Ana Helena Pereira Correia

Clotrimazole disrupts glycolysis in human breast cancer without affecting non-tumoral tissues

Human breast cancer tissues, as well as normal tissues from the same patients, were treated with clotrimazole (CTZ) and have their capacities for glucose consumption and lactate production evaluated. This treatment strongly decreased the lactate production rate by tumor tissues (85% inhibition) without affecting the other measurements made, i.e. lactate production by control tissues or glucose consumption by both, control and tumor tissues. This result directly correlates with the inhibition promoted by CTZ on the activity of the major regulatory glycolytic enzyme 6-phosphofructo-1-kinase (PFK) that was observed in tumor tissues (84% inhibition) but not in control tissues. Fractionation of the tissues revealed that this inhibition does not occur in the soluble fraction of the enzyme, but is exclusive of a particulate fraction. It has been previously shown that the particulate fraction of PFK activity in tumors is associated to actin filaments (f-actin). Thus, we investigated whether CTZ would affect the association between PFK and f-actin and we found that the drug directly induces the dissociation of the two proteins in the same extent that it inhibits lactate production, total PFK activity and the particulate PFK activity. We concluded that CTZ disrupts glycolysis on human breast tumor tissues, inhibiting PFK activity by dissociating the enzyme from f-actin.

The orthotopic xenotransplant of human glioblastoma successfully recapitulates glioblastoma-microenvironment interactions in a non-immunosuppressed mouse model

BackgroundGlioblastoma (GBM) is the most common primary brain tumor and the most aggressive glial tumor. This tumor is highly heterogeneous, angiogenic, and insensitive to radio- and chemotherapy. Here we have investigated the progression of GBM produced by the injection of human GBM cells into the brain parenchyma of immunocompetent mice.MethodsXenotransplanted animals were submitted to magnetic resonance imaging (MRI) and histopathological analyses.ResultsOur data show that two weeks after injection, the produced tumor presents histopathological characteristics recommended by World Health Organization for the diagnosis of GBM in humans. The tumor was able to produce reactive gliosis in the adjacent parenchyma, angiogenesis, an intense recruitment of macrophage and microglial cells, and presence of necrosis regions. Besides, MRI showed that tumor mass had enhanced contrast, suggesting a blood–brain barrier disruption.ConclusionsThis study demonstrated that the xenografted tumor in mouse brain parenchyma develops in a very similar manner to those found in patients affected by GBM and can be used to better understand the biology of GBM as well as testing potential therapies.

Glioblastoma entities express subtle differences in molecular composition and response to treatment

Glioblastoma (GBM) is a grade IV astrocytoma. GBM patients show resistance to chemotherapy such as temozolomide (TMZ), the gold standard treatment. In order to simulate the molecular mechanisms behind the different chemotherapeutic responses in GBM patients we compared the cellular heterogeneity and chemotherapeutic resistance mechanisms in different GBM cell lines. We isolated and characterized a human GBM cell line obtained from a GBM patient, named GBM11. We studied the GBM11 behaviour when treated with Tamoxifen (TMX) that, among other functions, is a protein kinase C (PKC) inhibitor, alone and in combination with TMZ in comparison with the responses of U87 and U118 human GBM cell lines. We evaluated the cell death, cell cycle arrest and cell proliferation, mainly through PKC expression, by flow cytometry and western blot analysis and, ultimately, cell migration capability and F-actin filament disorganization by fluorescence microscopy. We demonstrated that the constitutive activation of p-PKC seems to be one of the main metabolic implicated on GBM malignancy. Despite of its higher resistance, possibly due to the overexpression of P-glycoprotein and stem-like cell markers, GBM11 cells presented a subtle different chemotherapeutic response compared to U87 and U118 cells. The GBM11, U87, U118 cell lines show subtle molecular differences, which clearly indicate the characterization of GBM heterogeneity, one of the main reasons for tumor resistance. The adding of cellular heterogeneity in molecular behaviour constitutes a step closer in the understanding of resistant molecular mechanisms in GBM, and can circumvents the eventual impaired therapy.

Asma e síndrome de Churg-Strauss

We report the case of a 25-year-old woman with Churg-Strauss syndrome, the symptoms of which had first appeared soon after she began taking oral contraceptive at the age of sixteen. The clinical profile evolved rapidly to severe persistent asthma, nasal polyposis, perennial obstructive rhinitis, eosinophilia (peripheral/tissue) and mononeuritis. Churg-Strauss syndrome is the type of disease that demands early detection, accurate diagnosis, aggressive treatment and periodic monitoring. It should be considered in the differential diagnosis of moderate and severe persistent asthma. The case reported calls attention to possibility that there is a hormonal component and that the disease can present early onset.

Granulomas hialinizantes pulmonares: aspectos na tomografia computadorizada - relato de caso

Hyalinizing granulomas are benign fibrotic lesions that generally present multiple nodules seen on radiological examinations, which are frequently cavitary and/or calcified lesions. We report a case of a 28 year-old-woman with hyalinizing granulomas probably secondary to a previous tuberculosis infection. Hyalinizing granulomas should be included in the differential diagnosis of patients with multiple pulmonary nodules.

Valor do exame citológico per-operatório em neurocirurgias

INTRODUCAO: Mais de 90% dos resultados citologicos per-operatorios neurocirurgicos correlacionam-se com o histopatologico. Porem, a sua real necessidade e por vezes questionada. OBJETIVO: Avaliar a necessidade do exame per-operatorio tendo-se em vista a conduta neurocirurgica imediata. MATERIAL E METODOS: Revimos 130 casos de exames per-operatorios solicitados de um total de 293 procedimentos cirurgicos para tratamento de lesoes expansivas do sistema nervoso central (SNC), extra ou intra-axiais, sendo 46 biopsias estereotaxicas e 84 cirurgias abertas, realizados de 1998 a 2001. Foram realizados esfregacos, o diagnostico foi comparado com o histopatologico, e os neurocirurgioes, questionados sobre a implicacao do resultado do exame na conduta, caso a caso. RESULTADOS: O exame per-operatorio foi solicitado em 44,4% do total de cirurgias, tendo sido considerado relevante para a conduta em 84% destes casos ou, nas biopsias, para avaliar a representatividade do material, o que corresponde a 37,2% do total de cirurgias realizadas no periodo. Excluindo-se as biopsias estereotaxicas, com indicacao inquestionavel, o exame foi necessario em 75%, sendo considerado desnecessario, sobretudo nas lesoes extra-axiais, em geral solicitado por curiosidade do cirurgiao. CONCLUSAO: Apesar de ser um exame com acuracia demonstrada, a realizacao de exames per-operatorios sem utilidade para a conduta neurocirurgica pode vir a sobrecarregar patologistas em tarefas desnecessarias. Nossos resultados demonstraram que o exame foi necessario na grande maioria dos casos, mesmo apos a exclusao das biopsias estereotaxicas, sobretudo nas lesoes intra-axiais, auxiliando na avaliacao da demanda desses exames, por vezes excessiva, apesar de util para treinamento e ensino.