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Epigenetics and pancreatic cancer:pathophysiology and novel treatment aspects

World Journal of Gastroenterology 2014年第24期20卷 7830-7848页

作者： daniel Neureiter Tarkan Jger Matthias Ocker Tobias Kiesslich Institute of pathology Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Department of Surgery Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Experimental Medicine Oncology Bayer Pharma AG13342 BerlinGermany Department of Internal Medicine I Paracelsus Medical University/Salzburger Landeskliniken (SALK)5020 SalzburgAustria Institute of physiology and pathophysiology Paracelsus Medical University5020 SalzburgAustria

An improvement in pancreatic cancer treatment represents an urgent medical goal. Late diagnosis and high intrinsic resistance to conventional chemotherapy has led to a dismal overall prognosis that has remained unchanged during the past decades. Increasing knowledge about the molecular pathogenesis of the disease has shown that genetic alterations, such as mutations of K-ras, and especially epigenetic dysregulation of tumor-associated genes, such as silencing of the tumor suppressor p16p>ink4ap>, are hallmarks of pancreatic cancer. Here, we describe genes that are commonly affected by epigenetic dysregulation in pancreatic cancer via DNA methylation, histone acetylation or miRNA (microRNA) expression, and review the implications on pancreatic cancer biology such as epithelial-mesenchymal transition, morphological pattern formation, or cancer stem cell regulation during carcinogenesis from panIN (pancreatic intraepithelial lesions) to invasive cancer and resistance development. Epigenetic drugs, such as DNA methyltransferases or histone deactylase inhibitors, have shown promising preclinical results in pancreatic cancer and are currently in early phases of clinical development. Combinations of epigenetic drugs with established cytotoxic drugs or targeted therapies are promising approaches to improve the poor response and survival rate of pancreatic cancer patients.

关键词： pancreatic cancer Epigenetics DNA methylation Histone modification microRNA Targeted therapy Epithelial-mesenchymal transition

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primary malignant melanoma of the biliary tract: A case report and literature review

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World Journal of Clinical Cases 2019年第16期7卷 2302-2308页

作者： Soledad Cameselle-García José Luis Fírvida pérez María C Areses Jesús daniel Fernández de Castro Juan Mosquera-Reboredo Jesús García-Mata Department of Medical Oncology Complejo Hospitalario Universitario de OurenseSERGASOurense 32005Spain Department of Digestive Complejo Hospitalario Universitario de OurenseSERGASOurense 32005Spain Department of pathology Hospital San RafaelA Coruna 15009Spain

BACKGROUND primary malignant melanoma of the biliary tract (MBT) is a rare condition whose diagnosis requires excluding a primary origin in another *** paper reviews the most important characteristics of MBT cases published in the literature and reports a new *** patient reported here is the first case of primary malignant melanoma of the biliary tract with pulmonary metastasis treated with *** patient remains disease-free 36 mo after the treatment of metastatic lung *** SUMMARY A 51-year-old man was admitted to the gastrointestinal department to study obstructive jaundice of a 1 wk clinical *** resonance cholangiopancreatography revealed dilatation of the intrahepatic biliary tract and stenosis of the common hepatic *** the suspicion of biliary tract neoplasia,cholecystectomy and resection of the common hepatic duct were performed with hepatic jejunostomy free of ***-pathological diagnosis was *** intervention,the patient was referred to the Department of Medical Oncology,where a primary origin was excluded in the skin,mucosa,and *** confirmed diagnosis of primary biliary tract *** tomography was performed 12 mo after the procedure revealed several subcentimetric lung *** resection was *** confirming the diagnosis of pulmonary metastasis of primary melanoma of the biliary tract,the patient was started on immunotherapy with *** to treatment was *** patient remains disease-free 36 mo after the treatment of metastatic lung *** The patient reported here is the first case of primary malignant melanoma of the biliary tract with lung metastases successfully treated with immunotherapy.

关键词： Biliary tract Case report Immunotherapy Malignant melanoma

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Targeted delivery of RNAi to cancer cells using RNA-ligand displaying exosome

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Acta pharmaceutica Sinica B 2023年第4期13卷 1383-1399页

作者： Nasir Uddin daniel WBinzel Dan Shu Tian-Min Fu peixuan Guo Center for RNA Nanobiotechnology and Nanomedicine Division of Pharmaceutics and PharmacologyCollege of Pharmacythe Ohio State UniversityColumbusOH 43210USA Dorothy M.Davis Heart and Lung Research Institute the Ohio State UniversityColumbusOH 43210USA James Comprehensive Cancer Center College of Medicinethe Ohio State UniversityColumbusOH 43210USA Department of Biological Chemistry&pharmacology College of Medicinethe Ohio State UniversityColumbusOH 43210USA

Exosome is an excellent vesicle for in vivo delivery of therapeutics,including RNAi and chemical *** extremely high efficiency in cancer regression can partly be attributed to its fusion mechanism in delivering therapeutics to cytosol without endosome ***,being composed of a lipidbilayer membrane without specific recognition capacity for aimed-cells,the entry into nonspecific cells can lead to potential side-effects and *** engineering approaches for targeting-capacity to deliver therapeutics to specific cells is *** with chemical modification in vitro and genetic engineering in cells have been reported to decorate exosomes with targeting *** nanoparticles have been used to harbor tumor-specific ligands displayed on exosome *** negative charge reduces nonspecific binding to vital cells with negatively charged lipid-membrane due to the electrostatic repulsion,thus lowering the side-effect and *** this review,we focus on the uniqueness of RNA nanoparticles for exosome surface display of chemical ligands,small peptides or RNA aptamers,for specific cancer targeting to deliver anticancer therapeutics,highlighting recent advances in targeted delivery of siRNA and miRNA that overcomes the previous RNAi delivery *** understanding of exosome engineering with RNA nanotechnology promises efficient therapies for a wide range of cancer subtypes.

关键词： RNA interference RNA nanotechnology Endolysosome trapping Exosome engineering Targeted delivery Chemical drug delivery

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Slowβrelaxation in La-based metallic glasses based on mechanical spectroscopy measurements

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Journal of Iron and Steel Research International 2017年第4期24卷 397-401页

作者： Ji-chao Qiao Jean-marc pelletier Ning Li daniel Crespo Yao Yao School of Mechanics Civil Engineering and ArchitectureNorthwestern Polytechnical UniversityXi'an 710072ShaanxiChina Universite de Lyon MATEISUMR-CNRS5510Bat.B.PascalINSA LyonF-69621 Villeurbanne cedexFrance Department of Materials Science and Engineering State Key Laboratory for Materials Processing and Die&Mould TechnologyHuazhong University of Science and TechnologyWuhan 430074HubeiChina Departament de Fisica EETACUniversitat Politecnica de CatalunyaCastelldfels 08860BarcelonaSpain

Dynamic mechanical relaxations of La-based metallic glasses were investigated by mechanical *** the framework of the mixing enthalpy of constituent atoms,it was found thatβrelaxation was less evident by the addition of Cu to replace Ni in the LaCuNiAl glassy *** introducing Cu into the LaNiAl metallic glass,the mixing enthalpy was less negative,which led to weakerβrelaxation of the metallic ***αrelaxation of the La-based metallic glasses could be described by a Kohlrausch-Williams-Watts（KWW）function with a Kohlrausch exponentβKWW around *** should be noted that physical aging above the glass transition temperature Tginduced a decrease ofβrelaxation intensity in the La-based metallic glass.

关键词： Metallic glass Mechanical relaxation βrelaxation Mixing enthalpy

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Helicobacter pylori infection in patients with selective immunoglobulin E deficiency

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World Journal of Gastroenterology 2015年第1期21卷 240-245页

作者： Eli Magen Menachem Schlesinger Itzhak Ben-Zion daniel Vardy Leumit Health Services Ashdod 77456Israel Allergy and Clinical Immunology Unit Barzilai University Medical CenterAshkelon 78278Israel Ben-Gurion University of Negev Beer-Sheva 8410501Israel

AIM: To investigate the prevalence and clinical characteristics of Helicobacter pylori(***)-infected dyspeptic patients with selective immunoglobulin E deficiency(IgE d).METHODS: All individuals who underwent serum totalimmunoglobulin E(Ig E) measurement at the Leumit Healthcare Services(Israel) in 2012 were identified in an electronic database search(n = 18487).From these,selected case group subjects were ≥ 12 years of age and had serum total Ig E p was selected from a random sampling of the remaining subjects ≥ 12 years of age to obtain a case-control ratio of 1:20(n = 3160).Dyspeptic diseases,diagnosed no more than 5 years before serum total Ig E testing,were identified and retrieved from the electronic database using specific International Classification of Diseases diagnostic *** of C13-urea breath tests were used to identify subjects infected with *** variables between case and control subjects were analyzed using Fisher's exact tests,whereas continuous variables were analyzed using χ2 ***: Dyspepsia was present in 27.2%(43/158) of case subjects and 22.7%(718/3160) of *** these,significantly more case subjects(32/43,74.4%) than controls(223/718,31.1%) were positive for ***(p phagogastroduodenoscopy was performed in 19 case and 94 control subjects,revealing that gastritis was more prevalent in IgE d case subjects than in controls(57.9% vs 29.8%,p proportion of case subjects presented with peptic duodenal ulcers(63.2% vs 15.9%,p pathologic examination showed marked chronic inflammation,lymphoid follicle formation and prominent germinal centers,with polymorphonuclear cell infiltration of gastric glands,that was similar in case and control biopsy ***,Ig Ed case subjects that underwent esophagogastroduodenoscopy were more likely to exhibit treatment-refractory *** infections that require seco

关键词： Selective IgE deficiency Helicobacter pylori Dyspe

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Gamma-aminobutyric acid(GABA) promotes recovery from spinal cord injury in lampreys: role of GABA receptors and perspective on the translation to mammals

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Neural Regeneration Research 2019年第10期14卷 1695-1696页

作者： daniel Romaus-Sanjurjo María Celina Rodicio Antón Barreiro-Iglesias Department of Functional Biology CIBUS Faculty of BiologyUniversidade de Santiago de Compostela

In mammals, spinal cord injury (SCI) is a devastating event that can lead to a permanent loss of motor, sensory and autonomic functions below the site of injury. In the last years, the role of different neurotransmitter systems on regeneration and recovery from SCI has been deciphered. For example, studies in lampreys have shown that neurotransmitters play a key role in modulating the survival and regeneration of brainstem descending neurons after SCI (Romaus-Sanjurjo et al., 2018;Sobrido-Camean et al., 2018).

关键词： In mammals devastating event regeneration

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Diagnosing gastrointestinal illnesses using fecal headspacevolatile organic compounds

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World Journal of Gastroenterology 2016年第4期22卷 1639-1649页

作者： daniel K Chan Cadman L Leggett Kenneth K Wang Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55905United States

Volatile organic compounds(VOCs) emitted from stool are the components of the smell of stool representing the end products of microbial activity and metabolism that can be used to diagnose disease. Despite the abundance of hydrogen, carbon dioxide, and methane that have already been identified in human flatus, the small portion of trace gases making up the VOCs emitted from stool include organic acids, alcohols, esters, heterocyclic compounds, aldehydes, ketones, and alkanes, among others. These are the gases that vary among individuals in sickness and in health, in dietary changes, and in gut microbial activity. Electronic nose devices are analytical and pattern recognition platforms that can utilize mass spectrometry or electrochemical sensors to detect these VOCs in gas samples. When paired with machine-learning and pattern recognition algorithms, this can identify patterns of VOCs, and thus patterns of smell, that can be used to identify disease states. In this review, we provide a clinical background of VOC identification, electronic nose development, and review gastroenterology applications toward diagnosing disease by the volatile headspace analysis of stool.

关键词： Electronic nose Volatile organic compounds Feces Mass spectrometry Odors

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Assessment of widely used methods to derive depositional ages from detrital zircon populations

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Geoscience Frontiers 2019年第4期10卷 1421-1435页

作者： daniel S.Coutts William A.Matthews Stephen M.Hubbard Department of Geoscience University of Calgary

The calculation of a maximum depositional age(MDA)from a detrital zircon sample can provide insight into a variety of geological ***,the impact of sample size and calculation method on the accuracy of a resulting MDA has not been *** use large populations of synthetic zircon dates(N≈25,000)to analyze the impact of varying sample size(n),measurement uncertainty,and the abundance of neardepositional-age zircons on the accuracy and uncertainty of 9 commonly used MDA calculation ***,a new method,the youngest statistical population is *** each method,500 samples of n synthetic dates were drawn from the parent population and MDAs were *** mean and standard deviation of each method ove r the 500 trials at each n-value(50-1000,in increments of 50)were compa red to the known depositional age of the synthetic population and used to compare the methods quantitatively in two simulation *** first simulation scenario varied the proportion of near-depositional-age grains in the synthetic *** second scenario varied the uncertainty of the dates used to calculate the *** sample size initially decreased the mean residual error and standard deviation calculated by each *** higher n-values(>~300 grains),calculated MDAs changed more slowly and the mean resid ual error increased or decreased depending on the method *** the p roportion of near-depositional-age grains and lowering measurement uncertainty decreased the number of measurements required for the calculated MDAs to stabilize and decreased the standard deviation in calculated MDAs of the 500 *** of the two simulation scenarios show that the most successful way to increase the accuracy of a calculated M DA is by acquiring a large number of low-uncertainty measurements(300300)approach is used if the calculation of accurate MDAs are key to research *** acquisition method s,such as high-to moderate-precision m

关键词： Detrital zircon Maximum depositional age Geochronology Basin chronology LA-ICp-MS

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Effectiveness of peer-Led Intervention on KAp Related to Sexual Reproductive and Mental Health Issues among Adolescents in Low Resource Settings India: A Comparative Study among participants and Non-participants

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Health 2020年第9期12卷 1151-1168页

作者： Kavya p Sonali daniel Shumayla Shumayla Rajesh Sinha Sunil Mehra Mental Health Department Mamta-Health Institute for Mother and Child Delhi India Chronic Diseases and Adolescent Health Department Mamta-Health Institute for Mother and Child Delhi India Research Department Mamta-Health Institute for Mother and Child Delhi India Mamta-Health Institute for Mother and Child Delhi India

Background: India being the country with largest adolescent population in the world, needs a special focus on the health services as the status of an adolescent determines the health status in his/her adulthood. Some of the major issues faced by the adolescents include: mental health problems, early pregnancy and childbirth, (HIV/STI) and other infectious diseases, violence, injuries and malnutrition. The present study aims to understand the effectiveness of peer-led intervention on knowledge, attitude and practices related to sexual reproductive and mental health issues in adolescents among participants and non-participants. The study was carried out to improve the health-seeking behaviour of adolescents on sexual reproductive and mental health issues in low resource setting across four states in India. Methods: The study adopted a cross-sectional survey which was conducted on 400 adolescents from each of the four districts namely Bangalore, Khagaria-Bihar, Khed-pune and Sahinganj-Jharkhand. A comparative analysis was conducted between the participants and the non-participants of the intervention to understand the effectiveness of the intervention on the KAp related to sexual reproductive and mental health of adolescents. Results: The study shows that the participants from Karnataka and Maharashtra had better knowledge in emergency contraception, HIV awareness, use of contraceptives and consumption of IFA’s than the non-participants;both the participants and the non-participants showed a positive behaviour in help-seeking in case of psychological challenges. Conclusion: The peer-led approach was found to be an effective strategy for learning, sharing and monitoring adolescent sexual reproductive and mental health.

关键词： Adolescent Health Mental Health peer-Led Approach Sexual Reproductive Health

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Evolution of heart transplant donor characteristics in the 21st century: A United States single center’s experience

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World Journal of Transplantation 2024年第3期14卷 22-29页

作者： Alexander M Spring Christiana Gjelaj Shivank Madan Snehal R patel Omar Saeed Sandhya Murthy Yogita Rochlani daniel B Sims Sasha Vukelic Stephen J Forest Jamil F Borgi daniel J Goldstein Ulrich p Jorde Montefiore-Einstein Center for Heart and Vascular Care Montefiore Medical CenterAlbert Einstein College of MedicineBronxNY 10467United States Division of Cardiothoracic Surgery Tulane UniversityNew OrleansLA 70112United States

Despite a record setting number of heart transplants performed annually,the national donor shortage continues to plague transplant teams across the United *** we describe the barriers to adaptation of numerous“non-traditional”orthotopic heart transplant donor characteristics including donors with hepatitis C virus,those meeting criteria for donation after cardiac death,donors with coronavirus disease 19 infection,donors with the human immunodeficiency virus,and grafts with left ventricular systolic *** center’s objective was to increase our transplant volume by expanding our donor pool from“traditional”donors to these“non-traditional”*** detail how medical advances such as certain laboratory studies,pharmacologic interventions,and organ care systems have allowed our center to expand the donor pool thereby increasing transplantation volume without adverse effects on outcomes.

关键词： Orthotopic heart transplantation Hepatitis C virus COVID-19 Left ventricular systolic dysfunction Human immunodeficiency virus Donation after cardiac death

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