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Phytochemicals and cancer chemoprevention

Journal of Cancer Metastasis and Treatment 2020年第1期6卷 575-610页

作者： Asim Dave Falguni Parande Eun-Jung Park John M.Pezzuto arnold&marie schwartz college of pharmacy and health sciences Long Island UniversityBrooklynNY 11201USA college of pharmacy and health sciences Western New England UniversitySpringfieldMA 01119-2684USA

The unending morbidity and mortality that results from cancer,as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization,advocates for the necessity of chemopreventive *** chemoprevention refers to the use of agents capable of reversing,reducing,or slowing down the pathology of cancer at various ***,a few therapeutic drugs with relatively low toxicity(e.g.,tamoxifen,finasteride),and a sparse number of vaccines(hepatitis B,HPV),are used to prevent specific *** the general population,however,therapeutic options for cancer prevention are not ***,it is generally agreed that diet affects the genesis of cancer,and phytochemicals have the capacity of functioning as cancer chemoprevention *** is supported by epidemiological studies and clearly documented with animal models designed to mimic human ***,some public health strategies,such as recommendations for greater consumption of fruits and vegetables,reflect the merits of cancer ***,we focus on some well-established natural product cancer chemopreventive agents,including resveratrol(grapes),epigallocatechin-3-gallate(green tea),sulforaphane(cruciferous vegetables),anthocyanins(grapes and berries),curcumin(turmeric),silibinin(milk thistle),and lycopene(tomatoes).As aptly demonstrated by genomic analysis and other methods,the mechanistic underpinning is variable and *** addition,responses may be mediated through indirect mechanisms,such as interaction with the ***,ancillary applications of chemopreventive agents are worthy of consideration,such as management of sequelae induced by *** the loss of millions of cancer patients every year,it is obvious that negating malignant metastatic conditions remains of paramount *** meeting this objective,cancer chemoprevention offers great promise.

关键词： Chemoprevention phytochemicals resveratrol curcumin anthocyanins silibinin lycopene epigallocatechin-3-gallate anti-cancer activity

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Pentoxifylline suppressed LPS-induced inflammatory and apoptotic signaling in neuronal cells

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Advances in Bioscience and Biotechnology 2012年第6期3卷 731-739页

作者： Sameer K. Muchhala Kenza E. Benzeroual Division of Pharmaceutical sciences Arnold & Marie Schwartz college of Pharmacy & Health Sciences Long Island University Brooklyn NY 11201 USA

Several studies have reported a relation between increased pro-inflammatory mediators such as TNF-α and apoptosis in neurodegenerative diseases such as Alzheimer’s disease (AD). It is known that lipopoly-saccharide (LPS) treatment induces neuroinflammation and memory deterioration, and it has been reported that LPS induces apoptosis mostly through the production of TNF-α. Pentoxifylline (PTX), is a vascular protective agent and a potent TNF-alpha inhibitor. However, the molecular neuroprotective mechanisms of PTX against LPS-induced neurotoxicity have not been well studied. In this study, we investigated the direct protective effect of PTX against LPS-induced toxicity in Rat pheochromocytoma (PC12) cell line. The results showed that a pretreatment with PTX prior exposure to LPS signifycantly decreased LPS-induced cell death. Mechanisms study showed that PTX has the potential to inhibit pro-inflammatory and pro-apoptotic pathways via the suppression of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. This is the first study to report the anti-inflammatory and anti-apoptotic effects of PTX via inhibition of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. Altogether, these observations indicate that PTX is capable of promoting neuroprotective effects, meanwhile also present some insights into the potential signaling pathways that are involved. Thus, these findings support the potential for PTX to be investigated as a potential agent for the treatment of neurodegenerative diseases such as AD.

关键词： Pentoxifylline Lipopolysaccharide (LPS) Neuronal Cells Apoptosis Inflammatory Cytokines Neurodegeneration Tnf-Alpha Alzheimer’s Disease

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Ionization and transfection activity of n-methyl-substituted carbamoyl-cholesterol derivatives

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Journal of Biophysical Chemistry 2011年第2期2卷 53-62页

作者： Samuel Acheampong Michalakis Savva Division of pharmaceuticals sciences Arnold & Marie Schwartz College of Pharmacy & Health Sciences Long Island University New York United States

Five novel cationic lipids, the polar head group of which was attached to the cholesterol backbone via a tertiary carbamate linker, were synthesized and their physicochemical properties were compared to their transfection efficiencies. Transfection activity of the primary amine analog was highest among the series, while the quaternary ammonium iodide salt was essentially transfection incompetent. Contrary to DC-Chol, methyl and ethyl carbamoyl derivatives of DC-Chol mediated high levels of transfection in the absence of DOPE. Ionization of the cationic assemblies in 40 mM Tris buffer pH 7.2 exactly correlated with the competitive nature of the inductive and steric effects of the methyl groups on the aliphatic nitrogen of the lipids’ polar moiety. Interestingly, the pH interaction zone of all lipid dispersions at 25°C was extended by ± 2 pH units from the pKa, while the pKa of the cationic lipids determined in mixed vesicles composed of 90 % DOPC and cholesterol was approximately 1.3 to 1.5 times higher than that of pure cationic assemblies. The interaction of cationic lipids with plasmid DNA was correlated with pKa, but not the transfection activity.

关键词： Cationic Lipids DC-Chol Transfection Pka Plasmid DNA Monolayer Surface Pressure.

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Synthesis, Biophysical Characterization and <i>in Vitro</i>Transfection Activity of Novel Bivalent Amine Cationic Lipids in the Absence of Dioleoylphosphatidylethanolamine (DOPE)

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Pharmacology & pharmacy 2014年第11期5卷 1015-1028页

作者： Addai-Mensah Donkor Micheal Spelios Michalakis Savva Division of Pharmaceutical sciences Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University New York USA Faculty of Applied sciences Department of Applied Chemistry and Biochemistry University for Development Studies Navrongo Campus Upper East Region Ghana

In this paper, a novel series of bis [(aminoethyl)]-amine cationic lipid derivatives have been synthesized and identified to purity by NMR and Elemental analysis. B16-F0 cells were transfected with cationic lipid/pEGFP-N1 and cationic lipid/ß-gal lipoplexes complexed at +/- charge ratios of 1:1, 2:1, and 4:1. Dimyristoyl derivative showed highest activity at charge ratio 2:1 and both dimyristoyl and dioleoyl derivatives showed similar ß-gal activity at charge ratios 4:1. In 40 mM tris buffer pH 7.2 the dioleoyl derivative was able to fully complex with and retard pDNA at charge ratios above 2:1. None of the other lipid derivatives, dilauroyl, dimyristoyl, dipalmitoyl and distearoyl were able to fully neutralize the plasmid DNA at charge ratios similar to those used in the transfection experiment. The gel-to-liquid phase transition temperatures for dimyristoyl, dipalmitoyl and distearoyl were determined by a fluorescence anisotropy method to be 27.5°C, 32.5°C and 39°C, respectively. A gel-to-liquid crystalline phase transition temperature below 37°C, appears to be the crucial property that cationic lipids have to possess in order to mediate high levels of in vitro transfection activity in the absence of other helper lipids.

关键词： Gene Delivery Cationic Lipid Acyl Chain Fluidity Elasticity Lipoplex Transfection Non-Viral Vector DOPE Endosomal Release TNS

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2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

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Acta Pharmaceutica Sinica B 2017年第1期7卷 73-79页

作者： Erin marie Kirwen Tarun Batra Chandrabose Karthikeyan Girdhar Singh Deora Vandana Rathore Chaitanya Mulakayala Naveen Mulakayala Amy Catherine Nusbaum Joel Chen Haneen Amawi Kyle Mc Intosh Sahabjada Neelam Shivnath Deepak Chowarsia Nisha Sharma Md Arshad Piyush Trivedi Amit KTiwari Department of Pharmacology and Experimental Therapeutics College of Pharmacy & Pharmaceutical SciencesUniversity of Toledo School of Pharmaceutical sciences Rajiv Gandhi Technical University The University of Queensland School of Pharmacy Dr. Reddy’s Institute of Life sciences University of Hyderabad Campus The University of Queensland School of Biomedical Sciences Department of Biosciences Sri Satya Sai Institute of Higher LearningAnantapur campus Clearsynth Labs Ltd. Research CentreIDA-Mallapur Molecular Endocrinology Lab Department of ZoologyUniversity of Lucknow University Institute of pharmacy Chhatrapati Shahu Ji Maharaj University

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC_(50) values of 9.2 and 21.8 mmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.

关键词： 3H-Imidazo[4,5-b]pyridine Cytotoxicity MTT assay COX inhibitors Docking studies

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Dynamic epi-transcriptomic landscape mapping with disease progression in estrogen receptor-positive breast cancer

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Cancer Communications 2023年第5期43卷 615-619页

作者： Stephen Keelan Mihaela Ola Sara Charmsaz Sinéad Cocchiglia Daniela Ottaviani Seán Hickey Siobhan Purcell Fiona Bane Aisling Hegarty Ben Doherty Katherine Sheehan Lance Hudson Nicola Cosgrove Benjamin Roux Muriel Laine Geoffrey Greene Damir Varešlija arnold Konrad Hill Leonie Young Endocrine Oncology Research Group Department of SurgeryRoyal College of Surgeons in IrelandUniversity of Medicine and Health SciencesDublinIreland Department of Surgery Beaumont HospitalDublinIreland Department of Pathology Beaumont HospitalDublinIreland Ben May Department for Cancer Research Department of Biochemistry and Molecular BiologyThe University of ChicagoChicagoILUSA The School of pharmacy and Biomolecular sciences The Royal College of Surgeons University of Medicine and Health SciencesDublinIreland Beaumont Royal college of Surgeons in Ireland Cancer Centre Beaumont HospitalDublinIreland

Dear Editor,The molecular determinants that drive breast cancer progression to metastasis are complex and partly controlled by nucleic acid epi-modifications[1].Although DNA-methyl modifications in breast cancer metastasis have been well described,there is limited understanding of the role of RNA methylation in advanced disease[2].This study aimed to provide an understanding on the role of the epitranscriptome in estrogen receptor-positive(ER+)breast cancer progression to metastasis.

关键词： breast metastasis cancer

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Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

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World Journal of Cardiology 2020年第5期12卷 192-202页

作者： Natalie Cora Jennifer Ghandour Celina marie Pollard Victoria Lynn Desimine Krysten Elaine Ferraino Janelle marie Pereyra Rachel Valiente Anastasios Lymperopoulos Laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences(Pharmacology)College of PharmacyNova Southeastern UniversityFort LauderdaleFL 33328-2018United States

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart *** the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)***,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in *** has various direct and indirect adverse cardiac *** is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 *** activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease *** We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and *** In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R ***,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 *** Adrenalβarrestin1 upregulation is one of the mechanisms by whic

关键词： Adrenocortical zona glomerulosa cell Aldosterone βarrestin Nicotine Signal transduction Tobacco-related heart disease

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SARS-CoV-2, surgeons and surgical masks

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World Journal of Clinical Cases 2021年第10期9卷 2170-2180页

作者： Mohammad Ibrahim Khalil Gouri Rani Banik Sarab Mansoor Amani S Alqahtani Harunor Rashid Department of Surgery Dhaka Medical College HospitalDhaka 1000Bangladesh Clinical Research Unit The Department of MedicineUniversity of New South WalesSydney 2217New South WalesAustralia National Centre for Immunisation Research and Surveillance The Children’s Hospital at Westmead and the University of SydneyWestmead 2145New South WalesAustralia The University of Sydney School of pharmacy Faculty of Medicine and HealthThe University of SydneySydney 2006New South WalesAustralia Research Department Saudi Food and Drug AuthorityRiyadh 13312Saudi Arabia National Centre for Immunisation Research and Surveillance The Children's Hospital at Westmeadand the University of SydneyWestmead 2145New South WalesAustralia Discipline of Child and Adolescent health the Faculty of Medicine and HealthThe University of SydneySydney 2145New South WalesAustralia marie Bashir Institute for Infectious Diseases and Biosecurity School of Biological Sciences and Sydney Medical SchoolThe University of SydneyWestmead 2145New South WalesAustralia

The exact risk association of coronavirus disease 2019(COVID-19)for surgeons is not quantified which may be affected by their risk of exposure and individual *** objective of this review is to quantify the risk of COVID-19 among surgeons,and explore whether facemask can minimise the risk of COVID-19 among surgeons.A systematised review was carried out by searching MEDLINE to locate items on severe acute respiratory syndrome coronavirus 2 or COVID-19 in relation to health care workers(HCWs)especially those work in surgical specialities including surgical nurses and ***,systematic reviews that assessed the effectiveness of facemask against viral respiratory infections,including COVID-19,among HCWs were *** from identified articles were abstracted,synthesised and *** primary studies that provided data on severe acute respiratory syndrome coronavirus 2 infection or experience among surgeons and 11 systematic reviews that provided evidence of the effectiveness of facemask(and other personal protective equipment)were *** the risk of COVID-19 could not be quantified precisely among surgeons,about 14%of HCWs including surgeons had COVID-19,there could be variations depending on *** was found to be somewhat protective against COVID-19,but the HCWs’compliance was highly variable ranging from zero to 100%.Echoing surgical societies’guidelines we continue to recommend facemask use among surgeons to prevent COVID-19.

关键词： COVID-19 health care worker Personal protective equipment SARS-CoV-2 Surgeon Surgical mask

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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public health sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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Microscopic enteritis:Bucharest consensus

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World Journal of Gastroenterology 2015年第9期21卷 2593-2604页

作者： Kamran Rostami David Aldulaimi Geoffrey Holmes Matt W Johnson marie Robert Amitabh Srivastava Jean-Francois Fléjou David S Sanders Umberto Volta Mohammad H Derakhshan James J Going Gabriel Becheanu Carlo Catassi Mihai Danciu Luke Materacki Kamran Ghafarzadegan Sauid Ishaq Mohammad Rostami-Nejad A Salvador Pe?a Gabrio Bassotti Michael N Marsh Vincenzo Villanacci Department of Gastroenterology Alexandra HospitalWorcestershire B98 7UBUnited Kingdom Department of Gastroenterology Royal Derby HospitalDerby DE22 3NEUnited Kingdom Gastroenterology Unit Luton Dunstable University FT Hospital LU4 0DZUnited Kingdom Department of Pathology and Medicine Yale University School of MedicineNew HavenCT 06520United States Department of Pathology Staff PathologistBrigham and Women’s HospitalHarvard Medical School BostonBostonMA 02115United Sates Department of Pathology Serviced’Anatomie PathologiqueHopital Saint-AntoineAP-HPUniversité Pierre et Marie Curie75005 ParisFrance Department of Gastroenterology University of SheffieldSouth Yorkshire S10 2TNUnited Kingdom Department of Gastroenterology Department of Medical and Surgical SciencesUniversity of Bologna40126 BolognaItaly Section of Gastroenterology Institute of Cardiovascular and Medical SciencesUniversity of GlasgowGlasgow G12 8QQUnited Kingdom Department of Pathology Southern General HospitalLanarkshire G51 4TFUnited Kindom Department of Pathology Carol Davila Univerity of Medicine and PharmacyBucharest 050474Romania Università Politecnica delle Marche AnconaItalyPresidente Società Italiana di GastroenterologiaEpatologia e Nutrizione PediatricaCo-DirectorCenter For Celiac Research University of Maryland School of Medicine BaltimoreMD 21201United States Grigore T Popa" University of Medicine and pharmacy Iasi 747800Romania Laboratory Department Mashad Razavi HospitalKhorasan Razavi ***Iran Dudley group of Hospitals Birmingham City UniversityBirmingham B42 2SUUnited Kindom Gastroenterology and Liver Diseases Research Institute Shahid Beheshti University of Medical SciencesTehran ***Iran Laboratory of Immunogenetics Department of Medical Microbiology and Infection ControlVrije Universiteit medical centre (VUmc)1081 HZ AmsterdamThe Netherlands Gastroenterology Section Department of MedicineUniversity of Perugia Medical School06100 PerugiaItaly Wolfson college University of OxfordOxford

Microscopic enteritis(ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms,nutrient and micronutrient *** is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern *** work recognises a need to characterize disorders with microscopic and submicroscopic features,currently regarded as functional or non-specific entities,to obtain further understanding of their clinical *** consensus working party reviewed statements about the aetiology,diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and *** the 5th International Course in Digestive Pathology in Bucharest in November 2012,an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME.A five-step agreement scale(from strong agreement to strong disagreement) was used to score 21 statements,*** was strong agreement on all statements about ME histology(95%-100%).Statements concerning diagnosis achieved 85% to 100% agreement.A statement on the management of ME elicited agreement from the lowest rate(60%) up to 100%.The remaining two categories showed general agreement between experts on clinical presentation(75%-95%) and pathogenesis(80%-90%) of *** was strong agreement on the histological definition of *** agreement on management indicates a need for further investigations,better definitions and clinical trials to produce quality guidelines for *** ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.

关键词： Microscopic enteritis Enteropathy Gluten Malabsorption Non-celiac gluten Bucharest consensus

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