SERGIO ROSEMBERG
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Patologia, Faculdade de Medicina - Docente
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
LIM/14 - Laboratório de Investigação em Patologia Hepática, Hospital das Clínicas, Faculdade de Medicina
33 resultados
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conferenceObject Expression of CXCR7 and CXCR4 in diffuse astrocytomas and its interaction with HIF1 alpha expression and IDH1 mutation(2014) OBA-SHINJO, S. M.; MARIE, S. K. N.; BIANCO, A.; CLARA, C.; GALATRO, T.; ROSEMBERG, S.; TEIXEIRA, M. J.; UNO, M.conferenceObject ATYPICAL TERATOID RHABDOID TUMORS (ATRT): RESULTS FROM A SINGLE INSTITUTION IN BRAZIL - SAO PAULO UNIVERSITY(2022) BARRETO, Juliana Silveira; GOMEZ, Karen Nirit Melo; DUTRA, Alvaro Pimenta; AZAMBUJA, Alessandra Milani Prandini De; CRISTOFANI, Lilian Maria; SANDERS, Felipe Hada; PETITO, Carlo; BARALDI, Helena Espindola; WELTMAN, Eduardo; FERRACIOLLI, Suely Fazio; FRASSETTO, Fernando Pereira; LUCATO, Leandro Tavares; ROSEMBERG, Sergio; ODONE FILHO, Vicente- Activation of EGFR signaling from pilocytic astrocytomas to glioblastomas(2014) CARVALHO, Priscila O.; UNO, Miyuki; OBA-SHINJO, Sueli M.; ROSEMBERG, Sergio; WAKAMATSU, Alda; SILVA, Clemar C. da; TEIXEIRA, Manoel J.; MARIE, Suely K. N.Introduction: EGFR analyses allow for better correlation between genotype and phenotype in astrocytomas and represent an attractive therapeutic target. Most studies emphasize analyses of EGFR in glioblastomas (GBMs) but do not analyze all grades of astrocytomas (from pilocytic to GBM). The purpose of our study was to evaluate the status of EGFR (expression, deletion, and amplification) and EGFR protein expression in all grades of astrocytomas. Patients and methods: We analyzed a total of 145 surgical tumor specimens that included: 22 pilocytic astrocytomas, 22 grade II astrocytomas, 17 grade III astrocytomas and 84 GBMs. The specimens were compared to 17 non-neoplastic brain tissues obtained from epilepsy surgery. EGFR expression, EGFR amplification and EGFRvIII analyses were performed by quantitative real-time PCR, and protein expression was evaluated by immunohistochemistry. Results: EGFR relative overexpression and EGFR amplification were observed, respectively, in 50% and 20% of astrocytomas, while EGFRvIII was only found in GBMs (34.5%, p=0.005). Amongst EGFR-amplified GBM cases, 59% also presented EGFRvIII (p<0.001). Cytoplasmic accumulation of EGFR protein was detected in 75% of astrocytomas, and 21% of the astrocytomas showed nuclear localization (p=0.003). Conclusions: EGFR alterations were found in all grades of astrocytomas, from pilocytic to GBMs, while EGFRvIII was exclusively found in GBMs. These findings provide important information on the mechanisms involved in the progression of astrocytomas for determining whether EGFR status can be used for effective and specific therapy.
- Long-term epilepsy associated-tumors (LEATs): what is new?(2023) ROSEMBERG, SergioLong-term epilepsy-associated tumors (LEATs) include a series of neoplasms that commonly occur in children, adolescents, or young adults, have an astrocytic or glioneuronal lineage, are histologically benign (WHO grade1) with a neocortical localization predominantly situated in the temporal lobes. Clinically, chronic refractory epilepsy is usually the unique symptom. Gangliogliomas (GG) and dysembryoplastic neuroepithelial tumors (DNT) are the most common representative entities besides pilocytic astrocytomas (PA) and angiocentric gliomas (AG). Recent molecular studies have defined new clinicopathological entities, which are recognized by the WHO 2021 classification of brain tumors. Some of them such as diffuse astrocytoma MIB or MYBL1 altered, polymorphous low-grade neuroepithelial tumor of the young (PLNTY), and multilocular and vacuolating neuronal tumor (MVNT) are currently considered LEATs. The relationship between LEATs and epilepsy is still a matter of debate, and there is a general agreement about the beneficial effects of an early neurosurgical intervention on the clinical outcome.
- Cor pulmonale in a patient with Brown-Vialetto-Van Laere syndrome: A case report(2011) SILVA-JUNIOR, Francisco Pereira da; MOURA, Rafael de Deus; ROSEMBERG, Sergio; MARCHIORI, Paulo Euripedes; CASTRO, Luiz Henrique MartinsBrown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by sensorineural hearing loss and multiple cranial nerve palsies, usually involving the VIIth and IXth to XIIth cranial nerves. We describe the clinical and pathological features of a 33-year-old woman with BVVLS. The patient developed progressive exertional dyspnea, with clinical and laboratory findings of right-sided heart failure and pulmonary hypertension. She developed status epilepticus in the setting of cardiac deterioration and respiratory infection, and died of cardiogenic and septic shock. Autopsy disclosed bilateral neuronal loss and gliosis in the inferior colliculi, locus coeruleus and facial and vestibular nuclei. Cor pulmonale is a complication of hypoventilation-induced hypoxia and hypercapnia and had not yet been reported in BVVLS.
conferenceObject HIGH-GRADE NEUROEPITHELIAL TUMOR (HGNET) IN A PEDIATRIC CASE-SERIES(2020) SANDERS, Felipe Hada; AZAMBUJA, Alessandra; FRASSETO, Fernando; ROSEMBERG, Sergio; MATUSHITA, Hamilton- CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1 alpha Expression and IDH1 Mutation(2015) BIANCO, Andre Macedo; UNO, Miyuki; OBA-SHINJO, Sueli Mieko; CLARA, Carlos Afonso; GALATRO, Thais Fernanda de Almeida; ROSEMBERG, Sergio; TEIXEIRA, Manoel Jacobsen; MARIE, Suely Kazue NagahashiThe CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1 alpha expression and IDH1 mutation. CXCR7, CXCR4 and HIF1 alpha mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p < 0.001). AGII showed no significant correlation between CXCR7/HIF1 alpha (p = 0.548); there was significant correlation between CXCR7/CXCR4 (p = 0.042) and CXCR7/IDH1 (p = 0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p < 0.001) and CXCR7/HIF1 alpha (p = 0.008). HIF1 alpha overexpression was associated with higher expressions of CXCR7 (p = 0.01) and CXCR4 (p < 0.0001), while IDH1 mutation was associated with lower CXCR7 (p = 0.009) and CXCR4 (p = 0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1 alpha in GBM. Overexpression HIF1 alpha was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.
- Angiogenesis and expression of PDGF-C, VEGF, CD105 and HIF-1 alpha in human glioblastoma(2014) CLARA, Carlos Afonso; MARIE, Suely K. N.; ALMEIDA, Jose Reynaldo Walther de; WAKAMATSU, Alda; OBA-SHINJO, Sueli Mieko; UNO, Miyuki; NEVILLE, Munro; ROSEMBERG, SergioGlioblastoma (GBM), the most frequent and aggressive brain tumor, is characterized by marked angiogenesis directly related to invasiveness and poor prognosis. Hypoxia is considered to be an important stimulus for angiogenesis by inducing hypoxia-inducible factor 1-alpha (HIF-1 alpha) overexpression that activates platelet-derived growth factor (PDGF) and VEGF. The aim of this study is to analyze the expression of PDGF-C, VEGFin endothelial and tumor cells of GBM and their relation to HIF-1 alpha expression. Two hundred and eight GBM cases were studied by tissue microarray immunohistochemical preparation. Expression of HIF-1 alpha, VEGF and PDGF-C was observed in 184 (88.5%), 131 (63%) and 160 (76.9%) tumor cases, respectively. The numbers of vessels were quantified by CD34, PDGF-C, VEGF and CD105 staining, and were in median 20, 16, 5 and 6, respectively. The GBMs that showed positive or negative expression for HIF-1 alpha showed a median vascular density of 30 and 14, respectively, for CD34 (P < 0.015). Positive expression for HIF-1 alpha was correlated with VEGF and PDGF-C expression in tumors (P < 0.001). There was a significant correlation between VEGF and PDGF-C expression in the cytoplasm of GBM tumor cells (P < 0.0001). We showed that VEGF expression in tumor cells was correlated with its expression in blood vessels (P < 0.0001). Endothelial cells with PDGF-C and VEGF positive expression were also positive for CD105 and their nuclei for Ki-67, confirming the neoangiogenic and proliferative influence of VEGF and PDGF-C. VEGF nuclear staining in tumor cells (P = 0.002) as well as nuclear staining for HIF-1 alpha and VEGF (P = 0.005) correlated with survival. In summary, our present findings of the concomitant upregulation of PDGF-C with VEGF in GBM tumor cells and vessels further reinforce the benefit of using combined anti-angiogenic approaches to potentially improve the therapeutic response for GBM.
conferenceObject DIFFUSE LEPTOMENINGEAL DISSEMINATED GLIONEURONAL TUMOR: CASE-SERIES(2020) SANDERS, Felipe Hada; MATUSHITA, Hamilton; AZAMBUJA, Alessandra; FRASSETO, Fernando; ROSEMBERG, Sergio; ODONE, Vicente; TEIXEIRA, Manoel JacobsenconferenceObject Neuropathological Alterations in Cases of Yellow Fever Submitted to Autopsy(2019) FRASSETTO, Fernando; ROSEMBERG, Sergio