Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47.080
Filtrar
1.
Anticancer Res ; 39(10): 5541-5549, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570448

RESUMO

BACKGROUND/AIM: The connection between prostate cancer and inflammation has been proposed many years ago, but very little is known about the metabolic adaptations of prostate cells in case of infection or inflammation. The aim of this study was to examine the effect of the stimulation of Toll-like receptor 3 (TLR3) on the metabolism of prostate cancer (PCa) cell lines and benign prostate cells. MATERIALS AND METHODS: Cytofluorimetry, qRT-PCR, western blot and Gas-chromatography/Mass-spectrometry were used. RESULTS: Reprogramming of glucose utilization involving hypoxia-inducible factor 1-alpha (HIF-1α) and the extracellular adenosine axis was observed. TLR3 stimulation synergized with adenosine receptor A2b on PCa cells, and induced a strong production of lactate, exacerbating the Warburg effect. Moreover, stimulation of benign prostate cells with poly I:C reduced lactate secretion, a characteristic typical of the neoplastic transformation. CONCLUSION: TLR3 stimulation promotes metabolic adaptations likely involved in the mechanisms of disease onset and progression.


Assuntos
Glucose/metabolismo , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Receptor 3 Toll-Like/metabolismo , Adenosina/metabolismo , Linhagem Celular Tumoral , Progressão da Doença , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Células PC-3 , Poli I-C/metabolismo , Neoplasias da Próstata/patologia , Receptores Purinérgicos P1/metabolismo
2.
Adv Exp Med Biol ; 1164: 207-224, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576551

RESUMO

Prostate cancers have a justified reputation as one of the most heterogeneous human tumours. Indeed, there are some who consider that advanced and castration-resistant prostate cancers are incurable, as a direct result of this heterogeneity. However, tumour heterogeneity can be defined in different ways. To a clinician, prostate cancer is a number of different diseases, the treatments for which remain equally heterogeneous and uncertain. To the pathologist, the histopathological appearances of the tumours are notoriously heterogeneous. Indeed, the genius of Donald Gleason in the 1960s was to devise a classification system designed to take into account the heterogeneity of the tumours both individually and in the whole prostate context. To the cell biologist, a prostate tumour consists of multiple epithelial cell types, inter-mingled with various fibroblasts, neuroendocrine cells, endothelial cells, macrophages and lymphocytes, all of which interact to influence treatment responses in a patient-specific manner. Finally, genetic analyses of prostate cancers have been compromised by the variable gene rearrangements and paucity of activating mutations observed, even in large numbers of patient tumours with consistent clinical diagnoses and/or outcomes. Research into familial susceptibility has even generated the least tractable outcome of such studies: the genetic loci are of low penetrance and are of course heterogeneous. By fractionating the tumour (and patient-matched non-malignant tissues) heterogeneity can be resolved, revealing homogeneous markers of patient outcomes.


Assuntos
Células Endoteliais , Neoplasias da Próstata , Células Endoteliais/citologia , Heterogeneidade Genética , Humanos , Masculino , Mutação , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia
3.
Medicine (Baltimore) ; 98(38): e17257, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567999

RESUMO

Recent availability of immune checkpoint inhibitors has facilitated research involving programmed cell death protein 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1). However, the incidence and clinical implication of PD-1 and PD-L1 expression in prostate cancer remain poorly understood. The current study aimed to determine the status of PD-1/PD-L1 expression in prostate cancer specimens and its prognostic significance.We immunohistochemically stained for PD-1 and PD-L1 in our tissue microarray (TMA) consisting of radical prostatectomy specimens. The expression of PD-1/PD-L1 was designated as positive when moderate to strong staining or weak staining was seen in at least 1% or 10%, respectively, of tumor cells and/or associated immune cells. We then evaluated the relationship between the expression of each protein and clinicopathological features available for our patient cohort.PD-1 and PD-L1 were positive in 3 (1.5%) and 1 (0.5%) of 201 non-neoplastic prostate tissues, and also in 17 (7.7%) and 29 (13.2%) of 220 prostate cancers, respectively. PD-1 and PD-L1 were also expressed in tumor-infiltrating lymphocytes/macrophages in 172 (78.2%) and 33 (15.0%) cases, respectively. PD-L1 expression in tumor cells was more often seen in high pT stage (pT2: 10.8% vs pT3/4: 20.4%; P = .072; pT2/3a: 11.4% vs pT3b/4: 31.6%; P = .013) or lymph node-positive (pN0: 10.1% vs pN1: 27.3%; P = .086) cases, whereas PD-1 expression in tumor cells was not significantly associated with pT/pN stage. In addition, there were no statistically significant associations between PD-1/PD-L1 expression in tumor cells or tumor-infiltrating lymphocytes/macrophages versus patient age, preoperative prostate-specific antigen level, or Gleason score. Kaplan-Meier analysis coupled with log-rank test further revealed no significant associations between PD-1/PD-L1 expression in tumor cells (P = .619/P = .315), tumor-infiltrating lymphocytes/macrophages (P = .954/P = .155), or either or both of them (P = .964/P = .767) versus disease recurrence after radical prostatectomy.PD-1/PD-L1 expression was detected in a subset of prostate cancers. In particular, PD-L1 expression was considerably up-regulated in nonorgan-confined tumors. However, PD-1/PD-L1 expression in our TMA was found to be not very helpful in predicting tumor recurrence in prostate cancer patients who underwent radical prostatectomy.


Assuntos
Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias da Próstata/metabolismo , Antígeno B7-H1/imunologia , Biomarcadores , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Receptor de Morte Celular Programada 1/imunologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Análise Serial de Tecidos
4.
Nihon Yakurigaku Zasshi ; 154(3): 108-113, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527359

RESUMO

Similar to calcium (Ca2+) and chloride (Cl-) ion channels/transporters, potassium (K+) channels have been recognized as a crucial cancer treatment target. Recent studies have provided convincing evidences of positive correlation between elevated expression levels of Ca2+-activated K+ (KCa) channels and cancer proliferation, metastasis, and poor patient prognosis. In cancer cells, KCa1.1 and KCa3.1 KCa channels are co-localized with Ca2+-permeable Orai/TRP channels to provide a positive-feedback loop for Ca2+ entry. They are responsible for the promotion of cell growth and metastasis in the different types of cancer, and are therefore potential therapeutic targets and biomarkers for cancer. We determined the epigenetic and post-transcriptional dysregulation of KCa3.1 by class I histone deacetylase inhibitors in breast and prostate cancer cells. We further determined the transcriptional repression and protein degradation of KCa1.1 by vitamin D receptor agonists and androgen receptor antagonists, which are expected as potential therapeutic drugs for triple-negative breast cancer. The anti-inflammatory cytokine, interleukin-10 (IL-10) is an immunosuppressive factor involved in tumorigenesis, and plays a crucial role in escape from tumor immune surveillance. We determined KCa3.1 activators are a possible therapeutic option to suppress the tumor-promoting activities of IL-10. These results may provide new insights into cancer treatment focused on Ca2+-activated K+ channels.


Assuntos
Neoplasias da Mama/patologia , Inibidores de Histona Desacetilases/farmacologia , Canais de Potássio Cálcio-Ativados/metabolismo , Neoplasias da Próstata/patologia , Antagonistas de Receptores de Andrógenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Epigênese Genética , Feminino , Humanos , Vigilância Imunológica , Interleucina-10/metabolismo , Masculino , Proteólise , Processamento Pós-Transcricional do RNA , Receptores de Calcitriol/agonistas
5.
Nihon Yakurigaku Zasshi ; 154(3): 97-102, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31527367

RESUMO

Among voltage-gated Ca2+ channels, T-type Ca2+ channels, which are activated by low voltages, regulate neuronal excitability, spontaneous neurotransmitter release, hormone secretion, etc. and also participate in proliferation of distinct cancer cells. Among three isoforms of T-type Ca2+ channels, Cav3.2 is detectable in 100% of biopsy samples from prostate cancer patients. In general, prostate cancer cells are highly sensitive to androgen deprivation therapy, but often acquire hormone-therapy resistance. The androgen deprivation may trigger neuroendocrine (NE)-like differentiation of some prostate cancer cells. We have analyzed the expression and function of Cav3.2 in human prostate cancer LNCaP cells during NE-like differentiation. NE-like LNCaP cells overexpress Cav3.2 through the CREB/Egr-1 pathway and also cystathionine-γ-lyase (CSE), which generates H2S that enhances the channel activity of Cav3.2. H2S generated by upregulated CSE appears to enhance the activity of upregulated Cav3.2 after the differentiation. The enhanced Cav3.2 activity in NE-like cells may contribute to increased secretion of mitogenic factors essential for androgen-independent proliferation of surrounding prostate cancer cells. It is known that increased extracellular glucose levels enhance Cav3.2 activity through asparagine (N)-linked glycosylation of Cav3.2, which might contribute to diabetic neuropathy. We then found that high glucose accelerates the enhanced channel function and overexpression of Cav3.2 in NE-like LNCaP cells, which might be associated with clinical evidence for diabetes-related poor prognosis of prostate cancer and development of hormone therapy resistance. Thus, Cav3.2 is considered to play a role in the pathophysiology of prostate cancer, and may serve as a therapeutic target.


Assuntos
Canais de Cálcio Tipo T/fisiologia , Sistemas Neurossecretores/citologia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/farmacologia , Diferenciação Celular , Linhagem Celular Tumoral , Proliferação de Células , Cistationina gama-Liase/fisiologia , Humanos , Sulfeto de Hidrogênio , Masculino
6.
Anticancer Res ; 39(9): 4811-4816, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519583

RESUMO

BACKGROUND/AIM: γ-Glutamylcyclotransferase (GGCT) is highly expressed in many forms of cancer, and is a promising therapeutic target. The present study investigated whether inhibition of GGCT enhanced the antiproliferative effects of the drug docetaxel in prostate cancer cells. MATERIALS AND METHODS: Immunohistochemistry and western blot analysis were conducted to measure GGCT expression in prostate cancer tissue samples and cell lines. GGCT was inhibited using RNAi and a novel enzymatic inhibitor, pro-GA, and cell proliferation was evaluated with single and combination treatments of GGCT inhibitors and docetaxel. RESULTS: GGCT was highly expressed in cultured prostate cancer cells and patient samples. GGCT inhibition alone inhibited prostate cancer cell line proliferation and induced cellular senescence. GGCT inhibition in combination with apoptosis-inducing docetaxel had more potent antiproliferative effects than either drug used alone. CONCLUSION: GGCT inhibition may potentiate anticancer drug efficacy.


Assuntos
Antineoplásicos/farmacologia , Docetaxel/farmacologia , Inibidores Enzimáticos/farmacologia , gama-Glutamilciclotransferase/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/genética , gama-Glutamilciclotransferase/genética , gama-Glutamilciclotransferase/metabolismo
7.
Anticancer Res ; 39(9): 5065-5069, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519616

RESUMO

BACKGROUND/AIM: The primary endpoint of this phase I study was the maximum tolerated dose (MTD) of middle half body (MHB) accelerated radiotherapy (RT) in multiple bone metastatic (BM) prostate cancer (PCa) patients. PATIENTS AND METHODS: Three step dose escalation [13 Gy (3.25 Gy/fraction), 14 Gy (3.5 Gy/fraction), and 15 Gy (3.75 Gy/fraction)] in three consecutive patient cohorts were planned. RT was delivered in two consecutive days and two daily fractions. Six patients were enrolled in the first two cohorts and 12 in the third cohort. Grade ≥3 toxicity was considered as a dose-limiting toxicity (DLT). RESULTS: Twenty-five patients (median age=71 years, median follow-up=7.4 months) were enrolled. Defined MTD dose was 15 Gy. Overall pain response rate was 76%: 9 patients (36%) showed complete and 10 patients (40%) reported partial response of pain. CONCLUSION: MHB accelerated RT (total dose: 15 Gy) delivered in two consecutive days and two daily fractions is well tolerated.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias da Próstata/patologia , Radioterapia , Idoso , Terapia Combinada , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Qualidade de Vida , Radioterapia/efeitos adversos , Radioterapia/métodos , Dosagem Radioterapêutica , Resultado do Tratamento
8.
BMC Surg ; 19(1): 138, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31533681

RESUMO

BACKGROUND: Neck hematoma is a complication of carotid endarterectomy, usually occurring in the comparatively early stage postoperatively. CASE PRESENTATION: We described a patient developing life-threatening hemorrhage and non-clotting hematoma at a comparatively later stage after CEA. DIC was diagnosed according to the lab results, and the patient underwent re-operation and was supported with blood products until the coagulopathy was corrected. The patient had a history of prostatic hyperplasia and experienced malaise during the hospitalization. Prostate cancer with bone metastases was diagnosed. CONCLUSIONS: This case report describes a rare underlying cause of hematoma after CEA, which reminds us to pay attention to prostate symptoms or related medical history, especially malignancy, in surgical patients, which may result in severe complications.


Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Neoplasias Ósseas/complicações , Endarterectomia das Carótidas/efeitos adversos , Hematoma/etiologia , Neoplasias da Próstata/complicações , Idoso , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/terapia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Hematoma/diagnóstico , Hematoma/terapia , Humanos , Masculino , Pescoço , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Reoperação , Fatores de Tempo , Resultado do Tratamento
9.
Cancer Radiother ; 23(6-7): 503-509, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471253

RESUMO

There are many treatment options for localized prostate cancers, including active surveillance, brachytherapy, external beam radiotherapy, and radical prostatectomy. Quality of life remains a primary objective in the absence of superiority of one strategy over another in terms of specific survival with similar long-term biochemical control rates. Despite a significant decrease in digestive and urinary toxicities thanks to IMRT and IGRT, external radiotherapy remains a treatment that lasts approximately 2 months or 1.5 months, when combined with a brachytherapy boost. Given the specific radiosensitivity of this tumor, several randomized studies have shown that a hypofractionated scheme is not inferior in terms of biochemical control and toxicities, allowing to divide the number of fractions by a factor 2 to 8. Given that SBRT becomes a validated therapeutic option for a selected population of patients with localized prostate cancer, extreme hypofractionation is becoming a strong challenger of conventional external radiotherapy or brachytherapy.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Hipofracionamento da Dose de Radiação , Braquiterapia , Ensaios Clínicos Fase III como Assunto , Estudos de Equivalência como Asunto , Humanos , Irradiação Linfática/métodos , Masculino , Seleção de Pacientes , Cuidados Pós-Operatórios , Qualidade de Vida , Hipofracionamento da Dose de Radiação/normas , Tolerância a Radiação , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Cancer Radiother ; 23(6-7): 486-495, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31501025

RESUMO

The basis of treatment of primary disease in case of metastatic cancer at diagnosis is based on the knowledge of the natural history of the disease, the biology of the primary tumour and its metastases, advances in modern radiotherapy techniques (modulated intensity, stereotactic radiotherapy) in order to improve the survival of patients with advanced disease. The clinical concept of oligometastatic disease at diagnosis has repositioned the interest of local treatment for primitive disease because these patients have a slower evolutionary profile than metastatic disease extended from the outset. This article reviews the indication of radiotherapy as a local treatment for primary cancer in a de novo metastatic diagnosed disease in the case of breast cancer, non-small cell lung cancer and prostate cancer.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Neoplasias da Próstata/radioterapia , Neoplasias da Mama/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metástase Neoplásica , Estudos Prospectivos , Neoplasias da Próstata/patologia , Estudos Retrospectivos
12.
Curr Urol Rep ; 20(10): 63, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478109

RESUMO

PURPOSE OF REVIEW: Although still considered experimental, focal irreversible electroporation (IRE) as a primary treatment for prostate cancer (PCa) is considered one of the most promising ablative technologies for focal therapy. This review provides a description of the principle of IRE for the treatment of PCa, combined with an overview of the recent research. RECENT FINDINGS: It has been almost a decade since the first human studies of focal IRE for PCa were trying to demonstrate its feasibility and safety, and recently new data are emerging regarding the functional and oncological outcomes. It was shown that the expected ablation efficacy of IRE is dependent on increased safety margins of > 9 mm and an uninterrupted IRE procedure, but these findings need further investigation in larger cohorts and randomized control trials (RCT). Recent data from larger cohorts with a longer follow-up of up to 12 months prove that focal IRE as primary treatment for localized PCa is indeed safe, has effective short-term oncological control in selected patients, and it has good functional outcomes by retaining urinary function and causing only mild erectile dysfunction.


Assuntos
Técnicas de Ablação/métodos , Eletroporação/métodos , Neoplasias da Próstata/terapia , Disfunção Erétil/etiologia , Humanos , Masculino , Margens de Excisão , Neoplasias da Próstata/patologia , Recuperação de Função Fisiológica
13.
Curr Urol Rep ; 20(10): 59, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478111

RESUMO

PURPOSE OF REVIEW: The purpose of this review is to summarize the most current literature regarding the most important aspects to consider when developing a center of excellence for prostate imaging and biopsy. RECENT FINDINGS: Multiparametric MRI (mp-MRI) has changed the way we diagnose and treat prostate cancer. This imaging modality allows for more precise identification of areas suspicious in terms of harboring prostate cancer, enabling performance of targeted mp-MRI-guided biopsies that have been demonstrated to yield superior cancer detection rates. Centers worldwide are increasingly adopting this technology. However, obtaining results comparable with those findings published in the literature can be challenging. The imaging and biopsy process entails the need for a multidisciplinary team including a dedicated radiologist, urologist, and pathologist. Adequate mp-MRI interpretation for accurate lesion identification, acquaintance with the biopsy technique selected, and precise characterization of Gleason Score/Grade Groupings are equal determinants of accurate biopsy results. Furthermore, all specialists are required to attain appropriate learning curves to ensure optimal results. In this review, we characterize crucial aspects to consider when developing a center of excellence for prostate imaging and biopsy as well as insights regarding how to implement them.


Assuntos
Instalações de Saúde/normas , Biópsia Guiada por Imagem/normas , Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Biópsia/métodos , Biópsia/normas , Humanos , Biópsia Guiada por Imagem/métodos , Curva de Aprendizado , Masculino , Gradação de Tumores , Equipe de Assistência ao Paciente/normas , Desenvolvimento de Programas/normas , Neoplasias da Próstata/patologia , Estados Unidos
14.
Curr Urol Rep ; 20(10): 60, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31478113

RESUMO

PURPOSE OF REVIEW: With the long-standing controversy surrounding the use of prostate-specific antigen (PSA) for the detection, evaluation, and surveillance of prostate cancer, there is a need for a minimally invasive technique to identify and risk-stratify these patients. Additionally, in an effort to reduce the number of unnecessary biopsies and identify clinically significant prostate cancer (csPCa), there has been a shift in practice towards the use of multiparametric magnetic resonance imaging (mpMRI) in conjunction with decision-making regarding prostate cancer diagnosis and management. In the current review, we summarize the data regarding the use of mpMRI in the detection, evaluation, and surveillance of csPCa. RECENT FINDINGS: Recent prospective clinical trials have determined that a pre-biopsy mpMRI may rule out insignificant prostate cancers, thereby reducing the number of patients who require a biopsy. The anatomic information gathered from these pre-biopsy mpMRI performed during MRI fusion biopsy in csPCa increases the accuracy of pathologic staging in terms of Gleason scores. In regard to active surveillance, prospective trials suggest little to no clinical utility for mpMRI and fusion biopsy in the surveillance of prostate cancer despite conflicting findings from retrospective studies. Recent trials suggest that mpMRI can play an important role in the detection and evaluation of csPCa. The ideal role for mpMRI in active surveillance remains limited.


Assuntos
Imagem por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biomarcadores Tumorais/sangue , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Vigilância da População , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Medição de Risco
15.
Arch Esp Urol ; 72(7): 677-689, 2019 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31475679

RESUMO

Prostate Cancer (PC) is the most common malignancy in men, and a diagnosis can only be confirmed following a prostate biopsy (PB). 10-12 cores ultrasound-guided PB is currently the state of the art in the primary diagnosis of PC, presenting clear advantages in terms of detection rate of clinically significant PC, pathology concordance, and both positive and negative predictive value, when compared with the former classical sextant biopsy. Persistent clinical suspicion of PC despite previous negative PB is a challenging topic, with several serum and urinary markers, as well as imaging techniques, aiming to help in the optimal management of these patients.Currently, the most accepted and used methods in clinical practice to reduce the number of unnecessary PBs in this subset of patients are Prostate Cancer Antigen 3 (PCA3) and multiparametric MRI (mpMRI). These methods have shown to improve the diagnostic accuracy of prostatic rebiopsy, but there still aren't clear guidelines defining the optimal strategy in this setting. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PC, highlighting the emerging role of the Prostate Health Index (PHI) and the Four Kallikrein (4k) score. The aim of this review is to demonstrate the evolution to the actual standard 10-12 core ultrasound-guided PB, the indications and controversies concerning repeated PB and to explore the data regarding the potential role of the leading methods affecting the decision to rebiopse - PCA3 and mpMRI -, as well as new PC biomarkers used in the clinical practice (PHI and 4K score).


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Próstata/patologia , Biópsia , Humanos , Biópsia Guiada por Imagem , Imagem por Ressonância Magnética , Masculino
16.
Expert Opin Drug Saf ; 18(11): 1065-1076, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31495240

RESUMO

Introduction: The use of testosterone therapy (TTh) in men with prostate cancer (PCa) is relatively new, and controversial, due to the longstanding maxim that TTh is contraindicated in men with PCa. Scientific advances have prompted a reevaluation of the potential role for TTh in men with PCa, particularly as TTh has been shown to provide important symptomatic and general health benefits to men with testosterone deficiency (TD), including many men with PCa who may expect to live 30-50 years after diagnosis. Areas covered: This review outlines the historical underpinnings of the historical belief that TTh 'fuels' PCa and the experimental and clinical studies that have radically altered this view, including description of the saturation model. The authors review studies of TTh in men with PCa following radical prostatectomy and radiation therapy, in men on active surveillance, and in men with advanced or metastatic PCa. Expert opinion: TTh provides important symptomatic and overall health benefits for men with PCa who have TD. Although more safety studies are needed, TTh is a reasonable therapeutic option for men with low-risk PCa after surgery or radiation. Data in men on active surveillance are limited, but initial reports are reassuring.


Assuntos
Androgênios/administração & dosagem , Neoplasias da Próstata/terapia , Testosterona/administração & dosagem , Animais , Sobreviventes de Câncer , Humanos , Masculino , Metástase Neoplásica , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Testosterona/deficiência
17.
Medicine (Baltimore) ; 98(36): e16705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490362

RESUMO

Deregulation of miR-153 has recently been observed in several common human cancer, while miR-153 serves an oncogene or tumor suppressive role in different cancer types. Previously, miR-153 has been identified to be overexpressed in prostate cancer. miR-153 played an important role in promoting proliferation of human prostate cancer cells and presented a novel mechanism of microRNA-mediated direct suppression of phosphatase and tensin homolog (PTEN) expression in prostate cancer cells. Until now, little is known about the clinical significance of miR-153 expression in prostate cancer.The miR-153 expression in 143 pairs of prostate cancer and adjacent non-cancerous prostate tissues was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Student t test was conducted for intergroup comparison. Pearson correlation test was used for correlation analysis. Survival curves were carried out by the Kaplan-Meier method and evaluated using the log-rank test. Multivariable Cox proportional hazard risk regression model was performed to screen the independent factor affected the prognosis of prostate cancer patients.qRT-PCR analysis showed that the expression of miR-153 was significantly increased in the prostate cancer tissues in comparison with the adjacent noncancerous prostate tissues (P < .001). The high expression of miR-153 in prostate cancer tissues is closely correlated with aggressive clinical pathological parameters such as lymph node metastasis (P = .001); bone metastasis (P < .001); Gleason score (P < .001); and tumor-node-metastasis (TNM) stage (P < .001). Prostate cancer patients with a high expression of miR-153 had an evidently lower 5-year overall survival as compared with those with a low expression of miR-153 (P = .019). Notably, the multivariate Cox regression analysis indicated that miR-153 expression was an independent factor for predicting the 5-year overall survival of prostate cancer patients (hazard ratio [HR] = 2.481, 95% confidence interval [CI]: 1.582-10.727; P = .018).Our study demonstrated that high miR-153 expression was significantly associated with a poor overall survival independently of other factors in prostate cancer. Therefore, miR-153 may be an available biomarker for prostate cancer prognosis.


Assuntos
MicroRNAs/biossíntese , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais , Intervalo Livre de Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Chem Biol Interact ; 311: 108798, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31433962

RESUMO

Natural products are a valuable source of anticancer agents, with many naturally derived compounds currently used in clinical and preclinical treatments. This study aims to investigate the antiproliferative activity and potential mechanism of action of the xanthoquinodin JBIR-99, isolated from fungi Parengyodontium album MEXU 30,054 and identified by single-crystal X-ray crystallography. Cytotoxicity of xanthoquinodin was evaluated in a panel of human cancer cells lines and CCD-112-CoN normal colon cells, using the sulforhodamine B assay. PC-3 prostate cancer cells were used in biochemical assays including cell cycle, mitochondrial transmembrane potential (MTP), reactive oxygen species (ROS) and caspase activity. Expression levels of apoptosis-pathway-related proteins were analyzed by Western blot. The in vivo toxicity of xanthoquinodin was determined using a zebrafish model. Xanthoquinodin showed cytotoxicity in all cancer cell lines but demonstrated relative selective potency against PC-3 cells with an IC50 1.7 µM. In CCD-112-CoN cells, xanthoquinodin was non-cytotoxic at 100 µM. In PC-3 cells, the compound induced loss of MTP, production of ROS, and cell cycle arrest in S phase. The expression and activity of caspase-3 was increased, which correlates with the upregulation of Cyt c, Bax, nuclear factor kappa-B (NF-κB) (p65) and IKKß, and downregulation of poly ADP ribose polymerase (PARP-1) and Bcl-2. Lastly, xanthoquinodin did not cause any visible developmental toxicity in zebrafish at 50 µM. These results demonstrate xanthoquinodin induces apoptosis in PC-3 prostate cancer cells by activation of both intrinsic and extrinsic apoptotic pathways. In addition, the non-toxic effect in vivo indicates that xanthoquinodin could be a useful lead in the development of a novel, anti-cancer agent that is selective for prostate cancer.


Assuntos
Apoptose/efeitos dos fármacos , Ascomicetos/química , Cromonas/farmacologia , Ascomicetos/metabolismo , Linhagem Celular Tumoral , Cromonas/química , Cristalografia por Raios X , Citocromos c/metabolismo , Humanos , Quinase I-kappa B/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Conformação Molecular , Poli(ADP-Ribose) Polimerase-1/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/metabolismo , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
19.
Anticancer Res ; 39(8): 4171-4177, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366502

RESUMO

BACKGROUND/AIM: Identification of prostatic stem cells in primary prostate tissue sections, organ cultures of prostate and cell lines requires a range of techniques that allows characterization of stem cells for their potential use in the treatment of patients. Isolated cells usually round-up and develop changes in shape, size and cellular characteristics. The aim of this study was to provide a range of methods for identifying prostatic stem cells and characterizing them with regard to ultrastructure, nuclear morphology, cytoplasmic organelles, and/or expression stem cell marker CD133. MATERIALS AND METHODS: Prostate biopsy and prostatectomy specimens were used for studying prostatic stem cells and their known marker CD133 in tissue sections by light and/or electron microscopy. Inverted capsule embedding was used to study archival metastatic prostate in pelvic nodes and Du145 cell line in a monolayer culture. RESULTS: Staining for CD133 positively identified stem cells that were found in benign prostatic hyperplasia, benign prostate, and prostate cancer cells. Paraffin embedded sections showed a single type of stem cells, whereas methylene blue-stained Epon sections showed both light and dark stem cells. Electron microscopy showed that both basal and stem cells were closely associated with the basement membrane (basal lamina). Stem cells had smooth plasma and nuclear membranes, a prominent nucleolus, small mitochondria, and few ribosomes. Du145 cells were separated by intercellular spaces in monolayer culture. CONCLUSION: The inverted capsule embedding method allowed the study of metastasized prostate cancer in pelvic lymph nodes. Our approach enabled the assessment of stem cells in tissue sections by light and electron microscopy.


Assuntos
Antígeno AC133/genética , Membrana Basal/ultraestrutura , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Membrana Basal/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Microscopia Eletrônica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/ultraestrutura , Próstata/metabolismo , Próstata/patologia , Próstata/ultraestrutura , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA