Related Articles

Treating skin and lung fibrosis in systemic sclerosis: a future filled with promise?

Curr Opin Pharmacol. 2013 Jun 6;

Authors: Antic M, Distler JH, Distler O

Abstract
Systemic sclerosis (SSc) is a rare autoimmune disorder characterized by immune activation, vascular damage and an excessive accumulation of extracellular matrix proteins in the skin and internal organs. Despite its high morbidity and increased mortality, currently available treatment options for fibrotic manifestations of SSc remain limited and their clinical antifibrotic effects are borderline. In this review, novel insights from recently published clinical trials in SSc on treatment concepts such as mycophenolate mofetil, oral type I collagen, recombinant human relaxin and autologous hematopoietic stem cell transplantation are discussed. In the past decade the most significant progress in this field has been made by the identification of a large number of cellular and molecular key players in the pathogenesis of fibrotic disease manifestations. This has led to the identification of novel candidates as molecular targets for treatment of fibrotic diseases. On the basis of their level of evidence from preclinical studies and based on the availability of first clinical results, the most promising targets are presented including inhibitors of B-cells, tyrosine kinases, 5-hydroxytryptamin receptors, interleukin-6 and Wnt signalling.

PMID: 23747024 [PubMed - as supplied by publisher]

5-Lipoxygenase Antagonist therapy: a new approach towards targeted cancer chemotherapy.

Acta Biochim Biophys Sin (Shanghai). 2013 Jun 9;

Authors: Bishayee K, Khuda-Bukhsh AR

Abstract
Leukotrienes are the bioactive group of fatty acids and major constituents of arachidonic acid metabolism molded by the catalytic activity of 5-lipoxygenase (5-LOX). Evidence is accumulating in support of the direct involvement of 5-LOX in the progression of different types of cancer including prostate, lung, colon, and colorectal cancers. Several independent studies now support the correlation between the 5-LOX expression and cancer cell viability, proliferation, cell migration, invasion through extracellular matrix destruction, metastasis, and activation of anti-apoptotic signaling cascades. The involvement of epidermal growth factor receptor and 5-oxo-ETE receptor (OXER1) is the major talking point in the downstream of the 5-LOX pathway, which relates the cancer cells to the proliferative pathways. Antisense technology approaches and use of different kinds of blocker targeted to 5-LOX, FLAP (5-LOX-activating protein), and OXER1 have shown a greater efficiency in combating different cancer cell types. Lastly, suppression of 5-LOX activity that reduces the cell proliferation activity also induces intrinsic mitochondrial apoptotic pathway in either p53-dependent or independent manner. Pharmacological agents that specifically inhibit the LOX-mediated signaling pathways have been used during last few years to treat inflammatory diseases such as asthma and arthritis. Studies of these well-characterized agents are therefore warranted for their use as possible candidates for chemotherapeutic studies against the killer disease cancer.

PMID: 23752617 [PubMed - as supplied by publisher]