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CDC7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYC degradation

Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga kenta kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.karthaus Samir Zaidi Yingqian A.Zhan Parvathy manoj harsha Sridhar Dennis kinyua hong Zhong Barbara P.Mello Metamia Ciampricotti Umesh k.Bhanot Irina Linkov Juan Qiu Radhika A.Patel Colm Morrsey Sanjoy Mehta Jesse Barnes Michael C.haffner Nichlas D.Socci Richard P.koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi helena A.Yu Joseph M.Chan Charles M.Rudin Department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos College of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill Cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Center for Epigenetics Research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology Core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment Core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof human Biology and Clinical Research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening Core Facility Memorial Sloan kettering Cancer Center New YorkNYUSA Department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics CoreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA Institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain Computational Oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well Cornell Medical College New York NYUSA Present address:Swiss Institute for Experimental Cancer Research(ISREC) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional Corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase Cell Division Cycle 7(CDC7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the CDC7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen(MYC),implicated in stemness and histological *** overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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Development of an automated system for continuous monitoring of powered roof support in longwall panel

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Journal of Coal Science & Engineering(China) 2010年第4期16卷 337-340页

作者： ATULkumar DhEERAJkumar SINGhU.k. GUPTAP.S. Department of Mining Engineering Indian School of Mines

Described the development of an Intrinsically Safe System for continuous monitoring of load and convergence of powered roof supports installed at Iongwall faces. The system developed for monitoring of behavior of a powered support in a mechanized Iongwall sublevel caving face. The logging system can be programmed for logging the data from the sensors at different logging intervals ranging from 16 h to 1 ms for logging variation in hydraulic pressures in legs and convergence of the support during progressive face advance. For recording dynamic loads, the data logger can be programmed to start fast logging, say at 10 ms intervals, when the pressure in a leg reaches a pre-specified threshold value, and continue fast logging until the pressure drops below this threshold value. This fast logging automatically stops when the pressure drops below this threshold value.

关键词： data logging system convergence leg pressure software analysis

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