A5088340237- Nitric Oxide and Endothelin Effects
- Cancer, Hypoxia, and Metabolism
- Renin-Angiotensin System Studies
- Optical Coherence Tomography Applications
- Hormonal Regulation and Hypertension
- AI in cancer detection
- Drug Transport and Resistance Mechanisms
- Cancer Genomics and Diagnostics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Renal Diseases and Glomerulopathies
- Cancer Research and Treatments
- Blood Pressure and Hypertension Studies
- Glioma Diagnosis and Treatment
- Photoacoustic and Ultrasonic Imaging
- Biochemical and Molecular Research
- Tumors and Oncological Cases
- Chronic Kidney Disease and Diabetes
- Retinal Imaging and Analysis
- Cancer Cells and Metastasis
- ATP Synthase and ATPases Research
- Eicosanoids and Hypertension Pharmacology
- Retinal and Macular Surgery
- Sarcoma Diagnosis and Treatment
- Advanced Glycation End Products research
- Renal and Vascular Pathologies
MGH Institute of Health Professions
2025
Massachusetts General Hospital
2013-2024
Vertex Pharmaceuticals (United States)
2024
Harvard University
2011-2023
Center for Cancer Research
2016-2017
Brigham and Women's Hospital
2015
University of Alberta
2015
Fundación Santa Fe de Bogotá
2015
Universidad de Los Andes
2015
Universidad Nacional de Colombia
2015
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well composition tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq 165 samples. Differences between IDH-mutant astrocytoma oligodendroglioma can be primarily explained distinct TME signature genetic events, whereas both types share similar...
Phagocytes generate superoxide anion (O 2 − ) by a classic, 5-component NADPH oxidase. O contributes to hypertension in spontaneously hypertensive rats (SHR). Therefore, we tested the hypothesis that oxidase expression is enhanced SHR kidney. We also analyzed localization of components Renal was quantified reverse transcription-polymerase chain reaction and Western blotting localized Wistar Kyoto rat (WKY) kidney immunohistochemistry. The mRNA for 5 subunits phagocyte oxidase, MOX1 RENOX...
The tubular secretion of diuretics in the proximal tubule has been shown to be critical for action drugs. To elucidate molecular mechanisms excretion diuretics, we have elucidated interactions human organic anion transporters (hOATs) with using cells stably expressing hOATs. Diuretics tested were thiazides, including chlorothiazide, cyclothiazide, hydrochlorothiazide, and trichlormethiazide; loop bumetanide, ethacrynic acid, furosemide; carbonic anhydrase inhibitors, acetazolamide...
Tumor islands—large collections of tumor cells isolated within alveolar spaces—can be seen in lung adenocarcinomas. Recently we observed by 3-dimensional reconstruction that these structures were connected with each other and the main different tissue planes, raising possibility islands being a means extension. However, clinical prognostic significance remains unknown. In this study, compared clinicopathologic molecular characteristics prognosis stages I to II adenocarcinomas (n=58) those...
Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, facilitates renewal tumor-initiating reservoir contributing maintenance. We investigated whether targeting Myc-driven state could be a selectively toxic therapeutic strategy glioblastoma.The glycolytic dependency glioblastoma was tested using (13)C flux analysis, glucose-limiting culture...
Inhibition of the PD‐L1 (CD274) – PD‐1 axis has emerged as a powerful cancer therapy that prevents evasion tumor cells from immune system. While immunohistochemical detection was introduced predictive biomarker with variable power, much less is known about copy number alterations (CNA) affecting and their associations expression levels, mutational load, survival. To gain insight, we employed The Cancer Genome Atlas (TCGA) datasets to comprehensively analyze 22 major types for CNAs. We...
Asymmetric dimethylarginine (ADMA), which inhibits NO synthase, is inactivated by N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH). We tested whether DDAH-1 or -2 regulates serum ADMA (S(ADMA)) and/or endothelium-derived relaxing factor (EDRF)/NO. Small inhibitory (si)RNAs targeting -2, an siRNA control were given intravenously to rats. After 72 hours, EDRF/NO was assessed from acetylcholine-induced, synthase-dependent relaxation and 4-amino-5-methylamino-2',7'-difluorofluorescein...
Reactive oxygen species have an important pathogenic role in organ damage. We investigated the of oxidative stress via nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase kidney Dahl salt-sensitive (DS) rats with heart failure (DSHF). Eleven-week-old DS fed 8%-NaCl diet received either vehicle or imidapril (1 mg/kg per day) for 7 weeks. The renal expression NAD(P)H p47phox and endothelial NO synthase were evaluated. In DSHF rats, associated increased angiotensin II, mRNA protein...
The nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) is generated by protein arginine N-methyltransferase (PRMT)-1 and metabolized N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH). We tested the hypothesis that increased serum ADMA (S(ADMA)) in streptozotocin (STZ)-induced diabetic rat model of diabetes mediated an angiotensin receptor blocker-sensitive change DDAH or PRMT expression.Data were compared from four groups rats: sham-injected controls, untreated...
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) may play an important role in atherosclerosis by inducing leukocyte adhesion molecules, such as intercellular and vascular cell molecule-1 (intercellular [ICAM-1], [VCAM-1]). We hypothesized that eplerenone, a novel selective aldosterone blocker, produces inhibition of LOX-1-mediated suppresses mitogen-activated protein (MAP) kinase its downstream effector p90 ribosomal S6 (p90RSK) through the Cepsilon (PKCepsilon) pathway,...
Hypertensive cardiovascular damage is accelerated by salt loading but counteracted dietary potassium supplementation. We suggested recently that antioxidant actions of contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression oxidative stress. Four-week–old Dahl rats were fed a normal-salt (0.3% NaCl), high-salt (8% or plus high-potassium KCl) diet...
Angiotensin II blockade and spironolactone effectively reduces proteinuria in humans. To clarify the mechanisms of beneficial effect both aldosterone angiotensin II, we associated antagonist eplerenone to an angiotensin-converting enzyme inhibitor (ACEI) examined on renal transforming growth factor (TGF)-beta expression oxidative stress by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase Dahl salt-sensitive rat with heart failure (DSHF).Dahl salt-resistant control rats DSHF were...
Background : Three-dimensional (3D)-reconstruction from paraffin embedded sections has been considered laborious and time-consuming. However, the high-resolution images of large object areas different fields view obtained by 3D-reconstruction make one wonder whether it can add a new insight into lung adenocarcinoma, most frequent histology type cancer characterized its morphological heterogeneity. Objective In this work, we tested an automated tissue sectioning machine slide scanning system...