Targeting Nuclear Factor-Kappa B Signaling Pathway by Curcumin: Implications for the Treatment of Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which involves an auto-immune mechanism that leads to perivascular demyelination. The role of nuclear factor-kappa B (NF-κB) signaling pathway in the pathogenesis of MS has been suggested by genome-wide association studies. Therefore, strategies targeting this pathway could be potentially beneficial. Curcumin is the active component of turmeric and a phenolic phytochemical. This phytochemical has anti-inflammatory properties and has been shown by multiple studies to downregulate NF-κB and its downstream gene targets including cyclooxygenase-2, tumor necrosis factor-α, interleukin-1, and interleukin-6. This review discusses the modulatory effects of curcumin on the NF-κB signaling pathway and its downstream effectors, and the therapeutic implications of this modulation on MS.

Therapeutic Potential of Targeting Transforming Growth Factor-beta in Colorectal Cancer: Rational and Progress.

BACKGROUND: Colorectal cancer (CRC) is one of the most common types of cancer and is associated with an increasing rate of mortality. Transforming Growth Factor-Beta (TGF-ß) is often upregulated in CRC, and appears to play an important role in regulating cell proliferation, migration, immune surveillance, apoptosis, cell differentiation, drug-resistance and many cellular processes that may be involved in CRC, and therefore underscores its potential value as a therapeutic target in the treatment of CRC. An increased expression of the TGF- ß pathway has been associated with poor prognosis in several cancer types, including CRC. METHODS: Here, we describe the critical role of the TGF-ß pathway in CRC as well as the preclinical and clinical investigations on TGF-ß inhibitors, with particular emphasis on recent findings with small-molecule inhibitors in CRC. Several TGF-ß inhibitors (e.g., Trabedersen, Galunisertib, Gradalis, PF-03446962, NIS793) have been generated over the past decade for targeting this pathway. RESULTS: There is accumulating evidence of the therapeutic potential of this and other TGF-ß inhibitors for the treatment of other malignancies. These inhibitors might be used in combination with chemotherapy as well as with other biological agents, in order to overcome different resistance mechanisms. However, further studies are needed to identify determinants of the activity of TGF-ß inhibitors, through the analysis of genetic and environmental alterations affecting TGF-ß and parallel pro-cancer pathways. CONCLUSION: These studies will be critical to improving the efficacy and selectivity of current and future anticancer strategies targeting TGF-ß.

The Impact of Statin Therapy on the Survival of Patients with Gastrointestinal Cancer.

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins affect several potential pathways, including cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk.