Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Existing treatments for cutaneous T cell lymphoma (topical agents, chemotherapy, photopheresis, interferon alfa) have cosmetic benefits but no impact on survival. (2) Bexarotene, a synthetic retinoid, is approved for the treatment of adults with advanced-stage cutaneous lymphoma refractory to at least one systemic treatment. (3) Two non comparative trials included patients who were refractory or in relapse after various systemic treatments: one included 58 patients at an early stage of the disease, and the other 94 patients at an advanced stage. The evidence from these trials is weak for several reasons such as the lack of a standard endpoint for efficacy and numerous protocol modifications. The optimal dose of bexarotene is unknown. No comparative trials are available, and indirect comparisons are often misleading. (4) Nearly all patients treated with bexarotene suffer adverse effects, which can include hyperlipidemia (risk of pancreatitis), hypothyroidism, and haematological reactions (leukopenia, anemia). There is also an unconfirmed risk of cataract. (5) In practice, bexarotene is a highly toxic drug with uncertain efficacy, and there is no reason to prescribe it. Bexarotene should never have been authorised on the basis of such a bad evaluation.
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PMID:Bexarotene: new preparation. Cutaneous lymphoma: too many adverse effects. 1523 46

Neovascularization (NV) in the cornea is a major cause of vision impairment and corneal blindness. Hemangiogenesis and lymphangiogenesis induced by inflammation underlie the pathogenesis of corneal NV. The current mainstay treatment, corticosteroid, treats the inflammation associated with corneal NV, but is not satisfactory due to such side effects as cataract and the increase in intraocular pressure. It is imperative to develop a novel therapy that specifically targets the hemangiogenesis, lymphangiogenesis, and inflammation pathways underlying corneal NV. Histone deacetylase inhibitors (HDACi) have been in clinical trials for cancer and other diseases. In particular, HDACi suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The functional mechanism of SAHA in cancer and especially in corneal NV remains unclear. Here, we show that topical application of SAHA inhibits neovascularization in an alkali-burn corneal injury model. Mechanistically, SAHA inhibits corneal NV by repressing hemangiogenesis, inflammation pathways, and previously overlooked lymphangiogenesis. Topical SAHA is well tolerated on the ocular surface. In addition, the potency of SAHA in corneal NV appears to be comparable to the current steroid therapy. SAHA may possess promising therapeutic potential in alkali-burn corneal injury and other inflammatory neovascularization disorders.
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PMID:Inhibition of multiple pathogenic pathways by histone deacetylase inhibitor SAHA in a corneal alkali-burn injury model. 2318 11