Results 21 to 30 of about 927 (145)

PAK1 activation drives divergent resistance mechanisms to aromatase inhibition and tamoxifen in a luminal: A breast cancer model

Molecular Oncology, EarlyView.
Breast cancer remains a major cause of cancer death in women, frequently developing endocrine therapy resistance. This study demonstrates that upregulated p21‐activated kinase 1 (PAK1) activity drives resistance to tamoxifen and long‐term estrogen deprivation in ER+ breast cancer models.
Luisa Schwarzmüller, Janina Müller, Efstathios‐Iason Vlachavas, Lukas Beumers, Lena Fleischhacker, Sara Burmester, Angelika Wörner, Sabine Karolus, Dominic Helm, Cindy Körner, Stefan Wiemann   +10 more
wiley   +1 more source

Palmitic Acid Promotes Antiviral Innate Immunity via ZDHHC20‐Mediated CMPK2 Palmitoylation

Advanced Science, EarlyView.
Metabolites have important functions in innate immune activation and regulation. Wang et al. uncover metabolic regulation of antiviral immunity through CMPK2 palmitoylation, which regulates CMPK2 mitochondrial localization and is promoted by ZDHHC20 but reversed by PPT1, inhibition of which antagonizes viral infection in mice.
Yujia Wang, Zenghui Cui, Yunkai Zhang, Zhiqing Li, Xuetao Cao   +4 more
wiley   +1 more source

Cholesterol‐Mediated Metabolic‐mechanotransductive Crosstalk Orchestrates Castration Resistance in Prostate Cancer

Advanced Science, EarlyView.
Full androgen deprivation (FAD) induces paracrine cholesterol in prostate cancer that drives the polarization of cancer‐associated fibroblasts (CAFs) and subsequent elevated matrix stiffness. Matrix stiffness in turn potentiates tumor cell survival under FAD pressure via dual mechanotransductive activation of the IRE1α‐XBP1s stress‐response axis ...
Shaojie Liu, Chao Xu, Jun Jiang, Limin He, Yike Zhou, Zhengxuan Li, Yu Li, Keying Zhang, Fa Yang, Tong Lu, Hongtao Song, Hai Zhu, Zhihao Hu, Xiaolong Zhao, Kai Gan, Hongji Li, Bo Yang, Rui Zhang, Weihong Wen, Donghui Han, Weijun Qin   +20 more
wiley   +1 more source

Functional Suppression of SCAP Triggers Endoplasmic Reticulum Stress‐Dependent Ferroptosis by Impairing Cholesterol Metabolism in Gastric Cancer

Advanced Science, EarlyView.
This study reveals a novel GC therapy targeting cholesterol homeostasis. Inhibiting the SCAP sterol‐sensing domain causes lethal ER stress via cholesterol accumulation, paradoxically forcing continuous synthesis that triggers ferroptosis. The findings link sterol sensing, metabolic dysregulation, and ferroptosis, establishing an anti‐cancer paradigm ...
Qianqian Xu, Guangzhao Pan, Lele Zhang, Xiangliu Chen, Kui Zhang, Yang Lu, Zibo Duan, Aiping Chen, Hailong Shen, Yuxi Zhang, Xiaowu Dong, Jinzhou Huang, Xing Huang, Kai Miao, Qian Hua, Fangfang Tao, Weidong Zhang, Jiang‐Jiang Qin   +17 more
wiley   +1 more source

Pharmacokinetic profiling of imatinib in relation to CYP3A4 activity in leukaemia patients

British Journal of Clinical Pharmacology, EarlyView.
Aim Imatinib pharmacokinetics exhibit large interindividual variability because of differences in CYP3A4 activity—the main imatinib‐metabolizing enzyme. While therapeutic drug monitoring is effective, it requires steady‐state conditions and frequent sampling.
Anna Sofie Buhl Rasmussen, Mathilde Rønne Koch, Cecilie Utke Rank, Christen Lykkegaard Andersen, Allan Weimann, Maria Thastrup, Tianwu Yang, Trine Meldgaard Lund, Ib Jarle Christensen, Flemming Nielsen, Tore Bjerregaard Stage, Sara Bisgaard Jensen, Mette Klarskov Andersen, Kjeld Schmiegelow, Kim Dalhoff   +14 more
wiley   +1 more source

Orchestrating the metastatic symphony: the role of extracellular vesicles in the epithelial–mesenchymal transition and pulmonary niche formation of breast cancer

Biological Reviews, EarlyView.
ABSTRACT The complexity of breast cancer (BC) lung metastasis lies in the capacity of tumour cells to interact efficiently with distant organs to promote colonisation, a process that involves the sophisticated coordination of inherent cellular plasticity and the remodelling of the distant microenvironment.
Jian Lu, Reza Shirazi Nia, Junjie Sun, Chrysa Filippopoulou, Daniel De Vega, Pengtao Hu, Heng Liang, Hang Yao, Chaoyue Pan, Xiaoyan Wu, Xidong Gu, Xiaohong Xie, Georgios Giamas   +12 more
wiley   +1 more source

Plasma 4β-Hydroxycholesterol: An Endogenous CYP3A Metric? [PDF]

Clinical Pharmacology & Therapeutics, 2009
We assessed the suitability of 4beta-hydroxycholesterol (4betaOH-C) as an endogenous cytochrome P450 3A (CYP3A) phenotyping metric. 4betaOH-C and its ratio to cholesterol (4betaOH-C/C) were determined in five cocktail phenotyping studies, with and without co-medication with a potential CYP3A inhibitor.
Tomalik-Scharte, D, Lütjohann, D, Doroshyenko, O, Frank, D, Jetter, A, Fuhr, U   +5 more
openaire   +2 more sources

Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data

Clinical Pharmacology &Therapeutics, EarlyView.
Plasma 4β‐hydroxycholesterol (4β‐OHC) normalized for the levels of its parent cholesterol (4β‐OHC/C) is an endogenous biomarker for hepatic CYP3A4. This study evaluated CYP3A4 activity longitudinally in individuals while their obesity status was changing. 4β‐OHC/C was measured pre‐surgery (n = 54) and 2 years after Roux‐en‐Y gastric bypass (n = 30) and
Nihan Izat, Haribhau Kangne, Rasmus Jansson‐Löfmark, Jens K. Hertel, Amin Rostami‐Hodjegan, Ida Robertsen, Aleksandra Galetin   +6 more
wiley   +1 more source

A phase 3, randomized clinical trial of soticlestat as adjunctive therapy for Lennox–Gastaut syndrome

Epilepsia, EarlyView.
Soticlestat as adjunctive therapy for Lennox–Gastaut syndrome. Abstract Objective There remains a need for new treatments for Lennox–Gastaut syndrome (LGS), a developmental and epileptic encephalopathy with a heterogenous patient population that often requires polytherapy. The phase 3, randomized SKYWAY study (NCT04938427) investigated the efficacy and
Renzo Guerrini, Eric D. Marsh, Wei‐Ping Liao, Katsumi Imai, Ruzica Kravljanac, Anna Altmann, Cecil D. Hahn, Stéphane Auvin, Jimmy Schiemann, Yasir Khan, Pranab Mitra, Sarah I. Sheikh, Philipp von Rosenstiel, Mahnaz Asgharnejad, Dennis Dlugos, Venkatesha Murthy   +15 more
wiley   +1 more source

Bile Acid Synthesis in Man: Metabolism of 7α-Hydroxycholesterol-14C and 26-Hydroxycholesterol-3H [PDF]

Journal of Clinical Investigation, 1972
The pathways of bile acid synthesis in man were evaluated by studying the metabolism of 7alpha-hydroxycholesterol-4-(14)C and 26-hydroxycholesterol-16, 22-(3)H administered parenterally to individuals requiring external biliary drainage. Techniques for the identification of metabolites were thin-layer chromatography, column chromatography, gas-liquid ...
K E, Anderson, E, Kok, N B, Javitt
openaire   +2 more sources