Articles Related to Kinase

Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder characterized by an extreme sensitivity to UV rays from sunlight, a high incidence of skin cancer and occasional neurological symptoms. XP, primarily defined as a DNA repair syndrome, has been found associated with defects in the Nucleotide Excision Repair (NER) pathway, and more recently by transcriptional deregulation. XP results from mutations in eight genes (XPA to XPG and XPV) coding for proteins involved in NER.

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The clinical outcomes of chronic myeloid leukemia (CML) have been improved by tyrosine kinase inhibitors (TKIs). However, there is no established consensus for TKI selection in de novo CML. We investigated TKI treatment patterns in a real-world setting. Among 95 chronic-phase CML patients, 44% were initiated treatment with imatinib, 26% with dasatinib, and 30% with nilotinib. Our data suggest that imatinib remains applicable and that dasatinib has a favorable therapeutic effect, although pleural effusion can arise. Nilotinib was the most prevalent TKI as the treatment-associated adverse events were deemed more manageable than those associated with imatinib and dasatinib.

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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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Homocysteine is a parameter that plays an important role for diagnosing several diseases mainly cardiovascular diseases. In this study, the first time reference values for homocysteine levels detected in healthy Golden Retriever, Terrier, German Shepherd and Labrador Retriever breeds of dogs play an important role in the prognosis of many diseases.

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Primary small cell lung cancer (SCLC) showing epidermal growth factor receptor (EGFR) mutation is extremely rare. Transformation into SCLC has been reported as an evolution of lung adenocarcinoma acquiring resistance to EGFR tyrosine kinase inhibitors (TKI) and is considered to be a rare resistance mechanism of EGFR-TKI therapy.

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Human epidermal growth factor receptor 2 (HER2) is responsible for the pathogenesis and poor outcomes of several types of cancers, including advanced gastric and gastroesophageal junction cancer. Molecular-targeted drugs on the other hand, such as trastuzumab, prolong overall survival and progression-free survival in HER2-positive gastric cancer. The purpose of the case report is to evaluate the impact of delivering trastuzumab in advanced gastric cancer with concomitant HER2 mutation and amplification.

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Spontaneous coronary artery dissection (SCAD) is a rare myocardial ischemic disease that threatens patients’ life. Various risk factors are associated with SCAD, such as smoking, severe hypertension and psychological reasons. Considering the formation of dissection, SCAD can be divided into intimal tear type or intraluminal hemorrhage type.

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Increased life style changes have led to global epidemic of obesity. The global prevalence of obesity protracts to increase, with devastating consequences for overall health. Thus by exploring novel beneficial properties of natural products and their scientific indications are the need of the hour and can bring about a whole new revolution in nutraceutical industries and health care sectors.

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Fish oils are the most common source of omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly eicosapentaenoic acid (EPA). It has been pointed out protective effects and beneficial effects of EPA on body weight reduction, heart health, blood lipid profile, cardiovascular diseases and other diseases. Based on its biological activities, EPA may be developed to a complementary and alternative medicine through further research. In this paper, the pharmacological effects of EPA were summarized by reviewing the recent related literatures.

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The C28/I2 line of immortalized juvenile human chondrocytes was employed to determine the extent to which recombinant human (rh) interleukin-6 (rhIL-6), the interleukin-6-like cytokine, rh-oncostatin M, and the adipokine, rh-adiponectin, activated extracellularsignal regulated kinase (ERK1/2), p38α mitogen-activated protein kinase (p38α MAPK) and c-Jun-amino-terminal kinase (JNK).

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The aim of this study was to determine preventive effects of premedication with combination of cilostazol and ginkgo biloba extract during vertebrobasilar ischemia (VBI) induced by global hypoperfusion in rats.

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A fifty three year old white female smoker with Lynch Syndrome was receiving adjuvant chemotherapy for node positive caecal adenocarcinoma. Interval investigations demonstrated a second primary gastric cancer with bilateral pulmonary nodules of indeterminate significance. Lung biopsy revealed Langerhans cell histiocytosis (LCH).

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Decreases in muscle mass, strength and power are associated with ageing, all of which increase the risk of falls, and cause a loss of independence. Creatine supplementation is often used in younger athletes to improve anaerobic performance, power and strength, however the potential benefits of creatine supplementation in older individuals are less clear.

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The recent resurgence of interest in m6A has been spurred by some intriguing findings detailing the effects and dynamics of this epigenetic modification. The m6A modification is a highly reactive and fluid modification which can respond rapidly to a broad variety of stimuli, and translate these signals into cellular activity. The little information that has been established on its functional capacity has opened up many new avenues of research and has tremendous implications for several fields of study.

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The primary aim of the present study was to evaluate the effects of creatine ingestion on the metabolic hormone cortisol in male swimmers. Seventeen male swimmers (24.5 ± 3.9 years) with at least 5 years of competitive swimming experience and engaged in swimming training at least 4 times per week participated in the study. Subjects supplemented with creatine (20 g/day) + maltodextrin (1g/kg/day) or maltodextrin (1g/kg/day) only for 6 days prior to a progressive swim-sprint workout. The swim-sprint workout consisted of 8 progressive 100 meter freestyle sets starting at 65% of maximal intensity leading up to a 100% maximum capacity set on the eighth and final set.

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