Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
1.
Diagnostics (Basel) ; 13(16)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37627895

RESUMO

Bladder cancer is a common urological cancer and has the highest recurrence rate of any cancer. The aim of our study was to profile and characterize the protein expression of homeobox A13 (HOXA13) and homeobox B13 (HOXB13) genes in Malaysian bladder cancer patients. The protein expression of HOXA13 and HOXB13 in formalin-fixed paraffin-embedded (FFPE) bladder cancer tissues was determined by immunohistochemistry (IHC) analysis. The association between HOXA13/HOXB13 protein expression and demographic/clinicopathological characteristics of the bladder cancer patients was determined by chi-square analysis. Approximately 63.6% of the bladder cancer tissues harbored high HOXA13 expression. High HOXA13 expression was significantly associated with non-muscle invasive bladder cancer, lower tumor grade, higher number of lymph node metastases, and recurrence risk. In contrast, low HOXB13 expression (including those with negative expression) was observed in 71.6% of the bladder cancer tissues analyzed. Low HOXB13 expression was significantly associated with muscle-invasive bladder cancer, higher tumor stage, tumor grade, and metastatic risk. Both HOXA13 and HOXB13 protein expression were found to be associated with bladder tumorigenesis. The putative oncogenic and tumor suppressive roles of HOXA13 and HOXB13, respectively, suggest their potential utility as biomarkers in bladder cancer.

2.
Sci Rep ; 13(1): 7323, 2023 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-37147328

RESUMO

Bladder cancer cells can acquire persistent infection of oncolytic Newcastle disease virus (NDV) but the molecular mechanism(s) remain unelucidated. This poses a major barrier to the effective clinical translation of oncolytic NDV virotherapy of cancers. To improve our understanding of the molecular mechanism(s) associated with the development of NDV persistent infection in bladder cancer, we used mRNA expression profiles of persistently infected bladder cancer cells to construct PPI networks. Based on paths and modules in the PPI network, the bridges were found mainly in the upregulated mRNA-pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling and downregulated mRNA-pathways of antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades in persistent TCCSUPPi cells. In persistent EJ28Pi cells, connections were identified mainly through upregulated mRNA-pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle and the downregulated mRNA-pathways of Wnt signalling, HTLV-I infection and pathways in cancers. These connections were mainly dependent on RPL8-HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1-TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the networks that include RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction networks identified several putative drug targets that could be used to disrupt the linkages between the modules and prevent bladder cancer cells from acquiring NDV persistent infection. This novel PPI network analysis of differentially expressed mRNAs of NDV persistently infected bladder cancer cell lines provide an insight into the molecular mechanisms of NDV persistency of infection in bladder cancers and the future screening of drugs that can be used together with NDV to enhance its oncolytic efficacy.


Assuntos
Doença de Newcastle , Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias da Bexiga Urinária , Animais , Humanos , Vírus da Doença de Newcastle/genética , Transcriptoma , Linhagem Celular Tumoral , Infecção Persistente , Vírus Oncolíticos/genética , Neoplasias da Bexiga Urinária/genética , RNA Mensageiro/genética
3.
J Cell Mol Med ; 25(17): 8187-8200, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34322995

RESUMO

Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel-based therapy remains the first-line treatment for metastatic castration-resistant prostate cancer. However, dose-limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high-throughput kinome-wide loss-of-function screen. Further drug-gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA-approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel-induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)-negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers.


Assuntos
Azetidinas/farmacologia , Docetaxel/farmacologia , Janus Quinase 1/antagonistas & inibidores , Nitrilas/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Purinas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Masculino
4.
Biomed Res Int ; 2020: 3682086, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802842

RESUMO

BACKGROUND: The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer. OBJECTIVE: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant. RESULTS: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC. CONCLUSION: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.


Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Leptina/biossíntese , Obesidade/metabolismo , Receptores para Leptina/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/patologia , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/patologia , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptores para Leptina/metabolismo , Taxa de Sobrevida
5.
Asian J Surg ; 43(1): 87-94, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30962017

RESUMO

OBJECTIVES: To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. METHODS: Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis. RESULTS: A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p < 0.05), compared to their Malay (9.8%) and Chinese (14.0%) counterparts. Multivariable analysis revealed that ethnicity and PSA density (PSAD) are independent factors associated with overall prostate cancer detection rate. A unit increase of PSAD reflected an increase in PSA after controlling for prostate volume. CONCLUSION: Prostate cancer detection in Malaysia is comparatively lower. Our study suggests that ethnicity and PSA density should be considered when recommending first or repeat TRUS-guided prostate biopsy for prostate cancer detection in a multi-ethnic Malaysian population.


Assuntos
Biomarcadores Tumorais/sangue , Valor Preditivo dos Testes , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Humanos , Biópsia Guiada por Imagem/métodos , Malásia , Masculino , Neoplasias da Próstata/patologia , Ultrassonografia
6.
BJU Int ; 125(4): 541-552, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31868997

RESUMO

OBJECTIVES: To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real-world practice in Asia using the United in Fight against prOstate cancer (UFO) registry. PATIENTS AND METHODS: We established a multi-national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high-risk localised prostate cancer (HRL), non-metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed-up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient-reported quality of life was prospectively assessed using the European Quality of Life-five Dimensions, five Levels (EQ-5D-5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017. RESULTS: Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co-morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of <2 and the mean EQ-5D-5L visual analogue score was 74.6-79.6 across cohorts. Treatment of M1 patients was primarily with combined androgen blockade (58%) or androgen-deprivation therapy (either orchidectomy or luteinising hormone-releasing hormone analogues) (32%). Decisions to start therapy were mainly driven by treatment guidelines and disease progression. Decision to discontinue therapy was most often due to disease progression (hormonal drug therapy) or completion of therapy (chemotherapy). CONCLUSION: In the UFO registry of advanced prostate cancer in Asia, regional differences exist in prostate cancer treatment patterns that will be explored more deeply during the follow-up period; prospective follow-up is ongoing. The UFO registry will provide valuable descriptive data on current disease characteristics and treatment landscape amongst patients with prostate cancer in Asia.


Assuntos
Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Sistema de Registros , Idoso , Ásia , Estudos de Coortes , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Resultado do Tratamento
7.
Front Med (Lausanne) ; 6: 277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850355

RESUMO

Objectives: While the negative impact of falls in older persons has been recognized, the association between knee pains and falls remains inconclusive due to underreporting and undertreatment of knee pain. This study was conducted to evaluate the relationship between knee pain and knee pain severity with falls risk and to further determine factors which influence this potential relationship. Design: This was cross-sectional study from the Malaysian Elders Longitudinal Research (MELoR) study. Setting: Urban community dwellers in a middle-income South East Asian country. Participants: One thousand two hundred twelve of a representative sample of community dwelling older persons aged 55 years and older. Outcome measures: Falls in the preceding 12 months and knee pain were collected during a home-based computer-assisted interview. Physical and functional performance were measured using the Timed Up and Go test and the Katz and Lawton scales, respectively. Psychological status was determined using the Depression Anxiety and Stress Scale (DASS-21). Results: Of the 1,212 participants included in this analysis, knee pain was present in 402 (33.17%) individuals (124 (30.85%) mild, 210 (52.24%) moderate, 68 (16.92%) severe). The presence of knee pain was associated with increased risk of falls [odds Ratio, OR(95% confidence interval, CI): 1.81 (1.37-2.38)]. Severe knee pain was an independent predictor for falls after adjustment for functional impairment and psychological status. Mild, moderate, and severe knee pain had a specific indirect effect on falls through reducing functional impairment, which in turn increases their psychological concern. Conclusion: Future studies should explore this relationship prospectively and evaluate whether interventions which alleviate psychological concerns and improve function will reduce falls risk in those with mild to moderate knee pain.

8.
Dis Markers ; 2019: 3875147, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31636736

RESUMO

The ceramide synthase 2 (CERS2) gene has been linked to tumour recurrence and invasion in many different types of cancers including bladder cancer. In this study, the expression levels of CERS2 in bladder cancer cell lines were analysed using qRT-PCR and the protein expression in clinical bladder cancer histopathological specimens were examined via immunohistochemistry. The potential utility of CERS2 as a predictive biomarker of response to oncolytic virotherapy was assessed by correlating the CERS2 mRNA expression to IC50 values of cells treated with the Newcastle disease virus (NDV), AF2240 strain. This study demonstrates that CERS2 is differentially expressed in different types of bladder cancer cell lines and that the siRNA-mediated downregulation of the expression of CERS2 reduces the migratory potential of UMUC1 bladder cancer cells. However, there were no significant correlations between the expression levels of the CERS2 protein with bladder cancer grade/stage or between the IC50 values of cells treated with NDV and CERS2 expression. Although the utility of CERS2 expression may be limited, its potential as an antimigration cancer therapeutic should be further examined.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/metabolismo , Esfingosina N-Aciltransferase/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Humanos , Concentração Inibidora 50 , Recidiva Local de Neoplasia , Vírus da Doença de Newcastle , Terapia Viral Oncolítica , Fenótipo , RNA Interferente Pequeno/metabolismo
9.
Pathology ; 50(5): 511-518, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29935727

RESUMO

Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.


Assuntos
Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/metabolismo , NF-kappa B/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico , Núcleo Celular/metabolismo , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Transdução de Sinais/fisiologia , Análise Serial de Tecidos/métodos
10.
Urology ; 118: 145-151, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29746873

RESUMO

OBJECTIVES: To develop a simple prostate volume (PV) calculator that can aid in managing patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement at daily urology services in developing Asian countries. MATERIALS AND METHODS: We conducted a cross-sectional study of men aged above 40 years with no history of prostate cancer, prostate surgery, or 5α-reductase inhibitor treatment. Serum prostate-specific antigen (PSA) and total PV were measured in each subject. Potential sociodemographic and clinical variables including age, weight, comorbidities, and International Prostate Symptom Score (IPSS) were collected. Of 1034 subjects, 837 were used in building the PV calculator using regression analysis. The remaining 1/5 (n = 197) was used for model validation. RESULTS: There were 1034 multiethnic Asian men (Chinese 52.9%, Malay 35.4%, and Indian 11.7%) with mean age of 60 ± 7.6 years. Average PV was 29.4 ± 13.0 mL while the overall mean of PSA was 1.7 ± 1.7 ng/mL. We identified age, IPSS, weight, and PSA (all P <.05) in the PV regression model. Using the validation set, the coefficient of determination (R2) of this PV calculator was 0.47 where PV = 20.6 + (age - 60) × 0.1 + (IPSS score) × 0.1 + (Weight - 70) × 0.3 + (history of alpha-blocker treatment for LUTS) × 9.6 + PSA × 3.7. The area under curve of this model in predicting PV above 30 mL and 40 mL were 0.82 (95% confidence interval, 0.75-0.88) and 0.91 (95% confidence interval, 0.87-0.96), respectively. CONCLUSION: We develop a PV calculator that is simple and accurate to be used in routine clinical consultation for patients with LUTS. A separate study is important to confirm and to validate the findings in other populations.


Assuntos
Sintomas do Trato Urinário Inferior/patologia , Próstata/patologia , Hiperplasia Prostática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Técnicas de Diagnóstico Urológico , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Hiperplasia Prostática/complicações , Análise de Regressão
11.
Braz. J. Pharm. Sci. (Online) ; 54(3): e17552, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-974395

RESUMO

The incidence of erectile dysfunction (ED) is rising worldwide and its prevalence is one of the main health concerns that affect overall men well-being in Malaysia. The cluster of demographic, clinical and lifestyle factors may have contributed to the severity of ED and changes in biomarkers level; nevertheless these have not been studied extensively. This cross sectional study involved a total of 276 patients with 138 was diagnosed with ED. The demographic, clinical, lifestyle factors and severity of ED were assessed using a set of questionnaire and the International Index of Erectile Function (IIEF-5). Meanwhile, Total Testosterone (TT) and Asymmetric dimethylarginine (ADMA) levels were determined using the enzyme-linked immunosorbant assay (ELISA). Binary logistic regression test was used to demonstrate the predictors of severity of ED, TT and ADMA levels. Significant predictors for worsening of severity of ED are self-employed [10.55 (0.43 - 257.06), p=0.004], pensioner [8.07 (0.19 - 352.45), p=0.026], non-government employee [1.16 (0.05 - 26.26), p=0.04] and TT [0.41 (0.25 - 0.69), p=0.001]. Nevertheless, pensioner [0.08 (0.01 - 0.87), p=0.038] and unemployed [0.04 (0.01 - 0.42), p=0.007], were the predictors that may influence the changes of TT levels. On the other hand, academic qualification (secondary) [4.51 (0.48 - 42.83), p=0.014] and intensity of physical activities (< 1 hour/day) [2.61 (0.65 - 10.48), p=0.008] were the predictors which were more likely to influence the changes of ADMA levels in ED patients. TT and ADMA levels were influenced by demographic and lifestyle factors whilst severity of ED was predicted by demographic and clinical factors in Malaysian ED population. These predictors may provide new knowledge on risk factors of severity of ED and help in management of ED. Thus, the predictive models could serve as a primary guidance to physicians to ensure ED being managed and treated more effectively.


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Disfunção Erétil/prevenção & controle , Malásia/etnologia , Demografia/estatística & dados numéricos , Saúde do Homem/etnologia , Estilo de Vida
12.
Urol Oncol ; 35(9): 545.e1-545.e11, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28527622

RESUMO

BACKGROUND: Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease. METHODS: To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method. RESULTS: A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation. CONCLUSION: In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa.


Assuntos
Variações do Número de Cópias de DNA/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Neoplasias da Próstata/genética , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia
13.
Singapore Med J ; 58(10): 574-575, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28367582

RESUMO

A doctor's attire is important in making a positive first impression and enhancing the overall healthcare experience for patients. We conducted a study to examine the perceptions and preferences of patients and doctors regarding six types of dress codes used by doctors in different scenarios and locations. A total of 87 patients and 46 doctors participated in the study. Separate sets of questionnaires containing four demographic questions and 14 survey questions were distributed to the two groups. Most patients preferred doctors to dress formally in white coats regardless of the scenario or location, whereas the majority of doctors preferred formal attire without white coats. Both groups preferred operating theatre attire in the emergency department. Our findings confirmed that patients perceived doctors in white coats to be more trustworthy, responsible, authoritative, confident, knowledgeable and caring. There is a need to educate the public about the reasons for changes in doctors' traditional dress codes.


Assuntos
Vestuário , Percepção , Relações Médico-Paciente , Profissionalismo , Adolescente , Adulto , Idoso , Serviço Hospitalar de Emergência , Empatia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Médicos , Inquéritos e Questionários , Adulto Jovem
14.
Ther Clin Risk Manag ; 13: 407-419, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28408836

RESUMO

This study was conducted in a tertiary medical center in Kuala Lumpur, Malaysia. A total of 200 erectile dysfunction (ED) patients with 499 cases who had received pharmacological treatments for their ED participated in this study. Types, causes and factors associated with drug-related problems (DRPs) in ED patients with multiple comorbidities were assessed. A total of 244 DRPs with an average of 1.2±2.1 DRPs per patient were identified. Drug interaction contributed the most to DRPs occurrence. There was a significant higher risk of DRPs in patients with benign prostatic hyperplasia, lower urinary tract infection and elderly and end-stage renal disease. Early identification of types of DRPs and factors associated may enhance their prevention and management.

16.
Asian J Surg ; 40(2): 171-174, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24210538

RESUMO

Ureteric strictures are common and can be due to benign or malignant causes. Various surgical treatments can be used from minimally invasive endoscopic retrograde JJ stent insertion, balloon dilatation, ureterolithotomy, to open surgical exploration and repair. Memokath 051 stent is a metallic stent designed for long-term ureteral stenting in the management of ureteral strictures. The insertion of this device is usually a straightforward procedure performed endoscopically in a retrograde fashion via cystoscopy. However, this procedure can be difficult in complicated scenarios when the bladder has been removed with neoureteral reimplantations or high-grade strictures. Here, we report a case of Memokath stent insertion complicated by placement difficulties in a lady with ileal conduit due to previous ovarian cancer complicated by vesicovaginal fistula, who presented with malignant stricture of the ureteroileal anastomosis. We describe a simple yet effective antegrade technique to precisely reposition the malpositioned Memokath stent, along with illustrations.


Assuntos
Neoplasias Ovarianas/patologia , Falha de Prótese , Radiologia Intervencionista/métodos , Stents , Obstrução Ureteral/terapia , Derivação Urinária/efeitos adversos , Cistectomia/efeitos adversos , Cistectomia/métodos , Remoção de Dispositivo , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/cirurgia , Ovariectomia/efeitos adversos , Ovariectomia/métodos , Desenho de Prótese , Retratamento/métodos , Medição de Risco , Resultado do Tratamento , Obstrução Ureteral/diagnóstico por imagem
17.
Patient Prefer Adherence ; 10: 807-23, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27257374

RESUMO

BACKGROUND: Erectile dysfunction (ED) is one of the most common health problems in men. ED can significantly affect a man's psychological well-being and overall health. PURPOSE: To investigate the association of psychological factors, patients' knowledge, and management among ED patients. PATIENTS AND METHODS: A total of 93 patients with an age range from 31 to 81 years who have undergone treatment for ED were included in this study. RESULTS: It was found that the feeling of blame (P=0.001), guilt (P=0.001), anger or bitterness (P=0.001), depression (P=0.001), feeling like a failure (P=0.001), and the feeling of letting down a partner during intercourse (P=0.001) were significantly associated with ED. Age was also found to be significantly associated with patients' psychological scale (P=0.004). In addition, the majority of patients in this study practice the right method of administration of ED therapy. However, no significant correlation was found between patients' knowledge of ED therapy and demographic characteristics. CONCLUSION: This study concluded that ED does affect psychological well-being of people. In addition, patient's knowledge about ED and its management is also crucial in ensuring that the patient achieves optimal therapeutic outcomes from ED therapy.

18.
PLoS One ; 10(11): e0142812, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26559947

RESUMO

AIM: To explore the views of Malaysian healthcare professionals (HCPs) on stakeholders' decision making roles in localized prostate cancer (PCa) treatment. METHODS: Qualitative interviews and focus groups were conducted with HCPs treating PCa. Data was analysed using a thematic approach. Four in-depth interviews and three focus group discussions were conducted between December 2012 and March 2013 using a topic guide. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. FINDINGS: The participants comprised private urologists (n = 4), government urologists (n = 6), urology trainees (n = 6), government policy maker (n = 1) and oncologists (n = 3). HCP perceptions of the roles of the three parties involved (HCPs, patients, family) included: HCP as the main decision maker, HCP as a guide to patients' decision making, HCP as a facilitator to family involvement, patients as main decision maker and patient prefers HCP to decide. HCPs preferred to share the decision with patients due to equipoise between prostate treatment options. Family culture was important as family members often decided on the patient's treatment due to Malaysia's close-knit family culture. CONCLUSIONS: A range of decision making roles were reported by HCPs. It is thus important that stakeholder roles are clarified during PCa treatment decisions. HCPs need to cultivate an awareness of sociocultural norms and family dynamics when supporting non-Western patients in making decisions about PCa.


Assuntos
Atitude do Pessoal de Saúde , Tomada de Decisões , Oncologia/métodos , Neoplasias da Próstata/terapia , Urologia/métodos , Características Culturais , Família , Grupos Focais , Política de Saúde , Humanos , Malásia , Masculino , Participação do Paciente , Projetos de Pesquisa
19.
Urology ; 86(3): 487-91, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26142713

RESUMO

OBJECTIVE: To evaluate the effectiveness of pelvic floor muscle exercises (PFMEs) performed with the new biofeedback Vibrance Kegel Device (VKD), compared to PFMEs alone, in treating stress urinary incontinence (SUI). MATERIALS AND METHODS: This was a pilot prospective, randomized trial of women aged ≥18 years with SUI symptoms who underwent PFMEs at University Malaya Medical Centre from October 2011 to October 2013. The patients were randomly divided into two groups: control (PFMEs alone) and VKD (PFMEs with VKD biofeedback). The patients underwent 16 weeks of pelvic floor training, during which they were assessed using Australian pelvic floor questionnaires and modified Oxford scales for pelvic floor muscle strength at week 0, 4, and 16. RESULTS: Forty patients were recruited (control 19, VKD 21). Three patients in the control group dropped out during week 16 training, whereas the VKD group had no dropouts. The VKD group reported significantly earlier improvement in SUI scores, as assessed by the Australian pelvic floor questionnaires (P = .035) at week 4. However, there was no significant difference between the groups' SUI scores at week 16. Pelvic floor muscle strength was significantly better in the VKD group at week 4 (P = .025) and week 16 (P = 0.001). The subjective cure rate was similar in both groups at week 16 (62.5% for control and 61.9% for VKD) (P = 0.742). CONCLUSION: Using the VKD resulted in significant early improvement in SUI scores, and pelvic muscle strength had improved significantly by the end of the study. The VKD proved useful as an adjunct for pelvic floor training.


Assuntos
Biorretroalimentação Psicológica/instrumentação , Treinamento Resistido/instrumentação , Incontinência Urinária por Estresse/terapia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Força Muscular , Projetos Piloto , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento
20.
PLoS One ; 10(6): e0130820, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26098884

RESUMO

OBJECTIVES: To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting. MATERIALS AND METHODS: We conducted a cross-sectional study of 1021 men aged 40-79 years with no clinical evidence of prostate cancer, prostate surgery or 5α-reductase inhibitor treatment of known prostate conditions. The severity of LUTS was assessed using the International Prostate Symptom Score (IPSS). Potential factors associated with LUTS including age, ethnicity, education, history of hypertension, diabetes and hypercholesterolemia, height, weight, and prostate volume were evaluated using univariable and multivariable analyses. RESULTS: There were 506 (50%) men found to have moderate-to-severe LUTS attaining an IPSS above 7. Overall, nocturia (45.5%) was the most frequently reported symptom. Multivariable analysis showed that age, ethnicity, prostate volume and history of hypertension and hypercholesterolemia were independent factors associated with severity of LUTS (p < 0.05). Considering individual lower urinary tract symptoms, we found a strong association of storage symptom with history of hypertension and hypercholesterolemia. Malay men were significantly bothered by post micturition symptom compared to their Chinese and Indian counterparts. Stratified analyses of LUTS demonstrated a mutually exclusive cardiovascular risk factors profile defined by ethnicity. CONCLUSION: Severity of LUTS varies between different ethnicities across all age groups. In addition to age and prostate volume, ethnicity and cardiovascular risk factors including hypertension and hypercholesterolemia may also need to be taken into account in managing men with LUTS.


Assuntos
Doenças Cardiovasculares/patologia , Sintomas do Trato Urinário Inferior/patologia , Adulto , Idoso , Povo Asiático , Estudos Transversais , Etnicidade , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Micção/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...