Apoptose no carcinoma de próstata

Pós-graduação em Patologia - FMB

La força de prensió manual com a factor pronòstic de mortalitat en pacients oncològics terminals a una unitat de cures pal•liatives.

L’objectiu de l’estudi va ser determinar si la força de prensió manual (FPM) era factor pronòstic de mortalitat en malalts amb càncer avançant ingressats a una Unitat de cures pal•liatives (UCP). Es va determinar la força de prensió a l’ingrés i l’evolució de la FPM els primers 12 dies mitjançant un dinamòmetre. Ni la FPM inicial ni a l’evolució va demostrar diferències significatives entre els malalts donats d’alta vius i els que van morir a la UCP. Conclusions: la determinació de FPM no va ser factor pronòstic de supervivència en malalts ingressats per càncer en una UCP.

Enfermera Gestora de Casos Hospitalaria: en pacientes Paliativos Oncológicos

La enfermedad y la muerte son un elemento integral de la propia vida del ser humano. La respuesta aportada a las necesidades de las personas ante una enfermedad avanzada y sin posibilidades de curación, así como el apoyo a sus familias, ayuda a mejorar la calidad de vida y a disminuir el sufrimiento. Para todo ello, Cicely Saunders estableció un tipo de cuidados activos e integrales para todos los pacientes con enfermedades avanzadas y progresivas, que pretenden el control del dolor y otros síntomas, y ofrecen soporte psicológico, emocional y espiritual. Los cuales reciben el nombre de Cuidados Paliativos (C.P). Esta tipología de cuidados han tenido siempre un reconocimiento importante en el marco de la Unión Europea desde que el Comité Europeo de Sanidad en 1980 emitiera el informe sobre “Problemas relacionados con la muerte: cuidados para el moribundo”

Endorectal Magnetic Resonance Imaging and Spectroscopy Are Useful for Selecting Candidates for Biopsy among Patients with Persistently Elevated Prostate Specific Antigen

To evaluate the efficacy of endorectal Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spetroscopic Imaging (MRSI) combined with total prostate-specific antigen (tPSA) and free prostate-specific antigen (fPSA) in selecting candidates for biopsy. Subjects and Methods: 246 patients with elevated tPSA (median: 7.81 ng/ml) underwent endorectal MRI and MRSI before Transrectal Ultrasound (TRUS) biopsy (10 peripheral + 2 central cores); patients with positive biopsies were treated with radical intention; those with negative biopsies were followed up and underwent MRSI before each additional biopsy if tPSA rose persistently. Mean follow-up: 27.6 months. We compared MRI, MRSI, tPSA, and fPSA with histopathology by sextant and determined the association between the Gleason score and MRI and MRSI. We determined the most accurate combination to detect prostate cancer (PCa) using receiver operating curves; we estimated the odds ratios (OR) and calculated sensitivity, specificity, and positive and negative predictive values. Results: No difference in tPSA was found between patients with and without PCa (p = 0.551). In the peripheral zone, the risk of PCa increased with MRSI grade; patients with high-grade MRSI had the greatest risk of PCa over time (OR = 328.6); the model including MRI, MRSI, tPSA, and fPSA was more accurate (Area under Curve: AUC = 95.7%) than MRI alone (AUC = 85.1%) or fPSA alone (AUC = 78.1%), but not than MRSI alone (94.5%). In the transitional zone, the model was less accurate (AUC = 84.4%). The association (p = 0.005) between MRSI and Gleason score was significant in both zones. Conclusions: MRSI is useful in patients with elevated tPSA. High-grade MRSI lesions call for repeated biopsies. Men with negative MRSI may forgo further biopsies because a significantly high Gleason lesion is very unlikely

Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

Background: We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. Results: Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. Conclusion: Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer.

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design

INTRODUCTION: We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. METHODS: Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. DISCUSSION: This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain.

A human ribonuclease induces apoptosis associated with p21WAF1/CIP1 induction and JNK inactivation

Ribonucleases are promising agents for use in anticancer therapy. Among the different ribonucleases described to be cytotoxic, a paradigmatic example is onconase which manifests cytotoxic and cytostatic effects, presents synergism with several kinds of anticancer drugs and is currently in phase II/III of its clinical trial as an anticancer drug against different types of cancer. The mechanism of cytotoxicity of PE5, a variant of human pancreatic ribonuclease carrying a nuclear localization signal, has been investigated and compared to that of onconase. Methods: Cytotoxicity was measured by the MTT method and by the tripan blue exclusion assay. Apoptosis was assessed by flow cytometry, caspase enzymatic detection and confocal microscopy. Cell cycle phase analysis was performed by flow cytometry. The expression of different proteins was analyzed by western blot.n Results: We show that the cytotoxicity of PE5 is produced through apoptosis, that it does not require the proapoptotic activity of p53 and is not prevented by the multiple drug resistance phenotype. We also show that PE5 and onconase induce cell death at the same extent although the latter is also able to arrest the cell growth. We have compared the cytotoxic effects of both ribonucleases in the NCI/ADR-RES cell line by measuring their effects on the cell cycle, on the activation of different caspases and on the expression of different apoptosis- and cell cycle-related proteins. PE5 increases the number of cells in S and G2/M cell cycle phases, which is accompanied by the increased expression of cyclin E and p21WAF1/CIP1 together with the underphosphorylation of p46 forms of JNK. Citotoxicity of onconase in this cell line does not alter the cell cycle phase distribution and it is accompanied by a decreased expression of XIAP. Conclusions: We conclude that PE5 kills the cells through apoptosis associated with the p21WAF1/CIP1 induction and the inactivation of JNK. This mechanism is significantly different from that found for onconase

Glycan alterations of serum proteins as tumour markers. Prostate-specific antigen in prostate cancer and acute-phase proteins in pancreatic cancer

Els pacients amb càncer presenten una taxa de supervivència superior si es diagnostiquen a estadis inicials, per la qual cosa és indispensable disposar de marcadors tumorals adequats. Glicoformes de proteïnes específiques es podrian utilizar com marcadors tumorals. S’han investigat les subformes i glicosilació de l’Antígen Prostàtic Específic (PSA) per millorar la seva capacitat de diagnosis de pacients amb càncer de pròstata vs aquells amb hiperplàsia benigna prostàtica. També s’han avaluat glicoproteïnes sèriques amb alteracions glucídiques en pacients de càncer de pàncrees, comparat amb pacients amb pancreatitis crònica i controls. S’ha observat una disminució de la fucosilació core i sialilació del PSA en càncer de pròstata i un augment de la fucosilació core i Sialyl-Lewis X en algunes Proteïnes de fase Aguda en càncer de pàncrees. Aquest canvis s’haurien d’avaluar en un cohort de pacients més gran per determinar el seu paper en el cribratge, diagnòstic o monitorització dels cancers estudiats.

Exposição in utero ao desregulador endocrino bisfenol A e ao agente quimiopreventivo indol-3-carbinol: efeitos sobra a morfogênese e a suscetibilidade à carcinogênese prostática

Pós-graduação em Biologia Geral e Aplicada - IBB

Efeitos da finasterida sobre culturas de células epiteliais prostáticas normais e tumorais em diferentes sistemas in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exposição in utero ao desregulador endócrino Bisfenol A e à Genisteína: efeitos sobre a morfogênese e a susceptibilidade a carcinogênese prostática em ratos Sprague-Dawley

Pós-graduação em Patologia - FMB

Análise histopatológica de biópsia prostática guiada pelo ultrassom transretal com 10 e 12 fragmentos: ensaio clínico prospectivo controlado

Pós-graduação em Bases Gerais da Cirurgia - FMB

Braquiterapia com sementes de iodo-125: manufatura e tratamento

According to the National Institute of Cancer – INCA, 466.730 new cancer cases will occur in Brazil in 2009. Prostate and Lung cancer in man are the most incident types (in exception of the non-melanoma cancer). The brachytherapy with 125-iodine sources is an important method of prostate cancer treatment. The implant with iodine-125 seeds uses aproximately 100 seeds that are imported impossibilitating the treatment in large scale. For this reason, a multidisciplinary group was created at the Energetic and Nuclear Research Institute – Radiation Technology Center (IPEN –CTR / SP) to develop a national 125-iodine source and established a facility for local production. The seeds manufacture in Brazil will diminish the cost of treatment and prostate brachytherapy will be offered to more patients. This work aim is to observe and discuss the methods used in seeds manufacture there are being developed in Brazil and to present an prostate cancer case folloied in A.C. Camargo Hospital. The 125-iodine is adsorbed in an silver wire, then deposited at titanium coat. The weld is made by an process of plasm sealing. The seeds goes through several test to guarantee that there is no leakage. The result is an high quality and cheaper product. The implant tecnique is an fast and save procedure. The medical physicst preplan the case to stipulate the quantity of seeds there will be used. At the dat of the implant the medical physicst replan the procedure due to changes of volume in the organ. That assure the correct dose distribution in the target. Besides, the 125-iodine low energy is absorbed at the volume of interrest saving sourronding healthy tissues such as the rectum and the urethra

Potential quimioprotetor do DIM (3, 3' - Di-indolil-metano) e da Genisteína em linhagens de células tumorais prostáticas humanas LNCaP e PC-3 expostas ao Bisfenol A

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reabilitação do assoalho pélvico em pacientes com incontinência urinária pós prostatectomia radical

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)