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1.
Int J Cancer ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924042

RESUMO

Several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC) are available, including radium-223 dichloride (223Ra), which was approved based on phase 3 data demonstrating improved overall survival (OS) and a favorable safety profile. To date, real-world evidence for 223Ra use in Taiwan is from three studies of <50 patients. This observational study (NCT04232761) enrolled male patients with histologically/cytologically confirmed mCRPC with bone metastases from centers across Taiwan. 223Ra was prescribed as part of routine practice by investigators. Patients with prior 223Ra treatment were excluded. The primary objective was to assess 223Ra safety; secondary objectives evaluated efficacy parameters, including OS. Overall, 224 patients were enrolled. Most patients had an Eastern Cooperative Oncology Group performance status of 0/1 (79.0%) and ≤20 bone metastases (69.2%); no patients had visceral metastases. 223Ra was first- or second-line therapy in 23.2% and 47.7% of patients, respectively. The total proportion of patients who received 5-6 223Ra cycles was 68.8%; this proportion was greater with first-line use (84.3%) than second- (65.7%) or third-/fourth-line use (64.1%). More chemotherapy-naïve patients (61.9%) completed the 6-cycle 223Ra treatment than chemotherapy-exposed patients (56.7%). Any-grade treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 54.0% and 28.6% of patients, respectively, while 12% experienced 223Ra-related adverse events. Median OS was 15.7 months (95% confidence interval 12.13-19.51); patients receiving 5-6 223Ra injections and earlier 223Ra use had longer OS than those receiving fewer injections and later 223Ra use. 223Ra provides a well-tolerated and effective treatment for Taiwanese patients with mCRPC and bone metastases.

2.
Prostate ; 83(6): 602-611, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36794287

RESUMO

BACKGROUND: Controlling the asymmetric distribution of phospholipids across biological membranes plays a pivotal role in the life cycle of cells; one of the most important contributors that maintain this lipid asymmetry are phospholipid-transporting adenosine triphosphatases (ATPases). Although sufficient information regarding their association with cancer exists, there is limited evidence linking the genetic variants of phospholipid-transporting ATPase family genes to prostate cancer in humans. METHODS: In this study, we investigated the association of 222 haplotype-tagging single-nucleotide polymorphisms (SNPs) in eight phospholipid-transporting ATPase genes with cancer-specific survival (CSS) and overall survival (OS) of 630 patients treated with androgen-deprivation therapy (ADT) for prostate cancer. RESULTS: After multivariate Cox regression analysis and multiple testing correction, we found that ATP8B1 rs7239484 was remarkably associated with CSS and OS after ADT. A pooled analysis of multiple independent gene-expression datasets demonstrated that ATP8B1 was under-expressed in tumor tissues and that a higher ATP8B1 expression was associated with a better patient prognosis. Moreover, we established highly invasive sublines using two human prostate cancer cell lines to mimic cancer progression traits in vitro. The expression of ATP8B1 was consistently downregulated in both highly invasive sublines. CONCLUSION: Our study indicates that rs7239484 is a prognostic factor for patients treated with ADT and that ATP8B1 can potentially attenuate prostate cancer progression.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Prognóstico , Próstata/patologia , Antagonistas de Androgênios/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Adenosina Trifosfatases/metabolismo
3.
World J Urol ; 41(5): 1373-1379, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36971826

RESUMO

PURPOSE: Abnormalities in autonomic function are associated with an overactive bladder (OAB). Heart rate variability is generally used as the sole assessment of autonomic activity; however, we utilized neuECG, a novel method of recording skin electrical signals, to assess autonomic nervous function in healthy controls and patients with OAB before and after treatment. METHODS: The prospective sample included 52 participants: 23 patients newly diagnosed with OAB and 29 controls. Autonomic function was assessed in all participants in the morning using neuECG, which analyzed the average skin sympathetic nerve activity (aSKNA) and electrocardiogram simultaneously. All patients with OAB were administered antimuscarinics; urodynamic parameters were assessed before treatments; autonomic and bladder functions using validated questionnaires for OAB symptoms were evaluated before and after OAB treatment. RESULTS: Patients with OAB had significantly higher baseline aSKNA (p = 0.003), lower standard deviation of the normal-to-normal beat intervals, lower root mean square of the successive differences, lower high-frequency, and higher low-frequency than did controls. Baseline aSKNA had the highest value in predicting OAB (AUROC = 0.783, p < 0.001). The aSKNA was negatively correlated with first desire and normal desire in urodynamic studies (both p = 0.025) and was significantly decreased after treatment at rest, stress, and recovery phases, as compared to those before treatment (p = 0.046, 0.017, and 0.017, respectively). CONCLUSION: Sympathetic activity increased significantly in patients with OAB compared to that in healthy controls, and decreased significantly post-treatment. Higher aSKNA is associated with decreased bladder volume at which voiding is desired. SKNA may be a potential biomarker for diagnosing OAB.


Assuntos
Bexiga Urinária Hiperativa , Humanos , Estudos Prospectivos , Micção/fisiologia , Antagonistas Muscarínicos/uso terapêutico , Biomarcadores , Urodinâmica
4.
BMC Public Health ; 23(1): 1189, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340386

RESUMO

BACKGROUND: Tobacco use and secondhand smoke (SHS) are risk factors of kidney stone disease (KSD). The hypothesis is that tobacco produces chemicals that increase oxidative stress and vasopressin, which leads to decreased urine output, and contributes to stone formation. The aim of this study was to examine the effects of smoking and SHS on the development of KSD. MATERIALS AND METHODS: We analyzed a total of 25,256 volunteers with no history of KSD participated in the Taiwan Biobank. The presence of underlying and follow-up KSD was surveyed by a self-administrated questionnaire. They were classified into three groups on the basis of smoking and SHS exposure, accessed with survey questionnaires; never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups. RESULTS: KSD was noted in 352 (2.0%), 50 (3.3%) and 240 (4.1%) subjects in the never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups, respectively, with a mean follow-up of 4 years. The odds ratio (OR) of KSD was higher in the never-smokers with SHS exposure (OR, 1.622; 95% confidence interval [95% CI], 1.225 to 2.255) and ever-smokers groups (OR, 1.282; 95% CI, 1.044 to 1.574) than in the never-smokers with no SHS exposure group after adjustment of confounders. In addition, never-smokers with SHS exposure had similar effects on the development of KSD than ever-smokers (OR, 1.223; 95% CI, 0.852 to 1.756). CONCLUSION: Our study suggests that both smoking and SHS are a risk factor for developing KSD and that the impact of SHS is not inferior to that of smoking. TRIAL REGISTRATION: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20,210,058).


Assuntos
Cálculos Renais , Poluição por Fumaça de Tabaco , Humanos , Poluição por Fumaça de Tabaco/efeitos adversos , Estudos Longitudinais , Fumar/efeitos adversos , Fumar/epidemiologia , Estudos de Coortes , Cálculos Renais/etiologia , Cálculos Renais/induzido quimicamente
5.
J Formos Med Assoc ; 122(4): 299-308, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36797129

RESUMO

Darolutamide, a second-generation androgen receptor inhibitor (SGARI), has been shown to increase metastasis-free survival and overall survival among men with non-metastatic castration-resistant prostate cancer (nmCRPC). Its unique chemical structure potentially provides efficacy and safety advantages over the SGARIs apalutamide and enzalutamide, which are also indicated for nmCRPC. Despite a lack of direct comparisons, the SGARIs appear to have similar efficacy, safety, and quality of life (QoL) results. Indirect evidence suggests that darolutamide is preferred for its good adverse event profile, an attribute valued by physicians, patients, and their caregivers for maintaining QoL. Darolutamide and others in its class are costly; access may be a challenge for many patients and may lead to modifications to guideline-recommended regimens.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Qualidade de Vida , Resultado do Tratamento , Antagonistas de Receptores de Andrógenos/efeitos adversos
6.
Int J Mol Sci ; 24(8)2023 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-37108458

RESUMO

Microglia-associated neuroinflammation is recognized as a critical factor in the pathogenesis of neurodegenerative diseases; however, there is no effective treatment for the blockage of neurodegenerative disease progression. In this study, the effect of nordalbergin, a coumarin isolated from the wood bark of Dalbergia sissoo, on lipopolysaccharide (LPS)-induced inflammatory responses was investigated using murine microglial BV2 cells. Cell viability was assessed using the MTT assay, whereas nitric oxide (NO) production was analyzed using the Griess reagent. Secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) was detected by the ELISA. The expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs) and NLRP3 inflammasome-related proteins was assessed by Western blot. The production of mitochondrial reactive oxygen species (ROS) and intracellular ROS was detected using flow cytometry. Our experimental results indicated that nordalbergin ≤20 µM suppressed NO, IL-6, TNF-α and IL-1ß production; decreased iNOS and COX-2 expression; inhibited MAPKs activation; attenuated NLRP3 inflammasome activation; and reduced both intracellular and mitochondrial ROS production by LPS-stimulated BV2 cells in a dose-dependent manner. These results demonstrate that nordalbergin exhibits anti-inflammatory and anti-oxidative activities through inhibiting MAPK signaling pathway, NLRP3 inflammasome activation and ROS production, suggesting that nordalbergin might have the potential to inhibit neurodegenerative disease progression.


Assuntos
Lipopolissacarídeos , Doenças Neurodegenerativas , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Microglia/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças Neuroinflamatórias , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Doenças Neurodegenerativas/metabolismo , Transdução de Sinais , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo
7.
Cancer Cell Int ; 22(1): 180, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35524261

RESUMO

BACKGROUND: Immunodeficiencies are genetic diseases known to predispose an individual to cancer owing to defective immunity towards malignant cells. However, the link between immunodeficiency and prostate cancer progression remains unclear. Therefore, the aim of this study was to evaluate the effects of common genetic variants among eight immunodeficiency pathway-related genes on disease recurrence in prostate cancer patients treated with radical prostatectomy. METHODS: Genetic and bioinformatic analyses on 19 haplotype-tagging single-nucleotide polymorphisms in eight immunodeficiency pathway-related genes were conducted in 458 patients with prostate cancer after receiving radical prostatectomy. Furthermore, the TNFRSF13B was knocked down in 22Rv1 and PC-3 human prostate cancer cell lines via transfecting short hairpin RNAs and cell proliferation and colony formation assays were performed. The molecular mechanisms underlying the effects of TNFRSF13B were further explored by microarray gene expression profiling. RESULTS: TNFRSF13B rs4792800 was found to be significantly associated with biochemical recurrence even after adjustment for clinical predictors and false discovery rate correction (adjusted hazard ratio 1.78, 95% confidence interval 1.16-2.71, p = 0.008), and the G allele was associated with higher TNFRSF13B expression (p = 0.038). Increased TNFRSF13B expression suggested poor prognosis in four independent prostate cancer datasets. Furthermore, silencing TNFRSF13B expression resulted in decreased colony formation of 22Rv1 and PC-3 cells through modulating the cell cycle and p53 signalling pathways. CONCLUSIONS: The present study suggests the potential role of immunodeficiency pathway-related genes, primarily TNFRSF13B, in prostate cancer progression.

8.
Int J Med Sci ; 19(10): 1596-1602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36185328

RESUMO

We aimed to investigate the association between habitual tea consumption and the risk of developing cataracts in a large community-based cohort study. We prospectively collected volunteers from 29 recruitment centers that were ≧ 55 years old with no history of cataracts at the beginning of the study. There were 12,080 participants with available information in our study and were divided into two groups according to habitual tea consumption; non-tea-drinking and tea-drinking groups. The mean age was 59 years. Compared to the non-tea-drinking group, the tea-drinking group had a significantly lower incidence of developing cataracts (15.5% vs 12.1%) during follow-up of 46 months. In multivariate Cox proportional hazards regression analysis, the relative risk (RR) of incident cataracts was lower in the tea-drinking group than the non-tea-drinking group (RR = 0.848; 95% confidence interval [CI] = 0.751 to 0.957). Participants with ≧ 2 cups per day were associated with almost 16% reduction in the risk of developing cataracts compared with the non-tea-drinking group (RR = 0.844; 95% CI = 0.741 to 0.961). Our study suggests that habitual tea consumption can reduce the incidence of cataracts and raises the possibility that the tea content may slow the progression of cataracts.


Assuntos
Catarata , Catarata/epidemiologia , Catarata/etiologia , Catarata/prevenção & controle , Estudos de Coortes , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Risco , Fatores de Risco
9.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769200

RESUMO

In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes DNTT, EXO1, NEIL3, and EME2 genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.


Assuntos
Dano ao DNA , Reparo do DNA , Neoplasias da Próstata/genética , Transcriptoma , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Humanos , Masculino , Mutação , Prognóstico , Neoplasias da Próstata/diagnóstico
10.
Acta Cardiol Sin ; 37(6): 625-631, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34812236

RESUMO

BACKGROUND: High electromechanical activation time (EMAT) is associated with paroxysmal atrial fibrillation and heart failure. Little is known about the association between EMAT and metabolic syndrome (MetS), a precursor of cardiovascular disease. OBJECTIVES: To explore the association between EMAT and MetS. METHODS: A total of 429 male volunteers were divided into MetS (n = 135, age 60.3 ± 3.7 years) and non-MetS (n = 294, age 58.1 ± 26.6 years) groups in this cross-sectional study. A complete medical history, fasting blood analysis and phonoelectrocardiographic parameters were recorded. EMAT was defined as the time from the onset of Q- wave to the peak first heart sound (Q-S1 interval), and this interval divided by the R-R interval for heart rate correction was calculated as normalized EMAT (nEMAT). RESULTS: The subjects with MetS had a significantly higher rate of positive nEMAT (nEMAT ≥ 15%: 6.7% vs. 2%, p = 0.015), higher heart rate (HR, 71.9 ± 12.0 vs. 69.2 ± 11.1 bpm, p = 0.022) but shorter left ventricular ejection time (LVST = 312.4 ± 33.5 vs. 319.8 ± 31.8 msec, p = 0.029). However, the normalized LVST (nLVST) was not significantly different after adjusting for HR. In multivariate analysis, nEMAT was significantly associated with MetS (odds ratio = 3.43, 95% confidence interval = 1.195-9.837, p = 0.022). CONCLUSIONS: Positive nEMAT, a prolonged early phase of contraction, was significantly associated with MetS in males. High nEMAT may be an earlier sign of cardiac function abnormality in MetS.

11.
Cancer Cell Int ; 19: 87, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30996687

RESUMO

BACKGROUND: To determine the association between circadian pathway genetic variants and the risk of prostate cancer progression. METHODS: We systematically evaluated 79 germline variants in nine circadian pathway genes in a cohort of 458 patients with localized prostate cancer as the discovery phase. We then replicated the significant findings in another cohort of 324 men with more advanced disease. The association of each variant with prostate cancer progression was evaluated by a log-rank test and Cox regression. RESULTS: A single nucleotide polymorphism of the neuronal PAS domain protein 2 (NPAS2) gene (rs6542993 A>T) was found to be associated with a significantly higher risk of disease progression in both localized (P = 0.001) and advanced (P = 0.039) prostate cancer cases. In silico analysis revealed decreased expression levels of NPAS2 in carriers of the T allele of rs6542993 compared with those carrying the A allele. Consistently, downregulation of NPAS2 expression was associated with more aggressive prostate cancer and poor progression-free survival (log-rank P = 0.002). CONCLUSIONS: The NPAS2 rs6542993 polymorphism may be a promising biomarker, and may shed light on the pathways that govern prostate cancer progression.

12.
Urol Int ; 102(4): 495-498, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30343289

RESUMO

Bladder migration of a Hem-o-lok® clip, due to robotic-assisted radical prostatectomy (RARP), is uncommon, and would form a foreign body in the bladder and present as lower urinary tract symptoms after the early postoperative period. We hereby report a rare, delayed appearance of a secondary bladder stone due to the migration of a Hem-o-lok® clip that occurred 5 years after RARP.


Assuntos
Adenocarcinoma/cirurgia , Corpos Estranhos/cirurgia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Instrumentos Cirúrgicos/efeitos adversos , Bexiga Urinária/cirurgia , Adenocarcinoma/diagnóstico por imagem , Idoso , Migração de Corpo Estranho/diagnóstico , Humanos , Masculino , Período Pós-Operatório , Neoplasias da Próstata/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos , Bexiga Urinária/diagnóstico por imagem , Cálculos da Bexiga Urinária/diagnóstico por imagem , Cálculos da Bexiga Urinária/cirurgia
13.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987073

RESUMO

Current clinical challenges of prostate cancer management are to restrict tumor growth and prohibit metastasis. AICAR (5-aminoimidazole-4-carbox-amide-1-ß-d-ribofuranoside), an AMP-activated protein kinase (AMPK) agonist, has demonstrated antitumor activities for several types of cancers. However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Cell growth was performed by MTT assay and soft agar assay; cell apoptosis was examined by Annexin V/propidium iodide (PI) staining and poly ADP ribose polymerase (PARP) cleavage western blot, while cell migration and invasion were evaluated by wound-healing assay and transwell assay respectively. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. In addition, our results demonstrated that AICAR induces apoptosis, attenuates transforming growth factor (TGF)-ß-induced cell migration, invasion and EMT-related protein expression, and enhances the chemosensitivity to docetaxel in prostate cancer cells through regulating the AMPK/mTOR-dependent pathway. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ribonucleotídeos/farmacologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Aminoimidazol Carboxamida/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel/farmacologia , Sinergismo Farmacológico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Masculino , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia
14.
J Cell Mol Med ; 22(7): 3661-3670, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29682886

RESUMO

Single nucleotide polymorphisms (SNPs) within the regulatory elements of a gene can alter gene expression, making these SNPs of prime importance for candidate gene association studies. We aimed to determine whether such regulatory variants are associated with clinical outcomes in three cohorts of patients with prostate cancer. We used RegulomeDB to identify potential regulatory variants based on in silico predictions and reviewed genome-wide experimental findings. Overall, 131 putative regulatory SNPs with the highest confidence score on predicted functionality were investigated in two independent localized prostate cancer cohorts totalling 458 patients who underwent radical prostatectomy. The statistically significant SNPs identified in these two cohorts were then tested in an additional cohort of 504 patients with advanced prostate cancer. We identified one regulatory SNPs, rs1646724, that are consistently associated with increased risk of recurrence in localized disease (P = .003) and mortality in patients with advanced prostate cancer (P = .032) after adjusting for known clinicopathological factors. Further investigation revealed that rs1646724 may affect expression of SLC35B4, which encodes a glycosyltransferase, and that down-regulation of SLC35B4 by transfecting short hairpin RNA in DU145 human prostate cancer cell suppressed proliferation, migration and invasion. Furthermore, we found increased SLC35B4 expression correlated with more aggressive forms of prostate cancer and poor patient prognosis. Our study provides robust evidence that regulatory genetic variants can affect clinical outcomes.


Assuntos
Proteínas de Transporte de Nucleotídeos/genética , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Estudos de Coortes , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Prostatectomia , Neoplasias da Próstata/cirurgia , Taiwan/epidemiologia , Análise Serial de Tecidos
15.
J Sex Med ; 15(11): 1527-1536, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30415809

RESUMO

BACKGROUND: Hepatocyte nuclear factor-4α (HNF4A) can influence the risk of insulin resistance that is postulated to be an important link between metabolic syndrome (MetS) and testosterone deficiency (TD) in men. AIM: To investigate the relationship between single-nucleotide polymorphisms (SNPs) of HNF4A and the risk of developing MetS and TD in a population of aging Taiwanese men. METHODS: A free health screening of men over 40 years of age was conducted in a medical center in Kaohsiung City, Taiwan. All participants underwent a physical examination, answered a questionnaire on demographics and medical history, completed the Androgen Deficiency in The Aging Male questionnaire to assess clinical symptoms of TD, and provided 20-mL whole blood samples for biochemical, hormonal, and genetic evaluation. MAIN OUTCOME MEASURE: 3 common SNPs (rs11574736, rs1884613, and rs2144908) of HNF4A were selected and identified using a TaqMan 5' allelic discrimination assay. RESULTS: 559 men were enrolled for this study (mean age, 55.8± 4.9 years). Prevalence of TD was significantly higher (P = .031) in subjects with MetS (16.8%) than those without MetS (10.1%). In SNP rs1884613 of HNF4A, subjects with the C allele carried a 1.31- and 1.50-times higher risk of developing MetS and TD, respectively, compared to those with the G allele, after adjusting for potential covariates. In addition, subjects with the CC genotype were exposed to a 1.91- and 2.20-times higher risk of developing MetS and TD, respectively, compared to those with the GG genotype. CLINICAL IMPLICATIONS: Our findings may point to the importance of the role played by insulin resistance in the link between MetS and TD. STRENGTH & LIMITATIONS: Our current work is the first report with adequate sample size to evaluate the role of genetic variants of HNF4A on the risk of both MetS and TD in men. The limitations included subjects enrolled from a free health screening and single measurement of serum testosterone levels. CONCLUSION: The rs1884613 SNP marker of HNF4A is significantly associated with an increased risk for developing both MetS and TD in aging Taiwanese men. Further population-based studies utilizing larger samples of different ethnicities may be needed to confirm these preliminary results. Liu C-C, Lee Y-C, Hung S-P. Hepatocyte Nuclear Factor-4α P2 Promoter Variants Are Associated With the Risk of Metabolic Syndrome and Testosterone Deficiency in Aging Taiwanese Men. J Sex Med 2018;15:1527-1536.


Assuntos
Disfunção Erétil/genética , Fatores Nucleares de Hepatócito/genética , Síndrome Metabólica/genética , Regiões Promotoras Genéticas/genética , Testosterona/deficiência , Adulto , Idoso , Envelhecimento , Povo Asiático , Disfunção Erétil/sangue , Disfunção Erétil/epidemiologia , Genótipo , Humanos , Masculino , Saúde do Homem , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Inquéritos e Questionários , Taiwan , Testosterona/sangue
16.
Int Braz J Urol ; 44(6): 1122-1128, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30088727

RESUMO

OBJECTIVES: Previous studies have compared infectious outcomes on the basis of whether rectal preparation was performed; however, they failed to evaluate the quality of each rectal preparation, which may have led to confounding results. This study aimed to compare hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy between patients with adequate and traditional rectal preparations. MATERIALS AND METHODS: Between January 2011 and December 2016, a total of 510 patients who underwent transrectal ultrasound - guided prostate biopsy at our institutions and were orally administered prophylactic antibiotics (levofloxacin) were included. Two rectal preparations were performed: (1) adequate rectal preparation confirmed by digital rectal examination and transrectal ultrasound (Group A, n = 310) and (2) traditional rectal preparation (Group B, n = 200). All patient characteristics were recorded. A logistic regression model was used to assess the effects of the two different rectal preparations on urosepsis, adjusted by patient characteristics. RESULTS: There were a total of three and nine hospitalizations for urosepsis in Groups A and B, respectively. Differences in the demographic data between the two groups were insignificant. Logistic regression showed that adequate rectal preparation before biopsy significantly decreased the risk for urosepsis after biopsy (adjusted odds ratio: 0.2; 95% confidence interval: 0.05 - 0.78; P = 0.021). CONCLUSIONS: Adequate rectal preparation could significantly reduce hospitalizations for urosepsis within 1 month after transrectal ultrasound-guided prostate biopsy. The quality of rectal preparation should be evaluated before biopsy. If adequate rectal preparation is not achieved, postponing the biopsy and adjusting the rectal preparation regimen are suggested.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Enema/métodos , Próstata/patologia , Sepse/prevenção & controle , Infecções Urinárias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
17.
J Sex Med ; 14(4): 510-517, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28364978

RESUMO

BACKGROUND: Repeated evidence from animal models suggests a strong link between vascular endothelial growth factor (VGEF) and penile vasculature and erectile function because VEGF can alter the physiologic pathways involved in the regulation of penile vasomotor tone. AIM: To investigate three VEGF polymorphisms and their link to erectile dysfunction (ED). METHODS: We enrolled 688 Taiwanese men with a mean age of 55.6 years (SD = 4.5) during a free health screening. All participants provided complete medical histories and underwent physical examinations. Fasting blood samples were obtained for biochemical analysis and hormone profiling. The allelic discrimination of three VEGF gene polymorphisms (460T/C [rs833061], 1154G/A [rs1570360], and 2578A/C [rs699947]) was performed using validated TaqMan single-nucleotide polymorphism genotyping assays. OUTCOMES: Subjects underwent assessment using the simplified five-item International Index of Erectile Function to diagnose and assess ED severity. RESULTS: The results showed that diabetes mellitus (odds ratio [OR] = 3.27, P < .01), hypertension (OR = 3.47, P < .01), and having the VEGF 2578A allele (OR = 1.54, P = .01) were the three most independent risk factors for ED. In univariate analysis, all three VEGF polymorphisms (460C, 1154A, and 2578A) were significantly associated with a higher prevalence of coronary artery disease (P < .01) and greater frequencies of hypertension were found in carriers of the 1154A allele and the 2578A allele (P = .01). Multiple logistic regression analysis showed a significant association between VEGF 2578A allele carrier status and ED (OR = 1.54, 95% CI = 1.10∼2.15, P = .01). Furthermore, the prevalence and severity of ED were significantly increased with an increment of the 2578A allele number (P < .05). CLINICAL IMPLICATIONS: VEGF 2578C/A gene polymorphisms could be a genetic susceptibility factor for the development of ED. STRENGTH AND LIMITATION: This is the first study to investigate the genetic susceptibility of VEGF polymorphisms to ED. This study was cross-sectional with a lack of functional and molecular production investigations. Data on the association among conditions might not allow definitive conclusions about causal links. CONCLUSION: This study showed that VEGF 2578A allele carriers in a Taiwanese population are at greater risk for ED. Lee Y-C, Huang S-P, Tsai C-C, et al. Associations of VEGF Gene Polymorphisms With Erectile Dysfunction and Related Risk Factors. J Sex Med 2017;14:510-517.


Assuntos
Disfunção Erétil/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Estudos Transversais , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
18.
Int J Med Sci ; 14(12): 1301-1306, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29104488

RESUMO

Background: Cancer stem cells (CSCs) are involved in tumor progression and drug resistance. We hypothesized that variants in CSC marker genes influence treatment outcomes in prostate cancer. Methods: Ten potentially functional single nucleotide polymorphisms (SNPs) in seven prostate CSC marker genes, TACSTD2, PROM1, ITGA2, POU5F1, EZH2, PSCA, and CD44, were selected for analysis of their association with disease recurrence by Kaplan-Meier analysis and Cox regression in a cohort of 320 patients with localized prostate cancer receiving radical prostatectomy. Results: We identified one independent SNP, rs2394882, in POU5F1 that was associated with prostate cancer recurrence (hazard ratio 0.32, 95% confidence interval 0.14-0.71, P = 0.005) after adjustment for known clinical predictors. Further in silico functional analyses revealed that rs2394882 affects POU5F1 expression, which in turn is significantly correlated with prostate cancer aggressiveness and patient prognosis. Conclusion: Our results suggest that rs2394882 is prognostically relevant in prostate cancer, possibly by modulating the expression of the CSC gene POU5F1.


Assuntos
Biomarcadores Tumorais/genética , Recidiva Local de Neoplasia/genética , Células-Tronco Neoplásicas/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Neoplasias da Próstata/genética , Idoso , Biomarcadores Tumorais/metabolismo , Moléculas de Adesão Celular , Estudos de Coortes , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Fator 3 de Transcrição de Octâmero/metabolismo , Polimorfismo de Nucleotídeo Único , Prognóstico , Modelos de Riscos Proporcionais , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Taiwan/epidemiologia
19.
J Formos Med Assoc ; 116(11): 825-836, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29046247

RESUMO

Radium-223 is a first-in-class α-emitting radiopharmaceutical that targets bone metastases associated with metastatic castration-resistant prostate cancer (mCRPC). In the pivotal phase III trial ALSYMPCA, radium-223 significantly increased overall survival (OS), compared with placebo (median 14.9 vs 11.3 months; hazard ratio 0.70; 95% CI 0.58-0.83; p < 0.001), in patients with mCRPC and symptomatic bone metastases-with a comparable safety profile. To optimize treatment outcomes, selection of appropriate patients is important. As well as osteoblastic bone metastases, mCRPC patients should be well enough to receive six doses of radium-223 as this treatment duration has been shown to greatly improve OS outcomes compared with administration of four or fewer doses. Additionally, alkaline phosphatase and lactate dehydrogenase are emerging as important biomarkers during radium-223 treatment. Optimal concomitant standard-of-care therapies (such as abiraterone or enzalutamide) to be administered with radium-223 have yet to be defined as does the most efficacious dose and duration of radium-223 treatment. In conclusion, radium-223 is an important addition to the mCRPC treatment landscape and marks a paradigm shift in the treatment of bone metastases.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias de Próstata Resistentes à Castração/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
20.
BMC Cancer ; 16: 242, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-26996776

RESUMO

BACKGROUND: This study investigated the effects that hair dye use and regular exercise exert on the risk and prognosis of prostate cancer. METHODS: We studied 296 cases of histologically confirmed prostate cancer and 296 age- (in 2-y bands), ethnicity-, and hospital-matched controls in Taiwan between August 2000 and December 2008. To determine the rate of prostate cancer survival, another 608 incident prostate cancer cases occurring between August 2000 and December 2007 were investigated. Information on hair dye use and regular exercise was obtained using a standardized questionnaire. RESULTS: The use of hair dyes was associated with a significant 2.15-fold odds of developing prostate cancer (adjusted odds ratio = 2.15, 95% confidence interval [CI] = 1.32-3.57), but was not associated with prostate cancer survival, compared with no use. The significant risks were more prominent in users aged < 60 years who had used hair dyes for > 10 years, > 6 times per year, and started using hair dyes before 1980. By contrast, regular exercise significantly reduced the number of prostate-cancer-specific death (adjusted hazard ratio = 0.37, 95% CI = 0.16-0.83); the protective effect of exercise was more prominent among cancer patients who exercised daily (≥ 7 times/week). However, exercise could not prevent the development of prostate cancer. CONCLUSIONS: Hair dye use increased the risk of prostate cancer, whereas regular exercise reduced the number of prostate-cancer-specific deaths.


Assuntos
Terapia por Exercício , Tinturas para Cabelo/efeitos adversos , Prognóstico , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/induzido quimicamente , Neoplasias da Próstata/fisiopatologia , Fatores de Risco , Taiwan
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