A5068016531- Colorectal Cancer Treatments and Studies
- Gut microbiota and health
- Gastrointestinal motility and disorders
- Cancer Genomics and Diagnostics
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- Lung Cancer Treatments and Mutations
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Treatment and Pharmacology
- Pancreatic and Hepatic Oncology Research
- Infant Health and Development
- Histone Deacetylase Inhibitors Research
- Vagus Nerve Stimulation Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Diet and metabolism studies
- Colorectal and Anal Carcinomas
- Neuroendocrine regulation and behavior
- Neutropenia and Cancer Infections
- Neuropeptides and Animal Physiology
- RNA modifications and cancer
- Cancer-related gene regulation
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Genetic factors in colorectal cancer
Rockefeller University
2019-2025
Johns Hopkins University
2016-2019
Johns Hopkins Medicine
2016-2019
University of Baltimore
2016-2018
University of Wisconsin–Madison
2008
Despite improvements in cancer management, most pancreatic cancers are still diagnosed at an advanced stage. We have recently identified promoter DNA methylation of the genes ADAMTS1 and BNC1 as potential blood biomarkers pancreas cancer. In this study, we validate biomarker panel peripheral cell-free tumor patients with cancer.Sensitivity specificity for each gene follows: 87.2% 95.8% (AUC = 0.91; 95% CI 0.71-0.86) 64.1% 93.7% 0.79; 0.63-0.78). When using either a combination panel,...
The gut microbiota affects tissue physiology, metabolism, and function of both the immune nervous systems. We found that intrinsic enteric-associated neurons (iEANs) in mice are functionally adapted to intestinal segment they occupy; ileal colonic more responsive microbial colonization than duodenal neurons. Specifically, a microbially subset viscerofugal CART
Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of administration hypomethylating agents. We evaluated the safety and tolerability guadecitabine irinotecan mCRC previously treated irinotecan.In this 3+3 dose-escalation study, exposed to received days 1 5 a 28-day cycle 125 mg/m2 8 15 [dose level (DL) 1, 45 mg/m2; DL -1: 30 -1G: growth factor support...
Colorectal cancer (CRC) is the second leading cause of death in United States. In metastatic setting, majority patients respond to initial therapies but eventually develop resistance and progress. this study, we test hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant subsequent chemotherapeutic agents. When multiple lines are first exposed 500 nM DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, cells then established as in-vivo...
Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was first cytokine to be evaluated for cancer biotherapy. However, clinical use TNF-α is severely limited by its toxicity. Currently, administered only through locoregional drug delivery systems such as isolated limb perfusion and hepatic perfusion. To reduce systemic toxicity TNF-α, various strategies have been explored over last several decades. This review summarizes current state-of-the-art targeted therapy using...
We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested prognostic value this in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP-/MLH1-U, or CIMP-/MLH1-M groups. Age, location, lymphovascular invasion, mucin production differed among four patient...
Microbial density and diversity increases from proximal to distal regions of the intestine, affecting tissue physiology, metabolism, function immune nervous systems. Both intrinsic extrinsic enteric–associated neurons (EAN) continuously monitor modulate homeostatic intestinal functions, including nutrient absorption motility. However, a systemic circuit-based link between gut microbes system has yet be established. Through combination molecular, anatomic functional approaches, we...
ABSTRACT Increased tumour innervation is associated with adverse survival outcomes in multiple cancers 1–4 . To better understand the mechanisms underlying this, we studied impact of on breast cancer metastatic progression. Metastatic mammary tumours mice were substantially more innervated than non-metastatic isogenic tumours. Three dimensional co-cultures and vivo models revealed that sensory dorsal root ganglion (DRG) neurons enhanced growth, invasion, systemic dissemination cells—thereby...
Summary Enteric–associated neurons (EANs) are closely associated with immune cells and continuously monitor modulate homeostatic intestinal functions, including motility. Bidirectional interactions between neuronal altered during disease processes such as neurodegeneration or irritable bowel syndrome. We investigated how infection-induced inflammation affects intrinsic EANs the role of muscularis macrophages (MMs) in this process. Using murine model bacterial infection, we observed long-term...
Abstract Background: Treatment of IRI-resistant CRC lines with a DNA methyltransferase inhibitor (DNMTi) can induce IRI re-sensitization. We theorized that combination next generation DNMTi GUA+IRI would overcome resistance in previously IRI-treated mCRC pts. Methods: pts prior exposure were enrolled 3+3 Phase I, dose escalation study to define the maximum tolerated (MTD) and limiting toxicities GUA+IRI. Pharmacodynamics studies planned on pre- post-treatment tumor biopsies (C1D8); serial...
<p>LINE1 changes in tumor CpG 1-3 on cycle 1 day 8 from baseline. LINE1 DNA individual patient biopsy samples.</p>
<p>Pharmacokinetic parameters of guadecitabine and decitabine after injection</p>
<p>LINE1 changes in circulating DNA CpG 1-3 as compared to baseline.</p>
<div>AbstractPurpose:<p>Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of administration hypomethylating agents. We evaluated the safety and tolerability guadecitabine irinotecan mCRC previously treated irinotecan.</p>Patients Methods:<p>In this 3+3 dose-escalation study, exposed to received days 1 5 a 28-day cycle 125...
<div>AbstractPurpose:<p>Chemotherapeutic resistance eventually develops in all patients with metastatic colorectal cancer (mCRC). Gene silencing through promoter demethylation is one potential reversible mechanism of administration hypomethylating agents. We evaluated the safety and tolerability guadecitabine irinotecan mCRC previously treated irinotecan.</p>Patients Methods:<p>In this 3+3 dose-escalation study, exposed to received days 1 5 a 28-day cycle 125...
<p>Pharmacokinetic parameters of guadecitabine and decitabine after injection</p>
<p>LINE1 changes in tumor CpG 1-3 on cycle 1 day 8 from baseline. LINE1 DNA individual patient biopsy samples.</p>