Articles Related to mechanisms

Targeting mutant proteins and associated signaling pathways of driver oncogenes by small molecule kinase inhibitors (KIs) are a promising strategy of cancer therapy. However, despite the initial success of treatment, KIs often become ineffective as intrinsic and acquired resistance. This article reviews the English-language literature to explore the underlying mechanisms of drug resistance and to present a challenge for developing drugs to overcome resistance. Mechanisms of acquired resistance include 1) the selection of pre-existing subclones with other mutations, 2) the emergence of secondary mutations in the target kinase domain, 3) upregulation of kinases both within the same kinase family and their related kinase families, as well as activation of alternative bypass pathways, 4) epithelial-mesenchymal transition, 5) overexpression of pro-survival Bcl-2 family proteins and 6) drug efflux mechanisms. Currently available methods are to obtain tumor biopsy samples at recurrence or progression if the tumor lesion is accessible to a biopsy and to use the second- and third-generation KIs based on the individual need of each patient. Furthermore, recent computational challenges provide design principles to prevent the development of drug resistance. In conclusion, we provide an overview of the postulated resistance mechanisms and highlight the future direction of computational structure-based design of new potent KIs.

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The prevalence of overweight and obesity among US adults is well-documented and lifestyle intervention remains the foundation for all overweight and obesity treatment interventions, even when bariatric surgery is offered. Unfortunately, lifestyle intervention, though clearly a vital part of any obesity treatment, including bariatric surgery, has not been found to be as effective in achieving health benefits as hoped for.

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This article summarizes the advantages of orally disintegrating tablets (ODTs) as well as critical issues during evaluation of ODTs such as bioequivalence and challenges and limitations of ODTs and finally present and the future of ODTs. ODTs have received everincreasing demand and the field has become a rapidly growing area in the pharmaceutical industry.

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The DNA mismatch repair (MMR) system is necessary for the maintenance of genomic stability. The MMR system promotes genomic fidelity by repairing base-base mismatches, insertion-deletion loops (IDLs) and heterologies generated during DNA replication and recombination.

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Salmonella is a causative agent for a wide variety of pathological diseases in humans, cattle, poultry and other farm animals and hence Salmonella infections are a major cause of concern to humans, veterinary animals and to food industry.

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