A5075934968- Advanced Breast Cancer Therapies
- Lung Cancer Research Studies
- HER2/EGFR in Cancer Research
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Neuroendocrine Tumor Research Advances
- Biochemical Analysis and Sensing Techniques
- Energy, Environment, Economic Growth
- Diabetes Treatment and Management
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Brain Metastases and Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Inflammatory Biomarkers in Disease Prognosis
- Cancer Treatment and Pharmacology
- Hemoglobinopathies and Related Disorders
- Chromatography in Natural Products
- Head and Neck Cancer Studies
- Pancreatic function and diabetes
- Antibiotic Resistance in Bacteria
- Cancer-related Molecular Pathways
- Iron Metabolism and Disorders
- Diabetes and associated disorders
- Alkaloids: synthesis and pharmacology
- Energy, Environment, and Transportation Policies
Eli Lilly (United States)
2015-2025
The People's Hospital of Guangxi Zhuang Autonomous Region
2019-2023
Jiangxi University of Finance and Economics
2018-2023
Ningxia University
2008-2023
Chinese Medical Association
2023
First Affiliated Hospital of GuangXi Medical University
2023
Guangxi Medical University
2023
Peking University Cancer Hospital
2021-2022
Garvan Institute of Medical Research
2022
Centre for Cancer Biology
2022
Fibroblast growth factor 21 (FGF21) is a metabolic regulator that provides efficient and durable glycemic lipid control in various animal models. However, its potential to treat obesity, major health concern affecting over 30% of the population, has not been fully explored. Here we report systemic administration FGF21 for 2 wk diet-induced obese ob/ob mice lowered their mean body weight by 20% predominantly via reduction adiposity. Although no decrease total caloric intake or effect on...
The primary objective was to evaluate intracranial response rate (iORR) in patients receiving abemaciclib with brain or leptomeningeal metastases (LM) secondary hormone receptor-positive (HR+) metastatic breast cancer (MBC). Secondary objectives evaluated extracranial response, pharmacokinetics, tissue exposure, and safety.This nonrandomized, phase II study (NCT02308020) enrolled tumor subtype-specific cohorts A-D: A (HR+, HER2- MBC), B HER2+ C (HR+ MBC LM), D (brain surgical resection)....
The hypothalamic neuropeptide melanin-concentrating hormone (MCH) has been implicated in a variety of physiological functions including the regulation feeding and energy homeostasis. Two MCH receptors (MCHR1 MCHR2) have identified so far. To decipher functional role receptors, we generated phenotypically characterized mice rendered deficient MCHR1 expression by homologous recombination. Inactivation results (MCHR1-/-) that are resistant to diet-induced obesity. With high-fat diet, body fat...
Abstract This nonrandomized, open-label, multi-cohort Phase 1b study (NCT02779751) investigated the safety and efficacy of abemaciclib plus pembrolizumab with/without anastrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC) without prior CDK4 6 inhibitor exposure. Patients were divided into two cohorts: treatment naïve (cohort 1) pretreated 2). received or 2) over 21-day cycles. The primary...
Activation of free fatty acid receptor 1 (GPR40) by synthetic partial and full agonists occur via distinct allosteric sites. A crystal structure GPR40-TAK-875 complex revealed the site for agonist. Here we report 2.76-Å human GPR40 in with a agonist, compound 1, bound to second site. Unlike TAK-875, which acts as Gαq-coupled is dual Gαq Gαs-coupled binds lipid-rich region near intracellular loop 2 (ICL2), stabilization ICL2 ligand likely primary mechanism enhanced G protein activities. The...
We investigated antimicrobial resistance trends and characteristics of ESBL-producing Escherichia coli isolates from pets whether this correlates with antibiotic usage in the clinic. Clinical samples containing E. diseased cats dogs were screened for sensitivity associated genotypic features. identified 127 1886 (n = 1565) 321) majority urinary tract infections 108, 85%). High rates observed β-lactams fluoroquinolones to > 3 classes (MDR) increased 67% 2012 75% 2017 (P < 0.0001). This was...
The positive correlation between leptin and body fat mass has caused some investigators to speculate that resistance contributes obesity. Loss of ovarian function in human rat is associated with increased gain circulating levels. To study whether ovariectomy produces resistance, Sprague-Dawley female rats were ovariectomized or sham operated injected for 35 days. Ovariectomy (OVX) produced hyperphagia both lean mass. Daily injections initially decreased food intake significantly, but feeding...
Within the human <i>ERBB-2</i> gene promoter, a 100-base pair region 5′ to TATA box enhances basal transcription 200-fold. Two palindromes present within this are important for transcription. The palindrome binding protein was purified homogeneity and found be identical RBPJκ, mammalian homolog of Drosophila Suppressor Hairless (Su(H)). Recombinant RBPJκ bound promoter with affinity comparable that seen well characterized sites. activated an palindrome-containing in 293 cells. Because...
The mammalian neuropeptide, melanin-concentrating hormone, interacts with two G protein-coupled receptors, hormone receptor (MCHR) 1 and MCHR2; however, only MCHR1 is expressed in rats mice. In the present study, we evaluated antagonism preclinical models believed to be predictive of antiobesity antidepressant activity. Central activity selective antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one], was using ex vivo...
The G protein-coupled receptor 40 (GPR40) also known as free fatty acid 1 (FFAR1) is highly expressed in pancreatic, islet β-cells and responds to endogenous acids, resulting amplification of insulin secretion only the presence elevated glucose levels. Hypothesis driven structural modifications FFAs, focused on breaking planarity reducing lipophilicity, led identification spiropiperidine tetrahydroquinoline derivatives GPR40 agonists with unique pharmacology, selectivity, pharmacokinetic...
Purpose To evaluate the diagnostic values of systemic immune-inflammation index (SII) and neutrophil–lymphocyte ratio (NLR) in patients with localized prostate cancer (PCa). Methods Between January 2014 December 2019, 117 benign hyperplasia (BPH) 278 PCa who underwent radical prostatectomy (RP) were included this study. The inflammatory markers including SII, NLR, platelet–lymphocyte (PLR), lymphocyte–monocyte (LMR), lymphocyte (LR), neutrophil (NR), mean platelet volume (MPV), red cell...
Abstract China Antimicrobial Resistance Surveillance Network for Pets (CARPet) was established in 2021 to monitor the resistance profiles of clinical bacterial pathogens from companion animals. From 2018 2021, we recovered and tested 4,541 isolates dogs cats across 25 Chinese provinces, with Escherichia coli (18.5%) Staphylococcus pseudintermedius (17.8%) being most predominant species. The Enterobacterales were highly susceptible tigecycline, meropenem, colistin, amikacin (70.3%–100.0%),...
To investigate stearoyl-coenzyme A desaturase (SCD) 1 expression in obesity-prone C57BL/6 mice and obesity-resistant FVB to explore the relationship of SCD1 susceptibility diet-induced obesity.Nine-week-old were fed either a high- or low-fat diet for 8 weeks. Body weight body composition measured before at weeks 4 study. Energy expenditure was 5 Hepatic mRNA 72 hours end Plasma leptin insulin concentrations study.When switched calorie-dense high-fat diet, animals gained significantly more...
Objective: We applied a comparative functional genomics approach to evaluate whether diet-induced obese (DIO) rats serve as an effective obesity model. Methods and Procedures: Gene-expression profiles of epididymal fat from DIO lean were generated using microarrays compared with the published array data non-obese human subcutaneous adipocytes. Results: Caloric intake fuel efficiency significantly higher in rats, which resulted increased body weight adiposity. Circulating glucose,...
1051 Background: Abemaciclib is an orally administered, selective small molecule cyclin-dependent kinase (CDK)4 and 6 inhibitor, approved to treat HR+, HER2- MBC patients (pts) on a continuous twice daily dosing schedule as monotherapy or in combination with aromatase inhibitor initial endocrine based therapy fulvestrant. increased tumor immunogenicity synergized anti-PD-1 boost antitumor efficacy murine models. Here we report safety activity of abemaciclib plus pembrolizumab pts. Methods:...
1017 Background: Abemaciclib is a selective CDK4 & 6 inhibitor approved to treat HR+, HER2- MBC pts on continuous dosing schedule as monotherapy or in combination with endocrine therapy (ET). Clinical data demonstrate abemaciclib penetrates the blood brain barrier resulting comparable concentrations tissues and plasma. Methods: JPBO Simon 2-stage trial evaluating pt cohorts BM secondary HR+ MBC, non-small cell lung cancer, melanoma. Here, we report pts. Eligible had ≥1 new not previously...
Abstract Aims This participant‐level exploratory analysis assessed the continuous time spent in glycaemic control and/or with sustained weight reductions tirzepatide treatment participants type 2 diabetes (T2D) from SURPASS programme. Materials and Methods Participants ( N = 6246) 1–5 were randomized to once weekly (5, 10 or 15 mg) comparator (once placebo, semaglutide 1 mg, insulin degludec glargine). Continuous HbA1c < 7.0% (53 mmol/mol), ≤6.5% (48 mmol/mol) ≥5% body reduction combined...
Abemaciclib is an oral, selective small-molecule CDK 4 and 6 inhibitor. In preclinical models, abemaciclib synergized with programmed cell death protein-1 blockade to enhance antitumor efficacy. Here, we report the safety anticancer activity of plus pembrolizumab in two cohorts NSCLC.
Abstract Purpose Resistance to endocrine therapy poses a major clinical challenge for patients with hormone receptor-positive (HR +), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC). We present the preplanned 24-month final overall survival (OS) results, alongside updated progression-free (PFS), and objective response rate (ORR) results. Methods nextMONARCH is an open-label, controlled, randomized, Phase 2 study of abemaciclib alone or in combination...
Abstract Purpose: The monarcHER trial has shown that abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, combined with fulvestrant trastuzumab, improves progression-free survival (PFS) in hormone receptor–positive (HR+), HER2-positive (HER2+) advanced breast cancer (ABC) compared standard-of-care (SOC) chemotherapy trastuzumab. We report the final overall (OS) analysis, updated safety efficacy data, exploratory biomarker results from monarcHER. Patients Methods: (NCT02675231),...