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Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome

World Journal of Clinical Oncology 2022年第1期13卷 49-61页

作者： Muhammad S Faisal Carol A Burke David Liska Amy L Lightner Brandie Leach Margaret O’Malley Lisa LaGuardia benjamin click JP Achkar Matthew Kalady JM Church Gautam Mankaney Department of Internal Medicine Cleveland Clinic FoundationClevelandOH 44195United States Department of Gastroenterology and Hepatology Cleveland ClinicClevelandOH 44195United States Department of Colorectal Surgery Cleveland ClinicClevelandOH 44195United States Center for Personalized Genetic Healthcare Genomic Medicine InstituteClevelandOH 44195United States Department of Gastroenterology Hepatology&NutritionCleveland ClinicClevelandOH 44195United States Center for Inflammatory Bowel Disease Department of GastroenterologyHepatology and NutritionCleveland ClinicClevelandOH 44195United States Department of Colorectal Surgery Ohio State UniversityColumbusOH 43210United States Department of Gastroenterology and Hepatology Virginia Mason Franciscan HealthSeattleWA 98101United States

BACKGROUND Individuals with Lynch syndrome(LS)and hereditary non-polyposis colorectal cancer(HNPCC)are at increased risk of both colorectal cancer and other *** interplay between immunosuppression,a comorbid inflammatory condition(CID),and HNPCC on cancer risk is *** To evaluate the impact of CIDs,and exposure to monoclonal antibodies and immunomodulators,on cancer risk in individuals with *** Individuals prospectively followed in a hereditary cancer registry with LS/HNPCC with the diagnosis of inflammatory bowel disease or rheumatic disease were *** compared the proportion of patients with cancer in LS/HNPCC group with and without a *** also compared the proportion of patients who developed cancer following a CID diagnosis based upon exposure to immunosuppressive *** A total of 21 patients with LS/HNPCC and a CID were compared to 43 patients with LS/HNPCC but no *** occurred in 84.2% with a CID compared to 76.7% without a CID(P=0.74)with no difference in age at first cancer diagnosis 45.5±14.6 vs 43.8±7.1 years(P=0.67).LS specific cancers were diagnosed in 52.4% with a CID vs 44.2% without a CID(P=0.54).Nine of 21(42.9%)patients were exposed to biologics or immunomodulators for the treatment of their *** after diagnosis of CID was seen in 7(77.8%)of exposed individuals vs 5(41.7%)individuals unexposed to biologics/immunomodulators(P=0.18).All 7 exposed compared to 3/5 unexposed developed a LS specific *** exposed and unexposed groups were followed for a median 10 years and 8.5 years,*** hazard ratio for cancer with medication exposure was 1.59(P=0.43,95%CI:0.5-5.1).CONCLUSION In patients with LS/HNPCC,the presence of a concurrent inflammatory condition,or use of immunosuppressive medication to treat the inflammatory condition,might not increase the rate of cancer occurrence in this limited study.

关键词： Lynch syndrome Hereditary non-polyposis colorectal cancer Inflammatory bowel disease Immunosuppression Biologics

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Thiol-yne click Adamantane Monolithic Stationary Phase for Capillary Electrochromatography

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Chinese Journal of Chemistry 2012年第10期30卷 2281-2284页

作者： Dao,Thi Thu Hien Guerrouache,Mohamed Carbonnier,benjamin Institut de Chimie et des Materiaux Paris Est UMRCNRS 7182&Universite Paris-Est Creteil2-8 rue Henri Dunant94320 ThiaisFrance

A porous crosslinked organic polymer based on N-acryloxysuccinimide （NAS） and ethylene dimethacrylate （EDMA） was prepared inside 75 μm i.d. fused silica capillary as functionalizable monolithic stationary phase for electrochromatographic applications. Succinimide groups on the monolith surface provide reactive sites able to re- act readily through standard electrophile-nucleophile chemistry. Propargylamine was used to prepare alkyne func- tionalized poly（NAS-co-EDMA）. Onto this thiol-reactive polymer surface was grafted adamantane units via a photochemically-driven addition reaction. Chemical characterization was performed in situ after each synthetic step by means of Raman spectroscopy and grafting kinetics was investigated to ensure quantitative grafting of 1-adamantanethiol. The as-designed monolithic stationary phase exhibited typical reversed-phase separation mechanism as evidenced by the linear increase of the logarithm of retention factor of neutral aromatic solutes with the increase of the aqueous buffer content in the mobile phase.

关键词： adamantane electrochromatography porous monolith surface chemistry thiol-yne click

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Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

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Acta Pharmaceutica Sinica B 2023年第1期13卷 204-212页

作者： benjamin L.Prather Shuyue Ji Yue Zhao Femil Joseph Shajan Mi Zhao Zakey Yusuf Buuh Robert Maloney Rui Zhang Carson Cohen Rongsheng E.Wang Department of Chemistry Temple UniversityPhiladelphiaPA 19122USA

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity,and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration(FDA).Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs’toxicities,but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common“click chemistry”*** the widely used non-steroidal anti-inflammatory drug acetaminophen(APAP)as an example,we hereby designed and synthesized an APAP analogue using fluorine as a steric-free *** toxicity studies indicated our analogue has similar activity to the parent *** analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotinSH probe for subsequent fluorine-thiol displacement reactions(FTDRs).This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western *** preliminary validation results supported the interaction of APAP with the thioredoxin protein,which is an important redox protein for normal liver *** results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest,allowing for global profiling of interacting *** fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

关键词： Acetaminophen(APAP) Liver Hepatotoxicity Bioorthogonal click chemistry Fluorinedisplacement Fluorinethiol displacementreaction FTDR

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