• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.5807-5815
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• 2015

Background: Ovarian cancer is the most common gynecological malignancy and constitutes the fifth leading cause of female cancer death. Some biological parameters have prognostic roles in patients with advanced ovarian cancer and their expression may contribute to tumor progression. The aim of this study was to investigate the potential prognostic value of SKP2, genes P27Kip1, K-ras, c-Myc, COX2 and HER2 genes expression in ovarian cancer. Materials and Methods: This study was performed on two hundred formalin fixed paraffin embedded ovarian cancer and normal adjacent tissues (NAT). Gene expression levels were assessed using real time PCR and Western blotting. Results: Elevated expression levels of SKP2, K-ras, c-Myc, HER2 and COX2 genes were observed in 61.5% (123/200), 92.5% (185/200), 74% (148/200), 96 % (192/200), 90% (180/200) and 78.5% (157/200) of cancer tissues, respectively. High expression of SKP2 and down-regulation of P27 was associated with advanced stages of cancer. Conclusions: The association between high expression of c-Myc and SKP2 with low expression of P27 suggested that the Skp2-P27 pathway may play an important role in ovarian carcinogenesis. Reduced expression of P27 is associated with advanced stage of cancer and can be used as a biological marker in clinical routine assessment and management of women with advanced ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8963-8967
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• 2014

Background: Colon cancer is one of the most common cancers worldwide. Apoptosis is a necessary physiological process for cell elimination which is very important both cellular homeostasis and cell proliferation and differantiation. Dysregulation can lead to uncontrolled cell growth and tumor development. Survivin, a member of the IAP family, plays a key role in promotion of cell proliferation as well as inhibition of apoptosis in cancer cells. The aim of this study was to investigate whether specific genetic polymorphisms of survivin could be associated with colon cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between colon cancer risk and survivin gene polymorphisms. Materials and Methods: The relation between colon cancer and survivin -31 G/C (rs9904341), -241 C/T (rs17878467) and -625 C/G (rs8073069) polymorphism in promotor site of survivin gene associated with apoptosis was investigated using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Individuals with -31C allele and CC genotype were found to have a higher risk of developing colon cancer (OR=13.4, p=0.01). The -241 CT genotype considerably increased the risk of colon cancer (OR=12.0, p=0.0001). However, there was no significant varaition of the survivin -625 C/G polymorphism among colon cancer patients and controls in our study. Conclusions: This study provides the first evidence that survivin -31 G/C and -241 C/T SNP significantly contribute to the risk of colon cancer in the Turkish population.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.1875-1879
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• 2016

Background: Breast cancer is the most common cancer among women worldwide. A very important factor in the timely treatment and prevention of progression is high breast cancer awareness. Rural women are at risk of latte stage breast cancer due to poor education and lack of access to medical facilities. Materials and Methods: This cross-sectional-descriptive study was conducted on 266 women (out of 300) aged over 18 in rural areas of Zabol, Southeastern Iran during July 2015 to October 2015. The data collection tool was a researcher-made questionnaire that measured participant knowledge of breast cancer in four aspects (general awareness, risk factors, mammography, and symptoms). SPSS 22 was used for statistical analysis. Results: Out of 266 participants, age information was available for 261. The age range was between 19 and 62, with a mean of $27{\pm}2.1years$. Most participants (154, 57.9%) had an average overall awareness of breast cancer. In the general awareness dimension, most participants (130, 48.9%) had poor scores. Most (166, 62.4%) also had average awareness about risk factors and many (137, 51.5%) had good awareness about mammography. Most participants did not know that changes in breast shape (232, 88.2%), dimpling of breast skin (192, 72.3%) and nipple discharge (183, 69.6%) are the main symptoms of breast cancer. ANOVA statistical analysis showed a significant relationship between awareness level and participant education and occupation (P<0.05). Conclusions: This study indicated average awareness of participants about breast cancer. Since rural women have lower levels of education, it is recommended that educational courses with contents about breast cancer, its risk factors, and symptoms be held for these women.

• Asian Pacific Journal of Cancer Prevention
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• 제13권3호
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• pp.979-983
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• 2012

Background : Previous studies have suggested a lack of complete cross-resistance between steroidal (exemestane) and non-steroidal aromatase inhibitors (nSAI). Methods : Eighty-eight metastatic breast cancer (MBC) patients who received 25 mg of exemestane orally once a day at the National Cancer Center, Korea, between 2003 and 2009, were reviewed retrospectively. All patients had received nSAI for metastatic disease prior to exemestane therapy. Results : The median age was 52 years (range, 33-79), and 13 (14.8%) patients were premenopausal who concomitantly received GnRH agonist. Exemestane was given as a second- (80.7%) or third-line (19.3%) hormone therapy. The clinical benefit (CB) rate (complete response + partial response + stable disease ${\geq}$ 24 weeks) was 30.7%, with a median CB duration of 10.0 months (range, 6.3-78.7). The median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI], 1.99-4.01) and the overall survival (OS) 21.5 months (95% CI, 17.96-25.04), with a median followup of 50.3 months. Patients who achieved CB had longer OS than those patients who did not (29.6 vs 17.9 months; P=0.002). On univariate analysis of predictive factors, patients who had achieved CB from previous nSAI tended to show lower CB rate (24.6% vs 44.4%, respectively; P=0.063) and shorter PFS (2.8 vs 4.8 months, respectively; p=0.233) than patients who had not. Achieving CB from previous nSAI became independent predictive factor for CBR to exemestane on multivariable analysis (Odds ratio = 2.852, P = 0.040). Conclusions : Exemestane after nSAI failure was effective in prolonging CB duration. The drug's efficacy seemed to be inferior in patients who had benefit from previous nSAI use.

• Journal of Chest Surgery
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• 제24권4호
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• pp.376-381
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• 1991

From June 1979 to July 1988 for 9 years, total 440 cases of lung cancer[including biopsy and surgical specimen] of the Pusan Paik hospital were examined for the clinical and pathology study. The findings of the study are as follows; [1] The incidence of lung cancer started to increase from 1982, and it again remarkably increased since 1987. Such increase was solely brought by the increase of male lung cancer. Male and female ratio is 5.6: 1. [2] Histopathologically, the most prevalent type is squamous cell carcinoma[60.ado], and next are adenocarcinoma[15.6%] and small cell carcinoma[15.0%]. But in female alone, the most prevalent type is adenocarcinoma[40.3%], and next are squamous cell carcinoma[37.3%] and small cell carcinoma[11.9%]. [3] The absolute number of adenocarcinoma are approximately equally distributed among both sexes until 60 years of age. Above 61 years of age, mostly male was shown while female was not. Most probably, many female patient.- of that old age simply did not visit general hospitals for surgery in Korea. [4] Surgical treatment was performed in 8% of total cases of lung cancer. And most cases showed stage I progression of the cancer. Average size of the cancer was 5 cm in diameter in the operated 35 cases suggesting that the cancer could be detected more than 10 years ago before the time of surgery. [5] Lung cancer affected more in the right lung [right: left=1.6: 1], and each upper lobe of both lungs are affected about 1/4 of cases indicating that about 1/2 of all lung cancer develop from the upper lobes. [6] There are more nonsmokers[67.6%] among the lung cancer patients[male 64.6%, female 82.1%]. Probably, this will mean that there are other potent carcinogenic agents in our environment like automobile exhaust beside tobacco smoke. For the past history of lung disease other than cancer, tuberculosis is the most prevalent disease[16.1%, male 17.4%, female 9.0%]. Most of them is probably not related etiologically though this possibility is not completely denied.

• 한국환경성돌연변이발암원학회지
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• 제24권1호
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• pp.1-9
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• 2004

Three D-type cyelins (D1, D2, and D3) are expressed in G1 phase of the cell cyele and have been implicated in cell transformation and neoplasia in human and mouse. Cyclin D1 overexpression or amplification was described in various human cancers. However, there is controversy about the role of cyclin D2 in cell cyele progression and human carcinogenesis. Specially, loss of cyelin D2 is involved in a vital tumor suppressor function in normal breast tissue, and that its loss may be related to tumorigenesis. The author examined to effect over-expression of cyclin D2 on the cell proliferation, apoptosis, and cell cycle using cyclin D2 transfected stable T47D breast cancer cells to investigate whether cyclinD2 functions as a positive regulator or negative regulator in cell proliferation. Overexpression of cyclin D2 led to the suppression of cell growth in cyclin D2 transfected T47D in both in its expression level and a time dependent manner with up to 50% reduction of cell growth at 72 hours. Therefore, the authors performed the cell cycle phase analysis using the flow cytometry to investigate the effect of cyclin D2 on the cell cycle phase in cyclin D2 transfected stable T47D cells. The flow cytometry analysis revealed increased sub G0 phase in cyclin D2 transfeted cells up to 23% at 72 hours. To confirm these results induced by overexpression of cyclinD2, the apoptotic bodies were counted in control and cyclin D2 transfected T47 cells. There are markedly increases of apoptotic bodies in cyclin D2-transfected cells up to 18%. These results suggested that Cyclin D2 suppresses the cell proliferation in breast cancers cells via the induction of apotosis.

• Journal of Microbiology and Biotechnology
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• 제20권2호
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• pp.433-437
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• 2010

In the course of screening for novel modulators of cell cycle progression and apoptosis as anticancer drug candidates, we generated an analog of sangivamycin, MCS-C2, which was elucidated as 4-amino-6-bromo-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide. In the present study, we evaluated the molecular mechanisms of MCSC2-induced cell cycle arrest and apoptosis in A549 human lung cancer cells. To investigate the effects of MCS-C2 on cell cycle progression in A549 cells, we measured the DNA content of A549 cells treated with $5\;{\mu}M$ MCS-C2 using flow cytometry. The analysis revealed an appreciable $G_2$ phase arrest in treated cells. This event was associated with significant upregulation of p53 and $p21^{Cip1}$. In addition, the TUNEL assay was used to examine apoptotic induction in treated cells, and the effects of MCS-C2 on the expression of apoptosis-associated proteins were examined by Western blot. Apoptotic induction in MCS-C2-treated A549 cells was associated with cytochrome c release from mitochondria, which in turn resulted in the activation of caspase-9 and -3 and the cleavage of poly(ADP-ribose) polymerase (PARP). Based on these results, we conclude that MCS-C2 is a candidate therapeutic agent for the treatment of human lung cancer via upregulation and activation of p53.

• Molecules and Cells
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• 제40권9호
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• pp.621-631
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• 2017

Vaccinia-related kinase 1 (VRK1) and VRK3 are members of the VRK family of serine/threonine kinases and are principally localized in the nucleus. Despite the crucial roles of VRK1/VRK3 in physiology and disease, the molecular and functional interactions of VRK1/VRK3 are poorly understood. Here, we identified over 200 unreported VRK1/VRK3-interacting candidate proteins by affinity purification and LC-MS/MS. The networks of VRK1 and VRK3 interactomes were found to be associated with important biological processes such as the cell cycle, DNA repair, chromatin assembly, and RNA processing. Interactions of interacting proteins with VRK1/VRK3 were confirmed by biochemical assays. We also found that phosphorylations of XRCC5 were regulated by both VRK1/VRK3, and that of CCNB1 was regulated by VRK3. In liver cancer cells and tissues, VRK1/VRK3 were highly upregulated and its depletion affected cell cycle progression in the different phases. VRK3 seemed to affect S phase progression and G2 or M phase entry and exit, whereas VRK1 affects G1/S transition in the liver cancer, which could be explained by different interacting candidate proteins. Thus, this study not only provides a resource for investigating the unidentified functions of VRK1/VRK3, but also an insight into the regulatory roles of VRK1/VRK3 in biological processes.

• Molecules and Cells
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• 제41권3호
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• pp.188-197
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• 2018

Benzidine, a known carcinogen, is closely associated with the development of bladder cancer (BC). Epithelial-mesenchymal transition (EMT) is a critical pathophysiological process in BC progression. The underlying molecular mechanisms of mitogen-activated protein kinase (MAPK) pathway, especially extracellular regulated protein kinases 5 (ERK5), in regulating benzidine-induced EMT remains unclarified. Hence, two human bladder cell lines, T24 and EJ, were utilized in our study. Briefly, cell migration was assessed by wound healing assay, and cell invasion was determined by Transwell assay. Quantitative PCR and western blot were utilized to determine both gene expressions as well as protein levels of EMT and MAPK, respectively. Small interfering RNA (siRNA) was transfected to further determine ERK5 function. As a result, the migration and invasion abilities were enhanced, epithelial marker expression was decreased while mesenchymal marker expression was increased in human BC cell lines. Meanwhile, benzidine administration led to activation of ERK5 and activator protein 1 (AP-1) proteins, without effective stimulation of the Jun N-terminal kinase (JNK) or p38 pathways. Moreover, Benzidine-induced EMT and ERK5 activation were completely suppressed by XMD8-92 and siRNAs specific to ERK5. Of note, ERK1/2 was activated in benzidine-treated T24 cells, while benzidine-induced EMT could not be reversed by U0126, an ERK1/2 inhibitor, as indicated by further study. Collectively, our findings revealed that ERK5-mediated EMT was critically involved in benzidine-correlated BC progression, indicating the therapeutic significance of ERK5 in benzidine-related BC.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2061-2067
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• 2014

Background: It has been demonstrated that neutrophil:lymphocyte (NLR) and platelet:lymphocyte (PLR) ratios are associated with prognosis in cancer patients. The aim of this study was to investigate whether pretreatment white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, basophil and eosinophil counts, LDH level, NLR and PLR are associated with prognosis in patients with malignant pleural mesothelioma (MPM). Materials and Methods: We retrospectively reviewed files of 50 patients who were managed with a diagnosis of MPM between 2005 and 2010. Demographic and clinical characteristics, treatments, response to treatment and prognostic factors were evaluated, along with relationships between pretreatment blood parameters and prognosis. Results: Overall, 38 men and 12 women were included to the study. Mean age was $61.5{\pm}9.4$ years (range: 39-83 years). There was advanced disease in 86% (n=43) and the histological type was epithelial mesothelioma in the majority (82%). Of the cases, 17 (34%) received radiotherapy, while 42 cases underwent first- and second-line chemotherapy, with cisplatin plus pemetrexed as the most commonly used regimen. In the assessment after therapy, it was found that there was complete response in 4 cases (8%), partial response in 10 cases (20%), stable disease in 17 cases (34%) and progression in 19 cases (38%). Median follow-up was 10 months (range: 10 day-30 months). Median overall survival was found to be 20.7 months while median progression-free survival as 10 months. In univariate and multivariate analyses, it was found that factors significantly affecting overall survival included stage (p=0.030), response to treatment (p=0.026) and monocyte count (p=0.004), while factors affecting disease-free survival included NLR (p=0.018), response to treatment (p=0.001), and PLR score (p=0.003). Conclusions: Overall and disease-free survival was found to be better in cases with a WBC count<8.000, platelet count<300,000, and low NLR and PLR scores in malignant pleural mesothelioma.