Asian Pacific Journal of Cancer Prevention
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
- 월간
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
과학기술표준분류
- 보건의료 > 의약품/의약품개발
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.
KSCI제15권6호
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Ghafouri-Fard, Soudeh;Nekoohesh, Leili;Motevaseli, Elahe 2395
As the recurrence and mortality rates of bladder cancer are high, research is needed to find suitable biomarkers for early detection, evaluation of prognosis, and surveillance of drug responses. We performed a computerized search of the Medline/PubMed databases with the key words bladder cancer, biomarker, early detection, prognosis and drug response. Several markers were identified at DNA, RNA and protein levels with different sensitivities and specificities. Only a few of the potential bladder cancer biomarkers have been approved for clinical use. Efforts now should be concentrated on finding a panel of markers with acceptable sensitivity and specificity for early detection of bladder cancer. -
Radiation exposure leads to several pathophysiological conditions, including oxidative damage, inflammation and fibrosis, thereby affecting the survival of organisms. This review explores the radiation countermeasure properties of fourteen (14) plant extracts or plant-derived compounds against these cellular manifestations. It was aimed at evaluating the possible role of plants or its constituents in radiation countermeasure strategy. All the 14 plant extracts or compounds derived from it and considered in this review have shown some radioprotection in different in vivo, ex-vivo and or in vitro models of radiological injury. However, few have demonstrated advantages over the others. C. majus possessing antioxidant, anti-inflammatory and immunomodulatory effects appears to be promising in radioprotection. Its crude extracts as well as various alkaloids and flavonoids derived from it, have shown to enhance survival rate in irradiated mice. Similarly, curcumin with its antioxidant and the ability to ameliorate late effect of radiation exposure, combined with improvement in survival in experimental animal following irradiation, makes it another probable candidate against radiological injury. Furthermore, the extracts of P. hexandrum and P. kurroa in combine treatment regime, M. piperita, E. officinalis, A. sinensis, nutmeg, genistein and ginsan warrants further studies on their radioprotective potentials. However, one that has received a lot of attention is the dietary flaxseed. The scavenging ability against radiation-induced free radicals, prevention of radiation-induced lipid peroxidation, reduction in radiation cachexia, level of inflammatory cytokines and fibrosis, are some of the remarkable characteristics of flaxseed in animal models of radiation injury. While countering the harmful effects of radiation exposure, it has shown its ability to enhance survival rate in experimental animals. Further, flaxseed has been tested and found to be equally effective when administered before or after irradiation, and against low doses (
${\leq}5Gy$ ) to the whole body or high doses (12-13.5 Gy) to the whole thorax. This is particularly relevant since apart from the possibility of using it in pre-conditioning regime in radiotherapy, it could also be used during nuclear plant leakage/accidents and radiological terrorism, which are not pre-determined scenarios. However, considering the infancy of the field of plant-based radioprotectors, all the above-mentioned plant extracts/plant-derived compounds deserves further stringent study in different models of radiation injury. -
Triple-negative breast cancers (TNBC), characterized by absence of the estrogen receptor (ER) and progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), have a poor prognosis. To overcome therapy limitations of TNBC, various new approaches are needed. This mini-review focuses on discovery of new targets and drugs which might offer new hope for TNBC patients.
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Karimi, Parisa;Shahrokni, Armin;Nezami Ranjbar, Mohammad R. 2433
Cancer is the leading cause of the death, accounts for about 13% of all annual deaths worldwide. Many different fields of science are collaborating together studying cancer to improve our knowledge of this lethal disease, and find better solutions for diagnosis and treatment. Proteomics is one of the most recent and rapidly growing areas in molecular biology that helps understanding cancer from an omics data analysis point of view. The human proteome project was officially initiated in 2008. Proteomics enables the scientists to interrogate a variety of biospecimens for their protein contents and measure the concentrations of these proteins. Current necessary equipment and technologies for cancer proteomics are mass spectrometry, protein microarrays, nanotechnology and bioinformatics. In this paper, we provide a brief review on proteomics and its application in cancer research. After a brief introduction including its definition, we summarize the history of major previous work conducted by researchers, followed by an overview on the role of proteomics in cancer studies. We also provide a list of different utilities in cancer proteomics and investigate their advantages and shortcomings from theoretical and practical angles. Finally, we explore some of the main challenges and conclude the paper with future directions in this field. -
Zhou, Jun;Xu, Xiao-Zhen;Hu, Yao-Ren;Hu, Ai-Rong;Zhu, Cheng-Liang;Gao, Guo-Sheng 2439
Cryptotanshinone (CPT), is a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miotiorrhiza bunge. Numerous researchers have found that it could work as a potent antitumor agent to inhibit tumor growth in vitro, buith there has been much less emphasis on its in vivo role against breast tumors. Using a mouse tumor model of MCF7 cells, we showed that CPT strongly inhibited MCF7 cell growth in vivo with polarization of immune reactions toward Th1-type responses, stimulation of naive CD4+ T cell proliferation, and also increased IFN-${\gamma}$ and perforin production of CD4+ T cells in response to tumor-activated splenocytes. Furthermore, data revealed that the cytotoxic activity of CD4+ T cells induced by CPT was markedly abrogated by concanamycin A(CMA), a perforin inhibitor, but not IFN-${\gamma}$ Ab. On the other hand, after depletion of CD4+ T cells or blocked perforin with CMA in a tumor-bearing model, CPT could not effectively suppress tumor growth, but this phenomenon could be reversed by injecting naive CD4+ T cells. Thus, our results suggested that CPT mainly inhibited breast tumor growth through inducing cytotoxic CD4+ T cells to secrete perforin. We further found that CPT enhanced perforin production of CD4+ T cells by up-regulating JAK2 and STAT4 phosphorylation. These findings suggest a novel potential therapeutic role for CPT in tumor therapy, and demonstrate that CPT performs its antitumor functions through cytotoxic CD4+ T cells. -
Wu, Xiang-Mei;Liu, Xing;Jiao, Qing-Fang;Fu, Shao-Yue;Bu, You-Quan;Song, Fang-Zhou;Yi, Fa-Ping 2447
Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer. -
Li, Jing;Wei, Qiang;Zuo, Guo-Wei;Xia, Jing;You, Zhi-Mei;Li, Chun-Li;Chen, Di-Long 2453
Ginsenoside Rg1 is one effective anticancer and antioxidant constituent of total saponins of Panax ginseng (TSPG), which has been shown to have various pharmacological effects. Our previous study demonstrated that Rg1 had anti-tumor activity in K562 leukemia cells. The aim of this study was designed to investigate whether Rg1 could induce apoptosis in TF-1/Epo cells and further to explore the underlying molecular mechanisms. Here we found that Rg1 could inhibit TF-1/Epo cell proliferation and induce cell apoptosis in vitro in a concentration and time dependent manner. It also suppressed the expression of EpoR on the surface membrane and inhibited JAK2/STAT5 pathway activity. Rg1 induced up-regulation of Bax, cleaved caspase-3 and C-PAPR protein and down-regulation of Bcl-2 and AG490, a JAK2 specific inhibitor, could enhance the effects of Rg1. Our studies showed that EpoR-mediated JAK2/STAT5 signaling played a key role in Rg1-induced apoptosis in TF-1/Epo cells. These results may provide new insights of Rg1 protective roles in the prevention a nd treatment of leukemia. -
Arab, Maliheh;Noghabaei, Giti;Kazemi, Seyyedeh Neda 2461
Background: Cancer accounts for 12.6% of total deaths in the world (just after heart disease). Materials and Methods: Frequency and age-specific incidence rates of breast and gynecologic cancers in Iran are calculated based on the dataset of the National Cancer Registry of Iran in 2005. Results: Gynecologic and breast cancer accounted for 7.6% and 25.6% of total cancer cases, respectively. Ovarian cancer was the most frequent gynecologic cancer followed by endometrium. Endometrial cancer revealed the highest age specific incidence rate followed by ovary (after 59 years). Conclusions: Regarding disease burden, breast and gynecologic cases account for 33.4% of total cancer patients. The age specific incidence rate is a useful guide in epidemiologic and future plans. -
Arslan, Deniz;Bozcuk, Hakan;Gunduz, Seyda;Tural, Deniz;Tattli, Ali Murat;Uysal, Mukremin;Goksu, Sema Sezgin;Bassorgun, Cumhur Ibrahim;Koral, Lokman;Coskun, Hasan Senol;Ozdogan, Mustafa;Savas, Burhan 2465
Background: The American Joint Committee on Cancer (AJCC) published a new staging system ($7^{th}$ edition) in 2009. In our study, we evaluated the survival results and prognostic factors among T4 local advanced non-small cell lung cancer (LA-NSCLC) patients in a large heterogeneous group, in accordance with this new system. Materials and Methods: We retrospectively evaluated the files of 122 T4 N0-3 M0 LA-NSCLC patients, identified according to the new staging system, treated at two centers between November 2003 and June 2012. Variables correlating with univariate survival at p<0.20 were later included in multivariate Cox regression analysis. Here, selection of relevant predictors of survival was carried out in accordance with the likelihood ratio formula with p<0.05 regarded as significant. Results: The median age was 60 and the median follow-up period was 17.4 months. Median overall survival (OS) was 18.3 months, the 1 year overall survival (OS) rate was 72%, and the 5 year OS rate was 28%. Statistically significant predictors of survival were (p<0.20) ECOG-PS (Eastern Cooperative Oncology Group Performance Status), age, T4 factor subgroup, stage and primary treatment in OS univariate analysis. On multivariate analysis for OS ECOG-PS (p=0.001), diagnostic stage (p=0.021), and primary treatment (p=0.004) were significant. In the group receiving non-curative treatment, the median OS was 11.0 months, while it was 19.0 months in the definitive RT group and 26.6 months in the curative treatment group. There was a significant difference between the non-curative group and the groups which had definitive RT and curative operations (respectively p<0.001 and p=0.001) in terms of OS, but not between the groups which had definitive RT and curative operations. The median event free survival (EFS) rate was 9.9 months, with rates of 46% and 19% at 3 and 5 years, respectively. On univariate analysis of EFS rate with ECOG-PS, weight loss and staging, statistical significance was found only for thorax computerized tomography (CT)+18F-fluorodeoxy-glucose positron emission tomography-CT (PET-CT) use, stage and primary treatment (p<0.20). In multivariate analysis with EFS, only the primary treatment was statistically significant (p=0.001). In the group receiving non-curative treatment, the median EFS was 10.5 months while in the curative operation group it was 14.7 months. When all the primary treatment groups were taken into consideration, grade III/IV side effect swas observed in 57 patients (46.6%). Esophagitis was most prominent among those that received definitive radiotherapy. Conclusions: Independent prognostic factors among these 122 heterogeneous LA-NSCLC T4 N0-3 M0 patients were age at diagnosis, ECOG-PS, stage and primary treatment, the last also being a significant prognostic indicator of EFS. Our findings point to the importance of appropriate staging and a multidisciplinary approach with modern imaging methods in this patient group. In those with T4 lesions, treatment selection and the effective use of curative potential should be the most important goal of clinical care. -
Background: Little is known about the cancer screening prevalence and correlates in older adults from different racial backgrounds. In the context of heightened efforts for prevention and early diagnosis, we collected information on screening for two major types of cancers: cervical and breast cancer in order to establish their prevalence estimates and correlates among older South African women who participated in the Study of Global Ageing and Adults Health (SAGE) in 2008. Materials and Methods: We conducted a national population-based cross-sectional study with a multi-stage stratified cluster sample of 3,840 individuals aged 50 years or older in South Africa in 2008. In this analysis, we only considered the female subsample of (n=2202). The measures used included socio-demographic characteristics, health variables, anthropometric and blood pressure measurements. Multivariable regression analysis was performed to assess the association of socio-demographic factors, health variables and cancer screening. Results: Overall, regarding cervical cancer screening, 24.3% ever had a Papanicolaou (PAP) smear test, and regarding breast cancer screening, 15.5% ever had a mammography. In multivariate logistic regression analysis, younger age, higher education, being from the White or Coloured population group, urban residence, greater wealth, and suffering from two or more chronic conditions were associated with cervical cancer screening, and higher education, being from the White or Indian/Asian population group, greater wealth, having a health insurance, and suffering from two or more chronic condtions were associated with breast cancer screening. Conclusions: Cancer screening coverage remains low among elderly women in South Africa in spite of the national guideline recommendations for regular screening in order to reduce the risk of dying from these cancers if not detected early. There is a need to improve accessibility and affordability of early cervical and breast cancer screening for all women to ensure effective prevention and management of cervical and breast cancer.
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He, Xiao-Qiong;Cichello, Simon Angelo;Duan, Jia-Li;Zhou, Jin 2477
Azoxymethane (AOM) is a potent genotoxic carcinogen which specifically induces colon cancer. Hyperlipidemia and diabetes have several influences on colon cancer development, with genetic and environmental exposure aspects. Here, we investigated plasma lipid and glucose concentrations in Kunming mice randomized into four groups; control (no AOM or oil exposure), AOM control, AOM + pork oil, and AOM + canola oil. Aberrant crypt foci (ACF), plasma cholesterol, plasma triglyceride, plasma glucose and organ weight were examined 32 weeks after AOM injection. Results revealed that AOM exposure significantly increased ACF number, plasma triglyceride and glucose level. Further, male mice displayed a much higher plasma triglyceride level than female mice in the AOM control group. Dietary fat significantly inhibited AOM-induced hypertriglyceridemia, and canola oil had stronger inhibitory effect than pork oil. AOM-induced hyperglycemia had no sex-difference and was not significantly modified by dietary fat. However, AOM itself not change plasma cholesterol level. AOM significantly increased liver and spleen weight in male mice, but decreased kidney weight in female mice. On the other hand, mice testis weight decreased when fed canola oil. AOM could induce colorectal carcinogenesis, hypertriglyceridemia and hyperglycemia in Kunming mice at the same time, with subsequent studies required to investigate their genome association. -
Epigenetic Regulation of Human Riboflavin Transporter 2(hRFT2) in Cervical Cancers from Uighur WomenMa, Jun-Qi;Kurban, Shajidai;Zhao, Jun-Da;Li, Qiao-Zhi;Hasimu, Ayshamgul 2485
In the present study, we studied the hypermethylation of the human riboflavin transporter 2 (hRFT2) gene and regulation of protein expression in biopsies from resected tissues from Uighur cervical squamous cell carcinoma (CSCC) patients and their neighboring normal tissues. hRFT2 gene promoter region methylation sequences were mapped in cervical cancer cell line SiHa by bisulfite-sequencing PCR and quantitative detection of methylated DNA from 30 pairs of Uighur's CSCCs and adjacent normal tissues by MassARRAY (Sequenom, San Diego, CA, USA) and hRFT2 protein expression was analyzed by immunohistochemistry. In SiHa, we identified 2 CG sites methylated from all of 12CpG sites of the hRFT2 gene. Analysis of the data from quantitative analysis of single CpG site methylation by Sequenom MassARRAY platform showed that the methylation level between two CpG sites (CpG 2 and CpG 3) from CpG 1~12 showed significant differences between CSCC and neighboring normal tissues. However, the methylation level of whole target CpG fragments demonstrated no significant variation between CSCC ($0.476{\pm}0.020$ ) and neighboring normal tissues ($0.401{\pm}0.019$ , p>0.05). There was a tendency for translocation the hRFT2 proteins from cytoplasm/membrane to nucleus in CSCC with increase in methylation of CpG 2 and CpG 3 in hRFT2gene promoter regions, which may relate to the genesis of CSCC. Our results suggested that epigenetic modifications are responsible for aberrant expression of the hRFT2 gene, and may help to understand mechanisms of cervical carcinogenesis. -
Ma, Chun-Hua;Jiang, Rong;Li, Jin-Duo;Wang, Bin;Sun, Li-Wei;Lv, Yuan 2491
Objective: To explore the mechanism and significance of tumor angiogenesis by observing changes of microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in residual tumor tissues after cryoablation. Materials and Methods: A total of 18 nude mice xenograft models with transplanted lung adenocarcinoma cell line A549 were established and randomly divided into 3 groups when the maximum diameter of tumor reached 1 cm: control, cisplatin (DDP) and cryoablation. The nude mice were sacrificed after 21-d cryoablation to obtain the tumor tissues. Then immunohistochemistry was applied to determine MVD and the expression of VEGF in tumor tissues. Results: The tumor volumes of control group, DDP group and cryoablation group were$1.48{\pm}0.14cm^3$ ,$1.03{\pm}0.12cm^3$ and$0.99{\pm}0.06cm^3$ respectively and the differences were significant (P<0.01), whereas MVD values were$21.1{\pm}0.86$ ,$24.7{\pm}0.72$ and$29.2{\pm}0.96$ (P<0.01) and the positive expression rates of VEGF were$36.2{\pm}1.72%$ ,$39.0{\pm}1.79%$ and$50.8{\pm}2.14%$ (P<0.01), respectively, showing that MVD was proportional to the positive expression of VEGF (r=0.928, P<0.01). Conclusions: Cryoablation can effectively inhibit tumor growth, but tumor angiogenesis significantly increases in residual tumors, with high expression of VEGF playing an important role in the residual tumor angiogenesis. -
Hajmanoochehri, Fatemeh;Mohammadi, Navid;Zohal, Mohammad Ali;Sodagar, Abolfazl;Ebtehaj, Mehdi 2495
Background: Lung cancer is one of the most commonly diagnosed cancers and the most frequent cause of cancer-related death worldwide. In Iran, it ranks second and third as the cancer-causing death in men and women, respectively. We carried out this study to find out the demographic, clinical, and histological characteristics and risk factors of lung cancer in a referral tertiary center in Iran. Materials and Methods: A retrospective study was conducted on cases of primary lung cancer based on the results of registered cancer reports of cytological and pathological specimens between March 2001 and March 2012. Demographic variables, clinical manifestations, histology and location of tumors were determined based on the data found in the medical records of each patient. Definite or probable etiologic factors were identified. Data analysis was performed with SPSS version 16 and a p-value${\leq}0.05$ was considered as significant. Results: A total of 203 patients, with a mean age of 65.7 years (SD=11.2), with primary lung cancer were identified, 81.3% being men. Of the total, 110 cases (54.2%) were living in urban areas. In 53.2% of cases, the site of tumor was on the right side and in 72.9% of cases the lesion was centrally located. The histological types of lung cancer were squamous cell carcinoma (SCC) in 107 cases (52.7%), adenocarcinoma (AC) in 30 cases (14.8%), and small cell carcinoma (SC) in 27 cases (13.3%). Significant correlations between the gender and residence, smoking, and the histological type and location (central or peripheral) of tumor were found. The percentage of smokers was 75.2% in men and 15.8% in women. Conclusions: Smoking was the most important risk factor and squamous cell carcinoma the most common histological type of lung cancer in our study. Male sex and being a smoker was associated with histological types of SCC while being nonsmoker had relationship with adenocarcinoma. -
Bozkurt, Oktay;Berk, Veli;Kaplan, Muhammed Ali;Cetin, Bulent;Ozaslan, Ersin;Karaca, Halit;Inanc, Mevlude;Duran, Ayse Ocak;Ozkan, Metin 2501
Background: Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. Materials and Methods: The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV${\geq}100$ fl was considered as macrocytosis. Capecitabine was given at a dose of$2500mg/m^2$ daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. Results: The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median${\Delta}MCV$ level (post-treatment values at sixth week - baseline) was 6.4. Whilst${\Delta}MCV$ was${\geq}6.4$ in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median${\Delta}MCV$ ${\geq}6.4$ and in 30 (75%) of 40 patients with${\Delta}MCV$ <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with${\Delta}MCV$ ${\geq}6.4$ and the group with${\Delta}MCV$ <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). Conclusions: The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not. -
Nandi, Moujhuri;Mahata, Anurupa;Mallick, Indranil;Achari, Rimpa;Chatterjee, Sanjoy 2505
Background: The standard radiotherapy (RT) fractionation practiced in India and worldwide is 50Gy in 25 fractions over 5 weeks to the chest wall or whole breast followed by tumour bed boost in case of breast conservation (BCS). A body of validated data exists regarding hypofractionation in breast cancer. We here report initial results for 135 patients treated at our center with the START-B type of fractionation. Materials and Methods: From May 2011 till July 2012, women with all stages of breast cancer (excluding metastatic), who had undergone BCS or mastectomy were planned for 40Gy in 15 fractions over 3weeks to chest wall/whole breast and supraclavicular fossa (where indicated) followed by tumour bed boost in BCS patients. Planning was done using Casebow's technique. The primary end point was to assess the acute toxicity and the cosmetic outcomes. Using cosmetic scales; patients were assessed during radiotherapy and at subsequent follow up visits with the radiation oncologist. Results: Of the 135 patients, 62 had undergone BCS and 73 mastectomy. Median age of the population was 52 years. Some 80% were T1&T2 tumours in BCS whereas most patients in mastectomy group were T3&T4 tumours (60%). 45% were node negative in BCS group whilst it was 23% in the mastectomy group. Average NPI scores were 3.9 and 4.9, respectively. Most frequently reported histopathology report was infiltrating ductal carcinoma (87%), grade III being most common (58%), and 69% were ER positive tumours, and 30% were Her 2 Neu positive. Triple negative tumours accounted for 13% and their mean age was young (43 yrs.) The maximum acute skin toxicity at the end of treatment was Grade 1 in 94% of the mastectomy grouppatients and 71% in BCS patients. Grade 2 toxicity was 6% in mast group and 23% in BCS group. Grade 3 was 6% in BCS group, no grade 3 toxicity in mastectomy patients and there was no grade 4 skin toxicity in any case. Post RT at 1 month; 39% of BCS patients had persisting Grade I skin reaction which was only 2% in mastectomy patients. At 3 months post RT, 18% patients had persisting hyperpigmentation. At 6 months 8% patients had persisting erythema in the BCS group only. Some 3% BCS and 8% mastectomy patients had lymph edema till the date of evaluation. Cosmetic outcome in BCS patients remained good to excellent 6 months post surgery and radiotherapy. 1 patient of BCS and 3 patients of mast had developed metastatic disease at the time of evaluation. Conclusions: Hypofractionated RT is well tolerated in Indian population with reduced acute skin toxicity and good cosmetic outcome. Regimens such as these should be encouraged in other centers to increase machine output time. The study is on-going to assess long term results. -
Liu, Lian-Ke;Wu, Heng-Fang;Guo, Zhi-Rui;Chen, Xiang-Jian;Yang, Di;Shu, Yong-Qian;Zhang, Ji-Nan 2511
Objective: Lung cancer is one of the malignant tumors with greatest morbidity and mortality around the world. The keys to targeted therapy are discovery of lung cancer biomarkers to facilitate improvement of survival and quality of life for the patients with lung cancer. Translationally controlled tumor protein (TCTP) is one of the most overexpressed proteins in human lung cancer cells by comparison to the normal cells, suggesting that it might be a good biomarker for lung cancer. Materials and Methods: In the present study, the targeted efficacy of dihydroartemisinin (DHA) on TCTP expression in the A549 lung cancer cell model was explored. Results and Conclusions: DHA could inhibit A549 lung cancer cell proliferation, and simultaneously up-regulate the expression of TCTP mRNA, but down-regulate its protein expression in A549 cells. In addition, it promoted TCTP protein secretion. Therefore, TCTP might be used as a potential biomarker and therapeutic target for non-small cell lung cancers. -
Gao, Yue;Liu, Yan;Liu, Ge-Li;Ran, Long-Ke;Zeng, Fan;Wu, Jia-Yan;Song, Fang-Zhou 2517
Background: Several recent studies have explored associations between pre-mir-218 polymorphism (rs11134527) and cancer risk. However, published data are still inconclusive. To obtain a more precise estimation of the relationship in the Chinese population, we carried out a meta-analysis for the first time. Materials and Methods: Through retrieval from the PubMed, Medline, Embase, Web of Science databases, China National Knowledge Infrastructure and the Chinese BioMedical Literature Database, a total of four studies were analyzed with 3,561 cases and 3,628 controls for SNP pre-mir-218 rs11134527. We calculated odds ratios (ORs) and 95% confidence intervals (95%CIs) to explore the strength of associations. Results: The results showed that the rs11134527 polymorphism was associated with decreased cancer risk in GG versus AA and GG versus AA+AG models tested ( GG vs AA: OR=0.82, 95%CI: 0.71-0.94; GG vs AA+AG: OR=0.84, 95%CI: 0.74-0.96), and significantly decreased cervical cancer risk was observed in GG versus AA and GG versus AA+AG models (GG vs AA: OR=0.79, 95%CI: 0.66-0.94; GG vs AA+AG: OR=0.80, 95%CI: 0.68-0.94). However, no significant association between the rs11134527polymorphism and hepatocellular carcinoma risk was observed in all comparison models tested (AG vs AA: OR=0.94, 95%CI: 0.79-1.11; GG vs AA: OR=0.88, 95%CI: 0.70-1.10; GG+AG vs AA: OR=0.92, 95%CI: 0.79-1.08; GG vs AA+AG: OR=0.91, 95%CI: 0.75-1.11). Conclusion: The findings suggest that pre-miR-218 rs11134527 polymorphism may have some relation to cancer development in Chinese. However, well-designed studies with larger sample size and more detailed data are needed to confirm these conclusions. -
Hasbek, Zekiye;Turgut, Bulent;Kilicli, Fatih;Altuntas, Emine Elif;Yucel, Birsen 2523
Background: Serum thyroglobulin detection plays an essential role during the follow-up of thyroid cancer patients treated with total/near total thyroidectomy and radioiodine ablation. The aim of this retrospective study was to evaluate the relationship between stimulated serum thyroglobulin (Tg) level at the time of high dose$^{131}I$ ablation and risk of recurrence, using a three-level classification in patients with differentiated thyroid cancer (DTC) according to the ATA guidelines. Also we investigated the relationship between postoperative stimulated Tg at the time of ablation and DxWBS results at 8-10 months thereafter. Materials and Methods: Patients with radioiodine accumulation were regarded as scan positive (scan+). If there was no relevant pathological radioiodine accumulation or minimal local accumulation in the thyroid bed region, this were regarded as scan negative (scan-) at the time of DxWBS. We classified patients in 3 groups as low, intermediate and high risk group for assessment of risk of recurrence according to the revised ATA guidelines. Also, we divided patients into 3 groups based on the stimulated serum Tg levels at the time of$^{131}I$ ablation therapy. Groups 1-3 consisted of patients who had Tg levels of${\leq}2ng/ml$ , 2-10 ng/ml, and${\geq}10ng/ml$ , respectively. Results: A total of 221 consecutive patients were included. In the high risk group according to the ATA guideline, while 45.5% of demonstrated Scan(+) Tg(+), 27.3% of patients demonstrated Scan(-) Tg(-); in the intermediate group, the figures were 2.3% and 90.0% while in the low risk group, they were 0.6% and 96.4%. In 9 of 11 patients with metastases (81.8%), stimulated serum Tg level at the time of radioiodine ablation therapy was over 10, however in 1 patient (9.1%) it was <2ng/mL and in one patient it was 2-10ng/mL (p=0.005). Aggressive subtypes of DTC were found in 8 of 221 patients and serum Tg levels were${\leq}2ng/ml$ in 4 of these 8. Conclusions: We conclude that TSH-stimulated serum thyroglobulin level at the time of ablation may not determine risk of recurrence. Therefore, DxWBS should be performed at 8-12 months after ablation therapy. -
Al-Darwish, Abdulaziz Ahmed;Al-Naim, Abdullah Fouad;Al-Mulhim, Khalid Saleh;Al-Otaibi, Nasser Khaled;Morsi, Mohammed Saad;Aleem, Ansari Mukhtar 2529
Background: Cervical cancer is the second most common cancer among females and also the most preventable. In the literature there is abundant evidence that awareness regarding cervical cancer and its prevention is low in the developing countries. Medical students are the future health professionals and can play an important role in increasing awareness among the general population. To assess the knowledge regarding symptoms, risk factors and prevention of cervical carcinoma among medical students in th Kingdom of Saudi Arabia, the present study was planned. Materials and Methods: This cross-sectional study was conducted using a self-administered questionnaire with students at the College of Medicine, King Faisal University, Al-Ahsa, KSA, from December 2012 to May 2013. Results: The responses of 188 students (males 111, females 77) in their second, third, fourth, and fifth years were recorded and used in the data analysis. The majority of the students were not aware of the early warning signs, symptoms and risk factors. On average, only 43.7% males and 56% of females were aware about the early signs and symptoms whereas 51.4% males and 57.8% females had knowledge about the risk factors of cervical cancers. Some 55% males and 46.8% females were unable to select the correct answer regarding human papilloma virus (HPV) infection as the cause of cervical cancer. Majority of the students (67%) were not aware about the availability of vaccine against HPV. Conclusions: Lack of knowledge regarding early signs and symptoms, risk factors and prevention of cervical cancer was observed in the present study. -
Yang, Xiao-Fei;Li, Guo-Xin;Luo, Guang-Heng;Zhong, Shi-Zhen;Ding, Zi-Hai 2533
Aim: To take a deeper insight into the relationship between the root of the inferior mesenteric artery (IMA) and the autonomic nerve plexuses around it by cadaveric anatomy and explore anatomical evidence of autonomic nerve preservation in high ligation of the IMA in laparoscopic surgery for colorectal cancer. Methods: Anatomical dissection was performed on 11 formalin-fixed cadavers and 12 fresh cadavers. Anatomical evidence-based autonomic nerve preservation in high ligation of the IMA was performed in 22 laparoscopic curative resections of colorectal cancer. Results: As the upward continuation of the presacral nerves, the bilateral trunks of SHP had close but different relationships with the root of the IMA. The right trunk of SHP ran relatively far away from the root of IMA. When the apical lymph nodes were dissected close to the root of the IMA along the fascia space in front of the anterior renal fascia, the right trunk of SHP could be kept in suit under the anterior renal fascia. The left descending branches to SHP constituted a natural and constant anatomical landmark of the relationship between the root of IMA and the left autonomic nerves. Proximal to this, the left autonomic nerves surrounded the root of the IMA. Distally, the left trunk of the SHP departed from the root of IMA under the anterior renal fascia. When high ligation of the IMA was performed distal to it, the left trunk of SHP could be preserved. The distance between the left descending branches to SHP and the origin of IMA varied widely from 1.3 cm to 2.3 cm. Conclusions: The divergences of the bilateral autonomic nerve preservation around the root of the IMA may contribute to provide anatomical evidence for more precise evaluation of the optimal position of high ligation of the IMA in the future. -
Wang, Li-Ming;An, Song-Lin;Wu, Jian-Xiong 2541
Background: Primary hepatic neuroendocrine carcinoma (PHNEC) is rarer than extrahepatic gastrointestinal neuroendocrine carcinoma (NEC). It is difficult to make a correct diagnosis and poses a challenge for management. Materials and Methods: Ten PHNEC patients were admitted to our hospital from June 2006 to June 2011. Laboratory tests and imaging scans were performed for diagnosis and exclusion of extrahepatic NEC. All patients were AFP - and CA199-. Seven patients had solid tumors with cystic changes on ultrasonography, CT and/or MRI. For the initial treatment, four patients received combined-therapy and six monotherapy. Considering overall treatment, six patients received combined-therapy and four patients monotherapy. Staging criteria of primary hepatocellular carcinoma (PHC, AJCC 7th edition) were used to differentiate the stage of all patients: 3 patients were stage I, 2 stageII, 4 patients stageIII and 1 stageIV. All patients were followed up and clinical data were gathered. Results: The median follow-up duration was 38.5 months. The 1-year, 2-year, 3-year and 6-year disease-free survival was 80.0%, 46.2% and 46.2% and 0% respectively. The overall survival rates were 100%, 67.1%, 67.1% and 33.6% respectively. Patients in early-stages (I/II) had similar disease-free and overall survival as those in advanced-stages (III/IV). Patients with monotherapy had significant shorter disease-free and overall survival than the patients with combination-therapy. Conclusions: PHNEC has a unique specificity during its occurrence and development. The staging criteria of PHC might not be suitable for the PHENT. More convenient and effective features need to be found in imaging and laboratory detection. Surgical resection, TACE, chemotherapy and radiofrequency ablation should be performed in combination and actively for patients with PHNEC or recurrence to get the best effectiveness; they might extend the disease-free and overall survival. -
Sait, Khalid Hussain;Anfinan, Nisrin Mohammad;Eldeek, Basem;Al-Ahmadi, Jawher;Al-Attas, Maha;Sait, Hesham Khalid;Basalamah, Hussain Abdullah;Al-Ama, Nabeel;El Sayed, Mohamed Ezzat 2547
Background: To evaluate the perception of cancer patients toward treatment services and influencing factors and to inquire about the use of complementary alternative medicine (CAM). Materials and Methods: Information was obtained through pre-tested structured questionnaires completed by cancer patients during treatment at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Results: Of 242 patients, 137 (64.6%) accepted to enter this study. Most were Saudi (n=93, 68%), female (n=80, 58%), educated at university (n=71, 52%), married (n=97, 72%) and with breast cancer (n=36, 26%). One-hundred (73%) patients were satisfied with the services provided; 61% were Saudi. Ninety-four (68%) respondents were satisfied with the explanation of their cancer. Twenty-eight (21.6%) patients received CAM, of them 54.0% received herbal followed by rakia (21.0%), nutritional supplements/vitamins (7.0%) and Zamam water (18.0%), with significant differences among them (p =0.004). Seven (5%) patients believed this therapy could be used alone; 34 (25%) patients believed it could be used with other treatments, regardless of whether they themselves used this therapy. Fifty-three (53%) satisfied patients felt they received enough support; 31 (58%) patients received support from family and friends; 22 (41.6%) patients received support from the health-care team. Patients who received information about their disease from their physicians and those who felt they had enough support were more satisfied. The patients who took alternative treatment were older age, mostly female and highly educated but values did not reach significance. Conclusions: We stress enhancing the educational and supportive aspects of cancer-patient services to improve their treatment satisfaction and emphasize the need for increasing the educational and awareness programs offered to these patients. -
Ozbek, Emin;Otunctemur, Alper;Dursun, Murat;Sahin, Suleyman;Besiroglu, Huseyin;Koklu, Ismail;Erkoc, Mustafa;Danis, Eyyup;Bozkurt, Muammer 2555
Pirpose: The aim of this study to analyze the association between history of diabetes mellitus (DM) with risk of prostate cancer (PCa) and cancer grade among men undergoing radical prostatectomy for PCa. Materials and Methods: 50 patients with DM and 50 patients without DM who undervent radical prostatectomy (RP) were included in the study. Age at biopsy, height, weight, digital rectal examination (DRE), pre-biopsy PSA levels, prostate volume, histopathologic diagnosis after surgery and gleason scores were collected data from all patients. Histologic material obtained at biopsy was given a Gleason score; tumours with a Gleason score${\geq}7$ were considered high grade and <7 were considered low grade. Results: The mean age at the time of biopsy was 63.7 in patients with DM and 61.6 in patients without DM. Diabetic men had significantly lower PSA levels (p=0.01). Mean PSA level$7.04{\pm}2.85$ in patients with DM and$8.7{\pm}2.86$ in patients without DM, respectively. Also, diabetic men had higher RP tumor grade than men without DM (p=0.04). We found that HbA1c levels were higher in patients who have high grade prostate cancer (p<0.05). Conclusions: Diabetic men undergoing RP have lower PSA levels and have significantly higher grade PCa. We must be careful for screening PCa in patients with DM. Although the patients had lower PSA levels, they might have high grade disease. -
Purpose: We investigated the expression of epithelial
$Ca^{2+}$ channel transient receptor potential vanilloid (TRPV) 5 and 6 in non-small-cell lung cancer (NSCLC) and assessed their prognostic role in patients after surgical resection. Materials and Methods: From January 2008 to January 2009, 145 patients who had undergone surgical resection of NSCLCs were enrolled in the study. Patient clinical characteristics were retrospectively reviewed. Fresh tumor samples as well as peritumor tissues were analyzed for TRPV5/6 expression using immune-histochemistry (IHC) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Patients were grouped based on their TRPV5 and TRPV6 levels in the tumor tissues, followed up after surgery, and statistically analyzed to examine the prognostic roles of TRPV5 and TRPV6 on patients' survival after surgical resection of NSCLCs. Results: Using IHC, among the 145 patients who had undergone surgical resection of NSCLCs, strong protein expression (grade${\geq}2$ ) of TRPV5 and TRPV6 was observed in a lower percentage of primary tumor tissues than in non-tumor tissues of same patients. Similar findigns were obtained with the RT-PCR test for mRNA levels. Decreased overall mRNA levels of TRPV5 and TRPV6 were associated with a worse overall survival rate (p=0.004 and p=0.003 respectively) and shorter recurrence-free survival (p<0.001 and p<0.001 respectively). The combining effect of TRPV5 and TRPV6 on survival was further investigated using multivariate analysis. The results showed that a combination of low expression of TRPV5 and TRPV6 could be an independent predictor of poor recurrence-free survival (p=0.002). Conclusions: Decreased expression of TRPV5/6 in tumor tissues was observed in NSCLC patients and was associated with shorter median survival time after surgical resection. Combined expression of TRPV5 and TRPV6 in tumor tissues demonstrated promising prognostic value in NSCLC patients. -
Lv, Jun;Yu, Ya-Qun;Li, Shu-Qun;Luo, Liang;Wang, Qian 2565
H19 is an imprinted oncofetal gene, and loss of imprinting at the H19 locus results in over-expression of H19 in cancers. Aflatoxin B1(AFB1) is regarded as one of the most dangerous carcinogens. Exposure to AFB1 would most easily increase susceptibility to diseases such as hepatocellular carcinoma(HCC) but any possible relationship between AFB1 and H19 is not clear. In present study, we found that AFB1 could up-regulate the expression of H19 and promote cell growth and invasion by hepatocellular carcinoma HepG2 cells. Knocking down H19 RNA co ld reverse the effects of AFB1 on cell growth and invasion. In addition, AFB1 induced the expression of E2F1 and its knock-down could down-regulate H19 expression and suppress cell growth and invasion in hepatocellular carcinoma HepG2 cells. Furthermore, E2F1 over-expression could up-regulate H19 expression and promote cell growth and invasion, with binding to the H19 promoter being demonstrated by chromatin immunoprecipitation assays (ChIP). In summary, our results suggested that aflatoxin B1could promote cell growth and invasion in hepatocellular carcinoma HepG2 cells through actions on H19 and E2F1. -
Background: Published studies on the association between the exonuclease 1 (EXO1) Glu589Lys polymorphism and cancer susceptibility have yielded conflicting results. Thus, a meta-analysis of published studies was performed to assess the possible association. Materials and Methods: All eligible case-control studies published up to January 2013 on the association between the EXO1 Glu589Lys polymorphism and cancer susceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Either fixed-effect or random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs) using the Comprehensive Meta-Analysis software version 2.2. Results: A total of 4,391 cancer cases and 4,339 controls from 10 studies were included. Overall, no significant association between the EXO1 Glu589Lys polymorphism and cancer susceptibility was observed in either genetic model. However; in subgroup analyses by cancer type, a significant association between EXO1 Glu589Lys and lung cancer risk was found (Lys vs Glu: OR=1.23, 95%CI=1.07-1.41,
$p_{heterogeneity}$ =0.05). Further, subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (Lys vs Glu: OR=1.42, 95%CI=1.30-1.55,$p_{heterogeneity}$ =0.07; Lys/Lys vs Glu/Glu: OR=1.93, 95%CI=1.20-3.12,$p_{heterogeneity}$ =0.01; Lys/Lys+Glu/Lys vs Glu/Glu: OR=1.52, 95%CI=1.37-1.68,$p_{heterogeneity}$ =0.42; Lys/Lys vs Glu/Lys+Glu/Glu: OR=1.68, 95%CI=1.07-2.65,$p_{heterogeneity}$ =0.02). However, significant association was absent in Caucasians. Conclusions: This meta-analysis suggests, for the first time, that the EXO1 Glu589Lys polymorphism is not associated with overall cancer susceptibility, although marginal associations were found for lung cancer and Asian subgroups. Additional well-designed studies with larger sample size focusing on different ethnicities and cancer types are needed to confirm these findings. -
Bhatti, Abu Bakar Hafeez;Khan, Amina Iqbal;Siddiqui, Neelam;Muzaffar, Nargis;Syed, Aamir Ali;Shah, Mazhar Ali;Jamshed, Arif 2577
Background: Triple negative breast cancer is associated with aggressive behavior and high risk of local and regional failure. Aggressive surgical intervention is considered suitable. This makes role of breast conserving therapy (BCT) debatable in these patients. The objective of this study was to compare outcome of BCT for triple negative versus non-triple negative breast cancer. Materials and Methods: Medical records of patients who underwent breast conserving therapy from 1999 to 2009 at Shaukat Khanum Cancer Hospital and had complete receptor status information were extracted. Patients were divided into triple negative breast cancer (TNBC) and non-TNBC. Patient characteristics, medical treatment modalities and adverse events were compared. Expected five year locoregional recurrence free, disease free and overall survival was calculated. The Cox proportional hazard model was used to identify independent predictors of outcome. Results: A total of 194 patients with TNBC and 443 with non-TNBC were compared. Significant difference was present for age at presentation (p<0.0001), family history (p=0.005), grade (p<0.0001) and use of hormonal therapy (p<0.0001). The number of locoregional failures, distant failures and mortalities were not significantly different. No significant difference was present in 5 year locoregional recurrence free (96% vs 92%, p=0.3), disease free (75% vs 74%, p=0.7) and overall survival (78% vs 83%, p=0.2). On multivariate analysis, tumor size, nodal involvement and hormonal treatment were independent predictors of negative events. Conclusions: Breast conserving therapy has comparable outcomes for triple negative and non-triple negative breast cancers. -
Li, Yang;Ma, Wen-Jun;Qi, Bao-Kun;Rokayya, Sami;Li, Dan;Wang, Jing;Feng, Hong-Xia;Sui, Xiao-Nan;Jiang, Lian-Zhou 2583
Background: Soybean oil may protect against cancer of the breast and prostate. It may also exert beneficial influence in combination with other oils. Here, blends (20%, v/v) of sea buckthorn oil (SEBO), camellia oil (CAO), rice bran oil (RBO), sesame oil (SEO) and peanut oil (PEO) with soybean oil (SBO) were formulated. Materials and Methods: Oxidative stability (OS) and radical scavenging activity (RSA) of SBO and blends stored under oxidative conditions ($60^{\circ}C$ ) for 24 days were studied. By blending with different kinds oils, levels of polyunsaturated fatty acids (PUFA) decreased, while monounsaturated fatty acid (MUFA) content increased. Progression of oxidation was followed by measuring peroxide value (PV), p-anisidine (PAV), conjugated dienes (CD) and conjugated trienes (CT). Results: Inverse relationships were noted between PV and OS at termination of storage. Levels of CD and CT in SBO, and blends, increased with increase in time. The impact of SEO as additives on SBO oxidation was the strongest followed by RBO, CAO, SEBO and PNO. Conclusions: Oxidative stability of oil blends was better than SBO, most likely as a consequence of changes in fatty acids and tocopherols' profile, and minor bioactive lipids found in selected oils. The results suggest that these oil blends could contribute as sources of important antioxidant related to the prevention of chronic diseases associated to oxidative stress, such as in cancer and coronary artery disease. -
Xie, Ke-Jie;He, Hong-Er;Sun, Ai-Jing;Liu, Xi-Bo;Sun, Li-Ping;Dong, Xue-Jun 2591
Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation group l (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lung cancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancer paraffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used to determine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled 111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%, 36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with the survival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negative cancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positive alone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter than those with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1 negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy. -
Amin, Tarek Tawfik;Al-Hammam, Abudllah Mohammed;AlMulhim, Nasser Abdullah;Al-Hayan, Mohammed Ibrahim;Al-Mulhim, Mona Mohammed;Al-Mosabeh, Modhahir Jawad;Al-Subaie, Mohammed Ali;Al-Hmmad, Qassem Ahmed;Al-Omran, Ahmed Adi 2597
Background: There is a scarcity of information about the proportion of the adult Saudi population that meet the recommended guidelines of physical activity (PA) to reduce cancer risk. Moreover, their awareness about the role of PA in cancer prevention is unclear. Objectives: This cross-sectional study aimed at estimating the proportion of adult Saudis meeting the PA guidelines, specifically those recommended by American Cancer Society (ACS) for cancer prevention, and to assess the public awareness about the role of PA in cancer prevention. Materials and Methods: Using a multistage sampling method, 2,127 adult Saudis of both genders were recruited from 6 urban and 4 rural primary health care centers in Al Hassa, Saudi Arabia. Participants were personally interviewed to gather information about their sociodemographic characteristics, searching activity about PA and cancer, and the time spent in leisure time PA (moderate and vigorous)/week using the Global Physical Activity Questionnaire with show cards. Finally, items about the role of PA in cancer risk reduction were inquired. Results: Of the included participants, 11.6% met the recommendations for cancer prevention (${\geq}45$ minutes of moderate-vigorous PA activity/${\geq}5$ days/week or 225 minutes/week). Multivariate regression showed that being male (AOR=1.49, CI=1.09-2.06), <20 years of age (AOR=3.11, CI=2.03-4.76), and unemployed (AOR=2.22, CI=1.57-3.18) were significant predictors for meeting PA recommendations for cancer prevention. Only 11.4% of the sample indicated correctly the frequency and duration of PA required for an average adult to be physically active and while >70% of them indicated the role of PA in prevention of hypertension, coronary heart disease and lowering elevated blood cholesterol, only 18.6% and 21.7% correctly mentioned the role of PA in reducing colon and breast cancer risk, respectively. Poor knowledge was found among those with less than college education and aged${\geq}50$ years. The level of knowledge was significantly positively correlated with total leisure time PA of the participants. Conclusions: A minority of adult Saudis in Al Hassa was aware about the role of PA in cancer prevention and engaged in sufficient LTPA for cancer risk reduction benefits, highlighting the need for public health actions to include policies and programs that address factors deterring their participation in LTPA and increasing their awareness with remedies to manage the prevalent misconceptions. -
Sano, Hiroshi;Goto, Rei;Hamashima, Chisato 2607
Background: Cancer screening rates in Japan are much lower than those in Western countries. This study evaluated the relationship between cancer screening rates and strategies used to improve screening rates, and determined which strategy is the most effective. Materials and Methods: All municipalities are responsible for conducting gastric, lung, colorectal, cervical, and breast cancer screenings in Japan. Of the 1,746 municipalities in total, 92-99% were included in the analyses for each cancer screening. Using national data in 2009, the correlations between cancer screening rates and strategies for improving screening rates of all municipalities, both large (populations of over 30,000) and small (populations of under 30,000), were determined. The strategies used were as follows: sending personal invitation letters, personal visits by community health workers, use of a clinical setting for screening, and free screening. Results: Of all four strategies used to improve cancer screening rates, sending personal invitation letters had the highest correlations with all screening rates, with the exception of breast cancer screening. The partial correlation coefficients linking this strategy with the screening rates in all municipalities were 0.28, 0.32, 0.30, and 0.26 for gastric, lung, colorectal, and cervical cancer screening, respectively. In large municipalities, the correlations between the number of examinees in a clinical setting and the screening rates were also relatively high, particularly for cervical cancer screening (r=0.41). Conclusions: Sending personal invitation letters appears to be particularly effective in improving cancer screening rates in all municipalities. All municipalities should implement a system that sends personal invitation letters for cancer screening. In large municipalities, increasing the availability of screening in a clinical setting is also effective in improving cancer screening rates. -
Guo, Cun-Li;Yang, Xiu-Hua;Cheng, Wen;Xu, Yi;Li, Jie-Bing;Sun, Yi-Xin;Bi, Yu-Mei;Zhang, Lei;Wang, Qiu-Cheng 2613
Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that$Foxp3^+T$ cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis,$CD8^+T$ cells and$Foxp3^+T$ cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in$CD8^+T$ lymphocytes and$Foxp3^+T$ cells in patients with HCC. Methods:$CD8^+T$ cells and$CD3^+Foxp3^+T$ cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in$CD8^+T$ cells and FasL in$CD3^+Foxp3^+T$ cells were evaluated. Serum TGF-${\beta}1$ levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in$CD3^+Foxp3^+T$ cells was then evaluated. Results: The frequency of$CD8^+T$ cells binding annexin V and Fas expression in$CD8^+T$ cells, were all higher in HCC patients than normal controls and the proportion of apoptotic$CD8^+T$ cells correlated with their Fas expression. Serum TGF-${\beta}1$ levels correlated inversely with$CD3^+Foxp3^+T$ cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of$CD8^+T$ cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in$Fas^+CD8^+T$ cells in vitro are required. -
Yan, Feng;Bai, Li-Ping;Gao, Hua;Zhu, Chang-Ming;Lin, Li;Kang, Xiang-Peng 2619
Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein. -
Kaba, Mehmet;Pirincci, Necip;Yuksel, Mehmet Bilgehan;Gecit, Ilhan;Gunes, Mustafa;Ozveren, Huseyin;Eren, Huseyin;Demir, Halit 2625
Background: Trace elements are major components of biological structures; however, excessive levels of these elements can be toxic. Materials and Methods: In the present study, serum levels of trace elements were measured in 30 patients with newly diagnosed as prostate cancer and 32 healthy volunteer by using furnace atomic absorption spectrophotometry. Results: It was found that there was an increase in serum levels of Co, Cu, Mg and Pb (p<0.05), whereas a decrease in serum levels of Fe, Mn, and Zn levels in patients with prostate cancer (p<0.05). Conclusions: These changes may be important in the pathogenesis of prostate cancers; however, further prospective studies are needed to identify relationships between prostate cancer and trace elements. -
Pouladi, Nasser;Kouhsari, Shideh Montasser;Feizi, Mohammadali Hosseinpour;Dehghan, Roghayeh;Azarfam, Parvin;Farajzadeh, Davoud 2631
Background: p53 gene is a well-known tumor suppressor gene that has several polymorphisms in both its exons and introns. It has been suggested that intron 3 16 bp duplication polymorphism may affect the gene function resulting in reduction or suppression of p53 anti tumor activity. In most case control studies a duplicated allele has been noticeably more frequent in cases rather than controls but there are also conflicting results. The aim of this study was to assess the association of intron 3 16 bp duplication polymorphism of p53 with breast cancer risk among Iranian-Azeri population. We also analyzed the clinicopathological information of patients as an epidemiological description of breast cancer in the north-west of Iran. Materials and Methods: This case-control study was performed on 221 breast cancer patients and 170 controls. Genomic DNA was extracted from peripheral blood samples and tumor tissues. p53 PIN3 genotype was determined using electrophoresis of PCR products on 8% non-denaturing polyacrylamide gels and silver staining. Results: In the control and case groups, respectively, 62.9% and 61.1% had no 16 bp insertion (A1A1 genotype), 7.1% and 7.7% had insertion in both p53 alleles (A2A2) and 30% and 31.2% were heterozygous (A1A2). There was no significant difference between genotype frequencies as well as allelic frequencies in two case and control groups. Conclusions: According to the result of the present study, the intron 3 16 bp duplication polymorphism of p53 could not be assessed as a marker of risk factor for predisposition to breast cancer in Azeri population. However, a high frequency of A2 allele (22.1%) in our population suggested that intron 3 16 bp duplication polymorphism may be a valuable marker for study in other cancers with well designed large groups. -
Qin, Jie-Jie;Wang, Xiao-Rui;Wang, Peng;Ren, Peng-Fei;Shi, Jian-Xiang;Zhang, Hong-Fei;Xia, Jun-Fen;Wang, Kai-Juan;Song, Chun-Hua;Dai, Li-Ping;Zhang, Jian-Ying 2635
Sera of cancer patients may contain antibodies that react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). The present study aimed to determine whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach in esophageal cancer detection and diagnosis. Our mini-array of multiple TAAs consisted of eleven antigens, p53, pl6, Impl, CyclinB1, C-myc, RalA, p62, Survivin, Koc, CyclinD1 and CyclinE full-length recombinant proteins. Enzyme-linked immunosorbent assays (ELISA) were used to detect autoantibodies against eleven selected TAAs in 174 sera from patients with esophageal cancer, as well as 242 sera from normal individuals. In addition, positive results of ELISA were confirmed by Western blotting. In a parallel screening trial, with the successive addition of antigen to a final total of eleven TAAs, there was a stepwise increase in positive antibody reactions. The eleven TAAs were the best parallel combination, and the sensitivity and specificity in diagnosing esophageal cancer was 75.3% and 81.0%, respectively. The positive and negative predictive values were 74.0% and 82.0%, respectively, indicating that the parallel assay of eleven TAAs raised the diagnostic precision significantly. In addition, the levels of antibodies to seven antigens, comprising p53, Impl, C-myc, RalA, p62, Survivin, and CyclinD1, were significantly different in various stages of esophageal cancer, which showed that autoantibodies may be involved in the pathogenesis and progression of esophageal cancer. All in all, this study further supports our previous hypothesis that a combination of antibodies might acquire higher sensitivity for the diagnosis of certain types of cancer. A customized mini-array of multiple carefully-selected TAAs is able to enhance autoantibody detection in the immunodiagnosis of esophageal cancer and autoantibodies to TAAs might be reference indicators of clinical stage. -
Li, Ming-Yi;Liu, Jin-Quan;Chen, Dong-Ping;Qi, Bin;Liang, Yu-Ying;Yin, Wen-Jing 2641
Background: To evaluate efficacy and side effects of glycididazole sodium (CMNa) combined with chemotherapy (cisplatin plus 5-FU/folic acid, PLF) and radiotherapy in treating patients with locally advanced nasopharyngeal carcinoma. Materials and Methods: Patients with III~IV stage nasopharyngeal carcinoma (NPC),were randomly divided into treatment group (46 patients) and control group (45 patients). Both groups received radiotherapy concomitant with PLF chemotherapy. The treatment group at the same time cwas given CMNa ($800mg/m^2$ before radiotherapy), by l h intravenous drip, three times a week. Results: When the dose of radiation was over 60 Gy, complete response rates of nasopharyngeal tumor and lymph node metastases in treatment group were significantly higher than in the control group (93.5% vs 77.8%; 89.1% vs 93.5%, p<0.05). Three months after radiotherapy, complete response rate of nasopharynx cancer and lymph node metastases in treatment group was both 97.8%, again higher than in the control group (84.4% and 82.2%) (p<0.05). In the treatment group, 1, 3, 5 year disease-free survival rates were 95.7%, 86.7% and 54.5%; and in control group, the corresponding disease-free survival rates were 93.3%, 66.2% and 38.6%, respectively, the difference being statistically significant (log-rank =5.887, p=0.015). One, 3, 5 year overall survival rates in two groups of patients were 97.8%, 93.5%, 70.4% and 95.5%, 88.07%, 48.4%, respectively, again with a statistically significant difference (log-rank=6.470, p=0.011). Acute toxicity and long-term radiotherapy related toxicity in the two groups did not differ (p>0.05). Conclusions: Glycididazole sodium could improve curative effects without increasing adverse reactions when treating paitents with locally advanced nasopharyngeal carcinoma. -
Ozdemir, Yavuz;Akin, Mehmet Levhi;Sucullu, Ilker;Balta, Ahmet Ziya;Yucel, Ergun 2647
Background: Colorectal cancers(CRC) are the third most common cancer in the western world, with surgery preferred for management of non-metastatic disease and post surgical treatment usually arranged according to the TNM staging system. However, there is still prognostic variation between patients who have the same stage. It is increasingly recognized that variations within disease course and clinical outcome in colorectal cancer patients are influenced by not only oncological characteristics of the tumor itself but also host response factors. Recent studies have shown correlation between the inflammatory response and clinical outcomes in various cancers. The neutrophil/lymphocyte ratio (NLR) has been described as a marker for immune response to various stimuli including cancer. Material-Methods: Two hundred eighty-one CRC patients were included in our retrospective analysis, separated into two groups according to a cut-off value for the NLR. Patient data including age, gender, vertical penetration, anatomic location, and differentiation of the tumor, TNM stage, survival rate, and disease-free survival were analyzed for correlations with the NLR. Results: Using ROC curve analysis, we determined a cut-off value of 2.2 for NLR to be best to discriminate between patient survival in the whole group. In univariate analysis, high pretreatment NLR (p=0.001, 95%CI 1.483-4.846), pathologic nodal stage (p<0.001, 95%CI 1.082-3.289) and advanced pathologic TNM stage (p<0.001, 95%CI 1.462-4.213) were predictive of shorter survival. In multivariate analysis, advanced pathologic TNM stage (p=0.001, 95%CI 1.303-26.542) and high pretreatment NLR (p=0.005, 95%CI 1.713-6.378) remained independently associated with poor survival. Conclusions: High pre-treatment NLR is a significant independent predictor of shorter survival in patients with colorectal cancer. This parameter is a simple, easily accessible laboratory value for identifying patients with poorer prognosis. -
Kemal, Yasemin;Yucel, Idris;Ekiz, Kubilay;Demirag, Guzin;Yilmaz, Bahiddin;Teker, Fatih;Ozdemir, Meltem 2651
Background: Lung cancer (LC) is still the primary cause of cancer deaths worldwide, and late diagnosis is a major obstacle to improving lung cancer outcomes. Recently, elevated preoperative or pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) detected in peripheral blood were identified as independent prognostic factors associated with poor survival with various cancers, including colon cancer, esophageal cancer, gastric cancer and breast cancer. Objective: The aim of this study was to examine whether MPV, NLR and PLR could be useful inflammatory markers to differentiate lung cancer patients from healthy controls. An investigation was also made of the relationship between these markers and other prognostic factors and histopathological subgroups. Materials and Methods: Retrospectively eighty-one lung cancer patients and 81 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. The preoperative or pretreatment blood count data was obtained from the recorded computerized database. Results: NLR and PLR values were significantly higher in the LC patients compared to the healthy subjects.( NLR: 4.42 vs 2.45 p=0.001, PLR: 245.1 vs 148.2 p=0.002) MPV values were similar in both groups (7.7 vs 7.8). No statistically significant relationship was determined between these markers (MPV, NLR and PLR) and histopathological subgroups and TNM stages. Conclusions: NLR and PLR can be useful biomarkers in LC patients before treatment. Larger prospective studies are required to confirm these findings. -
Fang, Kun-Peng;Zhang, Jian-Lin;Ren, Yan-Hong;Qian, Ye-Ben 2655
Background: Talin-1 is a cytoskeleton protein that participates in cell migration and plays a role in tumor formation, migration, and metastasis in different types of cancer. Chinese investigators have observed that the levels of Talin-1 protein and mRNA expression in HCC tissues are significantly lower than in the adjacent non-cancerous tissue. However, Japanese investigators have reported that Talin-1 is upregulated in HCC. Tln2 as homologous gene of Tln-1, which encodes a very similar protein, but the role of Talin-2 is very little known in primary liver cancer (PLC). We investigated whether the expression of Talin-1 in PLC may be associated with the histological subtype as well as the role of Talin-1 in tumor cell invasion and migration using human hepatocellular carcinoma cell lines. Materials and Methods: We measured the mRNA expression levels of Talin-1 and Talin-2 in five human liver cancer cell lines and normal human liver cell ($LO_2$ cell line) by real-time PCR and the protein expression levels of Talin-1 by Western blot. Migration and invasion of the cells were assessed using transwell assays and cell scratch experiments, respectively, and proliferation was assessed by soft AGAR colony formation. Results: Talin-1 and Talin-2 expression differed significantly between the five human liver cancer cell lines and$LO_2$ cell line (p<0.05). Compared with the$LO_2$ cell line, the invasion and migration capabilities of the five cancer cell lines differed significantly (p<0.05). Similarly, the colony-forming ability differed (p<0.05). Conclusions: High levels of Talin-1 expression are correlated with reduced invasion and migration as well as decreased malignancy in human liver cancer cell lines; the suppression of Talin-1 promotes invasion and migration. In addition, Talin-2 may be correlated with invasion and migration in human hepatocellular carcinoma. -
Chen, Xiao-Lin;Liao, Yong-Qiang;Liu, Jian-Rong 2663
Background: Single nucleotide polymorphisms of C-reactive protein (CRP) have been shown to be related to circulating CRP level, risk and prognosis in cancer patients. However, accumulating evidence of rs1800947 involvement in risk of cancer is inconsistent. Thus, a meta-analysis was performed to obtain a more precise relationship. Materials and Methods: The pooled odds ratio (OR) and its 95% confidence interval were assessed in 10 eligible articles with 12 studies containing 5,601 cancer cases and 8,669 cancer-free controls. Results: No significant association was observed overall and in subgroups in comparison of genotype GC vs GG ($P_H$ =0.847, OR=0.939, 95%CI=0.810-1.087), GC/CC vs GG ($P_H$ =0.941, OR=1.021, 95%CI=0.901-1.157) and allele C vs G ($P_H$ =0.933, OR=1.026, 95%CI=0.909-1.159). However, statistically significance was evident in comparison of genotype CC vs GG in cancer risk ($P_H$ =0.586, OR=2.854, 95%CI= 1.413-5.763), especially in colorectal cancer ($P_H$ =0.481, OR=4.527, 95%CI= 1.664- 12.315). Conclusions: Genotype CC of rs1800947 in the CRP gene is strongly associated with increased cancer risk, particularly in colorectal cancer. -
Albasri, Abdulkader;Yosef, Hala;Hussainy, Akbar;Bukhari, Saud;Alhujaily, Ahmed 2669
Aim: To evaluate the predominant colorectal polyps in the Almadinah region of Saudi Arabia. Materials and Methods: In this iretrospective study, we analyzed pathology reports of colonoscopies performed in King Fahad Hospital, Madinah, Saudi Arabia during the period 2006 to 2013. Data based on patient age, gender, size, site and type of polyps and the degree of dysplasia were analyzed by software SPSS 17 and compared with other published studies from different geographic regions of the world. Results: During these years, 224 patients had colonic polyps, of whom 149 (66.5%) were men and 75 (33.5%) were women. The most common types of polyps were adenomatous (166), followed by hyperplastic polyps (24), juvenile (18), inflammatory (13), lipomatous (2) and one patient with Peutz-Jegher polyps. Tubulovillous adenoma was the commonest adenomatous polyp (102), followed by tubular (41) and villous (23) types. The sigmoid colon was the most commonly involved region (36.6%). Dysplasia was significantly associated with female patients who had large size tubulovillous polyps located in the left colon. Conclusions: The type and distribution of colorectal polyps in Saudi Arabia is very similar to Western countries. Patient gender, and size, histological type and location of polyps are closely related to dysplastic change in colonic polyps. -
Xhaard, Constance;Ren, Yan;Clero, Enora;Maillard, Stephane;Brindel, Pauline;Rachedi, Frederique;Boissin, Jean-Louis;Sebbag, Joseph;Shan, Larrys;Bost-Bezeaud, Frederique;Petitdidier, Patrick;Drozdovitch, Vladimir;Doyon, Francoise;Rubino, Carole;de Vathaire, Florent 2675
Background: To investigate differentiated thyroid cancer risk factors in natives of French Polynesia is of interest because of the very high incidence of this cancer in the archipelago. Materials and Methods: To assess the role of various potential risk factors of thyroid cancer in the natives of French Polynesia we performed a case-control study. The study included almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) and 373 French Polynesian control individuals from the general population without cancer. Results: Thyroid radiation dose received from nuclear fallout before the age of 15, a personal history of neck or/and head medical irradiation, obesity, tallness, large number of children, an artificial menopause, a familial history of thyroid cancer, a low dietary iodine intake, and having a spring as the main source of drinking water were found to be significant risk factors. No roles of smoking habits, alcohol consumption, iodine containing drugs, and exposure to pesticides were evidenced. Conclusions: Except for smoking, differentiated thyroid carcinoma risk factors in natives of French Polynesia are similar to those in other populations. Our finding on the role of having a spring as a drinking water origin is coherent with some other studies and could be due to geological factors. -
Xu, Chuan;Huang, Xin-En;Wang, Shu-Xiang;Lv, Peng-Hua;Sun, Ling;Wang, Fu-An;Wang, Li-Fu 2681
Aim: To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. Materials and Methods: We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Results: Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Conclusions: Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only. -
Yu, Da-Ping;Han, Yi;Zhao, Qiu-Yue;Liu, Zhi-Dong 2685
Background: To explore the prevalence of lymphocyte subgroups$CD3^+$ $CD4^+$ and$CD3^+$ $CD8^+$ and their surface receptors NKG2D and NKG2A in patients with non-small cell lung cancer (NSCLC). Materials and Methods: A total of 40 patients with NSCLC were divided into different groups according to different clinical factors (TNM staging, pathological patterns and genders) for assessment of relations with$CD3^+$ $CD4^+$ and$CD3^+$ $CD8^+$ and the surface receptors NKG2D and NKG2A of T lymphocytes in peripheral blood by flow cytometry. Results: Patients in the advanced group had evidently lower levels of$CD3^+$ $CD4^+$ but markedly higher levels of$CD3^+$ $CD8^+$ in peripheral blood than those with early lesions (p<0.05). In addition, NSCLC patients in the advanced group had obviously higher$CD3^+$ $CD4^+$ NKG2D and$CD3^+$ $CD8^+$ NKG2A expression rates but lower$CD3^+$ $CD4^+$ NKG2A and$CD3^+$ $CD8^+$ NKG2D expression rates (p<0.05). However, there were no significant differences between NSCLC patients with different genders and pathological patterns in expression levels of lymphocyte subgroups$CD3^+$ $CD4^+$ and$CD3^+$ $CD8^+$ and their surface receptors NKG2D and NKG2A. Conclusions: Unbalanced expression of surface receptors NKG2D and NKG2A in$CD3^+$ $CD4^+$ and$CD3^+$ $CD8^+$ lymphocytes may be associated with a poor prognosis, greater malignancy and immunological evasion by advanced cancers, related to progression of lung cancer. -
Kokanali, Mahmut Kuntay;Guzel, Ali Irfan;Erkilinc, Selcuk;Tokmak, Aytekin;Topcu, Hasan Onur;Gungor, Tayfun 2689
Purpose: To investigate the risk factors for appendiceal metastasis of epithelial ovarian cancer and compare findings with the previous studies. Materials and Methods: One hundred and thirty-four patients with epithelial ovarian cancer were assessed in this study. All of them had undergone a surgical procedure including appendectomy. Of these, 21 (15.7%) patients who had appendiceal metastasis were analyzed as the case group and the patients with no metastasis were the controls, compared according to stage, grade, histology of tumor, preoperative Ca125 levels, presence of ascites, peritoneal cytology, diameter and site of tumor considered as risk factors. Results: We found statistically significant differences between the groups in terms of stage, grade, right-sided tumor location, presence of ascites, diameter of tumor${\geq}10cm$ and positive peritoneal cytology (p<0.05). In the logistic regression model, stage, grade, presence of ascites, right-sided location and diameter of tumor were independent risk factors. ROC curve analysis showed that stage, grade and diameter of the tumor were discriminative factors for appendiceal metastasis. Conclusions: In epithelial ovarian cancer, stage, grade, presence of ascites, right-sided location and large tumor size have importance for estimation of risk of appendiceal metastasis. As we compare our findings with previous studies, there is no definite recommendation for the risk factors of appendiceal metastasis in epithelial ovarian cancer and more studies are needed. -
Sugiyama, Yukiko;Nagata, Yoshie;Fukuta, Fumimasa;Takayanagi, Akio;Masumori, Naoya;Tsukamoto, Taiji;Akasaka, Hiroshi;Ohnishi, Hirofumi;Saito, Shigeyuki;Miura, Tetsuji;Moriyama, Kaoru;Tsuji, Hirokazu;Akaza, Hideyuki;Mori, Mitsuru 2693
Background: Isoflavones, which are included in soybeans, have been suggested to protect against prostate cancer. Equol, one of isoflavones, is an intestinally derived bacterial metabolite of daidzein. A newly identified equol-producing bacterium, Slackia sp. strain NATTS, with a high equol-producing activity was isolated from human feces in Japanese adults. Counts of Slackia sp. strain NATTS in intestinal flora have not been assessed with regard to prostate cancer risk. In this study, we investigated the association of serum isoflavones and counts of Slackia sp. strain NATTS with prostate cancer risk in a case-control study. Materials and Methods: Concentrations of isoflavones and counts of Slackia sp. strain NATTS in feces were measured from 44 patients with prostate cancer and 28 hospital controls. The risk of prostate cancer was evaluated in terms of odds ratios (ORs) and 95% confidence intervals (CIs) by the logistic regression analysis. Results: The detection proportions of Slackia sp. strain NATTS in cases and controls were 34.1% and 25.0%, respectively. Counts of Slackia sp. strain NATTS were significantly correlated with serum concentrations of equol both in cases and controls (Spearman correlation coefficients,$r_s$ =0.639 and$r_s$ =0.572, p<0.01, respectively). Serum concentrations of genistein, daidzein, glycitein, and equol were not significantly associated with risk of prostate cancer. Conclusions: This study found that counts of Slackia sp. strain NATTS correlated with serum concentrations of equol both in prostate cancer cases and controls, but serum isoflavone concentrations were not associated with risk of prostate cancer in our patients. -
Gao, Meili;Li, Yongfei;Xue, Xiaochang;Long, Jiangang;Chen, Lan;Shah, Walayat;Kong, Yu 2699
This study was to undertaken to investigate the impacts of AhR, CYP1A1, GSTM1 genetic polymorphisms on the R273G mutation in exon 8 of the tumor suppressor p53 gene (TP53) among polycyclic aromatic hydrocarbons (PAHs) exposed to coke-oven workers. One hundred thirteen workers exposed to PAH and 82 control workers were recruited. We genotyped for polymorphisms in the AhR, CYP1A1, GSTM1, and TP53 R273G mutation in blood by PCR methods, and determined the levels of 1-hydroxypyrene as PAH exposure marker in urine using the high pressure liquid chromatography assay. We found that the distribution of alcohol users and the urinary excretion of 1-OHP in the exposed workers were significantly higher than that of the control workers (p=0.004, p<0.001, respectively). Significant differences were observed in the p53 genotype distributions of smoking subjects (p=0.01, 95%CI: 1.23-6.01) and PAH exposure (p=0.008, 95%CI: 1.24-4.48), respectively. Further, significant differences were observed in the p53 exon 8 mutations for the genetic polymorphisms of Lys/Arg for AhR (p=0.02, 95%CI: 0.70-15.86), Val/Val for CYP1A1 (p=0.04, 95%CI: 0.98-19.09) and null for GSTM1 (p=0.02, 95%CI: 1.19-6.26), respectively. Our findings indicated that polymorphisms of PAH metabolic genes, such as AhR, CYP1A1, GSTM1 polymorphisms may interact with p53 genetic variants and may contribute to PAH related cancers. -
Jiang, Chao;Sun, Wen-Jie;Wan, Yan-Chun;Wei, Ming-Wei;Mu, Yong-Ping;Tarver, Siobhan L.;Gao, Yong-Qing;Hu, Tian;Xu, Chao;Gordon, James;Feng, Cindy Xin;Wen, Yu-Feng 2707
Introduction: Smoking prevalence among the medical students is high in China. Therefore, understanding the smoking motivations of medical students is crucial for smoking control, but currently there are no scales questionnaires customized for probing the smoking motivations of medical students. This aim of study was to test and modify a questionnaire for investigating smoking motivations among medical students. Methods: A cross-sectional survey was conducted among 1,125 medical students at Xuzhou Medical College in China in 2012.The model fit and validity was assessed by confirmatory factor analysis (CFA) and the reliability was tested by single-item reliability, composite reliability, and item-total correlation. Results: The prevalence of smoking was 9.84 % among study population. In the modified scales, the global fit indices identified a CFI value of 0.96, TLI was 0.96, and the RMSEA was 0.063. CFA supported the two dimensional structure of the instrument. The average variance extracted ranged from 0.45 to 0.62. All single-item reliability scores were greater than 0.20, and the composite reliability ranged from 0.74 to 0.91. Conclusion: Modified scales could be the preliminary instrument used in evaluating the smoking motivations of medical students. However, it should be further assessed using other forms and methods of validity and reliability, additional motivations of smoking, and the survey of other medical colleges in China. -
Choi, Jae-Woo;Cho, Kyoung-Hee;Choi, Young;Han, Kyu-Tae;Kwon, Jeoung-A;Park, Eun-Cheol 2713
Background: Cancer imposes significant economic challenges for individuals, families, and society. Households of cancer patients often experience income loss due to change in job status and/or excessive medical expenses. Thus, we examined whether changes in economic status for such households is affected by catastrophic health expenditures. Materials and Methods: We used the Korea Health Panel Survey (KHPS) Panel$1^{st}-4^{th}$ (2008-2011 subjects) data and extracted records from 211 out of 5,332 households in the database for this study. To identify factors associated with catastrophic health expenditures and, in particular, to examine the relationship between change in economic status and catastrophic health expenditures, we conducted a generalized linear model analysis. Results: Among 211 households with cancer patients, 84 (39.8%) experienced catastrophic health expenditures, while 127 (40.2%) did not show evidence of catastrophic medical costs. If a change in economic status results from a change in job status for head of household (job loss), these households are more likely to incur catastrophic health expenditure than households who have not experienced a change in job status (odds ratios (ORs)=2.17, 2.63, respectively). A comparison between households with a newly-diagnosed patient versus households with patients having lived with cancer for one or two years, showed the longer patients had cancer, the more likely their households incurred catastrophic medical costs (OR=1.78, 1.36, respectively). Conclusions: Change in economic status of households in which the cancer patient was the head of household was associated with a greater likelihood that the household would incur catastrophic health costs. It is imperative that the Korean government connect health and labor policies in order to develop economic programs to assist households with cancer patients. -
Al-Shabanah, Othman Abdulla;Hafez, Mohamed Mahmoud;Hassan, Zeinab Korany;Sayed-Ahmed, Mohamed Mohamed;Abozeed, Waleed Nabeel;Alsheikh, Abdulmalik;Al-Rejaie, Salem Saleh 2719
Background: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. Materials and Methods: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. Results: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. Conclusion: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation. -
Wu, Li-Zhu;Han, Ren-Qiang;Zhou, Jin-Yi;Yang, Jie;Dong, Mei-Hua;Qian, Yun;Wu, Ming 2727
Objectives: The aim of this study was to describe and analyze the incidence and mortality of female breast cancer in Jiangsu Province of China. Methods: Incidence and mortality data for female breast cancer and corresponding population statistics from eligible cancer registries in Jiangsu from 2006 to 2010 were collected and analyzed. Crude rates, age-specific rates and age-standardized rates of incidence and mortality were calculated, and annual present changes (APCs) were estimated to describe the time trends. Results: From 2006 to 2010, 11,013 new cases and 3,068 deaths of female breast cancer were identified in selected cancer registry areas of Jiangsu. The annual average crude incidence and age-standardized incidence by world population (ASW) were 25.2/ and 17.9/100,000 respectively. The annual average crude and ASW for mortality rates were 7.03/ and 4.81/100,000. The incidence was higher in urban areas than that in rural areas, and this was consistent in all age groups. No significant difference was observed in mortality between urban and rural areas. Two peaks were observed when looking at age-specific rates, one at 50-59 years and another at over 85 years. During the 5 years, incidence and mortality increased with APCs of 4.47% and 6.89%, respectively. Compared to the national level, Jiangsu is an area with relatively low risk of female breast cancer. Conclusion: Breast cancer has become a main public health problem among Chinese females. More prevention and control activities should be conducted to reduce the burden of this disease, even in relatively low risk areas like Jiangsu. -
Hu, Yu-Chang;Zhang, Qian;Huang, Yan-Hua;Liu, Yu-Fei;Chen, Hong-Lei 2733
Objective: Molecular pathology tests are often carried for clinicopathological diagnosis and pathologists have established large collections of formalin-fixed, paraffin-embedded tissue (FFPE) banks. However, extraction of DNA from FFPE is a laborious and challenging for researchers in clinical laboratories. The aim of this study was to compare two widely used DNA extraction methods: using a QIAamp DNA FFPE kit from Qiagen and a Cobas Sample Preparation Kit from Roche, and evaluated the effect of the DNA quality on molecular diagnostics. Methods: DNA from FFPE non-small cell lung carcinoma tissues including biopsy and surgical specimens was extracted with both QIAamp DNA FFPE and Cobas Sample Preparation Kits and EGFR mutations of non-small cell lung carcinomas were detected by real-time quantitative PCR using the extracted DNA. Results and Conclusion: Our results showed that DNA extracted by QIAamp and Cobas methods were both suitable to detect downstream EGFR mutation in surgical specimens. Howover, Cobas method could yield more DNA from biopsy specimens, and gain much better EGFR mutation results. -
Hesari, Ali Esmaeili;Lari, Mohsen Asadi;Shandiz, Fatemeh Homai 2739
Background: Health-related quality of life (HRQL) is a fundamental outcome in oncology patients and quality of life (QOL) assessment requires clinically relevant questionnaires. The purpose of this study was translation and definition of measurement properties and the clinical validity of Quality of Life Questionnaire (QLQ)-OG25 module in Persian patients with oesophagus, oesophagogastric junction (OGJ) or gastric cancers. Materials and Methods: The translation procedure followed European Organization for Research and Treatment of Cancer (EORTC) guidelines. Both EORTC QLQ-OG25 and a core questionnaire (EORTC QLQ-C30) were administered to patients with oesophagus (150), OG junction (93) and gastric (32) cancer undergoing multi-modal treatments. Convergent and discriminant validity, Cronbach's alpha coefficient and known-groups comparisons were used to examine reliability and validity. Results: In all, 275 patients (mean age 62 years) completed both questionnaires. Compliance rate was high and the questionnaire module was well accepted. We found good reliability for multi-item subscales of QLQ-OG25 (Cronbach's alpha coefficients 0.76-0.89). About 73% had TNM staging and scales distinguished between clinically distinct groups of patients. However, patients in palliative group experienced compromised functional status and worse treatment-associated symptoms than those in the potentially curative group. Test-retest scores were consistent. Multi-trait scaling analysis demonstrated good convergent and discriminant validity. Conclusions: Overall, the Persian version of QLQ-OG25 demonstrated psychometric and clinical validity that supports its application as a supplement to the original tool (EORTC QLQ-C30) when assessing HRQL in patients with upper-gastrointestinal (GI) cancer both in curative and palliative phases. -
Visuvanathan, Shaneeta;Chong, Pei-Pei;Yap, Yoke-Yeow;Lim, Chin-Chye;Tan, Meng-Kuan;Lye, Munn-Sann 2747
Background: DNA repair pathways play a crucial role in maintaining the human genome. Previous studies associated DNA repair gene polymorphisms (XPD Lys751Gln, XRCC1 Arg280His and XRCC1 Arg399Gln) with nasopharyngeal carcinoma. These non-synonymous polymorphisms may alter DNA repair capacity and thus increase or decrease susceptibility. The present study aimed to determine the genotype distribution of XPD codon 751, XRCC1 codon 280 and codon 399 polymorphisms and haplotype associations among NPC cases and controls in the Malaysian population. Materials and Methods: We selected 157 NPC cases and 136 controls from two hospitals in Kuala Lumpur, Malaysia for this study. The polymorphisms studied were genotyped by PCR-RFLP assay and allele and genotype frequenci es, haplotype and linkage disequilibrium were determined using SNPstat software. Results: For the XPD Lys751Gln polymorphism, the frequency of the Lys allele was higher in cases than in controls (94.5% versus 85.0%). For the XRCC1 Arg280His polymorphism, the frequency of Arg allele was 90.0% and 89.0% in cases and controls, respectively and for XRCC1 Arg399Gln the frequency of the Arg allele was 72.0% and 72.8% in cases and controls respectively. All three polymorphisms were in linkage disequilibrium. The odds ratio from haplotype analysis for these three polymorphisms and their association with NPC was 1.93 (95%CI: 0.90-4.16) for haplotype CGC vs AGC allele combinations. The global haplotypte association with NPC gave a p-value of 0.054. Conclusions: Our study provides an estimate of allele and genotype frequencies of XRCC1Arg280His, XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in the Malaysian population and showed no association with nasopharyngeal cancer. -
Li, Jing-Ping;Cao, Nai-Xia;Jiang, Ri-Ting;He, Shao-Jian;Huang, Tian-Ming;Wu, Bo;Chen, De-Feng;Ma, Ping;Chen, Li;Zhou, Su-Fang;Xie, Xiao-Xun;Luo, Guo-Rong 2753
Background: GC-binding factor 2 (GCF2) is a transcriptional regulator that represses transcriptional activity of the epidermal growth factor receptor (EGFR) by binding to a specific GC-rich sequence in the EGFR gene promoter. In addition to this function, GCF2 has also been identified as a tumor-associated antigen and regarded as a potentially valuable serum biomarker for early human hepatocellular carcinoma (HCC) diagnosis. GCF2 is high expressed in most HCC tissues and cell lines including HepG2. This study focused on the influence of GCF2 on cell proliferation and apoptosis in HepG2 cells. Materials and Methods: GCF2 expression at both mRNA and protein levels in HepG2 cells was detected with reverse transcription (RT) PCR and Western blotting, respectively. RNA interference (RNAi) technology was used to knock down GCF2 mRNA and protein expression. Afterwards, cell viability was analyzed with a Cell Counting Kit-8 (CCK-8), and cell apoptosis and caspase 3 activity by flow cytometry and with a Caspase 3 Activity Kit, respectively. Results: Specific down-regulation of GCF2 expression caused cell growth inhibition, and increased apoptosis and caspase 3 activity in HepG2 cells. Conclusions: These primary results suggest that GCF2 may influence cell proliferation and apoptosis in HepG2 cells, and also provides a molecular basis for further investigation into the possible mechanism at proliferation and apoptosis in HCC. -
Aim: This study aims to investigate the manifestation of CT, MRI and dynamic enhanced scans for primary hepatic neuroendocrine cell carcinoma. Methods: CT or MRI arterial and venous phase scan images of 19 cases of pathologically confirmed PHNEC were retrospectively analyzed. Results: 14 cases (73.68%) with single lesion, 5 cases (26.3%) with multiple lesions, with an average diameter of 13.2 cm. Some 12 cases (63.16%) showed inhomogeneous enhancement, seven cases (36.8%) showed homogeneous enhancement, 13 cases (68.4%) demonstrated significant enhancement in the arterial phase, 13 cases (68.4%) had significantly enhanced portal venous phase including 7 cases (36.8 %) with portal venous phase density or signal above the arterial phase and 5 cases (26.3%) with the portal vein density or signal below the arterial phase. Seven cases (36.8%) had continued strengthened separate shadows in the center of the lesion. Thrombosis were not seen in portal veins. Conclusion: CT and MRI images of liver cell neuroendocrine carcinoma have certain characteristics that can provide valuable information for diagnosis and differential diagnosis.
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De Stefani, Eduardo;Deneo-Pellegrini, Hugo;Ronco, Alvaro L.;Boffetta, Paolo;Correa, Pelayo;Mendilaharsu, Maria;Acosta, Gisele;Quarneti, Aldo;Silva, Cecilia 2765
Background: Oesophageal cancer presents high incidence rates in the so-called Brazilian-Uruguayan belt. Materials and Methods: The present study included 1,170 participants (234 cases and 936 controls) which were analyzed by unconditional multiple logistic regression in order to examine risk of oesophageal squamous cell carcinoma (OESCC) associated with several food groups. Results: Boiled red meat (OR 2.59, 95%CI 1.69-3.97), lamb meat (OR 1.64, 95%CI 1.07-2.51), processed meat (OR 1.49, 95%CI 1.01-2.21), whole milk (OR 1.78, 1.19-1.68), fresh vegetables and fruits (OR 0.42, 95%CI 0.27-0.63), mate consumption (OR 2.04, 95%CI 1.32-3.16), and black tea (OR 0.10, 95%CI 0.04-0.28) were significantly associated with risk of OESCC. Conclusions: Hot beverages (mate) and hot foods (boiled meat) appear to be important determinants in the risk of OESCC, allowing the penetration of carcinogens in tobacco and alcohol into the oesophageal mucosa. -
Omranipour, Ramesh;Alipour, Sadaf;Hadji, Maryam;Bagheri, Khojasteh 2771
Background: Breast cancer screening and higher quality mammography have resulted in an increase in the diagnosis of ductal carcinoma in situ worldwide. We compared the incidence and other factors in our cases of ductal carcinoma in situ between two recent decades. Materials and Methods: Medical records of cases of ductal carcinoma in situ who had been admitted to the surgery wards of the Cancer Institute of Tehran, Iran were evaluated from March 1993 to March 2003 as phase 1, and from April 2003 to April 2013 as phase 2. Results: Ratio of ductal carcinoma in situ to overall breast cancer was 1.27 and 3.93 in phases 1 and 2, respectively. Rates of excisional or incisional biopsies versus core needle biopsies and clinically versus mammographically detected cases as well as median size of tumors dropped between the 2 phases while a substantial rise in the number of patients attending for screening was seen in this time period. Surgical treatments followed a trend from modified radical mastectomy and axillary lymphatic dissection toward breast conserving surgery and sentinel node dissection or no axillary intervention. Conclusions: Our study shows a considerable trend toward earlier detection of breast cancer and evolution of treatment strategies toward standard less invasive surgery of DCIS in Iran. -
Wan, Wei-Na;Zhang, Yi-Xia;Wang, Xue-Mei;Liu, Yan-Jun;Zhang, Yu-Qin;Que, Yan-Hong;Zhao, Wen-Jing 2777
The purpose of this study was to explore the expression of ATAD2 in ovarian tumor tissue as well as its relationship with degree of malignancy. Tumor tissue from 110 cases of ovarian cancer was collected in accordance with the Declaration of Helsinki for evaluation of ATAD2 expression iimmunohistochemistry, quantitative PCR (qPCR) and Western blotting. The correlation between the ATAD2 expression and and the prognosis of ovarian cancer was evaluated by Cox regression model. In addition, HO-8910 and OVCAR-3 cells were transfected with two siRNAs targeting ATAD2. Cell viability was evaluated with MTT assay, and cell migration by transwell migration assay. ATAD2 was shown to be highly expressed in 65.5% (72/110) of ovarian cancer cases, both at transcriptional and protein levels. Moreover, highly expression was positively correlated with degree of malignancy. Knock-down of ATAD2 in HO-8910 and OVCAR-3 cells was found to reduce cell migration. In addition, follow-up visits of the patients demonstrated that the 5-year survival rate was lower in patients with high expression of ATAD2. Our study suggested that ovarian tumor tissue may have highly expressed ATAD2, which is associated with tumor stage, omentum-metastasis, ascites and CA-125. Increased ATAD2 may play important roles in tumor proliferation and migration. ATAD2 could serve in particular as a prognostic marker and a therapeutic target for ovarian cancer. -
Shi, Xiao-Jun;Au, William W.;Wu, Ku-Sheng;Chen, Lin-Xiang;Lin, Kun 2785
Aims: To analyze time-dependent changes in female breast cancer (BC) mortality in China, forecast the trend in the ensuing 5 years, and provide recommendations for prevention and management. Materials and Methods: Mortality data of breast cancer in China from 1991 to 2011 was used to describe characteristics and distribution, such as the changes of the standardized mortality rate, urban-rural differences and age differences. Trend-surface analysis was used to study the geographical distribution of mortality. In addition, curve estimation, time series modeling, Gray modeling (GM) and joinpoint regression were performed to estimate and predict future trends. Results: In China, the mortality rate of breast cancer has increased yearly since 1991. In addition, our data predicted that the trend will continue to increase in the ensuing 5 years. Rates in urban areas are higher than those in rural areas. Over the past decade, all peak ages for death by breast cancer have been delayed, with the first death peak occurring at 55 to 65 years of age in urban and rural areas. Geographical analysis indicated that mortality rates increased from Southwest to Northeast and from West to East. Conclusions: The standardized mortality rate of breast cancer in China is rising and the upward trend is predicted to continue for the next 5 years. Since this can cause an enormous health impact in China, much better prevention and management of breast cancer is needed. Consequently, disease control centers in China should place more focus on the northeastern, eastern and southeastern parts of China for breast cancer prevention and management, and the key population should be among women between ages 55 to 65, especially those in urban communities. -
Pashaki, Abdolazim Sedighi;Hamed, Ehsan Akbari;Mohamadian, Kamal;Abassi, Mohammad;Safaei, Afsane Maddah;Torkaman, Tayebe 2793
Background: Glioblastoma multiform (GBM) is a highly aggressive tumor with median survival of approximately 14 months. Management consists of maximal surgical resection followed by post-operative chemoradiation with concurrent then adjuvant temozolamide. The standard radiotherapy dose is 60Gy in 2-Gy fractions recommended by the radiation therapy oncology group (RTOG). With the vast majority of tumor recurrences occurring within the previous irradiation field and the poor outcome associated with standard therapy, regimens designed to deliver higher radiation doses to improve local control and enhance survival are needed. In this study, we report a single institutional experience in treatment of 68 consecutive patients with GBM, treated with resection, and given post-operative radiotherapy followed by concurrent and/or adjuvant chemotherapy. Results: Of the 80 patients who entered this study, 68 completed the treatment course; 45 (66.2%) males and 23 (33.8%) females with a mean age at diagnosis of$49.0{\pm}12.9$ (21-75) years. At a median follow up of 19 months, 39 (57.3%) patients had evidence of tumor progression and 36 (52.9%) had died. The median over all survival for all patients was 16 months and progression free survival for all patients was 6.02 months. All potential prognostic factors were analyzed to evaluate their effects on overall survival. Age${\leq}50$ year, concurrent and adjuvant chemotherapy and extent of surgery had significant p values. We found lower progression rate among patients who received higher doses of radiotherapy (>60Gy). Higher radiation doses improved progression free survival (p=0.03). Despite increasing overall survival, this elevation was not significant. Conclusions: This study emphasize that higher radiation doses of (>60Gy) can improve local control and potentially survival, so we strongly advise prospective multi centric studies to evaluate the role of higher doses of radiotherapy on GBM patient outcome. -
Binesh, Fariba;Akhavan, Ali;Behniafard, Nasim;Jalilian, Samaneh 2797
Background: Endometrial adenocarcinoma is the most common gynecological cancer in the Western world and its incidence appears to be rising. However, population-based studies on endometrial cancer providing survival estimates by age, histology, and stage in Asia have been sparse. The aim of this study was to evaluate the clinicopathological data and survival for patients with endometrial adenocarcinoma treated at three institutions in Yazd, Iran. Materials and Methods: Medical and anatomicopathological records at the Department of Pathology and Radiotherapy of the Shahid Sadoughi University of Medical Sciences and Madar private hospital, between 2005 and 2012 were reviewed. All cases of endometrial adenocarcinoma were included. The Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Results: The study included 84 patients. Stages I, II, III, and IV were identified in 65.4%, 21.5%, 11.9% and 1.2%, respectively. Disease-free survival rate was$73.9{\pm}3.77$ months (95% confidence interval, 64.51-83.22 months) and relapse occurred in 12.3% of the patients. The overall survival rate was$78.2{\pm}3.65$ months (95% confidence interval, 71.0-85.3 months). A multivariate analysis revealed that stage and grade were associated with overall survival. Conclusions: In this survival analysis of patients with endometrial cancer, we found that the prognosis of endometrial cancer was fair but strongly varied by stage and grade, and moderately varied by histology and age. -
Chen, Hui;Jiang, He-Zhong;Li, Yong-Chao;Wei, Guo-Qing;Geng, Yun;Ma, Chao-Ying 2803
Bioassay-guided chemical investigation of the roots of Anthriscus sylvestris (L.) Hoffm. resulted in the isolation of nine compounds, whose structures were determined by spectroscopic methods. Compound 1 was isolated from this plant for the first time and compounds 3 and 9 were first found from this genus. Different polar fractions of A. sylvestris extract and compounds 1, 6-8 and 9 were evaluated for antitumor activities against HepG2 (human hepatocellular carcinoma), MG-63 (human osteosarcoma cells), B16 (melanoma cells) and HeLa (human cervical carcinoma cells) lines by the MTT method. The petroleum ether fraction of A. sylvestris extract exhibited excellent inhibitory activity with an$IC_{50}$ value of$18.3{\mu}g/ml$ . Among the isolates from the petroleum ether fraction, compound 7 showed significant inhibition against the growth of the four tumor cells with$IC_{50}$ values ranging from$12.2-43.3{\mu}g/ml$ . -
Zhao, Meng-Meng;Zhang, Yue;Shen, Li;Ren, Yang-Wu;Li, Xue-Lian;Yin, Zhi-Hua;Zhou, Bao-Sen 2809
Background: This study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) in telomerase reverse transcriptase (TERT) and cleft lip and palate transmembrane1-like (CLPTM1L) and lung cancer risk in a Chinese population. Methods: We performed a hospital-based case-control study, including 980 lung cancer cases and 1000 cancer-free controls matched for age and sex. Each case and control was interviewed to collect information by well-trained interviewers. A total of 5 ml of venous blood was collected for genotype testing of TERT rs2736098 and CLPTM1L rs401681 using TaqMan methodology. Results: The results revealed that the variant homozygote TERT rs2736098TT was associated with an increased risk of lung cancer (OR=2.017, 95%CI=1.518-2.681), especially lung adenocarcinoma (OR=2.117, 95%CI=1.557-3.043) and small cell carcinoma (OR=1.979, 95%CI: 1.174-3.334), compared with the TERT rs2736098CC genotype. Similar results were observed in non-smokers. Conclusion: The TERT rs2736098 polymorphism might affect the susceptibility to lung cancer in Chinese populations. The associations need to be verified in larger and different populations. -
Teke, Fatma;Yoney, Adnan;Teke, Memik;Inal, Ali;Urakci, Zuhat;Eren, Bekir;Zincircioglu, Seyit Burhanedtin;Buyukpolat, Muhammed Yakup;Ozer, Ali;Isikdogan, Abdurrahman;Unsal, Mustafa 2815
Background: The aim of this study was to evaluate the prognosis of patients with stage IA-IIB cervical carcinoma and to investigate a possible correlation of histology with prognosis. Materials and Methods: Two hundred fifty one patients with adenocarcinoma and squamous cell carcinoma (SCC) histology for FIGO (International Federation of Gynecology and Obstetrics) stage IA-IIB uterine cervical carcinomas at the Radiation Oncology Clinic of GH Okmeydan Training and Research Hospital between January 1996 and December 2006 were selected, analyzed retrospectively and evaluated in terms of general characteristics and survival. Disease-free survival (DFS) and overall survival (OS) was calculated using the Kaplan-Meier method and differences were compared with the log-rank test. Multivariate analysis using a Cox-proportional hazards model was used to adjust for prognostic factors and to estimate hazard ratio (HR) with 95% confidence interval (CI). Results: There was no differences between the two tumour types in age, stage, pelvic nodal metastasis, parametrial invasion, surgical margin status, DSI, LVSI, maximal tumor diameter, grade, and treatment modalities. 5-year OS and DFS were 73% and 77%, versus 64% and 69%, for SCC and adenocarcinoma, respectively (p> 0.05). Multivariate analysis revealed independent prognostic factors including pelvic nodal metastasis and resection margin status for OS (p=0.008, p=0.002, respectively). Conclusions: Prognosis of FIGO stage IA-IIB cervical cancer patients was found to be the same for those with adenocarcinoma and SCC. -
Yildirim, Mustafa;Kaya, Vildan;Yildiz, Mustafa;Demirpence, Ozlem;Gunduz, Seyda;Dilli, Utku Donem 2821
Background: Esophageal and gastric cancer generally have a poor prognosis and may share common risk factors. It has been demonstrated that the pesticide usage may contribute to development of many cancer types. In this study, the relation between amount of pesticides used in agriculture and esophageal and gastric cancer incidence was researched. Materials and Methods: Findings from the data bank of the Ministry of Health Provincial Health Directorate Cancer Records Center between the years of 1998-2010 were used. All patients who were diagnosed with gastric and esophageal cancer histopathologically were included. Data for annual pesticide usage were obtained from Provincial Agriculture Directorate for the same time period. Statistical analysis was performed using the Spearman test. Results: One thousand eight hundred and ninety-six patients were involved in the study, 1,233 males (65%) and 663 females (35%), 230 with esophageal cancer (12.1%) and 1,666 with gastric cancer (87.9%). No statistically significant relation was apparent between pesticide amount used and esophageal cancer (p: 0.87). Conclusions: In our study, there was no relationship between pesticide usage and esophageal or gastric cancer. However, the time between pesticide usage and cancer development was not known, qualifying the comparison. -
Taya, Sirinya;Punvittayagul, Charatda;Inboot, Wanida;Fukushima, Shoji;Wongpoomchai, Rawiwan 2825
Purpose: To study the effect of Cleistocalyx nervosum extract (CE) on diethylnitrosamine (DEN) and phenobarbital (PB) induced oxidative stress in early stages of rat hepatocarcinogenesis. Materials and Methods: Male Wistar rats were divided into 4 groups, with Group 1 as a negative control and Group 2 was a positive control receiving DEN injections once a week and PB in drinking water for 6 weeks. Two weeks before DEN initiation and PB treatment, Groups 3 and 4, were fed with 500 and 1000 mg/kg of CEs, respectively, for 8 weeks. Results: A number of GST-P-positive foci, preneoplastic lesions, in the liver were markedly increased in carcinogen administered rats, but was comparatively decreased in rats treated with 1000 mg/kg of CE. The CE reduced malondialdehyde in serum and in the livers of rats treated with DEN and PB. Moreover, CE significantly increased the activities of glutathione peroxidase and catalase in rat liver. Conclusions: CE appeared to exert its chemopreventive effects by modulating antioxidant status during DEN and PB induced early stages of hepatocarcinogenesis in rats. -
Xin, Ke-Peng;Du, Mao-Lin;Li, Zhi-Jun;Li, Yun;Li, Wuyuntana;Su, Xiong;Sun, Juan 2831
The aim of this study was to determine the mortality rate and burden of urinary tract cancers among residents of Inner Mongolia. We analyzed mortality data reported by the Death Registry System from 2008 to 2012. The rate of mortality due to urinary tract cancer was 2.04 per 100,000 person-years for the total population, 2.91 for men, and 1.11 for women. Therefore, the mortality rate for men was 2.62-fold the mortality rate for women, constituting a statistically significant difference (p<0.001). Over the period 2008 through 2012, the total potential years of life lost was 1388.1 person-years for men and 777.1 person-years for women, and the average years of life lost were 7.71 years per male decedent and 12.0 years per female decedent. Mortality due to urinary tract cancers is substantially greater among the elderly population. Further, the mortality rate associated with urinary tract cancers is greater for elderly men than it is for elderly women. Therefore, in Inner Mongolia, urinary tract cancers appear to pose a greater mortality risk for men than they do for women. -
Liu, Xiao-Jia;Li, Yun-Qian;Chen, Qiu-Yue;Xiao, Sheng-Jun;Zeng, Si-En 2835
Prostate cancer is one of the most prevalent malignant cancers in men. The isoflavone formononetin is a main active component of red clover plants. In the present study, we assessed the effect of formononetin on human prostate cancer DU-145 cells in vitro, and elucidated posssible mechanisms. DU-145 cells were treated with different concentrations of formononetin and cell proliferation was assessed by MTT assay, cell apoptosis by Hoechst 33258 and flow cytometry, and protein levels of RASD1, Bcl-2 and Bax by Western blotting. The results showed that formononetin inhibited the proliferation of DU-145 cells in a dose-dependent manner. DU-145 cells treated with different concentrations of formononetin displayed obvious morphological changes of apoptosis under fluorescence microscopy. In addition, formononetin increased the proportion of early apoptotic DU-145 cells, down-regulated the protein levels of Bcl-2 and up-regulated those of RASD1 and Bax. The level of RASD1 reached its maximum at 48h post-treatment, and rapidly decreased thereafter. Together, we present evidence that formononetin triggered cell apoptosis through the mitochondrial apoptotic pathway by up-regulating RASD1. -
Gokdemir-Yazar, Ozden;Yaprak, Seval;Colak, Muhteber;Yildirim, Ediz;Guldal, Dilek 2841
Background: When dealing with breast cancer, early detection is closely associated with determining and closely monitoring high risk groups. The aim of this study was to determine the preventable risk factors that are specific for our country, and to understand which risk factors were most predominant. Materials and Methods: The study was planned as a case-control design. Women diagnosed with breast cancer who visited the Surgery, Obstetrics and Gynaecology, and Radiation Oncology outpatient clinics of the Izmir Dokuz Eylul University (DEU) School of Medicine were accepted as the case group. Then a control group matched for age was established among females who visited the outpatient clinics on the same days. A questionnaire prepared by the researchers was implemented using a face-to-face interview technique. The Mann-Whitney U test was used in the comparisons of the group averages, and the Pearson chi-square test in the comparisons between groups. In order to determine the dominant risk factors, binary logistical regression test was implemented. Results: A total of 138 patients, 69 cases and 69 controls, were included in the study. A significant difference can be detected between the groups in terms of BMI, smoking, breast cancer prevalence among first degree family members, presence of breast cancer among distant family members, existence of other types of cancers among family members and the age of onset of menopause (p<0.05). Logistical regression analysis revealed that the presence of breast cancer among first degree relatives increased the risk of developing breast cancer 5.7 times. Conclusions: Although some results of this study are compatible with findings in the literature, some are not. In order to determine unique risk factors, there is a clear need for large-scale studies. -
Saremi, Leila;Imani, Saber;Rostaminia, Maryam;Nadeali, Zakiye 2847
Background: Retinoblastoma is a rare malignant intraocular neoplasm. About 90% of cases feature a germline mutation in the RB1 gene and these will develop retinoblastoma during their early childhood. An association between mutations in germline cells and aging has been demonstrated. This suggests a higher incidence of childhood cancer including retinoblastoma among children of older parents. Materials and Methods: In the present study we aimed to determine the association of paternal and maternal age with an increased risk of retinoblastoma in a case-control study in Iranian population. The study was carried out on 240 persons who were born during 1984-2012 in Mahak and Mofid hospitals in Tehran, Iran. The statistical analysis included studying the mean age of parents and in order to know whether parental age of patients is different from parental age of control group, (t-test) compare averages test is used perfectly. By binary logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: The results of statistical analysis including the study of mean parental age by the use of (t-test) compare averages test showed a significant difference between parental ages of patients and controls. Logistic regression showed that coefficients were significant for maternal but not paternal age. Conclusions: Our findings indicate that advanced maternal age can increase the risk of retinoblastoma in offspring, but the paternal age has no significant effect. -
Gultekin, Melis;Eren, Gulnihan;Babacan, Taner;Yildiz, Ferah;Altundag, Kadri;Guler, Nilufer;Ozisik, Yavuz;Yazici, Gozde;Hurmuz, Pervin;Gurkaynak, Murat 2851
The aim of this study is to evaluate clinicopathologic characteristics and the multi-disciplinary treatment results of metaplastic breast cancer (MBC) patients treated in a single institute. Seventeen female patients with MBC treated in our department between June 2000 and January 2012 were identified and retrospectively evaluated. The median age at diagnosis was 46 years (range, 26-66 years). The median tumor size at diagnosis was 3.5 cm (range 1.5-12 cm). Six (35%) patients underwent breast conservation surgery and 11 (65%) mastectomy. Axillary lymph node metastasis was found in 6 (35%) patients. Twelve (71%) had triple negative tumors. Postoperative RT and systemic adjuvant treatment was given to all patients accordingly to stage and biological characteristics. Median follow-up time was 27 months (range, 12-151 months). At the time of this analysis, 14 (82%) patients were alive with no evidence of disease, and 1 (6%) was alive with disease. The 3-year OS was 91% and 5-year 80%, and DFS rates were 76% and 76%, respectively. Despite the young age of our patients with mostly high grade tumors, larger tumor size and higher rates of lymph node metastasis, the survival outcomes in our study are favorable in comparison with previously reported series. -
More and more evidence indicates that the G801A polymorphism in the CXCL12 gene might be associated with susceptibility to breast carcinoma in humans being. However, individually published results have been inconsistent. The purpose of this meta-analysis was to investigate the association between the G801A polymorphism in the CXCL12 gene and breast carcinoma risk. A complete search strategy was done by the electronic databases including PubMed and Chinese Biomedical Literature Database. A meta-analysis including seven individual studies was carried out in order to explore the association between the G801A polymorphism in the CXCL12 gene polymorphisms and breast carcinoma. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95%CIs) between the G801A polymorphism in the CXCL12 gene and breast carcinoma risk were assessed by the random-effects model. A significant relationship between the G801A polymorphism in the CXCL12 gene and breast carcinoma was discovered in an allelic genetic model (OR: 1.214, 95%CI: 1.085-1.358, p=0.001), a homozygote model (OR: 1.663, 95%CI: 1.240-2.232, p=0.001), a heterozygote model (OR: 1.392, 95%CI: 1.190-1.629, p=0.000), a recessive genetic model (OR: 1.407, 95%CI: 1.060-1.868, p=0.018) and a dominant genetic model (OR: 1.427, 95%CI: 1.228-1.659, p=0.000). On sub-group analysis based on ethnicity, significance was observed between the European group and the mixed group. A significant relationship was found between the G801A polymorphism in the CXCL12 gene and breast carcinoma risk. Individuals with the A allele of the G801A polymorphism in the CXCL12 gene are under a higher risk for breast carcinoma.
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Zhao, Fen;Zhu, Hong;Huang, Min;Yi, Cheng;Huang, Ying 2863
Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigated for association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aim of this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene for GC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10, 2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874 cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated that the variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG (odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18, and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07, 95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysis by Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58, 95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions: This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GC in Asians and Indians. -
Kahla, Saloua;Kochbati, Lotfi;Maalej, Mongi;Oueslati, Ridha 2869
Background: Human papillomavirus (HPV) integration within the E2 gene has been proposed as a critical event in cervical carcinogenesis. This study concerned whether HPV16 status and E2 gene intactness are predictive of radiation response in patients with cervical cancer. Materials and Methods: Biopsies of 44 patients with cervical cancer were collected before or after radiotherapy. The presence of HPV16 was assessed by polymerase chain reaction (PCR) using specific primers for the L1 region. E2 disruption was detected by amplifying the entire E2 gene. Results: HPV16 DNA was found in 54.5% of the clinical samples. Overall, 62.5% of the HPV16 positive tumors had integrated viral genome and 37.5% had episomal genome. There was a tendency of increase of HPV16 E2 negative tumors compared with HPV16 L1 ones in advanced stages (75% versus 20% in stage III respectively). Detection of E2 gene appeared influenced by the radiotherapy treatment, as the percentage of samples containing an intact HPV16 E2 was more frequent in pretreated patients compared to radiotherapy treated patients (66.6% versus 20%). The radiation therapy caused an eight-fold [OR= 8; CI=1.22-52.25; p=0.03] increase in the risk of HPV16 genome disruption. The integration status is influenced by the irradiation modalities, interestingly E2 disruption being found widely after radiotherapy treatment (75%) with a total fractioned dose of 50Gy. Conclusions: This study reveals that the status of the viral DNA may be used as a marker to optimize the radiation treatment. -
Malik, Prabhat Singh;Malik, Anita;Deo, Suryanarayana Venkata;Mohan, Anant;Mohanti, Bidhu Kalyan;Raina, Vinod 2875
Background: Lung cancer is one of the commonest and most lethal cancers throughout the world. The majority of the patients present at advance stage and are not suitable for curative intent treatment. Even among patients with localized disease, there has been underutilization of curative treatment modalities. The aim of this study was to analyze the radical treatment utilization rates in patients with non small cell lung cancer (NSCLC) treated at our centre. Materials and Methods: We analyzed case records of 104 patients with a pathologically confirmed diagnosis of NSCLC having stage 1-3B disease who were treated at our centre over last 3 years, to assess the utilization of curative treatment modalities i.e. surgery or radical radiotherapy. Results: The median age of this cohort was 58 years. Out of 104 patients only 33 (31.7%) received curative intent treatment, 14 undergoing curative resection and 19 receiving radical doses of radiotherapy. The baseline characteristics of both the groups (with or without radical treatment) were not different. Major factors associated with underutilization with curative treatment were progressive disease or loss of follow up after chemotherapy and inappropriate use of TKI and/or palliative radiotherapy in patients with stage 1-3B disease. Patients who did not receive radical treatment had inferior PFS and OS than those who received radical treatment. Conclusions: In our practice we observed gross underutilization of curative intent treatment modalities in patients with NSCLCs which is associated with inferior survival. -
Najmabadi, Khadijeh Mirzaii;Azarkish, Fatemeh;Latifnejadroudsari, Robab;Shandiz, Fatemeh Homaei;Aledavood, Seyed Amir;Kermani, Ali Taghizadeh;Esmaily, Habib Ollah 2879
Background: Breast cancer (BC) is the most common form of cancer in Iranian women, and it remains a major health problem. An increasing number of young women are being diagnosed with BC, and therefore, there is an increasing likelihood that more women will survive breast cancer for many years. Many opine that self-disclosure of BC diagnosis is important because talking about cancer helps people to make sense of their experiences; in fact, self-disclosure appears to play an important role in many health outcomes. However, this has not yet been studied in BC patients in Iran. Therefore, this study aimed to explore the status of self-disclosure of BC diagnosis by Iranian women to friends and colleagues. Materials and Methods: All BC records for 2001-2011 of employed women were studied at five hospitals in Mashhad. Data about the self-disclosure of BC diagnosis were gathered through telephone interviews, and the participants filled out a questionnaire about their status of self-disclosure of BC diagnosis to various groups of people. Results: The mean age of employed women at the time of diagnosis was$44.3{\pm}6.7$ years. Over 60% self-disclosed to work colleagues and over 90% to bosses/managers. Seventy per cent reported that they had support from their family and husband's family, while 95% reported that they had support from parents, siblings, children and friends. Conclusions: Most employed women self-disclosed freely to family, friends, colleagues and bosses/managers. Apparently, self-disclosure of breast cancer diagnosis may have negative effects at work. About half of patients reported that they had support from family, managers and colleagues; however, for nearly 28% of employed women, disclosure had less positive effects. In particular, it altered their perception of others, produced difficulties with work and family and diminished closeness with the people who were told. However, the stigma of BC is far less than it once was. -
Xie, Qin-Jian;Cao, Xin-Li;Bai, Lu;Wu, Zheng-Rong;Ma, Ying-Ping;Li, Hong-Yu 2883
Background: Realgar which contains arsenic components has been used in traditional Chinese medicine (TCM) as an anticancer drug. However, neither Realgar nor its formula are soluble in water. As a result, high dose of Realgar has to be administered to achieve an effective blood medicine concentration, and this is associated with adverse side effects. The objective of the present study was to increase the solubility of a formula using hydrometallurgy technology as well as investigating its effects on in vitro and in vivo cell proliferation and apoptosis in Sarcoma-180 cell line. Materials and Methods: Antiproliferative activity of Realgar Bioleaching Solution (RBS) was evaluated by MTT assay. Further, effects of RBS on cell proliferation and apoptosis were studied using flow cytometry and transmission electron microscopy. Kunming mice were administered RBS in vivo, where arsenic specifically targeted solid tumors. Results: The results indicated that RBS extract potently inhibited the tumor growth of Sarcoma-180 cell line in a dose-dependent manner. Flow cytometry and transmission electron microscopy further indicated that RBS significantly induced cell apoptosis through the inhibition of cell cycle pathway in a dose-dependent manner. Further, on RBS administration to mice, arsenic was specifically targeted to solid tumor.s Conclusions: RBS could substitute for traditional Realgar or its formula to work as a potent tool in cancer treatment. -
Association of DR4 (TRAIL-R1) Polymorphisms with Cancer Risk in Caucasians: an Updated Meta-analysisChen, Wei;Tang, Wen-Ru;Zhang, Ming;Chang, Kwenjen;Wei, Yun-Lin 2889
Death receptor 4 (TRAIL-R1 or DR4) polymorphisms have been associated with cancer risk, but findings have been inconsistent. To estimate the relationship in detail, a meta-analysis was here performed. A search of PubMed was conducted to investigate the association between DR4 C626G, A683C and A1322G polymorphisms and cancer risk, using odds ratios (ORs) with 95% confidence intervals. The results suggested that DR4 C626G and A683C polymorphisms were indeed associated with cancer risk (for C626G, dominant model, OR 0.991, 95%CI 0.866-1.133, p=0.015; for A683C, additive model, OR=1.140, 95%CI: 0.948-1.370, p=0.028; dominant model, OR=1.156, 95%CI: 0.950-1.406, p=0.080) in the Caucasian subgroup. However, the association was not significant between DR4 polymorphism A1322G with cancer risk in Caucasians (For A1322G, additive model: OR 1.085, 95%CI 0.931-1.289, p=0.217; dominant model: OR 1.379, 95%CI 0.934-2.035, p=0.311; recessive model: OR 1.026, 95%CI 0.831-1.268 p=0.429.). In summary, our finding suggests that DR4 polymorphism C626G and A683 rather than A1322G are associated with cancer risk in Caucasians. -
Khan, Hafiz Mohammad Rafiqullah;Saxena, Anshul;Gabbidon, Kemesha;Rana, Sagar;Ahmed, Nasar Uddin 2893
Background: Statistical methods are very important to precisely measure breast cancer patient survival times for healthcare management. Previous studies considered basic statistics to measure survival times without incorporating statistical modeling strategies. The objective of this study was to develop a data-based statistical probability model from the female breast cancer patients' survival times by using the Bayesian approach to predict future inferences of survival times. Materials and Methods: A random sample of 500 female patients was selected from the Surveillance Epidemiology and End Results cancer registry database. For goodness of fit, the standard model building criteria were used. The Bayesian approach is used to obtain the predictive survival times from the data-based Exponentiated Exponential Model. Markov Chain Monte Carlo method was used to obtain the summary results for predictive inference. Results: The highest number of female breast cancer patients was found in California and the lowest in New Mexico. The majority of them were married. The mean (SD) age at diagnosis (in years) was 60.92 (14.92). The mean (SD) survival time (in months) for female patients was 90.33 (83.10). The Exponentiated Exponential Model found better fits for the female survival times compared to the Exponentiated Weibull Model. The Bayesian method is used to obtain predictive inference for future survival times. Conclusions: The findings with the proposed modeling strategy will assist healthcare researchers and providers to precisely predict future survival estimates as the recent growing challenges of analyzing healthcare data have created new demand for model-based survival estimates. The application of Bayesian will produce precise estimates of future survival times. -
Norwati, Daud;Harmy, Mohamed Yusoff;Norhayati, Mohd Noor;Amry, Abdul Rahim 2901
The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics. -
Jaishuen, Atthapon;Kunakornporamat, Kate;Viriyapak, Boonlert;Benjapibal, Mongkol;Chaopotong, Pattama;Petsuksiri, Janjira;Therasakvichya, Suwanit 2905
Background: To study the incidence of non-endometrioid carcinoma of endometrium and compare the clinical characteristics and treatment outcomes with endometrioid carcinoma patients. Materials and Methods: This study included 236 patients with endometrial carcinoma at Siriraj Hospital whom were diagnosed and treated from 2003 through 2006. The clinical characteristics, pathological features, treatment and clinical outcomes were collected from the medical records. The 5-year survival was calculated according to 2009 FIGO staging. Results: Non-endometrioid carcinoma of endometrium accounted for 10.2% of all endometrial carcinomas (24/236 patients). The 5-year survival rate was significantly lower in the non-endometrioid group compared to the endometrioid group (77.3% vs 96%, p<0.001) and clinical data pointed to greater malignancy. Conclusions: Non-endometrioid carcinoma of endometrium is relative rare but is more aggressive, has more distant metastasis at diagnosis with a worse survival rate than endometrioid carcinoma. Only patients in stage IA with no residual disease on a hysterectomy specimen may not need adjuvant treatment. -
Chian, Song;Li, Yin-Yan;Wang, Xiu-Jun;Tang, Xiu-Wen 2911
Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromises its efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620) long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX). Compared with parental cell lines,$IC_{50}$ s for various chemotherapeutic agents (oxaliplatin, cisplatin and doxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclear factor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1). Furthermore, luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin also inhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and$GST{\alpha}1/2$ ] expression and decreased reduced glutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolin combined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined index values below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to the development of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell lines to chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeutic response. -
Liu, Lei;Zhang, Dong;Jiao, Jing-Hua;Wang, Yu;Wu, Jing-Yang;Huang, De-Sheng 2917
Background: The p53-binding protein 1 (TP53BP1) gene may be involved in the development of cancer through disrupting DNA repair. However, investigation of associations between TP53BP1 rs2602141 A/C polymorphism and cancer have yielded contradictory and inconclusive outcomes. We therefore performed a meta-analysis to evaluate the association between the TP53BP1 rs2602141 A/C polymorphism and cancer susceptibility. Materials and Methods: Published literature from PubMed, Medline, the Cochrane Library, EMbase, Web of Science, Google (scholar), CBMDisc, Chongqing VIP database, and CNKI database were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models. Publication bias was estimated using funnel plots, Begg's and Egger's test. Results: A total of seven studies (3,018 cases and 5,548 controls) were included in the meta-analysis. Our results showed that the genotype distribution of TP53BP1 rs2602141 A/C was not associated with cancer risk overall. However, on subgroup analysis, we found that TP53BP1 rs2602141 A/C was associated with cancer risk within an allele model (A vs C, OR=1.14, 95%CI: 1.01-1.29) and a codominant model (AA vs CC, OR=1.36, 95%CI: 1.06-1.74) in Asians rather than in Caucasians. Subgroup analysis by cancer type, genotype, and with or without adjustment for controls showed no significant association. Conclusions: The findings suggested an association between rs2602141 A/C polymorphism in TP53BP1 gene and increased risk of cancer in Asians. -
Can, Alper;Dogan, Erkan;Bayoglu, Ibrahim Vedat;Tatli, Ali Murat;Besiroglu, Mehmet;Kocer, Murat;Dulger, Ahmet Cumhur;Uyeturk, Ummugul;Kivrak, Derya;Orakci, Zuat;Bal, Oznur;Kacan, Turgut;Olmez, Sehmus;Turan, Nedim;Ozbay, Mehmet Fatih;Alacacioglu, Ahmet 2923
Background: Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. Materials and Methods: Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. Results: Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. Conclusions: According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients. -
Arun-Muthuvel, Veluswamy;Jaya, Vijayaraghavan 2929
Purpose: To evaluate the diagnostic performances of risk of malignancy index (RMI), CA-125 and ultrasound score in differentiating between benign and borderline or malignant ovarian tumors and find the best diagnostic test for referral of suspected malignant ovarian cases to gynaecologic oncologists. Materials and Methods: This prospective study covered 467 women with pelvic tumors scheduled for surgery at our hospital between July 2011 and July 2013. The RMI was obtained from ultrasound score, CA125 and menopausal status. The diagnostic values of each parameter and the RMI were determined and compared using Statistical Packages for Social Sciences Version 14.0.1. Results: In our study, 61% of ovarian tumors were malignant in the post-menopausal age group. RMI with a cut-off 150 had sensitivity of 84% and specificity of 97% in detecting ovarian cancer. CA-125>30 had a sensitivity of 84% and a specificity of 83%. An ultrasound score more than 2 had a sensitivity of 96% and specificity of 81%. RMI had the least false malignant cases thus avoiding unnecessary laparotomies. Ultrasound when used individually had the best sensitivity but poor specificity. Conclusions: Our study has demonstrated the RMI to be an easy, simple and applicable method in the primary evaluation of patients with pelvic masses. It can be used to refer suspected malignant patients to be operated by a gynaecologic oncologist. Other models of preoperative evaluation should be developed to improve the detection of early stage invasive, borderline and non-epithelial ovarian cancers. -
Involvement of a multidisciplinary team in cancer care may have added benefits over the existing system of patient management. A paradigm shift in the current patient management would allow more focus on nutritional support, in addition to clinical care. Malnutrition, a common problem in cancer patients, needs special attention from the early days of cancer care to improve quality of life and treatment outcomes. Patient management teams with trained oncology dietitians may provide quality personalized nutritional care to cancer patients.
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Studies of the causes of cancer, early detection, prevention or treatment need accurate, comprehensive, and timely cancer data. The clinical laboratory provides important cancer information needed for physicians which influence clinical decisions regarding treatment, diagnosis and patient monitoring. Poor communication between health care providers and clinical laboratory personnel can lead to medical errors and wrong decisions in providing cancer care. Because of the key impact of laboratory information on cancer diagnosis and treatment the quality of the tests, lab reports, and appropriate lab management are very important. A laboratory information management system (LIMS) can have an important role in diagnosis, fast and effective access to cancer data, decrease redundancy and costs, and facilitate the integration and collection of data from different types of instruments and systems. In spite of significant advantages LIMS is limited by factors such as problems in adaption to new instruments that may change existing work processes. Applications of intelligent software simultaneously with existing information systems, in addition to remove these restrictions, have important benefits including adding additional non-laboratory-generated information to the reports, facilitating decision making, and improving quality and productivity of cancer care services. Laboratory systems must have flexibility to change and have the capability to develop and benefit from intelligent devices. Intelligent laboratory information management systems need to benefit from informatics tools and latest technologies like open sources. The aim of this commentary is to survey application, opportunities and necessity of intelligent clinical laboratory as a tool to increase cancer care management productivity.