UNIPROT:P10415 - FACTA Search

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Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various types of carcinoma cells have been shown to escape immune recognition by constitutive resistance to Fas receptor (Fas)-mediated apoptosis. The purpose of this study was to examine the sensitivity to Fas-mediated apoptosis of human head and neck squamous cell carcinoma (HNSCC) cells. We applied an anti-Fas monoclonal antibody (CH11) to HNSCC cell lines and monitored their cell death. All three HNSCC cell lines examined expressed Fas protein but not Fas-ligand mRNA. CH11 did not induce cell death (CH11-resistant) in any of the three HNSCC cell lines examined. Treatment with actinomycin D (ActD) converted the phenotypes of the CH11-resistant HNSCC cell lines from CH11-resistant to CH11-sensitive, suggesting that the resistance to CH11-induced apoptosis was dependent on RNA synthesis. Western blot analysis did not show any differences in expression of Bcl-2 between the non-treated and ActD-treated HNSCC cell lines. Expression of Bcl-XL, on the other hand, was greatly reduced in the ActD-treated HNSCC cell lines, implying that Fas signaling in the CH11-resistant HNSCC cell lines might be regulated by an Bcl-XL-inhibitable step.
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PMID:[Resistance to Fas-mediated apoptosis in head and neck squamous cell carcinoma cells]. 1110 27

Bcl-2 protein together with the pro-apoptotic protein bax, are thought to function by forming homo- and heterotypic dimers which control the progression to apoptosis. In this immunohistochemical study we investigated the expression of bcl-2 and bax apoptosis related proteins in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. Twenty-four cervical intraepithelial neoplasias grade 1-2 (CIN I/II), 38 grade 3 (CIN III), and 53 invasive squamous cell carcinomas (ISCC) were investigated by immunohistochemical staining for bcl-2 and bax protein. Bcl-2 immunoreactivity was found in five of the 24 CIN I/II cases (20.8%), 18 of 38 CIN II cases (47.4%) and nine of 53 ISCC cases (17%). The positivity for CIN III was significantly higher than for CIN I/II or ISCC (p=0.0351 and p=0.0018, respectively). The percentage of bax immunopositivity was somewhat higher in CIN III than in CIN I/II but this slight difference was not statistically significant. Correlation of the immunostaining results with tumor grade revealed a significant difference for bcl-2 which was more frequently immunopositive in well-differentiated tumors than in poorly-differentiated tumors. There was no significant relation between bax expression and tumor differentiation. Our results suggest that alterations of bcl-2 and bax expression may occur as a relatively early event in cervical tumorigenesis.
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PMID:Expression of bcl-2 and bax in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the uterine cervix. 1119 41

Photodynamic therapy (PDT), a promising treatment modality, is an oxidative stress that induces apoptosis in many cancer cells in vitro and tumors in vivo. Understanding the mechanism(s) involved in PDT-mediated apoptosis may improve its therapeutic efficacy. Although studies suggest the involvement of multiple pathways, the triggering event(s) responsible for PDT-mediated apoptotic response is(are) not clear. To investigate the role of Bcl-2 in PDT-mediated apoptosis, we employed Bcl-2-antisense and -overexpression approaches in two cell types differing in their responses toward PDT apoptosis. In the first approach, we treated radiation-induced fibrosarcoma (RIF 1) cells, which are resistant to silicon phthalocyanine (Pc 4)-PDT apoptosis, with Bcl-2-antisense oligonucleotide. This treatment resulted in sensitization of RIF 1 cells to PDT-mediated apoptosis as demonstrated by i) cleavage of poly(ADP-ribose) polymerase, ii) DNA ladder formation, iii) terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, and iv) DEVDase activity. This treatment also resulted in oligonucleotide concentration-dependent decrease in cell viability and down-regulation of Bcl-2 protein with a concomitant increase in apoptosis. However, the level of Bax, a pro-apoptotic member of Bcl-2 family, remained unaltered. In the second approach, an overexpression of Bcl-2 in PDT apoptosis-sensitive human epidermoid carcinoma (A431) cells resulted in enhanced apoptosis and up-regulation of Bax following PDT. In both the approaches, the increased Bax/Bcl-2 ratio was associated with an increased apoptotic response of PDT. Our data also demonstrated that PDT results in modulation of other Bcl-2 family members in a way that the overall ratio of pro-apoptotic and anti-apoptotic member proteins favors apoptosis.
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PMID:Involvement of Bcl-2 and Bax in photodynamic therapy-mediated apoptosis. Antisense Bcl-2 oligonucleotide sensitizes RIF 1 cells to photodynamic therapy apoptosis. 1127 20

Vascular endothelial growth factor (VEGF) has been shown to be a potent mediator of angiogenesis that functions as a survival factor for endothelial cells by up-regulating Bcl-2 expression. We have recently reported that human dermal microvascular endothelial cells (HDMECs) seeded in biodegradable sponges and implanted into severe combined immunodeficient (SCID) mice organize into functional human microvessels that transport mouse blood cells. In this study, we implanted sponges seeded with OSCC-3 (oral squamous cell carcinoma) or SLK (Kaposi's sarcoma) together with endothelial cells into SCID mice to generate human tumors vascularized with human microvessels. This model system was used to examine the role of both endothelial cell Bcl-2 and the proangiogenic chemokine interleukin-8 (IL-8) on tumor growth and intratumoral microvascular density. Coimplantation of HDMECs overexpressing Bcl-2 (HDMEC-Bcl-2) and tumor cells resulted in a 3-fold enhancement of tumor growth when compared with the coimplantation of control HDMECs and tumor cells. This was associated with increased intratumoral microvascular density and enhanced endothelial cell survival. To determine whether the enhanced neovascularization mediated by Bcl-2 overexpression in endothelial cells was influenced by the synthesis of endogenous mediators of angiogenesis, we screened these cells for expression of VEGF, basic fibroblast growth factor (bFGF), and IL-8 by ELISA. HDMEC-Bcl-2 cells and VEGF-treated HDMECs exhibited a 15-fold and 4-fold increase, respectively, in the expression of the proangiogenic chemokine IL-8 in vitro, whereas the expression of VEGF and bFGF remained unchanged. Transfection of antisense Bcl-2 into HDMECs blocked VEGF-mediated induction of IL-8. Conditioned media from HDMEC-Bcl-2 induced proliferation and sprouting of endothelial cells in vitro and neovascularization in rat corneas. Anti-IL-8 antibody added to HDMEC-Bcl-2 conditioned media markedly reduced the potency of these responses. SCID mice bearing VEGF-producing tumor implants that were treated with anti-lL-8 antibody exhibited a 43% reduction in microvessel density and a 50% reduction in tumor weight compared with treatment with a nonspecific antibody. These results demonstrate that the up-regulation of Bcl-2 expression in endothelial cells that constitute tumor microvessels enhances intratumoral microvascular survival and density and accelerates tumor growth. Furthermore, endothelial cells that overexpress Bcl-2 have more angiogenic potential than control cells, and IL-8-neutralizing antibodies attenuate their angiogenic activity in vitro and in vivo.
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PMID:Up-Regulation of Bcl-2 in microvascular endothelial cells enhances intratumoral angiogenesis and accelerates tumor growth. 1128 Jul 84

We demonstrated that calcitriol has antiproliferative activity in squamous cell carcinoma and prostatic adenocarcinoma and enhances the antitumor activity of platinum-based agents. In this study, we examined whether calcitriol also increases paclitaxel cytotoxicity. The effect of treatment on growth of the murine squamous cell carcinoma (SCCVII/SF) and human prostatic adenocarcinoma (PC-3) was determined by clonogenic assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and monitoring tumor growth. Treatment of SCC or PC-3 cells in vitro with calcitriol prior to paclitaxel significantly reduced clonogenic survival compared with either agent alone. Median-dose effect analysis revealed that calcitriol and paclitaxel interact synergistically. Treatment of SCC or PC-3 tumor-bearing mice with calcitriol prior to paclitaxel resulted in substantially greater growth inhibition than was achieved with either agent alone, supporting the combined use of calcitriol and paclitaxel in the treatment of solid tumors. To explore the molecular basis for the enhanced antitumor activity of this combination, the effect of treatment on p21(Waf-1) (p21), Bcl-2, and poly(ADP-ribose) polymerase expression was evaluated in PC-3. A 72-h pretreatment with calcitriol reduced p21 expression and increased paclitaxel cytotoxicity (measured after 24 h) without evidence of apoptosis [poly(ADP-ribose) polymerase cleavage]. After 48 h, paclitaxel induced apoptosis, the extent of which was increased similarly by pretreatment or concurrent treatment with calcitriol. We therefore propose a model for calcitriol enhancement of paclitaxel cytotoxicity in which the "early" (24 h) effects are schedule dependent and not attributed to enhancement of paclitaxel-induced apoptosis. In contrast, the "delayed" (48-h) enhancement of paclitaxel activity by calcitriol is schedule independent and associated with acceleration of apoptosis.
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PMID:Calcitriol (1,25-dihydroxycholecalciferol) enhances paclitaxel antitumor activity in vitro and in vivo and accelerates paclitaxel-induced apoptosis. 1130 56

Apoptosis plays a crucial role in determining net cell proliferation and cell turnover in various tumors. The rate of apoptosis in tumor cells has been reported to be a useful prognostic indicator in colorectal carcinoma. We examined apoptosis in 72 specimens of esophageal squamous cell carcinoma, by the terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) digoxigenin-nick end labeling (TUNEL) method. We examined correlation of apoptosis with outcome, clinicopathological features, and expression of the apoptosis-related proteins p53 and Bcl-2. The percentage of apoptotic cells, or apoptotic index (AI), ranged from 0.8 to 9.4 (mean: 3.47; SD: 2.02). Overall, 5-year survival of patients with high AI (AI > or = 5.0; n = 18) tumors was significantly higher than that of patients with low AI tumors (AI < 5.0; n = 58; 76.9% versus 44.9%; P = 0.042). AI did not correlate significantly with the clinicopathological features of patient age and sex, depth of tumor and histological differentiation, lymph node metastasis, lymphatic invasion, or venous invasion. In p53-negative tumors, the AI was significantly higher than in p53-positive tumors. We concluded that AI may be a useful prognostic indicator in esophageal squamous cell carcinoma following curative surgery, and that apoptosis in this tumor is related to relative underexpression of p53 protein.
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PMID:Apoptosis as an independent prognostic indicator in squamous cell carcinoma of the esophagus. 1147 61

The oral cavity is continually exposed to various traumas due to the effect of thermal, mechanical and chemical stimuli, which when accompanied by inflammatory states may promote the growth of neoplastic changes. Numerous studies have revealed a correlation between the expression of p53 and Bcl-2 proteins and the progression of neoplastic disease. It cannot be excluded that these proteins act as biomarkers of a neoplastic transformation threatening in precancerous states (including leukoplakia) or the already existing neoplastic transformation (e.g. in oral squamous cell carcinoma). The aim of the study was to evaluate the expression of p53 and Bcl-2 proteins in the proliferating epithelium in relation to leukoplakia degree and with regard to the lesions accompanied and not accompanied by squamous cell carcinomas. Fifty-five cases of proliferating changes in the oral epithelium (leukoplakia) were investigated. Group I contained 20 leukoplakias not accompanied by oral squamous cell carcinomas. Groups II, III and IV included 35 cases of changes in the vicinity of carcinomas on the lower lip (group II), in the front 2/3 of the tongue (group III) and in the oral floor (group IV). Staining was performed according to the immunohistochemical method with the use of monoclonal antibodies against human p53 protein (DAKO No M7001) and Bcl-2 (DAKO No M0887). A higher expression of p53 protein (54%) was found in leukoplakia changes coexisting with squamous cell carcinomas, compared with the non-accompanied ones (p53--45%). The results indicate a correlation between epithelial dysplasia degree and p53 and Bcl-2 protein expression--severe dysplasia occurred with an increase in the expression of both proteins. Leukoplakias situated in the vicinity of squamous cell carcinomas showed higher expression of p53 and Bcl-2 compared with the non-accompanied alterations. A correlation was also revealed between the location and p53 and Bcl-2 protein expression degree in the non-accompanied changes; no such correlations were found in proliferating epithelial changes adjacent to neoplastic tumors.
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PMID:Evaluation of p53 and bcl-2 oncoprotein expression in precancerous lesions of the oral cavity. 1147

The rate of tumor growth depends on the balance between proliferation and death of tumor cells. It is known that Bax, caspase-3, and p53 proteins are death-promoting factors, whereas Bcl-2 protein is a death antagonist. We immunohistochemically examined the expression of Bax and apoptosis-related proteins such as caspase-3, p53, and Bcl-2 in 76 patients with human esophageal squamous cell carcinoma (SCC) including dysplasia to determine the relationship of expression of each protein to tumor behavior and patients' prognosis. No significant relationships in immunopositivity were found among these proteins in SCCs. Cytoplasmic Bax expression was exhibited in 63 cases of SCCs (82.9%). The apoptotic index of caspase-3-positive lesions was significantly higher than that of caspase-3-negative lesions in both dysplasia and SCC (P =.016, P =.012). On the other hand, the apoptotic index (1.18%) was significantly correlated with Bax overexpression in dysplasia (P =.006), but not in SCC lesions (P =.129). The patients with Bax-positive SCCs were found to have a poor prognosis by the Kaplan-Meier method (P =.043). These findings suggested that Bax expressed in dysplasia may play a role as an apoptotic factor, but that it may be functionally inactive in some cancerous lesions and thus not contribute to suppression of the tumor progression in some cases of human esophageal SCCs.
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PMID:Expression of Bax and apoptosis-related proteins in human esophageal squamous cell carcinoma including dysplasia. 1150 32

Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum. The study investigated the effects and mechanisms of aloe-emodin-induced cell death in human lung squamous cell carcinoma cell line CH27. Aloe-emodin (40 microM)-induced CH27 cell apoptosis was confirmed by DNA fragmentation (DNA ladders and sub-G(1) formation). Aloe-emodin-induced apoptosis of CH27 cells involved modulation of the expression of Bcl-2 family proteins, such as BclX(L), Bag-1, and Bak, and was associated with the translocation of Bak and Bax from cytosolic to particulate fractions. Aloe-emodin-treated CH27 cells had an increased relative abundance of cytochrome c in the cytosolic fraction. Results demonstrated that the activation of caspase-3, caspase-8, and caspase-9 is an important determinant of apoptotic death induced by aloe-emodin. These results suggest that aloe-emodin induces CH27 cell death by the Bax and Fas death pathway.
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PMID:Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma. 1173 Jul 20

The antitumor effects of the green tea compound epigallocatechin-3-gallate (EGCG) have not been studied in detail previously in head and neck squamous cell carcinoma (HNSCC) cells. Overexpression of the epidermal growth factor receptor (EGFR) occurs frequently in HNSCC, which is an adverse prognostic factor. Therefore, we examined in detail the molecular effects of EGCG on two human HNSCC cell lines, YCU-N861 and YCU-H891, focusing on the EGFR signaling pathway. The 70% lethal dose (IC(70)) of EGCG for both cell lines was 10 microg/ml. Treatment with EGCG increased the proportion of cells in the G(1) phase of the cell cycle and induced apoptosis. In cells treated with EGCG, there was a decrease in the cyclin D1 protein, an increase in the p21(Cip1) and p27(Kip1) proteins, and a reduction in the hyperphosphorylated form of pRB, changes that may account for the arrest in G(1). EGCG also caused a decrease in the Bcl-2 and Bcl-X(L) proteins, an increase in the Bax protein, and activation of caspase 9, suggesting that EGCG induces apoptosis via a mitochondrial pathway. Treatment with EGCG inhibited phosphorylation of the EGFR, signal transducer and activator of transcription3 (Stat3), and extracellular regulated kinase (ERK) proteins and also inhibited basal and transforming growth factor-alpha-stimulated c-fos and cyclin D1 promoter activity. EGCG at 0.1 microg/ml (a concentration found in serum after oral administration) markedly enhanced the growth-inhibitory effects of 5-fluorouracil. Taken together, these findings provide insights into molecular mechanisms of growth inhibition by EGCG and suggest that this naturally occurring compound may be useful, when used alone or in combination with other agents, in the chemoprevention and/or treatment of HNSCC.
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PMID:Effects of epigallocatechin-3-gallate on growth, epidermal growth factor receptor signaling pathways, gene expression, and chemosensitivity in human head and neck squamous cell carcinoma cell lines. 1175 23

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