Articles Related to inhibitor
Prevalence of Minority Mutations That Confer Multi-Drug Resistance Among Patients Failing a Nucleoside Reverse Transcriptase Inhibitor Based Regimen in Uganda
Background:The extensive use of antiretroviral therapy has favored the emergence of multiple patterns of drug resistance mutations. These mutations evolve over time and are only detected by the conventional Sanger sequencing technology when they exceed 20% at which time there may be cross resistance. Unfortunately, the controversy surrounding the significance of these minority drug resistance mutations is still overwhelming.
Methods: Samples were obtained from patients who were failing on an NRTI based regimen between 2010 and 2019. For the subtype A and D analysis, 1000 patient samples were analyzed while the subtype C sub-analysis was comprised of 363 samples. Sanger based sequencing was performed as part of the standard of care. A subset of these samples was further analyzed using the Next Generation Sequencing (NGS) technology and analysis of the drug resistance mutations was performed at the 20% and 1% cut off to determine the prevalence of minority multi-drug resistant variants.
Results: Although Thymidine analog mutations (TAMs) were prevalent in all subtypes, our analyses showed that these mutations occurred in significantly less proportions among subtype C infections when compared with the subtype A and D counterparts. On the other hand, the Q151M mutation complex was significantly more predominant among patients harboring subtype C variants. Analysis using NGS revealed that minority drug resistant mutations that confer multi-drug resistance (MDR) were present even in patients who exhibited a susceptible genotype based on the Sanger sequencing technique.
Conclusion: Although HIV-1 MDR variants occur in all subtypes, their predominance is subtype specific with TAMs being significantly more predominant among subtype A and D while the Q151M complex more predominant among patients harboring subtype C viruses. Even in patients with a fully susceptible genotype based on Sanger technology, minority variants are present and their evolution to full blown MDR occurs over time such that if their early detection is missed, cross resistance is inevitable.
Tofacitinib as a Therapeutic Option in the Treatment of Refractory Scleritis: A Case Report
This was a 50-year-old patient with recurrent bilateral nodular anterior scleritis refractory to several treatments, including immunosuppressants and anti Tnfα. She was assessed for the different causes of immune-mediated and infectious diseases, but nothing was found. Tofacitinib was started 5 mg twice a day, which led to the spacing of crises until their total disappearance. At present, the patient has been crisis-free for nine months. In conclusion, the use of Janus Kinase inhibitor (Tofacitinib) alone was effective in the treatment of refractory recurrent nodular anterior scleritis.
Safety Concerns of Glaucoma Chemotherapy among G6PD Deficient Glaucoma Patients: A Pilot Study
The aim of this study was to assess the potential acute adverse effects associated with the use of anti-glaucoma medications
among glaucoma patients with Glucose-6-Phosphate Dehydrogenase deficiency.
How to select Tyrosine Kinase Inhibitor for the patients with newly diagnosed Chronic Myeloid Leukemia?
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.
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.
Former Effective Immunotherapy without Adverse Events of Inoperable Epithelial Ovarian Cancers and a Prospect for the Immune Prophylaxis
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.
DNA Polymerase as Therapeutic Intervention for Treating Patients with Multiple Sclerosis
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).
Pulmonary Adenocarcinoma Transforming into Small Cell Carcinoma: An Extreme Rarity
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.
An Introduction to the Approaches of Novel Drug Delivery Systems for Acquired Immune Deficiency Syndrome (AIDS)
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.
IL-8 Regulates Epithelial-Mesenchymal Transition through pERK1/2 in AGS Cells
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.
Pharmacokinetics, Biotransformation, Distribution and Excretion of Empagliflozin, a Sodium-Glucose Co-Transporter (SGLT 2) Inhibitor, in Mice, Rats, and Dogs
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.
Nanotechnology Approaches for Antiretroviral Drugs Delivery
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.
Development and Validation of UV Spectroscopic First Derivative Method for Simultaneous Estimation of Dapagliflozin and Metformin Hydrochloride in Synthetic Mixture
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).
AIDS: Signs to Management of the Disease
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.
Amyloid beta precursor protein: forgotten facts of the most studied protein in the 21st Century*
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.
Editorial Board Members Related to inhibitor
Anthony Joseph Berdis
Assistant Professor
Departments of Chemistry and Biology
Cleveland State University
United States
Departments of Chemistry and Biology
Cleveland State University
United States
Daniela Iannazzo
University Researcher
Department of Electronic Engineering, Industrial Chemistry and Engineering
University of Messina
Italy
Department of Electronic Engineering, Industrial Chemistry and Engineering
University of Messina
Italy
Frank Portugal
Associate Professor
Department of Biology
The Catholic University of America
United States
Department of Biology
The Catholic University of America
United States
Robert R. Redfield
Professor
Department of Immunology and Microbiology
University of Maryland
United States
Department of Immunology and Microbiology
University of Maryland
United States
