Asian Pacific Journal of Cancer Prevention
Asian Pacific Journal of Cancer Prevention (APOCP)
- Monthly
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- 1513-7368(pISSN)
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- 2476-762X(eISSN)
Domain
- Health Sciences > Development of Pharmaceutical
Aim & Scope
Cancer is a very complex disease. While many aspects of carcinoge-nesis and oncogenesis are known, cancer control and prevention at the community level is however still in its infancy. Much more work needs to be done and many more steps need to be taken before effective strategies are developed. The multidisciplinary approaches and efforts to understand and control cancer in an effective and efficient manner, require highly trained scientists in all branches of the cancer sciences, from cellular and molecular aspects to patient care and palliation. The Asia Pacific Organization for Cancer Prevention (APOCP) and its official publication, the Asia Pacific Journal of Cancer Prevention (APJCP), have served the community of cancer scientists very well and intends to continue to serve in this capacity to the best of its abilities. One of the objectives of the APOCP is to provide all relevant and current scientific information on the whole spectrum of cancer sciences. They aim to do this by providing a forum for communication and propagation of original and innovative research findings that have relevance to understanding the etiology, progression, treatment, and survival of patients, through their journal. The APJCP with its distinguished, diverse, and Asia-wide team of editors, reviewers, and readers, ensure the highest standards of research communication within the cancer sciences community across Asia as well as globally. The APJCP publishes original research results under the following categories: - Epidemiology, detection and screening. - Cellular research and bio-markers. - Identification of bio-targets and agents with novel mechanisms of action. - Optimal clinical use of existing anti-cancer agents, including combination therapies. - Radiation and surgery. - Palliative care. - Patient adherence, quality of life, satisfaction. - Health economic evaluations. All research and manuscript published by the Asia Pacific Journal of Cancer Prevention, are under the terms of the Creative Commons Attribution License. This permits anyone to copy, distribute, transmit and adapt the published work, provided the original work and source are appropriately cited. The APJCP strongly supports the Open Access initiative. Each published article is assigned a Crossref Digital Object Identifier (DOI), and full texts (HTML, PDF and XML format) of all articles published by the Asia Pacific Journal of Cancer Prevention, are freely accessible to everyone immediately after publication. Asia Pacific Journal of Cancer Prevention supports the Bethesda Statement on Open Access Publishing.
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Volume 13 Issue 7
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Mozaheb, Zahra;NazarAbadi, Mohamad Hasan Hasanzadeh;Aghaee, Monavar Afzal 3009
Background: The clinical course of individual chronic lymphocytic leukemia (CLL) is highly variable and clinical staging systems do not help us to predict if and at what rate there will be disease progression in an individual patient diagnosed with early stage disease. Recently, several important observations related to other prognostic factors including lymphocyte doubling time (LDT),${\beta}_2$ -microglobulin (${\beta}_2$ -MG), and percent of smudge cell in peripheral blood smears, cytogenetic and molecular analysis have been made. The aim of this study was to evaluate a range of prognostic factors in our CLL patients. Design and methods: Seventy patients with CLL were enrolled. Prognostic factors of disease including Binet staging, LDT,${\beta}_2$ -MG, ESR, LDH, percent of smudge cell in peripheral blood smear, absolute lymphocyte count, and conventional cytogenetic (CC) analysis were evaluated at diagnosis, and the patients were followed up to determine their outcome. We compared factors with each other and with Binet staging and prognosis. Results: Enrolled patients aged 37-85 years at diagnosis or during follow up. There was no relationship between serum LDH level (P=0.3), ESR (P=0.11), percent of smudge cells in peripheral blood smear (P=0.94), and absolute lymphocyte count (P=0.18) with the stage of disease and prognosis, but the${\beta}_2$ macroglobulin level (p<0.0001), LDT (p<0.001) had direct and significant relation with staging and outcome. In 19% of patients cytogenetic alteration were seen. Conclusion: The detection of cytogenetic alteration only using the CC method is not sufficient and we need to use FISH, but because FISH study is an expensive method not available in all areas, instead we believe that${\beta}_2$ MG can be applied in its place as a good prognostic factor for CLL at diagnosis and during follow up. We suggest to add it to Binet staging for prognostic subgrouping of CLL. -
Sun, Guo-Gui;Hu, Wan-Ning;Wang, Ya-Di;Yang, Cong-Rong;Lu, Yi-Fang 3015
The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells. -
Emri, Salih;Kilickap, Saadettin;Kadilar, Cem;Halil, Meltem Gulhan;Akay, Hadi;Besler, Tanju 3025
The aim of this study was to investigate the possible relationship between antioxidant vitamin levels and malignant pleural mesothelioma (MPM). For this purpose, we measured the serum levels of 4 antioxidant vitamins,${\beta}$ -carotene,${\alpha}$ -tocopherol, retinol, and ascorbic acid, in patients with environmentally induced MPM and in healthy controls from one tremolite village (Kureysler), the biggest erionite village (Tuzkoy) and Ankara. A total of 160 subjects were enrolled in the study, 42 (26.3%) diagnosed with MPM and 118 (73.7%) healthy subjects. A comparison was made between the MPM group and three control groups of which two were exposed and one was unexposed to mineral fibers. The study population consisted of 82 males (51%) and 78 females (49%) with a mean of age of$44.8{\pm}14$ years (range; 20-65 years). Lowest levels of${\beta}$ -carotene, ascorbic acid, and${\alpha}$ -tocopherol were found in MPM patients (MPM vs control groups combined, p<0.0001 for each antioxidant vitamin), without any relation to age or sex. There was no significant difference between the antioxidant levels of healthy controls of Tuzkoy and Ankara. In conclusion; our findings suggested an increased risk of MPM being associated with low levels of${\alpha}$ -tocopherol and ascorbic acid in patients with MPM. -
Chakrabarti, Sudipta;Datta, Alok Sobhan;Hira, Michael 3031
Background: Though open surgical biopsy is the procedure of choice for the diagnosis of bone tumors, many disadvantages are associated with this approach. The present study was undertaken to evaluate the role of fine needle aspiration cytology (FNAC) as a diagnostic tool in cases of bony tumors and tumor-like lesions which may be conducted in centers where facilities for surgical biopsies are inadequate. Methods: The study population consisted of 51 cases presenting with a skeletal mass. After clinical evaluation, radiological correlation was done to assess the nature and extent of each lesion. Fine needle aspiration was performed aseptically and smears were prepared. Patients subsequently underwent open surgical biopsy and tissue samples were obtained for histopathological examination. Standard statistical methods were applied for analysis of data. Results: Adequate material was not obtained even after repeated aspiration in seven cases, six of which were benign. Among the remaining 44 cases, diagnosis of malignancy was correctly provided in 28 (93.3%) out of 30 cases and categorical diagnosis in 20 (66.67%). Interpretation of cytology was more difficult in cases of benign and tumor-like lesions, with a categorical opinion only possible in seven (50%) cases. Statistical analysis showed FNAC with malignant tumors to have high sensitivity (93.3%), specificity (92.9%) and positive predictive value of 96.6%, whereas the negative predictive value was 86.7%. Conclusion: FNAC should be included in the diagnostic workup of a skeletal tumor because of its simplicity and reliability. However, a definitive pathologic diagnosis heavily depends on compatible clinical and radiologic features which can only be accomplished by teamwork. The cytological technique applied in this study could detect many bone tumors and tumor-like conditions and appears particularly suitable as a diagnostic technique for rural regions of India as other developing countries. -
Bodoor, Khaldon;Matalka, Ismail;Hayajneh, Rami;Haddad, Yazan;Gharaibeh, Waleed 3037
The diffuse large B-cell lymphoma (DLBCL) encompasses two major groups of tumors with uneven survival outcomes - germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB). In the present study, we investigated the expression of GCB markers (BCL-6 and CD10) and non-GCB markers (CD138 and MUM-1) in an effort to evaluate their prognostic value. Paraffin-embedded tumor biopsies of 46 Jordanian DLBCL patients were analyzed, retrospectively, by immunohistochemistry to investigate the expression of BCL-6, CD10, CD138 and MUM-1. In addition, survival curves were calculated with reference to marker expression, age, sex and nodal involvement. Positive expression of BCL-6, CD10, CD138 and MUM-1 was shown in 78%, 61%, 39% and 91% of the cases, respectively, that of BCL-6 being associated with better overall survival (p = 0.02), whereas positive CD138 was linked with poor overall survival (p = 0.01). The expression of CD10 and MUM-1 had no impact on the overall survival. Among the clinical characteristics studied, diagnosis at an early age, nodal involvement and maleness were associated with a higher overall survival for DLBCL patients. Our results underline the importance of BCL-6 as a marker of better prognosis and CD138 as a marker of poor prognosis for DLBCL patients. -
Shah, Mohd A.;Shaffi, Sheikh M.;Lone, Ghulam Nabi;Jan, Syed Mudassar 3047
The enzyme encoded by the MGMT gene is involved in the repair of alkylated lesions formed in DNA by carcinogenic nitrosamines. Since dietary items consumed by the Kashmiri population contain high concentrations of these agents, it is biologically plausible that MGMT polymorphic variants may be associated with their risk of esophageal cancer. The present study was performed to assess whether non-synonymous SNPS at codon Leu84Phe and codon Ileu143Val of the MGMT gene, close to the active site of the protein, might be linked to predisposition of Kashmiris to esophageal cancer. Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on 92 cases and 77 healthy controls. Codon 84 and codon 143 SNPs of the MGMT gene were not associated with any increase in risk. While the frequency of the Phe allele at codon 84 in cases was (0.16), slightly higher than controls (0.12), the difference was not statistically significant. Similarly, the frequency of Valine allele in cases at codon 143 (0.08) and controls (0.09) was nearly equal. Moreover, no significant association of MGMT genotypes with the clinicopatholgic variables of esophageal cancer patients was observed. In conclusion, MGMT variants at codon 84 and codon143 may not be involved in the susceptibility of the Kashmiri population to esophageal cancer. -
Mahdavi, Manijeh;Mohabatkar, Hassan;Keyhanfar, Mehrnaz;Dehkordi, Abbas Jafarian;Rabbani, Mohammad 3053
Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of receptor tyrosine kinases that plays important roles in all processes of cell development. Their overexpression is related to many cancers, including examples in the breast, ovaries and stomach. Anticancer therapies targeting the HER2 receptor have shown promise, and monoclonal antibodies against subdomains II and IV of the HER2 extra-cellular domain (ECD), Pertuzumab and Herceptin, are currently used in treatments for some types of breast cancers. Since anti HER2 antibodies targeting distinct epitopes have different biological effects on cancer cells; in this research linear and conformational B cell epitopes of HER2 ECD, subdomain III, were identified by bioinformatics analyses using a combination of linear B cell epitope prediction web servers such as ABCpred, BCPREDs, Bepired, Bcepred and Elliprro. Then, Discotope, CBtope and SUPERFICIAL software tools were employed for conformational B cell epitope prediction. In contrast to previously reported epitopes of HER2 ECD we predicted conformational B cell epitopes$P1_C$ : 378-393 (PESFDGDPASNTAPLQ) and$P2_C$ : 500-510 (PEDECVGEGLA) by the integrated strategy and P4: PESFDGD-X-TAPLQ; P5: PESFDGDP X TAPLQ; P6: ESFDGDP X NTAPLQP; P7: PESFDGDP-X-NTAPLQ; P8: ESFDG-XX-TAPLQPEQL and P9: ESFDGDP-X-NTAPLQP by SUPERFICIAL software. These epitopes could be further used as peptide antigens to actively immune mice for development of new monoclonal antibodies and peptide cancer vaccines that target different epitopes or structural domains of HER2 ECD. -
Sharma, Munesh Kumar;Gour, Neeraj;Pandey, Avadesh;Wallia, Dinesh;Kislay, Dimri 3061
Aim: An epidemiological shift has resulted in increase in the prevalence of non-communicable diseases (NCD). Unlike other NCDs which are easily and definitely preventable, the knowledge of cancer prevention is still limited at present. Various aetiological factors are difficult to control since those are habit forming. Hence an available remedy remains its secondary and tertiary prevention for which appropriate planning is of paramount importance. Evidence based planning requires careful analysis of data with a view to prioritize various cancers. Keeping in view the fact that the adaptation of smoking free status in Chandigarh city might have a far reaching positive effect on the cancer related morbidity of the people, the following study was undertaken to provide base line data to be used for future comparisons. Methods: The registers maintained in the Department of Radiotherapy were checked and those belonging to the years 1999 to 2009 were utilized to analyze the cancer morbidity in respect to age, sex, and year of presentation to health care facility. Results: A total of 4,600 cancer patients (males=2276, females=2324) demonstrated a gradual increase in the number of cancer cases from 150 in the year 1999 to 783 in the year 2009. The most common cancers amongst males were cancer of gastro-intestinal tract (GIT) and lung (including larynx) constituting 37.3% and 27.1% of the total, respectively. In females these were cancers of breast and cervix representing 33.3% & 17.6% of total cancer cases, respectively, and lung cancer constituted 5.3%. The maximum cases of bone cancer (53.8% of all bone cancers) were observed amongst children aged less than 20 years and lung cancer (48.2% of all lung cancers) among the elderly aged 60-69 years. The. -
Aim: The present investigation was to evaluate the effects of essential oils of Wedelia chinensis (Osbeck) on free radicals and in vivo antioxidant properties. Methods: Essential oils were extracted using hydro-distillation and compound analysis was performed by GC-MS analysis. Screening for inhibitory activity was conducted by DPPH and OH-scavenging assays. In addition an in vivo study was carried out in cell line implanted cancer bearing mice with assessment of levels of catalase, superoxide dismutase, glutathione peroxidase, lipid peroxidation, nitric oxide and reduced glutathione. Finally, lungs were dissected out for histopathology study of metastasis. Results: GC-MS analysis revealed the presence of carvocrol and trans-caryophyllene as the major compounds with 96% comparison with the Wilily and NBS libraries. The essential oil exhibited significant inhibition in DPPH free radical formation. Whereas reducing power and hydroxyl radical scavenging activity are dose dependent. When compared with the standard, it was found that the essential oil has more or less equal activity in scavenging free radicals produced. In the animal studies, the level of antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase, as well as glutathione, were found to be increased in treated groups whereas lipid peroxidation and nitric oxide were reduced. Histopathology report also shows that the essential oil has a significant combating effect against cancer development. Conclusion: In all the in vitro assays, a significant correlation existed between the concentrations of the essential oil and percentage inhibition of free radicals. The in vivo studies also has shown a very good antioxidant property for the essential oil during cancer development. From, these results the essential oil can be recommended for treating disease related to free radicals and to prevent cancer development.
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Khaw-On, Patompong;Banjerdpongchai, Ratana 3073
Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways. -
Glew, Robert H.;Wold, Rosemary S.;VanderJagt, Dorothy J. 3077
Aim: The incidence of biliary tract cancer (BTC) is many-fold higher for American Indians (AI) relative to non-Hispanic whites (NHW). Neither gallstones nor genetics can account for this difference. There is speculation that certain fatty acids in bile may play a role in preventing BTC. Since diet may influence composition of bile, we compared the dietary intakes of urban AI and NHW adult women in New Mexico. Methods: Design, a cross-sectional study of the diets of lactating AI and NHW women was conducted. Setting, the University of New Mexico Hospital. Participants, healthy lactating women 18 to 39 years of age were recruited. Main outcome measures, a three-day diet record for each participant was analyzed. Results: The AI women consumed less calcium (p = 0.04) and significantly less short and intermediate chain-length fatty acids (C4-C12), but nearly twice as much proinflammatory arachidonic acid as the NHWs (p <0.01). The intake of dairy products by AI women was less than NHW women (p = 0.01) while the intake of processed meat products was higher (p <0.01). Conclusion: Dietary factors may account for the difference in the risk of BTC between AI and NHW women. -
Cao, Xi-Liang;Gao, Jiang-Ping;Wang, Wei;Xu, Yong;Shi, Huai-Yin;Zhang, Xu 3083
We investigated the prognostic value of pituitary tumor transforming gene 1 (PTTG1) expression according to clinicopathological features among localized or locally advanced prostate cancer cases receiving hormone therapy. A retrospective study involved 64 patients receiving combined androgen blockade treatment was performed. PTTG1 expression was determined by immunohistochemical staining using initial needle biopsy specimens for diagnosis. Associations of PTTG1 with various clinicopathological features and disease-free survival were examined via uni- and multivariate analyses. No association between PTTG1 expression and clinical T stage, Gleason score, pretreatment PSA levels, risk groups was found (p =0.682, 0.184, 0.487, 0.571, respectively). Univariate analysis revealed that increased PTTG1 expression, T3 stage and high risk group were associated with increased risk of disease progression (p =0.000, 0.042, and 0.001), and high PSA level had a tendency to predict disease progression (p =0.056). Cox hazard ratio analysis showed that PTTG1 low expression (p =0.002), PTTG1 high expression (p =0.000) and high risk group (p =0.0147) were significantly related to decreased disease-free survival. In conclusion, PTTG1 expression determined by immunohistochemical staining in needle biopsy specimens for diagnosis is a negative prognostic factor for progression in localized or locally advanced prostate cancer receiving hormone therapy. -
Liu, Lei;Ma, Xue-Lei;Xiao, Zhi-Lan;Li, Mei;Cheng, Si-Hang;Wei, Yu-Quan 3089
Background and Aims: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker for patients with resected gastric cancer. However, its role remains controversial. The objective of this study was to conduct a systematic review and meta-analysis of published literature. Methods: Relevant literature was identified using Medline and survival data from published studies were collected following a methodological assessment. Quality assessment of eligible studies and meta-analysis of hazard ratio (HR) were performed to review the correlation of VEGF overexpression with survival and recurrence in patients with gastric cancer. Results: Our meta-analysis included 44 published studies with 4,794 resected patients. VEGF subtype for the prediction of overall survival (OS) included tissue VEGF (HR=2.13, 95% CI 1.71-2.65), circulating VEGF (HR=4.22, 95% CI 2.47-7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58-3.09), tissue VEGF-D (HR=1.73, 95% CI 1.25-2.40). Subgroup analysis showed that HRs of tissue VEGF for OS were, 1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) in non-Asians and Asians, respectively. The meta-analysis was also conducted for disease free survival (DFS) and disease specific survival (DSS). Conclusion: Positive expression of tissue VEGF, circulating VEGF, VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer. However, VEGF demonstrated no significant prognostic value for non-Asian populations. Circulating VEGF may be better than tissue VEGF in predicting prognosis. -
Health-related Quality of Life After Treatment for Malignant Bone Tumors: A Follow-up Study in ChinaSun, Yong-Jian;Hu, Yan-Jun;Jin, Dan;Li, Jian-Wei;Yu, Bin 3099
Aim: We conducted the present study to assess health-related quality of life (HRQoL) among bone cancer patients after surgical treatment in one large teaching hospitals in China, and assess the risk factors for improving the physical or mental HRQoL. Methods: 344 eligible adult patients who were admitted to the hospital with malignant bone tumors during the period of Jun. 2008 to Dec. 2011, and a reference group with 361 health cases was recruited in the same hospital during the same period. All 344 patients were followed up for one year. The HRQoL before treatment and after one year was evaluated with the Medical Outcome Short Form 36 (SF-36). Results: All 8 domains of HRQoL had the lowest scores greatly improved over the first year after discharge. However, the patients still had significantly lower scores in every domain than the reference group one year after discharge. Age and type of surgery were associated with HRQoL in the mental domain. Conclusion: The HRQoL of patients with malignant bone tumors greatly improved one year after the treatment. This study also highlighted the utility of HRQoL assessment for prognostic evaluation of patients after surgical treatment for bone cancer. -
Gong, Chen;Liao, Hui;Wang, Jiang;Lin, Yang;Qi, Jun;Qin, Liang;Tian, Lin-Qiang;Guo, Feng-Jing 3103
Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a critical role in tumorigenesis and drug-resistance. It is known that phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell fates, such as proliferation, cell cycling, survival and apoptosis. Whether and how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which are involved in the mitochondrial apoptosis pathway. Therefore, our results indicate PI3K inhibitors may represent a potential strategy for managing human osteosarcoma via affecting CSCs. -
Liu, Rui;Wang, Xiao-Hua;Liu, Li;Zhou, Qiang 3109
Background: Many studies have focused on possible associations between the glutathione S-transferase M 1 (GSTM1) null genotype and risk of renal cell carcinoma (RCC), but the impact remains unclear owing to obvious inconsistencies among the findings. The present study aimed to quantify the strength of any association in a meta-analysis. Methods: We searched the PubMed, Embase and CBM databases for studies concerning the association between the GSTM1 null genotype and risk of RCC. We estimated the summary odds ratio (OR) with its 95% confidence intervals (95% CI) to assess the association. Results: The meta-analysis showed the GSTM1 null genotype was not associated with risk of RCC overall (OR = 1.04, 95% CI 0.92-1.18, P = 0.501). For Caucasians, the GSTM1 null genotype was also not associated with risk of RCC (OR=1.02, 95% CI 0.90-1.16, P = 0.761). The cumulative meta-analyses showed a trend of no obvious association between GSTM1 null genotype and risk of RCC as information accumulated. Sensitivity analyses by omitting those studies also did not materially alter the overall combined ORs. No evidence of publication bias was observed. Conclusion: Meta-analyses of available data show that the GSTM1 null genotype is not significantly associated with risk of renal cell carcinoma. -
El-Basmy, A.;Al-Mohannadi, S.;Al-Awadi, A. 3113
Introduction: Cancer is the second cause of death in Kuwaiti people after cardiovascular diseases. This study is the first in the country to describe epidemiological measures related to cancer in this population. Methods: Data obtained from the Kuwait cancer registry included all Kuwaiti patients between years 2000-2009. Analyses were conducted using age-specific rates, the age-standardization-direct method, 95% confidence intervals (95% CI), cumulative risk by the age of 74 years, limited-duration prevalence, mortality and forecasting to year 2029. Results: It was noted that the commonest cancer sites were colorectal with an age standardized incidence rate (ASIR) of 16.1/100,000 in males and breast (49.4/100,000) in the female population. The trend of cancer incidence (1974-2009) showed no statistically significant change. First causes of death due to cancer were female breast 8(6.4-9.6)/100,000 and lung (males) 8.1/100,000 (6.6-10.0). The risk of developing cancer by the age of 74 was 13.4% (1/8) and 14.3% (1/7) in males and females respectively, and the risk of dying from cancer in the same age group was 1/17 and 1/23. By the end of 2009, prevalent cases represented 0.52% of the Kuwaiti population. In the year 2029, the total number of cancer cases is expected to reach 1200 cases compared to 889 cases in 2009. Conclusions and recommendations: The most common cancers in Kuwait (breast, colorectal and lung) are largely preventable. Prompt and effective interventional prevention programs that vigorously involve diet, anti-smoking and physical activity for both sexes are urgently required. -
Non-small-cell lung cancer (NSCLC) is a leading cause of cancer deaths worldwide. Crizotinib has been approved by the U.S. Food and Drug Administration for the treatment of patients with advanced NSCLC. However, understanding of mechanisms of action is still limited. In our studies, we confirmed crizotinib-induced apoptosis in A549 lung cancer cells. In order to assess mechanisms, small molecular docking technology was used as a preliminary simulation of signaling pathways. Interesting, our results of experiments were consistent with the results of computer simulation. This indicates that small molecular docking technology should find wide use for its reliability and convenience.
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Association Between Green Tea and Colorectal Cancer Risk: A Meta-analysis of 13 Case-control StudiesWang, Xue-Jun;Zeng, Xian-Tao;Duan, Xiao-Li;Zeng, Huan-Chao;Shen, Rui;Zhou, Ping 3123
Objective: Experimental studies have suggested green tea to be a chemopreventive agent for colorectal cancer, and many studies have examined possible associations. However, the conclusions were inconsistent or even contradictory, so we performed a meta-analysis based on published case-control studies to explore if green tea is indeed a protective factor. Methods: PubMed was searched up to May$10^{th}$ , 2012 for relevant studies, and references of included studies were manually searched. Finally 13 eligible studies, involving 12,636 cases and 38,419 controls were identified. After data extraction, a meta-analysis was performed using CMA v2 software. Results: The results indicated there may be a weak but not statistically significant reduced risk of colorectal cancer with high dose of green tea intake (OR=0.95, 95% CI:0.81-1.11, p=0.490.69-0.98). This protective effect was also found in all subgroups, except in American and European populations. Sensitivity analysis indicated the result to be robust. Publication bias was not detected by either funnel plot or Egger tests. Conclusion: The results of this meta-analysis indicate a weak lower tendency for colorectal cancer development with green tea consumption, but available epidemiologic data are insufficient to conclude that green tea may protect against colorectal cancer in humans. -
Nazik, Evsen;Arslan, Sevban;Nazik, Hakan;Narin, Mehmet Ali;Karlangic, Hatice;Koc, Zeynep 3129
Diagnosis and treatment procedures in cancers and resulting anxiety negatively affect the individual and the family. Particularly treatment methods may generate psychological symptoms. The aim of this study was to determine the level of such symptoms in Turkish gynecologic cancer patients receiving chemotherapy. A total of 41 patients who were referred to our gynecologic oncology research clinic between January-March 2012, receiving 3 months or more chemotherapy and who agreed to participate were enrolled in study. All the data were collected using a personal information form, Edmonton Symptom Assesment System and State-Trait Anxiety Inventory. Patients received highest point average from fatigue symptom ($6.53{\pm}2.67$ ) and lowest point average from dyspnea ($1.53{\pm}3.03$ ) according to Edmonton Symptom Assesment System. The mean State Anxiety score of patients was$43.1{\pm}9.77$ and mean Trait Anxiety score was$46.7{\pm}7.01$ . Comparing symptoms of patients and mean State Anxiety score it was found that there was a statistically significant corelation with symptoms like pain (p<0.05), sadness (p<0.001), insomnia (p<0.05), state of well being (p<0.001) and dyspnea (p<0.05). Similarly comparing symptoms of patients and mean Trait Anxiety score demonstrated significant correlations for fatigue (p<0.05), sadness (p<0.01), insomnia (p<0.01) and state of well-being (p<0.01). As a result, patients with gynecological cancers experienced symptoms related to chemotherapy and a moderate level of anxiety. In accordance, appropriate interventions should recommended for the evaluation and improvement of anxiety and symptoms related to treatment in cancer patients. -
Gerceker, Gulcin Ozalp;Yilmaz, Hatice Bal 3135
This study was designed to adapt the Turkish versions of scales to evaluate fatigue in children with cancer from the perspectives of the children, parents and staff. The objective of this study was to validate "Child Fatigue Scale-24 hours" (CFS-24 hours), "Parent Fatigue Scale-24 hours" (PFS-24 hours) and "Staff Fatigue Scale-24 hours" (SFS-24 hours) for use in Turkish clinical research settings. Translation of the scales into Turkish and validity and reliability tests were performed. The validity of the translated scales was assessed with language validity and content validity. The reliability of the translated scales was assessed with internal consistency. The scales were evaluated by considering the following: calculation of the Cronbach alpha coefficient for parallel form reliability with 52 pediatric cancer patients, 86 parents and 43 nurses. The internal consistency was estimated as 0.88 for the Child Fatigue Scale-24 hours, 0.77 for the Parent Fatigue Scale-24 hours, and 0.72 for the Staff Fatigue Scale-24 hours (Cronbach's${\alpha}$ ). The Turkish version of the Child Fatigue Scale -24 hours, the Parent Fatigue Scale -24 hours and the Staff Fatigue Scale -24 hours were judged reliable and valid instruments to assess fatigue in children and showed good psychometric properties. These scales should assist in understanding to what extent initiatives can minimize or eliminate fatigue. Our scales are recommended for further studies and use in pediatric oncology clinics as routine measurements and nursing initiatives should be planned accordingly. -
Sun, Jia-Yang;Shi, Lei;Gao, Xu-Dong;Xu, Shao-Fa 3143
Background: Previous studies investigating the association of physical activity with risk of lung cancer reported conflicting results. In order to update and improve available evidence on any link, a meta-analysis was performed. Method: We searched the PubMed database for prospective cohort studies investigating the relation of physical activity with risk of lung cancer. The pooled relative risk (RR) with its 95% confidence intervals (95%CI) was used to assess the association. Results: We included 14 prospective studies with a total of 1,644,305 participants, with 14,074 incident lung cancer cases documented during follow-up. Meta-analysis of all 14 studies suggested both high and medium levels of physical activity to be associated with decreased risk of lung cancer compared to the reference group with low level of physical activity (for high level, RR = 0.77, 95%CI 0.73-0.81, P < 0.001; for medium level, RR = 0.87, 95%CI 0.83-0.90, P < 0.001). Subgroup analyses by gender found obvious associations in both men and women. No publication bias was observed. Conclusion: Our findings suggest that high and medium levels of physical activity have a beneficial effect on lung cancer by reducing the overall risk of tumour development among both men and women. -
Selcukbiricik, Fatih;Tural, Deniz;Buyukunal, Evin;Serdengecti, Suheyla 3149
Objective: The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated but not clearly clarified. The objective of our study was to investigate the role of PNI as prognostic factor in patients undergoing curative surgical resection and without distant metastasis in comparison with other clinicopathological factors. Methods: Between 2001 and 2010, 287 cases of gastric adenocarcinoma underwent radical gastrectomy recorded in hospital based registries. PNI was assessed as positive when cancer cells were seen in the perinerium or neural fascicles intramurally. Categorical and continuous variables were summarized using descriptive statistics and compared using chi-square and Mann-Whitney U tests, respectively. Cancer related survival rates were estimated by the Kaplan-Meier method. Results: PNI was positive in 211 of 287 cancers (73%), with a positive relation to lymph node metastases and advanced stage (p=0.0001, p=0.0001, respectively), mural invasion, and lymphatic and blood vessel invasion (p=0.0001, p=0.0001, respectively). The median survival of the PNI positive patients was significantly shorter than that of their PNI negative counterparts (24.1 versus 38.2 months, p=0.008). In the multivariate analysis, we detected PNI was an independent prognostic factor (p=0.025, HR=1.21, 95% CL 1.08-2.3) along with classical clinicopathological variables such as lymph node involvement (p=0.001), pT stage (p=0.03), and LVI (p=0.017), but not age, gender, tumour localization, stage, histologic type, and surgery procedure. Conclusions: PNI positivity in gastric cancers was related mural invasion, lymph node involvement, advanced stage and lymphatic and venous blood vessels. The presence of PNI appeared as an independent prognostic factor on survival on multivariate analysis, not influenced by tumor stage, lymph node metastases and other classical factors. -
Berraho, Mohamed;Bendahhou, Karima;Obtel, Majdouline;Zidouh, Ahmed;Benider, Abdellatif;Errihani, Hassan;Nejjari, Chakib 3153
Background: In Morocco, the epidemiological profile of cervical cancer is not well established. The focus of the present study was both epidemiological and pathological characteristics. Methods: For all cases of cervical cancer treated between 2003 and 2007 in the National Institute of Oncology and the Oncology Department of the IbnRochd hospital (Casablanca), 900 cases were randomly selected. Results: The mean age was$52.1{\pm}11.8$ years. The most (90.5%) represented histological type was squamous cell carcinoma. For more than 57.0% cases the mean distance between patient's origin and center of treatment was greater than 100km. According to the FIGO classification, only 17.2% of patients were identified as being in early stages (0 and I). For 72.2% patients the follow-up did not exceed 2 years. At 1 year of following-up 55.8% of patients were alive and 43.4% were lost to following-up. Conclusion: Our study addressed the issue of the burden of cervical cancer in Morocco. The result provides a basis for decision-makers for the development of strategic measures to implement the fight against cervical cancer in Morocco. -
Berraho, Mohamed;Najdi, Adil;Mathoulin-Pelissier, Simone;Salamon, Roger;Nejjari, Chakib 3159
Background: For cervical cancer the epidemiological profile is poorly known in Morocco and no data is available concerning the direct medical costs. The purpose of this work is to estimate the direct cost of medical management of invasive cervical cancer during the first year after diagnosis in Morocco. Methods: The estimation of direct costs of medical management of invasive cervical cancer during the first year after diagnosis in Morocco is based on the estimation of individual cost in each stage which covers diagnosis, treatment and follow-up during first year. The cost was estimated per patient and whole cycle-set using the costs for each drug and procedure as indicated by the Moroccan National Agency for Health Insurance. Extrapolation of the results to the whole country was used to calculate the total annual cost of cervical cancer treatments in Morocco. Results: Overall approximately 1,978 new cases of cervical cancer occur each year in Morocco. The majority (82.96%) of these cases were diagnosed at a late stage (stageII or more). The cost of one case of cervical cancer depends on stage of diagnosis, the lowest cost is $382 for stageCis followed by the cost of stageIA1 for young women (< 40 years) which is $2,952. The highest cost is for stageIV, which is $7,827. The total cost of cervical cancer care for one year after diagnosis is estimated at $13,589,360. The share allocated to treatment is the most important part of the global care budget with an annual sum of $13,027,609 whereas other cost components are represented as follows: $435,694 for annual follow-up activity and $126,057 for diagnosis and preclinical staging. Conclusion: This study provides health decision-makers with a first estimate of costs and the opportunity to achieve the optimal use of available data to estimate the needs of health facilities in Morocco. -
Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Man, Dong-Liang;Shang, Hong 3165
Objective: Genetic polymorphisms in metabolic enzymes are associated with numerous cancers. A large number of single nucleotide polymorphisms (SNPs) in the CYP2D6 gene have been reported to associate with cancer susceptibility. However, the results are controversial. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to summarize the evidence for associations. Methods: Studies focusing on the relationship between CYP2D6 gene polymorphisms and susceptibility to cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software. Odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated. Results: According to the inclusion criteria, forty-three studies with a total of 7,009 cancer cases and 9,646 healthy controls, were included in the meta-analysis. The results showed that there was a positive association between heterozygote (GC) of rs1135840 and cancer risk (OR=1.92, 95%CI: 1.14-3.21, P=0.01). In addition, we found that homozygote (CC) of rs1135840 might be a protective factor for cancer (OR=0.58, 95%CI: 0.34-0.97, P=0.04). Similarly, the G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 had negative associations with cancer risk (OR=0.69, 95%CI: 0.48-0.99, P=0.04; OR=0.60, 95%CI: 0.38-0.94, P=0.03; OR=0.50, 95%CI: 0.26-0.95, P=0.03; respectively). Conclusion: This meta-analysis suggests that CYP2D6 gene polymorphisms are involved in the pathogenesis of various cancers. The heterozygote (GC) of rs1135840 in CYP2D6 gene might increase the risk while the homozygote (CC) of rs1135840, G allele and G carrier (AG + GG) of rs16947 and heterozygote (A/del) of rs35742686 might be protective factors. -
He, Long-Jun;Cai, Mu-Yan;Xu, Guo-Liang;Li, Jian-Jun;Weng, Zi-Jin;Xu, Da-Zhi;Luo, Guang-Yu;Zhu, Sen-Lin;Xie, Dan 3173
The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis. -
Chia, Sin-Eng;Wong, Kin-Yoke;Cheng, Christopher;Lau, Weber;Tan, Puay-Hoon 3179
Background: Most of the epidemiology studies on the effects of sun exposure and prostate cancer were conducted among the temperate countries of North America and Europe. Little is known about the influence on Asian populations. The purpose of current study was to evaluate any association of sun exposure with risk of prostate cancer in Chinese, Malays and Indians who reside in the tropics. Methods: The Singapore Prostate Cancer Study is a hospital-based case-control study of 240 prostate cancer incident cases and 268 controls conducted in Singapore between April 2007 and May 2009. Detailed information on outdoor activities in the sun, skin colour, sun sensitivity and other possible risk factors were collected in personal interviews. Cases were further classified by Gleason scores and TNM staging. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis, adjusted for age, ethnicity, education, family history of any cancers, BMI and skin colour. Results: We found that prostate cancer risk was increased in subjects with black/dark-brown eyes (OR 5.88, 95%CI 3.17-10.9), darker skin colour e.g. tan/dark brown/black (OR 7.62, 95%CI 3.41-17.0), frequent sunburn in lifetime (OR 4.30, 95%CI 1.7-11.2) and increased general sun exposure in adulthood per week (OR 2.03, 95%CI 1.09-3.81). The increased risk was consistent for high grade tumours and advanced stage prostate cancers. Conclusion: The findings from this study suggest that excessive sun exposure is a risk factor for prostate cancer in Asians. -
This study evaluated the relationship between pretreatment hemoglobin (Hb) and prognostic factors in Thai patients with endometrial cancer. Medical records of 228 patients who had undergone surgery between January 2005 and December 2007 were retrospectively reviewed. Associations between clinicopathological variables and pretreatment Hb levels were described using Pearson's chi square test or two-tailed Fisher's exact test. Survival analysis was performed with Kaplan-Meier estimates. Univariate and Cox-regression models were used to evaluate the prognostic impact of various factors, including Hb levels, in term of disease-free survival. The median duration of follow-up was 38.2 months. Eighty-nine patients (39%) had a preoperative Hb level of <12 g/dL, these having significantly higher rates of non-endometrioid histology, advanced FIGO stage, lymphovascular space invasion, cervical involvement, adnexal involvement, positive peritoneal cytology, and lymph node involvement than patients with Hb
${\geq}12$ g/dL. The 5-year disease-free and overall survival were significantly lower in patients with pretreatment Hb levels <12 g/dL compared with those with Hb${\geq}12$ g/dL (79.3% vs. 89.2%, p=0.044 and 87.6% vs. 99.3%, p<0.001, respectively). In the multivariate analysis only histology, myometrial invasion, and lymphovascular invasion proved to be independent prognostic factors, whereas tumor grading, stage, cervical involvement, adnexal involvement, positive peritoneal cytology, lymph node involvement, and low Hb were not. In conclusion, presence of anemia before treatment may reflect poor prognostic factors in patients with endometrial cancer and low pretreatment hemoglobin level may have a prognostic impact on clinical outcome. -
Xiong, Zheng-Ping;Huang, Fang;Lu, Meng-Hou 3191
Objective: To investigate the association between the change of IGF-2 level in serum after transcatheter arterial chemoembolization (TACE) and hepatocellular carcinoma (HCC) progression, especially in relation to metastasis. Methods: IGF-2 in serum was measured by quantitative sandwich enzyme-linked immunosorbent assaybefore, 3 days and 4 weeks after TACE in 60 patients with HCC. The occurrence of HCC metastasis was also evaluated, 3 months after TACE. Results: (1) The average serum level of IGF-2 in the 60 patients with HCC was$136.5{\pm}87.3$ pg/ml; (2) A tendency for increase was observed with heterogenous uptake of octreotide and portal vein thrombosis. Metastatic foci were found in 37/38 patients in the group with IGF-2 increasing (97.0%), in contrast to 3/22 (13.6%) patients with IGF-2 decrease. Conclusion: The increase of IGF-2 level in serum appears to be associated with the occurrence of metastatic HCC after TACE and chemotherapy. -
Aims: This study was designed to describe the personal life experiences of breast cancer survivors regarding their efforts to recover and preserve their health in Taiwan. Method: The study utilized a qualitative research method, wherein purposive sampling, one-on-one, face-to-face, in-depth semi-structured interviews were conducted. The data were then analyzed using content analysis. Data were saturated after interviewing 15 cancer survivors. Results: Three common themes emerged: introspection on the cause of the cancer, realization of a harmonized lifestyle, and reflecting on the strong will to survive. Conclusions: These findings are helpful in understanding the relationship between breast cancer survival and individual efforts to restore and preserve health.
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Xu, Ling;Dai, Wei-Qi;Xu, Xuan-Fu;Wang, Fan;He, Lei;Guo, Chuan-Yong 3203
Backgrounds: To investigate the inhibiting effects of multi-target anti-microRNA antisense oligonucleotide (MTg-AMOs) on proliferation and migration of human gastric cancer cells. Methods: Single anti-microRNA antisense oligonucleotides (AMOs) and MTg-AMOs for miR-221, 21, and 106a were designed and transfected into SGC7901, a gastric cancer cell line, to target the activity of these miRNAs. Their expression was analyzed using stem-loop RT-PCR and effects of MTg-AMOs on human gastric cancer cells were determined using the following two assay methods: CCK8 for cell proliferation and transwells for migration. Results: In the CCK-8 cell proliferation assay,$0.6{\mu}mol/L$ was selected as the preferred concentration of MTg-AMOs and incubation time was 72 hours. Under these experimental conditions, MTg-AMOs demonstrated better suppression of the expression of miR-221, miR-106a, miR-21 in gastric cancer cells than that of single AMOs (P = 0.014, 0.024; 0.038, respectively). Migration activity was also clearly decreased as compared to those in randomized and blank control groups ($28{\pm}4$ Vs$54{\pm}3$ , P <0.01;$28{\pm}4$ Vs$59{\pm}4$ , P < 0.01). Conclusions: MTg-AMOs can specifically inhibit the expression of multiple miRNAs, and effectively antagonize proliferation and migration of gastric cancer cells promoted by oncomirs. -
Introduction: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the older population, but it is also quite frequent among young adults in developing countries. The aim of this study was to update the trends of clinicopathological features of CRC in young Nepalese. Methods: A retrospective comparative study on the data retrieved from the surgical records of all patients between 20 to 39 years of age with CRC was carried out for periods of 5 years each from 1999 to 2003 (early) and 2004 to 2008 (recent), treated at Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Results: The number of young adults with CRC increased from 28 to 34. However, the proportion of young patients in both groups was 28% of all CRC patients. The mean ages were
$34{\pm}4.7$ and$31.8{\pm}5.1$ years in early and recent 5 years, respectively, and the male female ratio changed from 2:3 to 4:3. Abdominal pain as the most common presenting symptom was replaced by bleeding per rectum in recent years. The mean duration from onset of symptoms to seeking medical advice decreased from 7.8 months to 5.6 months in recent years. More patients (85.3%) were subjected to endoscopic examination in recent years than early years (60.7%) and right colonic cancer increased from 10.7% to 26.5%. However, the rectum was the commonest site in both early (71.4%) and recent (50%) groups. CRC was detected significantly at an earlier stage (7.1% vs 32.4%) in recent years with large proportion of modified Dukes B stage. Poorly differentiated adenocarcinoma was the predominant histology in both groups (50% vs 60.7%). Curative resection had risen in recent years (39.3% vs 73.6%). Conclusion: CRC among Nepalese young adults accounts for a high incidence (28%) of all CRC cases. Although right sided colonic cancer has been increasing, rectum is the commonest site. There is also an increasing trend for diagnosis at earlier stages of the disease which can be treated with curative intent. -
Khokher, Samina;Qureshi, Muhammad Usman;Chaudhry, Naseer Ahmad 3213
When patients with advanced breast cancer (ABC) are treated with neoadjuvant chemotherapy (NACT), efficacy is monitored by the extent of tumor shrinkage. Since their publication in 1981, World Health Organization (WHO) guidelines have been widely practiced in clinical trials and oncologic practice, for standardized tumor response evaluation. With advances in cancer treatment and tumor imaging, a simpler criterion based on one-dimensional rather than bi-dimensional (WHO) tumor measurement, named Response Evaluation Criteria in Solid Tumors (RECIST) was introduced in 2000. Both approaches have four response categories: complete response, partial response, stable disease and progressive disease (PD). Bi-dimensional measurement data of 151 patients with ABC were analysed with WHO and RECIST criteria to compare their response categories and inter criteria reproducibility by Kappa statistics. There was 94% concordance and 9/151 patients were recategorized with RECIST including 6/12 PD cases. RECIST therefore under-estimates and delays diagnosis of PD. This is undesirable because it may delay or negate switch over to alternate therapy. Analysis was repeated with a new criteria named RECIST-Breast (RECIST-B), with a lower threshold for PD (${\geq}10%$ rather than${\geq}20%$ increase of RECIST). This showed higher concordance of 97% with WHO criteria and re-categorization of only 4/151 patients (1/12 PD cases). RECIST-B criteria therefore have advantages of both ease of measurement and calculations combined with excellent concordance with WHO criteria, providing a practical clinical tool for response evaluation and offering good comparison with past and current clinical trials of NACT using WHO guidelines. -
Chowdhury, Chitta Ranjan;Kirita, Tadaaki;Jose, Maji;Abdullah, Riaz 3219
A comparative study between 17 Japanese and 19 Indian patients with oral squamous cell carcinomas (OSCCs) revealed that the tumour prognostic indicator mean vessel density (MVD) count for angiogenesis was relatively high at 57.1 in Indian as compared to 39.3 in Japanese (P=0.001) cases, whereas the lymph-vessel density (LVD) count for lymphangiogenesis was lower (12.8 vs 48.0, P=0.002). Both male and female Indians had higher MVD counts, but LVD counts were only slightly lower in females. MVD count was relatively high among the cases below 65 years old in both the countries (P=0.4). Japanese cases with Tongue cancer had higher MVD count, but the Indian cases had lower LVD counts. Size-wise, T2 and T3 had higher counts of MVD both in Indian and Japanese cases. MVD and LVD count was higher in grades II and III both in Japanese and Indian cases. There was insignificant difference of the MVD counts among smokers, but the tobacco chewers in Indian cases had higher counts of MVD and LVD (P value by Bartlett test 0.35, 0.57 respectively). The hot-spots of tumour sites had variable rates of lymphocyte infiltration showed higher MVD counts in all the cases. Although the clinical characteristics and demographic variables usually relate to MVD and LVD counts, the tendency of higher values, especially among tobacco chewers, identified as the highest risk group for occurrence of oral cancer needs to be investigated further. -
Chen, Peng;Wang, Xiu-Li;Ma, Zhong-Sen;Xu, Zhong;Jia, Bo;Ren, Jin;Hu, Yu-Xin;Zhang, Qing-Hua;Ma, Tian-Gang;Yan, Bing-Di;Yan, Qing-Zhu;Li, Yan-Lei;Li, Zhen;Yu, Jin-Yan;Gao, Rong;Fan, Na;Li, Bo;Yang, Jun-Ling 3223
HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding protein) family which may function as a nucleosomal binding and transcriptional activating protein. Overexpression of HMGN5 has been observed in several human tumors but its role in tumorigenesis has not been fully clarified. To investigate its significance for human lung cancer progression, we successfully constructed a shRNA expression lentiviral vector in which sense and antisense sequences targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU incorporation and colony formation assays. Furthermore, flow cytometry analysis showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1 phase and decreased the populations of A549 and H1299 cells at the S and G2/M phases. Taken together, these results suggest that HMGN5 is directly involved in regulation cell proliferation in A549 and H1299 cells by influencing signaling pathways involved in cell cycle progression. Thus, our finding suggests that targeting HMGN5 may be an effective strategy for human lung cancer treatment. -
Haroon, A.S.;Gupta, S.M.;Tyagi, B.B.;Farhat, J. 3229
In this study, cancer incidence data were assessed to provide various rates of five year age groups for a given year, lying between two census years. The individual exponential growth rate method is most useful in both population-based and non-population cased cancer registries in India to estimate the population by five yearly age groups and also find the rates of crude rates, age standard rates and cumulative rates. This method has been shown to endure from bias and often results sacrificing the overall growth rate and correction factor must be needful in five year age group population to maintain it. A second method, the difference distribution method is also able to maintain the overall growth rate and overcome the bias in estimation of five yearly age group populations. From this point of view these methods serving a new technique for population estimation by five yearly age groups for inter census years. -
Xu, Chun-Sheng;Zheng, Jian-Yong;Zhang, Hai-Long;Zhao, Hua-Dong;Zhang, Jing;Wu, Guo-Qiang;Wu, Lin;Wang, Qing;Wang, Wei-Zhong;Zhang, Jian 3233
Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor prognosis. Understanding the molecular mechanisms underlying esophageal cancer progression is a high priority for improved EC diagnosis and prognosis. Recently, MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas. However, little is known about its function in esophageal carcinomas. We therefore examined the effects of MSP58 knockdown on the growth of esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a better understanding of its potential as a tumor therapeutic target. We employed lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of ESCC cell proliferation and colony formation in vitro. Furthermore, flow cytometry and western blot analyses revealed that MSP58 depletion induced cell cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably, the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts in nude mice. Our results suggest that MSP58 may play an important role in ESCC progression. -
Wang, Dong-Chun;Zhang, Yan;Chen, Hai-Yan;Li, Xiao-Li;Qin, Li-Juan;Li, Ya-Juan;Zhang, Hong-Yi;Wang, Shuo 3239
Gliomas are a group of heterogeneous primary central nervous system tumors. Hyperthermia has proven to be a potential therapeutic tool for cancers in the clinic. However, the molecular mechanisms of hyperthermia remain unclear. The objective of this study was to investigate the effects of hyperthermia on the invasiveness in C6 glioma cells and related molecular pathways. Here our data show hyperthermia stimulated the release of tumor necrosis factor-alpha (TNF-${\alpha}$ ) and decreased C6 glioma cell migration and invasive capability at 30, 60, 120 and 180 min; with increased spontaneous apoptosis in C6 glioma cells at 120 min. We also found mitogen-activated protein kinase (P38 MAPK) protein expression to be increased and nuclear factor-kappa B (NF-${\kappa}B$ ) protein expression decreased. Based on the results, we conclude that hyperthermia alone reduced invasion of C6 glioma cells through stimulating TNF-${\alpha}$ signaling to activate apoptosis, enhancing P38 MAPK expression and inhibiting the NF-${\kappa}B$ pathway, a first report in C6 rat glioma cells. -
Li, Cheng-Gang;Zhao, Zhi-Ming;Hu, Ming-Geng;Liu, Rong 3247
Aim: We conducted a prospective study in an Chinese population to detect associations of GSTM, GSTT and GSTP polymorphisms with hepatocellular carcinoma (HCC), and analyze roles in determining survival outcome. Methods: A prospective follow-up study was conducted with 476 HCC patients and 481 controls collected from May 2005 to May 2007. All patients were followed up until the end of Dec. 2011. GSTM1, GSTT1 and GSTP1 genotyping were performed by PCR-CTPP methods. Results: Null GSTM1 carriers had a 1.64 fold risk of HCC compared with non-null genotype, while GSTP1 Val/Val carriers had a 93% increased risk over the GSTP1 IIe/IIe genotype. The median follow-up time for the 476 patients was 34.2 months (range: 1 to 78 months). Individuals with null GSTM1 genotype had better survival of HCC than non-null genotype carriers (HR=0.71, 95%CI=0.45-0.95). Similarly, GSTP1 Val/Val genotypes had significant better survival than the GSTP1 IIe/IIe genotype (HR=0.34, 95%CI=0.18-0.65). Individuals carrying null GSTM1 and GSTP1 Val/Val who received chemotherapy had lower risk of death from HCC than those without chemotherapy. Conclusion: This study indicated carriage of null GSTM1 and GSTP1 Val/Val genotypes to have roles in susceptibility to and survival from HCC. -
Liu, Wen-Jing;Zeng, Xian-Tao;Qin, Hai-Feng;Gao, Hong-Jun;Bi, Wei-Jing;Liu, Xiao-Qing 3253
Objective: To evaluate the efficacy and safety of whole brain radiotherapy (WBRT) plus chemotherapy versus WBRT alone for treating brain metastases (BM) from lung cancer by performing a meta-analysis based on randomized controlled trials (RCTs). Methods: The PubMed, Embase, CENTRAL, ASCO, ESMO, CBM, CNKI, and VIP databases were searched for relevant RCTs performed between January 2000 and March 2012. After quality assessment and data extraction, the meta-analysis was performed using the RevMan 5.1 software, with funnel plot evaluation of publication bias. Results: 19 RCTs involving 1,343 patients were included. The meta-analyses demonstrated that compared to WBRT alone, WBRT plus chemotherapy was more effective with regard to the objective response rate (OR = 2.30, 95% CI = 1.79 - 2.98; P < 0.001); however, the incidences of gastrointestinal reactions (RR = 3.82, 95% CI = 2.33 - 6.28, P <0.001), bone marrow suppression (RR = 5.49, 95% CI = 3.65 - 8.25, P < 0.001), thrombocytopenia (RR = 5.83, 95% CI = 0.39 - 86.59; P = 0.20), leukopenia (RR = 3.13, 95% CI = 1.77 - 5.51; P < 0.001), and neutropenia (RR = 2.75, 95% CI = 1.61 - 4.68; P < 0.001) in patients treated with WBRT plus chemotherapy were higher than with WBRT alone. There was no obvious publication bias detected. Conclusion: WBRT plus chemotherapy can obviously improve total efficacy rate, butalso increases the incidence of adverse reactions compared to WBRT alone. From the limitations of this study, more large-scale, high-quality RCTs are suggested for further verification. -
Hassan, Zeinab Korany;Daghestani, Maha Hassan 3259
Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and$40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells. -
Clinically, elevated cancer antigen 125 (CA-125) in blood predicts tumor burden in a woman's body, especially in the ovary, but cannot differentiate between malignant or benign. We here used intensive modern proteomic approaches to identify predictive proteins in the serum of women with elevated CA-125 to differentiate malignant from benign ovarian tumors. We identified differentially expressed proteins in serum samples of ovarian cancer (OC) patients, benign ovarian tumor (BT) patients, and healthy control women using mass spectrometry-based quantitative proteomics. Both the OC and BT patients had elevated CA-125. Quantitation was achieved using isobaric tags for relative and absolute quantitation. We obtained 124 quantified differential serum proteins in OC compared with BT. Two proteins, apolipoprotein A-4 (APOA4) and natural resistance-associated macrophage 1, were verified using Western blotting. Proteome profiling applied to OC cases identified several differential serum proteins in the serum of women with elevated CA-125. A novel protein, APOA4, has the potential to be a marker for malignant tumor differentiation in the serum of women with elevated CA-125.
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Park, Jin Kyun;Park, Hyun Ah;Park, Jin Joo;Cho, Young Gyu 3271
Purpose : This study was performed to assess whether the weight status is associated with screening rates of breast and cervical cancer in Korean women. Methods: Study participants included women aged between 30 and 80 years from the 4th Korea National Health and Nutrition Examination Survey from 2007 to 2009. Body mass index was classified into${\sim}18.4kg/m^2$ (underweight),$18.5{\sim}22.9kg/m^2$ (normal),$23{\sim}24.9kg/m^2$ (overweight),$25.0{\sim}29.9kg/m^2$ (moderate obesity) and$30.0kg/m^2$ ~ (severe obesity) according to the Asia Pacific Standards of WHO recommended definition of obesity. Screening rates of breast and cervical cancer were estimated by the recommendation of the National Cancer Screening Program of the National Cancer Center, Korea. Results : The overall screening rates for breast and cervical cancer were 51.3% and 50.1%, respectively. After covariate adjustment, the screening rates for breast cancer (adjusted odds ratio, 0.70; 95% confidence interval, 0.51 to 0.97) and cervical cancer (adjusted odds ratio, 0.71; 95% confidence interval, 0.53 to 0.94) were significantly lower in the women with severe obesity. Conclusion: Obesity is associated with lower compliance with breast and cervical cancer screening guidelines in Korean women. -
Xiong, Yu;Lu, Qing-Jun;Zhao, Jing;Wu, Guo-Yang 3275
Recently, population-based studies of type 2 diabetes patients have provided evidence that metformin treatment is associated with a reduced cancer incidence and mortality, but its mode of action remains unclear. Here we report effects of metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular mechanisms of metformin activity. Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Furthermore, we showed that metformin strongly attenuated colony formation and dramatically inhibited Hep-G2 tumor growth in vivo. In conclusion, our studies suggested that metformin might have potential as a cytotoxic drug in the prevention and treatment of HCC. -
Siriaunkgul, Sumalee;Utaipat, Utaiwan;Suwiwat, Supaporn;Settakorn, Jongkolnee;Sukpan, Kornkanok;Srisomboon, Jatupol;Khunamornpong, Surapan 3281
Objectives: To evaluate the clinicopathologic correlation and prognostic value of HPV18 DNA viral load in patients with early-stage cervical neuroendocrine carcinoma (NECA). Methods: Formalin-fixed, paraffin-embedded tissue of cervical NECA patients with known HPV18 infection and clinicopathologic data including follow-up results were collected. The HPV18 DNA load was assessed with quantitative PCR targeting the HPV18 E6E7 region. Results: Twenty-one patients with early-stage (IB-IIA) cervical NECA were identified. HPV18 DNA viral load ranged from 0.83 to 55,174 copies/cell (median 5.90). Disease progression, observed in 10 cases (48%), was not significantly associated with any clinicopathologic variables. However, the group of patients with progressive disease tended to have a higher rate of pelvic lymph node metastasis (50% versus 9%, p=0.063) and a lower median value of HPV18 DNA viral load (4.37 versus 8.17 copies/cell, p=0.198) compared to the non-recurrent group. When stratified by a cut-off viral load value of 5.00 copies/cell, the group of patients with viral load${\leq}5.00$ copies/cell had a significantly shorter disease-free survival than the group with viral load >5.00 copies/cell (p=0.028). The group with a lower viral load also tended to have a higher rate of disease progression (75% versus 31%, p=0.080). No significant difference in the other clinicopathologic variables between the lower and higher viral load groups was identified. Conclusion: HPV18 DNA viral load may have a prognostic value in patients with early-stage NECA of the cervix. A low viral load may be predictive of shortened disease-free survival in these patients. -
Phua, Chee Ee;Tan, Boon Seang;Tan, Ai Lian;Eng, Kae Yann;Ng, Bong Seng;Malik, Rozita Abdul;Ishak, Wan Zamaniah Wan 3287
Purpose: To study the overall treatment time (OTT) and acute toxicity of intensity-modulated radiotherapy (IMRT) treatment for nasopharyngeal carcinoma (NPC). Methods: This retrospective study covered all NPC patients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February 2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Information was collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/or concurrent chemotherapy, acute toxity and completion of IMRT within the OTT. Results: A total of 26 NPC patients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% received neo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed the treatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade 2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis (57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in 19.2%. However, haematological toxicity was mild with only one patient having leucopaenia. Conclusion: IMRT treatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT in the majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional and analgesic support is required throughout the treatment. -
Anchuri, Shyam Sunder;Thota, Sreekanth;Yerra, Rajeshwar;Devarakonda, Krishna Prasad;Dhulipala, Satyavati 3293
The present study was conducted to evaluate in vivo anticancer activity of two novel mononuclear ruthenium(II) compounds, namely Ru(1,10-phenanthroline)$_2$ (2-nitro phenyl thiosemicarbazone)$Cl_2$ (Compound$R_1$ ) and Ru (1,10-phenanthroline)$_2$ (2-hydroxy phenyl thiosemicarbazone)$Cl_2$ (Compound$R_2$ ) against Ehrlich ascites carcinoma (EAC) mice and in vitro cytotoxic activity against IEC-6 (small intestine) cell lines and Artemia salina nauplii using MTT [(3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide)] and BLT [brine shrimp lethality] assays respectively. The tested ruthenium compounds at the doses 2 and 4 mg/kg body weight showed promising biological activity especially in decreasing the tumor volume, viable ascites cell counts and body weights. These compounds prolonged the life span (% ILS), mean survival time (MST) of mice bearing-EAC tumor. The results for in vitro cytotoxicity against IEC-6 cells showed the ruthenium compound$R_2$ to have significant cytotoxic activity with a$IC_{50}$ value of$20.0{\mu}g/mL$ than$R_1$ ($IC_{50}=78.8{\mu}g/mL$ ) in the MTT assay and the$LC_{50}$ values of$R_1$ and$R_2$ compounds were found to be 38.3 and$43.8{\mu}g/mL$ respectively in the BLT assay. The biochemical and histopathological results revealed that there was no significant hepatotoxicity and nephrotoxicity associated with the ruthenium administration to mice. -
Association Between XPD Asp312Asn Polymorphism and Esophageal Cancer Susceptibility: A Meta-analysisDuan, Xiao-Li;Gong, Heng;Zeng, Xian-Tao;Ni, Xiao-Bing;Yan, Yan;Chen, Wen;Liu, Guo-Lei 3299
Objective: To investigate the association between xeroderma pigmentosum group D (XPD) Asp312Asn polymorphism and esophageal cancer (EC) susceptibility by meta-analysis. Methods: We searched PubMed up to April 9th, 2012, to identify relevant papers, and 8 published case-control studies including 2165 EC patients and 3141 healthy controls were yielded. Odds ratios (ORs) with relevant 95% confidence intervals (CIs) were applied to assess the association between XPD Asp312Asn polymorphism and EC susceptibility with the Comprehensive Meta-Analysis software, version 2.2. Results: Overall, the meta-analysis results suggested the XPD Asp312Asn polymorphism to be significantly associated with EC susceptibility [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.20, 95%CI=1.05-1.36, p=0.01; and Asp/Asn vs. Asp/Asp: OR=1.15, 95%CI =1.01-1.31, p=0.04]. In the subgroup analysis by ethnicity and cancer type, significantly associations were found for Caucasian populations [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.26, 95%CI =1.08-1.47, p<0.001; Asp/Asn vs. Asp/Asp: OR=1.19, 95%CI =1.02-1.40, p=0.03] and esophageal squamous cell carcinoma [(Asn/Asn+Asp/Asn) vs. Asp/Asp: OR=1.19, 95%CI=1.01-1.41, p=0.04]. There was no heterogeneity and no publication bias existed. Conclusions: This meta-analysis shows that the XPD Asp312Asn polymorphism may be a risk factor for developing EC, especially for Caucasian populations and esophageal squamous cell carcinoma. -
Guleria, Kamlesh;Sharma, Sarika;Manjari, Mridu;Uppal, Manjit Singh;Singh, Neeti Rajan;Sambyal, Vasudha 3305
Background: The present study aimed to find the prognostic implications of two polymorphisms in TP53 (p.R72P, PIN3 Ins16bp) and one in CCR5 ($CCR5{\Delta}32$ ) in sporadic breast cancer patients. Methods: DNA samples of 80 breast cancer patients and 80 age and gender matched unrelated healthy control individuals from Punjab, North West India were analyzed. Results: For p.R72P, the genotype frequency was 13.8% (RR), 58.8% (RP), 27.5% (PP) in patients and 33.9% (RR), 40.0% (RP), 26.5% (PP) in controls. For PIN3 Ins16bp, the genotype frequencies were 53.75% (A1A1), 37.5% (A1A2), 8.75% (A2A2) in patients and 66.3% (A1A1), 31.3% (A1A2), 2.5% (A2A2) in controls. Only 4 (5%) breast cancer patients were heterozygous for$CCR5{\Delta}32$ deletion. Common RR-A1A1-WT/WT genotype was lower while RP-A1A2-WT/WT genotype was higher in patients as compared to controls. RP-A1A1-WT/WT genotype was significantly higher in patients as compared to control individuals (p = 0.008). Conclusion: Though a clear association of any particular genotype with sporadic breast cancer or stage was not apparent, the results of present study were suggestive that sporadic breast cancer patients with RR-A1A1-WT/WT genotype might have a better response to chemotherapy, thus improving their chances of survival. -
Liu, Dong-Fu;Wu, Ji-Tao;Wang, Jian-Ming;Liu, Qing-Zuo;Gao, Zhen-Li;Liu, Yun-Xiang 3313
Prostate cancer is a highly prevalent disease in older men of the western world. MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression via posttranscriptional inhibition of protein synthesis. To identify the diagnostic potential of miRNAs in prostate cancer, we downloaded the miRNA expression profile of prostate cancer from the GEO database and analysed the differentially expressed miRNAs (DE-miRNAs) in prostate cancerous tissue compared to non-cancerous tissue. Then, the targets of these DE-miRNAs were extracted from the database and mapped to the STRING and KEGG databases for network construction and pathway enrichment analysis. We identified a total of 16 miRNAs that showed a significant differential expression in cancer samples. A total of 9 target genes corresponding to 3 DE-miRNAs were obtained. After network and pathway enrichment analysis, we finally demonstrated that miR-20 appears to play an important role in the regulation of prostate cancer onset. MiR-20 as single biomarker or in combination could be useful in the diagnosis of prostate cancer. We anticipate our study could provide the groundwork for further experiments. -
Zhou, Tian-Biao;Yin, Sheng-Sheng;Huang, Jian-Jian;Ou, Chao 3319
Objective: The results from the published studies on the association between prohibitin 3' untranslated region C > T gene polymorphism and cancer risk are conflicting. This meta-analysis was performed to evaluate the relationship with cancer susceptibility overall, and to explore whether the T allele or TT genotype could become a predictive marker for cancer risk. Methods: Association studies were identified from the databases of PubMed, Embase, and Cochrane Library as of March 1, 2012, and eligible investigations were synthesized using the meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Results: Six investigations were identified for the analysis of association between the prohibitin 3' untranslated region C > T gene polymorphism and cancer risk, covering of 1,461 patients with cancer and 1,197 controls. There was a positive association between the T allele and cancer susceptibility (OR=1.20, 95% CI: 1.03-1.39, P=0.02), and CC homozygous might play a protective role (OR=0.80, 95% CI: 0.68-6.11, P=0.95). In the sub-group analysis, prohibitin 3' untranslated region C > T gene polymorphism and cancer risk appeared associated with the risk of breast cancer, but not ovarian cancer. Conclusions: Our results indicate that T allele is a significant genetic molecular marker to predict cancer susceptibility and CC genotype is protective, especially for breast cancer. However, more investigations are required to further clarify the association of the prohibitin 3' untranslated region C > T gene polymorphism with cancer susceptibility. -
Jing, Chen;Huang, Zhi-Jie;Duan, Yu-Qin;Wang, Pei-Hong;Zhang, Ru;Luo, Ke-Shu;Xiao, Xin-Rong 3325
Aim: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastric cancer, with reference to smoking and Helicobacter pylori infection. Methods: We conducted a 1:1 matched case-control study with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 and GSTP1 were determined using PCR-CTPP. Results: The GSTM1 and GSTT1 null genotypes were significantly associated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1 and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was found for GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer. Conclusion: GSTM1 and GSTT1 null genotypes are associated with increased risk of gastric cancer, and smoking modifies the association. -
Fan, Rong;Zhang, Lu-Yao;Wang, Hong;Yang, Bo;Han, Tao;Zhao, Xiao-Li;Wang, Wei;Wang, Xiao-Qin;Lin, Guo-Wei 3329
Background: Several potential risk factors have been identified for diffuse large B-cell lymphoma (DLBCL); however, epidemiological studies investigating the association between these risk factors and DLBCL have yielded inconsistent results. Objectives: To investigate potential medical, lifestyle, and environmental risk factors of DLBCL in Shanghai, China through a hospital-based case-control study. Method: One-hundred-and-forty-seven newly diagnosed DLBCL patients and 294 sex- and age-matched controls were recruited from 11 hospitals in Shanghai between 2003 and 2007. A standardized structured questionnaire was used to obtain patient data on demographics, medical history, family history, lifestyle, and environmental exposures. Conditional logistic regression models were used to estimate odds ratios (ORs), with 95% confidence intervals (CIs), for risk associated with each data category. Results: History of tuberculosis (TB) infection and "living on a farm" were positively associated with DLBCL (TB: OR=3.05, 95% CI: 1.19-7.80; farm: OR=1.82, 95% CI: 1.21-2.73). In contrast, taking traditional Chinese medicine was negatively associated with DLBCL (OR=0.36, 95% CI: 0.14-0.89). No significant correlation with DLBCL risk was found for any of the other potential risk factors (p>0.05), including but not limited to hair dyes, alcohol drinking, smoking, and home/workplace renovation within one year. Conclusions: Consistent with results from previous studies in other DLBCL case populations, traditional Chinese medicine appeared to have a direct or indirect protective effect against DLBCL. However, this study also identified a possible predisposition for DLBCL in TB sufferers and farmers. -
Haidari, Mohmmad;Nikbakht, Mohammad Reza;Pasdar, Yahya;Najafi, Farid 3335
Objective: gastric cancer is the fourth most common cancer worldwide. While it is one of the most common cancers in Iran, there are only limited data regarding incidence trends in the country. This study is the first of its type to investigate trends across six geographical areas during 2000-2005 using cancer registry data. Materials and methods: The registered data for gastric cancer cases in National Cancer Registry System were extracted from the Ministry of Health and Medical Education, Center for Disease Control & Management, code C16. First, according to WHO population, the sex-standardized incidence rate in both sexes and then the trends of incidence rate during 2000-2005 were investigated separately for different geographical areas of the country. Results: the incidence rates of gastric cancer in Iran and its six geographical areas during 2000-2005 were increasing albeit with differences in their slopes. The overall incidence rate increased from 2.8 in 2000 to 9.1 per 100,000 persons per year in 2005, rising from 4.1 to 13.2 in men. The average six-year incidence of gastric cancer in the central and northwestern border of Caspian Sea was 7.8 per 100,000 persons per year, while it was 0.9 per 100,000 persons per year in the border of the Persian Gulf. Generally the incidence rate in men was higher than in women. Conclusion: Iran is one of the high-risk areas for gastric cancer. Increase in incidence might continue in the future partly because of improvement in cancer registry systems as well as increase in risk of this cancer. -
Promkum, Chadamas;Butryee, Chaniphun;Tuntipopipat, Siriporn;Kupradinun, Piengchai 3343
The aim of this study was to investigate the anticlastogenicity as well as the clastogenicity of Eryngium foetidum leaf (EF) using the in vivo mouse peripheral blood erythrocyte micronucleus assay. Eighty ICR male mice were fed AIN-76 diet supplemented with ground freeze-dried EF at 0.0%, 0.8%, 1.6% and 3.2% for 2 weeks prior to the administration of both direct-acting, mitomycin C (MMC), and indirect-acting, 7, 12-dimethylbenz(a) anthracene (DMBA) clastogens. Peripheral blood samples were collected from mice just before administration of clastogen and at 24 and 48 h thereafter for MMC. Blood samples were collected at the same times and after 72 h for DMBA. Then, reticulocytes in blood samples were counted using fluorescent microscopy. The results indicated that EF had no clastogenic effect in mice. All doses of diets supplemented with EF decreased the number of micronucleated peripheral reticulocytes in all the MMC-treated groups in a dose dependent manner, but significant reduction was found only at 1.6% and 3.2% EF in the DMBA-treated groups. It can be concluded that EF has no clastogenicity, but possesses anticlastogenic potential against both direct- and indirect-acting types of clastogen in mice. -
Sabir, Noreen;Iqbal, Zafar;Aleem, Aamer;Awan, Tashfeen;Naeem, Tahir;Asad, Sultan;Tahir, Ammara H;Absar, Muhammad;Hasanato, Rana MW;Basit, Sulman;Chishti, Muhammad Azhar;Ul-Haque, Muhammad Faiyaz;Khalid, Ahmad Muktar;Sabar, Muhammad Farooq;Rasool, Mahmood;Karim, Sajjad;Khan, Mahwish;Samreen, Baila;Akram, Afia M;Siddiqi, Muhammad Hassan;Shahzadi, Saba;Shahbaz, Sana;Ali, Agha Shabbir 3349
Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than$50{\times}10^9/l$ . Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of5 fusion oncogenes in adult ALL patients, and their association with clinical features, treatment response and outcome. Frequencies of some of the oncogenes were different from those reported elsewhere and they appear to be associated with distinct clinical characteristics and treatment outcome. This information will help in the prognostic stratification and risk adapted management of adult ALL patients. -
Objective: This study was to present the survival of advanced cancer patients and explore the influence of various factors on survival time as well as survival rate. The results provide guidelines for clinical practice of cancer treatment. Methods: Follow-up of 674 advanced cancer patients was performed in a hospice. The median survival time and survival rate were calculated, and survival analysis was carried out. Results: The median survival time of all patients dying from cancer was 12.0 months and the average survival time was 25.1 months. The 1-year cumulative survival rate was
$0.518{\pm}0.020$ and the 5-year cumulative survival rate was$0.088{\pm}0.012$ . The following factors showed significant impacts on survival rate: gender, age, primary diagnosis, surgery and the time when pain appeared. Conclusions: The survival time of patients with advanced cancer was relatively short. Major approaches to extend the survival time include early detection, early diagnosis, effective surgical treatment, pain control, reasonable supply of nutrients and multiple interventions. -
Mansour-Ghanaei, Fariborz;Joukar, Farahnaz;Soati, Fatemeh;Mansour-Ghanaei, Alireza;Naserani, Sara Bakhshizadeh 3361
Background & Objectives: The most northern and northwestern regions of Iran are at a high risk for gastric cancer. The aim of this study was to assess the general population's awareness about risk factors, symptoms and signs, preventive methods and management of gastric carcinoma in a high prevalence city in the North of Iran. Methods: A cross-sectional population-based telephone survey which was conducted on 3,457 residents of Rasht, the capital city of Guilan Province, to assess their awareness regarding gastric carcinoma. The questionnaires contained demographic data and statements on respondents' knowledge about risk factors, symptoms and signs, prevention and management of gastric cancer which were filled by general practitioners after asking the subjects. Data were analyzed in SPSS14. P<0.05 was considered significant. Results: The mean knowledge score of the respondents was$5.05{\pm}1.37$ regarding risk factors of gastric carcinoma,$4.39{\pm}1.99$ regarding symptoms and signs,$6.0{\pm}1.22$ regarding preventive strategies, and$1.6{\pm}1.16$ regarding management. Totally the mean knowledge level of the respondents toward gastric carcinoma would be$17.1{\pm}3.97$ from the maximum grade of 29. The age group of 45-55 y/o, bachelor degree and higher, physicians and nurses, those who had cancer history in friends or had the history of gastrointestinal diseases showed significantly higher knowledge scores (P=0.001). Conclusion: There is a general lack of awareness of cancer risk factors, symptoms and signs, methods of prevention, and importance of early diagnosis and treatment. Educational programs should be developed to promote adherence to recommended screening guidelines. -
Qin, Hai-Xia;Cui, Hong-Kai;Pan, Ying;Yang, Jun;Ren, Yan-Fang;Hua, Cai-Hong;Hua, Fang-Fang;Qiao, Yu-Huan 3367
Objective: To investigate the effects of histone deacetylase 6 (HDAC6) siRNA on cell proliferation and cell apoptosis of the HeLa cervical carcinoma cell line and the molecular mechanisms involved. Methods: Division was into three groups: A, the untreated group; B, the control siRNA group; and C, the HDAC6 siRNA group. Lipofectamine 2000 was used for siRNA transfection, and Western blot analysis was used to determine the protein levels. Cell proliferation and apoptosis were characterized using a CCK-8 assay and flow cytometry, respectively. Results: HDAC6 protein expression in the HDAC6 siRNA-transfection group was significantly lower (P < 0.05) than in the untreated and control siRNA groups. The CCK-8 kit results demonstrated that the proliferation of HeLa cells was clearly inhibited in the HDAC6 siRNA transfection group (P < 0.05). In addition, flow cytometry revealed that the early apoptotic rate ($26.0%{\pm}0.87%$ ) was significantly elevated (P < 0.05) as compared with the untreated group ($10.6%{\pm}1.19%$ ) and control siRNA group ($8.61%{\pm}0.98%$ ). Furthermore, Western blot analysis indicated that bcl-2 protein expression in the HDAC6 siRNA-transfection group was down-regulated, whereas the expression of p21 and bax was up-regulated. Conclusion: HDAC6 plays an essential role in the occurrence and development of cervical carcinoma, and the down-regulation of HDAC6 expression may be useful molecular therapeutic method. -
Mafi, Negar;Kadivar, Maryam;Hosseini, Niloufar;Ahmadi, Sara;Zare-Mirzaie, Ali 3373
Background: Head and neck squamous cell carcinoma (HNSCC) is the 8th most common cancer worldwide. Although older age, male gender, smoking and alcohol consumption are known risk factors, an increasing number of HNSCC patients are without typical risk factors. Our aim was to define demographics of HNSCC in Iran and the potential risk factors related to Iranian ethnicity and lifestyle. Methods: We conducted a cross-sectional analytical study on 262 patients with primary SCC of the larynx, hypopharynx or tongue referred to our pathology department during 1995-2010. Patients' demographics, tumor characteristics and risk factors such as smoking, alcohol consumption and anemia were analyzed and compared in two groups of patients: over 40 years (older group) and 40 years or less (young group); Chi-square and Mann-Whitney analytical tests were employed. Results: 5.7% of patients were young adults. The male to female ratio was 1.5 in the younger group and 5.6 in the older group. In young adults, 40% of tumors were located in larynx and 40% in the tongue. Age >40 was significantly associated with laryngeal location (P<0.001). History of smoking and drinking was significantly associated with age >40 and SCC of larynx in both age groups. Cervical lymph node involvement was significantly correlated with SCC of tongue (P<0.001), however, considering young adults only, SCC of hypopharynx was most frequently accompanied by lymph node involvement (60%). The most prevalent tumor among men was SCC of larynx whereas SCC of hypopharynx was the most prevalent tumor among women (61%), of whom 18.2% were${\leq}40$ . Conclusions: The incidence of HNSCC among young adults seems to be higher in Iran compared to other countries. Reduction in exposure to known risk factors, especially tobacco smoking in forms of cigarettes and bubble pipes, and search for other causative agents of HNSCC in young population is recommended. -
Jiang, Jian-Tao;Zhang, Lan-Fang;Zhou, Bin;Zhang, Shun-Qun;Li, Shao-Min;Zhang, Wei;Zhang, Jin;Qiao, Zhe;Kong, Ran-Ran;Ma, Yue-Feng;Chen, Sheng 3379
Objective: To investigate uPA and VEGF expression in esophageal cancer and relations with tumorous invasion and metastasis. Methods: Immunohistochemistry was used to detect uPA and VEGF expression in the normal epithelial tissue of esophageal mucosa and cancer tissue and detect CD34 labeled micrangium and analyze the relationships with clinical pathological features and tumor angiogenesis. Results: Positive rates for uPA and VEGF protein expression were significantly greater in esophageal cancer than normal epithelial tissue (P < 0.05), the two being linked (P <0.05). In addition, uPA and VEGF protein expression of the high microvessel density (MVD) group was significantly lower than in the low MVD group (P < 0.05), with relation to clinical pathological staging, differentiation and lymph node metastasis (P < 0.05). Conclusion: In esophageal cancer tissue, uPA and VEGF proteins are overexpressed and promote tumor angiogenesis, indicative of a poor prognosis. -
Yadav, Naval Kishor;Poudel, Bibek;Thanpari, C.;Koner, Bidhan Chandra 3385
Objective: The study was conducted to assess biochemical profiles in premenopausal and postmenopausal women having breast cancer. Materials and Methods: A hospital based case control study was carried out at Manipal Teaching Hospital (MTH), Pokhara, Nepal. The analysed variables were age, metabolic profile including total cholesterol, triglycerides, HDL-C, LDL-C, blood sugar, insulin concentration, C-peptide, HbA1c and selenium. Descriptive statistics and testing of hypothesis were used for the analysis using EPI INFO and SPSS 16 software. Results: In premenopausal women, significant differences were noted for total cholesterol (P value <0.001), triglycerides (P value 0.002), HbA1c level (P value <0.001), insulin concentration (P value 0.030), C-peptide concentration (P value 0.001), and selenium (P value <0.001) between cases and controls. Insignificant results were found for HDL-C (P value 0.749), LDL-C (P value 0.933), blood sugar (P value 0.59) and BMI (P value 0.746). Similarly, significant difference in total cholesterol (P value <0.001), triglycerides (P value 0.001), LDL-C (P value <0.001), HDL-C (P value 0.025), blood sugar (P value <0.001), insulin concentration (P value <0.001), c-peptide concentration (P value <0.001), HbA1c level (P value <0.001) and selenium (P value <0.001) were observed for postmenopausal patients and controls. Conclusions: Assessing metabolic changes and their management may be important for control of breast cancer and increased survival. -
Ergin, Ayla Berkiten;Sahin, Nevin Hotun;Sahin, Fezan Mutlu;Yaban, Zuleyha Simsek;Acar, Zeynep;Bektas, Hatice 3389
Aim: The aim of this study was to analyze studies in Turkey about self-breast examination and produce conclusive, reliable and detailed basis for future studies. Methods: Studies performed between 2000 and 2009 (until the end of September) were retrieved from databases using breast cancer, breast examination, breast cancer screening and risk factors as key words. Fifty-nine studies were identified and 18 of them (15 journal articles and three theses) were used for the meta-analysis. Results: Married women and women with a family history of breast cancer were found to perform self-breast examination more frequently than single women and women without a family history of breast cancer, respectively (OR=1.02 %CI 0.82-1.63; OR=1.16 %CI 0.82-1.63). According to the health belief model scales, women performing self-breast examination were determined to have 1.7 times higher susceptibility (OR=1.70), 1.34 times higher seriousness perception (OR=1.34), 3.32 times higher health motivation (OR=3.32), 5.21 times more self-efficacy/confidence (OR=5.21) and 2.56 times higher self-breast examination benefit perception (OR=2.56). Conclusion: Nursing care models caused an increase in self-breast examination by women, and thus, it may be useful to organize and evaluate such health-related programs and consider women health perceptions. -
Saengsawang, Phubet;Promthet, Supannee;Bradshaw, Peter 3399
A liver fluke, Opisthorchis viverrrini (OV), is the major cause of the high incidence of cholangiocarcinoma in Thailand. The prevalence of OV infection remains high in various parts of the country, especially in Northeast Thailand and particularly in wetland rural areas where a large proportion of the community work in agriculture and continue the traditional practice of eating raw or uncooked cyprinoid fish products. The national control program seems to have had little impact in many of these areas, and it has been difficult to make precise assessments of the overall effectiveness of the program. This paper is the first report of prospective research project designed to monitor the impact of the national control program in rural communities located in a northeastern province and at high risk of OV infection. The participants in this initial survey were 1,569 villagers, aged 20-65 years, living in two subdistricts of Yasothon Province. Stool examinations showed that 38.68% were infected with OV. Males were slightly more likely to be infected than females, but the difference was not statistically significant. Infection was found to be positively associated with age in both males and females. The preliminary data indicate that the population selected for study is suitable for the purpose of the monitoring project. -
Cui, Zhi-Wen;Xia, Ye;Ye, Yi-Wang;Jiang, Zhi-Mao;Wang, Ya-Dong;Wu, Jian-Ting;Sun, Liang;Zhao, Jun;Fa, Ping-Ping;Sun, Xiao-Juan;Gui, Yao-Ting;Cai, Zhi-Ming 3403
The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$ -test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor. -
Giri, Shiv Kumar;Yadav, Anita;Kumar, Anil;Dev, Kapil;Gulati, Sachin;Gupta, Ranjan;Aggarwal, Neeraj;Gautam, Sanjeev Kumar 3409
Aim: It is well known that polycyclic aromatic hydrocarbons (PAHs) such as benzo (a) pyrene have carcinogenic properties and may cause many types of cancers in human populations. Genetic susceptibility might be due to variation in genes encoding for carcinogen metabolizing enzymes, such as cytochrome P-450 (CYP450). Our study aimed to investigate the effect of genetic polymorphisms of CYP1A1 (m1 and m2) on genetic damage in 115 coal-tar workers exposed to PAHs at their work place. Methods: Genetic polymorphisms of CYP1A1 were determined by the PCR-RFLP method. Comet and buccal micronucleus assays were used to evaluate genetic damage among 115 coal tar workers and 105 control subjects. Results: Both CYP1A1 m1 and CYP1A1 m2 heterozygous and homozygous (wt/mt+mt/mt) variants individually as well as synergistically showed significant association (P<0.05) with genetic damage as measured by tail moment (TM) and buccal micronuclei (BMN) frequencies in control and exposed subjects. Conclusion: In our study we found significant association of CYP1A1 m1 and m2 heterozygous (wt/mt)+homozygous (mt/mt) variants with genetic damage suggesting that these polymorphisms may modulate the effects of PAH exposure in occupational settings. -
Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Man, Dong-Liang;Shang, Hong 3417
Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer. -
Chen, Yan;Huang, Xian-He;Shi, Hua-Shan;Mu, Bo;Lv, Qun 3423
Background: The objective of this study was to measure the antibody content of NuTu-19 ovarian cancer cells in serum samples using a quartz crystal microbalance (QCM) immunosensor. Materials and Methods: NuTu-19 cells were first cultured onto the electrode surfaces of crystals in Dulbecco's modified Eagle medium, and then specified amounts of immunized serum samples of immunized rabbit were also added. The change in mass caused by specific adsorbtion of antibodies of NuTu-19 to the surfaces of the crystals was detected. Results: The change in resonance frequency of crystals caused by immobilization of NuTu-19 cells was from 83 to 429Hz. The antibody content of NuTu-19 detected was 341ng/ul. The frequency shifts were linearly dependent on the amount of antibody mass in the range of 69 to 340ng. The positive detection rate and the negative detection rate were 80% and 100%, respectively. Conclusion: This immunoassay provides a viable alternative to other early ovarian cancer detection methods and is particularly suited for health screening of the general population. -
Chen, Jing-Xiang;Tang, Xu-Dong;Xiang, De-Bing;Dong, Xiao-Ling;Peng, Fang-Yi;Sun, Gui-Yin 3427
Aim: The significance of the mucinous adenocarcinoma in TNM staging and prognosis for colorectal tumor patients is still controversial. The aim was to provide a meta-analysis for TNM staging and prognostic features of colorectal tumors. Methods: 30 individual case-control studies were finally included into this meta-analysis, involving a total of 444,489 cancer cases and 45,050 mucinous adenocarcinomas, of relations with TNM staging and prognostic features. Results: Compared to non-mucinous adenocarcinoma patients, the TNM IV stage accounted for a larger percentage of mucinous adenocarcinomas (OR=1.48, 95%CI 1.28-1.71, POR<0.001) and the prognosis was significantly poor (HR=1.06, 95%CI 1.04-1.08, P<0.001). After heterogeneity testing, the results was similar to the holistic approach outcome (HR=1.48, 95%CI 1.35-1.62, P<0.001). Conclusion: Compared to patients with non-mucinous adenocarcinomas, mucinous adenocarcinoma patients with later TNM staging make up a big percentage, and mucinous adenocarcinoma is an independent risk factor for poor prognosis. -
Zhou, Li-Ping;Luan, Hong;Dong, Xi-Hua;Jin, Guo-Jiang;Ma, Dong-Liang;Shang, Hong 3431
Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks (DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of the XRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusive results. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and the risk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searched for all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons of the total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases and controls. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studies were included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showed that mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increased risk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer. However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms of XRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from the current meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 gene might increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protective factors. -
Lu, Hang;Sun, Hong-Zhi;Li, Hua;Cong, Ming 3437
Background: Oncogenic Bmi-1 (B-lymphoma Moloney murine leukemia virus insertion region-1) belongs to the Polycomb-group (PcG) family of proteins and plays an important role in the regulation of proliferation, senescence, cell cycle and apoptosis, chromosome stability, activation of gene transcription. Methods: To clarify the roles of Bmi-1 in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) and real-time RT-PCR in gastric carcinomas, dysplasia, intestinal metaplasia (IM), and gastritis with a comparison of its expression with clinicopathological parameters of carcinomas. Results: There was gradually increased Bmi-1 protein expression from gastritis, IM, dyplasia to carcinoma (p<0.001). Bmi-1 expression was positively linked to tumor size, depth of invasion, lymph node metastasis and worse prognosis of carcinomas (p<0.001), but not to age or sex of carcinoma patients (p>0.05). There was higher Bmi-1 protein expression in intestinal-type carcinomas than diffuse-type ones (p<0.001). At mRNA level, Bmi-1 protein expression was increased from gastritis, IM, dysplasia and carcinoma (p<0.001). Bmi-1 overexpression was observed in gastric carcinoma with larger diameter, deeper invasion, lymph node metastasis, and intestinal-type carcinoma (p<0.05). Conclusion: These findings indicate that up-regulated Bmi-1 expression is positively linked to pathogenesis, growth, invasion, metastasis and differentiation of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviors and prognosis of gastric carcinomas. -
Dahlui, Maznah;Gan, Daniel Eng Hwee;Taib, Nur Aishah;Pritam, Ranjit;Lim, Jennifer 3443
Introduction: Despite health education efforts to educate women on breast cancer and breast cancer screening modalities, the incidence of breast cancer and presentation at an advanced stage are still a problem in Malaysia. Objectives: To determine factors associated with the uptake of breast cancer screening among women in the general population. Methods: This pre-intervention survey was conducted in a suburban district. All households were approached and women aged 20 to 60 years old were interviewed with pre-tested guided questionnaires. Variables collected included socio-demographic characteristics, knowledge on breast cancer and screening practice of breast cancer. Univariate and multivariate analysis were performed. Results: 41.5% of a total of 381 respondents scored above average; the mean knowledge score on causes and risks factors of breast cancer was 3.41 out of 5 (SD1.609). 58.5% had ever practiced BSE with half of them performing it at regular monthly intervals. Uptake of CBE by nurses and by doctors was 40.7% and 37.3%, respectively. Mammogram uptake was 14.6%. Significant predictors of BSE were good knowledge of breast cancer (OR=2.654, 95% CI: 1.033-6.816), being married (OR=2.213, 95% CI: 1.201-4.076) and attending CBE (OR=1.729, 95% CI: 1.122-2.665). Significant predictors for CBE included being married (OR=2.161, 95% CI: 1.174-3.979), good knowledge of breast cancer (OR=2.286, 95% CI: 1.012-5.161), and social support for breast cancer screening (OR=2.312, 95% CI: 1.245-4.293). Women who had CBE were more likely to undergo mammographic screening of the breast (OR=5.744, 95% CI: 2.112-15.623), p<0.005. Conclusion: CBE attendance is a strong factor in promoting BSE and mammography, educating women on the importance of breast cancer screening and on how to conduct BSE. The currently opportunistic conduct of CBE should be extended to active calling of women for CBE. -
Mirinezhad, Seyed Kazem;Somi, Mohammad Hossein;Jangjoo, Amir Ghasemi;Seyednezhad, Farshad;Dastgiri, Saeed;Mohammadzadeh, Mohammad;Naseri, Ali Reza;Nasiri, Behnam 3451
Background: Esophageal cancer in Iran is the sixth most common cancer and is particularly important in east Azerbaijan. The aim of this study was to calculate survival rates and define prognostic factors in esophageal cancer patients. Methods: In this study, all patients with esophageal cancer registered in the Radiation Therapy Center, during March 2006 to March 2011, were analyzed and followed up for vital status. Data were analyzed using the Kaplan-Meier method and the Cox proportional hazard models. Results: Out of 532 patients, survival information was available for 460, including 205 (44/ 5%) females and 255 (55/4%) males. The mean age was$65.8{\pm}12.2$ , ranging from 29 to 90 years at the time of diagnosis. 1-, 3- and 5-year survival rates after diagnosis were 55%, 18% and 12%, respectively, with a median survival time of$13.2{\pm}.7$ (CI 95% =11.8-14.6) months. In the univariate analysis, age (P=0/001), education (P=0/001), smoking status (P= 0/001), surgery (P= 0/001), tumor differentiation (P= 0/003) and tumor stage (P= 0/001) were significant prognostic factors. Tumor morphology, sex, place of residence, tumor histology and tumor location did not show any significant effects on the survival rate. In multivariate analysis, age (P = 0/003), smoking (P= 0/01) and tumor stage (P= 0/001) were significant independent predictors of survival. Conclusion: In summary, prognosis of esophageal cancer in North West of Iran is poor. Therefore, reduction in exposure to risk factors and early detection should be emphasized to improve survival. -
Pity, Intisar S.;Shamdeen, Maida Y.;Wais, Shawnim A. 3455
Objectives: To report the prevalence of atypical squamous cells of undetermined significance and atypical squamous cells-cannot exclude high squamous intraepithelial lesions and to determine the possible association of Pap test results with high-risk human papillomavirus and high squamous intraepithelial lesions in women from Duhok, Iraq. Design: A prospective, observational study was conducted between January 2005 and December 2011. Overall, 596 women with a cervicovaginal Pap test showing atypical squamous cells of undetermined significance and 93 atypical squamous cells-cannot exclude high squamous intraepithelial lesion for whom pathologic follow-up was available were studied. Follow-up consisted of repeat cytology, colposcopy and histology. High risk human papillomavirus DNA testing was performed on exfoliated cervical cells from 106 women, using conventional PCR after at least 36 months from the initial Pap smear. Results: Significantly high proportions of both atypical squamous cells of undetermined significance (87.9%) and atypical squamous cells-cannot exclude high squamous intraepithelial lesion (62.4%) demonstrated no significant lesion on subsequent follow up. Low squamous intraepithelial lesions were observed in 1.7% of cases of atypical squamous cells of undetermined significance and in 5.4% of atypical squamous cells-cannot exclude high squamous intraepithelial lesion. High squamous intraepithelial lesion was demonstrated in 0.8% and 16.1% respectively. In the latter there was also one case of invasive carcinoma. High-risk HPV DNA was demonstrated in 40% of atypical squamous cells of undetermined significance and 57.1% of atypical squamous cells-cannot exclude high squamous intraepithelial lesions. Conclusions: Since both atypical squamous cells of undetermined significance and atypical squamous cells-cannot exclude high squamous intraepithelial lesion identify patients who are at an increased risk for the development of high squamous intraepithelial lesions and a considerable percentage harbor high risk-HPV, both should be retained as diagnostic categories and patients warrant a diligent follow up and testing for high risk-HPV DNA. Colposcopic evaluation and biopsy, when indicated, are a must. -
Koomdee, Napatrupron;Hongeng, Suradej;Apibal, Suntaree;Pakakasama, Samart 3461
Methotrexate (MTX) is an important drug for the treatment of childhood acute lymphoblastic leukemia (ALL). However, related toxicity occurs in many organs which may cause interruption of treatment, morbidity, and mortality. Single nucleotide polymorphisms (SNPs) of dihydrofolate reductase (DHFR) and gamma glutamyl hydrolase (GGH) are known to alter their enzymatic activity and thus affect the metabolism of MTX and influence the effectiveness. Therefore, we hypothesized that genetic variations of DHFR and GGH genes may influence the risk of toxicity after high dose MTX. The study population comprised of 105 children with ALL who were treated according to the modified St Jude Total XV protocol. The patients received 2.5 or$5g/m^2$ of MTX for 5 doses during the consolidation phase. Genotyping of DHFR 829C>T and GGH-401C>T was performed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The GGH-401CT and TT genotypes were associated with increased risk of leukopenia and thrombocytopenia after high dose MTX (OR 2.97, 95%CI; 1.24-7.13 and OR 4.02, 95%CI; 1.58-10.26). DHFR 829C>T was not associated with toxicity. In conclusion, the GGH-401CT and TT genotypes were found to increase the risk of severe leukopenia and thrombocytopenia after exposure to high dose MTX for childhood ALL therapy. -
Li, Hui-Yan;Ge, Xin;Huang, Guang-Ming;Li, Kai-Yu;Zhao, Jing-Quan;Yu, Xi-Miao;Bi, Wen-Si;Wang, Yu-Lin 3465
Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessed using TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up period was 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for colorectal cancer patients. -
Zhang, Qun-Cheng;Jiang, Shu-Juan;Zhang, Song;Ma, Xiao-Bin 3471
Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of${\alpha}$ -tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the$G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of${\alpha}$ -tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer. -
Huang, Tao;Gong, Wei-Hua;Li, Xiu-Cheng;Zou, Chun-Ping;Jiang, Guang-Jian;Li, Xu-Hui;Qian, Hao 3477
Purpose: To investigate the killing effect on OS cells of a combination of oxaliplatin and TRAIL and related molecular mechanisms. Methods: TRAIL and oxaliplatin were applied to OS732 cells singly or jointly and survival inhibition rates were measured by MTT assay, changes of cellular shape being assessed with inverted phase contrast and fluorescence microscopy. Apoptotic rates were analyzed by flow cytometry (FCM) and immunocytochemistry was used to examine Mcl1 expression of OS732 cells. Results: The survival inhibition rate of combined application of$100{\mu}g/ml$ TRAIL and$1{\mu}g/ml$ oxaliplatin on OS-732 cells was significantly higher than that of either agent singly (p<0.01). Changes of cellular shape and apoptotic rates also indicated apoptosis-inducing effects of combined application to be much stronger than those of individual application. Oxaliplatin had the effect of down-regulating Mcl1 expression and sensitizing OS cells to TRAIL-induced apoptosis. Conclusion: A combination of TRAIL and oxaliplatin exerts strong killing effects on OS-732 cells which might be related to down-regulation of Mcl1 expression. -
Qi, Hao-Yu;Zou, Peng;Zhao, Lin;Zhu, Jue;Gu, Ai-Hua 3483
Objective: Several studies have demonstrated associations between the TERT rs2736098 single nucleotide polymorphisms (SNPs) and susceptibility to cancer development. However, there are conflicting results. A systematic meta-analysis was therefore performed to establish the cancer risk associated with the polymorphism. Methods: In this meta-analysis, a total of 6 case-control studies, including 5,567 cases and 6,191 controls, were included. Crude odds ratios with 95% confidence intervals were used to assess the strength of associations in several genetic models. Results: Our results showed no association reaching the level of statistical significance for overall risk. Interestingly, in the stratified analyses (subdivided by ethnicity), significantly increased risks were found in the Asian subgroup which indicates the TERT rs2736098 polymorphism may have controversial involvement in cancer susceptibility. Conclusions: Overall, this meta-analysis indicates that the TERT rs2736098 polymorphism may have little involvement in cancer susceptibility. -
Saelee, Pensri;Chuensumran, Ubol;Wongkham, Sopit;Chariyalertsak, Sunanta;Tiwawech, Danai;Petmitr, Songsak 3489
Hepatocellular carcinoma (HCC), the most common primary hepatic tumor, is highly prevalent in the Asia-Pacific region, including Thailand. Many genetic and epigenetic alterations in HCC have been elucidated. The aim of this study was to determine whether aberrant methylation of the suppressor of cytokine signaling 1 gene (SOCS1) occurs in HCCs. Methylation specific-PCR assays were performed to identify the methylation status of SOCS1 in 29 tumors and their corresponding normal liver tissues. An abnormal methylation status was detected in 17 (59%), with a higher prevalence of aberrant SOCS1 methylation significantly correlating with HCC treated without chemotherapy (OR=0.04, 95%CI=0.01-0.31; P=0.001). This study suggests that epigenetic aberrant SOCS1 methylation may be a predictive marker for HCC patients. -
Bunjhoo, Hansvin;Wang, Zheng-Yun;Chen, Hui-Long;Cheng, Sheng;Xiong, Wei-Ning;Xu, Yong-Jian;Cao, Yong 3495
The aim of this study was to evaluate the diagnostic value of interleukin 21(IL-21) and carcinoembryonic antigen (CEA) in tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs). Pleural effusion samples from 103 patients were classified on the basis of diagnosis as TPE (n=51) and MPE (n=52). The concentration of IL-21 was determined by ELISA. Lactate dehydrogenase (LDH), adenosine dehydrogenase (ADA) and CEA levels were also determined in all patients. A significant difference was observed in the levels of ADA and CEA (P<0.01), but not in the levels of LDH (P>0.05) between TPE and MPE. The concentration of IL-21 in MPE was significantly higher compared to TPE (P<0.01). With a threshold value of 4.32 pg/ml, IL-21 had a sensitivity of 76.9% (40/52) and a specificity of 80.4% (41/51). Combined detection of IL-21 and CEA had a sensitivity of 69.2% (36/52) and a specificity of 92.2% (47/51). These two markers can contribute to the differential diagnosis of MPEs. -
Yang, Yuan;Zhang, Fan;Wang, Yang;Liu, Sheng-Chun 3501
Links between the CHEK2 1100delC heterozygote and breast cancer risk have been extensively explored. However, both positive and negative associations with this variant have been reported in individual studies. For a detailed assessment of the CHEK2 1100delC heterozygote and breast cancer risk, relevant studies published as recently as May 2012 were identified using PUBMED and EMBASE and selected using a priori defined criteria. The strength of the relationship between the CHEK2 1100delC variant and breast cancer risks was assessed by odds ratios (ORs) under the fixed effects model. A total of 29,154 cases and 37,064 controls from 25 case-control studies were identified in this meta-analysis. The CHEK2 1100delC heterozygote was more frequently detected in cases than in controls (1.34% versus 0.44%). A significant association was found between CHEK2 1100delC heterozygote and breast cancer risk (OR=2.75, 95% CI: [2.25, 3.36]). The ORs and CIs were 2.33 (95% CI: [1.79, 3.05]), 3.72 (95% CI: [2.61, 5.31]) and 2.78 (95% CI: [2.28, 3.39]) respectively in unselected, family, early-onset breast cancer subgroups. The CHEK2 1100delC variant could be a potential factor for increased breast cancer risk in Caucasians. However, more consideration is needed in order to apply it to allele screening or other clinical work. -
Liu, Jian-Lun;Wei, Wei;Tang, Wei;Jiang, Yi;Yang, Hua-Wei;Li, Jing-Tao;Zhou, Xiao 3507
Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. Methods: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. Results: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9. Conclusion: LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM). -
Nagamma, T.;Bhutia, Rinchen Doma;Pokharel, Daya Ram;Yadav, Saraswati;Baxi, J. 3513
Aim: The present study assess the effect of consumption of alcohol on oxidative stress and antioxidant status in patients suffering from different types of cancer. Methods: This hospital based case control study conducted in the Western part of Nepal covered a total of 93 cancer patients with or without alcohol intake and smoking habits, along with 94 age, sex and habit-matched individuals serving as controls. Plasma thiobarbituric acid reacting substances (TBARS), total antioxidant activity (TAA), vitamin C,${\alpha}$ -tocopherol and erythrocyte reduced glutathione (GSH) were estimated and compared. Results: The TBARS level was found to be significantly higher ($p{\leq}0.001$ ) in all types of cancer patients when compared to controls, being aggravated in alcoholics with a smoking habit. No statistical significance ($p{\geq}0.05$ ) was observed in the level of vitamin C and${\alpha}$ -tocopherol. GSH and TAA level were significantly decreased ($p{\leq}0.001$ ) in all the groups except those who consumed both branded as well as homemade alcohol and non-alcoholics without smoking habit. Conclusion: Alcohol, irrespective of its commercial brand, increases oxidative stress in all types of cancer patients. This is even higher when alcohol intake is combined with a smoking habit. Decreased TAA and GSH are major risk factors for cancer development. -
Siripong, Pongpun;Rassamee, Kitiya;Piyaviriyakul, Suratsawadee;Yahuafai, Jantana;Kanokmedhakul, Kwanjai 3519
Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for the treatment of cancers, on metastatic potential of highly metastatic B16F10 melanoma cells were investigated in vitro. Cell proliferation was assessed using the MTT colorimetric assay. Details of metastatic capabilities including invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden Chamber invasion and migration, scratch motility and cell attachment assays, respectively. The results demonstrated that n-hexane and chloroform extracts exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity-guided chromatographic fractionation of both active n-hexane and chloroform extracts led to the isolation of two main prenylated xanthones and characterization as macluraxanthone and gerontoxanthone-I, respectively, their structures being identified by comparison with the spectral data. Interestingly, both exhibited potent effective effects. At non-toxic effective doses, n-hexane and chloroform extracts (10 and$30{\mu}g/ml$ ) as well as macluraxanthone and gerontoxanthone-I (3 and$10{\mu}M$ ) significantly inhibited B16F10 cell invasion, to a greater extent than$10{\mu}m$ doxorubicin, while reducing migration of cancer cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells to high concentrations of chloroform ($30{\mu}g/ml$ ) and geratoxanthone-I ($20{\mu}M$ ) for 24 h resulted in delayed adhesion and retarded colonization. As insights into mechanisms of action, typical morphological changes of apoptotic cells e.g. membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow cytometry were observed, suggesting DNA damage and subsequent apoptotic cell death. Taken together, our findings indicate for the first time that active n-hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis processes including proliferation, adhesion, invasion and migration, possibly through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based on these data, M. amboinensis Bl. represents a potential candidate novel chemopreventive and/or chemotherapeutic agent. Additionally, they also support its ethno-medicinal usage for cancer prevention and/or chemotherapy. -
Li, Zhi-Fang;Wang, Shao-Ming;Shi, Ju-Fang;Zhao, Fang-Hui;Ma, Jun-Fei;Qiao, You-Lin;Feng, Xiang-Xian 3529
Objectives: To investigate the current prevalence and knowledge of cervical cancer, breast cancer and reproductive tract infections (RTIs) in rural Chinese women, and to explore the acceptance and feasibility of implementing a combined screening program in rural China. Methods: A population-based, cross-sectional study was conducted among women aged 30 to 59 years old in Xiangyuan County, Shanxi Province from 2009 to 2010. Socio-demographic characteristics, knowledge of cervical cancer, breast cancer and RTIs, and the attitude toward single or combined screening were collected by an interview questionnaire. Each participant received a clinical examination of the cervix, breast and reproductive tract. Examinations included visual inspection, mammography, laboratory tests and pathological diagnosis. Results: A total of 1,530 women were enrolled in this study. The prevalence of cervical precancerous lesions, suspicious breast cancer, suspicious benign breast disease and RTIs was 1.4%, 0.2%, 14.0% and 54.3%, respectively. Cervicitis, trichomonas vaginitis, and bacterial vaginitis were the three most common RTIs among our participants. Television, radio broadcast, and public education during screening were the major source of healthcare knowledge in rural China. Moreover 99.7% of women expressed great interest in participating in a combined screening project. The affordable limit for combined screening project was only 50 RMB for more than half of the rural women. Conclusion: A combined screening program would be more effective and popular than single disease screening projects, while appropriate accompanied education and a co-pay model for its successful implementation need to be explored, especially in low-resource settings.