A5101745077- Advanced Breast Cancer Therapies
- Neuroendocrine Tumor Research Advances
- Pancreatic and Hepatic Oncology Research
- PARP inhibition in cancer therapy
- Chronic Lymphocytic Leukemia Research
- Heat shock proteins research
- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Genomics, phytochemicals, and oxidative stress
- Lung Cancer Research Studies
- Multiple Myeloma Research and Treatments
- ATP Synthase and ATPases Research
- BRCA gene mutations in cancer
- Cytomegalovirus and herpesvirus research
- Bioactive Compounds and Antitumor Agents
- Phytochemicals and Medicinal Plants
- Lung Cancer Treatments and Mutations
- DNA Repair Mechanisms
- Statistical Methods in Clinical Trials
- Biosimilars and Bioanalytical Methods
- Monoclonal and Polyclonal Antibodies Research
- Gastric Cancer Management and Outcomes
Pfizer (United States)
2016-2025
Shanghai Jiao Tong University
2023
Shanghai Chest Hospital
2023
University of Florida
2017-2019
Columbus Oncology and Hematology Associates
2017-2019
Pfizer (France)
2018
Centre Eugène Marquis
2018
Institut Curie
2018
Reckitt Benckiser (United States)
2017
Eisai (United States)
2013-2016
The existence of cancer stem cells (CSCs) in breast has profound implications for prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, its efficacy to inhibit CSCs and potential mechanism.Aldefluor assay mammosphere formation were used evaluate the effect sulforaphane on vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was determine whether could target vivo, as assessed by Aldefluor assay, tumor growth...
Highlights•Atirmociclib (PF-07220060) is a next-generation CDK4 selective inhibitor•Impact reduction on neutrophils was in proportion to increase selectivity•Greater target coverage results deeper anti-tumor responses•Combinatorial agents further atirmociclib efficacySummaryCDK4/6 inhibitors have revolutionized treatment of hormone receptor positive (HR+), HER2 non-amplified (HER2−) breast cancer. Yet, all "dual" CDK4/6 show common dose-limiting hematologic toxicities, foremost neutropenia....
The molecular chaperone heat shock protein 90 (Hsp90) is required for the stabilization and conformational maturation of various oncogenic proteins in cancer. loading kinases to Hsp90 actively mediated by cochaperone Cdc37. crucial role Hsp90-Cdc37 complex has made it an exciting target cancer treatment. In this study, we characterize Cdc37 interaction drug disruption using a reconstituted system. GST pull-down assay ELISA show that binds ADP-bound/nucleotide-free but not ATP-bound Hsp90....
Palbociclib is an orally available CDK4/6 inhibitor. In humans, palbociclib undergoes metabolism mediated primarily by CYP3A and SULT2A1, it also a weak time-dependent The objectives of the current study are to (1) develop physiologically based pharmacokinetic (PBPK) model on in silico, vitro, vivo data palbociclib, (2) verify PBPK with clinical drug-drug interaction (DDI) results strong inhibitor (itraconazole), inducer (rifampin), sensitive substrate (midazolam), (3) predict DDI risk...
Transforming growth factor β (TGF-β) causes arrest at the G1 phase of cell cycle in most types. Both cyclin dependent kinase inhibitor p15INK4B and p21(Cip1/WAF1) genes have been found to be induced by TGF-β human keratinocyte HaCaT cells. Analyses p15 p21 promoters led identification GC-rich sequences capable binding Sp1 transcription factors as necessary elements for induction both promoters. We report here that canonical sites derived from SV40 21 bp repeat could also support promoter...
Abstract Chemotherapy-induced peripheral neuropathy is a dose-limiting side effect of many antineoplastic agents, but the mechanisms underlying toxicities are unclear. At their MTDs, microtubule-binding drugs paclitaxel and ixabepilone induce more severe in mice relative to eribulin mesylate, paralleling toxicity profiles clinic. We hypothesized that severity neurotoxic effects might be explained by levels at which they accumulate nervous system. To test this hypothesis, we compared...
E2212, a novel γ-secretase modulator, is under development for the treatment of Alzheimer's disease. The safety, tolerability, pharmacokinetics, and pharmacodynamics single ascending oral doses (10-250 mg, double-blind, placebo-controlled, randomized) E2212 were evaluated. In this phase I clinical trial, was found to be well tolerated in doses. Maximum dose not achieved up 250 mg. Most AEs mild moderate severity with no identifiable related pattern. There clinically significant findings on...
The small heat shock protein 27 (Hsp27) is a molecular chaperone that involved in variety of cellular functions cancer cells. purpose this research to study Hsp27 vitro metastatic behaviors head and neck squamous cell carcinoma cells (HNSCC). expression primary lines derived from the HNSCC synchronous lymph node metastasis same patient was determined using real-time PCR Western blotting. Proliferation evaluated MTS proliferation assay. Metastatic behavior assessed migration invasion assays....
Abstract Poly(ADP‐ribose) polymerase (PARP) inhibitors have been developed to treat cancers associated with somatic BRCA mutations and germline genetic aberrations involved in the DNA damage response. The efficacy, tolerability, pharmacokinetic/pharmacodynamic (PK/PD) profile of talazoparib, a potent small‐molecule PARP inhibitor, was established 4 clinical studies cancer patients (2 phase 1 PRP‐001 PRP‐002, 2 ABRAZO trial, 3 EMBRACA trial). current study aimed describe population PK...
Palbociclib is indicated for hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer (ABC). Exposure-response analyses were conducted to evaluate efficacy in Asian versus non-Asian patients and with without dose reduction PALOMA-2. PALOMA-2 compared palbociclib plus letrozole placebo ABC. Population pharmacokinetic analysis provided apparent clearance (CL/F) each patient. The time-varying exposure metric, Cavg,t, was calculated using average...
Hsp90 requires cochaperone Cdc37 to load its clients the superchaperone complex. The purpose of this study was utilize split Renilla luciferase protein fragment-assisted complementation (SRL-PFAC) bioluminescence full-length human Hsp90-Cdc37 complex and identity critical residues their contributions for Hsp90/Cdc37 interaction in living cells. SRL-PFAC showed that restored dramatically high activity through Hsp90-Cdc37-assisted N C termini (compared with set controls). Immunoprecipitation...
Abstract This paper describes the pharmacokinetics (PK), mass balance, metabolic profiling, and safety of talazoparib after a single oral dose 14 C‐talazoparib in 6 patients with advanced solid tumors. Patients were aged ≥18 years, histologically confirmed tumor at screening. A 1‐mg solution supplemented 100 µCi C‐labeled was administered. Blood, urine, feces samples collected various time points analyzed for C radioactivity. Metabolic profiling identification also carried out. Mean recovery...
Abstract Poly(ADP‐ribose) polymerase inhibitors, such as talazoparib, may affect hematopoiesis. This analysis characterized the relationship between talazoparib exposure and most common grade ≥ 3 hematopoietic adverse events (AEs) leading to dose modification in phase 2 (ABRAZO) (EMBRACA) trials. The time‐varying average concentration (C avg,t ), along with other baseline variables, anemia, thrombocytopenia, neutropenia were evaluated both by graphical examination using univariate...
This phase I study investigated talazoparib pharmacokinetics (PK) and safety in patients with advanced solid tumours varying degrees of hepatic function.Patients normal function or impairment (mild, moderate severe, based on National Cancer Institute Organ Dysfunction Working Group classification) received 0.5 mg once daily for 22 calendar days. Plasma urine samples after single multiple doses were collected analysed using validated assays. PK data from all the population method. parameters...
Purpose. The two purposes of this study were evaluating preclinical pharmacokinetics MI-219 and predicting clearance (CL) volume distribution at steady-state (Vdss) in humans. Methods. Pharmacokinetic studies conducted on mice, rats, dogs, monkeys. Human CL was predicted using allometric scaling (SA), multi-exponential (ME), rule exponents (RoE), single species scaling, two-term power equation (TTPE), physiologically based vitro-in vivo extrapolation (IVIVE), fu corrected intercept method...