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

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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

RABL-regulated pathways： a new tale in sperm function

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Asian Journal of Andrology 2013年第1期15卷 87-88页

作者： charles m Allan ANZAC Research Institute Concord Hospital Universityof Sydney Sydney NSW 2139 Australia

mammalian sperm have a specialized motile flagellum to provide the unidirectional propulsion required to achieve fertilisation of the egg. Defective flagella development and/or function is a significant cause of reduced sperm motility （asthenospermia） and male infertility. Over the past decade, a growing number of distinct proteins with crucial roles in sperm flagella have been identified by genetic loss-offunction approaches in mice, in which the deliberately engineered or spontaneous mutation of individual genes have lead to anomalies in sperm tail assembly,

关键词： PROTEIN FLAGELLUm

Nanoscience and the nano-bioelectronics frontier

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Nano Research 2015年第1期8卷 1-22页

作者： Xiaojie Duan charles m. Lieber Department of Biomedical Engineering College of Engineering Peking University Beijing 100871 China Department of Chemistry and Chemical Biology Harvard University Cambridge MA 02138 USA School of Engineering and Applied Sciences Harvard University Cambridge MA 02138 USA

This review describes work presented in the 2014 inaugural Tsinghua University Press-Springer Nano Research Award lecture, as well as current and future opportunities for nanoscience research at the interface with brain science. First, we briefly summarize some of the considerations and the research journey that has led to our focus on bottom-up nanoscale science and technology. Second, we recapitulate the motivation for and our seminal contributions to nanowire- based nanoscience and technology, including the rational design and synthesis of increasingly complex nanowire structures, and the corresponding broad range of ＂applications＂ enabled by the capability to control structure, com- position and size from the atomic level upwards. Third, we describe in more detail nanowire-based electronic devices as revolutionary tools for brain science, including （i） motivation for nanoelectronics in brain science, （ii） demonstration of nanowire nanoelectronic arrays for high-spatial/high-temporal resolution extracellular recording, （iii） the development of fundamentally-new intracellular nanoelectronic devices that approach the sizes of single ion channels, （iv） the introduction and demonstration of a new paradigm for innervating cell networks with addressable nanoelectronic arrays in three-dimensions. Last, we conclude with a brief discussion of the exciting and potentially transformative advances expected to come from work at the nanoelectronics-brain interface.

关键词： one-dimensional materials two-dimensional materials nanowires carbon nanotubes bottom-up paradigm nanoelectronics nanoelectronic arrays neural probes electrophysiolog35neural circuits brain activity map chronic recording and stimulation brain-machine interfaces

ABC‘s of relationship selling 7th ed.

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ABC‘s of relationship selling

The police in America : 5th ed.

2003年

作者： charles m. Futrell.

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The skeleton gets a （reproductive） life

2005年

作者： Samuel Walker charles m. Katz.

Includes registration code for access to mcGraw-Hill online resources.

ISBN: (数字)0072873256

ISBN: (纸本)0072873256

Includes registration code for access to mcGraw-Hill online resources.

关键词： Police

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Asian Journal of Andrology 2011年第5期13卷 651-652页

作者： charles m Allan David l Handelsman ANZAC Research Institute Concord Hospital Universityof Sydney Sydney NSW 2139 Australia

To most well-informed scientists who do not work on bone, the idea that bones determine anything other than your posture and location for the miseries of arthritis would come as quite a surprise. It would be like imagining that the walls of our home played something more than a passive role in the complexities of the lives conducted within. Yet something precisely as radical as that is what Karsenty and his colleagues boldly imagined,1 and then provocatively established in a series of studies over the past decade.20steocalcin （OCN） is a vitamin K- dependent peptide hormone secreted by the bone-formine osteoblasts.

关键词： Transcription