Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:A9QXG9 (bcl-2)
 7,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-four nude mice bearing MCF-7 breast cancer cells grown as xenografts and treated with tamoxifen (2.5 mg slow-release pellet) were studied for up to 35 days. Tumour size was measured in 2 dimensions at regular time-intervals and tumours were harvested on each of days 2, 4, 7, 14, 28 and 35 after the start of treatment. Control animals (8) received no treatment and the tumours were harvested after 0 or 35 days. Tumour sections were assessed for prevalence of apoptosis and mitosis and examined immunocytochemically for Ki(67)(MIB-1) and bcl-2 expression. Tumours increased in size during tamoxifen-treatment, but at a significantly slower rate (max. 2.6-fold) than in the untreated control animals; thus tumours not actually regressing may, nevertheless, be responding significantly to tamoxifen. MIB-1 and bcl-2 immunostaining and mitosis failed to show any consistent change over the period of study. Apoptosis, however, increased progressively and significantly to day-28 in tamoxifen-treated tumours, reaching approximately a 5-fold increase over day-0 values, then decreasing again to nearly 3-fold by day-35 (P= 0.0002). The apoptosis: mitosis ratio in treated tumours also increased to approximately 10-fold on day-28 over day-0 values, decreasing to nearly 4-fold by day-35 (P= 0.037). Within the treated group, apoptosis was significantly inversely correlated with both mitosis (R = -0.38, P= 0.03) and expression of bcl-2 (R = -0.48, P= 0.0056) and strongly positively correlated with both time on tamoxifen (R = +0.63, P= 0.0003) and the % inhibition of growth by tamoxifen (R = +0.58,P = 0.0012) in the 28 individual, treated tumours (estimated relative to the mean growth rate in the controls). The apoptosis: mitosis ratio was also inversely correlated with bcl-2 expression (R = -0.56, P= 0.0021) and positively correlated with both time on tamoxifen (R = +0.50, P= 0.0068) and % inhibition of growth (R = +0.56, P= 0.0019). In this hormone-sensitive tumour model for breast cancer, in which tamoxifen caused inhibition rather than regression, it was not possible to detect significant changes in the marker proteins Ki(67)and bcl-2, or in the prevalence of mitosis in relation to treatment; these factors may therefore not be accurate indices of response to tamoxifen in all situations. By contrast, however, tamoxifen induced a significant, early increase in the prevalence of apoptosis associated with inhibition of tumour growth and an inverse relationship in both mitosis and bcl-2 expression, suggesting that apoptosis may be an accurate and sensitive early marker of even a moderate response to tamoxifen.
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PMID:Tamoxifen increases apoptosis but does not influence markers of proliferation in an MCF-7 xenograft model of breast cancer. 1473 8

When does proliferating breast epithelium turn malignant? Single parameter analyses have not answered this question. We have tried to answer this through an analysis of immunohistochemical staining patterns in the following morphologically defined breast lesions: atypical ductal hyperplasia (ADH, 23 cases), papilloma (12 cases), ductal cancer in situ (DCIS, 28 cases), and mammographically detected small primary cancers (34 cases). The seven antibodies used were c-neu, bcl-2, p53, p21, CD44, MIB 1, and FAS. Staining patterns were compared within groups and between groups of lesions. Interesting differences in staining patterns were seen between invasive ductal cancer and invasive lobular cancer: invasive lobular cancer was less p53-positive and more CD44-positive than invasive ductal cancer. We found no common pattern in the different proliferating epithelia to show when they become malignant.
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PMID:Expression patterns of biologic markers in small breast cancers and preneoplastic breast lesions. 1473 79

Muscle invasion is the usual presentation of schistosomal squamous cell carcinoma of the urinary bladder. It is unclear whether this invasive behavior is secondary to the aggressive nature of the disease or to delay in diagnosis. Fixed paraffin-embedded hematoxylin and eosin-stained sections of 15 cystectomy specimens from 15 patients (14 males, 1 female) (age range, 40 to 67 years), histologically confirmed as schistosomal squamous cell carcinoma, were assessed for grade (G1, n = 3; G2, n = 7; G3, n = 5) and pathological stage (PT category: PT2, n = 4; PT3a, n = 9; PT3b, n = 2). Immunostaining was performed for mutant p53, bcl-2, HER2/neu, and MIB-1 (proliferation), using steam antigen retrieval and an avidin-biotin complex method. Frequency of strong immunoreactivity was high for mutant p53 (73%) and MIB-1 (87% intermediate or high) but low for bcl-2 (20%) and HER2/neu (27%). There was no significant correlation of any of the four markers with either grade or stage. Hence, schistosomal bladder squamous cell carcinoma is felt to be an aggressive carcinoma de novo. The high frequency of mutant p53 expression (73%) and an intermediate to high proliferation index (87%) suggests this. The lack of correlation between histological grade and all four markers studied suggests that grading is not of prognostic value.
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PMID:Muscle invasive schistosomal squamous cell carcinoma of the urinary bladder: frequency and prognostic significance of p53, BCL-2, HER2/neu, and proliferation (MIB-1). 1534 22

Somatostatin receptors (SSTRs) have been detected in many normal and malignant tissues. This wide expression has been used for diagnostic, prognostic and therapeutic purposes. Five SSTR subtypes (SSTR 1-5) have been identified whose activation is responsible for the signal transduction through many different intracellular pathways. In the present study the expression of SSTR mRNA was determined by reverse-transcriptase (RT)-PCR in 42 meningiomas. About 88% of the tumors analyzed (37/42) were positive for at least one of the five SSTR subtypes displaying a variable pattern of expression of the different SSTR subtypes. SSTRI and SSTR2 were the most frequently mRNA detected (69% and 79% of the sample analyzed, respectively). The other subtypes were found in the 43%, 33% and 33% of cases for SSTR3, SSTR4 and SSTR5, respectively. In 22, out of 42 patients (52%) three or more SSTRs were detected. The expression of the different SSTR subtypes did not correlate with the expression of bcl-2 (apoptosis-associated protein) and MIB-1 (a proliferation marker), assessed by immunohistochemistry in a series of 34 tumor samples, while a correlation between the expression of SSTR3 and p53 was observed (p = 0.08). To evaluate a possible role of SSTR in the control of human meningioma cell proliferation, seven primary cell cultures obtained from fresh meningioma surgical tissues, were analyzed for their proliferative behavior by MTT assay and for their response to SST by [3H]-thymidine incorporation. In four out of six tumors (in one case no SSTR were detected) the treatment with SST caused a significant inhibition of DNA synthesis induced by the tumor-promoter phorbol myristate acetate. The evidence of the expression of SSTRs, mainly of SSTR2, in this series of specimens we analyzed altogether with in vitro antiproliferative effects of SST may open interesting perspectives for the diagnosis and the therapy of meningiomas.
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PMID:Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity. 1501 81

Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) account for nearly all pediatric nonlymphoblastic B-cell lymphomas. Because clinical behavior, prognosis, and response to therapy might differ, diagnostic accuracy is important. Morphologic examination often is sufficient, but occasionally, diagnostic ancillary studies are required. In adults, immunophenotyping is useful; however, pediatric data are limited. We characterized the immunohistochemical expression of 6 proteins (c-myc, CD10, bcl-6, bcl-2, CD138, and MIB-1) in pediatric BL (33 cases) and DLBCL (20 cases) with classic morphologic features. Significant differences in c-myc (BL, 30/33 [91%] vs DLBCL, 5/20 [25%]; P < .0001), bcl-2 (BL, 1/25 [4%] vs DLBCL, 7/19 [37%]; P < .02), and mean MIB-1 (BL, 99% vs DLBCL, 56%; P < .0001) expression were observed. There were no significant differences for CD10 (100% expression in BL and DLBCL), bcl-6 (BL, 23/33 [70%] vs DLBCL, 15/20 [75%]), or CD138 (no expression). Thus, pediatric BL and DLBCL have distinctive immunohistochemical profiles, and staining for c-myc, MIB-1, and bcl-2 might be useful in morphologically difficult cases.
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PMID:Comparative immunohistochemical analysis of pediatric Burkitt lymphoma and diffuse large B-cell lymphoma. 1502 43

The purpose of the present study was to analyze the relation between the expression of p53, bcl-2, p21WAF1, MIB-1, HER-2/neu, DNA ploidy and HPV16 or 18 infections with clinical parameters. HPV-DNA was evaluated in 171 early cervical carcinomas treated from 1965 to 1990 and detected by PCR (polymerase chain reaction) on paraffin specimens obtained before therapy was started. HPV-DNA of any type was detected in 78% (86/110) of all tumors, HPV16 was the predominant type and was seen in 56% (62/110), HPV18 in 8% (9/110) and HPV35 in 21% (23/110). Patients with HPV16 or 18 were significantly (P=0.011) younger than patients with tumors not containing these two HPV subtypes. Lymph node metastases were seen more frequently (P=0.047) in tumors expressing HPV16 or 18. Tumor size was associated with the HPV-type. The frequency of DNA aneuploidy was lower in high-risk HPV tumors than in tumors with other HPV subtypes (P=0.014). MIB-1 expression was highly significantly (P=0.00007) associated with presence of HPV16 or 18. The cancer-specific survival rate was lower for patients with HPV16 and 18 positive tumors, but the difference was not statistically significant. The overall 5-year survival rate of the complete series was 91%. In conclusion, the HPV DNA subtype was a prognostic factor in early stage cervical cancer and it was associated with age, positive lymph nodes, tumor size, DNA ploidy and the proliferation marker MIB-1.
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PMID:Relation between HPV-DNA and expression of p53, bcl-2, p21WAF-1, MIB-1, HER-2/neu and DNA ploidy in early cervical carcinoma: correlation with clinical outcome. 1520 79

Through careful clinicopathologic correlation, we identified 37 metastatic melanomas in the skin, all of which had intraepidermal components. These were compared with 43 microscopically similar primary melanomas with a predetermined panel of immunostains in general use in surgical pathology, including bcl-2 protein, mutant p53 protein, Ki-67 (MIB-1), proliferating cell nuclear antigen (PCNA), alpha-isoform actin, and CD117 (c-kit protein). There was no significant difference in bcl-2 or alpha-isoform actin staining patterns of primary vs secondary cutaneous melanomas. The expression of Ki-67 generally was higher in metastatic melanomas than in primary lesions, and the same was true of mutant p53 protein labeling; however, some overlap was observed. CD117 staining was retained in 65% of metastatic melanomas (24/37) when they originated from ocular primary tumors; nevertheless, that marker was lost in virtually all of the other metastatic melanocytic neoplasms, whereas primary melanomas demonstrated consistent reactivity for c-kit protein. Although they are not definitive, these trends in immunoreactivity could facilitate the process of distinguishing the multiple primary melanoma syndrome from melanomatous metastases to the skin. That undertaking is best approached with circumspection, because clinicopathologic discriminators for this diagnostic separation are still imperfect.
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PMID:Primary melanoma of the skin and cutaneous melanomatous metastases: comparative histologic features and immunophenotypes. 1527 32

A case of synchronous multiple thymomas is reported. The patient was an 81-year-old woman with 2 separate thymomas in the anterior mediastinum. A histological study revealed that both thymomas consisted of dense lymphocyte infiltration in the stroma and a small number of polygonal epithelial tumor cells with clear nuclei and distinct nucleoli. Immunohistochemical staining using the antibodies to 2 antigens, bcl-2, and MIB-1 showed identical staining patterns. In spite of these findings, we considered their origin to be synchronous multicentric development rather than intra-thymic metastasis, based on the non-invasive nature of these tumors.
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PMID:Synchronous independent bifocal orthotopic thymomas. A case report. 1574 41

Serrated adenomas of the colon are characterized by epithelial neoplasia combining the architectural features of hyperplastic polyps and the cytological features of adenomas. Cell turnover, which is related to the malignant potential of these polyps, has not been thoroughly investigated. The aim of this study was to investigate epithelial cell proliferation, apoptosis, and oncoprotein expression in serrated adenomas. Twenty-five hyperplastic polyps, 25 serrated adenomas, and 25 tubulovillous adenomas resected from the colons of 75 patients were studied by immunohistochemical staining using monoclonal antibodies against MIB-1, Bcl-2, Bax, p53, and the TUNEL method for the detection of apoptosis. In serrated adenomas, the proliferation rate was significantly lower than in tubulovillous adenomas in both the lower and the upper parts of the crypts, and higher than that of hyperplastic polyps. Apoptosis was also significantly lower in serrated than in tubulovillous adenomas, but higher than in hyperplastic polyps. p53 oncoprotein expression was significantly greater in both serrated and tubulovillous adenomas than in hyperplastic polyps. bcl-2 protein expression was higher only in tubulovillous adenomas. Bax index was significantly different between tubullovillous and serrated adenomas, but the lowest values were observed in hyperplastic polyps. Serrated adenomas are highly proliferative polyps. They should be considered a biologically different entity from hyperplastic polyps. The intermediate features between serrated adenomas, hyperplastic polyps, and tubulovillous adenomas using the antibodies analysed in this study could have implications for the rate or the mechanism of development of malignancy in this type of polyp.
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PMID:Cell turnover of serrated adenomas. 1575 Oct 53

Pediatric glioblastoma multiforme (GBM) tumors, which have been established as 'de novo' neoplasms, are known to differ from their adult counterparts in terms of biology, genetics and ultimately survival of patients. In order to evaluate the utility of markers of tumor biology for refining prognostic assessment, we retrospectively analyzed 54 pediatric GBMs (age range 9 months to 15 years) occurring at different anatomical sites in the brain, operated at our institute between 1995 and 2001. The expression of p53, epidermal growth factor receptor (EGFR), bcl-2 and retinoblastoma proteins (pRb) was analyzed by immunohistochemistry and the results were compared with the clinical profile, MIB-1 labeling index (LI) and patient survival. p53 immunoreactivity was noted in 53.7% of cases, predominantly in thalamic (75%) and cerebral lobar (62.2%), followed by brainstem tumors (30%). It was absent in cerebellar tumors. p53-positive tumors had a higher MIB-1 LI, compared to p53-negative tumors (p=0.003). EGFR and bcl-2 overexpression was observed in 25.9% and 33.3% of cases, respectively, and loss of pRb expression was evident in only 7.4% of cases, indicating that loss of this gene function is not significantly involved in pediatric GBMs. p53 and bcl-2 expression were maximally noted in patients with poorer outcome. Our results indicate that p53 expression status is noted in a significant number of pediatric supratentorial neoplasms. p53 with bcl-2 overexpression is more often associated with ominous prognosis. Further molecular characterization would provide newer insights into the biology of these neoplasms and form a basis for future therapeutic decision making.
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PMID:Expression of p53, EGFR, pRb and bcl-2 proteins in pediatric glioblastoma multiforme: a study of 54 patients. 1629 48


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