Therapeutic potential of tranilast, an anti-allergy drug, in proliferative disorders.

Tranilast (N-[3,4-dimethoxycinnamoyl]-anthranilic acid; Rizaben®) is an anti-allergy drug approved for use in Japan and South Korea, also used against asthma, autoimmune diseases, and atopic and fibrotic pathologies. The antitumor potential of tranilast is attracting considerable interest. This review summarizes recent evidence concerning the effect of tranilast on different tumor types and discusses the drug's possible mode of action in this area. In vivo and in vitro studies are covered, as well as evidence from clinical trials, in which tranilast was evaluated in various models of proliferative disorders. The findings presented in this report, demonstrate the excellent potential of tranilast in the management of certain types of tumor, and provide a strong rationale for the initiation of controlled clinical trials in this area.

Intravenous immunoglobulin for the treatment of Crohn's disease.

Crohn's disease (CD) is a debilitating condition which still requires improvement in its management. There is a need for alternatives to anti-tumour necrosis factor drugs which are costly and beneficial in less than 50% of patients. Intravenous immunoglobulin (IVIG) has been used in the management of aminosalicylate- and steroid-resistant CD for more than 20 years, although the published literature available is limited. A literature search identified 17 relevant publications since 1969, including five case reports of single patients, two abstracts, three conference papers, one review paper and six book or journal articles. No randomised controlled trials of IVIG in CD have been published. A review of the evidence identified indicates that IVIG can induce a rapid and significant improvement in aminosalicylate- and steroid-resistant CD, often within days of the initial administration. Data from longer-term studies show that maintenance of remission over the medium term is also possible. These encouraging findings provide a rationale for the initiation of larger randomised controlled trials of IVIG in CD with the aim of providing further treatment options for this difficult-to-manage condition.

Therapeutic potential of the biscoclaurine alkaloid, cepharanthine, for a range of clinical conditions.

Cepharanthine (CEP) is a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata. It has been widely used in Japan for more than 40 years to treat a wide variety of acute and chronic diseases. CEP inhibits tumor necrosis factor (TNF)-α-mediated NFκB stimulation, plasma membrane lipid peroxidation and platelet aggregation and suppresses cytokine production. It has also been shown to scavenge free radicals and to have a protective effect against some of the responses mediated by pro-inflammatory cytokines such as TNF-α, interleukin (IL)-1ß and IL6. CEP has successfully been used to treat a diverse range of medical conditions, including radiation-induced leukopenia, idiopathic thrombocytopenic purpura, alopecia areata, alopecia pityrodes, venomous snakebites, xerostomia, sarcoidosis, refractory anemia and various cancer-related conditions. No safety issues have been observed with CEP, and side effects are very rarely reported.

Validation of blood testing for K-ras mutations in colorectal and pancreatic cancer.

BACKGROUND: K-ras mutation in a tumour is a powerful negative predictor for treatment success. Identifying tumour K-ras mutation is complex, and could be simplified by an appropriate blood test. Clinical studies were identified in which K-ras mutation status was assessed in both blood and tumour to ascertain whether blood K-ras mutation is predictive of tumour K-ras mutation. Between 29% and 100% of patients with a tumour K-ras mutation in 11 studies presented the same mutation in peripheral blood. Only 5/272 patients presented blood K-ras mutation in the absence of the same tumour mutation, possibly due to sampling errors. K-ras mutation in blood appears to indicate K-ras mutation in tumour, while the absence of blood K-ras mutation does not prove lack of mutation in the tumour. This suggests that a blood test for the detection of tumour K-ras may be possible, and could direct cancer treatment strategies.