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

Abnormalities of the tumour suppressor gene p53 have been shown in approximately 60% of advanced gastric adenocarcinomas and it has been suggested that the immunohistochemical finding of increased p53 expression is a prognostic marker in gastric cancer. No studies of early (T1) tumours have been reported. Over expression of p53 protein in 95 early gastric carcinomas and in adjacent mucosa was investigated using immunohistochemistry with antibody CM1. Thirty five per cent of the tumours were positive. The frequency of p53 positivity in tumours of tubular histological type (46%) was significantly higher than that in signet ring tumours (10%) (p = 0.006), and neoplasms that invaded deeply into the submucosa were more frequently positive (45%) than others (30%). Five of eight (62%) T1 tumours with lymph node metastases showed immunoreactive p53. In signet ring tumours, immunopositivity correlated with the frequency of DNA aneuploidy. p53 Over expression was also found in 15% of 26 examples of high grade dysplasia in mucosa adjacent to invasive tumours. No positivity was found in intestinal metaplasia or in normal mucosa. The findings show that immunocytochemically demonstrable over expression of p53 correlates with other morphological markers of aggressiveness in T1 gastric adenocarcinoma. The increasing frequency of p53 immunoreactivity in the sequence of high grade dysplasia-->early gastric cancer-->advanced gastric cancer supports the view that abnormalities of p53 are related to tumour progression in gastric carcinogenesis.
 ...
PMID:Expression of p53 in early (T1) gastric carcinoma and precancerous adjacent mucosa. 782 4

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.
 ...
PMID:Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. 783 39

The syndrome of multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant tumour disease of the neuroendocrine system with manifestations in the parathyroids, pancreas, duodenum and pituitary gland and rarely also in the stomach and thymus. Recently, the MEN 1 gene locus has been mapped to the long arm of chromosome 11. This gene most likely belongs to the tumour suppressor genes, the allelic loss of which causes tumour development. The pancreatic and duodenal tumours may metastasize, but usually have a low malignant potential. Clinically, most MEN 1 patients present between the age of 20 and 35 with hyperparathyroidism and/or Zollinger-Ellison syndrome.
 ...
PMID:[Multiple endocrine neoplasia type 1 (MEN 1). Molecular genetics, morphology and prognosis]. 791 16

Mutations in the p53 tumour suppressor gene, with consequent accumulation of the p53 protein, are frequently observed in non-small cell lung cancer (NSCLC). Little is known, however, about the timing of their appearance or their maintenance through cancer progression and metastatic spread. We have examined the normal epithelium and a panel of bronchial lesions, including dysplastic, neoplastic, and metastatic lesions, for p53 immunoreactivity and for expression of proliferating cell nuclear antigen (PCNA). No p53 immunoreactivity was found in normal and hyperplastic epithelium, nor in squamous metaplastic lesions. Twenty out of 30 invasive tumours and 13 out of 17 in situ carcinomas adjacent to an invasive tumour showed p53 immunoreactivity. There was a strict correlation between the level of p53 expression in the non-invasive and the invasive components of the tumours. Five out of eight pairs of primary tumours and matching metastases expressed p53, at identical levels in both compartments. These data indicate that p53 overexpression can occur in the earliest recognized phase of NSCLC and that the alteration is maintained during progression from in situ to invasive carcinoma and metastatic spread. PCNA expression increased from early to advanced phases of NSCLC. High PCNA immunoreactivity was observed in tumours expressing high p53 levels. A significant association was observed for PCNA expression between preinvasive and invasive lesions.
 ...
PMID:Human non-small cell lung cancer: p53 protein accumulation is an early event and persists during metastatic progression. 767 94

The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21. Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the status of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reaction (PCR). Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of the remaining six lines expressed a normal p16 mRNA. These latter six cell lines expressed p16 transcripts that had suffered deletions ranging in size from 2-16 base pairs. In each case, deletions led to a change of reading frame. Furthermore, in two cases abnormalities in the MTS1/CDK4I gene were identical in cells derived from metastatic tumours as compared to cells derived independently from the corresponding primary tumour. The identical nature of mutations observed in primary tumours and metastases derived from the same patient provides strong evidence that inactivation of p16 function was an in vivo event.
 ...
PMID:MTS1/CDK4I is altered in cell lines derived from primary and metastatic oral squamous cell carcinoma. 800 Dec 21

Expression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM-1, an antiserum raised against recombinant human p53 protein. Because wild-type p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post-translational mechanisms or gene mutation. A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P < 0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P = 0.008). These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.
 ...
PMID:p53 immunoreactivity in human malignant melanoma and dysplastic naevi. 833 44

Considerable evidence is gathering for the involvement of vascular endothelial growth factor (VEGF) in the vascularization and growth of primary tumours as well as in the formation of metastases. The expression of VEGF depends on activated oncogenes and inactivated tumour suppressor genes as well as several other factors (e.g. growth factors, tumour promoters and hypoxia). Substantial expression of the receptors for VEGF is restricted mainly to the tumour blood vessels. The causal involvement of this angiogenic factor in the progression of disease has been successfully evaluated by means of monoclonal antibodies against VEGF, dominant-negative receptor mutants and the use of antisense oligonucleotides against the VEGF mRNA. Thus, the VEGF signalling system seems to be an appropriate target to inhibit tumour angiogenesis and metastases formation.
 ...
PMID:VEGF-mediated tumour angiogenesis: a new target for cancer therapy. 852 39

Mutations of the TP53 tumour suppressor gene have been reported for many human cancers. A variety of TP53 mutations have also been reported for both primary non-small cell lung cancer (NSCLC) and associated metastases. To assess the pathogenetic significance of TP53 gene alterations in NSCLC, 24 paired samples of primary NSCLC and the corresponding normal lung tissue were analysed for mutations of the TP53 gene (exons 5-8) using exon-specific PCR, single-strand conformation polymorphism PCR (SSCP-PCR) and direct DNA sequencing; for p53 protein accumulation by immunohistochemistry and for 17p allelic loss using restriction fragment length polymorphism (RFLP) probes on Southern blots and amplified fragment length polymorphism-PCR. TP53 point mutations were observed in 9/24 (38%) tumours encompassing a total of 14 mutations. Two tumours displayed the same double mutation while a third harboured four different mutations. Seventeen of 24 NSCLCs (71%) overexpressed p53 protein and all 17 immunopositive tumours (100%) showed a mutation and/or allelic loss at the D17S30 locus. Of the 17 NSCLCs informative at the DS17S30 locus, 10 (59%) showed allelic loss, of which five (50%) were also mutated on the remaining TP53 allele. These results suggest that TP53 gene alterations are involved in the pathogenesis of primary NSCLC and that such alterations may serve a selective role in the development of NSCLC by diminishing the apoptotic potential of bronchial epithelial cells heterozygous for a TP53 point mutation. This may also explain the accumulation of multiple TP53 point mutations in 3/24 of our NSCLC samples.
 ...
PMID:Frequent TP53 gene alterations (mutation, allelic loss, nuclear accumulation) in primary non-small cell lung cancer. 866 51

There have been many recent advances in our understanding of thyroid disease, including thyroid physiology, the molecular biology of thyroid neoplasms, guidelines for the management of surgical thyroid disease and the operative approach to thyroidectomy. The control of thyroid growth and function is better understood now that the thyroid stimulating hormone (TSH) receptor has been characterized as a G-protein coupled transmembrane receptor. The peripheral action of thyroid hormones is also better understood in terms of their interaction with nuclear thyroid hormone receptors. An adenoma-carcinoma sequence for the development of thyroid neoplasms has been proposed based on the characterization of a number of proto-oncogenes and tumour suppressor genes, and different pathways for the development of papillary and follicular thyroid carcinoma have been demonstrated. Fine needle biopsy has become, over the past few years, the principal diagnostic technique for evaluation of thyroid nodules, and has resulted in a significant reduction in the need for surgery for benign thyroid nodules. The approach to the management of thyroid carcinoma can now be based on comprehensive scoring systems for assigning patients to a particular risk group, the most recent of which is the MACIS system based on distant metastases (M), age (A), completeness of resection (C), invasion (I) and size (S). The capsular technique of thyroidectomy as described has now been shown to be the best method to preserve parathyroid blood supply, protect the recurrent laryngeal nerve and minimize the complications of thyroid surgery.
 ...
PMID:The aetiology, investigation and management of surgical disorders of the thyroid gland. 867 80

The DCC (deleted in colorectal cancer) gene was originally identified as a candidate tumour suppressor gene in colon carcinogenesis on the basis of allelic losses in chromosome 18q.21 in 70% of colon cancers. Reverse transcriptase polymerase chain reaction (RT-PCR) of DCC mRNA suggests that DCC expression may also be reduced in colon cancers. We have used monoclonal antibodies generated against the DCC immunoglobulin-like domain to investigate DCC isoforms and DCC protein expression during colon cancer progression. Normal mucosa and colonic tumour specimens representative of the range of colonic tumour progression from benign adenomatous polyps to metastases were compared by Western blot analyses. We show that while M(r) 194 000 DCC is present in normal colonic mucosa and adenomatous polyps, it is also similarly expressed in colorectal carcinomas and colonic metastases in the liver. The presence of DCC protein is consistent with the presence of DCC mRNA transcripts in the same tissue specimens. Notably DCC was not completely lost in any colonic tumour specimens examined, even those that had progressed to metastatic cancers. Quantitation of DCC protein expression in tissue specimens by densitometry demonstrated that both normal and malignant specimens exhibit a wide range of DCC protein levels and there was no significant correlation between diminished DCC protein expression and colon cancer progression. These results demonstrate the pattern of expression of the DCC gene product in colonic tumour progression and show that absence of DCC expression is not associated with colonic tumour progression.
 ...
PMID:The deleted in colon cancer (DCC) gene is consistently expressed in colorectal cancers and metastases. 876


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>