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 ability to metastasize requires that tumor cells be able to degrade matrix. Nontoxic compounds that inhibit matrix digestion might be useful as anti-metastatic agents. We have investigated whether phenytoin, a drug commonly used in clinical practice that inhibits the production of collagenase by some cells, inhibits metastases in a standard animal model of metastasis: In vitro, phenytoin inhibited the proliferative response of B16 F10 melanoma cells to serum-containing media (75% inhibition at 25 micrograms/ml) but had no effect on their ability to degrade a type I collagen gel (1-100 micrograms/ml). Treatment of these cells with phenytoin prior to inoculation in vivo did not inhibit tumor growth, implantation in a surgical wound, or incidence of spontaneous metastases from a primary tumor growing in the foot. Pretreatment of mice with phenytoin (15, 40, and 75 mg/kg/day) diminished pulmonary metastases following tail vein injection in a minimal but dose dependent fashion; mean number of pulmonary colonies 4.6 +/- 3.1 (75/mg/kg/day) vs. 10.2 +/- 9.9 (control). However, tumor growth, implantation, and spontaneous metastases were not inhibited by pretreating the mice with the same doses of phenytoin. It is concluded that phenytoin has an insignificant inhibitory effect on tumor growth and metastasis.
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PMID:Search for anti-metastatic therapy: effects of phenytoin on B16 melanoma metastasis. 173 31

Over the past several years, many tumor markers, including cell surface antigens, T-antigen, ras p55, and ras p52 proteins, have been studied as potential tumor markers of bladder cancer. The lack of specificity and inconsistency of these markers led us to develop a new method for studying the urinary excretion of autocrine motility factor (uAMF) and tumor cell collagenase stimulating factor (TCSF) in 24-hour and first morning voided specimens. AMF is a glycoprotein secreted by the malignant cells and is responsible for cell locomotion, a key event in invasion and metastases of the malignant cells. TCSF is a membrane bound glycoprotein of tumor cells that stimulates fibroblast collagenase production. We have utilized an enzyme-linked immunoabsorption assay to detect the levels of uAMF and TCSF in urine samples collected from normal volunteers, patients with benign diseases, and patients with bladder cancer. Our data indicate that urinary concentrations of uAMF and TCSF are elevated in patients with bladder cancer. Furthermore, the levels of uAMF and TCSF are more elevated in invasive tumors as compared with benign counterparts. We have localized uAMF and TCSF in bladder cancer cells, utilizing immunohistologic techniques.
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PMID:A new method for evaluation of urinary autocrine motility factor and tumor cell collagenase stimulating factor as markers for urinary tract cancers. 212 27

Human fibrosarcoma cells derived from a patient with multiple metastases extensively degrade artificial basement membranes (BM) and secrete interstitial type of collagenase, a proteolytic enzyme responsible for degradation of type I collagen. Exposure of invasive cell line to TGF beta abrogates destruction of BM.TGF beta reduces collagenase activity and stimulates specific metalloproteinase inhibitor (TIMP) in invasive tumor cells. We preassume that TGF beta could play a protective role in tumor invasion.
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PMID:Protective role of transforming growth factor beta (TGF beta) in tumor-induced degradation of basement membranes. 216 65

In order to investigate the role of collagenase in cancer invasion and metastasis, two collagenase activities of interstitial collagenase and type IV collagen degrading enzyme (type IV collagenase) were determined in 40 cases of human stomach cancer tissue. Elevated cancers which are known to have a propensity to cause blood-borne metastases showed higher activities of both interstitial collagenase and type IV collagenase than flat or ulcerous type of cancer. Using the parameters of lymph node metastasis vs tumor size or vs depth of cancerous invasion into the stomach wall, classification of the cases was attempted according to the degree of malignancy. In the cases with marked lymph node metastases in spite of small tumor size and/or shallow cancerous invasion into the stomach wall, type IV collagenase activity was higher than that in the cases with lower malignancy (p less than 0.025, p less than 0.05, respectively). These results suggest that collagenase in stomach cancer tissue play an important role in the invasion and metastasis of cancer cells. Type IV collagenase activity in stomach cancer tissue could be one of the useful biological markers for the degree of malignancy.
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PMID:The collagenase activities, interstitial collagenase and type IV collagenase, in human stomach cancer: with special reference to local spreading and lymph node metastasis. 217 1

Of 8 tumors surgically extirpated from 8 patients with renal cell carcinoma, 7 were successfully processed in short-term culture by collagenase method, and 130 metaphases were extracted from these 7 tumors and were subjected to chromosomal analysis according to the G banding technique. As for karyotype, 4, 2 and 1 cases were mainly diploid, hypodiploid and aneuploid, respectively. The highest incidence of chromosome aberration was marked by #3 chromosome (5 of 7 cases of which 4 and 1 showed monosomy as clonal aberration and trisomy as non-clonal aberration, respectively). The commonest gain of chromosome was noted for #7 trisomy (4 of 7 cases). Two cases had already had metastases at the time of surgery, each showing #7 trisomy. Marker chromosome was noted in 6 of 7 cases. Structural chromosome aberration had a lesser incidence compared with numerical aberration; only clonal aberrations were long-arm aberrations (2q+, 6q+) of #2 and #6 chromosomes. Short-arm aberrations (3p-, 8p-) of #3 and #8 chromosomes were noted in one case each. 3p deletion, which is reported to be predominant in the literature, was noted only in one case. This was observed in triploid cells. However, all of metaphases showing 2q+ and 6q+ had concomitant #3 monosomy, and excess portions of #2 and #6 chromosomes were in good agreement with the band pattern of #3 chromosomal long-arm. Therefore, translocation of 3q12-qter in #2 and #6 chromosomes is supposed to lead to 3p deletion. A similar mechanism seems to be involved in the formation of marker chromosomes, suggesting the involvement of deleted #3 chromosome in marker chromosomes.
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PMID:[Chromosome analysis of renal cell carcinoma]. 223 31

Digestion of primary breast cancers and their metastases with collagenase yields cell clusters which can be selectively isolated from stromal cells and from the less malignant-looking epithelium of the primary tumors by their failure to attach as rapidly to collagen gel. Continued passage in culture of one preparation of cell clusters has yielded a continuously growing cell strain, termed Ca2-83. This strain continues to grow mainly as cell clusters with doubling times of 10 to 14 days, although some clusters eventually adhere to plastic substrata. Two morphological extremes of cell were observed, smaller polygonal or cuboidal cells and larger, often-multinucleated cells which contain fat droplets. Cell clusters grew in a gland-like pattern similar to those of the original carcinoma and formed small nodules in 50% of recipient nu/nu mice. Both morphological forms of Ca2-83 in culture or in tumor nodules stained immunocytochemically with epithelial cell-specific antisera to epithelial membrane antigens and to human keratins but not to laminin or actin. Cultures of Ca2-83 failed to synthesize laminin under conditions where its synthesis was observed in a rat myoepithelial cell line. Ultrastructural analysis of the cell clusters has identified microvilli coated with epithelial membrane antigens and junctional complexes typical of secretory epithelia in both morphological forms, but no characteristics of myoepithelial cells or basement membranes were observed. The DNA content of the cultures increased in response to serum, a bovine pituitary fraction, and insulin. Numbers of cell clusters were also increased in the presence of culture medium exposed to preadipocytes, myoepithelial- or mesothelial-like cells/stromal cells, or to prostaglandin E2.
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PMID:Loss of production of myoepithelial cells and basement membrane proteins but retention of response to certain growth factors and hormones by a new malignant human breast cancer cell strain. 241 Jan 3

Despite adequate locoregional control, colorectal metastasis to the liver remains a significant cause of death. Resection of hepatic metastasis improves five-year survival 18% to 34%. A study of the impact of 40% partial hepatectomy on cytokine production in the liver was undertaken. Nonparenchymal liver cells (NPCs) were prepared by collagenase perfusion and metrizamide gradient from partially hepatectomized and laparotomized control C57BL/6Ros mice. Nonparenchymal cell from partially hepatectomized mice compared with laparotomized mice showed a twofold to threefold increase in interferon (IFN) activity. Both interferon alpha/beta and supernatants from cultured NPCs of partially hepatectomized mice suppressed the proliferation of liver-derived MCA-38 colon adenocarcinoma cells in vitro. This tumor has been shown to metastasize to the liver of C57BL/6Ros mice. The production of various cytokines by NPCs induced by partial hepatectomy may provide a possible antimetastatic mechanism.
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PMID:Partial hepatectomy augments the liver's antitumor response. 246 82

We employed a sensitive in vitro amnion invasion assay to examine the relationship of the invasive ability of numerous mouse and human tumor cell lines and their variants to their ability to spontaneously or artificially metastasize; we also studied possible enzymatic activities involved in the in vitro invasion process. In vitro invasive ability of tumor cells was strongly correlated with spontaneous metastatic ability from the subcutaneous site, regardless of the ability of tumor cells to form artificial metastases when introduced intravenously. However, normal nontumorigenic human trophoblast cells were also highly invasive. Various collagenase inhibitors totally abrogated amnion penetration by all invasive cells; various inhibitors of plasmin, plasminogen, and plasminogen activators prevented invasion in most, but not all, cases. Thus, amnion penetration provides a rigorous test for tumor cell invasiveness required for spontaneous metastasis in vivo, and invasiveness is strongly dependent on metalloproteinase activity, which usually follows plasmin activation.
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PMID:Mechanisms of cellular invasiveness: a comparison of amnion invasion in vitro and metastatic behavior in vivo. 254 Dec 59

We used flow cytometry to measure the expression of human melanoma antigens on cell suspensions dissociated from metastatic masses. The objective was to study the heterogeneity between tumor samples from different patients and between different tumors excised from a single patient. Fifty-three metastases excised from 34 melanoma patients were analyzed with a panel of nine murine monoclonal antibodies (MOABs). Melanoma cells were stained by an indirect fluorescent method and analyzed on a Coulter EPICS C flow cytometer after gating to exclude tumor-infiltrating leukocytes and dead cells. The most consistently and most strongly expressed antigen was the high-molecular-weight proteoglycan (detected by the MOAB 9.2.27), which was expressed on 95% of the melanoma specimens and by a high proportion of cells within each specimen (mean +/- SE, 79.2 +/- 5.5). However, strong expression of this antigen was limited to melanoma cells that had been dissociated mechanically and was markedly diminished by exposure to collagenase. Culture of collagenase-dissociated tumor cells for 24 to 48 h resulted in reexpression of the antigen. The expression of other melanoma-associated antigens was not affected by collagenase treatment, but for these antigens there was more variability between cells from an individual tumor and between tumors from different patients. The percentage of enzyme-dissociated tumors considered positive for MOAB binding (defined as at least 10% of cells positive) and the mean +/- SE of the percentage of positive cells within a tumor were as follows: MOAB ME-9-61 (antigen, p97) = 84% + (41.2 +/- 5.4%); MOAB ME-20.4 (antigen, nerve growth factor receptor) = 40% + (18.7 +/- 5.1%); MOAB ME-24 (antigen, ganglioside GD3) = 84% + (50.8 +/- 4.8%); MOAB ME-311 (antigen, ganglioside 9-O-acetyl-GD3) = 76% + (42.5 +/- 5.1%); MOAB ME-361 (antigen, mainly ganglioside GD2) = 3% + (1.9 +/- 0.8%); MOAB 3F8 (antigen, ganglioside GD2) = 36% (10.5 +/- 3.8%); MOAB 14G2a (antigen, ganglioside GD2) = 86% + (46.0 +/- 6.7%); MOAB L243 (antigen, HLA-DR) = 56% + (22.5 +/- 5.5%). In 19 cases, we were able to compare the antigenic profiles of two tumors excised from the same patient at different times. Analysis by nonindependent t test showed no significant differences in MOAB binding between the paired tumors. Moreover, linear regression analysis indicated that there was a linear relationship, with a slope approximately = 1, between the percentage of positive cells in Tumor 1 versus Tumor 2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Flow cytometric determination of the frequency and heterogeneity of expression of human melanoma-associated antigens. 258 30

To determine whether the production of experimental hepatic metastases in athymic nude mice by human colorectal carcinomas (HCC) correlated with the clinical outcome in patients, we harvested colorectal carcinomas from 82 patients, dissociated the tumors with collagenase and DNase, and injected them into groups of nude mice, either in the flank to assess experimental tumorigenicity or into the spleen to produce experimental metastasis in the liver. Growth in mice was then associated with clinicopathological factors and clinical outcome. Growth of HCC in either the flanks or the livers of nude mice was associated with the time to recurrence in a Wilcoxon analysis. Analysis of the outcome data in a Cox proportional hazards model suggested that there was an interaction between tumorigenicity and metastatic potential of HCC in nude mice and serum CEA concentration in the patient and stage of disease. A univariate analysis indicated that both tumorigenicity and metastatic potential of HCC in nude mice were significantly associated with the serum CEA concentration of the patient but not with the other variables of stage of disease, mucin production, local tissue invasion, state of differentiation, or sex. A subset of 57 patients was operated upon for cure and followed prospectively for up to 61 months. Tumorigenicity and, to a lesser extent, experimental metastatic potential were associated with disease recurrence in 23 of these patients. Seventy-eight % of the subset of patients who were operated upon for cure developed liver metastasis as one site of their progressive disease. Thus, the ability of HCC cells isolated from surgical specimens to grow in athymic nude mice correlates with the development of advanced disease in patients.
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PMID:Metastatic potential of human colorectal carcinomas implanted into nude mice: prediction of clinical outcome in patients operated upon for cure. 258 33


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