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Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1632-1647页

作者： Katharina Joechle Jessica Guenzle Claus Hellerbrand Pavel Strnad Thorsten Cramer ulf peter neumann Sven Arke Lang Visceral and Transplantation Surgery University Hospital Rheinisch-Westfalisch Technische Hochschule AachenAachen 52074Germany Department of General and Visceral Surgery Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Institute of Biochemistry Friedrich-Alexander University Erlangen-NurnbergErlangen 91054Germany Department of Internal Medicine Ⅲ University Hospital Rheinisch-Westfalisch Technische Hochschule AachenAachen 52074Germany

The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated with multiple processes involved in tumor growth and *** with mTORC1,much less is known about mTORC2 in cancer,mainly because of the unavailability of a selective ***,existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so *** is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth,cell survival,metabolism,and cytoskeletal *** is not only implicated in tumor progression,metastasis,and the tumor microenvironment but also in resistance to ***,the central subunit of mTORC2,was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad ***,AKT,the main downstream regulator of mTORC2/Rictor,is one of the most highly activated proteins in *** and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment,emphasizing the need for further therapeutic *** review,therefore,summarizes the role of mTORC2/Rictor in cancer,with special focus on primary liver cancer but also on liver metastases.

关键词： Mammalian target of rapamycin Mammalian target of rapamycin complex 2 Rictor Liver cancer Liver metastases Hepatocellular carcinoma Cholangiocellular carcinoma

Liver transplantation in malignant disease

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World Journal of Clinical Oncology 2021年第8期12卷 623-645页

作者： Sven Arke Lang Jan Bednarsch Zoltan Czigany Katharina Joechle Andreas Kroh Iakovos Amygdalos Pavel Strnad Tony Bruns Daniel Heise Florian Ulmer ulf peter neumann Department of Surgery and Transplantation University Hospital RWTH AachenAachen 52074Germany Department of Internal Medicine III University Hospital RWTH AachenAachen 52074Germany

Liver transplantation for malignant disease has gained increasing attention as part of transplant *** the implementation of the Milan criteria,hepatocellular carcinoma(HCC)was the first generally accepted indication for transplantation in patients with ***,more liberal criteria for HCC have been developed,and research on this topic is still *** evident success of liver transplantation for HCC has led to the attempt to extend its indication to other *** perihilar cholangiocarcinoma,more and more evidence supports the use of liver transplantation,especially after neoadjuvant *** addition,some data also show a benefit for selected patients with very early stage intrahepatic *** epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver *** contrast,patients with hepatic angiosarcoma are currently not considered to be optimal *** secondary liver tumors,neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver ***,some evidence has been published supporting the use of liver transplantation even for colorectal liver *** review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.

关键词： Liver transplantation Hepatocellular carcinoma Cholangiocellular carcinoma Hepatic epithelioid hemangioendothelioma Undifferentiated embryonal sarcoma of the liver Colorectal cancer liver metastases Neuroendocrine cancer liver metastases

Biliary complications in liver transplantation: Impact of anastomotic technique and ischemic time on short- and long-term outcome

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World Journal of Transplantation 2015年第4期5卷 300-309页

作者： Stefan Kienlein Wenzel Schoening Anne Andert Daniela Kroy ulf peter neumann Maximilian Schmeding Department of General Visceral and Transplantation SurgeryUniversity Hospital Aachen Department of Gastroenterology and Hepatology University Hospital Aachen

AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver ***: We retrospectively reviewed 200 patients of our newly established liver transplantation(LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side(SS), end-to-end(EE) anastomosis or hepeaticojejunostomy(HJ). Biliary complications(BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion(ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography(ERCP)]. Laboratory results included alanine aminotransferase(ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional(e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by ***: A total of 200 patients [age: 56(19-72), alcoholic cirrhosis: n = 64(32%), hepatocellular carcinoma: n = 40(20%), acute liver failure: n = 23(11.5%), cryptogenic cirrhosis: n = 22(11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13(6.5%), primary sclerosing cholangitis: n = 13(6.5%), others: n = 25(12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5%(n = 75) with anastomotic stric

关键词： Liver transplantation Biliary complications Anastomotic stenosis Ischemic type biliary lesion Nonanastomotic strictures Bile leak Ischemic time Biliary drain complications

Exploring Biocomplexity in Cancer: A Comprehensive Review

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Open Journal of Biophysics 2024年第2期14卷 154-238页

作者： Andras Szasz Gyula peter Szigeti Department of Biotechnics Hungarian University of Agriculture and Life Sciences G&#246d&#246ll&#337 Hungary John von neumann Faculty of Informatics O&#769buda University Budapest Hungary

Living objects have complex internal and external interactions. The complexity is regulated and controlled by homeostasis, which is the balance of multiple opposing influences. The environmental effects finally guide the self-organized structure. The living systems are open, dynamic structures performing random, stationary, stochastic, self-organizing processes. The self-organizing procedure is defined by the spatial-temporal fractal structure, which is self-similar both in space and time. The system’s complexity appears in its energetics, which tries the most efficient use of the available energies;for that, it organizes various well-connected networks. The controller of environmental relations is the Darwinian selection on a long-time scale. The energetics optimize the healthy processes tuned to the highest efficacy and minimal loss (minimalization of the entropy production). The organism is built up by morphogenetic rules and develops various networks from the genetic level to the organism. The networks have intensive crosstalk and form a balance in the Nash equilibrium, which is the homeostatic state in healthy conditions. Homeostasis may be described as a Nash equilibrium, which ensures energy distribution in a “democratic” way regarding the functions of the parts in the complete system. Cancer radically changes the network system in the organism. Cancer is a network disease. Deviation from healthy networking appears at every level, from genetic (molecular) to cells, tissues, organs, and organisms. The strong proliferation of malignant tissue is the origin of most of the life-threatening processes. The weak side of cancer development is the change of complex information networking in the system, being vulnerable to immune attacks. Cancer cells are masters of adaptation and evade immune surveillance. This hiding process can be broken by electromagnetic nonionizing radiation, for which the malignant structure has no adaptation strategy. Our objective is to review

关键词： Complexity Networks Small-World Genetic Mutations Self-Organizing Self-Symmetry Energetic Balance Entropy Nash Equilibrium Games Evolution Cancer Therapy

Extended surgical resection for xanthogranulomatous cholecystitis mimicking advanced gallbladder carcinoma: A case report and review of literature

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World Journal of Gastroenterology 2006年第14期12卷 2293-2296页

作者： Antonino Spinelli Guido Schumacher Andreas Pascher Enrique Lopez-Hanninen Hussain Al-Abadi Christoph Benckert Igor M Sauer Johann Pratschke ulf P neumann Sven Jonas Jan M Langrehr peter Neuhaus Department of General Visceral and Transplantation Surgery Charitè-Universitatsmedizin BerlinCampus Virchow KlinikumAugustenburger Platz 113353 BerlinGermany Department of Radiology Charitè-Universitatsmedizin Berlin Campus Virchow KlinikumAugustenburger Platz 113353 BerlinGermany

Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.

关键词： Xanthogranulomatous cholecystitis Gallbladder cancer Gallbladder carcinoma

Multiple mating by both sexes in an invasive insect species,Aethina tumida(Coleoptera:Nitidulidae)

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Insect Science 2023年第2期30卷 517-529页

作者： Anna Papach Alexis Beaurepaire Orlando Yanez Meret Huwiler Geoffrey R.Williams peter neumann Institute of Bee Health Vetsuisse FacultyUniversity of BernBernSwitzerland Agroscope Swiss Bee Research CentreBernSwitzerland Department of Entomology&Plant Pathology Auburn UniversityAuburnAlabamaUSA

Multiple mating by both sexes is common among sexually reproducing *** hive beetles(SHB),Aethina tumida,are parasites of bee nests endemic to sub-Saharan Africa and have become a widespread invasive *** the considerable economic damages they can cause,their basic biology remains poorly *** we show that male and female small hive beetles can mate multiple times,suggesting that costs for mating are low in this *** an invasive *** population in the United States,a combination of laboratory experiments for males and paternity analysis with eight polymorphic DNA microsatellite markers for field-caught females were used to estimate the number of mating by both *** data show that females and males can mate multiple times—females mated with up to eight males,whereas males mated with at least seven *** results also showed that *** displayed a skewed paternity,although this was not consistent among the tested ***,first or last male advantage seem to be unlikely in *** observations that individuals of both sexes of *** can mate multiple times opens new research avenues for examining drivers of multiple mating and determining the role it may play in promoting biological invasions.

关键词： evolution of sex invasive species multiple partners polygynandry reproductive biology

Non-compliant and compliant balloons for endovascular rescue therapy of cerebral vasospasm after spontaneous subarachnoid haemorrhage: experiences of a single- centre institution with radiological follow- up of the treated vessel segments

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Stroke & Vascular Neurology 2021年第1期6卷 16-24页

作者： Alexander neumann Jan Küchler Claudia Ditz Kara Krajewski Jan Leppert peter Schramm Hannes Schacht Neuroradiology University Medical Center Schleswig Holstein Lubeck CampusLubeckGermany Neurosurgery University Medical Center Schleswig Holstein Lubeck CampusLubeckGermany

Background For endovascular rescue therapy(ERT)of cerebral vasospasm(CVS)due to spontaneous subarachnoid haemorrhage(sSAH),non-compliant(NCB)and compliant(CB)balloons are used with both balloon types bearing the risk of vessel injury due to specific mechanical *** severe delayed arterial narrowing after transluminal balloon angioplasty(TBA)for CVS has sporadically been described,valid data concerning incidence and relevance are *** aim was to analyse the radiological follow-up(RFU)of differently TBA-treated arteries(CB or NCB).Methods Twelve patients with utilisation of either NCB or CB for CVS were retrospectively analysed for clinical characteristics,ERT,functional outcome after 3 months and *** with the initial angiogram,we classified delayed arterial narrowing as mild,moderate and severe(60% calibre reduction).Results Twenty-three arteries were treated with CB,seven with *** median first RFU was 11 months after TBA with CB and 10 after *** was performed with catheter angiography in 18 arteries(78%)treated with CB and in five(71%)after NCB;magnetic resonance angiography was acquired in five vessels(22%)treated with CB and in two(29%)after *** arterial narrowing was detected in three arteries(13%)after CB and in one(14%)after *** or severe findings were neither detected after use of CB nor *** We found no relevant delayed arterial narrowing after TBA for CVS after *** previous assumptions that CB provides for more dilatation in segments adjacent to CVS,we observed no disadvantages concerning long-term adverse *** data support TBA as a low-risk treatment option.

关键词： balloon cerebral after

Reduced expression of Ca^(2+)-regulating proteins in the upper gastrointestinal tract of patients with achalasia

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World Journal of Gastroenterology 2006年第37期12卷 6002-6007页

作者： Harald Fischer Judith Fischer peter Boknik Ulrich Gergs Wilhelm Schmitz Wolfram Domschke Jan W Konturek Joachim neumann Medizinische Klinik und Poliklinik B Universittsklinikum Mnster 48129 Mnster Germany Institut fr Pharmakologie und Toxikologie Universittsklinikum Mnster 48149 Mnster Germany Institut fr Pharmakologie und Toxikologie Martin-Luther-Universitt Halle-Wittenberg 06112 Halle (Saale) Germany Klinik fr Innere Medizin/Gastroenterologie Elbe Klinikum Stade 21682 Stade Germany

AIM: To compare expression of Ca2+-regulating proteins in upper gastrointestinal (GI) tract of achalasia patients and healthy volunteers and to elucidate their role in achalasia. METHODS: Sarcoplasmic reticulum Ca2+ ATPase (SERCA) isoforms 2a and 2b, phospholamban (PLB), calsequestrin (CSQ), and calreticulin (CRT) were assessed by quantitative Western blotting in esophagus and heart of rats, rabbits, and humans. Furthermore, expression profi les of these proteins in biopsies of lower esophageal sphincter and esophagus from patients with achalasia and healthy volunteers were analyzed. RESULTS: SERCA 2a protein expression was much higher in human heart (cardiac ventricle) compared to esophagus. However, SERCA 2b was expressed predominantly in the esophagus. The highest CRT expression was noted in the human esophagus, while PLB, although highly expressed in the heart, was below our detection limit in upper GI tissue. Compared to healthy controls, CSQ and CRT expression in lower esophageal sphincter and distal esophageal body were signif icantly reduced in patients with achalasia (P < 0.05). CONCLUSION: PLB in the human esophagus mightbe of lesser importance for regulation of SERCA than in heart. Lower expression of Ca2+ storage proteins (CSQ and CRT) might contribute to increased lower esophageal sphincter pressure in achalasia, possibly by increasing free intracellular Ca2+.

关键词： Esophageal and gastric motility Esophagus Calsequestrin Calreticulin

First detection of viruses in Africanized honey bees from Peru

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Virologica Sinica 2014年第5期29卷 321-323页

作者： Orlando Yaez Graciano Tejada peter neumann Institute of Bee Health University of Bern Schwarzenburgstrasse 161Bern CH-3003Switzerland Swiss Bee Research Centre Federal Department of Economic Affairs EVD.Research Station Agroscope-Haras Liebefeld-Posieux ALP Schwarzenburgstrasse 161Bern CH-3003Switzerland Servicio Nacional de Sanidad Agraria del Peru(Senasa) Av.La Molina 1915 La MolinaLimaPeru Social Insect Research Group Zoology and Entomology DepartmentUniversity of Pretoria Private Bag X20 HatfieldPretoria 0028South Africa

Dear Editor,The ability of the Western honey bee,Apis mellifera,to adapt to most climates of the world and the ongoing standardization of colony management has made this species of honey bees the most important species for crop *** recent years,Peru emerged as a main exporter of industrial *** industry is mainly concentrated in the Peruvian coastal region,because the local climate permits off-season production

关键词： honey mellifera Apis season colony adapt coastal crops emerged concentrated