Results 121 to 130 of about 102,812 (293)

Targeting PRKCN, an Essential Driver Orchestrating mTOR‐IRF4 Axis Independently of Kinase Activity, in Multiple Myeloma

Advanced Science, EarlyView.
Constitutive PRKCN expression is driven by super‐enhancers and modulated by NF‐κB signaling in multiple myeloma (MM). PRKCN activates mTORC1/2‐IRF4 signaling axis and favors tumor cell growth independently of its kinase activity. IRF4 reciprocally promotes PRKCN transcription, creating a feed‐forward loop.
Koukou Tang, Dongpeng Jiang, Peng Ke, Xiaosen Bian, Lili Zhang, Ying Zhang, Tingting Zhu, Weiwei Qu, Wenhui Qi, Yang Xu, Chengcheng Fu, Depei Wu, Jianhong Chu   +12 more
wiley   +1 more source

Regulation of mTORC1 by lysosomal calcium and calmodulin

eLife, 2016
Blockade of lysosomal calcium release due to lysosomal lipid accumulation has been shown to inhibit mTORC1 signaling. However, the mechanism by which lysosomal calcium regulates mTORC1 has remained undefined.
Ruo-Jing Li, Jing Xu, Chenglai Fu, Jing Zhang, Yujun George Zheng, Hao Jia, Jun O Liu   +6 more
doaj   +1 more source

Mechanistic target of rapamycin (mTOR) activation during ruminant mammary development and function : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Palmerston North, New Zealand [PDF]

, 2013
This thesis examines the abundance of total and activated mechanistic target of rapamycin (mTOR) pathway components in the developing and functional ruminant mammary gland. mTOR pathway activation is stimulated by a wide range of intra- and extracellular
Sciascia, Quentin Leon
core  

Vascular Growth in the Fetal Lung [PDF]

, 2011
The structure of the lung is truly remarkable. It is primarily composed of three branched tubular networks (the airway, pulmonary artery and vein, bronchial artery and vein) which supply blood and air to the site of gas exchange and which maintain ...
Land, Stephen
core   +4 more sources

Integrative Approaches to Treating Cellular Senescence in Kidney Disease

Advanced Science, EarlyView.
ABSTRACT Cellular senescence in the kidney plays a crucial role in the progression of acute kidney injury and chronic kidney disease. Therapeutic approaches targeting senescent cells, such as small molecule senolytic and senomorphic drugs, display efficacy in preclinical models.
Tomoka Misawa, Amruta A, LaTonya J. Hickson, Joy Wolfram   +3 more
wiley   +1 more source

Humanized and Charge‐Optimized CSPG4‐Specific CAR‐T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma

Advanced Science, EarlyView.
CSPG4 is identified as a high‐value, stemness‐associated target in HPV‐negative HNSCC. By implementing rational biophysical engineering, a humanized and charge‐optimized CAR is developed to overcome tonic signaling‐induced exhaustion. This strategy induces a profound transcriptomic shift toward a rejuvenated, stem‐like memory state, significantly ...
Xiang Xu, Shizhen Qiu, Zhitong Wang, Dan Li, Min Chen, Yinying Chu, Guangfei Li, Yi Fang, Changjiang Li, Fang Shi, Peijie He, Haitao Wu, Haopeng Wang, Jian Chen   +13 more
wiley   +1 more source

T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities

Advanced Science, EarlyView.
T cell exhaustion limits immunotherapy efficacy. This article delineates its progression from stem‐like to terminally exhausted states, governed by persistent antigen, transcription factors, epigenetics, and metabolism. It maps the exhaustion landscape in the TME and proposes integrated reversal strategies, providing a translational roadmap to overcome
Yang Yu, Xiaoyu Yao, Qingyang Wang, Mengrui Yang, Runze Li, Jiangjiang Qin, Jing Zhuang, Changgang Sun   +7 more
wiley   +1 more source

The mTORC1 Signaling Network Senses Changes in Cellular Purine Nucleotide Levels

Cell Reports, 2017
Summary: Mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1) integrates signals from growth factors and nutrients to control biosynthetic processes, including protein, lipid, and nucleic acid synthesis.
Gerta Hoxhaj, James Hughes-Hallett, Rebecca C. Timson, Erika Ilagan, Min Yuan, John M. Asara, Issam Ben-Sahra, Brendan D. Manning   +7 more
doaj   +1 more source

A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer. [PDF]

, 2017
Lessons learnedThe combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate ...
Friedlander, Terence, Hsieh, Andrew C, Kim, Won, Lin, Amy M, Louttit, Mirela, Ryan, Charles J, Wei, Xiao X   +6 more
core   +1 more source

Pancancer Fine‐Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma

Advanced Science, EarlyView.
This study identifies mutation‐intolerant genes (MIGs), which are mutationally constrained in tumors despite normal‐tissue variability. Using miDriver, the authors pinpoint MIGs essential for tumor‐intrinsic fitness and immune evasion. Focusing on CHEK1, they show it drives tumor fitness and sculpts an immunosuppressive niche via the MIF–CD74 axis ...
Tao Wang, Hongyu Zhao, Xiaojie Sun, Yuqi Ding, Zhipeng Zhu, Xiaotong Yu, Rongyi Zhu, Dan Wang, Kailong Li, Yang Liu, Li‐Bin Wang, Xiaolu Zhao, Baojun Suo, Hongsen Bi, Peipei Zhang, Tong Liu, Fengbiao Mao   +16 more
wiley   +1 more source