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)

Although reversibility of acute ifosfamide-induced nephrotoxicity is well documented, there is a paucity of data concerning the long-term outcome of chronic renal toxicity, and full recovery from established damage has not been reported. A 4-year-old boy presented with hypophosphatemic rickets 9 months after completion of combination chemotherapy (including ifosfamide) for prostatic rhabdomyosarcoma. Further investigation confirmed glomerular and generalised tubular dysfunction with a Fanconi syndrome. However, serial investigation over the next 4 years revealed complete and sustained recovery of this chronic nephrotoxicity.
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PMID:Late reversibility of chronic ifosfamide-associated nephrotoxicity in a child. 895 Mar 39

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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PMID:Stem cell transplantation; Iranian experience. 1911 Oct 33

Deregulation of the mTOR pathway is closely associated with tumorigenesis. Accordingly, mTOR inhibitors such as rapamycin and mTOR-selective kinase inhibitors have been tested as cancer therapeutic agents. Inhibition of mTOR results in sensitization to DNA-damaging agents; however, the molecular mechanism is not well understood. We found that an mTOR-selective kinase inhibitor, AZD8055, significantly enhanced sensitivity of a pediatric rhabdomyosarcoma xenograft to radiotherapy and sensitized rhabdomyosarcoma cells to the DNA interstrand cross-linker (ICL) melphalan. Sensitization correlated with drug-induced downregulation of a key component of the Fanconi anemia pathway, FANCD2 through mTOR regulation of FANCD2 gene transcripts via mTORC1-S6K1. Importantly, we show that FANCD2 is required for the proper activation of ATM-Chk2 checkpoint in response to ICL and that mTOR signaling promotes ICL-induced ATM-Chk2 checkpoint activation by sustaining FANCD2. In FANCD2-deficient lymphoblasts, FANCD2 is essential to suppress endogenous and induced DNA damage, and FANCD2-deficient cells showed impaired ATM-Chk2 and ATR-Chk1 activation, which was rescued by reintroduction of wild-type FANCD2. Pharmacologic inhibition of PI3K-mTOR-AKT pathway in Rh30 rhabdomyosarcoma cells attenuated ICL-induced activation of ATM, accompanied with the decrease of FANCD2. These data suggest that the mTOR pathway may promote the repair of DNA double-strand breaks by sustaining FANCD2 and provide a novel mechanism of how the Fanconi anemia pathway modulates DNA damage response and repair.
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PMID:Regulation of FANCD2 by the mTOR pathway contributes to the resistance of cancer cells to DNA double-strand breaks. 2363 93

mTOR is a serine/threonine kinase and plays a critical role in mammalian cell growth, survival, and metabolism. mTOR is present in two cellular complexes: mTORC1 and mTORC2. Dysregulation of the mTOR pathway has been related to tumorigenesis, poor prognosis and/or chemotherapy resistance in a variety of malignancies. Inhibition of mTORC1 by Rapamycin and its analogs has been explored to treat a number of tumors. However, the effectiveness of patient response is limited and not all patients respond. Second generation of mTOR inhibitors have recently been developed to target mTOR kinase activity and to suppress both mTORC1 and mTORC2. Dual mTORC1/mTORC2 inhibitors generally are more efficacious in preclinical studies and clinical trials. We and others have recently found that dual mTORC1/mTORC2 inhibitors sensitize T-cell acute lymphocytic leukemia and rhabdomyosarcoma cells to DNA damaging agents by suppression of expression of FANCD2 of the Fanconi anemia pathway, an important DNA repair mechanism that is associated with drug resistance of multiple types of cancer. This review will highlight mTOR and the Fanconi anemia pathway in cancer, with a particular attention to our newly discovered connection between mTOR and the Fanconi anemia pathway.
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PMID:Mtor-Fanconi Anemia DNA Damage Repair Pathway in Cancer. 2562 Dec 86