Resistance mutations. Medical search. Frequent questions

This assay detects mutations in genes of the HIV-1 virus from a sample of a patient's blood using NGS. (fda.gov)
Most studies addressing travel-related changes in the faecal flora have focused on specific mobile resistance genes, or depended on culturing of individual bacterial isolates. (biomedcentral.com)
Bacteria can acquire resistance by gaining mobile antibiotic resistance genes or by de novo mutations in pre-existing DNA. (biomedcentral.com)
RNA expression analysis suggests that the increased mutation rate is due to downregulation of key DNA repair genes (mutS, mutY, and recA), associated with DNA breaks caused by massive prophage inductions. (tau.ac.il)
Using a panel of 33 genes, they first found a BCL2 coding mutation (affecting the protein Gly101Val) in 4 patients with CLL-type progression who were taking venetoclax. (cancertherapyadvisor.com)
Several molecular mechanisms with antifungal agents have been reported for C. albicans where insertions, deletions, and point mutations in genes codifying target proteins are frequently related to the antifungal drug resistance. (intechopen.com)
We discovered two new genes (rv1979c and rv2535c) associated with clofazimine resistance in mutants without rv0678 mutations. (johnshopkins.edu)
In the tabs below you can see any other genes that have resistance mutations to the same drug(s), and the distribution of mutations that occur in those genes. (sanger.ac.uk)
Alternative transcripts are also displayed here for genes where reported resistant mutations are not located on the canonical transcript but are on the alternative, and also where reported resistant mutations are located at the same genomic position on both the canonical and alternative transcripts or on overlapping genes and/or fusions and share a COSM id. (sanger.ac.uk)
BACKGROUND: The identification of oncogenic driver mutations has largely relied on the assumption that genes that exhibit more mutations than expected by chance are more likely to play an active role in tumorigenesis. (pubchase.com)
Although most of our variety comes from reshuffling of genes from our parents, new mutations are the ultimate source from which new variation is drawn. (uncommondescent.com)
Antimicrobial resistance occurs through different mechanisms, which include spontaneous (natural) genetic mutations and horizontal transfer of resistant genes through deoxyribonucleic acid (DNA). (who.int)
This report presents the status of AMR in Africa by analysing the main types of resistance and the underlying genes where possible. (who.int)

Genetic analysis of the resistant virus revealed a single mutation in the gene that codes for the endonuclease enzyme. (stjude.org)
As full genome bisulfite sequencing failed to uncover an epigenetic mechanism for this loss of resistance, whole genome sequencing and genetic variant analysis was performed and the CMD2 locus was fine-mapped to a 190 kilobase interval. (uzh.ch)
Genetic variation of MePOLD1, therefore, could represent an important genetic resource for resistance breeding and/or genome editing, and elucidating mechanisms of resistance to geminiviruses. (uzh.ch)
Mutations in the insulin receptor gene can cause genetic syndromes such as leprechaunism that are associated with extreme insulin resistance. (bmj.com)
Genetic markers of resistance are therefore required urgently. (gla.ac.uk)
However, in specific genetic contexts, low frequency mutations may also be capable of participating in oncogenic processes. (pubchase.com)
They sought to understand whether new genetic mutations occurring after chemotherapy erupted spontaneously due to acquired resistance, or whether the mutations already existed at very low levels prior to treatment. (medindia.net)
Average child has 60 genetic mutations? (uncommondescent.com)
IGF-I deficiency can be the result of GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency (growth hormone receptor deficiency [GHRD], Laron syndrome) or postreceptor defects, including the principal transduction agent STAT5b, the IGF-I/IGFBP3 stabilizer acid labile subunit (ALS), the IGF-I gene, or the IGF-I receptor. (medscape.com)

Lung cancer with epidermal growth factor receptor (EGFR)-activating mutations responds favorably to the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. (aacrjournals.org)
However, 25% to 30% of patients with EGFR -activating mutations show intrinsic resistance, and the responders invariably acquire resistance to gefitinib. (aacrjournals.org)
Here, we showed that hepatocyte growth factor (HGF), a ligand of MET oncoprotein, induces gefitinib resistance of lung adenocarcinoma cells with EGFR -activating mutations by restoring the phosphatidylinositol 3-kinase/Akt signaling pathway via phosphorylation of MET, but not EGFR or ErbB3. (aacrjournals.org)
Dr. Jack West reviews treatment options for patients with an EGFR activating mutation and acquired resistance but no T790M mutation, focusing on a clinical trial with the novel hypoxia-induced pan-HER inhibitor TH4000. (cancergrace.org)
EGFR tyrosine kinase inhibitors (TKIs) are the established first-line option in patients with EGFR -mutated NSCLC, although resistance inevitably develops in the long run. (memoinoncology.com)
A wide variety of genomic alterations has been identified in the context of EGFR TKI resistance [1, 2]. (memoinoncology.com)
HER3, which is expressed in 83 % of NSCLC tumors [3], is not known to confer resistance to EGFR TKI therapy in EGFR -mutant disease. (memoinoncology.com)
this group included all patients in dose escalation and in dose expansion Cohort 1 (i.e., pretreated patients with adenocarcinoma histology and EGFR mutations) [4]. (memoinoncology.com)
HER3-Dxd proved active across diverse EGFR resistance mechanisms, as well as across the spectrum of baseline HER3 expression according to membrane H scores. (memoinoncology.com)
Forty of the 57 patients in the efficacy population had detectable EGFR exon 19 deletions or L858R mutations in plasma at baseline. (memoinoncology.com)
In patients who have developed disease progression on treatment with the third-generation TKI osimertinib, resistance mutations are most commonly either EGFR-dependent (e.g. (memoinoncology.com)
Both agents have shown clinical activity across various EGFR mutations [7-11]. (memoinoncology.com)
Based on these observations, 45 chemotherapy-naïve patients with EGFR exon 19 deletions or L858R mutations who had progressed on osimertinib were treated with amivantamab plus lazertinib in the dose-expansion phase of the phase I CHRYSALIS trial. (memoinoncology.com)
the challenge is once a patient develops resistance to an EGFR TKI. (egfrcancer.org)
Two abstracts presented at the 2019 ASCO Annual Meeting analyzed potential combinations with osimertinib (Tagrisso), a third-generation EGFR TKI, with additional agents to potentially overcome resistance mutations following progression in patients with EGFR -mutant NSCLC. (egfrcancer.org)
We are a group of lung cancer patients with EGFR mutations who have developed resistance to at least one targeted treatment drug, or who face probable resistance in the future. (egfrcancer.org)

Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. (lu.se)
We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis. (lu.se)
In this research, the scientists explored if influenza viruses would evolve resistance when exposed to an experimental endonuclease inhibitor called RO-7, a drug similar to others in advanced clinical trial. (stjude.org)
There is early evidence that the mutation is clinically significant, because scientists conducting clinical trials have observed the same mutation in patients undergoing treatment with similar drugs. (stjude.org)
Lead compound 4b (BSc5371) displays superior cytotoxicity in FLT3-dependent cell lines to compounds in recent clinical trials and overcomes drug-resistant mutations. (tu-darmstadt.de)
In spite of a homozygous abnormality of the insulin receptor gene and many of the clinical features of severe insulin resistance, the proband's clinical syndrome was noticeably different from previously described patients with leprechaunism who usually die within the first six months of life. (bmj.com)
Commercial HIV drug resistance mutation detection kits such as TruGene and ViroSeq are FDA-approved HIV-1 genotyping products, but the home-brew Sanger sequencing methods widely used in clinical labs are more cost-effective and flexible. (stratech.co.uk)
Although the clinical relevance of these low-frequency mutations is difficult to interpret, an NGS detection method, Sentosa SQ HIV genotyping assay, has recently been approved by the FDA. (stratech.co.uk)
It seems that NGS for HIV drug resistance testing is a trend, but Sanger sequencing may remain to be the standard method for a while unless the clinical necessity, cost, and turn-around time are justified in the majority of labs. (stratech.co.uk)
Our study provides evidence of novel RT mutational patterns that regulate positively and/or negatively NRTI resistance and strongly suggests that other mutations beyond those currently known to confer resistance should be considered for improved prediction of clinical response to antiretroviral drugs. (mpg.de)
Through nextgeneration sequencing and clinical follow-up, we correlated tumour response and resistance to the BRCA2 mutational status in the tumour. (gla.ac.uk)
Researchers identified a single heterozygous nucleotide variant that confers resistance to venetoclax, and it's a mutation that may be detected years before clinical relapse occurs. (cancertherapyadvisor.com)
They designed a highly sensitive digital-drop PCR assay (ddPCR), where they found that the mutation emerged in the bone marrow of these 4 patients up to 25 months prior to the criteria for clinical progression were met. (cancertherapyadvisor.com)
Therefore, not only does the Gly101Val mutation make cells increasingly less susceptible to killing by venetoclax, but we identified a selective advantage and gradual enrichment over time of cells carrying the mutation in the presence of venetoclax exposure - highly analogous to the clinical scenarios seen in our patient cohort," Dr Blombery added. (cancertherapyadvisor.com)
Whilst any of the newly observed BCL2 mutations in our patient may have contributed to clinical resistance, our experimental data strongly suggest the Phe104Ile as an important candidate resistance mutation in this patient," the researchers wrote. (hematologyadvisor.com)
The choice of a subsequent therapy after nevirapine should be based on clinical experience and resistance testing (see section 5.1). (who.int)
The table below compares the clinical and biochemical features associated with these various causes of GH resistance. (medscape.com)
Drug resistance val (CI) = 1.4-62) did not outperform corresponding classifiers based on clinical variables. (lu.se)

Proposal for a unified nomenclature for target-site mutations associated with resistance to fungicides. (jic.ac.uk)

Overall, these data show the persistence of viable SARS-CoV-2 in patients after Sotrovimab infusions and the rapid development of spike gene mutations associated with high-level Sotrovimab resistance in vitro. (thasso.com)

Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. (lu.se)
The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. (lu.se)
The virus can develop resistance to these existing drugs, known as neuraminidase inhibitors. (stjude.org)
Significantly, the emergence of resistance to RO-7 took a similar time course as viral resistance to the current neuraminidase inhibitors. (stjude.org)
HIV protease inhibitors against the viral protease are often hampered by drug resistance mutations in protease and in the viral substrate Gag. (a-star.edu.sg)
Through structural studies to unravel how Gag mutations contributes to protease drug resistance synergistically, it is thus possible to glean insights to design novel Gag inhibitors. (a-star.edu.sg)
Our model correctly predicts for HIV-1 that resistance against nucleoside analog reverse transcriptase inhibitors (NRTIs) can be conferred by decreasing their incorporation rate, increasing their excision rate, or decreasing their affinity for the polymerase enzyme. (plos.org)
Through mathematical modeling, we assess the mechanisms by which HIV-1 can develop resistance against nucleoside analog reverse transcriptase inhibitors (NRTI). (plos.org)
Therapy failing to invert transcriptase (RT) and protease (PR) inhibitors is principally due to mutations within the gene. (healthweeks.com)

It has been reported that CMD2-type landraces lose resistance after regeneration through de novo morphogenesis. (uzh.ch)
We demonstrate that Bartonella acquire de novo single mutations during rifampicin exposure at suprainhibitory concentrations at a much higher rate than expected from spontaneous fluctuations. (tau.ac.il)
have no family history of dwarfism and thus represent new (de novo) mutations. (msdmanuals.com)

RESULTS: We identified 6 putatively damaging non-synonymous somatic mutations among the three cALL patients. (pubchase.com)
These results highlight the importance of rare/private somatic mutations in understanding cALL etiology, even within well-characterized molecular subgroups. (pubchase.com)

of SARS-CoV-2-specific monoclonal antibodies to target a single viral epitope warrants caution because of the risk of rapid development of mutations that confer resistance after exposure to such antibodies. (thasso.com)

At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability, and cytokine production. (lu.se)
Confirmation of the mutational status in these additional patients meant that in total, 7 out of the 15 (46%) patients who experienced CLL-type progression while on venetoclax actually had the mutation. (cancertherapyadvisor.com)
The research team confirmed ex vivo that cells carrying the mutation were resistant to venetoclax at disease progression - a resistance characterized by a markedly decreased affinity for venetoclax, as the mutation occurred at the drug's binding site. (cancertherapyadvisor.com)
However, a key caveat of DT is that patients eventually develop resistance mutations, leading to disease progression. (medscape.com)

The dominant CMD2 locus confers resistance to cassava mosaic geminiviruses. (uzh.ch)
The mutation causing sickle cell disease confers resistance to malaria. (msdmanuals.com)

So are you going to tackle my posts regarding the distribution of mutations along the selection coefficient axis? (uncommondescent.com)

In key experiments, the team's structural biologists established how the resistance mutation warped the viral endonuclease molecule to render the drug unable to plug into its target. (stjude.org)
For instance, many mutations lie in the HIV pol gene that encodes viral protease, reverse transcriptase, integrase and other proteins. (stratech.co.uk)
The advantage of NGS is its ability to identify low frequency mutations (the threshold at 5%, for instance) in the viral population missed by Sanger sequencing. (stratech.co.uk)
OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs. (ox.ac.uk)
To overcome this drug resistance and inhibit viral maturation, targeting Gag alongside protease rather than targeting protease alone may be more efficient. (a-star.edu.sg)
In effect, in March 2022, Australian virologists observed that sotrovimab may cause a drug-resistant mutation, as they describe in a very recent report to the New England Journal of Medicine ( NEJM ) showing that apparently mutations at viral genome positions S:E340K/A/V and S:P337L/T have been associated with a reduction by a factor of 100 to 297 in neutralization by Sotrovimab. (thasso.com)
To date, an integrated mathematical model that could allow the analysis of their mechanism of action, of the various resistance mechanisms, and their effect on viral fitness is still lacking. (plos.org)
Our model also allows quantification of the selective advantage of mutations by integrating their effects on viral fitness and drug susceptibility. (plos.org)
We correctly predict that HIV-1 can develop resistance by decreasing NRTI incorporation rate, increasing its excision rate, or decreasing its affinity for the viral polymerase enzyme. (plos.org)

The main mechanism of quinolone resistance in Klebsiella (K) pneumoniae is caused by mutation of porin-related proteins and efflux pumps. (uwi.edu)
For this reason, 52 K pneumoniae samples were collected from burns patients and evaluated for the mechanism of ciprofloxacin resistance. (uwi.edu)
Future studies are needed to understand this important mechanism of resistance and how it may impact the choice of therapy for patients with pancreatic cancer. (gla.ac.uk)
Conclusions: Mutations in rv0678 are a major mechanism of clofazimine resistance. (johnshopkins.edu)
Our observations in this case provide a strong rationale for investigating the role of acquired BCL2 mutations as a result of [aberrant somatic hypermutation] as a venetoclax resistance mechanism in patients with follicular lymphoma. (hematologyadvisor.com)
Even if the model is granted, it can be shown that this mechanism fails to stop degeneration when linkage and the interaction between mutations and non-mutations are also taken into account. (uncommondescent.com)
In many of these people, the mechanism is a spontaneous mutation occurring early in their embryonic life. (msdmanuals.com)

METHODS Here, for a mutant P. chabaudi malaria parasite and its immediate progenitor, the in vivo artemisinin resistance phenotypes and the mutations arising using Illumina whole-genome re-sequencing were compared. (gla.ac.uk)
The emerged resistant mutants acquired a single rpoB mutation, whereas no other mutations were found in their whole genome. (tau.ac.il)

Most of these resistant lines also failed to down-regulate the mRNA levels of the NOTCH targets MYC and DELTEX1 after treatment with MRK-003, implying that residual NOTCH signaling in T-ALLs with FBW7 mutations contributes to GSI resistance. (nih.gov)
International travel can alter the composition of the Escherichia communities in the faecal flora, favouring bacteria carrying certain resistance mutations, and, thereby, contributes to the global spread of antibiotic resistance. (biomedcentral.com)

Under this is shown the amino acid sequence and the Pfam protein structures, followed by complex mutations and insertions and deletions. (sanger.ac.uk)

Each one of us receives approximately 60 new mutations in our genome from our parents. (uncommondescent.com)
In theory, the father was favoured as a source of mutations because of " the additional number of times that the genome needs to be copied to make a sperm, as opposed to an egg. (uncommondescent.com)

The individual mutations are described in detail. (who.int)

We demonstrate that TaHRC encodes a nuclear protein conferring FHB susceptibility and that a deletion spanning the start codon of this gene results in FHB resistance. (nature.com)
Fig. 3: Haplotype and association analyses in natural populations identify the deletion in TaHRC as the likely causal mutation for Fhb1 . (nature.com)
Methods: Here we present a case of a 63-year-old female patient with a germ line pathogenic BRCA2 mutation (6714 deletion) who developed pancreatic cancer and had an exceptional response to platinum and PARP inhibitor therapy. (gla.ac.uk)
Each of the seven cell lines examined and 7 of 81 (8.6%) primary T-ALL samples harbored either a mutation or homozygous deletion of the gene FBW7, a ubiquitin ligase implicated in NICD turnover. (nih.gov)

Sub-microscopic Plasmodium falciparum parasitaemia, dihydropteroate synthase (dhps) resistance mutations to sulfadoxine-pyrimethamine, transmission intensity and risk of malaria infection in pregnancy in Mount Cameroon Region. (bvsalud.org)
Plasmodium falciparum resistance to intermittent preventive treatment with sulfadoxine - pyrimethamine (IPTp-SP) continues to spread throughout sub-Saharan Africa . (bvsalud.org)

Here, we investigated the molecular basis of clofazimine resistance using resistant mutants isolated in vitro. (johnshopkins.edu)
Methods: We isolated 96 mutants of Mycobacterium tuberculosis resistant to clofazimine and performed WGS and Sanger sequencing to identify possible mutations associated with clofazimine resistance. (johnshopkins.edu)
Results:We found that 97% (93/96) of clofazimine-resistant mutants had a mutation in rv0678 encoding a transcription repressor for efflux pump MmpL5. (johnshopkins.edu)
The previously reported A202G mutation (S68G) in rv0678 occurred less frequently, in 5 of 96 mutants. (johnshopkins.edu)

Today's authorization can help health care providers better tailor drug treatment for patients who are beginning antiviral therapy and also for those who have developed resistance to HIV drugs by helping to identify mutations in the HIV-1 virus that can impact the effectiveness of certain drugs. (fda.gov)
The Sentosa SQ HIV-1 Genotyping Assay detects HIV-1 drug resistance mutations in patients taking or about to start antiviral therapy. (fda.gov)
Precision use of postoperative radiation therapy (PORT) may benefit patients with high tumor mutational burden (TMB) or DNA damage response and repair (DDR) mutations compared with patients who have resistant mutations. (medpagetoday.com)
The researchers exposed cultures of virus-infected cells to the drug to induce resistance mutations to occur - the method mimics the process that can occur in patients during antiviral treatment. (stjude.org)
A BTK mutation in ibrutinib-resistant patients prevents ibrutinib from binding irreversibly. (aacrjournals.org)
Although few ibrutinib-treated patients have relapsed to date, as the number of patients receiving ibrutinib increases it is crucial to characterize ibrutinib resistance mechanisms in order to devise treatment strategies for those who have relapsed and guide development of combination approaches to prevent resistance from developing. (aacrjournals.org)
Strikingly, 5 of 6 patients had acquired a C481S mutation in BTK affecting the residue to which ibrutinib binds, and 2 patients had distinct mutations in phospholipase C gamma 2 ( PLCG2 ), which encodes a kinase that acts immediately downstream of BTK in the B-cell receptor (BCR) signaling pathway. (aacrjournals.org)
Although additional ibrutinib resistance mechanisms likely remain to be discovered, this characterization of patients who have relapsed on ibrutinib may help initiate strategies to prevent or overcome ibrutinib resistance. (aacrjournals.org)
Therefore, it could be concluded that the high rate of mutation on the gyrA locus in combination with quinolone resistance was responsible for ciprofloxacin resistance and by inhibition of AcrA, the resistance rate showed a significant decrease in K pneumoniae isolated from burns patients. (uwi.edu)
We characterized 16 additional mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) whose role in drug resistance is still unknown by analyzing 1,906 plasma-derived HIV-1 subtype B pol sequences from 551 drug-naïve patients and 1,355 nucleoside RT inhibitor (NRTI)-treated patients. (mpg.de)
There were no significant differences in cure rates, but parasite reduction ratios at 48 h were significantly lower for patients whose samples showed triple mutations than for those whose samples showed double mutations ( P = 0.01). (ox.ac.uk)
Genomic analysis showed that 4 of these 8 patients (R001 through R004) acquired previously defined receptor-binding domain mutations within 6 to 13 days after they received Sotrovimab. (thasso.com)
A retrospective review of 11,841 SARS-CoV-2 genomes in the Global Initiative on Sharing All Influenza Data database (a site for compiling sequence data on viruses) and reported in New South Wales, Australia, identified 4 additional patients with S:E340 mutations. (thasso.com)
Dr Blombery and his team sought to harness the power of genomics to characterize the CLL-type progressions on venetoclax to help them identify the exact mechanisms of drug resistance at play in certain patients with CLL, with the goal of determining what drives that transformation of effect. (cancertherapyadvisor.com)
Then, using a digital assay in the sensitivity as low as .01%, they detected the mutation in 3 additional patients with CLL - and only 1.4% to 4.3% of these cells carried the mutation. (cancertherapyadvisor.com)
Through the analysis of these data, they concluded that the mutation was not present in any of these patients prior to venetoclax administration, nor had it been identified in cancer population databases. (cancertherapyadvisor.com)
A audience member asked Dr Blombery if it were reasonable to assume that the resistance could have occurred as a result of patients not being 100% compliant to their treatment regimens, comparing what was seen here with what can sometimes happen when patients with chronic myeloid leukemia are not adherent to their medications. (cancertherapyadvisor.com)
While NAC is effective in some TNBC patients, approximately half will develop chemotherapy resistance, leading to poor overall survival. (medindia.net)
Possible mechanisms for gram for breast cancer in southern Sweden issued 1991, pre- recurrence after treatment are low initial drug sensitivity or menopausal lymph node positive (N+) breast cancer patients an acquired drug resistance. (lu.se)
Radiotherapy was delivered to ipsilateral axil- cancer patients in the future, it is essential to increase our lary and supraclavicular lymph nodes and the remaining knowledge in mechanisms responsible for drug resistance, breast parenchyma after breast conservation surgery or tho- and to define reliable indicators for response to therapy. (lu.se)

The Sentosa SQ HIV Genotyping Assay is the first HIV drug resistance assay that uses NGS technology that the FDA has authorized for marketing in the U.S. (fda.gov)
The FDA reviewed data from performance studies, which demonstrated a greater than 95% sensitivity and specificity in detecting 342 HIV drug resistant mutations and determined the Sentosa SQ HIV-1 Genotyping Assay provides a reasonable assurance of safety and effectiveness for its intended use. (fda.gov)

Phylogenetic analysis suggested that most RAM/VEMs arose independently, however RAMs including A194T, M204V and L180M formed clusters in genotype B. We show evidence that polymorphisms associated with drug and vaccine resistance may have been present in the mid 20th century suggesting that they can arise independently of treatment/ vaccine exposure.DiscussionHBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C variants. (ox.ac.uk)
The aim of AT9283 the current research was to look for the aftereffect AT9283 of the scale-up of Artwork in Zambia on Artwork resistance-associated polymorphisms and drug-resistant mutations. (healthweeks.com)
Polymorphisms begin as mutations. (msdmanuals.com)
Mutations (including polymorphisms) involve random changes in DNA. (msdmanuals.com)

Mechanisms of resistance to platinum-based and PARP inhibitor therapy in other cancer types include secondary mutations, which restore the integrity of DNA repair through an increasing number of different mechanisms. (gla.ac.uk)
Understanding the mechanisms of resistance would help to prolong the effective lifetime of these drugs. (gla.ac.uk)
This suggests that endocytosis and trafficking of membrane proteins may be involved, generating new insights into possible mechanisms of resistance. (gla.ac.uk)
However, the mechanisms of resistance to clofazimine are poorly understood. (johnshopkins.edu)
It can readily be embedded in extended models of the complete HIV-1 reverse transcription process, or analogous processes in other viruses and help to guide drug development and improve our understanding of the mechanisms of resistance development during treatment. (plos.org)
The mechanisms of resistance development are, however, still poorly understood. (plos.org)

Drug resistance mutations (DRMs) testing allows the selection of the right therapy with optimized virologic response in people with HIV. (stratech.co.uk)
Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate-/high-level resistance and factors including REGA subtype, first-line antiretroviral therapy drugs, CD4, and VL at failure. (ox.ac.uk)
HIV-1 drug resistance mutations (DRMs) can be dangerous not only on the individual level but also for the whole population. (pasteur.fr)

Conclusions: To our knowledge, this is the first report of a BRCA2 reversion mutation that conferred resistance to PARP inhibitorbased therapy in a pancreatic ductal adenocarcinoma patient. (gla.ac.uk)

In order to successfully inhibit Gag, understanding of its drug resistance mutations and the elicited structural changes on protease binding needs to be investigated. (a-star.edu.sg)
While mutations on Gag have already been mapped to protease inhibitor resistance, there remain many mutations, particularly the non-cleavage mutations, that are not characterized. (a-star.edu.sg)

Resistance mutations are mutations producing a resistant phenotype. (wikipedia.org)
Virus-induced gene silencing of MePOLD1 in a CMD-susceptible cassava variety produced a recovery phenotype typical of CMD2-type resistance. (uzh.ch)
RESULTS An increased artemisinin resistance phenotype is accompanied by one non-synonymous substitution. (gla.ac.uk)
CONCLUSION An increased artemisinin-resistant phenotype occurs along with a mutation in a functional element of the AP2 adaptor protein complex. (gla.ac.uk)

The C481S mutation significantly reduced the affinity of ibrutinib for BTK and prevented its irreversible binding, leading to diminished inhibition of signaling downstream of BTK upon BCR activation in vitro . (aacrjournals.org)
The PLCG2 mutations also were found to reduce ibrutinib sensitivity in vitro , but appeared to have a gain-of-function effect, as they promoted BTK-independent BCR pathway activation in the presence of ibrutinib. (aacrjournals.org)
Top-ranked candidate mutations were subsequently validated at high sequencing depth on an independent platform and in vitro expression assays were performed to evaluate the impact of identified mutations on cell growth and survival. (pubchase.com)

2021. "Untangling a Gordian Knot : The Role of a GluCl3 I321T Mutation in Abamectin Resistance in Tetranychus Urticae. (ugent.be)

von Kleist M, Metzner P, Marquet R, Schütte C (2012) HIV-1 Polymerase Inhibition by Nucleoside Analogs: Cellular- and Kinetic Parameters of Efficacy, Susceptibility and Resistance Selection. (plos.org)

However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). (ox.ac.uk)
These classes of anti-fungals suffer from restrictions in route of administration, spectrum of activity, poor bioavailability in target tissues, undesirable drug interactions, limited therapeutic index and the emergence of drug resistance 2 . (nature.com)

Resistance development also changes drug susceptibility distinctly and we show, for the first time, that selection of drug resistance can occur in particular target cells. (plos.org)
Mutations that occur in sperm or egg cells will be 'new' mutations not seen in our parents. (uncommondescent.com)
When and in what cell type mutations occur can explain certain abnormalities in inheritance patterns. (msdmanuals.com)

Thus, the mutant allele encodes a receptor that has a mutation in the putative insulin binding domain. (bmj.com)
The [variant allele frequency] of the Phe104Ile mutation (12.3%) was the highest of the newly acquired BCL2 mutations in the post-venetoclax sample (estimated cancer cell fraction approximately 50% based on immunohistology) consistent with its presence in a significant proportion of the tumor compartment. (hematologyadvisor.com)

The patient was homozygous for a point mutation in exon 2 of the insulin receptor gene which results in the substitution of methionine for isoleucine at codon 119. (bmj.com)
However, by causing symptoms and complications of sickle cell disease, the mutation also has harmful effects usually when present in the homozygous state. (msdmanuals.com)

In addition to mutations in CREBBP, KMT2D, and EZH2, there was an aberrant somatic hypermutation of the BCL2 gene with the presence of multiple mutations in the 5ʹ untranslated region and the first coding exon. (hematologyadvisor.com)

Met mutation in the insulin receptor gene, and are clinically affected with varying degrees of severity. (bmj.com)
Fluoroquinolone antibiotics are a clinically important class of broad-spectrum antibiotics to which bacteria have acquired a high frequency of resistance in many parts of the world [ 9 ]. (biomedcentral.com)

We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations.MethodsWe analysed sequences downloaded from the Hepatitis B Virus Database, and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. (ox.ac.uk)
We performed phylogenetic molecular clock analyses using BEAST to estimate the age of mutations.ResultsRAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our dataset, and a significantly higher rate in genotype C sequence at 5.4% (60/1102, p=0.0007). (ox.ac.uk)
prevalence of antiretroviral therapy (ART) resistance mutations within HIV-1 subtype C and parts of the proviral DNA was analyzed and compared from therapy-naive individuals before (Cohort A) and after (Cohort B) the option of free ART in Zambia. (healthweeks.com)
To do this goal we examined and likened the prevalence of Artwork resistance mutations. (healthweeks.com)

triphosphate(MBIFermentas),0.5M genotypes with hypervirulence and The88samples,providedbytheMin- ofeachofthe4primers(MWGBiotech, multi-resistance[5]. (who.int)

Advance the use of genomics and metagenomics for detecting fungal pathogens and antifungal drug resistance. (cdc.gov)
This chapter summarizes the main molecular mechanisms to C. albicans antifungal drug resistance, besides offering an overview of new antifungal agents and new antifungal targets to combat fungal infections. (intechopen.com)

CONCLUSION: Three different techniques were used to characterize the role of I321T in GluCl3 in abamectin resistance and, combining all results, our analysis suggests that the I321T mutation has a complex role in abamectin resistance. (ugent.be)

Here we show that TaHRC , a gene that encodes a putative histidine-rich calcium-binding protein, is the key determinant of Fhb1 -mediated resistance to FHB. (nature.com)
Through protein binding studies, they found the mutation to Gly101Val was associated with an approximately 180-fold reduction in the ability of venetoclax to bind to BCL2 . (cancertherapyadvisor.com)
Strikingly, one of the mutations acquired during venetoclax treatment was predicted to result in a phenylalanine substitution to an isoleucine at amino acid 104 of the BCL2 protein, which is located at the venetoclax binding site of BCL2," the researchers wrote. (hematologyadvisor.com)
Three of these mutations were well-characterized common cALL mutations involved in constitutive activation of the mitogen-activated protein kinase pathway (FLT3 p.D835Y, NRAS p.G13D, BRAF p.G466A). (pubchase.com)

Met) in the insulin receptor gene in five sibs with familial insulin resistance. (bmj.com)
Loss-of-Function Mutation in Toll-Like Receptor 4 Prevents Diet-Induced Obesity and Insulin Resistance. (diabetesjournals.org)
A few affected individuals have developed problems with blood sugar (glucose) regulation including insulin resistance and diabetes. (medlineplus.gov)
PI3K's role in insulin activity may be related to the development of insulin resistance and diabetes, and problems with adipocyte maturation might contribute to lipoatrophy in affected individuals. (medlineplus.gov)

Here we aimed at exploring the abundance of chromosomal quinolone resistance mutations in Escherichia communities residing in the gut of Swedish travellers, and to determine potential changes after visiting India. (biomedcentral.com)
Sweden is a country with a comparably low degree of quinolone use and quinolone resistance, whereas the opposite is true for India. (biomedcentral.com)
Massively parallel amplicon sequencing targeting the quinolone-resistance determining region of gyrA and parC was applied to total DNA extracted from faecal samples. (biomedcentral.com)
No other substitution, including others commonly associated with quinolone resistance (D87N in GyrA, S80I in ParC) changed significantly. (biomedcentral.com)
Plasmid-mediated quinolone resistance, however, usually confers a lower level of resistance than chromosomal mutations. (biomedcentral.com)

Furthermore, gene overexpression is also frequently associated to antifungal resistance as well as an increase in the activity of proteins that reduce oxidative damage. (intechopen.com)

Today, the U.S. Food and Drug Administration authorized marketing of a test to detect human immunodeficiency virus (HIV) Type-1 drug resistance mutations using next generation sequencing (NGS) technology. (fda.gov)
Once the virus has mutated and drug resistance develops, a person generally must change medications as different drugs will be needed to keep the virus from multiplying. (fda.gov)
They discovered resistance to RO-7 emerged after 5 to 10 passages, and that the resistance persisted even in the absence of the drug. (stjude.org)
That mutation subtly alters the enzyme's shape such that the drug no longer fits into the enzyme molecule to inactivate it. (stjude.org)
However, drug resistance can be developed during the therapy due to the high mutation rate of the RNA virus. (stratech.co.uk)
These mutations abolish drug functions against HIV DNA production and virus replication. (stratech.co.uk)
Recently, a few research labs have published papers on comparing Sanger sequencing and NGS for HIV drug resistance genotyping. (stratech.co.uk)
BACKGROUND The control of malaria, caused by Plasmodium falciparum, is hampered by the relentless evolution of drug resistance. (gla.ac.uk)
Title : Simple PCR Assays Improve the Sensitivity of HIV-1 Subtype B Drug Resistance Testing and Allow Linking of Resistance Mutations Personal Author(s) : Johnson, Jeffrey A.;Li, Jin-Fen. (cdc.gov)
HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa. (ox.ac.uk)
Acquired drug resistance (ADR) appears under drug selective pressure and limits the choice of treatment for the individual in question, while transmitted drug resistance (TDR) limits the treatment choice on the population level. (pasteur.fr)
The report also includes a summary on the status of drug resistance for TB, HIV and malaria. (who.int)
With research in recent years showing that as many as 40% of anaplastic thyroid cancers harbor BRAF V600E mutations, the door has opened for potential benefits with the combination of the BRAF inhibitor dabrafenib with the MEK-inhibitor drug trametinib. (medscape.com)

The wild-type (PP) genotype remained predominant within all the three districts, whereas the homogenous (QQ) mutation genotype occurred only in minority. (hindawi.com)
Screening for the genotype and for resistant mutations may help to improve stratified patient treatment. (ox.ac.uk)

The investigators also determined there are alternative mediators of resistance to venetoclax aside from BCL2 Gly101Val. (cancertherapyadvisor.com)
The researchers then investigated whether the Phe104Ile mutation conferred resistance to venetoclax, and found the RS4;11 cells that overexpressed the mutant were more than 40 times less sensitive to venetoclax than RS4;11 BCL2 wildtype cells. (hematologyadvisor.com)

Last, functional analysis in Xenopus oocytes revealed that the I321T mutation might reduce GluCl3 sensitivity to abamectin, but also suggested that all three T. urticae Rdls are affected by abamectin. (ugent.be)

The results demonstrated that 40 isolates of K pneumoniae were ciprofloxacin-resistant and 35 showed the mutation on gyrA locus. (uwi.edu)

Where FATHMM-MKL scores are ≥ 0.7 the mutation is classified as 'pathogenic', or 'neutral' if the score is ≤ 0.5. (sanger.ac.uk)

Regardless of their efficacy, the constant use of insecticides has induced insecticide resistance mechanisms, such as knockdown resistance ( kdr ) in mosquitoes. (hindawi.com)

The fact that this mutation was found in a "highly preserved" site of BCL2 prompted the researchers to analyze the issue further. (cancertherapyadvisor.com)
The posttreatment biopsy sample had 7 BCL2 mutations that were not found in the initial biopsy sample. (hematologyadvisor.com)

This striking value is reported in the first-ever direct measure of new mutations coming from mother and father in whole human genomes. (uncommondescent.com)

In addition, a minority variant developed in Patient R002 at position P337L after fixation of the S:E340K mutation. (thasso.com)

ABSTRACT Mutations in the Plasmodium falciparum gene ( dhfr ) encoding dihydrofolate reductase are associated with resistance to antifols. (ox.ac.uk)

Such information is critical because without it, clinicians do not know the molecular marker(s) of resistance, so monitoring resistance in trials is like searching in a darkened room. (stjude.org)
Molecular analyses were performed for the identification of species within the Anopheles gambiae ( s.l. ) complex and kdr L1014F and G119S Ace-1 mutations. (biomedcentral.com)
Our findings provide useful information for the design of new molecular tests for rapid detection of clofazimine resistance. (johnshopkins.edu)

Antibiotic resistance can, however, also spread via travellers colonized by bacteria carrying chromosomal antibiotic resistance mutations, but this has received little attention so far. (biomedcentral.com)
Bacterial antibiotic resistance is one of the greatest threats to public health globally. (biomedcentral.com)

Previously, a mutation in a de-ubiquitinating enzyme was shown to confer artemisinin resistance in the rodent malaria parasite Plasmodium chabaudi. (gla.ac.uk)
This resistance conferred a survival advantage in areas where malaria was endemic and often fatal. (msdmanuals.com)

However, the primary lesion recurred while on PARP inhibitor therapy and contained a secondary mutation in BRCA2, which mostly likely restored BRCA2 function in PARP inhibitor-resistant tumour cells. (gla.ac.uk)

Cytotoxicity assays demonstrated a protective effect of the ACD p.G223V mutation against apoptosis in leukemia cells. (pubchase.com)

Anatomy4

Organisms10

Diseases9

Chemicals and Drugs108

Analytical, Diagnostic and Therapeutic Techniques and Equipment37

Phenomena and Processes90

Anthropology, Education, Sociology and Social Phenomena1

Information Science5

Health Care8

Geographicals6

Genes13

Genetic9

EGFR16

Clinical18

Target-site mutations1

Gene Mutations Associated1

Inhibitors9

Novo3

Somatic Mutations2

Confer resistance1

Progression4

Confers resistance2

Distribution of mutations1

Viral9

Mechanism7

Whole genome2

Contributes2

Deletions1

Genome2

Individual mutations1

Deletion4

Sulfadoxine-Pyrimethamine2

Mutants4

Patients20

Assay2

Polymorphisms4

Mechanisms of resistance6

DRMs3

Conclusions1

Protease2

Phenotype4

Vitro3

20211

Nucleoside1

Emergence of drug2

Occur3

Allele2

Homozygous2

Exon1

Clinically2

Prevalence4

Genotypes1

Antifungal drug resistance2

Suggests1

Protein4

Insulin resistance4

Quinolone resistance5

Proteins1

Drug13

Genotype2

Venetoclax2

Sensitivity1

Isolates1

Pathogenic1

Efficacy1

BCL22

Genomes1

Variant1

Abstract1

Molecular3

Antibiotic resistance2

Malaria2

Secondary1

Assays1