Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1261473 (sarcoma)
 25,952 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the advent of hybridoma technology, monoclonal antibodies (MAbs) can be produced against specific human tumor cell-surface antigens. 44X14, an MAb produced in our laboratory by the immunization of BALB/c mice with colon carcinoma cells, exhibits high affinity for breast, lung, and colon carcinomas. However, this MAb shows little evidence of in vitro cytotoxicity. To enhance the potency of this MAb, it was coupled to the A chain (RTA) of the castor-bean protein ricin. Ricin is composed of two subunits--RTA, which binds to ribosomes and inhibits protein synthesis, and the B chain (RTB), which binds to galactose residues on all human cells and facilitates entry of RTA into the cell. By chemically separating RTA from RTB, RTA can then be coupled to MAb 44X14 so as to redefine its specific toxicity. This immunotoxin 44X14-RTA was assayed for protein-synthesis inhibition in HT-29 colon carcinoma and HT-1080 sarcoma cells by [3H]leucine uptake. Intact ricin (RTA + RTB) inhibited protein synthesis by 50% at concentrations of 0.76 and 4.8 ng/ml in HT-29 and HT-1080 cells, respectively. MAb 44X14 showed the same level of inhibition on HT-29 cells at 6.4 micrograms/ml, whereas the immunotoxin MAb 44X14-RTA showed 50% inhibition at 0.15 micrograms/ml. No effect of either MAb 44X14 or MAb 44X14-RTA at concentrations up to 200 micrograms/ml was seen on HT-1080 cells. Thus, the coupling of RTA to carcinoma-specific MAb 44X14 increased its potency 50-fold without increasing its nonspecific binding to cells that do not contain the appropriate antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monoclonal antibody-ricin A chain conjugates (immunotoxins): potential therapeutic agents for human colon carcinoma. 394 71

Transformed cell lines have been selected following exposure of NIH 3T3 cells to a calcium phosphate precipitate containing DNA from: the human colon carcinoma cell line, SW 480; the cloned Harvey sarcoma virus ras gene; the parental NIH 3T3 cell line; or no DNA (a spontaneous transformant). Unlike the parental 3T3 cells, each of these lines readily formed malignant spindle cell tumors in Swiss nu/mu mice. Southern blots confirmed the presence of the human homologue of the Kirsten ras gene in the cells transformed by SW480 DNA, and the Harvey ras gene in the cells transformed with that cloned sequence. The morphology of each of the lines was different, the cells transformed with the human and viral ras genes being the most aberrant (but not identical) and forming the most extensive foci in culture. These ras transformed lines also exhibited anchorage-independent growth, while the two other transformed lines did not. Both of the ras transformed lines, as well as the spontaneously transformed line, exhibited a pronounced disruption of actin microfilament structure. Two-dimensional gel electrophoresis of 35S-methionine-labeled peptides revealed that these three lines also had a marked decrease in an acidic peptide of 32K daltons.
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PMID:Cellular and molecular changes in 3T3 cells transformed spontaneously or by DNA transfection. 402 62

We isolated cDNA clones corresponding to the normal human Ki-ras2 gene and to the transforming allele of the Ki-ras2 gene present in the human colon carcinoma cell line SW480. These two cDNAs encode p21 proteins which differ only at the amino acid at position 12. The normal cDNA encodes a glycine at this position, and the transforming allele encodes a valine. Expression of these cDNAs indicates that this amino acid 12 alteration confers oncogenic activity on the mutated gene. Analysis of the relationship of the cDNAs and Kirsten sarcoma virus ras gene to a genomic clone allowed us to identify two alternative 3' coding exons for the Ki-ras2 gene, suggesting that the Ki-ras2 gene encodes two p21 proteins which differ at their carboxy termini. Our data also show that only one of the p21s is necessary to convert cells to a tumorigenic phenotype.
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PMID:Human colon carcinoma Ki-ras2 oncogene and its corresponding proto-oncogene. 609 20

The human colon carcinoma cell line HT-29 was adapted to grow in chemically defined medium (CDM). The spent CDM (S-CDM) was concentrated by Amicon filtration and the crude HT-29 S-CDM purified by 40% saturated (NH4)2 SO4 precipitation. The purified antigen was tested by a microcomplement fixation (MCF) assay against the sera of cancer patients of various histologic types and against the sera of normal donors. Fifteen of 20 (75%) colon cancer, 16/20 (80%) breast cancer sera, 14/19 (74%) lung cancer sera, and 13/20 (65%) miscellaneous carcinoma sera were positive in the MCF. By contrast, 2/21 (10%) melanoma sera, 7/20 (35%) sarcoma sera, and 2/19 (11%) normal sera were positive. These data suggest the presence of a carcinoma-associated antigen in the spent CDM of the HT-29 colon carcinoma cell line adapted to grow in CDM.
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PMID:Presence of a carcinoma-associated antigen(s) in the spent chemically defined medium of a human colon carcinoma cell line. 615 28

DNA sequences capable of inducing oncogenic transformation of NIH3T3 mouse cells are found in a number of human tumour cell lines. When DNAs of these cell lines are applied to monolayer cultures of the mouse fibroblasts, foci of transformed cells are observed 2-3 weeks later. DNA from cells of such primary foci can be used in turn to induce foci in a second cycle of gene transfer. The human DNA sequences responsible for transformation have been called oncogenes, the best characterized of which is closely related to the Harvey murine sarcoma virus oncogene. Here we present a characterization of an oncogene which we found originally to be present in DNA of the SW480 colon carcinoma cell line. We indicate its structural outlines and demonstrate, in extension of reported results, its presence in an activated form in the genome of several types of human tumour cell lines as well as in biopsy tissue from an adenocarcinoma of the large bowel. We identify this tumour oncogene with c-Ki-ras2, one of two known members of the Kirsten ras family of human proto-oncogenes, extending a series of recent reports which have demonstrated homologies between human oncogenes and those of Harvey and Kirsten murine sarcoma viruses. The c-Ki-ras2 oncogene of several tumour cell lines is shown to be amplified.
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PMID:Characterization of a human colon/lung carcinoma oncogene. 629 38

In vitro and in vivo animal studies and some clinical trials have shown apparent benefit from thermochemotherapy; however, this treatment modality has not been adequately tested in humans. This investigation evaluated response to and toxicity of secondary thermochemotherapy, using each patient as his own control. Patients with advanced cancer who had documented disease progression while receiving chemotherapy alone were subsequently treated with the same drug, by the same dose and route, combined with localized hyperthermia. Thirty-four patients whose diseases included metastatic colon carcinoma, melanoma, sarcoma and hepatoma in viscera (29) or surface tissues (5) were treated with combination thermochemotherapy for 1 hour daily for 5 days/month. Effective heating from 41 to 45 degrees C minimum tumor temperature was possible in 17/19 (89%) tumors in which temperatures could be measured safely. The authors observed 5 (15%) tumor regressions for 1 to 5 months (median, 2 months), and 19 (56%) tumor stabilizations (growth arrest of previously progressive disease) for 1 to 9 months (median, 4 months). Subjective improvement in activity and/or pain control occurred in 6 (18%) patients and 20 (59%) had no progression of symptoms during treatment. Moreover, there was no detectable morbidity from localized hyperthermia, and no evidence of increased chemotherapy toxicity. While the mechanism(s) of response is poorly understood, the documented disease regressions and stabilizations of previously progressive disease in 24 (71%) patients during secondary combination thermochemotherapy indicates that the addition of hyperthermia may have useful anticancer activity. Expanded trials are warranted.
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PMID:Clinical thermochemotherapy. A controlled trial in advanced cancer patients. 636 31

Several groups have shown that the malignant phenotype can be transferred to NIH/3T3 fibroblasts by incorporation of DNA isolated from tumour cell lines. These studies have demonstrated that the transforming activity of DNA isolated from human bladder, lung and colon carcinoma cell lines is related to an alteration of the cellular homologues of the ras genes of Harvey or Kirsten murine sarcoma viruses. It is, however, unclear what relevance these observations have to the multi-stage nature of tumorigenesis in vivo, in which several independent events are required in both humans and experimental animals. The activation of a cellular oncogene in a defined experimental system for the progressive induction of solid tumours has not yet been demonstrated. We report here that high molecular weight DNA from transplanted squamous cell carcinomas induced by sequential treatment of mouse skin with initiators and promoters of carcinogenesis causes morphological transformation of NIH/3T3 fibroblasts at high frequency. The transforming properties are due to the transfer of an activated cellular homologue of the Harvey-ras (rasH) oncogene.
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PMID:Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. 684 61

A Ewing sarcoma grown in immunosuppressed mice was eradicated with a single lethal dose of dimethylmyleran (DMM) followed by autologous or syngeneic bone marrow. Sarcomas treated 2 weeks after grafting in a phase of rapid proliferation disappeared and large sarcomas treated after 6 or 10 weeks were reduced to necrotic tissue. A human osteosarcoma also regressed distinctly after this therapy while a human colon carcinoma responded poorly. Sub-lethal DMM treatment induced complete remissions in only 62% of the mice. Tumours which display sensitivity in this model may be treated clinically with lethal doses of DMM and autologous marrow transplantations.
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PMID:Control of a human tumour (Ewing sarcoma) in mice by a single lethal dose of dimethyl-myleran and bone marrow. 702 62

Of 1,014 human solid tumors of various histologic types, 690 (68%) showed evidence of colony formation within 2 to 4 weeks. Tumors which grew particularly well were colon carcinoma (104/175), melanoma (134/155), lung carcinoma (62/85), breast cancer (100/140), ovarian carcinoma (50/67), and sarcoma (72/122). Histologic examination indicated that the colony-forming cells retained functional and morphologic features similar to those of the original tumor. Plating efficiencies varied between 0.01% and 0.2%, and the numbers of colonies observed formed a direct linear correlation with the number of cells plated. Recovery of viable tumor cells was increased when enzymatic tumor dissociation was used rather than a mechanical method. A simplified, supplemented medium resulted in improved cloning efficiencies when compared to previously reported methods (Hamburger and Salmon, 1977 b).
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PMID:Cloning of human solid tumors in soft agar. 716 Sep 42

In a previous study, Ewing's sarcoma cells and colon carcinoma cells failed to attach to plastic and to dishes coated with various collagen types I, III and IV, but adhered rapidly to extracellular matrix (ECM) produced by cultured corneal endothelial cells. However, although carcinoma cells required ECM and did not adhere to fibronectin, the sarcoma cells adhered and flattened almost equally well on either substrate. Thus, different adhesive proteins may mediate the attachment of sarcoma- and carcinoma-derived cells to extracellular matrices, the most likely being fibronectin and laminin. Fibronectin stimulates the adhesion of fibroblasts, but not epidermal cells, to collagen type IV (ref. 7) and could mediate the attachment of sarcoma cells. Laminin is confined to the lamina lucida region of basement membranes and has been localized to cellular adhesion sites. Studies of the attachment of epidermal cells in vitro (V.P. Terranova, personal communication) suggest that it is adhesive for epithelial cells, and so could have the same role for carcinoma cells as that played by fibronectin for sarcoma cells. Cultured vascular endothelial cells secrete fibronectin and laminin into both the ECM and the culture medium, and we report here that pre-exposure of plastic dishes to such conditioned medium induces the attachment and flattening of both human colon carcinoma and Ewing's sarcoma cells. While laminin mediates the attachment and spreading of the former fibronectin is responsible for the attachment and flattening of the latter.
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PMID:Respective roles of laminin and fibronectin in adhesion of human carcinoma and sarcoma cells. 745 26


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