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)

For the typical patient who has newly diagnosed prostate cancer, clinically organ-confined disease of moderate grade, and a PSA less than 10 ng/mL, the current role of imaging studies and molecular biomarkers is limited. Bone scans are not necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful diagnostic or staging information when the PSA is less the 20 ng/mL and is indicated rarely. Endorectal coil MR imaging adds staging information for patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and 50% or more positive biopsies on a sextant sampling. Indium 111 capromab pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed patients at high risk for metastases. These patients have a Gleason score of 7 or greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater. RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer-specific gene expression, or "molecular staging," is a promising technique whose current use is still investigational. Much useful information may be gained by careful study of prostate needle biopsy material. Aside from current Gleason grading and the number or percentage of cores involved with cancer, no molecular biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the assessment of neovascularity hold promise, but prospective multicenter studies are needed. In the long-term, multiple gene expression profiling of biopsy material using gene chips may revolutionize the care of patients with prostate cancer and those who elect radical prostatectomy.
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PMID:The role of imaging studies and molecular markers for selecting candidates for radical prostatectomy. 1159 Aug 6

Programmed cell death (apoptosis) may play a role in tumor development and progression. The importance of apoptosis dysregulations in ductal carcinoma in situ (DCIS) and its relationships with p53 mutations and expression of bcl-2 has received little attention in the literature. In a series of 58 DCIS patients, we evaluated the number of apoptotic cells by the TUNEL technique in subgroups of DCIS and correlated it with immunohistochemical expression of hormone receptors, c-erbB-2, p53, bcl-2, and Ki-67 (MIB-1) and DNA content measured by image cytometry. High apoptotic index (greater than 3%) was related to high tumor grade, negative hormone receptors, c-erbB-2 overexpression, aneuploidy and lack of bcl-2 immunohistochemical stain. Apoptosis was not related to p53 or proliferative index. The findings are similar to those found in infiltrating breast cancer.
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PMID:Apoptosis in ductal carcinoma in situ of the breast. 1167 2

We investigated the expression of oncogenes p53, c-erbB-2, and bcl-2 and cell proliferative activity in 62 newly diagnosed superficial pTa papillary bladder tumors. Based on the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications, 19 were urothelial neoplasias of low malignant potential (LMP) and 43 low-grade (grade 1) papillary carcinomas. All the patients underwent transurethral resection and were followed up to 97 months; 42 had recurrences. Initial biopsies were tested for p53, c-erbB-2, and bcl-2 proteins using DO7, CB11, and bcl-2 124 monoclonal antibodies. Cell proliferation was assessed by MIB-1 mAb and mitotic count. LMP had significantly lower MIB-1 (p = 0.002) and p53 immunopositivity (p = 0.03), mitotic count (p = 0.006), and recurrence rates (p = 0.04) than did grade 1 cases, whereas no difference was observed for c-erbB-2 and bcl-2 expression. The median disease-free survival for LMP was 76 months but only 15 months for grade 1 cases (p = 0.002). Although the cohort is small, the results indicate that the distinction between LMP and low-grade (grade 1) papillary urothelial neoplasias, as proposed by the 1998 WHO/ISUP and 1999 WHO classifications, reflects different biologic activity and clinical behavior; however, a long-term follow-up is advisable also for patients with LMP.
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PMID:Biologic differences between noninvasive papillary urothelial neoplasms of low malignant potential and low-grade (grade 1) papillary carcinomas of the bladder. 1171 43

Leydig cell tumors of the testis are rare, mostly presenting as a testicular mass or as endocrinological symptoms. Here, three patients who were admitted for investigation of primary infertility and one patient presenting with a testicular mass are reported. The histological features were reviewed and an immunohistochemical study was done using a panel of antibodies against cytokeratin, vimentin, inhibin A, S-100, Ki-67, follicle-stimulating hormone, luteinizing hormone, prolactin, p53, bcl-2, and c-erbB2. The latter case (lost during follow up of metastatic disease) demonstrated massive tumor necrosis, extension through the tunica albuginea, and a high mitotic activity and MIB-1 score. Only this malignant case was bcl-2 positive. Of the two oncogenic markers studied, none of the cases were positive for c-erb2, while p53 was positive in more than 50% of cells in the malignant case and in one case of infertility with a large tumor, hemorrhage, focal necrosis and atypical cytological features. We recommend the evaluation of infertile men for Leydig cell tumors, and we believe that a panel of antibodies, including Ki-67, p53 and bcl-2, used for immunohistochemical analysis could be of diagnostic value in the identification of malignant and borderline cases of Leydig cell tumor.
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PMID:Leydig cell tumor of the testis: comparison of histopathological and immunohistochemical features of three azoospermic cases and one malignant case. 1188 32

Recent reports have shown that gamma-knife radiosurgery provides a safe and effective strategy for the management of brain tumors. To evaluate the role of stereotactic radiosurgery in the management of meningiomas, we investigated the histopathology of two patients. The patients, a 37-year-old man and a 54-year-old woman, presented with visual field disturbance or headache. Imaging studies demonstrated intracranial meningiomas--tentorial and sphenoid ridge, respectively. Each patient undewent subtotal surgical resection (more than 90% in both patients), followed by gamma-knife radiosurgery of the remnant tumor marginal doses of 15 Gy. Pathological examination of the original tumors revealed a meningothelial meningioma and an atypical meningioma, respectively. Enlargement of the remnant tumors 4 months after radiosurgery resulted in total surgical resection in both patients. Thirteen months later, the patient with the atypical meningioma underwent a third operation for early recurrence of the tumor. Histopathology was investigated, and MIB-1, p53, and bcl-2 labeling indexes (LI) were analyzed immunohistochemically. Histopathologically, the specimens showed necrosis and intratumoral vessel obliteration after radiosurgery in both cases. However, more remnant tumor cells survived in the atypical meningioma. Immunohistochemically, increased wild-type p53, decreased bcl-2 expression, and decreased MIB-1 LI were observed in the benign meningioma. In the atypical meningioma, on the contrary, MIB-1 LI was decreased and mutant-type p53 and bcl-2 expression were unchanged. The specimen from the third operation revealed an anaplastic meningioma, and MIB-1 LI was markedly increased. These findings suggest that the efficacy of radiosurgery may differ between benign and atypical meningiomas.
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PMID:Different responses of benign and atypical meningiomas to gamma-knife radiosurgery: report of two cases with immunohistochemical analysis. 1190 75

A complete series of 40 cervical carcinomas with pelvic lymph node metastases were analysed immunohistochemically for prognostic markers. The aims of this study were to examine whether the detection of MIB-1, p53, bcl-2, and WAF-1 could be used as a prognostic marker for tumor recurrence and survival rate. During the period of observation (mean 222, range 72-360 months) 22 (55%) recurrences were encountered and 20 patients died of the disease. There were 35 squamous cell carcinomas (87.5%), 2 adenosquamous carcinomas (5.0%), and 3 pure adenocarcinomas (7.5%). One tumor (2.5%) was well differentiated, 12 tumors (30%) were moderately differentiated, and 27 tumors (67.5%) were poorly differentiated. The primary tumor grade (P=0.037) and radicality of the surgical margins (P=0.021) were significant prognostic factors with regard to tumor recurrence. The site and number of lymph nodes with metastases had no prognostic value. P53, bcl-2, and WAF-1 were not predictive factors for recurrences or the cancer-specific survival rate. The concordant expression of WAF-1 in the primary tumor and in lymph node metastases was lower than for p53 and bcl-2. The proliferative activity (MIB-1) seemed to be lower in tumor cells metastasized to the pelvic lymph nodes than in cells of the primary tumor. Expression of MIB-1 in lymph nodes was predictive of disease-free survival in both univariate and multivariate proportional hazard Cox analyses.
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PMID:MIB-1, p53, bcl-2, and WAF-1 expression in pelvic lymph nodes and primary tumors in early stage cervical carcinomas: correlation with clinical outcome. 1195 2

The clinical behaviour of melanoma is often unpredictable using clinical and histological criteria. Tumour cell markers related to cell cycle regulation, apoptosis, cell-cell interactions and cell proliferation might improve the possibility of predicting the clinical course of melanoma. The aim of the present study was to refine prognostic criteria by an immunocytochemical investigation of CD44, CD40, bcl-2 antigens and cell proliferation in tumour cells aspirated from metastases of malignant melanoma. CD40 is a cell surface receptor shown to be expressed by lymphomas as well as carcinomas, and is thought to play a central role in the process of tumour progression. CD44 is a transmembrane glycoprotein, which is involved in growth signal transmission of importance in the binding of tumour cells to endothelium, cell migration and enhancement of cell motility, which makes it of interest to study in relation to the metastasizing capacity of tumours. The bcl-2 protein is active in the process of programmed cell death (apoptosis) as an antiapoptotic agent and its expression may reflect tumour progression. Mean/median percentages of tumour cell positivity were 8.5/3.0 for CD40, 76.1/86.3 for CD44 and 7.4/3.3 for bcl-2. A significant correlation was observed between expression of apoptosis-associated bcl-2 antigen and overall survival (r = 0.33). The CD44 positive cell fraction was higher in patients with short overall survival than those with long survival but this difference was not statistically significant. The expression of CD40 did not correlate with overall survival. The mean/median proliferation fraction assessed by MIB-1 monoclonal antibody was 25.8/23.9 and showed a significant correlation with survival after diagnosis of melanoma metastasis (r = 0.32). Lack of bcl-2 expression and a high proportion of tumour cells expressing Ki-67 antigen are predictors of poor prognosis that are independent of the traditionally accepted Breslow's thickness of the primary melanomas.
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PMID:Expression of CD40, CD44, bcl-2 antigens and rate of cell proliferation on fine needle aspirates from metastatic melanoma. 1198 64

There appears to be a relationship between mitotic activity and malignant behavior in adrenocortical tumors, and carcinomas with a high mitotic index may have a poorer prognosis. This has been investigated further by quantifying and comparing the Ki-67 index using antibody MIB-1 in a series of 14 adrenocortical adenomas and 40 carcinomas. The levels have been correlated with survival and disease-free survival in carcinomas and with evidence of abnormal p53 expression as detected by immunohistochemistry. Nevertheless, many carcinomas have a low level of proliferation that may reflect varying abnormalities within the regulation of both cell division and apoptosis. Expression of bcl-2 protein, an inhibitor of apoptosis has therefore also been examined. The Ki-67 index in carcinomas was significantly higher than in adenomas, but below 4% there was overlap. There was no significant difference in survival between carcinomas with MIB-1 index <3% and those greater, but the lower group had significantly longer disease-free survival (p = 0.02). There was no significant difference between p53 immunopositive and p53 immunonegative carcinomas. No tumor showed immunopositivity for bcl-2 protein. It is concluded that MIB-1 index may contribute additional prognostic information in adrenocortical tumors. Inhibition of apoptosis by bcl-2 does not appear to play a role in tumor growth.
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PMID:Proliferation in Adrenocortical Tumors: Correlation with Clinical Outcome and p53 Status. 1211 69

Identification of patients with a low grade glioma with a long-term recurrence-free survival is of clinical value as radiotherapy can be postponed until recurrence. The recurring glioma may increase in malignancy compared to the original tumor, which is possibly related to radiotherapy. We studied proliferation by counting mitotic figures and by MIB-1 labeling, apoptosis by TUNEL and expression of proteins related to cell cycle regulation by immunohistochemical analysis of p53, p21, bcl-2 and bax expression in 48 low grade gliomas. Astrocytomas (A, n = 14) and oligodendrogliomas (O, n = 4) with a recurrence-free survival of more than 9 years after surgery had a signficantly lower p53 index compared to A (n = 18) and O (n = 12) with a histopathologically documented recurrence. Additionally, the recurrence-free A had a higher p21 index. No significant differences were observed in MIB-LI, TUNEL-LI, bcl-2 and bax expression. Initially low grade gliomas and their corresponding recurrences were compared (n = 30). In the gliomas without radiotherapy (n = 15), no differences in mitotic rate, TUNEL-LI, p53, p21, bcl-2 and bax expression were found between primary tumors and their recurrences. Only MIB-LI was higher in the recurrent tumors. In the gliomas with radiotherapy (n = 15) no differences were detected in these parameters between the original tumor and the recurrent tumor except for a higher number of mitoses in the recurrent tumors. We conclude that low grade gliomas with a long-term recurrence-free survival were characterized by a low p53 protein expression and, in the case of A, a higher p21 index. We found no evidence that radiotherapy is involved in changes of proliferation, apoptosis or expression of proteins related to cell cycle regulation in recurring gliomas.
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PMID:Proliferation and apoptosis in long-term surviving low grade gliomas in relation to radiotherapy. 1216 88

Few studies have examined the role of cell proliferation and apoptotic markers in chordomas. This study retrospectively reviews the clinicopathologic features of 26 chordomas and examines MIB-1, p53, bcl-2, and cyclin D1 immunoreactivity in these neoplasms. Patients ranged in age from 34 to 78 years (mean, 60.7 years) and included 14 females. The most common presentations included lower back pain (N = 15) and headaches (N = 10). Sixteen tumors arose in the lumbosacral region and 10 in the clivus. Initial surgery included biopsy (N = 17), subtotal resection (N = 4), and gross total resection (N = 5). The single highest mitosis count per 10 high power fields ranged from 0 to 6 (mean, 1). Marked nuclear pleomorphism was identified in seven tumors. Marked hypercellularity was seen in two tumors. Focal necrosis was identified in seven tumors. MIB-1 labeling indices (LI) in 22 tumors ranged from 0 to 3.8 (mean, 0.5). Cyclin D1 LI ranged from 0 to 82.4 (mean, 35.6). Seven tumors had positive p53 immunostaining and three demonstrated focal positive staining with bcl-2 antibody. Five tumors locally recurred; two patients developed metastatic disease. Thirteen patients received adjuvant chemotherapy and/or radiation therapy. At last known follow-up, seven patients died with tumor (12 to 132 months follow-up). Five additional patients died, two without tumor at 36 and 72 months follow-up and three patients in whom the tumor status at death was not known. Seven patients were alive with evidence of tumor (1 to 120 months) and five patients were alive without evidence of tumor (12 to 84 months). Clinical follow-up was not available in one patient. In conclusion, the low MIB-1 LIs and the lack of p53 and bcl-2 staining is in keeping with the low-grade nature of most chordomas. High cyclin D1 LIs may be reflective of a tendency to accumulate cyclin D1 protein; however, there appears to be a block in the effect of cyclin D1 on cell proliferation in these tumors. Cyclin D1, MIB-1, p53, and bcl-2 immunostaining does not appear to improve one's ability to predict behavior versus routine light microscopy.
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PMID:Apoptotic and proliferative markers in chordomas: a study of 26 tumors. 1217 Apr 53


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