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)

Benzoporphyrin derivative, monoacid ring A (BPD-MA), currently in clinical trials as a photosensitizer for photodynamic therapy for cancer, consists of two regioisomers (A1 and A2) present in equal proportions. The contribution of the regioisomers to the overall photosensitizing potency of BPD-MA was tested in vitro and in vivo. The in vitro photosensitizing potencies of BPD-MA-A1 and -A2 were tested in a standard cytotoxicity assay using M1 (rhabdomyosarcoma of DBA/2 mice) tumor cells and were found to be equivalent. The in vivo photosensitizing efficacies of the regioisomers were tested in the M1 tumor model in DBA/2 mice and were also found to be equivalent. Biodistribution of the regioisomers in mouse plasma, tumor and liver was studied in M1 tumor-bearing DBA/2 mice at 15 min and 3 hr post intravenous injection of [14C]BPD-MA-A1/A2 at 4 mg/kg body weight. Plasma and extracts from tumor and liver were analysed by HPLC and tested for radioactivity. The two regioisomers were eliminated from plasma and liver at different rates, which resulted in A1:A2 ratios of 1:0.28 in plasma and 1:0.75 in liver at 3 hr post injection. The differential elimination was not observed to any significant degree in the tumor, where even at 3 hr post injection the A1:A2 ratio was 1:1.15. Therefore, we concluded that in tumor tissue, at 3 hr post injection, the time at which laser photodynamic therapy is carried out, both regioisomers were present in about equal proportions. Further, both regioisomers were fully active as determined by an in vitro cytotoxicity assay following extraction.
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PMID:Photosensitizing efficiency of two regioisomers of the benzoporphyrin derivative monoacid ring A (BPD-MA). 161 Apr

Rhabdomyosarcoma (RMS) is a pediatric tumor, which arises from muscle precursor cells. Recently, it has been demonstrated that Hippo Pathway (Hpo), a pathway that regulates several physiological and biological features, is involved in RMS tumorigenesis. For instance, an upregulation of the Hpo downstream effector Yes-Associated Protein 1 (YAP) leads to the development of embryonal rhabdomyosarcoma (eRMS) in murine activated muscle satellite cells. On the other hand, the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ) is overexpressed in alveolar rhabdomyosarcoma (aRMS) patients with poor survival. YAP and TAZ exhibit both cytoplasmic and nuclear functions. In the nucleus, YAP binds TEADs (TEA domain family members) factors and together they constitute a complex that is able either to activate the transcription of several genes such as MYC, Tbx5 and PAX8 or to maintain the stability of others like p73. Due to the key role of YAP and TAZ in cancer, the identification and/or development of new compounds able to block their activity might be an effective antineoplastic strategy. Verteporfin (VP) is a molecule able to stop the formation of YAP/TEAD complex in the nucleus. The aim of this study is to evaluate the action of VP on RMS cell lines. This work shows that VP has an anti-proliferative activity on all RMS cell lines analyzed. Depending on RMS cell lines, VP affects cell cycle differently. Moreover, VP is able to decrease YAP protein levels, and to induce the activation of apoptosis mechanism through the cleavage of PARP-1. In addition, Annexin V assay showed the activation of apoptosis and necrosis after VP treatment. In summary, the ability of VP to disrupt RMS cell proliferation could be a novel and valuable strategy to improve the therapeutic approaches in treating rhabdomyosarcoma.
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PMID:"Verteporfin exhibits anti-proliferative activity in embryonal and alveolar rhabdomyosarcoma cell lines". 3149 5