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.
KSCI제15권19호
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Cervical cancer is the most common gynecologic malignancy worldwide and development of new therapeutic strategies and anticancer agents is an urgent priority. Plants have remained an important source in the search for novel cytotoxic compounds and several polyphenolic flavonoids possess antitumor properties. In this review article, data about potential anticarcinogenic activity of common natural flavonoids on various human cervical cancer cell lines are compiled and analyzed showing perspectives for the use of these secondary metabolites in the treatment of cervical carcinoma as well as in the development of novel chemotherapeutic drugs. Such anticancer effects of flavonoids seem to differentially depend on the cellular type and origin of cervical carcinoma creating possibilities for specific targeting in the future. Besides the cytotoxic activity per se, several flavonoids can also contribute to the increase in efficacy of conventional therapies rendering tumor cells more sensitive to standard chemotherapeutics and irradiation. Although the current knowledge is still rather scarce and further studies are certainly needed, it is clear that natural flavonoids may have a great potential to benefit cervical cancer patients.
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Imani-Saber, Zeinab;Ghafouri-Fard, Soudeh 8019
The promyelocytic leukemia (PML) gene is a gene known to be a tumor suppressor, although recent data suggest that it has a dual function in tumorigenesis. It was initially discovered in acute promyelocytic leukemia (APL) in which a t(15; 17) chromosomal translocation fused it to the retinoic acid receptor alpha ($RAR{\alpha}$ ). It has been shown to be involved in various types of cancer. It has at least 6 nuclear isoforms and a cytoplasmic type with different characteristics. Its multiple functions in growth inhibition, apoptosis induction, replicative senescence, inhibition of oncogenic transformation, and suppression of migration and angiogenesis have made it a therapeutic target for cancer therapy. However, its dual role in the process of tumorigenesis has made this field challenging. In this review, we discuss PML structure, functions and expression in tumors. -
Genetic instability contributes to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Microsatellite instability (MSI) has been hypothesized to be involved in carcinogenesis, althgough its mechanisms and exact roles in gastric cancer remain largely unknown. Our aim was to identify associated clinicopathological characteristics and prognostic value of MSI in gastric cancer and precancerous lesions including gastritis, metaplasia, dysplasia, and adenoma. Because mitochondrial DNA has a different genetic system from nuclear DNA, the results of both nuclear MSI and mitochondrial MSI in gastric cancer were reviewed. This review provides evidence that genetic instability of nuclear and mitochondrial DNAs contributes to early stages of gastric carcinogenesis and suggests possible roles in predicting prognosis.
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Dang, Yuan;Wang, Ying-Chao;Huang, Qiao-Jia 8035
Gastric cancer is the second after lung cause of cancer-related mortality in the world. Early detection and treatment can lead to a long survival time. Recently microarrays and next generation sequencing (NGS) have become very useful tools of comprehensive research into gastric cancer, facilitating the identification of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discovery to practical clinical benefits. Although there are many biomarkers and target agents, only a minority of patients are tested and treated accordingly. Microarray technology with maturity was established more than 10 years ago, and has been widely used in the study of functional genomics, systems biology, and genomes in medicine. Second generation sequencing technology is more recent, but development is very fast, and it has been applied to the genome, including sequencing and epigenetics and many aspects of functional genomics. Here we review insights gained from these studies regarding the technology of microarray and NGS, how to elucidate the molecular basis of gastric cancer and identify potential therapeutic targets, and how to analyse candidate genes. We also discuss the challenges and future directions of such efforts. -
Rana, Aamir;Attar, Rukset;Qureshi, Muhammad Zahid;Gasparri, Maria Luisa;Donato, Violante Di;Ali, Ghulam Muhammad;Farooqi, Ammad Ahmad 8041
In-depth analysis of how TRAIL signals through death receptors to induce apoptosis in cancer cells using high throughput technologies has added new layers of knowledge. However, the wealth of information has also highlighted the fact that TRAIL induced apoptosis may be impaired as evidenced by experimental findings obtained from TRAIL resistant cancer cell lines. Overwhelmingly, increasing understanding of TRAIL mediated apoptosis has helped in identifying synthetic and natural compounds which can restore TRAIL induced apoptosis via functionalization of either extrinsic or intrinsic pathways. Increasingly it is being realized that biologically active phytochemicals modulate TRAIL induced apoptosis, as evidenced by cell-based studies. In this review we have attempted to provide an overview of how different phytonutrients have shown efficacy in restoring apoptosis in TRAIL resistant cancer cells. We partition this review into how the TRAIL mediated signaling landscape has broadened over the years and how TRAIL induced signaling machinery crosstalks with autophagic protein networks. Subsequently, we provide a generalized view of considerable biological activity of coumarins against a wide range of cancer cell lines and how coumarins (psoralidin and esculetin) isolated from natural sources have improved TRAIL induced apoptosis in resistant cancer cells. We summarize recent updates on piperlongumine, phenethyl isothiocyanate and luteolin induced activation of TRAIL mediated apoptosis. The data obtained from pre-clinical studies will be helpful in translation of information from benchtop to the bedside. -
Aras, Aliye;Iqbal, Muhammed Javed;Naqvi, Syed Kamran-Ul-Hassan;Gercek, Yusuf Can;Boztas, Kadir;Gasparri, Maria Luisa;Shatynska-Mytsyk, Iryna;Fayyaz, Sundas;Farooqi, Ammad Ahmad 8047
Cancer is a multifaceted and genomically complex disease and research over decades has gradually and sequentially shown that essential biological mechanisms including cell cycle arrest and apoptosis are deregulated. The benefits of essential oils from different plants have started to gain appreciation as evidenced by data obtained from cancer cell lines and xenografted mice. Encouraging results obtained from preclinical studies have attracted considerable attention and various phytochemicals have entered into clinical trials. -
Hong, Yuan;Chen, Xue-Qin;Li, Jiao-Yuan;Liu, Cheng;Shen, Na;Zhu, Bei-Bei;Gong, Jing;Chen, Wei 8051
Background: A common genetic variant rs3757318, located in intron of C6orf97, was firstly identified to be associated with breast cancer (BC) risk by a genome-wide association (GWA) study. However, subsequent validation studies with different ethnicities have yielded conflicting results. Materials and Methods: We performed a meta-analysis to synthesize all available data for evaluating the precise effect of this variant on BC susceptibility. Results: A total of 8 articles containing 11 studies with 62,891 cases and 65,635 controls were included in this meta-analysis. When compared to the G allele, the rs3757318-A allele was significantly associated with BC risk with the pooled OR of 1.21 (95% CI=1.15 - 1.29, P<0.001) but with obvious between-study heterogeneity (P=0.040). Stratified analysis suggested that diversity of ethnicity along with control source may explain part of the heterogeneity. Similarly, significant associations were also identified in heterozygote, homozygote, dominant and recessive genetic models. Sensitivity and publication bias analyses indicated robust stability of our results. Conclusions: Our present meta-analysis demonstrated that the variant rs3757318 is associated with increased BC risk. Nevertheless, further studies are needed to clarify the underlying biological mechanisms. -
Zhang, Lei;Liu, Yu-Jie;Jiang, Shuang-Quan;Cui, Hao;Li, Zi-Yao;Tian, Jia-Wei 8057
Purpose: The aim of the study was to evaluate the correlation of ultrasound features with breast cancer molecular status. Materials and Methods: A retrospective review was performed of ultrasound findings in 263 patients diagnosed with breast invasive ductal carcinoma for comparison with immunohistochemistric results were obtained from each lesion. Relationships between ultrasound findings and molecular status were investigated by using multiple regression analysis by means of stepwise logistic regression. Differences in ultrasound criteria were assessed among women with different molecular status. Results: ER positivity was associated with small size, lobulate, angular or spiculated margin contours, absence of calcification, posterior tumor shadowing and low elasticity score; PR positivity was associated with small size, lobulate or angular or spiculated margin contours and absence of calcification; HER2 positivity was associated with presence of calcification and absence of any echogenic halo. The calculated models of predicted molecular status were accurate and discriminating with AUCs of 0.78, 0.74, and 0.74, respectively. Conclusions: Breast cnacer ultrasound features show some correlation with the molecular status. These models may help to expand the scope of ultrasound in predicting tumor biology. -
Nessa, Ashrafun;Rashid, Mohammad Harun Ur;Jahan, Munira;Ferdous, Noor-E;Nahar, Pervin Akhter Shamsun;Chowdhury, Afroza 8063
Background: Cervical cancer is a major public health problem in Bangladesh. Persistence of high risk human papillomavirus (HRHPV) influences the progression of the disease, with an important role in followup for cervical intraepithelial neoplasia (CIN). Objective: To establish application of high risk HPV DNA test in the follow-up of women after treatment of CIN. Materials and Methods: This cross-sectional and hospital based study was carried out among 145 CIN treated women during the previous six months to three years at the colposcopy clinic of Bangabandhu Sheikh Mujib Medical University, Dhaka, between January 2011 and June 2012. Pap smear and HPV samples were collected and colposcopy was performed to find out the persistence of the disease. Cervical samples obtained were tested for HPV DNA using the Hybrid Capture II (HC-II) test. A cervical biopsy was collected whenever necessary. The results were compared to assess the efficacy of different methods during follow up such as Pap smear, HPV test and colposcopy. Results: Mean age of the recruited women (n=145) was 33.6 (${\pm}7.6$ ), mean age of marriage was 16.8 (${\pm}2.9$ ) and mean age of 1st delivery was 18.8 (${\pm}3.5$ ) years. More than half had high grade CIN before treatment and 115 (79.3%) women were managed by LEEP and 20.7% were managed by cold coagulation. Among the 145 treated women, 139 were negative for HPV DNA and six of them (4.1%) were HPV positive. Sensitivity of Pap smear (40.0) and HPV DNA test (40.0) was poor, but specificity was quite satisfactory (>93.0) for all the tests. Conclusions: The high risk HPV DNA test can be an effective method of identifying residual disease. It can be added to colposcopy and this should be applied to all treated women attending for their first or second post-treatment follow-up visit at 6 months to one year, irrespective of the grade of treated CIN. -
Cioca, Andreea;Cimpean, Anca;Ceausu, Raluca;Fit, Ana-Maria;Zaharie, Teodor;Al-Hajjar, Nadim;Puia, Vlad;Raica, Marius 8069
Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide, with a high mortality. Most patients present with late stage disease, when the treatment options are limited to systemic chemotherapy. The purpose of our study was to evaluate the significance of p53 and EGFR expression in HCC, and to determine whether these two markers correlate with conventional parameters of prognosis. Materials and Methods: Our study included a total of 45 patients, diagnosed histopathologically with HCC. Clinicopathological data including sex, age, tumor necrosis, tumor size, histologic grading, tumor stage, the presence of cirrhosis and chronic hepatitis, were recorded from the Institute database. Three independent microscopic fields were selected for each sample and all the tumor cells within each microscopic field were counted, and then the positive percent of p53 cells were calculated. Three staining patterns were recognized: diffuse, heterogenous and focal. The intensity of EGFR staining was scored on a scale of 0-3+: 0 no staining; 1+ when a weak membrane staining was observed; 2+ when membrane staining is more intense than in 1+, but less than 3+, and 3+ when intense dark brown staining delineated the membrane. To determine the relationship between EGFR expression and p53, we performed double staining in the same HCC specimens. Results: By immunohistochemical staining, p53 protein was detected in tumor cell nuclei in 20 HCCs (44%). We found a significant correlation between the intensity of p53 expression and the histological grade (p=0.008). EGFR expression was detected in 17 (38%) cases, linked to histological grade (p=0.039). Moreover, the intensity of p53 expression was significantly correlated with EGFR intensity (p=0.014). Conclusions: Our results suggest that overexpression of p53 and EGFR plays an important role in hepatocarcinogenesis and contributes to more advanced disease. These markers are not only valuable predictors of prognosis in HCC, but they are also rational targets for new anti-tumor strategies. -
Zheng, Tian-Liang;Cao, Ke;Liang, Cui;Zhang, Kai;Guo, Hai-Zhou;Li, De-Ping;Zhao, Song 8075
Background: The classical inflammatory biomarker, C-reactive protein (CRP), has been identified to be related to progression of esophageal cancer. Some research showed that elevated pretreatment serum CRP indicated a poor prognosis, but results have been inconsistent. Materials and Methods: We searched the Medline, Embase and the Cochrane Central Search Library for suitable studies and a meta-analysis of eleven (1,886 patients) was conducted to examine the relationship between elevated serum CRP level and overall survival (OS) in esophageal cancer cases. Moreover, correlation analyses were conducted to assess links between pretreatment serum CRP level and tumor node metastasis (TNM) stage as well as T, N, M grade, respectively. Results: The pooled analysis showed that elevated pretreatment serum CRP level was significantly associated with poorer overall survival (HR 2.09, 95%CI 1.52-2.87, p<0.01). Subgroup analyses were conducted by "country", "cut-off value", "treatment" and "number of patients", and no single factor could alter the result. Elevated pretreatment serum CRP was significantly correlated with more advanced TNM stage and T, N, M grade respectively. Conclusions: Elevated pretreatment serum CRP levels are associated with poorer prognosis in esophageal cancer patients, and could serve as a useful biomarker for outcome prediction. -
Chen, Xiang-Jun;Zhou, Tao-You;Chen, Min;Pu, Dan 8083
Purpose: To investigate the association of IL-17F rs763780T>C with cancer risk. Materials and Methods: We searched the Cochrane Central Library, PubMed, MEDLINE, EMBASE, CNKI (China National Knowledge Infrastructure) and WangFang databases until May 2014 for a meta-analysis conducted using RevMan 5.2 software. Results: A total of ten papers were included into this meta analysis, involving 3, 336 cases and 4, 217 healthy people. There were no significant differences on association of IL-17F rs763780T>C polymorphism with cancer risk except in the CC vs TT genetic model. Although the the risk in the gastric cancer group is higher than that in control group, there were no significant differences on the association of IL-17F rs763780T>C polymorphism with other cancers. Conclusions: Our meta analysis reveal the IL-17A rs763780T>C gene polymorphism is involved in risk of gastric cancer but not other tumor types. -
Bano, Nusrat;Najam, Rahila;Qazi, Faaiza;Mateen, Ahmed 8089
Background: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX. Materials and Methods: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared. Results: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin$130mg/m^2$ ). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin$85mg/m^2$ ). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin$100mg/m^2$ ). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05). Conclusions: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm. -
Yusof, Azianey;Chia, Yook Chin;Hasni, Yasmin Mohd 8095
Background: Worldwide, over half a million women died of breast cancer in 2011 alone. Mammography screening is associated with a reduction of 20 to 35% in breast cancer mortality. The aim of this study was to determine the awareness and practice of mammography screening and predictors of its uptake in Malaysian women attending a primary care clinic. Materials and Methods: A cross-sectional study was carried out among women aged 40 to 74 years attending a primary care clinic in Selangor, Malaysia. An assisted structured questionnaire included questions on socio-demography, source of information and level of knowledge. An adapted version of the revised Champion Health Belief Model Scale plus other associated factors for mammography screening up-take were also included as part of the questionnaire. Predictors for mammography screening uptake were only determined in those who were aware about mammography screening. Significant predictors were determined by logistic regression. Results: 447 women were recruited for this study; 99.1% of them (n: 411) were aware about breast cancer. Only 50.1% (n: 206) had knowledge about mammography screening. Prevalence of clinical breast-examination (CBE) was 23.3% (n: 104) and mammography screening up-take was 13.2% (n: 59). The predictors for the latter were those who have had clinical breast-examination (aOR=17.58, 95%CI: 7.68-39.82) and those aged between 50 to 59 years (aOR=3.94, 95%CI: 1.61-9.66) as well as those aged 60 years and above (aOR=6.91, 95%CI: 2.28-20.94). Good knowledge and positive beliefs about mammography screening were not associated with mammography screening uptake. Conclusions: Half of our Malaysian women were aware about mammography screening. However, the uptake of mammography was low. Previous CBE and older age were significant predictors of mammography screening uptake. Increasing CBE services may increase compliance with guidelines. -
Wang, Meng;Zhang, Yuan-Chuan;Yang, Xu-Yang;Wang, Zi-Qiang 8101
Background: Although mucinous adenocarcinoma has been recognized for a long time, whether it is associated with a poorer prognosis in colorectal cancer patients is still controversial. Many studies put emphasis on mucinous adenocarcinoma containing mucin component${\geq}50%$ . Only a few studies have analyzed cases with a mucin component <50%. Objectives: This study aimed to analyze the prognostic value of different mucin component proportions in patients with stage III rectal cancer. Materials and Methods: Clinical, pathological and follow-up data of 136 patients with the stage III rectal cancer were collected. Every variable was analyzed by univariate analysis, then multivariate analysis and survival analysis were further performed. Results: Univariate analysis showed pathologic T stage, lymphovascular invasion, and histological subtype were statistically significant for DFS. Pathologic T stage was significant for OS. Histological subtype and lymphovascular invasion were independent prognostic factors in multivariate analysis for DFS, and histological subtype was the only independent prognostic factor for OS. Survival curves showed the survival time of mucinous adenocarcinoma (MUC) was shorter than non-MUC (adenocarcinomas with a mucin component <50% and without mucin component). Conclusions: Histological subtype (tumor with different mucin component) was an independent prognostic factor for both DFS and OS. Patients with MUC had a worse prognosis than their non-MUC counterparts with stage III rectal carcinoma. -
Wang, Yi-Xuan;Xu, Shu-Qing;Chen, Xiang-Hui;Liu, Rui-Si;Liang, Zhong-Qin 8107
The aim of this study was to investigate the effects of olanzapine on growth inhibition as well as autophagy in glioma cells in vitro and in vivo. The proliferation of both LN229 and T98 glioma cells, measured by MTT assay, was suppressed in a concentration-dependent and time-dependent manner. Moreover, apoptosis of both cells was significantly increased with the treatment of olanzapine as evidenced by increased Bcl-2 expression, Hoechst 33258 staining and annexinV-FITC/PI staining. Olanzapine treatment also enhanced activation of autophagy with increased expression of LC3-II, expression of protein p62, a substrate of autophagy, being decreased. The growth inhibition by olanzapine in both glioma cell lines could be blocked by co-treatment with 3-MA, an autophagy inhibitor. Furthermore, olanzapine effectively blocked the growth of subcutaneous xenografts of LN229 glioma cells in vivo. The increased level of protein LC3-II and decreased level of p62 followed by a decreased level of Bcl-2, suggesting that autophagy may contribute to apoptosis. In addition, reduced proliferation of glioma cells was shown by a decrease of Ki-67 staining and increased caspase-3 staining indicative of apoptosis in mouse xenografts. These results indicated that olanzapine inhibited the growth of glioma cells accompanied by induction of autophagy and apoptosis both in vitro and in vivo. Olanzapine-induced autophagy plays a tumor-suppressing role in glioma cells. -
Ameade, Evans Paul Kwame;Amalba, Anthony;Kudjo, Theresa;Kumah, Mark Kojo;Mohammed, Baba Sulemana 8115
Background: Breast cancer continues to be the most common type of cancer afflicting many women worldwide. Presently, educational campaigns and research target only women as if men have no role in the management of this disease. The study examined the willingness of male partners to assist in early female breast cancer detection as well as their awareness and knowledge levels. Materials and Methods: Using a semi-structured questionnaire, data was collected from 500 public servants within the Tamale Metropolis and analyzed in SPSS. Results: The level of awareness of breast cancer was very high (98.8%) but there was a low level of knowledge of breast cancer among the male population. Marital status and religion had no effect on attitude, but increasing educational status significantly increased knowledge and positive attitude towards breast cancer examination (${\chi}^2$ =4.255, p=0.0391). The majority (92.0%) agreed that men can assist in early breast cancer detection and 96.2% were willing to be provided with breast examination skills. Conclusions: Although level of awareness on female breast cancers among the men was high, they generally lack knowledge of the disease. Majority of male partners want to assist in early breast cancer detection if provided with the necessary skills. -
Missaoui, Nabiha;Abdelkarim, Soumaya Ben;Ayachi, Malak;Hmissa, Sihem 8121
Background: Ovarian mucinous carcinoma has a poor prognosis in advanced stages and a poor response to conventional chemotherapy. An efficient treatment is not yet available. We heere investigated HER2 expression and the potential for trastuzumab therapy in ovarian mucinous tumors. Materials and Methods: Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tissue from 27 ovarian mucinous tumors including 14 carcinomas and 13 borderline tumors diagnosed in the Pathology Department, Farhet Hached Hospital, Sousse, between 1993 and 2013. The HercepTest (DAKO) was used for immunohistochemistry. Results: HER2 expression was observed in only one borderline tumor (7.7%) and in 14.3% of mucinous carcinomas of the ovary. Conclusions: Our results suggest that trastuzumab therapy would be an option for patients with mucinous carcinoma when the tumor has HER2 overexpression. -
Loh, Siew Yim;Lee, Shing Yee;Murray, Liam 8127
Background: Qigong is highly favoured among Asian breast cancer survivors for enhancing health. This study examined the hypothesis that quality of life (QoL) in the Qigong group is better than the placebo (aerobic) or usual care group. Materials and Methods: A total of 197 participants were randomly assigned to either the 8-week Kuala Lumpur Qigong Trial or control groups in 2010-2011. Measurement taken at baseline and post-intervention included QoL, distress and fatigue. Analysis of covariance (ANCOVA) and Kruskal Wallis were used to examine for differences between groups in the measurements. Results: There were 95 consenting participants in this 8week trial. The adherence rates were 63% for Qigong and 65% for the placebo group. The Qigong group showed significant marginal improvement in Quality of life scores compared to placebo (mean difference=7.3 unit; p=0.036), compared to usual care (mean difference=6.7 unit; p=0.048) on Functional Assessment Cancer Therapy-Breast measure. There were no significant changes between the placebo and usual care groups in fatigue or distress at post intervention (8-week). Conclusions: Cancer survivors who participated in the Qigong intervention showed slightly better QOL. Follow up studies are greatly needed to evaluate which subgroups may best benefit from Qigong. With a steep rise of cancer survivors, there is an urgent need to explore and engage more cultural means of physical activity to fight side effects of treatment and for cancer control in developing countries. -
Khakbazan, Zohreh;Roudsari, Robab Latifnejad;Taghipour, Ali;Mohammadi, Eesa;Pour, Ramesh Omrani 8135
Background: Breast cancer is the most common cancer in Iranian women and usually features delayed presentation and late diagnosis. Interpretation of symptoms, as the most important step, has a significant impact on patient delay in seeking treatment. There is a dearth of studies on symptom appraisal and the process leading to seeking help in breast cancer patients. This study explored the perceptions and experiences of Iranian women with self-detected possible breast cancer symptoms. Materials and Methods: A qualitative method was conducted involving in-depth semi-structured interviews with 27 Iranian women with self-discovered breast cancer symptoms. Participants were purposefully selected from women who attended Cancer Institute of Tehran University of Medical Sciences during June 2012 to August 2013. The audiotaped interviews were transcribed and analyzed using conventional content analysis with MAXQDA soft ware version 10. The trustworthiness of the study was verified by prolonged engagement, member validation of codes, and thick description. Results: The main concepts emerging from data analysis were categorized in four categories: symptom recognition, labeling of symptoms, interactive understanding, and confronting the fear of cancer. Symptom recognition through breast self-examination, symptom monitoring and employing prior knowledge distinguished normal from abnormal symptoms and accompanied with perception of being at risk of breast cancer led to symptom labeling. Social interaction by selective disclosure and receiving reassurance from a consultant led to confirmation or redefinition of the situation. Perceived seriousness of the situation and social meanings of breast cancer as a stigmatized and incurable illness associated with loss of femininity were reasons for patient worries and fear. Conclusions: This study emphasized that entangled cognitive, emotional and socio-cultural responses affecting understanding of symptom seriousness require further investigation. It is suggested that programs aimed at shortening patient delay in breast cancer should be focused on improving women's knowledge and self-awareness of breast cancer, in addition to correcting their social beliefs. -
Huang, Ai-Li;Liu, Shu-Guang;Qi, Wen-Juan;Zhao, Yun-Fei;Li, Yu-Mei;Lei, Bin;Sheng, Wen-Jie;Shen, Hong 8143
To investigate the expression intensity and prognostic significance of TGF-${\beta}1$ protein in non-small cell lung cancer (NSCLC), immunohistochemistry was carried out in 194 cases of NSCLC and 24 cases of normal lung tissues by SP methods. The PU (positive unit) value was used to assess the TGF-${\beta}1$ protein expression in systematically selected fields under the microscope with Leica Q500MC image analysis. We found that the TGF-${\beta}1$ PU value was nearly two-fold higher in NSCLC than in normal lung tissues (p=0.000), being associated with TNM stages (p=0.000) and lymph node metastases (p=0.000), but not to patient age, gender, smoking history, tumor differentiation, histological subtype and tumor location (P>0.05). Univariate analysis indicated that patients with high TGF-${\beta}1$ protein expression and lymph node metastases demonstrated a poor prognosis (both p=0.000,). Multivariate analysis showed that TGF-${\beta}1$ protein expression (RR = 2.565, p=0.002) and lymph node metastases (RR=1.874, p=0.030) were also independent prognostic factors. Thus, TGF-${\beta}1$ protein expression may be correlated to oncogenesis and serve as an independent prognostic biomarker for NSCLC. -
Liu, Jian;Gao, Yun-Hua;Li, Ding-Dong;Gao, Yan-Chun;Hou, Ling-Mi;Xie, Ting 8149
Background: To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Materials and Methods: Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. Results: The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (P<0.05). Conclusions: The ability of CEUS qualitative analysis to identify breast tumor lumps is better than with quantitative analysis. -
Suganya, Jeyabaskar;Radha, Mahendran;Naorem, Devi Leimarembi;Nishandhini, Marimuthu 8155
Background: Breast cancer is the serious health concern in India causing the highest mortality rate in females, which occurs due to uncontrolled cell division and can be metastasize to other parts of the human body. Interactions with estrogen receptor (ER) alpha are mainly responsible for the malignant tumors with regulation of the transcription of various genes as a transcription factor. Most of the drugs currently used for the breast cancer treatment produce various side effects and hence we focused on natural compounds which do not exhibit any toxic effect against normal human cells. Materials and Methods: Structure of human ER was retrieved from the Protein Data Bank and the structures of flavonoid compounds have been collected from PubChem database. Molecular docking and drug likeness studies were performed for those natural compounds to evaluate and analyze the anti-breast cancer activity. Results: Finally two compounds satisfying the Lipinski's rule of five were reported. The two compounds also exhibited highest binding affinity with human ER greater than 10.5 Kcal/mol. Conclusions: The results of this study can be implemented in the drug designing pipeline. -
Sabet, Mehrdad Nasrollahzadeh;Rakhshan, Azadeh;Erfani, Elham;Madjd, Zahra 8161
Background: Cancer stem cells (CSC) are populations of cells responsible for tumor initiation, progression and therapeutic resistance in many cancers. In the present study, we aimed to investigate the expression pattern and clinical significance of two CSC markers, CD133 and Nestin, in a series of skin tumors. Materials and Methods: One hundred and thirteen paraffin blocks from skin cancers including 16 (14%) cases of melanoma, 37 (33%) of squamous cell cancer (SCC) and 60 (53%) of basal cell cancer (BCC) were collected and assembled in a tissue microarray (TMA). The samples were immunohistochemically examined for the expression of CD133 and Nestin. Expression of these markers was also correlated with clinicopathological parameters. Results: A significant difference was observed in the expression of CD133 and Nestin in melanomas, SCC and BCC (p value=0.001). Furthermore, the level of expression was significantly higher in the melanomas compared to the SCC and BCC tumors. Expression of CD133 in the melanoma was significantly associated with increased tumor invasiveness (p value=0.05), a higher rate of metastasis (p value=0.04) and the presence of ulceration (p value=0.02). Increased expression of Nestin was observed in metastatic melanoma (p value=0.04), while no statistically significant correlation was found with other clinicopathological parameters including Breslow thickness, Clark level and ulceration. Conclusions: Elevated expression levels of CD133 and Nestin in the melanomas are associated with advanced disease, with more aggressive and metastatic skin tumors. Therefore, these markers could be potential therapeutic targets for malignant tumors of the skin. -
Xu, Ping;Zhang, Wen-Bo;Cai, Xin-Hua;Lu, Dan-Dan;He, Xiao-Yang;Qiu, Pei-Yong;Wu, Jiao 8171
Background: To study the radioprotective effects of flavonoids from Rosa roxburghii Tratt (FRT). Materials and Methods: The radioprotective effects of FRT were investigated by examining cell viability, 30-day survival of mice and the number of colony-forming units in spleen (CFU-S) after total-body 60Co irradiation. Results: The survival rates of irradiated cells gradually increased with increasing concentrations of FRT. The survival rate was the highest at 87% with a concentration of$30{\mu}g/mL$ . Pretreatment with FRT was needed to realize its radioprotective activity in mice at the dose of 60 mg/kg. With the increasing doses of 30 mg/kg, 60 mg/kg and 120 mg/kg, the numbers of CFU-S increased, and were significantly different compared with the control group. Conclusions: Pretreatment with FRT prior to irradiation resulted in significantly higher cell survival at 24 h after 5 Gy radiation, increased 30-day survival in mice after exposure to a potentially lethal dose of 8 Gy, and resulted in a higher number of CFU-S in mice after exposure to a dose of 6 Gy. These results collectively indicate that FRT is an effective radioprotective agent. -
Qi, Wei-Xiang;Fu, Shen;Zhang, Qing;Guo, Xiao-Mao 8177
Background: Blocking angiogenesis by targeting vascular endothelial growth factor (VEGF) signaling pathway to inhibit tumor growth has proven to be successful in treating a variety of different metastatic tumor types, including kidney, colon, ovarian, and lung cancers, but its role in castration-resistant prostate cancer (CRPC) is still unknown. We here aimed to determine the efficacy and toxicities of anti-VEGF agents in patients with CRPC. Materials and Methods: The databases of PubMed, Web of Science and abstracts presented at the American Society of Clinical Oncology up to March 31, 2014 were searched for relevant articles. Pooled estimates of the objective response rate (ORR) and prostate-specific antigen (PSA) response rate (decline${\geq}50%$ ) were calculated using the Comprehensive Meta-Analysis (version 2.2.064) software. Median weighted progression-free survival (PFS) and overall survival (OS) time for anti-VEGF monotherapy and anti-VEGF-based doublets were compared by two-sided Student's t test. Results: A total of 3,841 patients from 19 prospective studies (4 randomized controlled trials and 15 prospective nonrandomized cohort studies) were included for analysis. The pooled ORR was 12.4% with a higher response rate of 26.4% (95%CI, 13.6-44.9%) for anti-VEGF-based combinations vs. 6.7% (95%CI, 3.5-12.7%) for anti-VEGF alone (p=0.004). Similarly, the pooled PSA response rate was 32.4% with a higher PSA response rate of 52.8% (95%CI: 40.2-65.1%) for anti-VEGF-based combinations vs. 7.3% (95%CI, 3.6-14.2%) for anti-VEGF alone (p<0.001). Median PFS and OS were 6.9 and 22.1 months with weighted median PFS of 5.6 vs. 6.9 months (p<0.001) and weighted median OS of 13.1 vs. 22.1 months (p<0.001) for anti-VEGF monotherapy vs. anti-VEGF-based doublets. Conclusions: With available evidence, this pooled analysis indicates that anti-VEGF monotherapy has a modest effect in patients with CRPC, and clinical benefits gained from anti-VEGF-based doublets appear greater than anti-VEGF monotherapy. -
Athirajan, Vimmitra;Razak, Ishak Abdul;Thurairajah, Nalina;Ghani, Wan Maria Nabillah;Ching, Helen-Ng Lee;Yang, Yi-Hsin;Peng, Karen-Ng Lee;Rahman, Zainal Ariff Abdul;Mustafa, Wan Mahadzir Wan;Abraham, Mannil Thomas;Kiong, Tay Keng;Mun, Yuen Kar;Jalil, Norma;Zain, Rosnah Binti 8183
Background: A comparative cross-sectional study involving oral cancer patients and healthy individuals was designed to investigate associations between retinol,${\alpha}$ -tocopherol and${\beta}$ -carotene with the risk of oral cancer. Materials and Methods: This study included a total of 240 matched cases and controls where subjects were selected from the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). Retinol,${\alpha}$ -tocopherol and${\beta}$ -carotene levels and intake were examined by high-performance liquid chromatography (HPLC) and food frequency questionnaire (FFQ) respectively. Results: It was found that results from the two methods applied did not correlate, so that further analysis was done using the HPLC method utilising blood serum. Serum levels of retinol and${\alpha}$ -tocopherol among cases ($0.177{\pm}0.081$ ,$1.649{\pm}1.670{\mu}g/ml$ ) were significantly lower than in controls ($0.264{\pm}0.137$ ,$3.225{\pm}2.054{\mu}g/ml$ ) (p<0.005). Although serum level of${\beta}$ -carotene among cases ($0.106{\pm}0.159{\mu}g/ml$ ) were lower compared to controls ($0.134{\pm}0.131{\mu}g/ml$ ), statistical significance was not observed. Logistic regression analysis showed that high serum level of retinol (OR=0.501, 95% CI=0.254-0.992, p<0.05) and${\alpha}$ -tocopherol (OR=0.184, 95% CI=0.091-0.370, p<0.05) was significantly related to lower risk of oral cancer, whereas no relationship was observed between${\beta}$ -carotene and oral cancer risk. Conclusions: High serum levels of retinol and${\alpha}$ -tocopherol confer protection against oral cancer risk. -
Rezaianzadeh, Abbas;Sepandi, Mojtaba;Akrami, Majid;Tabatabaee, Hamidreza;Rajaeefard, Abdolreza;Tahmasebi, Sedigheh;Talei, Abdolrasoul 8191
Background: Around 200,000 breast disorders are annually diagnosed all over the world. Fibrocystic changes are the most common breast disorder and fibroadenoma is the most prevalent benign breast tumor. The present study aimed to determine the spectrum, type and prevalence of breast masses in women referred to Shiraz University of Medical Sciences between 2004 and 2012. Materials and Methods: A cross-sectional study was conducted on the diagnostic reports data. Results: A total of 640 samples were studied. Most 57.3% of masses were detected in the left breast, 65%, 28.2% and 6.1% of cases presenting with benign, malignant, and inflammatory lesions, respectively. Among all the samples the most prevalent diagnosis (37.7%) was fibroadenoma and fibrocystic lesions (17%). 174 samples (96% of the malignant cases) were invasive. 6.5% of the benign, and 37% of the malignant cases occurred in post menopause women and the differences were statistically significant. Among those with malignant tumors lymph nodes were involved in 25.6% of menopausal women and 44.2% of non-menopausal ones, and the difference was statistically significant. Conclusions: Regular clinical breast examination beside mammographic follow-ups, especially during menopause, should be carried out as a priority and a national organized program should be designed for screening breast disorders. -
Su, Ling-Yan;Li, Xue-Lian;Shen, Li;Zhang, Yue;Zhao, Meng-Meng;Yin, Zhi-Hua;Su, Hong-Ying;Zhou, Bao-Sen 8197
Background: Telomerase reverse transcriptase (TERT) and cleft lip and palate trans-membrane 1 like (CLPTM1L) genes located on chromosome 5p15.33 are known to influence the susceptibility to various cancers. Here, we examined the association of TERT and CLPTM1L single nucleotide polymorphisms (SNPs) with hepatocellular carcinoma (HCC). Materials and Methods: Genotyping of TERT SNP rs2736098 and CLPTM1L SNP rs401681 was performed using TaqMan allelic discrimination assays in a case-control study of 201 HCC cases and 210 controls in a Chinese male population. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analyses. Results: Both the rs2736098 T allele of TERT and the rs401681 T allele of CLPTM1L were associated with a significantly increased risk of HCC (adjusted odds ratio [OR]=1.605, 95% confidence interval [CI]=1.164-2.213; adjusted OR=1.399, 95%CI=1.002-1.955, respectively). Individuals carrying both TERT and CLPTM1L risk genotypes had an even higher risk of HCC (adjusted OR=4.420, 95%CI= 2.319-8.425). The TERT rs2736098 T allele was also significantly associated with the level of the HCC clinical indicator alpha-fetoprotein (P=0.026). Conclusions: Our results show that genetic variants of TERT and CLPTM1L may contribute to HCC susceptibility in Chinese males. -
Lin, Ding-Sheng;Cai, Le-Yi;Ding, Jian;Gao, Wei-Yang 8203
Purpose: The aim of this study was to investigate the relationship between cell adhesion and anoikis evasion among human osteosarcoma cells (MG-63), and to further study the molecular mechanisms. Materials and Methods: Human osteosarcoma cells (MG-63) were assessed for apoptosis, and caspase-3, E-cadherin and${\beta}$ -catenin expression in EDTA and control non-EDTA groups. Results: MG-63 cells were predominantly aggregated when in suspension, and the suspended cells were more dispersed in the EDTA group. Following culture in suspension for 24 h, 48 h, or 72 h, the rates of apoptosis were$34.88%{\pm}3.64%$ ,$59.3%{\pm}7.22%$ and$78.5%{\pm}5.21%$ in the experimental group and$7.34%{\pm}2.13%$ ,$14.7%{\pm}3.69%$ , and$21.4%{\pm}3.60%$ in the control group, respectively. Caspase-3 expression progressively increased and E-cadherin and${\beta}$ -catenin were decreased in the experimental group, whereas there was no change in the control group. Conclusions: MG-63 cells could avoid anoikis through cell adhesion, and E-cadherin might play a role in this process. -
Nahvijou, Azin;Sari, Ali Akbari;Zendehdel, Kazem;Marnani, Ahmad Barati 8209
Background: Cervical cancer is a common, preventable and manageable disease in women worldwide. Objectives: This study was conducted to determine the cost of follow-up for suspicious precancerous cervical lesions within a screening program using Pap smear or HPV DNA test through the decision tree. Materials and Methods: Patient follow-up processes were determined using standard guidelines and consultation with specialists to design a decision tree model. Costs of treatment in both public and private sectors were identified according to the national tariffs in 2010 and determined based on decision tree and provided services (visits to specialists, colposcopy, and conization) with two modalities: Pap smear and HPV DNA test. The number of patients and the mean cost of treatment in each sector were calculated. The prevalence of lesions and HPV were obtained from literature to estimate the cost of treatment for each woman in the population. Results: Follow-up costs were determined using seven processes for Pap smear and 11 processes for HPV DNA test. The total cost of using Pap smear and HPV DNA process for each woman in the population was 36.1$ and 174$ respectively. Conclusions: The follow-up process for patients with suspicious cervical lesions needs to be included in the existing screening program. HPV DNA test is currently more expensive than Pap smear, it is suggested that we manage precancerous cervical lesions with this latter test. -
Saricanbaz, Irem;Karahacioglu, Eray;Ekinci, Ozgur;Bora, Huseyin;Kilic, Diclehan;Akmansu, Muge 8215
CD133 is one of the most important stem cell markers in solid cancers and Ki-67 is a marker that reflects cell proliferation. The relationships between the expression of CD133 and Ki-67 and prognosis in gastric carcinoma are unknown and need exploring. We examined 50 gastric cancer patients retrospectively in the Radiation Oncology Department of the Faculty of Medicine, Gazi University. CD133 and Ki-67 expression was examined using immunohistochemical staining. The survival rate in patients with CD133 positive expression was significantly worse than that in the patients with negative expression (p=0.04). Expression of CD133 had a positive correlation with that of Ki-67 (r=0.350; p=0.014). Multivariate analysis revealed that the expression of CD133 was an independent prognostic factor in gastric cancer (p=0.02). Conclusion, expression of CD133 may be a useful prognostic marker in gastric cancer. -
Huang, Hua;Jin, Jie-Jie;Long, Zi-Wen;Wang, Wei;Cai, Hong;Liu, Xiao-Wen;Yu, Hong-Mei;Zhang, Li-Wen;Wang, Ya-Nong 8221
Gastric cancer continues to be a leading cause of cancer death. The majority of patients with gastric adenocarcinoma in China present with advanced disease. Ruling out unresectable cancers from an unnecessary "open" exploration is very important. The aim of this study was to assess the value of five-port anatomical laparoscopic exploration in T4 gastric cancer in comparison with three-port laparoscopic exploration and laparotomy exploration. We conducted a retrospective study on 126 patients with T4 stage scheduled for D2 curative gastrectomy based on computed tomography (CT) staging at Department of Gastric Cancer and Soft Tissue Sarcoma, Fudan University Shanghai Cancer Center, from Apr. 2011 to Apr. 2013. Laparotomy exploration (Group I), three-port laparoscopic exploration (Group II) or five-port anatomical laparoscopic exploration (Group III) were performed prior to radical gastrectomy. Accuracy rate for feasibility of D2 curative gastrectomy in laparotomy exploration and five-port anatomical laparoscopic exploration groups was higher than that in the three-port laparoscopic exploration group. Five-port anatomical laparoscopic exploration group had the highest accuracy resection rate (Group I vs Group II vs Group III,92.6% vs78.6% vs 97.7%; p<0.05) and shorter length of hospitalization (Group I vs Group II vs Group III,$9.58{\pm}4.17$ vs$6.13{\pm}2.85$ vs$5.00{\pm}1.81$ ; p<0.001). Three-port laparoscopic exploration has low accuracy rate for assessing feasibility of D2 curative gastrectomy and five-port anatomical laparoscopic exploration should be performed on patients with T4 gastric cancer. -
Zhu, Yu;Zhang, Ling;Zhang, Guo-Dong;Wang, Hong-Ou;Liu, Ming-Yan;Jiang, Yuan;Qi, Li-Sha;Li, Qi;Yang, Ping 8225
Glioma is one of the most common tumors in China and chemotherapy is critical for its treatment. Recent studies showed that benzyl isothiocyanate (BITC) could inhibit the growth of glioma cells, but the mechanisms are not fully understood. This study explored the inhibitory effect of BITC on invasion and angiogenesis of U87MG human glioma cells in vitro and in vivo, as well as potential mechanisms. It was found that BITC could inhibit invasion and angiogenesis of human glioma U87MG cells by inducing cell cycle arrest at phase G2/M. It also was demonstrated that BITC decreased expression of cyclin B1, p21, MMP-2/9, VE-cadherin, CD44, CXCR4 and MTH1, the activity of the telomerase and$PKC{\zeta}$ pathway. Microarray analysis was thus useful to explore the potential target genes related to tumorigenic processes. BITC may play important roles in the inhibition of invasion and angiogenesis of human glioma cells. -
Nahvijou, Azin;Hadji, Maryam;BaratiMarnani, Ahmad;Tourang, Fatemeh;NedaBayat, NedaBayat;Weiderpass, Elisabete;Daroudi, Rajabali;AkbariSari, Ali;Zendehdel, Kazem 8229
Background: Organized cervical screening has decreased the incidence of cervical cancer. However, screening strategies vary in different countries. Objectives: We performed a systematic review to evaluate the economic aspects of different screening methods. Materials and Methods: We searched databases and then data were abstracted from each study. We evaluated articles based on different types of screening tests as well as screening age and intervals, and using incremental cost effectiveness ratio via calculating quality adjusted life years (QALY), or life years gained (LYG) per cost. We compared the incremental cost-effectiveness ratio (ICER) of each study using GDP per capita. Furthermore, we compared national guidelines with recommendations of cost-effectiveness studies in different countries. Results: A total of 21 articles met our criteria, of which 19 studies showed that HPV DNA testing, 13 suggested an age of 30 years or more, and 10 papers concluded that at least a 5-year or longer interval were the most cost-effective strategies. In some countries, the national guidelines did not match the recommendations of the cost-effectiveness studies. Conclusions: HPV testing, starting at age 30 years or older and repeated at 5-year or longer intervals, is the most cost-effective strategy in any setting. Closer collaboration with health economists is required during guideline development. -
Yako-Suketomo, Hiroko;Katanoda, Kota;Sobue, Tomotaka;Imai, Hirohisa 8239
The Cancer Control Act in Japan became effective in 2006. In Ibaraki, Toyama, and Hyogo prefectures, the Cancer Control Promoter (CCP) plan was created to strengthen partnerships for cancer prevention. This study aimed to examine the curre nt status of CCP utilization and analyze relationships with intersectoral collaboration, both within the government and with outside partners. In 2008, we mailed questionnaires to 100 administrators responsible for disease prevention and health promotion in municipal governments of the three prefectures. Ninety-one administrators responded (response rate, 91.0%). We analyzed responses to questions regarding whether or not the municipalities had used CCPs. Items assessing intersectoral collaboration examined municipality characteristics and relationships with outside partners and sectors specializing in areas other than community health. Among 90 administrators with valid data, 33 municipalities (36.7%) used CCPs while 57 (63.3%) did not. The Fisher's exact test revealed that intersectoral collaboration for using CCPs was associated with communication with all of the municipal government sectors not related to health. The present study indicated that CCPs were not consistently used in municipalities. However, we found that intersectoral collaborations, especially within the local government, may be related to the practical use of CCPs. This, in turn, may result in effective cancer control and prevention, as well as improvement in community health. -
Fang, Xin-Yu;Xu, Wang-Dong;Huang, Qian;Yang, Xiao-Ke;Liu, Yan-Yan;Leng, Rui-Xue;Pan, Hai-Feng;Ye, Dong-Qing 8245
Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis was to clarify the precise association. A systematic literature search was conducted to identify all relevant studies. Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association. In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria. Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism (TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667 was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89, p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated that MTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85, 95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup (TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFR A1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83, p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CC vs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that the MTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations. -
Zhang, Bo;Yin, Cui-Ping;Zhao, Qian;Yue, Shou-Wei 8251
Apoptosis is one of main types of neural cell death and is reversible and is a major target of therapeutic interventions. However, detailed apoptotic cascades still need to be recognized. In present study, we determined the promotion of HIF-$1{\alpha}$ and survivin in brain samples of a mouse model of hypoxic-ischemia and in neuroblastoma SH-SY5Y cells post hypoxia treatment. Then gain-of-function and loss-of-function strategies were adopted to manipulate the HIF-$1{\alpha}$ in SH-SY5Y cells, and hypoxia-induced survivin upregulation and cell apoptosis were determined. Results demonstrated that the HIF-$1{\alpha}$ and survivin were significantly promoted in a mouse model of hypoxic-ischemia or in SH-SY5Y cells post hypoxia in vitro. Manually upregulated HIF-$1{\alpha}$ could promote the hypoxia-induced survivin upregulation and improve the hypoxia-induced SH-SY5Y cell apoptosis. On the other hand, the HIF-$1{\alpha}$ knockdown by RNAi reduced the hypoxia-induced survivin upregulation and cell apoptosis. Therefore, the present study confirmed the protective role of HIF-$1{\alpha}$ and survivin in the hypoxia-induced SH-SY5Y cell apoptosis, and the survivin upregulation by hypoxia is HIF-$1{\alpha}$ -dependent. Promotion of HIF-$1{\alpha}$ and survivin might be a valuable stragegy for therapeutic intervention for hypoxic-ischemic encephalopathy. -
Kaur, Jaspreet;Goyal, Shikha;Muzumder, Sandeep;Bhasker, Suman;Mohanti, Bidhu Kalyan;Rath, Goura Kishore 8259
Aims: To determine the clinical characteristics, pathological features, local and distant failure patterns in patients with carcinoma of major salivary glands treated with surgery and postoperative radiotherapy (PORT). Materials and Methods: We retrospectively reviewed 106 cases of major salivary gland tumor seen at our centre (1998-2008). Sixty five cases of major salivary gland carcinoma were selected for analysis (exclusions: benign, palliative, non-carcinomas). The patient population treated by surgery and PORT was divided into two groups: 1) Patients who underwent surgery and immediate PORT (Primary PORT); 2) Patients with recurrent carcinoma who underwent at least two surgeries and received PORT in the immediate post-operative period of the last performed surgery (Recurrent PORT). Recurrence free survival (RFS) was assessed using the Kaplan-Meier method. Results: Median age was 35 years with a male: female ratio of 1.3:1. The majority of cancers were located in the parotid gland (86.2%) and the most common histology was mucoepidermoid carcinoma (43%). Thirty nine cases (60%) were primary while 26 (40%) were recurrent. Optimal surgery was performed in 59/65 patients (90.8%). 43 patients (66.2%) underwent neck dissection, of which 14 (32.5%) had nodal metastasis. Overall, 61 (93.8%) patients complied with the prescribed radiotherapy. Median dose of PORT was 60 Gy. Median follow-up was 13.1 months (range 2-70). Relapse free survival was 50.4% at 60 months. Some 12 cases (18.5%) recurred with a median time to recurrence of 16.9 months. Conclusions: Surgery and PORT is an effective treatment for major salivary gland carcinoma with over 90% compliance and <20% recurrence. Early treatment with postoperative radiotherapy may increase the survival rate in major salivary gland carcinoma patients. -
Mallikarjun, Sajjanshetty;Rao, Ashwini;Rajesh, Gururaghavendran;Shenoy, Ramya;Mithun, Pai B.H. 8265
Background: Smoking tobacco is considered as a leading cause of preventable death, mostly in developing countries like India. One of the primary goals of international tobacco control is to educate smokers about the risks associated with tobacco consumption. Tobacco warning labels (TWLs) on cigarette packages are one of the most common statutory means to communicate health risks of smoking to smokers, with the hope that once educated, they will be more likely to quit the habit. Materials and Methods: The present survey was conducted to assess the effectiveness of TWLs in communicating health risks of tobacco usage among 263 adult smokers working as bus drivers in Karnataka State Road Transport Corporation (KSRTC), Mangalore, India. Information was collected on demographic details, exposure and response to health warnings on tobacco products, intention to quit and nicotine dependency. Results: The majority (79.5%) of the respondents revealed negative intentions towards quitting smoking. Nearly half of the participants had a 'low' nicotine dependency (47.5%) and 98.1% of the respondents had often noticed warning labels on tobacco packages. These health warnings made 71.5% of the respondents think about quitting smoking. Respondents who noticed advertisement or pictures about dangers of smoking had better knowledge, with respect to lung cancer and impotence as a consequence of tobacco. A higher exposure to warning labels was significantly associated with lower nicotine dependency levels of smokers among the present study population. A significantly higher number of respondents who noticed advertisement or pictures about the dangers of smoking thought about the risks of smoking and were more inclined to think about quitting smoking. As exposure increased, an increase in the knowledge and response of participants was also observed. Conclusions: Exposure to tobacco warning labels helps to educate smokers about health risks of tobacco smoking. It may be possible to promote oral health among bus drivers by developing strategies to educate them about these risk factors. -
Sun, Jiang-Hong;Jiang, Li;Guo, Fei;Zhang, Xiu-Shi 8271
Aims: Apparent diffusion coefficient (ADC) values of nodes in diffusion-weighted imaging (DWI) are widely used in differentiating metastatic from non-metastatic lymph nodes. The purpose of this meta-analysis was to demonstrate whether DWI could contribute to the precise diagnosis of breast cancer (BC) with and without lymph node metastasis (LNM). Materials and Methods: English and Chinese electronic databases were searched for relevant studies followed by a comprehensive literature search. Two reviewers independently assessed the methodological quality of the included trials based on the quality assessment of diagnostic accuracy studies (QUADAS). Summary odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Results: Final analysis of 624 BC subjects (patients with LNM = 254, patients without LNM = 370) were incorporated into the current meta-analysis from 9 eligible cohort studies. Combined ORs of ADCs suggested that ADC values in BC patients without LNM were higher than in patients with LNM (OR=0.56, 95%CI: 0.11-1.01, p=0.015). Subgroup analysis stratified by country indicated a low ADC value in BC patients with LNM rather than those without LNM among Chinese (OR=1.27, 95%CI: 0.89-1.66, p<0.001), Italians (OR=0.75, 95%CI: 0.13-1.38, p=0.018), and Egyptians (OR=1.27, 95%CI: 0.71-1.84, p<0.001). The findings of subgroup analysis by MRI machine type revealed that ADC values from diffusion MRI may be potential diagnostic indicators for BC using Non-Philips 1.5T (OR=1.10, 95%CI: 0.84-1.36, p<0.001). Conclusions: The main findings of our meta-analysis demonstrated that increased signal intensity on DWI and decreased signals on ADC are helpful in diagnosis of BC patients with or without LNM. DWI could therefore be an important imaging investigation in patients suspected of BC. -
Wan, Guo-Xing;Cao, Yu-Wen;Li, Wen-Qin;Li, Yu-Cong;Zhang, Wen-Jie;Li, Feng 8279
A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488 controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084, rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk were systematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals (CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphism was significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28), specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CC vs TT: OR=1.31, 95% CI=1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association was significantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphism had a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836 polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98). In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancer risk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breast and digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-control studies are warranted to verify associations between TLR9 polymorphisms and cancer. -
Johnson, Derek Christopher;Bhatta, Madhav Prasad;Gurung, Santosh;Aryal, Shilu;Lhaki, Pema;Shrestha, Sadeep 8287
Background: This study assessed human papillomavirus (HPV), cervical cancer, and HPV vaccine knowledge and awareness among women in two sub-populations in Nepal - Khokana, a traditional Newari village in the Lalitpur District about eight kilometers south of Kathmandu, and Sanphebagar, a village development committee within Achham District in rural Far-Western Nepal. Methods: Study participants were recruited during health camps conducted by Nepal Fertility Care Center, a Nepali non-governmental organization. Experienced staff administered a Nepali language survey instrument that included questions on socio-demographics, reproductive health and knowledge on HPV, cervical cancer, and the HPV vaccine. Results: Of the 749 participants, 387 (51.7%) were from Khokana and 362 (48.3%) were from Sanphebagar. Overall, 53.3% (n=372) of women were aware of cervical cancer with a significant difference between Khokana and Sanphebagar (63.3% vs 43.0%; p=0.001). Overall, 15.4% (n=107) of women had heard of HPV and 32% (n=34) of these women reported having heard of the HPV vaccine. If freely available, 77.5% of the women reported willingness to have their children vaccinated against HPV. Factors associated with cervical cancer awareness included knowledge of HPV (Khokana: Odds Ratio (OR)=24.5; (95% Confidence Interval (CI): 3.1-190.2, Sanphebagar: OR=14.8; 95% CI: 3.7-58.4)) and sexually transmitted infections (Khokana: OR=6.18; 95% CI: 3.1-12.4; Sanphebagar: OR=17.0; 95% CI: 7.3-39.7) among other risk factors. Conclusions: Knowledge and awareness of HPV, cervical cancer, and the HPV vaccine remains low among women in Khokana and Sanphebagar. Acceptance of a freely available HPV vaccine for children was high, indicating potentially high uptake rates in these communities. -
Aghdam, Saeed Mahboubi;Sardari, Zeinab;Safaralizadeh, Reza;Bonyadi, Mortaza;Abdolmohammadi, Reza;Moghadam, Mostafa Soltani;Khalilnezhad, Ahad 8295
Background: H pylori is the main causative agent of Gastric cancer and chronic gastritis. Genetic diversity of H. pylori has major contribution in its pathogenesis. We investigated the prevalence of oipA and iceA1/iceA2 positive strains of H. pylori among patients with gastric cancer and gastritis. Materials and Methods: Sampling performed by means of endoscopy from 86 patients. DNA was extracted from tissue samples using DNA extraction kit. PCR assay was performed and products were monitored by Agarose Gel Electrophoresis. Results: Urease Test and 16S rRNA PCR did not show significant differences in detection of H. pylori. The frequency of iceA1 allele in patients with gastric cancer was significantly higher than those with gastritis (p<0.05). However, there was no significant difference in prevalence of oipA and iceA2 genes among the two groups of patients (p>0.05). Conclusions: The iceA1 gene, but the oipA and iceA2 genes, is associated with H. pylori-induced gastric cancer. However, confirmatory studies must be performed in future. -
Zhao, Fen;Cao, Yue;Zhu, Hong;Huang, Min;Yi, Cheng;Huang, Ying 8301
Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2 (COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensively evaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materials and Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBM databases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results: A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. The results indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer when compared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CC vs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers (GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, and p< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type (GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk for gastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophageal cancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in then population-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC) studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is a potential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall. -
Zhao, Cheng-Xiao;Liu, Ming;Xu, Yong;Yang, Kuo;Wei, Dong;Shi, Xiao-Hong;Yang, Fan;Zhang, Yao-Guang;Wang, Xin;Liang, Si-Ying;Zhao, Fan;Zhang, Yu-Rong;Wang, Na-Na;Chen, Xin;Sun, Liang;Zhu, Xiao-Quan;Yuan, Hui-Ping;Zhu, Ling;Yang, Yi-Ge;Tang, Lei;Jiao, Hai-Yan;Huo, Zheng-Hao;Wang, Jian-Ye;Yang, Ze 8311
Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism and prostate cancer (PCa) risk has been reported in North American and Europe populations, though data from Asian populations remain limited. We therefore investigated this association by clinical detection in China, and meta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samples and clinical information were collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphism was genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed the associations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed using genotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studies in American and European populations, to determine the association between PCa and risk genotype. Results: The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140,$P=7.3{\times}10^{-5}$ ), suggesting that the 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjects were in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91,$Padj=1.1{\times}10^{-4}$ ). Presence of the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis${\geq}65$ years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared with the non-risk genotype ($P=4.6{\times}10^{-5}-3.0{\times}10^{-2}$ ). Meta-analysis confirmed the association between 8q24 rs4242382-A polymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88,$P=1.0{\times}10^{-5}$ ) across Asian, Caucasian and African American populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation might be associated with increased PCa susceptibility in Asian, Caucasian and African American populations. These results imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations. -
Erturk, Elif;Cecener, Gulsah;Polatkan, Volkan;Gokgoz, Sehsuvar;Egeli, Unal;Tunca, Berrin;Tezcan, Gulcin;Demirdogen, Elif;Ak, Secil;Tasdelen, Ismet 8319
Although genetic markers identifying women at an increased risk of developing breast cancer exist, the majority of inherited risk factors remain elusive. Mutations in the BRCA1/BRCA2 gene confer a substantial increase in breast cancer risk, yet routine clinical genetic screening is limited to the coding regions and intronexon boundaries, precluding the identification of mutations in noncoding and untranslated regions. Because 3' untranslated region (3'UTR) polymorphisms disrupting microRNA (miRNA) binding can be functional and can act as genetic markers of cancer risk, we aimed to determine genetic variation in the 3'UTR of BRCA1/BRCA2 in familial and early-onset breast cancer patients with and without mutations in the coding regions of BRCA1/BRCA2 and to identify specific 3'UTR variants that may be risk factors for cancer development. The 3'UTRs of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis and DNA sequencing in 100 patients from 46 BRCA1/2 families, 54 non-BRCA1/2 families, and 47 geographically matched controls. Two polymorphisms were identified. SNPs$c.^*1287C$ >T (rs12516) (BRCA1) and$c.^*105A$ >C (rs15869) (BRCA2) were identified in 27% and 24% of patients, respectively. These 2 variants were also identified in controls with no family history of cancer (23.4% and 23.4%, respectively). In comparison to variations in the 3'UTR region of the BRCA1/2 genes and the BRCA1/2 mutational status in patients, there was a statistically significant relationship between the BRCA1 gene polymorphism$c.^*1287C$ >T (rs12516) and BRCA1 mutations (p=0.035) by Fisher's Exact Test. SNP$c.^*1287C$ >T (rs12516) of the BRCA1 gene may have potential use as a genetic marker of an increased risk of developing breast cancer and likely represents a non-coding sequence variation in BRCA1 that impacts BRCA1 function and leads to increased early-onset and/or familial breast cancer risk in the Turkish population. -
Minatoya, Machiko;Kutomi, Goro;Shima, Hiroaki;Asakura, Sumiyo;Otokozawa, Seiko;Ohnishi, Hirofumi;Akasaka, Hiroshi;Miura, Tetsuji;Mori, Mitsuru;Hirata, Koichi 8325
Background: It is known that obesity is one of the risk factors for breast cancer although the association may differ between ethnic groups and with the menopausal status. Recently obesity-related risk factors including serum adiponectin and insulin levels have been analyzed together with BMI in association with breast cancer risk. Materials and Methods: We measured serum high molecular weight (HMW) adiponectin and insulin levels in a hospital based case-control study, including 66 sets of Japanese female breast cancer cases and age and menopausal status matched controls. Serum levels of HMW adiponectin, insulin levels and body mass index (BMI) were examined in association with breast cancer risk with adjustment for the various known risk factors by menopausal status. Results: Women in the highest HMW adiponectin levels showed significant reduced risk of breast cancer in both pre and postmenopausal women (odds ratio (OR), 0.01; 95% confidence interval (CI), 0.00-0.26 and 0.13; 0.03-0.57, respectively). Lower BMI showed decreased breast cancer risk in both pre and postmenopausal women (OR, 0.04; 95% CI, 0.00-0.69, OR, 0.28; 95% CI, 0.07-1.11, respectively). Conclusions: These results indicated that higher serum HMW adiponectin levels and lower BMI are associated with a decreased breast cancer risk in both pre and postmenopausal women in Japan, adding evidence for the obesity link. -
Bai, Lan;He, Juan;He, Gong-Hao;He, Jian-Chang;Xu, Fan;Xu, Gui-Li 8331
Background: Previous studies accessing the association of CYP2C19 with outcomes of patients using tamoxifen for breast cancer have yielded conflicting results. The aim of this meta-analysis is to obtain a more precise estimate of effects of CYP2C19 polymorphisms and to clarify their effects on survival of the breast cancer patients using tamoxifen. Materials and Methods: A systematic search of PubMed and Embase was performed, comparing patients with or without$CYP2C19^*2$ and$CYP2C19^*17$ , relevant articles searched for. The following outcomes were included from the eligible studies: disease-free survival (DFS) and overall survival (OS), expressed by hazard ratios (HR) with corresponding 95% confidence interval (CI). Subgroup analysis by genotypes was also performed. Pooled estimates were calculated using random-effect model in accordance to the heterogeneity. Results: Six studies met the inclusion criteria. The integrated OR on the association between CYP2C19 and DFS, calculated by the random-effect model, was 0.54 (95%CI=0.34-0.84, p=0.013). Subgroup analysis showed that both$CYP2C19^*2$ and$CYP2C19^*17$ were associated with increased survival. The pooled results of two studies for OS were OR=0.46 (95%CI=0.21-1.01, p=0.233). Conclusions: This meta-analysis suggests that the$CYP2C19^*2$ and$CYP2C19^*17$ genotypes are associated with increased survival in breast cancer patients using tamoxifen. -
Zeng, Qi-Yan;Huang, Yu;Zeng, Lin-Jie;Huang, Min;Huang, Yong-Qi;Zhu, Qi-Fang 8337
Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 ($8-60hIPP5^m$ ), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of$8-60hIPP5^m$ with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that$8-60hIPP5^m$ enhances paclitaxel-induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to downregulation of NF-${\kappa}B$ activation and serine/threonine kinase Akt pathways. We noted that$8-60hIPP5^m$ downregulated the paclitaxel-induced NF-${\kappa}B$ activation,$I{\kappa}B{\alpha}$ degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-${\kappa}B$ . Together, our observations indicate that paclitaxel in combination with$8-60hIPP5^m$ may provide a therapeutic advantage for the treatment of human cervical carcinoma. -
Amoori, Neda;Mirzaei, Masoud;Cheraghi, Maria 8345
Background: Cancer is an increasing cause of mortality and morbidity worldwide. Incidences of common cancers has been growing in different provinces of Iran in recent years but trends in Khuzestan which shares a border with Iraq and is located in south west of Iran have not been investigated. This study aimed to assess secular changes in incidences of common cancers in Khuzestan province from 2004 to 2008. Materials and Methods: Data were collected from Khuzestan cancer registry which is a branch of Iranian Ministry of Health Cancer Registry (http://ircancer.ir) for the period 2004-2008. Data were presented as incidence rates by site, sex, age, using the crude rate and age-standardized rate (ASR) per$10^5$ persons. A direct method of standardization was applied according to the WHO guideline and data analysis was performed using the SPSS package. Results: During the 2004-2008 period, 14,893 new cases of cancer were registered in Khuzestan cancer registry. The age-standardized incidence rate of all cancers was 153.7 per$10^5$ in males and 156.4 per$10^5$ in females. The incidence was increased over the period of five years. The most incident cancers among males were skin cancer ($ASR=18.7/10^5$ ), stomach cancer ($ASR13.8/10^5$ ), lung cancer ($ASR12.9/10^5$ ), leukemia ($ASR=12.6/10^5$ ) and prostate cancer ($ASR=12.4/10^5$ ). In females, the most incident cancers were breast cancer ($ASR=41/10^5$ ), skin cancer ($ASR=16.4/10^5$ ), colorectal cancer ($ASR=10.0/10^5$ ), leukemia ($ASR=8.1/10^5$ ) and lung cancer ($ASR=6.9/10^5$ ). Conclusions: Incidences of various cancers are rising in Khuzestan. It is necessary to develop and implement comprehensive cancer control programs in this region which could be monitored and evaluated by the future trend data from Khuzestan cancer registry. -
Ramshankar, Vijayalakshmi;Soundara, Viveka T.;Shyamsundar, Vidyarani;Ramani, Prathiba;Krishnamurthy, Arvind 8351
Background: Recent epidemiological data have implicated human papilloma virus (HPV) infection in the pathogenesis of head and neck cancers, especially oropharyngeal cancers. Although, HPV has been detected in varied amounts in persons with oral dysplasia, leukoplakias and malignancies, its involvement in oral tongue carcinogenesis remains ambiguous. Materials and Methods: HPV DNA prevalence was assessed by PCR with formalin fixed paraffin embedded sections (n=167) of oral tongue squamous cell carcinoma patients and the physical status of the HPV16 DNA was assessed by qPCR. Immunohistochemistry was conducted for p16 evaluation. Results: We found the HPV prevalence in tongue cancers to be 51.2%, HPV 16 being present in 85.2% of the positive cases. A notable finding was a very poor concordance between HPV 16 DNA and p16 IHC findings (kappa<0.2). Further molecular classification of patients based on HPV16 DNA prevalence and p16 overexpression showed that patients with tumours showing p16 overexpression had increased hazard of death (HR=2.395; p=0.005) and disease recurrence (HR=2.581; p=0.002) irrespective of their HPV 16 DNA status. Conclusions: Our study has brought out several key facets which can potentially redefine our understanding of tongue cancer tumorigenesis. It has emphatically shown p16 overexpression to be a single important prognostic variable in defining a high risk group and depicting a poorer prognosis, thus highlighting the need for its routine assessment in tongue cancers. Another significant finding was a very poor concordance between p16 expression and HPV infection suggesting that p16 expression should possibly not be used as a surrogate marker for HPV infection in tongue cancers. Interestingly, the prognostic significance of p16 overexpression is different from that reported in oropharyngeal cancers. The mechanism of HPV independent p16 over expression in oral tongue cancers is possibly a distinct entity and needs to be further studied. -
Song, Xu-Ping;Tian, Jin-Hui;Cui, Qi;Zhang, Ting-Ting;Yang, Ke-Hu;Ding, Guo-Wu 8361
This meta-analysis was performed to assess the implementation effects of clinical pathways in patients with gastrointestinal cancer. A comprehensive search was conducted in the Cochrane Library, PubMed, EMBASE, Web of Science and Chinese Biomedical Literature Database (from inception to May 2014). Selection of studies, assessing risk of bias and extracting data were performed by two reviewers independently. Outcomes were analyzed by fixed-effects and random-effects model meta-analysis and reported as mean difference (MD), standardized mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI). The Jadad methodological approach was used to assess the quality of included studies and the meta-analysis was conducted with RevMan 5.1 software. Nine citations (eight trials) involving 642 patients were included. The aggregate results showed that a shorter average length of stay [MD = -4.0; 95% CI (-5.1, -2.8); P < 0.00001] was observed with the clinical pathways as compared with the usual care. A reduction in inpatient expenditure [SMD = -1.5; 95% CI (-2.3, -0.7); P = 0.0001] was also associated with clinical pathways, along with higher patient satisfaction [OR = 4.9; 95% CI (2.2, 10.6); P < 0.0001]. Clinical pathways could improve the quality of care in patients with gastrointestinal cancer, as evidenced by a significant reduction in average length of stay, a decrease in inpatient expenditure and an improvement in patient satisfaction. Therefore, indicators and mechanisms within clinical pathways should be a focus in the future. -
Ye, Yang;Miao, Shu-Han;Lu, Rong-Zhu;Zhou, Jian-Wei 8367
The relationship between caveolin-1 (Cav-1) and clinicopathological characteristics of gastric cancer is controversial, although Cav-1 plays an important role in tumor metastasis. To evaluate the clinicopathological and prognostic value of expression in patients with gastric cancer, a meta-analysis was performed to investigate the impact on clinicopathological parameters and prognosis in gastric cancer cases. Studies assessing these parameters for Cav-1 in gastric cancer were identified up to June 2014. Finally, a total of six studies met the inclusion criteria. Our combined results showed that Cav-1 expression was significantly associated with the Lauren classification (pooled OR=0.603, 95% CI: 0.381-0.953, P=0.030). Furthermore, we found that Cav-1 expression predicted a better overall survival in gastric cancer patients (pooled OR=0.590, 95% CI: 0.360-0.970, P=0.038, fixed-effect). In conclusion, the overall data of the present meta analysis showed that Cav-1 expression was not correlated with clinicopathological features except for the Lauren classification. Simultaneously, Cav-1 overexpression predicted a better overall survival in gastric cancer. Cav-1 expression in tumors is a candidate positive prognostic biomarker for gastric cancer patients. -
Khan, Hafiz Mohammad Rafiqullah;Ibrahimou, Boubakari;Saxena, Anshul;Gabbidon, Kemesha;Abdool-Ghany, Faheema;Ramamoorthy, Venkataraghavan;Ullah, Duff;Stewart, Tiffanie Shauna-Jeanne 8371
Background: The use of statistical methods has become an imperative tool in breast cancer survival data analysis. The purpose of this study was to develop the best statistical probability model using the Bayesian method to predict future survival times for the black non-Hispanic female breast cancer patients diagnosed during 1973-2009 in the U.S. Materials and Methods: We used a stratified random sample of black non-Hispanic female breast cancer patient data from the Surveillance Epidemiology and End Results (SEER) database. Survival analysis was performed using Kaplan-Meier and Cox proportional regression methods. Four advanced types of statistical models, Exponentiated Exponential (EE), Beta Generalized Exponential (BGE), Exponentiated Weibull (EW), and Beta Inverse Weibull (BIW) were utilized for data analysis. The statistical model building criteria, Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) were used to measure the goodness of fit tests. Furthermore, we used the Bayesian approach to obtain the predictive survival inferences from the best-fit data based on the exponentiated Weibull model. Results: We identified the highest number of black non-Hispanic female breast cancer patients in Michigan and the lowest in Hawaii. The mean (SD), of age at diagnosis (years) was 58.3 (14.43). The mean (SD), of survival time (months) for black non-Hispanic females was 66.8 (30.20). Non-Hispanic blacks had a significantly increased risk of death compared to Black Hispanics (Hazard ratio: 1.96, 95%CI: 1.51-2.54). Compared to other statistical probability models, we found that the exponentiated Weibull model better fits for the survival times. By making use of the Bayesian method predictive inferences for future survival times were obtained. Conclusions: These findings will be of great significance in determining appropriate treatment plans and health-care cost allocation. Furthermore, the same approach should contribute to build future predictive models for any health related diseases. -
Abbasi, Mehran Mesgari;Khiavi, Monir Moradzadeh;Monfaredan, Amir;Hamishehkar, Hamed;Seidi, Khaled;Jahanban-Esfahlan, Rana 8377
Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy worldwide. Cancer development and progression require inactivation of tumor suppressor genes and activation of proto-oncogenes. The well recognized mechanism of action demonstrated for chemotherapeutic agents is induction of apoptosis via reactivation of p53. In this context, we evaluate the efficacy of IV and oral routes of our novel PH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NP) in affecting p53 profile in an OSCC rat model. Methods: In this study, 120 male rats were divided into 8 groups of 15 animals each. The new formulated DOX-MTX NP and free doxorubicin were IV and orally given to rats with 4-nitroquinoline-1-oxide induced OSCC. Results: Results showed that both DOX and DOX-MTX-NP caused significant increase in mRNA levels of P53 compared to the untreated group (p<0.000). With both DOX and DOX-MTX NP, the IV mode was more effective than the oral (gavage) route (p<0.000). Surprisingly, in oral mode, p53 mRNA was not affected in DOX treated groups (p>0.05), Nonetheless, both IV and oral administration of MTX-DOX NP showed superior activity (~3 fold) over free DOX in reactivation of p53 in OSCC (p<0.000). The effectiveness of oral route in group treated with nanodrug accounts for the enhanced bioavailability of nanoparticulated DOX-MTX compared to free DOX. Moreover, in treated groups, tumor stage was markedly related to the amount of p53 mRNA (p<0.05). Conclusion: Both oral and IV application of our novel nanodrug possesses superior activity over free DOX-in up-regulation of p53 in a OSCC model and this increase in p53 level associated with less aggressive tumors in our study. Although, impressive results obtained with IV form of nanodrug (-21 fold increase in p53 mRNA level) but both forms of nanodrug are effective in OSCC, with less toxicity normal cells. -
Qian, Ying-Ying;Liu, Xin-You;Wu, Qian;Song, Xian;Chen, Xiao-Feng;Liu, Yi-Qian;Pei, Dong;Shen, Li-Zong;Shu, Yong-Qian 8383
Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy. -
Zhang, Hui-Qing;Lian, Chang-Hong;Ping, Yao-Dong;Song, Wen-Bin;Lu, Qing-Pu;Xie, Shu-Zhe;Lin, Tao;Cheng, Lin-Zhong 8391
Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed based salvage chemotherapy for treatment of patients with metastatic colorectal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for patients with colorectal cancer were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed based regimens, 4 clinical studies including 201 patients with advanced colorectal cancer were considered eligible for inclusion. The analysis suggested that, in all patients, pooled RR was 20.4% (41/201). Major adverse effects were neutropenia, anorexia, fatigue, and anemia. No treatment related death occurred with pemetrexed based treatment. Conclusion: This systematic analysis suggests that pemetrexed based regimens are associated with mild activity with good tolerability in treating patients with metastatic colorectal cancer. -
In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer death in the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate, these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. The present report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal and lobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors (age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety nine cases of breast tumors were recruited from the pathology department archive of King Abdulaziz University Hospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductal carcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59 (62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order. Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal and lobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 in Saudi female is different from that of Tunisian and Jordanian female populations and closer to the expression pattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found two IHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reported in other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation among Arabic female populations.
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Nartthanarung, Adisak;Thanapprapasr, Kamolrat;Udomsubpayakul, Umaporn;Thanapprapasr, Duangmani 8401
Background: To determine survival times of cervical cancer patients with bone metastasis related to the effect of age at the time of cervical cancer diagnosis, we performed the retrospectively analytical study. Methods: A total of 68 cervical cancer patients with bone metastasis were treated at a single hospital, during January 1998 to December 2010. Fifty-two medical records were identified and collected, the remaining sixteen medical records were not found. Main outcome measures were patient characteristics, clinical information, duration from cervical cancer diagnosis to bone metastasis diagnosis, survival time after bone metastasis and overall survival time. Results: Among fifty-two cervical cancer patients with bone metastasis, there were 13 patients who were less than 45 years old, and 39 patients were 45 years old or more at the time of cervical cancer diagnosis. The younger group had less median overall survival than the older group, with a statistically significant difference (21 months, 95% CI 19.93-22.06; 34 months, 95% CI 23.27-44.72, p = 0.021). However, they were comparable in the duration from cervical cancer diagnosis to bone metastasis diagnosis and the survival time after bone metastasis. Conclusion: Young patients with bone metastasis aged less than 45 years old at the time of cervical cancer diagnosis have a poorer prognosis than the elderly patients. Impact: To improve survival and quality of life, more intensive and novel multimodal treatments at the time of cervical cancer diagnosis should be considered in patients less than forty-five years, who can tolerate the side effects better. -
Yang, Wen-Bing;Xing, Bian-Zhi;Liang, Hua 8405
Background: This analysis was conducted to evaluate the efficacy and safety of temozolomide based chemotherapy in treating patients with glioma. Methods: Clinical studies evaluating the efficacy and safety of temozolomide based regimens for patients with glioma were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: In temozolomide based regimens, 5 clinical studies including 152 patients with advanced glioma were considered eligible for inclusion. Four clinical studies included temozolomide. Systematic analysis suggested that, in all patients, pooled CR was 21% (32/152), and PR was 21% (32/152). Grade 3/4 toxicity included neutropenia, thrombocytopenia, and anemia. No grade 3 or 4 renal or liver toxicity was observed. No treatment related death occurred with temozolomide based treatment. Conclusion: This systematic analysis suggests that temozolomide based regimens are associated with mild response rate and acceptable toxicity for treatment of glioma patients. -
Bian, Jing;Li, Bo;Kou, Xian-Juan;Wang, Xu-Na;Sun, Xiao-Xu;Ming, Liang 8409
Purpose: To assess the value of multi-tumor marker protein chips in the diagnosis and treatment of ovarian cancer. Materials and Methods: Twelve tumor markers (CA19-9, NSE, CEA, CA242, CK19,${\beta}$ -HCG, AFP, SCC, c-PSA, CA125, CA724 and CA15-3) were detected by protein biochip in 220 patients with ovarian carcinomas, 205 with benign ovarian tumors and 200 healthy subjects. Results: The positivity rate was obviously higher in ovarian cancer (77.7%), than that in the benign cases (26.3%, p<0.01) and healthy subjects (4.5%, p<0.01). Serum levels of tumor markers were furthermore significantly higher in cases with lymph node metastasis (86.8%) than those without metastasis (44.7%), p<0.01. Conclusions: Multi-tumor marker protein chips provide important assistance in the diagnosis and treatment evaluation in ovarian cancers. -
Kaur, Sukhpreet;Sambyal, Vasudha;Guleria, Kamlesh;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan;Singh, Gursimran;Singh, Harpreet 8413
Background: To investigate the relationship of five TP53 polymorphisms (p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a) with the esophageal cancer (EC) risk in North Indians. Materials and Methods: Genotyping of p.P47S, p.R72P, PIN3 ins16bp, p.R213R and r.13494g>a polymorphisms of TP53 in 136 sporadic EC patients and 136 controls using polymerase chain reaction and PCR-RFLP. Results: The frequencies of genotype RR, RP and PP of p.R72P polymorphism were 16.91 vs 26.47%, 58.82 vs 49.27% and 24.27 vs 24.27% among patients and controls respectively. We observed significantly increased frequency of RP genotype in cases as compared to controls (OR=1.87, 95% CI, 1.01-3.46, p=0.05). The frequencies of genotype A1A1, A1A2 and A2A2 of PIN3 ins16bp polymorphism were 69.12 vs 70.59%, 27.20 vs 25% and 3.68 vs 4.41% among patients and controls. There was no significant difference among genotype and allele distribution between patients and controls. The frequencies of genotype GG, GA and AA of r.13494g>a polymorphism were 62.50 vs 64.70%, 34.56 vs 30.15% and 2.94 vs 5.15% among patients and controls respectively. No significant difference between genotype and allele frequency was observed in the patients and controls. For p.P47S and p.R213R polymorphisms, all the cases and controls had homozygous wild type genotype. The RP-A1A1-GG genotype combination shows significant risk for EC (OR=2.01, 95%CI: 1.01-3.99, p=0.05). Conclusions: Among the five TP53 polymorphisms investigated, only p.R72P polymorphism may contributes to EC susceptibility. -
Wirasorn, Kosin;Suwanrungruag, Krittika;Wiangnon, Surapon;Punjaruk, Wiyada 8423
Background: Cancer is the most common cause of death in Thailand, where treatment outcomes and prognosis are poor and mortality rates remain high. This study reports new cancer cases and trends of all cancers registered in Srinagarind Hospital from 1993 to 2012 and also provides a picture of the cancer situation in Northeast Thailand. Materials and Methods: All new cases of cancer registered in the hospital-based cancer registry at Faculty of Medicine, Srinagarind Hospital, Khon Kaen University during 1993-2012 were included in the study. Results and Conclusions: The number of new cancer cases has gradually increased each year during the last 20 years. The three most common cancers at present in males are liver and bile duct cancer, lung cancer and colorectal cancer, respectively. In females, liver and bile duct, breast and thyroid cancers are now the most frequent. Interestingly, the number of cases of both liver and bile duct cancer and colorectal cancer in males noticeably increased during the second decade of the study. Additionally, breast cancer greatly increased in the same decade and lung cancer in females climbed into the top five most common cancers. Thyroid cancer has also risen steadily in the last decade. Trends of common cancers are similar to those throughout Thailand. -
Circulating tumor cells (CTCs) are believed to be particularly important and a reliable marker of malignancy. However, the prognostic significance of CTCs detected in patients with small cell lung cancer (SCLC) is still unclear. We therefore aimed to assess the prognostic relevance of CTCs using a meta-analysis. We searched PubMed for relevant studies and statistical analyses were conducted to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) using fixed or random-effect models according to the heterogeneity of included studies. A total of 7 papers covering 440 SCLC patients were combined in the final analysis. The meta-analysis revealed that CTCs were significantly associated with shorter overall survival (HR=1.9; 95%CI: 1.19-3.04; Z=2.67; P<0.0001) and progression-free survival (HR=2.6; 95%CI: 1.9-3.54; Z=6.04; P<0.0001). The results thus suggest that the presence of CTCs indicates a poor prognosis in patients with SCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in SCLC.
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Zhang, Yu;Yu, Li-Ke;Lu, Guo-Jun;Xia, Ning;Xie, Hai-Yan;Hu, Wei;Hao, Ke-Ke;Xu, Chun-Hua;Qian, Qian 8435
Aims: Angiogenesis is important in malignant pleural effusion (MPE) formation and it is regulated by a number of pro- and anti-angiogenic cytokines. The purpose of this study was to evaluate the prognostic value of angiogenic factor vascular endothelial growth factor (VEGF) and angiogenesis inhibitor endostatin in lung cancer patients with MPE, and investigate the relationship between these two kinds of agent. Methods: Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and endostatin were measured in pleural effusions (PE) and serum from a total of 70 lung cancer patients with MPE and 20 patients with tuberculosis. Results: Compared to patients with tuberculosis, the levels of VEGF and endostatin in both PE and serum were significantly higher in patients with lung cancer. There were statistically significant correlations between VEGF levels in PE and serum (r=0.696, p<0.001), endostatin levels in PE and serum (r=0.310, p=0.022), and VEGF and endostatin levels in PE (r=0.287, p=0.019). Cox multivariate analysis revealed that elevated pleural VEGF and endostatin levels and serum endostatin level were independent predictors of shorter overall survival. Conclusion: Both pro- and anti-angiogenic factors are likely contributors to PE formation. Our results suggest that the levels of VEGF and endostatin in PE, together with endostatin in serum, may be potential prognostic parameters for lung cancer patients with MPE. -
Rahman, Wan Faiziah Wan Abdul;Fauzi, Mohd Hashairi;Jaafar, Hasnan 8441
Background: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). Methods: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH). Results: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). Conclusion: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis. -
Yesilyurt, Huseyin;Tokmak, Aytekin;Guzel, Ali Irfan;Simsek, Hakki Sencer;Terzioglu, Serdar Gokay;Erkaya, Salim;Gungor, Tayfun 8447
Background: To evaluate factors for predicting the granulosa cell tumor of the ovary (GCTO) pre-operatively. Materials and Methods: This retrospective designed study was conducted on 34 women with GCTO as the study group and 76 women with benign ovarian cysts as the control group. Data were recorded from the hospital database and included age, body mass index (BMI), parity, serum estradiol ($E_2$ ) levels, diameter of the mass, ultrasonographic features, serum CA125 level, risk of malignancy index (RMI), duration of menopause, postoperative histopathology result, and the neutrophil/lymphocyte ratio (NLR). Results: The demographic parameters showed no statistically significant difference between the groups. Preoperative diameter of the mass, CA125, duration of menopause, and neutrophil/lymphocyte ratio were significantly different between the groups. ROC curve analysis demonstrated that diameter of the mass, serum estradiol and Ca125 levels, RMI and NLR may be discriminative factors in predicting GCTO preoperatively. Conclusions: In conclusion, we think that a careful preoperative workshop including diameter of the mass, serum estradiol ($E_2$ ) and Ca125 levels, RMI and NLR may predict GCTO and may prevent incomplete approaches. -
Wu, Xiao-Ming;Chen, Yu;Shao, Yang;Zhou, Xiao-Long;Tang, Wen-Ru 8451
Objectives: Epidemiological studies have shown that molecular mechanisms underlying the development of lung cancers differ between smokers and unsmokers. Aberrant promoter methylation in some tumor suppressor genes is frequent in lung tumors from smokers but rare in those from non-smokers. Recently, many studies have investigated the association between cigarette smoking and RASSF1A gene promoter hypermethylation in lung cancer patients, but a unanimous conclusion could not be reached. We therefore performed this meta-analysis to derive a more precise estimation of any association. Study Design: An electronic search of PubMed and Chinese Biomedicine databases was conducted to select studies. A total of 19 case-control studies were chosen, and odds ratios (ORs) with confidence intervals (CIs) were used to assess the strength of associations. Results: The case-control studies covered 2, 287 lung cancer patients: 63.4%(1449) of the patients were smokers, 36.6% (838) were unsmokers. The overall results suggested that smokers with lung cancer had a 1.297-fold (95% CI: 1.066~1.580, p=0.010, p=0.087) higher risk for RASSF1A gene hypermethylation than the non-smokers. In the stratified analysis, an increased risk of RASSF1A gene hypermethylation in smokers than in non-smokers was found in Asian (OR=1.481, 95%CI: 1.179~1.861, p=0.001, p=0.186). Conclusions: This meta-analysis supports the idea that RASSF1A gene hypermethylation is associated with cigarette smoking-induced lung cancer. -
Zheng, Zhao-Xu;Zheng, Rong-Shou;Zhang, Si-Wei;Chen, Wan-Qing 8455
Background: The National Central Cancer Registry of China (NCCR) affiliated to the Bureau of Disease Control, National Health and Family Planning Commission of China is responsible for cancer surveillance in the entire country. Cancer registration data from each local registry located in each province are collected by NCCR annually to be analyzed and published to provide useful information for policy makers and cancer researchers. Materials and Methods: Until 1st June, 2013, 219 population-based cancer registries submitted data of 2010 to the National Central Cancer Registry of China covering about 207,229,403 population, and 145 cancer registries were selected after quality evaluation for this study. Colorectal cancer cases were selected from the database according to ICD-10 coded as "C18-C20". We calculated the crude incidence and mortality rates by sex, age groups and location (urban/rural). The China population in 2000 and Segi's population were used as standardized populations for the calculation of age-standardized rates. The 6th National Population Census data of China was used to combined with the cancer registries' data to estimate the colorectal cancer burden in China in 2010. Results: Colorectal cancer was the sixth most common cancer in China. It was estimated that there were 274,841 new cases diagnosed in 2010 (157,355 in males and 117,486 in females), with the crude incidence rate of 20.1/100,000, highest in males in urban areas. Age-standardized rates by China standard population of 2000 (ASRcn) and World standard population (Segi's population, ASRwld) for incidence were 16.1/100,000 and 15.9/100,000 respectively. There were 132,110 cases estimated to have died from colorectal cancer in China in 2010 (76,646 men and 55,464 women) with the crude mortality rate of 10.1/100,000. The ASRcn and ASRwld for mortality were 7.55/100,000 and 7.44/100,000 respectively, higher in males and urban areas than in females and rural areas. The incidence and mortality rates increased with age, reaching peaksin the 80-84 year old, and oldest age groups, respectively. Conclusions: Colorectal cancer is one of the most common incident cancers and cause of cancer death in China. Primary and secondary prevention, with attention to a health lifestyle, physical activity and screening should be enhanced in the general population. -
Kim, Hee-Jung;Yim, Hyun-Woo;Kim, Nam-Cho 8461
Background: In this study we investigated factors influencing cancer screening intention and behavior to develop measures to increase the rate of cancer screening in the Korean elderly. Materials and Methods: Participants included 425 elderly subjects 65 years of age or older from D city, South Korea. The health behavior characteristics and cancer screening-related and theory of planned behavior (TPB) factors influencing the participant attitudes on cancer screening were examined to identify determinants significantly affecting cancer screening intentions and behavior. Results: Predictive factors influencing cancer screening behavior included smoking, exercise, cancer concerns, preference for the type of cancer screening, prior experience with the National Cancer Screening Program, perception of the National Cancer Screening Program, behavioral control with respect to cancer screening and cancer screening intentions. The factors influencing cancer screening behavior were different from those for cancer screening intentions. Conclusions: Increasing the cancer screening intentions of the elderly is necessary to raise the rates of cancer screening. Additionally, identifying the inhibitory factors that serve as obstacles to cancer screening in the elderly and changing screening intentions into actual screening behavior is necessary. This study provides a reference for developing and applying policy measures and intervention strategies to increase the cancer screening rates of the elderly in Korea. -
Ayyildiz, Talat;Dolar, Enver;Adim, Saduman Balaban;Eminler, Ahmet Tarik;Yerci, Omer 8469
Introduction: Recent studies have indicated that down-regulation of the suppressor of cytokine signaling-1 (SOCS-1) gene results in tumor formation and that SOCS-1 acts as a tumor suppressor gene. SOCS-1 has been also suggested to function as a tumor suppressor with colorectal cancer. Objectives: In the present study, we aimed to determine the association of SOCS-1 expression in colorectal cancer tissues with clinicopathologic characteristics immunohistochemically and also to identify its prognostic significance. Materials and Methods: SOCS-1 expression was studied immunohistochemically in 67 patients diagnosed with resected colorectal carcinomas and 30 control subjects. Results: SOCS-1 expression was found in 46.3% of tumor tissues and 46.7% of the control group. Statistical analyses did not establish any significant association between SOCS-1 expression and clinicopathologic characteristics. Also, no significant association with SOCS-1 expression was found using progression-free survival and overall survival analyses (p=0.326 and p=0.360, respectively). Conclusions: Our results show that SOCS-1 has no prognostic significance in colorectal cancer. -
Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed-based chemoradiotherapy in treating patients with locally advanced or metastatic esophageal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for relevant patients were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed-based regimens, 4 clinical studies including 47 patients with locally advanced or metastatic esophageal cancer were considered eligible for inclusion. Systematic analysis showed that, in all patients, the pooled RR was 51% (24/47). Major adverse effects of grade III/IV were esophagitis, neutropenia, thrombocytopenia, anemia anorexia, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusion: This systematic analysis suggests that pemetrexed based radiotherapy is associated with reasonable activity and good tolerability in treating patients with locally advanced or metastatic esophageal cancer.
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Krishnatreya, Manigreeva;Rahman, Tashnin;Kataki, Amal Chandra;Sharma, Jagannath Dev;Nandy, Pintu;Baishya, Nizara 8479
Performance status (PS) is a key factor in the selection of treatment in head and neck cancer patients (HNC). There is a probability in the development of an unfavorable PS with HNC advancing stages. This retrospective study was done on data of patients registered during the period from January 2010 to December 2012 at a cancer registry in the North Eastern India. PS was recorded according to the WHO scale. Multinomial logistic regression analysis was conducted to assess the probability of poor performance status with advancing stage. Out of 3,593 patients, there were 78.9% (2,836) males and 21.1% (757) females. Average PS0 was seen in 57.4% of all HNCs, less than 1% of all cases in HNCs with poor PS3-4 except in cases with thyroid, parotid and nose and PNS cancers, 0.7% stage IV (${\pm}M1$ ) HNC with PS4, favorable PS0-1 was seen in 84% to 100% of cases, RR=57.1 (CI=21.2-154.1) in M1 for PS4 and with advancing stages the probability of worsening of PS0 to PS4 was 3 times (P=0.021, 95% CI= 1.187-8.474). In HNC, the majority of patients presents with a favorable PS0-1 with different odds of worsening of PS with advancing stages and the presence of metastasis in stage IV is significantly associated with a poor PS. -
Karimi, Asrin;Delpisheh, Ali;Sayehmiri, Kourosh;Saboori, Hojjatollah;Rahimi, Ezzatollah 8483
Background: Breast cancer is the most common cancer and the second most common cause of cancer-induced mortalities in Iranian women, following gastric carcinoma. The survival of these patients depends on several factors, which are very important to identify in order to understand the natural history of the disease. Materials and Methods: In this retrospective study, 313 consecutive women with pathologically-proven diagnosis of breast cancer who had been treated during a seven-year period (January 2006 until March 2014) at Towhid hospital, Sanandaj city, Kurdistan province of Iran, were recruited. The Kaplan-Meier method was used for data analysis, and finally those factors that showed significant association on univariate analysis were entered in a Cox regression model. Results: the mean age of patients was$46.10{\pm}10.81$ years. Based on Kaplan-Meier method median of survival time was 81 months and 5 year survival rate was$75%{\pm}0.43$ . Tumor metastasis (HR=9.06, p=0.0001), relapse (HR=3.20, p=0.001), clinical stage of cancer (HR=2.30, p=0.03) and place of metastasis (p=0.0001) had significant associations with the survival rate variation. Patients with tumor metastasis had the lowest five-year survival rate (37%)and among them patients who had brain metastasis were in the worst condition (5 year survival rate=$11%{\pm}0.10$ ). Conclusions: Our findings support the observation that those women with higher stages of breast malignancies (especially with metastatic cancer) have less chance of surviving the disease. Furthermore, screening programs and early detection of breast cancer may help to increase the survival of those women who are at risk of breast cancer. -
Karadag, Burak;Kocak, M.;Kayikcioglu, F.;Ercan, F.;Dilbaz, B.;Kose, M.F.;Haberal, A. 8489
Objective: To verify the basic preoperative evaluation in the discrimination between benign and malignant adnexal masses in our clinical practice. Materials and Methods: Data were collected on the records of 636 women with adnexal masses who had undergone surgery either by open or endoscopic approaches. Those with obvious signs of malignancy, any history of cancer, emergency surgeries without basic evaluation were excluded. The preoperative features by age, ultrasound and serum Ca125 level were compared with final histopathological diagnosis at the four departments of the institution. These are the general gynecology (Group 1: exploratory laparotomy), the gynecologic endoscopy (Group 2: laparoscopy and adnexectomy), the gynecological oncology (Group 3: staging laparotomy) and the gynecologic endocrinology and infertility (Group 4: laparoscopy and cystectomy). Results: There were simple and complex cyst rates of 22.3% and 77.2%, respectively. There were 86.3% benign, 4.1% (n:20) borderline ovarian tumor (BOT) and 6.4% (n:48) malignant lesions. There were 3 BOT and 9 ovarian cancers in Group 1 and one BOT and two ovarian cancer in the Group 2. During the surgery, 15 BOT (75%) and 37 ovarian cancer (77%) were detected in the Group 3, only one BOT was encountered in the Group 4. The risk of rate of unsuspected borderline or focally invasive ovarian cancer significantly increased by age, size, complex morphology and Ca125 (95% CI, OR=2.72, OR=6.60, OR=6.66 and OR=4.69, respectively). Conclusions: Basic preoperative evaluation by comprehensive ultrasound imaging combined with age and Ca125 level has proved highly accurate for prediction of unexpected malignancies. Neither novel markers nor new imaging techniques provide better information that allow clinicians to assess the feasibility of the planned surgery; consequently, the risk of inadvertent cyst rupture during laparoscopy may be significantly decreased in selected cases. -
Huang, Xin-En;Cao, Jie;Qian, Zhi-Ying;Xu, Xia;Shi, Lin;Wu, Xue-Yan;Liu, Jin;Wang, Lin 8495
Purpose: To investigate whether it is safe to use leucogen tablets 60 mg three times per day (180 mg for a day) and whether this regimen could reduce the incidence of febrile neutropenia caused by chemotherapy. Methods: This prospectively designed study focused on the safety and effectiveness of leucogen tablets 60mg three times per day for a group of cancer patients during chemotherapy for mainly lung or gastric cancers. The tablets were administered from 5 days before until the termination of chemotherapy. Neutropenia and other healthcare encounters were defined as events and occurrence was estimated for comparison. Results: We identified 39 patients receiving leucogen tablets 60mg three times per day, including 11 with gastric, 12 with lung and 16 with other sites of cancer. The mean age was 65 (29-75) years and there were 27 male and 12 female patients. The mean duration of leucogen tablets intake was 59 days. Eighteen patients were treated with taxane-based, 4 with irinotecan-based and 17 with other chemotherapy. The incidence of febrile neutropenia was 0%. Twelve patients were found severe neutropenia (grade III/IV), and the duration of severe neutropenia (grade III/IV) was 5 days. Treatment-emergent adverse events were attributable to complications of myelosuppressive chemotherapy or the primary disease (i.e., alopecia, nausea, asthenia, neutropenia, and severe hepatic renal dysfunction). No chemotherapy was delayed and no treatment related death was observed. Conclusions: This study suggested that leucogen tablets 60mg three times per day (180mg for a day) are safe and could be effective for preventing febrile neutropenia in patients with chemotherapy. -
Sepandi, Mojtaba;Akrami, Majid;Tabatabaee, Hamidreza;Rajaeefard, Abdolreza;Tahmasebi, Sedigheh;Angali, Kambiz Ahmadi;Rezaianzadeh, Abbas;Talei, Abdolrasoul 8499
The incidence rate of breast cancer in developed countries is almost three-fold higher than in developing countries. Iran has had one of the lowest incidence rates for breast cancer in the world, but during the recent decades a marked increase has been seen. The purpose of this study was to investigate some established risk factors of breast cancer in Iranian women. A study of 11,850 women participating in abreast screening program was conducted. The 197 women diagnosed with breast cancer and 11,653 healthy women were compared. Logistic regression was performed to investigate associations of reproductive and anthropometric factors with breast cancer risk. Family history of breast cancer (OR=1.94, 95%CI=1.35-2.78), occupation (OR= 1.65,95%CI=1.20-2.25), education level (OR=0.50,95%CI=0.28-0.91), parity (OR=0.27, 95%CI=0.12-0.59), menopausal status (OR=3.15, 95%CI=2.35-4.21), age at menarche (OR=0.33, 95%CI=0.15-0.70), and age at the first pregnancy (OR=4.10, 95%CI=1.13-14.77) were related to the risk of breast cancer. Decrease in parity may to some extent explain the rising trend of incidence of breast cancer incidence in Iranian women. -
Han, Kyu-Tae;Kim, Sun Jung;Lee, Seo Yoon;Park, Eun-Cheol 8503
Background: After the WHO recommended HPV vaccination of the general population in 2009, government support of HPV vaccination programs was increased in many countries. However, this policy was not implemented in Korea due to perceived low cost-effectiveness. Thus, the aim of this study was to analyze the cost-utility of HPV vaccination programs targeted to high risk populations as compared to vaccination programs for the general population. Materials and Methods: Each study population was set to 100,000 people in a simulation study to determine the incremental cost-utility ratio (ICUR), then standard prevalence rates, cost, vaccination rates, vaccine efficacy, and the Quality-Adjusted Life-Years (QALYs) were applied to the analysis. In addition, sensitivity analysis was performed by assuming discounted vaccination cost. Results: In the socially vulnerable population, QALYs gained through HPV vaccination were higher than that of the general population (General population: 1,019, Socially vulnerable population: 5,582). The results of ICUR showed that the cost of HPV vaccination was higher for the general population than the socially vulnerable population. (General population: 52,279,255 KRW, Socially vulnerable population: 9,547,347 KRW). Compared with 24 million KRW/QALYs as the social threshold, vaccination of the general population was not cost-effective. In contrast, vaccination of the socially vulnerable population was strongly cost-effective. Conclusions: The results suggest the importance and necessity of government support of HPV vaccination programs targeted to socially vulnerable populations because a targeted approach is much more cost-effective. The implementation of government support for such vaccination programs is a critical strategy for decreasing the burden of HPV infection in Korea. -
Woo, Hae Dong;Park, Sohee;Oh, Kyungwon;Kim, Hyun Ja;Shin, Hae Rim;Moon, Hyun Kyung;Kim, Jeongseon 8509
Many studies have found links between diet and cancer. The summary estimates of the association between dietary factors and cancer risk were investigated using previously reported studies of the Korean population. Gastric cancer risk was inversely associated with the high intake of soy foods [OR (95% CI): 0.32 (0.25-0.40) for soybean, 0.56 (0.45-0.71) for soybean curd, and 0.67 (0.46-0.98) for soymilk], allium vegetables [OR (95% CI): 0.37 (0.26-0.53) for green onion, 0.54 (0.40-0.73) for garlic, and 0.54 (0.35-0.85) for onion], fruits [OR (95% CI): 0.61 (0.42-0.88)], and mushrooms [OR (95% CI): 0.43 (0.21-0.88)]. Salt and Kimchi were associated with an increased gastric cancer risk [OR (95% CI): 1.92 (1.52-2.43) and 2.21 (1.29-3.77), respectively]. Colorectal cancer risk was positively associated with meat intake [OR (95% CI): 1.25 (1.15-1.36)]. Total soy products, soybean curd, and soymilk showed an inverse association with breast cancer risk [OR (95% CI): 0.61 (0.38-0.99), 0.47 (0.34-0.66), and 0.75 (0.57-0.98), respectively]. Green/yellow and light colored vegetables were associated with a reduced risk of breast cancer [OR (95% CI): 0.34 (0.23-0.49) and 0.44 (0.21-0.90), respectively]. Mushroom intake was inversely associated in pre-menopausal women only [OR (95% CI): 0.47 (0.26-0.86)]. In conclusion, soy foods, fruits and vegetables might reduce cancer risk in the Korean population. High salt food might be risk factor for gastric cancer, and intake of high amount of meat might cause colorectal cancer. -
In many countries of the Association of Southeast Asian Nations (ASEAN), cancer is an increasing problem due to ageing and a transition to Western lifestyles. Governments have been slow to react to the health consequences of these socioeconomic changes, leading to the risk of a cancer epidemic overwhelming the region. A major limitation to motivating change is the paucity of high-quality data on cancer, and its socioeconomic repercussions, in ASEAN. Two initiatives have been launched to address these issues. First, a study of over 9000 new cancer patients in ASEAN - the ACTION study - which records information on financial difficulties, as well as clinical outcomes, subsequent to the diagnosis. Second, a series of roundtable meetings of key stakeholders and experts, with the broad aim of producing advice for governments in ASEAN to take appropriate account of issues relating to cancer, as well as to generate knowledge and interest through engagement with the media. An important product of these roundtables has been the Jakarta Call to Action on Cancer Control. The growth and ageing of populations is a global challenge for cancer services. In the less developed parts of Asia, and elsewhere, these problems are compounded by the epidemiological transition to Western lifestyles and lack of awareness of cancer at the government level. For many years, health services in less developed countries have concentrated on infectious diseases and mother-and-child health; despite a recent wake-up call (United Nations, 2010), these health services have so far failed to allow for the huge increase in cancer cases to come. It has been estimated that, in Asia, the number of new cancer cases per year will grow from 6.1 million in 2008 to 10.6 million in 2030 (Sankaranarayanan et al., 2014). In the countries of the Association of Southeast Asian Nations (ASEAN), corresponding figures are 770 thousand in 2012 (Figure 1), rising to 1.3 million in 2030 (Ferlay et al., 2012). ASEAN consists of Brunei Darussalam, Cambodia, Indonesia, Lao, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. It, thus, includes low- and middle-income countries where the double whammy of infectious and chronic diseases will pose an enormous challenge in allocating limited resources to competing health issues. Cancer statistics, even at the sub-national level, only tell part of the story. Many individuals who contract cancer in poor countries have no medical insurance and no, or limited, expectation of public assistance. Whilst any person who has a family member with cancer can expect to bear some consequential burden of care or expense, in a poor family in a poor environment the burden will surely be greater. This additional burden from cancer is rarely considered, and even more rarely quantified, even in developed nations.
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Bae, Jong-Myon;Park, Boyoung;H, Eun-Heem;Ha, Mina 8527