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Articles Related to Mechanism

Mechanisms of Resistance to Kinase Inhibitors and Strategies to Prevent the Development of Drug Resistance

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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A New Mechanism of the Nanoindentation Process

A new mechanism of the nanoindentation process based on the consideration of the decrease the energy of the chemical bonds as a result of the pressure of the indenter on the material is proposed. This leads to an increase the mobility of the atoms, which in the beginning creates point defects and as the external force increases, melting and material destruction occurs.
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Combating Childhood Obesity with an Integrated School Curriculum

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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Orally Disintegrating Tablets: A Short Review

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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Molecular Mechanism Linking BRCA1 Dysfunction to High Grade Serous Epithelial Ovarian Cancers with Peritoneal Permeability and Ascites

Ovarian cancer constitutes the second most common gynecological cancer with a five-year survival rate of 40%. Among the various histotypes associated with hereditary ovarian cancer, high-grade serous epithelial ovarian carcinoma (HGSEOC) is the most predominant and women with inherited mutations in BRCA1 have a lifetime risk of 40-60%. HGSEOC is a challenge for clinical oncologists, due to late presentation of patient, diagnosis and high rate of relapse. Ovarian tumors have a wide range of clinical presentations including development of ascites as a result of deregulated endothelial function thereby causing increased vascular permeability of peritoneal vessels.
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Case Studies of 17 Patients

This retrospective review of 17 patients suggests an increased risk of adverse events including premature death with opiate discontinuation long after withdrawal stage. The results are consistent with previously reported yet not fully understood – opiate associated neuro protective mechanism – against premature death for some vulnerable subgroups.
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Examination of Some Country made Smooth Bore Firearms

Present trend of the crimes in India reveals that a wide variety of firearms including factory /country made are illegally used in crimes like murder, armed robbery, riot, poaching etc. Out of the total firearms received in Tripura State Forensic Science Laboratory, Agartala for the last ten years, about 30% of the firearms are observed to be belonging to country made pistol/pipe guns.
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Molecular Mechanisms of Mismatch Repair Genes in Cancer – A Brief Review

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 Serovars and Their Host Specificity

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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Editorial Board Members Related to Mechanism

CHIA-YI KUAN

Associate Professor
Department of Pediatrics
Center for Neurodegenerative Disease
Emory University School of Medicine
United States

YUNBO LI

Professor
Department of Pharmacology
Campbell University School of Osteopathic Medicine
United States

Rashmi Bansal

Professor
Department of Neuroscience
University of Connecticut Health Center
United States

ASISH K. SAHA

Associate Professor
Department of Medicine
Boston University
United States

Lina H K LIM

Associate Professor
Department of Physiology
National University of Singapore
Singapore

MAHENDRA PRATAP SINGH

Toxicogenomics and Predictive Toxicology Division
India

Walter J. Lukiw

Professor
Neurology, Neuroscience and Ophthalmology
Louisiana State University
United States

Maria Amália da Silva Jurado

Assistant Professor
Department of Life Sciences
University of Coimbra
Portugal

Sarah Hall

Senior Lecturer
Department of Life Sciences
Anglia Ruskin University
United Kingdom

MICHAEL P. SHERMAN

Professor Emeritus
Department of Child Health
Division of Neonatology
University of California-Davis School of Medicine
United States
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