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)

The c-src proto-oncogene has been implicated in the progression of primary human colorectal carcinoma to hepatic metastasis. To determine if increased pp60c-src tyrosine kinase activity is a colon-specific phenomenon present in colorectal metastases to all sites, the pp60c-src-specific kinase activity of noncolon tumor metastases to the liver was compared to that of colorectal liver metastases. Activity of extrahepatic colon carcinoma metastases was compared to that of colorectal liver metastases as well as that of normal colonic mucosa. The specific activity of pp60c-src in multiple synchronous metastases from colon carcinoma was also examined. Tyrosine kinase activity was determined by immune complex kinase assay; protein levels were determined by immunoblotting. Specific activity was calculated for each group by dividing the total activity by protein level. Colon carcinoma metastases to the liver had significantly (P < 0.04) increased pp60c-src activity with an average 2.2-fold increase over normal mucosa. In contrast, noncolon tumor metastases to the liver showed minimal pp60c-src kinase activity. Extrahepatic colorectal metastases demonstrated significantly increased (P < 0.005) pp60c-src activity with an average 12.7-fold increase over normal mucosa. When compared to colon liver metastases, extrahepatic colorectal tumor metastases show a significant difference in activity (P < 0.05) with an average 5.7-fold increase. Examination of multiple synchronous colon carcinoma metastases confirmed these results. In summary, we conclude that (1) the activation of pp60c-src between primary tumors and metastases is specific to colon metastases, and (2) although pp60c-src activity is significantly increased in colorectal metastases, site-specific differences in the magnitude of activity are evident.
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PMID:Site-specific differences in pp60c-src activity in human colorectal metastases. 768 14

The oncoprotein encoded by bc1-2 is unique because of its intracellular location (a mitochondrial membrane protein) and apparent mode of action (suppression of apoptosis). To date, this oncogene has been associated only with the development of certain forms of human B-cell lymphoma. In this report, we describe our experience with a monoclonal antibody made against a synthetic peptide for bc1-2 that can recognize the bc1-2 protein and identify cells in human prostate glands expressing this proto-oncogene with in situ immunohistochemical procedures. These procedures were utilized to survey a series of 62 human tissues to evaluate whether bc1-2 might have a role in the developing prostate gland or in prostate oncogenesis. While all primordial epithelial cells in a fetal prostate gland immunostain for bc1-2, normal and hypertrophic prostate glands of the adult show bc1-2 expression restricted to the basal cells. All epithelial cells in areas of prostatic intraepithelial neoplasia were stained by this antibody, as were most (62%) localized invasive prostatic carcinomas. In contrast, all primary prostatic carcinomas and metastases obtained from metastatic prostate cancer patients after hormone treatment (hormone-refractory tumors) stained positive for bc1-2. This study demonstrates that the oncoprotein encoded by bc1-2 can be detected at sequential stages in the natural history of human prostate cancer. Since the bc1-2 oncoprotein is known to suppress the cellular response to apoptotic stimuli, it will be important to determine whether bc1-2 expression is a factor in the development of prostate cancers and in the survival of hormone-refractory prostate cancer cells.
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PMID:Detection of the apoptosis-suppressing oncoprotein bc1-2 in hormone-refractory human prostate cancers. 768 82

Since the discovery of bcl-2 proto-oncogene in follicular lymphomas, the protein product has been detected in a variety of normal tissues including skin, where it is expressed in basal keratinocytes. Recent studies indicate that bcl-2 protein is detected in nonlymphoid malignancies such as neuroblastoma and carcinomas of the lung and prostate. This study investigates the presence of bcl-2 protein in benign and malignant melanocytic neoplasms of the skin. Immunohistochemical analysis of bcl-2 protein expression was performed on 39 nevi and 60 malignant melanomas, including 21 metastases. There was diffuse strong immunopositivity for bcl-2 protein in 100% of nevi and 65% (43/60) of primary and metastatic melanomas. bcl-2 protein was diffusely expressed in 67% (30/39) of primary melanomas and 54% (11/21) of metastases. Although bcl-2 immunoreactivity was observed in all levels of primary cutaneous malignant melanomas, in 43% (9/21) of deep melanomas (Clark level > or = III), and 100% (7/7) of thick tumors (thickness > or = 4.00 mm), there was focal loss of immunoreactivity. Metastatic melanomas showed focal loss of bcl-2 expression in 10% (2/21) of cases and total loss of bcl-2 protein in 39% (8/21). We conclude from our results that bcl-2 protein is expressed by benign and malignant melanocytic tumors of the skin, but there is loss of bcl-2 protein expression with increasing tumor progression.
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PMID:bcl-2 protein expression in melanocytic neoplasms of the skin. 777 75

Tumor progression of cancers is manifested by phenotypic property changes including development of hormone/growth factor independence and metastatic ability. The progression results from acquired genomic alterations leading to clonal heterogeneity and outgrowth of more aggressive and therapy-resistant sublines. Previously, a cultured rat "Nb2 lymphoma" cell line was established, whose viability depends critically on the hormone, prolactin, acting as the principal growth factor. By prolactin starvation, prolactin-independent sublines were generated which possessed the parent karyotype plus extra acquired chromosomal changes (clonal evolution). In this study, the parent line (Nb2-U17) and a cloned subline (SFJCD1) were compared for metastatic ability using single s.c. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 tumors showed no evidence of metastases at autopsy, even when tumors at implantation site reached a size of 9 cm (length + width). In contrast, rats (19) bearing SFJCD1 tumors showed multiple metastases (liver, kidney) when transplants exceeded 5 cm. This difference in metastatic ability may be related to the acquisition of an inversion in chromosome 1, i.e. inv(1)(q31q41). The 1q41 locus is adjacent to the reported H-ras-1 proto-oncogene locus (1q41-q42). In another subline, tetraploidization (flow cytometric analysis, karyotyping) occurred spontaneously following prolonged culturing (20 mo). Together, the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellular and molecular mechanisms underlying tumor progression to the metastatic phenotype.
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PMID:The rat Nb2 lymphoma: a novel model for tumor progression. 787 71

The histopathological characteristics, proto-oncogene amplification, immunohistopathology of the c-erbB-2 product distribution, and the DNA content of nuclei were examined in metastatic brain tumors, which consisted of seven adenocarcinomas, a large cell carcinoma, a squamous cell carcinoma, a renal cell carcinoma and a mucoepidermoid carcinoma. A very high incidence of DNA changes was seen in these tumors. Proto-oncogene amplification and abnormal DNA content in the nuclear portion were found in 64% (7/11) and 67% (6/9) of cases, respectively. We also found double oncogene alteration in three cases metastasizing from lung, esophagus and kidney, and triple oncogene alteration in one case metastasizing from breast. We could not identify the common alterations in the group of metastatic brain tumor cells. These data suggest that the proto-oncogene amplifications and the alteration of DNA ploidy pattern may contribute to the metastatic process.
Clin Exp Metastasis 1994 Jul
PMID:DNA amplifications and elevated expression of proto-oncogene in addition to altered DNA ploidy in metastatic brain tumors. 791 69

During an immunohistochemical study of the distribution of the Bcl-2 proto-oncogene product in frozen sections of normal human skin, a hitherto unrecognized strong reactivity with melanocytes was observed. This prompted us to study Bcl-2 expression in a variety of pigment lesions. In nevocellular nevi, immunoreactivity gradually diminished or even disappeared toward the deeper dermal component. In malignant melanomas of all stages and histological subtypes, the neoplastic cells expressed Bcl-2 oncoprotein, the most intense positivity being restricted to cells in the radial growth phase. Cutaneous and lymph node metastases of malignant melanomas were negative or showed only weak and focal reactivity. The specificity of the staining was confirmed by Western blotting of tissue lysates. The loss of Bcl-2 expression in the deeper parts of nevi may offer an explanation for the "maturation" and final disappearance of dermal nevocellular nevi. The expression of Bcl-2 oncoprotein by malignant melanomas adds these neoplasms to a growing list of tumors expressing this oncoprotein. Bcl-2 in malignant melanoma may play a role in tumor development by sparing the cells from apoptotic death (and thereby exposing them to secondary events) or through cooperation with other oncogenes. The lack of reactivity in metastatic melanoma suggests that mechanisms other than Bcl-2 are involved in the survival and growth of metastatic melanoma cells.
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PMID:Bcl-2 expression in human melanocytes and melanocytic tumors. 805 90

The c-MET proto-oncogene encodes the receptor for the Hepatocyte Growth Factor/Scatter Factor, which is known to mediate mitogenic, motogenic and invasive responses of several cell types. We have analysed by immunohistochemistry and biochemically the expression of c-MET in benign and malignant melanocytic lesions. The Met/HGF receptor which in the melanocytic lineage displays the structural features of the authentic receptor was undetectable in tissue melanocytes and in nevocytic nevi. Only four out of 23 primary melanomas scored positive. Expression was increased to a significant level in 17 out of the 44 metastatic lesions examined. The c-MET expression was homogeneous in multiple metastases from the same patients. Comparative analyses showed both lack of correlation with the expression of the tumour progression associated ICAM-1 adhesion molecule and, in 23% of cases, co-expression with the c-KIT encoded receptor. These findings show that the c-MET gene is expressed at late stages of melanoma progression and suggest that the presence of Met/HGF receptor may contribute to the acquisition of an invasive phenotype.
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PMID:Expression of the c-Met/HGF receptor in human melanocytic neoplasms: demonstration of the relationship to malignant melanoma tumour progression. 810 62

The Ki-ras proto-oncogene is converted into an active oncogene by mutations in codon 12, 13, or 61. The incidence of mutations in the Ki-ras oncogene in colorectal adenomas and primary colorectal carcinomas has been shown to be 50-75 and 40-65%, respectively. To determine the role activation of the Ki-ras oncogene plays in the progression of colorectal carcinoma, we analyzed DNA from 11 nude-mouse xenografts and from 24 metastases of 22 patients with colorectal carcinoma, using the polymerase chain reaction technique and hybridization with labeled mutation-specific oligomers. Eleven of the 24 metastases (46%) carried mutations, 7 in codon 12 and 4 in codon 13, whereas only 1 nude-mouse tumor (9%) harbored a Ki-ras codon-12 mutation. Eleven of these 12 mutations in advanced stages of colorectal cancer were localized to the second position of either codon 12 or codon 13, whereas a majority of published ras mutations in earlier stages are in the first position of codon 12 of the Ki-ras oncogene. We conclude that there is a position specificity of Ki-ras oncogene mutations in advanced stages of colorectal carcinoma. In general, however, these mutations do not seem to play an important role in the progression of this cancer.
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PMID:Position specificity of Ki-ras oncogene mutations during the progression of colorectal carcinoma. 842 1

Relationships between the incidence of metastatic spread and microvessel density, expression of proto-oncogene products, or expression of resistance-related proteins were investigated in human ovarian carcinomas by immunohistochemistry. Ovarian carcinomas with a high microvessel density showed a significantly increased formation of metastases (P = 0.005). Tumors with positive immunoreactivity of c-jun and c-myc products had a higher metastatic spread; however, these results were not statistically significant. A marginally significant correlation existed between the expression of erbB1 (EGFR) and metastatic spread (P = 0.05). No significant relationship was found between the expression of the resistance-related proteins P-glycoprotein or glutathione S-transferase-pi and the incidence of metastases. Furthermore, no correlation was detected between expression of the heat shock protein 70 and the occurrence of metastases.
Clin Exp Metastasis 1996 May
PMID:Microvessel density, expression of proto-oncogenes, resistance-related proteins and incidence of metastases in primary ovarian carcinomas. 867 74

Mutations involving the K-ras proto-oncogene are believed to play an important role in the mechanism of tumorigenesis for many human cancers and occur in 10-30% of endometrial carcinomas. In the present study 221 cases of endometrioid endometrial carcinoma obtained from Japanese patients with average follow-up of 41 months were examined for point mutations in codon 12 of K-ras through use of the polymerase chain reaction. In 103 cases lymph node dissection had been performed. K-ras mutations were significantly associated with the presence of lymph node metastases (P < 0.04). Since endometrial carcinoma in premenopausal women generally behaves less aggressively than tumors of similar histologic grade arising in postmenopausal patients, we evaluated the effect of K-ras mutation on outcome in patients stratified into three different age categories (<53 years, premenopausal; 54-59 years, perimenopausal; >60 years, postmenopausal). In the postmenopausal age group (>60 years), the presence of K-ras mutations was statistically significantly associated with patients who died or experienced recurrence (41.2% vs 13.0%; P < 0.03). This was related to a dramatic (greater than eightfold; P = 0.011) increase in the likelihood of adverse outcome between the premenopausal and postmenopausal states for patients whose tumors contained mutant K-ras. These findings point to a possible role for K-ras activation in the mechanism(s) responsible for more aggressive clinical behavior of endometrioid endometrial cancer that is observed in postmenopausal patients.
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PMID:K-ras point mutations in endometrial carcinoma: effect on outcome is dependent on age of patient. 891 Jun 34


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