A5058837925- Prostate Cancer Treatment and Research
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Radiation Therapy and Dosimetry
- Prostate Cancer Diagnosis and Treatment
- Cell death mechanisms and regulation
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Drug-Induced Hepatotoxicity and Protection
- Pancreatic and Hepatic Oncology Research
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Radiation Effects in Electronics
- Groundwater flow and contamination studies
- Cancer Treatment and Pharmacology
- Esophageal and GI Pathology
- Plant-derived Lignans Synthesis and Bioactivity
- Liver Diseases and Immunity
- Cardiac Structural Anomalies and Repair
- NF-κB Signaling Pathways
- Pharmacogenetics and Drug Metabolism
- Immune Response and Inflammation
- Birth, Development, and Health
AstraZeneca (United States)
2019-2023
Nanjing University of Science and Technology
2023
Ningbo Medical Center Lihuili Hospital
2021-2022
Ningbo University
2016-2022
AstraZeneca (Japan)
2019
University of Bergen
2017
BeiGene (China)
2017
Tianjin University
2016
University of Duisburg-Essen
2008-2009
Multiple loss-of-function alterations in genes that are involved DNA repair, including homologous recombination associated with response to poly(adenosine diphosphate–ribose) polymerase (PARP) inhibition patients prostate and other cancers.
We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease progressed during previous treatment a next-generation hormonal agent. The results final analysis overall have not yet been reported. In an open-label, phase 3 trial, we randomly...
BACKGROUND: Preclinical studies and results of a phase 2 trial abiraterone olaparib suggest combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor is with next-generation hormonal agent to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted double-blind, 3 versus placebo in patients mCRPC first-line setting. Patients were enrolled regardless homologous recombination repair gene mutation (HRRm) status. HRRm status was...
11 Background: Preclinical studies have shown combined anti-tumor effect through interactions between poly(adenosine diphosphate–ribose) polymerase and androgen receptor signaling pathways. A Phase II trial (NCT01972217) in pts with mCRPC unselected by homologous recombination repair (HRR) status who previously received docetaxel demonstrated improved radiographic progression-free survival (rPFS) for treated ola + abi vs pbo (Clarke N, 2018). The III PROpel study (NCT03732820) evaluates the...
Abstract Purpose: Successful implementation of genomic testing in clinical practice is critical for identification men with metastatic castration-resistant prostate cancer (mCRPC) eligible olaparib and future molecularly targeted therapies. Patients Methods: An investigational trial assay, based on the FoundationOneCDx tissue test, was used to prospectively identify patients qualifying homologous recombination repair gene alterations phase III PROfound study. Evaluation next-generation...
Olaparib improved PFS and OS across subgroups of BRCA1/2mut #prostatecancer patients in the PROFOUND phase III trial.
Abstract Purpose: The phase III PROfound study (NCT02987543) evaluated olaparib versus abiraterone or enzalutamide (control) in metastatic castration-resistant prostate cancer (mCRPC) with tumor homologous recombination repair (HRR) gene alterations. We present exploratory analyses on the use of circulating DNA (ctDNA) testing as an additional method to identify patients mCRPC HRR alterations who may be eligible for treatment. Patients and Methods: Plasma samples collected during screening...
Phase III randomized trial data have confirmed the activity for olaparib in homologous recombination repair (HRR) mutated metastatic castration-resistant prostate cancer (mCRPC) post next-generation hormonal agent (NHA) progression. Preclinical suggested potential a combined effect between and NHAs irrespective of whether an HRR gene alteration was present. NCT01972217 randomised double-blind II study which evaluated abiraterone versus placebo mCRPC patients who had received prior...
27 Background: ctDNA testing offers additional opportunities for homologous recombination repair (HRR) gene alteration determination in patients who are not able to access tumor tissue testing. Alteration ctDNA, BRCA1, BRCA2 and ATM alterations was performed retrospectively the PROfound study (phase 3 trial of olaparib versus physician’s choice abiraterone or enzalutamide men with HRR gene-mutated mCRPC [NCT02987543]). Methods: samples were sequenced at FMI, using FoundationOne Liquid CDx...
Groundwater vulnerability assessment has been regarded as the initial step to understand and evaluate susceptibility of subsurface contamination. As one most widely used models, DRASTIC applied worldwide. However, problems associated with model, such subjectivity in rating weighting schemes, have led modified versions this model for better representing aquifer. In study, a was formulated by adjusting scores based on Wilcoxon rank-sum test Analytic Hierarchy Process. The then evaluation...
126 Background: The Phase 3 PROfound trial (NCT02987543) met its primary endpoint and key secondary endpoints, including improved overall survival (OS) for olaparib in men with mCRPC alterations BRCA1, BRCA2, or ATM (Cohort A). We report gene-by-gene analysis of antitumor activity among the 15 prespecified homologous recombination repair (HRR) genes. Methods: Pts were randomized to (300 mg bid; n=256) physician’s choice enzalutamide abiraterone (control; n=131). Exploratory analyses pts...
Dendritic cell (DC) frequencies in the blood of patients with chronic hepatitis C virus (HCV) infection have been shown to be reduced significantly compared those healthy individuals. There is a further reduction circulating myeloid DCs (MDCs) and plasmacytoid (PDCs) HCV receiving alpha interferon (IFN-alpha)-based antiviral therapy. Altered homing behaviour may possible mechanism for their 'loss' peripheral these clinical conditions. Systemic chemokine levels were measured by ELISA....
Rationale: Light pollution leads to high risk of obesity but the underlying mechanism is not known except for influence altered circadian rhythm. Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism, its role in circadian-related clear. Methods: Wild-type (WT) and Ppara-null (KO) mice on a high-fat diet (HFD) were treated with neon light at night 6 weeks. Body weights recorded consumption measured. The hypothalamus, liver, adipose serum collected experimentation....
TPS340 Background: A Phase II trial showed olaparib (tablets, 300 mg bid) in combination with abiraterone (1000 od plus prednisone/prednisolone 5 significantly prolonged radiologic progression-free survival (rPFS) compared alone (median 13.8 vs 8.2 months; hazard ratio 0.65, 95% CI 0.44–0.97, P=0.034) patients (pts) mCRPC the second-line metastatic setting who received prior docetaxel (Clarke et al. Lancet Oncol 2018). Treatment benefits were achieved irrespective of homologous recombination...
134 Background: Optimal sequencing of therapies for mCRPC is not established. In the Phase III PROfound study (NCT02987543), ola significantly prolonged radiographic progression-free survival (rPFS) vs physician’s choice new hormonal agent (pcNHA) in pts with and an alteration genes a direct or indirect role HRR. We report exploratory subgroup analyses by prior taxane (yes no). Methods: Men that had progressed on NHA were randomized to (tablets; 300 mg bid) pcNHA (enzalutamide abiraterone)....
Interferon-α (IFN-α) is widely used for the treatment of malignant and viral diseases. Conflicting results IFN-α–mediated effects on dendritic cell (DC) homeostasis have been reported its impact human blood DC largely unknown. We investigated phenotypic, migratory, allostimulatory activities plasmacytoid DCs (PDCs) myeloid (MDCs) upon in vitro exposure to IFN-α without addition exogenous growth factors. IFN-α–exposed PDCs exhibited an increase viability but showed immature phenotype a...
The recombinant adeno‑associated virus 8 (rAAV8) vector is a widely used tool in basic research and clinical trials. cytomegalovirus immediate‑early enhancer/chicken β‑actin (CAG) promoter synthetic adenoviral constructs with wide spectrum notable efficiency. thyroxine binding globulin (TBG) liver‑specific promoter, which directs transgene expression hepatocytes. However, the transduction efficiency of rAAV dependent on both administration routes elements. In present study, liver following...