Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A boy with characteristic facial features, pulmonary valvular stenosis, ectodermal abnormalities, growth failure, and mental retardation was admitted for intestinal occlusion at 20 months of age. Clinical findings were consistent with a diagnosis of cardio-facio-cutaneous syndrome (CFC-s), and a huge abdominal mass was evident on computed tomography scan. A biopsy was performed, and embryonal rhabdomyosarcoma was diagnosed. Molecular analysis was performed by reverse transcription (RT) polymerase chain reaction (PCR) on tumor RNA to seek the chimerical transcript of the most common soft tissue sarcoma translocations and analyze neurofibromatosis 1 (NF1) gene expression. Translocations involving 1;13, 2;13, and 11;22 were not found, and the specific transcripts of the NF1 gene were present. Chemotherapy was implemented, but the child died 7 months later of tumor progression. Few patients with CFC-s have been described, and their follow-up is not well known. The association of CFC-s with rhabdomyosarcoma has not been reported previously, but other neoplasms have been reported in patients with Noonan syndrome, a condition similar to CFC-s. More observations are needed, but this and other reports suggest there could be a higher risk of malignancy in patients with syndromes in the Noonan phenotype category.
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PMID:Rhabdomyosarcoma in a patient with cardio-facio-cutaneous syndrome. 1113 27

We report a case of primary intraosseous pleiomorphic rhabdomyosarcoma located in the pelvis of a 21-year-old woman followed for 4 years. The lytic tumor involved the acetabulum and the isthma with moderate extension to soft tissue. First line chemotherapy was unable to arrest tumor progression. Hemipelvectomy with saddle prosthesis reconstruction was performed, but septic complications dictated a secondary inter-ilio-abdominal amputation. Recurrence-free remission was achieved for 4 years, suggesting this was indeed a primary tumor. Primary intraosseous rhabdomyosarcomas are exceptional. Bone localizations generally suggest metastasis from a primary tumor often situated in an intraperitoneal localization. When search for a primary tumor is negative, intraosseous lesions can be considered as primary tumors warranting curative treatment. Radical surgical resection is recommended within the framework of a multidiscipinary management protocol associating radiotherapy and chemotherapy to improve prognosis.
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PMID:[Primary intraosseous rhabdomyosarcoma]. 1084 60

The role of high-dose chemotherapy; with subsequent autologous bone marrow rescue (AutoBMR) for high risk or recurrence of advanced solid tumor was evaluated in 16 children (August 1998-March 2001). At present, 11 (69%) patients are still alive, showing no evidence of the disease, 11-31 mo after therapy (median follow-up of 17 mo). Tumor progression was reported in 5 (31%) at months 5, 6, 8, 9 and 11 (after AutoBMR rhabdosarcoma--3; Ewing's sarcoma--2). Overall and recurrence-free survival among all patients was 74 and 66%, respectively.
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PMID:[High-dose chemotherapy with autologous bone marrow transplantation in children with high-risk malignant neoformations]. 1245 56

Rhabdomyosarcoma (RMS) has deregulated proliferation and is blocked in the differentiation program despite Myf-5, MyoD and myogenin expression. Here we show that ectopic expression of MRF4, which is not subject to an autoregulatory pathway but regulated by the other MRFs protein family, induces growth arrest and terminal differentiation in RD cells. Deletion mapping identified a positive-acting C-terminal domain in MRF4 as the mediator of transcriptional activity, revealing a conserved motif with helix III in MyoD previously found to initiate expression of endogenous skeletal muscle genes. By using chimeric MyoD/MRF4 proteins, we observe that the C-terminal motif of MRF4 rescues MyoD activity in RD cells. Moreover, comparative induction of muscle-specific genes following activation of MyoD, through the expression of a constitutively activated MKK6 either in the absence or presence of MRF4, shows that MyoD and MRF4 can differently regulate muscle genes expression. Together, these results demonstrate that the MRF4 C-terminus functions as specification as well as activation domain in tumor cells. They provide a basis to identify gene products necessary for b-HLH-mediated differentiation versus tumor progression.
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PMID:Muscle regulatory factor MRF4 activates differentiation in rhabdomyosarcoma RD cells through a positive-acting C-terminal protein domain. 1294 14

The Fos protein, a major component of the AP-1 transcription factor, is essential for osteoclast differentiation, acts as an oncogene, potentiates transforming signals, and controls invasive growth and angiogenesis during tumor progression. To investigate a potential genetic interaction between the Trp53 and Fos pathways, Trp53/Fos double knockout mice were generated. These mice develop highly proliferative and invasive rhabdomyosarcomas of the facial and orbital regions, with more than 90% penetrance at 6 months of age. Rhabdomyosarcoma cell lines established from the primary tumors express characteristic muscle-specific markers, and reexpression of Fos is associated with enhanced apoptosis in vitro. Moreover, Fos is able to repress Pax7 expression in rhabdomyosarcoma cell lines and primary myoblasts, suggesting a molecular link to genetic alterations involved in human rhabdomyosarcomas.
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PMID:Rhabdomyosarcoma development in mice lacking Trp53 and Fos: tumor suppression by the Fos protooncogene. 1470 32

Rhabdomyosarcoma is the most commonly occurring soft-tissue sarcoma in children. Some reports have discussed the altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma; however, variable frequencies of occurrence have been noted. In the current study, among 72 cases of rhabdomyosarcoma, the authors evaluated for the expression of p53, MDM2, p16, p21/WAF1, p27, cyclin D1, cyclin E, pRb and E2F-1 protein immunohistochemically and assessed for proliferative activities using MIB-1. We also analyzed the mutation of the p53 gene in 45 cases, the amplification of the MDM2 gene in 18 cases and the mutation of the H-ras gene in 29 cases, using formalin-fixed paraffin-embedded materials. Furthermore, we assessed the correlation between clinicopathologic factors and the results of both immunohistochemical and molecular analyses. Alveolar type affected older patients, and it had a significantly higher mitotic rate compared with the embryonal type (P=0.0226). p53 overexpression was detected in 22 (30.6%) of 72 cases, and 10 (22.2%) of 45 cases had p53 gene abnormalities. As for MDM2, its overexpression was found in nine (12.5%) of 72 cases, and three (16.7%) of 18 cases showed MDM2 amplification. A statistically significant association was observed between immunoreaction for MDM2 and p53 overexpression (P=0.0002), and p53 and MDM2 overexpression was significantly correlated with high MIB-1 labeling indices. E2F-1 labeling indices showed a significantly higher score in alveolar type compared with that seen in embryonal type (P=0.0334), but MIB-1 did not. In conclusion, our study suggests that p53 overexpression may be related to tumor progression because tumors with p53 overexpression have a high proliferative activity in the current study. Alveolar type had a significantly higher both mitotic rate and E2F-1 labeling indices when compared with the embryonal type. The current study is the first report of the correlation of E2F-1 with alveolar rhabdomyosarcoma.
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PMID:Altered expression and molecular abnormalities of cell-cycle-regulatory proteins in rhabdomyosarcoma. 1509 8

Although accumulating evidence suggests the importance of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)) in the pathogenesis of many cancers, the mechanism by which this enzyme and its metabolite promote cancer progression is unknown. In this study, we investigated the role of COX-2 in fibronectin-induced up-regulation of rhabdomyosarcoma matrix metalloproteinase (MMP)-2 activity and cellular invasiveness. We tested three human rhabdomyosarcoma cell lines: RMS559, RD, and SJRH30. Cell attachment to fibronectin up-regulated both COX-2 expression and PGE(2) production and concomitantly enhanced MMP-2 activity. Exogenous PGE(2) stimulated MMP-2 promoter activity, increased MMP-2 expression, and increased cellular invasiveness. Aspirin and rofecoxib (non-selective and selective COX-2 inhibitor, respectively) each abolished fibronectin-associated induction of MMP-2 and induced dose-dependent reductions in cellular invasiveness. These data implicated a role for inducible COX-2 and PGE(2) in the regulation of rhabdomyosarcoma cellular invasiveness and MMP-2 activity.
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PMID:Fibronectin-induced COX-2 mediates MMP-2 expression and invasiveness of rhabdomyosarcoma. 1512 Jun 41

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. Improved treatment strategies have increased overall survival, but the response of approximately one-third of the patients is still poor. To increase the knowledge of RMS pathogenesis, we performed the first full transcriptome analysis of RMS using serial analysis of gene expression (SAGE). With a G-test for the simultaneous comparison of subsets of SAGE libraries of normal skeletal muscle, embryonal (ERMS) and alveolar (ARMS) RMS, we identified 251 differentially expressed genes. A literature-mining procedure demonstrated that 158 of these genes have not previously been associated with RMS or normal muscle. Gene Ontology (GO) analysis assigned 198 of the 251 genes to muscle-specific classes, including those involved in normal myogenic development, as well as tumor-related classes. Prominent GO classes were those associated with proliferation and actin reorganization, which are processes that play roles during early muscle development, muscle function, and tumor progression. Using custom microarrays, we confirmed the (up- or down-) regulation of 80% of 98 differentially expressed genes. Another SAGE library of 19- to 22-week-old fetal skeletal muscle was compared with the RMS and normal muscle transcriptomes. Cluster analysis showed that the RMS and fetal muscle SAGE libraries formed one cluster distinct from normal muscle samples. Moreover, the expression profile of 86% of the differentially expressed genes between normal muscle and RMS was highly similar in fetal muscle and RMS. In conclusion, the G-test is a robust tool for analyzing groups of SAGE libraries and correctly identifies genes marking the difference between fully differentiated skeletal muscle and RMS. This study not only substantiates the close association between embryonic myogenesis and RMS development but also provides a rich source of candidate genes to further elucidate the etiology of RMS or to identify diagnostic and/or prognostic markers.
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PMID:Full transcriptome analysis of rhabdomyosarcoma, normal, and fetal skeletal muscle: statistical comparison of multiple SAGE libraries. 1562 88

Rhabdomyosarcoma is the most common soft tissue sarcoma in children, yet the genetic changes causing this disease are poorly understood. The Fos protein, a major component of the AP-1 transcription factor, is essential for osteoclast differentiation, acts as an oncogene, potentiates transforming signals and controls invasive growth and angiogenesis during tumor progression. To genetically investigate a potential interaction between the p53 and Fos pathways, Trp53/Fos double knock-out mice were generated. These mice develop highly proliferative and invasive rhabdomyosarcomas of the facial and orbital regions with more than 90% penetrance at 6 months of age. Expression of Fos in Trp53/Fos mutant rhabdomyosarcoma cell lines established from primary tumors is associated with enhanced apoptosis and downregulation of Pax7 expression. Our results show that Trp53/Fos double knock-out mice recapitulate major aspects of human rhabdomyosarcoma development and therefore provide a mouse model for the human disease. Furthermore, this study identifies a novel and unexpected tumor suppressive function of the Fos proto-oncogene.
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PMID:[Rhabdomyosarcoma development in Trp53/fos mutant mice: tumor suppressor functions of the Fos protooncogene]. 1689 56

The p53 family comprises the tumor suppressor p53 and the structural homologs p63 and p73. How the three family members cooperate in tumor suppression remains unclear. Here, we report different but complementary functions of the individual members for regulating retinoblastoma protein (RB) function during myogenic differentiation. Whereas p53 transactivates the retinoblastoma gene, p63 and p73 induce the cyclin-dependent kinase inhibitor p57 to maintain RB in an active, hypophosphorylated state. DeltaNp73 inhibits these functions of the p53 family in differentiation control, prevents myogenic differentiation, and enables cooperating oncogenes to transform myoblasts to tumorigenicity. DeltaNp73 is frequently overexpressed in rhabdomyosarcoma and essential for tumor progression in vivo. These findings establish differentiation control as a key tumor suppressor activity of the p53 family.
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PMID:p53 family members in myogenic differentiation and rhabdomyosarcoma development. 1704 6


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