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)

Expression of the bcl-2 gene was investigated in 218 human breast carcinomas by immunohistochemical analysis. Immunodetections were assessed using (1) frozen sections, (2) documented commercially available monoclonal antibody (bcl-2/124, Dako), (3) automation of immunoperoxidase technique (Ventana) and (4) quantitative evaluation of results by image analysis (SAMBA) and statistical analysis of quantitative data (BMDP software). Bcl-2 protein expression was correlated with current prognostic indicators and with molecular markers detected by the same procedure as for Bcl-2. It was shown that Bcl-2 expression is not related to patients' age, tumour size and type or lymph node status, but an inverse relationship was observed between Bcl-2 and tumour grade (P < 0.0001). An inverse relationship was also observed between Bcl-2 expression and p53 (P < 0.0001), Ki67/MIB1 antigen- (P = 0.0012), and P-gp- (P = 0.002) positive immunoreactions. In contrast, anti-Bcl-2 positive reaction was significantly associated with ER-positive (P < 0.001) and with ER/PR-positive or ER/PR/pS2-positive immunoreactions (P < or = 0.005). Bcl-2 expression was independent of CD31 and cathepsin D expression. Thus, Bcl-2 protein, thought to be antiapoptotic, exhibits parodoxical expression in human breast carcinomas. It is strongly detected in low-grade tumours (well-differentiated) with low (MIB1) growth fraction, but is independent of the tumour progression (size, node status, CD31, and cathepsin D). Bcl-2 acting on apoptosis is related to p53 gene abnormalities in breast carcinomas. Bcl-2 protein expression may also be involved in response to endocrine therapy (associated to ER/PR/pS2 positive immunoreactions) and probably with chemoresistance mechanisms (inverse relationship with P-gp).
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PMID:Automated and quantitative immunocytochemical assays of Bcl-2 protein in breast carcinomas. 925 1

Expression of vascular cell adhesion molecules (VCAM) in tumors is associated with endothelial cell activation and may facilitate adherence of carcinomatous cells to the vessel wall, promoting bloodborne metastases. Expression of VCAM was investigated in 202 breast carcinomas using automated (Ventana System) and quantitative (SAMBA image analyzer) immunoperoxidase staining of frozen sections. Positive VCAM immunoreactivity was observed in 83 tumors (41%) (mean immunostained surface, 12.4%; SD, 10.5). The mean area of immunostaining was correlated with clinical and pathologic prognostic indicators and with the immunohistochemical expression in tissue sections of various indicators of cell proliferation, metastatic potential, and drug resistance or sensitivity, evaluated according to the same method. There was no correlation of VCAM immunoreactivity with tumor size, type, or grade or with nodal status. Also, no significant correlation was observed between VCAM and MIB1/Ki67, p53, Bcl-2, E cadherin, CD44v, cathepsin D, CD31, P-gp, ER, PR, or pS2. However, VCAM immunoreactivity was significantly correlated with ELAM and VLA2 (P = .001) and VLAs (P = .008) expression. The results suggest that VCAM expression in breast carcinoma tissue sections is likely not a prognostic indicator. Its practical clinical relevance, if any, must be established by correlation with patients' outcomes and tumor sensitivity to drugs.
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PMID:VCAM (IGSF) adhesion molecule expression in breast carcinomas detected by automated and quantitative immunocytochemical assays. 974 2

A spontaneously EBV transformed follicular lymphoma (FL) cell line, Tat-1, was established from the lymph node biopsy specimen of a patient with B cell FL, grade 1 in transformation to high grade disease. Tat-1 cells expressed lymphoid markers and developed tumor masses in immunodeficient mice. Bcl-2, Bcl-X(L), Bax and p53 protein expression was revealed by Western blotting. Flow cytometric analysis confirmed P-gp expression. Cytogenetically, the Tat-1 cell line showed identical chromosomal alterations to that of the initial biopsy specimen, among which the most notable were the t(14;18) typical of FL and additional abnormalities involving chromosomes 1, 8 and 13. Multicolor FISH analysis delineated all abnormalities, including a t(1p;8q), a der(8)(8q24::14q32::18q21) and a der(13)(13q32::8q24::14q32::18q21). Further FISH investigations using a locus-specific probe cocktail containing c-myc, IgH and bcl-2 revealed fusion of these three loci on the derivatives 8 and 13, in addition to the derivative 14 IgH/bcl-2 fusion and an extra copy of c-myc on derivative chromosome 1. These results demonstrate an additional example of the deregulation of bcl-2 and c-myc expression through recombination with a single IgH enhancer region. The unusual molecular features of the Tat-1 cell line render it a unique tool for studies focused on cytogenetic alterations, expression of multidrug resistance phenotype and expression of anti-apoptotic proteins in FL.
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PMID:Establishment and comprehensive analysis of a new human transformed follicular lymphoma B cell line, Tat-1. 1184 Feb 95

The resistant problem is the main restriction factor for clinical usage of taxol. The main mechanism of its resistance includes the high expression of P-gp, beta- and alpha-tubulin isotypes, the alteration expression of PKC, Bcl-2, p53, and ErbB2. The reversing method includes the use of analogues of taxol to reduce the expression of P-gp, or the use of antibody, immunotoxin, antisence oligonucleotide, and liposomes. The combination with other drugs can also be a method to reverse the resistance of taxol.
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PMID:[Development of research for drug-resistance mechanism of taxol]. 1245 28

The effect of PIC-BE on the expression of mdr-1, bcl-2 and bax genes and their protein products (P-gp, Bcl-2 and Bax) was observed respectively in a multidrug resistance (MDR) cell variant K562/ADM. The results showed that PIC-BE could significantly inhibit the expression of mdr-1 and bcl-2 genes at both mRNA and protein levels in K562/ADM cell line, and the effect was dose- and time-dependent within limited range. Under same condition, although PIC-BE could increase the expression of Bax slightly, there was no statistically significant difference. These results suggest that the reversal of the MDR of K562/ADM cell line by PIC-BE may result from its effect on the expression of mdr-1, bcl-2 genes and their protein products.
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PMID:[Effect of PIC-BE on the expression of MDR-1 and bcl-2 genes in a multidrug resistance cell variant K562/ADM]. 1254 76

The apoptosis failure in cytostatic treatment of haemoblastosis is one of the means of chemoresistance. We were interested in the relationship of the after-doxorubicin-treatment-AML cells apoptosis and the immunophenotype, selected clinical and laboratory parameters, and also the P-gp, MRP, LRP, Bcl-2, Bax proteins expression. All analysis were evaluated with the flow cytometry method. To detect apoptotic cells in the sample, we used three methods: annexin test, TUNEL (TdT-mediated dUTP nick end labeling) test, and caspase 8 detection. After the cell cultivation the statisticaly important increase of apoptotic cells in the culture was apparent. The relation between the AML blast in vitro reaction and some clinical parameters such as the age of patient, white blood cell count, and blast percentage was also observed.
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PMID:The multidrug resistance and apoptosis evaluation in acute myeloid leukemia cells after the in vitro doxorubicin treatment. 1556 36

The Runx3 gene is a member of the runt domain family transcription factors, key regulators of development and differentiation in metazoan. Recently, Runx3 was identified as a tumor suppressor gene. Loss of Runx3 was found to be associated with genesis and progression of gastric cancer. In this study, we transfected the gastric cancer cell line SGC7901 with eukaryotic expression vector of Runx3. In vitro drug sensitivity assay suggested that SGC7901/Runx3 cells were more sensitive to various chemotherapeutic drugs. Blocking Runx3 expression in immortalized stomach mucosal cells (GES-1) or gastric cancer cells (SGC7901) by Runx3-specific small interfering RNA conferred the cells resistance to chemotherapeutic drugs. Flow cytometry examination suggested that expression of Runx3 in gastric cancer cells increased the intracellular accumulation and retention of adriamycin. Semiquantitative RT-PCR and Western blot suggested that Runx3 downregulated expression of Bcl-2, MDR-1 (P-gp) and MRP-1. Binding of Runx3 to promoter sequences of Bcl-2, MDR-1 and MRP-1 gene was detected by eletrophoretic mobility shift assay (EMSA) and supershift EMSA. We cloned the MDR-1 and MRP-1 gene promoters containing Runx binding sites and constructed the luciferase reporter vectors of these 2 promoters. Luciferase reporter assay suggested that Runx3 inhibited the promoter activity of the MDR-1 and MRP-1 promoter in SGC7901 cells. Taken together, our findings suggested that overexpression of Runx3 could sensitize gastric cancer cells to chemotherapeutic drugs by downregulating the Bcl-2, MDR-1 and MRP-1.
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PMID:Tumor suppressor gene Runx3 sensitizes gastric cancer cells to chemotherapeutic drugs by downregulating Bcl-2, MDR-1 and MRP-1. 1575 76

In a previous study, we observed that cytokine-induced apoptosis inhibitor 1 (CIAPIN1), a newly identified apoptosis inhibitor, was upregulated at the mRNA level in a multidrug-resistant gastric cancer cell line SGC7901/VCR. The aim of this study was to explore the role of CIAPIN1 in the development of multidrug resistance (MDR) in gastric cancer cells. Upregulation of CIAPIN1 in MDR gastric cancer cells was confirmed by semiquantitative RT-PCR and Western blotting. Using cDNA transfection and RNA interference, we successfully established stable transfectants with upregulation (i.e., SGC7901-pCIAPIN1) or downregulation (i.e., SGC7901-pSiCIAPIN1 and SGC7901/ADR-pSiCIAPIN1) of CIAPIN1 expression, respectively. In vitro drug sensitivity assay demonstrated that overexpression of CIAPIN1 conferred MDR in SGC7901 cells whereas downregulation of CIAPIN1 sensitized SGC7901 and SGC7901/ADR cells to anticancer drugs. CIAPIN1 protected both SGC7901 and SGC7901/ADR cells from ADR-induced apoptosis and reduced intracellular accumulation and retention of adriamycin. Moreover, expression of P-glycoprotein (P-gp or MDR-1, a product of MDR-1 gene) and MDR-related protein-1 (MRP-1) was upregulated by CIAPIN1. In addition, Western blotting revealed that CIAPIN1 decreased the expression of Bcl-2, Bax and p53. Therefore, it is concluded that CIAPIN1 confers MDR in gastric cancer cells, likely by upregulating MDR-1 and MRP-1.
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PMID:CIAPIN1 confers multidrug resistance by upregulating the expression of MDR-1 and MRP-1 in gastric cancer cells. 1641 Jul 21

Targeting the "weak point" of cancers, especially the apoptotic/drug resistant cancers, is critical for the success of cancer chemotherapy. We found that the drug resistant cancer cell lines overexpressing P-gp, MRP1, BCRP, Bcl-2 and Bcl-xL are susceptible to shikonin, a necroptotic inducer, despite the fact that they are highly resistant to a variety of anticancer agents such as anthracycline antibiotics, vinca alkaloids, taxanes, epipodophylotoxins, etc. These findings reveal that, although apoptotic/drug resistance is a formidable "stronghold" of cancer against chemotherapy, necroptotic susceptibility is an intrinsic "weak point" of cancer. Therefore, targeting the weakness of cancer by induction of necroptosis may have significant potential in cancer chemotherapy, especially in the apoptotic/drug resistant cancers.
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PMID:Targeting the weak point of cancer by induction of necroptosis. 1761 36

This study was purposed to investigate the inhibitory effect, apoptosis, Bcl-2 and P-gp expression of K562/AO2 cells by hyperthermia combined with adriamycin. The working concentration of adriamycin against K562/AO2 was determined by MTT assay. The hyperthermia and chemotherapy were used alone or in combination, then the cell survival rate was detected at 48 hours. The inhibitory effect was evaluated by MTT assay. The apoptosis rate, Bcl-2 and P-gp expression of K562/AO2 were determined by flow cytometry. The concentration of adriamycin in the experiment was defined as its IC(50) at 48 hours action. The results indicated that the hyperthermia at 40, 41 and 42 degrees C for 60 minutes showed obvious inhibitory effect on K562/AO2 cells (p < 0.01). Adriamycin chemotherapy combined with hyperthermia showed more obvious inhibitory effect on K562/AO2. According to flow cytometric analysis, the hyperthermia and adriamycin used alone or in combination could obviously increase the apoptosis rate and down-regulate Bcl-2 and P-gp expression of K562/AO2 cells (p < 0.01). It is concluded that the adriamycin chemotherapy combined with hyperthermia for 60 minutes shows obvious inhibitory effect on K562/AO2 cells, which increases the apoptosis rate and down-regulates expression of Bcl-2 and P-gp.
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PMID:[Effect of hyperthermia in combination with chemotherapy on K562/AO2 cells in vitro]. 1770 91


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