[Usefulness of the antisense and triplex anti-IGF-1 techniques for postoperative cellular gene therapy of malignant gliomas expressing IGF-1]. / Pooperacyjna terapia genokomórkowa z ekspresja IGF-1 glejaka wielopostaciowego przy zastosowaniu techniki antysensu i tripleksu anty-IGF-1.

BACKGROUND AND PURPOSE: The aim of the study was to estimate the usefulness of the antineoplastic vaccination in treatment of malignant brain tumors. According to medical knowledge there is no cure for this kind of tumors. MATERIAL AND METHODS: Between 2001 and 2005, ten patients suffering from malignant glial tumors were treated. There were 5 male and 5 female individuals, aged from 17 to 76 (mean age: 40.8 years). The histopathological examination showed 4 cases of glioblastoma and 6 cases of anaplastic astrocytoma. Initially, patients were operated on with dissection of 1 cm(3) of the most representative part of tumor. The neoplasm cells were cultured, transfected with episomal pMT EP vector (expressing alternatively oligonucleotide sequence forming triple helix with IGF-I gene or antisense against IGF-1 mRNA), re-cultured, irradiated and resuspended in medium to prepare antineoplastic vaccine. The patients were vaccinated subcutaneously. We examined peripheral blood lymphocyte subsets to assess the immunological response of the patients. RESULTS: We observed prolongation of the survival time to 21.7 months compared to 9-11 months observed in literature. The patients were additionally treated oncologically with radiotherapy and chemotherapy (temozolomide) according to the reasonable indications. Therefore, the comprehensive assessment of the genotherapy as the supplemental monotherapy was impossible. CONCLUSIONS: The method of treatment used in this study prolongs the survival time of patients with high-grade gliomas of the central nervous system. This gene therapy needs further investigations as a method of oncological monotherapy of brain malignant gliomas.

[Apoptosis of alveolar lymphocytes in sarcoidosis and in control group is more frequent in smokers than in nonsmoking persons]. / Apoptoza limfocytów pecherzykowych w sarkoidozie i w grupie kontrolnej wystepuje czesciej u palaczy papierosów niz u osób niepalacych.

Cigarette smoking enhances apoptosis rate of alveolar macrophages. However, little is known about the appearance and extension of apoptosis in bronchoalveolar lavage (BAL) lymphocytes originating from smoker individuals, both in pulmonary sarcoidosis (the disease characterized by lymphocytic alveolitis) and in controls. BAL was carried out in 60 nontreated patients with pulmonary sarcoidosis, subdivided acc. smoking status and in 22 control persons, free of any lung pathology. BAL (alveolar) lymphocytes were a) stained for TUNEL; b) permeabilized and stained with PI for late apoptosis/cell cycle analyses; c) immunophenotyped, including CD95, CD95 Ligand, Bcl-2, Bcl-XL, Bak and insulin-like growth factor-I (IGF-I) expression. BD FACSCalibure flow cytometer, PC Lysys and ModFit software were applied. The low number of AL entered apoptosis, which was confirmed by both techniques. Cigarette smokers were characterized by higher AL apoptosis percentage in respective subgroups (sarcoidosis: 0.6 +/- 0.13 in nonsmokers vs 0.9 +/- 0.23 in smokers; controls: 0.85 +/- 0.23 in nonsmokers vs 1.5 +/- 0.35 smokers, median +/- SEM, p < 0.05); the proliferation rate was lower. Decreased IGF-I expression in AL of sarcoidosis smokers was observed (13.5 +/- 9.2 vs 46.0 +/- 6.0 in nonsmokers, p < 0.05). No differences were found between studied groups in expression of Bcl-2, Fas and FasL molecules (except significantly declined ratio of CD8+FasL+ cells in sarcoidosis nonsmokers). AL apoptosis rate was positively correlated with respective alveolar macrophage results (Rs = +0.59, p < 0.00001) and negatively with CD4/CD8 ratio (Rs = -0.32, p < 0.001); no correlation was found with lung function test results and with Bcl-2, Fas and FasL expression in BAL cells. Apoptosis of alveolar lymphocytes was more frequent in nonsmokers both in pulmonary sarcoidosis and in controls; lower AL percentage proliferates. These phenomena seem to participate in lower AL percentage, observed in smoker subgroup of sarcoidosis. Some mechanisms of local apoptosis alterations in smokers may be common for alveolar lymphocytes and macrophages.