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

STIM1 is a novel candidate growth suppressor gene mapping to the human chromosome region 11p15.5 that is associated with several malignancies. STIM1 overexpression studies in G401 rhabdoid tumour, rhabdomyosarcoma and rodent myoblast cell lines causes growth arrest, consistent with a potential role as a tumour growth suppressor. We used highly specific antibodies to show by immunofluorescence and cell surface biotinylation studies that STIM1 is located at the cell surface of K562 cells. Western blot analysis revealed that the 90-kDa STIM1 protein is ubiquitously expressed in various human primary cells and tumour cell lines. STIM1 is not secreted from cells and does not appear to undergo proteolytic processing. We show evidence of post-translational modification of STIM1, namely phosphorylation and N-linked glycosylation. Phosphorylation of STIM1 in vivo occurs predominantly on serine residues. Thus, STIM1, the putative tumour growth suppressor gene is ubiquitously expressed and has features of a regulatory cell-surface phosphoprotein.
 ...
PMID:STIM1: a novel phosphoprotein located at the cell surface. 1100 85

The MYCN oncogene encodes a phosphoprotein that acts as a transcription factor and is involved in the regulation of cell proliferation and differentiation in normal as well as in cancer cells.MYCN amplification and expression have been reported in various tumours, including neuroblastoma and lung cancer, but little is known about its expression in human rhabdomyosarcoma. MYCN expression and amplification were studied in five alveolar and five embryonal rhabdomyosarcoma cell lines and in 19 tumour biopsies. All the cell lines studied expressed MYCN RNA, as demonstrated by northern blot analysis and RT-PCR, but the oncogene was amplified in only one. Similarly, MYCN protein was detected in all cell lines by western blot analysis, with higher levels of expression in alveolar than in embryonal rhabdomyosarcoma cells. RT-PCR analysis of tumour samples demonstrated 18/19 cases positive for MYCN RNA. Although MYCN expression was higher in alveolar than in embryonal rhabdomyosarcoma cell lines, no clear relationship between histology and level of MYCN expression could be established in this tumour series. These data suggest that MYCN expression is a common feature of rhabdomyosarcoma, independent of gene amplification and without a clear relationship with specific histological and clinical features.
 ...
PMID:MYCN expression in human rhabdomyosarcoma cell lines and tumour samples. 1192 Jul 42

Rhabdomyosarcoma is a rare malignant tumor that may occur in the spermatic cord in childhood. So far, 62 cases have been reported in the English literature. We describe a case of embryonal rhabdomyosarcoma of the spermatic cord in a 15-year-old boy, detailing clinical history, light microscopy, immunohistochemistry and treatment. In order to unquestionably demonstrate the myogenic differentiation of the neoplasm, it was decided to use a monoclonal antibody against MyoD1. The nuclear positivity of this phosphoprotein in the tumor cells confirmed the diagnosis of embryonal rhabdomyosarcoma. Consequently, the patient was treated with right radical orchiectomy and retroperitoneal lymph node dissection (RPLND). The latter is usually required because of the high incidence (more than 50% of cases) of positive retroperitoneal nodes, whereas subsequent adjuvant therapy is occasionally necessary. In the present case, we decided for a careful follow-up on the basis of the small size of the tumor and the absence of metastasis at diagnosis. The patient is alive and free of disease 12 months after surgery.
 ...
PMID:Rhabdomyosarcoma of the spermatic cord. A case report with review of the literature. 1284 75

Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains approximately 60%. A critical goal is to identify functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) IV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser(473) (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBP1 Thr(37/46) (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser(1108) (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr(389) (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR pathway proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy.
 ...
PMID:Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival. 1740 54

Chandipura virus (CHPV) (Vesiculovirus: Rhabdoviridae) garnered global attention as an emerging neurotropic pathogen inflicting high mortality in children within 24 h of commencement of symptoms. The 2003-2004 outbreaks in Central India witnessed case fatality rates ranging from 56-75 per cent in Andhra Pradesh and Gujarat with typical encephalitic symptoms. Due to the acute sickness and rapid deterioration, the precise mechanism of action of the virus is still unknown. Recent studies have shown increased expression of CHPV phosphoprotein upto 6 h post infection (PI) demonstrating CHPV replication in neuronal cells and the rapid destruction of the cells by apoptosis shed light on the probable mechanism of rapid death in children. Phlebotomine sandflies are implicated as vectors due to their predominance in endemic areas, repeated virus isolations and their ability to transmit the virus by transovarial and venereal routes. Significant contributions have been made in the development of diagnostics and prophylactics, vaccines and antivirals. Two candidate vaccines, viz. a recombinant vaccine and a killed vaccine and siRNAs targeting P and M proteins have been developed and are awaiting clinical trials. Rhabdomyosarcoma and Phlebotomus papatasi cell lines as well as embryonated chicken eggs have been found useful in virus isolation and propagation. Despite these advancements, CHPV has been a major concern in Central India and warrants immediate attention from virologists, neurologists, paediatricians and the government for containing the virus.
 ...
PMID:Changing clinical scenario in Chandipura virus infection. 2774 95