A5100436604- PARP inhibition in cancer therapy
- Neutropenia and Cancer Infections
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- CAR-T cell therapy research
- Integrated Circuits and Semiconductor Failure Analysis
- DNA Repair Mechanisms
- Cell death mechanisms and regulation
- Antimicrobial Resistance in Staphylococcus
- Metal complexes synthesis and properties
- Lung Cancer Treatments and Mutations
- Toxin Mechanisms and Immunotoxins
- CRISPR and Genetic Engineering
- Cancer Diagnosis and Treatment
- Calcium signaling and nucleotide metabolism
- Antibiotics Pharmacokinetics and Efficacy
- Phytochemistry and biological activities of Ficus species
- Ovarian cancer diagnosis and treatment
- Cancer survivorship and care
- Chronic Kidney Disease and Diabetes
- Bioactive Compounds and Antitumor Agents
- Inflammatory Biomarkers in Disease Prognosis
- Protein Interaction Studies and Fluorescence Analysis
- Cancer-related cognitive impairment studies
- Radiopharmaceutical Chemistry and Applications
Sichuan Cancer Hospital
2023-2024
University of Electronic Science and Technology of China
2023-2024
Fujian Medical University
2020-2024
Wenzhou Medical University
2023
First Affiliated Hospital of Wenzhou Medical University
2023
Soochow University
2022
First Affiliated Hospital of Soochow University
2022
Beijing University of Chinese Medicine
2022
People's Hospital of Xinjiang Uygur Autonomous Region
2022
Novartis (Switzerland)
2020-2022
Abstract Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors are undergoing clinical evaluation for cancer therapy. Because PARP inhibition has been shown to enhance tumor cell sensitivity radiation, we investigated the in vitro and vivo effects of novel inhibitor E7016. Experimental Design: The effect E7016 on radiosensitivity lines was evaluated using clonogenic survival. DNA damage repair were measured γH2AX foci neutral comet assay. Mitotic catastrophe determined by immunostaining....
PARP is essential for recognition and repair of DNA damage. In preclinical models, inhibitors modulate topoisomerase I inhibitor-mediated This phase study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), pharmacodynamics (PD) veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan.
The DREAM complex orchestrates cell quiescence and the cycle. However, how is deregulated in cancer remains elusive. Here, we report that PAF (PCLAF/KIAA0101) drives exit to promote lung tumorigenesis by remodeling complex. highly expressed adenocarcinoma (LUAD) associated with poor prognosis. Importantly, Paf knockout markedly suppressed LUAD development mouse models. depletion induced growth arrest. required for global expression of cell-cycle genes controlled repressive Mechanistically,...
The nuclear enzyme poly(ADP-ribose) polymerase (PARP), which has been shown to be activated following experimental traumatic brain injury (TBI), binds DNA strand breaks and utilizes nicotinamide adenine dinucleotide (NAD) as a substrate. Since consumption of NAD may deleterious recovery in the setting CNS injury, we examined effect potent PARP inhibitor, GPI 6150, on histological outcome TBI rat. Rats (n = 16) were anesthetized, received preinjury dose 6150 (30 min; 15 mg/kg, i.p.),...
This study evaluated poly(ADP-ribose) polymerase (PARP) inhibition as a new therapeutic approach for peripheral diabetic neuropathy using clinically relevant animal model and endpoints, nitrotyrosine (NT), TNF-α, nitrite/nitrate potential biomarkers of the disease. Control streptozotocin-diabetic rats were maintained with or without treatment orally active PARP inhibitor 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]anthracen-3-one (GPI-15,427), 30 mg kg−1 d−1, 10 wk after...
In this study, we tested the ability of a novel poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor, 10-(4-methyl-piperazin-1-ylmethyl)-2H-7-oxa-1,2-diaza-benzo[de]-anthracen-3-one (GPI-15427), to enhance effect radiotherapy in xenograft model human head and neck squamous cell carcinoma (HNSCC).Human HNSCC tumors were established female nude mice: animals treated with orally administered GPI-15427 at varied doses prior tumor irradiation. vitro vivo apoptosis analyses neutral...
Abstract Poly(ADP‐ribose) polymerase‐1 (PARP‐1) safeguards genomic integrity by limiting sister chromatid exchanges. Overstimulation of PARP‐1 extensive DNA damage, however, can result in cell death, as prolonged activation depletes NAD + , a substrate, and elevates nicotinamide, product. The decline the rise nicotinamide may downregulate activity Sir2, ‐dependent deacetylases, because deacetylation Sir2 is dependent on high concentration inhibited physiologic level nicotinamide. deacetylase...
A series of aza-5[H]-phenanthridin-6-ones were synthesized and evaluated as inhibitors poly ADP-ribose polymerase-1 (PARP-1). Inhibitory potency the unsubstituted (i.e., benzonaphthyridones) was dependent on position nitrogen atom within core structure. The ring analogues (7-, 8-, 10-aza-5[H]-phenanthridin-6-ones) an order magnitude less potent than C (1-, 2-, 3-, 4-aza-5[H]-phenanthridin-6-ones). Preliminary stroke results from 1- 2-aza-5[H]-phenanthridin-6-one prompted structure-activity...
Objective: Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide by poly(ADP-ribose) polymerase (PARP) and degraded glycohydrolase (PARG). The activation of the PARP/PARG pathway has been found in a variety animal models diseases, including septic shock-like syndrome. We have previously demonstrated that PARP inhibition 3-ami-nobenzamide or GPI 6150 ameliorates multiple organ dysfunctions induced zymosan. In present study, we investigated whether similar effect could be...
Poly (ADP-ribosyl)ation, an early post-translational modification in response to DNA damage, is catalyzed by poly (ADP-ribose) polymerase (PARP-1) and catabolized poly(ADP-ribose) glycohydrolase (PARG). The aim of this study was investigate the role PARG on modulation inflammatory caused splanchnic ischemia reperfusion. SAO shock rats wild-type (WT) mice associated with a significant neutrophil infiltration ileum production tumor necrosis factor-alpha (TNF-alpha). Reperfused tissue sections...
Long-term clinical outcomes are necessary to assess the cost-effectiveness of new treatments over a lifetime horizon. Without long-term trial data, current practice extrapolate survival beyond period involves fitting alternative parametric models observed survival. Choosing most appropriate model is based on how well each fits data. Supplementing data with feedback from experts may improve plausibility extrapolations. We demonstrate feasibility formally integrating estimates empirical...
ABSTRACT T cell exhaustion is the main cause of sepsis-induced immunosuppression and associated with poor prognosis. Nicotinamide adenine dinucleotide (NAD + ) well known for its anti-aging effect, but role in remains to be elucidated. In present study, using a classic septic animal model, we found that levels NAD downstream molecule, which sirtuins 1 (SIRT1), cells sepsis were decreased. Supplementation nicotinamide ribose (NR), precursor , right after cecal ligation puncture significantly...