Ischemic stroke after chemotherapy with cisplatin, etoposide and bleomycin: case report

A 20-year-old man with a germ cell tumor who experienced an ischemic stroke as a complication of cisplatin/etoposide/bleomycin based chemotherapy is reported. The previously reported cases are reviewed as well as the different physiopathologic mechanisms associated with vascular toxicity of this regimen.Relatamos o caso de um homem de 20 anos, com diagnóstico de tumor de células germinativas, que apresentou acidente vascular cerebral isquêmico durante quimioterapia com cisplatina, etoposide e bleomicina. Os casos relatados na literatura foram revisados, bem como os diferentes mecanismos fisiopatológicos implicados na toxicidade vascular deste esquema quimioterápico.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

IDH1 mutations in a Brazilian series of Glioblastoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Albert Einstein Jewish HospitalUniversidade de São Paulo Faculdade de Medicina Department of NeurologyUniversidade de São Paulo Faculdade de Medicina Department of PathologyCancer Institute of São PauloFundação Pio XII Barretos Cancer HospitalFederal University of São Paulo School of Medicine Department of NeurologyFederal University of São Paulo School of Medicine Department of PathologyNove de Julho HospitalAlbert Einstein Jewish HospitalUNIFESP, EPM, Department of NeurologyUNIFESP, EPM, Department of PathologyFAPESP: 04/12133-6SciEL

Imune response against HERV-K in patients with localized and metastatic prostate cancer

Objetivo: Retrovirus Endógeno Humano (HERV) compreende ao redor de 8% do genoma humano. Apesar do fato de que em sua maioria são genes não-funcionais devido a processos de mutação ou perda de material genético no processo de retrotransposição, existem evidências do aumento da expressão de HERVs em tecido de câncer de próstata. Nós estudamos e comparamos a imunogenicidade de peptídeos da família HERV em 2 coortes de pacientes com câncer de próstata. Posteriormente examinamos o estado de ativação e senescência linfocitária nestas coortes. Desenho Experimental: Células Mononucleares de Sangue Periférico (CMSP) de 65 pacientes com câncer localizado da próstata em situação de hormônio-sensibilidade e de 24 pacientes com câncer de próstata metastático e em situação de resistência à castração, comparados a um grupo controle de 12 indivíduos normais foram avaliados em relação ao seu estado de resposta imune pela técnica de ELISPOT contra um conjunto de peptídeos derivados dos exons gag e env do gene da família HERV-K HML-2. Como parte de nosso estudo, foi realizado de forma preliminar uma análise genômica in silico de 500 pacientes com câncer de próstata sequenciados e disponíveis para análise pública do banco de dados TCGA, com o objetivo de reforçar o racional de nossa interrogação científica. Além disso , como estudo de correlação, fizemos uma análise por citometria de fluxo da ativação celular de linfócitos T de nossas coortes para determinarmos a imunofenotipagem e ontogenia linfocitária em nossos indivíduos investigados, no momento de nossa pesquisa de sua resposta imune. Resultados: Nossa análise da resposta imune contra peptídeos de HERV-K HML-2 por ELISPOT-Interferon Gama não mostrou nenhum resultado significativo. Nenhum paciente apresentou dados significativos de resposta de acordo com nossos critérios, apesar de nossos dados preliminares de expressão gênica terem mostrado expressão gênica em torno de 17% em pacientes com doença localizada. Nossos dados de ativação linfocitária mostraram maior ativação e senescência nos pacientes com doença disseminada e resistente à castração. Conclusões: Este parece ser o primeiro estudo a interrogar a presença de resposta celular imune contra peptídeos de HERV-K em pacientes com câncer de próstata. Nosso achados não mostraram resposta imune relevante em doença localizada ou disseminada e em diferentes estados de ativação linfocitária ou status de integridade hormonal. Apesar destes resultados, pesquisa posterior poderia utilizar diferente metodologia, como por exemplo a utilização de citometria de fluxo bem como a busca de diferentes citoquinas envolvidas, tais como as relacionadas a resposta Th2, ao invés de Th1Purpose: Human Endogenous Retrovirus (HERV) comprises 8% of human genome. Despite the fact that most of it is non-functional due to mutations or loss of genetic material in the process of retrotransposition, there are some evidence of increased expression of HERV in prostate cancer tissue. We studied the cellular immunogenicity of peptides from HERV-K family in 2 cohorts of prostate cancer patients. Experimental Design: PBMCs from 65 patients with hormone-intact localized prostate cancer and 24 patients with castrate-metastatic disease, matched with 12 normal controls were evaluated for cellular immune response by ELLISPOT against a pool of gag and env peptides from HERV-K family of HML-2 type. As an independent supportive study we did in silico genomic analysis of 500 prostate cancer patients from TCGA database to give another evidence of the prevalence of HERV-K gene expression in prostate cancer genome, reinforcing the rational of our questions. Results: Our analysis of cellular immune response against HERV-K HML-2 peptides by Interferon-gama ELISPOT did not show any meaningful results. No patient showed any minimal criteria of response, despite the fact that in our preliminary genomic analysis we obtained HERV expression in about 17% of a cohort of 500 patients with localized prostate cancer. In regards to the flow cytometry data of the lymphocytes we showed stronger activation and senescence status in the cohort of patients with castration sensitive and resistant disseminated disease, compared to the localized disease cohort. Conclusions: To the authors\'s knowledge this is the first study to look for cellular immune response against peptides derived from coding HERV-K transcripts in prostate cancer patients. Our findings did not show relevant immune response in neither localized nor metastatic castrate prostate cancer patients. Despite those results, further research could continue using different methodology, like flow cytometry as well as looking for different cytokines involved, such as those related to a Th2 response, instead of Th

Renal medullary carcinoma response to chemotherapy: a referral center experience in Brazil

Renal medullary carcinoma (RMC) is rare, accounting for less than 1% of all renal neoplasms. Case reports suggest RMC is highly aggressive, poorly responsive to chemotherapy, often metastatic at diagnosis, affects young men with sickle cell trait, and median overall survival (mOS) is less than 12 months. We report the epidemiological characteristics, treatments performed, response rate to each treatment and mOS of five patients with RMC. All patients had sickle cell trait, four were male, three had metastatic disease at diagnosis and mean age at diagnosis was 25 years. Non-metastatic patients were submitted to nephrectomy. Two patients had partial response to first line chemotherapy including cisplatin and gemcitabine. There was no response to sunitinib or second line chemo - therapy; mOS was 6 months. Due to its rarity, case series are the only evidence available to discuss the treatment for RMC. In our experience, only cisplatin and gemcitabine based regimen offered response

Pattern of prolactin secretion after administration of gonadotropin-releasing hormone agonist at the preovulatory phase of intrauterine insemination cycles

CONTEXT AND OBJECTIVE: Administration of a gonadotropin-releasing hormone (GnRH) agonist at the preovulatory phase is an option for triggering ovulation in assisted reproductive technology cycles. The aim of this work was to investigate the pattern of prolactin secretion after the administration of a single dose of GnRH-agonist at the preovulatory phase. DESIGN AND SETTING: Descriptive study at a tertiary referral center. PARTICIPANTS: Fifteen normally ovulating patients undergoing ovarian stimulation for intrauterine insemination were studied. METHODS: Ovarian stimulation was carried out using human menopausal gonadotropin (intramuscular 75 IU daily). When at least one follicle reached 17 mm (observed echographically), 0.5 mg of buserelin acetate was administered. Blood samples were taken to determine prolactin concentrations, at the time of agonist injection and 4, 8, 12, 24 and 48 hours later. RESULTS: A statistically significant increase in serum levels of prolactin was observed 4, 8 and 12 hours after GnRH-agonist administration, with a peak at 8 hours. CONCLUSION: The administration of a single dose of GnRH-agonist at the preovulatory phase in patients undergoing ovarian stimulation performed with human menopausal gonadotropin causes a significant increase in serum prolactin levels