A5005410041- Cancer Immunotherapy and Biomarkers
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Liver Disease Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Cancer, Stress, Anesthesia, and Immune Response
- CAR-T cell therapy research
- Hepatitis B Virus Studies
- Psoriasis: Treatment and Pathogenesis
- Cancer Cells and Metastasis
- Antibiotic Use and Resistance
- NF-κB Signaling Pathways
- Antibiotics Pharmacokinetics and Efficacy
- Ovarian cancer diagnosis and treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Hepatitis C virus research
- Radiomics and Machine Learning in Medical Imaging
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- Esophageal Cancer Research and Treatment
- Intraperitoneal and Appendiceal Malignancies
- Monoclonal and Polyclonal Antibodies Research
- Brain Metastases and Treatment
Merck & Co., Inc., Rahway, NJ, USA (United States)
2022-2025
Harvard University
2017-2021
Dana-Farber Cancer Institute
2019-2021
Dana-Farber Brigham Cancer Center
2019
Brigham and Women's Hospital
2019
GITAM University
2017
Christian Medical College & Hospital
2012-2016
Biocon (India)
2016
<h3>Background</h3> A male gender driven obesity paradox (improved survival for overweight/obese patients compared to normal weight) was recently shown in melanoma the context of checkpoint inhibition (anti-PD-1/anti-CTLA4 monotherapy) a pooled meta-analysis. We characterized relationship Body Mass Index (BMI) with and explored gender-based interactions surrogates body composition/malnutrition PD-1 blockade as monotherapy or combination ipilimumab real-world setting. <h3>Methods</h3>...
TRX518 is a mAb engaging the glucocorticoid-induced TNF receptor-related protein (GITR). This open-label, phase I study (TRX518-003) evaluated safety and efficacy of repeated dose monotherapy in combination with gemcitabine, pembrolizumab, or nivolumab advanced solid tumors.
Introduction: Rising antibiotic resistance may negatively affect the health and cost of care for patients. This study aimed to determine impact on costs consequences Methodology: A one-year observational was conducted at Christian Medical College, Vellore, a tertiary hospital, patients admitted into medical wards with preliminary diagnosis suspected sepsis. Patients confirmed bacteremia were analysed in two groups – resistant susceptible based susceptibility causative bacteria empiric...
Therapeutic combinations targeting innate and adaptive immunity predictive biomarkers of response in esophagogastric cancer (EGC) are needed. We assessed safety clinical utility DKN-01 (a novel DKK1-neutralizing IgG4 antibody) combined with pembrolizumab retrospectively determined DKK1 tumoral expression as a biomarker. Patients advanced EGC received intravenous (150 or 300 mg) on days 1 15 200 mg day 21-day cycles. Clinical was by RECIST v1.1. Association mRNA (H-score: high ≥...
534 Background: Pts with VHL disease are at risk of developing malignant tumors such as renal cell carcinoma (RCC) due to gene inactivation, leading activation hypoxia-inducible factors (HIFs). In the phase 2 LITESPARK-004 study, HIF-2α inhibitor belzutifan (MK-6482) demonstrated antitumor activity and a manageable safety profile in pts disease–associated tumors; however, study did not include from Asia. We present results for mainland China localized enrolled cohort B1 2, open-label,...
Introduction Antibiotic pressure contributes to rising antibiotic resistance. Policy guidelines encourage rational prescribing behavior, but effectiveness in containing use needs further assessment. This study therefore assessed the patterns of over a decade and analyzed impact different modes guideline development dissemination on inpatient use. Methods was calculated monthly as defined daily doses (DDD) per 100 bed days for nine groups overall. time series compared trends five adjacent...
Background: Pharmacokinetics of meropenem differ widely in the critically ill population. It is imperative to maintain concentrations above inhibitory for most interdose interval. A population pharmacokinetic/pharmacodynamic model was developed determine probability target attainment 3-hour and 30-minute infusion regimens this Methods: This study performed an intensive care setting among adult patients who were initiated on at a dose 1000 mg. Multiple blood specimens collected predetermined...
Background: This study was a retrospective assessment of the therapeutic drug monitoring data collected for levetiracetam and lamotrigine from clinical setting. The proportion patients in relation to ranges serum concentrations estimated, influence age anticonvulsant comedications on their clearances were studied. Methods: Information (2011–2013) (2008–2013) dose, trough concentration, age, sex, body weight, prescribed obtained register archived medical records. Patients categorized into 4...
357 Background: Dickkopf-1 (DKK1) modulates Wnt signaling and contributes to an immune suppressive tumor microenvironment. DKN-01 (D), a neutralizing DKK1 antibody + pembrolizumab (P) has demonstrated safety clinical activity in advanced GEA. We report response survival outcomes anti-PD-1/anti-PD-L1 naïve GEA patients by high/low tumoral expression. Methods: enrolled anti-PD-1/PD-L1 (pts) Phase 1b/2a study of D P (NCT02013154). Tumoral mRNA expression was assessed situ hybridization RNAscope...
Long-term survival outcomes among melanoma patients with brain metastases treated immune checkpoint inhibitors are limited. In this retrospective study at 2 centers, metastatic radiographic evidence of who received anti-programmed death-1 (PD-1) monotherapy or nivolumab in combination ipilimumab between 2014 and 2017 were included. Overall (OS) was assessed diagnosis-specific graded prognostic assessment (ds-GPA) melanoma-molecular (molGPA) risk groups. Baseline clinical covariates used to...
We have modified an assay utilizing ion-pair high-performance liquid chromatography with electrochemical detection to measure dihydroxyphenylalanine and dyhydroxyphenylglycol simultaneously noradrenaline. measured these agents at control, 1 3 weeks following the onset of rapid ventricular pacing, as well 4 after cessation a 3-week period pacing. Our findings were follows. Plasma noradrenaline increased significantly week further pacing (control, 202 ± 16; week, 528 62; weeks, 750 139 pg∙mL...
TPS425 Background: Initial signal finding studies demonstrated promising antitumor activity with the anti–PD-1 antibody pembrolizumab in combination anti-angiogenic multikinase inhibitor lenvatinib patients advanced gastric cancer or head and neck squamous cell carcinoma. Because hypoxia is common many solid tumors known to induce an immunosuppressive tumor microenvironment, targeting hypoxia-inducible factor-2 alpha (HIF-2α) may enhance of immune checkpoint inhibitors. The ongoing phase 2...
Hypoxia-inducible factor-2α (HIF-2α) modulates the hypoxic response pathway in tumors; however, mutations pathways (including SDHA, SDHB, SDHC, SDHD, FH, and VHL genes) that are suspected to activate HIF-2α poorly understood, with limited understanding of prevalence clinical prognosis.
Abstract T cell dysfunction in the tumor microenvironment (TME) is a hallmark of many cancers. Reinvigoration function by PD-1 checkpoint blockade can result striking clinical responses, but only effective minority patients. The basis for TME, as well mechanisms which anti-PD-1 therapy acts on dysfunctional cells are not fully understood. Here we show that specific subpopulation CD8+ tumor-infiltrating lymphocytes (TILs) melanoma mouse models, also be found patients with melanoma. We find...
TPS4173 Background: There is an unmet medical need in patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and biliary tract (BTC), that progresses after standard therapy. The combination of pembrolizumab (pembro; anti–PD-1 antibody) lenvatinib (len; anti-angiogenic multikinase inhibitor) demonstrated antitumor activity manageable toxicity many tumor types. Hypoxia-inducible factor-2 alpha (HIF-2α) acts on...
Abstract T-cell dysfunction in the tumor microenvironment (TME) is a hallmark of many cancers. Reinvigoration function by PD-1 checkpoint blockade can result striking clinical responses, but only effective minority patients. The mechanisms which anti-PD-1 therapy acts on exhausted T cells are not fully understood. Here we show that specific subpopulation CD8+ tumor-infiltrating lymphocytes (TILs) melanoma mouse models, also be found patients with melanoma. Exhausted TILs contain “progenitor...