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1.
Prostate ; 84(8): 738-746, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38528654

RESUMO

BACKGROUND: The occurrence of castration-resistant prostate cancer (CRPC) varies in patients with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). The rate of occurrence of CRPC may be related to the presence of prostate cancer stem cells (CSC). Thus, this study aims to evaluate the presence of CSC markers (CD44 and CD133) in histopathology tissue at the time of diagnosis and their correlation with the occurrence of CRPC in patients with advanced PCa within 2 years of ADT. METHOD: A retrospective case-control study was conducted to evaluate the incidence of CRPC within 2 years. The inclusion criteria were patients with PCa who had received treatment with ADT and a first-generation anti-androgen (AA) for 2 years. We classified patients based on whether they developed CRPC within 2 years (CRPC) of the therapy or did not experience CRPC within 2 years (non-CRPC) of the therapy. We performed immunohistochemical (IHC) staining for CD44 and CD133 on the prostate biopsy tissue samples. RESULTS: Data were collected from records spanning 2011-2019. We analyzed a total of 65 samples, including 22 patients with CRPC and 43 patients with non-CRPC who had received treatment with LHRH agonists and AA for up to 2 years. Our findings showed a significant H-score difference in CD44 protein expression between CRPC prostate adenocarcinoma samples 869 (200-1329) and non-CRPC 524 (154-1166) (p = 0.033). There was no significant difference in CD133 protein expression between the two groups (p = 0.554). However, there was a significant difference in the nonoccurrence of CRPC between the high expressions of both CD44 and CD133 groups with other expressions of CD44/CD133 groups (25% vs. 75%; p = 0.011; odds ratio = 4.29; 95% confidence interval [1.34, 13.76]). CONCLUSION: This study found a low expression of at least one CD44/CD133 protein in the patients without early occurrence of CRPC. This result might suggest that CD44/CD133 may function as a potential prognostic marker for PCa, especially in a low expression, to identify patients who have a better prognosis regarding the occurrence of early CRPC.


Assuntos
Antígeno AC133 , Antagonistas de Androgênios , Biomarcadores Tumorais , Receptores de Hialuronatos , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/análise , Receptores de Hialuronatos/biossíntese , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antígeno AC133/metabolismo , Estudos Retrospectivos , Idoso , Prognóstico , Estudos de Casos e Controles , Antagonistas de Androgênios/uso terapêutico , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia
2.
Int J Urol ; 31(7): 764-770, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641982

RESUMO

OBJECTIVES: Penile carcinoma (PC) is a rare disease with considerable physical and psychological impact. To date, there is no data regarding PC prevalence and characteristics in Indonesia. This study aimed to analyze the characteristics of patients with PC in Indonesia and determine cumulative survival rates and time to disease progression. METHODS: This was a retrospective study of all patients diagnosed with PC at Cipto Mangunkusumo General Hospital from 1995 to 2014, with a minimum of 1 year follow-up. The outcomes of the study were cumulative survival rates and time-to-disease progression. RESULTS: Ninety-three subjects were recruited, with a mean age of 49.44 ± 13.62. Inguinal lymph node dissection (ILND) was performed in 49 (53%) patients. The mean survival in the ILND group was better compared to the non-ILND group (80.7 months vs. 67.1 months; p = 0.032). Time-to-progression in the ILND group was significantly longer than in the non-ILND group (71.7 months vs. 54.3 months; p = 0.022). No significant difference in survival between the total and partial penectomy (PP) groups was observed (p = 0.701). Time-to-progression in total penectomy (TP) was significantly longer than in PP (68 months vs. 56.0 months; p = 0.023). In Cox-regression analysis, after adjustment of other variables, history of ILND, higher stage of cancer, and older age were found to affect the survival of patients. CONCLUSION: ILND in PC led to better survival and reduced disease progression. The type of penectomy is only associated with progression but not survival. TP had a longer time to disease progression compared to PP.


Assuntos
Progressão da Doença , Excisão de Linfonodo , Neoplasias Penianas , Centros de Atenção Terciária , Humanos , Masculino , Estudos Retrospectivos , Indonésia/epidemiologia , Pessoa de Meia-Idade , Neoplasias Penianas/cirurgia , Neoplasias Penianas/patologia , Neoplasias Penianas/mortalidade , Neoplasias Penianas/epidemiologia , Centros de Atenção Terciária/estatística & dados numéricos , Adulto , Excisão de Linfonodo/estatística & dados numéricos , Idoso , Taxa de Sobrevida , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/epidemiologia , Seguimentos
3.
Ann Surg ; 277(1): 50-56, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491983

RESUMO

OBJECTIVE: To assess the degree of psychological impact among surgical providers during the COVID-19 pandemic. SUMMARY OF BACKGROUND DATA: The COVID-19 pandemic has extensively impacted global healthcare systems. We hypothesized that the degree of psychological impact would be higher for surgical providers deployed for COVID-19 work, certain surgical specialties, and for those who knew of someone diagnosed with, or who died, of COVID-19. METHODS: We conducted a global web-based survey to investigate the psychological impact of COVID-19. The primary outcomes were the depression anxiety stress scale-21 and Impact of Event Scale-Revised scores. RESULTS: A total of 4283 participants from 101 countries responded. 32.8%, 30.8%, 25.9%, and 24.0% screened positive for depression, anxiety, stress, and PTSD respectively. Respondents who knew someone who died of COVID-19 were more likely to screen positive for depression, anxiety, stress, and PTSD (OR 1.3, 1.6, 1.4, 1.7 respectively, all P < 0.05). Respondents who knew of someone diagnosed with COVID-19 were more likely to screen positive for depression, stress, and PTSD (OR 1.2, 1.2, and 1.3 respectively, all P < 0.05). Surgical specialties that operated in the head and neck region had higher psychological distress among its surgeons. Deployment for COVID- 19-related work was not associated with increased psychological distress. CONCLUSIONS: The COVID-19 pandemic may have a mental health legacy outlasting its course. The long-term impact of this ongoing traumatic event underscores the importance of longitudinal mental health care for healthcare personnel, with particular attention to those who know of someone diagnosed with, or who died of COVID-19.


Assuntos
COVID-19 , Cirurgiões , Humanos , Saúde Mental , SARS-CoV-2 , Pandemias , Depressão/psicologia , Ansiedade/psicologia , Pessoal de Saúde/psicologia , Inquéritos e Questionários , Estresse Psicológico/psicologia
4.
World J Urol ; 38(11): 2907-2914, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32020273

RESUMO

PURPOSE: This study would like to develop a novel model similar to human prostate in terms of its texture profile, sensation upon resection, and anatomical hallmarks for resident transurethral resection of the prostate (TUR-P) training. METHODS: Ten phantom designs were proposed, using broadly available ingredients and a homemade protocol. Three steps of evaluation and development were done: objective measurement measuring texture profile (e.g. hardness, elasticity, cohesiveness/consistency, and adhesiveness/stickiness) using TA-XT2i Texture Analyzer (Llyod Instruments, Ametek Inc) to compare the designs with human prostate, finding the most similar design to prostate; expert consensus by a panel of urologist/senior residents comparing the simulation of TUR-P on the selected design with pre-existing control phantom; and anatomical design development using 3D printing for molding. RESULTS: Texture profile analysis for mean hardness, elasticity, cohesiveness/consistency, and adhesiveness/stickiness of human prostate was 3753.4 ± 673.4, 85 ± 1.9, 0.7 ± 0.03, and 0, respectively, and design IX was the most similar to human prostate (3660.7 ± 465.6, 87.0 ± 2.5, 0.6 ± 0.05, 0). Furthermore, expert consensus showed superiority of design IX compared with pre-existing control phantom (16.95 ± 1.36 vs 8.86 ± 3.10; P < 0.001). Most of the respondents agreed that the texture, consistency, and phantom ability to mimic human prostate upon resection were similar with human prostate, though hallmarks of the prostate e.g. veromontanum, and lobes were lacking. We used these feedbacks to develop a mold, designed to produce these important anatomical hallmarks. CONCLUSION: This study developed a cost-effective prostate model from a food-based design that is similar to human prostate in terms of its texture and sensation upon TUR-P resection provided with important anatomical hallmarks.


Assuntos
Internato e Residência/métodos , Modelos Anatômicos , Próstata , Ressecção Transuretral da Próstata/educação , Animais , Humanos , Masculino , Imagens de Fantasmas
5.
BMC Urol ; 20(1): 158, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054762

RESUMO

BACKGROUND: Most patients with muscle-invasive bladder cancer (MIBC) developed metastasis within 2 years, even after radical cystectomy (RC). The recurrence rate of MIBC was more than 50% of the cases. A meta-analysis conducted by Yin et al. showed that neoadjuvant chemotherapy (NAC) + RC improves overall survival in MIBC compared with RC only. However, a new meta-analysis by Li et al. concluded that NAC + RC was not superior to RC only in improving overall survival. The inconsistencies of these studies required further comprehensive analysis to recommend NAC use in bladder cancer treatment. Therefore, this meta-analysis aims to analyze previous studies that compare the efficacy of NAC + RC versus RC only to improve overall survival of MIBC. METHODS: The articles were searched using Pubmed with keywords "muscle-invasive bladder cancer", "neoadjuvant chemotherapy", "cystectomy", and "overall survival". The articles that were published until June 2020 were screened. The overall survival outcome was analyzed as hazard ratio (HR) and presented in a forest plot. RESULT: Seventeen studies were included in meta-analysis with a total sample of 13,391 patients, consist of 2890 received NAC followed by RC and 10,418 underwent RC only. Two studies used methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), two studies used gemcitabine/cisplatin (GC), one study used Cisplatin-based regimen, one study used MVAC or GC, one study used gemcitabine/carboplatin (GCarbo) or GC or MVAC, one study used Cisplatin/Gemcitabine or MVAC, one study used Cisplatin only, one study used Cisplatin-based (GC, MVAC) or non-Cisplatin-based (combined paclitaxel/gemcitabine/carboplatin), one study used GC, MVAC, Carboplatin, or Gemcitabine/Nedaplatin (GN), and five studies did not mention the regimen The overall survival in the NAC + RC only group was significantly better than the RC only group (HR 0.82 [0.71-0.95], p = 0.009). CONCLUSION: NAC + RC is recommended to improve overall survival in MIBC patients. A further study assessing side effects and quality of life regarding NAC + RC is needed to establish a strong recommendation regarding this therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistectomia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Quimioterapia Adjuvante , Cistectomia/métodos , Humanos , Terapia Neoadjuvante , Invasividade Neoplásica , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
6.
BMC Urol ; 20(1): 71, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32560654

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT. METHODS: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n = 10) and were further subgrouped into ADT ≤12 months (n = 4) and ADT > 12 months (n = 6). The ADT-PCa tissues were then compared with BPH (n = 12) and primary (no treatment) PCa tissues (n = 16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies. RESULTS: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p < 0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT > 12 months subgroup compared with the PCa group (100%; p < 0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups. CONCLUSION: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Orquiectomia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/terapia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/análise , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/biossíntese , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Idoso , Idoso de 80 Anos ou mais , Membro C3 da Família 1 de alfa-Ceto Redutase/análise , Membro C3 da Família 1 de alfa-Ceto Redutase/biossíntese , Membro C3 da Família 1 de alfa-Ceto Redutase/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Neoplasias da Próstata/química , Neoplasias da Próstata/genética , Receptores Androgênicos/análise , Receptores Androgênicos/biossíntese , Receptores Androgênicos/genética , Fatores de Tempo , Regulação para Cima
7.
World J Urol ; 37(5): 751-757, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30350016

RESUMO

Accumulating evidence has shown that intracrinology in prostate cancer (PCa) has a pivotal role in survival of cancer cell. PCa cells are able to produce androgens from different androgen precursors, such as dehydroepiandrosterone, thereby maintaining androgen receptor signaling. Several drugs have been developed that target intracrinology, some of which are now being used as standard treatment for the so-called castrate-resistant prostate cancer (CRPC) patients. Recently, the US FDA approval has changed the indication of drugs targeting intracrinology, e.g., abiraterone and enzalutamide where it evolved from post-chemotherapy CRPC to hormone-naive metastatic PCa cases. This approval raises question whether those drugs can also be used as the first-line treatment in localized stage PCa cases. In addition, development of additional drugs targeting major components of intracrinology is ongoing. Application of these new drugs and administration of combinations of existing drugs will ultimately lead to an increase in the efficacy of such treatments as well as to reduce the toxicity of the therapy and to prevent the risk of resistance.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/uso terapêutico , Androgênios/metabolismo , Benzamidas , Desidroepiandrosterona/metabolismo , Di-Hidrotestosterona/metabolismo , Humanos , Masculino , Nitrilas , Feniltioidantoína/análogos & derivados , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Testosterona/metabolismo
8.
Int J Urol ; 26(1): 83-89, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30269369

RESUMO

OBJECTIVES: To analyze predictive clinical factors of survival in bone-metastatic prostate cancer, and to develop a prognostic nomogram for patients with this condition. METHODS: The present study included 392 patients with bone-metastatic prostate cancer treated with androgen deprivation therapy. Pretreatment parameters were analyzed using the Cox proportional hazards model to identify the predictors of overall survival. Covariates - which showed statistical significance on multivariate analysis - were used to develop a nomogram. A linear predictor model was utilized to develop the nomogram. RESULTS: The median overall survival was 40.3 months (95% confidence interval 32.2-48.5). Univariate analysis showed that clinical T stage, Gleason score, initial prostate-specific antigen value and the number of metastatic lesions were independent prognostic factors for overall survival. These predictors remained significant as independent prognostic factors for overall survival after analysis using the multivariate Cox regression model. The nomogram constructed from those prognostic factors showed good discrimination for predicting the 5-year overall survival, with an area under the curve of 0.69. Acceptable agreement of the observed and predicted probabilities was observed in the calibration plot. CONCLUSIONS: The present prognostic nomogram might be a useful tool for predicting overall survival in pretreatment bone-metastatic prostate cancer, specifically among Indonesian patients. Further studies are required to provide external validation to support the utilization of this nomogram.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Neoplasias Ósseas/tratamento farmacológico , Humanos , Indonésia/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Nomogramas , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/análise , Neoplasias da Próstata/tratamento farmacológico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
9.
Acta Med Indones ; 48(4): 335-347, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28143997

RESUMO

In the past 10 years, recent development of targeted therapy in metastatic renal cell carcinoma (mRCC) has provided a new hope and significantly enhanced the prognosis of the disease. Three class of targeted therapy were developed, including multi-targeted tyrosine kinase inhibitors (TKI), the mammalian target of rapamycin (mTOR) complex-1 kinase inhibitors, and the humanized antivascular endothelial growth factor (VEGF) monoclonal antibody. Hence, the objective of this article was to critically examine the current evidence of targeted therapy treatment for patients with mRCC. In the majority of trials evaluating targeted therapy, patients were stratified according to Memorial Sloan Kattering Cancer Center (MSKCC) risk model and the recommendation of targeted treatment based on risk features. In first-line setting (no previous treatment), sunitinib, pazopanib, or bevacizumab plus IFN-α were recommended as treatment options for patient with favorable- or intermediate- risk features and clear cell histology. Patients who progressed after previous cytokine therapy would have sorafenib or axitinib as treatment options. Clear-cell mRCC with favorable- or intermediate- risk features and failure with first-line TKI therapy might be treated with sorafenib, everolimus, temsirolimus or axitinib. However, the current evidence did not show the best treatment sequencing after first-line TKI failure. In patients with poor-risk clear-cell and non-clear cell mRCC, temsirolimus was the treatment option supported by phase III clinical trial. In addition, several new drugs, nowadays, are still being investigated and waiting for the result of phase II or III clinical trial, and this might change the standard therapy for mRCC in the future.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Fatores Imunológicos/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Axitinibe , Bevacizumab/uso terapêutico , Everolimo/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Indazóis/uso terapêutico , Indóis/uso terapêutico , Interferon-alfa/uso terapêutico , Neoplasias Renais/patologia , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Prognóstico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sorafenibe , Sulfonamidas/uso terapêutico , Sunitinibe
10.
Acta Med Indones ; 48(3): 228-238, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27840359

RESUMO

This is a literature review study. Data was obtained from several literature reviews and journal resources that have correlation with the risk factors involved in PCa including age, ethnicity, family history, insulin-Like growth factor, sexually transmitted disease, obesity, smoking, alcohol consumption, vasectomy, and diet, and the prevention of PCa including soy, lycopene, green tea, supplementation, and exercise.Numerous epidemiologic studies have linked PCa risk to various factors, i.e. age, ethnicity, family history, insulin like-growth factors, lifestyle, diet, environmental and occupational exposures. The results of epidemiological, In vivo, in vitro, and early clinical studies suggested that selected dietary products and supplementation may play a role in PCa prevention. More studies are still needed to explore and find the risk factors and preventive methods of PCa development. It is important for clinician to ellaborate these informations for education to lower PCa risks and prevent PCa.


Assuntos
Neoplasias da Próstata/etiologia , Neoplasias da Próstata/prevenção & controle , Humanos , Masculino , Fatores de Risco
11.
Prostate ; 75(16): 1868-76, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26310814

RESUMO

BACKGROUND: Homeobox (HOX) genes, which are involved in organ development and homeostasis, have been shown to be involved in normal prostate- and PCa development. In this study, we investigate the expression levels of the HOX A-D genes in PCa. The functional relevance and potential of HOX gene as biomarkers are explored. METHODS: We evaluated HOX gene expression in prostate tissues of different grade and stage and related the outcome to clinical parameters. We analyzed AR regulation and function of HOXC6 in PCa cell lines. We developed a urine-based HOXC6 mRNA assay for diagnostic purposes. RESULTS: HOXC6 was one of the most upregulated HOX genes in all primary, metastasized, and castration-resistant PCa. HOXC6 upregulation was specific to the epithelial component of PCa, and HOXC6 was shown to be involved in epithelial cell proliferation. HOXC6 expression was not influenced by androgens nor by treatments targeting the AR signaling pathway. HOXC6 expression was not related to a prognosis after radical prostatectomy, that is, biochemical or local recurrence. We successfully developed an assay for HOXC6 mRNA detection in urine and confirmed that HOXC6 levels are higher in PCa patients. CONCLUSIONS: HOXC6 has a role in all PCa stages, particularly in PCa cell proliferation. Due to its stable expression, HOXC6 is a novel candidate biomarker for PCa not only in early detection but also for monitoring of progression or response to therapy.


Assuntos
Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proliferação de Células , Progressão da Doença , Proteínas de Homeodomínio/genética , Humanos , Masculino , Gradação de Tumores , Prognóstico , Próstata/patologia , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Regulação para Cima
12.
J Urol ; 193(3): 1023-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25242390

RESUMO

PURPOSE: Dihydrotestosterone is the main active androgen in the prostate and it has a role in prostate cancer progression. After androgen deprivation therapy androgen receptor signaling is still active in tumor cells. Persistent intratumor steroidogenesis and androgen receptor changes are responsible for this continued activity, which influences the efficacy of prostate cancer treatment. We hypothesized that combining a 5α-reductase inhibitor and an antiandrogen would block intratumor androgen synthesis and androgen receptor protein activity. Thus, it would act synergistically to reduce tumor cell proliferation. MATERIALS AND METHODS: The expression level of 5α-reductase and androgen receptor in endocrine therapy naïve prostate cancer and castration resistant prostate cancer tissues, and cell line models was determined by microarray and quantitative polymerase chain reaction analysis. Intracellular androgen was measured with radioimmunoassay. Tumor cell proliferation was determined using coloric MTT assay. The synergistic effects of combination treatments on tumor cell proliferation were calculated using the Chou-Talalay equation. RESULTS: In all prostate cancer cases 5α-reductase-1 and 3 were up-regulated. Androgen receptor was up-regulated in metastatic prostate cancer and castration resistant prostate cancer cases. The 5α-reductase inhibitor dutasteride effectively decreased dihydrotestosterone production in prostate cancer and castration resistant prostate cancer cell lines. Furthermore, dutasteride combined with the novel antiandrogen enzalutamide synergistically suppressed endocrine therapy naïve prostate cancer and castration resistant prostate cancer cell proliferation. CONCLUSIONS: In this study the combination of a 5α-reductase inhibitor and (novel) antiandrogens synergistically inhibited tumor cell proliferation. These findings support clinical studies of combinations of a 5α-reductase inhibitor and (novel) antiandrogens as first line treatment of prostate cancer and castration resistant prostate cancer.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Azasteroides/farmacologia , Proliferação de Células/efeitos dos fármacos , Feniltioidantoína/análogos & derivados , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias da Próstata/patologia , Benzamidas , Sinergismo Farmacológico , Quimioterapia Combinada , Dutasterida , Humanos , Masculino , Nitrilas , Feniltioidantoína/farmacologia , Células Tumorais Cultivadas
13.
Jpn J Clin Oncol ; 45(8): 708-12, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26085688

RESUMO

Non-communicable diseases, including cancer, start to become more common in Indonesia. According to the government statement, incidence of malignant diseases increased annually up to 8% in the last decade and these diseases become the seventh leading cause of death in Indonesia. On the basis of the latest Globocan report on cancer incidence in Indonesia, prostate cancer ranks sixth; followed by bladder (12th) and kidney (18th). More than half of patients with kidney cancer are diagnosed in the advanced stage. Besides renal cell carcinoma, there are significant number of people affected with squamous cell and transitional cell carcinoma because of kidney stones. Radical nephrectomy or cytoreductive nephrectomy was the primary treatment, mostly done as an open procedure. Transitional cell carcinoma is the commonest histology type in bladder cancer cases followed by squamous cell carcinoma, which almost always related to bladder stones. Unfortunately, >70% of our cases were diagnosed with muscle invasive bladder cancer, and ∼60% of these patients refused further radical treatment. Incidence of prostate cancer is increasing rapidly and it becomes the third most common cancer in men. However, most of our patients are diagnosed in the advanced stage. Radical prostatectomy or external beam radiotherapy is the treatment of choice in localized disease. Nearly 40% of the elderly patients are treated with primary androgen deprivation therapy. Therefore, it requires more research by the Indonesian urologists and other healthcare providers to diagnose these cancers in earlier stage as well as community education for prevention.


Assuntos
Carcinoma/epidemiologia , Carcinoma/terapia , Neoplasias Renais/epidemiologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Bexiga Urinária/epidemiologia , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/terapia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/terapia , Cistectomia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Incidência , Indonésia/epidemiologia , Neoplasias Renais/terapia , Masculino , Nefrectomia , Prostatectomia , Neoplasias da Próstata/terapia , Recusa do Paciente ao Tratamento , Neoplasias da Bexiga Urinária/terapia
14.
Acta Med Indones ; 47(2): 95-103, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26260551

RESUMO

AIM: to develop a prediction risk model of prostate cancer based on Indonesia population. METHODS: we included all benign prostate hyperthrophy (BPH) and PCa patients who had prostate biopsy and prostatectomy between January 2009 and December 2013 from 5 urology centers in Indonesia. The relationship between the possibility of PCa with the following variables including: age; PSA level, prostate volume (by transabdominal ultrasound or transrectal ultrasound) and digital rectal examination (DRE) finding. We calculated a predictive scoring equation to predict the possibility of PCa using chi-square analysis, Kolmogorov-Smirnov test, multiple logistic regression and ROC curve. Then, we designed an application for predicting prostate cancer risk called Indonesian Prostate Cancer Risk Calculator (IPCRC). RESULTS: there were 784 PCa and 1173 BPH patients were used for developing the risk calculator in our study. The mean ages, PSA and prostate volume are 66.9±8.1 years old; 72.4±248.9 ng/ml and 49.6±28.2 ml, respectively. Abnormal DRE was found in 637 PCa and 56 BPH. We included age, PSA level, abnormal DRE finding (all showed significant p<0.05 in univariate model). Additionally, although not significant, we included prostate volume (p=0.157) due to its clinical importance. The corrected ROC analysis showed AUC 0.935, sensitivity of 90.1% and specificity 80% in predicting the prostate cancer in our population. CONCLUSION: we have developed the Indonesian Prostate Cancer Risk Calculator which includes age, PSA, DRE, and prostate volume as its variables. Future prospective study to validate the risk calculator is needed.


Assuntos
Antígeno Prostático Específico/sangue , Hiperplasia Prostática/epidemiologia , Neoplasias da Próstata/epidemiologia , Risco Ajustado , Idoso , Biópsia , Exame Retal Digital , Humanos , Indonésia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Prostatectomia , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Curva ROC , Sensibilidade e Especificidade
15.
Acta Med Indones ; 46(4): 298-307, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25633546

RESUMO

AIM: To evaluate the effective dose and adverse effects of BCG doses. METHODS: We searched published RCTs in Medline and Cochrane database before October 2013. Article using maintenance BCG after TUR in intermediate-high risk non-muscle invasive bladder cancer (NMIBC) and followed for effectiveness, local and systemic side effect are included. Low risk patients, other dose and MIBC were excluded. RESULTS: Meta-analysis of 6 clinical trials involving 2719 intermediate-high risk NMIBC patients showed recurrence rate in full dose (81 mg), low dose (27 mg) and very low dose (13.5 mg) were 33.3%, 34.7% and 30%, respectively. Meta-analysis of 2175 patients, 81 mg BCG was found to be superior to 27 mg in reducing tumour recurrences (RR 0.86; 95% CI 0.77-0.96, I2=0% and p=0.008). Meta-analysis of 544 patients, the effectiveness reducing tumour recurrences in 27 mg BCG was found to be superior to 13,5 BCG (RR 0.66; 95% CI 0.49-0.89, I2=8.8% and p=0.006). Systemic side effects were happened in 25%, 28.5%, and 15.5% in the doses 81.27 and 13.5 mg BCG, respectively. Low dose was superior to full dose in affecting systemic side effect (p=0,000) but no difference in affecting local side effect (p=0.137) in the meta-analysis of 1816 patients in 2 clinical trials. CONCLUSION: Full dose BCG had superior outcome to reduce recurrences compared to low dose and very low dose. There were no significant differences between each dose in local side effect. However full dose regimen has higher systemic side effect compared to low and very low dose.


Assuntos
Vacina BCG/administração & dosagem , Carcinoma/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Intravesical , Carcinoma/patologia , Relação Dose-Resposta a Droga , Humanos , Invasividade Neoplásica , Recidiva Local de Neoplasia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Bexiga Urinária/patologia
16.
Int J Surg Case Rep ; 114: 109118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38159392

RESUMO

INTRODUCTION AND IMPORTANCE: Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor that can manifest in a variety of locations, including the retroperitoneum. The most effective standard diagnostic approach and treatment is yet to be determined due to unpredictable behavior of SFT, including retroperitoneal SFT. CASE PRESENTATION: A 43-year-old female with a retroperitoneal SFT presented with a palpable mass and symptomatology. Surgical exploration disclosed a tumor encompassing the left renal artery and vein, necessitating left nephrectomy and retroperitoneal mass removal. Initial histological examination suggested rhabdomyosarcoma, but subsequent immunohistochemistry confirmed the diagnosis of retroperitoneal SFT. No adjuvant therapy was administered, and there was no detectable mass on follow-up imaging. The patient remained symptom-free. CLINICAL DISCUSSION: Retroperitoneal SFTs are difficult to diagnose due to their non-specific morphology, thus immunohistochemistry plays a crucial role in confirming its diagnosis. Surgical excision with negative resection margins continues to be the standard treatment. Recurrence rates are low in comparison to other retroperitoneal sarcomas, hence routine chemotherapy or radiation therapy is not advised. CONCLUSION: This case demonstrates the significance of contemplating SFT as the differential diagnosis of retroperitoneal tumors and the role of immunohistochemistry in confirming the diagnosis. The optimal management strategies for retroperitoneal SFTs should be determined by additional research.

17.
Ther Adv Med Oncol ; 16: 17588359231216582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38249332

RESUMO

Background: Prostate cancer (PC) has a serious public health impact, and its incidence is rising due to the aging population. There is limited evidence and consensus to guide the management of PC in Southeast Asia (SEA). We present real-world data on clinical practice patterns in SEA for advanced PC care. Method: A paper-based survey was used to identify clinical practice patterns and obtain consensus among the panelists. The survey included the demographics of the panelists, the use of clinical guidelines, and clinical practice patterns in the management of advanced PC in SEA. Results: Most panelists (81%) voted prostate-specific antigen (PSA) as the most effective test for early PC diagnosis and risk stratification. Nearly 44% of panelists agreed that prostate-specific membrane antigen positron emission tomography-computed tomography imaging for PC diagnostic and staging information aids local and systemic therapy decisions. The majority of the panel preferred abiraterone acetate (67%) or docetaxel (44%) as first-line therapy for symptomatic mCRPC patients. Abiraterone acetate (50%) is preferred over docetaxel as a first-line treatment in metastatic castration-sensitive prostate cancer patients with high-volume disease. However, the panel did not support the use of abiraterone acetate in non-metastatic castration-resistant prostate cancer (nmCRPC) patients. Apalutamide (75%) is the preferred treatment option for patients with nmCRPC. The cost and availability of modern treatments and technologies are important factors influencing therapeutic decisions. All panelists supported the use of generic versions of approved therapies. Conclusion: The survey results reflect real-world management of advanced PC in a SEA country. These findings could be used to guide local clinical practices and highlight the financial challenges of modern healthcare.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38628049

RESUMO

AIM: The aim of the third Asia-Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia-Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022). METHODS: The one-day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate- and high-risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone-sensitive prostate cancer; (3) Management of non-metastatic castration-resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration-resistant prostate cancer. Pre- and post-symposium polling gathered APAC-specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region. RESULTS: APAC APCCC highlights APAC-specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision-making. CONCLUSION: The use of next-generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality-of-life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC-specific issues and considerations in areas of low evidence where clinical experience is growing.

19.
Mol Med ; 18: 1449-55, 2013 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-23196782

RESUMO

Current endocrine treatment for advanced prostate cancer does not result in a complete ablation of adrenal androgens. Adrenal androgens can be metabolized by prostate cancer cells, which is one of the mechanisms associated with progression to castration-resistant prostate cancer (CRPC). Aldo-keto reductase family 1 member C3 (AKR1C3) is a steroidogenic enzyme that plays a crucial role in the conversion of adrenal androgen dehydroepiandrosterone (DHEA) into high-affinity ligands for the androgen receptor (testosterone [T] and dihydrotestosterone [DHT]). The aim of this study was to examine whether AKR1C3 could be used as a marker and therapeutic target for CRPC. AKR1C3 mRNA and protein levels were upregulated in CRPC tissue, compared with benign prostate and primary prostate cancer tissue. High AKR1C3 levels were found only in a subset of CRPC patients. AKR1C3 can be used as a biomarker for active intratumoral steroidogenesis and can be measured in biopsy or transurethral resection of the prostate specimens. DuCaP (a CRPC cell line that has high AKR1C3 expression levels) used and converted DHEA under hormone-depleted conditions into T and DHT. The DHEA-induced growth of DuCaP could be antagonized by indomethacine, an inhibitor of AKR1C3. This study indicates that AKR1C3 can be considered a therapeutic target in a subgroup of patients with high AKR1C3 expression.


Assuntos
3-Hidroxiesteroide Desidrogenases/metabolismo , Biomarcadores Tumorais/metabolismo , Hidroxiprostaglandina Desidrogenases/metabolismo , Terapia de Alvo Molecular , Orquiectomia , Neoplasias da Próstata/enzimologia , Neoplasias da Próstata/cirurgia , Membro C3 da Família 1 de alfa-Ceto Redutase , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Di-Hidrotestosterona/metabolismo , Humanos , Indometacina/farmacologia , Masculino , Neoplasias da Próstata/patologia , Testosterona/metabolismo
20.
Urol Case Rep ; 50: 102527, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37649689

RESUMO

Renal cell carcinoma not otherwise specified (RCC NOS) is a very rare type of kidney cancer which used for renal tumors that do not fit into any of the well-recognized subtypes. We reported a case of RCC NOS of a 64-year-old male presenting an enlarging left flank mass. Abdominal CT showed a left kidney mass infiltrating to the adrenal, with pulmonary metastases. Cytoreductive nephrectomy and lymphadenectomy were performed and diagnosis of RCC NOS was confirmed through histopatological and immunohistochemistry examination.

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