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)

We investigated the effects of black tea (BT) and green tea (GT) infusion on the spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice. Female A/J mice, 6 weeks of age, were allocated into five groups (50 per group) and were given the following as the sole source of drinking fluid: (i) deionized water (control group), (ii) 0.5% BT, (iii) 1% BT, (iv) 2% BT and (v) 1% GT. After 60 weeks, the mice were killed by decapitation. Lung tumor incidence, multiplicity and volume were significantly lower in the 2% BT group as compared with the controls (27 versus 52%, 0.33 versus 0.72 tumors/mouse and 4.27 versus 38.3 mm3, respectively). The 1% GT group had significantly lower lung tumor multiplicity (0.41/mouse), while the 1% BT group had significantly decreased tumor volume (7.17 mm3). Rhabdomyosarcomas were found in 34% of the mice in the control group, and both the 1 and 2% BT groups had significantly lower incidences at 13 and 14%, respectively. The mice in the 2% BT group weighed 16% less than those in the control group, although they consumed more food than the control group. The other tea-consuming groups also weighed less than the control group (7.8-11%) while consuming more food and fluid. In a separate experiment, similar carcinogenesis inhibition was also observed in female A/J mice that were given 0.6% and then 0.3% instant black tea for 52 weeks. These results demonstrate the inhibitory activity of BT against the spontaneous formation of lung tumors and rhabdomyosarcomas in mice.
Carcinogenesis 1998 Mar
PMID:Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice by black and green tea. 952 86

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
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PMID:Colorectal adenocarcinoma as a second malignant neoplasm following rhabdomyosarcoma of the urinary bladder: a case report. 1098 2

We exposed embryos (83 hours postfertilizaton) and fry (3 weeks posthatch) to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by immersion in aqueous solutions of 0-10 ppm for 1 hour (embryo) or 0-2 ppm for 24 hours (fry). Zebrafish embryos were microinjected with MNNG at levels of 0 or 96 ng/egg. Diets containing 0-2,000 ppm MNNG were fed to juvenile zebrafish for 3 months beginning at 2 months posthatch. Fish were sampled for histopathologic study at 6-12 months after initiation of carcinogen exposure. Embryos and fry were both quite responsive to MNNG; however, juvenile zebrafish were remarkably refractory to MNNG-induced neoplasia. Principal target organs in zebrafish treated as embryos with MNNG were liver and testis, with hepatocellular adenoma the most prevalent hepatic neoplasm. A variety of mesenchymal neoplasms occurred in zebrafish following embryo exposure to MNNG, including chondroma, hemangioma, hemangiosarcoma, leiomyosarcoma, and rhabdomyosarcoma. Testis and blood vessels were primary target organs for MNNG following fry exposure, with seminoma, hemangioma, hemangiosarcoma, and various other epithelial and mesenchymal neoplasms occurring. The zebrafish is a responsive, cost-effective lower vertebrate model system in which to study mechanisms of carcinogenesis.
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PMID:Neoplasia in zebrafish (Danio rerio) treated with N-methyl-N'-nitro-N-nitrosoguanidine by three exposure routes at different developmental stages. 1102 8

Inherited mutations of Patched (PTCH) in the nevoid basal cell carcinoma syndrome (NBCCS) lead to several developmental defects and contribute to tumor formation in a variety of tissues. PTCH mutations have been also identified in sporadic tumors associated with NBCCS including basal cell carcinoma (BCC) and medulloblastoma. Mice heterozygous for Ptch recapitulate the typical developmental symptoms of NBCCS and develop rhabdomyosarcoma (RMS) and medulloblastoma. PTCH is assumed to act as a tumor suppressor gene although inactivation of both alleles has been demonstrated only in a fraction of tumors. We have investigated the status of Ptch in RMS of heterozygous Ptch neo67/+ mice. Although the wild-type Ptch allele was retained in tumor tissue, the high levels of Ptch mRNA in these tumors result from overexpression of the mutant Ptch transcript. Our results suggest that the wild-type Ptch allele might be selectively silenced in RMS tissue or, alternatively, that haploinsufficiency of Ptch is sufficient to promote RMS formation in mice.
Carcinogenesis 2002 May
PMID:Unbalanced overexpression of the mutant allele in murine Patched mutants. 1201 44

2,6-Xylidine is a chemical intermediate used principally in the production of dyes. It is also a component of tobacco smoke, a degradation product of aniline-based pesticides, and a metabolite of certain drugs, particularly the xylide group of local anesthetics. The National Toxicology Program (NTP) sponsored single-administration, 2-week, and 13-week studies of 2,6-xylidine by gavage in F344/N rats. The U.S. Environmental Protection Agency (EPA) sponsored short-term gavage studies and 10-week range-finding studies in Charles River CD rats (a Sprague Dawley-derived strain). A carcinogenesis study of 2,6-xylidine was initiated by the EPA, which designed and monitored the study during the 2-year exposure period. The NTP then assumed responsibility for the study, conducting terminal kill, necropsy, histopathologic evaluation, data analysis, and report preparation. Oral LD50 values of 1.2-1.3 g/kg were calculated for F344/N and Charles River CD rats administered single doses of 2,6-xylidine. Marginally toxic effects occurred in the hepatic, renal, and hematopoietic systems of dosed rats in the single-administration, 2-week, 10-week, and 13-week studies. The 56 male and 56 female Charles River CD rats used in the 104-week carcinogenesis studies were the offspring of animals fed diets containing 0, 300, 1,000, or 3,000 ppm 2,6-xylidine before breeding, during pregnancy, and through the lactation period. The concentrations of 2,6-xylidine offered to animals in the 104-week studies were the same as those given to their parents. During most of the 2-year studies, high dose male and female rats showed a reduction (greater than 10%) in body weight gain. Survival in the high dose male rats was significantly reduced (P<0.001) relative to that in controls. Survival also was reduced in the 1,000-ppm group. There was no significant relationship between concentration and mortality in female rats, but mortality was high for all groups of female rats during the second year of the study. The epithelium of the nasal cavity was the primary site of compound-related neoplastic and nonneoplastic lesions. The incidences of both papillomas and carcinomas of the nasal cavity were significantly increased in high dose male and female rats. Carcinomas or adenocarcinomas (combined) occurred in 28/56 high dose males, 24/56 high dose females, and 1/56 mid dose females. Papillary adenomas occurred in 10/56 high dose males, 2/56 mid dose males, and 6/56 high dose females. None occurred in the other groups. The carcinomas were highly invasive and frequently destroyed the nasal turbinates and nasal septum. Metastasis to the brain was present in 5/56 male and 7/56 females high dose rats. Malignant mesenchymal tumors were observed in the nasal cavity. Rhabdomyosarcomas occurred in two high dose male rats and two high dose female rats. These rare malignant tumors have not been previously reported at this site in Sprague Dawley rats. Malignant mixed tumors having features of adenocarcinomas and rhabdomyosarcomas were reported in one high dose male and one high dose female rat. One undifferentiated sarcoma was seen in a high dose female rat. The nonneoplastic lesions observed in the nasal cavity included acute inflammation, epithelial hyperplasia, and squamous metaplasia. The incidences of subcutaneous tissue fibromas were increased in high dose male and female rats (male: control, 0/56; low dose, 1/56; mid dose, 2/56; high dose, 4/56; female: 0/56; 2/56; 1/56; 4/56) and were dose related. Subcutaneous fibrosarcomas were observed in three high dose females, one high dose male, one mid dose female, one low dose male, and one control female. A significant dose-related increase occurred in the incidence of female rats with neoplastic nodules of the liver (0/56; 1/56; 2/56; 4/55). This increase was significant in the high dose group by the incidental tumor test. Conclusions: Under the conditions of these 2-year feed studies, 2,6-xylidine was clearly carcinogenic for male and female Charles River CD rats, causing significant increases in the incidences of adenomas aadenomas and carcinomas of the nasal cavity. A rhabdomyosarcoma, a rare tumor of the nasal cavity, was observed in dosed rats of each sex. In addition, the increased incidences of subcutaneous fibromas and fibrosarcomas in male and female rats and the increased incidence of neoplastic nodules of the liver in female rats may have been related to the administration of 2,6-xylidine. Levels of Evidence of Carcinogenicity: Male Rats: Positive Female Rats: Positive Synonym: 2,6-Dimethylaniline
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PMID:NTP Toxicology and Carcinogenesis Studies of 2,6-Xylidine (2,6-Dimethylaniline) (CAS No. 87-62-7) in Charles River CD Rats (Feed Studies). 1274 1

The long-term genetic consequences of chronic exposure to low-dose irradiation constitutes a major concern to the general public and research community, especially as chronic radiation has recently been proven to be much more mutagenic and carcinogenic than previously thought. Here we report the results of the first ever comparison of the effects of acute and chronic whole body low-dose radiation exposure on global gene expression. We found a substantial difference between males and females in the expression of genes involved in signaling, growth control, transcription and other pathways upon acute and chronic radiation exposure. Specifically, we found sex differences in the expression of genes coding for G protein-coupled receptors and nuclear receptors. We also found different induction of PKCdelta, PKCbeta and PKCmu, members of PKC signaling pathway as well as in TGF and WNT signaling in males and females. Very pronounced difference, that was confirmed on the level of protein, was observed in the expression of WNT5A that plays an important role in carcinogenesis and muscle regeneration. WNT5A expression was significantly elevated only in chronically exposed females. We also provide the first evidence of the effect of ionizing radiation on the estrogen receptor in females. Repetitive irradiation of muscle tissue has been linked to development of rhabdomyosarcoma (RMS), which, enigmatically, occurs more frequently in males. Our data may be used to study possible mechanisms of RMS development upon chronic radiation exposure. They may provide some clues about the molecular background of the sex differences of RMS occurrence and may in the future lead to the discovery of new biomarkers for RMS predisposition in the irradiated tissue. Overall, differences in male and female responses to acute and chronic low-dose radiation obtained by this study were more drastic than we could have predicted. If confirmed in other experimental systems, these findings could potentially lead to fundamental changes in radiation safety regulations.
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PMID:Dissimilar genome response to acute and chronic low-dose radiation in male and female mice. 1513 41

Human Forkhead-box (FOX) gene family consists of at least 43 members, including FOXA1, FOXA2, FOXA3, FOXB1, FOXC1, FOXC2, FOXD1, FOXD2, FOXD3, FOXD4, FOXD5 (FOXD4L1), FOXD6 (FOXD4L3), FOXE1, FOXE2, FOXE3, FOXF1, FOXF2, FOXG1 (FOXG1B), FOXH1, FOXI1, FOXJ1, FOXJ2, FOXJ3, FOXK1, FOXK2, FOXL1, FOXL2, FOXM1, FOXN1, FOXN2 (HTLF), FOXN3 (CHES1), FOXN4, FOXN5 (FOXR1), FOXN6 (FOXR2), FOXO1 (FOXO1A), FOXO2 (FOXO6), FOXO3 (FOXO3A), FOXO4 (MLLT7), FOXP1, FOXP2, FOXP3, FOXP4, and FOXQ1. FOXE3-FOXD2 (1p33), FOXQ1-FOXF2-FOXC1 (6p25.3), and FOXF1-FOXC2-FOXL1 (16q24.1) loci are FOX gene clusters within the human genome. Members of FOX subfamilies A-G, I-L and Q were grouped into class 1 FOX proteins, while members of FOX subfamilies H and M-P were grouped into class 2 FOX proteins. C-terminal basic region within the FOX domain was the common feature of class 1 FOX proteins. FOXH1 and FOXO1 mRNAs are expressed in human embryonic stem (ES) cells. FOXC1, FOXC2, FOXE1, FOXE3, FOXL2, FOXN1, FOXP2 and FOXP3 genes are mutated in human congenital disorders. FOXA1 gene is amplified and over-expressed in esophageal and lung cancer. FOXM1 gene is up-regulated in pancreatic cancer and basal cell carcinoma due to the transcriptional regulation by Sonic Hedgehog (SHH) pathway. FOXO1 gene is fused to PAX3 or PAX7 genes in rhabdomyosarcoma. FOXO3 and FOXO4 genes are fused to MLL gene in hematological malignancies. Deregulation of FOX family genes leads to congenital disorders, diabetes mellitus, or carcinogenesis. Expression profiles, genetic alterations and epigenetic changes of FOX family genes as well as binding proteins and target genes of FOX family transcription factors should be comprehensively investigated to develop novel therapeutics and preventives for human diseases.
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PMID:Human FOX gene family (Review). 1549 44

Vaccines effectively prevent the onset of tumors in transgenic mice carrying activated oncogenes; however, human tumors are caused by combined alterations in oncogenes and oncosuppressor genes. We evaluated the impact of prophylactic vaccines in HER-2/neu transgenic, p53 wild-type/null mice that succumb to an aggressive cancer syndrome comprising mammary and salivary gland carcinomas and rhabdomyosarcoma. A vaccine made of allogeneic mammary carcinoma cells expressing HER-2/neu and interleukin 12 afforded long-term protection from tumor onset. Tumor prevention was mediated by T cell-derived cytokines, in particular gamma-interferon, and by anti-HER-2/neu antibodies. HER-2/neu expression was inhibited in target tissues of vaccinated mice, and somatic loss of the wild-type p53 allele did not occur. A highly effective vaccine against a single oncoprotein induced a powerful immune response that arrested multistep carcinogenesis in distinct target tissues.
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PMID:Immunological prevention of a multigene cancer syndrome. 1554 14

Hedgehog, FGF, VEGF, and Notch signaling pathways network together for vascular remodeling during embryogenesis and carcinogenesis. HHIP1 (HHIP) is an endogenous antagonist for SHH, IHH, and DHH. Here, comparative integromics analyses on HHIP family members were performed by using bioinformatics and human intelligence. HHIP1, HHIP2 (HHIPL1 or KIAA1822) and HHIP3 (HHIPL2 or KIAA1822L) constitute human HHIP gene family. Rat Hhip1, Hhip2, and Hhip3 genes were identified within AC107504.4, AC094820.6, and AC134264.2 genome sequences, respectively. HHIP-homologous (HIPH) domain with conserved 18 Cys residues was identified as the novel domain conserved among mammalian HHIP1, HHIP2, and HHIP3 orthologs. HHIP1 mRNA was expressed in coronary artery endothelial cells, prostate, and rhabdomyosarcoma. HHIP2 mRNA was expressed in trabecular bone cells. HHIP3 mRNA was expressed in testis, thyroid gland, osteoarthritic cartilarge, pancreatic cancer, and lung cancer. Promoters of HHIP family genes were not well conserved between human and rodents. Although GLI-, CSL-, and HES/HEY-binding sites were not identified, eleven bHLH-binding sites were identified within human HHIP1 promoter. Expression of HES/HEY family members, including HES1, HES2, HES3, HES4, HES5, HES6, HES7, HEY1, HEY2 and HEYL, in coronary artery endothelial cells was not detected in silico. Up-regulation of HHIP1 due to down-regulation of Notch-CSL-HES/HEY signaling cascade repressing bHLH transcription factors results in down-regulation of the Hedgehog-VEGF-Notch signaling cascade. On the other hand, down-regulation of HHIP1 due to up-regulation of Notch signaling in vascular endothelial cells during angiogenesis results in up-regulation of the Hedgehog-VEGF-Notch signaling cascade. Because HHIP1 is the key molecule for vascular remodeling, HHIP1 is the pharmacogenomics target in the fields of oncology and vascular medicine.
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PMID:Comparative genomics on HHIP family orthologs. 1639 42

Plakoglobin (gamma-catenin) and beta-catenin are pivotal components of cell-cell adherent junctions that link cadherin receptors to the actin cytoskeleton. Whereas beta-catenin overexpression induces cell proliferation and tumor formation, plakoglobin induces tumor suppressor activity. We investigated the expression of plakoglobin in alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma (RMS) cell lines and tumors, and found that plakoglobin is present both in the cytoplasm and in the nucleus of ERMS cells, whereas it is absent or detectable at extremely low levels in ARMS. As gene silencing can be mediated by methylation and/or deacetylation of promoter regions, we assessed the effects of the DNA demethylating agent 5-Aza-2'-deoxycytidine (5AzadC) and of the histone deacetylase inhibitor Trichostatin A (TSA), and obtained restoration of plakoglobin expression in ARMS cells cultivated in the presence of 5AzadC and TSA. By methylation-specific PCR, ARMS cells were shown to contain methylated CpG dinucleotides in CpG islands located around the transcriptional start site of one or both alleles, whereas ERMS cells did not. Furthermore, we demonstrated that promoter regions (P1-P3) of plakoglobin gene were associated with hypoacetylated H4 histone in ARMS cells RH4, suggesting that aberrant DNA methylation of the 5' CpG island and histone deacetylation play key roles in silencing the plakoglobin gene. These results demonstrate that plakoglobin is differentially expressed in ARMS and ERMS and that its expression depends on the methylation and acetylation status of the gene.
Carcinogenesis 2006 Sep
PMID:Plakoglobin is differentially expressed in alveolar and embryonal rhabdomyosarcoma and is regulated by DNA methylation and histone acetylation. 1653 59


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