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Cancer Drug Resistance 2021年第4期4卷 984-995页

作者： Montserrat Estruch Camilla Vittori Teresa Muñoz Montesinos Kristian Reckzeh Kim Theilgaard-Mönch The finsen laboratory Rigshospitalet/National University HospitalFaculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Biotech Research and Innovation Centre Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Novo Nordisk Foundation Centre for Stem Cell Biology DanStemFaculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Department of Hematology Rigshospitalet/National University HospitalUniversity of CopenhagenCopenhagen DK-2200Denmark

Resistance of cancer patients to DNA damaging radiation therapy and chemotherapy remains a major problem in the *** current review discusses the molecular mechanisms of therapy resistance in acute myeloid leukemia(AML)conferred by cooperative chemotherapy-induced DNA damage response(DDR)and mutational activation of PI3K/AKT *** addition,strategies to overcome resistance are discussed,with particular focus on studies underpinning the vast potential of therapies combining standard chemotherapy AML regimens with small molecule inhibitors targeting key regulatory hubs at the interface of DDR and oncogenic signaling pathways.

关键词： DNA damage response PI3K/AKT chemotherapy resistance AML

Crystal structure of a cell surface receptor（uPAR） in its ligand-free conformation reveals the exposure of an unusually large hydrophobic area

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Crystal structure of a cell surface receptor（uPAR） in its ...

Olivine-norite rock detected by the lunar rover Yutu-2 likely crystallized from the SPA-impact melt pool

第四届中国结构生物学学术讨论会

作者： Baoyu Zhao Cai Yuan Rui Li Michael Ploug Nicolai Sidenius Mingdong Huang Fujian Institute of Research on the Structure of Matter The Chinese Academy of Sciences finsen laboratory Rigshospitalet & Biotech Research and Innovation Centre (BRIC) Copenhagen Biocenter Ole Maal?es Vej 5 DK-2200 Copenhagen N Denmark San Raffaele Scientific Institute

Proteins typically fold in a way to have their hydrophobic residues buried in the core of proteins while the hydrophilic residues exposed on protein surface. The exposure of large hydrophobic patch to solvent is thermodynamically unfavorable, and is not commonly observed. Cell surface receptor urokinase-type plasminogen activator receptor（uPAR） has a large hydrophobic patch in its central ligand binding pocket. Upon the ligand（uPA） binding, this hydrophobic patch on uPAR is sequestered, forming a highly stable and tight-binding complex（Qing Huai, 2006）. The crystallization of uPAR ectodomains in its ligand-free conformation is expected to be difficult, but has been a long sought goal. With the help of an anti-uPAR antibody（8B12）, we recently succeed to crystallize the uPAR:8B12 complex in the absence of any ligands, and determined the crystal structure of uPAR in the ligand-free conformation. Surprisingly, uPAR adopts a conformation similar to its ligand-bound state, exposing a large hydrophobic area to solvent. This observation is different from the previous speculation and biochemical studies（Cai Yuan, 2007 and Haydyn D. T. Mertens, 2012）. uPAR is a glycolipid-anchored cell surface receptor and consists of three Ly6/uPAR/α-neurotoxin-like（LU） domains. Extensive degree of inter-domain flexibility was expected and was indeed observed in solution by biochemical studies including small angle X-ray scattering. However, Our recent uPAR:8B12 structure showed no inter-domain flexibility and the conformation of unliganded uPAR is identical to the ligand-bound conformation. Further functional studies are underway to examine the functional consequences of these structural observations.

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National Science Review 2020年第5期7卷 913-920页

作者： Honglei Lin Zhiping He Wei Yang Yangting Lin Rui Xu Chi Zhang Meng-Hua Zhu Rui Chang Jinhai Zhang Chunlai Li Hongyu Lin Yang Liu Sheng Gou Yong Wei Sen Hu Changbin Xue Jianfeng Yang Jie Zhong Xiaohui Fu Weixing Wan Yongliao Zou Key laboratory of Earth and Planetary Physics Institute of Geology and Geophysics Chinese Academy of Sciences Key laboratory of Space Active Opto-Electronics Technology Shanghai Institute of Technical Physics Chinese Academy of Sciences State Key laboratory of Lunar and Planetary Sciences Macau University of Science and Technology Beijing Institute of Space Mechanics and Electricity State Key laboratory of Space Weather National Space Science CenterChinese Academy of Sciences State Key laboratory of Remote Sensing Science Institute of Remote Sensing and Digital Earth Chinese Academy of Sciences Key laboratory of Electronics and Information Technology for Space System National Space Science Center Chinese Academy of Sciences Xi'an Institute of Optics and Precision Mechanics Chinese Academy of Sciences Institute of Optics and Electronics Chinese Academy of Sciences Shandong Provincial Key laboratory of Optical Astronomy and Solar-Terrestrial Environment Institute of Space SciencesShandong University

Chang’E-4 landed in the South Pole-Aitken (SPA) basin,providing a unique chance to probe the composition of the lunar *** landing site is located on ejecta strips in Von Karman crater that possibly originate from the neighboring finsen crater.A surface rock and the lunar regolith at 10 sites along the rover Yutu-2 track were measured by the onboard Visible and Near-Infrared Imaging Spectrometer in the first three lunar days of mission *** situ spectra of the regolith have peak band positions at 1and 2μm,similar to the spectral data of finsen ejecta from the Moon Mineralogy Mapper,which confirms that the regolith’s composition of the landing area is mostly similar to that of finsen *** rock spectrum shows similar band peak positions,but stronger absorptions,suggesting relatively fresh *** rock may consist of 38.1±5.4%low-Ca pyroxene,13.9±5.1%olivine and 48.0±3.1%plagioclase,referred to as *** plagioclase-abundant and olivine-poor modal composition of the rock is inconsistent with the origin of the mantle,but representative of the lunar lower ***,the rock crystallized from the impact-derived melt pool formed by the SPA-impact event via mixing the lunar crust and mantle *** scenario is consistent with fast-cooling thermal conditions of a shallow melt pool,indicated by the fine to medium-sized texture (<3 mm) of the rock and the SPA-impact melting model[Icarus2012;220:730-43].

关键词： impact basin lunar interior composition visible and near-infrared spectra lunar rover Yutu-2 Chang’E-4 mission

C4.4A as a biomarker in pulmonary adenocarcinoma and squamous cell carcinoma

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World Journal of Clinical Oncology 2014年第4期5卷 621-632页

作者： Benedikte Jacobsen Mette Camilla Kriegbaum Eric Santoni-Rugiu Michael Ploug The finsen laboratory Rigshospitalet Copenhagen Biocenter 2200 Copenhagen Denmark Biotech Research and Innovation Centre University of Copenhagen 2200 Copenhagen Denmark Department of Pathology Diagnostic Center Rigshospitalet Copenhagen University Hospital 2100 Copenhagen Denmark 2^(nd) Danish-Chinese Centre for Proteases and Cancer

The high prevalence and mortality of lung cancer, together with a poor 5-year survival of only approximately 15%, emphasize the need for prognostic and predictive factors to improve patient treatment. C4.4A, a member of the Ly6/uP AR family of membrane proteins, qualifies as such a potential informative biomarker in non-small cell lung cancer. Under normal physiological conditions, it is primarily expressed in suprabasal layers of stratified squamous epithelia. Consequently, it is absent from healthy bronchial and alveolar tissue, but nevertheless appears at early stages in the progression to invasivecarcinomas of the lung, i.e., in bronchial hyperplasia/metaplasia and atypical adenomatous hyperplasia. In the stages leading to pulmonary squamous cell carcinoma, expression is sustained in dysplasia, carcinoma in situ and invasive carcinomas, and this pertains to the normal presence of C4.4A in squamous epithelium. In pulmonary adenocarcinomas, a fraction of cases is positive for C4.4A, which is surprising, given the origin of these carcinomas from mucin-producing and not squamous epithelium. Interestingly, this correlates with a highly compromised patient survival and a predominant solid tumor growth pattern. Circumstantial evidence suggests an inverse relationship between C4.4A and the tumor suppressor LKB1. This might provide a link to the prognostic impact of C4.4A in patients with adenocarcinomas of the lung and could potentially be exploited for predicting the efficacy of treatment targeting components of the LKB1 pathway.

关键词： LYPD3 Non-small cell lung cancer Prognosis Solid growth pattern Liver kinase B1 Precursor lesions Atypical adenomatous hyperplasia Metaplasia Squamous differentiation Ly6/Urokinase-type plasminogen activator receptor

The subsurface structure and stratigraphy of the Chang’E-4 landing site:orbital evidence from small craters on the Von Kármán crater floor

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Research in Astronomy and Astrophysics 2020年第1期20卷 57-68页

作者：付晓辉乔乐张江凌宗成李勃 Shandong Provincial Key laboratory of Optical Astronomy and Solar-Terrestrial Environment Institute of Space SciencesShandong UniversityWeihai 264209China State Key laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyTaipaMacaoChina CAS Center for Excellence in Comparative Planetology Hefei 230026China State Key laboratory of Remote Sensing Science Institute of Remote Sensing and Digital EarthChinese Academy of SciencesBeijing 100101China

Chang’E-4(CE-4)successfully landed on the floor of the Von Kármán crater within the South Pole-Aitken basin(SPA).One of its scientific objectives is to determine the subsurface structure and the thickness of lunar regolith at the landing site and along the traverse route of the Yutu-2 *** orbital data,we employed small craters(diametersfinsen ejecta and excavate underlying mare deposits were identified,and 77 bright ray craters that expose only the underlying fresh materials but do not penetrate through the surface finsen ejecta were *** excavation depths of these craters and their distances from the finsen crater center were calculated,and the thickness distribution of finsen ejecta on the Von Kármán floor was systematically *** boundary between finsen ejecta and underlying mare basalt at the CE-4 landing site is constrained to a depth of 18 *** have proposed the stratigraphy for the CE-4 site and interpreted the origins of different layers and the geological history of the Von Kármán *** results provide valuable geological background for interpreting data from the Lunar Penetrating Radar(LPR)and Visible and Near-infrared Imaging Spectrometer(VNIS)on the Yutu-2 *** CE-4 landing site could provide a reference point for crater ejecta distribution and mixing with local materials,to test and improve ejecta thickness models according to the in situ measurements of the CE-4 LPR.

关键词： Chang’E-4 dark-haloed crater ejecta thickness Moon

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Mineralogy of Chang'e-4 landing site:preliminary results of visible and near-infrared imaging spectrometer

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Science China(Information Sciences) 2020年第4期63卷 195-206页

作者： Jian CHEN Zongcheng LING Le QIAO Zhiping HE Rui XU Lingzhi SUN Jiang ZHANG Bo LI Xiaohui FU Changqing LIU Xiaobin QI Shandong Key laboratory of Optical Astronomy and Solar-Terrestrial Environment School of Space Science and PhysicsInstitute of Space Sciences Shandong University Key laboratory of Space Active Opto-Electronics Technology Shanghai Institute of Technical PhysicsChinese Academy of Sciences Hawai'i Institute of Geophysics and Planetology Department of Earth Sciences University of Hawai'i at Manoa

The exploration of mafic anomaly in South Pole-Aitken(SPA, the largest confirmed) basin on the Moon provides important insights into lunar interior. The landing of Chang’e-4(CE-4) and deployment of Yutu-2 rover on the discontinuous ejecta from finsen crater enabled in-situ measurements of the unusual mineralogy in the central portion of SPA basin with visible and near-infrared imaging spectrometer(VNIS).Here we present detailed processing procedures based on the level 2B data of CE-4 VNIS and preliminary mineralogical results at the exploration area of Yutu-2 rover. A systematic processing pipeline is developed to derive credible reflectance spectra, based on which several spectral and mineral indices are calculated to constrain the mafic mineralogy. The mafic components in the soils and boulder around CE-4 landing site are concluded as clinopyroxene-bearing with intermediate composition and probably dominated by pigeonite although the possibility of mixing orthopyroxen(OPX) and calcic clinopyroxene(CPX) also exists. These mineralogical results are more consistent with a petrogenesis that the CE-4 regolith and rock fragment are derived from rapid-cooling magmatic systems and we interpret that the materials at the CE-4 landing site ejected from finsen crater are probably recrystallized from impact melt settings.

关键词： Chang’e-4 visible and near-infrared spectroscopy mineralogy impact melt the Moon

An updated constraint on the local stratigraphy at the Chang'E-4 landing site

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Earth and Planetary Physics 2021年第1期5卷 19-31页

作者： YiRen Chang ZhiYong Xiao YiChen Wang ChunYu Ding Jun Cui YuZhen Cai State Key laboratory of Lunar and Planetary Sciences Macao University of Science and TechnologyMacao 999078China Planetary Environmental and Astrobiological Research laboratory School of Atmospheric SciencesSun Yat-sen UniversityZhuhaiGuangdong 519000China Center for Excellence in Comparative Planetology Chinese Academy of SciencesHefei 230000China National Astronomical Observations of China Chinese Academy of SciencesBeijing 100000China

The Chang’E-4 mission has been exploring the lunar *** scientific targets of the rover onboard are(1)resolving the possible mineralogy related to the South Pole-Aitken basin and(2)understanding the subsurface processes at the lunar *** to date that are based on the reflectance spectra and radar data obtained by the rover have shown a persistent inconsistency about the local *** explain both the abnormal surface topography at the landing site and the unexpected radargram observed by the rover,the Alder crater has been frequently reported to be older than the mare basalts at that landing ***,this argument is not supported by earlier geological mapping nor recent crater *** this controversy is critical for a full understanding of the geological history of the landing area and for correct interpretations of the scientific data *** detailed crater statistics,rigorous statistical analyses,and an updated crater chronology function,this study is determined to resolve the relative ages of the Alder crater,finsen crater,and the mare basalts on the floor of Von Kármá*** results reveal that while background secondaries and local resurfacing have widely occurred in the study area,affecting age determinations,the statistics are significant enough to conclude that the Alder crater is the oldest among the three *** independent constraint is consistent with both the crosscutting relationships of different terrains in this area and global stratigraphic *** results exclude Alder as a possible contributor of the post-mare deposits at the landing site,appealing for a more systematic stratigraphy study to resolve the provenances of these deposits.

关键词： Moon Chang'E-4 impact craters absolute model age stratigraphy

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使用紫杉醇-铂类预处理的卵巢癌患者二线治疗中疾病稳定状况是否为存活的有效指标

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世界核心医学期刊文摘（妇产科学分册） 2005年第1期1卷 50-50页

作者： Gronlund B. Hdall C. Christensen I.J. 王刚 Department of Onco logy The Finsen CenterRigshospitalet Copenhagen Univ. H. Copenhagen Denmark

Objective. Recurrent ovarian carcinoma is considered an incurable dis ease and second-line chemotherapy is administered for extension of survival and palliati on. The impact of continued antineoplastic treatment in patients with stable dis ease without a demonstrable response is uncertain. The aim of this analysis was to assess the value of a stabilization of the tumor size in second-line chemoth erapy as an indicator of survival. Methods. Retrospective, single-institution s tudy of 487 consecutive patients with primary epithelial ovarian carcinoma. Incl usion criteria: (1) FIGO stage IC-IV epithelial ovarian carcinoma; (2) first-l ine chemotherapy with Paclitaxel and a Platinum-compound; (3) refractory, persi stent, or recurrent disease diagnosed by imaging methods; and (4) intravenous se cond-line chemotherapy with single Topotecan or Paclitaxel-Carboplatin. Univar iate and multivariate analyses of survival with theWorld Health Organization (WH O) tumor response parameter included as a time-dependent variable were performe d. Results. The response rates were (N = 100): complete response (CR) 27%, part ial response (PR) 14%, stable disease (SD) 41%and progressive disease (PD) 18 %. In a multivariate Cox regression analysis of survival, SD was found to be an independent prognostic factor for survival and the death hazard ratio was 0.37 (SD versus PD; 95%CI: 0.16-0.86; P = 0.02). There was no statistically signifi cant difference in survival between patients with PR and SD (P = 0.09). Conclusi on. In secondline chemotherapy of ovarian cancer,patients demonstrating SD have a survival benefit compared to patients with PD measured by theWHO tumor respons e criteria.

关键词：二线治疗复发性卵巢癌肿瘤预后生存分析生存优势一线化疗独立预后因素影像学诊断多变量回归持续性

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