Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TNF-related apoptosis-inducing ligand (TRAIL) shares significant homology with CD95 (Fas) ligand and has the ability to induce apoptosis in sensitive cells through a caspase-mediated pathway. We have evaluated the activity of purified human recombinant soluble TRAIL (S-TRAIL, comprising residues 114-281; Biomol, Plymouth Meeting, PA, USA) and a leucine zipper construct of TRAIL (LZ-TRAIL; Immunex, Seattle WA, USA) against myeloma cell lines NCI H929, U266, RPMI 8226, the FasL-sensitive Jurkat T cell ALL line, the lymphoblastoid cell line MC/CAR and primary tumour cells from 16 myeloma patients. Furthermore, we examined the relationship between TRAIL-induced apoptosis and TRAIL receptor expression utilising RT-PCR and flow cytometry. Two of three myeloma cell lines and Jurkat were TRAIL sensitive whereas MC/CAR was relatively resistant. Five of 16 (31%) primary tumours demonstrated > or =20% reduction in myeloma cells following TRAIL incubation (20-59%). This did not correlate with prior therapy. Four cell lines (two sensitive) and five primary tumours (two sensitive) demonstrated mRNA expression of the intra-cellular death domain containing TRAIL-R1. Variable expression of the two decoy (TRAIL-R3 and R4) and soluble (osteoprotegerin) receptors was seen and this did not correlate with TRAIL resistance. We conclude that myeloma cell expression of death effector receptors for TRAIL is insufficient to confer sensitivity to TRAIL-induced apoptosis but that in a significant minority of patients, irrespective of prior therapy, tumour cells are sensitive to TRAIL. The further investigation of TRAIL as an adjunct to presently available therapies for myeloma is justified.
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PMID:TRAIL-induced eradication of primary tumour cells from multiple myeloma patient bone marrows is not related to TRAIL receptor expression or prior chemotherapy. 1158 25

The precise mechanisms of vascular diseases in patients with insulin-dependent diabetes mellitus (IDDM) are not clearly understood. There are evidences of alteration in mechanisms involved in regulating vascular tone including increased ACE activity and decreased NO production in STZ diabetic rats. Insulin treatment may reverse these changes by an unknown mechanism. This study sought to examine the interaction of ACE activity and NO and how insulin treatment affected these mechanisms. Four groups of eight male Sprauge-Dawely rats including control (C) and three diabetic groups (D, IT and LIT) were used in this study. Diabetes induced by injection of 60 mg kg(-1) STZ i.p. After induction of diabetes IT group treated with insulin (10 units kg(-1) daily s.c.) for 4 weeks. LIT group received the same amount of insulin and N(omega)-nitro-l-arginine methyl ester (L-NAME; 20 mg kg(-1) i.p.) for the same period. The D group was diabetic control that treated with saline. ACE activity was determined by HPLC method. At the end of study in D group ACE activity was increased in aorta, heart, lung and serum but Serum NO(x) (nitrate and nitrite) concentration decreased compared to C group. These values were reversed to normal by insulin treatment in IT group. In LIT group the ACE activity remained elevated only in aorta and heart while the serum NO(x) was lower than control group. It is concluded that ACE reducing activity of insulin in aorta and heart of STZ-induced diabetic rats may be mediated by elevation of NO by insulin treatment.
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PMID:Study of interaction between nitric oxide and ACE activity in STZ-induced diabetic rats: role of insulin. 1522 68