• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1977-1980
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• 2015

Objective: The Von Hippel-Lindau syndrome (VHLD), an inherited neoplastic syndrome predisposing to central nervous system hemangioblastoma (CNS), pheochromocytoma (PCC), renal cell carcinoma(RCC), retinal hemangioma (RA) and renal cysts, is caused by mutations or deletions of the VHL tumor-suppressor gene. To assess VHL genotype-phenotype correlations with function of pVHL a gene mutation analysis of members in a Chinese family with non-syndromic PCCs and individuals with apparently sporadic pheochromocytoma (ASP) was performed. Materials and Methods: DNA samples of 20 members from the Chinese family with non-syndromic PCCs and 41 patients with ASP were analyzed by polymerase chain reaction and direct sequencing, confirmed by Taqman probe. Results: Three novel mutations (H125P, 623(^TTTGTtG) and R120T) were identified in the Chinese family and in 3 among 41 ASP patients. The mutations were all located in exon 2 of VHL gene encoding ${\beta}$-domain of pVHL. The tumor type in H125P carriers and R120T carriers was VHL type 2C. And 623(^TTTGTtG) carriers presented VHL type 2B or type 2C. Conclusions: VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs and patients with APS, resulting in dysfunction of pVHL. H125P and R120T could be associated with VHL type 2C, while 623(^TTTGTtG) might be linked with VHL type 2B or type 2C. Not only is the genetic analysis helpful for early diagnosis and treatment of patients with VHLD, it is also benefitial for research intoVHLD pathogenesis.

• BMB Reports
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• v.44 no.8
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• pp.541-546
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• 2011

It is generally accepted that spermatozoa capacitation is associated with protein kinase A-mediated tyrosine phosphorylation. In our previous study, we identified the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA. However, the phosphorylation status of FSCB protein during spermatozoa capacitation should be further investigated. To this aim, in this study, we found that phosphorylation of this 270-kDa protein occurred as early as 1 min after mouse spermatozoa capacitation, which increased over time and remained stable after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The extent of phosphorylation and was closely associated with the PKA activity and spermatozoa motility characteristics. FSCB phosphorylation could be induced by PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB contributes to spermatozoa capacitation in a tyrosine-phosphorylated format, which may help in further elucidating the molecular mechanism of spermatozoa capacitation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.23
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• pp.10079-10083
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• 2015

Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasis and invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancer cells. Materials and Methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells. Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was used to estimate invasion and signaling pathways were studied by Western blotting. Results: ET-1 mRNA and protein in ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively. ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells. From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least related to some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 and MMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective than single treatment. Conclusions: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3 cells, but combined treatment might be a better therapeutic schedule.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1459-1463
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• 2014

Background: Urological cancers represent a major public problem associated with high mortality and morbidity. The pattern of these cancers varies markedly according to era, region and ethnic groups, but increasing incidence trends overall makes focused epidemiological studies important. The aim of the present study was to assess the incidence of most prevalent urological cancers in Iran from 2003 to 2009. Materials and Methods: The data for this study were obtained from the population-based Cancer Registry Center of the Iran Ministry of Health and Medical Education. Differences of mean age and age distributions of each cancer were compared between 2003 and 2009 in men and women. Results: Bladder cancer was the most common urologic cancer in both genders. The rate difference of age standardized ratio (ASR) of bladder and renal cell carcinoma in women were 1.54 and 2.01 percent per 100,000 population from 2003 to the 2009, respectively. In men, the rate difference of age standardized ratio of prostate, testis, kidney and bladder cancer was also 2.23, 1.2, 1.8 and 1.5 percent per 100,000 population from 2003 to 2009, respectively. The mean ages of patients in all cancers in both genders did not differ significantly through time (p value>0.05) but the distribution of ages of patients with bladder and prostate cancer changed significantly from 2003 to 2009 (p value<0.001). Conclusions: The results of present study suggest the general pattern and incidence of urological cancers in Iran are changing, the observed increase pointing to a need for urological cancer screening programs.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6519-6524
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• 2014

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033) but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.

• Molecules and Cells
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• v.41 no.3
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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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• v.17 no.3
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• pp.1399-1404
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• 2016

We investigated the urinary levels of 14-3-3 protein beta/alpha to evaluate their diagnostic significance with regard to clear cell renal cell carcinoma (ccRCC) and angiomyolipoma (AML). Urine samples from 91 patients with ccRCC, 16 patients with AML and 24 healthy volunteers were assessed. We used an enzyme-linked immunosorbent assay (ELISA) to quantify 14-3-3 protein beta/alpha levels in urine. Values were higher in patients with ccRCC than in those with AML and in healthy volunteers. High levels were associated with pathologic stage, lymph node status, distant metastasis and poor survival. Urinary levels of 14-3-3 protein beta/alpha were significantly increased in patients with small-sized carcinoma, irrespective of being less than 4.0 cm and 2.0 cm, compared with levels in patients with AML. This study is the first to report that increased expression of 14-3-3 protein beta/alpha in urine is associated with advanced stage and poor survival in patients with ccRCC. In addition, urinary 14-3-3 protein beta/alpha may differentiate AML from RCC, even when small sized. These results suggest that examination of urinary 14-3-3 protein beta/alpha could serve as a diagnostic and prognostic marker in patients with ccRCC.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6407-6412
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• 2015

Purpose: To predict prostatic carcinoma using a logistic regression model on prebiopsy peripheral blood samples. Materials and Methods: Data of a total of 873 patients who consulted Urology Outpatient Clinics of Fatih Sultan Mehmet Training and Research Hospital between February 2008 and April 2014 scheduled for prostate biopsy were screened retrospectively. PSA levels, prostate volumes, prebiopsy whole blood cell counts, neutrophil and platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), biopsy results and Gleason scores in patients who had established diagnosis of prostate cancer (PCa) were evaluated. Results: This study was performed on a total of 873 cases, with an age range 48-76 years, divided into three groups as for biopsy results. with diagnoses of benign prostatic hyperplasia (BPH) (n=304, 34.8 %), PCa (n=265, 30.4 %) and histological prostatitis (n=304; 34.8 %). Intra- and intergroup comparative evaluations were performed. White blood cell and neutrophil counts in the histological prostatitis group were significantly higher than those of the BPH and PCa groups (p=0.001; p=0.004; p<0.01). A statistically significant intergroup difference was found for PLR (p=0.041; p<0.05) but not lymphocyte count (p>0.05). According to pairwise comparisons, PLR were significantly higher in the PCa group relative to BPH group (p=0.018, p<0.05, respectively). Though not statistically significant, higher PLR in cases with PCa in comparison with the prostatitis group was remarkable (p=0.067, and p>0.05, respectively). Conclusions: Meta-analyses showed that in patients with PSA levels over 4 ng/ml, positive predictive value of PSA is only 25 percent. Therefore, novel markers which can both detect clinically significant prostate cancer, and also prevent unnecessary biopsies are needed. Relevant to this issue in addition to PSA density, velocity, and PCA3, various markers have been analyzed. In the present study, PLR were found to be the additional predictor of prostatic carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1639-1644
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• 2012

The aim of this study was to investigate the expression and significance of microsomal prostaglandin synthase-1 (mPGES-1) and Beclin-1 in the development of prostate cancer (PCa). Immunohistochemistry was performed on paraffin-embedded sections with rabbit polyclonal against mPGES-1 and Beclin-1 in 40 PCa, 40 benign prostatic hyperplasia (BPH) and 10 normal prostate specimens for this purpose. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for mRNA expression of mPGES-1 and Beclin-1, while MTT assays were used to ascertain the best working concentration of the mPGES-1 inhibitor (CAY10526). The effect of CAY10526 treatment on expression of Beclin-1 in DU-145 cells was studied using Western blot analysis. Localization of Beclin-1 and mPGES-1 was in endochylema. Significant differences in expression was noted among PCa, BPH and normal issues (P<0.05). Beclin-1 expression inversely correlated with mPGES-1 expression in PCa tissue (P<0.05). CAY10526 could significantly block mPGES-1 expression and the proliferation of DU-145 cells (P<0.05), while increasing Beclin-1 levels (P<0.05). Overexpression of mPGES-1 could decrease the autophagic PCa cell death. Inhibiting the expression of mPGES-1 may lead to DU-145 cell death and up-regulation of Beclin-1. The results suggest that inhibition of mPGES-1 may have therapeutic potential for PCa in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6327-6330
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• 2013

Haematuria is a common presentation of bladder cancer and requires a full urologic evaluation. This study aimed to develop a scoring system capable of stratifying patients with haematuria into high or low risk groups for having bladder cancer to help clinicians decide which patients need more urgent assessment. This cross-sectional study included all adult patients referred for haematuria and subsequently undergoing full urological evaluation in the years 2001 to 2011. Risk factors with strong association with bladder cancer in the study population were used to design the scoring system. Accuracy was determined by the area under the receiver operating characteristic (ROC) curve. A total of 325 patients with haematuria were included, out of which 70 (21.5%) were diagnosed to have bladder cancer. Significant risk factors associated with bladder cancer were male gender, a history of cigarette smoking and the presence of gross haematuria. A scoring system using 4 clinical parameters as variables was created. The scores ranged between 6 to 14, and a score of 10 and above indicated high risk for having bladder cancer. It was found to have good accuracy with an area under the ROC curve of 80.4%, while the sensitivity and specificity were 90.0% and 55.7%, respectively. The scoring system designed in this study has the potential to help clinicians stratify patients who present with haematuria into high or low r isk for having bladder cancer. This will enable high-risk patients to undergo urologic assessment earlier.