Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interest in translational studies on breast cancer is presently devoted to identifying biological predictors of disease prognosis and response to treatment. In this study, we determined the plasma levels of bcl-2 and nitric oxide in 45 patients with metastatic breast cancer using an ELISA technique and correlated them with clinical and biological factors that may affect the outcome of disease. The results were as follows. The mean level of bcl-2 was 278.44 +/- 383.2 U/L compared with 64.42 +/- 14.4 U/L (p = 0.007) for controls. Levels of bcl-2 were higher in patients less than 50 yr old, premenopausals., GIII tumors, positive nodes, ER positive tumors (p = 0.6, 0.5, 0.9, 0.4, and 0.005, respectively). The site of metastatic disease and the number of metastatic sites did not show statistically significant influences over bcl-2 levels. Furthermore, there was a trend, although not significant, toward improvement of survival in patients with higher levels of bcl-2. The mean level of the nitric oxide (NO) was 297.12 +/- 220.54 microM compared with 13.91 +/- 1.1 microM for controls (p = 0.003). The levels were higher in patients over 50 yr, postmenopausal patients, those with visceral deposits, grade III tumors, positive lymph nodes, and those with disease-free survival of less than 6 mo following primary treatment (p = 0.1, 0.2, 0.1, 0.09, 0.4, and 0.08 respectively). Furthermore, there was no correlation between NO levels and survival (r = 0.002). This study demonstrates a potential role for NO and bcl-2 as prognostic factors in patients with metastatic breast cancer. However, larger studies with more patients together with a comparison of serum levels (ELISA) and tissue levels (MOAb) are still required.
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PMID:Plasma bcl-2 and nitric oxide: possible prognostic role in patients with metastatic breast cancer. 1191 41

Several studies have shown that extracellular matrix reduces chemotherapeutic drugs-induced apoptosis in small cell lung cancer cells, myelomas and gliomas. We have investigated the protective effect of defined extracellular matrix components and of extracellular matrix from different cell types (fibroblasts, hepatocytes and intestinal epithelial cells) on the toxicity of three types of chemotherapeutic drugs on colon cancer cells. Human colon cancer cell lines LS174T and LiM6 were plated on plastic, on hepatocyte-derived ECM or on stromal ECM and in the presence of the antimetabolite 5-fluorouracil (5-FU). the topoisomerase I inhibitor camptothecin and the topoisomerase II inhibitor etoposide. We determined IC50 for the drugs for each of these culture conditions. We also determined the expression of the anti-apoptotic proteins bcl-2 and bcl-x (L) under these culture conditions. We found that stromal ECM protected LiM6 cells from the toxicity of etoposide and LS174T, but not LiM6 cells, from the toxicity of camptothecin. Collagen 1, fibronectin and fibroblast-derived ECM rendered LiM6 cells, but not LS174T, more sensitive to the harmful effect of 5-FU. Both colon cell lines had increased expression of anti-apoptotic proteins bcl-2 and bcl-x(L) when cultured on the various ECMs and with the drugs, but there was no correlation between a protective ECM effect and expression of the anti-apoptotic proteins. Stromal-derived ECM may protect colon cancer cells from etoposide and camptothecin-induced apotosis, through a mechanism that is not bcl-2 or bcl-x(L) dependant.
Clin Exp Metastasis 2002
PMID:Stromal extracellular matrix reduces chemotherapy-induced apoptosis in colon cancer cell lines. 1191 83

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

Apoptosis dysfunction in metastases has been suggested to participate in their poor response to conventional anticancer treatments. To address this question, we have analyzed the sensitivity to cell death induced by non-steroid anti-inflammatory drug, Sulindac, the most common drug used in colon cancer chemotherapy, 5-fluorouracil (5-FU) and the short chain fatty acid, butyrate (Bu) in cell lines derived from a primary colorectal tumor (ALT-I) as well as the liver (ALT-F) and the lymph-node (ALT-G) metastases. We have previously shown both in vitro by analyzing anchorage-independent cell proliferation and in vivo by subcutaneous injection into athymic nude mice that the ALT-F and ALT-G cells were more tumorigenic than the primary ALT-I cells. All these cell lines, derived from an untreated patient, were highly resistant to apoptosis induced by 5-FU and Sulindac but were sensitive to Bu-induced apoptosis. The resistance to apoptosis was, as quantified by the induction of caspase activity and the relative percentage of apoptotic cells, higher in the metastatic cell lines, than in the ALT cell line. When compared to the primary tumor, more anti-apoptotic bcl-2 and less pro-apoptotic bax were expressed in the liver and lymph node metastatic cell lines. Quite remarkably, the expression of bax was up-regulated during Bu-treatment, a feature that could explain its powerful pro-apoptotic activity.
Clin Exp Metastasis 2002
PMID:Resistance to apoptosis is increased during metastatic dissemination of colon cancer. 1196 82

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

It has been shown that atypical reactive bile ductules (ARBD) display positive immunoreactivity of neural cell adhesion molecules (NCAM) and bcl-2. We investigated the clinicopathological features of intrahepatic cholangiocarcinoma (CC) arising in cases of viral hepatitis B or C (VHBC) and examined their relation to ARBD by means of immunohistochemical analysis. Sixty-eight surgical cases with CC were included in this study. The cause of the background liver disease was hepatitis B surface antigen (HBsAg)(+) in eight cases, antihepatitis C virus antibody (HCVAb)(+) in 13 cases, both HBsAg(+) and HCVAb(+) in one case, and both HBsAg(-) and HCVAb(-) in 46 cases. The average age of patients with CC arising in the HBsAg(+) group was significantly less than that of patients with CC in the HCVAb(+) group (P = 0.0192). Immunohistochemically, CC arising in the HBsAg(+) and HCVAb(+) groups was correlated with coexpression of NCAM/bcl-2 in the tumor cells (P = 0.0068 and P = 0.0382, respectively). Among the 12 cases of CC coexpressing NCAM/bcl-2, 11 were of mass-forming and peripheral type (P = 0.0437), and lymph node metastasis was a rare finding compared with CC showing negative coexpression of NCAM/bcl-2 (P = 0.0213). The tumor cells of CCs arising in VHBC have some characteristics of ARBD. In such tumors, because lymph node metastases were rarely seen and lymph node dissection did not improve patient's survival, lymph node dissection can be limited.
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PMID:Coexpression of neural cell adhesion molecules and bcl-2 in intrahepatic cholangiocarcinoma originated from viral hepatitis: relationship to atypical reactive bile ductule. 1203 Oct 86

The objective of this study was to assess the value of p53, bcl-2, and p21(WAF1/CIP1) immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21(WAF1/CIP1). None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21(WAF1/CIP1) appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
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PMID:Immunohistochemical expression of p53, bcl-2, and p21(WAF1/CIP1) in early cervical carcinoma: correlation with clinical outcome. 1206 Apr 51

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

Recent technological advances now allowing both large scale data generation and its in-depth analysis have opened new avenues to identify and target genes involved in neoplastic transformation and tumor progression. This accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anti-cancer agents. It is anticipated, that these agents will show enhanced specificity for malignant cells and a more favorable side-effect profile due to well-defined and tailored modes of action. Antisense oligonucleotides (ASOs) are short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene are close, after decades of challenges, close to fulfilling their promise in the clinical setting. Emerging clinical evidence supports the notion that ASOs stand a realistic chance of developing into one of the main players of rationally designed anti-cancer agents, although certainly not all of the challenges have been met to date. The status of antisense targeting of genes relevant to prostate cancer, including bcl-2, bcl-xL, clusterin, androgen receptor (AR) and IGFBPs, are reviewed.
Cancer Metastasis Rev 2002
PMID:Antisense therapy: current status in prostate cancer and other malignancies. 1240 Sep 97

The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include 1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor; 2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion; 3) inducing differentiation of cancer cells; 4) suppressing nuclear factor-kappaB activation and bcl-2 expression, thus allowing apoptosis of cancer cells; and 5) reducing cancer-induced cachexia. It seems reasonable to assume that after appropriate cancer therapy, consumption of omega-3 fatty acids might slow or stop the growth of metastatic cancer cells, increase longevity of cancer patients and improve their quality of life.
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PMID:Omega-3 fatty acids to augment cancer therapy. 1242 78


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