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Therapeutic resistance in cancer: microRNA regulation of EgFR signaling networks

Cancer Biology & Medicine 2013年第4期10卷 192-205页

作者： german g.gomez Jill Wykosky Ciro Zanca Frank B.Furnari Webster K.Cavenee Ludwig Institute for Cancer Research University of California San Diego

Receptor tyrosine kinases(RTKs)such as the epidermal growth factor receptor(EgFR)regulate cellular homeostatic *** activates downstream signaling cascades that promote tumor cell survival,proliferation and *** of EgFR signaling as a consequence of overexpression,amplification and mutation of the EgFR gene occurs frequently in several types of cancers and many become dependent on EgFR signaling to maintain their malignant ***,concerted efforts have been mounted to develop therapeutic agents and strategies to effectively inhibit ***,limited therapeutic benefits to cancer patients have been derived from EgFR-targeted therapies.A well-documented obstacle to improved patient survival is the presence of EgFR-inhibitor resistant tumor cell variants within heterogeneous tumor cell ***,we summarize the mechanisms by which tumors resist EgFR-targeted therapies and highlight the emerging role of microRNAs(miRs)as downstream effector molecules utilized by EgFR to promote tumor initiation,progression and that play a role in resistance to EgFR *** also examine evidence supporting the utility of miRs as predictors of response to targeted therapies and novel therapeutic agents to circumvent EgFR-inhibitor resistance mechanisms.

关键词：表皮生长因子受体 microRNA 治疗药物癌症患者信号网络抗药性受体抑制剂受体酪氨酸激酶

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In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

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Journal of Pharmaceutical Analysis 2023年第10期13卷 1195-1204页

作者： Nikita Looby Anna Roszkowska Miao Yu german Rios-gomez Mauricio Pipkin Barbara Bojko Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of Waterloo200 University Avenue WestWaterlooONN2L 3G1Canada Department of Pharmaceutical Chemistry Medical University of Gdansk80-416GdanskPoland Division of Thoracic Surgery University Health NetworkTGH200 Elizabeth StTorontoONM5G 2C4Canada Department of Pharmacodynamics and Molecular Pharmacology Collegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089BydgoszczPoland

In vivo lung perfusion(IVLP)is a novel isolated lung technique developed to enable the local,in situ administration of high-dose chemotherapy to treat metastatic lung *** therapy using folinic acid(FOL),5-fluorouracil(F),and oxaliplatin(OX)(FOLFOX)is routinely employed to treat several types of solid tumours in various ***,F is characterized by large interpatient variability with respect to plasma concentration,which necessitates close monitoring during treatments using of this *** plasma drug concentrations often do not reflect tissue drug concentrations,it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target *** this work,in vivo solid-phase microextraction(in vivo SPME)is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous(IV)*** concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry(LC-HRMS)enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration(IVLP ***)and the therapy *** study also shows that the immediate instrumental analysis of metabolomic samples is ideal,as long-term storage at80℃ results in changes in the metabolite content in the sample extracts.

关键词： In vivo lung perfusion Solid-phase microextraction Chemotherapy Metabolomics Therapeutic drug monitoring

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Projections of Incidence, Prevalence and Mortality from Melanoma in Spain

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Journal of Cosmetics, Dermatological Sciences and Applications 2013年第2期3卷 1-6页

作者： Milagros Bernal Dyego L. B. Souza german gomez Francisco J. gomez Atención Primaria de Salud Zaragoza Spain Universidad de Rio grande Port Alegre Brazil Universidad de Zaragoza Zaragoza Spain

Objective: The incidence and mortality rates for cutaneous melanoma (CM) have increased markedly in the last few years. As such, the aim of this study was to forecast their progression in Spain up until 2022. Design: A prospective epidemiological study using the Miamod technique. The primary data source was the mortality statistics released by the National Statistics Institute. Study selection: The MIAMOD method was used. Data extraction: Cases of death due to general and melanoma-related mortality in Spain between 1998 and 2007. Results: In men, the incidence is expected to increase from 11.85 (adjusted: 8.52) to 14.79 (adjusted: 9.43) per 100,000 inhabitants over the period 1998-2022. Similarly, the mortality is expected to increase slightly from 5.84 (adjusted: 4.12) to 7.19 (adjusted: 4.49) per 100,000 inhabitants, and the prevalence from 73.72 (adjusted: 52.31) to 95.46 (adjusted: 60.02) per 100,000 inhabitants over the same period. In women, the incidence is expected to increase from 3.79 (adjusted: 3.04) to 6.46 (adjusted: 4.21) per 100,000 inhabitants between 1998 and 2022, although this increase is not statistically significant. The mortality is expected to increase from 1.67 (adjusted: 1.24) to 2.98 (adjusted: 1.86) per 100,000 inhabitants, and the prevalence from 50.04 (adjusted: 44.54) to 84.81 per (adjusted: 56.18) 100,000 inhabitants over the same period. Conclusions: Primary and secondary prevention programs for this disease must be maintained.

关键词： Projections Cutaneous Melanoma Incidence Mortality

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Arabidopsis thaliana AtUTr7 Encodes a golgi-Localized UDP-glucose/UDP-galactose Transporter that Affects Lateral Root Emergence

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Molecular Plant 2012年第6期5卷 1263-1280页

作者： Michael Handford Cecilia Rodriguez-Furlan Lorena Marchan Marcelo Segura Daniela gomez Elena Alvarez-Buyllal guang-Yan Xiong Markus Pauly Ariel Orellana Department of Biology Faculty of Sciences University of Chile Santiago Chile Present address: Department of Biochemistry University of Cambridge Cambridge CB2 1QW UK Centro de Biotecnologia Vegetal Facultad de Ciencias Biologicas Universidad Andres Bello Republica 217 Santiago Chile Present address: Facultad de Ciencias Biologicas Universidad AndrOs Bello Vina del Mar Chile Present address: Department of Pathobiology School of Veterinary Medicine University of Pennsylvania Philadelphia PA USA Instituto de Ecologia UNAM Mexico City Mexico Department of Plant and Microbial Biology University of California Berkeley CA 94720 USA FONDAP Center for genome Regulation

Nucleotide sugar transporters （NSTs） are antiporters comprising a gene family that plays a fundamental role in the biosynthesis of complex cell wall polysaccharides and glycoproteins in plants. However, due to the limited number of related mutants that have observable phenotypes, the biological function（s） of most NSTs in cell wall biosynthesis and assembly have remained elusive. Here, we report the characterization of AtUTr7 from Arabidopsis （Arabidopsis thaliana （L.） Heynh.）, which is homologous to multi-specific UDP-sugar transporters from Drosophila melanogaster, humans, and Caenorhabditis elegans. We show that AtUTr7 possesses the common structural characteristics conserved among NSTs. Using a green fluorescent protein （gFP） tagged version, we demonstrate that AtUTr7 is localized in the golgi apparatus. We also show that AtUTr7 is widely expressed, especially in the roots and in specific floral organs. Additionally, the results of an in vitro nucleotide sugar transport assay carried out with a tobacco and a yeast expression system suggest that AtUTr7 is capable of transferring UDP-gal and UDP-gIc, but not a range of other UDP- and gDP-sugars, into the golgi lumen. Mutants lacking expression of AtUTr7 exhibited an early proliferation of lateral roots as well as distorted root hairs when cultivated at high sucrose concentrations. Furthermore, the distribution of homogalacturonan with a low degree of methyl esterification differed in lateral root tips of the mutant compared to wild-type plants, although additional analytical procedures revealed no further differences in the composition of the root cell walls. This evidence suggests that the transport of UDP-gal and UDP-gIc into the golgi under conditions of high root biomass production plays a role in lateral root and root hair development.

关键词： nucleotide sugars nucleotide sugar transporters golgi apparatus cell wall.

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Effects of yttria content on the CMAS infiltration resistance of yttria stabilized thermal barrier coatings system

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Journal of Materials Science & Technology 2020年第8期36卷 74-83页

作者： Juan Jgomez Chavez Ravisankar Naraparaju Peter Mechnich Klemens Kelm Uwe Schulz C.V.Ramana University of Texas at El Paso Department of Mechanical EngineeringEl PasoTX79968USA german Aerospace Center(DLR) Institute of Materials ResearchCologne51170Germany

The effects of YO(1.5)doping in yttria-zirconia based thermal barrier coatings(TBCs)against CMAS interaction/infiltration are *** TBCs with an YO(1.5)content ranging from 43–67 mol.%(balance Zr O2)were produced by electron beam physical vapor deposition(EB-PVD)*** results reveal a trend of higher apatite formation probability with the higher free YO(1.5)available in the yttriazirconia ***,the infiltration resistance and amount of consumed coating appears to be strongly dependent on the YO(1.5)content in the *** thinnest reaction layer and lowest infiltration was found for the highest produced 67 YO(1.5)*** XRD experiments with volcanic ash/YO(1.5)powder mixtures with higher yttria contents than in the coatings(80 YO(1.5)and pure YO(1.5))also showed higher apatite formation with respect to increasing yttria *** threshold composition to promote apatite-based reaction products was found to be around 50 YO(1.5)in zirconia which was proved in the coatings and XRD powder *** YO(1.5)-ZrO2-Fe O-TiO2 bearing zirconolite-type phase was formed as a reaction product for all the coating compositions which implicates that TiO2 in the melt acts as a trigger for zirconolite *** phase could be detrimental for CMAS/volcanic ash infiltration resistance since it can be formed alongside with apatite which controls or limits the amount of Y^(3+)available for glass *** Fe rich garnet phase containing all the possible elements exhibited a slower nucleation compared to apatite and its growth was enhanced with slow cooling *** implications of phase stability and heat treatment effects on the reaction products are discussed for tests performed at 1250°C.

关键词： CMAS Volcanic ash Infiltration Electron beam physical vapor deposition Thermal barrier coating

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