scholarly journals Phenotypic transformation as a cause of secondary drug resistance to osimetinib clinical observation

2018 ◽  
pp. 130-135
Author(s):  
L. A. Nelyubina ◽  
E. V. Reutova ◽  
K. K. Laktionov ◽  
D. I. Yudin ◽  
D. T. Marinov ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Clinical Observation ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Acquired Drug Resistance ◽  
Full Control ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Phenotypic Transformation ◽  
First And Second Generation

Targeted therapy is the optimal treatment of patients with advanced EGFR-positive NSCLC. The first- and second-generation EGFR tyrosine kinase inhibitors provide a durable antitumor response in most patients during the year. Due to appearance of T790M secondary mutation of resistance at progression of the disease, the administration of osimertinib leads to full control of the tumour for another 10 months. However, this is not the only mechanism of acquired drug resistance. A repeated biopsy of the tumour followed by histological and molecular genetic research makes it possible to clarify the cause of resistance and personalize the further disease management.

scholarly journals During’s herpetiform dermatitis in pediatric dermatology: issues of diagnostics and treatment

2020 ◽  
Vol 11 (6) ◽  
pp. 79-86
Author(s):  
Yuri A. Novikov ◽  
Denis V. Zaslavsky ◽  
Olga V. Pravdina ◽  
Elena A. Zykova ◽  
Anastasia S. Lipatnikova ◽  
...  
Keyword(s):  
Clinical Observation ◽  
Dermatitis Herpetiformis ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Hla Typing ◽  
Rare Occurrence ◽  
Pediatric Dermatology ◽  
Gluten Sensitive Enteropathy ◽  
Childhood Form ◽  
Immunohistochemical Studies

This article presents a case of clinical observation of a 5-year-old child with herpetiformis dermatitis (Duhrings). This rare dermatosis is characterized by a chronic relapsing course, the presence of itching polymorphic rashes, typical histological and immunomorphological signs. The diagnosis was made on the basis of the clinical picture, histological and immunohistochemical studies of skin biopsy, as well as the results of HLA typing by PCR. Clinical observation of this case is of interest to practicing physicians-dermatologists due to the rare occurrence of Duhrings herpetiformis in children, the complexity of differential diagnostic search, which requires further generalization of experience using histological, immunohistochemical and molecular genetic research methods. The disease is clearly differentiated from other rashes with the formation of subepidermal blisters according to histological, immunological and gastrointestinal criteria. The prevalence of dermatosis in various populations of the Europian race ranges from 10 to 39 cases per 100,000 population. Duhrings dermatitis herpetiformis can develop at any age (cases of the childhood form of Dhrings dermatitis herpetiformis have been reported), but most often the disease occurs at the age of 4050 years. Dermatitis herpetiformis persists indefinitely with variable severity. In patients with Duhrings dermatitis, associated gluten-sensitive enteropathy is often noted, which in most cases is asymptomatic.

scholarly journals Current Therapeutic Strategies and Prospects for EGFR Mutation-Positive Lung Cancer Based on the Mechanisms Underlying Drug Resistance

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3192
Author(s):  
Yukari Tsubata ◽  
Ryosuke Tanino ◽  
Takeshi Isobe
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Radical Cure ◽  
Primary Therapy ◽  
T790m Mutation ◽  
Acquired Drug Resistance ◽  
Egfr Tkis

The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene and the development of EGFR tyrosine kinase inhibitors (TKIs) have led to a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). EGFR mutation-positive NSCLC is common in East Asia, and approximately 50% of adenocarcinomas harbor EGFR mutations. Undoubtedly, EGFR-TKIs, with their promising efficacy, are the mainstay of primary therapy. However, even if tumor shrinkage is achieved, most patients become resistant to EGFR-TKIs and relapse; hence, EGFR-TKIs do not achieve a radical cure. The problem of the development of resistance to targeted drugs has been a persistent challenge. After the role of EGFR T790M mutation in acquired drug resistance was reported, osimertinib, a third-generation irreversible EGFR-TKI, was designed to overcome the resistance conferred by T790M mutation. In addition, some studies have reported the mechanism of drug resistance caused by mutations other than the T790M mutation and strategies to overcome them. Elucidating the mechanism underlying drug resistance development and combining therapeutic approaches are expected to further improve NSCLC prognosis.

SKULL TRAUMA AS ONE OF THE CAUSES FOR SUBDURAL HEMATOMA DEVELOPMENT IN AN INFANT WITH GLUTARIC ACIDURIA TYPE 1: A BRIEF REVIEW OF THE LITERATURE AND CLINICAL OBSERVATION

2021 ◽  
Vol 100 (1) ◽  
pp. 287-293
Author(s):  
Z.G. Tadtaeva ◽  
◽  
A.N. Galustyan ◽  
O.A. Gromova ◽  
P.A. Popov ◽  
...  
Keyword(s):  
Clinical Observation ◽  
Brain Mri ◽  
Molecular Genetic ◽  
Genetic Research ◽  
Glutaric Aciduria Type ◽  
Review Of The Literature ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Subdural Hematomas

The article presents a brief review of the literature and clinical observation of glutaric aciduria type 1 (GA1) in a child, manifested by encephalitis-like crisis and subdural hematomas, which were initially regarded as the consequences of traumatic brain injury. Based on the analysis of clinical and neuroimaging data, the diagnosis of GA1 was assumed, which was later confirmed by molecular genetic research. After therapy with the inclusion of a specialized diet with protein restriction, some improvement in motor activity was noted. The presence of bilateral subdural hematomas dictates the need for differential diagnosis with GA1. A highly informative method of diagnosing GA1 is brain MRI.

ACQUIRED DRUG RESISTANCE TO NRTI CLASS IN TREATMENT-EXPERIENCED HIV INFECTED PATIENTS FROM THE CONSTANTA COUNTY: THERAPEUTIC IMPLICATIONS

2017 ◽  
Vol 20 (3) ◽  
pp. 140-147
Author(s):  
Roxana-Carmen Cernat ◽  
◽  
Irina Magdalena Dumitru ◽  
D. Otelea ◽  
Sorin Rugina ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Option ◽  
Molecular Genetic ◽  
Therapeutic Options ◽  
Acquired Drug Resistance ◽  
Therapeutic Implications ◽  
Graphic Representations ◽  
Resistance Patterns ◽  
R Project ◽  
Version 2.0

Objective. To determine the prevalence of acquired drug resistance (ADR) and of resistance patterns in treatment-experienced HIV infected patients from Constanta in order to establish the best therapeutic options in NRTI class. Material and methods. A retrospective study which included 144 treatment-experienced HIV patients with confirmed viral failure. The strains isolated from these patients were analysed in the Molecular Genetic Laboratory of „Matei Bals“ National Institute of Infectious Diseases, Bucharest and the resulting sequences were saved in FASTA format. The HIV-1 subtyping was based on „REGA HIV01&2 Automated subtyping tool version 2.0“ algorithm. „Stanford HIVdb Program version 8.4“ was used in order to determine the therapeutic options. For statistical calculations, the R-Project software was used. Graphic representations were performed using GNUPLOT program. Results. The prevalence of the acquired drug resistance was 92.36%. The most frequent mutation occurred at the level of the codon 184. The TAM-2 path was more frequently selected compared to TAM-1. Association between TAM1 and TAM 2 were also found, mutation K65R being rarely met. Conclusions. The prevalence of the acquired drug resistance in our study was high, The most valuable therapeutic option in the INRT class remains tenofovir, due to the mutational profile, which was selected on account of the extensive use of thymidine analogues.

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