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)

"New" carbohydrate structures on the surface of or secreted by cancer cells, identified as epitopes by monoclonal antibodies, are reviewed. These structures may represent the accumulation of precursor chains because of decreased activity of synthesizing enzymes, the production of new oligosaccharides due to increased or aberrant glycosylation of carbohydrate chains, a change in density of carbohydrates on the cell surface, or exposure of chains usually covered by other structures. Alterations in glycolipid synthesis include aberrant fucosylation and/or sialyation of the lacto series, sialylation or fucosylation of the globo series, and sialyation of the ganglio series. Many of these carbohydrate epitopes have become useful for the diagnosis, prognosis, and monitoring of patients with cancer. Some of the important markers include CA 15.3, CA 19.9, CA 50, CA 125, CA 242, MCA, SLEX, etc. Incomplete glycosylation of O-linked mucin oligosaccharide is recognized as the important "cancer antigen" B72.3, which is sialyated Tn. The oligosaccharide components of alpha-fetoprotein, carcinoembryonic antigen, and epidermal growth factor receptor are also reviewed. In many instances the glycosylation seen in cancer cells or their products reflects patterns seen during normal development. Thus, cancer-associated oligosaccharides are oncodevelopmental in nature. The biologic significance of carbohydrates on cell surfaces is not known, but several possibilities include a role in cell to cell recognition, intracellular processing of glycoproteins, cell activation, and ability of cancer cells to metastasize.
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PMID:Cancer-associated carbohydrates identified by monoclonal antibodies. 221 Jul 23

The very rapidly expanding knowledge and technologies of molecular biology are reviewed with special reference to problems in the clinical management of lung cancer. Genetic events, tumor-associated antigens, production of murine and human monoclonal antibodies, culture of cell lines, intratumoral phenotypic diversity and squamous-lung-cancer-associated antigens are discussed and related to possible therapeutical approaches. A monoclonal antibody with high specificity for squamous cell lung cancer reacted positively in blood samples and tissue extracts in about 80%. Its use as a marker during follow-up after surgical treatment is demonstrated by examples. It is concluded that there will be limiting factors in the therapeutic use of monoclonal antibodies, such as intratumoral phenotypic diversity. Genetic analysis might be a method for selecting a high risk group of individuals in whom exposure to carcinogenic factors, such as cigarette smoking, would be fatal. Murine monoclonal antibodies can be used in vitro for screening, for histological examination and for prognostic studies. Human monoclonal antibodies should be used for in vivo purposes as well as for the screening of primary tumor and metastases for the therapy. To achieve usable results, the monoclonal antibodies should be raised against the cell membranes that, in particular, are expressed on the stem cells of the neoplastic cell population.
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PMID:On the advent and necessity of molecular biology in the clinical management of lung cancer. 243 92

Mucin-like cancer-associated antigen (MCA), a new tumor marker using the mouse monoclonal antibody b-12 is thought to be of value in the management of patients with breast cancer. In this study sera from 191 female patients with breast cancer (112 with progressive disease [PD] and 79 with no evidence of disease [NED]) were analyzed for MCA levels and compared with those of cancer antigen 15-3 (CA 15-3) in single determination and in combination with carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA). A cut-off level of 14 U/ml for MCA seems to be more appropriate than the recommended 11 U/ml to distinguish between PD and NED in patients with breast cancer. Although there was a fairly good correlation of MCA to CA 15-3, MCA was inferior in sensitivity and specificity to CA 15-3. Patients with osseous metastases and those with more than one metastatic site showed higher MCA levels than patients with visceral or soft tissue metastases, a fact which was comparable to CA 15-3. Combining MCA and CA 15-3 resulted in a gain in specificity but marked loss of sensitivity. The combination of MCA and CEA results also in a loss of sensitivity whereas the combination of CA 15-3 and CEA showed an increased specificity and only a negligible loss of sensitivity. The combination of MCA with TPA is of little value in the follow-up of breast cancer, as is the combination of CA 15-3 with TPA. The combination of CA 15-3 with CEA can be still recommended for follow-up for early detection of metastases in breast cancer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mucin-like cancer-associated antigen (MCA) compared with CA 15-3 in advanced breast cancer. 279 51

The pathophysiological mechanisms of hypercalcaemia were assessed in 50 rehydrated patients with cancer-associated hypercalcaemia. Surprisingly, renal tubular calcium reabsorption appeared to increase progressively as serum calcium rose, suggesting that the nomogram used for the calculation may have been inaccurate, in absolute terms, probably due to its failure to take account of the levels of urinary sodium excretion. There were significant differences in the mechanisms of hypercalcaemia in different patient subgroups, however, independent of differences in urinary sodium excretion. In those with few or no bone metastases, increased renal tubular calcium reabsorption was the principal cause of hypercalcaemia, often in association with increased bone resorption. These abnormalities were thought to reflect the renal and skeletal actions of a tumour-associated humoral mediator. The main cause of hypercalcaemia in those with extensive metastatic bone disease was increased bone resorption, with contributions from impairment of glomerular filtration rate and, to a minor extent, increased renal tubular calcium reabsorption. These abnormalities were thought to reflect a mainly local-osteolytic mechanism of hypercalcaemia with secondary impairment of GFR. Of all the biochemical variables assessed pre-treatment, the renal tubular component of hypercalcaemia correlated most strongly with post-treatment serum calcium values (r = 0.61, P less than 0.001). Because of their generally lower levels of renal tubular calcium reabsorption, patients with extensive skeletal metastases also had significantly lower post treatment calcium values than patients with few or no metastases (P less than 0.05). These data indicate that the pathophysiological mechanisms of hypercalcaemia are a major determinant of the calcium lowering response after antihypercalcaemic treatment. This should be taken into account during comparative studies of antihypercalcaemic therapy in patients with malignancy.
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PMID:Malignancy-associated hypercalcaemia: relationship between mechanisms of hypercalcaemia and response to antihypercalcaemic therapy. 297 9

Platelet-adhesive protein-tumor cell interaction was studied in vitro and in vivo. Monoclonal antibody 10E5, which inhibits binding of fibronectin and von Willebrand factor to the platelet membrane glycoprotein GPIIb-GPIIIa complex, inhibited the binding of mouse CT26 and human HCT8 colon carcinoma cells to platelets by 63-65%, whereas an irrelevant monoclonal antibody, 3B2, had no effect. Monoclonal antibody 6D1, which inhibits binding of von Willebrand factor to GPIb, also had no effect. RGDS, a tetrapeptide that represents the adhesive domain of fibronectin and von Willebrand factor inhibited binding of the tumors to platelets by 64-69%. Monospecific polyclonal antifibronectin antibody inhibited binding by 60-82%; anti-von Willebrand factor antibody inhibited binding by 75-81%. In vivo, polyclonal monospecific anti-mouse von Willebrand factor antibody inhibited pulmonary metastases induced by CT26 tumor cells by 53-64%, B16a amelanotic melanoma cells by 45% and T241 Lewis bladder cells by 46% without induction of thrombocytopenia. Pulmonary metastases with CT26 cells could be inhibited by induction of thrombocytopenia, and reconstituted by infusion of either murine or human platelets. Reconstitution of pulmonary metastases with human platelets could be inhibited 77% by preincubation of human platelets with monoclonal antibody 10E5 before infusion of platelets into mice. Thus, platelets appear to contribute to metastases by their adhesive interaction with tumor cells via the adhesive proteins fibronectin and von Willebrand factor.
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PMID:Role of adhesive proteins in platelet tumor interaction in vitro and metastasis formation in vivo. 328 May 98

We reviewed the clinical records and over 1900 chest radiographs of 218 patients with carcinoma of the breast. The patients were treated with surgery and radiation therapy. During the two-year follow-up pathological signs were seen in the chest radiographs of 103 patients (47%). Irradiation changes were found in 51 patients (23%); in 28 patients (13%) there were pulmonary metastases; and eleven patients had metastases of bony thoracic cage. 36% of patients with metastases had no symptoms. In eight patients other unexpected findings were observed, such as tuberculosis and sarcoidosis. Obviously, periodical chest radiographs are beneficial and advisable in the follow-up of patients with carcinoma of the breast.
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PMID:Value of chest radiography in follow-up of treated breast carcinoma. 378 55

To demonstrate that the anorexia and depletion of cachexia reverses on tumor removal, F344 rats underwent sarcoma resection when their food intake fell to 0 g/day. In survivors of surgery, reversal in food intake was apparent within 3 days postoperatively, followed after 2 days by gain in host weight. To detect whether the transmission of anorexia/cachexia in these tumor-bearing (TB) rats was via the circulation, four groups were studied: single non-tumor bearing (NTB); single TB; parabiotic NTB; and parabiotic TB. The measured blood exchange rate between parabiotic halves was 1.2-1.5%/min. No cachectic effect was detected in either half of the NTB parabionts. There was no evidence of sarcoma metastases in the tumor-free half of the parabiotic TB pair. All the rats associated with the presence of tumor showed cachectic effects but the degree and timing of effect varied among the three conditions, single TB, parabiotic TB half, and parabiotic tumor-free half. In all variables examined (fall in food intake, time of first fall in food intake, host weight loss, elevation of blood urea nitrogen) the severities were always in the same sequence: single TB greater than parabiotic TB half greater than parabiotic tumor-free half greater than NTB. In addition, the TB parabiotic pair had a significantly longer survival time and grew a significantly larger tumor than did the single TB animal. The parabiotic tumor had a slower initial growth rate and a slower deceleration rate than the singlet tumor. These results provide evidence for the humoral mediation of cancer-associated cachexia.
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PMID:Parabiotic transfer of cancer anorexia/cachexia in male rats. 386 7

Because tumor-induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor-induced platelet aggregation as well as the effect of various anti-platelets agents. Two mechanisms for tumor-induced platelets aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo-lipo-protein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phospholipid component of the tumor membrane. We now report a new mechanism of tumor-induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen-induced metastatic murine colon carcinoma, CT26. These tumors do not require cell-surface sialic acid or serum complement as does the first mechanism. They do not require cell-surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin-sensitive surface protein for activity. The ability of the thrombin-generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin-competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacyclin, 6-keto-PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor-induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti-platelet pharmacologic agents. Sensitivity to anti-platelet agents correlates with the mechanism by which tumor cells aggregate platelets.
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PMID:A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases. 629 77

Honn et al. [Science (Wash. DC), 212: 1270, 1981] have recently reported a 93% reduction in the development of metastases of B16 amelanotic tumor cells given i.v. following a single dose of prostacyclin (PGI2) (100 micrograms) and theophylline (100 micrograms) 30 min prior to the injection of tumor cells. We have been unable to reduce pulmonary metastases induced by the i.v. injection of CT26 colon adenocarcinoma, Lewis lung carcinoma, or B16 amelanotic melanoma cells with a similar regimen. Thus, PGI2 and theophylline given prior to injection of tumor cells and 2 hr postinjection had no effect on the number or volume of pulmonary tumor nodules for CT26 cells, using 15 experimental and 14 control animals; Lewis lung cells, using 14 experimental and 13 control animals; or B16 amelanotic cells, using 26 experimental and 12 control animals. The PGI2 used was shown to be active in vitro, inhibiting tumor-induced platelet aggregation by all three tumors at 10(-9)M; and in vivo by inhibition of Lewis lung-induced thrombocytopenia at 1 hr, using 100 micrograms PGI2 prior to the injection of tumor cells.
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PMID:Lack of effect of in vivo prostacyclin on the development of pulmonary metastases in mice following intravenous injection of CT26 colon carcinoma, Lewis lung carcinoma, or B16 amelanotic melanoma cells. 637 76

The antitumor activity of a glycopeptide purified from human malignant effusion, termed cancer-associated galactosyltransferase acceptor (CAGA), was assessed in BALB/c mice bearing primary and metastatic tumors. Initial studies with the fast-growing KA31 and slow-growing KB521 Kirsten sarcoma-transformed mouse fibroblast cell lines confirmed their tumorigenicity and metastatic potential. Inoculation of 1 X 10(5) KA31 cells s.c. resulted in palpable tumor formation in recipient animals within 14 days and death within 42 days from primary tumor growth (mean survival, 26 days; total survival, 0%). Inoculation of the slower-growing KB521 resulted in tumor formation in 85% of recipients, and tumor-bearing animals succumbed within 56 days after primary inoculation (mean survival, 48 days; total survival, 15%). Administration of CAGA by i.p. injection as a single dose or series of five daily doses (each 50 micrograms) inhibited primary tumor growth by 35 to 68% in animals receiving KA31 cells and by 25 to 70% in animals receiving KB521 cells. CAGA increased mean survival 50% from 26 to 38 days and total survival from 0 to 27% in animals bearing KA31-derived primary tumors. In animals bearing KB521-derived tumors, CAGA increased mean survival from 48 to 90 days and total survival from 15 to 50%. Similarly, CAGA was also found to significantly inhibit formation of pulmonary metastases in animals after excision of primary tumors. CAGA administration reduced death from metastatic deposits by 55 to 66% in animals initially inoculated with the KA31 cell line and by 58 to 90% in animals initially bearing primary tumors derived from the KB521 line. There was a corresponding decrease in the number of metastatic deposits per lung after administration of CAGA. Thus, CAGA appears to have potential antitumor activity against tumors with a range of growth rates and appears to inhibit both primary and metastatic tumor growth.
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PMID:Inhibition of primary and metastatic tumor growth in mice by cancer-associated galactosyltransferase acceptor. 640 94


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