Articles Related to inhibitor

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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Current cancer treatments by immune checkpoint blockades are limited due to severe adverse events caused by alteration of the immune system required for homeostasis of normal tissues. Common cancer chemotherapy alters the quality of patients’ lives. Platinum-based treatment can lead to severe neurotoxicity with chronic debilitation. Additionally, survival of patients with epithelial ovarian cancers (EOCs) has remained poor despite extensive cytoreductive surgery, high dose chemotherapy, checkpoint blockades and immunotherapies effective in some other types of cancer. The pathobiology of EOC cancer stem cells (CSCs) is not well understood. Observations demonstrate that EOCs exhibit in vivo two distinct CSC types - perivascular diploid CSCs dividing asymmetrically with the help of the host suicidal CD8+ T cells, and haploid CSCs at the cancer abdominal surface originating from meiosis I cytokinesis of bulk surface cancer cells. The perivascular CSCs contribute to the cancer cell bulk and, via left ovary venous blood, can cause EOC liver metastases. Haploid CSCs released from the bulk cancer surface cause the common pelvic and abdominal EOC spread. Former elimination of the host antibodies blocking T cell effectors by intermittent doses of cyclophosphamide exhibiting significant immunomodulatory anticancer effects, facilitation of the immune system reactivity against alloantigens of cancer cells by blood transfusions, and augmentation of anticancer immunity by bacterial toxins, resulted during the subsequent treatment-free period into rejection of inoperable EOCs without any adverse events during the treatnment. To help prevent cancer relapses, patients treated for advanced primary epithelial cancers should be considered as candidates for continuously stimulating immune anticancer activity by treatments such as daily metformin and weekly lentinan consumptions.

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In recent years, increasing evidence has pointed to the potential role of fibrinolysis in the pathogenesis of MS. Based on hypotheses describing the aggressive autoimmune responses observed in MS patients, a result of impaired between (t-PA and PA1-1) which are a key molecules in both fibrinolysis and extracellular proteolysis. The present study was done to investigate the therapeutic potential of polymerase enzyme in modulating the changes occurred between levels of Tissue- type plasminogen activator (t-PA) and its inhibitor (PAI-1) in patients with multiple sclerosis. A pilot study was carried out on a total of twenty-one patients (17 females, 4 males; aged 22-46 years) with demyelination suggestive of MS and clinically silent T2 brain lesions on magnetic resonance imaging (MRI).

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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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The currently available anti HIV agents have several drawbacks such as short half life, low bioavailability, poor CNS penetration and retention, hepatic first pass metabolism, undesirable side effects and frequent dosing regimen.

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The aim of this project was to evaluate the influence of inflammatory cytokines IL-1β and IL-8 on gastric epithelial-mesenchymal transition in gastric epithelial cells.

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The metabolism, pharmacokinetics, excretion and distribution of a sodium-glucose co-transporter (SGLT 2) inhibitor, empagliflozin, were studied in mice, rats and beagle dogs following a single oral or intravenous administration of [14C]-empagliflozin. Empagliflozin was well absorbed in all species after oral administration.

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The development of effective drug delivery approaches for the treatment of AIDS and HIV infection is a global challenge. The advent of multidrug, highly active antiretroviral therapy (HAART), have increased the life span of HIV-infected patients.

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The Novel, simple, sensitive, rapid, accurate and economical and reliable First derivative spectroscopic method has been developed for synthetic mixture of Dapagliflozin (DAPA) and Metformin hydrochloride (MET).

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Acquired Immune Deficiency Syndrome (AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). They get it after being infected with the HIV virus. HIV (human immunodeficiency virus) is a retrovirus that primarily infects components of the immune system.

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The amyloid precursor protein (APP) is mainly known for being the precursor of the ß-amyloid peptide, which accumulates in plaques found in the brain of Alzheimer’s disease patients. Expression in different tissues and the degree of sequence identity among mammals indicate an essential and non-tissue specific physiological function.

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The Health Improvement Network (THIN) provided data from UK General Practitioners (GPs) for 144 pregnant women who were prescribed zanamivir and 144 age- and date-matched untreated comparators with no recorded diagnosis of influenza. Groups were assessed for baseline characteristics, treatment-emergent diagnoses in the mother, pregnancy outcomes and congenital malformations diagnosed in the offspring within 28 days of birth.

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Streptococcus pneumoniae is a leading cause of meningitis. Although rates of bacterial meningitis have decreased after pneumococcal conjugate vaccine introduction, pneumococcal meningitis has not been eliminated. In this case series, we describe the presentation, serotypes, and outcomes of 11 children with pneumococcal meningitis at a tertiary children’s hospital after the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced, from 2011-2013. The median age of children with meningitis was 7 years. The majority of the isolates (82%) were susceptible to penicillin. Most isolates (73%) were serotyped and there was no evidence of disease caused by serotypes contained in PCV7

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At the beginning of 2009, Dianne Wysowski of the US Food and Drug Administration summarized 23 reports of esophageal1 cancer following alendronate use. Wysowski also noted that there had been 31 cases following alendronate use in Europe and Japan and ten cases in which other bisphosphonates had been reported as concomitant or suspect treatment.

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