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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the expression of p21, the ras encoded protein, in primary tumour of 45 patients with papillary thyroid cancer (PTC). Patients were grouped according to outcome so that one group (31 patients) had a good outcome and the other (14 patients) a fatal outcome, after a follow-up of at least 5 years. The presence of p21 ras protein was assessed by immunohistochemistry with a specific monoclonal antibody (MAb Y-13259). The results were correlated with the outcome, with the expression of proliferating cell nuclear antigen (PCNA)/cyclin (as a marker of cell proliferation) and with other well established prognostic factors for PTC (age, grading, extension and tumour size; Endocrinol Metab Clin North Am 1990, 19, 545-576). p21 staining in tumours of living patients was negative in 15, weakly positive (1+) in 10 and strongly positive (2+ or more) in 6 patients. In tumours from deceased patients, p21 staining was negative in 1, weakly positive in 2 and strongly positive in the remaining 11 patients (P < 0.001, chi 2). PCNA immunostaining was increased in 63.6% (7/11) of the tumours from deceased patients compared to 17.8% (5/28) of the tumours of living patients, but no direct correlation was found between p21 and PCNA expression. Among the other prognostic factors studied, only age > or = 40 years was a significant predictor of poor outcome. The survival curve of patients with strongly positive p21 staining was similar to that of patients aged > or = 40 years at the time of diagnosis. The combination of p21 > or = 2+ and age > or = 40 was superior to age alone (P < 0.05) as a prognostic indicator of poor outcome. In conclusion, our results indicate that the p21 product of the ras (proto)oncogene is differently expressed in PTC, in relation to the degree of aggressiveness. Regardless of the pathogenetic role of the ras oncogene in thyroid tumorigenesis, our data indicate that the expression of the p21 ras protein may be regarded as a prognostic indicator in PTC. Furthermore, overexpression of p21 ras protein is associated with patients in the older age groups, and might contribute to the poor prognosis of elderly patients.
Eur J Cancer 1994
PMID:Expression of p21 ras protein as a prognostic factor in papillary thyroid cancer. 790 18

Gene amplification/overexpression was analyzed in 23 cell lines derived from human esophageal squamous-cell-carcinoma tissues by Southern and Northern hybridizations to c-myc, c-erbB, hst-1 and cyclin-D1 probes. Amplification of the c-myc gene was observed in 5 cell lines derived from well-differentiated carcinomas and all of them were accompanied by co-amplification of other examined oncogenes. The c-erbB gene was amplified in 3 cell lines. Co-amplification of hst-1 and cyclin D1, both of which are located in chromosome 11q13, was found in 9 cell lines. Without exception their amplification was simultaneous and the magnitudes were similar. Their amplification, but not their overexpression, was significantly correlated with poor prognosis in patients from whom the cell lines were established. While hst-1-gene expression was not detected, at least 1 of the genes analyzed was overexpressed in 20 cell lines vs. its expression in normal esophageal mucosal tissues. However, gene amplification was not necessarily accompanied by overexpression of the corresponding genes. Expression of the cyclin D1 gene, which has been assumed to be a target gene for 11q13 amplification, was not detected in one particular cell line with amplification of 11q13. These results suggest that the amplification/overexpression of more than I oncogene is involved in the carcinogenic process of esophageal carcinoma and that c-myc-gene amplification is associated with a well-differentiated subtype. There remains a possibility that key oncogenes other than cyclin D1 are involved in 11q13 amplification.
Int J Cancer 1994 Jul 15
PMID:Analysis of gene amplification and overexpression in human esophageal-carcinoma cell lines. 791 84

To evaluate the correlation between the polyamine metabolism and the degree of malignancy in hepatocellular carcinoma, we measured ornithine decarboxylase activity and polyamine concentrations in neoplastic tissue and adjacent noncancerous tissue from resected specimens of liver from 30 patients. Ornithine decarboxylase activity, polyamines (putrescine, spermidine and spermine) and ornithine decarboxylase mRNA levels were significantly higher in hepatoma tissue than in noncancerous tissue. The activity of this enzyme in the tumor tissue had a negative correlation with the histological degree of differentiation judged according to a modification of the Edmondson and Steiner classification. Resected hepatoma tissue was stained immunohistochemically with antibodies for proliferating cell nuclear antigen (also called cyclin), a marker of cell proliferation. We noted correlation between ornithine decarboxylase activity and the number of cells stained for this antigen (r = 0.882, p < 0.001). These results indicate that ornithine decarboxylase activity is high in human hepatocellular carcinoma, leading to increased intracellular concentrations of polyamines. Ornithine decarboxylase activity also reflected the rate of tumor proliferation and was correlated with the histological findings.
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PMID:Relationship of ornithine decarboxylase activity and histological findings in human hepatocellular carcinoma. 792 50

Cell kinetic data are an important adjunct to histologically based tumor classifications and provide reliable information about future tumor behaviour. The growth fraction of 62 transitional cell carcinomas was assessed using Ki-67 and PCNA (Proliferating cell nuclear antigen/cyclin) immunostainings. Ki-67 recognises an unknown nuclear antigen expressed in dividing cells and requires the use of frozen sections. PCNA, a non histone nuclear protein, identifies proliferating cells within fixed, embedded tissue sections. The percentage of labeled cells was expressed as the labeling index (LI). The median LI in normal urothelium and transitional cell carcinoma were 0.5% and 8%, respectively for Ki-67, and 1.5% and 12% for PCNA. A general agreement between indices of cell proliferation and histological grade and stage was demonstrated. Although some discrepancies were observed, there was a strong correlation between Ki-67 and PCNA Lis (r = 0.8308, P < 0.01). In addition, tumor EGFR positive had PCNA values greater than those found in cancer EGFR negative (P = 0.01). These findings suggest that immunohistochemical nuclear labeling with anti-PCNA on routinely processed tissue is a simple technique for the assessment of transitional cell carcinomas.
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PMID:PCNA/cyclin expression in transitional cell carcinomas of the human bladder: its correlation with Ki-67 and epidermal growth factor receptor immunostainings. 793 59

Progression of the eukaryotic cell division cycle is regulated by a series of structurally related serine/threonine protein kinases known as cyclin-dependent kinases (CDKs). The D-type cyclin-dependent kinases, CDK4 and CDK6, have been strongly implicated in the control of G1 progression and the phosphorylation of the retinoblastoma protein, pRb. The formation of complexes and enzymatic activity of cyclin D-CDK4 and cyclin D-CDK6 kinases is negatively regulated by p16INK4 (MTS1/CDK4I/CDKN2) via its specific interaction with CDK4 and CDK6 catalytic subunits. Here we report that the p16 mRNA accumulates to a high level in cells lacking pRb function and transcription of p16 is repressed by pRb. Our results provide evidence supporting a feedback regulatory loop involving pRb, p16, and cyclin-dependent kinases.
Cancer Res 1994 Dec 01
PMID:Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb. 795 50

Multiple genetic changes occur during the evolution of normal cells into cancer cells. This evolution is facilitated in cancer cells by loss of fidelity in the processes that replicate, repair, and segregate the genome. Recent advances in our understanding of the cell cycle reveal how fidelity is normally achieved by the coordinated activity of cyclin-dependent kinases, checkpoint controls, and repair pathways and how this fidelity can be abrogated by specific genetic changes. These insights suggest molecular mechanisms for cellular transformation and may help to identify potential targets for improved cancer therapies.
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PMID:Cell cycle control and cancer. 799 77

The p53-inducible gene WAF1/CIP1 encodes a M(r) 21,000 protein (p21) that has been shown to arrest cell growth by inhibition of cyclin-dependent kinases. Induction of WAF1/CIP1 in cells undergoing p53-dependent G1 arrest or apoptosis supports the idea that WAF1/CIP1 is a critical downstream effector of p53. In the present study, we used embryonic fibroblasts from p53 "knock-out" mice to demonstrate p53-independent induction of WAF1/CIP1. We show that serum or individual growth factors such as platelet-derived growth factor, fibroblast growth factor, and epidermal growth factor but not insulin are able to induce WAF1/CIP1 in quiescent p53-deficient cells as well as in normal cells. The kinetics of this transient induction, which is enhanced by cycloheximide, demonstrates that WAF1/CIP1 is an immediate-early gene the transcript of which reaches a peak at approximately 2 h following serum or growth factor stimulation. On the other hand, DNA damage elicited by gamma-irradiation induces WAF1/CIP1 in normal human and mouse fibroblasts but does not affect WAF1/CIP1 expression in p53-deficient cells. These results suggest the existence of two separate pathways for the induction of WAF1/CIP1, a p53-dependent one activated by DNA damage and a p53-independent one activated by mitogens at the entry into the cell cycle. The possible function of p21 at this early stage is discussed.
Cancer Res 1994 Jul 01
PMID:Induction of WAF1/CIP1 by a p53-independent pathway. 801 56

Normal, nontumorous cells express cyclin proteins in an orderly, scheduled fashion, at a given phase of the cell cycle. Thus, cyclin B1 is synthesized during G2 and abruptly degraded during mitosis. The onset of cyclin E synthesis takes place in mid-G1, its maximal expression is at the time of cell entrance to S, and its degradation occurs during cell progression through S phase. In the present study, multiparameter flow cytometry was used to correlate expression of cyclin B1 or cyclin E with cell cycle position (estimated by cellular DNA content) in normal human proliferating lymphocytes as well as in T-cell MOLT-4 leukemia; promyelocytic HL-60 leukemia; histiocytic U937 lymphoma; MCF-7, T-47D, and Hs 587T breast carcinoma; Colo 320DM colon carcinoma; and the T-24 transitional cell carcinoma cell line. The scheduled expression of both cyclins, namely of cyclin B1 restricted to G2 + M cells and of cyclin E restricted to late G1 and early S cells, was observed only in normal lymphocytes and MOLT-4 cells. The cells of HL-60, U937, T-47D, and Hs 587T lines expressed both cyclins in an unscheduled ("ectopic") fashion, i.e., unrelated to cell cycle position. Colo 320DM cells showed unscheduled expression of cyclin E (i.e., during G2) but expression of cyclin B1 in this line was generally restricted to G2 + M cells. There were relatively few (10-12%) cells in MCF-7 and T-24 cell lines that expressed cyclin B1 or E in an unscheduled manner. It may be expected that the unscheduled expression of cyclins in tumor cells may lead to a loss of the regulatory mechanisms of cell cycle progression and that such feature of the tumor may be of prognostic value. There is a need, therefore, to conduct similar studies in primary tumor cells.
Cancer Res 1994 Aug 15
PMID:Unscheduled expression of cyclin B1 and cyclin E in several leukemic and solid tumor cell lines. 804 72

PRAD-1 is a putative oncogene localized on chromosome 11q13 which encodes cyclin D1, a novel cyclin involved in cell cycle regulation. Amplification of this gene has recently been reported in several human tumors including breast and head and neck carcinomas. In this study we have analyzed the presence of PRAD-1/cyclin D1 gene amplification and mRNA overexpression in a series of 46 matched normal mucosas and squamous cell carcinomas of the larynx. PRAD-1/cyclin D1 was found to be amplified 2- to 12-fold in 17 carcinomas (37%). DNA amplification correlated with advanced local invasion (P = 0.0015), presence of lymph node metastases (P = 0.0078), and stage IV of the tumors (P = 0.0021). mRNA overexpression was found in 15 of the 43 (35%) cases examined and it was also significantly associated with advanced local invasion (P = 0.0025) and stage IV carcinomas (P = 0.0032). A significant association was observed between gene amplification and mRNA overexpression (P < 0.0001) with only 3 discordant cases (2 amplifications with no overexpression and 1 overexpressed carcinoma with no gene amplification). Furthermore, the degree of DNA amplification correlated with the levels of mRNA expression (r = 0.6; P = 0.024). These findings suggest that the PRAD-1/cyclin D1 gene may be an important target of 11q13 amplifications in laryngeal carcinomas and the activation of this gene may be involved in the progression of these tumors. Its association with advanced-stage tumors indicates that PRAD-1/cyclin D1 gene amplification and overexpression may be of prognostic significance.
Cancer Res 1994 Sep 01
PMID:PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas. 806 83

Gene amplification in stomach and oesophageal cancers was reviewed. In stomach cancers, two receptor type tyrosine kinases, c-erbB-2 and K-sam, are frequently amplified and overexpressed. c-erbB-2 seems to be preferentially amplified in well-differentiated, and K-sam in poorly-differentiated, gastric adenocarcinomas. 11q13 genes are amplified in about 50% of the oesophageal cancers. These genes include hst-1, int-2 and cyclin D/prad1, all of which are mapped to chromosome 11 at band q13. Although hst-1 and int-2 are usually not expressed despite amplification, elevated transcription of the cyclin D gene is accompanied by its amplification, suggesting a role of a G1 cyclin in oesophageal carcinogenesis.
Semin Cancer Biol 1993 Feb
PMID:Amplified genes in cancer in upper digestive tract. 809 12


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