Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overproduced Bcl-2 oncoprotein has been shown to suppress cell death induced by a variety of stimuli in many cell types, including neuronal cells. Because bcl-2 is expressed in the nervous system where massive cell death is observed during development, endogenous Bcl-2 is likely to be involved in regulating neuronal cell death. Here we examined the possible role of endogenous Bcl-2 in the regulation of neuronal cell survival in the central nervous system using primary cultured cerebellar granule neurons from bcl-2-deficient, wild-type and NSE-bcl-2-transgenic mice. Cerebellar granule neurons from bcl-2-deficient mice were more susceptible than those from normal littermates to death induced by reducing the K+ concentration of the medium from high (25 mM) to low (5 mM), and neurons from bcl-2-transgenic mice were least susceptible. Similar results were obtained when cell death was induced by serum withdrawal under high K+ conditions or by the presence of etoposide, A23187 or nimodipine. Consistently, bcl-2 deficiency reduced the number of cerebellar granule neurons per mouse. These results indicate that Bcl-2 impedes neuronal cell death induced by various stimuli in a dose-dependent manner, and that endogenous levels of Bcl-2 are able to regulate neuronal cell survival in the central nervous system.
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PMID:Susceptibility of cerebellar granule neurons derived from Bcl-2-deficient and transgenic mice to cell death. 915 92

Comparisons of the developing human sympathetic nervous system (SNS) to tumors presumed to derive from these cells may suggest tumor progenitors and predict tumor biologic behavior. Classic neuroblastoma (NB) and its more highly differentiated stroma-rich subtypes, extra-adrenal sympathetic paraganglioma, and pheochromocytoma were examined for the presence of the developmentally characterized gene products NSE, S-100, CD44, Bcl-2, HNK-1, PNMT, TrkA, IGF2, and tyrosine hydroxylase. The marker gene expression profiles of these tumors were compared with those similarly determined for a number of normal prenatal and postnatal human SNS cell types. Sympathetic paraganglioma, pheochromocytoma, and stroma-rich NB display marker expression profiles mimicking those of childhood sympathetic paraganglia, adrenal chromaffin cells, and sympathetic neurons, respectively. A selection of differentiating, extra-adrenal NB tumors with prognostically favorable features possess marker gene expression profiles paralleling that observed for fetal extra-adrenal sympathetic paraganglia/small intensely fluorescent cells. In contrast, undifferentiated, clinically aggressive NB tumors manifest characteristics mirroring that of embryonic/early fetal sympathetic neuroblasts of sympathetic ganglia and of the adrenal gland. These findings suggest that clinical features, such as primary tumor location and age at diagnosis, provide prognostic information for NB patients by virtue of the existence and biology of the presumed tumor progenitor cell type.
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PMID:Developmental gene expression of sympathetic nervous system tumors reflects their histogenesis. 946 Nov 20

The protooncogene bcl-2 inhibits neuronal apoptosis during normal brain development as well as that induced by cytotoxic drugs or growth factor deprivation. We have previously demonstrated that neurons of mice deficient in Bcl-2 are more susceptible to neurotoxins and that the dopamine (DA) level in the striatum after systemic 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) administration was significantly lower than in wild-type mice. In the present study we have used transgenic mice overexpressing human Bcl-2 under the control of neuron-specific enolase promoter (NSE-hbcl-2) to test the effects of the neurotoxins 6-hydroxydopamine (6-OHDA) and MPTP on neuronal survival in these mice. Primary cultures of neocortical neurons from normal and transgenic mice were exposed to these dopaminergic neurotoxins. Addition of 6-OHDA resulted in cell death of essentially all neurons from normal mice. In contrast, in cultures generated from heterozygous NSE-hbcl-2 transgenic mice, only 69% of the cells died while those generated from homozygous transgenic mice were highly resistant and exhibited only 34% cell death. A similar effect was observed with neurons treated with MPP+. Moreover, while the striatal dopamine level after MPTP injections was reduced by 32% in the wild type, the concentration remained unchanged in the NSE-hbcl-2 heterozygous mice. In contrast levels of glutathione-related enzymes were unchanged. In conclusion, overexpression of Bcl-2 in the neurons provided protection, in a dose-dependent manner, against neurotoxins known to selectively damage dopaminergic neurons. This study provides ideas for inhibition of neuronal cell death in neurodegenerative diseases and for the development of efficient neuroprotective gene therapy.
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PMID:Transgenic mice expressing human Bcl-2 in their neurons are resistant to 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine neurotoxicity. 957 63

In contrast to its known anti-apoptotic activity in sympathetic neurons, immortal neuronal cell lines, and primary cultured immature neurons of the central nervous system (CNS), the role of Bcl-2 in CNS neurons in the adult brain is poorly understood. In the present study, we examined effects of overexpression of Bcl-2 on selective neuronal death of the hippocampal CA1 neurons and the dentate granule cells induced by hypoxic ischemia in adult transgenic mice overexpressing human Bcl-2 under the control of neuron-specific enolase (NSE-hbcl-2). At the light microscopic level, numbers of TUNEL-positive cells with pyknotic nuclei were observed in the CA1 subfield of NSE-hbcl-2 transgenic mice, as well as that of wild-type mice, after hypoxic ischemic insult, although the onset of neuronal death was apparently delayed in NSE-hbcl-2 transgenic mice. The electron microscopic studies showed that morphological changes of the degenerating CA1 neurons from both groups were clearly distinct from ordinary apoptosis. In contrast, a significant amount of degenerating dentate granule cells from wild-type but not from transgenic mice had typical apoptotic nuclei by the treatment. The activation of caspase-3 was detected in the dentate granule cells but not that of the CA1 neurons. These results indicate that the overexpression of Bcl-2 effectively suppressed dentate granule cell apoptosis but only delayed cell death of the CA1 neurons induced by hypoxic ischemia, suggesting the occurrence of a non-apoptotic, caspase-3-independent mechanism for neuronal death in the CA1 subfield.
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PMID:Differential effects of Bcl-2 overexpression on hippocampal CA1 neurons and dentate granule cells following hypoxic ischemia in adult mice. 1039 30

The autopsy of a 76-year-old Japanese female patient, which revealed thymic carcinoma with various tumor markers such as NSE, CYFRA, and CA-125, is presented. The patient died from hepatic failure because the liver was overtaken by the tumors. At autopsy, the thymic carcinoma was found to have metastased only in the liver. From microscopical analyses and electron microscopical findings, we diagnosed poorly differenciated squamous cell carcinoma of thymic origin. In the histochemical analyses, the tumor cells were positively stained in CA 125, CA 19-9, EMA, NSE, AE 1, AE 3, CEA, S-100, glimerius and Bcl-2. These date suggest that the tumor cells produced various tumor markers. In 222 autopsy cases of thymic malignant tumor observed in Japan over a period of 4 years, the dominant pathohistological image was squamous cell carcinoma. It is interesting that the greatest number of combined malignant tumors with thymic malignancies were thyroid papillary carcinomas.
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PMID:[An autopsy case of thymic carcinoma producing various tumor markers and the examination of 222 autopsy cases of thymic malignant tumor in Japan]. 1084 55

Allergic sensitisation of the airways occurs in the mucosa of the shock organ, or in the lymphatic stations draining these structures. The lymphatic structure closest to the nasal mucosa in humans is the adenoid and tonsils. Research done in respect to Waldeyer's ring on people dealing at the same time with allergy, is seldom the subject of dissertation in polish as well as world wide medical literature. In the enclosed dissertation, writers present the results of histopathological and immunohistochemical analysis of hyperplastic tonsils and adenoid, taken from children with coexisting atopy. The authors describe an immunohistochemical analyses of the hyperplastic human palatine tonsil. They present the expression of antigen CD3, CD20, CD45, CD68, EMA, SMA, Vimentin, Desmin, S-100, von Willebrand Factor, p35, Bcl-2, melanin, cytokeratin, estrogen receptor, progesteron receptor, kolagen IV and NSE in every region of pallatine tonsil. It is worthwhile to remark, that many of these cases, the presence of eosinophilia and subepithelial oedema was observed. Our immunohistochemical findings support the hypothesis that allergic sensitization takes place in the adenoid and tonsils. Furthermore, this study confirms that dendritic cells ad macrophages are involved and important in allergic disease.
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PMID:[Histopathological and immunological analysis of hyperplastic palatine tonsils and adenoids in children with coexisting atopic dermatitis]. 1459 70

Some murine leukemia viruses (MuLVs), among them Cas-Br-E and ts-1 MuLVs, are neurovirulent, inducing spongiform myeloencephalopathy and hind limb paralysis in susceptible mice. It has been shown that the env gene of these viruses harbors the determinant of neurovirulence. It appears that neuronal loss occurs by an indirect mechanism, since the target motor neurons have not been found to be infected. However, the pathogenesis of the disease remains unclear. Several lymphokines, cytokines, and other cellular effectors have been found to be aberrantly expressed in the brains of infected mice, but whether these are required for the development of the neurodegenerative lesions is not known. In an effort to identify the specific effectors which are indeed required for the initiation and/or development of spongiform myeloencephalopathy, we inoculated gene-deficient (knockout [KO]) mice with ts-1 MuLV. We show here that interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS), ICE, Fas, Fas ligand (FasL), and TNF-R1 KO mice still develop signs of disease. However, transgenic mice overexpressing Bcl-2 in neurons (NSE/Bcl-2) were largely protected from hind limb paralysis and had less-severe spongiform lesions. These results indicate that motor neuron death occurs in this disease at least in part by a Bcl-2-inhibitable pathway not requiring the ICE, iNOS, Fas/FasL, TNF-R1, and IL-6 gene products.
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PMID:Protection against murine leukemia virus-induced spongiform myeloencephalopathy in mice overexpressing Bcl-2 but not in mice deficient for interleukin-6, inducible nitric oxide synthetase, ICE, Fas, Fas ligand, or TNF-R1 genes. 1464 73

This study has investigated a panel of immunomarkers in non-small cell lung carcinoma (NSCLC). Unsupervised hierarchical clustering analysis was used to investigate the possibility of identifying different subgroups in NSCLC based on their molecular expression profile rather than morphological features. A tissue microarray consisting of 284 cases of NSCLC was constructed. Immunohistochemistry was used to detect the presence of 18 biomarkers including synaptophysin, chromogranin, bombesin, NSE, GFI1, ASH-1, p53, p63, p21, p27, E2F-1, cyclin D1, Bcl-2, TTF-1, CEA, HER2/neu, cytokeratin 5/6, and pancytokeratin. Univariate analysis of all 18 markers for prognostic significance was performed. Immunohistochemical scoring data for NSCLC were analysed by unsupervised hierarchical clustering analysis. Kaplan-Meier survival curves were plotted for the different cluster groups of lung tumours identified by this method. Analysis of the three different World Health Organization (WHO) subtypes (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) of NSCLC individually showed that different markers were significant in different subtypes. For example, p53 and p63 were significant for squamous cell carcinoma (p = 0.007 and p = 0.03, respectively), whereas cyclin D1 and HER2/neu were significant prognostic markers for adenocarcinoma (p = 0.025 and p = 0.015, respectively). These markers were not significant prognostic predictors for NSCLC as a group. Hierarchical clustering analysis of NSCLC produced four separate cluster groups, although the vast majority of cases were found in two cluster groups, one dominated by squamous cell carcinoma and the other by adenocarcinoma. The clinical outcomes of cases from the four cluster groups were not significantly different. Prognostic indicators vary between different morphological subtypes of NSCLC. Unsupervised hierarchical clustering analysis, based on an extended immunoprofile, identifies two main cluster groups corresponding to adenocarcinoma and squamous cell carcinoma; cases of large cell carcinomas are assigned to one of these two groups based on their molecular phenotype.
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PMID:Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. 1530 43

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.
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PMID:The value of serum Bcl-2 levels in advanced lung cancer patients. 1596 76

Neuronal progenitors in the adult hippocampus continually proliferate and differentiate to the neuronal lineage, and ischemic insult promotes hippocampal neurogenesis. However, newborn neurons show a progressive reduction in numbers during the initial few weeks, therefore, enhanced survival of newborn neurons seems to be essential for therapeutic strategy. Bcl-2 is a crucial regulator of programmed cell death in CNS development and in apoptotic and necrotic cell death. Therefore, we tested whether Bcl-2 overexpression enhances survival of newborn neurons in the adult mouse hippocampus under normal and ischemic conditions. Many newborn neurons in the hippocampal dentate gyrus undergo apoptosis. Human Bcl-2 expression in NSE-bcl-2 transgenic mice began at the immature neuronal stage and remained constant in surviving mature neurons. Bcl-2 significantly increased survival of newborn neurons under both conditions, but particularly after ischemia, with decreased cell death of newborn neurons in NSE-bcl-2 transgenic mice. We also clarified the effect by Bcl-2 overexpression of enhanced survival of newborn neurons in primary hippocampal cultures with BrdU labeling. These findings suggest that Bcl-2 plays a crucial role in adult hippocampal neurogenesis under normal and ischemic conditions.
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PMID:Bcl2 enhances survival of newborn neurons in the normal and ischemic hippocampus. 1694 50


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