Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of multi-drug resistance (MDR1) and its product, P-glycoprotein (P-gp) on 5-aminolevulinic acid hexyl ester (Hexyl-ALA) mediated phototoxicity was determined with human uterine sarcoma cells, MES-SA control and MDR1 expressing MES-SA-Dx5. MDR1 expression reduced intracellular levels of the Hexyl-ALA metabolite, protoporphyrin IX (PpIX) to a limited degree and could be reversed with a P-gp inhibitor, verapamil. P-gp expression also reduced Hexyl-ALA photosensitivity. More importantly, photoactivated Hexyl-ALA reduced at the mRNA and protein levels without altering housekeeping GAPDH mRNA. These findings suggest that Hexyl-ALA could be used to selectively reduce P-gp expression in overcoming resistance to chemotherapy agents such as doxorubicin and paclitaxel.
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PMID:Effects of photoactivated 5-aminolevulinic acid hexyl ester on MDR1 over-expressing human uterine sarcoma cells. 1862 94

In patients with metastatic melanoma, standard cytotoxic drugs such as dacarbazine have no proven impact on survival. Vemurafenib is the first BRAF protein inhibitor to be approved for the treatment of melanoma. In about half of patients with melanoma, this protein, important for cell growth, is dysregulated owing to a mutation (V600) in the gene that encodes it. An unblinded clinical trial that included 675 patients with metastatic melanoma harbouring a V600 BRAF mutation compared oral vemurafenib with intravenous dacarbazine. An interim analysis showed a statistically significant increase in the median overall survival time of about 1.5 months with vemurafenib (9.2 versus 7.7 months). These results are too preliminary to determine the survival advantage, if any, conferred by vemurafenib. About 20% of patients treated with vemurafenib developed skin cancer. The most common adverse effects were skin rash (37%), photosensitivity (33%), diarrhoea (28%), and arthralgia (54%). Vemurafenib also causes ocular disorders, including uveitis, and prolongs the QT interval in a dose-dependent manner. The potential for pharmacokinetic interactions is high: vemurafenib inhibits P-glycoprotein and CYP 1A2, and induces CYP 3A4. In practice, vemurafenib should only be used in rigorous clinical trials, on a case-by-case basis.
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PMID:Vemurafenib. Value unclear in metastatic melanoma. 2337 92