Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repeated observations in our laboratory show that the chloroethylnitrosourea of cysteamine ( CNCC ) induces slowed tumor growth rate and decreased lymph node metastasis in rats bearing a rhabdomyosarcoma but concomitantly enhances metastatic dissemination in the lung. Tumors obtained by sc graft of tumor cells, in syngeneic rats, gave a reproducible pattern of metastases at nodal and pulmonary sites after a 60-80-day period. CNCC was administered orally at a dose of 50 mg/kg once a week for 5 weeks beginning at the time of tumor appearance. Forty-five of 46 CNCC -treated rats had lung metastases with 95 (+/- 9.7) nodules; in the control group 29 of 41 rats had lung metastases with 7 (+/- 1.5) nodules. This amplifying effect was found after treatment with two other nitrosoureas (chlorozotocin and hydroxyethylchloroethylnitrosourea ) but not with cyclophosphamide and methotrexate. Lung metastatic amplification was also observed after treatment of the 13762 mammary adenocarcinoma in Fischer rats and treatment of nickel-induced soft tissue tumor. Several hypotheses have been proposed. The dissociated effect of nitrosourea on local tumor, lymph nodes, and pulmonary metastases does not support the concept of systemic immunosuppression as the main mechanism of this phenomenon, but a decrease of local immunological defenses exerted by NK cells, for example, could be possible. Alternatively, a direct effect of the drug on lung tissue, especially lesions of endothelial tissue, could be responsible for the observed effect. Nitrosourea treatment of rats after surgical excision of the tumor, as adjuvant chemotherapy, was responsible for an amplification effect in association with local recurrences. From this fact we hypothesized that nitrosourea treatment could modify the equilibrium of cell subpopulations in the tumor by selecting highly metastatic drug-resistant variants. Although the mechanism of the amplifying effect of nitrosoureas has not been elucidated, our study shows a possible risk in the use of these drugs for inductive or adjuvant chemotherapy.
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PMID:Amplified pulmonary metastases of a rat rhabdomyosarcoma in response to nitrosourea treatment. 623 4

Seventeen nickel compounds were administered to Fischer-344 rats (N = 270) by intrarenal injection (7 mg Ni/rat); the compounds included nickel sulfides, selenides, arsenides, oxide, antimonide, telluride, titanate, ferronickel alloy and metallic nickel dust. Erythrocytosis, as defined by peak hematocrit values that averaged greater than 55% during 1-4 months post-injection, occurred in nine of 17 Ni-treated groups (NiS2, beta NiS, alpha Ni3S2, Ni4FeS4, NiSe, Ni3Se2, NiAsS, NiO, Ni dust). Renal cancers (N = 23) developed within 2 years post-injection in nine of 17 Ni-treated groups (NiS2, beta NiS, alpha Ni3S2, Ni4FeS4, NiSe, Ni3Se2, NiAsS, NiAs, NiFe alloy). The renal cancers included eight fibrosarcomas, five mesangial cell sarcomas, two renal cell carcinomas, two carcinosarcomas, two leiomyosarcomas, two undifferentiated sarcomas, one rhabdomyosarcoma and one nephroblastoma. No erythrocytosis or renal cancers occurred in control rats (N = 97) in three groups treated with the vehicles or metallic iron dust. Rank correlation (p less than 0.0001) was observed between the incidences of erythrocytosis and renal cancers in the 17 Ni-treated groups. Rank correlation (p less than 0.001) was observed between the present incidences of renal cancers and the sarcoma incidences previously reported following intramuscular administration of the 17 nickel compounds to Fischer-344 rats (14 mg Ni/rat). The incidences of renal cancer were not correlated with the mass-fractions of nickel in the 17 compounds, the dissolution half-times of the compounds in rat serum or renal cytosol, or the phagocytic indices of the compounds in rat peritoneal macrophages.
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PMID:Association between erythrocytosis and renal cancers in rats following intrarenal injection of nickel compounds. 648 75

Karyotype patterns, growth, metastasis, and immunogenicity were compared in a rhabdomyosarcoma induced by a single injection of metallic nickel with those in subsequent tumor-cloned cell lines. The primary tumor was induced in a male WAG rat by im injection of 20 mg nickel powder. The parental cell line (9-4/0) and 8 cell subpopulations (J 9-4) isolated from a primary tumor by cloning on agarose were examined. The tumor cell dose inducing tumors in 50% of the animals after sc injection (TD50) and the in vitro growth characteristics showed a marked heterogeneity between parental and cloned tumor cell lines. In vitro doubling times and saturation densities were also heterogeneous without showing a discernible relationship with TD50. Chromosome patterns of the cell lines exhibited very similar modal numbers, whereas chromosome numbers were somewhat different; neither of these exhibited any correlation with tumorigenicity. Parental cell line 9-4/0 expressed a significant degree of immunogenicity, but it did not protect against pulmonary metastasis in immunized rats. Among 6 clones studied, only clone J 9-4/2 appeared to be immunogenic and reduced metastatic spread. The relevance of the comparison between the different characteristics is discussed.
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PMID:Growth, metastasis, immunogenicity, and chromosomal content of a nickel-induced rhabdomyosarcoma and subsequent cloned cell lines in rats. 658 60

In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to their osmotic fragility. Tumour cell lines derived from metastatic lung nodules presented similar NK susceptibilities to cells originating from the primary tumour. However, cloned cell lines differed in their capacity to form lung colonies after i.v. injection, and in their potential for invading lungs after s.c. primary tumour development. No correlation was found between lung colonization potential and NK resistance. Studies of the correlation between metastatic potential and NK sensitivity revealed that (1) all the NK resistant tumour cells were highly metastatic; (2) NK susceptible tumour cells could be either highly or weakly metastatic. Therefore, highly metastatic tumour cells could be either resistant or susceptible to NK lysis. We conclude that the property of resistance to NK contributes to a high metastatic potential. However, other properties could counterbalance and finally prevail over NK susceptibility thus enabling NK susceptible cell lines to be also highly metastatic.
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PMID:Variable susceptibility to NK activity of cloned cell lines derived from a primary rat rhabdomyosarcoma: relationship to metastatic potential. 687 Oct 80

In order to study the heterogeneity of the metastatic and tumorigenic behaviors of malignant neoplasms, we have isolated a series of cloned cell lines from a primary nickel-induced rat rhabdomyosarcoma. The growth characteristics in vitro and in vivo and metastatic capacity following s.c. or i.v. injection of cells were compared to those of the parental cell line. Differences between the cloned cell lines themselves and between the clones and the parental cells were found in the number of metastases provoked by both i.v. and s.c. injections, in the number of cells required to induce s.c. tumors, and in the growth rate of those tumors. In vitro, the doubling times and saturation densities of the different cell lines varied greatly. A direct correlation was observed between the 50% tumoral dose and the initial tumor growth phase. We found that there was a tendency for lines which were highly metastatic after s.c. injection to have a low metastatic capacity after i.v. injection and inversely. The two types of metastasis (spontaneous and experimental) appear therefore to depend on different characteristics of the cells used.
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PMID:Heterogeneity of the growth and metastatic behavior of cloned cell lines derived from a primary rhabdomyosarcoma. 710 43

Tungsten-based materials have been proposed as replacements for depleted uranium in armor-penetrating munitions and for lead in small-arms ammunition. A recent report demonstrated that a military-grade composition of tungsten, nickel, and cobalt induced a highly-aggressive, metastatic rhabdomyosarcoma when implanted into the leg muscle of laboratory rats to simulate a shrapnel wound. The early genetic changes occurring in response to embedded metal fragments are not known. In this study, we utilized two cultured rodent myoblast cell lines, exposed to soluble tungsten alloys and the individual metals comprising the alloys, to study the genotoxic effects. By profiling cell transcriptomes using microarray, we found slight, yet distinct and unique, gene expression changes in rat myoblast cells after 24 h metal exposure, and several genes were identified that correlate with impending adverse consequences of ongoing exposure to weapons-grade tungsten alloy. These changes were not as apparent in the mouse myoblast cell line. This indicates a potential species difference in the cellular response to tungsten alloy, a hypothesis supported by current findings with in vivo model systems. Studies examining genotoxic-associated gene expression changes in cells from longer exposure times are warranted.
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PMID:Genotoxic changes to rodent cells exposed in vitro to tungsten, nickel, cobalt and iron. 2461 24

Continued improvements in the ballistic properties of military munitions have led to metal formulations for which little are known about the long-term health effects. Previously we have shown that a military-grade tungsten alloy comprised of tungsten, nickel, and cobalt, when embedded into the leg muscle of F344 rats to simulate a fragment wound, induces highly aggressive metastatic rhabdomyosarcomas. An important follow-up when assessing a compound's carcinogenic potential is to test it in a second rodent species. In this study, we assessed the health effects of embedded fragments of 2 military-grade tungsten alloys, tungsten/nickel/cobalt and tungsten/nickel/iron, in the B6C3F1 mouse. Implantation of tungsten/nickel/cobalt pellets into the quadriceps muscle resulted in the formation of a rhabdomyosarcoma around the pellet. Conversely, implantation of tungsten/nickel/iron did not result in tumor formation. Unlike what was seen in the rat model, the tumors induced by the tungsten/nickel/cobalt did not exhibit aggressive growth patterns and did not metastasize.
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PMID:Induction of rhabdomyosarcoma by embedded military-grade tungsten/nickel/cobalt not by tungsten/nickel/iron in the B6C3F1 mouse. 2554 65

The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91-6-3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91-6-3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91-6-3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91-6-3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91-6-3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97-2-1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97-2-1 elicited similar responses to WNC 91-6-3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes.
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PMID:Molecular basis of carcinogenicity of tungsten alloy particles. 2562 57


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