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)

An H-2 heterozygous sarcoma, MDAY, originally induced with methylcholanthrene in an (A X DBA/2)F1 ((H-2a X H-2d) hybrid host was selected for growth in the H-2d homoxygous parental DBA/2 strain by serial intraperitoneal transplantation of ascites tumor cells. An apparent variant, designated MDAY-D2, was obtained which showed the expected loss of the private and public H-2Kk haplotype antigens normally associated with the A strain parent and the original MDAY tumor. Comparison of the original and variant lines revealed a wide variety of a cell surface antigen and receptor differences. Both tumors were found to be highly anaplastic and histologically unclasssifiable. Examination of the two tumor lines growing in vivo revealed a remarkable difference in their metastatic growth potential. The original MDAY line showed little propensity to spread to any organ site, with the occasional exception of liver, after subcutaneous inoculation of (A X DBA/2)F1 mice. In striking contrast, there was a rapid and massive spread of MDAY-D2 to liver, spleen, lungs and kidneys within 12-16 days: liver and spleen could be totally replaced by tumor within 2-3 weeks. These characteristics were observed in both (A X DBA/2)F1 and DBA/2 mice. The tendency to metastasize, as well as loss of the H-2Kk haplotype, appeared stable and irreversible. Although the precise origin of MDAY-D2 is not clear, its metastasizing properties are unique, making it a useful and desirable model to study the biology of metastasis.
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PMID:Induction of a tumor with greatly increased metastatic growth potential by injection of cells from a low-metastatic H-2 heterozygous tumor cell line into an H-2 incompatible parental strain. 72 18

We examined 76 bladder tumors of various stages and grades for the presence of the ABO (H) cell surface antigen, using the specific red cell adherence technique. Of the grade I lesions studied 70 per cent were positive for the cell surface antigen and none of the 26 grade III tumors retained the antigens. When correlated with clinical stage the tumors showed no antigens for those of stages B1 to D, while 12 of 16 stage A lesions were positive for the antigen. When stage A lesions were studied and the findings were correlated with recurrence and metastasis/invasion rates the cell surface antigen was present on the initial tumor in only 1 lesion that recurred at an invasive stage. The findings of this study show that the specific red cell adherence technique may be valuable for predicting malignant potential in low grade, low stage cancer of the bladder. If supported by further investigation this technique may offer the capability of selecting low grade, low stage bladder tumors that are destined to invade or metastasize while they are at curable stages.
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PMID:Correlation of the cell surface antigens with stage and grade in cancer of the bladder. 75 41

Covalent linkage of an antitumour antibody specific for a tumour cell surface antigen to an antilymphocyte antibody specific for the T lymphocyte receptor complex produces a heteroconjugated antibody that can activate and redirect cytotoxic T lymphocytes to lyse tumour cells. The ability of an antilymphocyte-antitumour heteroconjugate (500A2 x 96.5) to direct the lysis of murine melanoma cells by cultured murine lymphocytes was tested in vitro using a 4-h chromium release assay and in vivo with a tumour neutralization assay. In vitro, the addition of heteroconjugated antibody significantly increased tumour lysis by murine C3H/HeN lymphocytes (median specific lysis 82.7 per cent with lymphocytes plus heteroconjugate versus 9.5 per cent for lymphocytes alone, P less than 0.001). In vivo, treatment with heteroconjugated antibody plus lymphocytes significantly reduced the development of pulmonary metastases after intravenous tumour administration (median number of pulmonary metastases 28.5 for combined treatment versus 250 for heteroconjugate or lymphocytes alone, P less than 0.001).
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PMID:Heteroconjugated antibodies enhance lymphocyte-mediated tumour cell lysis in vitro and in vivo. 138 50

We have established a large library of monoclonal antibodies against a human hepatoma cell line called FOCUS. One such monoclonal antibody (SF-25) detects a 125-kilodalton cell surface antigen found on FOCUS cells. As both the liver and the colon are of endodermal origin, we examined the possibility of expression in colon adenocarcinomas. This antigen was found in all 23 colon adenocarcinoma tissues surgically obtained but was absent in the adjacent normal mucosal counterpart as determined by a direct radioimmunohistologic technique. In the present study, we have established a model for human metastatic colon adenocarcinoma using the LS 180 cell line. Athymic mice were further immunosuppressed by intravenous injection of anti-NK cell antibodies (antiasialo GM1). After 24 h, mice were injected with LS 180 cells either via the tail vein or into the spleen followed by splenectomy. Macroscopic pulmonary and lymphatic metastasis developed within 2-3 wk after injection of cells and 9 of 10 mice died with advanced metastatic disease 2-3 wk later. In addition, macroscopic hepatic metastases were evident in 4 of 5 mice 3-4 wk after intrasplenic injection. Both hepatic as well as pulmonary and lymphatic tumor spread was localized by nuclear imaging with 125I-SF-25. Furthermore, micrometastases were detected by autoradiography 5-10 days later. Monoclonal antibody SF-25 is a potential candidate for tumor localization and the experimental metastatic colon cancer animal model may be useful for treatment evaluation of monoclonal antibody SF-25 either alone or in combination with other monoclonal antibodies when conjugated to radionucleotides and chemotherapeutic agents.
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PMID:Radioimmunolocation of hepatic and pulmonary metastasis of human colon adenocarcinoma. 270 16

A mouse monoclonal antibody (BLMRL-HMFG-Mc5) prepared against a defined cell surface antigen of human mammary epithelial cells, non-penetrating glycoprotein (NPGP), was used in imaging and distribution studies in athymic nude mice grafted with human breast tumors. For in vivo tissue distribution studies, 125I-labeled monoclonal antibody was injected into nude mice carrying simulated metastases of human tumors (breast and colon carcinomas). After 22-24 hr the amount of radioactivity per gram of tissue was 3-4 times higher in the breast tumor than in liver, brain, lung, muscle, or spleen. In contrast, colon carcinoma tissue, grafted and treated likewise, did not show higher accumulation of radioactivity relative to other tissues. At 4 days, the incorporation in breast tumors remained almost as high, while the circulating radioactive tracer and the incorporation in tissues other than breast had fallen significantly. In tumor imaging studies, breast tumor masses as small as 4 mm in diameter were clearly localized on a whole body scan using 131I-labeled BLMRL-HMFG-Mc5 antibodies with a High-Purity germanium gamma camera. Normalization of 131I-distribution to that of 99mTc-pertechnetate increased the specificity of this imaging methodology. The quantitative density of 131I-label was 2-3 fold higher over the breast tumor than over comparable areas of the mouse. No positive localization images were obtained for similar implants of colon and lung carcinomas or melanomas after injections of 131I-labeled BLMRL-HMFG-Mc5. Localization of human breast tumors in this model can be achieved with 131I-labeled anti-breast epithelial monoclonal antibodies.
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PMID:Localization of human breast tumors grafted in nude mice with a monoclonal antibody directed against a defined cell surface antigen of human mammary epithelial cells. 307 29

A B16 melanoma clone and four derived subclones exhibiting markedly different tumorigenic and metastatic potentials in young C57BL/6 mice were investigated comparatively to determine relative immunogenicities and capacities to induce humoral and cell-mediated immune responses following subcutaneous injection. All five populations stimulated some production of circulating antibody to a cell surface antigen complex (B16-gp70/80/85) specified by endogenous murine leukemia virus, as well as spleen-cell-mediated cytolytic and cytostatic activity apparently directed to the same antigens, but to varying extents. Immunogenicity and relative capacity to induce immunity were inversely related to tumorigenicity and tumor growth rate but were not obviously correlated with metastatic behavior. There were indications that tumor behavior might be influenced by developing or naturally acquired host immunity. The most rapidly growing clone, G3.26, which was poorly immunogenic and nonmetastatic in young mice, grew more slowly and was markedly metastatic in normal-aged mice in which some natural humoral and cellular responses cross-reactive with B16-gp70/80/85 antigens were detected. Furthermore, the highly immunogenic and normally nonmetastatic clone, G3.15, was appreciably metastatic in mice immunosuppressed by T lymphocyte depletion. In other cases, however, tumor behavior in immunosuppressed and immunopotentiated mice did not consistently indicate a critical role for host immunity in determining metastatic or nonmetastatic activity.
Invasion Metastasis 1987
PMID:Development of host immunity to phenotypically diverse B16 melanoma clones. Implications for tumor growth and metastasis. 343 37

Fifty-six patients with gastrointestinal cancers and four patients with benign colorectal tumours have been injected with radiolabelled anti-tumour monoclonal antibody ( 791T /36) to assess the degree of localization of the antibody by external scintiscanning and measurements on resected specimens. Twenty-nine patients with primary colorectal cancer showed increased uptake of the radiolabelled antibody in the resected tumours, with a tumour to normal tissue (T:NT) ratio of 2.5:1. All but two of fifteen patients with recurrent or metastatic tumour showed positive images of the deposits on external scintiscanning. Twelve patients with noncolonic gastrointestinal malignancy were studied and in only two patients were tumours demonstrated by external scanning. There were no positive images in four patients with benign colonic disease nor could increased uptake of radiolabelled antibody be demonstrated in the resected specimens. Immunohistology and autoradiography have shown that the antibody can be demonstrated in the pseudoacini and stroma of colon cancer. There are indications that this may represent localization to a cell surface antigen which becomes detached in the processing of the histological sections. It seems that in the gastrointestinal tract the monoclonal antibody 791T /36 is consistently taken up by colorectal cancer. Only a few noncolonic cancers and no benign colonic tumours take up the antibody. This antibody uptake may prove of value in the detection of occult metastases and in the targeting of antitumour agents.
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PMID:The localization of an anti-tumour monoclonal antibody (791T/36) in gastrointestinal tumours. 637 36

Thirty bladder tumours of various stages and grades were examined for the presence of A.B.O. (H) cell surface antigen using specific red cell adherence (SCRA) technique. Ten patients with stage A disease and low grade tumour (grade I) retained the antigens, whereas all patients with high stage disease (B,C,D) and high grade tumours showed absence of antigen. When these data were correlated with recurrence pattern and metastasis or invasion rate, patients who did not show the antigen at the initial visit developed metastases and had poor prognoses. The patient who had expressed the antigen by positive SCRA had fewer recurrences and a longer tumour-free interval. Hence if SCRA is done in all bladder tumours at the initial visit and at subsequent follow-up, it can be used as a biological marker.
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PMID:Cell surface antigen -- a study in bladder tumours. 705 38

To investigate critical factors influencing the localization and antitumor effects of monoclonal antibodies (MAb) or toxic conjugates, we have adapted a single rat sarcoma, HSN, for preferential growth in the lungs, liver, and lymph nodes (the major sites of metastasis in humans) and have raised a panel of syngeneic rat MAbs to a stably-expressed cell surface antigen. Using this model we have shown that localization in tumors is significantly influenced by their anatomical location and vascularization, and the degree of MAb interaction with host cells. Uptake in small hepatic tumors was excellent, but access to lung tumors was limited by the poor permeability of pulmonary vessels. HSN cells transfected with th human IL-2 gene and coinjected in low numbers with parental tumors secreted sufficient cytokine to enhance the local permeability of vessels and doubled MAb localization in tumors without any systemic toxicity, suggesting that regional delivery of IL-2 may be used to enhance MAb localization in this situation. In order to extent the applicability of the model to studies of MAbs raised against human tumor targets, we have transfected the human c-erb B-2 gene (homolog of the rat neu) into the highly metastatic HSN.LV subline. MAbs raised against the external domain of the p185 product can now be screened for their ability to localize in metastases, and for various conjugates to inhibit tumor growth either independently of, or in association with, a fully functional immune system.
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PMID:Monoclonal antibodies for the treatment of metastases. Evaluation of strategies using a syngeneic rat model. 788 38

Various tumours, classically specified as either neuroendocrine or non-neuroendocrine, contain high numbers of somatostatin receptors, which enable in vivo localization of the primary tumour and its metastases by scintigraphy with the radiolabelled somatostatin analogue octreotide. In addition granulomas and autoimmune processes can be visualized because of local accumulation of somatostatin receptor-positive activated mononuclear leucocytes. In many instances a positive scintigram predicts a favourable response to treatment with octreotide. It is tempting to speculate that octreotide labelled with an appropriate radionuclide might be used in cancer therapy. The successful application of radiolabelled octreotide in scintigraphy indicates the possible usefulness of other radiolabelled peptides, either native peptides or derivatives of these, in, for example, nuclear oncology. The small size of these peptides, e.g. bombesin and substance P, is of the utmost importance for a relatively fast blood clearance, thus leading to low background radioactivity. In this way peptides are powerful alternatives to (fragments of) monoclonal antibodies, the application of which to scintigraphic localization of specific cell surface antigen-bearing tumours is plagued by slow blood clearance and, hence, high background levels.
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PMID:Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. 840 61


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