A5102855835- Pancreatic and Hepatic Oncology Research
- Cancer, Hypoxia, and Metabolism
- Medical Imaging Techniques and Applications
- MRI in cancer diagnosis
- Radiomics and Machine Learning in Medical Imaging
- Nanoparticle-Based Drug Delivery
- Nanoplatforms for cancer theranostics
- Glioma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Cancer, Lipids, and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Cell Adhesion Molecules Research
- Cerebrovascular and Carotid Artery Diseases
- Cancer Research and Treatments
- Protease and Inhibitor Mechanisms
- Synthesis and bioactivity of alkaloids
- Coronary Interventions and Diagnostics
- RNA modifications and cancer
- Electrospun Nanofibers in Biomedical Applications
- PARP inhibition in cancer therapy
- Folate and B Vitamins Research
- Lipoproteins and Cardiovascular Health
- Metabolomics and Mass Spectrometry Studies
- Pancreatitis Pathology and Treatment
- Anodic Oxide Films and Nanostructures
University of Pennsylvania
2004-2025
California University of Pennsylvania
2024-2025
Children's Hospital of Philadelphia
2005-2008
Johnson Foundation
2008
Hospital of the University of Pennsylvania
2005
Abstract Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [18F](2S,4R)4-fluoroglutamine ([18F]4F-Gln) PET measure tumor cellular pool size, whose change might reveal pharmacodynamic (PD) effect drugs targeting cancer-specific pathway. High glutaminase (GLS) activity in TNBC tumors resulted low size assayed via high-resolution 1H...
The clinical use of metallic expandable intravascular stents has resulted in improved therapeutic outcomes for coronary artery disease. However, arterial reobstruction after stenting, in-stent restenosis, remains an important problem. Gene therapy to treat restenosis by using gene vector delivery from the stent surfaces never been demonstrated. present studies investigated hypothesis that metal–bisphosphonate binding can enable site-specific metal surfaces. Polyallylamine bisphosphonate...
Background— Local drug delivery from polymer-coated stents has demonstrated efficacy for preventing in-stent restenosis; however, both the inflammatory effects of polymer coatings and concerns about late outcomes drug-eluting stent use indicate need to investigate innovative approaches, such as combining localized gene therapy with angioplasty. Thus, we investigated hypothesis that adenoviral vectors (Ad) could be delivered bare-metal surfaces a synthetic complex reversible vector binding....
Abstract We seek to establish a parsimonious mathematical framework for understanding the interaction and dynamics of response pancreatic cancer NGC triple chemotherapy regimen (mNab-paclitaxel, gemcitabine, cisplatin), stromal-targeting drugs (calcipotriol losartan), an immune checkpoint inhibitor (anti-PD-L1). developed set ordinary differential equations describing changes in tumor size (growth regression) under influence five cocktails treatments. Model calibration relies on three volume...
Abstract Purpose: In pancreatic ductal adenocarcinoma (PDAC), KRAS mutations drive both cancer cell growth and formation of a dense stroma. Small molecule inhibitors (KRASi) represent promising new treatment hence clinical tools that can assess early response, detect resistance and/or predict prolonged survival are desirable to understand biology KRASi. We hypothesized diffusion-weighted MRI (DWI) death while dynamic contrast enhanced (DCE) magnetization transfer ratio (MTR) imaging...
The dense stroma underlies the drug resistance of pancreatic ductal adenocarcinoma (PDA) and has motivated development stroma-directed drugs. Our objective is to test concept that dynamic contrast-enhanced (DCE) MRI using FDA-approved contrast media, an imaging method sensitive tumor microenvironment, can detect early responses drug.Imaging studies were performed in three mouse models exhibiting high desmoplastic reactions: autochthonous PDA genetically engineered mice (KPC), orthotopic...
Low-density lipoprotein (LDL) provides a highly versatile natural nanoplatform for delivery of visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI) contrast agents photodynamic therapy chemotherapeutic to normal neoplastic cells that overexpress low-density receptors (LDLRs). Extension other lipoproteins ranging in diameter from about 10 nm (high-density [HDL]) over micron (chylomicrons) is feasible. Loading therapeutic onto into these particles has been achieved...
The poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit.
Aggressive cancers such as triple-negative breast cancer (TNBC) avidly metabolize glutamine a feature of their malignant phenotype. The conversion to glutamate by the glutaminase enzyme represents first and rate-limiting step this pathway target for drug development. Indeed, novel inhibitor (GLSi) has been developed tested in clinical trials but with limited success, suggesting potential biomarker select patients who could benefit from therapy. Here, we studied nonmetabolized amino acid...
KPC (KrasG12D:Trp53R172H:Pdx1-Cre) and CKS (KrasG12D:Smad4L/L:Ptf1a-Cre) mice are genetically engineered mouse (GEM) models that capture features of human pancreatic ductal adenocarcinoma (PDAC) intraductal papillary mucinous neoplasms (IPMN), respectively. We compared these autochthonous tumors using quantitative imaging metrics from diffusion-weighted MRI (DW-MRI) dynamic contrast enhanced (DCE)-MRI in reference to histological including cell density, fibrosis, microvasculature density....
In triple-negative breast cancer (TNBC) that relies on catabolism of amino acid glutamine, glutaminase (GLS) converts glutamine to glutamate, which facilitates glutathione synthesis by mediating the enrichment intracellular cystine via xCT antiporter activity. To overcome chemo resistant TNBC, we have tested a strategy disrupting cellular redox balance inhibition GLS and CB839 Erastin, respectively. Key findings our study include: 1. Dual metabolic (CB839+Erastin) led significant increases...
Abstract Hypothesis: The dense stroma present in pancreatic ductal adenocarcinoma (PDA) harbors a unique tumor microenvironment (TME) that is immune suppressive and underlies the chemo-resistance of PDA. We have evaluated synthetic vitamin D combined with chemoimmunotherapy pilot clinical study (NCT03519308). To elucidate underlying mechanisms this treatment, we designed matched genetically engineered mouse model PDA (KPC mice) to test hypothesis enhances effect chemotherapy or without...
Abstract Introduction Pancreatic ductal adenocarcinoma (PDA) is a deadly cancer with limited treatment options. Oncogene KRAS mutations found in majority of PDA patients KRAS(G12D) mutation being the most common. A new specific inhibitor, MRTX1133 has been shown to induce rapid tumor regression models while effect on stroma only revealed by postmortem analyses specimens, making it hard assess dynamics remodeling. Furthermore, clinical testing KRAS(G12C) ~50% responded despite presence...
Abstract In pancreatic ductal adenocarcinoma (PDAC), KRAS mutations drive both cancer cell growth and formation of a dense stroma. Small molecule inhibitors (KRASi) represent breakthrough for PDAC treatment hence clinical tools that can assess early response, detect resistance and/or predict prolonged survival are desirable management patients undergoing KRASi therapy. We hypothesized diffusion-weighted MRI (DWI) death while dynamic contrast enhanced (DCE) magnetization transfer ratio (MTR)...
Motivation: KRAS mutations occur in 90% of pancreatic ductal adenocarcinoma(PDA) with G12Dmutation being the most common.Recent KRAS(G12D) inhibitors have unraveled an exciting therapeutic opportunity for this deadly cancer,as they are tested clinical trials. Goal(s): However, prior use KRAS(G12C)inhibitors lung cancer treatment showed mere 50% patient response,despite accurate genetic mutation,calling biomarkers which can assess drug-target engagement early on and predict outcome. Approach:...
Cytotoxic chemotherapy plays an important role for extending the survival of patients with pancreatic ductal adenocarcinoma (PDAC). To enhance efficacy eradicating cancer cells, we have compared standard care (combination nab-paclitaxel, gemcitabine and cisplatin, NGC) versus NGC plus stroma-directed agents (calcipotriol losartan, respectively) in a genetically engineered mouse model PDAC. Over 2-week study period, MRI was conducted to measure tumor size test sensitivity imaging markers...
It was previously reported that a nanoparticle made of ultra pH‐sensitive peptides (pH‐NP) undergoes self‐dissolution in moderately acidic (pH ≤ 6.9) condition mimics the pH extracellular tumor environment, leading to release drug cargo molecules. Herein, it is demonstrated this peptide‐based nanodelivery platform can be used formulate poorly water‐soluble small molecules improve cancer diagnosis and treatment. Indocyanine green (ICG) encapsulated pH‐NP (ICG‐pH‐NP) significantly increases...
Abstract Background: Glutamine is an important metabolic substrate in many aggressive tumors, with comparable importance to glucose metabolism. Utilizing human breast cancer mouse xenograft models, we studied the kinetics of PET imaging agent, [5-11C] glutamine, a biochemical authentic for glutamine metabolism, further characterize metabolism and downstream labeled metabolites. Studies were performed without inhibition enzyme, glutaminase (GLS), first step catabolism that generates...
Cancer Detection In article number 2100081, I-Wei Chen, Rong Zhou, and co-workers demonstrate that a peptide-based nanodelivery platform made of pH-sensitive peptides (blue, turning red when protonated in low pH) decorated by PEG (yellow) can be used to formulate poorly water-soluble small molecules improve cancer diagnosis treatment. The nanoparticles, stable blood, self-dissolve mildly acidic extracellular space the tumor, thereby releasing encapsulated molecular drug cargos (silver...