PARADIGM SHIFT IN RESEARCH FOCUS:COMPUTATIONAL SOFTWARES IN CANCER BIOLOGY

摘要

In the recent time field of analysis,systems biology has gained its momentum.Simulation can play a major role in selection of studies to be performed;clinical trial simulation covers multi-disciplinary individual's i.e.preclinical pharmacologist,statistician,computer programmer,etc.Although widely used,the physiologically-based pharmacokinetic approach requires intense resources to generate the data on the various parameters described in the models.1 For example,an available software package called PK-Sim developed by Bayer Technology Services2 can be employed for such purpose.Oral Submucous fibrosis(OSF)was recognized as a definitive lesion by Schwartz who described it as a fibrosing condition in 1952 and named it as"atrophicaidiopathica mucosae oris(tropica)".4 It was described as precancerous condition by Paymaster in 1956.5 This apparent incongruity was corrected by the WHO(2007),and the lesion along with other similar ones are now labelled as"potentially malignant oral disorders".6 There is increased accumulation,decreased degradation of collagen fibres and altered collagenase activity is found in oral submucous fibrosis affected mucosa.7 One enzyme that increasingly is associated with extra cellular matrix(ECM)is the protein-cross-linking enzyme tissue transglutaminase(TG2).Tissue transglutaminase(TG2)catalyzes the cross-linkage between glutamine(Gin)and lysine(Lys)side chains.Although TG2 is essential for the stabilization of the extracellular matrix.8 G.S.Thangjam et al(2009),conducted a study to know the possible role of transglutaminase(TG2)in OSMF pathogenesis.Biopsy tissues were obtained from OSMF affected patients and subjected to RT-PCR.They found overregulation of TGM-2 suggesting the importance of TGM-2 in the pathogenesis of OSMF.9 With the knowledge of molecular pathogenesis,role of transglutaminase enzyme in oral submucous fibrosis and use of pharmacokinetic simulation software-PK Sim,a research is formulated to find out the bioavailability and efficacy of cysteamine hydrochloride(transglutaminase inhibitor)in management of the progression of the disease.