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Development of CAR T cell therapy targeting glypican-3 in liver cancer

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Cancer Biology & Medicine 2018年第S1期15卷 17-17页

作者： Dan Li Nan Li Yifan Zhang Haiying fu Madeline B.Torres tim f.greten Mitchell Ho Center for Cancer Research National Cancer InstituteBethesdaMarylandUSA

Objective:Glypican-3(GPC3)is a promising therapeutic target in hepatocellular carcinoma(HCC).We have generated the HN3 and h YP7 antibodies that recognize the N-lobe and C-lobe of GPC3,***,we engineered human T cells ... 详细信息

关键词： Development CAR liver cancer

Like a G6-nal:transcriptional control of G-protein coupled receptors during oligodendroglial development

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Neural Regeneration Research 2025年第7期20卷 2001-2002页

作者： tim Aberle Michael Wegner Institut für Biochemie Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

Multilayered control of myelination:Quick,saltatory conduction of action potentials along nerve fibers requires the electrical insulation of axons by myelinating *** the central nervous system,this role is taken up by *** are marked by the expression of the lineage determinants Sox10 and Olig2 and arise from oligodendrocyte precursor cells(OPCs)during embryonal *** the majority of OPCs differentiate into mature oligodendrocytes when nearby axonal segments require myelination,a small subpopulation of OPCs persist as a progenitor ***,the timing of myelination and maintenance of the OPC pool both need to be precisely *** transcription factors either positively or negatively affect oligodendrocyte differentiation and maintenance of the OPC pool as components of a complex gene regulatory network(reviewed in Sock and Wegner,2021).Network activity is additionally influenced by extracellular signaling molecules that bind to receptors on the oligodendroglial cell surface and activate intracellular signaling *** the receptors are linked to the network is poorly understood so far,but pivotal to understanding the overall regulation of central nervous system(CNS)myelination in response to environmental *** insights were recently gained for Gpr37(Schmidt et al.,2024),a G-protein coupled receptor(GPCR)with known relevance in differentiating oligodendrocytes(Yang et al,2016).

关键词： gained insulation conduction

Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第20期12卷 3275-3282页

作者： Lars A Ormandy Anatol frber Tobias Cantz Susanne Petrykowska Heiner Wedemeyer Monique Hrning frank Lehner Michael P Manns firouzeh Korangy tim f.greten Department of Gastroenterology Hepatology and Endocrinology Hannover Medical SchoolGermany Departments of Visceral and Transplantation Surgery Hannover Medical School Germany

AIM： To analyze the phenotype and function of dendritic cells （DC） from patients with hepatocellular carcinoma （HCC） in order to understand their role in this disease. METHODS： Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. Phagocytosis was analyzed using fITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dZ：dC was tested. RESULTS： Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion. CONCLUSION： Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.

关键词： Myeloid DC Hepatocellular carcinoma CD80 CD83 CD86

Transarterial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma: evaluation of tumor response, toxicity, and survival

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Hepatobiliary & Pancreatic Diseases International 2007年第3期6卷 259-266页

作者： timm D Kirchhoff Joerg S Bleck Arne Dettmer Ajay Chavan Herbert Rosenthal Sonja Merkesdal Bernd frericks Lars Zender Nisar P Malek tim f.greten Stefan Kubicka Michael P Manns Michael Galanski Department of Diagnostic Radiology Hannover Medical School Germany Department of Gastroenterology Hepatology and Endocrinology Hannover Medical School Germany Department of Diagnostic and Interventional Radiology Klinikum Oldenburg Germany Division of Rheumatology Hannover Medical School Germany Department of Radiology and Nuclear Medicine Campus B.F-Charité-University Medicine Berlin Germany

BACKGROUND: In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratified according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratified to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efficiency and low toxicity. METHODS: fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics,toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS: 112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68% there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identified tumor size ≤75 mm, tumor number ≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (ficantly associated with long term survival (>30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6% (n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major

关键词： carcinoma, hepatocellular transarterial chemoembolization degradable starch microspheres Lipiodol tumor response survival

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肝细胞癌的免疫治疗（上）

传染病网络动态 2007年第1期 16-17页

作者： tim f.greten Michael P.Manns firouzeh Korangy 姚勤伟（编译）杨月（审校）

肝细胞癌（HCC）是世界第五大常见肿瘤，5年生存率低于5％，每年至少100万新发病例。其中一小部分病人可能适合外科切除或者局部消融治疗。但是，这些治疗受到肿瘤大小、肝脏储备功能和肝内转移的限制。因此，对于绝大多数晚期HCC患者... 详细信息

肝细胞癌（HCC）是世界第五大常见肿瘤，5年生存率低于5％，每年至少100万新发病例。其中一小部分病人可能适合外科切除或者局部消融治疗。但是，这些治疗受到肿瘤大小、肝脏储备功能和肝内转移的限制。因此，对于绝大多数晚期HCC患者来说，这些有望治愈的治疗手段都是不可能的。肝动脉化疗栓塞术（TACE）延长了已无条件行外科手术切除、肝移植或肿瘤消融治疗的患者的生存期，但是只有那些肝功能适当的患者才能够进行此项治疗。因为HCC患者基本上都有肝硬化基础，全身化疗耐受性较差，并且效果不佳。因此，根据全球性的指南（EASL或AASLD），像免疫治疗一类的备选方案最近正在晚期HCC患者中进行评估。

关键词：免疫治疗肝细胞癌肝动脉化疗栓塞术局部消融治疗肿瘤大小肝脏储备功能外科手术切除 5年生存率

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肝细胞癌的免疫治疗（下）

传染病网络动态 2007年第2期 15-18页

作者： tim f.greten Michael P.Manns firouzeh Korangy 姚勤伟（编译）杨月（审校）

5．肿瘤逃逸机制肿瘤从免疫系统产生了很多逃逸机制来抑制抗肿瘤反应。产生免疫抑制因子、增加调节性T细胞、下调肿瘤抗原和MHC分子都是肿瘤细胞用以逃避免疫识别的机制。已有很清楚的证据显示发生HCC能导致肿瘤特异性免疫反应受到抑制... 详细信息

5．肿瘤逃逸机制肿瘤从免疫系统产生了很多逃逸机制来抑制抗肿瘤反应。产生免疫抑制因子、增加调节性T细胞、下调肿瘤抗原和MHC分子都是肿瘤细胞用以逃避免疫识别的机制。已有很清楚的证据显示发生HCC能导致肿瘤特异性免疫反应受到抑制。尤其是我们已经证实尽管在超过50％的HCC患者中检测到肿瘤特异性的细胞和体液免疫反应，但是HCC仍然有所进展。虽然有抗原特异性T细胞的出现但HCC肿瘤仍然进展，这增加了对免疫治疗该肿瘤的有效性的关注。因为下面会展示，HCC的发展导致一系列不同的免疫机制，结果就是HCC患者中肿瘤特异性免疫反应的抑制。

关键词：免疫治疗肝细胞癌特异性免疫反应抗原特异性T细胞肿瘤逃逸免疫抑制因子调节性T细胞体液免疫反应

Early terrestrial and lunar anorthosites:Comparative geochemistry and evolutionary processes

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Geoscience frontiers 2024年第6期15卷 348-366页

作者： Paul Sotiriou Ali Polat tim Kusky Brian f.Windley School of the Environment University of WindsorWindsorON N9B 3P4Canada GeoZentrum Nordbayern Friedrich-Alexander-UniversitätErlangen 91054BayernGermany Center for Global Tectonics State Key Laboratory for Geological Processes and Mineral ResourcesChina University of GeosciencesWuhanHubei ProvincePR China School of Geography Geology and the EnvironmentUniversity of LeicesterLeicester LE17RHUK

In a paper in 1970,Brian Windley first recognised that early terrestrial and lunar anorthosites both have calcic plagioclase,and low TiO_(2)and high CaO and Al_(2)O_(3)*** these similarities,the geochemistry of early terrestrial and lunar anorthosites has not been rigorously compared and *** this end,we compiled 425 analyses from 212 early terrestrial anorthosite occurrences and 306 analyses from 16 lunar anorthosite *** was supplemented by a compilation of plagioclase anorthite(An)contents and pyroxene Mg#from early terrestrial and lunar *** terrestrial anorthosites have lower whole-rock An contents but similar Mg#to lunar *** CaO contents of lunar anorthosites are higher than those of early terrestrial anorthosites for a given MgO and Al_(2)O_(3)content,early terrestrial anorthosites have higher SiO_(2)contents than lunar anorthosites at a given MgO content,and lunar anorthosites have higher Eu/Eu*anomaly ratios yet broadly similar La/Yb and Nd/Sm ratios than early terrestrial *** early terrestrial anorthosites have less fractionated chondrite-normalised rare earth element(REE)patterns and less prominent positive Eu anomalies than lunar *** anorthosites have higher plagioclase An contents,yet a similar range of pyroxene Mg#compared to their early terrestrial *** early terrestrial anorthosites are more fractionated than some lunar *** interpretations imply that most early terrestrial anorthosites crystallised from basaltic parental magmas that were generated by high-degree partial melting of sub-arc asthenosphere mantle wedge sources that were hydrated by slab-derived fluids,with the remainder being associated with mid-ocean ridge and mantle plume *** of the arc-related early terrestrial anorthosites were influenced by crustal *** addition,early terrestrial anorthosites originated from partial melting of the mantle at variou

关键词： Early terrestrial anorthosites Lunar anorthosites Geochemistry Mineral chemistry

Connections Between Induction Generator Effect and Open-loop Modal Proximity to Cause Sub-synchronous Oscillations in Series-compensated Power System

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CSEE Journal of Power and Energy Systems 2024年第3期10卷 963-973页

作者： Wenjuan Du Yang Wang H.f.Wang Tao Zhao tim Littler College of Electrical Engineering Sichuan UniversityChengduChina School of Electrical Engineering the Queen’s University of BelfastBelfastUK IEEE

The induction generator effect(IGE)and the openloop modal proximity(OLMP)are two different reasons why subsynchronous oscillations(SSOs)in a series-compensated power system(SCPS)may *** IGE attributes the growing SSOs to negative resistance,while the OLMP explains the SSO mechanism from the standpoint of modal *** this paper,we investigate the connections between the IGE and the OLMP through equivalent RLC circuit and open-loop modal *** investigation is conducted for two types of seriescompensated power systems where either a synchronous generator or a DfIG is connected at the sending *** investigation reveals the conditions,in which the IGE and the OLMP may jointly cause the growing SSOs,i.e.,both the IGE and the OLMP can explain why the growing SSOs ***,the investigation indicates that the IGE and the OLMP may be totally irrelevant and lead to growing SSOs *** implies that it is possible that in a SCPS,the growing SSOs are only due to the IGE,and the OLMP is non-existent,and vice ***,when the growing SSOs occurs in a SCPS,examination based on both the IGE and the OLMP should be carefully conducted in order to find if the oscillatory instability is due to the IGE,or the OLMP,or both of them.

关键词： Induction generator effect open-loop modal proximity series compensation sub-synchronous oscillations

Solvable base change and Rankin-Selberg convolutions

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Science China Mathematics 2017年第1期60卷 99-112页

作者： GILLESPIE tim Department of Mathematics St. Ambrose University Davenport IA 52803 USA

Let π and π′ be unitary automorphic cuspidal representations of GL_n(A_E) and GL_m(A_f), and let E and f be solvable Galois extensions of Q of degrees ? and ?′, respectively. Using the fact that the automorphic induction and base change maps exist for E and f, and assuming an invariance condition under the actions of the Galois groups, we attach to the pair(π, π′) a Rankin-Selberg L-function L(s, π×E,fπ′) for which we prove a prime number theorem. This gives a method for comparing two representations that could be defined over completely different extensions, and the main results give a measure of how many cuspidal components the two representations π and π′ have in common when automorphically induced down to the rational numbers. The proof uses the structure of the Galois group of the composite extension Ef and the character groups attached to the fields via class field theory. The second main theorem also gives an indication of when the base change of π up to the composite extension Ef remains cuspidal.

关键词： automorphic L-function base change automorphic induction