular endothelial cell in the stroma of mild cervicitis, CIN and cervical carcinoma. AQP3 and AQP8 were localized in the membrane of normal squamous epithelium and carcinoma cells, local signals being more common than diffuse staining. AQP1 and AQP3 expression was remarkably stronger in cervical cancer than in mild cervicitis and CIN2-3 (P<0.05). AQP8 expression was highest in CIN2-3 (91.7%), but levels in cervical carcinoma were also higher than in mild cervicitis. AQP1, AQP3, AQP8 expression significantly increased in advanced stage, deeper infiltration, metastatic lymph nodes and larger tumor volume (P<0.05). Our findings showed that AQPs might play important roles in cervical carcinogenesis and tumour progression in Uygur women. -
Prommaban, Adchara;Kodchakorn, Kanchanok;Kongtawelert, Prachya;Banjerdpongchai, Ratana 1977
Houttuynia cordata Thunb (HCT) is a native herb found in Southeast Asia which features various pharmacological activities against allergy, inflammation, viral and bacterial infection, and cancer. The aims of this study were to determine the cytotoxic effect of 6 fractions obtained from silica gel column chromatography of alcoholic HCT extract on human leukemic Molt-4 cells and demonstrate mechanisms of cell death. Six HCT fractions were cytotoxic to human lymphoblastic leukemic Molt-4 cells in a dose-dependent manner by MTT assay, fraction 4 exerting the greatest effects. Treatment with$IC_{50}$ of HCT fraction 4 significantly induced Molt-4 apoptosis detected by annexinV-FITC/propidium iodide for externalization of phosphatidylserine to the outer layer of cell membrane. The mitochondrial transmembrane potential was reduced in HCT fraction 4-treated Molt-4 cells. Moreover, decreased expression of Bcl-xl and increased levels of Smac/Diablo, Bax and GRP78 proteins were noted on immunoblotting. In conclusion, HCT fraction 4 induces Molt-4 apoptosis cell through an endoplasmic reticulum stress pathway. -
Kaneko, Takaaki;Shimpo, Kan;Chihara, Takeshi;Beppu, Hidehiko;Tomatsu, Akiko;Shinzato, Masanori;Yanagida, Takamasa;Ieike, Tsutomu;Sonoda, Shigeru;Futamura, Akihiko;Ito, Akihiro;Higashiguchi, Takashi 1983
High temperature- and pressure-treated garlic (HTPG) has been shown to have enhanced antioxidative activity and polyphenol contents. Previously, we reported that HTPG inhibited 1,2-dimethylhydrazine-induced mucin depleted foci (premalignant lesions) and$O^6$ -methylguanine DNA adduct formation in the rat colorectum. In the present study, we investigated the modifying effects of HTPG on N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG)-induced pyloric stomach and small intestinal carcinogenesis in mice. Male C57BL/6 mice were given ENNG (100 mg/l) in drinking water for the first 4 weeks, then a basal diet or diet containing 2% or 5% HTPG for 30 weeks. The incidence and multiplicity of pyloric stomach and small intestinal (duodenal and jejunal) tumors in the 2% HTPG group (but not in the 5% HTPG group) were significantly lower than those in the control group. Cell proliferation of normal-appearing duodenal mucosa was assessed by MIB-5 immunohistochemistry and shown to be significantly lower with 2% HTPG (but again not 5% HTPG) than in controls. These results in dicate that HTPG, at 2% in the diet, inhibited ENNG-induced pyloric stomach and small intestinal (especially duodenal) tumorigenesis in mice, associated with suppression of cell proliferation. -
Goksel, Fatih;Peksoy, Irfan;Koc, Orhan;Gultekin, Murat;Ozgul, Nejat;Sencan, Irfan 1989
Background and Purpose: An analysis of the current nuclear medicine (NM) status and future demand in Turkey in line with the international benchmarks was conducted to establish a comprehensive baseline reference. Methods: Data from all NM centers on major equipment and manpower in Turkey were collected through a survey and cross-checked with the primary research and governmental data. Data regarding manpower currently working were obtained from the relevant academic centers and occupational societies. Results: The current numbers of NM laboratories, NM specialists, gamma cameras, PET/CT scanners, radioiodine treatment units for thyroid cancer are 217, 474, 287, 75 and 39, respectively. There was personnel and equipment need underestimated in the field compared to developed countries. Equipment insufficiency was more significant in the Ministry of Health (MoH) hospitals. These gaps should be eliminated with strategic planning of equipment and NM laboratories. Currently, the number of the PET/CT devices is at the level of the developed countries. The number of specialists in the field should reach the expected goal in 2023. By 2023, Turkey will need around 820 NM specialists, 498 gamma cameras and 99 PET/CT devices. In addition, further studies should be made regarding other related staff, particularly for health physicians, radiopharmacists and NM technicians. Conclusion: There is an insufficiency of personnel and equipment in Turkey's NM field. Comprehensive strategic planning is required to allocate limited resources and the purchase of the equipment and employment policies should be structured as part of "National Special Feature Requiring Health Service Plan". -
Chindaprasirt, Jarin;Sookprasert, Aumkhae;Sawanyawisuth, Kittisak;Limpawattana, Panita;Tiamkao, Somsak 1995
Background: Brain metastasis from cholangiocarcinoma (CCA) is a rare but fatal event. To the best of our knowledge, only few cases have been reported. Herein, we report the incident rate and a first case series of brain metastases from CCA. Methods: Between January 2006 and December 2010 5,164 patients were treated at Srinagarind hospital, Khon Kaen University; of those, 8 patients developed brain metastasis. Here we reviewed clinical data and survival times. Results: The incident rate of brain metastases from CCA was 0.15%. The median age of the patients was 60 years. Tumor subtypes were intrahepatic in 6 and hilar in 2 patients. All suffered from symptoms related to brain metastasis. Three patients were treated with whole-brain radiation therapy (WBRT), one of whom also underwent surgery. The median survival after the diagnosis of brain metastasis was 9.5 weeks (1-28 weeks). The longest survival observed in a patient in RPA class I with two brain lesions and received WBRT. Conclusion: This is a first case series of brain metastases from CCA with the incident rate of 0.15%. It is rare and associated with short survival time. -
Khanra, Kalyani;Bhattacharya, Chandan;Bhattacharyya, Nandan 1999
Background: DNA polymerase is a single-copy gene that is considered to be part of the DNA repair machinery in mammalian cells. The encoded enzyme is a key to the base excision repair (BER) pathway. It is evident that pol beta has mutations in various cancer samples, but little is known about ovarian cancer. Aim: Identification of any variant form of$pol{\beta}$ cDNA in ovarian carcinoma and determination of association between the polymorphism and ovarian cancer risk in Indian patients. We used 152 samples to isolate and perform RT-PCR and sequencing. Results: A variant of polymerase beta (deletion of exon 4-6 and 11-13, comprising of amino acid 63-123, and 208-304) is detected in heterozygous condition. The product size of this variant is 532 bp while wild type pol beta is 1 kb. Our study of association between the variant and the endometrioid type shows that it is a statistically significant factor for ovarian cancer [OR=31.9 (4.12-246.25) with p<0.001]. The association between variant and stage IV patients further indicated risk (${\chi}^2$ value of 29.7, and OR value 6.77 with 95% CI values 3.3-13.86). The correlation study also confirms the association data (Pearson correlation values for variant/stage IV and variant/endometrioid of 0.44 and 0.39). Conclusion: Individuals from this part of India with this type of variant may be at risk of stage IV, endometrioid type ovarian carcinoma. -
Purpose: E-cadherin is a transmemberane protein which is responsible for adhesion of endothelial cells. The aim of our study was to assess existing evidence of associations between reduced expression of E-cadherin and prognosis of ovarian cancer with a discussion of potential approaches to exploiting any prognostic value for improved clinical management. Methods: We conducted a meta-analysis of 9 studies (n=915 patients) focusing on the correlation of reduced expression of E-cadherin with overall survival. Data were synthesized with random or fixed effect hazard ratios. Results: The studies were categorized by author/year, number of patients, FIGO stage, histology, cutoff value for E-cadherin positivity, and methods of hazard rations (HR) estimation, HR and its 95% confidence interval (CI). Combined hazard ratios suggested that reduced expression of E-cadherin positivity was associated with poor overall survival (OS), HR= 2.10, 95% CI:1.13-3.06. Conclusion: The overall survival of the E-cadherin negative group with ovarian cancer was significant poorer than the E-cadherin positive group. Upregulation of E-cadherin is an attractive therapeutic approach that could exert significant effects on clinical outcome of ovarian cancer.
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He, Huai-Zhen;Wang, Nan;Zhang, Jie;Zheng, Lei;Zhang, Yan-Min 2009
Objective: Taspine, isolated from Radix et Rhizoma Leonticis has demosntrated potential proctiective effects against cancer. Tas13D, a novel taspine derivative synthetized by structure-based drug design, have been shown to possess interesting biological and pharmacological activities. The current study was designed to evaluate its antiproliferative activity and underlying mechanisms. Methods: Antiproliferative activity of tas13D was evaluated by xenograft in athymic mice in vivo, and by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and cell migration assays with human liver cancer (SMMC-7721) cell lines in vitro. Docking between tas13D and VEGFR and EGFR was studied by with a Sybyl/Surflex module. VEGF and EGF and their receptor expression was determined by ELISA and real-time PCR methods, respectively. Results: Our present study showed that tas13D inhibited SMMC-7721 xenograft tumor growth, bound tightly with the active site of kinase domains of EGFR and VEGFR, and reduced SMMC-7721 cell proliferation (IC=34.7${\mu}mol/L$ ) and migration compared to negative controls. VEGF and EGF mRNAs were significantly reduced by tas13D treatment in a dose-dependent manner, along with VEGF and EGF production. Conclusion: The obtained results suggest that tas13D inhibits tumor growth and cell proliferation by inhibiting cell migration, downregulating mRNA expression of VEGF and EGF, and decreasing angiogenic factor production. Tas13D deserves further consideration as a chemotherapeutic agent. -
George, V. Cijo;Kumar, D.R. Naveen;Suresh, P.K.;Kumar, R. Ashok 2015
Oleanolic acid (OA) is a naturally occurring triterpenoid in food materials and is a component of the leaves and roots of Olea europaea, Viscum album L., Aralia chinensis L. and more than 120 other plant species. There are several reports validating its antitumor activity against different cancer cells apart from its hepatoprotective activity. However, antitumor activity against skin cancer has not beed studied well thus far. Hence the present study of effects of OA against HaCaT (immortalized keratinocyte) cells - a cell-based epithelial model system for toxicity/ethnopharmacology-based studies - was conducted. Radical scavenging activity ($DPPH{\cdot}$ ) and FRAP were determined spectrophotometrically. Proliferation was assessed by XTT assay at 24, 48 and 72 hrs with exposure to various concentrations (12.5-200${\mu}M$ ) of OA. Apoptotic induction potential of OA was demonstrated using a cellular DNA fragmentation ELISA method. Morphological studies were also carried out to elucidate its antitumor potential. The results revealed that OA induces apoptosis by altering cellular morphology as well as DNA integrity in HaCaT cells in a dose-dependent manner, with comparatively low cytotoxicity. The moderate toxicity observed in HaCaT cells, with induction of apoptosis, possibly suggests greater involvement of programmed-cell death-mediated mechanisms. We conclude that OA has relatively low toxicity and has the potential to induce apoptosis in HaCaT cells and hence provides a substantial and sound scientific basis for further validation studies. -
Dong, Wei;Meng, Long;Shen, Hong-Chang;Du, Jia-Jun 2021
Purpose: DBC2 (Deleted in Breast Cancer 2) has been indicated to be a tumor suppressor gene in many cancers including lung adenocarcinoma recently. In this study, we aimed to explore the expression status of DBC2 in different subtypes of lung adenocarcinoma (from pre-invasive to invasive lesions), and to determine if downregulation becomes more marked with pathological progression. Methods: We collected 172 tissue samples from different subtypes of lung adenocarcinoma and investigated the frequency of DBC2 loss by immunohistochemistry. Results: Our results indicated that DBC2 downregulation is a relatively frequent event in lung adenocarcinoma. Moreover, as the adenocarcinoma subtype turns to be more invasive, more downregulation occurred. Conclusion: We conclude that loss of DBC2 expression is an early and progressive event in the pathogenesis of lung adenocarcinoma. Positive DBC2 immunohistochemistry may become an indicator for early stage disease and better prognosis of lung adenocarcinomas. -
Hou, Xin-Heng;Huang, Yu-Min;Mi, Yuan-Yuan 2025
Objective: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate and nucleotides needed for DNA synthesis and repair. Variations in MTHFR functions likely play roles in the etiology of lung cancer (LC). So far, several studies between MTHFR C677T polymorphism and LC provide controversial or inconclusive results. Methods: To better assess the purported relationship, we performed a meta-analysis of 14 publications. Eligible studies were identified by searching the Pubmed, Embase, Web of Science and Google Scholar databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Results: Overall, no significant association was detected between the MTHFR C677T polymorphism and LC risk, the same as in race subgroup. However, in the stratified analysis by histological type, significantly increased non-small-cell lung cancer (NSCLC) risk was indicated (T-allele vs. C-allele: OR = 1.11, 95%CI = 1.03-1.19; TT vs. CC: OR = 1.24, 95%CI = 1.09-1.41; TC vs. CC: OR = 1.11, 95%CI = 1.03-1.20 and TT+TC vs. CC: OR = 1.09, 95%CI = 1.03-1.15). At the same time, ever-smokers who carried T-allele (TT+TC) had a 10% decreased LC risk compared with CC genotype carriers. Conclusions: Our study provided evidence that the MTHFR 677T null genotype may increase NSCLC risk, however, it may protect ever-smokers against LC risk. Future studies with large sample sizes are warranted to further evaluate this association in more detail. -
Wu, Ya-Zhou;Yang, Huan;Zhang, Ling;Zhang, Yan-Qi;Liu, Ling;Yi, Dong;Cao, Jia 2031
Background: Analysis of gene-gene and gene-environment interactions for complex multifactorial human disease faces challenges regarding statistical methodology. One major difficulty is partly due to the limitations of parametric-statistical methods for detection of gene effects that are dependent solely or partially on interactions with other genes or environmental exposures. Based on our previous case-control study in Chongqing of China, we have found increased risk of colorectal cancer exists in individuals carrying a novel homozygous TT at locus rs1329149 and known homozygous AA at locus rs671. Methods: In this study, we proposed statistical method-crossover analysis in combination with logistic regression model, to further analyze our data and focus on assessing gene-environmental interactions for colorectal cancer. Results: The results of the crossover analysis showed that there are possible multiplicative interactions between loci rs671 and rs1329149 with alcohol consumption. Multifactorial logistic regression analysis also validated that loci rs671 and rs1329149 both exhibited a multiplicative interaction with alcohol consumption. Moreover, we also found additive interactions between any pair of two factors (among the four risk factors: gene loci rs671, rs1329149, age and alcohol consumption) through the crossover analysis, which was not evident on logistic regression. Conclusions: In conclusion, the method based on crossover analysis-logistic regression is successful in assessing additive and multiplicative gene-environment interactions, and in revealing synergistic effects of gene loci rs671 and rs1329149 with alcohol consumption in the pathogenesis and development of colorectal cancer. -
Maneeton, Benchalak;Maneeton, Narong;Mahathep, Pojai 2039
Objectives: Depression is common in cancer patients. However, only limited evidence is available for Asian populations. The authors therefore examine the prevalence of depression in Thai patients with cancer. In addition, associated factors were determined. Methods: This cross-sectional study was conducted in cancer patients admitted to a university hospital during December 2006 - December 2007. The Patient Health Questionnaire (PHQ-9) was used to assess all cancer patients. Suicidal risk was assessed by using the Mini-International Neuropsychiatric Interview (MINI) in the module of suicidal risk assessment. Results: Of 108 cancer patients, 29.6 % were diagnosed with a depressive disorder (mild, 14.8 %; moderate, 5.6 %; severe, 9.3 %). However, only 25.0 % of these were recognized as being depressed by the primary physician. According to the MINI., 28.1 % of these depressed cancer patients had a moderate to severe level of suicidal risk. In addition, the findings suggest that increased risk of depression is significantly associated with increased pain score, lower number of cancer treatments (< 2 methods), increased educational duration (>13 years), increased age (> 50 years old) and being female. Conclusions: The prevalence of depression is high in Thai cancer patients. However, depressive disorder in those patients is frequently undiagnosed. It is associated with several factors including pain, a number of cancer treatments, education duration, age and sex. To improve quality of life, increase compliance with treatments and prevent of suicide, screening for depressive disorders in this patient group is strongly recommended. -
Huang, Bin-Bin;Gao, Qing-Mei;Liang, Wei;Xiu, Bing;Zhang, Wen-Jun;Liang, Ai-Bin 2045
Objective: To investigate the effect of down-regulation of Sentrin/SUMO-specific protease 1 (SENP1) expression on the apoptosis of human Burkitt lymphoma cells (Daudi cells) and potential mechanisms. Methods: Short hairpin RNA (shRNA) targeting SENP1 was designed and synthesized and then cloned into a lentiviral vector. A lentiviral packaging plasmid was used to transfect Daudi cells (sh-SENP1-Daudi group). Daudi cells without transfection (Daudi group) and Daudi cells transfected with blank plasmid (sh-NC-Daudi group) served as control groups. Flow cytometry was performed to screen GFP positive cells and semiquantitative PCR and Western blot assays were employed to detect the inference efficiency. The morphology of cells was observed under a microscope before and after transfection. Fluorescence quantitative PCR and Western blot assays were conducted to measure the mRNA and protein expression of apoptosis related molecules (caspase-3, 8 and 9). After treatment with$COCl_2$ for 24 h, the mRNA and protein expression of hypoxia inducible factor -$1{\alpha}$ (HIF-$1{\alpha}$ ) was determined. Results: Sequencing showed the expression vectors of shRNA targeting SENP1 to be successfully constructed. Following screening of GFP positive cells by FCM, semiqualitative PCR showed the interference efficiency was$79.2{\pm}0.026%$ . At 48 h after transfection, the Daudi cells became shrunken, had irregular edges and presented apoptotic bodies. Western blot assay revealed increase in expression of caspase-3, 8 and 9 with prolongation of transfection (P<0.05). Following hypoxia treatment, mRNA expression of HIF-$1{\alpha}$ remained unchanged in three groups (P>0.05) but the protein expression of HIF-$1{\alpha}$ markedly increased (P<0.05). However, in the sh-SENP1-Daudi group, the protein expression of HIF-$1{\alpha}$ remained unchanged Conclusion: SENP1-shRNA can efficiently inhibit SENP1 expression in Daudi cells. SENP1 inhibition may promote cell apoptosis. These findings suggest that SENP1 may serve as an important target in the gene therapy of Burkitts lymphoma. -
Background: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of colorectal cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. Materials and Methods: We systematically searched PubMed, EMBASES, Elsevier and Springer for relevant articles before Apr 2012. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed-effects or random-effects models with Review Manager 5.0 software. Results: A total of seven studies including 4,029 cases and 13,844 controls based on the search criteria were included for analysis. A significant association of the CHEK2 I157T C variant with unselected CRC was found (OR = 1.61, 95% CI = 1.40-1.87, P < 0.001). We also found a significant association with sporadic CRC (OR = 1.48, 95% CI = 1.23-1.77, P < 0.001) and separately with familial CRC (OR = 1.97, 95% CI = 1.41-2.74, P < 0.001). Conclusion: This meta-analysis demonstrates that the CHEK2 I157T variant may be another important CRC-predisposing gene, which increases CRC risk, especially in familial CRC.
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Guo, Kun-Feng;Zhang, Zhe;Wang, Jun-Yong;Gao, Sheng-Lin;Liu, Jiao;Zhan, Bo;Chen, Zhi-Peng;Kong, Chui-Ze 2057
Backgrounds: Deficiency or excess of trace elements can induce body metabolic disorders and cellular growth disturbance, even mutation and cancerization. Since there are few studies of the effect of trace elements in bladder carcinoma in China, the aim of this study was thus to assess variation using a case control approach. Methods: To determine this, 81 patients with bladder carcinoma chosen as a study group and 130 healthy persons chosen as a control group were all assayed for urinary and serum trace elements (calcium [Ca], zinc [Zn], copper [Cu], selenium [Se]) using an atomic absorption spectrophotometer, and the results were analyzed by independent sample t tests. The correlative factors on questionnaires answered by all persons were analyzed by logistic regression. Results: The results showed urinary Ca, Zn and serum Cu levels of the study group to be significantly higher (P<0.05) than those of he control group. Serum Ca and Se levels of study group were significantly lower (P<0.05) than those of control group. Conclusion: There were higher urinary Zn and serum Cu concentrations in bladder carcinoma cases. Bladder carcinoma may be associated with Ca metabolic disorder, leading to higher urinary Ca and lower serum Ca. Low serum Se and smoking appear to be other risk factors for bladder carcinoma in China. -
Chen, Shao-Min;Lin, Wei;Liu, Xin;Zhang, You-Zhong 2063
Aim: Liquid-based cytology is the most often used method for cervical cancer screening, but it is relatively insensitive and frequently gives equivocal results. Used as a complementary procedure, the high-risk human papillomavirus (HPV) DNA test is highly sensitive but not very specific. The human telomerase RNA gene (TERC) is the most often amplified oncogene that is observed in cervical precancerous lesions. We assessed genomic amplification of TERC in liquid-based cytological specimens to explore the optimal strategy of using this for cervical cancer screening. Methods: Six hundred and seventy-one residual cytological specimens were obtained from outpatients aged 25 to 64 years. The specimens were evaluated by the Digene Hybrid Capture 2 (HC2) HPV DNA test and fluorescence in situ hybridization (FISH) with a chromosome probe to TERC (3q26). Colposcopic examination and histological evaluation were performed where indicated. Results: The TERC positive rate was higher in the CIN2+ (CIN2, CIN3 and SCC) group than in the normal and CIN 1 groups (90.0% vs. 10.4%, p < 0.01). In comparison with the HC2 HPV DNA test, the TERC amplification test had lower sensitivity but higher specificity (90.0% vs. 100.0%, 89.6% vs. 44.0%, respectively). TERC amplification test used in conjunction with the HC2 HPV DNA test showed a combination of 90.0% sensitivity and 92.2% specificity. Conclusion: The TERC amplification test can be used to diagnose cervical precancerous lesions. TERC and HPV DNA co-testing shows an optimal combination of sensitivity and specificity for cervical cancer screening. -
Li, Lun;Ying, Xiang-Ji;Sun, Tian-Tian;Yi, Kang;Tian, Hong-Liang;Sun, Rao;Tian, Jin-Hui;Yang, Ke-Hu 2069
Background and Objective: A comprehensive overall review of gastric cancer (GC) risk and protective factors is a high priority, so we conducted the present study. Methods: Systematic searches in common medical electronic databases along with reference tracking were conducted to include all kinds of systematic reviews (SRs) about GC risk and protective factors. Two authors independently selected studies, extracted data, and evaluated the methodological qualities and the quality of evidence using R-AMSTAR and GRADE approaches. Results: Beta-carotene below 20 mg/day, fruit, vegetables, non-fermented soy-foods, whole-grain, and dairy product were GC protective factors, while beta-carotene 20 mg/day or above, pickled vegetables, fermented soy-foods, processed meat 30g/d or above, or salty foods, exposure to alcohol or smoking, occupational exposure to Pb, overweight and obesity, helicobacter pylori infection were GC risk factors. So we suggested screening and treating H. pylori infection, limiting the amount of food containing risk factors (processed meat consumption, beta-carotene, pickled vegetables, fermented soy-foods, salty foods, alcohol), stopping smoking, avoiding excessive weight gain, avoidance of Pb, and increasing the quantity of food containing protective components (fresh fruit and vegetables, non-fermented soy-foods, whole-grain, dairy products). Conclusions: The conclusions and recommendations of our study were limited by including SRs with poor methodological bases and low quality of evidence, so that more research applying checklists about assessing the methodological qualities and reporting are needed for the future. -
Teng, Deng-Ke;Wang, Hui;Lin, Yuan-Qiang;Sui, Guo-Qing;Guo, Feng;Sun, Li-Na 2081
Background: To investigate the value of ultrasound elastography (UE) in the differentiation between benign and malignant enlarged cervical lymph nodes (LNs). Methods: B-mode ultrasound, power Doppler imaging and UE were examined to determine LN characteristics. Two kinds of methods, 4 scores of elastographic classification and a strain ratio (SR) were used to evaluate the ultrasound elastograms. Results: The cutoff point of SR had high utility in differential diagnosis of benign and malignant of cervical lymph nodes, with good sensitivity, specificity and accuracy. Conclusion: UE is an important aid in differential diagnosis of benign and malignant cervical LNs. -
Hua, Dong;Qin, Fang;Shen, Li;Jiang, Zhi;Zou, Shi-Tao;Xu, Lan;Cheng, Zhi-Hong;Wu, Shi-Liang 2087
Previous evidence showed${\beta}1$ , 3-N-acetylglucosaminyltransferase 8 (${\beta}3GnT8$ ), which can extend polylactosamine on N-glycans, to be highly expressed in some cancer cell lines and tissues, indicating roles in tumorigenesis. However, so far, the function of${\beta}3GnT8$ in laryngeal carcinoma has not been characterized. To test any contribution, Hep-2 cells were stably transfected with sense or interference vectors to establish cell lines that overexpressed or were deficient in${\beta}3GnT8$ . Here we showed that cell proliferation was increased in${\beta}3GnT8$ overexpressed cells but decreased in${\beta}3GnT8$ knockdown cells using MTT. Furthermore, we demonstrated that change in${\beta}3GnT8$ expression had significant effects on tumor growth in nude mice.We further provided data suggesting that overexpression of${\beta}3GnT8$ enhanced the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) at both the mRNA and protein levels, associated with shedding of tissue inhibitors of metalloproteinase TIMP-2. In addition, it caused increased production of transforming growth factor beta 1 (TGF-${\beta}1$ ), whereas${\beta}3GnT8$ gene knockdown caused the reverse effect. The results may indicate a novel mechanism by which effects of${\beta}3GnT8$ in regulating cellular proliferation are mediated, at least in partvia targeting MMPs/TIMPs and TGF-${\beta}1$ in laryngeal carcinoma Hep-2 cells. The finding may lay a foundation for further investigations into the${\beta}3GnT8$ as a potential target for therapy of laryngeal carcinoma. -
Sulforaphane (SFN) an isothiocyanate formed by hydrolysis of glucosinolates found in Brassica oleraceae is reported to possess anticancer and antioxidant activities. In this study, we isolated SFN from red cabbage (Brassica oleraceae var rubra) and evaluated the comparative antiproliferative activity of various fractions (standard SFN, extract and purified SFN) by MTT assay in human epithelial carcinoma HEp -2 and and Vero cells. Probable apoptotic mechanisms mediated through p53, bax and bcl-2 were also examined. The SFN fraction was collected by HPLC, enriched for its SFN content and confirmed. Expression of apoptosis-related proteins was detected by western blotting and RT PCR. Results showed that Std SFN and purified SFN concentration found to have closer
$IC_{50}$ which is equal to 58.96 microgram/ml (HEp-2 cells), 61.2 microgram/ml (Vero cells) and less than the extract which is found to be 113 microgram/ml (HEp-2 cells) and 125 microgram/ml (Vero cells). Further studies on apoptotic mechanisms showed that purified SFN down-regulated the expression of bcl-2 (antiapoptotic), while up-regulating p53 and Bax (proapoptotic) proteins, as well as caspase-3. This study indicates that purified SFN possesses antiproliferative effects the same as Std SFN and its apoptotic mechanism in HEp-2 cells could be mediated through p53 induction, bax and bcl-2 signaling pathways. -
Sun, Jian-Da;Chen, Chuang-Zhen;Chen, Jian-Zhou;Li, Dong-Sheng;Chen, Zhi-Jian;Zhou, Ming-Zhen;Li, De-Rui 2101
Treatment responses of$N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with$N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with$N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with$N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival. -
Ma, K.K.;Chau, Wai Wang;Wong, Connie H.N.;Wong, Kerry;Fung, Nicholas;Lee, J.T. Andrea;Choi, L.Y. Catherine;Suen, Dacita T.K.;Kwong, Ava 2109
Background: Ethnic variation in tumor characteristics and clinical presentation of breast cancer is increasingly being emphasized. We studied the tumor characteristics and factors which may influence the presentation and prognosis of triple negative breast cancers (TNC) in a cohort of Chinese women. Methods: A prospective cohort of 1800 Chinese women with breast cancer was recruited in a tertiary referral unit in Hong Kong between 1995 and 2006 and was followed up with a median duration of 7.2 years. Of the total, 216 (12.0%) had TNC and 1584 (88.0%) had non-TNC. Their clinicopathological variables, epidemiological variables and clinical outcomes were evaluated. Results: Patients with TNC had similar age of presentation as those with non-TNC, while presenting at earlier stages (82.4% were stage 1-2, compared to 78.4% in non-TNC, p=0.035). They were likely to be associated with grade 3 cancer (Hazard Ratio(HR)=5.8, p<0.001). TNC showed higher chance of visceral relapse (HR=2.69, p<0.001), liver metastasis (HR=1.7, p=0.003) and brain metastasis (HR=1.8, p=0.003). Compared with non-TNC group, TNC had similar 10-year disease-free survival (82% vs 84%, p=0.148), overall survival (78% vs 79%, p=0.238) and breast cancer-specific mortality (18% vs 16%, p=0.095). However, TNC showed poorer 10-year stage 3 and 4 specific survival (stage 3: 53% vs. 67%, p=0.010; stage 4: 0% vs. 40%, p=0.035). Conclusions: Chinese women with triple negative breast cancer do not have less aggressive biological behavior compared to the West and presentation at a later stage results in worse prognosis compared with those with non triple negative breast cancer. -
Hu, Ming-Dong;Xu, Jian-Cheng;Fan, Ye;Xie, Qi-Chao;Li, Qi;Zhou, Chang-Xi;Mao, Mei;Yang, Yu 2115
The presence of lung cancer cells in anoxic zones is a key cause od chemotherapeutic resistance. Thus, it is necessary to enhance the sensitivity of such lung cancer cells. However, loss of efficient gene therapeutic targeting and inefficient objective gene expression in the anoxic zone in lung cancer are dilemmas. In the present study, a eukaryotic expression plasmid pUC57-HRE-JAB1 driven by a hypoxia response elements promoter was constructed and introduced into lung cancer cell line A549. The cells were then exposed to a chemotherapeutic drug cis-diamminedichloroplatinum (C-DDP). qRT-PCR and western blotting were used to determine the mRNA and protein level and flow cytometry to examine the cell cycle and apoptosis of A549 transfected pUC57-HRE-JAB1. The results showed that JAB1 gene in the A549 was overexpressed after the transfection, cell proliferation being arrested in G1 phase and the apoptosis ratio significantly increased. Importantly, introduction of pUC57-HRE-JAB1 significantly increased the chemotherapeutic sensitivity of A549 in an anoxic environment. In conclusion, JAB1 overexpression might provide a novel strategy to overcome chemotherapeutic resistance in lung cancer. -
Zhang, Nian-Qu;Zhao, Lei;Ma, Shuai;Gu, Ming;Zheng, Xin-Yu 2121
Objective: Deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK) mutants have been reported to exert suicide gene effects in combined gene/chemotherapy of cancer. Here, we aimed to further evaluate the capacity of the mutanted enzyme and its potential for inhibiting cancer cell growth. Methods: We altered the sequence of the last 10 amino acids of Dm-dNK to perform site-directed mutagenesis and constructed active site mutanted Dm-dNK (Dm-dNKmut), RT-PCR and western bloting studies were used to reveal the expression of lentivirus mediated Dm-dNKmut in a breast cancer cell line (Bcap37), a gastric cancer cell line (SGC7901) and a colorectal cancer cell line (CCL187). [3H]-labeled substrates were used for enzyme activity assays, cell cytotoxicity was assessed by MTT assays, cell proliferation using a hemocytometer and apoptosis induction by thenannexin-V-FITC labeled FACS method. In vivo, an animal study was set out in which BALB/C nude mice bearing tumors were treated with lentivirus mediated expression of Dm-dNKmut with the pyrimidine nucleoside analog brivudine (BVDU, (E)-5-(2-bromovinyl)-(2-deoxyuridine). Results: The Dm-dNKmut could be stably expressed in the cancer cell lines and retained its enzymatic activity. Moreover, the cells expressing Dm-dNKmut exhibited increased sensitivity in combination with BVDU, with induction of apoptosis in vitro and in vivo. Conclusion: These findings underlined the importance of BVDU phosphorylated by Dm-dNKmut in transduced cancer cells and the potential role of Dm-dNKmut as a suicide gene, thus providing the basis for future intensive research for cancer therapy. -
Wang, Bu-Hai;Cao, Wen-Miao;Yu, Jie;Wang, Xiao-Lei 2129
Objective: To explore improved treatment by retrospectively comparing survival time of gemcitabine-based concurrent chemoradiotherapy (GemRT) versus chemotherapy (Gem) alone in patients with locally advanced pancreatic cancer (LAPC). Methods: From January 2005 to June 2010, 56 patients with LAPC from Subei People's Hospital were treated either with Gem (n=21) or GemRT (n=35). Gem consisted of 4-6 cycles gemcitabine alone (1000 mg/m2 on Days 1, 8, 15, 28-day a cycle). GemRT consisted of 50.4Gy/28F radiotherapy with concurrent 2 cycles of gemcitabine (1000$mg/m^2$ on days of radiation 1, 8, 15, 21-day a cycle). Radiation was delivered to the gross tumor volume plus 1-1.5 cm by use of a three-dimensional conformal technique. The follow-up time was calculated from the time of diagnosis to the date of death or last contact. Kaplan-Meier methodology wes used to evaluate survival. Results: Patient characteristics were not significantly different between treatment groups. The disease control rate and the objective response rate of GemRT versus Gem was 97.1% vs 71.4%, 74.3% vs 38.1%. The overall survival (OS) was significantly better for GemRT compared to Gem (median 13 months versus 8 months; 51.4% versus 14.3% at 1 year, respectively). Conclusion: Radiation therapy at 50.4Gy with 2 concurrent cycles of gemcitabine results in favorable rates of OS. Concurrent chemoradiotherapy should be the first choice for patients with LAPC. -
Zhang, Ying-Yao;Xu, Zhi-Na;Wang, Jun-Xi;Wei, Dong-Min;Pan, Xin-Liang 2133
Objective: To investigate the prognostic role of antigen KI-67 (Ki-67) and G1/S-specific cyclin-D1 (cyclin-D1) in patients with laryngeal squamous cell carcinoma (LSCC). Methods: Immunohistochemical staining (IHS) was used to determine the protein expression of Ki-67 and cyclin-D1 in LSCC tissues. Kaplan-Meier survival curves was calculated with reference to Ki-67 and cyclin-D1 levels. Results: Cyclin-D1 and Ki67 were expressed in the nuclei of cancer cells. Among the total of 92 cancer tissues examined by immunohistochemistry, 60 (65.22%) had cyclin-D1 overexpression and 56 (60.87%) had Ki67 overexpression. Cyclin-D1 overexpression is associated with the advanced stage of the cancer (P=0.029), but not with gender, age, stage of cancer, histological differentiation, anatomical site, smoking history and alcohol consumption history. Ki67 overexpression is not associated with the advanced stage, gender, age, histological differentiation, anatomical site, smoking history and alcohol consumption history. A statistically significant correlation was found between lymph node status and the expression of Ki67 (p = 0.025). Overexpression of cyclin-D1 was correlated to shorter relapse-free survival period (P<0.001). Conclusions: Overexpression of cyclin-D1 can be used as a marker to predict relapse in patients with LSCC after primary curative resection. -
Wen, Yuan-Yuan;Pan, Xiong-Fei;Loh, Marie;Tian, Zhi;Yang, Shu-Juan;Lv, Si-Han;Huang, Wen-Zhi;Huang, He;Xie, Yao;Soong, Richie;Yang, Chun-Xia 2139
Objective: Gastric cancer remains a major health problem in China. We hypothesized that XRCC1 Arg194Trp and ADPRT Val762Ala may be associated with risk. Methods: We designed a multicenter 1:1 matched case-control study of 307 pairs of gastric cancers and controls between October 2010 and August 2011. XRCC1 Arg194Trp and ADPRT Val762Ala were sequenced, and demographic data as well as lifestyle factors were collected using a self-designed questionnaire. Results: Individuals carrying XRCC1 Trp/Trp or Arg/Trp variant genotype had a significantly increased risk of gastric cancer (OR, 1.718; 95% CI, 1.190-2.479), while the OR for ADPRT Val762Ala variant genotype (Ala/Ala or Val/Ala) was 1.175 (95% CI, 0.796-1.737). No gene-gene or gene-environment interactions were found. In addition, family history of cancer and drinkers proportion were higher among cases than among controls (P<0.05). Conclusions: XRCC1 194 Arg/Trp or Trp/Trp genotype, family history of cancer, and drinking are suspected risk factors of gastric cancer from our study. Our findings may offer insight into further similar large gene-environment and gene-gene studies in this region. -
Liu, Yu-Hong;Gao, Xue-Mei;Ge, Fan-Mei;Wang, Zhe;Wang, Wen-Qing;Li, Xiao-Yong 2145
Objective: This study concerns expression of PBK/TOPK during differentiation of HL-60 leukemic cells induced by tetradecanoyl phorbol acetate (TPA). Methods: Wright-Giemsa staining was performed to observe morphological changes in the HL-60 cells, and flow cytometry was used to assess the cell cycle and CD11b, CD14, CD13, and CD33 expression. PBK/TOPK levels were determined by Western blot analysis. Results: After treating HL60 cells with$5.1{\times}10^{-9}$ mmol/L of TPA for three days, the number of nitroblue-tetrazolium-positive cells and CD11b, CD13, and CD14 expression increased, whereas the PBK/TOPK levels decreased. Conclusions: TPA can inhibit proliferation and induce differentiation of HL60 cells of the granulocytic or monocytic lineage. PBK/TOPK expression was downregulated during this process, whereas the Pho-PBK/TOPK expression was increased. -
Poudel, Bibek;Mittal, Ankush;Shrestha, Rojeet;Nepal, Ashwini Kumar;Shukla, Pramod Shanker 2149
Objective: This study was performed to assess prostate biomarkers with reference to body mass index and duration of prostate cancer. Materials and Methods: A hospital based retrospective study was undertaken using data retrieved from the register maintained in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between$1^{st}$ January, 2009 and$28^{th}$ February, 2012. Biomarkers studied were prostate specific antigen (PSA), acid phosphatase (ACP) and prostatic acid phosphatase (PAP), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (${\gamma}GT$ ). Demographic data including age, duration of disease, body weight, height and body mass index (BMI) were also collected. Duration of disease was categorized into three groups: <1 year, 1-2years and >2 years. Similarly, BMI ($kg/m^2$ ) was categorized into three groups: <23$kg/m^2$ , 23-25$kg/m^2$ and >25$kg/m^2$ . Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: Out of 57 prostate cancers, serum level of PSA, ACP and PAP were increased above the cut-off point in 50 (87.5%), 30 (52.63%) and 40 (70.18%) respectively. Serum levels of PSA, ACP and PAP significantly declined with the duration of disease after diagnosis. We observed significant and inverse relation between PSA and BMI. Similar non-signficiant tendencies were apparent for ACP and PAP. Conclusions: Decreasing levels of prostate biomarkers were found with the duration of prostate cancer and with increased BMI. Out of prostate biomarkers, PSA was found to be significantly decreased with the duration of disease and BMI. -
Poudel, Bibek;Mittal, Ankush;Shrestha, Rojeet;Farooqui, Mohammad Shamim;Yadav, Naval Kishor;Shukla, Pramod Shanker 2153
Objective: This study was to assess liver involvement in multiple myeloma with the aid of liver function tests. Materials and Methods: A hospital based retrospective study was undertaken using data retrieved of multiple myeloma from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between$1^{st}$ January, 2007 and$28^{th}$ February, 2012. We collected biomarkers of liver profiles including bilirubin (Total, Direct and Indirect), total protein, albumin, AG ratio, SGOT, SGPT, ALP,${\gamma}GT$ , LDH, ferritin, renal profile and hematological profile. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: Out of 37 cases of multiple myeloma, serum level of AST, ALT, ALP,${\gamma}GT$ and LDH were increased above the cut-off point in 22 (59.5%), 24 (64.86%), 13 (35.13%), 9 (24.3%) and 11 (29.7%) respectively. The mean values of AST ($65.5{\pm}28.18$ U/L), ALT ($68.37{\pm}29.74$ U/L), ALP ($328.0{\pm}148.4$ U/L),${\gamma}GT$ ($44.5{\pm}29.6$ U/L) and LDH ($361.7{\pm}116.5$ U/L), total protein ($9.79{\pm}1.03$ gm/dl) were significantly increased when compared with controls. In contrast, albumin ($3.68{\pm}0.43$ gm/dl) and the AG ratio ($0.62{\pm}0.15$ ) were significantly decreased. Similarly, anemia, hyperuricemia, azotemia, hypercalcaemia and Bence Jones proteinuria were found in 30 (78.9%), 27 (71.1%), 19 (51.5%), 15 (39.5%) and 16 (42.1%) respectively, in cases of multiple myeloma. Conclusions: While clinical manifestation of liver disease among the multiple myeloma was not common, abnormalities in liver function were characteristic. -
Xu, Jia-Li;Wang, Zhen-Wu;Hu, Ling-Min;Yin, Zhi-Qiang;Huang, Ming-De;Hu, Zhi-Bin;Shen, Hong-Bing;Shu, Yong-Qian 2157
Objective: The PI3K/PTEN/AKT/mTOR signaling pathway has been implicated in resistance to cisplatin. In the current study, we determined whether common genetic variations in this pathway are associated with platinum-based chemotherapy response and clinical outcome in advanced non-small cell lung cancer (NSCLC) patients. Methods: Seven common single nucleotide polymorphisms (SNPs) in core genes of this pathway were genotyped in 199 patients and analyzed for associations with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Results: Logistic regression analysis revealed an association between AKT1 rs2494752 and response to treatment. Patients carrying heterozygous AG had an increased risk of disease progression after two cycles of platinum-based chemotherapy compared to those with AA genotype (Adjusted odds ratio (OR)=2.18, 95% confidence interval (CI): 1.00-4.77, which remained significant in the stratified analyses). However, log-rank test and cox regression detected no association between these polymorphisms in the PI3K pathway genes and survival in advanced NSCLC patients. Conclusions: Our findings suggest that genetic variants in the PI3K/PTEN/AKT/mTOR pathway may predict platinum-based chemotherapy response in advanced NSCLC patients in a Chinese population. -
Aim: This one group semi-experimental study was performed to develop and adapt flow charts of nursing practices applied to gynecologic oncology patients to the field. Methods: The research was conducted between October 2008 and March 2009 in 6 hospitals in Istanbul (3 health ministry hospitals, 2 private hospitals and 1 university hospital) with effective programs. The scope of the study included 97 midwives/nurses who had been working as caregivers of gynecologic oncology patients in this unit at least for 6 months and who participated in this study voluntarily; 87 people composed the sample because of the absence of others on vacation or sick leave when the data were collected or who did not wish to participate. The data were in descriptive information form collected via "Forms to Determine the Efficiency of Flow Charts". Before data collection, risks related to gynecologic oncology problems were identified, a literature scanning was made for existing flow charts based on actual practices and the discovered charts were reviewed. As a result of the evaluations, it was decided to create 15 flow charts intended for risks, symptoms, operation processes and discharge. Questionnaires to determine activity were applied to participants before and after practice. Results: As a result of the study, it was determined that the efficiency of the flow charts increased significantly (p <0.01) after practice of the participants, nosignificant relationships (p>0.01) being apparent with age group, education level, occupational period in the job and in the gynecologic oncology field and evaluations of the practice before and after it was applied. Conclusion: The results of the study revealed that nursing participants in university and private hospitals and who supported the existence of a flow chart in the field evaluated the flow charts positively.
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Farooqui, Mohammad Shamim;Mittal, Ankush;Poudel, Bibek;Mall, Suhas Kumar;Sathian, Brijesh;Tarique, Mohammad;Farooqui, Mohammad Hibban 2171
Background: Pancreatic cancer is a distressing disease with a miserable prospects and early recognition remains a challenge due to ubiquitous symptomatic presentation, deep anatomical location, and aggressive etiology. False positives and problems in distinguishing pancreatitis from adenocarcinoma limit the use of CA 19-9 as both disorders can present with similar symptoms and share radiographic physiognomies. This study aimed to assess the relative increase in accuracy of diagnosing the patients with chronic pancreatitis, benign neoplasm of pancreas and adenocarcinomas with CA 19-9, haptoglobin, and serum amyloid A in comparison to CA 19-9 alone. Materials and Methods: This hospital based case control study was carried out in the Departments of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal, between$1^{st}$ January 2010 and$31^{st}$ December 2011. The variables assessed were age, gender, serum CA19-9, serum haptoglobulin, serum Amyloid A. The data were analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and the EPI Info 3.5.1 Windows Version. Results: Out of 197 cases of pancreatic disease, maximum number of assumed cases were of adenocarcinoma of pancreas (95). Number of males (59) were more than females (36) in assumed cases of adenocarcinoma of pancreas. The mean values of CA19-9 raised considerably in cases of chronic pancreatitis, benign neoplasm and adenocarcinoma of pancreas when compared to controls. The highest augmention in CA19-9 values were in cases of adenocarcinoma of pancreas. The p-value indicates that in cases of chronic pancreatitis, there was not significant increase in precision of diagnosis. Conclusions: These statistics established that haptoglobin and SAA are useful in discriminating cancer from benign conditions as well as healthy controls. -
Sanii, Sanaz;Saffar, Hiva;Tabriz, Hedieh M.;Qorbani, Mostafa;Haghpanah, Vahid;Tavangar, Seyed M. 2175
Purpose: Definite diagnosis of follicular thyroid carcinoma (FTC) is based on the presence of capsular or vascular invasion. To date, no reliable and practical method has been introduced to discriminate this malignant neoplasm from follicular thyroid adenoma (FTA) in fine needle aspiration biopsy material. Matrix metalloproteinase-2 (MMP-2), by degrading extracellular matrix, and caspase-3, by induction of apoptosis, have been shown to play important roles in carcinogenesis and aggressive behavior in many tumor types. The aim of this study was to examine expression of MMP-2 and caspase-3 in thyroid follicular neoplasms and to determine their usefulness for differential diagnosis. Method: Sixty FTAs and 41 FTCs were analysed immunohistochemically for MMP-2 and caspase-3. Result: MMP-2 was positive in 4 FTCs (9.8%), but in none of FTAs, with statistical significance (p= 0.025). Caspase-3 was positive in 30 (50%) of FTAs and in 27 (65.9%) of FTCs. Conclusion: Our results show MMP-2 expression only in FTCs and suggest that this protein may be a useful marker to confirm diagnosis of FTC versus FTA with 100% specificity and 100% predictive value of a positive test. We failed to show any differential diagnostic value for caspase-3 in thyroid follicular neoplasms. -
Yanhua, Che;Geater, Alan;You, Jing;Li, Li;Shaoqiang, Zhou;Chongsuvivatwong, Virasakdi;Sriplung, Hutcha 2179
Introduction and aim: To compare reproductive factor influence on patients with pathological diagnosed malignant and benign tumor in the Breast Department, The First Peoples' Hospital of Kunming in Yunnan province, China. Methods: A hospital-based case-control study was conducted on 263 breast cancer (BC) cases and 457 non-breast cancer controls from 2009 to 2011. The cases and controls information on demographics, medical history, and reproductive characteristics variables were collected using a self-administered questionnaire and routine medical records. Histology of breast cancer tissue and benign breast lesion were documented by pathology reports. Since some variables in data analysis had zero count in at least one category, binomial-response GLM using the bias-reduction method was applied to estimate OR's and their 95% confidence intervals (95% CI). To adjust for age and menopause status, a compound variable comprising age and menopausal status was retained in the statistical models. Results: multivariate model analysis revealed significant independent positive associations of BC with short menstrual cycle, old age at first live birth, never breastfeeding, history of oral contraception experience, increased number of abortion, postmenopausal status, and nulliparity. Categorised by age and menopausal status, perimenopausal women had about 3-fold and postmenopausal women had more than 5-fold increased risk of BC compared to premenopausal women. Discussion and Conclusion: This study has confirmed the significant association of BC and estrogen related risk factors of breast cancer including longer menstrual cycle, older age of first live birth, never breastfeeding, nulliparity, and number of abortions more than one. The findings suggest that female hormonal factors, especially the trend of menopause status play a significant role in the development of BC in Yunnan women. -
Zhang, Ru-Gang;Wang, Chang-Song;Gao, Cun-Fang 2185
Background: Prevalence of Barrett's esophagus (BE) in Luoyang, China, has not been reported, and its pathogenesis is controversial. The aim of this study was therefore to investigate the prevalence of BE and its underlying factors in the city of Luoyang. Method: This was a prospective study in one center. Many patients were analyzed using endoscopy who showed upper gastrointestinal symptoms between August 2006 and June 2007. In addition, the effect of apoptosis-related proteins and heat shock proteins upon BE's pathogenesis were also investigated by an immunohistochemical protocol. Results: Prevalence of BE was at 4.55% and the mean age of those affected was about 10 years older than for esophagitis. Typical reflux symptoms were significantly lower than with esophagitis, whereas signs of caspase-3 and HSP105 elevation were significantly higher. Expression of TERT, HSP70 and$HSP90{\alpha}$ in BE cases was significantly lower than in esophagitis. However, there was no statistical difference between the two groups in expression of HSP27. Conclusions: The prevalence of BE is high in Luoyang, which could result from esophagitis despite typical reflux symptoms being relatively uncommon. Initiation and development of BE might be the result of accelerated proliferation, apoptosis and differentiation of original cells to intestinal epithelium. -
Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the metabolism of folate, and the role of MTHFR C677T polymorphism in cervical carcinogenesis is still controversial. Method: We performed a meta-analysis of all relevant case-control studies that examined any association between the C677T polymorphism and cervical cancer risk. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess links. Results: Finally, 10 studies with a total of 2113 cervical cancer cases and 2804 controls were included. Results from this meta-analysis showed that significantly elevated cervical cancer risk was associated with the MTHFR T allele in the Asian population under conditions of two genetic comparison models (for TT vs. CC, OR = 1.37, 95%CI 1.00-1.87, P = 0.050; for TT vs. TC+CC: OR = 1.34, 95%CI 1.01-1.77, P = 0.039). However, there was no obvious association between the MTHFR C677T polymorphism and cervical cancer risk in the other populations. Conclusion: The MTHFR C677T polymorphism is associated with cervical cancer risk in Asians, while any possible link in the Caucasian population needs further studies.
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Wu, Xia-Yu;Ni, Juan;Xu, Wei-Jiang;Zhou, Tao;Wang, Xu 2199
Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls. -
Wang, Jing;Zhao, Shu-Lei;Li, Yan;Meng, Mei;Qin, Cheng-Yong 2207
Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of$RAR{\beta}$ . The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor${\beta}$ ($RAR{\beta}$ ). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of$RAR{\beta}$ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het-1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of$RAR{\beta}$ in esophageal SCC patients. NNK could induce$RAR{\beta}$ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis. -
Ibrahim, Nor Idawaty;Dahlui, M.;Aina, E.N.;Al-Sadat, N. 2213
Introduction: Worldwide, breast cancer is the commonest cause of cancer death in women. However, the survival rate varies across regions at averages of 73%and 57% in the developed and developing countries, respectively. Objective: This study aimed to determine the survival rate of breast cancer among the women of Malaysia and characteristics of the survivors. Method: A retrospective cohort study was conducted on secondary data obtained from the Breast Cancer Registry and medical records of breast cancer patients admitted to Hospital Kuala Lumpur from 2005 to 2009. Survival data were validated with National Birth and Death Registry. Statistical analysis applied logistic regression, the Cox proportional hazard model, the Kaplan-Meier method and log rank test. Results: A total of 868 women were diagnosed with breast cancer between January 2005 and December 2009, comprising 58%, 25% and 17% Malays, Chinese and Indians, respectively. The overall survival rate was 43.5% (CI 0.573-0.597), with Chinese, Indians and Malays having 5 year survival rates of 48.2% (CI 0.444-0.520), 47.2% (CI 0.432-0.512) and 39.7% (CI 0.373-0.421), respectively (p<0.05). The survival rate was lower as the stages increased, with the late stages were mostly seen among the Malays (46%), followed by Chinese (36%) and Indians (34%). Size of tumor>3.0cm; lymph node involvement, ERPR, and HER 2 status, delayed presentation and involvement of both breasts were among other factors that were associated with poor survival. Conclusions: The overall survival rate of Malaysian women with breast cancer was lower than the western figures with Malays having the lowest because they presented at late stage, after a long duration of symptoms, had larger tumor size, and had more lymph nodes affected. There is an urgent need to conduct studies on why there is delay in diagnosis and treatment of breast cancer women in Malaysia. -
Yu, Qi-Ming;Yu, Chuan-Ding;Ling, Zhi-Qiang 2219
Background: Circulating lymphocyte subsets reflect the immunological status and might therefore be a prognostic indicator in cancer patients. Our aim was to evaluate the clinical significance of circulating lymphocyte subset in gastric cancer (GC) cases. Methods: A retrospective study on a prevalent cohort of 846 GC patients hospitalized at Hospital from Aug 2006 to Jul 2010 was conducted. We calculated the patient's disease free survival (DFS) after first hospital admission, and hazard ratios (HR) from the Cox proportional hazards model. Results: Our findings indicated a significantly decreased percentage of CD3+, and CD8+ cells, a significantly increased proportion of$CD4^+$ ,$CD19^+$ ,$CD44^+$ ,$CD25^+$ , NK cells, and an increased$CD4^+/CD8^+$ ratio in GC patients as compared with healthy controls (all P < 0.05). Alteration of lymphocyte subsets was positively correlated with sex, age, smoking, tumor stage and distant metastasis of GC patients (all P<0.05). Follow-up analysis indicated significantly higher DFS for patients with high circulating$CD19^+$ lymphocytes compared to those with low$CD19^+$ lymphocytes (P=0.037), with$CD19^+$ showing an important cutoff of$7.91{\pm}2.98%$ Conclusion: Circulating lymphocyte subsets in GC patients are significantly changed, and elevated CD19+ cells may predict a favorable survival. -
Dede, Didem Sener;Aksoy, Sercan;Cengiz, Mustafa;Gullu, Ibrahim;Altundag, Kadri 2225
Background: We assessed the efficacy and toxicity of ifosfamide and doxorubicin combination chemotherapy (CT) regimen retrospectively in Turkish patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) previously treated with platinum-based chemotherapy. Methods: A total of thirty patients who had received cisplatin based chemotherapy/chemoradiotherapy as a primary treatment received ifosfamide 2500$mg/m^2$ days 1-3, mesna 2500$mg/m^2$ days 1-3, doxorubicin 60 mg/m2 day 1 (IMA), repeated every 21 days. Eligible patients had ECOG PS< 2, measurable recurrent or metastatic disease, with adequate renal, hepatic and hematologic functions. Results: Median age was 47 (min-max; 17-60). Twenty six (86.7 %) were male. Median cycles of chemotherapy for each patient were 2 (range:1-6). Twenty patients were evaluable for toxicity and response. No patient achieved complete response, with nine partial responses for a response rate of 30.0% in evaluable patients. Stable disease, and disease progression were observed in five (16.7%) and six (20.0%) patients, respectively. Clinical benefit was 46.7%. Median time to progression was 4.0 months. Six patients had neutropenic fever after IMA regimen and there were one treatment-related death due to tumor lysis syndrome in first cycle of the CT. No cardiotoxicity was observed after CT and treatments were generally well tolerated. Conclusion: Ifosfomide and doxorubicin combination is an effective regimen for patients with recurrent and metastatic NPC. For NPC patients demonstrating failure of cisplatin based regimens, this CT combination may be considered as salvage therapy. -
Chen, Jun-Xing;Deng, Nan;Chen, Xu;Chen, Ling-Wu;Qiu, Shao-Peng;Li, Xiao-Fei;Li, Jia-Ping 2229
Purpose: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). Materials: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. Results: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67$LI{\leq}25%$ , VEGF$scoring{\leq}8$ ), mG2 (Ki67 LI>25%, VEGF$scoring{\leq}8$ ; or Ki67$LI{\leq}25%$ , VEGF scoring > 8), and mG3 (Ki67 LI > 25%, VEGF scoring > 8), which can indicate favorable, intermediate and poor prognosis, respectively. Conclusions: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy. -
Nourazarian, Ali Reza;Pashaei-Asl, Roghiyeh;Omidi, Yadollah;Najar, Ahmad Gholamhoseinian 2235
c-Src is one member of non-receptor tyrosine kinase protein family that has over expression and activation in many human cancer cells. It has been shown that c-Src is implicated in various downstream signaling pathways associated with EGFR-dependent signaling such as MAPK and STAT5 pathways. Transactivation of EGFR by c-Src is more effective than EGFR ligands. To inhibit the c-Src expression, we used c-Src antisense oligonucleotide complexed with PAMAM Denderimes. The effect of c-Src antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay. Then, the expression of c-Src, EGFR and the genes related to EGFR-depended signaling with P53 was applied by real time PCR. We used western blot analysis to elucidate the effect of antisense on the level of c-Src protein expression. The results showed, c-Src antisense complexed with PAMAM denderimers has an effective role in decrease of c-Src expression and EGFR-dependent downstream genes. -
Objective: This qualitative study retrospectively examined the experience and psychological impact of contralateral prophylactic mastectomy (CPM) among Southern Chinese females with unilateral breast cancer history who underwent BRCA1/2 genetic testing. Limited knowledge is available on this topic especially among Asians; therefore, the aim of this study was to acquire insight from Chinese females' subjective perspectives. Methods: A total of 12 semi-structured in-depth interviews, with 11 female BRCA1/BRCA 2 mutated gene carriers and 1 non-carrier with a history of one-sided breast cancer and genetic testing performed by the Hong Kong Hereditary Breast Cancer Family Registry, who subsequently underwent CPM, were assessed using thematic analysis and a Stage Conceptual Model. Breast cancer history, procedures conducted, cosmetic satisfaction, pain, body image and sexuality issues, and cancer risk perception were discussed. Retrieval of medical records using a prospective database was also performed. Results: All participants opted for prophylaxis due to their reservations concerning the efficacy of surveillance and worries of recurrent breast cancer risk. Most participants were satisfied with the overall results and their decision. One-fourth expressed different extents of regrets. Psychological relief and decreased breast cancer risk were stated as major benefits. Spouses' reactions and support were crucial for post-surgery sexual satisfaction and long-term adjustment. Conclusions: Our findings indicate that thorough education on cancer risk and realistic expectations of surgery outcomes are crucial for positive adjustment after CPM. Appropriate genetic counseling and pre-and post-surgery psychological counseling were necessary. This study adds valuable contextual insights into the experiences of living with breast cancer fear and the importance of involving spouses when counseling these patients.
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Li, Lei;Wu, Sheng-Di;Wang, Ji-Yao;Shen, Xi-Zhong;Jiang, Wei 2249
Objective: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with pancreatic cancer, but the published studies had yielded inconsistent results.We therefore performed the present meta-analysis. Methods: A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012 was conducted to summarize associations of MTHFR polymorphisms with pancreatic cancer risk. Assessment was with odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias were also calculated. Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were involved in this meta-analysis. Overall, C667T(TT vs. CC : OR = 1.61, 95%CI = 0.78 - 3.34; TT vs. CT : OR = 1.41, 95%CI = 0.88-2.25; dominant model: OR = 0.68, 95%CI = 0.40-1.17; recessive model: OR = 0.82, 95%CI = 0.52-1.30) and A1298C(CC vs. AA:OR=1.01, 95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; dominant model: OR=1.01, 95%CI = 0.47-2.20; recessive model: OR = 1.01, 95%CI = 0.80-1.26) did not increase pancreatic cancer risk. Conclusion: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) were not associated with pancreatic cancer risk. -
Mittal, Ankush;Poudel, Bibek;Pandeya, Dipendra Raj;Gupta, Satrudhan Pd;Sathian, Brijesh;Yadav, Shambhu Kumar 2253
Objective: The objective of our present study was to assess the role of serum amyloid A (SAA) in stages and prognosis of renal cell carcinoma. Material and Methods: It was a hospital based retrospective study carried out in the Department of Medicine and Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between$1^{st}$ January 2008 and$31^{st}$ December 2011. The variables collected were SAA, CRP. Approval for the study was obtained from the institutional research ethical committee. Quantitative analysis of human SAA and C-reactive protein (CRP) was performed by radial immune diffusion (RID) assay for all cases. Results: Of the 422 total cases of renal cell carcinoma, 218 patients had normal and 204 abnormal SAA. SAA levels were grossly elevated in T3 stage ($122.3{\pm}SD35.7$ ) when compared to the mean for the T2 stage ($84.2{\pm}SD24.4$ ) (p value: 0.0001). Similarly, SAA levels were grossly elevated in M1 stage ($190.0{\pm}SD12.7$ ) when compared to the M0 stage ($160.9{\pm}SD24.8$ ) (p: 0.0001). There was no significant association with elevated CRP levels ($209.1{\pm}SD22.7$ , normal$199.0{\pm}SD19.5$ ). Conclusion: The validity of SAA in serum as being of independent prognostic significance in RCC was demonstrated with higher levels in advanced stage disease. -
Punvittayagul, Charatda;Pompimon, Wilart;Wanibuchi, Hideki;Fukushima, Shoji;Wongpoomchai, Rawiwan 2257
Pinocembrin (5, 7-dihydroxyflavanone) is a flavanone extracted from the rhizome of Boesenbergia pandurata. Our previous studies demonstrated that pinocembrin had no toxicity or mutagenicity in rats. We here evaluated its effects on the initiation and promotion stages in diethylnitrosamine-induced rat hepatocarcinogenesis, using short- and medium-term carcinogenicity tests. Micronucleated hepatocytes and liver glutathione-S-transferase placental form foci were used as end point markers. Pinocembrin was neither mutagenic nor carcinogenic in rat liver, and neither inhibited nor prevented micronucleus formation as well as GST-P positive foci formation induced by diethylnitrosamine. Interestingly, pinocembrin slightly increased the number of GST-P positive foci when given prior to diethylnitrosamine injection. -
Guo, Jian-Xin;Tao, Qing-Song;Lou, Peng-Rong;Chen, Xiao-Chun;Chen, Jun;Yuan, Guang-Bo 2263
Objective: MicroRNAs (miRNAs) play important roles in carcinogenesis. The aim of the present study was to explore the effects of miR-181b on gastric cancer. Methods: The expression level of miR-181b was quantified by qRT-PCR. MTT, flow cytometry and matrigel invasion assays were used to test proliferation, apoptosis and invasion of miR-181b stable transfected gastric cancer cells. Results: miR-181b was aberrantly overexpressed in gastric cancer cells and primary gastric cancer tissues. Further experiments demonstrated inducible expression of miR-181b by Helicobacter pylori treatment. Cell proliferation, migration and invasion in the gastric cancer cells were significantly increased after miR-181b transfection and apoptotic cells were also increased. Furthermore, overexpression of miR-181b downregulated the protein level of tissue inhibitor of metalloproteinase 3 (TIMP3). Conclusion: The upregulation of miR-181b may play an important role in the progress of gastric cancer and miR-181b maybe a potential molecular target for anticancer therapeutics of gastric cancer. -
Ay, Semra;Yanikkerem, Emre;Calim, Selda Ildan;Yazici, Mete 2269
Background: Health risks associated with unhealthy behaviours in adolescent and university students contribute to the development of health problems in later life. During the past twenty years, there has been a dramatic increase in public, private, and professional interest in preventing disability and death through changes in lifestyle and participation in screening programs. The aim of the study was to evaluate university students' health-promoting lifestyle behaviour for cancer prevention. Method: This study was carried out on university students who had education in sports, health and social areas in Celal Bayar University, Manisa, Turkey. The health-promoting lifestyles of university students were measured with the "health-promoting lifestyle profile (HPLP)" The survey was conducted from March 2011 to July 2011 and the study sample consisted of 1007 university students. T-test, ANOVA and multiple regression analyses were used for statistical analyses. Results: In the univariate analyses, the overall HPLP score was significantly related to students' school, sex, age, school grades, their status of received health education lessons, place of birth, longest place of residence, current place of residence, health insurance, family income, alcohol use, their status in sports, and self-perceived health status. Healthier behaviour was found in those students whose parents had higher secondary degrees, and in students who had no siblings. In the multiple regression model, healthier behaviour was observed in Physical Education and Sports students, fourth-year students, those who exercised regularly, had a good self-perceived health status, who lived with their family, and who had received health education lessons. Conclusion: In general, in order to ensure cancer prevention and a healthy life style, social, cultural and sportive activities should be encouraged and educational programmes supporting these goals should be designed and applied in all stages of life from childhood through adulthood. -
Rashwan, Hesham H.;Saat, Nur Zakiah N. Mohd;Manan, Dahlia Nadira Abd 2279
Human Papillomavirus (HPV) infection is one of the most common sexually transmitted infections and oncogenic HPV is the main cause of cervical cancer. However, HPV vaccination is already available as the primary preventive method against cervical cancer. The objective of this study was to determine the level of knowledge, attitude and practice of HPV vaccination among Universiti Kebangsaan Malaysia (UKM) and Universiti Malaya (UM) students. This study was conducted from March until August 2009. Pre-tested and validated questionnaires were filled by the third year UKM (n=156) and UM (n=149) students from medical, dentistry and pharmacy faculties. The results showed that the overall level of knowledge on HPV infection, cervical cancer and its prevention among respondents was high and the majority of them had positive attitude towards HPV vaccination. Medical students had the highest level of knowledge (p<0.05). Very few students (3.6%) had already taken the vaccine with no significant difference between the two Universities (p=0.399). In conclusion, the knowledge and attitude of the respondents were high and positive, respectively. Only few students took HPV vaccination. Thus, more awareness campaigns and HPV vaccination services should be provided at universities' campuses with the price of the HPV vaccine reduced for the students. -
Multidrug resistance (MDR) is a main cause of failure in the chemotherapeutic treatment of malignant disorders. One of the well-known genes responsible for drug resistance encodes the multidrug resistance-associated protein (MRP1). The association of MRP1 with clinical drug resistance has not systematically been investigated in Iranian pediatric leukemia patients. We therefore applied real-time RT-PCR technology to study the association between the MRP1 gene and MDR phenotype in Iranian pediatric leukemia patients. We found that overexpression of MRP1 occurred in most Iranian pediatric leukemia patients at relapse. However, no relation between MRP1 mRNA levels and other clinical characteristics, including cytogenetic subgroups and FAB subtypes, was found.
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Yassibas, Emine;Arslan, Perihan;Yalcin, Suayib 2291
Objective: Gastric cancer is an important public health problem in the world and Turkey. In addition to Helicobacter pylori (H. pylori), smoking, alcohol consumption and family history, certain dietary factors have been associated with its occurrence. The impact of dietary habits and life-style factors on the risk of gastric cancer in Turkey were evaluated in this study. Design: A questionnaire was applied to 106 patients with gastric adenocarcinoma and 106 controls without cancer matched for age (range 28-85 years) and gender selected from a hospital based population. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) were calculated with logistic regression analysis. Results: The incidence of H. pylori was 81.3% in patients. Frequent consumption of salty dishes, very salty foods like pickles, soup mixes, sausages, foods at hot temperature (ORs = 3.686, 7.784, 5.264, 3.148 and 3.273 respectively) and adding salt without tasting (OR = 4.198) were associated with increased gastric risk. Also heavy smoking and high amount of alcohol consumption (p = 0.000) were risk factors. Frequent consumption of green vegetables, onion, garlic and dried fruits (ORs = 0.569, 0.092, 0.795 and 0.041) was nonsignificantly associated with decreased risk. Conclusion: Improved dietary habits, reducing salt consumption and eradication of H. pylori infection may provide protection against gastric cancer in Turkey. -
Gichki, Abdul Samad;Buajeeb, Waranun;Doungudomdacha, Sombhun;Khovidhunkit, Siribang-On Pibooniyom 2299
Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the${\beta}$ -globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1${\mu}g$ of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p = 0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients. -
Crocin, the main pigment of Crocus sativus L., has been shown to have antiproliferative effects on cancer cells, but the involved mechanisms are only poor understood. This study focused on probable effect of crocin on the immortality of hepatic cancer cells. Cytotoxicity of crocin (
$IC_{50}$ 3 mg/ml) in hepatocarcinoma HepG2 cells was determined after 48 h by neutral red uptake assay and MTT test. Immortality was investigated through quantification of relative telomerase activity with a quantitative real-time PCR-based telomerase repeat amplification protocol (qTRAP). Telomerase activity in 0.5${\mu}g$ protein extract of HepG2 cells treated with 3 mg/ml crocin was reduced to about 51% as compared to untreated control cells. Two mechanisms of inhibition, i.e. interaction of crocin with telomeric quadruplex sequences and down regulation of hTERT expression, were examined using FRET analysis to measure melting temperature of a synthetic telomeric oligonucleotide in the presence of crocin and quantitative real-time RT-PCR, respectively. No significant changes were observed in the$T_m$ telomeric oligonucleotides, while the relative expression level of the catalytic subunit of telomerase (hTERT) gene showed a 60% decrease as compared to untreated control cells. In conclusion, telomerase activity of HepG2 cells decreases after treatment with crocin, which is probably caused by down-regulation of the expression of the catalytic subunit of the enzyme. -
Osawa, Kayo;Nakarai, Chiaki;Akiyama, Minami;Hashimoto, Ryuta;Tsutou, Akimitsu;Takahashi, Juro;Takaoka, Yuko;Kawamura, Shiro;Shimada, Etsuji;Tanaka, Kenichi;Kozuka, Masaya;Yamamoto, Masahiro;Kido, Yoshiaki 2311
Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7) may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interaction between polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68 individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups according to pack-years of smoking. Genetic polymorphisms of UGT1A6 and UGT1A7 were examined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found a weak association of UGT1A6 polymorphisms with CRC risk (crude odds ratio [OR], 1.65;95% confidence interval [95% CI], 0.9-3.1, P=0.107; adjusted OR 1.95%, 95% CI 1.0-3.8, P=0.051). The ORs for the UGT1A7 polymorphisms were statistically significant (crude OR: 26.40, 95% CI: 3.5-198.4, P=0.001; adjusted OR: 21.52, 95% CI: 2.8-164.1, P=0.003). The joint effect of tobacco exposure and UGTIA6 polymorphisms was significantly associated with colorectal cancer risk in non-smokers (crude OR, 2.11; 95% CI, 0.9-5.0, P=0.092; adjusted OR 2.63, 95% CI, 1.0-6.7, P=0.042). In conclusion, our findings suggest that UGT1A6 and UGT1A7 gene polymorphisms are associated with CRC risk in the Japanese population. In particualr, UGT1A6 polymorphisms may strongly increase CRC risk through the formation of carcinogens not associated with smoking. -
Valliani, Arif;Ahmed, Bilawal;Nanji, Kashmira;Valliani, Salimah;Zulfiqar, Beenish;Fakih, Misbah;Mehdi, Mehwish;Khan, Anam;Sheikh, Sana Arshad;Fatima, Nida;Ahmad, Sobia;Farah, Fariya;Saleem, Shaheera;Ather, Sana;Majid, Syed Khubaib;Hashmi, Syed Salman;Arjan, Sunil 2315
Background: Use of smoke-less tobacco (SLT) is very common in South and South-East Asian countries. It is significantly associated with various types of cancers. The objectives of this study were to assess the proportion of hospital staff that use SLT, and to identify the factors associated with its use and their practices. Methods: In a cross-sectional study, 560 staff of two tertiary care hospitals were interviewed in the year 2009. Nurses, ward boys and technicians were counted as a paramedic staff while drivers, peons, security guards and housekeeping staff were labeled as non-paramedic staff. SLT use was considered as usage of any of the following: betel quid (paan) with or without tobacco, betel nuts with or without tobacco (gutkha) and snuff (naswar). Results: About half (48.6%) of the hospital staff were using at least one type of SLT. Factors found to be statistically significant with SLT were being a male (OR=2.5; 95% CI=1.8-3.7); having no/fewer years of education (OR=1.7; 95% CI=1.2-2.4) and working as non-paramedic staff (OR=2.6; 95% CI=1.8-3.8). Majority of SLT users were using it on regular basis, for > 5 years and keeping the tobacco products in the oral cavity for >30 minutes. About half of the users started due to peer pressure and had tried to quit this habit but failed. Conclusion: In this study, about half of the study participants were using SLT in different forms. We suggest educational and behavioral interventions for control of SLT usage. -
Wang, Hong;Li, Yu-Yuan;Wu, Ying-Ying;Nie, Yu-Qiang 2319
Aim: To investigate the expression of three components of the Hedgehog (Hh) signaling pathway (SHH, SMO and GLI1) in human colorectal cancer (CRC) tissues and evaluate their association with clinicopathologic characteristics of the patients. Methods: Fresh tumor tissues and matched tissues adjacent to the tumor were collected from 43 CRC patients undergoing surgery. Normal colorectal tissues from 20 non-CRC cases were also sampled as normal controls. The expression of SHH, SMO, GLI1 mRNAs was assessed by RT-PCR and proteins were detected by immunohistochemical staining. Associations with clinicopathological characteristics of patients were analyzed. Results: SHH mRNA was expressed more frequently in tumor tissues than in normal tissues, but the difference did not reach significance in comparison to that in the adjacent tissues. SMO and GLI1 mRNAs were expressed more frequently in tumor tissues than in both adjacent andnormal tissues. The expression intensities of SHH, SMO, GLI1 mRNA in tumor tissues were significantly higher than those in adjacent tissues and normal tissues. Proteins were also detected more frequently in tumors than other tissues. No significant links were apparent with gender, age, location, degree of infiltration or Dukes stage. Conclusion: Positive rates and intensities of mRNA and protein expression of Hh signaling pathway related genes SHH, SMO, GLI1 were found to be significantly increased in CRC tissues. However, over-expression did not appear to be associated with particular clinicopathological characteristics. -
Li, Yue;Zhang, Shuai;Geng, Jian-Xiong;Yu, Yan 2325
Background: Cyclin D1 (CCND1) is critical in the transition of the cell cycle from G1 to S phases and unbalanced cell cycle regulation is a hallmark of carcinogenesis. A number of studies conducted to assess the association between CCND1 G870A polymorphism and susceptibility to lung cancer have yielded inconsistent and inconclusive results. In the present study, the possible association above was assessed by a meta-analysis. Methods: Eligible articles were identified for the period up to November 2011. Pooled odds ratios (OR) with 95% confidence intervals (95%CI) were appropriately derived from fixed effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from the Hardy-Weinberg equilibrium (HWE) was performed. Results: Ten case-control studies with a total of 10,548 subjects were eligible. At the overall analysis the CCND1 870A allele appeared to be associated with elevated lung cancer risk (for allele model, pooled OR = 1.24, 95% CI: 1.08-1.44, P = 0.004; for homozygous model, pooled OR = 1.45, 95% CI: 1.14-1.84, P = 0.003; for recessive model, pooled OR = 1.29, 95% CI: 1.06-1.58, P = 0.013; for dominant model, pooled OR = 1.33, 95% CI: 1.08-1.65, P = 0.009). Subgroup analyses by ethnicity and sensitivity analysis further pointed to associations, particularly in Asians. Conclusion: This meta-analysis suggests that the A allele of CCND1 G870A polymorphism confers additional lung cancer risk. -
Ma, Xue-Lei;Liu, Lei;Liu, Xiao-Xiao;Li, Yun;Deng, Lei;Xiao, Zhi-Lan;Liu, Yan-Tong;Shi, Hua-Shan;Wei, Yu-Quan 2329
Introduction: Many studies have reported that microRNA-21 (miR-21) mihght predict the survival outcome in non-small cell lung cancers (NSCLCs) but the opposite opinion has also been expressed. The aim of this study was to summarize the evidence for a prognostic role of miR-21. Materials and Methods: All the eligible studies was searched by Medline and EMBASE and patients' clinical characteristics and survival outcome were extracted. Then a meta-analysis was performed to clarify the prognostic role of the miR-21 expression in different subgroups. Results: A total of 8 eligible articles were yielded covering survival outcomes or clinical characteristics. The combined hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival (OS) was 2.19 [0.76, 6.30], while the combined HR (95% CI) of Asian group for OS had a significant result, 5.49 [2.46, 12.27]. The combined HR (95% CI) for recurrence free survival or disease free survival (RFS/DFS) was 2.31 [1.52, 3.49]. Odds ratios (ORs) showed that the miR-21 expression was associated with lymph node status and histological type. Conclusion: miR-21 expression could predict the prognostic outcome of NSCLC in Asians, despite some deficiencies in the study data. -
Mittal, Ankush;Poudel, Bibek;Pandeya, Dipendra Raj;Gupta, Satrudhan Pd;Sathian, Brijesh;Yadav, Shambhu Kumar 2335
Objective: To evaluate several metabolic changes in patients with differentiated thyroid carcinoma (DTC ) which enhance cardiovascular risk in the western region of Nepal. Materials and Methods: This hospital based case control study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Manipal Teaching Hospital, Pokhara, Nepal between$1^{st}$ January, 2009 and$31^{st}$ December, 2011. The variables collected were age, gender, BMI, glucose, insulin, HbA1C, CRP, fibrinogen, total cholesterol, triglycerides, HDL, LDL, VLDL, f-T3, f-T4, TSH. One way ANOVA was used to examine statistical significance of differences between groups, along with the Post Hoc test LSD for comparison of means. Results: fT3 values were markedly raised in DTC cases ($5.7{\pm}SD1.4$ ) when compared to controls ($2.2{\pm}SD0.9$ ). Similarly, fT4 values were also moderately raised in cases of DTC ($4.9{\pm}SD1.3$ and$1.7{\pm}SD0.9$ ). In contrast, TSH values were lowered in DTC cases ($0.39{\pm}SD0.4$ ) when compared to controls ($4.2{\pm}SD1.4$ ). Mean blood glucose levels were decreased while insulin was increased and HDL reduced ($39.5{\pm}SD4.7$ as compared to the control$43.1{\pm}SD2.2$ ). Conclusion: Cardiovascular risk may be aggravated by insulin resistance, a hypercoagulable state, and an atherogenic lipid profile in patients with differentiated thyroid cancer. -
Yu, Dong-Sheng;Huang, Xin-En;Zhou, Jian-Nong 2339
Objective: To compare the efficacy of anal preserving surgery for aged people with low rectal carcinoma. Methods: Clinical data for a consecutive cohort of 98 rectal cancer patients with distal tumors located within 3cm -7cm of the anal verge were collected. Among these, 42 received anal preserving surgery (35 with Dixon, 3 with Parks and 4 with transanal operations). The local recurrence and survival rates in the above operations were compared with those of the Miles operation in another 56 patients with rectal cancer. Results: The local recurrence and 3-, 5-year survival rates of anal preserving surgery were 16.7%, 64.3% and 52.4%, those of Miles operations were 16.1%, 67.9% and 51.8% respectively (P>0.05). Conclusion: Anal preserving surgery for aged people with low rectal cancer is not inferior to conventional operations in China, with satisfactory long term survival and comparable local recurrence rates. -
Bilyalova, Zarina;Igissinov, Nurbek;Moore, Malcolm;Igissinov, Saginbek;Sarsenova, Samal;Khassenova, Zauresh 2341
The aim of the research was to evaluate the incidence of breast cancer in the ecological areas of Kazakhstan and assess the potential. A retrospective study of 11 years (1999 to 2009) was conducted using descriptive and analytical methods. The incidence of breast cancer was the lowest in the Aral-Syr Darya area ($18.6{\pm}0.80$ /100,000), and highest in the Irtysh area ($48.9{\pm}1.90$ /100,000), with an increasing trends over time in almost all areas. A direct strong correlation between the degree of contamination with high pollution emissions in the atmosphere from stationary sources and the incidence of breast cancer ($r=0.77{\pm}0.15$ ; p=0.026). The results indicate an increasing importance of breast cancer in Kazakhstan and an etiological role for environmental pollution. -
Igissinov, Nurbek;Nuralina, Indira;Igissinova, Gulnur;Kim, Sergei;Moore, Malcolm;Igissinov, Saginbek;Khassenova, Zauresh 2345
Epidemiological studies of cancer incidence in Kazakhstan have revealed an uneven distribution for cervical cancer. Incidence and mortality rates were calculated for different regions of the republic, including the two major cities of Almaty and Astana, in 1999-2008. Defined levels for cartograms for incidence were low (up to 12.8/100,000), medium (12.8 to 15.9) and high (above 15.9) and for mortality were up to 7.1, 7.1 to 10.8 and more than 10.8, respectively. Basically high incidence rates were identified in the eastern, central and northern parts of the country and in Almaty. Such differences in cervical cancer data, and also variation in mortality/ incidence ratios, from a low of 0.4 in Almaty to a high of 0.71 in Zhambyl, point to variation in demographic and medical features which impact on risk and prognistic factors for cervical cancer in the country. Further research is necessary to highlight areas for emphasis in cancer control programs for this important cancer. -
Xu, Ting;Xu, Zi-Cheng;Zou, Qin;Yu, Bin;Huang, Xin-En 2349
Objective: Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship, we performed this systemic review and meta-analysis based on 15 publications. Methods: We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We found that there was no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg (OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32). However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison (Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Pro plus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of an association between bladder cancer risk and P53 genotype was observed among Caucasian population in any genetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.56 95%CI 0.26-1.20; Recessive model, OR=0.62 95%CI0.35-1.08) between P53 codon 72 polymorphism and bladder cancer in all comparisons. Conclusions: Despite the limitations, the results of the present meta-analysis suggest that, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancer in Asians; and there are no association between genotype distribution and the stage of bladder cancer. -
Zhang, Hang;Duan, Chao-Jun;Chen, Wei;Wang, Shao-Qiang;Zhang, Sheng-Kang;Dong, Shuo;Cheng, Yuan-Da;Zhang, Chun-Fang 2355
The SH2B1 adaptor protein is recruited to multiple ligand-activated receptor tyrosine kinases that play important role in the physiologic and pathologic features of many cancers. The purpose of this study was to assess SH2B1 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Methods: SH2B1 expression in 114 primary NSCLC tissue specimens was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patients' outcome. Additionally, 15 paired NSCLC background tissues, 5 NSCLC cell lines and a normal HBE cell line were evaluated for SH2B1 expression by RT-PCR and immunoblotting, immunofluorescence being applied for the cell lines. Results: SH2B1 was found to be overexpressed in NSCLC tissues and NSCLC cell lines. More importantly, high SH2B1 expression was significantly associated with tumor grade, tumor size, clinical stage, lymph node metastasis, and recurrence respectively. Survival analysis demonstrated that patients with high SH2B1 expression had both poorer disease-free survival and overall survival than other patients. Multivariate Cox regression analysis revealed that SH2B1 overexpression was an independent prognostic factor for patients with NSCLC. Conclusions: Our findings suggest that the SH2B1 protein may contribute to the malignant progression of NSCLC and could offer a novel prognostic indicator for patients with NSCLC. -
Jing, Yuan-Ming;Guo, Su-Xia;Zhang, Xiao-Ping;Sun, Ai-Jing;Tao, Feng;Qian, Hai-Xin 2363
Objective: To investigate the association between the connexin 37 C1019T polymorphism and Helicobacter pylori infection in patients with gastric cancer. Methods: 388 patients with gastric cancer (GC), 204 with chronic superficial gastritis (CSG) were studied. H. pylori was detected by gastric mucosal biopsies biopsy dyeing method. Connexin 37 gene polymorphism 1019 site genotypes were determined by gene sequencing technology. Genotypes and alleles frequencies were compared. Results: (1) Connexin37 gene 1019 site distribution frequency (CC type, TC type, TT type) in the CSG group was 18.1%, 45.1% and 36.8%; in the stomach cancer group it was 35.1%, 45.9% and 19.%, conforming to the Hardy-Weinberg euilibrium. (2) In comparison with CSG group, the frequency of Connexin37 C allele was higher in the gastric cancer group (58.0% vs 40.7%, OR = 2.01, 95%CI = 1.58-2.57, P < 0.01). The prevalence of gastric cancer risk was significantly increased in the carriers of C allele (CC+TC) than in TT homozygote (OR = 2.47, 5%CI = 1.68- 3.610. (3) Gastric cancer patients complicated with Hp infection 211 cases, gastric cancer group of the male patients with HP positive patients with 187 cases, 40 cases of female patients with negative patients, 24 cases were HP positive, negative in 137 cases, control group male patients, 28 cases were Hp positive, negative in 95 patients, female patients with Hp positive 6 cases, 75 cases were negative. On hierarchical analysis, the male group OR value was 15.9 (95%CI to 9.22-27.3), and the female OR was 2.19 (95%CI 0.88-5.59), indicating a greater contribution in males (P <0.01). After elimination of gender effects, positive HP and gastric cancer were closely related (OR 8.82, 95% CI: 5.45-14.3). (4) The distribution frequency of C allele in patients with Hp infection was much higher than that in Hp negative cases in the GC group (64.5% vs 47.0%, OR = 2.05, 95%CI = 1.54-2.74, P < 0.01). Compared with TT homozygotes, (CC+TC) genotype prevalence of gastric cancer risk increased significantly (OR = 2.96, 5%CI = 1.76-2.99 ). Conclusion: The T allele in the connexin37 gene might not only be associated with gastric cancer but also with H. pylori infection. -
Zhao, Fang-Hui;Tiggelaar, Sarah M.;Hu, Shang-Ying;Zhao, Na;Hong, Ying;Niyazi, Mayinuer;Gao, Xiao-Hong;Ju, Li-Rong;Zhang, Li-Qin;Feng, Xiang-Xian;Duan, Xian-Zhi;Song, Xiu-Ling;Wang, Jing;Yang, Yun;Li, Chang-Qin;Liu, Jia-Hua;Liu, Ji-Hong;Lu, Yu-Bo;Li, Li;Zhou, Qi;Liu, Jin-Feng;Xu, Li-Na;Qiao, You-Lin 2369
Objectives: To assess knowledge of HPV and attitudes towards HPV vaccination among the general female population, government officials, and healthcare providers in China to assist the development of an effective national HPV vaccination program. Methods: A cross-sectional epidemiologic survey was conducted across 21 urban and rural sites in China using a short questionnaire. 763 government officials, 760 healthcare providers, and 11,681 women aged 15-59 years were included in the final analysis. Data were analyzed using standard descriptive statistics and logistic regression. Results: Knowledge of HPV among the general female population was low; only 24% had heard of HPV. Less than 20% of healthcare providers recognized sexually na$\ddot{i}$ ve women as the most appropriate population for HPV vaccination. There was high acceptance of the HPV vaccine for all categories of respondents. Only 6% of women were willing to pay more than US $300 for the vaccine. Conclusions: Aggressive education is necessary to increase knowledge of HPV and its vaccine. Further proof of vaccine safety and efficacy and government subsidies combined with increased awareness could facilitate development and implementation of HPV vaccination in China. -
Objective: To investigate possible signal pathway involvement in multi-drug resistant P-glycoprotein (P-gp) expression induced by cyclooxygenase-2 (COX-2) in a human gastric adenocarcinoma cell line stimulated with pacliaxel (TAX). Methods: The effects of TAX on SGC7901 cell growth with different doses was assessed by MTT assay, along with the effects of the COX-2 selective inhibitor NS-398 and the nuclear factor-KB (NF-KB) pathway inhibitor pyrrolidine dithiocarbamate (PDTC). Influence on COX-2, NF-KB p65 and P-gp expression was determined by Western blotting. Results: TAX, NS-398 and PDTC all reduced SGC7901 growth, with dosedependence. With increasing dose of TAX, the expression of COX-2, p65 and P-gp showed rising trends, this being reversed by NS-398. PDTC also caused decrease in expression of p65 and P-gp over time. Conclusion: COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.
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Chen, Yue;Zou, Hong;Yang, Li-Ying;Li, Yuan;Wang, Li;Hao, Yan;Yang, Ju-Lun 2385
The lack of effective treatment targets for triple-negative breast cancers make them unfitted for endocrine or HER2 targeted therapy, and their prognosis is poor. Transcription factor ER81, a downstream gene of the HER2, is highly expressed in breast cancer lines, breast atypical hyperplasia and primary breast cancers including triple-negative examples. However, whether and how ER81 affects breast cancer carcinogenesis have remained elusive. We here assessed influence on a triple-negative cell line. ER81-shRNA was employed to silence ER81 expression in the MDA-MB-231 cell line, and MTT, colony-forming assays, and flow cytometry were used to detect cell proliferation, colony-forming capability, cell cycle distribution, and cell apoptosis in vitro. MDA-MB-231 cells stably transfected with ER81-shRNA were inoculated into nude mice, and growth inhibition of the cells was observed in vivo. We found that ER81 mRNA and protein expression in MDA-MB-231 cells was noticeably reduced by ER81-shRNA, and that cell proliferation and clonality were decreased significantly. ER81-shRNA further increased cell apoptosis and the residence time in$G_0/G_1$ phase, while delaying tumor-formation and growth rate in nude mice. It is concluded that ER81 may play an important role in the progression of breast cancer and may be a potentially valuable target for therapy, especially for triple negative breast cancer. -
Li, Hong-Sheng;Kong, Ling-Ling;Zhang, Jian;Li, Bao-Sheng;Chen, Jin-Hu;Zhu, Jian;Liu, Tong-Hai;Yin, Yong 2393
Objectives: The purpose of this study was to evaluate the geometric accuracy of thoracic anatomic landmarks as target surrogates of intrapulmonary tumors for manual rigid registration during image-guided radiotherapy (IGRT). Methods: Kilovolt cone-beam computed tomography (CBCT) images acquired during IGRT for 29 lung cancer patients with 33 tumors, including 16 central and 17 peripheral lesions, were analyzed. We selected the "vertebrae", "carina", and "large bronchi" as the candidate surrogates for central targets, and the "vertebrae", "carina", and "ribs" as the candidate surrogates for peripheral lesions. Three to six pairs of small identifiable markers were noted in the tumors for the planning CT and Day 1 CBCT. The accuracy of the candidate surrogates was evaluated by comparing the distances of the corresponding markers after manual rigid matching based on the "tumor" and a particular surrogate. Differences between the surrogates were assessed using 1-way analysis of variance and post hoc least-significant-difference tests. Results: For central targets, the residual errors increased in the following ascending order: "tumor", "bronchi", "carina", and "vertebrae"; there was a significant difference between "tumor" and "vertebrae" (p = 0.010). For peripheral diseases, the residual errors increased in the following ascending order: "tumor", "rib", "vertebrae", and "carina"; There was a significant difference between "tumor" and "carina" (p = 0.005). Conclusions: The "bronchi" and "carina" are the optimal surrogates for central lung targets, while "rib" and "vertebrae" are the optimal surrogates for peripheral lung targets for manual matching of online and planned tumors. -
Shu, Jian;Li, Cheng-Guang;Liu, Yang-Chen;Yan, Xiao-Chun;Xu, Xu;Huang, Xin-En;Cao, Jie;Li, Ying;Lu, Yan-Yan;Wu, Xue-Yan;Liu, Jin;Xiang, Jin 2399
Objective: To compare expression level of serum tumor associated materials (TAM) with several conventional serum tumor biomarkers, eg., carcinoembryonic antigen (CEA), carbohydrate antigen19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), alpha-fetoprotein(AFP), in selected solid tumors. Methods: Patients diagnosed histologically or cytologically with liver, breast, esophageal, gastric, colorectal or pancreatic cancers were enrolled into this study. After diagnosis, the level of TAM was determined by chemical colorimetry, and levels of conventional tumor markers was measured by chemiluminescence methods. Results: A total of 560 patients were enrolled into this study. No statistically significant difference was detected in TAM and the above mentioned tumor biomarkers in terms of their positivity and negativity ( P>0. 05). Conclusions: Detection of TAM in liver, breast, esophageal, gastric, colorectal, and pancreatic cancer patients demonstrates a good accordance with CEA, CA199, CA153, and AFP, thus suggesting that further study is warranted to verify whether TAM could be a surrogate for these conventional biomarkers. -
This descriptive study was performed to determine levels of the death anxiety levels of relatives of patients who being treated in a public hospital located in the Asian side of Istanbul and influencing factors. The sample was 106 patient relatives of patients from oncology or chemotherapy units of the hospital. Data were collected between May-June 2011 with the 15-item Death Anxiety Scale developed by Templer (1970) and adapted to Turkish by Senol (1989) and evaluated by number-percentage calculations, the Kruskal Wallis, Anova and t tests. Some 36.8% of the included group were aged 45 years and over, 57.5% were female and 65.1% were married. A statistically significant difference was found between the age groups, genders of the patient relatives, the period of cancer treatment regarding the death anxiety levels (p<0.05). The death anxiety levels of the patient relatives who were in the 17-39 age group, female and had a patient who was under treatment for less than 6 months were found to high as compared to others.
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Liu, Wei;Li, Su-Yi;Huang, Xin-En;Cui, Jiu-Jie;Zhao, Ting;Zhang, Hua 2409
Objective: Traditional Chinese herbal medicines have a very long history. Rosa roxburghii Tratt and Fagopyrum cymosum are two examples of plants which are reputed to have benefits in improving immune responses, enhancing digestive ability and demonstrating anti-aging effects. Some evidence indicates that herbal medicine soups containing extracts from the two in combination have efficacy in treating malignant tumors. However, the underlying mechanisms are far from well understood. The present study was therefore undertaken to evaluate anticancer effects and explore molecular mechanisms in vitro. Methods: Proliferation and apoptosis were assessed with three carcinoma cell lines (human esophageal squamous carcinoma CaEs-17, human gastric carcinoma SGC-7901 and pulmonary carcinoma A549) by MTT assay and flow cytometry, respectively, after exposure to extract from Rosa roxburghii Tratt (CL) and extract from Fagopyrum cymosum (FR).$IC_{30}$ of CL and FR were obtained by MTT assay. Tumor cells were divided into four groups : control with no exposure to CL or FR; CL with$IC_{30}$ CL; FR with$IC_{30}$ FR; CL+FR group with 1/2 ($IC_{30}$ CL +$IC_{30}$ FR). RT-PCR and Western blot analysis were used to detect the expression of Ki-67, Bax and Bcl-2 at mRNA and protein levels. Results: Compared with the CL or FR groups, the combination of CL+FR showed significant inhibition of cell growth and increase in apoptosis; the mRNA and protein expression levels of Ki-67 and Bcl-2 in CL+FR group were all greatly decreased, while the expression of Bax was markedly increased. Conclusions: These results indicate that the synergistic antitumor effects of combination of CL and FR are related to inhibition of proliferation and induction of apoptosis. -
Zhang, Xue-Zhong;Huang, Xin-En;Xu, Yan-Li;Zhang, Xiu-Qun;Su, Ai-ling;Shen, Zheng-Shan 2415
Objective: To investigate the efficacy and safety of voriconazole in treating Chinese patients with hematological malignancies and invasive aspergillosis. Methods: From March 2007 to April 2012, patients with diagnoses confirmed by CT, GM test and/or PCR assays, were recruited into this study. Aspergillosis of all patients were treated with voriconazole 6 mg/kg intravenous infusion (iv) every 12 h for 1 day, followed by 4 mg/kg IV every 12 h for 10-15 days; Then, switch to oral administration that was 200mg every 12h for 4-12 weeks. Efficacy and safety were evaluated according to Practice Guideline of Infectious Diseases Society of America. Results: The overall response rate of 38 patients after voriconazole treatment was 81.6%. The median time to pyretolysis was 4.5 days. Treatment related side effects were mild and found in only 15.8% of cases. No treatment related deaths occurred. Conclusions: Voriconazole can considered to be a safe and effective front-line therapy to treat patients with hematological malignancies and invasive aspergillosis. Alternatively it could be used as a remedial treatment when other antifungal therapies are ineffective. -
Context: Genuine community participation does not denote taking part in an action planned by health care professionals in a medical or top-down approach. Further, community participation and health education on breast cancer prevention are not similar to other activities incorporated in primary health care services in Iran. Objective: To propose a model that provides a methodological tool to increase women's participation in the decision making process towards breast cancer prevention. To address this, an evaluation framework was developed that includes a typology of community participation approaches (models) in health, as well as five levels of participation in health programs proposed by Rifkin (1985&1991). Method: This model explains the community participation approaches in breast cancer prevention in Iran. In a 'medical approach', participation occurs in the form of women's adherence to mammography recommendations. As a 'health services approach', women get the benefits of a health project or participate in the available program activities related to breast cancer prevention. The model provides the five levels of participation in health programs along with the 'health services approach' and explains how to implement those levels for women's participation in available breast cancer prevention programs at the local level. Conclusion: It is hoped that a focus on the 'medical approach' (top-down) and the 'health services approach' (top-down) will bring sustainable changes in breast cancer prevention and will consequently produce the 'community development approach' (bottom-up). This could be achieved using a comprehensive approach to breast cancer prevention by combining the individual and community strategies in designing an intervention program for breast cancer prevention.
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Ornithine decarboxylase (ODC), the first enzyme in the polyamine biosynthesis, plays an important role in tumor progression, cell proliferation and differentiation. In recent years, ODC has been the subject of intense study among researchers, as a target for anti-cancer therapy and specific inhibitory agents, have the potential to suppress carcinogenesis and find applications in clinical therapy. In particular, it is suggested that ODC is a promising candidate target for natural products in cancer chemoprevention. Future exploration of ornithine decarboxyalse inhitors present in nature may offer great hope for finding new cancer chemporeventive agents.