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| 1 | Cellular and molecular mechanisms in the pathogenesis of liver fibrosis:An update显示文摘There have been considerable recent advances towards a better understanding of the complex cellular and molecular network underlying liver fibrogenesis.Recent data indicate that the termination of fibrogenic processes and the restoration of deficient fibrolytic pathways may allow the reversal of advanced fibrosis and even cirrhosis.Therefore,efforts have been made to better clarify the cellular and molecular mechanisms that are involved in liver fibrosis.Activation of hepatic stellate cells(HSCs)remains a central event in fibrosis,complemented by other sources of matrix-producing cells,including portal fibroblasts,fibrocytes and bone marrow-derived myofibroblasts.These cells converge in a complex interaction with neighboring cells to provoke scarring in response to persistent injury.Defining the interaction of different cell types,revealing the effects of cytokines on these cells and characterizing the regulatory mechanisms that control gene expression in activated HSCs will enable the discovery of new therapeutic targets.Moreover,the characterization of different pathways associated with different etiologies aid in the development of disease-specific therapies.This article outlines recent advances regarding the cellular and molecular mechanisms involved in liver fibrosis that may be translated into future therapies.The pathogenesis of liver fibrosis associated with alcoholic liver disease,non-alcoholic fatty liver disease and viral hepatitis are also discussed to emphasize the various mechanisms involved in liver fibrosis. | Gülsüm ?zlem Elpek | 2014 | World Journal of Gastroenterology2014，20，23： | 82 |
| 2 | Angiogenesis and liver fibrosis显示文摘Recent data indicate that hepatic angiogenesis, regardless of the etiology, takes place in chronic liver diseases(CLDs) that are characterized by inflammat ion and progre s s ive f ibros is. B e c aus e ant iangiogenic therapy has been found to be efficient in the prevention of fibrosis in experimental models of CLDs, it is suggested that blocking angiogenesis could be a promising therapeutic option in patients with advanced fibrosis. Consequently, efforts are being directed to revealing the mechanisms involved in angiogenesis during the progression of liver fibrosis. Literature evidences indicate that hepatic angiogenesis and fibrosis are closely related in both clinical andexperimental conditions. Hypoxia is a major inducer of angiogenesis together with inflammation and hepatic stellate cells. These profibrogenic cells stand at the intersection between inflammation, angiogenesis and fibrosis and play also a pivotal role in angiogenesis. This review mainly focuses to give a clear view on the relevant features that communicate angiogenesis with progression of fibrosis in CLDs towards the-end point of cirrhosis that may be translated into future therapies. The pathogenesis of hepatic angiogenesis associated with portal hypertension, viral hepatitis, non-alcoholic fatty liver disease and alcoholic liver disease are also discussed to emphasize the various mechanisms involved in angiogenesis during liver fibrogenesis. | Gulsum Ozlem Elpek | 2015 | World Journal of Hepatology2015，7，3： | 24 |
| 3 | Thrombospondin-1 expression correlates with angiogenesis in experimental cirrhosis显示文摘AIM:To investigate the significance of Thrombospondin-1 (TSP-1) expression and its relationship with angiogenesis during experimental fibrosis. METHODS:Cirrhosis was induced in male Wistar rats by intraperitoneal administration of diethyl nitrosamine (DEN). The serial sections from liver tissues were stained with anti-CD34 and anti-TSP-1 antibodies before being quantitated by light microscopy. RESULTS:Our results showed that of TSP-1 expression gradually increases according to the severity of fibrosis (GroupⅠvs group Ⅱ, Group Ⅲ and Group Ⅳ;Group Ⅱ vs group Ⅲ and group Ⅳ;group Ⅲ vs group Ⅳ, P < 0.05). Moreover, TSP-1 expression was found to be correlated with angiogenesis (P < 0.05). CONCLUSION:The correlative evidence of the link between TSP-1 and fibrosis or angiogenesis provided by this study suggests that besides its role as a strong promoter of transforming growth factor-β1 (TGF-β1), TSP-1 might have an additional role in liver fibrogenesis by stimulating angiogenesis and this protein could be a potential target to prevent fibrogenesis in chronic inflammatory diseases of the liver. | Gülsüm zlem Elpek Güzide Ayse Gkhan Sevgi Bozova | 2008 | World Journal of Gastroenterology2008，14，14： | 7 |
| 4 | Expression of Notch pathway components (Numb, Itch, and Siah-1) in colorectal tumors: A clinicopathological study显示文摘BACKGROUND The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs,including the colon.Accordingly,studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression.Although Numb,Itch,and seven in absentia homolog-1(Siah-1)have been shown to contribute to the regulation of Notch signaling,their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.AIM To evaluate Numb,Itch,and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.METHODS Expression of Notch-1,Numb,Itch,and Siah-1 was investigated in 50 colorectal carcinomas,30 adenomas,and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(PCR)analyses.RESULTS In contrast to Notch-1,which is expressed at higher levels in tumor tissues and adenomas,expression of Numb,Itch,and Siah-1 was stronger and more frequent in normal mucosa(P<0.01).There was a positive correlation between Notch-1 expression and high histological grade,the presence of lymph node metastasis,and advanced-stage tumors,whereas expression of Numb,Itch,and Siah-1 was absent or reduced in tumors with these clinicopathological parameters(P<0.05).In survival analysis,expression of Notch was related to poor prognosis but that of Numb,Itch,and Siah-1 correlated with improved survival(P<0.05).Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis(P<0.05).CONCLUSION Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb,Itch,and Siah-1 expression is associated with carcinogenesis.Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma(CRC)progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC. | Sinem Cil Gonulcu Betul Unal Ibrahim Cumhur Bassorgun Mualla Ozcan Hasan Senol Coskun Gulsum Ozlem Elpek | 2020 | World Journal of Gastroenterology2020，26，26： | 5 |
| 5 | An unusual cause of cholecystitis:Heterotopic pancreatic tissue in the gallbladder显示文摘Gallbladder localization of heterotopic pancreas (HP) is uncommon and very rarely gives rise to symptoms. Herein we report a case of HP found in the gallbladder neck presented with signs and symptoms of cholecystitis. The patient was a 40-year old male, suffering from epigastric pain, abdominal fullness and fever. On physical examination, the right upper abdomen was tender with a positive Murphy’s sign. Ultrasonographic examination showed a hydropic gallbladder without stones and he underwent a cholecystectomy. Pathological examination revealed an intramural nodule (9 mm) in the neck region which is consisted of acini, ducts and islet cells of an aberrant pancreatic tissue. Although HP is encountered rarely in the gallbladder and is found incidentally during pathological studies, this case emphasizes that HP might cause symptoms and present clinically as cholecystitis. For this reason, in patients presenting with symptomatic gallbladder diseases, including cholecystitis without any other pathology, HP should be taken into consideration before it is diagnosed as 'idiopathic’’. | Glsm zlem Elpek Sevgi Bozova Gkben Y■d■r■m Kpesiz Mehmet ■■ | 2007 | World Journal of Gastroenterology2007，13，2： | 2 |
| 6 | Mixed neuroendocrine–nonneuroendocrine neoplasms of the gastrointestinal system:An update显示文摘Mixed neuroendocrine-nonneuroendocrine neoplasms(Mi NENs)of the digestive tract are a rare heterogeneous group of tumors that present many challenges in terms of diagnosis and treatment.Over the years,the diagnostic criteria,classification,and clinical behavior of these tumors have been the subjects of ongoing debate,and the various changes in their nomenclature have strengthened the challenges associated with Mi NENs.This review is performed to provide an understanding of the key factors involved in the evolution of the designation of these tumors as Mi NEN,highlight the current diagnostic criteria,summarize the latest data on pathogenesis and provide information on available treatments.Moreover,this work seeks to increase the awareness about these rare neoplasms by presenting the clinicopathological features and prognostic factors that play important roles in their behavior and discussing their different regions of origin in the gastrointestinal system(GIS).Currently,the Mi NEN category also includes tumors in the GIS with a nonneuroendocrine component and epithelial tumors other than adenocarcinoma,depending on the organ of origin.Diagnosis is based on the presence of both morphological components in more than 30%of the tumor.However,this value needs to be reconfirmed with further studies and may be a limiting factor in the diagnosis of Mi NEN by biopsy.Furthermore,available clinicopathological data suggest that the inclusion of amphicrine tumors in the definition of Mi NEN is not supportive and warrants further investigation.The diagnosis of these tumors is not solely based on immunohistochemical findings.They are not hybrid tumors and both components can act independently;thus,careful grading of each component separately is required.In addition to parameters such as the metastatic state of the tumor at the time of diagnosis and the feasibility of surgical resection,the aggressive potential of both components has paramount importance in the choice of treatment.Regardless of the organ of origin within the GIS,almost Mi NENs are tumors with poor prognosis and are frequently encountered in the elderly and men.They are most frequently reported in the colorectum,where data from molecular studies indicate a monoclonal origin;however,further studies are required to provide additional support for this origin. | Gulsum Ozlem Elpek | 2022 | World Journal of Gastroenterology2022，28，8： | 2 |
| 7 | Neuropilins and liver显示文摘Neuropilins(NRPs) are highly conserved transmembrane glycoproteins that possess pleiotropic functions. Neuropilin-1(NRP1) and its homologue neuropilin-2 interact as coreceptors with both class 3 semaphorins and vascular endothelial growth factor and are involved in neuronal guidance and angiogenesis, respectively. The contribution of NRPs to tumor angiogenesis has been highlighted in previous studies, leading to the development of NRP antagonists as novel anti-angiogenesis therapies. However, more recent studies have demonstrated that NRPs have a much broader spectrum of activity in the integration of different pathways in physiological and pathological conditions. A few studies investigated the role of NRPs in both malignant and non-neoplastic liver diseases. In normal liver, NRP1 is expressed in hepatic stellate cells and liver sinusoidal endothelial cells. NRP1 expression in hepatocytes has been associated with malignant transformation and may play an important role in tumor behavior. A contribution of NRPs in sinusoidal remodeling during liver regeneration has been also noted. Studies in chronic liver diseases have indicated that, besides its influence on angiogenesis, NRP1 might contribute to the progression of liver fibrosis owing to its effects on other growth factors, including transforming growth factor β1. As a result, NRP1 has been identified as a promising therapeutic target for future antifibrotic therapies based on the simultaneous blockade of multiple growth factor signaling pathways. In this review, the structure of NRPs and their interactions with various ligands and associated cell surface receptors are described briefly. The current understanding of the roles of the NRPs in liver diseases including tumors, regeneration and fibrogenesis, are also summarized. | Gulsum Ozlem Elpek | 2015 | World Journal of Gastroenterology2015，21，23： | 2 |
| 8 | CD4^+CD25^+ T regulatory cells dominate multiple immune evasion mechanisms in early but not late phases of tumor development in a B cell lymphoma model 显示文摘 | Elpek KG Lacelle C Singh NP | 2007 | J Immunol2007，178，11： | 1 |
| 9 | Hypoxia-inducible factor-1alpha expression in experimental cirrhosis:correlation with vascular endothelial growth factor expression and angiogenesis显示文摘 | Bozova S Elpek GO | | 0，，07： | 1 |
| 10 | Expression of heat-shock proteins hsp27,hsp70 and hsp90 in malignant epithelial tumour of the ovaries显示文摘 | Elpek GO Karaveli S Simsek T | 2003 | APMIS2003，111，4： | 1 |
| 11 | CD4^+CD25^+ T regulatory cells dominate multiple immune evasion mechanisms in early but not late phases of tumor development in a B cell lymphoma model显示文摘 | Elpek KG Lacelle C Singh NP | 2007 | J Immunol2007，178，11： | 1 |
| 12 | Clinicopathologic evaluation of CDw75 antigen expression in patients with gastric carcinoma显示文摘 | Gelen T Karpuzoglu G | 2001 | J Pathol2001，193，2： | 1 |
| 13 | Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors 显示文摘 | Sharma RK Elpek KG Yolcu ES | 2009 | Cancer Res2009，69，10： | 1 |
| 14 | Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes显示文摘 | ELPEK K G RUBINSTEIN M P BELLEMARE PELLETIER A | 2010 | Proc Natl Acad Sci U S A2010，107，21： | 1 |
| 15 | The prognostic relevance of angiogenes is and mast cells in squamous cell carcinoma of the oesophagus显示文摘 | Elpek G O Gelen T Aksov N H | 2001 | J Clin Patho2001，54，12： | 1 |
| 16 | Differential changes in Substance P,VIP as well as neprilysin levels in patients with gastritis or ulcer 显示文摘 | Erin N Trker S Elpek O | 2012 | Peptides2012，35，2： | 1 |
| 17 | p27 labeling Index and proliferation in gastrointestinal stromal tumors:correlations with clinicopathologic factors and recurrence显示文摘 | Gelen T Elpek GO Aksoy NH | 2003 | Jpn J Clin Oncol2003，33，7： | 1 |
| 18 | Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice显示文摘 | Gomez-Gutierrez JG Elpek KG Montes de Oca-Luna R | 2007 | Cancer Immunol Immunother2007，56，7： | 1 |
| 19 | p27 Labeling index and proliferation in gastrointestinal stromal tumors:correlations with clinicopathologic factors and recurrence显示文摘 | Gelen T Elpek G Aksoy N H | 2003 | JPN J Clin Oncol2003，33，7： | 1 |
| 20 | A novel technique of sutureless color- ectal anastomosis by bipolar coagulation显示文摘 | Asian A Elpek O | 2009 | Eur J Pediatr Surg2009，19，6： | 1 |
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