Induction of more aggressive tumoral phenotypes in LNCaP and PC3 cells by serum exosomes from prostate cancer patients.

Prostate cancer (PCa) is the second most frequent and sixth most fatal cancer in men worldwide. Despite its high prevalence, our understanding of its etiology and the molecular mechanisms involved in the progression of the disease is substantially limited. In recent years, the potential participation of exosomes in this process has been suggested. Therefore, we aim to study the effect of exosomes isolated from the serum of patients with PCa on various cellular processes associated with increased tumor aggressiveness in two PCa cell lines: LNCaP-FGC and PC3. The exosomes were isolated by filtration wand ultracentrifugation. Their presence was confirmed by immunodetection of specific markers and their size distribution was analyzed by Dynamic Light Scattering (DLS). The results obtained demonstrated that serum exosomes from PCa patients increased migration of PC3 cells and neuroendocrine differentiation of LNCaP-FGC cells regardless of the grade of the tumor. PCa serum exosomes also enhanced the secretion of enzymes related to invasiveness and resistance to chemotherapeutics, such as extracellular matrix metalloproteases 2 and 9, and gamma-glutamyltransferase in both cell lines. Altogether, these findings support the pivotal participation of exosomes released by tumoral cells in the progression of PCa. Future studies on the molecular mechanisms involved in the observed changes could provide crucial information on this disease and help in the discovery of new therapeutic targets.

Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion in the Clinical Decision-Making Process?

INTRODUCTION: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets the criteria to justify its inclusion in a predictive model of prostate cancer (PCa) diagnosis and in the clinical decision-making process. MATERIALS AND METHODS: A total 172 men with total prostate-specific antigen of 2-10 ng/mL underwent measurement of free PSA and p2PSA before prostate biopsy in an observational and prospective study. From these measurements, the Prostate Health Index (PHI) was calculated. Clinical and analytical predictive models were created incorporating PHI. RESULTS: Of 172 men, 72 (42%) were diagnosed with PCa, 33 (46%) of whom were found to be with high-grade disease. PHI score was the most predictive of biopsy outcomes in terms of discriminative ability (area under the curve = 0.79), with an added gain in predictive accuracy of 17%. All the models that incorporated PHI worked better in terms of calibration close to 45° on the slope. In the decision curve analysis, at a threshold probability of 40% we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors. CONCLUSIONS: PHI score is a more discriminant biomarker, has superior calibration and superior net benefit, and provides a higher rate of avoided biopsies; thus, it can be useful for aiding in making a more informed decision for each patient.

Does obesity modify prostate cancer detection in a European cohort?

INTRODUCTION: To investigate prostate-specific antigen (PSA) accuracy and digital rectal examination (DRE) accuracy in detecting prostate cancer according to body mass index (BMI) in Spanish men with an indication of the first prostate biopsy. MATERIAL AND METHODS: We reviewed the clinical and histopathological data of 1,319 patients who underwent transrectal ultrasound-guided prostate needle biopsy. The patients were categorised according to the BMI as follows: <25 kg/m2 (normal weight); 25-29.9 kg/m2 (overweight); and ≥30 kg/m2 (obese). Receiver operator characteristic curves were used to assess PSA accuracy and DRE accuracy by calculating the area under the curve. RESULTS: The obesity rate of the cohort was 14%. PSA accuracy for predicting prostate cancer in each BMI category was 0.52, 0.58 and 0.62, respectively (p = 0.01). After stratification by DRE findings, there was no difference in the performance accuracy of PSA in predicting the presence of cancer across BMI groups in abnormal DRE (p = 0.90). Serum PSA, DRE and BMI were strong predictors of prostate cancer diagnosis (odds ratio 1.07, 2.02 and 1.4, respectively; p <0.001). When the DRE was abnormal, a BMI ≥30 increased the risk of prostate cancer twice. With the addition of BMI to the model, the area under the curve of the combined PSA and DRE for diagnosing prostate cancer improved from 0.60 to 0.63. CONCLUSIONS: The predictive value of PSA in predicting prostate cancer is not poorer in the obese population and the predictive value of an abnormal DRE in cancer detection is significantly modified by the patient's BMI.

Análisis de las variables clínico-patológicas, grupos de estadiaje y pronósticos y resultados terapéuticos de 106 tumores testiculares germinales / Analysis of clinical-pathologic variables, staging and prognostic groups, and therapeutic results of 106 germ-cell testicular tumors

OBJETIVO: Revisión retrospectiva de 106 tumores germinales testiculares tratados en nuestro centro entre 1992 y 2009.METODOS: Descripción y análisis de determinadas variables clínico-patológicas, pronósticas y análisis de supervivencia(AU)

RESULTADOS: Un 68 % se diagnosticaron en los últimos 5 años. Un 54.7 % presentaron histología seminomatosa. La edad media (años) al diagnóstico para seminoma (S) y no seminoma (NS) fue de 33.47 y 27.63 respectivamente; p=0.001. El tamaño tumoral (TT) medio (mm) globalmente fue de 45.99 mm. 29.3% de S y 60.4 % de NS presentaron elevación de al menos un marcador tumoral (alfafetoproteina (AFP) o gonadotropina coriónica humana (HCG)); p= 0.02 . El porcentaje de pacientes con elevación de HCG para S y NS fue de 29.3 % y 52.1 % respectivamente ; p=0.017 y de AFP para S y NS de 5.2 % y 45.8 % respectivamente; p< 0.001. Atendiendo a la clasificación del Royal Marsden Hospital 96.5 % de S y 83.2% de NS respectivamente se presentaron como estadios I-II. Según la clasificación del International Germ Cell Cancer Collaborative Group (IGCCG) para pacientes con enfermedad avanzada 98.2 % de S y 89.6 % de NS pertenecieron al grupo de buen pronóstico (BP). En cuanto a los factores de riesgo para recidiva (FRR) en S en estadio I (invasión rete testis (IRT) y tamaño tumoral > 4 cm) un 28 % presentaron ambos FRR. Un 18 % de NS en estadio I presentaron invasión vascular o linfática (IVoL). En cuanto al protocolo de tratamiento por histología, estadio y FRR el 100% de S en estadio I con presencia de 2 FRR y el 100 %de NS en estadio I con IVoL recibieron adyuvancia. El resto de S y NS estadios II-IV recibieron e su inmensa mayoría tratamiento con distintos protocolos de quimioterapia (QT). En el 2.8% de NS estadio II se practico linfadenectomía retroperitoneal. Un 38.1 % de NS estadio II-IV fueron sometidos a cirugía de rescate de masa residual retroperitoneal. Con una mediana de seguimiento de 60 meses la supervivencia libre de eventos (SLE) global fue de 93.3 %CONCLUSIONES: Nuestra serie presenta características similares a los obtenidos en otros centros(AU)

OBJECTIVES: Retrospective review of 106 germ-cell testicular tumors treated in our center between 1992 and 2009.METHODS: Description and analysis of several clinical-pathologic and prognostic variables and survival analysis.RESULTS: 68% of our patients were diagnosed in the last 5 years. 54.7% presented seminoma histology. The mean age at diagnosis was 33.47 for the seminoma (S) and 27.63 for non seminoma (NS), p=0,001. The median tumoral size in mm was 45.99mm (globally). 44.3% presented elevation of at least one tumor marker; Alpha-fetoprotein(AFP) or Human chorionic gonadotropin (HCG) .29.3% in the S and 60.4% in NS; p=0.02. The percentage of patients with increased HCG in S was 29.3% and 52.1% in NS; p=0.017 and AFP was elevated in 5.2% of S and 45.8% of NS; P <0.001. Accordingly to the classification of The Royal Marsden Hospital 96.5% of S and 83.2% of NS were diagnosed in stage I-II. Using the classification of the International Germ Cell Cancer Collaborative Group (IGCCG) for patients with advanced disease, 98.2% of S and 83.2% of NS belonged to the good prognostic group. Regarding the risk factors for relapse in stage I S (Rete testis invasion (RTI) and tumoral size (TS)> 4cm) 28% of our patients presented both risk factors. 18% of stage I NS presented vascular (VI) or lymphatic invasion (LI). Following the treatment protocols in consideration with the histology, stage and risk factors, 100 % of stage I S with both risk factors and 100% of NS with vascular or lymphatic invasion received adjuvant therapy. Almost all the stage II-IV S and NS received different protocols of chemotherapy. In 2.8% of stage II NS a retroperitoneal lymph node dissection was performed. Residual tumor resection was documented in eight patients with stage II-IV NS. With a median follow-up of 60 months, the event free survival (EFS) was 93.3%.CONCLUSIONS: Our study has similar characteristics compared to other studies(AU)