Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Breast cancer primary prevention is a high research priority due to the high psychological and economic costs. The disease is a multistep process and several risk factors have been recognized. Over the past three decades numerous studies have investigated the association of lifestyle with breast cancer, showing independent effects of various factors. We report here a summary of the present state of knowledge on the role of lifestyle patterns, such as physical activity, diet, smoking, hormone therapy, and experience of psychological stress in the modulation of breast cancer in women, and discuss commonly accepted biological mechanisms hypothesized as responsible for the associations. The findings indicate that regular physical activity of moderate to vigorous intensity is probably linked with the decreased breast cancer risk among postmenopausal females and suggestive for a decrease of the risk in premenopausal women. In contrast, the consumption of high-fat diet, alcohol intake, and use of combined estrogen and synthetic progestagen hormonal therapy may increase the risk. Epidemiological findings dealing with a role of smoking and experience of psychological stress are conflicting.
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Zhang, Shu-Fang;Wang, Xiao-Lu;Yang, Xiao-Qi;Chen, Ning 10557
It is well known that conventional chemotherapy and radiation therapy can result in toxicity to both normal cells and tumor cells, which causes limitations in the application of these therapeutic strategies for cancer control. Novel and effective therapeutic strategies for cancers with no or low toxicity for normal cells are a high priority. Therefore, natural products with anticancer activity have gained more and more attention due to their favorable safety and efficacy profiles. Pre-clinical and clinical studies have demonstrated that several representative natural compounds such as resveratrol, epigallocatechin-3-gallate, curcumin, allicin and ginsenosides have obvious anticancer potential. In this article, we summarize autophagy-associated targeting pathways of such natural products for inducing the death of cancer cells, and discuss the core autophagic pathways involved in cancer treatments. Recent advances in the discovery, evaluation and exploitation of natural compounds as therapeutic agents for cancers will provide references and support in pre-clinical and clinical application of novel natural drugs for the treatment of primary and metastatic tumors in the future. -
Taylor, Victoria M.;Ko, Linda K.;Hwang, Joo Ha;Sin, Mo-Kyung;Inadomi, John M. 10565
Gastric cancer incidence rates vary dramatically by world region with East Asia having the highest rate. The Asian population of the United States (US) is growing rapidly and over 17 million Americans are of Asian descent. A majority of Chinese, Korean and Vietnamese Americans are immigrants. Americans of East and Southeast Asian descent experience marked gastric cancer disparities and the incidence rate among Korean men in the US is over five times higher than the incidence rate among non-Hispanic white men. Randomized controlled trials have provided evidence for the effectiveness of helicobacter pylori identification and eradication in preventing gastric cancer. Additionally, Japan and South Korea have both experienced improvements in gastric cancer mortality following the implementation of programs to detect early stage gastric cancers. There are currently no clear US guidelines regarding the primary and secondary prevention of gastric cancer in high-risk immigrant populations. However, it is likely that a proportion of US physicians are already recommending gastric cancer screening for Asian patients and some Asian immigrants to the US may be completing screening for gastric cancer in their native countries. Surveys of US primary care physicians and Asian American communities should be conducted to assess current provider practices and patient uptake with respect to gastric cancer prevention and control. In the absence of clinical guidelines, US health care providers who serve high-risk Asian groups could consider a shared decision-making approach to helicobacter pylori identification and eradication, as well as gastric endoscopy. -
Kazerouni, Iman Abaspur;Zadeh, Hossein Ghayoumi;Haddadnia, Javad 10573
Background: Accuracy in feature extraction is an important factor in image classification and retrieval. In this paper, a breast tissue density classification and image retrieval model is introduced for breast cancer detection based on thermographic images. The new method of thermographic image analysis for automated detection of high tumor risk areas, based on two-directional two-dimensional principal component analysis technique for feature extraction, and a support vector machine for thermographic image retrieval was tested on 400 images. The sensitivity and specificity of the model are 100% and 98%, respectively. -
Dogra, Atika;Doval, Dinesh Chandra;Sardana, Manjula;Chedi, Subhash Kumar;Mehta, Anurag 10577
Background: Triple-negative breast cancer (TNBC), characterized by the lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2, is typically associated with a poor prognosis. The majority of TNBCs show the expression of basal markers on gene expression profiling and most authors accept TNBC as basal-like (BL) breast cancer. However, a smaller fraction lacks a BL phenotype despite being TNBC. The literature is silent on non-basal-like (NBL) type of TNBC. The present study was aimed at defining behavioral differences between BL and NBL phenotypes. Objectives: i) Identify the TNBCs and categorize them into BL and NBL breast cancer. ii) Examine the behavioral differences between two subtypes. iii) Observe the pattern of treatment failure among TNBCs. Materials and Methods: All TNBC cases during January 2009-December 2010 were retrieved. The subjects fitting the inclusion criteria of study were differentiated into BL and NBL phenotypes using surrogate immunohistochemistry with three basal markers$34{\beta}E12$ , c-Kit and EGFR as per the algorithm defined by Nielsen et al. The detailed data of subjects were collated from clinical records. The comparison of clinicopathological features between two subgroups was done using statistical analyses. The pattern of treatment failure along with its association with prognostic factors was assessed. Results: TNBC constituted 18% of breast cancer cases considered in the study. The BL and NBL subtypes accounted for 81% and 19% respectively of the TNBC group. No statistically significant association was seen between prognostic parameters and two phenotypes. Among patients with treatment failure, 19% were with BL and 15% were with NBL phenotype. The mean disease free survival (DFS) in groups BL and NBL was 30.0 and 37.9 months respectively, while mean overall survival (OS) was 31.93 and 38.5 months respectively. Treatment failure was significantly associated with stage (p=.023) among prognostic factors. Conclusions: Disease stage at presentation is an important prognostic factor influencing the treatment failure and survival among TNBCs. Increasing tumor size is related to lymph node positivity. BL tumors have a more aggressive clinical course than that of NBL as shown by shorter DFS and OS, despite having no statistically significant difference between prognostic parameters. New therapeutic alternatives should be explored for patients with this subtype of breast cancer. -
Saelee, Pensri;Chaiwerawattana, Arkom;Ogawa, Kumiko;Cho, Young-Man;Tiwawech, Danai;Suktangman, Vimol 10585
Breast cancer susceptibility gene 1 (BRCA1), mapped on chromosome 17q21, is implicated in the mechanisms of cellular DNA repair. Inactivation of this gene is involved in the development of many human cancers, including breast cancer. This study aimed to investigate the prognostic value of BRCA1 promoter hypermethylation and expression in breast cancer cases. Sixty-one breast cancers were examined for BRCA1 hypermethylation by methylation-specific polymerase chain reaction (PCR), and 45 paired normal breast tissues were analyzed for altered BRCA1 mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Aberrant methylation status in BRCA1 was detected in 15 of 61 cases (24.6%), while reduced expression was found in 7 of 45 (15.6%). BRCA1 hypermethylation was statistically associated with tumor grade III (p=0.04), a high frequency of stage IIB (p=0.02), and triple-negative phenotype (OR= 3.64, 95%CI =1.1-12.3, p=0.03). Our findings indicated that BRCA1 promoter hypermethylation is a useful prognostic marker for breast cancer. -
Zhang, Xiu-Ling;Dang, Yi-Wu;Li, Ping;Rong, Min-Hua;Hou, Xin-Xi;Luo, Dian-Zhong;Chen, Gang 10591
Background: Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) has been reported to be associated with the development of various cancers. However, the role of TRAF6 in lung cancer remains unclear. Objective: To explore the expression and clinicopathological significance of TRAF6 protein in lung cancer tissues. Materials and Methods: Three hundred and sixty-five lung cancer samples and thirty normal lung tissues were constructed into 3 microarrays. The expression of TRAF6 protein was determined using immunohistochemistry (IHC). Furthermore, correlations between the expression of TRAF6 and clinicopathological parameters were investigated. Results: The expression of TRAF6 in total lung cancer tissues (365 cases), as well as in small cell lung cancer (SCLC, 26 cases) and non-small cell lung cancer (NSCLC, 339 cases) was significantly higher compared with that in normal lung tissues. The ROC curve showed that the area under curve of TRAF6 was 0.663 (95%CI 0.570~0.756) for lung cancer. The diagnostic sensitivity and specificity of TRAF6 were 52.6% and 80%, respectively. In addition, the expression of TRAF6 was correlated with clinical TNM stage, tumor size and lymph node metastasis in all lung cancers. Consistent correlations were also observed for NSCLCs. Conclusions: TRAF6 might be an oncogene and the expression of TRAF6 protein is related to the progression of lung cancer. Thus, TRAF6 might become a target for diagnosis and gene therapy for lung cancer patients. -
Shao, Shu-Li;Cui, Ting-Ting;Zhao, Wei;Zhang, Wei-Wei;Xie, Zhen-Li;Wang, Chang-He;Jia, Hong-Shuang;Liu, Qian 10597
Up-regulation of multidrug resistance-associated protein 1 (MRP1) is regarded as one of the main causes for multidrug resistance (MDR) of tumor cells, leading to failure of chemotherapy-based treatment for a multitude of cancers. However, whether silencing the overexpressed MRP1 is sufficient to reverse MDR has yet to be validated. This study demonstrated that RNAi-based knockdown of MRP1 reversed the increased efflux ability and MDR efficiently. Two different short haipin RNAs (shRNAs) targeting MRP1 were designed and inserted into pSilence-2.1-neo. The shRNA recombinant plasmids were transfected into cis-dichlorodiamineplatinum-resistant A549 lung (A549/DDP) cells, and then shRNA expressing cell clones were collected and maintained. Real time PCR and immunofluorescence staining for MRP1 revealed a high silent efficiency of these two shRNAs. Functionally, shRNA-expressing cells showed increased rhodamine 123 retention in A549/DDP cells, indicating reduced efflux ability of tumor cells in the absence of MRP1. Consistently, MRP1-silent cells exhibited decreased resistance to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and DDP, suggesting reversal of MDR in these tumor cells. Specifically, MRP1 knockdown increased the DDP-induced apoptosis of A549/DDP cells by increased trapping of their cell cycling in the G2 stage. Taken together, this study demonstrated that RNAi-based silencing of MRP1 is sufficient to reverse MDR in tumor cells, shedding light on possible novel clinical treatment of cancers. -
Pouresmaeili, Farkhondeh;Hosseini, S. Jalil;Farzaneh, Farah;Karimpour, Arezoo;Azargashb, Eznollah;Yaghoobi, Mohammad;Kamarehei, Maryam 10603
Background: The Prostate cancer is the 2nd most common cancer worldwide for males, and the 5th most common cancer overall, with an estimated 900,000 new cases diagnosed in 2008 (14% of the total in males and 7% of the total overall) aim of this study was to assess some of the most proposed environmental factors influencing the incidence of prostate cancer among Iranian men. Smoking, opioids, occupation and living location were considered as studied risk factors of the prostate cancer in this research. Material and methods: Two groups of affected men with prostate cancer and controls aged 50-75 years referred to medical clinics were subjects in this case-control study. Living and working place, smoking and drug consuming habits were assessed for any associations with prostate cancer. Results: The largest number, of patients, in order, belonged to Tehran, provincial capitals, major industrial cities, small towns and villages, respectively. The disease showed links with smoking and drugs with a significant difference between controls and patients (P value <0.0001). Conclusions: Our recent evidence duplicates previously done researches confirming the serious adverse effects of smoking and drugs on the prostate cancer occurrence in Iranian men. Living place bearings some hazardous behaviors which increases the rate of diseases as well as advanced chance for associated cancers like prostate. -
Selcukbiricik, Fatih;Erdamar, Sibel;Buyukunal, Evin;Serrdengecti, Suheyla;Demirelli, Fuat 10607
Background: HER2 expression in the primary tumor and its lymph node metastases vary in gastric cancer, reflecting intratumoral heterogeneity. This finding also suggests that proliferation of a different clone in metastatic nodes is possible. In the current study, we aimed to determine the cause of discordance in HER-2 expression in the primary tumor and lymph node metastases for patients with gastric cancer. Materials and Methods: Eighty-one patients with gastric cancer who had undergone radical gastrectomy and were found to have lymph node metastasis upon pathological examination were included. Histopathological samples were obtained from biopsies obtained during patient gastrectomies and lymph node dissection. HER2 status was evaluated by both immunohistochemistry (IHC) and silver in situ hybridization (SISH). Results: Sixty-four (79%) patients were SISH (-), while 17 (21%) were SISH (+) in the primary tumor. However, in metastatic lymph nodes, HER2 status was SISH positive in 5 (28.3%) of the 64 SISH (-) primary tumor specimens. One of the 17 SISH (+) primary tumors was SISH (-) in the metastatic lymph nodes. Thus, SISH results for HER2 in both primary tumors and lymph node metastases were comparable, showing a concordance of 92.5%. In total, six patients demonstrated discordance between the primary tumor and lymph node metastases. The prevalence of HER2 discordance was significantly higher for patients in the pN2 and N3 stages (p=0.007). Although discordant patients had worse survival rates than concordant patients, the differences were not significant (p>0.05).Conclusions: Our study indicates that the frequency of concordance in HER2 status, as determined by IHC or SISH, is high in primary tumors and their corresponding lymph node metastases for patients with gastric cancer. If there is a discrepancy in HER2 status, its evaluation by both IHC and SISH may be useful for detecting patients who would benefit from trastuzumab, and it would therefore help guide decision-making processes in administering treatment. -
Gao, Shi-Yong;Li, Jun;Wang, Long;Sun, Qiu-Jia;Gong, Yun-Fei;Gang, Jian;Su, Yi-Jun;Ji, Yu-Bin 10613
Background: Both alcohol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, the dried root tuber of which is named Baifuzi in Chinese, have been used for folklore treatment of cancer in Northeast of China. However, little is known about which is most suitable to the cancer therapy. Materials and Methods: Serum pharmacology and MTT assays were adopted to detect the effects of ethanol and aqueous extracts of Sauromatum giganteum(Engl.) Cusimano and Hett, prepared by heat reflux methods, on proliferation of different cancer cells. Results: Cancer cells treated with medium supplemented with 10%, 20%, 40% serum(v/v) containing ethanol extract had a decline in viability, with inhibition rates of 7.69%, 21.8%, 41.9% in MCF-7 cells, 42.8%, 48.1%, 51.8% in SGC-7901 cells, 44.1%, 49.2%, 53.7% in SMMC-7721 cells, 6.8%, 15.2%, 39.8% in HepG2 cells, 7.57%, 16.3%, 36.2% in HeLa cells, 6.24%, 12.5%, 27.4% in A549 cells, and 7.20%, 17.5%, 31.3% in MDA-MB-231 cells, respectively. Viability in the aqueous extract groups was no different with that of controls. Conclusions: An ethanol extract of Sauromatum giganteum(Engl.) Cusimano and Hett inhibited the proliferation of SMMC-7721, SGC-7901 and MCF-7 cells, which supports the use of alcoholic but not aqueous extracts for control of sensive cancers, which might include hepatocarcinoma, gastric cancer and breast cancer. -
Wang, Yao-Wu;Yin, Chun-Li;Zhang, Hong-Yi;Hao, Jin-Min;Yang, Yue-Ye;Liao, Heng;Jiao, Bao-Hua 10621
Background: Increasing evidence has indicated that high Forkhead box protein C2 (FOXC2) level is closely associated with the development, progression, and poor prognosis of a variety of tumors. However, the relationship between FOXC2 and the progression of human gliomas remains to be clarified. The aim of present study was to assess FOXC2 expression and to explore its contribution in human gliomas. Materials and Methods: Realtime quantitative PCR was performed to examine FOXC2 expression in 85 pairs of fresh frozen glioma tissues and corresponding non-neoplastic brain tissues. Associations of FOXC2 expression with clinicopathological factors and prognosis of glioma patients were statistically analyzed. Results: The relative mRNA expression of FOXC2 was significantly higher in glioma tissues than the corresponding non-neoplastic brain tissues (p<0.001). In addition, high FOXC2 expression was significantly associated with advanced pathological grade (P=0.005) and the low Karnofsky performance score (KPS) (p=0.003), correlating with poor survival (p<0.001). Furthermore, multivariate Cox regression analysis showed that high FOXC2 expression was an independent predictor of overall survival (p=0.006). Conclusions: FOXC2 may act as an oncogenic gene and represent a potential regulator of aggressive development and a candidate prognostic marker in human gliomas. -
Tomita, Masaki;Ayabe, Takanori;Chosa, Eiichi;Kawagoe, Katsuya;Nakamura, Kunihide 10627
Background: Epidermal growth factor receptor (EGFR) mutations play a vital role in the prognosis of patients with lung adenocarcinoma. Such somatic mutations are more common in women who are non-smokers with adenocarcinoma and are of Asian origin. However, to our knowledge, there are few studies that have focused on men. Materials and Methods: One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. Results: EGFR mutations were positive in 48.9% and negative (wild type) in 51.1%. Overall mutation was significant in women (66.0% vs. 32.2%) compared with men (p<0.001). For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure or mixed ground-glass nodule type on computed tomography and smoking status. However, in men, EGFR mutation status was only associated with lepidic dominant histologic subtype and not the other variables. Interestingly, the Brinkman index of men with mutant EGFR also did not differ from that for the wild type ($680.0{\pm}619.3$ vs.$813.1{\pm}552.1$ p=0.1077). Conclusions: The clinical characteristics of men with lung adenocarcinoma related to EGFR mutation are not always similar to that of overall patients. Especially we failed to find the relationship between EGFR mutations and smoking status in men. -
Alacacioglu, Ahmet;Ulger, Eda;Varol, Umut;Yildiz, Ibrahim;Salman, Tarik;Bayoglu, Vedat;Dirican, Ahmet;Demir, Lutfiye;Akyol, Murat;Yildiz, Yasar;Kucukzeybek, Yuksel;Ataman, Gorkem;Can, Huseyin;Alacacioglu, Inci;Tarhan, Mustafa Oktay 10631
Background: We aimed to investigate anxiety, depression and sexual satisfaction levels and the effects of depression and anxiety upon the sexual satisfaction of Turkish breast cancer patients and their partners. Materials and Methods: Data were collected from one hundred breast cancer patients and their partners, using three forms: one covering information about socio-demographic characteristics of the patients, the Hospital Anxiety and Depression Scale (HADs) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). Results: The frequencies, avoidance and touch subscores were statistically significantly high in the patients. Among those with high anxiety scores, the frequency, communication, satisfaction, touch, and anorgasmic subscale scores of GRISS were found to be significantly high. Among the partners whose anxiety scores were high, only the premature ejaculation subscale was statistically significant. It was determined that for partners with higher depression scores, the communication, satisfaction, avoidance, premature ejaculation and erectile dysfunction subscores of GRISS were statistically higher compared to partners with lower depression scores. Conclusions: Patients' quality of life may be increased by taking precautions to reduce their and their partners' psychosocial and psychosexual concerns. -
Goel, Sonu;Kumar, Ravinder;Lal, Pranay;Tripathi, J.P.;Singh, Rana J.;Rathinam, Arul;Christian, Anant 10637
Background: Section 5 of India's tobacco control legislation "Cigarettes and Other Tobacco Products Act (COTPA), 2003"comprehensively prohibits all kinds of tobacco advertisement, promotion and sponsorship (TAPS), but permits advertisments at the point-of-sale (POS) under certain conditions. This provision has been exploited by the tobacco companies to promote their products. Objective: To measure compliance with the provisions of Section 5 of Indian tobacco control legislation (COTPA, 2003) at point of sale. Materials and Methods: A cross-sectional survey using an observation checklist was conducted in 1860 POS across three jurisdictions (Chennai city, District Vadodara and District Mohali) in India. Results: The most common mode of advertisement of tobacco products was product showcasing (51.1%), followed by dangles (49.6%), stickers (33.8%) and boards (27.1%). More than one fourth of POS were found violating legal provisions for displaying advertisement boards in one or other forms (oversized, extended to full body lenth of POS, displayed brandname/packshot and promotional messages). Advertisement boards (16.3%) without health warnings were also found and wherever found, more than 90% health warning were not as per the specification in respect to size, font and background color. Conclusions: Point of sale advertising is aggressively used by the tobacco industry to promote their products. There is an urgent need of effective implementation of a comprehensive ban on tobacco product advertisement, promotion and sponsorship at point of sale. -
Li, Jun-Nan;Xu, Jing;Wang, Ju;Qing, Chun;Zhao, Yu-Mei;Liu, Pei-Fang 10643
Background: To study the relationship between mammographic findings and clinical/pathologic features in women with 1-15mm sized invasive breast cancer. Materials and Methods: We investigated a consecutive series of 134 cases diagnosed in Tianjin Medical University Cancer Institute and Hospital in 2007. Mammographic findings were classified into five groups as follows :1) stellate mass without calcification; 2) non-stellate mass without calcification; 3) intermediate suspicious calcification with or without associated mass; 4) higher probability malignant calcification with or without associated mass; 5) focal asymmetry/distortion without associated calcification. Associations between mammographic and clinical/pathological features (menopause status/family history/histologic grade/lymph node status and ER/PR/HER2 status) was analyzed through logistic regression and chi square tests. Results: Compared to the stellate mass without calcification group, higher probability malignant calcification patients were associated significantly with a positive lymph node status, always presenting in patients who were non-menopausal and with a family history of carcinoma. Conclusions: Higher probability malignant calcifications with or without associated tumor masses are associated with clinical/pathologic features of poor prognosis. -
Wu, Jiong;Zhou, Yan;Zhang, Chun-Yan;Song, Bin-Bin;Wang, Bei-Li;Pan, Bai-Shen;Lou, Wen-Hui;Guo, Wei 10647
Background: The aim of our study was to establish COLD-PCR combined with an unlabeled-probe HRM approach for detecting KRAS codon 12 and 13 mutations in plasma-circulating DNA of pancreatic adenocarcinoma (PA) cases as a novel and effective diagnostic technique. Materials and Methods: We tested the sensitivity and specificity of this approach with dilutions of known mutated cell lines. We screened 36 plasma-circulating DNA samples, 24 from the disease control group and 25 of a healthy group, to be subsequently sequenced to confirm mutations. Simultaneously, we tested the specimens using conventional PCR followed by HRM and then used target-DNA cloning and sequencing for verification. The ROC and respective AUC were calculated for KRAS mutations and/or serum CA 19-9. Results: It was found that the sensitivity of Sanger reached 0.5% with COLD-PCR, whereas that obtained after conventional PCR did 20%; that of COLD-PCR based on unlabeled-probe HRM, 0.1%. KRAS mutations were identified in 26 of 36 PA cases (72.2%), while none were detected in the disease control and/or healthy group. KRAS mutations were identified both in 26 PA tissues and plasma samples. The AUC of COLD-PCR based unlabeled probe HRM turned out to be 0.861, which when combined with CA 19-9 increased to 0.934. Conclusions: It was concluded that COLD-PCR with unlabeled-probe HRM can be a sensitive and accurate screening technique to detect KRAS codon 12 and 13 mutations in plasma-circulating DNA for diagnosing and treating PA. -
Saikia, Bhaskar Jyoti;Das, Mandakini;Sharma, Santanu Kumar;Sekhon, Gaganpreet Singh;Zomawia, Eric;Singh, Yanglem Mohen;Mahanta, Jagadish;Phukan, Rup Kumar 10653
Background: A very high incidence of lung cancer is observed in Mizoram and Manipur, North East India. We conducted a population based case control study to establish associations of p53 codon 72 polymorphisms and interactions with environmental factors for this high incidence. Material and Methods: A total of 272 lung cancer cases and 544 controls matched for age (${\pm}5years$ ), sex and ethnicity were collected and p53 codon 72 polymorphism genotypes were analyzed using a polymerase chain based restriction fragment length polymorphism assay. We used conditional multiple logistic regression analysis to calculate adjusted odds ratios and 95% confidence intervals after adjusting for confounding factors. Results: p53 Pro/Pro genotype was significantly associated with increased risk of lung cancer in the study population (adjusted OR=2.14, CI=1.35-3.38, p=0.001). Interactions of the p53 Pro/Pro genotype with exposure to wood smoke (adjusted OR=3.60, CI=1.85-6.98, p<0.001) and cooking oil fumes (adjusted OR=3.27, CI=1.55-6.87, p=0.002), betel quid chewing (adjusted OR=3.85, CI=1.96-7.55, p<0.001), tobacco smoking (adjusted OR=4.42, CI=2.27-8.63, p<0.001) and alcohol consumption (adjusted OR=3.31, CI=1.10-10.03, p=0.034) were significant regarding the increased risk of lung cancer in the study population. Conclusions: The present study provided preliminary evidence that a p53 codon 72 polymorphism may effect lung cancer risk in the study population, interacting synergistically with environmental factors. -
Tengku Din, Tengku Ahmad Damitri Al-Astani;Seeni, Azman;Khairi, Wirdatul-Nur Mohd;Shamsuddin, Shaharum;Jaafar, Hasnan 10659
Background: Rapamycin is an effective anti-angiogenic drug. However, the mode of its action remains unclear. Therefore, in this study, we aimed to elucidate the antitumor mechanism of rapamycin, hypothetically via apoptotic promotion, using MCF-7 breast cancer cells. Materials and Methods: MCF-7 cells were plated at a density of$1{\times}10^5$ cells/well in 6-well plates. After 24h, cells were treated with a series of concentrations of rapamycin while only adding DMEM medium with PEG for the control regiment and grown at$37^{\circ}C$ , 5%$CO_2$ and 95% air for 72h. Trypan blue was used to determine the cell viability and proliferation. Untreated and rapamycin-treated MCF-7 cells were also examined for morphological changes with an inverted-phase contrast microscope. Alteration in cell morphology was ascertained, along with a stage in the cell cycle and proliferation. In addition, cytotoxicity testing was performed using normal mouse breast mammary pads. Results: Our results clearly showed that rapamycin exhibited inhibitory activity on MCF-7 cell lines. The$IC_{50}$ value of rapamycin on the MCF-7 cells was determined as$0.4{\mu}g/ml$ (p<0.05). Direct observation by inverted microscopy demonstrated that the MCF-7 cells treated with rapamycin showed characteristic features of apoptosis including cell shrinkage, vascularization and autophagy. Cells underwent early apoptosis up to 24% after 72h. Analysis of the cell cycle showed an increase in the G0G1 phase cell population and a corresponding decrease in the S and G2M phase populations, from 81.5% to 91.3% and 17.3% to 7.9%, respectively. Conclusions: This study demonstrated that rapamycin may potentially act as an anti-cancer agent via the inhibition of growth with some morphological changes of the MCF-7 cancer cells, arrest cell cycle progression at G0/G1 phase and induction of apoptosis in late stage of apoptosis. Further studies are needed to further characterize the mode of action of rapamycin as an anti-cancer agent. -
Farshid, Gelareh;Sullivan, Thomas;Jones, Simeon;Roder, David 10665
Background: We wished to analyse patterns of use of needle biopsy procedures by BreastScreen Australia (BSA) accredited programs to identify areas for improvement. Design: BSA services provided anonymous data regarding percutaneous needle biopsy of screen detected lesions assessed between 2005-2009. Results: 12 services, from 5 of 7 Australian states and territories provided data for 18212 lesions biopsied. Preoperative diagnosis rates were 96.84% for lesion other than microcalcification (LOTM) and 93.21% for microcalcifications. At surgery 97.9% impalpable lesions were removed at the first procedure. Of 11548 Microcalcification (LOTM) biopsied, 46.9% were malignant. The final diagnosis was reached by conventional core biopsy (CCB) in 72.46%, FNAB in 21.33%, VACB in 1.69% and open biopsy in 4.52% of lesions. FNA is being limited to LOTM with benign imaging After FNAB, core biopsy was required for 38% of LOTM. In LOTM the mean false positive rate (FPR) was 0.36% for FNAB, 0.06% for NCB and 0% for VACB. Diagnostic accuracy was 72.75% for FNAB and 92.1% for core biopsies combined. Of 6441 microcalcifications biopsied 2305 (35.8%) were malignant. Microcalcifications are being assessed primarily by NCB but 6.57% underwent FNAB, 45.6% of which required NCB. False positive diagnoses were rare. FNR was 5% for NCB and 1.53% for VACB. Diagnostic accuracy was 73.52% for FNAB, 86.29% for NCB and 88.63% for VACB. Only 8 of 12 services had access to VACB facilities. Conclusions: BSA services are selecting lesions effectively for biopsy and are achieving high preoperative diagnosis rates. Gaps in the present accreditation standards require further consideration. -
Su, Meng;Yin, Zhi-Hua;Wu, Wei;Li, Xue-Lian;Zhou, Bao-Sen 10675
Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. Results: A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Conclusions: The TP53 Arg72Pro C allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted. -
Shen, Xing-Rong;Chai, Jing;Feng, Rui;Liu, Tong-Zhu;Tong, Gui-Xian;Cheng, Jing;Li, Kai-Chun;Xie, Shao-Yu;Shi, Yong;Wang, De-Bin 10683
The big gap between efficacy of population level prevention and expectations due to heterogeneity and complexity of cancer etiologic factors calls for selective yet personalized interventions based on effective risk assessment. This paper documents our research protocol aimed at refining and validating a two-stage and web-based cancer risk assessment tool, from a tentative one in use by an ongoing project, capable of identifying individuals at elevated risk for one or more types of the 80% leading cancers in rural China with adequate sensitivity and specificity and featuring low cost, easy application and cultural and technical sensitivity for farmers and village doctors. The protocol adopted a modified population-based case control design using 72, 000 non-patients as controls, 2, 200 cancer patients as cases, and another 600 patients as cases for external validation. Factors taken into account comprised 8 domains including diet and nutrition, risk behaviors, family history, precancerous diseases, related medical procedures, exposure to environment hazards, mood and feelings, physical activities and anthropologic and biologic factors. Modeling stresses explored various methodologies like empirical analysis, logistic regression, neuro-network analysis, decision theory and both internal and external validation using concordance statistics, predictive values, etc.. -
Phukan, Rup Kumar;Borah, Prasanta Kumar;Saikia, Bhaskar Jyoti;Das, Mandakini;Sekhon, Gaganpreet Singh;Mahanta, Jagadish 10691
Background: Association of angiotensin converting enzyme (ACE) gene polymorphisms with lung cancer susceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally, and ethnically isolated population. The area reports an especially high rate of tobacco usage in a variety of ways of consumption, compared with the rest of the Indian population. Materials and Methods: We conducted a population based case control study in two major high risk region for lung cancer from Northeast India. A total of 151 consecutive lung cancer cases diagnosed histopathologically and equal numbers of controls were recruited with record of relevant sociodemographic information. Blood samples were collected and processed to identify ACE gene polymorphism. Results: Significantly higher (40.4 % vs 29.1%, OR=1.97, CI=1.04-3.72; p=0.037) prevalence of the ACE II genotype was observed among lung cancer cases. Smoking was significantly associated with increased risk of lung cancer (OR=1.70, CI=1.02-2.81; p=0.041). An enhanced risk was also observed for interaction of ACE II genotype with tobacco smoking (OR=4.09, CI=1.51-11.05; p=0.005) and chewing (OR=3.68, CI=1.22-11.13; p=0.021). Conclusions: The present study indicates significant association s of the ACE II genotype with lung cancer in high risk Northeast India. -
Verim, Aysegul;Turan, Saime;Farooqi, Ammad Ahmad;Kahraman, Ozlem Timirci;Tepe-Karaca, Cigdem;Yildiz, Yemliha;Naiboglu, Baris;Ozkan, Nazli Ezgi;Ergen, Arzu;Isitmangil, Gulbu Aydinoglu;Yaylim, Ilhan 10697
The laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors occurring in the head and neck. Tumor necrosis factor related apoptosis induce ligand (TRAIL) and TRAIL-receptors (DR4, DR5, DcR1, DcR2) are known as important members of TRAIL-mediated biochemical signaling pathway. Associations between polymorphisms in these genes and clinicopathological characteristics of human laryngeal carcinoma are not well defined. This study therefore aimed to investigate a possible relationship among the TRAIL and TRAIL-DR4 polymorphisms and sTRAIL levels in the risk or progression of LSCC. A total of 99 patients with laryngeal cancer and 120 healthy subjects were enrolled in the study. DR4 C626G and TRAIL 1595 C/T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and sTRAIL levels were measured by ELISA. There were significant differences in the distribution of DR4 C626G genotypes and frequencies of the alleles between laryngeal cancer patients and controls (p<0.001) but not in TRAIL 1595 C/T. We found the increased frequency of the DR4 C626G homozygote CC genotype in patients than in controls (p<0.001). Haplotype analysis revealed that there was also a statistically significant relationship between TRAIL and TRAIL-DR4 polymorphisms and laryngeal cancer. Serum sTRAIL levels in the laryngeal patients with CC genotype who had advanced tumour stage were lower than those of patients with early tumor stage (p=0.014). Our findings suggest that DR4 C626G genotypes and sTRAIL levels might be associated with progression of laryngeal cancer in the Turkish population. -
Abbasi, Mehran Mesgari;Jahanban-Esfahlan, Rana;Monfaredan, Amir;Seidi, Khaled;Hamishehkar, Hamed;Khiavi, Monir Moradzadeh 10705
Oral cancer is one of the most common and lethal cancers in the world. Combination chemotherapy coupled with nanoparticle drug delivery holds substantial promise in cancer therapy. This study aimed to evaluate the efficacy and safety of two dosages of our novel pH and temperature sensitive doxorubicin-methotrexate-loaded nanoparticles (DOX-MTX NPs) with attention to the MMP-2 mRNA profile in a 4-nitroquinoline-1-oxide induced oral squamous cell carcinoma (OSCC) model in the rat. Our results showed that both IV and oral dosages of DOX-MTX NP caused significant decrease in mRNA levels of MMP-2 compared to the untreated group (p<0.003). Surprisingly, MMP-2 mRNA was not affected in DOX treated compared to cancer group (p>0.05). Our results indicated that IV dosage of MTX-DOX is more effective than free DOX (12 fold) in inhibiting the activity of MMP-2 in OSCCs (P<0.001). Furthermore, MMP-2 mRNA expression in the DOX-MTX treated group showed a significant relation with histopathological changes (P=0.011). Compared to the untreated cancer group, we observed no pathological changes and neither a significant alteration in MMP-2 amount in either of healthy controls that were treated with oral and IV dosages of DOX-MTX NPs whilst cancer group showed a high level of MMP-2 expression compared to healthy controls (p<0.001).Taking together our results indicate that DOX-MTX NPs is a safe chemotherapeutic nanodrug that its oral and IV forms possess potent anti-cancer properties on aggressive tumors like OSCC, possibly by affecting the expression of genes that drive tumor invasion and metastasis. -
Ni, Xiao-Chun;Yi, Yong;Fu, Yi-Peng;He, Hong-Wei;Cai, Xiao-Yan;Wang, Jia-Xing;Zhou, Jian;Fan, Jia;Qiu, Shuang-Jian 10713
Purpose: To investigate the prognostic value of serum amyloid A (SAA) in patients with hepatocellular carcinoma (HCC) undergoing surgery. Materials and Methods: Preoperative serum samples of 328 patients with HCC who underwent curative resection and of 47 patients with benign liver lesion were assayed. Serum levels of SAA were measured by enzyme-linked immunosorbent assay and its correlations with clinicopathological characteristics and survival were explored. Results: Levels of SAA were significantly higher in patients with HCC than those with benign liver lesion. There were strong correlations between preoperative serum SAA level and tumor size and more advanced BCLC stage. On univariate analysis, elevated SAA was associated with reduced disease-free survival and overall survival (p=0.001 and 0.03, respectively). Multivariate analyses showed that serum SAA level was an independent prognostic factor for overall survival (hazard ratio 2.80, p=0.01). Conclusions: High SAA serum level is a novel biomarker for the prognosis of HCC patients. -
Common Genetic Variations in the MUC5AC Gene are Not Related to Helicobacter pylori Serologic StatusZhou, Cheng-Jiang;Zhang, Liu-Wei;Gao, Fang;Zhang, Bin;Wang, Ying;Chen, Da-Fang;Jia, Yan-Bin 10719
Several lines of evidence suggest that MUC5AC genetic polymorphisms might confer susceptibility to H. pylori infection and therefore gastric cancer risk. We here assessed the association of common polymorphisms in the MUC5AC gene with H. pylori seroprevalence using an LD-based tagSNP approach in a north-western Chinese Han population. A total of 12 tagSNPs were successfully genotyped among 281 unrelated ethnic Han Chinese who had no cancer history, and no identifiable gastric disease or genetic disease. No significant association between any alleles, genotypes or haplotypes and H. pylori seroprevalence was observed. Our results suggest that common genetic variations in MUC5AC gene might not make a major contribution to the risk of H. pylori infection. -
Tolunay, Orkun;Celik, Umit;Karaman, Seyfettin Senih;Celik, Tamer;Resitoglu, Salim;Donmezer, Cigdem;Aydin, Fahri;Baspinar, Huseyin;Mert, Mustafa Kurthan;Samsa, Hasan;Arli, Sefa 10723
Background: To determine the level of knowledge on human papillomavirus (HPV) infection and vaccination, and the attitude towards HPV vaccination in pediatricians, obstetricians and gynecologists (OBG). Materials and Methods: Participants were administered a 40-question survey, investigating the demographic properties, the knowledge on the HPV infection-vaccination and attitudes towards vaccination. Results: The study enrolled a total of 228 participants (131 pediatricians and 97 OBGs). At a rate of 99.6%, the participants agreed with the fact that the HPV infection was the most common sexually transmitted disease and 33.8% of the participants had the opinion that the HPV vaccination should be administered only in women. The lowest level of HPV vaccine recommendation was among the pediatrics specialists (59.4%, p=0.012). When asked whether they would have their daughters receive HPV vaccination, 79.5% of the participants answered favorably; this rate was 36.7% for the sons. At a rate of 59.5% of the participants thought that the HPV vaccine needed to be included in the national vaccine schedule. Most of the participants (91.6%) had the idea that reduction of the vaccine costs would increase the vaccination frequency. Conclusions: We observed that the consideration of the costs and the prejudices relating to the inefficacy of vaccination as well as the inadequate level of knowledge were involved in the physicians' resistance to HPV vaccination. We believe that the healthcare professionals should be informed adequately to overcome false beliefs, thereby ensuring success of the HPV vaccine upon inclusion in the national vaccine schedule in the future. -
Taguchi, Satoru;Fukuhara, Hiroshi;Kakutani, Shigenori;Takeshima, Yuta;Miyazaki, Hideyo;Suzuki, Motofumi;Fujimura, Tetsuya;Nakagawa, Tohru;Igawa, Yasuhiko;Kume, Haruki;Homma, Yukio 10729
Background: Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Materials and Methods: We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Results: Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS${\geq}9$ and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS${\geq}9$ was an independent predictor of cancer-specific death. Conclusions: Pathologic GS${\geq}9$ and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS${\geq}9$ was an indispensable condition for bone metastasis, which may imply that patients with GS${\leq}8$ on adjuvant ADT are unlikely to develop bone metastasis. -
Krishnatreya, Manigreeva;Kataki, Aamal Chandra;Sharma, Jagannath Dev;Nandy, Pintu;Talukdar, Abhijit;Gogoi, Gayatri;Hoque, Nazmul 10735
Background: Cancers of the breast, uterine cervix and ovary are common cancers amongst females of North East India. Not much is known about the descriptive epidemiology of these cancers in our population. The present retrospective analysis was therefore performed. Materials and Methods: The data set available at the hospital based cancer registry of a regional cancer center of North-East India, containing information on patients registered during the period of January 2010 to December 2012, was applied. A total of 2,925 cases of breast, uterine cervix and ovarian cancer were identified. Results: Of the total, 1,295 (44.3%) were breast cancers, 1,214 (41.5%) were uterine cervix and 416 (14.2%) ovarian cancer, median age (range) for breast, uterine cervix and ovary were 45 (17-85), 48 (20-91) and 45 years (7-80), respectively. Some 43.5% of cases with uterine cervix patients were illiterate, 5.4% and 5.7% stage I in breast and cervix respectively and 96.4% of ovarian cancers in advanced stage. Conclusions: Improvement of female education can contribute to increase the proportion of early stage diagnosis of breast and uterine cervix in our population. Any population-based intervention for the detection of cancers of breast, uterine cervix and ovarian cancer should be started early in our population. -
Liu, Xue-Jing;Zhu, Ying;Liu, Pei-Fang;Xu, Yi-Lin 10739
The present study aimed at evaluating and comparing the diagnostic performance of B-mode ultrasound (US), elastography score (ES), and strain ratio (SR) for the differentiation of breast lesions. This retrospective study enrolled 431 lesions from 417 in-hospital patients. All patients were examined with both conventional ultrasound and elastography. Two experienced radiologists reviewed ultrasound and elasticity images. The histopathologic result obtained from ultrasound-guided core biopsy or operation excisions were used as the reference standard. Pathologic examination revealed 276 malignant lesions (64%) and 155 benign lesions (36%). A cut-off point of 4.15 (area under the curve, 0.891) allowed significant differentiation of malignant and benign lesions. ROC (receiver-operating characteristic) curves showed a higher value for combination of B-mode ultrasound and elastography for the diagnosis of breast lesions. Conventional ultrasound combined elastography showed high sensitivity, specificity, and accuracy for group II lesions (10mm${\leq}20mm$). Elastography combined with conventional ultrasound show high specificity and accuracy for differentiation of benign and malignant breast lesions. Elastography is particularly important for the diagnosis of BI-RADS 4 and small breast lesions. -
Irinotecan as a Palliative Therapy for Metastatic Breast Cancer Patients after Previous ChemotherapyBackground: This analysis was conducted to evaluate the efficacy and safety of irinotecan based chemotherapy for treatment of patients with metastatic breast cancer (MBC) who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based. Methods: Clinical studies were identified using a predefined search strategy. Pooled response rates (RR) to treatment were calculated. Results: As irinotecan based regimens, 5 clinical studies which including 217 patients with refractory MBC were considered eligible for inclusion, with irinotecan, cisplatin, capecitabine, or TS-1. Systemic analysis suggested that, in all patients, pooled RR was 48.8% (106/217) with irinotecan based regimens. Thrombocytopenia and leukocytopenia were the main side effects. No grade III or IV renal or liver toxicity was observed. No treatment related deaths occurred. Conclusion: This systemic analysis suggests that irinotecan based regimens are beneficial and safe for treating patients with MBC after other chemotherapy.
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Background: In both developed and developing countries; breast cancer is the major cancer observed in women. The aim of this study was to assess the effect of nursing and mammographic intervention on women with breast cancer between the ages of 50 and 70. Materials and Methods: A training program, which was quasi-experimental and had a pretest-protest design, was applied in Kemalpaaa district of Izmir, between October 2008 and August 2010. The target population was women between the ages of 50 and 70, who were registered in the list of 3rd Family Medicine Unit in Izmir's Kemalpasa metropolis. A total of 106 women who were in conformity with the study criteria participated in the study. Research data were collected through home visits that included face-to-face interviews; Ministry of Health education material and video films were modified and used for the training. Data analysis was performed through 82 women who were paired at the first and the second phase. Results: It was observed that although the rate of breast self examination significantly increased after the training (p=0.022), the rate of clinical breast examination (p=0.122) and mammographic screening (p=0.523) did not. Differences in the stages of change after training were found to be statistically significant (p<0.001) and the group showed a progression in the stages of change in general (46.3%). In women mean scores of breast cancer awareness (p<0.000), severity (p<0.000), health motivation (p<0.000) and perception of the benefits of mammography (p<0.000) increased significantly and mean score of perception of mammography barriers decreased significantly (p<0.000) after the training. Conclusions: After the training on breast cancer and mammography it was determined that nursing interventions provided positive progression of stages of change of women, affected health beliefs positively and significantly increased BSE incidences. However, it did not have a significant effect on CBE and mammographic screening.
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Fong, James;Gyaneshwar, Rajaneshwar;Lin, Sophia;Morrell, Stephen;Taylor, Richard;Brassil, Ann;Stuart, Anne;McGowan, Catherine 10757
The purpose of this study was to demonstrate the feasibility of VIA screening with cryotherapy and to record normative values for indicators anticipated in similar low resource settings. Women aged 30-49 years were targeted, resulting in 1961 women screened and treated at two primary health care (PHC) centres near Suva, Fiji. Recruitment was through provision of information, education and communication (IEC). Referrals to a gynaecology outpatient department (OPD) at a referral hospital occurred throughout the screening pathway. Participation was 32% (95%CI 31-33%), higher in iTaukei (Melanesians) women (34%, 95%CI 33-36) compared to Fijians of Indian descent (26%, 95%CI 24-28). Regression analysis, adjusted for confounders, indicated significantly lower participation in those of Indian descent, and age groups 35-39 and 45-49 years. Of those examined by VIA, 190 were positive with aceto-white lesions (9.9%), within the expected range of 8-15%, with minor geographic and ethnic variation. Positive VIA results were more common in the peri-urban area, and in those aged 35-39 years. Of women aged 30-49 years, 59 received cryotherapy (none of whom had significant complications), 91 were referred to OPD, two cervical carcinomas were identified and eight cervical intra-epithelial neoplasms (CIN) II-III were diagnosed. These results provide normative findings from a community-based VIA screening program for other similar low resource settings. -
Bhanthumkomol, Patommatat;Siramolpiwat, Sith;Vilaichone, Ratha-Korn 10763
Background: The incidence of inadequate bowel preparation before elective colonoscopy in this region has never been studied. Materials and Methods: The authors prospectively described the incidence and factors related to inadequate bowel preparation in Thammasat university hospital. Bowel preparation quality was accessed by using Aronchick scale. Factors associated with inadequate bowel preparation were also recorded. Results: Two hundred patients undergoing elective outpatient colonoscopy were enrolled. Inadequate and fair bowel preparation was documented in 9 and 43%, respectively. Factors associated with inadequate bowel preparation were incomplete cleansing agent ingestion (odds ratio 7.7; 95%CI 1.62-36.64) and patient's unrecognization of vegetable avoidance (odds ratio 3.26; 95%CI 1.14-9.28). Conclusions: Compared with previous reported, inadequate bowel preparation was seen less in our study, however, more patients with fair bowel preparation was documented. Further study aiming at investigating the type and amount of fiber contained in diet before elective colonoscopy should be commenced. -
Yu, Jing;Cao, Xu-Fen;Zheng, Ye;Zhao, Rong-Cheng;Yan, Li-Qiu;Zhao, Lei;Wang, Jia-Wang 10769
Purpose: This analysis was conducted to evaluate cardiovascular toxicity of commonly used anti-VEGF therapeutic agent, bevacizumab, in treating patients with cancer. Methods: Clinical studies evaluating the efficacy and safety of bevacizumab-based regimens on response and safety for patients with cancer were identified using a predefined search strategy, allowing cardiovascular toxicity and other side effects of treatment to be estimated. Results: In bevacizumab based regimens, 4 clinical studies including 282 patients with advanced cancer (including gliomas, cervical, breast and ovarian cancer) were considered eligible for inclusion. These bevacizumab-based regimens included docetaxel, irinitecan and carboplatin. Systematic analysis suggested that, of 282 patients treated by bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5% (7/282), while only 3 patients reported cardiovascular events (1.1%). No treatment related death occurred in bevacizumab based treatment. Conclusion: This systemic analysis suggests that bevacizumab based regimens are associated with reasonable and accepted cardiovascular toxicity when treating patients with gliomas, cervical, breast and ovarian cancer. -
Wu, Mei;Shao, Guang-Rui;Zhang, Fei-Xue;Wu, Wen-Xiu;Xu, Ping;Ruan, Zheng-Min 10773
Background: Treatment for breast cancer is mainly performed by surgical resection of primary tumors and chemotherapy. However, after tumor invasion and metastases, breast cancer is hard to control. Clarification of the pathogenic mechanisms would be helpful to the prognosis or therapy for the breast cancer. The aim of this study is to investigate the clinical and prognostic implications of legumain protein Materials and Methods: In this study, we examined mastectomy specimens from 114 breast cancer and matching, 26 adjacent non-cancerous tissues using immunohistochemistry. Results: The results indicated that positive expression of legumain protein in breast cancer was 51.8 % (59/114) and the positive expression of legumain protein in adjacent non-cancerous tissue was 11.5% (3/26). It appeared to be related with lymph node metastasis of breast cancer (p=0.02) and correlation analysis indicated that legumain expression was correlated positively with the estrogen receptor (ER) and mutant-type p53 expression (both p<0.05). Positive legumain expression was significantly associated with shorter overall survival time in breast cancer patients (log-rank p<0.01). Multivariate survival analysis suggested that the positive legumain expression was an independent predictor of poorer overall survival in patients with breast cancer (HR=0.24; 95%CI 0.11-0.65, p=0.03). Conclusions: Legumain might be a new potential biomarker for breast cancer, which may reflect the prognosis and overall survival. -
Smiljana, Rajcevic;Mikov, Marica Miladinov;Petrovic, Vasa;Jasna, Trifunovic;Tihomir, Dugandzija;Milanka, Tatic 10779
Purpose: Analysis of descriptive epidemiological characteristics of pancreatic cancer in Vojvodina, Serbia. Materials and Methods: The study covers population of Vojvodina in the period from 2000 to 2009. The method used for data processing was the descriptive. The data, referring to a specified period of time, were analyzed from chronological and demographic aspects and according to histological diagnosis. Results: In the period from 2000 to 2009, there were 2,108 registered cases of pancreatic cancer of which 1,886 had a fatal outcome. Standardized incidence rates varied between 5.7 and 9.1 per 100,000 population in males and between 4.2 and 5.3 in females. Linear incidence trends in males in the specified period of time, based on crude (r=0.7883, p<0.05) and standardized (r=0,6373, p<0,05) incidence rates, demonstrated increase. Annual percent increase in the crude incidence rate was 4.5% in males, and 2.8% in females. Age-standardized mortality rates varied between 5.2 and 7.5 per 100,000 population in males and 3.6 and 4.7 in females. Linear mortality trends in males in the specified period of time, based on crude (r=0.8795, p<0.05) and standardized (r=0.7669, p<0.05) mortality rates, also demonstrated annual percent increase. Conclusions: Data analysis shows unfavorable onco-epidemiological situation related to pancreatic cancer in Vojvodina, in aspects of both incidence and mortality. Absence of primary and secondary prevention does not allow medical institutions to successfully fight against this disease. -
Kristina, Susi Ari;Thavorncharoensap, Montarat;Pongcharoensuk, Petcharat;Montakantikul, Preecha;Suansanae, Thanarat;Prabandari, Yayi Suryo 10783
Background: Smoking remains the major preventable cause of death worldwide, especially cancer-related death. Evidence clearly indicates that tobacco-related morbidity and mortality is reduced by smoking cessation. Pharmacists are well-positioned to provide tobacco cessation services an involvement of pharmacists in smoking cessation is encouraged by several organizations. While Indonesia's prevalence of smoking is in the first rank in Asian countries, none of the pharmacy schools in Indonesia are currently offering tobacco-related courses in their existing curricula at present. Our study aimed to develop and to evaluate the effectiveness of tobacco education (TE) for pharmacy students in Indonesia. Materials and Methods: A 6-hour TE was developed and evaluated using pre-test/post-test with control group design. A total of 137 fifth-year pharmacy students at Gadjah Mada University (GMU), Yogyakarta, were chosen as an intervention group while a total of 105 fifth-year students of Islamic University of Indonesia, (UII) served as the control group. Knowledge, perceived-role, self-efficacy, and ability to perform counseling using the 5A's framework were evaluated. Results: A significant improvement (P < 0.001) in knowledge, perceived-role, and self-efficacy was found in the intervention group but not in the control group. In addition, we revealed that 89.7% of the intervention group were able to perform counseling using 5A's. Conclusions: The developed TE significantly improved student knowledge, perceived-rolse, self-efficacy, and created an ability to perform cessation counseling. Integration of TE education in curricula of Indonesian pharmacy schools nation-wide should be encouraged. -
Sharifian, Abdolhamid;Pourhoseingholi, Mohamad Amin;Norouzinia, Mohsen;Vahedi, Mohsen 10787
Background: Ovarian cancer is an important cause of mortality in women. The aim of this study was to evaluate the incidence and mortality rates and trends in the Iranian population and make predictions. Materials and Methods: National incidence from Iranian annual of National Cancer Registration report from 2003 to 2009 and National Death Statistics reported by the Ministry of Health and Medical Education from 1999 to 2004 were included in this study. A time series model (autoregressive) was used to predict the mortality for the years 2007, 2008, 2012 and 2013, with results expressed as annual mortality rates per 100,000. Results: The general mortality rate of ovarian cancer slightly increased during the years under study from 0.01 to 0.75 and reaching plateau according to the prediction model. Mortality was higher for older age. The incidence also increased during the period of the study. Conclusions: Our study indicated remarkable increasing trends in ovarian cancer mortality and incidence. Therefore, attention to high risk groups and setting awareness programs for women are needed to reduce the associated burden in the future. -
Wang, Hui;Wang, Xiang;Wang, Cheng-Feng 10791
Background: Phyllodes tumors of the breast are rare fibroepithelial lesions, so relatively little is known about this disease entity. The present study was designed to identify differences in clinical features between benign borderline and malignant phyllodes tumors. Materials and Methods: Data from 246 women with phyllodes tumors of the breast treated in Cancer Hospital Chinese Academy of Medical Sciences between 2002 and 2012 were collected and analyzed, including age at presentation, age at treatment, course, size of primary tumor, location, histological type, type of surgery and treatment, local recurrence, distant metastasis, fibroadenoma history, disease-free survival and number of mitosis per 10hpf. There are 125 (55%) benign, 55 (24%) borderline and 47 (21%) malignant tumors. Results: In univariate analysis, average age at presentation, average age at treatment, size of primary tumor, ulceration or not, type of primary surgery, distant metastasis and number of mitosis per 10 hpf turned out to be statistically different among the three PT types (p=0.014, 0.018, <0.000, 0.003, <0.000, 0.001 and <0.000, respectively), while recurrence and disease-free survival (DFS) demonstrated trends for statistical significance (P =0.055 and 0.060, respectively). Multivariate analysis revealed distant metastasis and excision were significantly different in benign, borderline and malignant phyllodes tumors of the breast (p=0.041 and 0.018, OR=0.061 and 0.051). At the same time, size of primary tumor with p=0.052 tended to be different between groups (OR=1.127). However, age at treatment, ulceration and DFS showed no statistically significant variation (p=0.400, 0.286 and 0.413, respectively). Conclusions: Benign borderline and malignant phyllode tumors have different distant metastasis risk, different primary tumor size and different surgical procedures, and malignant PTs are more likely to be bigger and to metastasize. -
Niu, Feng;Zhao, Song;Xu, Chang-Yan;Chen, Lin;Ye, Long;Bi, Gui-Bin;Tian, Gang;Gong, Ping;Nie, Tian-Hong 10797
Background: To explore the molecular mechanisms of metastatic osteosarcoma (OS) by using the microarray expression profiles of metastatic and non-metastatic OS samples. Materials and Methods: The gene expression profile GSE37552 was downloaded from Gene Expression Omnibus database, including 2 human metastatic OS cell line models and 2 two non-metastatic OS cell line models. The differentially expressed genes (DEGs) were identified by Multtest package in R language. In addition, functional enrichment analysis of the DEGs was performed by WebGestalt, and the protein-protein interaction (PPI) networks were constructed by Hitpredict, then the signal pathways of the genes involved in the networks were performed by Kyoto Encyclopaedia of Genes and Genomes (KEGG) automatic annotation server (KAAS). Results: A total of 237 genes were classified as DEGs in metastatic OS. The most significant up- and down-regulated genes were A2M (alpha-2-macroglobulin) and BCAN (brevican). The DEGs were significantly related to the response to hormone stimulus, and the PPI network of A2M contained IL1B (interleukin), LRP1 (low-density lipoprotein receptor-related protein 1) and PDGF (platelet-derived growth factor). Furthermore, the MAPK signaling pathway and focal adhesion were significantly enriched. Conclusions: A2M and its interactive proteins, such as IL1B, LRP1 and PDGF may be candidate target molecules to monitor, diagnose and treat metastatic OS. The response to hormone stimulus, MAPK signaling pathway and focal adhesion may play important roles in metastatic OS. -
Missaoui, Nabiha;Abdelkarim, Soumaya Ben;Mokni, Moncef;Hmissa, Sihem 10803
Background: The role of$p16^{INK4A}$ expression in uterine cervix cancer is well established. In the remaining female lower genital tract cancers, the importance of$p16^{INK4A}$ up-regulation is less clear. In our study, we analyzed the role of$p16^{INK4A}$ expression and HPV infection in carcinomas of the vulva and the vagina in Tunisian women. Materials and Methods: We conducted a retrospective study of 30 carcinomas including 15 vulvar squamous cell carcinomas (SCCs) and 15 vaginal SCCs. Immunohistochemistry was used to determine$p16^{INK4A}$ expression. HPV detection and typing was by in situ hybridization. Results:$p16^{INK4A}$ expression was detected in 86.7% of vaginal SCCs with a strong and diffuse immunostaining in 60% of cases, and also in 73.3% of vulvar SCCs with focal immunoreactivity in 53.3% The association between$p16^{INK4A}$ expression and HPV infection was significant in vaginal SCCs (p=0.001) but not vulvar SCCs (p>0.05). Conclusions:$p16^{INK4A}$ expression could be used as a useful marker for HPV positivity in vaginal SCCs similar to that described in uterine cervix cancers. However, our data support the presence of 2 different mechanisms for$p16^{INK4A}$ expression in HPV-related and HPV-unrelated vulvar carcinomas. -
Nilyanimit, Pornjarim;Wanlapakorn, Nasamon;Niruthisard, Somchai;Takahashi, Masayoshi;Vongpunsawad, Sompong;Poovorawan, Yong 10809
Background: Human papillomavirus (HPV) DNA testing is an effective method to screen for precancerous changes in the cervix. Samples from self-collection rather than Pap smear can potentially be used to test for HPV as they are more acceptable and preferred for use in certain settings. The objective of this study was to compare HPV DNA testing from self-collected vaginal swabs and physician-collected cervical swabs. Materials and Methods: A total of 101 self-collected vaginal and physician-collected cervical swabs of known cytology from Thai women were tested by electrochemical DNA chip assay. The specimens were divided into 4 groups: 29 with normal cytology, 14 with atypical squamous cells of undetermined significance (ASCUS), 48 with low-grade squamous intraepithelial lesion (LSIL), and 10 with high-grade squamous intraepithelial lesion (HSIL). Results: Positive detection rates of HPV from self-collected swabs were similar to those from physician-collected swabs. Among specimens with abnormal cytology, HPV was found in 50% of self-collected swabs and 47.2% of physician-collected swabs. In specimens with normal cytology, 17.2% of self-collected swabs and 24.1% of physician-collected swabs were positive for HPV. Concordance was relatively high between results from self-collected and physician-collected samples. The most common HPV genotype detected was HPV 51. Conclusions: HPV DNA testing using self-collected swabs is a feasible alternative to encourage and increase screening for cervical cancer in a population who might otherwise avoid this important preventive examination due to embarrassment, discomfort, and anxiety. -
Sen, Volkan;Bozkurt, Ozan;Demir, Omer;Tuna, Burcin;Yorukoglu, Kutsal;Ellidokuz, Hulya;Mungan, Ugur 10813
Background: Possible roles of nestin expression in terms of predicting intravesical BCG therapy response in T1 high grade bladder cancer patients were investigated. Materials and Methods: T1 high grade bladder cancer patients who were treated with intravesical BCG between 1990-2009 were included. Immunohistochemical staining for nestin expression was performed. Nestin(+) and nestin(-) patients were compared in terms of recurrence and progression rates. Results: Sixty-three patients were included and median follow-up time was twenty-five months. After staining; 33 patients (52.4%) were classified as nestin (+) and 30 (47.6%) as (-). Nestin (+) patients were more likely to recur compared to nestin (-) patients (60.6% vs. 30%, p<0.05). Progression rates were also higher in nestin (+) patients, although this result did not reach statistical significance (15.2 % vs. 10 %, p=0.710). Conclusions: Nestin expression, which seems effective in predicting recurrence, appears to have a potential role in the urothelial carcinoma tumorigenesis. Patients with high grade bladder cancer and positive nestin expression need close follow-up and might be informed about more tendency to recur. Further comprehensive studies including larger patient cohorts may clarify the role of nestin in bladder cancer. -
Wang, Bei;Yan, Yun-Wen;Zhou, Qing;Gui, Shu-Yu;Chen, Fei-Hu;Wang, Yuan 10819
Aims: To explore the effect and probable mechanism of a synthetic retinoid 4-amino-2-tri-fluoromethylphenyl ester (ATPR) on apoptosis of MDA-MB-231 breast cancer cells. Materials and Methods: MTT assays were performed to measure the proliferation of MDA-MB-231 cells treated with different concentrations of all-trans retinoic acid (ATRA) and ATPR. Morphologic changes were observed by microscopy. The apoptosis rates and cell cycling of MDA-MB-231 cells treated with ATRA or ATPR were assessed using flow cytometry analysis. Expression of retinoic acid receptor and phosphorylation of ERK, JNK, p38 proteins were detected by Western blotting. Results: Treatment of the cells with the addition of$15{\mu}mol/L$ ATPR for 48 h clearly demonstrated reduced cell numbers and deformed cells, whereas no changes in the number and morphology were observed after treatment with ATRA. The apoptosis rate was 33.2% after breast cancer MDA-MB-231 cells were treated by ATPR ($15{\mu}mol/L$ ) whereas ATRA ($15{\mu}mol/L$ ) had no apoptotic effect. ATPR inhibited the phosphorylation of ERK, JNK, and p38 while ATRA had no significant effect. ATPR inhibited the expression of BiP and increased the expression of Chop at the protein level compared with control groups, ATRA and ATPR both decreased the protein expression of$RXR{\alpha}$ , ATPR reduced the protein expression of$RAR{\beta}$ and$RXR{\beta}$ while ATRA did not decrease$RAR{\beta}$ or$RXR{\beta}$ . Conclusions: ATPR could induce apoptosis of breast cancer MDA-MB-231 cells, possible mechanisms being binding to$RAR{\beta}/RXR{\beta}$ heterodimers, then activation of ER stress involving the MAPK pathway. -
Zhang, Hong-Feng;Wu, Di;Du, Jian-Kuo;Zhang, Yan;Su, Yun-Ming 10825
The present study was conducted to investigate effects and mechanisms of action of phenolic alkaloids of Menispermum dauricum (PAMD) on gastric cancer in vivo. In vitro, cell apoptosis of human gastric cancer cell line SGC-7901 was observed using fluorescence staining. In vivo, a mice model was constructed to observe tumor growth with different doses. Cell apoptosis was examined using flow cytometry and K-RAS protein expression using Western blotting. The mRNA expression of P53, BCL-2, BAX, CASPASE-3, K-RAS was examined by real-time PCR. PAMD significantly suppressed tumor growth in the xenograft model of gastric cancer in a dose-dependent manner (p<0.01). Functionally, PAMD promoted cell apoptosis of the SGC-7901 cells and significantly increased the rate of cell apoptosis of gastric tumor cells (p<0.05). Mechanically, PAMD inhibited the expression of oncogenic K-RAS both at the mRNA and protein levels. In addition, PAMD affected the mRNA expression of the cell apoptosis-related genes (P53, BCL-2, BAX, CASPASE-3). PAMD could suppress gastric tumor growth in vivo, possibly through inhibiting oncogenic K-RAS, and induce cell apoptosis possibly by targeting the cell apoptosis-related genes of P53, BCL-2, BAX, CASPASE-3. -
Supoken, Amornrat;Kleebkaow, Pilaiwan;Chumworathayi, Bandit;Luanratanakorn, Sanguanchoke;Kietpeerakool, Chumnan 10831
This study was conducted to establish whether the preoperative platelet to lymphocyte ratio (PLR) is predictive of survival of women with ovarian clear cell carcinoma (OCCC). A PLR > 300 was deemed elevated. Progression-free survival (PFS) was estimated using the Kaplan-Meier method. Cox proportional hazard analysis was used to determine the independent effect of PLR. Thirty-six patients were reviewed. Elevated PLRs were more commonly noted in patients with an advanced vs an early stage of disease (88.9% vs 11.1%). Women with elevated PLR carried a higher rate of disease progression during primary therapy than that those in the normal PLR group (44.4 vs 22.2%). The median PFS for patients with elevated PLR was notably worse than that for patients with normal PLR (10 vs 34 months). Despite the impact of elevated PLR on PFS, it was found to be marginally significant when controlling for commonly applied prognostic markers. It, however, trended toward significance (HR=4.76; 95%CI, 0.95-23.8). In conclusion, an elevated PLR appears to be directly associated with adverse survival rather than being a surrogate for other indicators of a poor prognosis. PLR may be a useful biomarker for predicting survival of women with OCCC and merits further large-scale studies. -
To assess survival outcomes in a retrospective study, recurrent epithelial ovarian cancer patients were divided into three groups according to the platinum free interval as follows: platinum refractory that included the patients with tumor progression during treatment; platinum resistant and platinum sensitive that included the patients with tumor progression less than or more than six months, respectively. Clinical data for tumor progression in epithelial ovarian cancer patients treated at Chiang Mai University Hospital between January, 2006 and December, 2010 were reviewed. Thirty-nine patients were in the platinum refractory group while 27 were in the platinum resistant group and 75 in the platinum sensitive group. The mean age, the parity, the administration of neoadjuvant chemotherapy and the serous type did not significantly different across groups while the mean total number of chemotherapy regimens, the early stage patients, the patients with complete surgery and the surviving patients were significant more frequent in the platinum sensitive group. Regarding subsequent treatment after tumor recurrence, 87.2% underwent chemotherapy. With the median follow up time at 29 months, the median overall survival rates were 20 months, 14 months and 42 months in platinum refractory, platinum resistant and platinum sensitive groups, respectively (p<0.001). In addition, when the platinum sensitive patients developed the next episode of tumor progression, the median progression free interval time was only three to four months. In conclusion, the outcomes for platinum refractory the and platinum resistant groups was poorer than the platinum sensitive group. However, subsequent progression in the platinum sensitive group was also associated with a poor outcome.
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Al-Naggar, Redhwan A.;Bobryshev, Yuri V.;Anil, Shirin 10841
Background: Smoking is a primary risk factor for cancer development. While most research has focused on smoking cigarettes, the increasing popularity of shisha or water pipe smoking has received less attention. This study measured the prevalence and risk factors for shisha and cigarette smoking and related knowledge. Materials and Methods: This cross-sectional analytical study was conducted in Shah Alam, Malaysia. Participants aged${\geq}18years$ were selected from restaurants. Data regarding demographic variables, smoking patterns, and knowledge about shisha smoking were collected in local languages. Logistic regression was performed to assess risk factors. Results: Of 239 participants, 61.9 % were male and 99.2% revealed their smoking status. Some 57.4% were smokers: 50.7% only cigarettes, 5.9% only shisha and 42% both. Mean age of starting cigarette smoking was$17.5{\pm}2.4years$ and for shisha smoking$18.7{\pm}2.0years$ . In a univariate model, male gender, age 33-52 years and monthly income > MYR 4,000 increased the risk and unemployment and being a student decreased the risk. In a multivariate model, male gender increased the risk of smoking, while being a student decreased the risk, adjusting for age and income. The perception of shisha being less harmful than cigarettes was present in 14.6% and 7.5% had the opinion that shisha is not harmful at all, while 21.7% said that it is less addictive than cigarettes, 39.7% said that shisha did not contain tar and nicotine, 34.3% said that it did not contain carbon monoxide and 24.3% thought that shisha did not cause health problems. Conclusions: Prevalence of shisha and cigarette smoking is high in the general population in Malaysia and knowledge about shisha smoking is relatively low. The findings of our study might have implications for understanding similarities and differences in incidence of shisha and cigarette smoking in other cultural/geographic regions. -
Zhuo, Wen-Lei;Zhang, Liang;Xie, Qi-Chao;Zhu, Bo;Chen, Zheng-Tang 10847
Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment. -
Wu, Ting-Ting;Wang, Zhi-Gang;Ou, Wu-Ling;Wang, Jun;Yao, Guo-Qing;Yang, Bo;Rao, Zhi-Guo;Gao, Jian-Fei;Zhang, Bi-Cheng 10855
Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma${\beta}$ -endorphin levels in cancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma${\beta}$ -endorphin levels were measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma${\beta}$ -endorphin levels. After the treatment, plasma${\beta}$ -endorphin level in group B was$62.4{\pm}13.5pg/ml$ , which was higher than that in group A ($45.8{\pm}11.2pg/ml$ ) (p<0.05). Conclusions: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma${\beta}$ -endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment. -
Al-Maweri, Sadeq Ali;Addas, Abdallah;Tarakji, Bassel;Abbas, Alkasem;Al-Shamiri, Hashem M.;Alaizari, Nader Ahmed;Shugaa-Addin, Bassam 10861
Background: Oral cancer is in increasing in incidence in Yemen and indeed worldwide. Knowledge regarding risk factors and early signs in the general population can help in prevention and early detection of the disease. Purpose: The aim of this study was to assess the level of awareness and knowledge of oral cancer in the general population in Yemen. Materials and Methods: A cross-sectional survey using a self-administered questionnaire was conducted on Yemeni adults aged${\geq}15$ years old. A total of 543 persons participated, the collected data being analyzed using SPSS software. The significance level was set at p<0.05. Results: Two thirds (71.5%) of the participants had heard about oral cancer. Smoking and smokeless tobacco usage were identified as the major risk factors by 71.5% and 73.7% of the participants, respectively. Only 24.1% and 21.4%, respectively, were able to correctly identify red and white lesions as early signs of oral cancer. Knowledge of oral cancer was significantly associated with age (p<0.01), gender (p<0.05) and education level (p<0.001). Conclusions: The findings suggest that the knowledge regarding oral cancer in this population is low. Therefore, educational programs are highly needed to improve such knowledge. -
Krishnatreya, Manigreeva;Kataki, Amal Chandra;Sharma, Jagannath Dev;Nandy, Pintu;Rahman, Tashnin;Kumar, Mahesh;Gogoi, Gayatri;Hoque, Nazmul 10867
Background: There are various patient and professional factors responsible for the delay in start of treatment (SOT) for head and neck cancers (HNC). Materials and Methods: This retrospective study was conducted on data for HNC patients registered at the hospital cancer registry in North-East India. All cases diagnosed during the period of January 2010 to December 2012 were considered for the present analysis. Educational levels of all patients were clustered into 3 groups; illiterates (unable to read or write), qualified (school or high school level education), and highly qualified (college and above). Results: In the present analysis 1066 (34.6%) patients were illiterates, 1,869 (60.6%) patients were literates and 145 (4.7%) of all patients with HNC were highly qualified. The stage at diagnosis were stage I, seen in 62 (34.6%), stage II in 393 (12.8%), stage III in 1,371 (44.5%) and stage IV in 1,254 (40.7%). The median time (MT) to the SOT from date of attending cancer hospital (DOACH) was, in illiterate group MT was 18 days, whereas in the qualified group of patients it was 15 days and in the highly qualified group was 10 days. Analysis of variance showed there was a significant difference on the mean time for the delay in SOT from DOACH for different educational levels (F=9.923, p=0.000). Conclusions: Educational level is a patient related factor in the delays for the SOT in HNCs in our population. -
Leenharattanarak, Pattaramon;Lertkhachonsuk, Ruangsak 10871
Background: Gestational trophoblastic neoplasia (GTN) is a malignant disease which occurs in women of reproductive age. Treatment of GTN has an excellent outcome and further pregnancies can be expected. However, data concerning quality of life in these cancer survivor patients are limited. This study aimed to assess quality of life in women who were diagnosed with GTN and remission after treatment, and to determine factors that may affect quality of life status. Materials and Methods: This cross sectional study was conducted from July 2013 to May 2014 in the Gestational Trophoblastic Disease Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients who were diagnosed GTN and complete remission were recruited. Data collection was accomplished by interview with two sets of questionnaires, one general covering demographic data and the other focusing on quality of life, the fourth version of Functional Assessment of Cancer Therapy (FACT-G). Descriptive statistics were used to determine general data and quality of life scores. Students t-test and one way ANOVA were used to compare between categorical and continuous data. Results: Forty four patients were enrolled in this study. The overall mean quality of life score (FACT-G) was 98.2. The overall FACT-G score was not significantly correlated with age, education level, stage of disease, treatment modalities, and time interval from remission to enrollment. However, patients who needed further fertility showed significant lower FACT-G scores in the emotional well-being domain (p=0.02). Conclusions: Overall quality of life scores in post-treatment gestational trophoblastic neoplasia patients are in the mild impairment range. Patients who desire fertility suffer lower quality of life in the emotional well-being domain. -
Qiu, Hao;Duan, Wei-Ming;Shu, Jie;Cheng, Hong-Xia;Wang, Wei-Ping;Huang, Xin-En;Chen, Hui-Li 10875
The epidermal growth factor receptor (EGFR) is an important surface receptor with N-glycans in its extracellular domain, whose glycosylation is essential for its function, especially in tumor cells. Here, we demonstrated that polylactosamine is markedly increased in H7721 hepatocellular carcinoma cells after treatment with EGF, while it apparently declined after exposure to all-trans retinoic acid (ATRA). In the study of the enzymatic mechanism of this phenomenon, we explored changes in the expression of poly-N-acetyllactosamine (PLN) branching glycosyltransferases using RT-PCR. Among the four glycosyltransferases with altered expression, GnT-V was most elevated by EGF, while GnT-V and B3GNT2 were most declined by ATRA. Next, we conducted co-immunoprecipitation experiments to test whether B3GNT2 and EGFR associate with each other. We observed that EGFR is a B3GNT2-targeting protein in H7721 cells. Taken together, these findings indicated that the altered expression of B3GNT2 will remodel the PLN stucture of EGFR in H7721 cells, which may modify downstream signal transduction. -
Liu, Tie-Cheng;Liu, Qi-Ran;Huang, Ying 10879
Objective: To investigate the effect of intraoperative glucose fluctuation and postoperative interlukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$ ), C-reactive protein (CRP) levels on the short-term prognosis of patients with intracranial supratentorial neoplasms. Materials and Methods: Eighty-six patients undergoing intracranial excision were selected in The Second Hospital of Jilin University. According to the condition of glucose fluctuation, the patients were divided into group A (glucose fluctuation <2.2 mmol/L, n=57) and group B (glucose fluctuation${\geq}2.2mmol/L$ , n=29). Glucose was assessed by drawing 2 mL blood from internal jugular vein in two groups in the following time points, namely fasting blood glucose 1 d before operation ($T_0$ ), 5 min after anesthesia induction ($T_1$ ), intraoperative peak glucose ($T_2$ ), intraoperative lowest glucose ($T_3$ ), 5 min after closing the skull ($T_4$ ), immediately after returning to intensive care unit (ICU) ($T_5$ ) and 2 h after returning to ICU ($T_6$ ). 1 d before operation and 1, 3 and 6 d after operation, serum IL-6 and TNF-${\alpha}$ levels were detected with enzyme-linked immunosorbent assay (ELISA), and CRP level with immunoturbidimetry. Additionally, postoperative adverse reactions were monitored. Results: There was no statistical significance between two groups regarding the operation time, anesthesia time, amount of intraoperative bleeding and blood transfusion (P>0.05). The glucose levels in both groups at$T_1{\sim}T_6$ went up conspicuously compared with that at$T_0$ (P<0.01), and those in group B at$T_2$ ,$T_4$ ,$T_5$ and$T_6$ were significantly higher than in group A (P<0.01). Serum IL-6, TNF-${\alpha}$ and CRP levels in both groups 1, 3 and 6 d after operation increased markedly compared with 1 d before operation (P<0.01), but the increased range in group A was notably lower than in group B (P<0.05 or P<0.01). Postoperative incidences of hypoglycemia, hyperglycemia and myocardial ischemia in group A were significantly lower than in group B (P<0.05), and respiratory support time obviously shorter than in group B (P<0.01). Conclusions: The glucose fluctuation of patients undergoing intracranial excision is related to postoperative IL-6, TNF-${\alpha}$ and CRP levels and those with small range of glucose fluctuation have better prognosis. -
Akinci, Sema;Silay, Kamile;Ulas, Arife;Guney, Tekin;Hacibekiroglu, Tuba;Basturk, Abdulkadir;Akinci, Muhammed Bulent;Alkan, Afra;Dilek, Imdat 10883
Purpose: Neutrophil-to-lymphocyte ratio (NLR) was evaluated as a potential prognostic factor in patients with myelodysplastic syndrome (MDS). Materials and Methods: Between December 2009 and April 2014, 14 female (35%) and 26 male (65%) MDS patients who were followed up in our hematology clinic were included in the study for NLR during diagnosis. Division was into two groups according to the NLR, and the correlation with mortality was evaluated. The prognostic significance of NLR regarding treatment outcome was also evaluated with adjustment for known confounding risk factors. Results: The mortality rate of the patient group was 55%, and median survival was 18 months. There was no significant correlation between mortality and NLR at a median value of 1.8 (p=0.75). Thrombocytopenia was observed to increase mortality (p=0.027), and there was a significant correlation between mortality and pancytopenia (p=0.017). Conclusions: This first study of NLR and mortality did not show any significant correlation. In centres with limited access to genetic evaluation for the presence of pancytopenia and/or thrombocytopenia at the time of diagnosis, a platelet level less than$50{\times}10^9/l$ may be poor prognostic markers in MDS patients. -
Piriyapong, Kitiyawadee;Tangaroonsanti, Anupong;Mahachai, Varocha;Vilaichone, Ratha-Korn 10887
Background: Helicobacter pylori (H. pylori) is a well known major cause of gastric cancer and even when asymptomatic infected patients are at elevated risk. Functional dyspepsia (FD) is also one of the most common gastrointestinal diseases, which greatly impacts the quality of life. H. pylori infection and psychosocial stress are frequently associated with FD but limited studies have confirmed the relationships, especially in Southeast Asian countries. Here we aimed to investigate the prevalence and impact of H. pylori infection, anxiety and depression on Thai FD patients. Materials and Methods: This cross-sectional study was conducted in a tertiary care center in Thailand, during February 2013-January 2014. All FD patients were diagnosed and categorized by Rome III criteria into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) groups. The Hospital Anxiety and Depression Scale was used to evaluate psychological status. The presence of H. pylori was defined as positive with H. pylori culture, positive rapid urease test or positive histology. Results: Three hundred FD patients were included, 174 (58%) female. Overall mean age was 54.8+15.1 years. There were 192 (64%) patients with PDS and 108 (36%) with EPS. H. pylori infection was demonstrated in 70 (23.3%) patients. Anxiety and depression were documented in 69 (23%) and 22 (7.3%), respectively. H. pylori infection, anxiety and depression were significantly higher in PDS than EPS patients (27.1% vs 16.7%; p=0.04; OR=1.86; 95%CI=1.01-3.53 and 29.7% vs 11.1%; p=0.0002; OR=3.4; 95%CI=1.7-7.1 and 10.4% vs 1.9%; p=0.006; OR=6.2; 95%CI=1.4-38.9, respectively). Conclusions: H. pylori infection, anxiety and depression were commonly found in Thai FD patients and more prevalent in PDS than EPS. H. pylori eradication might be the key to success for the treatment of Thai FD patients and prevent the development of gastric cancer. -
Wang, Kai;Wang, Yin-Yan;Ma, Jun;Wang, Jiang-Fei;Li, Shao-Wu;Jiang, Tao;Dai, Jian-Ping 10893
Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas. We investigated the prognostic significance of$O^6$ -methylguanine-DNA methyltransferase (MGMT) promoter methylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastoma patients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy and chemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylation and TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealed that mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status (KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, those with an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, the presence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029 respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorable outcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas with MGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status. -
Arslan, Sonay;Abakay, Candan Demiroz;Sen, Feyza;Altay, Ali;Akpinar, Tayyar;Ekinci, Ahmet Siyar;Esbah, Onur;Uslu, Nuri;Kekilli, Kezban Esra;Ozkan, Lutfi 10899
Background: In this study, we aimed to investigate the benefits of 18F-deoxyglucose positron emission tomography/computed tomography (FGD-PET/CT) imaging for staging and radiotherapy planning in patients with head and neck cancer undergoing definitive radiotherapy. Materials and Methods: Thirty-seven head and neck cancer patients who had undergone definitive radiotherapy and PET/CT at the Uludag University Medical Faculty Department of Radiation Oncology were investigated in order to determine the role of PET/CT in staging and radiotherapy planning. Results: The median age of this patient group of 32 males and 5 females was 57 years (13-84years). The stage remained the same in 18 cases, decreased in 5 cases and increased in 14 cases with PET/CT imaging. Total gross tumor volume (GTV) determined by CT (GTVCT-Total) was increased in 32 cases (86.5%) when compared to total GTV determined by PET/CT (GTVPET/CT-Total). The GTV of the primary tumor determined by PET/CT (GTVPET/CT) was larger in 3 cases and smaller in 34 cases compared to that determined by CT (GTVCT). The GTV of lymph nodes determined by PET/CT (GTVLNPET/CT) was larger in 20 cases (54%) and smaller in 12 cases (32.5%) when compared to GTV values determined by CT (GTVLNCT). No pathological lymph nodes were observed in the remaining five cases with both CT and PET/CT. Conclusions: We can conclude that PET/CT can significantly affect both pretreatment staging and assessed target tumor volume in patients with head and neck cancer. We therefore recommend examining such cases with PEC/CT before treatment. -
Zhang, Hai-Shan;Wang, Ren-Jie;Fu, Qing-Feng;Gao, Shi;Sun, Bu-Tong;Sun, Hui;Ma, Qing-Jie 10905
Purpose: The aim of this study was to evaluate the diagnostic value of FNA-Tg for detecting lymph node metastases in patients with a history of differentiated thyroid cancer (DTC). Materials and Methods: A total of 58 patients with DTC diagnosis and evidence of single or multiple suspicious cervical lymph nodes were assessed. All underwent total or near-total thyroidectomy with (35 cases) or without (23 cases) radioiodine (RAI) ablation, followed by thyroid stimulating hormone (TSH) suppression therapy. A total of 68 lymph nodes were examined by ultrasound-guided fine needle aspiration (US-FNA) for both cytological examination and FNA-Tg measurement. Serum Tg and anti-thyroglobulin antibody (TgAb) levels were also measured. Diagnostic performance including sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) of FNAC and FNA-Tg were calculated and compared. The Spearman's rank correlation coefficient was used to estimate the relationship between FNA-Tg and serum TgAb. Results: The FNA-Tg levels were significantly higher with DTC metastatic lymph nodes (median 927.7 ng/mL, interquartile range 602.9 ng/mL) than non-metastatic lymph nodes (median 0.1 ng/mL, interquartile range 0.4 ng/mL) (p<0.01). Considering 1.0 ng/mL as a threshold value for FNA-Tg, the sensitivity, specificity, accuracy, PPV and NPV of FNA-Tg were 95.7%, 95.5%, 95.6%, 97.8% and 91.3%, respectively. The sensitivity and accuracy of the combination of FNAC and FNA-Tg were significantly higher than that of FNAC alone (p<0.05). The diagnostic performance of FNA-Tg was not significantly different between cases with or without RAI ablation, and the serum TgAb levels did not interfere with FNA-Tg measurements. Conclusions: Measurement of FNA-Tg is useful. The combination of FNAC and FNA-Tg is more sensitive and accurate for detecting lymph node metastases in patients with a history of DTC than FNAC alone. Serum TgAbs appear to be irrelevant for measurement of FNA-Tg. -
He, Hao;Zheng, Lei;Sun, Yan-Ping;Zhang, Guang-Wei;Yue, Zheng-Gang 10911
Background: Tumor metastases are the main reasons for oncotherapy failure. Paris polyphylla (Chinese name: Chonglou) has traditionally been used for its anti-cancer actions. In this article, we focus on the regulation of human lung cancer A549 cell metastases and invasion by Paris polyphylla steroidal saponins (PPSS). Materials and Methods: Cell viability was evaluated in A549 cells by MTT assay. Effects of PPSS on invasion and migration were investigated by wound-healing and matrigel invasion chamber assays. Adhesion to type IV collagen and laminin was evaluated by MTT assay. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. Results: PPSS exerted growth inhibitory effects on A549 cells, and effectively inhibited A549 cell adhesion, migration and invasion in a concentration-dependent manner. Western blotting and gelatin zymography analysis revealed that PPSS inhibited the expression and secretion of MMP-2 and MMP-9 in A549 cells. Conclusions: PPSS has the potential to suppress the migration, adhesion and invasion of A549 cells. PPSS could be a potential candidate for interventions against lung cancer metastases. -
Yuan, Sheng-Guang;Liao, Wei-Jia;Yang, Jian-Jun;Huang, Guo-Jin;Huang, Zhao-Quan 10917
Background: This study was conducted to determine DEPDC1 expression in hepatocelluar carcinomas (HCCs) and to reveal its potential role in diagnosis and prognosis of affected patients. Materials and Methods: DEPDC1 expression at the mRNA level was detected by quantitative real-time PCR (qRT-PCR) in 205 cases of HCC and paired adjacent normal liver tissues, and by semi-quantitative RT-PCR in 20 cases. Survival curves were obtained by using Kaplan-Meier method and Log-rank test. Independent predictors associated with regard to disease free survival (DFS) and overall survival (OS) were identified using the Cox proportional hazard model. Results: High DEPDC1 mRNA levels were detected in 144 out of 205 cases (70.24%) of HCC, significantly associated with clinicopathological parameters, including tumor size (${\geq}4cm$ ), alpha-fetoprotein (${\geq}100ng/ml$ ), B-C of BCLC stage and recurrence. Kaplan-Meier survival analysis revealed that HCC patients with high DEPDC1 expression had poor OS and DFS. Multivariate analysis demonstrated that high DEPDC1 expression was an independent predictor for OS (HR=1.651; 95% 95%CI, 1.041-2.617; p=0.033) and DFS (HR=1.583; 95%CI, 1.01-2.483; p=0.045). Conclusions: Our results indicate DEPDC1 might be a novel diagnostic marker and an independent prognostic predictor for HCC patients. -
Al Suhaibani, Entissar Sulaiman;Kizilbash, Nadeem Abbas;Al Beladi, Fatima 10923
Background: The aim of this study was to compare the characterization of prostate cancer using the conventional and 2005 ISUP modified Gleason systems. Materials and Methods: The study employed samples from 40 prostate cancer patients with resection, biopsy and RP materials. The majority of cases (95%) comprised adenocarcinoma of the prostate with a modified combined Gleason score of 7 in 20 of the cases (50%). Results: Upgrading of Gleason scores to a score of 7 occurred in more than 45% of the cases. Conclusion: The study successfully showed that by the use of the 2005 ISUP modified Gleason system, score 6 cancers decreased from 25% to 17.5% of cases, whereas score 7 cancers increased from 45% to 50%. -
Background: Older age is associated with an increase in the incidence of cancer cases. Diagnosis and treatment of cancer in older adults can be stressful because of health decline related to age, comorbidities and inadequate treatment for pain and other symptoms of the disease. This survey is one of the unique studies in Jordan and in the Arab world that aimed at exploring the predictors of older adult individuals awareness towards cancer. Materials and Methods: A stratified random sampling technique was followed to reach a representative sample of 753 participants. The questionnaire of the study consisted of parts regarding demographic variables, awareness about screening tests, and signs and symptoms of cancer. In addition, specific questions related to factors linked to cancer were included. Cross-sectional design was adopted with face-to-face interviews at the interviewees' households. Results: The mean age of the participants was about 63 years; around 44% of them are above the age of 65 years. 'Being convinced that having no health problem makes the individual feel safe and not at risk of getting cancer' was the major reason for not doing a routine health check-up. Conclusions: The low levels of awareness about cancer, as well as the low use of the screening methods were crucial outcomes of this study. Thus, raising the awareness among health care providers and policy makers in the country about older adults' perception of cancer is a high priority.
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Kalantar, Enayatollah;Assadi, Mojan;Pormazaheri, Helen;Hatami, Shiva;Barari, Maryam Agha;Asgari, Esfandiar;Mahmoudi, Elaheh;Kabir, Kourosh;Marashi, Seyed Mahmoud Amin 10933
Background: Many scientists have reported Candida species to be of great concern because of the high frequency that they colonize and infect human hosts, particularly cancer patients. Moreover, in the last decades Candida species have developed resistance to many antifungal agents. Based on this, we aimed to identify and determine the prevalence of Candida spp from blood culture bottles among cancer patients and their antifungal resistance pattern. Materials and Methods: From the blood culture bottles isolation and identification of the Candida spp were performed by conventional microbiological techniques. The in vitro antibiotic resistance pattern of the isolates was determined by CLSI guidelines. Genomic DNA was isolated and amplified. Each gene was separated by agar gel electrophoresis. Results: Identification of Candida spp was based on the presence of yeast cells in direct examination, culture and DNA extraction. Of the 68 blood samples collected during the study period (April 2013 to October 2013), five (7.35%) were positive for the presence of Candida spp, 2 (40%) of which were identified as Candida albicans and 3 (60%) were Candida non-albicans. Conclusions: High resistance to amphotricin B was observed among all the Candida non-albicans isolates. Regular investigations into antifungal resistance will help us to get an updated knowledge about their antibiotic resistance pattern which may help the physician in selecting the antibiotics for empirical therapy. -
Li, Wen;Deng, Jing;Wang, Shuang-Shuang;Ma, Liang;Pei, Jiang;Zeng, Xiao-Xi;Tang, Jian-Xin 10937
Pathogenesis of lung cancer is a complicated biological process including multiple genetic and epigenetic changes. Since cigarette smoking is confirmed as the most main risk factor of non-small cell lung cancer (NSCLC), the aim of this study was to determine whether tobacco exposure plays a role in gene methylation. Methylation of the RAR-${\beta}$ gene were detected using methylation-specific polymerase chain reaction in DNA from 167 newly diagnosed cases with NSCLC and corresponding 105 controls. A significant statistical association was found in the detection rate of the promoter methylation of RAR-${\beta}$ gene between NSCLC and controls ($x^2$ =166.01; p<0.01), and hypermethylation of the RAR-${\beta}$ gene was significantly associated with smoking status (p=0.038, p<0.05). No relationship was found between RAR-${\beta}$ gene methylation and pathologic staging including clinical stage, cell type, gender and drinking (p>0.05), and the methylation of RAR-${\beta}$ gene rate of NSCLC was slightly higher in stages III+IV (80.0%) than in I+II (70.8%). Similar results were obtained for methylation of the RAR-${\beta}$ gene between squamous cell carcinoma (77.9%) and other cell type lung cancer (73.9%). These results showed that the frequency of methylation increased gradually with the development of clinical stage in smoking-associated lung cancer patients, and tobacco smoke may be play a potential role in RAR-${\beta}$ gene methylation in the early pathogenesis and process in lung cancer, particularly squamous cell carcinoma. Aberrant promoter methylation is considered to be a promising marker of previous carcinogen exposure and cancer risk. -
Liu, Meng-Xue;Li, Jian;Geng, Yun-Long;Wang, Yan-Chun;Li, Jie;Chen, Yu-Juan;Ali, Gholam;Tarver, Siobhan L.;Wen, Yu-Feng;Sun, Wen-Jie 10943
Background: This study aimed to understand the relationship between knowledge level and behavior on breast care in Chinese students, so as to provide strategies for improving the health education of breast care and subsequently for aiding in breast cancer prevention. Materials and Methods: A self-designed questionnaire was used to evaluate breast care knowledge level and characterize related behavior. Correlation analysis was conducted for the knowledge level and behavior. The study was carried out using 597 female undergraduate students in medical and non-medical colleges in Wuhu, China. Results: The average score of breast care knowledge was$5.32{\pm}1.68$ ($5.62{\pm}1.68$ and$5.00{\pm}1.68$ for medical and non-medical students, respectively), with a greater score value for sophomores ($5.59{\pm}1.72$ ) than freshmen ($5.18{\pm}1.65$ ). The average score of breast care behavior was$2.21{\pm}1.13$ , again with a greater value in sophomores ($2.37{\pm}1.15$ ) than freshmen ($2.21{\pm}1.13$ ). A significant positive correlation (r=0.231, p<0.01) between knowledge scores and behavior scores was observed. In addition, various factors, including paying attention to breast care information, receiving breast self-examination guidance, TV program and Internet, were found to influence breast care knowledge. Conclusions: In general, female undergraduate students lack of self-awareness of breast care with a low rate of breast self-examination. It is necessary to carry out health education to improve early detection of breast cancer. -
Weng, Ling-Ling;Xiang, Jian-Feng;Lin, Jin-Bo;Yi, Shang-Hui;Yang, Li-Tao;Li, Yi-Sheng;Zeng, Hao-Tao;Lin, Sheng-Ming;Xin, Dong-Wei;Zhao, Hai-Liang;Qiu, Shu-Qi;Chen, Tao;Zhang, Min-Guang 10949
Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy. -
Jainan, Wannapa;Vilaichone, Ratha-Korn 10957
Background: The CYP2C19 genotype has been found to be an important factor for peptic ulcer healing and H. pylori eradication, influencing the efficacy of proton pump inhibitors (PPIs) and the pathogenesis of gastric cancer. The aim of this study was to investigate clinical correlations of the CYP2C19 genotype in patients with gastritis, peptic ulcer disease (PUD), peptic ulcer bleeding (PUB) and gastric cancer in Thailand. Materials and Methods: Clinical information, endoscopic findings and H. pylori infection status of patients were assessed between May 2012 and November 2014 in Thammasat University Hospital, Thailand. Upper GI endoscopy was performed for all patients. Five milliliters of blood were collected for H. pylori serological diagnosis and CYP2C19 study. CYP2C19 genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism analysis (RFLP) and classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: A total of 202 patients were enrolled including 114 with gastritis, 36 with PUD, 50 with PUB and 2 with gastric cancer. Prevalence of CYP2C19 genotype was 82/202 (40.6%) in RM, 99/202 (49%) in IM and 21/202 (10.4%) in PM. Overall H. pylori infection was 138/202 patients (68.3%). H. pylori infection was demonstrated in 72% in RM genotype, 69.7% in IM genotype and 47.6% in PM genotype. Both gastric cancer patients had the IM genotype. In PUB patients, the prevalence of genotype RM (56%) was highest followed by IM (32%) and PM(12%). Furthermore, the prevalence of genotype RM in PUB was significantly greater than gastritis patients (56% vs 36%: p=0.016; OR=2.3, 95%CI=1.1-4.7). Conclusions: CYP2C19 genotype IM was the most common genotype whereas genotype RM was the most common in PUB patients. All gastric cancer patients had genotype IM. The CYP2C19 genotype RM might be play role in development of PUD and PUB. Further study in different population is necessary to verify clinical usefulness of CYP2C19 genotyping in development of these upper GI diseases. -
Khunamornpong, Surapan;Settakorn, Jongkolnee;Sukpan, Kornkanok;Srisomboon, Jatupol;Suprasert, Prapaporn;Siriaunkgul, Sumalee 10961
Background: Minor cervical cytologic abnormalities include atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL). Approximately 10-20% of women with minor cytologic abnormalities have histologic high-grade squamous intraepithelial or worse lesions (HSIL+). In Thailand, women with minor cytologic abnormalities have a relatively high risk of cervical cancer, and referral for colposcopy has been suggested. A triage test is useful in the selection of women at risk for histologic HSIL+ to reduce the colposcopy burden. The aim of this study was to assess the performance of high-risk HPV DNA test in triage of women with minor cytologic abnormalities in northern Thailand. Materials and Methods: All women with ASC-US/LSIL cytology who were referred to our colposcopy clinic from October 2010 to February 2014 were included. HPV DNA testing was performed using Hybrid Capture 2 (HC2). All patients received colposcopic examination. Accuracy values of HC2 in predicting the presence of histologic HSIL+ were calculated. Results: There were 238 women in this study (121 ASC-US and 117 LSIL). The HC2 positivity rate was significantly higher in the LSIL group than in ASC-US group (74.8% versus 41.0%, p<0.001). Histologic HSIL+ was detected in 9 women (7.4%) in the ASC-US group and 16 women (13.7%) in the LSIL group (p=0.141). There was no histologic HSIL+ detected among HC2-negative cases (sensitivity and negative predictive value of 100%). The performance of HC2 triage was highest among women aged >50 years with ASC-US cytology. An increase in the cut-off threshold for positive HC2 resulted in a substantial decrease of sensitivity and negative predictive value. Conclusions: HPV DNA testing with HC2 shows very high sensitivity and negative predictive value in triage of women with minor cervical cytologic abnormalities in northern Thailand. An increase of the cut-off threshold for HC2 triage is not recommended in this region. -
Fang, Hong;Lin, Rong-Yan;Sun, Ming-Xia;Wang, Qian;Zhao, Yu-Liang;Yu, Jing-Lin;Tian, Yan;Wang, Xiao-Yun 10967
Objective: To analyze the efficacy and survival associated factors of gefitinib combined with cisplatin and gemcitabine for advanced non-small cell lung cancer. Materials and Methods: A total of 57 patients with advanced non-small cell lung cancer (NSCLC), who received platinum-based chemotherapy regimens for more than 1 cycle, were treated with gefitinib combined with cisplatin and gemcitabine until disease progression. Efficacy, survival time and adverse reactions were observed. The Kaplan-Meier method was adopted for analysis of survival and Cox regression for associated influencing factors. Results: The patients were followed up until October 31, 2013, and the median follow-up time was 19 months. Of 57 patients, there were 4 (7.0%) with complete remission (CR), 8 (14.0%) with partial remission, 31 (54.4%) with stable disease, and 14 (24.6%) with disease progression. The remission rate was 21.1% and the disease control rate was 75.4%. The median progression-free survival (PFS) time and the median overall survival time were 10 months and 15.2 months. The one-year, two-year and three-year survival rates were 47.4%, 23.3% and 10.0%. Gender and pathological types were the independent risk factors influencing PFS time (P=0.028, P=0.009). Tumor pathological type and early efficacy were independent factors for the prognosis (P=0.018, P=0.000). Adverse reactions were mostly rashes of I~II degree and diarrhea and slightly increasing level of aminopherase. The skin adverse event incidence of III degree or above was 1.8% (1/57) and brain metastasis was foudn in 31.6% (18/57). Conclusions: Gefitinib combined with cisplatin andgemcitabine, is effective for patients with IIIb~IV NSCLC who received multiple cycles of chemotherapy. -
Chen, Long;Zhang, Wei-Na;Zhang, Sheng-Miao;Yang, Zhi-Hao;Zhang, Ping 10971
Objective: To investigate bladder and intestinal function recovery and quality of sexual life after laparoscopic nerve-sparing radical hysterectomy (LNRH) for treatment of early invasive cervical carcinoma. Methods: Subjects included patients who underwent radical hysterectomy by laparotomy who were randomly assigned to 2 groups: 30 patients who underwent LNRH and 35 classical laparoscopic radical hysterectomy (LRH). We assessed the patients general clinical information, surgical characteristics, pathological findings, and adjuvant therapies. A urodynamic study was used to assess bladder function. Intestinal function recovery and quality of sexual life were evaluated by questionnaire. Results: No significant differences were found in age, surgery characteristics, pathological findings, adjuvant therapies, and main adverse effects between the 2 groups. The mean duration of the postoperative catheterization (DPC) in group LNRH was shorter than that in group LRH (P < 0.001). The maximum flow rate, maximum cystometric capacity, maximum detrusor pressure and urinary complications in group LNRH were better than those in group LRH. The quality of sexual life evaluated according to the female sexual function index (FSFI) was better in group LNRH than in those who underwent LRH. The intestinal function of patients in group LNRH also recovered better compared with patients in group LRH. -
Han, Li;Sun, Yi-Jie;Pan, Yong-Fu;Ding, Hao;Chen, Xi;Zhang, Xu 10977
Background: This systematic analysis was conducted to evaluate the efficacy and safety of cantharidin combined with chemotherapy in treating Chinese patients with metastatic colorectal cancer. Methods: Clinical studies evaluating the efficacy and safety of cantharidin combined with chemotherapy on response and safety for Chinese patients with colorectal cancer were identified using a predefined search strategy. Pooled response rate (RR) of treatment were calculated.Results: When cantharidin combined with chemotherapy, 4 clinical studies which included 155 patients with advanced colorectal cancer were considered eligible for inclusion. The systematic analysis suggested that, in all patients, pooled RR was 46.5% (72/155) in cantharidin combined regimens. Major adverse effects were neutropenia, leukopenia, fatigue, and anemia with cantharidin combined treatment; no treatment related deaths occurred. Conclusion: This systematic analysis suggests that cantharidin combined regimens are associated with high response rate and accepted toxicity in treating Chinese patients with metastatic colorectal cancer suggesting that randomized clinical trials are now warranted. -
Hamrah, Mohammad Shoaib;Hamrah, Mohammad Hashem;Rabi, Mirwais;Wu, Hong Xian;Hao, Chang-Ning;Harun-Or-Rashid, Mohammad;Sakamoto, Junichi;Ishii, Hideki 10981
Background: Esophagogastroduodenoscopy (EGD) is the standard technique for diagnosis of patients presenting with upper gastrointestinal symptoms. Some reports have shown high prevalence of esophageal cancer in the northern part of Afghanistan. The aim of this study was to investigate epidemiological profile of esophageal cancer among patients in this region. Materials and Methods: We identified 364 consecutive patients that received EGD examinations to examine upper gastrointestinal tract at the endoscopy unit of Balkh regional Hospital from March 2012 to March 2013. The case subjects included both in-patients and out-patients aged 16 years or more. We evaluated the results retrospectively. Results: The cases consisted of 184 (51%) males and 180 (49%) females. The mean age was$47.3{\pm}17.8$ and the age range 17-88 years. Ninety two cases had esophageal cancer, out of which 58 (63.0%) were male. The mean age at time of diagnosis was$57.8{\pm}13.2years$ . Uzbek-Turkmen peoples were more common among patients with esophageal cancer (52.2%). Dysphagia was the most frequent symptom among patients with esophageal cancer at the time of presentation, seen in 77 (84.8%) of cases. Conclusions: Our results showed high incidence of esophageal cancer in the northern part of Afghanistan, especially in the Uzbek-Turkmen ethnic group. -
Kim, Dong Hyun;Oh, Sung Yong;Kim, So Yeon;Lee, Seul;Koh, Myeong Seok;Lee, Ji Hyun;Lee, Suee;Kim, Sung-Hyun;Park, Heon Soo;Hur, Won Joo;Jeong, Jin Sook;Ju, Mi Ha;Seol, Young Mi;Choi, Young-Jin;Chung, Joo Seop;Kim, Hyo-Jin 10985
Background: The capability for DNA double-strand breaks (DSBs) repair is crucial for inherent radiosensitivity of tumor and normal cells. We have investigated the clinicopathologic significance of DNA repair gene expression in nasopharyngeal (NP) carcinoma. Materials and Methods: A total of 65 NP cancer patients who received radiotherapy were included. The immunopositivity to Ku 70, DNA-PKcs, MRN, RAD50, XRCC4, and LIG4 were examined in all tumor tissues. Results: The patients comprised 42 males and 23 females, with a median age of 56 years (range, 18-84). The expression levels of RAD50 (0,+1,+2,+3) were 27.7%, 32.3%, 21.5%, and 18.5%. LIG4 (${\pm}$ ) were 43.1% and 56.9% respectively. The 5-year OS rate of patients with LIG4 (${\pm}$ ) were 90% and 67.9%, respectively (p=0.035). The 5-year TTP rate of patients with LIG4 (${\pm}$ ) were 75.9%, 55.5%, respectively (P=0.039). Conclusions: Our results suggest the possibility of predicting the radiosensitivity of NP cancer by performing immunohistochemical analysis of LIG4. -
Tobacco is a well known cause of death worldwide. With existing comprehensive laws and various other measures for tobacco control, the mortality and morbidity due to tobacco usage have unfortunately not been reduced. A large number of tobacco users have altered their pattern of tobacco use after the gutka ban. Traditional gutka is sold in the open market in a pre-mixed format. Manufacturers are supplying pan masala and tobacco in separate pouches as there is no restriction for sale of pan masala and tobacco individually in many states. Although most of the population is aware of the health hazards of tobacco, it is necessary to develop an effective structured strategy. Tobacco control programs need to be strengthened by separate tobacco control measures at various levels.
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Substance P is a Major Mediator Causing Delayed Emesis in Anthracycline-Based Chemotherapy - Really?Ulas, Arife;Silay, Kamile;Akinci, Sema;Yalcin, Bulent 10993
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Shahab, Sadaf;Nisa, Khaleeq Un;Nadeem, Muhammad;Zahid, Danish;Ansari, Saqib;Farzana, Tasneem;Taj, Mehwesh;Borhany, Munira;Ahmed, Nuzhat;Shamsi, Tahir S. 10995
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Ulas, Arife;Dede, Didem Sener;Sendur, Mehmet Ali Nahit;Akinci, Muhammed Bulent;Yalcin, Bulent 10997
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Prinzi, Natalie;Baldini, Enke;Sorrenti, Salvatore;De Vito, Corrado;Tuccilli, Chiara;Catania, Antonio;Carbotta, Sabino;Mocini, Renzo;Coccaro, Carmela;Nesca, Angela;Bianchini, Marta;De Antoni, Enrico;D'Armiento, Massimino;Ulisse, Salvatore 10999
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Xie, Shao-Hua;Yang, Shu-Juan;Chen, Juan;Cheng, Jin-Quan 11001