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Indirect targeting of mYC sensitizes pancreatic cancer cells to mechanistic target of rapamycin (mTOR) inhibition

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Cancer Communications 2022年第4期42卷 360-364页

作者： Christian Schneeweis Zonera HassanKatja Ascherl matthias Wirth Stella Koutsouli Felix Orben Lukas Krauß carolin Schneider Rupert Ollinger Oliver HKrämer Roland Rad maximilian Reichert maria SRobles Dieter Saur Günter Schneider medical Clinic and Polyclinic II Klinikum rechts der IsarTechnical University MunichMunich 81675Germany Department of Hematology Oncology and Tumor ImmunologyCharite-Universitatsmedizin BerlinCorporate Member of Freie Universitat BerlinHumboldt-Universitat zu Berlin and Berlin Institute of HealthBerlin 12203Germany Institute of medical Psychology and Biomedical Center(BmC) Faculty of MedicineLMU MunichMunich 80336Germany Institute of molecular Oncology and Functional Genomics TUM School of MedicineTechnical University MunichMunich 81675Germany Department of Toxicology University of Mainz Medical CenterMainz 55131Germany German Cancer Research Center(DKFZ)and German Cancer Consortium(DKTK) Heidelberg 69120Germany Center for Protein Assemblies(CPA) Technical University of MunichGarching 85747Germany Institute for Translational Cancer Research and Experimental Cancer Therapy Technical University MunichMunich 81675Germany Department of General Visceral and Pediatric SurgeryUniversity Medical Center GottingenGottingen 37075Germany

Dear Editor,Pancreatic ductal adenocarcinoma(PDAC)remains a significant health problem with an increase in the incidence and a five-year survival rate of only 10%[1].The Phosphoinositide 3-kinase-protein kinase-B-mechanistic target of rapamycin(PI3K-AKT-mTOR)pathway is a driver pathway in PDAC and an important therapeutic target[2].We[3]and others[4–6]have demonstrated that the mTOR kinase is a therapeutic target in PDAC,and rationally designed mTOR inhibitor(mTORi)-based combination therapies are emerging[2].

关键词： rapamycin therapeutic adenocarcinoma

The microbiota is dispensable for the early stages of peripheral regulatory T cell induction within mesenteric lymph nodes

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Cellular & molecular Immunology 2021年第5期18卷 1211-1221页

作者： carolin Wiechers mangge Zou Eric Galvez michael Beckstette maria Ebel Till Strowig Jochen Huehn Joern Pezoldt Department Experimental Immunology Helmholtz Centre for Infection ResearchBraunschweigGermany Department microbial Immune Regulation Helmholtz Centre for Infection ResearchBraunschweigGermany Department of Computational Biology for Individualised medicine Centre for Individualised Infection MedicineHelmholtz Centre for Infection Research and Hannover Medical SchoolHannoverGermany Cluster of Excellence RESIST(EXC 2155) Hannover Medical SchoolHannoverGermany Laboratory of Systems Biology and Genetics École Polytechnique Fédérale de LausanneLausanneSwitzerland

Intestinal Foxp3+regulatory T cell(Treg)subsets are crucial players in tolerance to microbiota-derived and food-borne antigens,and compelling evidence suggests that the intestinal microbiota modulates their generation,functional specialization,and *** bacterial species and microbiota-derived metabolites,such as short-chain fatty acids(SCFAs),have been reported to promote Treg homeostasis in the intestinal lamina ***,gut-draining mesenteric lymph nodes(mLNs)are particularly efficient sites for the generation of peripherally induced Tregs(pTregs).Despite this knowledge,the direct role of the microbiota and their metabolites in the early stages of pTreg induction within mLNs is not fully ***,using an adoptive transfer-based pTreg induction system,we demonstrate that neither transfer of a dysbiotic microbiota nor dietary SCFA supplementation modulated the pTreg induction capacity of *** mice housed under germ-free(GF)conditions displayed equivalent pTreg induction within *** molecular characterization of these de novo induced pTregs from mLNs by dissection of their transcriptomes and accessible chromatin regions revealed that the microbiota indeed has a limited impact and does not contribute to the initialization of the Treg-specific epigenetic ***,our data suggest that the microbiota is dispensable for the early stages of pTreg induction within mLNs.

关键词： Peripheral regulatory T cells microbiota Tolerance

Pancreatic cancer–Surgery for recurrent disease

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The Chinese-German Journal of Clinical Oncology 2007年第2期6卷 159-161页

作者： carolin Reiser Jrg Kleeff Helmut Friess markus Büchler Department of General Surgery University of Heidelberg Im Neuenheimer Feld 110 69120 Heidelberg Germany

Recurrence of pancreatic ductal adenocarcinoma (PDAC) after a resection with curative intent is inevitable in the majority of cases. Approximately three-quarters of patients ultimately die from metastatic, local, or c... 详细信息

关键词：胰腺癌复发疾病外科手术死亡率存活率

Enzymatic and non-enzymatic isolationsystems for adipose tissue-derived cells:current state of the art

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Cell Regeneration 2015年第1期4卷 61-74页

作者： Eleni Oberbauer carolin Steffenhagen Christoph Wurzer Christian Gabriel Heinz Redl Susanne Wolbank Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research CenterLinz/ViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Red Cross Blood Transfusion Service of Upper Austria LinzAustria

In the past decade, adipose tissue became a highly interesting source of adult stem cells for plastic surgery andregenerative medicine. The isolated stromal vascular fraction (SVF) is a heterogeneous cell population including theadipose-derived stromal/stem cells (ASC), which showed regenerative potential in several clinical studies and *** should be provided in a safe and reproducible manner in accordance with current good manufacturing practices(cGmP). To ensure highest possible safety for patients, a precisely defined procedure with a high-quality control isrequired. Hence, an increasing number of adipose tissue-derived cell isolation systems have been *** systems aim for a closed, sterile, and safe isolation process limiting donor variations, risk for contaminations,and unpredictability of the cell material. To isolate SVF from adipose tissue, enzymes such as collagenase are ***, in order to avoid enzymes, isolation systems using physical forces are available. Here, we provide anoverview of known existing enzymatic and non-enzymatic adipose tissue-derived cell isolation systems, which arepatented, published, or already on the market.

关键词： Human adipose tissue Stromal vascular fraction Adipose-derived stromal/stem cells Enzymatic Non-enzymatic Isolation systems

Predator-induced changes of male and female mating preferences: innate and learned components

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Current Zoology 2019年第3期65卷 305-316页

作者： martin PLATH Kai LIU Diane UmUTONI Guilherme GOmES-SILVA Jie-Fei WEI Eric CYUBAHIRO Bo-Jian CHEN carolin SOmmER-TREmBO Department of Basic and Applied Zoology College of Animal Science and Technology Northwest A&F University Yangling China Shaanxi Key Laboratory for molecular Biology in Agriculture Northwest A&F University Yangling China Sino-Canadian Center for Environment & Sustainable Development Department of Geography ("Saude Ambiental") Universidade Federal de Uberlandia Minas Gerais Brazil College of Environmental Science and Engineering Tongji University Shanghai China Department of Environmental Sciences Institute of Zoology University of Basel Switzerland

While many mati ng pref ere nces have a genetic basis, the question remai ns as to whether and how learning/experience can modify individual mate choice decisions. We used wild-caught (predator-experienced) and Fi laboratory-reared (predator-naive) invasive Western mosquitofish Gambusia affinis from China to test whether mating preferences (assessed in a first mate choice test) would change under immediate predation threat. The same individuals were tested in a second mate choice test during which 1 of 3 types of animated predators was presented: 1) a co-occurring predator, 2) a co-evolved but not currently co-occurring predator, and 3) a non-piscivorous species as control. We compared preference scores derived from both mate choice tests to separate innate from experiential effects of predation. We also asked whether predator-induced changes in mating preferences would differ betwee n sexes or depend on the choosing individual's personality type and/or body size. Wild-caught fish altered their mate choice decisions most when exposed to the co-occurring predator whereas laboratory-reared individuals responded most to the co-evolved predator, suggesting that both innate mechanisms and learning effects are involved. This behavior likely reduces individuals' risk of falling victim to predation by temporarily moving away from high-quality (i.e., conspicuous) mating partners. Accordingly, effects were stronger in bolder than shyer, large- compared with small-bodied, and female compared with male focal individuals, likely because those phenotypes face an increased predation risk overall. Our study adds to the growing body of literature appreciating the complexity of the mate choice process, where an array of intrinsic and extrinsic factors interacts during decision-making.

关键词： female choice male mate choice non-independent mate choice predator recognition sexual selection

Development of Bulk Organic Chemical Processes—History,Status,and Opportunities for Academic Research

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CCS Chemistry 2021年第3期3卷 512-530页

作者： carolin Schneider Thomas Leischner Pavel Ryabchuk Ralf Jackstell Kathrin Junge matthias Beller Leibniz-Institut für Katalyse e.V. 18059 Rostock Galapagos NV 2800 Mechelen

The production of bulk organic chemicals has a strong impact on our daily *** this review,an overview of important industrial processes using homogeneous catalysts is *** specific carbonylation and hydrogenation case studies,we want to show how basic research can contribute to the development of such processes and what challenges exist in this area of academic research.

关键词： catalysis bulk chemicals chemical processes sustainability methanol carbonylation hydrogenation

Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor m2-PK

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World Journal of Gastroenterology 2006年第43期12卷 7007-7011页

作者： carolin Tonus Gero Neupert markus Sellinger Herz-Jesu-Hospital Surgical Clinic Buttlarstr. 74 Fulda 36039 Germany Offenbach municipal Hospital Surgical Clinic Starkenburgring 66 Offenbach 63069 Germany medical Practice for Gastroenterology and Hepatology Rheing?nheimer Str. 121 Ludwigshafen 67065 Germany

AIm: To evaluate the utility of the innovative fecal tumor m2-Pyruvate kinase (m2-PK) test in our daily clinical routine, as a marker for the pre-selection of patients who should subsequently undergo colonoscopy for the diagnosis or exclusion of colorectal cancer. mETHODS: Fecal tumor m2-PK was measured in stool samples of 96 study participants (33 patients with colorectal cancer, 21 patients with rectal carcinoma and 42 controls) who all underwent total colonoscopy. RESULTS: In 39 of 42 individuals in the control group, fecal tumor m2-PK was below 4.0 kU/L (93% specificity). Colorectal tumors were accompanied by a highly significant increase (P mor m2- PK levels (median: colon carcinoma, 23.1 kU/L; rectal carcinoma, 6.9 kU/L; colorectal carcinoma, 14.7 kU/L), which correlated with Duke’s staging and T-classification. The overall sensitivity was 78% for colorectal cancer, increasing from 60% for stage T1 to 100% for stage T4 and from 60% for Duke’s A to 90% for Duke’s D tumors. CONCLUSION: Fecal tumor m2-PK is an appropriately sensitive tool to pre-select those patients requiring colonoscopy for the further diagnostic confirmation or exclusion of colorectal cancer.

关键词：结肠癌直肠癌生物标志物肿瘤

Primary liver injury and delayed resolution of liver stiffness after alcohol detoxification in heavy drinkers with the PNPLA3 variant I148m

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World Journal of Hepatology 2016年第35期8卷 1547-1556页

作者： Vanessa Rausch Teresa Peccerella carolin Lackner Eray Yagmur Helmut-Karl Seitz Thomas Longerich Sebastian mueller Salem medical Center and Center for Alcohol Research University of Heidelberg Institute for Pathology Medical University Graz Laboratory Diagnostics Center RWTH-University Hospital Aachen Aachen and Medical Care Center Institute of Pathology RWTH-University Hospital Aachen

AIm To investigate the influence of PNPLA3 genotype in heavy drinkers on serum markers and liver stiffness(LS) during alcohol withdrawal and its association with *** Caucasian heavy drinkers(n = 521) with a mean alcohol consumption of 192.1 g/d(median alcohol consumption: 169.0 g/d; 95%CI: 179.0-203.3) were enrolled at the Salem medical Center, University of Heidelberg. LS was measured by transient elastography(Fibroscan, Echosens SA, Paris, France). LS and serum markers were prospectively studied in these patients with all stages of alcoholic liver disease(steatosis, steatohepatitis, fibrosis) prior and after alcohol detoxification with a mean observation interval of 6.2 ± 3.2 d. A liver biopsy with histological analysis including the Kleiner score was obtained in 80 *** The PNPLA3 rs738409 genotype distribution for CC, CG and GG was 39.2%, 52.6% and 8.2%. GG genotype primarily correlated with histological steatohepatitis(r = 0.404, P mean LS was lowest in CC carriers(13.1 k Pa) as compared to CG and GG carriers(17.6 and 17.2 kPa). Notably, LS primarily correlated with fibrosis stage(r = 0.828, P m 17.6 to 12.7 kPa but to a lesser extent in GG carriers from 17.6 to 14.5 kPa. This was due to prolonged resolution of inflammation with significantly elevated aspartate transaminase levels after alcohol withdrawal in GG carriers. Non-invasive fibrosis assessment by LS in all patients showed a significantly higher F0 rate as compared to the biopsy cohort(47% vs 6%) with 3.8% more CC carriers while 3.7% less were seen in the F4 cirrhosis group. Thus, about 20% of patients with alcoholic liver cirrhosis would be attributable to PNPLA3 G variants. The OR to

关键词：肝僵硬含酒精的肝疾病 Adiponutrin PNPLA3 短暂 elastography 白酒退却发炎

moving beyond the opposition of diverse knowledge systems for food security and nutrition

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Journal of Integrative Agriculture 2020年第1期19卷 291-293页

作者： Nathanaël PINGAULT Patrick CARON Alicia KOLmANS Stefanie LEmKE Carol KALAFATIC Sabine ZIKELI Ann WATERS-BAYER carolin CALLENIUS QIN Yong-jun High Level Panel of Experts Committee on World Food SecurityFood and Agriculture Orgnization of the United NationsRome 00153Italy Universitéde montpellier Montpellier 34090France Research Center Global Food Security and Ecosystems University of HohenheimStuttgart 70599Germany Centre for Agroecology Water and ResilienceCoventry UniversityCV83LG CoventryUK Center for Organic Farming University of HohenheimStuttgart 70593Germany Agrecol Association Guggenhausen 88379Germany Shanxi Academy of Agricutural Sciences Taiyuan 030031P.R.China

Food Security and Nutrition(FSN) is influenced by diverse and complex factors, and therefore requires a holistic approach to agriculture and food systems plus integration of knowledge from diverse sources in science and society. Using the results of a colloquium held at the University of Hohenheim(Germany) in September 2016 leading up to the recent High Level Panel of Experts(HLPE) Note on Critical and Emerging Issues for Food Security and Nutrition, this article underlines the role of research and innovation as a social and political process and draws attention to neglected types of knowledge. It illustrates the potential of knowledge co-production and co-innovation to transform food systems in order to achieve the Sustainable Development Goals.

关键词： food security nutrition innovation Sustainable Development Goals