Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of recent studies have suggested a relationship between Ewing's sarcoma (ES) and other small round cell tumours of childhood such as peripheral neuroepithelioma (PN). We report scanning electron microscopic studies on the character of induced neural differentiation in ES, neuroblastoma, PN, osteosarcoma and colon carcinoma. We found evidence of neural differentiation in both neural lines and in one of two Ewing's lines before treatment. After differentiation, both Ewing's and neural lines developed neuritic processes with varicosities and little arborization, except for the initially undifferentiated Ewing's line (A4573) which displayed extensive lateral sprouting from neuritic processes after differentiation. Neither treated nor untreated osteosarcoma or colon carcinoma displayed any evidence of neural differentiation. Further, neuroblastoma cells are easily distinguished from ES and PN by virtue of their single, unbranched neurites and lack of lateral sprouting or filopodia. These results provide further evidence for the neural character and close relationship between ES and PN.
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PMID:Scanning electron microscopic evidence for neural differentiation in Ewing's sarcoma cell lines. 210 25

Human colorectal carcinomas frequently express elevated levels of c-myc mRNA in the absence of a gross genetic change at the c-myc locus. To test the hypothesis that these tumors are defective in a gene function necessary for the regulation of c-myc expression, we fused an osteosarcoma cell line that exhibits normal c-myc regulation with two colon carcinoma cell lines that express deregulated levels of c-myc mRNA. The levels of c-myc transcripts in all of the hybrid clones examined were normal and were induced normally by a mitogenic stimulus. Since rates of c-myc mRNA turnover in the colon carcinoma cells were found to be comparable to those in normal cells, increased message stability cannot account for the increased steady-state levels of transcripts. Our findings suggest that loss of function of a trans-acting regulator is responsible for the deregulation of c-myc expression in a major fraction of colorectal carcinomas. Analysis of restriction fragment length polymorphisms in tumor/normal tissue pairs from patients with primary colorectal lesions indicated that deregulation of c-myc expression in the tumors is correlated with frequent loss of alleles of syntenic markers on chromosome 5q; allele loss on 5q could be detected in 9 of 19 tumors expressing deregulated levels of c-myc mRNA, but not in any of 8 tumors expressing normal levels of c-myc RNA. Chromosome 5q is the region known to contain the gene for familial adenomatous polyposis, an inherited predisposition to colon cancer. These findings, together with the earlier finding that the colonic distribution of tumors exhibiting deregulated c-myc expression is similar to that reported for familial polyposis, provide evidence that loss of function of the familial adenomatous polyposis gene is involved in a subset of colorectal cancers in which c-myc expression is deregulated.
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PMID:Evidence that the familial adenomatous polyposis gene is involved in a subset of colon cancers with a complementable defect in c-myc regulation. 254 67

By restriction fragment length polymorphism (RFLP) analysis, it was found that loss of heterozygosity (LOH) at three different chromosomal loci, 3p, 13q, and 17p, occurs simultaneously in nearly 100% of small-cell lung carcinomas (SCLC). This was observed even in stage I tumors and an untreated tumor, and it occurred prior to NMYC amplification. The common region of LOH on chromosome 3p was 3p14-24.1, and this region was also frequently lost in carcinoma of the uterine cervix (100% at D3S2 on 3p14-21) as well as renal cell carcinoma (56% at ERBA beta on 3p22-24.1), suggesting the presence of tumor suppressor gene(s) for these cancers in this region. On chromosome 13, LOH was observed commonly in the region between 13q12 and 13q22, including the RB locus on 13q14, and normal RB protein was not detected in any of 9 SCLC cell lines by immunoprecipitation analysis. The common region of LOH on chromosome 17 was 17p13 and is the same as that in colon carcinoma and osteogenic sarcoma. Since LOH is supposed to unmask the recessive mutation of tumor suppressor gene in the remaining allele, these results may imply that at least six genetic alterations are necessary to convert a normal cell into a fully malignant cancer cell in SCLC. RFLP analysis was performed on several other types of human cancers, including carcinoma of the uterine cervix, neuroblastoma, hepatocellular carcinoma, pheochromocytoma, and stomach cancer to determine the chromosomal loci of putative tumor suppressor genes in each tumor. Chromosomal loci showing frequent LOH were different among these tumors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple genetic alterations in small-cell lung carcinoma. 257 37

We have evaluated the level of pp60c-src protein kinase activity in a variety of human tumor tissues and human tumor cell lines, and have estimated the abundance of the c-src protein in several of these tissues and cell lines. All cell lines derived from tumors of neuroectodermal origin that express a neural phenotype were found to possess c-src molecules with high levels of tyrosine-specific protein kinase activity. In contrast, cell lines derived from tumors of neuroectodermal origin that do not express neural characteristics, such as glioblastomas and melanomas, were found to have pp60c-src molecules with low levels of protein kinase activity. A similar pattern was observed when we analyzed the activity of c-src molecules extracted directly from corresponding tumor tissues. Analysis of human tumor cell lines derived from tissues other than those of neuroectodermal origin revealed that pp60c-src protein kinase activity was low in most cases. Exceptions to this observation were all rhabdomyosarcoma, osteogenic sarcoma, Ewing's sarcoma, and colon carcinoma lines tested. Comparison of pp60c-src kinase activity in normal skeletal muscle and rhabdomyosarcoma tissue and in normal breast tissue and breast adenocarcinoma tissue revealed that pp60c-src kinase activity was specifically elevated in the tumor tissues in both cases. However, the amount of pp60c-src protein in both normal and tumor tissues was found to be similar. These observations suggest that increases in the specific activity of the pp60c-src phosphotransferase in some rhabdomyosarcomas and breast carcinomas may be a characteristic acquired during the malignant transformation of the cells that is retained in cell lines established from these tumors.
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PMID:Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. 309 83

Sparsomycin (Sm) is a known inhibitor of ribosomal protein synthesis with an attractive anticancer potential. Recently, several analogues of Sm which are more active than the parent drug were selected for further study on the basis of in vitro investigations. Six analogues as well as the parent drug were tested for their antitumor activity in eight in vivo murine tumor models: P388 and L1210 leukemias, RC renal cell carcinoma, B16 melanoma, C38 colon carcinoma, LL Lewis lung carcinoma, C22LR osteosarcoma and M5076 sarcoma. Sm itself appeared to have only borderline activity on L1210 leukemia. The analogues that were most active in vitro showed also the highest in vivo activity. The most sensitive tumors were RC, L1210 and P388. Minimal activity was found on B16 and no activity on C22LR, M5076, C38 and LL. The most active compounds are deshydroxy-Sm, ethyl-deshydroxy-Sm and n-pentyl-Sm. There was a considerable loss of activity when L1210 leukemia was implanted sc while the drugs were administered iv. Only one drug, ethyl-deshydroxy-Sm appeared to be active in this assay. No single most effective compound could be found in this study. The overall activity of Sm and its analogues is moderate. The three analogues which show high activity in three ascitic tumors will be further investigated using human tumor xenograft models.
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PMID:In vivo antitumor activity of sparsomycin and its analogues in eight murine tumor models. 322 41

A human tumor xenograft model using pharmacologically immunosuppressed mice was assessed for its suitability to test preclinically the sensitivity of colorectal carcinomas, bone sarcomas and melanomas against anticancer agents. Besides ionizing radiation, 14 cytotoxic drugs including 5-fluorouracil (5-FU), dimethylmyleran (DMM), cytosine arabinoside, cyclophosphamide, melphalan, BCNU, mitomycin C, adriamycin, bleomycin, etoposide, vinblastine, cisplatin, procarbazine and DTIC were assayed. Ionizing radiation, 5-FU and DMM were also applied at lethal doses followed by bone-marrow rescue heavy therapy. Four colon carcinomas responded poorly to most of the agents but one tumor displayed marked sensitivity to BCNU. Lethal doses of radiation, 5-FU and DMM could also show considerable activity. High sensitivity was shown by a Ewing sarcoma to DMM and cyclophosphamide and by an osteosarcoma to the latter drug. No strong effects were seen against melanomas. Lethal doses of DMM induced the best regression of one colon carcinoma. In general, the superiority of heavy therapy for solid human tumors compared to maximally tolerated doses was demonstrated. Individual carcinomas of the same type displayed different drug sensitivity.
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PMID:Xenografts in pharmacologically immunosuppressed mice as a model to test the chemotherapeutic sensitivity of human tumors. 345 87

A mouse monoclonal anti-CEA antibody (11.285.14) has been examined for tumour localization potential by assessing its distribution in immunodeprived mice with xenografts of human colon carcinoma cell lines HCT-8, HRT-18, HT-29, and LS174T and a xenograft (HRVB) established from a primary rectal carcinoma. With four carcinomas (HCT-8, HT-29, LS174T, and HRVB) preferential tumour localization of 125I anti-CEA was seen. Compared with 131I normal IgG1 localization indices of up to 4.4:1 were achieved. Up to 10% of the injected dose of 125I anti-CEA was present/g of tumour tissue and with the largest xenografts examined (3-4 g) up to 40% of the total body reactivity was localized in tumour tissue. The tumour localization of 131I labelled antibody was visualized by external gamma camera imaging. Overall antibody localization correlated with the CEA content of the xenografts and the fourth colon carcinoma xenograft (HRT-18) and an osteogenic sarcoma xenograft (791T), both with very low CEA levels, showed no localization of the monoclonal antibody.
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PMID:Localization of an anti-CEA monoclonal antibody in colo-rectal carcinoma xenografts. 384 77

The cytotoxic activity of 5'-deoxy-5-fluorouridine (5'-ddFUrd) was established in six cultured human tumor lines: 47-DN and MCF-7 breast carcinomas, MG-63 osteosarcoma, HCT-8 colon carcinoma, Colo-357 pancreatic carcinoma, and HL-60 promyelocytic leukemia. Cells were exposed to a wide range of 5'-dFUrd concentrations (from 0.1 microM to 1.0 mM) for 3, 6, or 24 hrs, and then cloned using standard in vitro clonogenic assays. 5'-dFUrd exhibited its best activity in the 47-DN and MCF-7 breast cell lines and in the MG-63 osteosarcoma line (3-hr LD50 values of 32, 34, and 38 microM, respectively). Less activity was observed in the HCT-8 colon (LD50 = 195 microM) and Colo-357 pancreatic (LD50 = 155 microM) tumor lines, and ver poor activity was noted in the HL-60 leukemia cell line (LD50 = 465 microM). The metabolism of 5'-dFUrd to 5-FU (FUra) and FUra-nucleotides was determined and found to directly correlate with the potency of 5'-FUrd in these cell lines. These results suggest that: (a) there is a marked variation in sensitivity of human cancer cells of different tissue origin to 5'-dFUrd, (b) there is a direct relationship between the sensitivity of human cells to 5'-dFUrd and the ability of the cell to metabolize 5'-dFUrd to FUra, and (c) increasing exposure period of cells to 5'-dFUrd did not markedly alter 5'-dFUrd potency in all human cancer cells examined, with the exception of the 47-DN breast cancer cells.
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PMID:Cytotoxic activity of 5'-deoxy-5-fluorouridine in cultured human tumors. 622 89

The murine monoclonal antibody 791T/36 cross-reacts with cells other than the immunizing osteogenic sarcoma cell line 791T, upon which the 791T/36-defined epitope is expressed on a protein of apparent molecular weight 72,000. An investigation was performed to determine whether the epitope occurred on similar molecules on other cell lines. Radiolabelled immunoprecipitates, prepared with the 791T/36 antibody, from three osteogenic sarcoma cell lines (2 OS, 788T and 278T), the prostate carcinoma EB33 and the colon carcinoma HcLo each contained a protein with a molecular weight of 72,000 as the major constituent, together with, in some cases, material of lower molecular weight. This heterogeneity was shown by neuraminidase treatment of the immune precipitates to be due to variations in sialic acid content of the antigens since, in five of the six cell lines tested, such treatment produced homogeneous material of apparent molecular weight 55,000. Chymotrypsin treatment of the immune precipitates produced in each instance a major polypeptide of molecular weight 47,000 which displayed no microheterogeneity. Immunoadsorbent-purified antigen from 791T cells was shown to bind strongly to Sepharose-wheat-germ agglutinin and less to Sepharose-concanavalin A, confirming the glycoprotein nature of this antigen. These studies demonstrate that molecules expressing the 791T/36-defined epitopes on different tumour cell lines are glycoproteins which display heterogeneity with respect to apparent molecular weight that is attributable to varying degrees of sialylation. No apparent differences were detected in the polypeptide "backbone" of these antigenic molecules.
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PMID:Analysis of a human osteogenic sarcoma antigen and its expression on various human tumour cell lines. 658 12

The growth of three human tumor xenografts, namely an Ewing sarcoma, a colon carcinoma and an osteosarcoma, was compared in nude and conditioned mice. Conditioning protocols included (1) immune deprivation (thymectomy, lethal irradiation and cytosine arabinoside pretreatment); (2) immunosuppression with procarbazine, cyclophosphamide and antithymocyte serum; and (3) continuous administration of cyclosporin A. Similar tumor growth was seen in nude mice, immune-deprived mice and mice treated with the medium and high-dose immunosuppressive protocol. Cyclosporin A allowed only very modest tumor growth. In the main comparative experiment with the Ewing sarcoma and the colon carcinoma, overall survival was lowest with nude mice (17%), higher with immune-deprived mice (61%) and best with immunosuppressed mice (81 and 87%). For the screening of anticancer agents the immunosuppressive protocol consisting of synergistic procarbazine, cyclophosphamide and antithymocyte serum may be added to the already available models. It allows adequate tumor growth with good animal survival and does not require operative procedures and irradiation.
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PMID:Comparative growth of human tumors in pharmacologically immunosuppressed, immune-deprived, cyclosporin A-treated and nude mice. 674 12


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