Antifolate Drug Resistance: Novel Mutations and Therapeutic Efficacy Study from Arunachal Pradesh, NE India

2016 ◽  
Author(s):  
Pradyumna K Mohapatra ◽  
Nilanju P Sarma ◽  
Devendra Bansal ◽  
Praveen K Bharti ◽  
Neeru Singh ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Efficacy ◽  
Efficacy Study ◽  
Arunachal Pradesh ◽  
Novel Mutations ◽  
Ne India

scholarly journals Assessment of molecular markers of anti-malarial drug resistance among children participating in a therapeutic efficacy study in western Kenya

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Winnie Chebore ◽  
Zhiyong Zhou ◽  
Nelli Westercamp ◽  
Kephas Otieno ◽  
Ya Ping Shi ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Molecular Markers ◽  
Therapeutic Efficacy ◽  
Efficacy Study ◽  
Western Kenya

Cisplatin Resistance Reversal of Lung Cancers by Tumor Acidity-Activable Vesicular Nanoreactors via Tumor Oxidative Stress Amplification

2021 ◽  
Author(s):  
Jean Felix Mukerabigwi ◽  
Yu Han ◽  
Nannan Lu ◽  
Wendong Ke ◽  
Yuheng Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Therapeutic Efficacy ◽  
Cisplatin Resistance ◽  
Clinical Applications ◽  
Lung Cancers ◽  
Resistance Reversal ◽  
Tumor Acidity ◽  
Stress Amplification ◽  
Novel Strategy

Drug resistance of cisplatin significantly limits its therapeutic efficacy in clinical applications against a variety of cancers. Herein, we develop a novel strategy to overcome cisplatin drug resistance through sensitizing...

scholarly journals Morphological and molecular characterization of Theloderma moloch (Anura: Rhacophoridae) from Indo-Burma biodiversity hotspot of northeast India

2017 ◽  
Vol 17 (3) ◽  
pp. 148-159
Author(s):  
Samuel Lalronunga ◽  
C. Lalrinchhana
Keyword(s):  
16S Rrna ◽  
First Record ◽  
Northeast India ◽  
Biodiversity Hotspot ◽  
Arunachal Pradesh ◽  
Ne India ◽  
Himalayan Foothills ◽  
India And China ◽  
Morphological And Molecular Characterization

Specimens of a rare rhacophorid frog of the genus Theloderma were collected from Hmuifang, Mizoram, India. Based on their morphology and molecular analysis (16S rRNA), the specimens were identified as Theloderma moloch, a rare species previously recorded only from the Himalayan foothills of India and China. The present record significantly extends the known range of the species and is a first record for the state of Mizoram and Indo-Burma biodiversity hotspot. The uncorrected p-distance between the specimen from Mizoram, NE India and the specimen from Arunachal Pradesh, India (KU169993) and Tibet, China (KU243081) are 0.0% and 1.2% respectively.

scholarly journals Missed Plasmodium falciparum and Plasmodium vivax Mixed Infections in Ethiopia Threaten Malaria Elimination

2021 ◽  
Author(s):  
Colleen M. Leonard ◽  
Hussein Mohammed ◽  
Mekonnen Tadesse ◽  
Jessica N. McCaffery ◽  
Doug Nace ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Plasmodium Falciparum ◽  
Lactate Dehydrogenase ◽  
Plasmodium Vivax ◽  
Therapeutic Efficacy ◽  
Dried Blood Spots ◽  
Mixed Infections ◽  
Efficacy Study ◽  
Chain Reaction ◽  
Polymerase Chain

Plasmodium falciparum and Plasmodium vivax are co-endemic in Ethiopia. This study investigated whether mixed infections were missed by microscopy from a 2017 therapeutic efficacy study at two health facilities in Ethiopia. All patients (N = 304) were initially classified as having single-species P. falciparum (n = 148 samples) or P. vivax infections (n = 156). Dried blood spots were tested for Plasmodium antigens by bead-based multiplex assay for pan-Plasmodium aldolase, pan-Plasmodium lactate dehydrogenase, P. vivax lactate dehydrogenase, and histidine-rich protein 2. Of 304 blood samples, 13 (4.3%) contained both P. falciparum and P. vivax antigens and were analyzed by polymerase chain reaction for species-specific DNA. Of these 13 samples, five were confirmed by polymerase chain reaction for P. falciparum/P. vivax co-infection. One sample, initially classified as P. vivax by microscopy, was found to only have Plasmodium ovale DNA. Plasmodium falciparum/P. vivax mixed infections can be missed by microscopy even in the context of a therapeutic efficacy study with multiple trained readers.

scholarly journals pH-sensitive CAP/SiO2 composite for efficient co-delivery of doxorubicin and siRNA to overcome multiple drug resistance

RSC Advances ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 4251-4257
Author(s):  
Zheng Cai ◽  
Yuezhu Chen ◽  
Yingwen Zhang ◽  
Zhimei He ◽  
Xiaoge Wu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Efficacy ◽  
Multiple Drug Resistance ◽  
Ph Sensitive ◽  
Multiple Drug ◽  
Good Biocompatibility

CAP/SiO2 composite with good biocompatibility and acid biodegradability has been prepared. The proposed drug and gene codelivery system based on it demonstrated enhanced therapeutic efficacy for multiple drug resistance cells.

NGS-Based Detection Of Multiple RAS-Mutated Clones In MLL-Rearranged Leukemias Suggests Strong Oncogenic Collaboration

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 744-744
Author(s):  
Vincent-Philippe Lavallée ◽  
Patrick Gendron ◽  
Geneviève Boucher ◽  
Marianne Arteau ◽  
Brian T Wilhelm ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Conflicts Of Interest ◽  
Clonal Selection ◽  
Exome Capture ◽  
Novel Mutations ◽  
Kras Mutations ◽  
Ras Mutation ◽  
Mutation Status ◽  
Ras Mutations ◽  
Fab Classification

Abstract Background Recent development in sequencing technologies with deep coverage for mutation analysis has enabled the identification of clonal architecture in some cancers. RAS mutations are observed in a large proportion of MLL leukemias. Our hypothesis is that determination of RAS mutation status in MLL leukemias should provide insights into the clonal make up of this disease and clues about the nature of clones that overcome therapy. Methods We combined exome and transcriptome sequencing in 32 adult MLL leukemias and results were compared to our cohort of 48 normal karyotype (NK) AML. Exome capture and paired-end sequencing (2 x 100bp, Illumina HiSeq 2000) were performed using TruSeq (Illumina) protocols. Mean coverage was 165X for transcriptome and 42X for exome. Initial analysis was focused on 25 known AML-associated genes and excluded all other novel mutations. Average transcriptome and exome coverage for N/KRAS alleles was 287X (25-846) and 42X (9-151), respectively. Clones were defined based on the identification of N/KRAS mutations in at least 1% of the reads. Results Figure 1 shows mutation status, MLL partners and FAB classification for each MLL leukemia. No mutations were observed in NPM1, FLT3 (ITD), CEBPA (biallelic), RUNX1, DNMT3A, IDH1, KIT, BCOR, SF3B1, U2AF1 or RAD21. On average, 1 mutated gene (range: 0-4) per sample was found compared to 3 (range 0-5) in NK-AML (p < 0.0001). We observed that 13/32 MLL leukemias (which include 2 paired samples) harbored N/KRAS mutations. There were no association between RAS mutation status and MLL partner, FAB classification, age, white blood cell count and overall survival. RAS mutations were found in 15% of NK-AML which contained on average 2.3 additional mutations in leukemia-associated genes compared to only 0.3 (p<0.0001) in MLL leukemias. Excluding 2 paired relapse specimens, a total of 24 N/KRAS mutated clones were identified in 11 of the 30 MLL leukemias. The first sample included 5 clones each containing different NRAS mutations (e.g. G13R, G13D, etc.) contributing to 17, 9, 4, 2 and 2 % of the reads. Since RAS mutations are mostly heterozygous, we estimated that the contribution of each clones varied between 34 (i.e. 17% x 2) to 4%. A similar analysis revealed 4 clones in another specimen, contributing to 22, 12, 12 and 4 % of the cells. In 4 additional samples, the proportions of N/KRAS mutated clones were 1) 42, 38 and 8% 2) 92, 4 and 2 %, 3) 78 and 12% and 4) 52 and 32%, establishing that 20% (6/30) of these MLL leukemias were oligo- to polyclonal. In comparison, our NK-AML cohort of 48 patients included 7 specimens mutated for N/KRAS in which a total of 10 different clones were identified for an average of 0.2 RAS mutated clones per NK-AML versus 0.8 in MLL leukemias (p=0.007). This result further strengthens the hypothesis that RAS and MLL-fusion genes are strong collaborators in human AML. Grossmann et al recently showed that RAS mutated clones can be lost at relapse (Leukemia, 2013), possibly suggesting that other genes are at play in collaborating with MLL-fusions and causing drug resistance. To identify such genes, we further analyzed paired diagnosis and relapse samples in 2 patients. In the first patient, the KRAS mutation that was found in 66% of the cells at diagnosis was identified in all cells at relapse. In the second patient, while KRAS G12V and G12D mutations were found in 78% and 12 % of the cells at diagnosis, only the G12V clone was detected in 100% of the cells at relapse indicating in vivo clonal selection in both cases. We then performed a comparative analysis of mutated/wild type allele ratios for other coding genes. This analysis enabled us to identify a subset of mutations in candidate genes that are present at relapse in the dominant clone but that were undetectable or at lower frequency at presentation, indicating they might be specifically involved into occurrence of relapse (i.e. drug resistance). Conclusion NRAS and KRAS are mutated in 37% of MLL leukemias in this cohort. In contrast to NK-AML, these leukemias are frequently oligo- to polyclonal and contain few additional mutations suggesting that RAS activation may be sufficient to induce AML in the presence of MLL fusions. Evidence from our limited number of relapse patients, and that of others, suggests that RAS does not confer drug resistance which could be explained by novel mutations in genes that were specifically detected in the dominant clones at relapse. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Status, distribution and research gaps of rodents (Mammalia: Rodentia) in North-Eastern States of India

2020 ◽  
Vol 63 (2) ◽  
pp. 261-277
Author(s):  
Paromit Chatterjee ◽  
Debashree Dam ◽  
Basudev Tripathy ◽  
Kailash Chandra
Keyword(s):  
Indian Subcontinent ◽  
Arunachal Pradesh ◽  
Research Gaps ◽  
Mammal Species ◽  
Number Of Species ◽  
The North ◽  
Ne India ◽  
North Eastern ◽  
Baseline Information ◽  
Data Deficient

In North Eastern states of India (NE India) there are almost 65% of mammal species of the country but baseline information on small mammals, particularly rodents, for the region is scanty. Present study recorded a total of 59 species of rodents from the NE India out of 100 species reported from Indian Subcontinent. The list contains all the valid taxonomic names and their distribution in the states of NE India. Additionally, five species has been added to the checklist of rodents in India. The list provided 59 species belonging to 30 genera under 5 families of 7 subfamilies. Among them Muridae was recorded to be with highest number of species (31 species), followed by Sciuridae with 22 species, Cricetidae with three species, while Spalacidae and Hystricidae have recorded only two species in each group. Among the eight states of NE India the highest number of species was recorded from Arunachal Pradesh (76 %) and the lowest, from Tripura (22%). Two Threatened, three Near Threatened, two Not Listed and six Data Deficient species have been listed from the present work with four endemic species from this region. The findings of this study indicated the requirements for intensive and extensive surveys in the north-eastern States of India and taxonomic revisions of many species.

scholarly journals Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China

2021 ◽  
Author(s):  
Rashmi S Mudliar ◽  
Umay Kulsum ◽  
Syed Beenish Rufai ◽  
Mika Umpo ◽  
Moi Nyori ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Drug Resistant ◽  
Second Line ◽  
Arunachal Pradesh ◽  
Tuberculosis Programme ◽  
Indian State ◽  
Northeastern State ◽  
Resistant Strains ◽  
Drug Resistant Strains

Uncontrolled transmission of Mycobacterium tuberculosis (M. tuberculosis, MTB) drug resistant strains is a challenge to control efforts of global tuberculosis programme. Due to increasing multi-drug resistant (MDR) cases in Arunachal Pradesh, a northeastern state of India, the tracking and tracing of these resistant MTB strains is crucial for infection control and spread of drug resistance. This study aims to correlate the phenotypic DST, genomic DST (gDST) and phylogenetic analysis of MDR-MTB strains in the region. Of total 200 suspected MDR-MTB isolates, 125(62.5%) were identified as MTB. MGIT-960 SIRE DST detected 71/125(56.8%) isolates as MDR/RR-MTB of which 22(30.9%) were detected resistant to second line drugs. Whole genome sequencing of 65 isolates and their gDST found Ser315Thr mutation in katG (35/45;77.8%) and Ser531Leu mutation in rpoB (21/41;51.2%) associated with drug resistance. SNP barcoding categorized the dataset with Lineage2 (41;63.1%) being predominant followed by Lineage3 (10;15.4%), Lineage1 (8;12.3%) and Lineage4 (6;9.2%) respectively. Phylogenetic assignment by cgMLST gave insights of two Beijing sub-lineages viz; 2.2.1 (SNP difference &amp;lt; 19) and 2.2.1.2 (SNP difference &amp;lt; 9) associated with recent ongoing transmission in Arunachal Pradesh. This study provides first insight in identifying the ongoing transmission of two virulent Beijing sub-lineages associated with TB drug resistance.

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