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Advances in preclinical evaluation of experimental antibody-drug conjugates

Cancer Drug Resistance 2021年第4期4卷 745-754页

作者： scott k.lyons Dennis Plenker Lloyd C.Trotman Cold Spring Harbor Laboratory Cold Spring HarborNY 11724USA

The ability to chemically modify monoclonal antibodies with the attachment of specific functional groups has opened up an enormous range of possibilities for the targeted treatment and diagnosis of cancer in the *** the number of such antibody-based drug candidates has increased,so too has the need for more stringent and robust preclinical evaluation of their in vivo performance to maximize the likelihood that time,research effort,and money are only spent developing the most effective and promising candidate molecules for translation to the *** with the development of antibody-drug conjugate(ADC)technology,several recent advances in preclinical research stand to greatly increase the experimental rigor by which promising candidate molecules can be *** include advances in preclinical tumor modeling with the development of patient-derived tumor organoid models that far better recapitulate many aspects of the human disease than conventional subcutaneous xenograft *** models are amenable to genetic manipulation,which will greatly improve our understanding of the relationship between ADC and antigen and stringently evaluate mechanisms of therapeutic ***,tumor development is often not visible in these in vivo *** discuss how the application of several preclinical molecular imaging techniques will greatly enhance the quality of experimental data,enabling quantitative pre-and post-treatment tumor measurements or the precise assessment of ADCs as effective *** our opinion,when taken together,these advances in preclinical cancer research will greatly improve the identification of effective candidate ADC molecules with the best chance of clinical translation and cancer patient benefit.

关键词： Antibody-drug conjugate tumor preclinical organoid CRISPR preclinical imaging theranostic

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Regulation of Power Conversion in Fuel Cells

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Chemical Research in Chinese Universities 2004年第4期20卷 466-469页

作者： ZHANG J. k. scott School of Chemical Engineering & Advanced Materials University of Newcastle upon Tyne Newcastle upon TyneSchool of Chemical Engineering & Advanced Materials University of Newcastle upon Tyne Newcastle upon Tyne NE1 7RU UK NE1 7RU UK

Here we report a regulation about power conversion in fuel cells. This regulation is expressed as that total power produced by fuel cells is always proportional to the square of the potential difference between the \{equilibrium\} potential and work potential. With this regulation we deduced fuel cell performance equation which can describe the potential *** current performance curves, namely, polarization curves of fuel cells with three power source parameters: equilibrium potential E_0; internal resistance R; and power conversion coefficient k. The concept of the power conversion coefficient is a new criterion to evaluate and compare the characteristics and capacity of different fuel cells. The calculated values obtained with this equation agree with practical performance of different types of fuel cells.

关键词： Fuel cell Power conversion coefficient Internal resistance Performance Potential

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Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors： retrospective analysis

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Asian Journal of Andrology 2013年第2期15卷 246-248,I0008页

作者： Anthony H Chavez k scott Coffield M Hasan Rajab Chanhee Joe Departments of Urology Scott & White Healthcare Temple Texas 76508 USA Departments of Biostatistics Scott & White Healthcare Temple Texas 76508 USA Deparment of Biostatistics College of Medicine Alfaisal University Riyadh 11533 Saudi Arabia

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction （ED） treated with phosphodiesterase type 5 inhibitors （PDE-5i） over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups： 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 （4.1%） men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 （9.9%） men with ED in the non-treated group （P〈00001）. A higher percentage of African Americans were treated with PDE-5i vs. those who were not （10.5% vs. 7.1%; P〈O.O001）. The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen （10.0% vs. 13.1%; P=-0.0008） and higher percentage of benign prostatic hyperplasia （38.4% vs. 35.1%; P=0.0149）. Men with ED treated with PDE-5i tended to have less chance （adjusted odds ratio： 0.4; 95% confidence intervals： 0.3-0.5; P〈0.0001） of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of beine diaenosed with orostate cancer. Further research is warranted.

关键词： erectile dysfunction (ED) phosphodiesterase 5 inhibitors (PDE-5i) prostate cancer prostatic neoplasms

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Effect of annealing on two different niobium-clad stainless steel PEMFC bipolar plate materials

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中国有色金属学会会刊：英文版 2009年第B09期19卷 56-60页

作者： Sung-Tae HONG Dae-Wook kIM Yong-Joo YOU k.scott WEIL School of Mechanical and Automotive Engineering University of Ulsan Department of Material Science and Engineering University of Ulsan Pacific Northwest National Laboratory

Niobium (Nb)-clad stainless steels(SS) produced via roll bonding are being considered for use in the bipolar plates of polymer electrolyte membrane fuel cell(PEMFC) stacks. Because the roll bonding process induces substantial work hardening in the constituent materials, thermal annealing is used to restore ductility to the clad sheet so that it can be subsequently blanked, stamped and dimpled in forming the final plate component. Two roll bonded materials, niobium clad 340L stainless steel (Nb/340L SS) and niobium clad 434 stainless steel (Nb/434 SS) were annealed under optimized conditions prescribed by the cladding manufacturer. Comparative mechanical testing conducted on each material before and after annealing shows significant improvement in ductility in both cases. However, corresponding microstructural analyses indicate an obvious difference between the two heat treated materials. During annealing, an interlayer with thick less than 1 μm forms between the constituent layers in the Nb/340L SS, whereas no interlayer is found in the annealed Nb/434 SS material. Prior work suggests that internal defects potentially can be generated in such an interlayer during metal forming operations. Thus, Nb/434 SS may be the preferred candidate material for this application.

关键词：质子交换膜燃料不锈钢材料双极板材料退火条件复合板铌聚合物电解质微观结构分析

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High temperature polymer electrolyte membrane fuel cell

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电池 2006年第5期36卷 347-353页

作者： k.scott M.Mamlouk School of Chemical Engineering & Advanced Materials Universityof NewcastleNE1 7RUUK

One of the majorissuesli mitingtheintroduction of polymer electrolyte membranefuel cells(PEMFCs) is thelowtemperature ofoperation which makes platinum-based anode catalysts susceptible to poisoning by the trace amount of CO,inevitably present in *** order to alleviate the problemof COpoisoning andi mprove the power density of the cell,operating at temperature above 100 ℃***-type perfluorosulfonated polymers have been typically used for ***,the conductivity of Nafion-typepolymers is not high enoughto be usedfor fuel cell operations at higher temperature(>90 ℃) and atmospheric pressure because they dehy-drate under these *** additional problem which faces the introduction of PEMFCtechnology is that of supplying or storing hydrogen for cell operation,especially for vehicular *** the use of alternative fuels such as methanol and ethanol is of interest,especially if thiscan be used directlyinthe fuel cell,without reformationto *** mitation of the direct use of alcohol is thelower activity of oxida-tionin comparison to hydrogen,which means that power densities are considerably *** to i mprove activity and power outputhigher temperatures of operation are *** achieve this goal,requires a newpolymer electrolyte membrane which exhibits stabilityand high conductivityin the absence of liquid *** mental data on a polybenzi midazole based PEMFC were *** mple steady-stateisothermal model of the fuel cell is alsoused to aidin fuel cell performance opti *** governing equations involve the coupling of kinetic,ohmic and mass *** also considers the advances madeinthe performance of direct methanol and solid polymer electrolyte fuel cells and considers theirli mi-tations in relation to the source and type of fuels to be used.

关键词： polybenzi midazole(PBI) high-temperature polymer electrolyte fuel cell methanol ethanol

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Anal squamous cell carcinoma: An evolution in disease and management

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World Journal of Gastroenterology 2014年第36期20卷 13052-13059页

作者： Marc C Osborne Justin Maykel Eric k Johnson scott R Steele University of Minnesota Minneapolis MN55415 United States University of Massachusetts Memorial Medical Center Worcester MA 01609 United States Department of Surgery Madigan Army Medical Center Tacoma WA 98431 United States

Anal cancer represents less than 1% of all new cancers diagnosed annually in the United States. Yet, despite the relative paucity of cases, the incidence of anal cancer has seen a steady about 2% rise each year over the last decade. As such, all healthcare providers need to be cognizant of the evaluation and treatment of anal squamous cell carcinoma. While chemoradiation remains the mainstay of therapy for most patients with anal cancer, surgery may still be required in recurrent, recalcitrant and palliative disease. In this manuscript, we will explore the diagnosis and management of squamous cell carcinoma of the anus.

关键词： Anal cancer Squamous cell cancer Nigro protocol Anal intraepithelial neoplasia Chemoradiation therapy Anal neoplasm Radiotherapy Cancer screening Drug therapy

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Routine colonic endoscopic evaluation following resolution of acute diverticulitis:Is it necessary?

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World Journal of Gastroenterology 2014年第35期20卷 12509-12516页

作者： Amit k Agarwal Burzeen E karanjawala Justin A Maykel Eric k Johnson scott R Steele Department of Surgery University of Texas Health Science Center-Houston Department of Surgery University of Texas Health Science Center-Houston and Lyndon B.Johnson General Hospital University of Massachusetts Memorial Medical Center Colon Rectal Surgery Department of SurgeryMadigan Army Medical Center

Diverticular disease incidence is increasing up to 65% by age 85 in industrialized nations,low fiber diets,and in younger and obese ***-five percent of patients with diverticulosis will develop acute *** imposes a significant burden on healthcare systems,resulting in greater than 300000 admissions per year with an estimated annual cost of $3 billion *** computed tomography(CT) is the diagnostic study of choice,with a sensitivity and specificity greater than 95%.Unfortunately,similar CT findings can be present in colonic neoplasia,especially when perforated or *** prompted professional societies such as the American Society of Colon Rectal Surgeons to recommend patients undergo routine colonoscopy after an episode of acute diverticulitis to rule out ***,the data supporting routine colonoscopy after acute diverticulitis is sparse and based small cohort studies utilizing outdated *** any patient with an indication for a colonoscopy should undergo appropriate endoscopic evaluation,in the era of widespread use of high-resolution computed tomography,routine colonic endoscopic evaluation following resolution of acute uncomplicated diverticulitis poses additional costs,comes with inherent risks,and may require further *** this manuscript,we review the current data related to this recommendation.

关键词： Colonic evaluation Colonoscopy Diverticulitis Acute diverticulitis Colonic neoplasia Endoscopy

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Sacroiliac joint stability: Finite element analysis of implant number, orientation, and superior implant length

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World Journal of Orthopedics 2018年第3期9卷 14-23页

作者： Derek P Lindsey Ali kiapour scott A Yerby Vijay k Goel Research and Development SI-BONE Inc. Engineering Center for Orthopaedic Research Excellence Departments of Bioengineering and Orthopaedic Surgery Colleges of Engineering and MedicineUniversity of Toledo

AIM To analyze how various implants placement variables affect sacroiliac(SI) joint range of motion. METHODS An experimentally validated finite element model of the lumbar spine and pelvis was used to simulate a fusion of the SI joint using various placement configurations of triangular implants(iF use Implant System~?). Placement configurations were varied by changing implant orientation, superior implant length, and number of implants. The range of motion of the SI joint was calculated using a constant moment of 10 N-m with a follower load of 400 N. The changes in motion were compared between the treatment groups to assess how the different variables affected the overall motion of the SI joint. RESULTS Transarticular placement of 3 implants with superior implants that end in the middle of the sacrum resulted in the greatest reduction in range of motion(flexion/extension = 73%, lateral bending = 42%, axial rotation = 72%). The range of motions of the SI joints were reduced with use of transarticular orientation(9%-18%) when compared with an inline orientation. The use of a superior implant that ended mid-sacrum resulted in median reductions of(8%-14%) when compared with a superior implant that ended in the middle of the ala. Reducing the number of implants, resulted in increased SI joint range of motions for the 1 and 2 implant models of 29%-133% and 2%-39%, respectively,when compared with the 3 implant *** Using a validated finite element model we demonstrated that placement of 3 implants across the SI joint using a transarticular orientation with superior implant reaching the sacral midline resulted in the most stable construct. Additional clinical studies may be required to confirm these results.

关键词： Fusion Biomechanics Minimally invasive surgery Sacroiliac joint dysfunction Finite element analysis

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Fruit fly courtship： The female perspective

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Current Zoology 2015年第6期61卷 1008-1014页

作者： Reuven DUkAS Andrew scott Animal Behaviour Group Department of Psychology Neuroscience and Behaviour McMaster University 1280 Main Street West Hamilton Ontario L8S 4K1 Canada

Research on fruit fly courtship has mostly focused on males＇ behavioral repertoire whereas females have been as- sumed to respond by either rejecting or accepting males. In many fruit fly species including Drosophila melanogaster, however, mating typically follows an extended period of courtship, which provides ample opportunities for females to inform males about their likelihood of mating. Our experiments indeed revealed that sexually immature females in both D. melanogasterand D. si- mulans showed responses to conspecific males that were distinct from those of sexually mature females. Furthermore, females＇ responses to conspecifie males were different from their responses to heterospecific males. Our data indicate that females＇ beha- vioral repertoire early in courtship can inform males about their probability of mating if they persist in courting. We hypothesize （i） that males can rely on behavioral feedback from females for optimally allocating their courtship efforts towards distinct female classes, （ii） that males may learn to modulate their courtship behavior based on specific feedback from females, and （iii） that fe- males may learn to alter their behavior towards distinct types of males in order to elicit the desired male response. Overall, we suggest that, although little explored, female behavior determines the dynamics of courtship and mating and can thus influence sexual selection and incipient speciation .

关键词： Courtship Female behavior Fruit flies Learning Mate choice Speciation

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Survival in unresectable sinonasal undifferentiated carcinoma treated with concurrent intra-arterial cisplatin and radiation

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World Journal of Clinical Cases 2015年第2期3卷 191-195页

作者： Sonal S Noticewala Loren k Mell scott E Olson William Read Department of Radiation Medicine and Applied Sciences Center for Advanced Radiotherapy TechnologiesUniversity of California San Diego Division of Neurosurgery University of California San Diego Department of Hematology and Medical Oncology Emory University

We report the successful use of RADPLAT to treat a patient with an unresectable T4N0 sinonasal undifferentiated carcinoma. This patient received 4 cycles of weekly intra-arterial cisplatin together with thiosulfate infusion with concurrent radiation therapy. Radiation therapy was given in 28 daily fractions to 54 Gy using intensity-modulated radiation therapy followed by a hypofractionated stereotactic boost of 3 fractions to 13 Gy to a total dose of 67 Gy in 31 fractions to the nasal sinus and bilateral neck. Intra-arterial cisplatin was administered using a bilateral approach due to the midline site of this tumor. Within days of the first intra-arterial cisplatin, there was an obvious decrease in tumor size. She has been followed with magnetic resonance imaging and positron emission tomography, and remains disease-free 47 mo post-treatment. Centers with expertise in intra-arterial chemotherapy could consider the RADPLAT approach for patients with unresectable sinonasal undifferentiated carcinoma.

关键词： Sinonasal undifferentiated carcinoma Radiation Intra-arterial cisplatin Survival RADPLAT

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