• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4183-4186
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• 2012

Background: Ovarian cancer is the number one killer among all the gynecological cancers. We undertook association study to identify potential alterations in the genomic DNA of a DNA repair gene, DNA polymerase beta ($pol{\beta}$), involved in base excision repair (BER), in ovarian carcinomas of patients from Haldia, India. Mutations, splice variants have been reported earlier in different tumors other than ovarian tumors. Aim: In this study we explored the possibility of association of any mutation of $pol{\beta}$ (Exon 8) with prognosis in 152 ovarian cancer samples. Results: Alteration in the exon 8 region (Exon 8:468, $A{\rightarrow}C$; 15.1%) was noted among fifty seven polymorphism positive samples. Alteration in the intervening sequence 8 (IVS8, -25, $A{\rightarrow}C$; 3.9%) was also noted. All alterations are heterozygous in nature. Conclusions: We found no significant association among the samples from serous type, stage IV, and the $pol{\beta}$ mutations ($P{\leq}0.01$). Only a slight tendency of association was evident between IVS8, -25, A to C; and stage III. Further analysis with a larger number of samples is needed.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8595-8601
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• 2014

Background: miR-200a expression is frequently altered in numerous cancers. The aim of the present study was to determine the role of microRNA-200a in advanced ovarian carcinomas. Materials and Methods: We measured miR-200a expression in 72 matched normal ovarian tissues and advanced ovarian carcinomas, and also two ovarian carcinoma cell lines (SKOV3 and SKOV3.ip1 - the latter being more invasive and metastatic than the parental SKOV3) by stem-loop real-time RT-PCR based on TaqMan microRNA assay using U6 as a reference. Levels of miR-200a expression were compared by disease stage, tumor grade, histology, and lymph node involvement. To evaluate the role of microRNA-200a, cell proliferation and invasion of SKOV-3 and SKOV-3.ip1 were analyzed with miR-200a inhibitor/mimic transfected cells. Results: Of 72 paired samples, 65 cancer tissues overexpressed microRNA-200a greater than two fold in comparison with matched normal epithelium. Specifically, patients with lymph node metastasis showed significant elevation. The level correlated with clinicopathological features, including high tumor grade, late disease stage, most notably with lymph node metastasis, but not with tumor histology. In addition, SKOV-3.ip1 cells also overexpressed miR-200a compared with SKOV-3, and miR-200a inhibitor transfected SKOV-3.ip1 cells showed significant reduction in cellular proliferation and invasion, while a miR-200a mimic stimulated the opposite behavior. Conclusions: We provide definitive evidence that miR-200a is up-regulated in a significant proportion of advanced ovarian carcinomas, and that elevated miR-200a expression facilitates tumor progression. Our findings support the notion that miR-200a is an onco-microRNA for ovarian cancer, and elevation is a useful potential diagnostic indicator. This study also provides a solid basis for further functional analysis of miR-200a in advanced ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3325-3331
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• 2015

Pim kinase-3(Pim-3), a member of serine/threonine protein kinases, has been implicated in multiple human cancers and involved in Myc-induced tumorigenesis. However, little is known regarding its expression and biological function in human ovarian cancer. In this study we showed that the clinical significance and biological functions of Pim-3 in ovarian cancer and found that higher Pim-3 mRNA level are detected in ovarian cancer tissues than those in normal ovarian tissues. There are significant correlations between higher Pim-3 expression levels with the FIGO stage, histopathological subtypes, and distant metastasis in ovarian cancer patients. Lentivirus-mediated gene overexpression of Pim-3 significantly promotes the proliferation and migration of SKOV3 cell lines. Furthermore, MACC1 and Pim-3 expression were significantly correlated in human ovarian cancer cells, and overexpression of Pim-3 in ovary cancer cells increased MACC1 mRNA and protein expression. The data indicate that Pim-3 acts as a putative oncogene in ovary cancer and could be a viable diagnostic and therapeutic target for ovarian cancer.

• 한국정밀공학회지
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• 제31권6호
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• pp.521-525
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• 2014

Circulating tumor cells (CTCs) in the bloodstream of cancer patients provide an accessible source for detection, characterization, and monitoring of nonhematological cancers. The effectiveness of the CTC-Chip for the isolation of ovarian cancer cells was demonstrated by adapting the herringbone-chip (HB-Chip). The motions of the particles on the HB chip were simulated by a unique combination of buoyant, gravitational forces, and helical flows with a computational modeling. The motions of cells are demonstrated by applying polystylene bead and ovarian cancer cells into the microfabricated HB-Chip. The experimental results from beads and cells are well accordance with the simulated ones, as previously reported by Toner group. Thus, I expect that these modeling and experimental skills will play key roles in the clinical applications on CTC isolation as well as the basic research on characterization of CTCs under flow.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9781-9784
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• 2014

Background: The study aimed to evaluate changes in hematologic parameters, including white blood cell, platelet count, platelet indices, the platelet to lymphocyte and neutrophil to lymphocyte ratios in patients with early and advanced stages of epithelial ovarian cancers. Materials and Methods: The study included 100 patients with epithelial ovarian cancer who underwent primary staging exploratory laparotomy. Preoperative hematologic parameters, tumor histopathologic type, grade, stage and serum CA-125 levels were retrospectively analyzed. These parameters were compared between the patients with early (stage I-II) and advanced (stage III-IV) ovarian cancer. Results: White blood cell count and platelet indices, including mean platelet volume, platelet distribution width and platelet crit did not show a statistically significant difference between groups with early and advanced ovarian cancer. However, the neutrophil to lymphocyte ratio, platelet count, the platelet to lymphocyte ratio and CA-125 level showed a statistically significant difference between the two groups (p<0.05, p<0.01, p<0.001, p<0.01 respectively). Conclusions: It was found that the neutrophil to lymphocyte ratio, platelet count and the platelet to lymphocyte ratio increased with the increasing stage of ovarian cancer. Furthermore, it was seen that the platelet to lymphocyte ratio is an independent prognostic factor related to the stage of epithelial ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9405-9410
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• 2014

Purpose: To evaluate the prognostic impact of peritoneal washing cytology in patients with endometrial and ovarian cancers. Materials and Methods: We retrospectively identified 86 individuals with ovarian carcinomas, ovarian borderline tumors and endometrial adenocarcinomas. The patients had been treated at Shahid Sadoughi Hospital and Ramazanzadeh Radiotherapy Center, Yazd, Iran between 2004 and 2012. Survival differences were determined by Kaplan-Meier analysis. Multivariate analysis was performed using the Cox regression method. A p<0.05 value was considered statistically significant. Results: There were 36 patients with ovarian carcinomas, 4 with borderline ovarian tumors and 46 with endometrial carcinomas. The mean age of the patients was $53.8{\pm}15.2years$. In patients with ovarian carcinoma the overall survival in the negative cytology group was better than the patients with positive cytology although this difference failed to reach statistical significance (p=0.30). At 0 to 50 months the overall survival was better in patients with endometrial adenocarcinoma and negative cytology than the patients with positive cytology but then it decreased (p=0.85). At 15 to 60 months patients with FIGO 2009 stage IA-II endometrial andocarcinoma and negative peritoneal cytology had a superior survival rate compared to 1988 IIIA and positive cytology only, although this difference failed to reach statistical significance(p=0.94). Multivariate analysis using Cox proportional hazards model showed that stage and peritoneal cytology were predictors of death. Conclusions: Our results show good correlation of peritoneal cytology with prognosis in patients with ovarian carcinoma. In endometrial carcinoma it had prognostic importance. Additional research is warranted.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1627-1632
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• 2014

Background: Several studies indicated that the diagnosis season affects the prognosis of some cancers, such as examples in the prostate, colon and breast. This retrospective study aimed to investigate whether the diagnosis and recurrent season impacts the prognosis of epithelial ovarian cancer patients. Methods: From January 2005 to August 2010, 161 epithelial ovarian cancer patients were analyzed and followed up until August 2013. Kaplan-Meier survival curves and the log-rank test were used to make the survival analysis. Multivariate analysis was conducted to identify independent prognostic factors. Results: The prognostic factors of overall survival in epithelial ovarian cancer patients included age, clinical stage, pathological type, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles. Moreover, clinical stage, histological grade, residual disease after primary surgery, recurrent season and adjuvant chemotherapy cycles also impacted the progression-free survival of epithelial ovarian cancer patients. The diagnosis season did not have a significantly relationship with the survival of operable epithelial ovarian cancer patients. Median overall survival of patients with recurrent month from April to November was 47 months, which was longer (P < 0.001) than that of patients with recurrence month from December to March (19 months). Median progression-free survival of patients with recurrence month from April to November and December to March was 20 and 8 months, respectively (P < 0.001). Conclusion: The recurrence season impacts the survival of epithelial ovarian cancer patients. However, the diagnosed season does not appear to exert a significant influence.

• Genomics & Informatics
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• 제8권4호
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• pp.194-200
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• 2010

The PIK3CA gene, oncogenic gene located on human chromosome 3q26.3, is an important regulator of cell proliferation, death, motility and invasion. To evaluate the role of PIK3CA gene in the risk of Korean lung cancer, genotypes of the PIK3CA polymorphisms (rs11709323, rs2699895, rs3729679, rs17849074 and rs1356413) were determined in 423 lung cancer patients and 443 normal controls. Statistical analyses revealed that the genotypes and haplotypes in the PIK3CA gene were not significantly associated with the risk of lung cancer in the Korean population, suggesting that these PIK3CA polymorphisms do not contribute to the genetic susceptibility to lung cancer in the Korean population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1145-1148
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• 2014

Background: Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 $mg/m^2$ every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8529-8538
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• 2014

According to the China tumor registry 2013 annual report, breast cancer, lung cancer, and ovarian cancer are three common cancers in China nowadays, with high mortality due to the absence of early diagnosis technology. However, proteomics has been widespreadly implanted into every field of life science and medicine as an important part of post-genomics era research. The development of theory and technology in proteomics has provided new ideas and research fields for cancer research. Proteomics can be used not only for elucidating the mechanisms of carcinogenesis focussing on whole proteins of the tissue or cell, but also seeking the biomarkers for diagnosis and therapy of cancer. In this review, we introduce proteomics principles, covering current technology used in exploring early diagnosis biomarkers of breast cancer, lung cancer and ovarian cancer.