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Sperm subpopulations in avian species： a comparative study between the rooster （Gallus domesticus） and Guinea fowl （Numida meleagris）

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Asian Journal of Andrology 2016年第6期18卷 889-894页

作者： Manuel Garcia-herreros National Secretariat of Higher Education Science Technology and Innovation (SENESCYT) Quito Ecuador

The main aims of this research were to study possible differences in objective morphometric sperm characteristics, establish normative sperm morphometry standards, and evaluate the presumed different subpopulation distribution of avian spermatozoa from the rooster （Gallus domesticus） and Guinea fowl （Numida meleagris） as model avian species. Seventy-two ejaculates （36 per species studied） were obtained manually, following a training period involving gently combined dorso-abdominal and *** massage of the birds. Ejaculates were processed for volume, sperm concentration, viability, motility, and morphology. Moreover, samples were submitted for sperm morphometric assessment using objective Computer-Assisted Semen Analysis for Morphometry （CASA-Morph） methods, with sperm morphometric descriptors evaluated by Principal Component Analysis （PCA） and multivariate clustering analyses. There were several differences observed between the avian species in values obtained for ejaculate volume and sperm concentration （P 〈 0.001）. Irrespective of species, PCA revealed two Principal Components （PCs） explaining more than 80% of the variance. In addition, the number of subpopulations differed with species （three and five subpopulations for rooster and Guinea fowl, respectively）. Moreover, the distribution of the sperm subpopulations was found to be structurally different between species. In conclusion, our findings from using CASA-Morph methods indicate pronounced sperm morphometric variation between these two avian species. Because of the strong differences observed in morphometric parameter values and their subpopulation distribution, these results suggest that application of objective analytical methods such as CASA-Morph could substantially improve the reliability of comparative studies and help establish valid normative sperm morphological values for avian species.

关键词： Gallus domesticus Numida meleaEris principal component analysis sperm morphometry sperm subpopulations

Normozoospermic versus teratozoospermic domestic cats： differential testicular volume, sperm morphometry, and subpopulation structure during epididymal maturation

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Asian Journal of Andrology 2016年第6期18卷 871-878页

作者： Miguel Angel Gutierrez-Reinoso Manuel Garcia-herreros National Secretariat of Higher Education Science Technology and Innovation (SENESCYT) Quito Ecuador

Teratozoospermia （〈40% morphologically normal spermatozoa/ejaculate） is a frequent phenomenon in feline species. This research was carried out to study the possible differences in testicular volume, differential sperm morphometric traits, and potential differences regarding the sperm subpopulational structure during epididymal sperm maturation in teratozoospermic feline donors. Epididymal sperm samples were collected from the caput （R1）, corpus （R2）, and cauda （R3） epididymidis in two donor groups （N： normozoospermic; T： teratozoospermic）. Aliquots were assessed for concentration, viability, motility, and acrosomal integrity. Sperm morphometric descriptors from CASA-Morph analysis were analyzed by the Principal Component Analysis （PCA） and clustering analyses. Irrespective of the group analyzed, PCA revealed two Principal Components （PCs） for each epididymal region explaining more than the 93% of the variance. Surprisingly, the number of subpopulations remained constant in regions R1-R2-R3 irrespective of the donor group analyzed. However, the distribution of these subpopulations was found to be structurally different and strongly influenced by the epididymal region and the donor group. In conclusion, testicular morphometry and the sperm subpopulation structure were different in N and T donors. The alterations in subpopulations during epididymal maturation could be used as a potential clinical indicator of teratozoospermic individuals since an important influence of teratozoospermia on sperm subpopulation structure has been demonstrated.

关键词： epididymis feline sperm morphometry sperm subpopulations teratozoospermia testicular volume

Spontaneous regression of pancreatic cancer: Real or a misdiagnosis?

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World Journal of Gastroenterology 2012年第23期18卷 2902-2908页

作者： Marta herreros-Villanueva Elizabeth Hijona Angel Cosme Luis Bujanda Schulze Center for Novel Therapeutics Division of Oncology Research Department of Medicine Mayo Clinic Rochester MN 55905 United States Department of Gastroenterology Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas University of the Basque Country Donostia Hospital-Biodonostia Institute 20014 San Sebastian Spain

Spontaneous tumor regression has been subject of numerous studies and speculations for many years. This phenomenon is exceptional, but well reported, in some types of tumors, but not in pancreatic cancer. Pancreatic cancer has the worst five-year survival rate of any cancer. Despite numerous molecular studies and clinical approaches, using several mouse models, this cancer responds poorly to the existing chemotherapeutic agents and progress on treatment remains elusive. Although pancreatic cancer tumors seldom undergo spontaneous regression, and some authors take that with skepticism, there are some cases reported in the literature. However, the variability in the description of the reports and technical details could make this process susceptible to misdiagnosis. Distinguishing between different types of pancreatic carcinoma should be taken with caution as they have wide differences in malignant potential. Diseases such as pancreatic benign tumors, insulinomas, or autoimmune pancreatitis could be responsible for this misdiagnosis as a pancreatic cancer. Here we review different cases reported, their clinical characteristics, and possible mechanisms leading to spontaneous regression of pancreatic cancer. We also discuss the possibilities of misdiagnosis.

关键词：胰腺癌误诊回归良性肿瘤实时临床特点分子生物学自身免疫性

Adjuvant and neoadjuvant treatment in pancreatic cancer

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World Journal of Gastroenterology 2012年第14期18卷 1565-1572页

Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United *** resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at *** studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and *** there is no consensus around the world on what constitutes"standard"adjuvant therapy for pancreatic *** controversy derives from several studies,each fraught with its own *** of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in *** of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more *** this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

关键词：辅助治疗胰腺癌恶性肿瘤癌症治疗手术切除治疗方案化疗标准

Mouse models of pancreatic cancer

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World Journal of Gastroenterology 2012年第12期18卷 1286-1294页

作者： Marta herreros-Villanueva Elizabeth Hijona Angel Cosme Luis Bujanda Schulze Center for Novel Therapeutics Division of Oncology ResearchDepartment of MedicineMayo ClinicRochesterMN 55905United States Department of Gastroenterology Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd)University of the Basque CountryDonostia HospitalSan Sebastian 20014Spain Department of Gastroenterology Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd)University of the Basque CountryDonostia Hospital

Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are *** during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and *** vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research *** the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been *** models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic *** alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic *** mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model *** models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer ***,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

关键词：小鼠模型胰腺癌胰脏治疗方案肿瘤抑制基因恶性肿瘤分子特征遗传工程

c-Met in pancreatic cancer stem cells: Therapeutic implications

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World Journal of Gastroenterology 2012年第38期18卷 5321-5323页

作者： Marta herreros-Villanueva Aizpea Zubia-Olascoaga Luis Bujanda Division of Oncology Research Department of Medicine Schulze Center for Novel Therapeutics Mayo Clinic Rochester MN 55905 United States IkerChem Oncology Therapeutics Department 20009 San Sebastian Spain Department of Gastroenterology Centro de Investigación Biomédica en Red en Enfermedades Hepáticasy Digestivas (CIBERehd) Donostia Hospital-Biodonostia Institute University of the Basque Country 20014 San Sebastian Spain

Pancreatic cancer is the deadliest solid cancer and currently the fourth most frequent cause of cancer-related deaths. Emerging evidence suggests that cancer stem cells (CSCs) play a crucial role in the development and progression of this disease. The identification of CSC markers could lead to the development of new therapeutic targets. In this study, the authors explore the functional role of c-Met in pancreatic CSCs, by analyzing self-renewal with sphere assays and tumorigenicity capacity in NOD SCID mice. They concluded that c-Met is a novel marker for identifying pancreatic CSCs and c-Met high in a higher tumorigenic cancer cell population. Inhibition of c-Met with XL184 blocks self-renewal capacity in pancreatic CSCs. In pancreatic tumors established in NOD SCID mice, c-Met inhibition slowed tumor growth and reduced the population of CSCs, along with preventing the development of metastases.

关键词：胰腺干细胞胰腺癌治疗 SCID小鼠肿瘤发生职能作用自我更新胰腺肿瘤

FRACTIONAL-STEP FINITE ELEMENT METHOD FOR CALCULATION OF 3-D FREE SURFACE PROBLEM USING LEVEL SET METHOD

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Journal of Hydrodynamics 2006年第6期18卷 742-747页

作者： ZHAO Lan-hao LI Tong-chun WANG Ling herreros M. I. PASTOR M. College of Water Conservancy and Hydropower Engineering Hohai University Naniing 210098 China Anhui Survey and Design Institute of Water Conservancy and Hydropower Hefei 230022 China CEDEX and E.T.S. de Caminos Madrid Spain

A two-step Taylor-Galerkin fractional-step finite element method, which is of second order accuracy in space and time, was proposed for the three-dimensional free surface problem. With this method, the intermediate velocity was explicitly obtained by neglecting pressure gradient term, and then the velocity was corrected by adding the effects of pressure once the pressure field had been obtained from the pressure Poisson equation. The level set approach was applied to track implicitly the free surface. In order to track the free surface, the transport equation of the level set function was solved at each time step and the level set function is reinitialized through iteration to maintain it as a distance function. The governing equations of the system were discretized by the two- step Taylor-Galerkin method, which is of high-order accuracy and easy to be used. The validity and reliability of this method in this article were proved by two numerical examples.

关键词： level set free surface two steps Taylor-Galerkin fractional step FEM

Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance

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World Journal of Gastroenterology 2017年第18期23卷 3367-3373页

作者： Angel Cosme Milagrosa Montes Begona Ibarra Esther Tamayo Horacio Alonso Usua Mendarte Jacobo Lizasoan Marta herreros-Villanueva Luis Bujanda Gastroenterology Department Hospital Universitario Donostia/Instituto BiodonostiaUniversidad del País VascoCentro de Investigación Biomédica en Red de Enfermedades Hepaticas y Digestivas Biomedical Research Center Network for Respiratory Diseases Microbiology Department Hospital Universitario Donostia-Instituto Biodonostia Faculty of Life Sciences Universidad Isabel I

AIM To evaluate the efficacy of antimicrobial susceptibilityguided therapy before first-line treatment for infection in patients with dual or triple antibiotic *** A total of 1034 patients infected by Helicobacter pylori(H. pylori) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034(15%) patients showed resistance to two(127/1034; 12%) and to three(30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori-resistance(clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL(omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43cases, OAM(omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC(omeprazole 20 mg ***., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori-resistance(clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR(omeprazole 20 mg ***., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. RESULTS Intention-to-treat eradication rates were: OAL(97.6%), OAM(91.6%), OAC(92.3%) and OAR(58.3%). Cure rate was significantly higher in na?ve patients treated with OAR-10 compared to patients who had two or three previous treatment failures(83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. CONCLUSION Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

关键词： Helicobacter pylori 抵抗根除率抗菌剂危险性治疗

Embryonic stem cell factors and pancreatic cancer

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World Journal of Gastroenterology 2014年第9期20卷 2247-2254页

作者： Marta herreros-Villanueva Luis Bujanda Daniel D Billadeau Jin-San Zhang Daniel D Billadeau Jin-San Zhang Division of Oncology Research Schulze Center for Novel Therapeutics Mayo Clinic College of Medicine Rochester MN 55905 United States Department of Gastroenterology Hospital Donostia/Instituto Biodonostia Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Universidad del País Vasco UPV/EHU20014 San Sebastián Spain School of Pharmaceutical Sciences Key Laboratory of Biotechnology and Pharmaceutical Engineering Wenzhou Medical University

Pancreatic ductal adenocarcinoma(PDAC),the most common type of pancreatic tumor,is a highly aggressive human cancer with the lowest five-year survival rate of any human maligancy primarily due to its earlymetastasis and lack of response to chemotherapy and *** research suggests that PDAC cells comprise a hierarchy of tumor cells that develop around a population of cancer stem cells(CSCs),a small and distinct population of cancer cells that mediates tumoregenesis,metastasis and resistance to standard ***,CSCs could be a target for more effective treatment ***,pancreatic CSCs are subject to regulation by some of key embryonic stem cell(ESC)transctiption factors abberently expressed in PDAC,such as SOX2,OCT4 and *** transcription factors are important DNA-binding proteins present in both embryonic and adult somatic *** critical role of these factors in reprogramming processes makes them essential not only for embryonic development but also *** we provide an overview of stem cell transcription factors,particularly SOX2,OCT4,and NANOG,on their expression and function in pancreatic *** contrast to embryonic stem cells,in which OCT4 and SOX2 are tightly regulated and physically interact to regulate a wide spectrum of target genes,de novo SOX2 expression alone in pancreatic cancer cells is sufficient to promote self-renewal,dedifferentiation and imparting stemness characteristics via impacting specific cell cycle regulatory genes and epithelial-mesnechymal transtion driver ***,targeting ESC factors,particularly SOX2,could be a worthy strategy for pancreatic cancer therapy.

关键词： Embryonic stem cells NANOG SOX2 OCT4 Pluripotency