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 report the outcome of growth hormone (GH) therapy in 34 children (17 boys and 17 girls) with brain tumors in whom hypopituitarism developed. The types of tumors included the following: craniopharyngiomas (18); germinomas (four); astrocytomas (three); chromophobe adenomas (three); medulloblastomas (two); glioma (one); dermoid (one); retinoblastoma (one); and metastatic rhabdomyosarcoma from the pelvis (one). Ninety-four percent of the patients were GH deficient post-tumor therapy, which consisted of surgery with and without radiotherapy. Twenty-four of 34 patients received GH. Eight of 24 patients receiving GH had recurrence of tumor; 16 were tumor free eight to 72 months after initial therapy. Eleven patients had 12 recurrences. Patients with tumor recurrence had a considerably lower growth rate during the first year of GH therapy than those without recurrence (mean, 3.5 +/- 1.3 cm/yr v 6.2 +/- 2.5 cm/yr). Three of 11 patients with recurrence had not received GH therapy; however, one was receiving testosterone intramuscularly monthly at the time of a second recurrence. Thus, 24 of 34 patients with brain tumors and hypopituitarism received GH therapy. Eight (33%) of 24 had tumor recurrence, compared with three (30%) of ten who did not receive GH. The data suggest that GH therapy is probably not associated with increased rate of tumor recurrence.
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PMID:Growth hormone therapy and tumor recurrence. Findings in children with brain neoplasms and hypopituitarism. 397 24

Lentiviral vectors have gained much attention in recent years mainly because they integrate into nondividing host-cell genomes. For clinical applications, a safe and efficient lentiviral vector system is required. Previously, we have established a human immunodeficiency virus type 1 (HIV-1)-derived three-plasmid lentiviral vector system for viral vector production which includes a packaging vector pHP, a transducing vector pTV, and an envelope-encoding plasmid pHEF-VSVG. Cotransfection of these three plasmids into TE671 human rhabdomyosarcoma cells routinely yields 10(5)-10(6) infectious units per milliliter in 24 h. Here we have extensively modified long terminal repeats (LTRs) of pTV to generate a safer lentiviral vector system. The 5' U3 was replaced with a truncated cytomegalovirus (CMV) immediate early (IE) enhancer/TATA promoter and the 3' U3 (except for the integration attachment site) was also deleted. These modifications resulted in a vector with 80% wild-type vector efficiency. Further deletion of 3' U5 impaired vector function; however, this problem was solved by replacing the 3' U5 with bovine growth hormone polyadenylation (bGHpA) sequence. The pTV vector containing all these modifications including the 5' promoter substitution, the 3' U3 deletion, and the substitution of 3' U5 with bGHpA exhibited a self-inactivating (SIN) phenotype after transduction, transduced both dividing and nondividing cells at similar efficiencies, and produced vector titers twice as high as that of the wild-type construct. Thus, both safety and efficacy of the HP/TV vector have been improved by these LTR modifications. Further deletion of 5' U5 impaired vector efficiency, suggesting that the 5' U5 has critical roles in vector function.
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PMID:Self-inactivating lentiviral vectors with U3 and U5 modifications. 1044 60

The radiation-inducible EGR-1-promoter has been used in different gene therapy approaches in order to enhance and locally restrict therapeutic efficacy. The aim of this study was to reduce nonspecific gene expression in the absence of irradiation (IR) in an adenoviral vector. Rat rhabdomyosarcoma R1H tumor cells were infected with adenoviral vectors expressing either EGFP or HSV-TK under control of the murine EGR-1 promoter/enhancer. Cells were irradiated at 0-6 Gy. Gene expression was determined by FACS-analysis (EGFP), or crystal violet staining (HSV-TK). The bovine growth hormone polyadenylation signal (BGH pA) was used as insulating sequence and was introduced upstream or upstream and downstream of the expression cassette. Infected R1H cells displayed IR dose-dependent EGFP expression. Cells treated with IR, AdEGR.TK and ganciclovir displayed a survival of 17.3% (6 Gy). However, significant gene expression was observed in the absence of IR with EGR.TK and EGR.EGFP constructs. Introduction of BGHpA upstream or upstream and downstream of expression cassette resulted in decreased nonspecific cytotoxicity by a factor of 1.6-2.3 with minor influence on the induced level of cytotoxicity. Introduction of insulating sequences in adenoviral vectors might allow tighter temporospatial control of gene expression by the radiation-inducible EGR-1 promoter.
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PMID:Optimization of radiation controlled gene expression by adenoviral vectors in vitro. 1580 45