Results 71 to 80 of about 81,917 (261)

Cannabinoid CB1 Receptor in Nociceptors Mediates Postoperative Analgesia via ASIC3 Inhibition

Advanced Science, EarlyView.
CB1R and ASIC3 are co‐expressed in CGRP+ nociceptors of mouse DRG. Plantar incision triggers an upregulation of ASIC3 and activation of ASIC3+ neurons, driving mechanical allodynia. CB1R activation suppresses ASIC3 function and downstream ERK1/2 phosphorylation, thereby braking nociceptive signaling and accelerating pain resolution.
Kangtai Xu, Luyao Ji, Haoyi Yang, Xiying Chen, Qiaodan Hu, Haimei He, Jiawei Wu, Leyan Shan, Shihui Feng, Yingzhi Li, Xiongchang Tan, Hao Wang, Zilong Wang, Chaoran Wu   +13 more
wiley   +1 more source

Transfer RNA‐Derived Small RNA‐5’tiRNAGln Drives HNRNPC Phase Separation to Promote Breast Cancer Bone Metastasis by Regulating IGF1R

Advanced Science, EarlyView.
This study reveals that 5'tiRNA‐Gln interacts with hnRNPC to promote IGF1R liquid‐liquid phase separation, which drives ERK1/2 signaling activation, EMT, and breast cancer bone metastasis. These findings highlight a novel mechanism of breast cancer bone metastasis and potential therapeutic target in metastatic breast cancer.
Bingnan Wang, Dongsong Liu, Xiaozhi Fan, Jiale Fan, Xuesi liu, Yu Wang, Zixin Wang, Mo Cheng, Ping Zhou, Wangjun Yan   +9 more
wiley   +1 more source

Combined inhibition of MEK and Aurora A kinase in KRAS/PIK3CA double-mutant colorectal cancer models

Frontiers in Pharmacology, 2015
Aurora A kinase and MEK inhibitors induce different, and potentially complementary, effects on the cell cycle of malignant cells, suggesting a rational basis for utilizing these agents in combination.
S. Lindsey eDavis, S. Lindsey eDavis, Kelli M. Robertson, Todd M. Pitts, Todd M. Pitts, John J. Tentler, John J. Tentler, Erica L. Bradshaw-Pierce, Erica L. Bradshaw-Pierce, Erica L. Bradshaw-Pierce, Peter J. Klauck, Stacey M. Bagby, Stephanie L. Hyatt, Heather M. Selby, Anna eSpreafico, Jeffrey A Ecsedy, John J. Arcaroli, John J. Arcaroli, Wells A. Messersmith, Wells A. Messersmith, Aik Choon eTan, Aik Choon eTan, S. Gail eEckhardt, S. Gail eEckhardt   +23 more
doaj   +1 more source

Versatile Microgel Platform for Intervertebral Disc Degeneration Therapy: Targeting Pericyte‐Mediated Fibrosis and Protecting Nucleus Pulposus Cells

Advanced Science, EarlyView.
The engineered MMS@TRP microgel enables targeted, acid‐responsive delivery of a miR‐21 inhibitor to pericytes. It effectively suppresses disc fibrosis by inhibiting TGF‐β signaling while protecting nucleus pulposus cells via sustained, antioxidant tannic acid release.
Fei Ma, Zhen Zhao, Chuan Guo, Yuheng Liu, Yu Wang, Dengbo Yao, Weiqiang Lan, Dejun Zhong, Chen Fan, Yao He, Mei Zhang, Qingquan Kong, Yunfeng Lin   +12 more
wiley   +1 more source

Low‐Density Lipoprotein Receptor‐Targeted Biomimetic Nanoplatform Suppresses Glioblastoma Stemness and Remodels Antitumor Immunity via Dual Metabolic Disruption

Advanced Science, EarlyView.
A low‐density lipoprotein receptor‐oriented biomimetic nanoplatform couples brain‐tumor delivery with a mechanistically matched regorafenib‐erythrodiol combination. Concurrent disruption of autophagic nutrient salvage and cholesterol homeostasis collapses bioenergetic and signaling support, suppresses glioblastoma stemness, and promotes immunogenic ...
Yining Jiang, Wenzhuo Yang, Wenting Cheng, Jing Zuo, Lin Pan, Sheng Zhong, Ren Geng, Yao Zhao, Zijian Chen, Canhua Huang, Yang Bai, Liyan Zhao, Yunqian Li   +12 more
wiley   +1 more source

Hepatic Lipid Stress Drives Metabolic Dysfunction‐Associated Steatohepatitis Progression through FTO O‐GlcNAcylation‐Induced m6A Demethylation of HRAS

Advanced Science, EarlyView.
Lipid stress drives O‐GlcNAcylation of the m6A demethylase FTO at Ser195, enhancing its stability and demethylase activity. This modification removes m6A from HRAS mRNA, preventing its degradation and activating PI3K/AKT signaling to promote hepatic steatosis and inflammation.
Jia‐Xin Yin, Yan‐Lai Zhang, Qun Liu, Rui Liu, Hai‐Yang Yuan, Sui‐Dan Chen, Ming‐Hua Zheng, Kai Wang, Ni Tang, Ai‐Long Huang   +9 more
wiley   +1 more source

MEK Inhibition Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia (B-ALL) Cells to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy.

PLoS ONE, 2016
Resistance to glucocorticosteroids (GCs) is a major adverse prognostic factor in B-ALL, but the molecular mechanisms leading to GC resistance are not completely understood. Herein, we sought to elucidate the molecular background of GC resistance in B-ALL
Anna Polak, Przemysław Kiliszek, Tomasz Sewastianik, Maciej Szydłowski, Ewa Jabłońska, Emilia Białopiotrowicz, Patryk Górniak, Sergiusz Markowicz, Eliza Nowak, Monika A Grygorowicz, Monika Prochorec-Sobieszek, Dominika Nowis, Jakub Gołąb, Sebastian Giebel, Ewa Lech-Marańda, Krzysztof Warzocha, Przemysław Juszczyński   +16 more
doaj   +1 more source

Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

Advanced Science, EarlyView.
EGFR mutations drive a substantial fraction of non‐small cell lung cancers (NSCLC) and are effectively targeted by tyrosine kinase inhibitors (TKIs), including osimertinib. However, resistance inevitably develops through secondary mutations and compensatory receptor activation, including the GAS6 receptor MERTK.
Suvendu Giri, Boobash Raj Selvadurai, Nitin Gupta, Arturo Simoni‐Nieves, Alessandro Genna, Moshit Lindzen, Rishita Chatterjee, Marieke Van Daele, Deepthi Ramesh Kumar, Mirie Zerbib, Roni Oren, Isabelle Sophie Meijer, Elisabeth Franziska Wippich, Yahel Avraham, Rony Dahan, Yuya Haga, Laura E. Kilpatrick, Simon Platt, Stephen J. Hill, Lipika R. Pal, Eytan Ruppin, Yasuo Tsutsumi, Eliane Hadas Yardeni, Muhammad Abu Ahmad, Olga Radinsky, Donatella Romaniello, Mattia Lauriola, Angel Porgador, Yosef Yarden   +28 more
wiley   +1 more source

Synergistic induction of autophagy in gastric cancer by targeting CDK4/6 and MEK through AMPK/mTOR pathway

Heliyon
KRAS is a commonly mutated oncogene in human gastric cancer and is often associated with drug resistance and poor prognosis. Co-clinical trial of combined MEK-CDK4/6 inhibition in KRAS mutated cancers demonstrated therapeutic efficacy in patient-derived ...
Hong Zhou, Guiling Li, Liuyue Kan, Mingyu Yang, Yu Liu, Xiaye Miu, Lei Shi, Zhanjun Yang, Xucai Zheng, Hui Chen, Chuanli Ren   +10 more
doaj   +1 more source

Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction

Platelets, 2019
The MEK inhibitors cobimetinib and trametinib are used in combination with BRAF inhibitors to treat metastatic melanoma but increase rates of hemorrhage relative to BRAF inhibitors alone.
Amanda J. Unsworth, Alexander P. Bye, Neline Kriek, Tanya Sage, Ashley A. Osborne, Dillon Donaghy, Jonathan M. Gibbins   +6 more
doaj   +1 more source