PubMed Journals Articles About "Blueprint Medicines Submits Avapritinib Treatment PDGFRA Exon Mutant" RSS

18:00 EDT 15th July 2019 | BioPortfolio

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Showing "Blueprint Medicines Submits Avapritinib Treatment PDGFRA Exon Mutant" PubMed Articles 1–25 of 31,000+

Mutual recognition in the European system: A blueprint for increasing access to medicines?

The European regulatory system for approval of medicinal products is globally recognised as a unique platform for regulatory work-sharing and mutual recognition. As such, it potentially serves as a role model for regulatory capacity building worldwide. While focusing on mutual recognition and decentralised procedures, this paper illustrates key success factors and structures allowing for the reliance-based authorisation of medicines in the European Economic Area from the perspective of a national regulatory...

A Novel Acquired Exon 20 EGFR M766Q Mutation in Lung Adenocarcinoma Mediates Osimertinib Resistance but is Sensitive to Neratinib and Poziotinib: a Brief Report.

Osimertinib is an effective third-generation tyrosine kinase inhibitor (TKI) for EGFR-mutant lung cancers. However, treatment for patients with acquired resistance to osimertinib remains challenging. We characterized a novel EGFR mutation in exon 20 that was acquired while on osimertinib.

Testing the Cre-mediated genetic switch for the generation of conditional knock-in mice.

The Cre-mediated genetic switch combines the ability of Cre recombinase to stably invert or excise a DNA fragment depending upon the orientation of flanking mutant loxP sites. In this work, we have tested this strategy in vivo with the aim to generate two conditional knock-in mice for missense mutations in the Impad1 and Clcn7 genes causing two different skeletal dysplasias. Targeting constructs were generated in which the Impad1 exon 2 and an inverted exon 2* and the Clcn7 exon 7 and an inverted exon 7* co...

Strong impact of MammaPrint and BluePrint on treatment decisions in luminal early breast cancer: results of the WSG-PRIMe study.

The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer.

Characterization of a novel alternatively-spliced 5' exon in the human insulin-like growth factor I (IGF-I) gene, expressed in liver and some cancers.

In mammals, the large IGF-I gene comprises 6 exons, which are subject to alternative splicing. All transcripts contain exons 3 and 4, encoding mature IGF-I, but the other exons are included in various combinations, giving at least 6 possible mature mRNAs. At the 5' end, exons 1 and 2 are spliced alternatively to exon 3, giving different leader/signal sequences. It is shown in this study that in human an additional exon (designated exon 0) is present, upstream of exon 1. This can be spliced directly to exon ...

Pre-clinical Modeling of Osimertinib for Non-small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations is the third most common type of EGFR-mutant NSCLC and is resistant to EGFR tyrosine kinase inhibitors (TKIs). This study was conducted to evaluate the efficacies of first- to third-generation EGFR TKIs against NSCLC cells harboring EGFR exon 20 insertion mutations.

Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington's disease patients.

Mutations in the HTT gene, consisting of expansion of CAG triplets, cause the Huntington's disease (HD), one of the major neurodegenerative disorders. Formation of aggregates of mutant huntingtin (mHTT, the product of the mutant HTT gene) leads to cellular dysfunctions, and subsequent neurodegeneration which manifest clinically as motor abnormalities and cognitive deficits. We recently used immortalized HEK-293 cells expressing the 1st exon of the mutant HTT gene as a cellular model of HD, and showed that t...

Investigation of medicines consumption and disposal in Brazil: A study case in a developing country.

The incorrect disposal of medicines can be harmful to the environment. Here, we aim to understand the consumption and disposal of medicines in Brazil using online forms. 64% of the respondents have the habit to self-medicate. 66% of respondents dispose the disused or expired medicines in the garbage. 71.9% of respondents never receive any information about correct disposal of medicines. 95.2% of respondents believe that residues of medicines can be harmful to the environment. Environmental education can pro...

Industrial perceptions of medicines regulatory harmonization in the East African Community.

Medicines regulatory harmonization has been recommended as one way to improve access to quality-assured medicines in low- and middle-income countries. The rationale is that by lowering barriers to entry more manufacturers will be enticed to enter the market, while the capacity at the national medicines regulatory authorities is strengthened. The African Medicines Regulatory Harmonization Initiative, agreed in 2009, is developing regional platforms with harmonized regulatory procedures for the registration o...

Sensitivity and Resistance of MET Exon 14 Mutations in Lung Cancer to Eight MET Tyrosine Kinase Inhibitors In Vitro.

MET exon 14 mutations, including exon 14 skipping and point mutations, in lung cancer have been attracting the attention of thoracic oncologists as new therapeutic targets. Tumors with these mutations almost always acquire resistance, which also occurs in other oncogene-addicted lung cancers. However, the resistance mechanisms and treatment strategies are not fully understood.

Stock-outs of antiretroviral and tuberculosis medicines in South Africa: A national cross-sectional survey.

HIV and TB programs have rapidly scaled-up over the past decade in Sub-Saharan Africa and uninterrupted supplies of those medicines are critical to their success. However, estimates of stock-outs are largely unknown. This survey aimed to estimate the extent of stock-outs of antiretroviral and TB medicines in public health facilities across South Africa, which has the world's largest antiretroviral treatment (ART) program and a rising multidrug-resistant TB epidemic.

Metals and metalloids in traditional medicines (Ayurvedic medicines, nutraceuticals and traditional Chinese medicines).

Traditional medicine (TM) including Ayurvedic medicines, traditional Chinese medicines and nutraceuticals are popular across the globe as dietary supplements and traditional and alternative medicines. Health risks from these remedies continue to present serious concerns, with occurrences of poisoning by metals and metalloids present at concentrations above acceptable regulatory standards. This review overviews the prevalence of TM use, cases of metal and metalloid poisoning following TM consumption, and for...

Availability in hospitals of medicines for acute cases.

Availability in hospitals of medicines for acute cases In acute situations it is important that essential medication is readily available. In this comment we discuss various challenges in determining the assortment of medicines that should be available, and the logistic and administrative obstacles for pharmacists when delivering unregistered medicines such as artesunate. With centralization of (emergency) care, we must ask ourselves whether every hospital pharmacy should have a wide range of medicines in s...

Network pharmacology study of traditional Chinese medicines for stroke treatment and effective constituents screening.

Stroke is one of the most frequent causes of death and disability. So far there are no effective preventives or treatments. The therapeutic system of traditional Chinese medicines (TCMs) has been in use for several thousand years and still affords a valuable resource for today's clinicians in preserving health.

Position-dependent correlation between TBX22 exon 5 methylation and palatal shelf fusion in the development of cleft palate.

DNA methylation is essential for spatiotemporally-regulated gene expression in embryonic development. TBX22 (Chr X: 107667964-107688978) functioning as a transcriptional repressor affects DNA binding, sumoylation, and transcriptional repression associated with X-linked cleft palate. This study aimed to explore the relationship and potential mechanism between TBX22 exon 5 methylation and palatal shelf fusion induced by all-trans retinoic acid (ATRA). We performed DNA methylation profiling, using Methyl...

Corrigendum to: Assessment of developmental risk information on medicines for inclusion on the WHO's Essential Medicines List.

Multiple configurations of EGFR exon 20 resistance mutations after first- and third-generation EGFR TKI treatment affect treatment options in NSCLC.

After sequential treatment with first- and third-generation EGFR tyrosine kinase inhibitors (TKIs), EGFR-mutant non-small cell lung cancers frequently harbor multiple resistance mutations in exon 20 of EGFR including T790M, mediating resistance to first-generation TKIs, and at codons 792, 796, or 797 mediating resistance to third-generation TKIs. However, whether these resistance mutations are in cis or trans has therapeutic implications for patients. We analyzed a cohort of 29 patients with NSCLC harboring...

Acral Lentiginous Melanomas Harbour Intratumor Heterogeneity in BRAF Exon 15, With Mutations Distinct From V600E/V600K.

The choice of appropriate therapeutic strategies may be influenced by intratumor heterogeneity and makes cancer treatment considerably more challenging. We aimed to evaluate the heterogeneity of BRAF exon 15 mutations in different areas of acral lentiginous melanoma (ALM). The entire exon 15 was sequenced in 4 different areas of paraffin-embedded samples from 26 patients with ALM. A total of 26 of 49 cases of ≥1 mm in depth of ALM identified by clinical, anatomical, and pathological data fulfilled the inc...

Miliary lung metastases from non-small cell lung cancer with Exon 20 insertion: A dismal prognostic entity: A case report.

Miliary lung metastases have been reported to be frequently observed in nοn-small cell lung cancer (NSCLC) with major EGFR mutations, which consist of exon 19 deletion and exon 21 L858R. However, it remains undetermined whether NSCLC with minor EGFR mutations possesses characteristics similar to those with major EGFR mutations. In the present study, two cases of miliary lung metastases from NSCLC with exon 20 insertion were reported. Both the patients visited our hospital because of cough and/or dyspnea an...

Evaluation of prices, availability and affordability of essential medicines in Lahore Division, Pakistan: A cross-sectional survey using WHO/HAI methodology.

Inadequate access to medicines affected by un-controlled prices is a major concern in developing countries, including Pakistan, which lacks comprehensive data on medicine prices. Thus, the objective of this study was to evaluate the prices, availability and affordability of essential medicines in Lahore division, Pakistan. The survey was undertaken from November, 2016 till March, 2017 by including 50 medicines, 14 from the WHO/HAI core list and 36 supplementary medicines from national essential medicine lis...

Mice with Calr mutations homologous to human CALR mutations only exhibit mild thrombocytosis.

Calreticulin (CALR) exon 9 frameshift mutations, commonly detected in essential thrombocythemia (ET) and primary myelofibrosis patients, activate signal transducer and activator of transcription (STAT) proteins in the presence of Myeloproliferative Leukemia Virus (MPL) and induce ET in vivo. Loss of the KDEL motif, an endoplasmic reticulum retention signal, and generation of many positively charged amino acids (AAs) in the mutated C-terminus are thought to be important for disease induction. To test this hy...

CRISPR/Cas9 deletions in a conserved exon of Distal-less generates gains and losses in a recently acquired morphological novelty in flies.

Distal-less has been repeatedly co-opted for the development of many novel traits. Here, we document its curious role in the development of a novel abdominal appendage ("sternite brushes") in sepsid flies. CRISPR/Cas9 deletions in the homeodomain result in losses of sternite brushes, demonstrating that Distal-less is necessary for their development. However, deletions in the upstream coding exon (Exon 2) produce losses or gains of brushes. A dissection of Exon 2 reveals that the likely mechanism for gains i...

A regulatory perspective on the availability of medicines and medicine shortages in outpatient care: case Finland.

The good availability of medicines and medicine shortages have become global issues during recent years. Medicine shortages are often affected by universal determinants, but the availability of medicines is also depending on national characteristics. This commentary aims to discuss the issue of the availability of medicines and medicine shortages in outpatient care in Finland, taking in consideration both national characteristics and global determinants that effect on the availability of medicines in other ...

Identification and validation of alternative splicing isoforms as novel biomarker candidates in hepatocellular carcinoma.

Alternative splicing (AS) is a transcriptional regulation mechanism that participates in multiple aspects of cancer. The present study aimed to identify differential AS events from tumor and non‑tumor samples and investigate the potential of AS as a source of candidate cancer diagnostic biomarkers. Deep RNA sequencing of three paired hepatocellular carcinoma (HCC) tumors and adjacent non‑tumors was applied to identify AS events. RT‑qPCR was performed on 45 HCC clinical samples to validate the splic...

SERPING1 exon 3 splicing variants using alternative acceptor splice sites.

Mutations in the C1 inhibitor (C1INH) encoding gene, SERPING1, are associated with hereditary angioedema (HAE) which manifests as recurrent submucosal and subcutaneous edema episodes. The major C1INH function is the complement system inhibition, preventing its spontaneous activation. The presented study is focused on SERPING1 exon 3, an alternative and extraordinarily long exon (499 bp). Endogenous expression analysis performed in the HepG2, human liver, and human peripheral blood cells revealed several exo...

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