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)

Doxorubicin (DOX) and ifosfamide (IFO) are the most active single agents in soft tissue sarcomas (STS). Tumour necrosis factor-alpha (TNF-alpha) is used for STS in the setting of isolated limb perfusions. Like TNF-alpha, TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis. In contrast to TNF-alpha preliminary studies suggest that TRAIL lacks systemic side effects. The effects of TRAIL alone and in combination with DOX or 4-hydroxy-IFO were evaluated in the TNF-alpha sensitive rhabdomyosarcoma cell line KYM-1, its 5-fold TNF-alpha sensitive subline KD4 and its >150-fold TNF-alpha resistant subline 37B8R. Membrane expression of TRAIL-receptors DR4 (death receptor 4), DR5 (pro-apoptotic), DcR1 (decoy receptor 1), DcR2 (anti-apoptotic) was assessed by flow cytometry. Cytotoxicity was determined by microculture tetrazolium assays. Apoptosis assays were performed with acridine orange. DOX (doxorubicin) and 4-OH-IFO decreased survival in all cell lines; a 2-fold resistance was observed for both drugs in 37B8R. All cell lines expressed DR4 and DR5, but hardly any DcR1 or DcR2. TRAIL was cytotoxic in KYM-1, even more in KD4 and induced massive apoptosis; 37B8R was >500-fold resistant to TRAIL and little apoptosis could be observed. TRAIL plus DOX showed synergistic cytotoxicity in KYM-1 and 37B8R. TRAIL plus 4-OH-IFO showed addition in all three cell lines. DOX plus TRAIL-induced more cytotoxicity and apoptosis in all cell lines compared to TRAIL alone. In 37B8R, DOX overcame resistance to TRAIL. In KYM-1, KD4 and 37B8R, sensitivity and resistance to TNF-alpha and TRAIL parallels. TRAIL-resistance was independent from expression of TRAIL-receptors. DOX with TRAIL could overcome TRAIL-resistance in 37B8R cells.
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PMID:Doxorubicin potentiates TRAIL cytotoxicity and apoptosis and can overcome TRAIL-resistance in rhabdomyosarcoma cells. 1528 69

Rhabdomyosarcoma is a common malignant soft tissue that frequently involves bone and major neurovascular structures and resection of deep-seated rhabdomyosarcoma can cause severe dysfunction in the affected limbs. Based on the mouse osteosarcoma model, we developed a new surgical approach involving photodynamic surgery (PDS), photodynamic therapy (PDT) and radiodynamic therapy (RDT) using acridine orange (AO). Six rhabdomyosarcoma cases were treated using this new modality after confirming the effectiveness of AO-PDT on human rhabdomyosarcoma cell lines. All patients had almost normal limb function after surgery, with only one recurrence. Based on these results, AO-PDS, PDT and RDT can be used to preserve excellent limb function in patients with rhabdomyosarcoma involving major nerves and vessels or bones.
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PMID:A new therapeutic modality involving acridine orange excitation by photon energy used during reduction surgery for rhabdomyosarcomas. 1908 47

We have previously reported the prevention of Hypoxia mediated apoptosis by Neferine, an alkaloid from Nelumbo nucifera. The present study was designed to assess the role of neferine in modulation of hypoxia induced autophagy in muscle cells. Cytoprotective dose of neferine in muscle cells (Rhabdomyosarcoma cells) exposed to hypoxia was determined by MTT assay. Hypoxia induced oxidative stress in muscle cells by enhancing lipid peroxidation and depleting cellular antioxidant enzymes. The inhibition of PI3K/Akt/mTOR cell survival signaling acts as a trigger for the hypoxia induced Autophagy. Hypoxia exposure in muscle cells resulted in acidic vesicular formation, as studied by acridine orange staining which serves as an indicator of autophagosome formation. Pretreatment with neferine inhibited autophagy induction by activating Akt/mTOR pathway and down regulating Beclin 1, PI3KCIII and LC3B-II in cells exposed to hypoxia. Further, Neferine also modulated hypoxia mediated changes in the cellular antioxidant levels by Nrf2 nuclear translocation. Collectively, results of the study suggest the role of neferine in preventing hypoxia induced autophagy in muscle cells.
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PMID:Neferine prevents autophagy induced by hypoxia through activation of Akt/mTOR pathway and Nrf2 in muscle cells. 2758 81