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)

Our purpose was to determine the predictive value of tumor biologic parameters in patients with HRPBC who received HDCT with ASCT as first-line treatment. From September 1992 to May 2000, 149 stage II or III HRPBC patients were enrolled in a single-arm trial using a tandem HDCT regimen followed by ASCT. Her2/neu, p53, Ki67 and bcl-2 protein expression was studied using immunohistochemic staining on formalin-fixed, paraffin-embedded primary tumor sections. DNA content of tumor cells (DNA index) and tumor cell proliferation (SPF) were measured by DNA flow cytometry. The relationship between these tumor biologic parameters, on the one hand, and DFS, DDFS and OS, on the other, was analyzed. With a median follow-up of 43 months (range 7-106), p53 protein accumulation (p = 0.000004), negative combined hormone receptor status (p = 0.003) and Her2/neu overexpression (p = 0.02) were significant negative predictors of OS in univariate analysis. A poorer DFS was associated with p53 positivity (p = 0.04) and nodal ratio > or = 0.8 (p = 0.008). Poorer DDFS was associated with p53 positivity (p = 0.03). In multivariate analysis, Her2/neu overexpression (RR = 3.86, 95% CI 1.48-10.1, p = 0.006) and p53 overexpression (RR = 6.06, 95% CI 2.22-16.52, p < 0.001) proved to be independent predictors of adverse OS. p53 overexpression was the only independent predictor of DFS (RR = 2.21, 95% CI 1.07-4.57, p = 0.03). p53 overexpression and Her2/neu overexpression are independent negative predictors of survival in HRPBC treated with HDCT. The adverse impact of these biologic features was probably not altered by HDCT. For HRPBC patients with tumors not overexpressing Her2/neu or p53, HDCT may be an appropriate approach to achieve long-term survival and tumor control.
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PMID:P53 is the strongest predictor of survival in high-risk primary breast cancer patients undergoing high-dose chemotherapy with autologous blood stem cell support. 1211 43

Metastasized neuroendocrine tumors of the gastrointestinal tract and of unknown origin show a highly variable clinical course. Within this group, low-grade and high-grade malignant tumors can be recognized based on the revised classification of neuroendocrine tumors of the lung, pancreas, and gut published by Capella et al in 1995. The present study investigated whether fine-tuning the prediction of prognosis was possible by dividing the group of low-grade malignant tumors of the midgut and of unknown origin into typical and atypical carcinoids by grading them according to the World Health Organization (WHO) classification criteria for neuroendocrine tumors of the lung. Moreover, the prognostic value of immunohistochemical stainings and clinical parameters was evaluated. The study group comprised patients diagnosed between 1983 and 1999 with liver metastases of a neuroendocrine tumor of the midgut n = 40) or of unknown origin (n = 16). As a control for the consistency of grading, 10 patients with metastasized neuroendocrine tumors of the lung also were evaluated. Immunohistochemical stainings for chromogranin A, synaptophysin, Leu 7/CD57, neural cell adhesion molecule/CD56, cytokeratin 8, bcl-2, p53, ki67, and HER2/neu were performed. The clinical parameters age, gender, urinary 5-HIAA level, and presence or absence of the carcinoid syndrome were evaluated. Tumors of the midgut and of unknown origin were evaluated together, because they were clinically similar. In this group of 56 patients, both the Capella and the WHO classification systems recognized the high-grade malignant tumors with a bad prognosis. When the low-grade malignant tumors (Capella) were divided into typical and atypical carcinoids (WHO), no difference in survival was observed, but when the dichotomy into typical and atypical was based on mitotic count alone, the difference became borderline significant (P =.072). Of the immunohistochemical stainings used, synaptophysin, cytokeratin 8, and ki67 had limited prognostic value. Age above 60 was the only clinical parameter of unfavorable prognostic significance. We conclude that high-grade malignant neuroendocrine tumors of the midgut and of unknown origin are recognized by both the Capella classification and the WHO classification of neuroendocrine tumors of the lung. Further subdividing low-grade malignant tumors at this location appears to be of less value than in the lung, but assessing the mitotic activity of these tumors might be of prognostic value.
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PMID:Classification of low-grade neuroendocrine tumors of midgut and unknown origin. 1245 18

The aim of this study was to perform a clinical and immunohistochemical comparison between simultaneous independent tumors involving endometrium and ovary and metastatic endometrial tumors, and to try to find clinical and /or immunohistochemical parameters differentiating between these two entities. Sixteen cases of simultaneous independent primaries of endometrium and ovary, presenting the same histologic type, were compared with 12 cases of primary endometrial cancer, demonstrating ovarian metastases. The comparison related to patients' characteristics and immunohistochemical expression of estrogen and progesterone receptors (ER,PR), bcl-2, HER-2 /neu, p53, and cell proliferation marker Ki-67 in endometrial and ovarian tumors. The only clinical parameter differentiating significantly between the groups was the prevalence of familial cancer, being more frequent in the group of metastatic tumors (P = 0.03). Immunohistochemical analysis demonstrated the same immunostaining in endometrium and ovary for all immunohistochemical parameters in cases of metastatic endometrial cancer. Conversely, 62.5% of cases with simultaneous tumors of endometrium and ovary could be differentiated from metastatic tumors by distinct immunohistochemical expression of ER and PR in endometrial and ovarian tumors (P = 0.0006), and 31.3% of cases could be differentiated by distinct immunostaining for bcl-2 (P = 0.03). Immunohistochemical parameters HER-2 /neu, p53 and Ki-67 were not appropriate for the distinction between the two study groups. We conclude that the application of immunohistochemical analysis may play an important role in the differentiation between cases of simultaneous independent carcinomas of endometrium and ovary vs. cases of endometrial carcinoma with ovarian metastases.
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PMID:Simultaneous carcinoma of the endometrium and ovary vs endometrial carcinoma with ovarian metastases: a clinical and immunohistochemical determination. 1263 Dec 17

Thirty-two normal LEW/Sea rats were transplanted a piece of syngeneic pancreas between the peritoneum and abdominal muscle. Among them, 17 (68%) of the 25 rats that received pancreatic transplantation at 41-50 days of age had a surviving beta-cell mass at 5.5-7.1 months after transplantation. Among the 25 rats, 12 rats injected with interleukin-1 receptor (IL-1R) and IL-2Rbeta peptides at post-transplantation showed better surviving grafts at 5.5 months' observation. Only 2 (25%) of the other 7 young rats that received a pancreatic graft at 20 days of age had a small mass at 21 days post-transplantation. Flow cytometer (FCM) analyses showed that thymus OX40(+) (CD134(+)) T-cells were increased up to 37+/-4% at the graft rejection in the 13 old rats without the IL-R peptide injections. The 7 young rats had 99% of thymus OX40(+) T-cells. However, the 12 old rats injected with the IL-R peptides showed suppressed numbers of thymus OX40(+) T-cells (8-13+/-3%). The long-term surviving, but apoptotic, grafted beta-cells were stained positively both with anti-insulin monoclonal antibody (mAb) and with anti-c-erbB-2/human epidermal growth factor receptor (HER)-2/neu mAb. Expression of a c-erb family oncogene was shown on the pancreatic graft surviving for 7.1 months. Electron microscopic analysis of the grafted beta-cells showed abnormally large beta granules and loss of functioning mitochondria in the cytoplasm. In 18 (56%) of the 32 rats, the 220-bp and 380-bp specific products of insulin-degrading enzyme (IDE) gene were amplified using the polymerase chain reaction (PCR) of the liver DNA. Among the 18 rats, 6 rats expressed 2 extra hands of 280-bp and 700-bp in a correlation with the high levels of the transforming growth factor-alpha (TGF-alpha) cDNA of 120-bp which was amplified in the quantitative reverse-transcriptase (RT)-PCR of the liver cDNA. Among the selected 11 rats, 5 rats showed large amounts of the 120-bp TGF-alpha cDNA. Host pancreatic RT-PCR showed 235-bp or 250-bp bcl-2 and 181-bp bcl-xS gene products. The bcl-2 cDNA of the host pancreas was amplified actively when the pancreatic graft was being rejected. Exceptionally, the one female injected with the IL-R peptides showed a low level of the liver TGF-alpha cDNA together with the pancreatic expressions of Bax (140-bp), bcl-2 and like interleukin converting enzyme (LICE) (318-bp) cDNA. Insulin secretion from the grafted beta-cells and IL-1beta-induced Fas-mediated apoptosis of the beta-cells were suspected to be present at the same time in the female with the best graft survival.
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PMID:Oncogene expression on the syngeneic beta-cells of long-term surviving pancreatic grafts and better effects of interleukin-1 receptor (IL-1R) and IL-2Rbeta on the grafted beta-cells in LEW/Sea strain rats. 1272 75

This study characterizes 3 cases of mesenchymal chondrosarcoma (MC) utilizing a proteomic approach that allows for the detection, visual quantification, cellular compartmentalization, and assessment of the functional state of certain proteins that may promote tumor growth and/or oppose apoptosis. Immunohistochemical procedures were performed to detect the following protein antigens: CD99, interleukin (IL)-1alpha, IL-6, transforming growth factor (TGF)-alpha, conventional (c) protein kinase C (cPKC)-alpha, cPKC-betaII, phosphorylated (p)-PKC-alpha/betaII, c-kit (CD117), platelet-derived growth factor receptor (PDGFR)-alpha, PDGFR-beta, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)-2/neu, cathepsin D, angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor, p21ras, the alpha subunit of farnesyl and geranylgeranyl transferase (FTalpha/GGTalpha), phospho (p)-c-Jun N-terminal kinase (p-JNK), p-p38 mitogen-activated protein kinase (MAPK), cyclin D1, c-Jun, Ki-67, bcl-2, TGF-beta1 latency-associated peptide (LAP), TGF-betaRII, and cyclooxygenase (COX)-2. Immunoreactivities were scored from 0 to 3+ positivity using bright-field microscopy. The results showed that malignant mesenchymal chondroblasts exhibit stronger expressions of CD99, IL-1alpha, cPKC-alpha, p-PKC-alpha/betaII, PDGFR-alpha, p-JNK, Ki-67, and bcl-2 antigens than their more mature-appearing chondrocytic counterparts in MC. In conclusion, molecular profiling of mesenchymal chondrosarcoma using a proteomic approach characterized the mesenchymal chondroblasts as possessing pathways that incorporate PKC-alpha and PDGFR-alpha signaling and anti-apoptotic bcl-2 expression. Specific therapies to target the mesenchymal chondroblasts in mesenchymal chondrosarcoma might include interferon-alpha, rapamycin, ciprofloxacin, and STI571.
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PMID:Mesenchymal chondrosarcoma: molecular characterization by a proteomic approach, with morphogenic and therapeutic implications. 1281 16

Racial disparity in the presentation of breast cancer and the outcome of its treatment is well established. However, the causes remain unexplained. The scarcity of reports about the prognostic significance of p53, bcl-2, and HER-2/neu in Arab females with breast cancer has been the impetus to this study. We evaluated the prognostic significance of altered expression of p53, bcl-2, HER-2/neu in Omani Arab females with non-metastatic breast cancer with correlation to other established prognostic factors. We have retrospectively analyzed the immunohistochemical expression of p53, HER-2/neu and bcl-2 in paraffin embedded blocks of 72 females diagnosed with invasive breast cancer between 1992 and 2002. The expression of the above proteins was correlated with other prognostic factors and univariate and multivariate analysis was carried out for all prognostic factors. Overexpression of p53 significantly correlated with younger age (<40), pre-menopausal status, poor differentiation with inverse correlation with bcl-2 expression. Expression of bcl-2 immunopostivity significantly correlated to low histological grade and positive estrogen and progesterone receptor status. On univariate and multivariate p53 overexpression and lack of bcl-2 immunostaining resulted in worse survival outcome, but not Her-2/neu overexpression. Expression patterns of p53 and bcl-2 are independent predictors of survival in Omani Arab population which may help to stratify these patients into different risk groups.
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PMID:Significance of p53, Bcl-2, and HER-2/neu protein expression in Omani Arab females with breast cancer. 1468 28

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

Mammary small cell carcinoma (SmCC) is a very rare neoplasm with a poor prognosis compared with other invasive carcinomas. We studied the histological and immunohistochemical profiles of two cases of mammary SmCC, and compared them with those of five cases of carcinoma with endocrine features (CEF) and five cases of invasive ductal carcinoma (IDC), to elucidate the correct diagnosis of mammary SmCC. Immunohistochemical analysis was performed with antibodies against cytokeratins (CKAE1/AE3, CK34betaE12, CKCAM5.2, CK7, CK8, CK19, CK20), epithelial membrane antigen (EMA), vimentin, CD10, neural cell adhesion molecule (NCAM; CD56), neuron-specific enolase (NSE), chromogranin A, S-100 protein, carcino-embryonic antigen (CEA), E-cadherin, N-cadherin, thyroid transcription factor-1 (TTF-1), p53, estrogen (ER), progesterone (PR), HER2/neu, bcl-2, synaptophysin, calcitonin and Leu7. SmCCs were diffusely and strongly positive for NCAM in comparison with CEFs and IDCs. SmCCs were negative for vimentin, whereas CEFs and IDCs were positive. Neuro-endocrine carcinomas, including SmCCs and CEFs, were diffusely and strongly positive for NSE, compared with IDCs. Moreover, neuroendocrine carcinomas were negative for CK34betaE12, CK20 and CD10, whereas IDCs were positive. Our study suggests that NCAM and vimentin are useful markers for the diagnosis of mammary SmCC. CK34betaE12, NSE, CD10, CK20 and chromogranin A appear to be useful for differentiating neuroendocrine carcinoma from IDCs.
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PMID:Comparative study of primary mammary small cell carcinoma, carcinoma with endocrine features and invasive ductal carcinoma. 1501 Aug 80

The recent observation that studies of BRCA1-associated tumors contain a high proportion of medullary carcinomas and ductal carcinomas with medullary features has re-introduced pathologists to an old diagnostic problem. The term "medullary carcinoma" dates to the 19th century, but the modern entity was introduced in 1949 by Moore and Foote, who described a carcinoma with a lymphoid infiltrate, a favorable prognosis, and low frequency of metastasis. Almost three decades later, Ridolfi et al proposed specific criteria for diagnosis, resulting in an entity with an even more favorable prognosis and a lower incidence. The reproducibility and clinical relevance of the diagnosis have been questioned recently, and new criteria have been proposed and compared. The tumors typically express cytokeratin 7, often vimentin and S100-protein, but not cytokeratin 20. The usual ones are positive for p53 and negative for estrogen receptor, Her2/neu, and bcl-2. Medullary carcinomas express e-cadherin and beta-catenin more often than ordinary high-grade ductal carcinomas, and the former have genetic differences from the latter. The lymphoid infiltrate of medullary carcinomas is related to beta-actin fragments exposed by apoptotic cells. The present review discusses historical and recent developments and emphasizes diagnostic criteria.
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PMID:Medullary carcinoma, provocative now as then. 1507 61


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