• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.10009-10013
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• 2014

Background: Vitamin D receptor (VDR) gene has been a subject of extensive pharmacogenetic research recently. Association studies between different types of cancers including prostate cancer (PCa) and VDR gene polymorphism have also been conducted. The objective of this study was to find possible associations between PCa and VDR gene polymorphisms in the Pakistani population. Materials and Methods: A total of 162 subjects, including prostate cancer patients and controls, were genotyped for Apa I, Taq I and Fok I polymorphisms in the VDR gene using allele specific PCR, PCR-RFLP and direct DNA sequencing. Allelic frequencies were tested for Hardy-Weinberg equilibrium and associations between the genetic markers and PCa were calculated using logistic regression. Results: Apa I CC genotype was found to have strongest association with PCa risk, and "A" genotype was found to have protective effect. Fok I and Taq I did not have appreciable levels of association with PCa, although Taq I "TC" heterozygotes seemed to have some protective effect. Similarly the "C" allele of Fok I also seemed to have protective effect. Conclusions: To our knowledge, this is the first report showing association between VDR gene polymorphisms and PCa in Pakistan. Our findings may be somewhat skewed because of small sample size and tendency of consanguineous marriages in Pakistani society; nevertheless, it shows the trend of association and protective effects of certain VDR gene polymorphisms against PCa.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6085-6088
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• 2013

Prostate specidic antigen (PSA) and digital rectal examination (DRE) are the known predictive factors for positive prostate biopsies differing according to the age, region and race. There have been only very limited studies about the impact of PSA on histological findings at prostate biopsy in Turkey. The aim of this study was to evaluate the impact of PSA and clinical stage on histologic findings of prostate biopsy in men older than 75 years of age as a first study in the Turkish population. A total of 1,645 consecutive prostate biopsies were included, with 194 men aged 75 or older. Cancer was identified in 104 patients (53.6%). Of the 104 positive biopsies, Gleason scores were less than 7 in 53 (49%) patients, 7 or greater in 51 (51%) patients. Positive prostate biopsies were significantly correlated with advanced age (p=0.0001), abnormal DRE (p=0.0001) and raised PSA (p=0.0001). The prostate volume was significantly correlated with advanced age especially in prostate cancer patients over 75 years, compared with those under 75 (p=0.0001). These results are useful for counseling men older than 75 years for prostate cancer detection. However, PCa screening decisions are currently based on urologist judgment and detection of latent asymptomatic disease is an important concern regarding costs, overdiagnosis, overtreatment and quality of life (QOL) for men aged 75 years and older. Healthy old patients with a long life expectancy need to be carefully evaluated for eligibility for PCa screening.

• Korean Journal of Radiology
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• v.24 no.6
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• pp.574-589
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• 2023

Radiopharmaceuticals targeting prostate-specific membrane antigens (PSMA) are essential for the diagnosis, evaluation, and treatment of prostate cancer (PCa), particularly metastatic castration-resistant PCa, for which conventional treatment is ineffective. These molecular probes include [⁶⁸Ga]PSMA, [¹⁸F]PSMA, [Al¹⁸F]PSMA, [^99mTc]PSMA, and [⁸⁹Zr]PSMA, which are widely used for diagnosis, and [¹⁷⁷Lu]PSMA and [²²⁵Ac]PSMA, which are used for treatment. There are also new types of radiopharmaceuticals. Due to the differentiation and heterogeneity of tumor cells, a subtype of PCa with an extremely poor prognosis, referred to as neuroendocrine prostate cancer (NEPC), has emerged, and its diagnosis and treatment present great challenges. To improve the detection rate of NEPC and prolong patient survival, many researchers have investigated the use of relevant radiopharmaceuticals as targeted molecular probes for the detection and treatment of NEPC lesions, including DOTA-TOC and DOTA-TATE for somatostatin receptors, 4A06 for CUB domain-containing protein 1, and FDG. This review focused on the specific molecular targets and various radionuclides that have been developed for PCa in recent years, including those mentioned above and several others, and aimed to provide valuable up-to-date information and research ideas for future studies.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3953-3958
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• 2016

Prostatic cancer is the second cause of cancer-related death among men worldwide. The human papilloma viruses (HPVs) are a family of sexually transmitted viruses which have may have roles in the ethiology of inflammation in prostate leading to benign prostatic hyperplasia (BPH) and prostate cancer (PCa). In this study, we evaluated the frequency of different HPV types in prostatic cancer and benign prostatic hyperplasia (BPH) in Kerman province, southeast of Iran, using real-time PCR techniques. The aim of the present research was to clarify any association with prostatic carcinogenesis. Real Time PCR showed that HPV DNA was found in 20% of 200 PCa samples, 80 percent of these with high-risk HPV types, 40% with type-16,18, 30 % type-31,33 and 10% type 54. High risk HPV DNA was detected in only 2% of BPH samples. Values for low risk types were much higher. Our study provided a support for the role of high risk HPV infection in prostatic disease in Iranian patients, and association between presence of HPV DNA and prostate carcinoma. In particular, HPV 16 and18 might have an important role in prostate cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2555-2558
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• 2014

Pirpose: The aim of this study to analyze the association between history of diabetes mellitus (DM) with risk of prostate cancer (PCa) and cancer grade among men undergoing radical prostatectomy for PCa. Materials and Methods: 50 patients with DM and 50 patients without DM who undervent radical prostatectomy (RP) were included in the study. Age at biopsy, height, weight, digital rectal examination (DRE), pre-biopsy PSA levels, prostate volume, histopathologic diagnosis after surgery and gleason scores were collected data from all patients. Histologic material obtained at biopsy was given a Gleason score; tumours with a Gleason score ${\geq}7$ were considered high grade and <7 were considered low grade. Results: The mean age at the time of biopsy was 63.7 in patients with DM and 61.6 in patients without DM. Diabetic men had significantly lower PSA levels (p=0.01). Mean PSA level $7.04{\pm}2.85$ in patients with DM and $8.7{\pm}2.86$ in patients without DM, respectively. Also, diabetic men had higher RP tumor grade than men without DM (p=0.04). We found that HbA1c levels were higher in patients who have high grade prostate cancer (p<0.05). Conclusions: Diabetic men undergoing RP have lower PSA levels and have significantly higher grade PCa. We must be careful for screening PCa in patients with DM. Although the patients had lower PSA levels, they might have high grade disease.

• Molecules and Cells
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• v.45 no.4
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• pp.202-215
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• 2022

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.4939-4944
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• 2016

Background: An upward trend has been noted for the incidence of prostate cancer (PCa) in Vietnam, but information is limited on modifiable factors associated with this form of cancer. This case-control study was conducted to ascertain any relationship between habitual tea consumption and PCa risk. Materials and Methods: Two hundred and fifty-three incident patients with histologically confirmed PCa and 419 (340 community-based and 79 hospital-based) controls, matched by age, were recruited in Ho Chi Minh City during 2013-2015. Information on frequency, quantity and duration of tea consumption, together with demographics, habitual diet and lifestyle characteristics, was obtained by direct interviews using a validated questionnaire. Logistic regression analyses were performed to assess associations between tea consumption variables and PCa risk. Results: The control subjects reported higher tea consumption levels in terms of cumulative exposure, frequency and quantity of tea drank than the PCa patients. After accounting for confounding factors, increasing tea consumption was found to be associated with reduced risk of PCa. The adjusted odds ratios (95% confidence intervals) were 0.52 (95% CI 0.35-0.79) and 0.30 (95% CI 0.18-0.48) for participants drinking 100-500 ml/day and > 500 ml/day, respectively, relative to those drinking < 100 ml/day. Significant inverse dose-response relationships were also observed for years of drinking and number of cups consumed daily (P <0.01). Conclusion: Habitual tea consumption is associated with a reduced risk of PCa in Vietnamese men.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3305-3308
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• 2013

Background: The role of inflammation in prostate diseases is suggested by the presence of inflammatory cells within the prostate in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) patients. In addition, bacterial and viral infection may lead to chronic and recurrent inflammation of the prostate. The human papillomaviruses (HPVs) are a family of sexually transmitted viruses which have been implicated in the aetiology of cervical cancer and several other malignancies. This study evaluated the frequency of HPV infection in individuals with prostatic disease in Iran. Materials and Methods: The study included formalin fixed paraffin- embedded tissue samples of 196 primary prostate cases, including 29 PCa and 167 BPH samples. HPV DNA was purified and amplified through MY09/MY11 and GP5+/GP6+ primers with nested PCR. All patients were interviewed using a questionnaire to collect demographic information. Results: Nested PCR showed that HPV DNA was found in 17.2 percent of PCa samples and 4.8 percent of BPH samples (not significant). Conclusions: Our data do not support a significant role of HPV infection in prostatic disease in Iranian patients, but demographic data indicated a probable association between presence of HPV DNA and risk of inflammation in prostate tissue which might lead to prostate carcinoma. Further studies are required to elucidate any roles of HPV infection in prostatic disease.

• Parasites, Hosts and Diseases
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• v.59 no.6
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• pp.547-556
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• 2021

Our objective was to investigate whether inflammatory microenvironment induced by Trichomonas vaginalis infection can stimulate proliferation of prostate cancer (PCa) cells in vitro and in vivo mouse experiments. The production of CXCL1 and CCL2 increased when cells of the mouse PCa cells (TRAMP-C2 cell line) were infected with live T. vaginalis. T. vaginalis-conditioned medium (TCM) prepared from co-culture of PCa cells and T. vaginalis increased PCa cells migration, proliferation and invasion. The cytokine receptors (CXCR2, CCR2, gp130) were expressed higher on the PCa cells treated with TCM. Pretreatment of PCa cells with antibodies to these cytokine receptors significantly reduced the proliferation, mobility and invasiveness of PCa cells, indicating that TCM has its effect through cytokine-cytokine receptor signaling. In C57BL/6 mice, the prostates injected with T. vaginalis mixed PCa cells were larger than those injected with PCa cells alone after 4 weeks. Expression of epithelial-mesenchymal transition markers and cyclin D1 in the prostate tissue injected with T. vaginalis mixed PCa cells increased than those of PCa cells alone. Collectively, it was suggested that inflammatory reactions by T. vaginalis-stimulated PCa cells increase the proliferation and invasion of PCa cells through cytokine-cytokine receptor signaling pathways.

• Parasites, Hosts and Diseases
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• v.58 no.3
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• pp.217-227
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• 2020

Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.