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)

We performed flow cytometric analysis of CD34+ cell apoptosis in 59 patients with myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) secondary to MDS (MDS-AML) using annexin V-FITC, which binds to exposed phosphatidylserine on apoptotic cells. Apoptosis was significantly increased in FAB subtypes RA, RARS and RAEB (<10% blasts) (56.5% (15.1-86.5%)) compared to normal controls (18.5% (3.4-33.4%), P<0.0001) and RAEB-t/MDS-AML (16% (2.1-43.2%), P<0.0001). There was no correlation between % apoptosis, Full blood count or cytogenetics in any disease category. Two-colour cytometric analysis of permeabilized CD34+ cells stained with antibodies to Bcl-2, Bcl-X (anti-apoptotic), Bax and Bad (pro-apoptotic), demonstrated significantly higher ratios of pro- v anti-apoptotic proteins in early MDS (2.47 (1.19-9.42) compared to advanced disease (1.14 (0.06-3.32), P=0.0001). Moreover, using repeated measures of variants (ANOVA), we found that variations between individual Bcl-2-related proteins differed significantly according to disease subtype (P<0.0005). Our results confirm that CD34+ cell apoptosis was significantly increased in MDS subtypes RA and RARS and fell with disease progression. Early MDS was also associated with a significantly higher CD34+ cell pro- v anti-apoptotic Bcl-2-family-protein ratio than advanced disease. Furthermore, patterns of expression of individual Bcl-2 related proteins differed significantly between different disease categories. However, no correlation between pro- v anti-apoptotic Bcl-2-family-protein ratios and the degree of apoptosis was observed.
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PMID:'Low-risk' myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins. 988 23

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a compound from cooked meat, is an established mammary gland carcinogen in female rats. Four doses of PhIP (150 mg/kg, p.o., once per day) were given to lactating Sprague-Dawley rats separated from their 10-day-old pups to initiate involution of the gland. Twenty-four hours after the last dose, apoptotic index in the mammary gland, as measured by the TUNEL assay, was significantly higher in the gland from control rats than in the PhIP-treated rats (4.757 +/- 1.066 versus 1.905 +/- 0.248%; P < 0.05). In comparison with controls, alveoli in the mammary gland of PhIP-treated rats were also visibly larger and contained more secretory epithelial cells. The expression of Bax, a stimulator of apoptosis, and Bcl-2, an inhibitor of apoptosis, were quantitated by western blotting. Accordingly, Bax expression was 2.7-fold higher in control rats, whereas Bcl-2 expression was 3.1-fold higher in PhIP-treated rats, both changes being statistically different (Student's t-test, P < 0.05). Immunohistochemistry further confirmed a lower expression of Bax and higher expression of Bcl-2 in secretory alveolar epithelial cells of the PhIP-treated mammary gland. The findings are consistent with the notion that exposure to PhIP retarded involution via partial inhibition of programmed cell death. To investigate possible mechanisms for the inhibitory effects of PhIP on mammary gland involution, serum levels of prolactin, an important hormone for the maintenance of lactation, were measured in virgin rats with regular estrous cycles given PhIP (150 mg/kg, p.o.) on the morning of diestrous. After one estrous cycle, on proestrous morning, serum prolactin levels were 1.3-fold higher after PhIP than after control vehicle (one-way ANOVA, Fisher LSD multiple comparison test, P < 0. 05). PhIP exposure during involution was associated with the induction of benign mammary tumors. Seven out of 12 rats developed fibroadenomas, and one developed a tubulopapillary carcinoma within 1 year of receiving PhIP administration during involution (150 mg/kg, p.o., once per day for 5 days), and a high-fat diet (23.5% corn oil). An increase in serum prolactin level and the effects on mammary gland apoptosis seen with PhIP may have implications for the mechanisms of carcinogenic targeting of PhIP to the mammary gland.
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PMID:2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) retards mammary gland involution in lactating Sprague-Dawley rats. 1038 5

Imbalance between pro-apoptotic and anti-apoptotic proteins, causing altered apoptosis, may lead to tumour development and tumour progression, and reduced response to adjuvant therapy. In this study, we evaluated the expression patterns of Bcl-2, Bcl-xL, and Bax protein in 126 primary invasive breast carcinomas, and the association with other clinicopathological parameters. We used immunohistochemical methods to evaluate protein expression. Reduced expression of both Bax and Bcl-2 was associated with lymphnode metastases in univariate analyses (one-way ANOVA) as well as in multivariate analysis (binary logistic regression) (Bcl-2 p=0.003 univariate, p=0.01 multivariate, Bax p=0.05 univariate, p=0.03 multivariate). Bcl-2 overexpression showed an inverse association with cyclin A (p=0.05), while expression of Bcl-xL showed an association only with cyclin D3 (p=0.04). Bcl-xL expression also showed a highly significant association with oestrogen receptor status (p=0.009). Bcl-2 and Bcl-xL showed an association with different D-type cyclins, indicating different pathways of pathogenesis. Expression of Bcl-2 was associated with better patient survival in univariate analysis (Kaplan meyer p=0.04), but lost its prognostic value in multivariate analysis (Cox regression p=0.2).
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PMID:Reduced expression of both Bax and Bcl-2 is independently associated with lymph node metastasis in human breast carcinomas. 1207 74

Apoptosis of tissues may contribute to ischaemia-reperfusion injury. The aim of the present study was to determine whether administration of a colloid solution would prevent apoptosis after liver ischaemia-reperfusion. New Zealand rabbits, weighing 1.5-2 kg, were randomized to receive either 4% SG (20 ml kg (-1)h(-1) ) by 30 min of intravenous (i.v.) infusion (Group I, n= 7) or equivalent volumes of 0.9% sodium chloride (Group II, n= 6) i.v. before a 45 min interruption of the portal vein blood flow and then 45 min of reperfusion. The animals were killed following the reperfusion period. Their livers were processed for histopathological examination and paraffin sections of these tissues were examined. The expression of Bcl-2, Bax and caspase 3 were analysed by immunohistochemistry. ANOVA and the Wilcoxon W -test were used for statistical analysis, and mean values were expressed +/-sd. Histologically, the foci of ischaemic necrosis were observed in liver specimens of the periportal area in one of the animals in Group I and in two in Group II. Immunhistochemical analysis demonstrated an increase in Bcl-2 protein levels in Group I compared to Group II ( P< 0.05). Bax expression was lower in Group I than in Group II. Immunoreactivity for caspase 3 did not differ significantly between the two groups (47.0 +/- 35.93 in Group I, 32.83 +/- 23.63 in Group II). Our results indicate that gelofusine did not protect the liver tissue against ischaemia-reperfusion-induced apoptosis.
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PMID:Anti-apoptotic effect of succinyl gelatine in a liver ischaemia-reperfusion injury model (Bcl-2, Bax, Caspase 3)? 1216 50

Reduction in apoptosis has been associated with tumor metastases and response to chemotherapy in breast cancer. We examine the influence of apoptosis status and the expression of antiapoptotic proteins Bcl-2 and Bcl-x(L) on metastatic progression and response to therapy in an experimental model of breast cancer. We used human breast cancer cells (MDA-MB 435, MDA-MB 468 and MCF-7) to induce orthotopic xenograft tumors in nude mice. The overexpression of Bcl-2 or Bcl-x(L) influenced tumorigenicity, 468 transfectants being less tumorigenic than control (p < 0.0001). Lung metastasis appeared at day 120 in animals injected with 435/Bcl-2 or 435/Bcl-x(L) and they showed higher metastatic activity than control 435/Neo tumors (p = 0.02). In contrast, mice with 468 tumors were followed for 1 year after tumor excision, but they did not develop metastatic foci. 435/Bcl-2 and 435/Bcl-x(L) transfectant cells bound less readily to laminin (ANOVA, p < 0.0001), fibronectin (ANOVA, p < 0.0001) and collagen type-IV (ANOVA, p < 0.0001) than 435/Neo cells. The overexpression of antiapoptotic proteins in 435 transfectants rescued 20-40% of cells from anoikis at 64 hr in rocking conditions. In contrast, at this time only 5-10% of 468 and MCF-7 transfectant cells were rescued. Thus, the overexpression of the Bcl-2 or Bcl-x(L) associated with the loss of apoptosis in breast cancer cells in vivo may account for their metastatic behavior. These genes increase tumor metastasis when the oncogenic background has triggered the metastatic process, in which anoikis might determine tumor progression when the life span of the cells is extended.
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PMID:Inhibition of apoptosis in human breast cancer cells: role in tumor progression to the metastatic state. 1220 55

We have shown previously that allyl isothiocyanate (AITC), a constituent of cruciferous vegetables, significantly inhibits survival of PC-3 and LNCaP human prostate cancer cells in culture, whereas proliferation of a normal prostate epithelial cell line is minimally affected by AITC even at concentrations that are highly cytotoxic to the prostate cancer cells. The present studies were designed to test the hypothesis that AITC administration may retard growth of human prostate cancer xenografts in vivo. Bolus i.p. injection of 10 micromol AITC, three times per week (Monday, Wednesday and Friday) beginning the day of tumor cell implantation, significantly inhibited the growth of PC-3 xenograft (P < 0.05 by two-way ANOVA). For example, 26 days after tumor cell implantation, the average tumor volume in control mice (1025 +/- 205 mm3) was approximately 1.7-fold higher compared with AITC-treated mice. Histological analysis of tumors excised at the termination of the experiment revealed a statistically significant increase in number of apoptotic bodies with a concomitant decrease in cells undergoing mitosis in the tumors of AITC-treated mice compared with that of control mice. Western blot analysis indicated an approximately 70% reduction in the levels of anti-apoptotic protein Bcl-2 in the tumor lysate of AITC-treated mice compared with that of control mice. Moreover, the tumors from AITC-treated mice, but not control mice, exhibited cleavage of BID, which is known to promote apoptosis. Statistically significant reduction in the expression of several proteins that regulate G2/M progression, including cyclin B1, cell division cycle (Cdc)25B and Cdc25C (44, 45 and 90% reduction, respectively, compared with control), was also observed in the tumors of AITC-treated mice relative to control tumors. In conclusion, the results of the present study indicate that AITC administration inhibits growth of PC-3 xenografts in vivo by inducing apoptosis and reducing mitotic activity.
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PMID:Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. 1289 4

The complement system represents an important mediator of neuroinflammation in traumatic brain injury. We have previously shown that transgenic mice with central nervous system-targeted overexpression of Crry, a potent murine complement inhibitor at the level of C3 convertases, are protected from complement-mediated neuropathological sequelae in brain-injured mice. This knowledge was expanded in the present study to a pharmacological approach by the use of a recombinant Crry molecule (termed Crry-Ig) which was recently made available in a chimeric form fused to the non-complement fixing mouse IgG1 Fc region. In a standardized model of closed head injury in mice, the systemic injection of 1 mg Crry-Ig at 1 h and 24 h after trauma resulted in a significant neurological improvement for up to 7 days, as compared to vehicle-injected control mice (P < 0.05, repeated measures ANOVA). Furthermore, the extensive neuronal destruction seen in the hippocampal CA3/CA4 sublayers in head-injured mice with vehicle injection only was shown to be preserved - to a similar extent as in "sham"-operated mice - by the posttraumatic injection of Crry-Ig. Real-time RT-PCR analysis revealed that the post-treatment with Crry-Ig resulted in a significant up-regulation of candidate neuroprotective genes in the injured hemisphere (Bcl-2, C1-Inh, CD55, CD59), as compared to the vehicle control group (P < 0.01, unpaired Student's t test). Increased intracerebral Bcl-2 expression by Crry-Ig treatment was furthermore confirmed at the protein level by Western blot analysis. These data suggest that pharmacological complement inhibition represents a promising approach for attenuation of neuroinflammation and secondary neurodegeneration after head injury.
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PMID:Pharmacological complement inhibition at the C3 convertase level promotes neuronal survival, neuroprotective intracerebral gene expression, and neurological outcome after traumatic brain injury. 1654 3

Expression of PERP (p53 apoptosis effector related to PMP-22) was investigated in primary uveal melanomas and its variation was analyzed in relation to clinico-pathological and cytogenetical characteristics of these tumors. The transcriptional level of PERP gene was measured by quantitative real-time RT-PCR in 26 uveal melanomas with known chromosomes 3 and 8 status. PERP protein levels were assessed by Western blot analysis of 22 fresh-frozen tumors and by immunohistochemical analysis of 16 paraffin-embedded tumor specimens. Differential expression of PERP was identified in primary choroidal melanoma specimens, both at transcriptional and protein level. Reduced PERP mRNA level was significantly associated with monosomy 3 (two-way ANOVA and t-test, p=0.004) but not with gains in chromosome 8. Transcriptional downregulation of PERP did not present a statistically significant association with ciliary body involvement, size, PAS-positive loops or cell type. Immunoblotting and immunohistochemistry further demonstrated significantly reduced PERP protein level in monosomy 3 melanomas, as compared with disomy 3 tumors. The altered expression of PERP highlighted this apoptosis-specific target of p53 as a possible contributor to apoptosis in uveal melanoma with PERP downregulation being particularly relevant to the aggressive (monosomy 3) type of uveal melanoma. As PERP is a novel type of p53 effector that is likely to stimulate apoptosis through a mechanism distinct from that of Bcl-2-related mitochondrial effectors, further elucidation of its role in uveal melanoma pathogenesis will assist in the design of novel therapeutic approaches aimed at increasing the rate of apoptosis in this tumor.
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PMID:Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: downregulation is associated with aggressive type. 1678 42

Recent evidence suggests that bombesin (BBS) is involved in modulation of growth and differentiation of normal small intestine. The purpose of the present study was to evaluate the effects of BBS on enterocyte turnover after massive small bowel resection in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats underwent bowel transection and re-anastomosis, short bowel syndrome (SBS) rats underwent a 75% small bowel resection, and SBS-BBS rats underwent bowel resection and were treated with BBS given subcutaneously at a dose of 20 mug/kg, once daily, from postoperative day 3 through 14. Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and protein, villus height and crypt depth), enterocyte proliferation and enterocyte apoptosis were determined in jejunum and ileum on day 15 following operation. RT-PCR technique was used to determine Bax and Bcl-2 gene expression in ileal mucosa. Statistical analysis was performed using the non-parametric Kruskal-Wallis ANOVA test, with P less than 0.05 considered statistically significant. Treatment with BBS resulted in a significant increase in ileal bowel and mucosal weight, ileal mucosal DNA and protein, jejunal and ileal villus height, jejunal crypt depth, and jejunal and ileal proliferation index compared to SBS-animals. SBS rats showed a significant increase in Bax and Bcl-2 expression in ileum that was accompanied by a significant increase in cell apoptosis compared to sham animals. SBS-BBS rats demonstrated a significant decrease in Bax and Bcl-2 expression in ileum and a decrease in apoptotic index compared to SBS-animals. In conclusion, in a rat model of SBS, BBS enhances enterocyte turnover and stimulates structural intestinal adaptation. Decreased Bax expression may be responsible for the inhibitory effect of BBS on enterocyte apoptosis.
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PMID:Bombesin stimulates enterocyte turnover following massive small bowel resection in a rat. 1744 Jul 64

The purpose of this study was to investigate the effect of aging on different parameters related to inflammation, oxidative stress and apoptosis in hearts from two types of male mice models: senescence-accelerated mice (SAM-P8) and senescence-accelerated-resistant (SAM-R1), and the influence of chronic administration of Growth Hormone (GH) on old SAM-P8 mice. Forty male mice were used. Animals were divided into five experimental groups: two 10 month old untreated groups (SAM-P8/SAM-R1), two 2 month old young groups (SAM-P8/SAM-R1) and one 10 month old group (SAM-P8) treated with GH for 30 days. The expression of tumor necrosis factor-alpha, interleukin 1, interleukin 10, heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases, NFkB, Bad, Bax and Bcl-2 were determined by real-time reverse transcription polymerase chain reaction (RT-PCR). Results were submitted to a two way ANOVA statistical evaluation using the Statgraphics program. Inflammation, as well as, oxidative stress and apoptosis markers were increased in the heart of old SAM-P8 males, as compared to young controls and this situation was not observed in the old SAM-R1 mice. Exogenous GH administration reverted the effect of aging in the described parameters of old SAM-P8 mice. Our results suggest that inflammation, apoptosis and oxidative stress could play an important role in the observed cardiovascular alterations related to aging of SAM-P8 mice and that GH may play a potential protective effect on the cardiovascular system of these animals.
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PMID:Cardiological aging in SAM model: effect of chronic treatment with growth hormone. 1973 Oct 67


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