A5028539956- Adenosine and Purinergic Signaling
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Pancreatic and Hepatic Oncology Research
- Adolescent and Pediatric Healthcare
- PI3K/AKT/mTOR signaling in cancer
- BRCA gene mutations in cancer
- Bioinformatics and Genomic Networks
- Colorectal Cancer Treatments and Studies
- Pancreatitis Pathology and Treatment
- Peptidase Inhibition and Analysis
- Lung Cancer Research Studies
- Gastric Cancer Management and Outcomes
- Genetic factors in colorectal cancer
- Neuroendocrine Tumor Research Advances
- Cancer-related Molecular Pathways
- Inflammatory mediators and NSAID effects
- Advanced Breast Cancer Therapies
- Cancer, Lipids, and Metabolism
- CAR-T cell therapy research
- NF-κB Signaling Pathways
- Breast Cancer Treatment Studies
- Immune Response and Inflammation
- Nutrition, Genetics, and Disease
- Lung Cancer Treatments and Mutations
The University of Texas MD Anderson Cancer Center
2015-2025
St. James's Hospital
2022
The University of Texas Health Science Center at Houston
2021
University of Pennsylvania
1981
University of Geneva
1981
Abstract Purpose: Genomic profiling studies suggest that triple-negative breast cancer (TNBC) is a heterogeneous disease. In this study, we sought to define TNBC subtypes and identify subtype-specific markers targets. Experimental Design: RNA DNA analyses were conducted on 198 tumors [estrogen receptor (ER) negativity defined as Allred scale value ≤ 2] with >50% cellularity (discovery set: n = 84; validation 114) collected at Baylor College of Medicine (Houston, TX). An external...
Basal-like breast cancers (BLBCs) are aggressive associated with poor survival. Defining the key drivers of BLBC growth will allow identification molecules for targeted therapy. In this study, we performed a primary screen integrating multiple assays that compare transcription factor expression and activity in non-BLBC at RNA, DNA, protein levels. This integrated identified 33 factors were elevated comparing mRNA expression, DNA cis-element sequences, or DNA-binding activity. secondary to...
Abstract The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process tumorigenesis would aid in establishing targets for effective prevention therapy. Here, we interrogated differential molecular mechanisms dependent on cell origin subtype promote PDAC initiation established tumors. Transcriptomic analysis cell-of-origin–dependent epithelial gene signatures...
Abstract Background The most aggressive form of breast cancer is triple-negative (TNBC), which lacks expression the estrogen receptor (ER) and progesterone (PR), does not have overexpression human epidermal growth factor 2 (HER2). Treatment options for women with TNBC tumors are limited, unlike those ER-positive that can be treated hormone therapy, or HER2-positive anti-HER2 therapy. Therefore, we sought to identify novel targeted therapies TNBC. In this study, investigated potential a...
Estrogen receptor–negative (ER-negative) breast cancers are extremely aggressive and associated with poor prognosis. In particular, effective treatment strategies limited for patients diagnosed triple cancer (TNBC), which also carries the worst prognosis of all forms cancer; therefore, extensive studies have focused on identification molecularly targeted therapies this tumor subtype. Here, we sought to identify molecular targets that capable suppressing tumorigenesis in TNBCs. Specifically,...
Abstract A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon‐γ signaling as a key pathway. In this study, we combine intermittent low‐dose ERL ± SUL treatment the rat colon (Pirc) model mechanistic studies on tumor‐associated modulation. At clinically relevant doses, short‐term (16 weeks) and long‐term (46 administration results near‐complete tumor suppression Pirc...
Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous intraepithelial neoplasia (PanIN), which a precursor to PDAC, results CD73 expression the neoplastic epithelium some populations infiltrating immune cells, macrophages CD8 T cells. ecto-enzyme converts extracellular adenosine monophosphate adenosine, critical inhibitory molecule PDAC. hypothesized...
Abstract A clinical trial in patients with familial adenomatous polyposis (FAP) demonstrated that sulindac plus erlotinib (SUL+ERL) had good efficacy the duodenum and colon, but toxicity issues raised concerns for long-term prevention. We performed a biomarker study rat colon (Pirc) model, observing phosphorylated Erk inhibition polyps up to 10 days after discontinuing ERL+SUL administration. In follow-up lasting 16 weeks, significant reduction of small intestine (SI) tumor burden was...
Abstract Prevention of estrogen receptor (ER)-positive breast cancer is now possible using anti-estrogen drugs; however, this treatment ineffective against ER-negative cancers. In study, we hypothesized that inhibition mTOR will suppress the growth and triple-negative To test hypothesis, used five models: MMTV-erbB2, C3 (1)/SV40TAg, p53-null mammary gland-transplant, p53-mutant BRCA1co/co; MMTV-Cre+/+; p53+/– mouse models to determine whether inhibitor everolimus effective in preventing...
A general strategy for the insertion of nuclear spin labels throughout sequence a protein is illustrated with Escherichia coli lac repressor. Examples are shown where 19F nucleus incorporated using 3-fluorotyrosine, as well selective additional protons. These selectively inserted nuclei give resonances in respective NMR spectra that can be used to probe structure and function proteins.
Abstract We evaluated the cancer preventive efficacy of TAK-242, an inhibitor Toll-like receptor 4 (TLR4), in a mouse model hepatocellular carcinoma (HCC) occurring context nonalcoholic steatohepatitis (NASH). also assessed cellular events associated with treatment efficacy. tested oral administration at clinically relevant but toxicity-reducing doses and scheduling, mice hepatocyte-specific deletion Pten (HepPten−). The optimal dose gavage formulation TAK-242 were determined to be 30 mg/kg...
Abstract A once-weekly optimized dosing regimen of erlotinib (ERL) in the polyposis rat colon (Pirc) model [1] was a reliable predictor antitumor efficacy familial adenomatous (FAP) patients [2]. Pirc rats are increasingly used as translational tool for FAP studies. Based on transcriptomic data from receiving ERL plus sulindac (SUL) vs. placebo [3], we determined timing changes interferon-γ signaling adenomas, while performing additional dose titration. In that were given administered at 5...
Abstract Background: Women with germline BRCA1 mutations are at an increased risk for developing breast cancer in their lifetime, often a young age more aggressive tumors. At present, prophylactic bilateral mastectomy is the most effective strategy reducing risk. However, this invasive procedure irreversible and associated potential complications. We others have found that PARP inhibitors can delay Brca1-mutant tumor formation mice could be beneficial prevention of cancer. currently...
<p>Supplementary Figure S2. AB-680 treatment significantly alters the gene expression profiles of each identified cluster.</p>
<p>Supplementary Figure S3. CD73 inhibitor treatment does not significantly change Granzyme B or B3GAT1 levels.</p>
<div>Abstract<p>Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous intraepithelial neoplasia (PanIN), which a precursor to PDAC, results CD73 expression the neoplastic epithelium some populations infiltrating immune cells, macrophages CD8 T cells. ecto-enzyme converts extracellular adenosine monophosphate adenosine, critical inhibitory...
<p>Supplementary Figure S5. Treatment with a CD73 small molecule inhibitor does not change AMP or inosine levels in pancreas tissue serum.</p>
<p>Supplementary Figure S1. Description of IHC quantification methods.</p>
<p>Supplementary Figure S4. AB-680 treatments results in distinct changes gene expression macrophages, dendritic cells and naïve T cells.</p>