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The role of systemic therapy in borderline resectable and locally advanced pancreatic ductal adenocarcinoma

Journal of Cancer metastasis and Treatment 2022年第1期8卷 281-292页

作者： Victor C.K.Lo Rachel A.Goodwin m.chael m.vickers Department of medicine Division of Medical OncologyThe Ottawa Hospital Cancer CentreOttawaON K1H 8L6Canada

Pancreatic ductal adenocarcinoma(PDAC)remains a deadly disease,even in patients whose cancer is localized and *** resection provides the only option for cure,but long-term survival rates remain *** patients with borderline resectable(BR)disease who undergo upfront resection,many patients are either too unwell for subsequent adjuvant systemic therapy,develop recurrence soon after,or are found to have unresectable disease *** is increasing evidence for a neoadjuvant approach,using more conventional multi-agent chemotherapy regimens,which have demonstrated higher activity in the metastatic setting compared to single *** patients with locally advanced(LA)disease,which is unresectable by current definitions,there is mounting evidence that effective neoadjuvant systemic therapy is able to convert some patients’disease to a resectable state,offering the potential for long-term survival and *** we present a review of key trials focusing on prospective,randomized studies to provide high-level evidence supporting a neoadjuvant approach to both BR and LA ***,many knowledge gaps exist,such as the optimal neoadjuvant multi-agent chemotherapy regimen,the role of radiotherapy,and the safety and efficacy of adding immunotherapy to chemo/radiation *** challenges in determining the optimal approach to patients with BR or LA PDAC include not only overcoming the inherent difficulties in conducting complex,multidisciplinary,multicentre randomized trials in patients with a high-morbidity and mortality disease,but also trying to standardize disease definitions,treatment regimens,and outcome measures.

关键词： Borderline resectable locally advanced pancreatic ductal adenocarcinoma neoadjuvant chemotherapy

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BRCA mutated pancreatic cancer:A change is coming

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World Journal of Gastroenterology 2021年第17期27卷 1943-1958页

作者： m.chael N Rosen Rachel A Goodwin m.chael m.vickers Faculty of medicine The University of OttawaOttawa K1H 8L6OntarioCanada The Ottawa Hospital Cancer Center The University of OttawaOttawa K1H 8L6OntarioCanada

Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced ***,patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast *** BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8%of patients with sporadic pancreatic *** patients with germline BRCA mutations,platinum-based chemotherapies and poly(ADP-ribose)polymerase inhibitors are effective treatment options which may offer survival *** review will focus on the molecular biology,epidemiology,and management of BRCA-mutated pancreatic ***-more,we will discuss future directions for this area of research and promising active areas of research.

关键词： Pancreatic cancer Systemic therapy Platinum chemotherapy BRCA Deoxyribonucleic acid repair Poly(ADP-ribose)polymerase inhibitors

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Clinical Assessment of a Pharmaceutical Polyphenol Fruit Extract Gel to Inhibit Dental Plaque

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Pharmacology & Pharmacy 2021年第9期12卷 177-189页

作者： Steven P. Goh David m. Goh E. Russell vickers Suite 1 76A Archer St Chatswood NSW 2067 Australia Clinical Stem Cells Sydney Australia

Oral bacteria (e.g. Porphyromonas gingivalis) are associated and potentially co-causative in several medical conditions including Alzheimer’s disease and increased cardiovascular risk. Naturally occurring polyphenols are a developing class of antimicrobial pharmaceutical agents. The use of plant-based polyphenol compounds is an attractive area of medical and dental research due to their high safety factor from their presence in vegetables and fruits. This preliminary study evaluated polyphenols found in berries to reduce bacterial dental plaque accumulation. The study was an in vivo single blind randomized controlled trial of seven subjects with a novel tooth gel using validated measurements. Results showed a significant reduction in plaque accumulation (p = 0.005) and a non-significant trend to reduce gingivitis (p = mily:Verdana;">0.08). The bioactive gel showed no local or systemic adverse effects and was well tolerated by subjects.

关键词： Dental Plaque Gingivitis Polyphenol Quercetin Randomized Controlled Trial

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New ordered mAX phase mo_2 TiAlC_2: Elastic and electronic properties from first-principles

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Chinese Physics B 2016年第10期25卷 323-329页

作者： m A Hadi m S Ali Department of Physics University of Rajshahi Department of Physics Pabna University of Science and Technology

First-principles computation on the basis of density functional theory(DFT) is executed with the CASTEP code to explore the structural, elastic, and electronic properties along with Debye temperature and theoretical vickers’ hardness of newly discovered ordered mAX phase carbide mo2TiAlC2. The computed structural parameters are very reasonable compared with the experimental results. The mechanical stability is verified by using the computed elastic constants. The brittleness of the compound is indicated by both the Poisson’s and Pugh’s ratios. The new mAX phase is capable of resisting the pressure and tension and also has the clear directional bonding between atoms. The compound shows significant elastic anisotropy. The Debye temperature estimated from elastic moduli(B, G) is found to be 413.6 K. The electronic structure indicates that the bonding nature of mo2TiAlC2is a mixture of covalent and metallic with few ionic characters. The electron charge density map shows a strong directional mo–C–mo covalent bonding associated with a relatively weak Ti–C *** calculated Fermi surface is due to the low-dispersive mo 4d-like bands, which makes the compound a conductive *** hardness of the compound is also evaluated and a high value of 9.01 GPa is an indication of its strong covalent bonding.

关键词： new ordered mAX phase density functional theory calculations Debye temperature vickers hardness

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Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars

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Protein & Cell 2010年第1期1卷 82-95页

作者： Isaac m.Westwood Sanjib Bhakta Angela J.Russell Elizabeth Fullam matthew C.Anderton Akane Kawamura Andrew W.mulvaney Richard J.vickers Veemal Bhowruth Gurdyal S.Besra Ajit Lalvani Stephen G.Davies Edith Sim Department of Pharmacology University of OxfordOxford OX13QTUnited Kingdom Chemistry Research Laboratory Department of Organic ChemistryUniversity of OxfordOxford OX13QLUnited Kingdom School of Biosciences University of BirminghamEdgbastonBirmingham B152TTUnited Kingdom Tuberculosis Immunology Group Department of Respiratory MedicineNational Heart and Lung InstituteWright Fleming Institute of Infection and ImmunityImperial College LondonNorfolk PlaceLondon W21PGUnited Kingdom Structure-Based Drug Design Team Sections of Structural Biology and Cancer TherapeuticsInstitute of Cancer ResearchChester Beatty LaboratoriesLondon SW36JBUnited Kingdom Institute of Structural and molecular Biology Department of Biological ScienceBirkbeckUniversity of LondonLondon WC1E 7HXUnited Kingdom

New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against mycobacterium tuberculosis persisting *** have a unique cell *** of the gene for arylamine N-acetyltransferase(NAT)decreases mycobacterial cell wall lipids,particularly the distinctive mycolates,and also increases antibiotic susceptibility and killing within macrophage of mycobacterium bovis *** nat gene and its associated gene cluster are almost identical in sequence in *** BCG and *** gene cluster is essential for intracellular survival of *** have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT ***,we characterize one class of such molecules—triazoles—in relation to its effects on the target enzyme and on both *** BCG and *** most potent triazole mimics the effects of deletion of the nat gene on growth,lipid disruption and intracellular *** also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth,and use ligand-protein analysis to give further insight into the structure-activity *** conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved.

关键词： N-acetyltransferase mycobacterium tuberculosis triazoles screening

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microstructure and mechanical Properties of Nano-crystalline Al-8 wt pct Ni Alloy

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Journal of materials Science & Technology 2006年第5期22卷 605-610页

作者： m.Abou Zied Physics Department Faculty of Science South Valley UniversityQena 83511Egypt

microstructure and mechanical properties of ball-milled Al-8 wt pct Ni ribbon have been investigated by X-ray diffraction （XRD） and continuous vickers hardness test, respectively. The results indicate that, the main phases of this alloy are α-Al and orthorhombic-Al3Ni. The lattice parameter of α-Al increases with increasing milling time. From the elastic constant of Al, the average contrast factors of the （111）, （200）, （220）, （311） and （222） Bragg＇s reflections for pure edge and pure screw dislocations in fcc crystals with α/2〈110〉{111} slip system were calculated. The average grain size and dislocation parameters as a function Of milling time have been investigated using the modified Williamson-Hall plot and the Warren-Averbach equation, *** attempt has been made to correlate the micro-hardness of milled ribbon with their grain size through the Hall-Patch relationship：HV0.01 = 742.45 〈 D 〉^-1/2 ＋401.55 （kg/mm^2）.

关键词： Aluminum microstructure Property X-ray diffraction

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Effect of ECAP temperature on microstructure and mechanical properties of Al–Zn–mg–Cu alloy

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Progress in Natural Science:materials International 2016年第2期26卷 182-191页

作者： m.H.Shaeri m.Shaeri m.Ebrahimi m.T.Salehi S.H Seyyedein Department of metallurgy and materials Engineering Engineering Faculty Imam Khomeini International University Department of materials Science and Engineering Sharif University of Technology Department of mechanical Engineering University of Maragheh Department of metallurgy and materials Engineering Iran University of Science and Technology

The effect of equal channel angular pressing(ECAP) at different temperatures(room temperature, 120,150 and 180 °C) on microstructure and mechanical properties of Al-7075 solid solution alloy was investigated. microstructure of the specimens was examined using orientation imaging microscopy,transmission electron microscopy as well as X-ray diffractometer, and mechanical properties were measured by vickers microhardness and tensile tests. microstructural investigations showed that after3 or 4 passes of ECAP, fi ne grains with average grain sizes in range of 300–1000 nm could be obtained at different ECAP temperatures. Increasing ECAP temperature from 120 to 180 °C caused a decrease in mechanical properties as a result of increasing grains and precipitates sizes, decreasing fraction of high angle boundaries and also transformation of η′ into η phase, while increasing ECAP temperature from RT to 120 °C leads to an increase in mechanical properties due to the formation of small η′ precipitates. So it can be concluded that ECAP process at 120 °C is the optimum process for attaining maximum mechanical properties. Quantitative estimates of various strengthening mechanisms revealed that the improvement of mechanical properties was mainly attributed to grain re fi nement strengthening, precipitation strengthening and dislocation strengthening.

关键词： Equal channel angular pressing microstructure Strengthening mechanisms mechanical properties

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Synthesis and Properties of Ag-doped Titanium-10 wt% 45S5 Bioglass Nanostructured Scaffolds

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Acta metallurgica Sinica(English Letters) 2015年第4期28卷 467-476页

作者： K.Jurczyk A.miklaszewski K.Niespodziana m.Kubicka m.U.Jurczyk m.Jurczyk Department of Conservative Dentistry and Periodontology Poznan University of Medical Sciences Institute of materials Science and Engineering Poznan University of Technology Department of Genetics and Pharmaceutical microbiology Faculty of PharmacyPoznan University of Medical Sciences Division mother’s and Child’s Health Poznan University of Medical Sciences

A new kind of biomedical Ti-45S5 Bioglass-Ag nanocomposites and their scaffolds with antibacterial function was developed by the introduction of 1.5 wt% Ag into the Ti-10 wt% 45S5 Bioglass matrix. The microstructure, hardness and corrosion resistance in Ringer solution of the Ag-doped Ti-45S5 glass were investigated. The vickers hardness of the bulk Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag nanocomposites reached 480 HVo.3. Contact angles of water on the micro- crystalline Ti and nanostructured Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag sample were determined and show visible decrease from 55.2° to 49.6°. In vitro tests culture of normal human osteoblast cells showed very good cells proliferation, colonization and multilayering. In vitro bacterial adhesion study indicated a significantly reduced number of bacteria （Staphylococcus aureus） on the bulk nanostructured Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag plate surface in comparison with that on microcrystalline Ti plate surface. Development of porous Ti-10 wt% 45S5 Bioglass-1.5 wt% Ag scaffolds aims in enhancing bone ingrowth and prosthesis fixation.

关键词： Biomaterials Nanocrystalline materials Titanium 45S5 Bioglass

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Effect of equal channel angular pressing on aging treatment of Al-7075 alloy

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Progress in Natural Science:materials International 2015年第2期25卷 159-168页

作者： m.H.Shaeri m.Shaeri m.T.Salehi S.H.Seyyedein m.R.Abutalebi Department of metallurgy and materials Engineering Engineering Faculty Imam Khomeini International University Department of materials Science and Engineering Sharif University of Technology Department of metallurgy and materials Engineering Iran University of Science and Technology (IUST)

The effect of aging treatment on microstructure and mechanical properties of equal channel angular pressed Al-7075 alloy was *** Al-7075 alloy in the solid solution heat-treated condition was processed by equal channel angular pressing through route BCat both the room temperature and 120 1C. Only three passes of equal channel angular pressing was possible due to the low ductility of the alloy at both temperatures. Followed by equal channel angular pressing, the specimens have been aged at 120 1C for different aging times. mechanical properties were measured by vickers microhardness and tensile tests and microstructural observations were undertaken using transmission electron microscopy, X-ray diffractometer as well as optical microscopy. microstructural investigations showed that ultrafine-grained materials with grain size in the range of 200–350 nm and 300–500 nm could be obtained after three passes of equal channel angular pressing at room temperature and 120 1C, respectively. Equal channel angular pressing of solid solution heat-treated Al-7075 alloy accelerates precipitation rate and subsequently leads to a significant decrease in aging time to attain maximum mechanical properties. Furthermore, it is possible to achieve maximum mechanical properties during equal channel angular pressing at 120 1C as a result of dynamic aging and formation of small η′ phase.

关键词： Equal channel angular pressing Grain refinement Aging treatment TEm mechanical properties

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Crystallization of mg-based bulk metallic glass

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中国有色金属学会会刊：英文版 2006年第4期16卷 833-837页

作者：陈刚 m. FERRY School of materials Science and Engineering Jiangsu University Zhenjiang 212013 China School of materials Science and Engineering Univers ity of New South Wales Sydney NSW 2054 Australia

mg-based bulk metallic glass fabricated by conventional copper mould method was aged at different temperatures. X-ray diffractometry(XRD), scanning electron microscopy(SEm), atomic force microscopy(AFm) and focused ion beam(FIB) miller were employed to examine specimens obtained under different conditions. The crystallization of mg-based bulk metallic glass depends upon both the aging temperature and the aging time. As temperature increases or the holding time increases, the microstructure of the aged specimen varies from glassy one to crystalline one plus glassy phase and then to absolutely multiphase crystalline one. From the FIB images, it is clear that mg-based bulk metallic glass could not only crystallize completely but also display dendrite-like growth style. From the AFm images, there are not only significant variations of microstructures but also surface morphology of specimens obtained under different conditions. It is proposed that the surface morphology varies as the treating temperature increases. The vickers hardness of different specimens increases as the fraction of crystalline phase (s) increases.

关键词：镁合金大块金属玻璃结晶化显微结构

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