- Estrogen and related hormone effects
- bioluminescence and chemiluminescence research
- Computational Drug Discovery Methods
- Nutrition, Genetics, and Disease
- Breast Lesions and Carcinomas
- Breast Cancer Treatment Studies
- DNA and Nucleic Acid Chemistry
- Cancer Diagnosis and Treatment
- Advanced Breast Cancer Therapies
- Pediatric health and respiratory diseases
- Plant Pathogens and Fungal Diseases
- ATP Synthase and ATPases Research
- Ovarian cancer diagnosis and treatment
- Parasites and Host Interactions
- Pneumocystis jirovecii pneumonia detection and treatment
- Helminth infection and control
- Kruppel-like factors research
- Congenital Diaphragmatic Hernia Studies
- Endometrial and Cervical Cancer Treatments
- Microbial Community Ecology and Physiology
- Agricultural Systems and Practices
- Genetic Mapping and Diversity in Plants and Animals
- Food Industry and Aquatic Biology
- BRCA gene mutations in cancer
- Transplantation: Methods and Outcomes
Hans Raj Mahila Maha Vidyalaya
2024
Institute of Cancer Research
2023-2024
Breast Cancer Now
2023
National Dairy Development Board
2022
Krishna Institute of Medical Sciences Deemed University
2016-2019
Public Health England
2018
Louisiana State University Health Sciences Center New Orleans
2016
Louisiana State University
2013-2016
Genomic information is essential for taxonomic, phylogenetic, and functional studies to comprehensively decipher the characteristics of microorganisms, explore microbiomes through metagenomics, answer fundamental questions nature human life. However, large gaps remain in available genomic sequencing published bacterial archaeal species, are even larger fungal type strains. The Global Catalogue Microorganisms (GCM) leads an internationally coordinated effort sequence strains close maps...
Fulvestrant is used to treat patients with hormone receptor-positive advanced breast cancer, but acquired resistance poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in activating ESR1 mutations circulating tumor DNA (ctDNA). Baseline Y537S are associated poor outcomes and Y537C good outcomes. Sequencing baseline EOT ctDNA samples (n = 69) revealed 3/69 (4%) novel F404 (F404L, F404I, F404V), cis mutations. In silico modeling that contributes...
Löffler syndrome, a fulminant eosinophilic pneumonitis associated with the larval migratory phase of human parasites, is rarely reported in United States. A previously healthy 8-year-old male was hospitalized tachypnea, cough, hypoxemia, and fever one week's duration. History revealed exposure to pigs on his family's farm southernmost Louisiana, where patient responsible for cleaning farm's pigpens. His fingernails were soiled extremely short, edge nail bed exposed secondary onychophagia....
<div>Abstract<p>Fulvestrant is used to treat patients with hormone receptor–positive advanced breast cancer, but acquired resistance poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in activating <i>ESR1</i> mutations circulating tumor DNA (ctDNA). Baseline Y537S are associated poor outcomes and Y537C good outcomes. Sequencing baseline EOT ctDNA samples (<i>n</i> = 69) revealed 3/69 (4%) novel F404 (F404L,...
<div>Abstract<p>Fulvestrant is used to treat patients with hormone receptor–positive advanced breast cancer, but acquired resistance poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in activating <i>ESR1</i> mutations circulating tumor DNA (ctDNA). Baseline Y537S are associated poor outcomes and Y537C good outcomes. Sequencing baseline EOT ctDNA samples (<i>n</i> = 69) revealed 3/69 (4%) novel F404 (F404L,...
<p>Supplementary Figure 1. Progression free survival of patients with selected mutations. Supplementary 2. H356Y does not activate estrogen signalling or alter fulvestrant sensitivity in combination L536P. 3. Acquired ESR1 F404 mutations treated Fulvestrant. 4. Expression individual ER target genes RNAseq experiment. 5. Loss F404L mutation long-term culture “E” mutant clones. 6. Response D538G+F404L models to elacestrant. 7. camizestrant. 8. 4OH tamoxifen. 9. giredestrant.</p>
<p>F404 does not activate estrogen signaling. <b>A,</b> CRISPR clones of MCF7 cells expressing <i>ESR1</i> F404L (1210T>C, edit indicated by red arrows) or D538G (1613A>G; black were identified RT-PCR followed Sanger sequencing (left-hand panels). Similarly, a second round was used to introduce (1210T>C) into clone (D6C) that expressed right-hand <b>B,</b> Estrogen-dependent growth assessed in colony formation assay. Parental and...
<p>Baseline <i>ESR1</i> mutations and fulvestrant efficacy. <b>A,</b> % Incidence of in indicated genes at baseline Cohort A (<i>n</i> = 79 assessable patients). <b>B,</b> alterations within <b>C,</b> PFS patients A, divided by Y537C mutation status (left) Y537S (right). <i>P</i> values from the log-rank test. HR >1 denotes worse for that group. WT, wild-type; mt, mutant. <b>D,</b> MCF7 cells were...
<p>Baseline <i>ESR1</i> mutations and fulvestrant efficacy. <b>A,</b> % Incidence of in indicated genes at baseline Cohort A (<i>n</i> = 79 assessable patients). <b>B,</b> alterations within <b>C,</b> PFS patients A, divided by Y537C mutation status (left) Y537S (right). <i>P</i> values from the log-rank test. HR >1 denotes worse for that group. WT, wild-type; mt, mutant. <b>D,</b> MCF7 cells were...
<p>Acquired mutations on fulvestrant. <b>A,</b> Incidence of acquired alterations (<i>n</i> = 69 assessable patients), colored by targetability the (Methods). Level 2B denotes highest level supporting evidence (“Standard care biomarker recommended National Comprehensive Cancer Network or other professional advice guidelines predictive response to an FDA-approved drug”), whereas 4 is lowest (“Compelling biochemical supports as being a drug”)....
<p>F404 does not activate estrogen signaling. <b>A,</b> CRISPR clones of MCF7 cells expressing <i>ESR1</i> F404L (1210T>C, edit indicated by red arrows) or D538G (1613A>G; black were identified RT-PCR followed Sanger sequencing (left-hand panels). Similarly, a second round was used to introduce (1210T>C) into clone (D6C) that expressed right-hand <b>B,</b> Estrogen-dependent growth assessed in colony formation assay. Parental and...
<p>Compound F404 mutations are sensitive to novel SERDs. <b>A</b>–<b>D,</b> Compound of D538G-F404L in MCF7 cells, along with single and wild-type, sensitivity elacestrant (<b>A</b>), camizestrant (<b>B</b>), 4OH tamoxifen (<b>C</b>), giredestrant (<b>D</b>), assessed after 6 days treatment CellTiter Glo viability assay. <i>n</i> = 4 mean SD. <b>E,</b> Representative clonongenic assays grown...
<p>Transcriptomic analysis of <i>ESR1</i>-mutant models. <b>A,</b> Gene set enrichment (GSEA) for D538G + F404L models compared with D6C cells maintained in 1 nmol/L estradiol. Pathways are highlighted red; false discovery rate-adjusted <i>q</i> value <0.05. <b>B,</b> GSEA treated μmol/L fulvestrant 24 hours. <b>C,</b> Normalized score (NES) is shown the indicated pathways. *, False <b>D,</b> Heat map “Estrogen...
<p>Compound F404 mutations are sensitive to novel SERDs. <b>A</b>–<b>D,</b> Compound of D538G-F404L in MCF7 cells, along with single and wild-type, sensitivity elacestrant (<b>A</b>), camizestrant (<b>B</b>), 4OH tamoxifen (<b>C</b>), giredestrant (<b>D</b>), assessed after 6 days treatment CellTiter Glo viability assay. <i>n</i> = 4 mean SD. <b>E,</b> Representative clonongenic assays grown...
<p>Supplementary Figure 1. Progression free survival of patients with selected mutations. Supplementary 2. H356Y does not activate estrogen signalling or alter fulvestrant sensitivity in combination L536P. 3. Acquired ESR1 F404 mutations treated Fulvestrant. 4. Expression individual ER target genes RNAseq experiment. 5. Loss F404L mutation long-term culture “E” mutant clones. 6. Response D538G+F404L models to elacestrant. 7. camizestrant. 8. 4OH tamoxifen. 9. giredestrant.</p>
<p>Compound F404L mutations induce resistance to fulvestrant. <b>A,</b> Compound of D538G-F404L in MCF7 cells, along with single and wild-type (WT), sensitivity fulvestrant assessed after 6 days treatment Cell-Titer Glo viability assay. <i>n</i> = 4 mean SD. <b>B,</b> Representative images clonongenic assays grown indicated concentrations for 14 days. <b>C,</b> Quantification colony formation <i>ESR1</i>-mutant models treated...
<p>Supplementary methods: Computer modeling of SERDs pi-stacking with ER</p>
<p>Compound F404L mutations induce resistance to fulvestrant. <b>A,</b> Compound of D538G-F404L in MCF7 cells, along with single and wild-type (WT), sensitivity fulvestrant assessed after 6 days treatment Cell-Titer Glo viability assay. <i>n</i> = 4 mean SD. <b>B,</b> Representative images clonongenic assays grown indicated concentrations for 14 days. <b>C,</b> Quantification colony formation <i>ESR1</i>-mutant models treated...