Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Volume 14 Issue 2
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Renal cell carcinomas make up 3% of all cancers and one in four patients is metastatic at time of diagnosis. This cancer is one of the most resistant to cytotoxic chemotherapy. Studies have shown that the efficiency of interferon-alpha and/or interleukin-2 based immune therapies is limited in patients with metastatic renal cell carcinoma but latest advances in molecular biology and genetic science have resulted in better understanding of its biology. Tumor angiogenesis, tumor proliferation and metastasis develop by the activation of signal message pathways playing a role in the development of renal cell carcinomas. Better definition of these pathways has caused an increase in preclinic and clinical studies into target directed treatment of renal cell carcinoma. Many recent studies have shown that numerous anti-angiogenic agents have marked clinical activity. In this article, the focus is on general characteristics of molecular pathways playing a major role in renal cell carcinoma, reviewing clinical information onagents used in the target directed treatment of metastatic lesions.
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Nizam, Zahary Mohd;Abdul Aziz, Ahmad Aizat;Kaur, Gurjeet;Abu Hassan, Muhammad Radzi;Mohd Sidek, Ahmad Shanwani;Lee, Yeong Yeh;Mazuwin, Maya;Ankathil, Ravindran 619
Background: Colorectal cancer (CRC) exists in a more common sporadic form and less common hereditary forms, associated with the Lynch syndrome, familial adenomatous polyposis (FAP) and other rare syndromes. Sporadic CRC is believed to arise as a result of close interaction between environmental factors, including dietary and lifestyle habits, and genetic predisposition factors. In contrast, hereditary forms such as those related to the Lynch syndrome result from inheritance of germline mutations of mismatch repair (MMR) genes. However, in certain cases, the influence of low penetrance alleles in familial colorectal cancer susceptibility is also undeniable. Aim: To investigate the genotype frequencies of MLH1 promoter polymorphism -93G>A and to determine whether it could play any role in modulating familial and sporadic CRC susceptibility risk. Methods: A case-control study comprising of 104 histopathologically confirmed CRC patients as cases (52 sporadic CRC and 52 Lynch syndrome patients) and 104 normal healthy individuals as controls was undertaken. DNA was extracted from peripheral blood and the polymorphism was genotyped employing PCR-RFLP methods. The genotypes were categorized into homozygous wild type, heterozygous and homozygous variants. The risk association between these polymorphisms and CRC susceptibility risk was calculated using binary logistic regression analysis and deriving odds ratios (ORs). Results: When risk association was investigated for all CRC patients as a single group, the heterozygous (G/A) genotype showed a significantly higher risk for CRC susceptibility with an OR of 2.273, (95%CI: 1.133-4.558 and p-value=0.021). When analyzed specifically for the 2 types of CRC, the heterozygous (G/A) genotype showed significantly higher risk for sporadic CRC susceptibility with and OR of 3.714, (95%CI: 1.416-9.740 and p-value=0.008). Despite high OR value was observed for Lynch syndrome (OR: 1.600, 95%CI: 0.715-3.581), the risk was not statistically significant (P=0.253). Conclusion: Our results suggest an influence of MLH1 promoter polymorphism -93G>A in modulating susceptibility risk in Malaysian CRC patients, especially those with sporadic disease. -
Kishore, Jugal;Jena, Pratap Kumar;Bandyopadhyay, Chandan;Swain, Monali;Das, Sagarika;Banerjee, Indrani 625
Background: Hardcore smoking is represented by a subset of daily smokers with high nicotine dependence, inability to quit and unwillingness to quit. Estimating the related burden could help us in identifying a high risk population prone to tobacco induced diseases and improve cessation planning for them. This study assessed the prevalence and associated factors of hardcore smoking in three South-East Asian countries and discussed its implication for smoking cessation intervention in this region. Materials and Methods: Global Adult Tobacco Survey (GATS) data of India, Bangladesh and Thailand were analyzed to quantify the hardcore smoking prevalence in the region. On the basis of review, an operational definition of hardcore smoking was adopted that includes (1) current daily smoker, (2) no quit attempt in the past 12 months of survey or last quit attempt of less than 24 hours duration, (3) no intention to quit in next 12 months or not interested in quitting, (4) time to first smoke within 30 minutes of waking up, and (5) knowledge of smoking hazards. Logistic regression analysis was carried out using hardcore smoking status as response variable and gender, type of residence, occupation, education, wealth index and age-group as possible predictors. Results: There were 31.3 million hardcore smokers in the three Asian countries. The adult prevalence of hardcore smoking in these countries ranges between 3.1% in India to 6% in Thailand. These hardcore smokers constitute 18.3-29.7% of daily smokers. The logistic regression model indicated that age, gender, occupation and wealth index are the major predictors of hardcore smoking with varied influence across countries. Conclusions: Presence of a higher number of hardcore smoking populations in Asia is a major public health challenge for tobacco control and cancer prevention. There is need of intensive cessation interventions with due consideration of contextual predictors. -
George, Vazhapilly Cijo;Kumar, Devanga Ragupathi Naveen;Suresh, Palamadai Krishnan;Kumar, Sanjay;Kumar, Rangasamy Ashok 631
Luteolin is a naturally occurring flavonoid present in many plants with diverse applications in pharmacology. Despite several studies elucidating its significant anti-cancer activity against various cancer cells, the mechanism of action in skin cancer is not well addressed. Hence, we investigated the effects of luteolin in HaCaT (human immortalized keratinocytes) and A375 (human melanoma) cells. The radical scavenging abilities of luteolin were determined spectrophotometrically, prior to a cytotoxic study (XTT assay). Inhibitory effects were assessed by colony formation assay. Further, the capability of luteolin to induce cell cycle arrest and apoptosis were demonstrated by flow cytometry and cellular DNA fragmentation ELISA, respectively. The results revealed that luteolin possesses considerable cytotoxicity against both HaCaT and A375 cells with$IC_{50}$ values of 37.1${\mu}M$ and 115.1${\mu}M$ , respectively. Luteolin also inhibited colony formation and induced apoptosis in a dose and time-dependent manner by disturbing cellular integrity as evident from morphological evaluation by Wright-Giemsa staining. Accumulation of cells in G2/M (0.83-8.14%) phase for HaCaT cells and G0/G1 (60.4-72.6%) phase for A375 cells after 24 h treatment indicated cell cycle arresting potential of this flavonoid. These data suggest that luteolin inhibits cell proliferation and promotes cell cycle arrest and apoptosis in skin cancer cells with possible involvement of programmed cell death, providing a substantial basis for it to be developed into a potent chemopreventive template for skin cancer. -
Zhao, Jun-Qiang;Sun, Fang-Jie;Liu, Shan-Shan;Yang, Jun;Wu, Yu-Quan;Li, Gui-Shan;Chen, Qing-Yong;Wang, Jia-Xiang 639
Aim: Connexin 43 (Cx43) and E-cadherin are important biomarkers related with cancer. Their expression at protein and mRNA levels was here investigated in 50 primary lung carcinoma tissues and 20 samples of adjacent normal tissue of Chinese patients with non-small cell lung cancer (NSCLC). Methods: Protein and mRNA expression were evaluated by ABC immunohistochemistry and RT-PCR. Results: (1) The positive expression rates of Cx43 and E-cadherin protein were higher in the adjacent normal tissues than those in the primary lung carcinoma tissues; (2) the positive expression rates of Cx43 and E-cadherin protein decreased with NSCLC progression; (3) the expression of E-cadherin protein was not related with the pathological type of NSCLC; and (4) the relative quantity of the Cx43 or E-cadherin mRNA expression was correlated with the the histological type, clinical stage, cancer cell differentiation and the lymph node metastasis. Conclusion: The data suggested that the Cx43 and E-cadherin are reduced with NSCLC progression, and might be important biomarkers for judging the metastasis and prognosis. -
Huang, Yu-Jing;Qi, Wei-Xiang;He, Ai-Na;Sun, Yuan-Jue;Shen, Zan;Yao, Yang 645
Objective: The prognostic role of vascular endothelial growth factor (VEGF) in bladder cancer remains controversial. This meta-analysis aimed to explore any association between overexpression and survival outcomes. Methods: We systematically searched for studies investigating the relationships between VEGF expression and outcome of bladder cancer patients. Study quality was assessed using the Newcastle-Ottawa Scale. After careful review, survival data were extracted from eligible studies. A meta-analysis was performed to generate combined hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS). Results: A total of 1,285 patients from 11 studies were included in the analysis. Our results showed that tissue VEGF overexpression in patients with bladder cancer was associated with poor prognosis in terms of OS (HR, 1.843; 95% CI, 1.231-2.759; P = 0.003), DFS (HR, 1.498; 95% CI, 1.255-1.787; P = 0.000) and DSS (HR, 1.562; 95% CI, 0.996-1.00; P = 0.052), though the difference for DSS was not statistically significant. In addition, there was no evidence of publication bias as suggested by Begg's and Egger's tests except for DFS (Begg's test, P = 0.221; Egger's test, P = 0.018). Conclusion: The present meta-analysis indicated elevated VEGF expression to be associated with a poor prognosis in patients with bladder cancer. -
Hakverdi, Sibel;Demirhan, Osman;Tunc, Erdal;Inandiklioglu, Nihal;Uslu, Inayet Nur;Gungoren, Arif;Erdem, Duygu;Hakverdi, Ali Ulvi 651
Uterine leiomyomas (UL) are extremely common neoplasms in women of reproductive age, and are associated with a variety of characteristic choromosomal aberrations (CAs). The p53 gene has been reported to play a crucial role in suppressing the growth of a variety of cancer cells. Therefore, the present study investigated the effects of CAs and the p53 gene on ULs. We performed cytogenetic analysis by G-banding in 10 cases undergoing myomectomy or hysterectomy. Fluorescence in situ hybridization (FISH) with a p53 gene probe was also used on interphase nuclei to screen for deletions. In patients, CAs were found in 23.4% of 500 cells analysed, significantly more frequent than in the control group (p<0.001). In the patients, 76% of the abnormalities were structural aberrations (deletions, translocations and breaks), and only 24% were numerical. Deletions were the most common structural aberration observed in CAs. Among these CAs, specific changes in five loci 1q11, 1q42, 2p23, 5q31 and Xp22 have been found in our patients and these changes were not reported previously in UL. The chromosome breaks were more frequent in cases, from high to low, 1, 2, 6, 9, 3, 5, 10 and 12. Chromosome 22, X, 3, 17 and 18 aneuploidy was observed to be the most frequent among all numerical aberrations. We observed a low frequency of p53 losses (2-11%) in our cases. The increased incidence of autosomal deletions, translocations, chromatid breaks and aneuploidy, could contribute to the progression of the disease along with other chromosomal alterations. -
Song, Qing-Kun;Zhao, Lin;Li, Jun;He, Yu-Ming;Jiang, Cui-Ping;Jiang, Hai-Dong;Qu, Chen-Xu 659
Introduction: Squamous cell carcinoma of esophagus (ESCC) is one of the most common cancers in China. Preserved vegetables are processed foods and consumed in high amounts in the high risk areas for ESCC. This study aimed to investigate the relationships of preserved vegetable consumption with ESCC and precancer lesions. Methods: Cases from Yanting cancer hospital with pathological diagnosis of primary cancer, along with controls and individuals diagnosed with precancer lesions by endoscopy with iodine staining were interviewed. Trained staff collected data on dietary habits 1 year before the interview. An unconditional logistic regression model was used to estimate odds ratios of preserved vegetable consumption for precancer lesions and cancer. Results: Adjusting for potential confounders, intake of preserved vegetables (OR=2.92, 95%CI 1.32~6.47) and longer intake period (OR=5.78, 95%CI 2.26~14.80) were associated with higher risk of ESCC. Compared with lowest intake frequency, the highest was associated with a 3.0-fold risk for precancer lesions and 3.59-fold risk for ESCC (both p<0.05). Conclusion: Consumption of preserved vegetables is a risk factor for esophageal lesions in high risk areas. The carcinogenicity of preserved vegetables needs investigation in further studies and the public health strategies for reducing the consumption might be initiated in high risk areas. -
Verim, Levent;Toptas, Bahar;Ozkan, Nazli Ezgi;Cacina, Canan;Turan, Saime;Korkmaz, Gurbet;Yaylim, Ilhan 665
Endothelial nitric oxide synthase (eNOS), encoded by the NOS3 gene, has been suggested to play an important role in uncontrolled cell growth in several cancer types. The objective of this study was to evaluate the role of the NOS3 Glu298Asp polymorphism in bladder cancer susceptibility in a Turkish population. We determined the genotypes of 66 bladder cancer cases and 88 healthy controls. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. A significant association for NOS3 Glu298Asp heterozygotes genotypes and T allele were found between healthy controls and bladder cancer, respectively (p<0.001: p=0.002). There were no significant associations between any genotypes and the stage, grade, and histological type of bladder cancer. Our study suggested an increased risk role of NOS3 GT genotype in bladder cancer susceptibility in our Turkish population. -
Wang, Wen-Shuang;Yu, Shou-Li;Yang, Xing-Sheng;Chang, Shu-De;Hou, Jian-Qing 669
Objective: To investigate the expression of Twist and E-cadherin in ovarian cancer tissues as well as the role of epithelial-mesenchymal transformation (EMT) in ovarian cancer metastasis. Method: The expressions of Twist and E-cadherin in 54 cases of ovarian cancer and paracancerous tissues were detected by Western blottin g and reverse transcriptase polymerase chain reaction. We used RNA interference to silence Twist expression in human ovarian cancer cell line, and detected E-cadherin expression using Western blotting. Results: There was an increase in the relative abundance of Twist proteins and a decrease in E-cadherin in ovarian cancer compared with normal ovary tissues (P < 0.05). The expression levels of Twist and E-cadherin mRNA were$1.49{\pm}0.53$ and$0.82{\pm}0.24$ in ovarian cancer, and$1.14{\pm}0.38$ and$1.08{\pm}0.19$ in paracancerous tissues, respectively. The difference between the indicators in ovarian cancer and in paracancerous tissues was statistically significant (P < 0.05). When the Twist expression was silenced in an ovarian cancer cell line, the expression of the E-cadherin protein increased (P<0.05). Conclusion: The expression of Twist is upregulated, whereas that of E-cadherin is downregulated in ovarian cancer. EMT, mediated by Twist, may be correlated with ovarian cancer metastasis. -
Aghaei, Abbas;Ahmadi-Jouibari, Toraj;Baiki, Omid;Mosavi-Jarrahi, Alireza 673
Introduction: Capture-recapture methods have been suggested for reducing costs of disease registration as well as reducing bias in incidence estimations. This study aimed to estimate the gastric cancer incidence in the Tehran metropolis population during 2002-2006. Materials and Methods: We investigated new cases of gastric cancer reported by three sources; death certificates, pathology reports, and medical records to Tehran population-based cancer registry during 2002-2006.$G^2$ statistics and the two-source capture-recapture method were used to select the best-fitted log-linear model and to estimate incidence, respectively. EXCEL software version 2007 and SPSS software version 16 were used for this research. Results: The number of reported cases was 4,463, with an average age of 68.5 (${\pm}12.9$ ) years. We found the model that combined two sources of data including pathology reports and medical records and furthermore complemented by death certificates as the best model. The reported and the estimated incidences were 11.0 and 27.1 per 100,000 respectively. Conclusions: The incidence estimated by two-source capture-recapture method is about three times higher than the incidence reported by the sources under investigation. It is recommended to move towards the implementation of population-based cancer registration using various sources of data collection to achieve more accurate data. -
Merchant, Nipun B.;Dutta, Sudhir K.;Girotra, Mohit;Arora, Manish;Meltzer, Stephen J. 679
Background: Dysplasia and adenocarcinoma developing in Barrett's esophagus (BE) are not always endoscopically identifiable. Molecular markers are needed for early recognition of these focal lesions and to identify patients at increased risk of developing adenocarcinoma. The aim of the current study was to correlate increased telomerase activity (TA) with dysplasia and adenocarcinoma occurring in the setting of BE. Materials and Methods: Esophageal mucosal biopsies were obtained from patients (N=62) who had pathologically verified BE at esophagogastroduodenoscopy (EGD). Mucosal biopsies were also obtained from the gastric fundus as controls. Based on histopathology, patients were divided into three groups: 1) BE without dysplasia (n=24); 2) BE with dysplasia (both high grade and low grade, n=13); and 3) BE with adenocarcinoma (n=25). TA was measured by a PCR-based assay (TRAPeze$^{(R)}$ ELISA Telomerase Detection Kit). Statistical analyses were performed using one-way ANOVA and post-hoc Bonferroni testing. Results: TA was significantly higher in biopsies of BE with dyplasia and BE with adenocarcinoma than in BE without dysplasia. Subgroup analyses did not reveal any significant correlations between TA and patient age, length of BE, or presence of gastritis. Conclusions: Telomerase activity in esophageal mucosal biopsies of BE may constitute a useful biomarker for the early detection of esophageal dysplasia and adenocarcinoma. -
Li, Ning;Tie, Xiao-Jing;Liu, Pei-Jie;Zhang, Yan;Ren, Hong-Zheng;Gao, Xin;Xu, Zhi-Qiao 685
Objective: To study the effects of down-regulation of HDAC6 expression on proliferation, cell cycling and migration of esophageal squamous cell carcinoma (ESCC) cells and related molecular mechanisms. Methods: ESCC cell line EC9706 cells were randomly divided into untreated (with no transfection), control siRNA (transfected with control siRNA) and HDAC6 siRNA (transfected with HDAC6 small interfering RNA) groups. Effects of HDAC6 siRNA interference on expression of HDAC6 mRNA and protein in EC9706 cells were investigated by semi-quantitative RT-PCR, Western blotting and immunocytochemistry methods. Effects of down-regulation of HDAC6 expression on cell proliferation, cell cycle, and cell migration were studied using a CCK-8 kit, flow cytometry and Boyden chambers, respectively. Changes of mRNA and protein expression levels of cell cycle related factor (p21) and cell migration related factor (E-cadherin) were investigated by semi-quantitative RT-PCR and Western blotting methods. Results: After transfection of HDAC6 siRNA, the expression of HDAC6 mRNA and protein in EC9706 cells was significantly downregulated. In the HDAC6 siRNA group, cell proliferation was markedly inhibited, the percentage of cells in G0/G1 phase evidently increased and the percentage of cells in S phase decreased, and the number of migrating cells significantly and obviously decreased. The mRNA and protein expression levels of p21 and E-cadherin in the HDAC6 siRNA group were significantly higher than those in the untreated group and the control siRNA group, respectively. Conclusions: HDAC6 siRNA can effectively downregulate the expression of HDAC6 mRNA and protein in EC9706 cells. Down-regulation of HDAC6 expression can obviously inhibit cell proliferation, arrest cell cycling in the G0/G1 phase and reduce cell migration. The latter two functions may be closely related with the elevation of mRNA and protein expression of p21 and E-cadherin. -
Wang, Zhao;Wu, Xiao-Ling;Zeng, Wei-Zheng;Xu, Gui-Sen;Xu, Hui;Weng, Min;Hou, Juan-Ni;Jiang, Ming-De 691
Purpose: By carrying out a meta-analysis of randomized controlled trials that compared sorafenib or combined chemotherapy with placebo or combined chemotherapy, the effectiveness of sorafenib in hepatocellular carcinoma was evaluated in the present study, which also provided clinical practice guidelines of evidence-based-medicine. Methods: We reviewed PubMed citations concerning sorafenib treating hepatocellular carcinoma in randomized controlled trials from Jan 2000 to July 2012. All the literature was extracted by Cochrane systematic reviews and underwent meta-analysis with RewMan 5.0 software. Results: Finally, four papers documenting randomized controlled studies were included. Compared with controls, sorafenib was shown to significantly increase overall survival (OS), time to progression (TTP), and disease control rates (DCR), but not the time to symptom progression (TTSP) in hepatocellular carcinoma patients. The incidence of grade-III/IV adverse reactions, including hand-foot-skin reactions, diarrhea, hypertension and skin rash or desquamation, in sorafenib treatment group was higher than that in controls. However, there was no significant difference in the incidence of hypodynamia between the two groups. Conclusions: Sorafenib exerts significant curative effects in hepatocellular carcinoma. -
Background: Mutations affecting the epidermal growth factor receptor (EGFR) are good predictors of clinical efficacy of EGFR tyrosine kinase inhibitors (TKI) in patients with non-small cell lung cancer. Serum carcinoembryonic antigen (CEA) levels are also regarded as predictive for the efficacy of EGFR-TKI and EGFR gene mutations. This study analyzed the association between EGFR gene mutations and clinical features, including serum tumor marker levels in lung adenocarcinomas patients. Patients and Methods: A total of 70 lung adenocarcinoma patients with complete clinical data and pathological specimens were investigated. EGFR gene mutations at exons 19 and 21 were assessed. Serum tumor markers were detected by protein chip-chemiluminescence at the corresponding time, and correlations were analyzed. Results: Mutations of the EGFR gene were detected in 27 of the 70 patients and the serum CEA and CA242 concentrations were found to be significantly associated with the incidence of EGFR gene mutations (P<0.05). The AUCs for CEA and CA242 were 0.724 (95% CI: 0.598~0.850, P<0.05) and 0.769 (95% CI: 0.523~0.800, P<0.05) respectively. Conclusions: Serum CEA and CA242 levels are associated with mutations of the EGFR gene in patients with lung adenocarcinomas.
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Zhang, Tian;Sun, Jing;Lv, Min;Zhang, Lin;Wang, Xia;Ren, Ji-Chen;Wang, Bin 701
Polymorphisms in XPG are considered to contribute to the clinical outcome of patients receiving platinum drug chemotherapy. We aimed to investigate the role of five potential SNPs of XPG gene on the response to platinum-based chemotherapy in advanced Chinese NSCLC patients. A total of 451 patients with newly diagnosed and histopathologically confirmed primary NSCLC were consecutively collected. XPG rs2296147, rs4150261, rs17655, rs1047768 and rs2094258 were genotyped by the Taqman real-time polymerase chain reaction (PCR). In our study, we found patients carrying rs1057768 TT genotype had a significantly lower treatment response when compared with the CC genotype (OR=0.38, 95% CI=0.18-0.78). Patients carrying rs1047768 TT genotype showed a significantly short median PFS (11.2 months) and OS (13.6 months) than CC genotype, and the hazard ratios (HR) for PFS and OS were 2.06 (1.01-4.50) and 2.29 (1.21-2.49), respectively. Moreover, we found a significant decreased risk of death from NSCLC among patients carrying the rs2296147 TT genotype when compared with the CC genotype, the HR (95% CI) for OS being 0.50 (0.27-0.95). In conclusion, our study found that polymorphisms in rs1047768 C/T and rs2296147 C/T are associated with response to platinum-based chemotherapy in advanced NSCLC, and XPG polymorphisms could be predictive of prognosis. -
Wang, Shi-Fu;Zhao, Wen-He;Wang, Wei-Bin;Teng, Xiao-Dong;Teng, Li-Song;Ma, Zhi-Min 707
Purpose: To investigate the clinical features and prognosis of papillary thyroid carcinoma (PTC) with a background of benign disease. Method: A total of 709 patients with papillary thyroid carcinoma undergoing surgical resection were analyzed retrospectively. In 147 patients who underwent surgery for benign thyroid disease, incidental PTC (IPC group) were identified by intraoperative or postoperative pathological examination of surgical specimens but were not detected by preoperative imaging studies. In the other group, according to the pathological examination with or without co-existing benign thyroid disease, 253 cases were clarified as concomitant PTC and 309 cases were clarified as dominant PTC. Results: Incidental PTC was more common in women, about 85.7%, the mean age was$47.6{\pm}11.3$ years old. Average tumor diameter was$4.4{\pm}2.2$ mm, multiple lesions accounted for 12.9% (19/147), and the cervical lymph node metastasis rate was 6.1% (9/147). After radical resection 8 cases recurred, the median time of recurrence was about 12 months (0.5 to 162), there was no tumor-related death. The tumor-free survival rates were 97.3%, 95.9%, 91.5%, and 79.3% in 1, 5, 10 and 14 year respectively. Conclusion: Incidental PTC with a background of benign lesions is common, and the generally good prognosis can be attributed to tumor early detection and early treatment. On the intraoperative finding of incidental PTC, lobectomy (unilateral) or total thyroidectomy (bilateral) should be the first choice, but with a postoperative pathologic finding of incidental PTC, further treatment, such as completion thyroidectomy or immediate lymph dissection is not necessary. Central lymph node dissection is also not needed unless lymphadenectasis is present. -
Liang, Shu-Yuan;Chen, Kang-Pan;Tsay, Shiow-Luan;Wu, Shu-Fang;Chuang, Yeu-Hui;Wang, Tsae-Jyy;Tung, Heng-Hsin;Cheng, Su-Fen 713
Social and behavioral scientists have proposed that a person's belief system crucially influences his or her behaviour, and therefore may affect outcomes of pain management. The purpose of this study was to explore the relationship between analgesic beliefs, analgesic adherence and pain experience amongst Taiwanese cancer outpatients. The cross-sectional study included 92 oncology outpatients in two teaching hospitals in the Taipei area of Taiwan. The research instruments included the Pain Opioid Analgesic Beliefs Scale-Cancer (POABS-CA), opioid adherence, and the Brief Pain Inventory-Chinese (BPI-Chinese). Beliefs about pain and opioids demonstrated a significant relationship with patients' opioid adherence (r = -0.30, p < 0.01). The more negative beliefs regarding opioids and pain the patient had, the worse their adherence to around the clock (ATC) analgesic regimen. However, there was no significant correlation between opioid belief and pain experience. As well, there were no significant relationships between adherence to opioid regimen and any of the measures of pain experience. The study highlights the potential importance of a patient's pain and opioid beliefs in adherence to pain medication. -
Orang, Elahe;Marzony, Eisa Tahmasbpour;Afsharfard, Aboulfazl 717
Background: Breast cancer is the most common cancer among women worldwide. The aim of this study was to investigate the relationship between tumor size and axillary lymph node involvement (ALNI) in patients with invasive lesions, to find the best candidates for a full axillary dissection. Additionally, we evaluated the association between tumor size and invasive behavior. The study was based on data from 789 patients with histopathologically proven invasive breast cancer diagnosed in Shohada University hospital in Tehran, Iran (1993-2009). Cinical and histopathological characteristics of tumors were collected. Patients were divided into 6 groups according to primary tumor size: group I ($0.1-{\leq}1cm$ ), II ($1.1-{\leq}2cm$ ), III ($2.1-{\leq}3cm$ ), IV ($3.1-{\leq}4cm$ ), V ($4.1-{\leq}5cm$ ) and VI (>5cm). The mean(${\pm}SD$ ) size of primary tumor at the time of diagnosis was$3.59{\pm}2.69$ cm that gradually declined during the course of study. There was a significant correlation between tumor size and ALNI (p<0.001). A significant positive correlation between primary tumor size and involvement of surrounding tissue was also found (p<0.001). The mean number of LNI in group VI was significantly higher than other groups (p<0.05). We observed more involvement of lymph nodes, blood vessels, skin and areola-nipple tissue with increase in tumor size. We found 15.3% overall incidence of ALNI in tumors${\leq}2cm$ , indicating the need for more investigation to omit full axillary lymph node dissection with an acceptable risk for tumors below this diameter. While in patients with tumors${\geq}2cm$ , 84.3% of them had nodal metastases, so the best management for this group would be a full ALND. Tumor size is a significant predictor of ALNM and involvement of surrounding tissue, so that an exact estimation of the size of primary tumor is necessary prior to surgery to make the best decision for management of patients with invasive breast cancer. -
Elalaoui, Siham Chafai;Jaouad, Imane Cherkaoui;Laarabi, Fatima Zahra;Elgueddari, Brahim El Khalil;Benjaafar, Noureddine;Sefiani, Abdelaziz 723
Background: Breast cancer is worldwide the most common cancer in women and is a major public health problem. Genes with high or low penetrance are now clearly implicated in the onset of breast cancer, mostly the BRCA genes. All women in families at high risk of breast cancer do not develop tumours, even when they carry the familial mutation, suggesting the existence of genetic and environmental protective factors. Several studies have shown that consanguinity is linked to a decreased or an increased risk of breast cancer, but to the best of our knowledge, there is no study concerning the association between consanguinity and the occurrence of tumours in women with high risk of breast cancer. The objective of this study was to examine whether parental consanguinity in families with genetic predisposition to breast cancer affect the risk of siblings for having this cancer. Materials and Methods: Over a six-year period, 72 different patients with a histological diagnosis of breast or ovarian cancer from 42 families were recruited for genetic counselling to the Department of Medical Genetics, Rabat. Consanguinity rate was determined in cases and compared to the consanguinity rate in the Moroccan general population. Results: Consanguinity rates were 9.72% in patients and 15.3% in controls, but the difference was statistically not significant (p>0.001) and the mean coefficient of consanguinity was lower in breast cancer patients (0.0034) than in controls (0.0065). Conclusions: Despite the relatively small sample size of the current study, our results suggest that parental consanguinity in Moroccan women might not be associated with an altered risk of breast cancer. Large scale studies should be carried out to confirm our results and to develop public health programs. -
Ambroise, M. Moses;Ghosh, Mitra;Mallikarjuna, V.S.;Annapurneswari, S.;Kurian, Ann;Chakravarthy, Ranjani 727
Background: The aim of this study was to analyze the clinicopathological and immunohistochemical features of primary central nervous system lymphoma (PCNSL) cases occurring in Indian patients and also study the utility of the crush smear preparation in intraoperative diagnosis. Materials and Methods: The immune status, clinical, radiological details, immunohistochemical profile, histopathological findings and cytological features in smear preparation of 32 cases of PCNSL were analyzed. Patients with systemic NHL and skull-base lymphomas were excluded. Results: The mean age of our patients was 52 years with a male: female ratio 1:1. A periventricular location was found in 62.5% of patients. None of our PCNSL cases were associated with AIDS. All cases except one were diffuse large B-cell lymphomas. Intraoperative diagnosis using crush smears allowed correct prediction in 93% of cases. Conclusions: Our study shows that PCNSL is seen predominantly in immunocompetent patients in India. The age of presentation is relatively young as compared to the West. Our study also stresses the utility of crush smear preparation in establishing an intraoperative diagnosis. -
Background: Breast and cervical cancers are significant causes of mortality and morbidity for Asian women, and poor English-speaking ability is a barrier to cancer prevention practices. Materials and Methods: This project tested relationships among English-speaking ability and early detection practices regarding to breast and cervical cancer among female Chinese immigrants. A descriptive cross-sectional survey was used. Results: 175 female Chinese immigrants completed the survey in the breast cancer prevention section, and 35 of them also completed the cervical cancer prevention section. Some 63% of them had heard about the clinical breast exam (CBE), but only 54% had had a CBE. While 46% of the participants were aware of their need for a Pap smear, only 31% had heard about it and had undergone a pelvic exam. Conclusions: English-speaking ability was strongly associated with immigrant women's knowledge of female cancer early detection. Culturally and linguistic issues should be considered as the first step to access immigrant population in designing future education intervention.
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Ibrahim, Noha;Abou-Elela, Enas;Darwish, Dalia 739
Background: This study was to evaluate the survival of patients with pleural and intraperitoneal malignant mesothelioma and to investigate the efficacy of chemotherapy (CT) as well as radiotherapy (RTH) and surgery compared to best supportive care (BSC). Materials and Methods: Forty patients with malignant mesothelioma (38 with pleural and 2 with intraperitoneal) were enrolled. Twenty seven patients underwent (CT) chemotherapy of which 2 also received (RTH) and surgery was only for biopsy in 15/40. Combination chemotherapy included cisplatin-gemcitabine, cisplatin-navelbine and cisplatin (or carboplatin) with premetrexed. Thirteen patients received only best supportive care. Results: A total of 12 (30%) patients were male, and 28 (70%) female. Median age was 54.0 years and the male/female ratio was 1/2.33 (P=0.210). Residential exposure played a major role in two regions, Helwan and Shoubra, in 20% and 15%, respectively. Overall mean survival time was$13.9{\pm}2.29$ months. That for patients who had received best supportive care was$7.57{\pm}1.85$ months, for chemotherapy was$16.5{\pm}3.20$ months, and multimodality treatment regimen$27{\pm}21.0$ months (P=0.028). Kaplan-Meier survival did not significantly vary for sex, residence and the pathological types epithelial, mixed and sarcomatous. The median survival for performance status and treatment modalities was significant (P=0.001 and 0.028). Best supportive care using opioids with a mean dose of 147.1 mg (range 0-1680) of morphine sulphate produced good subjective response and reasonable quality of life but did not affect survival. Conclusions: We conclude that CT prolongs survival compared to BSC in patients with malignant mesothelioma. Moreover, using escalating doses of opioids provides good pain relief and subjective responses. -
Mutlu, Hasan;Akca, Zeki;Cihan, Yasemin Benderli;Kurnaz, Fatih;Aslan, Tuncay;Erden, Abdulsamet;Ugur, Hediye;Aksahin, Arzu;Buyukcelik, Abdullah 743
Background: Some studies have indicated an inverse relationship between cancer risk and sunlight exposure. Others have reported that the prognosis of some cancers such as prostate, colon, ovarian and non melanoma skin cancer, were affected by the season in which the cancer was diagnosed. In our study, we evaluated whether season is prognostic in Turkish patients with breast cancer. Materials and Methods: A total of 517 patients from Kayseri Training and Research Hospital were analysed retrospectively. Patients were divided into 4 groups according to season of cancer diagnosis: winter, spring, summer and autumn. The prognostic factors for disease free survival and overall survival were investigated. Results: No significant differences were found among groups regarding prognostic factors overall. Only estrogen receptor status and lymphovascular invasion were independent prognostic factors (p=0.001 and p=0.001 respectively). We found significantly differences for mean disease free survival among groups (p=0.019). Winter group had better mean DFS while summer group had worse DFS. Mean overall survival was similar in the four groups (p=0.637). Conclusions: The season is not an independent predictive factor. However, due to interaction with other factors, we think that the season of cancer diagnosis is important for cancer prognosis. -
Kong, N.;Zhang, X.M.;Wang, H.T.;Mu, X.P.;Han, H.Z.;Yan, W.Q. 747
Oncostatin M (OSM) is a multifunctional cellular regulator acting on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. Previous studies have shown that OSM can induce morphological and/or functional differentiation and maturation of many tumor cells. However, the action of OSM on the induction of differentiation of human hepatocellular carcinoma (HCC) has not been reported. Here, we investigated the effects of different concentrations of OSM on human HCC cell line SMMC-7721 growth, proliferation, cell cycling, apoptosis and differentiation in vitro. Cell growth was determined via MTT assay, proliferation by cell cycle analysis, apoptosis by flow cytometry, morphology by transmission electronic microscopy, and cell function by detection of biochemical markers. Our results demonstrated that OSM strongly inhibited the growth of SMMC-7721 cells in a dose-dependent manner, associated with decreased clonogenicity. Cell cycle analysis revealed a decreased proportion of cells in S phase, with arrest at G0/G1. The apotosis rate was increased after OSM treatment compared to the control. These changes were associated with striking changes in cellular morphology, toward a more mature hepatic phenotype, accompanied by significant reduction of the expression of AFP and specific activity of${\gamma}$ -GT, with remarkable increase in secretion of albumin and ALP activity. Taken together, our findings indicate that OSM could induce the differentiation and reduce cell viability of SMMC-7721 cells, suggesting that differentiation therapy with OSM offers the opportunity for therapeutic intervention in HCC. -
Bai, Lian-Song;Chen, Chuang;Gong, Yi-Ping;Wei, Wen;Tu, Yi;Yao, Feng;Li, Juan-Juan;Wang, Li-Jun;Sun, Sheng-Rong 753
Objective: To evaluate the relationships between lymph node ratio (LNR, the ratio of positive lymph nodes in excised axillary lymph nodes) and disease-free survival (DFS) by comparing with traditional absolute positive lymph node number (pN classification) for prediction of breast cancer (BC) progrnosis. Methods and Patients: We retrospectively reviewed patients who received comprehensive therapy in Department of Breast Surgery, Hubei Cancer Hospital, China from Jan 2002 to Dec 2006 (Group A), and Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, China from Jun 2008 to May 2012 (Group B). Patients were allocated to low-risk (${\leq}0.20$ ), intermediate-risk (> 0.20 but${\leq}0.65$ ), high-risk (>0.65) groups by LNR. The primary endpoint was 5-DFS. Results: A total of 294 patients were included in our study. LNR was verified as a negative prognostic factor for DFS (P=0.002 in Group A, P<0.0001 in Group B). Then we found the effects of pN and LNR delamination on disease-free survival (DFS) had statistical significance (P=0.012 for pN and P=0.031 for LNR stratification in Group A, both of them P<0.001 in Group B). Compared to pN staging, LNR staging displayed superior performance in prognosis, the adjusted hazard ratio of recurrence being 2.07 (95%CI, 1.07 to 4.0) for intermediate risk group (P=0.030) and 2.44 (95%CI, 1.21 to 4.92) for high risk group (P=0.013) in Group A. Conclusions: LNR stratification proved an adverse prognostic factor of DFS in lymph nodes positive invasive BC using cut-off values 0.20 and 0.65, and was more predictive than traditional pN classification for 5-DFS. -
Chen, Peng;Hu, Ming-Dao;Deng, Xiao-Fan;Li, Bo 759
Background: The high recurrence rate after hepatic resection in hepatocellular carcinoma (HCC) is a major obstacle to improving prognosis. The objective of the present study was to explore the function of genistein, a soy-derived isoflavone, in enhancing the inhibitory effect of cisplatin on HCC cell proliferation and on tumor recurrence and metastasis in nude mice after curative hepatectomy. Methods: Proliferation of human HCC cells (HCCLM3) was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Synergistic effects of genistein and cisplatin were evaluated with the median-effect formula. Nude mice bearing human HCC xenografts underwent tumour resection (hepatectomy) 10 days post implantation, then received intraperitoneal administration of genistein or cisplatin alone or the combination of the two drugs. 33 days after surgery, recurrent tumours and pulmonary metastasis were evaluated individually. MMP-2 level in recurrent tumours was detected by immunohistochemistry and real-time PCR; MMP-2 expression in HCCLM3 was detected by immunocytochemistry. Results: Genistein and cisplatin both suppressed the growth and proliferation of HCCLM3 cells. The two drugs exhibited synergistic effects even at relatively low concentrations. In vivo, mice in the combined genistein and cisplatin group had a smaller volume of liver recurrent tumors and fewer pulmonary metastatic foci compared with single drug treated groups. Cisplatin upregulated the expression of MMP-2 in both recurrent tumours and HCCLM3, while genistein abolished cisplatin-induced MMP-2 expression. Conclusions: Genistein reinforced the inhibitory effect of cisplatin on HCC cell proliferation and tumour recurrence and metastasis after curative hepatectomy in nude mice, possibly through mitigation of cisplatin-induced MMP-2 upregulation. -
Avci, Cigir Biray;Harman, Ece;Dodurga, Yavuz;Susluer, Sunde Yilmaz;Gunduz, Cumhur 765
Background and Aims: Prostate cancer is the most commonly diagnosed cancer in males in many populations. Metformin is the most widely used anti-diabetic drug in the world, and there is increasing evidence of a potential efficacy of this agent as an anti-cancer drug. Metformin inhibits the proliferation of a range of cancer cells including prostate, colon, breast, ovarian, and glioma lines. MicroRNAs (miRNAs) are a class of small, non-coding, single-stranded RNAs that downregulate gene expression. We aimed to evaluate the effects of metformin treatment on changes in miRNA expression in PC-3 cells, and possible associations with biological behaviour. Materials and Methods: Average cell viability and cytotoxic effects of metformin were investigated at 24 hour intervals for three days using the xCELLigence system. The$IC_{50}$ dose of metformin in the PC-3 cells was found to be 5 mM. RNA samples were used for analysis using custom multi-species microarrays containing 1209 probes covering 1221 human mature microRNAs present in miRBase 16.0 database. Results: Among the human miRNAs investigated by the arrays, 10 miRNAs were up-regulated and 12 miRNAs were down-regulated in the metformin-treated group as compared to the control group. In conclusion, expression changes in miRNAs of miR-146a, miR-100, miR-425, miR-193a-3p and, miR-106b in metformin-treated cells may be important. This study may emphasize a new role of metformin on the regulation of miRNAs in prostate cancer. -
Arpaci, Erkan;Tokluoglu, Saadet;Yetigyigit, Tarkan;Alkis, Necati 769
Background: A literature review on 1,104,269 cancer patients concluded that the prevalence of multiple primary malignancies (MPM) is between 0.73% and 11.7%. MPMs seem to have higher incidence than that influenced by hazard only. The purpose of this study was to investigate clinically useful information for effective screening for synchronous and metachronous second primary cancers and to identify a potential surveillance protocol. Materials and Methods: Using statistical and epidemiological indicators we evaluated the patients with MPMs (double locations) admitted to Dr. Abdurrahman Yurtarslan Ankara Oncology Education and Research Hospital between 1981 and 2010. Results: Out of the 130 cases, 24 (18.4%) were synchronous while 106 cases (81.6%) were metachronous tumours. Mean interval time from first to second primary cancers was 4.65 years (0-27 years). The most frequent malignant associations were breast-breast, breast-endometrium and breast-ovary. Both primary and secondary tumors tended to be in an advanced stage explained by the low compliance of the patients to follow-up. Conclusions: The possibility that MPMs exist must always be considered during pretreatment evaluation. Screening procedures are especially useful for the early detection of associated tumors, whereas careful monitoring of patients treated for primary cancer and a good communication between patients and medical care teams should ensure early detection of secondary tumors, and subsequent appropriate management. -
Balasubramaniam, Ganesh;Saoba, Sushama;Sarade, Monika;Pinjare, Suvarna 775
Background: In the year 2010, it is estimated that nearly 0.36 million new cases and 0.19 million deaths with Non-Hodgkin lymphoma occurred. In India, among males, NHL incidence rates vary across the country which has encouraged us to conduct a case-control study to study risk factors. Materials and Methods: The present unmatched hospital-based case-control study conducted at Tata Memorial Hospital included subjects registered between the years 1997-99. There were 390 'lymphoma cases' and 1,383 'normal controls. Results: Data on age, tobacco habits, occupational history, dietary factors, tea, coffee were collected by the social investigators. Univariate and multivariate methods were applied for obtaining the odds ratios for risk factors. Conclusions: In the study, cigarette smoking (OR=2.0) and bidi smoking (OR=2.8), were associated with excess risk of lymphoma. Among the dietary items, only consumption of mutton showed 7.3-fold significant excess risk for lymphoma. Consumption of milk showed a 6-fold excess risk (OR=1.5); while coffee showed a 50% reduction in risk for lymphoma. Among occupational exposure, exposure to use of pesticides showed 3-fold excess risk for lymphoma. -
Zhong, Feng;Yang, Xue-Cai;Bu, Ling-Xue;Li, Ning-Yi;Chen, Wan-Tao 781
Aim: The purpose of this study was to determine whether susceptibility to oral tongue squamous cell carcinoma (OSCC) is related to polymorphisms in the u-PA gene. Methods: We examined the rs2227564 C/T and rs2227562 G/A single nucleotide polymorphisms (SNPs) in 196 OSCC patients and 201 age- and gender-matched controls via direct sequencing and PCR-RFLP methods. Results: Significant differences were found in allelic and genotypic distributions of the rs2227564 and rs2227562 loci when comparing cases and controls. In addition, logistic analyses indicated that the rs2227564 C/T genotype was related to a 1.52-fold increased risk of developing OSCC (adjusted OR=1.521, 95%CI: 1.144~2.022, P=0.004). Linkage disequilibrium analysis was conducted and no association between the two loci was found (D'=0.031,$r^2$ =0.000). Conclusions: Our findings provide evidence that the rs2227564 C/T SNP in the u-PA gene is associated with the development of OSCC. -
Das, Debabrata;Rai, Avdhesh Kumar;Kataki, Amal Chandra;Barmon, Debabrata;Deka, Pankaj;Sharma, Jagannath Dev;Sarma, Anupam;Shrivastava, Sushruta;Bhattacharyya, Mouchumee;Kalita, Apurba Kumar;Sharma, Mousumi;Ahmed, Shiraj 785
Background: Persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly HPV types 16/18, has a significant role in cervical cancer initiation and progression. There are limited data available from north-east India about HPV prevalence though this region has high incidence rates of cervical cancer. The aim of this study was to investigate the HPV genotypes prevalent in cervical cancer patients of north-east India. Materials and Methods: We analyzed 107 cervical cancer patient samples. Nested multiplex PCR assays were employed for detection of 13 high risk and 5 low risk HPV types. Results: HPV was confirmed in 105 samples. The presence of 6 'carcinogenic' HPV types, HPV-16 (88%), -18 (15%), -31(4%),-45 (3%), -59 (4%), -58(1%), and one non carcinogenic, HPV-6/11 (6%), was recorded. Among various demographic and clinical factors only tumour stage showed a statistically significant association with HPV type infection (P=0.019). Conclusions: We suggest that the most prevalent genotype is HPV-16 followed by HPV-18 in cervical carcinoma patients of the north-eastern region of India. Advanced tumour stage may be associated with increased possibility of harbouring multiple HPV genotypes. -
Colorectal cancer is one of the most common cancers. The aim of this study is determination its trends in Kerman province and individual cities separately until year 2016. This analytical and modeling study was based of cancer registry data of Kerman University of Medical Sciences, collected during 2001-2010. Among 20,351 cancer case, 792 were colorectal cancer cases in age group 18-93 years with a mean of 59.4 and standard deviation of 15.1. By applying time series and data trends, incidences were predicted until 2016 for the province and each city, with adjustment for population size. In colorectal cases, 413 (52%) were male, and 379 (48%) were female. The annual increasing rate in Kerman province overall was and can be expected to be 6%, and in the cities of the province Rafsanjan, Bardsir, Bam, Kerman, Baft, Sirjan, Jiroft, Kahnuj and Manujan had an increasing range from 5 to 14% by the year 2016. But in Ravar, Zarand and Shahrbabak reduction in rates of at least 2% could be predicted. The time series showed that the trend of colorectal cancer in female will increase 15% and in male 7% by year 2016. Given the trend of this cancer is increasing so that resources will be consumed in the treatment of the patients, efforts shoudlbe focused on prevention and early diagnosis of the disease. Screening could have an important role leading to improved survival.
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Hu, Liu;Wu, Qin-Qin;Wang, Wen-Bo;Jiang, Huan-Gang;Yang, Lei;Liu, Yu;Yu, Hai-Jun;Xie, Cong-Hua;Zhou, Yun-Feng;Zhou, Fu-Xiang 795
Ku70/80 heterodimer is a central element in the nonhomologous end joining (NHEJ) DNA repair pathway, Ku80 playing a key role in regulating the multiple functions of Ku proteins. It has been found that the Ku80 protein located at telomeres is a major contributor to radiosensitivity in some telomerase positive human cancer cells. However, in ALT human osteosarcoma cells, the precise function in radiosensitivity and telomere maintenance is still unknown. The aim of this study was to investigate the effects of Ku80 depletion in the U2OS ALT cell line cell line. Suppression of Ku80 expression was performed using a vector-based shRNA and stable Ku80 knockdown in cells was verified by Western blotting. U2OS cells treated with shRNA-Ku80 showed lower radiobiological parameters (D0, Dq and SF2) in clonogenic assays. Furthermore, shRNA-Ku80 vector transfected cells displayed shortening of the telomere length and showed less expression of TRF2 protein. These results demonstrated that down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening. -
Mutlu, Hasan;Buyukcelik, Abdullah;Colak, Taner;Ozdogan, Mustafa;Erden, Abdulsamet;Aslan, Tuncay;Akca, Zeki 801
Intraduction: There is known to be a relationship between vitamin D level and more aggresive breast cancer subtypes, especially triple-negative breast cancer (TNBC). It was reported that sunlight exposure has an effect on the prognosis of patients with cancer, possibly related to the conversion of vitamin D to its active form with sunlight. We aimed to evaluate the effect of sunlight exposure on patients with TNBC. Materials-Methods: A total of 1,167 patients with breast cancer from two different regions of Turkey (Antalya and Kayseri, regions having different climate and sunlight exposure intensity over the year) were analysed retrospectively. The ratio of patients with TNBC was identified in those two regions. Results: The ratio of patients with TNBC was 8% and 12% for Kayseri and Antalya regions, respectively, and this difference between the two groups was statistically significant (p=0.021). Discussion: Sunlight exposure may be associated with more prevalent TNBC. This finding should be investigated with a prospective study. -
Lim, Kuang Hock;Ibrahim, Normala;Ghazali, Sumarni Mohd;Kee, Chee Cheong;Lim, Kuang Kuay;Chan, Ying Ying;Teh, Chien Huey;Tee, Eng Ong;Lai, Wai Yee;Nik Mohamad, Mohd. Haniki;Sidek, Sherina Mohd 805
Increasing the rate of smoking cessation will reduce the burden of diseases related to smoking, including cancer. Understanding the process of smoking cessation is a pre-requisite to planning and developing effective programs to enhance the rate of smoking cessation.The aims of the study were to determine the demographic distribution of smokers across the initial stages of smoking cessation (the pre-contemplation and contemplation stages) and to identify the predictors of smoking cessation among Malaysian adult smokers. Data were extracted from a population-based, cross-sectional survey carried out from April 2006 to July 2006. The distribution of 2,716,743 current smokers across the pre-contemplation stage (no intention to quit smoking in the next six months) or contemplation stage (intended to quit smoking in the next six months) was described. Multivariable logistic regression analysis was used to examine the relationship between socio-demographic variables and the stages of smoking cessation. Of the 2,716,743 current smokers, approximately 30% and 70% were in the pre-contemplative and contemplative stages of smoking cessation respectively. Multivariable analysis showed that male gender, low education level, older age group, married and those from higher income group and number of cigarettes smoked were associated with higher likelihood of pre-contemplation to cease smoking in the next six months. The majority of current smokers in Malaysia were in the contemplative stage of smoking cessation. Specific interventions should be implemented to ensure the pre-contemplative smokers proceed to the contemplative stage and eventually to the preparation stage. -
Zheng, Rui-Zhi;Zhang, Qing-He;He, Yi-Xin;Zhang, Qian;Yang, Lin-Shen;Zhang, Zhi-Hua;Zhang, Xiu-Jun;Hu, Jing-Ting;Huang, Fen 811
Background: Pervious studies suggested occupational workers exposure to pentachlorophenol (PCP) might contribute to increased risk of cancer. However, few studies have focused on associations between PCP and cancer risk at the community level. Objective: The present study was to explore the cancer risk for the community population living long-term in a PCP contaminated area. Methods: All the cancer cases diagnosed in 2009-2011 in Tongling City were collected. The cancer patients' residencies were geo-referenced in each district. The historical PCP usage for each district of Tongling was calculated as the PCP pollution index, which was further used to divide into PCP exposure categories. Standardized rate ratios (SRRs) of cancer incidence were applied to detect the cancer risk as exposure grade elevated. Correlation analysis was performed to analyze the relationship between PCP pollution and cancer incidence. Results: A total of 5,288 cancer cases (3,451 male and 1,837 female) were identified. PCP usage was correlated with the incidence of leukemia (r=0.88, P=0.002) for males, and with cancer of the esophagus for males (r=0.83, P=0.008) and females (r=0.71, P=0.020). Compared with the low exposure category, significant SRRs for total cancer sites was obtained for high PCP exposure category (SRR=1.61, 95%CI=1.59-1.62). Most SRR values of the cancer sites were significantly increased as exposure grade elevated and exposure time extended. Conclusion: The present study found that community residents living in the PCP contaminated area had increased risk of cancers. Leukemias, lymphomas and nasopharyngeal and esophageal cancers are most possibly associated with PCP exposure. -
Yadav, Shambhu Kumar;Mittal, Ankush;Sapkota, Kumar;Gupta, Satrudhan Prasad;Sathian, Brijesh 817
Background: The present study was designed to comparatively assess alteration of biochemical parameters in bile duct cancer and gall stone disease. Materials and Methods: A hospital based case-control study was carried out in the Department of Biochemistry of Manipal Teaching Hospital, Pokhara, Nepal between$1^{st}$ January 2010 and$31^{st}$ December 2012. The variables collected were age, gender, serum total cholesterol, total bilirubin, AST, ALT, serum alkaline phosphatase, albumin and hemoglobin. One way ANOVA was used to examine the statistical significance of differences between groups. A post-hoc LSD test was applied for the comparison of means of control versus case groups. A p-value of <0.05 (two-tailed) was considered significant. Results: The mean age of cases and controls was$53.2{\pm}21.2$ years. The levels of serum cholesterol were higher in cases of cancer$192.5{\pm}21.5$ mg/dl in comparison to stone cases$168.7{\pm}16.1$ mg/dl (p value: 0.0001). The total bilirubin showed the marked difference in cases of cancer$7.6{\pm}3.2$ mg/dl in comparison to stone cases$2.5{\pm}0.8$ mg/dl of bile duct. There was discernible divergence in values of alkaline phosphatase in cases of cancer$251.5{\pm}20.1$ IU/l when compared to stone cases$173.2{\pm}12.6$ IU/l of bile duct. In contrast, there was no apparent deviation in values of aspartate transaminases and alanine transaminases in cases of cancer$59.1{\pm}8.9$ IU/l and$105.5{\pm}26.5$ IU/l when compared to stone cases$56.9{\pm}7.9$ IU/l and$84.5{\pm}13.5$ IU/l respectively. Conclusions: LFT analysis for pre-operative assessment was a good predictive marker in setting apart bile duct cancer and gall bladder stone. -
Wang, Xin-Feng;Wu, Yan-Hua;Jiao, Jin;Guan, Cui-Ping;Yang, Xiao-Guang;Wang, Mao-Shui 821
The aim of this study was to investigate the diagnostic value of superoxide dismutase (SOD) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion (PE) samples from 100 patients were classified on the basis of diagnosis as TPE (n=57) and MPE (n=43). The activity of SOD was determined by pyrolgallol assay. A significant difference was observed in SOD activity (P<0.01) between TPE and MPE, levels of being significantly higher in TPE compared to MPE. With a threshold value of 41 U/L, the area under the ROC curve was 0.653, SOD had a sensitivity of 61.4% and a specificity of 61.0% for differential diagnosis. Thus, SOD activity in PE was not a good biomarker in differentiating TPE and MPE. To the best of our knowledge, five SOD isoforms may be present in PE. Identification of which SOD contributes to the difference of SOD level between TPE and MPE is very important for illustrating mechanisms and improving the differential diagnostic value. -
Razak, Nuradhiathy Abd;Khattak, M.N.;Zubairi, Yong Zulina;Naing, Nyi Nyi;Zaki, Nik Mohamed 825
Objective: The objective of this study was to determine the five-year survival among patients with cervical cancer treated in Hospital Universiti Sains Malaysia. Methods: One hundred and twenty cervical cancer patients diagnosed between$1^{st}$ July 1995 and$30^{th}$ June 2007 were identified. Data were obtained from medical records. The survival probability was determined using the Kaplan-Meier method and the log-rank test was applied to compare the survival distribution between groups. Results: The overall five-year survival was 39.7% [95%CI (Confidence Interval): 30.7, 51.3] with a median survival time of 40.8 (95%CI: 34.0, 62.0) months. The log-rank test showed that there were survival differences between the groups for the following variables: stage at diagnosis (p=0.005); and primary treatment (p=0.0242). Patients who were diagnosed at the latest stage (III-IV) were found to have the lowest survival, 18.4% (95%CI: 6.75, 50.1), compared to stage I and II where the five-year survival was 54.7% (95%CI: 38.7, 77.2) and 40.8% (95%CI: 27.7, 60.3), respectively. The five-year survival was higher in patients who received surgery [52.6% (95%CI: 37.5, 73.6)] as a primary treatment compared to the non-surgical group [33.3% (95%CI: 22.9, 48.4)]. Conclusion: The five-year survival of cervical cancer patients in this study was low. The survival of those diagnosed at an advanced stage was low compared to early stages. In addition, those who underwent surgery had higher survival than those who had no surgery for primary treatment. -
Huang, Qiang;Liu, Lei;Liu, Chen-Hai;You, Hao;Shao, Feng;Xie, Fang;Lin, Xian-Sheng;Hu, San-Yuan;Zhang, Chuan-Hai 829
Background: MicroRNAs are noncoding RNA molecules that posttranscriptionally regulate gene expression. The aim of this study was to determine the role of microRNA-21 in cholangiocarcinomas and its relationship to cholangiocarcinoma RBE cell capacity for invasion and metastasis. Methods: MicroRNA-21 expression was investigated in 41 cases of cholangiocarcinoma samples by in situ hybridization and real-time PCR. Influence on cholangiocarcinoma cell line invasion and metastasis was analyzed with microRNA-21 transfected cells. In addition, regulation of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) by microRNA-21 was elucidated to identify mechanisms. Results: In situ hybridization and real-time quantitative PCR results for patients with lymph node metastasis or perineural invasion showed significantly high expression of microRNA-21 (P<0.05). There was a dramatic decrease in cholangiocarcinoma cell line invasion and metastasis ability after microRNA-21 knockdown (P<0.05). However, overexpression significantly increased invasion and metastasis (P<0.05). Real-time PCR and Western-blot analysis showed that microRNA-21 could potentially inhibit RECK expression in RBE cells. Survival analysis showed that patients with higher expression levels of microRNA-21 more often had a poor prognosis (P<0.05). Conclusions: MicroRNA-21 may play an important role in cholangiocarcinoma invasion and metastasis, suggesting that MicroRNA-21 should be further evaluated as a biomarker for predicting cholangiocarcinoma prognosis. -
Qin, Shuang;Ai, Fang;Ji, Wei-Fang;Rao, Wang;Zhang, He-Cheng;Yao, Wen-Jian 835
Accumulating evidence has shown that microRNAs are involved in cancer development and progression. However, it remains unknown about the potential role of miR-19a in the pathogenesis of gastric cancer. Here, we report that suppressor of cytokine signaling 1 (SOCS1) is a novel target of miR-19a in gastric cancer cells and that miR-19a expression is inversely correlated with SOCS1 expression in gastric cancer cells and a subset of gastric cancer tissues. Ectopic expression of miR-19a dramatically promoted proliferation and tumorigenicity of gastric cancer cells both in vitro and in vivo. Moreover, we showed that silencing of SOCS1 promoted cell growth and colony formation resembling that of miR-19a overexpression, whereas re-introduction of SOCS1 (without the 3'-UTR) attenuated the pro-tumorigenic functions. Taken together, our findings suggest that the SOCS1 gene is a direct target of miR-19a, which functions as an oncogenic miRNA in gastric cancer by repressing the expression of tumor suppressor SOCS1. -
Ali, Amanat;Al-Belushi, Buthaina S.;Waly, Mostafa I.;Al-Moundhri, Mansour;Burney, Ikram A. 841
Background: The incidence of various types of cancers including the non-Hodgkin's lymphoma (NHL) has increased during the recent years. Diet and lifestyle factors have been reported to play an important role in the etiology of NHL. However, no such data are available from the Middle Eastern countries, including Oman. Materials and Methods: Forty-three histologically confirmed cases of non-Hodgkin's lymphoma (NHL) diagnosed at the Sultan Qaboos University Hospital (SQUH) and the Royal Hospital (RH), Muscat, Oman and forty-three age and gender matched controls were the subjects of this study. Frequency matching was used to select the control population. Information on social and demographic data as well as the dietary intake was collected by personal interviews, using a 117-items semi-quantitative food frequency questionnaire. Results: A non-significant increased risk of NHL was observed with higher body mass index (BMI) (OR=1.20, 95%CI: 0.45, 2.93), whereas a significantly decreased risk of NHL was associated with a higher educational level (OR=0.12, 95%CI: 0.03, 0.53). A significantly increased risk was observed for higher intake of energy (OR=2.67, 95%CI: 0.94, 7.57), protein (OR=1.49, 95%CI: 0.54, 4.10) and carbohydrates (OR=5.32, 95%CI: 1.78, 15.86). Higher consumption of daily servings from cereals (OR=3.25, 95%CI: 0.87, 12.09) and meat groups (OR=1.55, 95%CI: 0.58, 4.15) were also found to be associated with risk of NHL, whereas a significantly reduced risk was associated with higher consumption of vegetables (OR=0.24, 95%CI: 0.07, 0.82). The consumption of fruits, milk and dairy products however showed no significant association with the risk of developing NHL. Conclusion: The results suggest that obesity, high caloric intake, higher consumption of carbohydrate and protein are associated with increased risk of NHL, whereas a significantly reduced risk was observed with higher intake of vegetables. -
Thippeveeranna, Chamaraja;Mohan, Surekha Sadhana;Singh, Laiphrakpam Ranjit;Singh, Naorem Nabakishore 849
Background: Cancer of the uterine cervix is one of the most common cancers among women worldwide. Industrialized countries have dramatically reduced the incidence of mortality from cervical carcinoma in the last 50 years through aggressive screening programs utilizing pelvic examinations and Papanicolaou (Pap) smears but it still remains a major problem in the developing world. Objectives: This study was performed to determine knowledge, attitude and practice of Pap smear as a screening procedure among nurses in a tertiary hospital in north eastern India. Material and Methods: This cross sectional study was carried out with a questionnaire survey covering the socio demographic factors, knowledge, attitude and practices about Pap smear screening among 224 nurses in Regional Institute of Medical Sciences, Imphal, Manipur, India during December 2011. Results: Two hundred and twenty one participants (98.6%) had heard about cervical carcinoma but 18.3% lacked adequate knowledge regarding risk factors. Knowledge about the Pap smear was adequate in 88.8% of the respondents. Out of these, only 11.6% had Pap smear at least once previously. The most common reasons for non-participation in screening were lack of any symptoms (58.4%), lack of counselling (42.8%), physician does not request (29.9%) and fear of vaginal examination (20.5%). Conclusion: Although knowledge of Pap smear as a screening procedure for cervical cancer is high, practice is still low. The nurses who should be responsible for opportunistic screening of women they care for are not keen on getting screened themselves. If we can improve the practice of Pap smear screening in such experts, they should be able to readily provide appropriate and accurate information and motivate the general population to join screening programs. -
Objectives: Breast cancer is a leading cause of morbidity and mortality in women worldwide. Breast screening in normal and/or asymptomatic women is essential to reduce the burden of breast malignancies. Our study aimed to identify possible risk- and/or co-factors associated with breast screening in North Indian women. Methods: A public health research survey was conducted among 100 women of North Indian ethnicity during clinic visits in a 6-month timeline (April-October 2012). Demographic and clinical data, including mammography screening, were recorded in the questionnaire-based proforma after conducting a 10 minute interview. Written informed consent was taken from all the participants. Results: The mean age of the participants was
$32.2{\pm}9.9$ years. Out of 100 women, 6% had family history of breast disease. Breast-related complaints/malignancy, including galactorrhoea, mastitis, axillary lump, fibrocystic disease, fibroadenosis and adenocarcinoma were observed in 41% participants; age stratification revealed that 82.9% of this group (n=41) were <30 years, while 9.7% and 7.3% were >30 years and 30 years of age, respectively. 32% participants underwent mammography screening and 8% had breast ultrasound imaging. Age stratification in the mammography screening group demonstrated that 24 women were <40 years, while 7 women were >40 years. Conclusions: Our pilot study identified possible co-factors affecting breast screening in North Indian women. These findings may be beneficial in early detection of breast abnormalities, including malignancies in women susceptible to breast cancer, and thus aid in future design of cost-effective screening strategies to reduce the increasing burden of breast carcinoma in women worldwide. -
Chaudhari, Amit;Hegde-Shetiya, Sahana;Shirahatti, Ravi;Agrawal, Deepti 859
Aim: To compare the effectiveness of self-examination, clinical examination and screening methods using 1% toluidine blue and Lugol's iodine in estimating the prevalence of lesions at risk of malignancy and oral malignant disease amongst the male inmates of Yerwada Central Jail, Pune. Material and Methods: Study was carried out on male inmates in two phases. In the first phase self-examination and clinical examination was carried out on 2,257 male inmates. 164 suspicious cases were subjected to phase II of the study out of whom, 82 participants were screened with 1% toluidine blue and 2% Lugol's iodine followed by biopsy procedure. Results: Sensitivity and specificity for self-examination with clinical examination was 92.2% and 96.6% respectively. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and positive (+LR) and negative likelihood ratio (-LR) for Toluidine Blue were 88.1%, 66.6% 97.1%, 30%, 2.63 and 0.17 respectively while for Lugol's Iodine they were 94.7%, 83.8%, 98.6%, 55.5%, 5.67 and 0.06 respectively. Conclusions: Prevalence of lesions at risk of malignancy and oral malignant disease by self-examination was 7.8% and by clinical examination was 6.3%. Self-examination is an effective tool in early detection of oral cancer. Use of Lugol's iodine as a screening tool for oral lesions is highly effective in inmate populations. -
Tahlil, Teuku;Coveney, John;Woodman, Richard J.;Ward, Paul R. 865
Background: The present qualitative study assessed the need, acceptability and appropriateness for implementing effective and culturally appropriate smoking prevention programs for adolescents in schools in Indonesia. Methods: Snowball sampling was used to recruit participants. The study sample comprised a mixture of staff in the education department, junior high school teachers and individuals who had taught junior high school students in Aceh Province, Indonesia. Data were collected through one hour in-depth face to face or telephone interviews and analyzed using a descriptive content analysis procedure. Results: School teachers and policy makers in education firmly supported the implementation of a school-based smoking prevention program in Aceh. An appropriate intervention for smoking prevention program in schools in Aceh should involve both health and Islamic based approaches, and be provided by teachers and external providers. Potential barriers to the program included smoker teachers and parents, time constraints of students and/or teachers, lack of teachers' ability, increase in students' load, the availability of tobacco advertising and sales, and lack of tobacco regulation and support from community and related departments. To increase program effectiveness, involvement of and coordination with other relevant parties are needed. Conclusions: The important stakeholders in Indonesian childhood education agreed that school-based smoking prevention program would be appropriate for junior high school students. An appropriate intervention for smoking prevention program for adolescents in schools in Indonesia should be appropriate to participants' background and involve all relevant parties. -
Gunes, Mustafa;Kemik, Ahu Serap;Pirincci, Necip;Gecit, Ilhan;Taken, Kerem;Yuksel, Mehmet Bilgehan;Kaba, Mehmet;Eryilmaz, Recep 873
Our aim was to test the hypothesis that preoperative serum levels of matrix metalloproteinase-7 (MMP-7) and -9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) levels correlate with pathological features. Serum levels of MMP-7, and MMP-9 and TIMP-1 were determined in 90 bladder cancer patients and 40 healthy controls using an enzyme linked immunosorbent assay. Preoperative serum MMP-7 and MMP-9 levels were significantly higher in cancer patients than control groups (p<0.001). In contast, serum TIMP-1 levels were lower (p<0.001). Alteration in MMP-7, and MMP-9, and TIMP-1 production may contribute to tumor angiogenesis and be associated with clinic-pathological features. -
Sun, Tian-Tian;Wang, Ji-Lin;Fang, Jing-Yuan 877
Background and Objective: There has been no universally agreed standard chemotherapy regimen for patients with advanced biliary tract carcinomas (BTC). We aimed to fully display and evaluate the clinical evidence for gemcitabine or gemcitabine-cisplatin combination for advanced BTC. Methods: Systematic searches were performed to identify relevant randomized controlled trials (RCTs) and uncontrolled trials. Overall survival (OS), progression-free survival (PFS), overall response rates (ORR), tumor control rates (TCR), and toxicity were evaluated. Evidence levels of the results were evaluated with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results: Results of the eleven gemcitabine-cisplatin trials and ten gemcitabine trials showed both chemotherapy regimens had benefits with reference to mean OS (8.63 vs. 8.79 months), mean PFS (4.86 vs. 4.72 months), pooled ORR (25.3% vs. 19.6%) and TCR (55.2% vs. 53.1%). Two RCTs showed the gemcitabine-cisplatin combination to prolong the mean PFS (mean difference [MD] 2.57, 95%CI 1.69 3.45), substantially increasing the mean OS (MD 3.59, 95% CI 3.48 3.71), and producing a similar effect in ORR (risk ratio [RR] 1.59, 95%CI 1.04 2.43), increasing TCR (RR 1.15, 95%CI 1.02 1.31) compared with gemcitabine alone, with generally manageable grade 3 or 4 adverse events. The evidence level of OS was moderate, and other outcomes (ORR, PFS, TCR, anaemia, neutropenia) were at low evidence levels. Conclusion: Available evidence was limited with low quality, which showed that both gemcitabine-cisplatin and gemcitabine alone had clinical activity with acceptable safety profiles, and gemcitabine-cisplatin appeared to be more useful for advanced BTC patients than gemcitabine alone. -
Wu, Xin-Jun;Li, Yan;Liu, Dong;Zhao, Lun-De;Bai, Bin;Xue, Ming-Hui 885
microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. miRNAs have recently emerged as key regulators of various cancers. Although miR-27a has been implicated in several other cancers, its role in hepatitis B virus-related hepatocellular carcinoma (HCC) is unknown. In this study, we showed miR-27a to be frequently up-regulated in HCC tissues and HCC cell lines (HepG2 and Huh7). Overexpression of miR-27a enhanced cell proliferation, promoted migration and invasion, and activated cell cycling in HepG2 and Huh7 cells. In summary, our results suggest that up-regulation of miR-27a may play an oncogenic role in the development of HCC and might thus be a new therapeutic target in HCC patients. -
Bandala, Cindy;Perez-Santos, Jose Luis Martin;Lara-Padilla, Eleazar;Delgado Lopez, Ma. Guadalupe;Anaya-Ruiz, Maricruz 891
The present study was performed to assess the activity of the botulinum toxin A on breast cancer cells. The T47D cell line was exposed to diverse concentrations of the botulinum toxin A and cell viability and apoptosis were estimated using MTT and propidium iodine/annexin V methods, respectively. Botulinum toxin A exerted greater cytotoxic activity in T47D cells in comparison with MCF10A normal cells; this appeared to be via apoptotic processes caspase-3 and -7. In conclusion, botulinum toxin A induces caspase-3 and -7 dependent apoptotic processes in the T47D breast cancer cell line. -
Resistance to induction of apoptosis is a major obstacle for bladder cancer treatment. Bcl-2 is thought to be involved in anti-apoptotic signaling. In this study, we investigated the effect of Bcl-2 overexpression on apoptotic resistance and intracellular reactive oxygen species (ROS) generation in bladder cancer cells. A stable Bcl-2 overexpression cell line, BIU87-Bcl-2, was constructed from human bladder cancer cell line BIU87 by transfecting recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. The sensitivity of transfected cells to adriamycin (ADR) was assessed by MTT assay. Apoptosis was examined by flow cytometry and acridine orange fluorescence staining. Intracellular ROS was determined using flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT) were also investigated by the xanthinoxidase and visible radiation methods using SOD and CAT detection kits. The susceptibility of BIU87-Bcl-2 cells to ADR treatment was significantly decreased as compared with control BIU87 cells. Enhanced expression of Bcl-2 inhibited intracellular ROS generation following ADR treatment. Moreover, the suppression of SOD and CAT activity induced by ADR treatment was blocked in the BIU87-Bcl-2 case but not in their parental cells. The overexpression of Bcl-2 renders human bladder cancer cells resistant to ADR-induced apoptosis and ROS might act as an important secondary messenger in this process.
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Junyangdikul, Pairoj;Tanchotsrinon, Watcharaporn;Chansaenroj, Jira;Nilyaimit, Pornjarim;Lursinsap, Chidchanok;Poovorawan, Yong 903
Primary screening by HPV DNA testing is an effective method for reducing cervical cancer and has proven more sensitive than cytology. To advance this approach, many molecular methods have been developed. Hybrid capture 2 provides semi-quantitative results in ratios of relative light units and positive cutoff values (RLU/PC). Twenty-five thousand and five patients were included in this study to analyze the correlation between the ratio of RLU/PC and stage of cervical dysplasia. The results show that the RLU/PC ratios ranged from 0-3500 while almost normal cases, ASC-US and ASC-H, had values below 200. Of those samples negative for cytology markers, 94.6% were normal and their RLU/PC ratios were less than 4. With an RLU/PC ratio greater than 4 and less than or equal to 300, the percentages in all age groups were normal 53.6%, LSIL 20.2%, ASC-US 17.2%, HSIL 6.13%, ASC-H 2.72%, and AGC 0.11%, respectively. In contrast, 64.0% of samples with a RLU/PC ratio greater than 300 and less than or equal to 3500 were LSIL. These results should contribute to cost effective cervical cancer management strategies. Further studies of associations with particular HPV genotypes would be useful to predict the risk of progression to cancer. -
Dong, Hang;Tang, Jie;Li, Long-Hao;Ge, Jun;Chen, Xin;Ding, Jing;Men, Hai-Tao;Luo, Wu-Xia;Du, Yang;Li, Cong;Zhao, Feng;Chen, Ye;Cheng, Ke;Liu, Ji-Yan 909
Purpose: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. Methods: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC-NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. Results: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9,${\gamma}$ -glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. Conclusion: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic. -
Farooq, Muhammad;Hozzein, Wael N.;Elsayed, Elsayed A.;Taha, Nael A.;Wadaan, Mohammad A.M. 915
Background: Hepatocellular carcinoma is one of the leading causes of mortalities worldwide. The search for new therapeutic targets is of utmost importance for improved treatment. Altered expression of HDAC1 in hepatocellular carcinoma (HCC) and its requirement for liver formation in zebrafish, suggest that it may regulate key events in liver carcinogenesis and organogenesis. However, molecular mechanisms of HDAC1 action in liver carcinogenesis are largely unknown. The present study was conducted to identify HDAC1 interacting proteins in HepG2 cells using modified SH-double-affinity purification coupled with liquid mass spectrophotemetery. Materials and Methods: HepG2 cells were transfected with a construct containing HDAC1 with a C-terminal strepIII-HA tag as bait. Bait proteins were confirmed to be expressed in HepG2 cells by western blotting and purified by double affinity columns and protein complexes for analysis on a Thermo LTQ Orbitrap XL using a C18 nano flow ESI liquid chromatography system. Results: There were 27 proteins which showed novel interactions with HDAC1 identified only in this study, while 14 were among the established interactors. Various subunits of T complex proteins (TCP1) and prefoldin proteins (PFDN) were identified as interacting partners that showed high affinity with HDAC1 in HepG2 cells. Conclusions: The double affinity purification method adopted in this study was very successful in terms of specificity and reproducibility. The novel HDAC1 complex identified in this study could be better therapeutic target for treatment of hepatocellular carcinoma. -
Song, Wen-Guang;Wang, Yi-Feng;Wang, Rui-Lin;Qu, Yin-E;Zhang, Zhi;Li, Guo-Zhong;Xiao, Ying;Fang, Fang;Chen, Hong 923
Objective: This work aims to investigate the therapeutic regimen of brain metastatic cancers and the relationship between clinical features and prognosis. Methods: Clinical data of 184 patients with brain metastatic cancers were collected and analysed for the relationship between survival time and age, gender, primary diseases, quantity of brain metastatic foci, their position, extra cranial lesions, and therapeutic regimens. Results: The average age of onset was 59.1 years old. The median survival time (MST) was 15.0 months, and the patients with breast cancer as the primary disease had the longest survival time. Females had a longer survival time than males. Patients with meningeal metastasis had extremely short survival time. Those with less than 3 brain metastatic foci survived longer than patients with more than 3. The MST of patients receiving radiotherapy only and the patients receiving chemotherapy only were all 10.0 months while the MST of patients receiving combination therapy was 16.0 months. Multiple COX regression analysis demonstrated that gender, primary diseases, and quantity of brain metastatic foci were independent prognostic factors for brain metastatic cancers. Conclusions: Chemotherapy is as important as radiotherapy in the treatment of brain metastatic cancer. Combination therapy is the best treatment mode. Male gender, brain metastatic cancers originating in the gastrointestinal tract, more than 3 metastatic foci, and involvement of meninges indicate a worse prognosis. -
Zhou, De;Xie, Wan-Zhuo;Hu, Ke-Yue;Huang, Wei-Jia;Wei, Guo-Qing;He, Jing-Song;Shi, Ji-Min;Luo, Yi;Li, Li;Zhu, Jing-Jing;Zhang, Jie;Lin, Mao-Fang;Ye, Xiu-Jin;Cai, Zhen;Huang, He 929
Aim: To analyze the significance of different clinical factors for prognostic prediction in diffuse large B-cell lymphoma (DLBCL) patients. Methods: Two hundred and twenty-seven DLBCL patients were retrospectively reviewed. Patients were managed with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen or rituximab plus the CHOP (RCHOP) regimen. Results: Lactate dehydrogenase (LDH),${\beta}2$ -microglobulin (${\beta}2$ -M), B symptoms, Ann Arbor stage and genetic subtypes were statistically relevant in predicting the prognosis of the overall survival (OS). In the CHOP group, the OS in patients with germinal center B-cell-like (GCB)(76.2%) was significantly higher than that of the non-GCB group (51.9%, P=0.032). With RCHOP management, there was no statistical difference in OS between the GCB (88.4%) and non-GCB groups (81.9%, P=0.288). Conclusion: Elevated LDH and${\beta}2$ -M levels, positive B symptoms, Ann Arbor stage III/IV, and primary nodal lymphoma indicate an unfavorable prognosis of DLBCL patients. Patients with GCB-like DLBCL have a better prognosis than those with non-GCB when treated with the CHOP regimen. The RCHOP treatment with the addition of rituximab can improve the prognosis of patients with DLBCL. -
Wu, Hong-Xun;Zhang, Bing-Jie;Wang, Jun;Zhu, Bei-Lin;Zang, Ya-Ping;Cao, Yue-Long 935
Background: To evaluate the diagnostic utility of conventional ultrasonography and real time ultrasound elastography in differentiating degenerating cystic thyroid nodules mimicking malignancy from papillary thyroid carcinoma. Methods: We retrospectively analyzed conventional ultrasonographic and elastographic characteristics of 19 degenerating cystic thyroid nodules mimicking malignancy in 19 patients, with 30 surgically confirmed PTCs as controls. Based on size, the nodules had been grouped into less than 10mm (group A) and greater than 10 mm (group B). We evaluated conventional parameters and elasticity pattern. Color-scaled elastograms were graded as to stiffness of nodules using an elasticity pattern from I (soft) to IV (stiff). Results: Degenerating cystic thyroid nodules were similar to PTCs in conventional ultrasonographic findings, but the former frequently showed oval to round in shape (group A, 69.2% vs 18.8%, P=0.017; group B, 66.7% vs 7.14%, P=0.017) and punctuate hyperechoic foci (group A, 61.5% vs 0, P<0.001; group B, 50% vs 0, P<0.001). On real time ultrasound elastography, 7 of 13 degenerating cystic thyroid nodules in group A were pattern I, 5 were pattern II, 1 was pattern III. One degenerating cystic thyroid nodule in group B was pattern II, 5 were pattern III. The area under the curve for elastography was 0.98 in group A (sensitivity 92.3%, specificity 100%, P = 0.002), and 0.88 in group B (sensitivity 16.7%, specificity 100%, P = 0.014). Conclusions: As a dependable imaging technique, elastography helps increase the performance in differential diagnosis of degenerating cystic thyroid nodule and malignancy. -
Kang, Shan;Sun, Hai-Yan;Zhou, Rong-Miao;Wang, Na;Hu, Pei;Li, Yan 941
Objective: The nucleotide excision repair (NER) and base excision repair (BER) pathways, two DNA repair pathways, are related to platinum resistance in cancer treatment. In this paper, we studied the association between single nucleotide polymorphisms (SNPs) of involved genes and response to platinum-based chemotherapy in epithelial ovarian cancer. Method: Eight SNPs in XRCC1 (BER), XPC and XPD (NER) were assessed in 213 patients with epithelial ovarian cancer using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) techniques. Results: The median progression-free survival (PFS) of patients carrying the Lys/Lys and Lys/Gln+Gln/Gln genotype of the XPC Lys/Gln polymorphism were 25 and 12 months, respectively (P=0.039); and the mean overall survival (OS) of patients was 31.1 and 27.8 months, respectively (P=0.048). Cox's multivariate analysis suggested that patients with epithelial ovarian cancer with the Gln allele had an increased risk of death (HR=1.75; 95% CI=1.06-2.91) compared to those with the Lys/Lys genotype. There are no associations between the XPC PAT+/-, XRCC1 Arg194Trp, Arg280His, Arg399Gln, and XPD Asp312Asn, Lys751Gln polymorphisms and the survival of patients with epithelial ovarian cancer when treated with platinum-based chemotherapy. Conclusion: Our results indicated that the XPC Lys939Gln polymorphism may correlate with clinical outcome of patients with epithelial ovarian cancer when treated with platinum-based chemotherapy in Northern China. -
Zhang, Pei-Zhen;Chong, Le;Zhao, Ye;Gu, Jing;Tian, Jin-Hui;Yang, Ke-Hu 947
Background: We performed this meta-analysis to assess the effectiveness and safety of axillary dissection in old women. Methods: The Cochrane Library, PubMed, EMBASE and Chinese Biomedical Literature Database were searched and all randomized controlled trials of axillary dissection in old women (at least 60 years old) were considered. Meta-analyses were completed using RevMan5.1. Results: Three eligible randomized controlled trials (RCTs) including 5,337 patients were considered. There was weak evidence in favour of axillary dissection (AD) in old women. The meta-analysis showed that the overall survival (OS) after 1, 3, 5 and 7 years and the disease free survival (DFS) after 1, 3 and 5 year were not statistically significantly different between AD and no AD groups. However, there was a difference in the 7 year DFS. Conclusions: Axillary dissection did not provide survival benefit to the old women with breast cancer analysed. Therefore, axillary dissection is not well-indicated in old women with breast cancer. -
Manoharan, Shanmugam;Wani, Shamsul Afaq;Vasudevan, Krishnamoorthy;Manimaran, Asokan;Prabhakar, Murugaraj Manoj;Karthikeyan, Sekar;Rajasekaran, Duraisamy 951
Our aim was to investigate the chemopreventive potential of saffron in DMBA-induced hamster buccal pouch carcinogenesis. Assessment was by monitoring the percentage of tumor bearing hamsters, tumor size as well as the status of detoxification agents, lipid peroxidation and antioxidants. Oral squamous cell carcinomas were induced in the buccal pouch of Syrian golden hamsters by painting them with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. We observed 100% oral tumor formation with severe histopathological abnormalities in all the hamsters treated with DMBA alone, activities of phase I and phase II detoxification enzymes, lipid peroxidation and antioxidants being significantly altered. Though oral administration of saffron completely prevented the formation of tumors, we noticed severe hyperplasia and dysplasia in hamsters treated with DMBA, suggesting that tumors might eventually develop. Oral administration of saffron return detoxification enzymes, lipid peroxidation and antioxidants to normal ranges. The chemopreventive potential of saffron thus is likely due to antioxidant properties and modulating effects on detoxification in favour of the excretion of carcinogenic metabolites during DMBA-induced hamster buccal pouch carcinogenesis. -
Tang, Yang;Sun, Li-Guang;Liu, Chun-Shui;Li, Yu-Ying;Jin, Chun-Hui;Li, Dan;Bai, Ou 959
Objective: HBV infection may cause damage to the immune system and induce lymphomas as a result. Some scholars have indicated that HBsAg(+) reflecting HBV infection may have a relationship with lymphoma development. This study was designed to find out the specific stage of HBV infection which may be related to lymphoma. Methods: HBV serum markers, including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb were tested among 100 lymphoma patients and 100 other patients who were diagnosed with non-lymphoma diseases in the First Hospital of Jilin University from 2010.1.1 to 2012.12.31. Three subgroups were established depending on different combinations of HBV serum markers. Subgroup 1 was HBsAg(+) representing the early stage of HBV infection. Subgroup 2 was HbsAb(+) representing convalescence and Subgroup 3 was "HbsAg and HbsAb negative combined with other positive markers" representing the intermediate stage of HBV infection. Chi square tests were used to compare the rates of three subgroups in lymphoma and control groups. Results: The rates of Subgroup were 13% and 5% respectively, an association between HBsAg and lymphoma being found (P<0.05). There was no difference between rate of Subgroup 2 of lymphoma group (15%) and that of control group (16%). In lymphoma group and control group, the rate of Subgroup 3 was different (12% vs 4%). This evidence was not specific to T cell lymphoma, B cell lymphoma or Hodgkin's lymphoma. Conclusions: Among serum markers of HBV, the combination of serum markers representing the early stage and intermediate stage of HBV infection have a relationship with lymphoma. Convalescence from HBV infection appears to have no relationship with lymphoma. -
Ge, Yun-Fei;Sun, Jun;Jin, Chun-Jie;Cao, Bo-Qiang;Jiang, Zhi-Feng;Shao, Jun-Fei 963
Objective: To study the effect of the antagomiR-27a inhibitor on glioblastoma cells. Methods: The miR-27a expression level in specimens of human glioblastoma and normal human brain tissues excised during decompression for traumatic brain injury was assessed using qRT-PCR; The predicted target gene of miR-27a was screened out through bioinformatics databases, and the predicted gene was verified using genetic report assays; the effect of antagomiR-27a on the invasion and proliferation of glioma cells was analyzed using MTT assays and 5-ethynyl-2'-deoxyuridine (EdU) labeling. A xenograft glioblastoma model in BALB-c nude mice was established to detect the effect of antagomiR-27a on tumour growth. Results: qRT-PCR results showed that miR-27a significantly increased in specimens from glioblastoma comparing with normal human brain tissues. Th miR-27a inhibitor significantly suppressed invasion and proliferation of glioblastoma cells. FOXO3a was verified as a new target of miR-27a by Western blotting and reporter analyzes. Tumor growth in vivo was suppressed by administration of the miR-27a inhibitor. Conclusion: MiR-27a may be up-regulated in human glioblastoma, and antagomiR-27a could inhibit the proliferation and invasion ability of glioblastoma cells. -
Yucel, Birsen;Okur, Yillar;Akkas, Ebru Atasever;Eren, Mehmet Fuat 969
Aim: The aim of this study was to determine the impact of age on the occurrence, severity, and timing of acute side effects related to radiotherapy. Materials and Methods: We analysed the data of 423 patients. Results: Of the patients, 295 (70%) were under the age of 65 (group 1) and 128 (30%) were over the age of 65 (group 2). The frequencies of radiotherapy-induced side effects were 89% in group 1 and 87% in group 2 (p=0.286). The mean times to occurrence were$2.5{\pm}0.1$ weeks in group 1 and$2.2{\pm}0.1$ weeks in group 2 (p=0.013). Treatment was ended in 2% of patients in group 1 and 6% of those in group 2 (p=0.062). Treatment interruption was identified in 18% of patients in group 1 and 23% in group 2 (p=0.142). Changes in performance status were greater in older patients (p=0.013). There were no significant differences according to the frequency or severity of side effects, except skin and genitourinary complications, between the groups. Conclusions: Early normal tissue reactions were not higher in older versus younger patients, though there was a tendency towards an earlier appearance. -
Balasubramaniam, Ganesh;Sushama, S.;Rasika, B.;Mahantshetty, U. 977
Background: Endometrial cancer is common in western women, and the rates are very high; however in India, the rates are as low as 4.3 per 100,000 (Delhi). Objective: To estimate the survival of endometrial cancer patients based on age, education, family history, tobacco habit, number of pregnancies, clinical extent of disease and treatment received. Materials and Methods: The present retrospective study was carried out at the Tata Memorial Hospital (TMH), Mumbai, India, between 1999-2002. 310 cases treated in TMH were considered as eligible entrants for the study. Five-year survival rates were estimated using actuarial and loss-adjusted (LAR) methods. Results: The proportions of patients dying above 50 years of age, non-residents and illiterates was higher than their counterparts. 54.8% of patients had some form of treatment before attending TMH. There were only 4.2% tobacco-chewers and only 6.1% had a family history of cancer. There were 25.8% who had 3-5 pregnancies (not living children) and 38.1% did not remember the pregnancy history. The 5-year overall survival rate was 92%. The five-year rates indicated better prognosis for those aged less than 50 years (97%), non-tobacco-chewers (94%), with no family history of cancer (93%), with localized disease (93%) and those treated with surgery either alone or as a combination treatment (95%). Conclusions: The present study showed that endometrial cancer patients with localized disease at diagnosis have a good outcome in India. A detailed study will help in understanding the prognostic indicators for survival especially with the newer treatment technologies now available. -
Background: The Pap smear has an important value in the early diagnosis of cervical cancer, a serious problem in womens health. This study aimed to determine the status of Turkish women regarding participation in Pap smear testing and affecting factors. Materials and Methods: This descriptive study was conducted on married women between 18-61 years of age selected from those who applied to the Obstetrics and Gynaecology Polyclinic of Atat
$\ddot{u}$ rk University in Erzurum between June-August 2010 for any reason. Data were collected using a questionnaire determining socio-demographic features and analyzed by descriptive statistics (mean, Sd, range, frequency, percentage) and Chi-square test. A level of p<0.05 was considered statistically significant. Results: Sixty six of the 301 women (21.9%) indicated that they heard a Pap smear test and 16.6% of women had experienced a test. The number of women participating increased with age, duration of marriage, number of births, knowledge about the Pap smear and perception of risk for cervical cancer. Conclusions: The importance of the Pap smear test needs to be explained to Turkish women by health staff, to increase awareness and participation in regular screening. -
Fan, Wen;Tian, Xing-De;Huang, E.;Zhang, Jia-Jun 987
Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. Methods: In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Results: Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced splenocyte proliferation and IFN-${\gamma}$ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-${\alpha}$ and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour-bearing mice. Conclusion: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates. -
Gao, Chang-Ming;Ding, Jian-Hua;Li, Su-Ping;Liu, Yan-Ting;Qian, Yun;Chang, Jun;Tang, Jin-Hai;Tajima, Kazuo 993
To evaluate the relation between smoking, alcohol drinking and risk of breast cancer in Chinese women, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The results revealed that smoking, whether active or passive through the husband, was related to increased risk of breast cancer. The ORs (adjusted for age, menopausal status, educational levels, occupation, body mass index and income) were 3.55 (95%CI: 1.27-9.91) for active smoking and 1.47 (95%CI: 1.18-1.84) for passive smoking from husbands, respectively. A significant positive relationship was observed between breast cancer risk and the degree of husbands' smoking. There were significant increase trend in ORs with the daily smoked number of cigarettes of husbands, the passive smoking years from husbands and the pack-years of husbands' smoking (trend test: p=0.00003, 0.00013 and 0.0001, respectively). Alcohol consumption was also found to be a risk factor. The findings of this study in particular suggest that husbands' smoking increases risk of breast cancer in Chinese women. -
Widodo, Irianiwati;Ferronika, Paranita;Harijadi, Ahmad;Triningsih, F.X. Ediati;Utoro, Totok;Soeripto, Soeripto 997
Background: Lymphangiogenesis, assessed as lymphovascular density (LVD), is the initial step of generalized tumor lymphovascular invasion (LVI). It also involves VEGF-C as the most important protein family. Lymphangiogenesis among breast cancer cases correlations with several clinicopathological factors are important to determine prognosis and treatment strategies, but results have been controversial and require clarification. Aim: To define correlations between VEGF-C expression, LVD and LVI with several clinicopathological parameters from Indonesian breast cancer patients. Materials and Methods: Using a cross-sectional study, a total of 48 paraffin-embedded tissues of breast cancer from Dr. Sardjito General Hospital Indonesia were assessed for VEGF-C expression, LVD and LVI by immunohistochemistry. Correlations of these markers with clinicopathological parameters like patient age, tumor size, lymph node status, grade, ER/PR and Her-2 status, cell proliferation and p-53 expression were investigated by linear analysis. Correlations of VEGF-C expression and LVI with several clinicopathological parameters were analyzed with Coefficient Contingency Chi-Square test. Results: The mean of patients age was 53.0 year, pre and post-menopausal patients accounting for 56.3% and 43.8%, respectively. Some 10.4% were well, 41.7% moderate and 47.9% poorly differentiated. ER positivity was evident in 50% while PR and Her-2 positivity was found in 31.3% and 33.3%, respectively. Breast cancer cells with over-expression of p-53 was 64.6% and with high cell proliferation was 56.3%. Lymph node metastasis was noted in 63.5%, and LVI in 72.9%. Significant correlations were found between LVD and tumor size (p:0.037), grade (p:0.000), lymphnode status (p:0.036), LVI (p:0.003), as well as with p-53 and cell proliferation. There were also significant correlation of VEGF-C (p:0.011) and LVI (p:0.001) with tumor grade. Only ER status was found to have a correlation with tumor size (p:0.027). Conclusions: This study suggested that in Indonesian breast cancer patients, lymphangiogenesis is correlated with tumor size, grade, lymph node status and tumor lymphovascular invasion, the latter also being related with p-53 over expression and high cell proliferation. -
Cui, Yun-Long;Li, Hui-Kai;Zhou, Hong-Yuan;Zhang, Ti;Li, Qiang 1003
Objective: This work aimed to investigate the correlations of tumor-associated macrophages (TAMs) and their subtypes M1 and M2 with liver metastasis of colorectal cancer, and provide useful references for seeking predictors of liver metastasis and studying mechanisms. Methods: 120 patients with colorectal cancer from 2000 to 2009 were divided into low, middle and high liver metastasis groups (group A, B and C, respectively). S-P immunohistochemical staining and microscopic observation were conducted to compare expression in CD68-positive cells (TAMs), CD80-positive cells (M1) and CD163-positive cells (M2) in three groups. Correlations of TAMs, M1, M2, and M2/M1 ratio with clinical and pathological parameters were analyzed. Results: With increase of liver metastatic ability, the number of TAMs decreased gradually, with no significant difference between any two of the three groups (P > 0.05), while the numbers of M1 and M2 were significantly decreased and increased, respectively, with significant difference between any two of three groups (P < 0.05 or P < 0.01). In addition, the M2/M1 ratio increased with increase of liver metastatic ability (P < 0.01). There was no statistical significance of correlation of TAMs with each clinical and pathological parameter. M1 was negatively related with lymphatic metastasis and liver metastatic ability. M2 was positively correlated with preoperative CEA level, lymphatic metastasis, tumor differentiation degree and liver metastatic ability. The same was the case for the M2/M1 ratio. Conclusions: Effects of TAMs on liver metastasis of colorectal cancer do not depend on the total number of TAMs, but on the number and proportion of functional subtypes M1 and M2. M2 number and M2/M1 ratio are more accurate predictors for liver metastasis of colorectal cancer. -
Background: The benefits of physical activity are well established and recognized to prevent adults from many chronic diseases and particularly some forms of cancers. Objectives: The present study was conducted to investigate the present status of physical activity among Saudi adults in Al-Ahsa, and to examine the association between the stages of change for physical activity and perceived barriers, and self efficacy. Methods: A cross-sectional study of 242 subjects (118 males and 124 females) attending health centers aged between 20-56 years, were personally interviewed for demographic data, anthropometric measurement, physical activity level, stages of change for physical activity, self efficacy and perceived barriers. Results: Forty eight percent of the females were overweight and 16.9% of the males were obese with no significant difference between the genders for BMI categories. More than half of the females were inactive and 39% of the males were physically active with a significant difference (P=0.007). Twenty percent of the males were in maintenance stage, while similar percentage of the females were in contemplation stage. However the majority of the subjects were in pre-contemplation stage with a significant difference across the stages. Males had a higher mean score of self efficacy and less external barriers of physical activity. The major barrier among the females was lack of time (
$7.2{\pm}1.4$ ) and in the males, lack of motivation ($7.7{\pm}1.4$ ). The females had less internal ($21.2{\pm}3.8$ ) barriers comparable to the males ($23.08{\pm}4.7$ ). Both genders had a significant relationship between stages of changes of physical activity and perceived barriers (internal and external), but in the females no significant difference across the stages was observed for self efficacy unlike the males who had a significant difference for self efficacy and self efficacy categories. Conclusion: The present study provided useful data on stages of change for physical activity and some psychosocial factors (self efficacy and perceived barriers) that can help to tailor strategies aiming at increasing physical activity level according to self efficacy and to the barriers detected, to prevent many chronic diseases including certain types of cancer in Saudi Arabia. -
Zhu, Jin-Hui;Hong, De-Fei;Song, Yong-Mao;Sun, Li-Feng;Wang, Zhi-Fei;Wang, Jian-Wei 1017
The cellular apoptosis susceptibility (CSE1L) gene has been demonstrated to regulate multiple cellular mechanisms including the mitotic spindle check point as well as proliferation and apoptosis. However, the importance of CSE1L in human colon cancer is largely unknown. In the present study, we examined expression levels of CSE1L mRNA by semiquantitative RT-PCR. A lentivirus-mediated small interfering RNA (siRNA) was used to knock down CSE1L expression in the human colon cancer cell line RKO. Changes in CSE1L target gene expression were determined by RT-PCR. Cell proliferation was examined by a high content screening assay. In vitro tumorigenesis was measured by colony-formation assay. Cell cycle distribution and apoptosis were detected by flow cytometric analysis. We found CSE1L mRNA to be expressed in human colon cancer cells. Using a lentivirus based RNAi approach, CSE1L expression was significantly inhibited in RKO cells, causing cell cycle arrest in the G2/M and S phases and a delay in cell proliferation, as well as induction of apoptosis and an inhibition of colony growth capacity. Collectively, the results suggest that silencing of CSE1L may be a potential therapeutic approach for colon cancer. -
Swangvaree, Sukumarn Sanersak;Kongkaew, Phon;Ngamkham, Jarunya 1023
Cervical cancer is the most important female gynecological cancer, the second leading cause of cancer mortality in women worldwide and the second most common cancer in Thai women. The major cause of cervical cancer is persistent infection of human papillomavirus (HPV), leading to abnormal epithelial lesions, with progression to precancerous and invasive cancer. This study was conducted to investigate the frequency and type distribution of HPV in Thai women who had abnormal cytology. HPV detection from FFPE confirmed abnormal of high grade cervical intraepithelial lesions were for SPF-10-Innogenic Line Probe Assay. HPV-positivity was detected in 320/355 cases (90.14%) and HPV-negativity in 35/355 (9.86%). HPV-positive was found 147/320 cases (41.4%) of single infection, whereas 173/320 cases (48.7%) showed the multiple HPV infection. The most common seven types were HPV-16, -52, -18, -11, -51, -31 and -33, in that order. HPV 16 and 18, the important oncogenic HPV type, were observed in 64.8% of HSIL cases. Interestingly, a high proportion of multiple infections was found in this study and more than ten types could be detected in one case. Therefore, HPV infection screening program in women is essential, particularly in Thailand. Effective primary and secondary prevention campaigns that reinforce HPV screening for HPV detection and typing may be decrease the incidence and mortality of cervical cancer in the future and may lead to significantly improve the quality of life in Thai women. -
Yildirim, Mustafa;Suren, Dinc;Yildiz, Mustafa;Alikanoglu, Arsenal Sezgin;Kaya, Vildan;Doluoglu, Suleyman Gunhan;Aydin, Ozgur;Yilmaz, Necat;Sezer, Cem;Karaca, Mehmet 1027
Background: Peritoneal washing cytology (PWC) that shows the microscopic intra-peritoneal spread of gynaecologic cancers is not used in staging but is known as prognostic factor and effective in planning the intensity of the therapy. False negative or false positive results clearly affect the ability to make the best decision for therapy. In this study we assessed levels of tumour markers, carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125) and carbohydrate antigen (CA19-9), in peritoneal washing fluid to establish any possible contribution to the peritoneal washing cytology in patients operated for gynaecologic cancer. Materials and Methods: Preoperative tumour markers were studied in serum of blood samples obtained from the patients for preoperative evaluation of a gynaecologic operation. In the same group peritoneal tumour markers were studied in the washing fluid obtained for intraoperative cytological evaluation. Results: This study included a total of 94 patients, 62 with malignant and 32 with benign histopathology. The sensitivity of the cytological examination was found to be 21% with a specificity of 100%. When evaluated with CEA the sensitivity of the cytological examination has increased to 37%. Conclusions: In addition to examination of PWC, the level of CEA, a tumour marker, in peritoneal washing fluid can make a diagnostic contribution. Determining the level of CEA in peritoneal washing fluid will be useful in the management of gynaecologic cancers. -
Demirbag, Birsel Canan;Kurtuncu, Meltem;Guven, Hadiye 1031
Background: There have been few studies in Turkey on the incidence of childhood cancers. A mother's knowledge about signs and symptoms of cancer is important for early diagnosis, effective treatment, and improvement of life expectancy. This study was conducted with a group of mothers of children, aged 0-13, at a Family Health Center (FHC) in Turkey's Eastern Black Sea Region, to analyze their knowledge about cancer symptoms in childhood. Materials and Methods: The study group of this descriptive/cross-sectional research comprised 2,061 mothers, ages 19-49, at an FHC in the Eastern Black Sea Region in February 1, 2011 - June 1, 2011. Before the study, permission was obtained from the local ethics board and the institutions concerned. A value of p<0.05 was accepted as statistically significant. Results: Of the mothers, 34.9% were between the ages of 40-47, 40.5% had three children, 73.8% had no experience with children with cancer, 45.9% said they learned about cancer on television, 39.7% stated that the primary reason for childhood cancer was the mother's smoking during pregnancy, 68.8% said that early diagnosis would save a child, and 98% wanted to learn about childhood cancer. Conclusion: It was determined that the mothers' knowledge of cancer was deficient. -
El-Mageed, Amal Abd El-Hafez Abd;Shawky Mohamed, Abd El-Aty;Elesawy, Basem Hasan 1037
Background: Prognostication of breast cancer using clinico-pathologic variables, although useful, remains imperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling. Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focused on Bcl-2 protein expression in triple-negative (TNBC) and non- triple-negative breast cancer (non-TNBC) with correlation to clinico-pathologic variables. Materials and methods: We analyzed Bcl-2 expression in 77 women with primary breast carcinoma divided into two groups; triple-negative and non- triple-negative according to expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2 expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. Results: Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non- triple-negative cancers. In TNBC, expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantly correlated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourable prognostic factors in breast cancer, but no significant statistical correlations were found. Conclusions: Frequency of Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlate with Bcl-2 in the two cases. -
Shi, Hua-Ping;Zhang, Jun;Shang, Xue-Chai;Xie, Xin-You 1043
Although there have been many studies investigating possible associations between the C1653T mutation and risk of HCC, the results have been inconsistent. We conducted searches of the published literature in Pubmed and Embase databases up to January 2013. Seventeen studies with a total of 1,085 HCC cases and 1,365 healthy controls were retrieved. We found a significant association between the C1653T mutation and HCC risk (OR = 2.01, 95%CI= 1.49-2.70). In the subgroup analysis by ethnicity, a significant association was also found in Asians (OR = 2.07, 95%CI= 1.71-2.51). In subgroup analysis by HBV genotype, B and C were linked with development of HCC (B:OR = 2.21, 95%CI= 1.13-4.34; C:OR = 2.26, 95%CI= 1.61-3.16). However, no significant association was found between the C1653T mutation and HCC risk in HBeAg positive cases. In conclusion, this meta-analysis suggests that the C1653T mutation may be associated with susceptibility to HCC. -
Karimpur-Zahmatkesh, Arezu;Farzaneh, Farah;Pouresmaeili, Farkhondeh;Hosseini, Jalil;Azarghashb, Eznollah;Yaghoobi, Mohammad 1049
Background: Studies have shown that alterations of steroid hormone metabolism, particularly involving testosterone, affect the risk of prostate cancer. Therefore, genetic variation in genes of enzymes which are involved could be of importance. The gene most interest is CYP17, whose enzyme product has an essential role in testosterone hormone synthesis. Some studies have indicated that the A2 allele polymorphism of CYP17 associated with increased risk of prostate cancer that could be affected by ethnicity. Therefore, the aim of this study was determination of presence or absence of the A2 allele in patients with prostate cancer. Materials and Methods: We studied the association of A2 allele and prostate cancer among 74 patients with prostate cancer and 128 healthy men which were referred to hospitals of SBMU. Results: This study revealed a significant association between prostate cancer risk and the A2 allele in an Iranian population so that A1A2 and A2A2 genotypes were more common in cases than controls with P-values of 0.029 and 0.010, respectively. Conclusions: Results of our study support a possible role of the A2 allele in sporadic prostate cancer development in Iran, in line with findings elsewhere. -
Tahmasby, Bahram;Marnani, Ahmad Barati;Maleki, Mohammadreza;Barouni, Mohsen;Mousavi, Seyyed Hamid;Naseriyan, Behjat;Nazarnezhad, Mirzaali;Alizadeh, Ali;Sabermahani, Asma 1053
Background: Leukemia and lymphoma demonstrate significantly incidence rates throughout the world and particularly in Iran they cause serious mortality and diagnosis and treatment expenditures for both families and the health system. Combined they account for about 11 percent of cancers in Mazandaran province, ranking number 2 in prevalent cancers. The purpose of this study was to provide a first general and specific description of leukemia and lymphoma in Mazandaran province. Materials and Methods: In this descriptive retrospective study, entire patient's data were reviewed which had confirmed diagnosis of leukemia and lymphoma with valid laboratory or pathology reports in the period 2001-2008. The data were collected by Babol health research site related to Tehran University of Medical Science. Incidence rates based on age groups, gender, city of residence and type of malignancy were calculated and analyzed. Results: In Mazandaran province, 1,146 cases of leukemia and lymphoma were encountered, 5.9 in 100,000 persons on average annually. The highest incidence rates were obtained at age of 70 or above (26.4) and the lowest at age of 0-9 (2.3).The incidence rates in males and females were 7.1 and 4.8 respectively with a ratio of 1.5. The highest incidence rate was in Babol (7.3) and the lowest was calculated in Neka and Tonekabon equally (1.5). According to the type of malignancy, non Hodgkin lymphoma, with 2.5/100,000 have the most incidence rate and myeloid leukemia with 1.8 had the lowest. Conclusions: The obtained findings indicate clear differences in incidence rates based on age, gender, residence, and type of malignancy. Therefore it's suggested that in addition to promote data collecting programs, research projects should be programmed to define leukemia and lymphoma risk factors in this province. -
Xu, Yun-Zhao;Xi, Qing-Hua;Ge, Wen-Liang;Zhang, Xiao-Qian 1057
Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC. -
Wang, Zhong-Tang;Wei, Li-Li;Ding, Xiu-Ping;Sun, Ming-Ping;Sun, Hong-Fu;Li, Bao-Sheng 1061
Objective: To investigate the treatment effect of additional information obtained by single photon emission computed tomography (SPECT) lung perfusion imaging (LPI) in the radiotherapy planning process for patients with stage III non-small cell lung cancer (NSCLC). Methods: 39 patients with stage III NSCLC were enrolled. Gross tumor volume (GTV) was outlined by SPECT/CT images, SPECT-LPIs being used to define functional lung (FL) and non-functional lung (NFL) regions. Two sets of IMRT plans were designed to deliver 64Gy to PTV. One was a regular IMRT plan using CT images only (Plan 1), and the other was a corresponding IMRT plan using co-registered images (Plan 2).$FL_{Vx}$ (the % volume of functional lung receiving${\geq}$ x Gy) and$WL_{Vx}$ (% volume of whole lung to receive${\geq}$ x Gy) were compared by paired Student's t test. Kendalls correlation was used to analyze the factor (s) related with the FLV20 decrease. Results: Compared with plan 1, both$WL_{Vx}$ and$FL_{Vx}$ were decreased in plan 2.$WL_{V10}$ ,$WL_{V15}$ ,$WL_{V20}$ ,$WL_{V25}$ ,$WL_{V30}$ and$WL_{V35}$ decreased 9.7%, 13.8%, 17.2%, 12.9%, 9.8% and 9.8%, and$FL_{V10}$ ,$FL_{V15}$ ,$FL_{V20}$ ,$FL_{V25}$ ,$FL_{V30}$ and$FL_{V35}$ decreased 10.8%, 14.6%, 17.3%, 14.5%, 14.5% and 10.5%.$FL_{Vx}$ decreased significantly compared with$WL_{Vx}$ . There were significant differences in$WL_{V10}$ ,$WL_{V15}$ ,$WL_{V20}$ ,$WL_{V25}$ ,$WL_{V3}$ and$FL_{V10}$ ,$FL_{V15}$ ,$FL_{V20}$ ,$FL_{V25}$ ,$FL_{V30}$ between plan 1 and plan 2 (P=0.002, 0.000, 0.000, 0.005, 0.027 and 0.002, 0.000, 0.000, 0.006, 0.010). According to Kendall correlation analysis, NFL had a negative relation with the percentage FLV20 decrease (r=-0.559, P<0.01), while the distance of PTV and NFL center had a significantly positive relation with the percentage of FLV20 decrease (r=0.768, P<0.01). Conclusion: Routine use of SPECT-LPI for patients undergoing radiotherapy planning for stage III NSCLC appears warranted. -
Liang, Dong;Dong, Min;Hu, Lin-Jie;Fang, Ze-Hui;Xu, Xia;Shi, En-Hui;Yang, Yi-Ju 1067
Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of$SSC^{lo}\;Alde^{br}$ cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell$SSC^{lo}\;Alde^{br}$ cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers. -
Rajendran, Senthilnathan;Muthupalani, Rajendran Shanmugam;Ramanathan, Arvind 1073
Background: In normal cells, activated epidermal growth factor receptor (EGFR) molecules are subjected to ubiquitination-mediated proteasome degradation pathway by c-Cbl, an ubiquitin ligase that checks uncontrolled proliferation. Hence expression of wild type c-Cbl molecule is essential to keep this degradation machinery in a functional state. Loss of expression or function of c-Cbl may consequently lead to sustained activation of EGFR and promote carcinogenesis, loss of function mutations in the c-Cbl gene already being reported in lung and hematopoietic cancers. However, the genetic status of c-Cbl in oral squamous cell carcinoma (OSCC) is not known. Hence in the present study we investigated the genomic DNA isolated from OSCC tissue biopsy samples for mutations in the RING finger domain coding region of c-Cbl gene, which has also been reported to be most frequently mutated in other cancers. Materials and Methods: Total genomic DNA isolated from thirty two post surgical OSCC tissue samples were amplified using primers flanking the exon 8 of c-Cbl gene that codes for the RING finger domain. The PCR amplicons were then resolved in a 1.2% agarose gel, purified and subjected to direct sequencing to screen for mutations. Results: The sequencing data of the thirty two OSCC samples did not identify mutations in the RING finger domain coding region of c-Cbl gene. Conclusions: To the best of our knowledge, this is the first time that the genetic status of c-Cbl gene in OSCC samples has been investigated. The present data indicates that genetic alteration of RING finger domain coding region of c-Cbl gene is relatively infrequent in OSCC samples. -
Qiao, Hui-Ping;Gao, Wei-Shi;Huo, Jian-Xin;Yang, Zhan-Shan 1077
Background: Renal cell carcinoma (RCC) is a malignancy with a poor prognosis. We aimed to explore whether the expression of Long Non-Coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5) is associated with RCC genesis. Methods: We selected twelve clinical samples diagnosed for renal clear cell carcinoma and found that the LncRNA GAS5 transcript levels were significantly reduced relative to those in adjacent unaffected normal renal tissues. Results: In addition, expression of GAS5 was lower in the RCC cell line A498 than that in normal renal cell line HK-2. Furthermore, using functional expression cloning, we found that overexpression of GAS5 in A498 cells inhibited cell proliferation, induced cell apoptosis and arrested cell cycling. At the same time, the migration and invasion potential of A498 cells were inhibited compared to control groups. Conclusion: Our study provided the first evidence that a decrease in GAS5 expression is associated with RCC genesis and progression and overexpression of GAS5 can act as a tumor suppressor for RCC, providing a potential attractive therapeutic approach for this malignancy. -
Morrison, David Stewart;Parr, Christine Louise;Lam, Tai Hing;Ueshima, Hirotsugu;Kim, Hyeon Chang;Jee, Sun Ha;Murakami, Yoshitaka;Giles, Graham;Fang, Xianghua;Barzi, Federica;Batty, George David;Huxley, Rachel Rita;Woodward, Mark 1083
Background: Colorectal cancer has several modifiable behavioural risk factors but their relationship to the risk of colon and rectum cancer separately and between countries with high and low incidence is not clear. Methods: Data from participants in the Asia Pacific Cohort Studies Collaboration (APCSC) were used to estimate mortality from colon (International Classification of Diseases, revision 9 (ICD-9) 153, ICD-10 C18) and rectum (ICD-9 154, ICD-10 C19-20) cancers. Data on age, body mass index (BMI), serum cholesterol, height, smoking, physical activity, alcohol and diabetes mellitus were entered into Cox proportional hazards models. Results: 600,427 adults contributed 4,281,239 person-years follow-up. The mean ages (SD) for Asian and Australia/New Zealand cohorts were 44.0 (9.5) and 53.4 (14.5) years, respectively. 455 colon and 158 rectum cancer deaths were observed. Increasing age, BMI and attained adult height were associated with increased hazards of death from colorectal cancer, and physical activity was associated with a reduced hazard. After multiple adjustment, any physical activity was associated with a 28% lower hazard of colon cancer mortality (HR 0.72, 95%CI 0.53-0.96) and lower rectum cancer mortality (HR 0.75, 95%CI 0.45-1.27). A 2cm increase in height increased colon and all colorectal cancer mortality by 7% and 6% respectively. Conclusions: Physical inactivity and greater BMI are modifiable risk factors for colon cancer in both Western and Asian populations. Further efforts are needed to promote physical activity and reduce obesity while biological research is needed to understand the mechanisms by which they act to cause cancer mortality. -
Aleem, Aamer;Anjum, Farhan;Algahtani, Farjah;Iqbal, Zafar;Alsaleh, Khalid;AlMomen, Abdulkareem 1089
Background: Elderly patients with acute myeloid leukemia (AML) have a poor outcome because of co-morbidities, poor tolerance to intensive chemotherapy and inherently more resistant disease. Clofarabine is a second generation nucleoside analogue which has shown promising activity in elderly patients with AML. This study was conducted to review the outcome of treatment with clofarabine in a group of such patients. Methods: The records of 5 elderly patients who were diagnosed to have AML and treated with clofarabine over a 12 month period were reviewed retrospectively. Results: There were 2 female and 3 male patients with a median age of 68 years (range 65-82). At the time of treatment, 2 patients had newly diagnosed AML not considered suitable for intensive therapy, while 3 patients had partial or no response to conventional chemotherapy. The overall response rate was 100%, all patients achieving a complete remission. Induction and consolidation were well tolerated. All patients developed neutropenia with a median duration of 20 days (range 17-42). One patient developed hand and foot syndrome and a generalized rash but recovered. There was no mortality and all patients remained in remission after a median follow-up of 5.2 months (Range 3-10). Conclusion: Clofarabine (alone or in combination) is active in elderly AML patients with an acceptable safety profile and should be considered a potential option in this group. -
Patel, Kinjal R.;Vajaria, Bhairavi N.;Begum, Rasheedunnisa;Shah, Franky D.;Patel, Jayendra B.;Shukla, Shilin N.;Patel, Prabhudas S. 1093
Background: p53 gene variants i.e. 16 bp duplication in intron 3, Arg72Pro in exon 4 and G>A in intron 6 have been reported to modulate susceptibility to various malignancies. Therefore, the present study evaluated the role of these p53 polymorphisms in oral cancer susceptibility in a population from Gujarat, West India. Method: Genotype frequencies at the three p53 loci in 110 controls and 79 oral cancer cases were determined by the PCR-RFLP method. Results: Heterozygous individuals at exon 4 showed protection from developing oral cancer. Homozygous wild and heterozygous individuals at intron 3 and those heterozygous at exon 4 in combination appeared to be at lowered risk. Furthermore, carriers of the 16 bp duplication allele at intron 3, proline allele at exon 4 and G allele at intron 6 were protected from oral cancer development. Conclusion: p53 polymorphisms, especially Arg72Pro in exon 4 could significantly modify the risk of oral cancer development in Gujarat, West Indian population. -
Choeyprasert, Worawut;Natesirinilkul, Rungrote;Charoenkwan, Pimlak;Sittipreechacharn, Somjai 1101
Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were$20.2{\pm}7.7%$ and$47.1{\pm}9.5%$ respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis ($28.1{\pm}13%$ ,$63.1{\pm}12.3%$ , respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen. -
Sriputtha, Sudarat;Khuntikeo, Narong;Promthet, Supannee;Kamsaard, Supot 1107
Intrahepatic cholangiocarcinoma (ICC), one of the primary liver cancers, is frequent in the northeastern part of Thailand. Surgical resection remains the best method of treatment, but patients suffering from ICC usually present at a late stage of the disease. Studies of survival and prognostic factors after surgery remain rare. The aim here was to evaluate the survival rate and factors affecting the survival of patients with intrahepatic cholangiocarcinoma after surgery. The study used a retrospective cohort design. The subjects were 73 consecutive patients with ICC, who were admitted for surgery to Srinagarind Hospital, Khon Kaen University, during the period 2005-2009. The censoring date was 31 December, 2011, data being evaluated using uni- and multivariate analyses. Postoperative survival analysis was performed by the Kaplan-Meier method, and the Cox proportional hazard model was used to identify independent prognostic factors. The total follow-up time was 99 person-years. The total number of deaths was 59, giving a mortality rate of 59 per 100 person-years. The cumulative 1-, 3-, and 5-year survival rates were 52.1%, 21.7%, and 11.2%, respectively. The median duration of survival after resection was 12.4 months. Univariate analysis revealed stage of disease, lymph node metastasis, histological type, histological grade and macroscopic classification to be statistically significant (p-value<0.05) prognostic factors. In the multivariate analysis, only macroscopic classification was statistically significant (p-value<0.05). In conclusion, macroscopic classification was the only independent factor found to be significantly associated with survival following surgical treatment of ICC. -
Kos, F. Tugba;Sendur, Mehmet Ali Nahit;Aksoy, Sercan;Celik, Huseyin Tugrul;Sezer, Sevilay;Civelek, Burak;Yaman, Sebnem;Zengin, Nurullah 1111
Background: For early detection of renal damage during the usage of cisplatin based chemotherapy, changes in renal function should be monitored carefully. In recent years, neutrophil gelatinase-associated lipocalin, a small polypeptide molecule, has shown promise as a marker of acute renal failure. The aim of this present study was to assess possible risk prediction of cisplatin-induced nephrotoxicity using serum NGAL. Materials and Methods: A total of 34 consecutive patients with documented serum creatinine at least 24 hours before every cycle of cisplatin-based chemotherapy were included in the study. Demographic and medical data including age, performance status, tumor characteristics and comorbid diseases were collected from medical charts. Renal function was evaluated at least 48 hours before the treatment and at the end of the treatment based on the Modification of Diet in Renal Disease (MDRD) formula. Before and after cisplatin infusion serum NGAL levels were measured for the first and 3rd cycles of chemotherapy. Results: The median age of the study population was 54 (32-70) years. Fifteen patients (41.1%) were treated on an adjuvant basis, whereas 19 patients (58.9%) were treated for metastatic disease. There was no correlation of serum NGAL levels with serum creatinine (r=0.20, p=0.26) and MDRD (r=-0.12, p=0.50) and creatinine clearance-Cockcroft-Gault (r=-0.22, p=0.22) after cisplatin infusion at the end of the 3rd cycle of chemotherapy. Conclusions: In our study, serum NGAL levels were not correlated with the cisplatin induced nephrotoxicity. Further prospective studies are needed to conclude that serum NGAL level is not a good surrogate marker to predict early cisplatin induced nephrotoxicity. -
Chindaprasirt, Jarin;Wanitpongpun, Chinadol;Limpawattana, Panita;Thepsuthammarat, Kaewjai;Sripakdee, Warunsuda;Wirasorn, Kosin;Sookprasert, Aumkhae 1115
Background: Febrile neutropenia (FN) is a serious complication following chemotherapy and is associated with significant mortality and financial expenditure. The aim of this study was to evaluate risk factors for longer length of stay (LOS) and mortality and cost of treatment among hospitalized adults with cancer who developed febrile neutropenia in Thailand. Materials and Methods: Information on illness of inpatients and casualties came from hospitals nationwide and from hospital withdrawals from the 3 health insurance schemes in fiscal 2010. The data covered 96% of the population and were analyzed by age groups, hospital level, and insurance year schemes in patients with febrile neutropenia. Results: A total of 5,809 patients were identified in the study. The mortality rate was 14%. The median LOS was 8.67 days and 69% of patients stayed for longer than 5 days. On bivariate analysis, age, cancer type, and infectious complications (bacteremia/sepsis, hypotension, fungal infections, and pneumonia) were significantly associated with longer LOS and death. On multivariate analysis, acute leukemia and infectious complications were linked with longer LOS and death significantly. The median cost of hospitalized FN was THB 33,686 (USD 1,122) with the highest cost observed in acute leukemia patients. Conclusions: FN in adult patients results in significant mortality in hospitalized Thai patients. Factors associated with increased mortality include older age (>70), acute leukemia, comorbidity, and infectious complications. -
Kua, Voon Fong;Ismail, Fuad;Phua, Vincent Chee Ee;Aslan, Nik Muhd 1121
Background: Palliative chemotherapy with cisplatin/5-fluorouracil (5FU) is the commonest regimen employed for metastatic and recurrent head and neck squamous cell carcinoma (SCCHN) and nasopharyngeal carcinoma (NPC). However, this regimen is cumbersome requiring 5 days of admission to hospital. Carboplatin/5FU may be an alternative regimen without compromising survival and response rates. This study aimed to compare the efficacy and toxicity of carboplatin/5FU regimen with the cisplatin/5FU regimen. Materials and Methods: This retrospective study looked at patients who had palliative chemotherapy with either cisplatin/5FU or carboplatin/5FU for metastatic and recurrent SCCHN and NPC. It included patients who were treated at UKMMC from$1^{st}$ January 2004 to$31^{st}$ December 2009 with either palliative IV cispaltin 75$mg/m^2$ D1 only plus IV 5FU 750$mg/m^2$ D1-5 infusion or IV Carboplatin AUC 5 D1 only plus IV 5FU 500$mg/m^2$ D1-2 infusion plus IV 5FU 500$mg/m^2$ D1-2 bolus. The specific objectives were to determine the efficacy of palliative chemotherapy in terms of overall response rate (ORR), median progression free survival (PFS) and median overall survival (OS) and to evaluate the toxicities of both regimens. Results: A total of 41 patients were eligible for this study. There were 17 in the cisplatin/5FU arm and 24 in the carboplatin/5FU arm. The ORR was 17.7 % for cisplatin/5FU arm and 37.5 % for carboplatin/5FU arm (p-value=0.304). The median PFS was 7 months for cisplatin/5FU and 9 months for carboplatin/5FU (p-value=1.015). The median OS was 10 months for cisplatin/5FU arm and 12 months for carboplatin/5FU arm (p-value=0.110). There were 6 treatment-related deaths (6/41=14.6%), four in the carboplatin/5FU arm (4/24=16.7%) and 2 in the cisplatin/5FU arm (2/17=11.8%). Grade 3 and 4 hematologic toxicity was also more common with carboplatin/5FU group, this difference being predominantly due to grade 3-4 granulocytopenia (41.6% vs. 0), grade 3-4 anemia (37.5% vs. 0) and grade 3-4 thrombocytopenia (16.6% vs. 0). Conclusions: Carboplatin/5FU is not inferior to cisplatin/5FU with regard to its efficacy. However, there was a high rate of treatment-related deaths with both regimens. A better alternative needs to be considered. -
Tharnprisan, Piangjit;Khiewyoo, Jiraporn;Sripraya, Piporn;Wiangnon, Surapon 1127
Background: The standard national protocol for treatment of acute lymphoblastic leukemia (ALL) in children was implemented in 2006. A systematic evaluation of the treatment outcome is needed. This study examined the relapse-free survival among childhood ALL cases treated with this protocol and related factors. Materials and Methods: A descriptive study was conducted in children aged between 0-15 years, newly diagnosed with ALL between March 2006 and March 2011 at Srinagarind Hospital, Department of Pediatrics, Faculty of Medicine, Khon Kaen University. The patients were treated on the basis of stratified risk as per the Thai national protocol. Data were compiled from the hospital records. The Kaplan-Meier method was used to describe relapse-free survival and the Cox proportional hazard model to investigate the associated factors. Results: Of the 103 children recruited, 86 (83.5%) achieved complete remission. The total follow-up time was 3132.5 person-months. Eighteen (20.9%) relapsed. The incidence density was 0.6 per 100 person-months (95%CI: 0.4, 0.9). The respective relapse-free rates at 1, 3 and 5 years were 93.0% (95%CI: 85.1, 96.8), 84.5% (95%CI: 74.0, 90.9) and 64.1% (95%CI: 45.6, 77.8). A factor associated with the relapse-free rate was age under 1 year (HR=6.0; 95%CI: 1.1, 33.8). Conclusions: The rate of being relapse-free in ALL children treated under the Thai national protocol at Srinagarind Hospital was better than with former protocols; however, it is still not as good as in developed countries. Further review of the treatment approach of ALL is needed. -
Demirci, Umut;Canda, Abdullah Erdem;Dede, Didem Sener;Cakici, Ozer Ural;Akinci, Muhammed Bulent;Yalcin, Bulent 1131
Background: Upper tract transitional cell carcinomas (UTCC) are relatively uncommon but prognosis is generally worse than TCC of bladder. Methods: Between March 2004 and June 2012, patients with initial non-metastatic UTCC were assessed in the Medical Oncology and Urology Departments of Ataturk Training and Research Hospital. Results: A total of 11 patients with initially non-metastatic UTCC were detected in the 8 year period, all males. Median age of was 62 (range, 38-74). Six lesions were located in the renal pelvis and 5 in the ureter. Nephroureterectomy was performed in 9 patients, and distal ureterectomy and cuff excision of the bladder in the remaining 2. The majority (n= 9) had high grade tumors. Median primary tumor diameter was 3.5 cm (range, 0.7-10). Five patients (45.5%) were stage I, 2 (18.2%) were stage II, and 4 (36.4%) were stage III. While adjuvant chemotherapy was not applied for stage I and II disease (n= 7), 4 to 6 courses were applied for 3 of the stage III patients. Also one stage III case received adjuvant radiotherapy. Up to 100 months follow-up, median overall survival was 13 months (range, 5-100 months). While stage I and II patients are following-up without muscle-invasive progression, 2 of stage III patients demonstrated progression. Conclusion: We need more collaborative studies to determine management of especially pT3-pT4 patients with UTCC. -
Savant, Suyog Chandrashekhar;Hegde-Shetiya, Sahana;Agarwal, Deepti;Shirhatti, Ravi;Shetty, Deeksha 1133
Background: In India, tobacco consumption is responsible for one of the highest rates of oral cancer in the world, the annual oral cancer incidence is steadily increasing among young tobacco users. Studies have documented efforts taken by physicians, doctors and even dentists, in the form of individual or group counseling to curb tobacco use in smoke or smokeless form. However, which one is more effective, still remains an unanswered question. The aim of the study was to compare the effectiveness of individual and group counseling for cessation of the tobacco habit amongst industrial workers in Pune and to compare quit rates. Materials and methods: An interventional study design was selected for 150 industrial workers which were stratified randomly into three groups (control, individual and group counseling groups) and interventions were provided to individual and group counseling groups over a period of six months, which were then compared with the control group that received brief intervention at the start of the study. Results: There was significant difference in the quit rates of the participants in the individual counseling group (ICG) and group counseling group (GCG) when compared at 6 months with the control counseling group (CCG). In the individual counseling group was 6% while in group counseling group it was 7.5% after six months of counseling. Conclusions: No conclusion could be drawn whether individual or group counseling were better interms of quit rates. Individual and group counseling groups were definitely better than the control group when compared at 3 and 6 months, respectively. -
Ghazali, Sumarni Mohd;Othman, Zabedah;Cheong, Kee Chee;Lim, Kuang Hock;Wan Mahiyuddin, Wan Rozita;Kamaluddin, Muhammad Amir;Yusoff, Ahmad Faudzi;Mustafa, Amal Nasir 1141
Delay in seeking treatment for breast cancer is a barrier to the early diagnosis and management of the disease, resulting in a poorer prognosis. We here estimated the prevalence of delayed presentation for breast cancer and identified possible influential sociodemographic factors in a cross-sectional study of 250 patients diagnosed with primary breast cancer at the Radiotherapy and Oncology Clinic in Kuala Lumpur Hospital. Data were collected by face-to-face interview using a structured questionnaire and from medical records. We examined associations between delayed presentation (presenting to a physician more than 3 months after self-discovery of a symptom) and sociodemographic characteristics, practice of breast self examination (BSE), history of benign breast disease, family history of breast cancer and type of symptom, symptom disclosure and advice from others to seek treatment using multiple logistic regression. Time from self-discovery of symptom to presentation ranged from tghe same day to 5 years. Prevalence of delayed presentation was 33.1% (95%CI: 27.4, 39.3). A significantly higher proportion of delayers presented with late stages (stage III/IV) (58.3% vs. 26.9%, p<0.001). Divorced or widowed women (OR: 2.23, 95% CI: 1.11, 4.47) had a higher risk of delayed presentation than married women and women who never performed breast self examination were more likely to delay presentation compared to those who regularly performed BSE (OR: 2.74, 95% CI: 1.33, 5.64). Our findings indicate that delayed presentation for breast cancer symptoms among Malaysian women is high and that marital status and breast self examination play major roles in treatment-seeking for breast cancer symptoms. -
Laljee, Rupesh Puthenparambil;Muddaiah, Sunil;Salagundi, Basavaraj;Cariappa, Ponappa Muckatira;Indra, Adarsh Surendran;Sanjay, Venkataram;Ramanathan, Arvind 1147
Background: Cancer diagnostic biomarkers have a wide range of applications that include early detection of oral precancerous lesions and oral squamous cell carcinomas, and assessing the metastatic status of lesions. The interferon stimulated ISG15 gene encodes an ubiquitin-like protein, which conjugates to stabilize activation status of associated proteins. Hence a deregulated expression of ISG15 may promote carcinogenesis. Indeed overexpression of ISG15 has been observed in several cancers and hence it has been proposed as a strong candidate cancer diagnostic biomarker. Given the emerging relationship between malignant transformation and ISG15, we sought to examine the expression pattern of this gene in tumor biopsies of oral squamous cell carcinoma (OSCC) tissues collected from Indian patients. Materials and Methods: Total RNA isolated from thirty oral squamous cell carcinoma tissue biopsy samples were subjected to semi-quantitative RT-PCR with ISG15 specific primers to elucidate the expression level. Results: Of the thirty oral squamous cell carcinomas that were analyzed, ISG15 expression was found in twenty four samples (80%). Twelve samples expressed low level of ISG15, six of them expressed moderately, while the rest of them expressed very high level of ISG15. Conclusions: To the best of our knowledge, the results show for the first time an overexpression of ISG15 in up to 80% of oral squamous cell carcinoma tissues collected from Indian patients. Hence ISG15 may be explored for the possibility of use as a high confidence diagnostic biomarker in oral cancers. -
Yusof, Afzaninawati Suria;Isa, Zaleha Md.;Shah, Shamsul Azhar 1151
Background: Changes in dietary practices are known to be associated with changes in the health and disease pattern of a population. This study aimed to qualitatively explore the perception of colorectal cancer patients regarding causes of colorectal cancer and the influence of diet. Materials and Methods: Twelve respondents from three major ethnicities in Malaysia were selected from the quantitative study on dietary pattern and colorectal cancer carried out earlier in this study. In-depth interviews (IDI), conducted from April until June 2012, were mainly in the Malay language with additional use of English and continued until the saturation point was reached. All interviews were autorecorded so that verbatim transcriptions could be created. Results: Causes of colorectal cancer were categorized into internal and external factors. The majority of respondents agreed that there is an association between Western foods and colorectal cancer. Malaysian traditional diet was not related to colorectal cancer as less preservative agents were used. Malaysian diet preparation consisting of taste of cooking (spicy, salty and sour foods) plus type of cooking (fry, grilled and smoked) were considered causes of colorectal cancer. All respondents changed their dietary pattern to healthy food after being diagnosed with colorectal cancer. Advice from doctors regarding suitable food for colorectal cancer was useful in this regard. Conclusions: Eating outside, use of food flavoring ingredients and preservative agents were considered to be the main factors causing colorectal cancer. All respondents admitted that they changed to a healthy diet after being diagnosed with colorectal cancer. -
Zhang, Jing-Yao;Xie, Lin;Tai, Ming-Hui;Wu, Qi-Fei;Liu, Chang 1155
Cancer is a highly complex medical problem with ramifications for public health throughout the world. Most studies have mainly focused on change in the nuclei as being aetiologically responsible. Few have examined the relationship between the cytoplasm and cancer, despite the fact that research has indicated that the cytoplasmic environment is an important factor for cellular differentiation and that the genetic information provided by the nucleus is entirely dependent on this environment for its expression. Gene mutations may be the result, rather than the cause of carcinogenesis. We submit a new concept - "short base sequences" (50-500 bps, including DNA or RNA sequences) in the cytoplasm which could play an important role in carcinogenesis. This is a new theory to explain the origin of the cancer. -
Sarwal, Kavita;Trapido, Edward J.;Sutcliffe, Simon;Qiao, You-Lin 1159
International meetings on various aspects of cancer- its etiology, its diagnosis, its treatment, its palliation, and its prevention and control are held frequently. Many have similar themes, and many seek and receive the same speakers and audiences. A fundamental question arises: what difference does any individual meeting/congress/conference make or add to our understanding of the relevant issues? While many meetings conduct evaluations at the end of the Congress, few use evaluation as a tool to guide design, implementation, and evaluation of both short and long term impacts, and address the question of "what difference did the Congress make". The International Cancer Control Congresses, which are held biennially in different regions of the world, took the opportunity to use evaluation in this way, and ask the relevant questions. This paper describes that evaluation session of the ICCC4, held in Seoul, Korea in November 2011, which was part of the larger evaluation issue.