A5103140401- Metal complexes synthesis and properties
- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- Cancer, Lipids, and Metabolism
- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- Cancer, Hypoxia, and Metabolism
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Diet, Metabolism, and Disease
- Click Chemistry and Applications
- Synthesis and biological activity
- Carcinogens and Genotoxicity Assessment
- Monoclonal and Polyclonal Antibodies Research
- Chemical Reactions and Isotopes
- Synthesis and Biological Evaluation
- Lipid Membrane Structure and Behavior
- Lubricants and Their Additives
- Lung Cancer Treatments and Mutations
- PI3K/AKT/mTOR signaling in cancer
- Bladder and Urothelial Cancer Treatments
- CRISPR and Genetic Engineering
Quantum Leap Healthcare Collaborative
2022
Comprehensive Blood & Cancer Center
2022
University of California, Davis
2010-2020
UC Davis Comprehensive Cancer Center
2013-2020
Accelerated Medical Diagnostics (United States)
2013-2020
University of California Davis Medical Center
2009-2019
Lawrence Livermore National Laboratory
2003-2011
In-Q-Tel
2010
Jilin University
2010
University of Georgia
2009
An anthraquinone-linked duplex DNA oligomer containing 60 base pairs was synthesized by PCR. The strand complementary to the quinone-containing has four isolated GG steps, which serve as traps for a migrating radical cation. Irradiation of quinone leads electron transfer from forming anthraquinone anion and cation migrates through DNA, causing reaction at steps revealed breaks. efficiency cleavage falls off exponentially with distance (slope = −0.02 Å −1 ). This finding necessitates...
Single-stranded DNA genomes have been constructed that site-specifically contain the 7,8-dihydro-8-oxo-2'-deoxyguanine (8-oxoG) oxidation products guanidinohydantoin (Gh) and two stable stereoisomers of spiroiminodihydantoin (Sp1 Sp2). The circular viral were transfected into wild-type AB1157 Escherichia coli, efficiency lesion bypass by polymerase(s) was assessed. Viral progeny analyzed for mutation frequency type using recently developed restriction endonuclease postlabeling (REAP) assay....
A G to T mutation has been observed at the third position of codon 249 p53 tumor-suppressor gene in over 50% hepatocellular carcinoma cases associated with high exposure aflatoxin B 1 (AFB ). Hypotheses have put forth that AFB , concert hepatitis virus (HBV), may play a role formation of, and/or selection for, this mutation. The primary DNA adduct is 8,9-dihydro-8-( N 7 -guanyl)-9-hydroxyaflatoxin -N7-Gua), which converted naturally two secondary lesions, an apurinic site and...
Three single-stranded DNA genomes have been constructed that contain the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) oxidation products oxaluric acid, oxazalone, and cyanuric acid. Oligonucleotides containing each lesion were synthesized by treating an oligonucleotide a single 8-oxodG with peroxynitrite, desired isolated HPLC. The modified oligonucleotides ligated into M13mp7L2 bacteriophage in such way was situated at known site lacZ gene fragment of viral genome. circular transfected...
Cisplatin and carboplatin are platinum-based drugs that widely used in cancer chemotherapy. The cytotoxicity of these is mediated by platinum−DNA monoadducts intra- interstrand diadducts, which formed following uptake the drug into nucleus cells. pharmacodynamics display fewer side effects than for cisplatin, albeit with less potency, may be due to differences rates DNA adduct formation. We report use accelerator mass spectrometry (AMS), a sensitive detection method often radiocarbon...
Abstract Limited sensitivity of existing assays has prevented investigation whether Adriamycin–DNA adducts are involved in the anti-tumour potential Adriamycin. Previous detection achieved a few adducts/104 bp DNA, but required use supra-clinical drug concentrations. This work sought to measure at sub-micromolar doses using accelerator mass spectrometry (AMS), technique with origins geochemistry for radiocarbon dating. We have used conditions previously validated (by less sensitive decay...
Spontaneous interaction of purified apolipoproteins and phospholipids results in formation lipoprotein particles with nanometer-sized dimensions; we refer to these assemblies as nanolipoprotein or NLPs. These bilayer constructs can serve suitable mimetics biological membranes are fully soluble aqueous environments. We made NLPs from dimyristoylphospatidylcholine (DMPC) combination each four different apolipoproteins: apoA-I, Δ-apoA-I fragment, apoE4 apolipophorin III (apoLp-III) the silk...
Biomarker-driven drug selection plays a central role in cancer discovery and development, diagnostic strategies to improve the use of traditional chemotherapeutic drugs. DNA-modifying anticancer drugs are still used as first line medication, but drawbacks such resistance side effects remain an issue. Monitoring formation level DNA modifications induced by is potential strategy for stratifying patients predicting efficacy. In this perspective, preclinical clinical data concerning relationship...
Purpose: Activation of the PI3K pathway occurs in over 40% bladder urothelial cancers. The aim this study is to determine therapeutic potential, underlying action, and resistance mechanisms drugs targeting pathway.Experimental Design: Urothelial cancer cell lines patient-derived xenografts (PDXs) were analyzed for alterations their sensitivity small-molecule inhibitor pictilisib alone combination with cisplatin and/or gemcitabine. Potential predictive biomarkers evaluated, RNA sequencing was...
(trans-R,R)-1,2-Diaminocyclohexaneoxalatoplatinum(II) (oxaliplatin) is a recently approved platinum analogue for use in the chemotherapy of metastatic colorectal cancer. Like many cytotoxic drugs, oxaliplatin exerts its antitumor effects by covalent modification DNA. We report an accelerator mass spectrometry (AMS) assay to measure kinetics oxaliplatin-induced DNA damage and repair. determined apparent rate adduction salmon sperm The oxaliplatin−DNA adduct distribution was further...
We report studies testing the importance of Watson–Crick hydrogen bonding, base-pair geometry, and steric effects during DNA replication in living bacterial cells. Nonpolar base shape mimics thymine adenine (abbreviated F Q, respectively) were introduced into Escherichia coli by insertion a phage genome followed transfection vector bacteria. Genetic assays showed that these two bypassed with moderate to high efficiency cells very under damage-response (SOS induction) conditions. Under both...
The technique of accelerator mass spectrometry (AMS) was validated successfully and used to study the pharmacokinetics disposition in dogs a preclinical drug candidate (7-deaza-29-<i>C</i>-methyl-adenosine; Compound A), after oral intravenous administration. primary objective this examine whether A displayed linear kinetics across subpharmacological (microdose) pharmacological dose ranges an animal model, before initiation human microdose study. AMS-derived properties were comparable data...
The in vivo mutagenic properties of 2-aminoimidazolone and 5-guanidino-4-nitroimidazole, two products peroxynitrite oxidation guanine, are reported. Two oligodeoxynucleotides identical sequence, but containing either or 5-guanidino-4-nitroimidazole at a specific site, were ligated into single-stranded M13mp7L2 bacteriophage genomes. Wild-type AB1157 Escherichia coli cells transformed with the site-specific 2-aminoimidazolone- 5-guanidino-4-nitroimidazole-containing genomes, analysis...
Growing evidence suggests that oxidative damage to cells generates mutagenic 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG), which may initiate diseases related aging and carcinogenesis. Kinetic measurement of 8-oxodG metabolism repair in has been hampered by poor assay sensitivity difficulty characterizing the flux oxidized nucleotides through relevant metabolic pathways. We report here development a sensitive quantitative approach kinetics sources MCF-7 human breast cancer accelerator mass...
There is a robust mechanistic basis for the role of oxidation damage to DNA in aetiology various major diseases (cardiovascular, neurodegenerative, cancer). Robust, validated biomarkers are needed measure oxidative context molecular epidemiology, clarify risks associated with stress, improve our understanding its health and disease test intervention strategies ameliorate it. Of urinary oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) most studied. However, there number factors which...
Introduction The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. Investigation of Serial studies Predict Your Therapeutic Response Imaging And moLecular Analysis (ISPY trial) was designed and implemented in early 2020 evaluate investigational agents rapidly simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation challenges ISPY trial during first activity...
The human endonuclease III homologue (hNTH1) removes premutagenic cytosine damage from DNA. This includes 5-hydroxycytosine, which has increased potential for pairing with adenine, resulting in C → T transition mutations. Here we report that hNTH1 acts on both 5-hydroxycytosine and abasic sites preferentially when these are situated opposite guanines Discrimination against other bases is strongly dependent the presence of magnesium. To further elucidate this effect, have introduced mutations...
Hydrogenases constitute a promising class of enzymes for ex vivo hydrogen production. Implementation such applications is currently hindered by oxygen sensitivity and, in the case membrane-bound hydrogenases (MBHs), poor water solubility. Nanolipoprotein particles (NLPs) formed from apolipoproteins and phospholipids offer novel means incorporating MBHs into well-defined water-soluble matrix that maintains enzymatic activity amenable to incorporation more complex architectures. We report...
Formation and repair of platinum (Pt)-induced DNA adducts is a critical step in Pt drug-mediated cytotoxicity. Measurement Pt-DNA adduct kinetics tumors may be useful for better understanding chemoresistance therapeutic response. However, this concept has yet to rigorously tested because technical challenges measuring the at low concentrations consistent access sufficient tumor biopsy material. Ultrasensitive accelerator mass spectrometry was used detect [(14)C]carboplatin-DNA monoadducts...