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Genomic landscape of pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2014年第46期20卷 17498-17506页

作者： Niklas Gebauer Christian Schmidt-Werthern Veronica Bernard Alfred C Feller Tobias Keck Nehara Begum Dirk Rades Hendrik Lehnert Georg Brabant Christoph Thorns Department of Pathology University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Surgery University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Radiation Oncology university hospital of schleswig-holstein 23538 LuebeckGermany Department of Internal Medicine I University Hospital of Schleswig-Holstein23538 LuebeckGermany

AIM: To investigate the prognostic role of genomic stability and copy number alterations (CNAs) pancreatic neuroendocrine tumors (PanNETs).

关键词： Array comparative genomic hybridization Copy number alterations Chromosomal aberrations Pancreatic neuroendocrine tumors Prognosis

Expression of L amino acid transport system 1 and analysis of iodine-123-methyltyrosine tumor uptake in a pancreatic xenotransplantation model using fused high-resolution-micro-SPECT-MRI

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Hepatobiliary & Pancreatic Diseases International 2011年第1期10卷 30-37页

作者： Corinna von Forstner Maaz Zuhayra Ole Ammerpohl Sanjay Tiwari Olav Jansen Holger Kalthoff Eberhard Henze Jan-Hendrik Egberts Department of Nuclear Medicine University Hospital of Schleswig-Holstein Institute for Experimental Cancer Research University Hospital of Schleswig-Holstein Institute of Neuroradiology University Hospital of Schleswig-Holstein Department of General Surgery and Thoracic Surgery University Hospital of Schleswig-Holstein

BACKGROUND:The specificity in discriminating pancreatitis is limited in the positron emission tomography(PET)using ***,PET is not widely available compared to the single photon emission computed tomography(SPECT).Since amino acids play a minor role in metabolism of inflammatory cells,the potential of the SPECT tracer,3-[ 123 I]iodo-L-α-methyltyrosine(123I-IMT),for detecting pancreatic cancer was examined in xenotransplantation models of human pancreatic carcinoma in mice. METHODS: 123 I-IMT was injected to eight mice inoculated with subcutaneous or orthotopic pancreatic *** high-resolution-micro-SPECT(Hi-SPECT)and magnetic resonance imaging were *** gene expression level of L amino acid transport-system 1(LAT1)was analyzed and correlated with tumor uptake of 123 I-IMT. RESULTS:A high uptake of 123 I-IMT was detected in all tumor-bearing *** median tumor-to-background ratio (T/B)was 12.1(2.0-13.2)for orthotopic and 8.4(1.8-11.1)for subcutaneous xenotransplantation,***, the LAT1 expression in transplanted Colo357 cells was increased compared to non-malignant ***:Our mouse model could show a high 123 I-IMT uptake in pancreatic *** MRI scans facilitate precise evaluation of uptake in the specific regions of *** studies are required to confirm these findings in tumors derived from other human pancreatic cancer *** amino acids play a minor role in the metabolism of inflammatory cells,the potential for application of 123 I-IMT to distinguish pancreatic tumor from inflammatory pancreatitis warrants further investigation.

关键词： pancreatic ductal adenocarcinoma iodine-123-methyltyrosine high-resolution-micro-SPECT L amino acid transport-system 1 xenotransplantation model

The Vγ4/butyrophilin conspiracy: novel role of intraepithelial γδ T cells in chronic inflammatory bowel disease

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5575-5577页

作者： Dieter Kabelitz Institute of Immunology Christian-Albrechts University Kiel and University Hospital Schleswig-Holstein Campus KielKielGermany

In a recent article published in Science,Dart and colleagues reported that colonic T cells expressing the Vγ4 T-cell receptor(TCR)interact with epithelial butyrophilin-like(BTNL)proteins BTNL3 and BTNL8 in healthy individuals,and they observed a depletion of Vγ4 T cells in inflammatory bowel diseases with renormalization associated with disease remission.1 This paper identifies the BTNL/Vγ4 axis as a new disease modifier in IBD.

关键词： bowel inflammatory diseases

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon:An open-label pilot study

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World Journal of Gastroenterology 2007年第4期13卷 579-584页

作者： Th Witthoeft M Fuchs D Ludwig university hospital schleswig- holstein campus luebeck Department of Medicine I Division of Gastroenterology Luebeck Germany university hospital Ulm Department of Medicine I Ulm Germany

AIM： To investigate the use of high dose consensusinterferon in combination with ribavirin in former iv drug users infected with hepatitis C. METHODS： We started, before pegylated （PEG）interferons were available, an open-label study to investigate the efficacy and tolerability of high dose induction therapy with consensus interferon （CIFN） and ribavirin in treatment of naiive patients with chronic hepatitis C. Fifty-eight patients who were former iv drug users, were enrolled receiving 18 μg of CIFN daily for 8 wk, followed by 9 μg daily for up to wk 24 or 48 and 800 mg of ribavirin daily. End point of the study was tolerability and eradication of the virus at wk 48 and sustained virological response at wk 72. RESULTS： More than 62% of patients responded to the treatment with CIFN at wk 24 or 48, respectively, showing a negative qualitative PCR [genotype 1 fourteen patients （56%）, genotype 2 five （50%）, genotype 3 thirteen （87%）, genotype 4 four （50%）]. Forty-eight percent of genotype 1 patients showed sustained virological response （SVR） six months after the treatment. CONCLUSION： CIFN on a daily basis is well tolerated and side effects like leuko- and thrombocytopenia are moderate. End of therapy （EOT） rates are slightly lower than the newer standard therapy with pegylated interferons. CIFN on a daily basis might be a favourable therapy regimen for patients with GTI and high viral load or for non-responders after failure of standard therapy.

关键词： Consensus-interferon Hepatitis C Poly-merase chain reaction Sustained virological response

Chemokines and their receptors:important mediators to be aware of in neuroregenerative approaches for spinal cord injury

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Neural Regeneration Research 2015年第4期10卷 562-564页

作者： Friederike Knerlich-Lukoschus Department of Neurosurgery University HospitalUniversity of Schleswig-Holstein

Curative therapy for spinal cord injury （SCI） remains elusive, however identifying options for tailored treatment strategies is in full swing. Like in the brain there are distinct regions in the adult spinal cord that harbor neural progenitor cells （NPCs）（Horner et al., 2000）. This offers the possibility of recruiting these cells in reparative approaches to support endogenous spinal cord regenerative capacities. Hereby, one challenge among many others is to overcome the already re- strictive microenvironment of potential endogenous NPCs, which is considerably akered by ongoing secondary lesion cascades by the initial lesion. Research addressing this aspect identified a plethora of mediators that hinder or promote neuroregeneration where at inflammatory mediators are known to play an essential role.

关键词： Chemokines and their receptors

Practical guidelines for the treatment of inflammatory bowel disease

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World Journal of Gastroenterology 2007年第8期13卷 1149-1155页

作者： T Kuhbacher UR Flsch Department of Internal Medicine University Hospital Schleswig-HolsteinCampus KielSchitten- helmstr.12 Kiel 24105Germany Department of Internal Medicine University Hospital Schleswig-HolsteinCampus KielSchitten- helmstr.12Kiel 24105 Germany

In recent years, great progress has been made regarding the treatment of inflammatory bowel disease (IBD), particularly in the field of biological therapies. Nevertheless, the ultimate treatment is not in sight. With the development of new medication, it has become clear that we need a new understanding of IBD. Therapy needs to fit the different subtypes of IBD; e.g. mild disease in comparison to severe chronic active disease or Crohn's disease with or without fistulation or stenosis. The following article gives a practical overview of actual treatments for IBD. The intention of this article is not to provide a complete review of all new scientific developments, but to give a practical guideline for therapy of IBD.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn's disease Immunomodulators Anti-tumor necrosis factor

Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina General Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

Do statins reduce the mortality rate in stroke patients treated with systemic thrombolysis in a 5-year single-center study?

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Neural Regeneration Research 2021年第9期16卷 1807-1812页

作者： Toralf Brüning Mohamed Al-Khaled Department of Neurology University Medical Center Schleswig-HolsteinCampus LübeckLübeckGermany

The present study investigated the association between pre-treatment with a cholesterol-lowering drug(statin) or new setting hereon and the effect on the mortality rate in patients with acute ischemic stroke who received intravenous systemic thrombolysis. During a 5-year period(starting in October 2008), 542 consecutive stroke patients who received intravenous systemic thrombolysis with recombinant tissue plasminogen activator(rt-PA) at the Department of Neurology, university hospital schleswig-holstein, campus Lübeck, Germany, were included. Patients were characterized according to statins. The primary endpoint was mortality;it was assessed twice: in hospital and 3 months after discharge. The secondary outcome was the rate of symptomatic intracerebral hemorrhage. Of the 542 stroke patients examined(mean age 72 ± 13 years;51% women, mean National Institutes of Health Stroke Scale(NIHSS) score 11), 138 patients(25.5%) had been pretreated with statin, while in 190 patients(35.1%) statin therapy was initiated during their stay in hospital, whereas 193(35.6%) never received statins. Patients pre-treated with statin were older and more frequently had previous illnesses(arterial hypertension, diabetes mellitus and previous cerebral infarctions), but were comparably similarly affected by the stroke(NIHSS 11 vs. 11;P = 0.76) compared to patients who were not on statin treatment at the time of cerebral infarction. Patients pretreated with statin did not differ in 3-month mortality from those newly treated to a statin(7.6% vs. 8%;P = 0.9). Interestingly, the group of patients pretreated with statin showed a lower rate of in hospital mortality(6.6% vs. 17.0;P = 0.005) and 3-month mortality(10.7% vs. 23.7%;P = 0.005) than the group of patients who had no statin treatment at all. The same effect was seen for patients newly adjusted to a statin during the hospital stay compared to patients who did not receive statins(3-month mortality: 7.1% vs. 23.7%;P < 0.001). With a good funct

关键词： acute ischemic stroke hemorrhage mortality outcome secondary prophylaxis statins stroke systemic thrombolysis

Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

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Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration