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RISS 인기검색어
- 검색키워드
- 저자 : ( Sakshi Mishra ) (검색결과 3 건)
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Sudhir Navathe,Sakshi Singh,Vinay Kumar Singh,Ramesh Chand,Vinod Kumar Mishra,Arun Kumar Joshi 한국유전학회 2019 Genes & Genomics Vol.41 No.9
Background Membrane-bound NADPH oxidases (Nicotinamide adenine ainucleotide phosphate oxidase) also called respiratory burst oxidase homologs (Rboh) play an essential role in ROS production under normal as well as environmental stress conditions in plants. Objective To identify and study respiratory burst homologs (Rboh) from the wheat genome as well as characterize their role in various biological and molecular processes along with expression in response to biotic and abiotic stresses. Methods The Rboh homologs in the wheat genome were predicted based on data processing, alignment of sequences and phylogenetic analysis of sequences in numerous plant species and wheat. The conserved motifs were known followed by domain design study. The 3-D structure prediction and similarity modeling were administered for NADPH enzyme domain. Gene ontology and a functional study were done in addition to expression analysis of Triticum aestivum respiratory burst oxidase (TaRboh) gene family in response to biotic as well as abiotic stress. Results Phylogenetic analysis of Rboh gene family members among seven plant species including wheat, classified the family into four subfamilies. Rboh genes are mainly involved in various biological processes such as Response to oxidative stress, Superoxide anion generation, Hydrogen peroxide biosynthetic process. Among the molecular functions, calcium ion binding, peroxidase activity, oxidoreductase activity, superoxide-generating NADPH oxidase activity are essential. Enzyme annotation of the family and superfamily revealed that it encodes to five structural clusters and coding to enzymes NAD(P)H oxidase ( H2O2-forming) (EC:1.6.3.1), Ferric-chelate reductase (NADH) (EC: 1.16.1.7), Peroxidase (EC: 1.11.1.7), Ribose-phosphate diphosphokinase (EC: 2.7.6.1). The enzymes contain six membrane-spanning domains, two hemes, and conserved motifs associated with NADPH, EF-hand and FAD binding. The outcomes additionally reflect a distinct role of this enzyme in different molecular functions which are responsible for the stress signaling. Further, the transcripts of TaRboh found expressed in various plant parts such as stem, leaves, spike, seed, and roots. We also observed expression of these gene family members under drought/combination of drought + heat and important wheat pathogens such as Puccinia striformis, Blumeria graminis f.sp. tritici, Fusarium graminiarum, F. pseudograminiarum, and Zymoseptoria tritici. Conclusions The investigation demonstrated that identified respiratory burst homologs (Rboh) in T. aestivum were involved in pathogen activated ROS production and have regulatory functions in cell death and defense responses.
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( Faiza Ahmed ),( Israr Khan ),( Nazma Hanif ),( Alaa Hamdan ),( Mohammad Ali Zaidi ),( Zeynep Yukselen ),( Umer Salman ),( Sakshi Mishra ),( Jack Michel ),( Muhammad Haris Khan ),( Andre Thompson ),( 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.-
Background Pralsetinib and selpercatinib are anticancer drugs targeting RET fusions (oncogenic drivers) in non-small cell lung cancer (NSCLC). The US FDA approved both drugs in 2020 for the treatment of RET-fusion positive NSCLC. Methods We assessed the efficacy & safety of pralsetinib versus selpercatinib in RET fusion-positive NSCLC in two clinical trials: phase1/2 ARROW trial (n=354) and phase 1/2 LIBRETTO-001 trial (n=144). Results In patients who had previously received platinum-based therapy (n=105), Drilon et al., 2020 showed an overall response rate (ORR) of 64% (95% CI, 54-73) and a median duration of response (mDOR) of 17.5 months (95% CI, 12.0-NE) with selpercatinib in phase 1/2 LIBRETTO-001 trial. Furthermore, a complete response (CR) of 2%, partial response (PR) of 62%, stable disease (SD) of 29%, and median progression-free survival (mPFS) of 16.5 months ( 95% CI, 13.7 - NE) were reported. Treatment naive patients (n=39) demonstrated an ORR of 85% (95% CI, 70-94) and PR of 85%. The responses were determined by the independent review committee. Lee et al., 2019 (n=111) demonstrated a rapid lowering of RET circulating tumor DNA (ctDNA) in 81% of NSCLC patients with pralsetinib therapy. A phase 1/2 ARROW trial (n= 116) exhibited a median follow-up of 8.8 months in patients who received pralsetinib 400 mg daily. Additionally, ORR was 65%, CR 6%, disease control rate 93 (95% CI, 87 - 97), and resulted in overall tumor size reduction in 96% of patients. Refer to (Table 1) for further details. Conclusion Pralsetinib and Selpercatinib have shown promising anti-tumor activity and an acceptable safety profile in RET fusion-positive NSCLC. However, we cannot draw a firm conclusion regarding which one is better due to insufficient data. Clinical trials, including AcceleRET, are still ongoing, and data is pending. Further comparative studies are needed to derive meaningful survival outcomes.
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( Faiza Ahmed ),( Israr Khan ),( Alejandra Castro-varela ),( Alanna Barrios-ruiz ),( Zarlakhta Zamani ),( Alaa Hamdan ),( Sakshi Mishra ),( Muhammad Khan ),( Umer Salman ),( Zeynep Yukselen ),( Kim An 대한결핵 및 호흡기학회 2021 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.129 No.0
Background The United States Food and Drug Administration (FDA) approved tepotinib and capmatinib for the treatment of mesenchymal-epithelial transition (MET) exon-14 mutated non-small cell lung cancer (NSCLC) in February 2021 and May 2020, but no comparative study has been done so far. Here we compare Results of two-phase 2 trials evaluating the efficacy and safety of these new drugs. Methods Studies demonstrating the role of tepotinib and capmatinib in NSCLC patients were identified using PubMed, Scopus, and Google Scholar databases from inception till February 2021. Results Participants received tepotinib (n=152) and capmatinib (n=97) in two distinct studies. The main efficacy measures in the combined-biopsy group were overall response rate (ORR) of 46% and 56% with tepotinib therapy in VISION trial as per independent review committee and investigator assessment. In contrast, ORR of 41% was noted in previously treated patients vs. 68% in treatment naive patients with capmatinib monotherapy in GEOMETRY mono-1 study. Patients in the tepotinib group showed a median duration of response (mDOR) and a median progression free survival (mPFS) of 11.1 months and 8.5 months, respectively. While with capmatinib study, the mDOR varied from 9.7 months with a mPFS of 5.4 months in those who received prior therapy to mDOR of 12.6 months with a mPFS of 12.4 months in capmatinib monotherapy. The most commonly reported toxicity was grade 3-4 peripheral edema in both arms (tepotinib: 7% vs. Capmatinib: 11%/14%). Conclusions Both drugs exhibited promising activity in the treatment of NSCLC carrying MET exon 14 skipping mutation. However, capmatinib showed an improved ORR, mDOR, and mPFS in treatment naive patients compared to patients treated with tepotinib. Further large and long-term direct comparative clinical trials are warranted to elaborate on beneficial outcomes.
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