A5079657944- Radiomics and Machine Learning in Medical Imaging
- AI in cancer detection
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- T-cell and Retrovirus Studies
- Renal cell carcinoma treatment
- Folate and B Vitamins Research
- Cancer therapeutics and mechanisms
- Cardiovascular Effects of Exercise
- Drug Transport and Resistance Mechanisms
- Amino Acid Enzymes and Metabolism
- Metabolism and Genetic Disorders
- Cancer, Hypoxia, and Metabolism
- Lung Cancer Treatments and Mutations
- Lymphoma Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Cancer Research and Treatments
- Glutathione Transferases and Polymorphisms
- Ovarian cancer diagnosis and treatment
- Alcoholism and Thiamine Deficiency
- Extracellular vesicles in disease
- Epigenetics and DNA Methylation
- Neutropenia and Cancer Infections
- HER2/EGFR in Cancer Research
- Immune Cell Function and Interaction
National Cancer Institute
2016-2025
National Institutes of Health
1990-2025
University of Kentucky
2007-2023
Markey Cancer Center
2009-2023
Center for Cancer Research
2020-2023
Lexington Clinic
2010-2022
Specim (Finland)
2017
University of Utah
2012
Intermountain Medical Center
2012
Arno Therapeutics (United States)
2009-2010
Abstract Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment propagation, affecting accuracy of modeling cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 matched patient (PT) samples from 509 models. CNA inferences based on DNA sequencing microarray data displayed substantially higher resolution...
Increased expression of the glutathione S-transferase (GST; E.C.2.5.1.18) pi class isozyme is associated with both malignant transformation and drug resistance, as well decreased estrogen receptor content in breast cancer. In order to further characterize role this enzyme we cloned cDNA encoding human GST developed two eukaryotic vectors using either metallothionein IIa or cytomegalovirus immediate-early promoters. These were cotransfected pSV2neo into drug-sensitive MCF-7 cancer cells,...
The gene that produces the precursor RNA transcript to three largest structural rRNA molecules (rDNA) is present in multiple copies and organized into clusters. 10 human rDNA clusters represent <0.5% of diploid genome but are critically important for cellular viability. Individual genes within possess very high levels sequence identity with respect each other local concentration, making them ideal substrates genomic rearrangement driven by dysregulated homologous recombination. We recently...
Abstract Microcystins are a family of cyclic peptides that potent inhibitors the protein phosphatase families PP1 and PP2A. Only three human proteins thought to be able mediate hepatic uptake microcystins (the organic anion-transporting polypeptides OATP1B1, OATP1B3, OATP1A2), predominant expression these transporters accounts for liver-specific toxicity microcystins. A significant obstacle in study as anticancer drugs is requirement specific transport cellular uptake. We report OATP1B3 mRNA...
Abstract Over the past decade, multiple trials, including precision medicine trial National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH, EAY131, NCT02465060) have sought to determine if treating cancer based on specific genomic alterations is effective, irrespective of histology. Although many therapies are now approved treatment cancers harboring alterations, most patients do not respond targeting a single alteration. Further, when antitumor responses occur, they often...
Abstract Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) patients platinum resistant/refractory HGOC (prrHGOC). Expiremental design: Following run-in phase I study to assess ARB prrHGOC...
Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is a key contributor to cancer, making PI3K inhibitors promising approach for targeted therapy. The selectivity available varies across different isoforms. Alpelisib and inavolisib are selective α-isoform, while duvelisib targets δ- γ-isoforms, copanlisib pan-PI3K inhibitor, active against all This study investigated activity these four in combination with other agents using multi-cell type tumor spheroids composed 60%...
Transporter-mediated processes in the lactating mammary gland may explain significant accumulation of certain drugs breast milk. The purpose this study was to identify potential candidate drug transport proteins involved Quantitative reverse transcription-polymerase chain reaction methods were developed determine relative RNA levels 30 different transporter genes. Transporter gene epithelial cells (MEC) purified from pooled fresh milk samples compared with nonlactating MEC, liver, and kidney...
The development of multidrug resistance in MCF7 human breast cancer cells is associated with overexpression P-glycoprotein, changes activities several detoxication enzymes, and loss hormone sensitivity estrogen receptors (ERs). We have cloned the cDNA for one drug-detoxifying enzymes overexpressed multidrug-resistant (AdrR MCF7), anionic isozyme glutathione S-transferase (GST pi). Hybridization this GST pi cDNA, pi-1, demonstrated that increased activity AdrR but not amplification gene....
The consistent deletion of 3p21 in lung cancer has led to intensive efforts identify a tumor suppressor gene at this locus. We recently mapped the for selenium-dependent drug-detoxifying enzyme glutathione peroxidase 1 (GPX1) location by situ hybridization. developed polymerase chain reaction-based assay which demonstrated existence three GPX1 alleles characterized number alanines polyalanine coding sequence exon 1. These produced heterozygote frequency 70% two separate populations: normal...
Purpose: Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues can be detected the blood. Here, we evaluate potential using circulating EVs as early diagnostic markers long-term cardiac injury.Experimental Design: Using mouse model doxorubicin (DOX)-induced injury, quantified serum EVs, analyzed proteomes, measured oxidized protein levels released...
Microcystins are potent phosphatase inhibitors and cellular toxins. They require active transport by OATP1B1 OATP1B3 transporters for uptake into human cells, the high expression of these in liver accounts their selective hepatic toxicity. Several tumors have been shown to levels but not OATP1B1, main transporter cells. We hypothesized that microcystin variants could be isolated transported preferentially relative advance as anticancer agents with clinically tolerable Microcystin tested...
Abstract Purpose: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible costimulator (ICOS) highly expressed by TFH, representing potential target. MEDI-570 monoclonal antibody against ICOS, which eliminates ICOS+ in preclinical models. Patients and Methods: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), clinical activity T-NHL. NCI-9930 phase I, first-in-human study...
Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone (PR) in human breast tumors. Because GST pi also is expressed normal epithelium, an immunohistochemical assay uses affinity-purified polyclonal antibodies was developed examine the possible relationship between expression cancer cells hormone expression, as well prognosis, patients with primary...
The nucleotide sequence of the mdr1 gene encoding a putative drug efflux pump (P-glycoprotein) is homologous to class bacterial membrane-associated transport proteins. These proteins are part multicomponent system that includes soluble periplasmic bind substrates, channeling them through membrane in an energy-dependent manner. We have investigated possibility similar exists multidrug-resistant human MCF-7 breast cancer cell line was initially selected for resistance doxorubicin (AdrR MCF-7)....