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SIBLINGs and SPArC families: Their emerging roles in pancreatic cancer

World Journal of Gastroenterology 2014年第40期20卷 14747-14759页

作者： Ferda Kaleagasioglu martin r berger Visiting Scientist at Toxicology and Chemotherapy Unit German Cancer Research Center D-69120 Heidelberg Germany Department of Pharmacology Faculty of Medicine University of Yeditepe 34755 Ata?ehir/?stanbul Turkey Toxicology and Chemotherapy Unit German Cancer Research Center D-69120 Heidelberg Germany

Pancreatic cancer has a considerably poor prognosis with a 5-year survival probability of less than 5% when all stages are combined. Pancreatic cancer is characterized by its dense stroma, which is involved in the critical interplay with the tumor cells throughout tumor progression and furthermore, creates a barrier restricting efficient penetration of therapeutics. Alterations in a large number of genes are reflected by a limited number of signaling pathways, which are potential targets. Understanding more about the molecular basis of this devastating cancer type regarding tumor microenvironment, distinct subpopulations of cells, epithelial-to-mesenchymal transition and inflammation will lead to the development of various targeted therapies for controlling tumor growth and metastasis. In this complex scenario of pancreatic cancer, especially members of the “small integrin binding ligand N-linked glycoproteins” (SIBLINGs) and “secreted protein acidic and rich in cysteine” (SPArC) families have emerged due to their prominent roles in properties including proliferation, differentiation, apoptosis, adhesion, migration, angiogenesis, wound repair and regulation of extracellular matrix remodeling. SIBLINGs consist of five members, which include osteopontin (OPN), bone sialoprotein, dentin matrix protein 1, dentin sialophosphoprotein and matrix extracellular phosphoglycoprotein. The SPArC family of modular extracellular proteins is comprised of SPArC/osteonectin (ON) and SPArC-like 1 (hevin); secreted modular calcium binding proteins; testicans and follistatin-like protein. In this review, we especially focus on OPN and ON, elaborating on their special and growing importance in pancreatic cancer diagnosis and prognosis.

关键词： Pancreatic cancer Microenvironment Signaling pathways Osteopontin Osteonectin Hevin Biomarker Therapeutic targeting

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Bcl-x_L and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells

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World Journal of Gastroenterology 2008年第24期14卷 3829-3840页

作者： Henning Schulze-Bergkamen roland Ehrenberg Lothar Hickmann Binje Vick Toni Urbanik Christoph C Schimanski martin r berger Arno Schad Achim Weber Steffen Heeger Peter r Galle Markus Moehler First Department of Medicine Johannes-Gutenberg-University Mainz German Cancer research Center Institute of Pathology University of Mainz Department of Pathology Institute of Surgical PathologyUniversity Hospital Merck Pharma GmbH

AIM： TO explore the role of Bcl-XL and Myeloid cell leukaemia （Mcl）-I for the apoptosis resistance of colorectal carcinoma （CrC） cells towards current treatment modalities. METHODS： Bcl-XL and Mcl-1 mrNA and protein expression were analyzed in CrC cell lines as well as human CrC tissue by Western blot, quantitative PCrand immunohistochemistry. Bcl-XL and Mcl-1 protein expression was knocked down or increased in CrC cell lines by applying specific sirNAs or expression plasmids, respectively. After modulation of protein expression, CrC cells were treated with chemotherapeutic agents, an antagonistic epidermal growth factor receptor （EGFr1） antibody, an EGFr1 tyrosine kinase inhibitor, or with the death receptor ligand TrAIL. Apoptosis induction and cell viability were analyzed. rESULTS： Here we show that in human CrC tissue and various CrC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CrC tissue than in surrounding non-malignant tissue, both on protein and mrNA level. Mcl-1 mrNA expression was significantly lower in malignant tissues. However, protein expression was slightly higher. Viability rates of CrC cells were significantly decreased after knock down of Bcl-xL expression, and, to a lower extent, after knock down of Mcl-1 expression. Furthermore, cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatinand irinotecan-induced apoptosis, and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand, upregulation of Bcl-xL by transfection of an expression plasmid decreased chemotherapeutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CrC cells. Apoptosis induction upon EGFr1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly, CD95- and TrAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION： Our data suggest that Bcl-xL and, to a lower extent, Mcl-1, are important anti-apoptotic

关键词： Colorectal carcinoma Bcl-XL Myeloid cellleukaemia-1 Epidermal growth factor receptor 1 Apoptosis 5-fluorouracil Irinotecan Oxaliplatin

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Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?

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World Journal of Gastroenterology 2007年第26期13卷 3605-3609页

作者： Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer martin r berger Theodor Junginger Peter r Galle Carl C Schimanski Department of General and Abdominal Surgery Johannes Gutenberg University of Mainz MainzGermany First Department of Internal Medicine Johannes Gutenberg University of Mainz MainzGermany Institute of Pathology Johannes Gutenberg University of MainzMainzGermany Third Department of Internal Medicine Johannes Gutenberg University of Mainz MainzGermany Unit of toxicology and chemotherapy German Cancer Research CenterGermany

AIM： To define the （co-）expression pattern of target receptor-tyrosine-kinases （rTK） in human gastric adenocarcinoma. METHODS： The （co-）expression pattern of VEGFr1-3, PDGFr（α/β and EGFr1 was analyzed by rT-PCr in 51 human gastric adenocarcinomas. In addition, IHC staining was applied for confirmation of expression and analysis of rTK localisation. rESULTS： The majority of samples revealed a VEGFr1 （98%）, VEGFr2 （80%）, VEGFr3 （67%）, PDGFrα （82%） and PDGFrβ （82%） expression, whereas only 62% exhibited an EGFr1 expression. 78% of cancers expressed at least four out of six rTKs. While VEGFr1-3 and PDGFrα revealed a predominantly cytoplasmatic staining in tumor cells, accompanied by an additional nuclear staining for VEGFr3, EGFr1 was almost exclusively detected on the membrane of tumor cells. PDGFrβ was restricted to stromal pericytes, which also depicted a PDGFrα expression. CONCLUSION： Our results reveal a high rate ofreceptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target rTK-inhibitors within a combination therapy.

关键词： VEGFr EGFr PDGFr Cancer Adeno-carcinoma Gastric Stomach

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Emerging insights into the function of very long chain fatty acids at cerebellar synapses

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Neural regeneration research 2025年第6期20卷 1709-1710页

作者： martin-Paul Agbaga Mohiuddin Ahmad Department of Cell Biology and Ophthalmology University of Oklahoma Health Sciences Centerand Dean McGee Eye InstituteOklahoma CityOKUSA

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

关键词： functions function insight

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Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of Methodology 2025年第1期15卷 20-25页

作者： Nadeesha r Samarasinghe Taniya S Nagpal Michele L Barbeau Charys M martin Division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement MSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： Medical education Musculoskeletal Anatomy Exercise Online learning

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Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural regeneration research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally martin Kopp Davide Malatesta Bastiaan rBloem Institute of Sport Sciences University of LausanneLausanneSwitzerland radboud University Medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands radboud University Medical Center Department of Medical BioSciencesNijmegenThe Netherlands research and Development Department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland Department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

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High mir-196a levels promote the oncogenic phenotype of colorectal cancer cells

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World Journal of Gastroenterology 2009年第17期15卷 2089-2096页

作者： Carl Christoph Schimanski Kirsten Frerichs Fareed rahman martin berger Hauke Lang Peter r Galle Markus Moehler Ines Gockel First Department of Internal Medicine Johannes Gutenberg University of Mainz 55131 Mainz Germany Unit of Toxicology and Chemotherapy GermanCancer Research Centre 69120 Heidelberg Germany Department of General and Abdominal Surgery Johannes Gutenberg University of Mainz 55131 Mainz Germany

AIM： To analyze the relevance of the microrNA mir-196a for colorectal ***： The impact of mir-196a on the restriction targets HoxA7, HoxBS, HoxC8 and HoxD8 was analyzed by reverse transcription polymerase chain reaction（rT-PCr） after transient transfection of SW480 cancer cells. The mir-196a transcription profile in colorectalcancer samples, mucosa samples and diverse cancercell lines was quantified by rT-PCr. Transiently mir-196a-transfected colorectal cancer cells were used for diverse functional assays in vitro and for a xenograft lung metastasis model in ***： HoxA7, HoxB8, HoxC8 and HoxD8 wererestricted by mir-196a in a dose-dependent andgene-specific manner. High levels of mir-196aactivated the AKT signaling pathway as indicated byincreased phosphorylation of AKT. In addition, highlevels of mir-196a promoted cancer cell detachment,migration, invasion and chemosensitivity towardsplatin derivatives but did not impact on proliferationor apoptosis. Furthermore, mir-196a increased thedevelopment of lung metastases in mice after tail veininjection.

关键词： Micro-rNA Cancer Colorectal mir-196a Migration Homeobox

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Aggregation-induced delayed fluorescence (AIDF) materials： a new break-through for nondoped OLEDs

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Science China Chemistry 2017年第12期60卷 1561-1562页

作者： martin r. Bryce Department of Chemistry Durham UniversityDurham DH1 3LEUK

Nowadays, purely organic materials with delayed fluorescence （DF） are being enthusiastically developed and extensively utilized as light-emitting materials to fabricate OLEDs because of their high exciton utilization and metal-flee nature. These DF materials usually have a small single-triplet splitting （AEsT）, and the nonradiative triplet excitons （75%） can be converted into radiative singlet excitons via thermally promoted reverse intersystem crossing （rISC） processes,

关键词： Aggregation-induced delayed fluorescence (AIDF) materials a new break-through nondoped OLEDs

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Palliative chemotherapy for gastroesophageal cancer in old and very old patients: A retrospective cohort study at the National Center for Tumor Diseases, Heidelberg

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World Journal of Gastroenterology 2015年第16期21卷 4911-4918页

作者： Anne Katrin berger Stefanie Zschaebitz Christine Komander Dirk Jger Georg martin Haag National Center for Tumor Diseases Heidelberg University Hospital NCT Clinical Cancer registry German Cancer Research Center

AIM:To investigate the outcome of palliative chemotherapy in old patients with gastroesophageal cancer at the National Center for Tumor Diseases,***:Using a prospectively generated database,we retrospectively analyzed 55 patients≥70years under palliative chemotherapy for advanced gastroesophageal cancer at the outpatient clinic of the National Center for Tumor Diseases Heidelberg,Germany between January 2006 and *** requirements for inclusion were(1)histologically proven diagnosis of gastroesophageal cancer;(2)advanced(metastatic or inoperable)disease;and(3)no history of radiation or *** clinical information included Eastern Cooperative Oncology Group performance status(ECOG PS),presence and site of metastases at diagnosis,date of previous surgery and perioperative chemotherapy,start and stop date of first-line treatment,toxicities and consecutive dosage reductions of first-line treatment,response to first-line therapy,date of progression,usage of second-line therapies and date and cause of *** times[progression-free survival(PFS),overall survival(OS)and residual survival(rS)]were *** and safety were *** factors including ECOG PS,age and previousperioperative treatment were ***:Median age of our cohort was 76 years.86%of patients received a combination of two cytotoxic drugs.76 percent of patients had an oxaliplatin-based first-line therapy with the oxaliplatin and 5-fluorouracil regimen being the predominantely chosen regimen(69%).Drug modifications due to toxicity were necessary in 56%of patients,and 11%of patients stopped treatment due to *** times of our cohort are in good accordance with the major phaseⅢtrials that included mostly younger patients:PFS and OS were 5.8 and 9.5 mo,*** differed significantly between patient groups with low(≤1)and high(≥2)ECOG PS(12.7 mo vs 3.8 mo,Pry old patients(≥75 years)did not sho

关键词： Gastroesophageal cancer Old patients Palliative chemotherapy Toxicity Eastern CooperativeOncology Group performance status

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Finding a home for hyoliths

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National Science review 2020年第2期7卷 470-471页

作者： martin r.Smith Department of Earth Sciences Durham University NSr

Many of the animal lineages that arose during the Cambrian evolutionary radiation, 540 million years ago, are difficult to relate to living taxa. Constraining the phylogenetic position of these highly disparate taxa allows their idiosyncratic morphologies to illuminate the stepwise establishment of modern body plans[1–3].Hyoliths are one such lineage; their operculate conical shells

关键词： Finding a home for hyoliths

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