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The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers

Cancer Drug Resistance 2023年第3期6卷 468-480页

作者： William J.E.Frye Lyn m.Huff Josém.González Dalmasy Paula Salazar rachel m.Carter Ryan T.Gensler Dominic Esposito Robert W.Robey Suresh V.Ambudkar michael m.Gottesman Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Protein Expression Laboratory Frederick National Laboratory for Cancer ResearchLeidos Biomedical ResearchIncFrederickMD 21704USA

Aim:Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid *** small molecule ferroptosis inducers(FINs)have been reported,yet little information is available regarding their interaction with the ATP-binding cassette(ABC)transporters P-glycoprotein(P-gp,ABCB1)and *** thus sought to characterize the interactions of FINs with P-gp and ABCG2,which may provide information regarding oral bioavailability and brain penetration and predict drug-drug ***:Cytotoxicity assays with ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2 were used to determine the ability of the transporters to confer resistance to FINs;confirmatory studies were performed in OVCAR8 and NCI/ADR-RES *** ability of FINs to inhibit P-gp or ABCG2 was determined using the fluorescent substrates rhodamine 123 or purpuin-18,***:P-gp overexpression conferred resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin.P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of *** FINs mL-162,GPX inhibitor 26a,and PACmA31 at 10µm were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing mDR-19 *** inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 ***:Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the *** ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions.

关键词： Ferroptosis drug resistance P-glycoprotein ABCG2

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音乐治疗

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作者： (英)rachel Darnley-Smith (英)Helen m. Patey

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Deep learning-based analysis of macaque corneal sub-basal nerve fibers in confocal microscopy images

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Eye and Vision 2020年第1期7卷 255-265页

作者： Jonathan D.Oakley Daniel B.Russakoff megan E.mcCarron rachel L.Weinberg Jessica m.Izzi Stuti L.misra Charles N.mcGhee Joseph L.mankowski Voxeleron LLC San FranciscoCAUSA Department of molecular and Comparative Pathobiology Johns Hopkins University School of MedicineBaltimoreMDUSA Department of Ophthalmology Faculty of Medical and Health SciencesNew Zealand National Eye CentreUniversity of AucklandAucklandNew Zealand

Background:To develop and validate a deep learning-based approach to the fully-automated analysis of macaque corneal sub-basal nerves using in vivo confocal microscopy(IVCm).methods:IVCm was used to collect 108 images from 35 macaques.58 of the images from 22 macaques were used to evaluate different deep convolutional neural network(CNN)architectures for the automatic analysis of sub-basal nerves relative to manual *** remaining images were used to independently assess correlations and interobserver performance relative to three ***:Correlation scores using the coefficient of determination between readers and the best CNN averaged *** inter-observer comparison,inter-correlation coefficients(ICCs)between the three expert readers and the automated approach were 0.75,0.85 and *** ICC between all four observers was 0.84,the same as the average between the CNN and individual ***:Deep learning-based segmentation of sub-basal nerves in IVCm images shows high to very high correlation to manual segmentations in macaque data and is indistinguishable across *** quantitative measurements of corneal sub-basal nerves are important biomarkers for disease screening and management,the reported work offers utility to a variety of research and clinical studies using IVCm.

关键词： Cornea Sensory nerves macaque Deep learning In vivo confocal microscopy

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The role of radiation for pancreatic adenocarcinoma

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Journal of Pancreatology 2020年第2期3卷 72-80页

作者： Gamboa Adriana C. Lee rachel m. maithel Shishir K. Division of Surgical Oncology Winship Cancer InstituteDepartment of SurgeryEmory UniversityAtlantaUSA

Pancreatic cancer is an aggressive malignancy with a high recurrence rate even after curative-intent *** in survival have not been achieved in the last 25 years thus highlighting the need for effective multimodal treatment *** role of radiation therapy for pancreatic cancer remains ill-defined due to historical lack of a standard definition of resectability,and the use of antiquated radiation delivery techniques and chemotherapy *** level I data regarding neoadjuvant chemoradiotherapy for resectable and borderline resectable pancreatic adenocarcinoma(PDAC)are limited to 2 randomized controlled trials and several retrospective studies and suggest that it may lead to an increased likelihood of a margin-negative resection and certainly allows for improved patient selection for pancreaticoduodenectomy when compared to upfront *** the adjuvant setting,data are similarly lacking but suggest that chemoradiotherapy may be beneficial for patients at high risk of locoregional *** we review existing data regarding the role of radiation in PDAC.

关键词： Adjuvant radiotherapy Neoadjuvant radiotherapy Pancreatic ductal adenocarcinoma Role of radiation for pancreas cancer

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Comparison of antibody detection with <i>Blastomycesdermatitidis</i>yeast lysate antigens in serum specimens from immunized rabbits and infected dogs

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Open Journal of Immunology 2011年第3期1卷 74-79页

作者： Will Christenson rachel Horton Kayla Campbell Kelly meacham Amber Schroeder Gene m. Scalarone 不详

This present study was designed to evaluate B. dermatitidis antigens, prepared from two isolates (B5896, 597), when the yeast cells were allowed to lyse in distilled water for one day or seven days. The indirect enzyme-linked immunosorbent assay (ELISA) was used to determine the ability of the lysate reagents to detect antibodies in 30 rabbit and 30 dog serum specimens. mean absorbance values with B5896 lysate antigen ranged from 1.637 (day 1) to 1.461 (day 7) and absorbance values with 597 antigen ranged from 1.579(day 1) to 1.396 (day 7) with the serum specimens from immunized rabbits. Serum specimens from infected dogs yielded absorbance values ranging from 1.672 (day 1) to 1.763 (day 7) with the B5896 and values ranging from 1.909 (day 1) to 1.224 (day 7) with the 597. Optimal reactivity was obtained with the day 1 lysate using both lysate antigens against the rabbit sera and with the 597 antigen against the dog sera. Slightly greater reactivity was evidenced with the day 7 B5896 antigen when the dog sera was tested. Comparative studies are continuing in order to produce an optimal anti-genic preparation for antibody detection in blastomycosis.

关键词： ELISA Blastomycesdermatitidis Antibody Detection Lysate Antigens

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Body-focused Anxiety in Women: Associations with Internalization of the Thin-ideal, Dieting Frequency, Body mass Index and media Effects

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Open Journal of medical Psychology 2013年第4期2卷 17-24页

作者： Aileen Pidgeon rachel A. Harker Bond University Australia

Exposure to media that portrays thin women as ideal and attractive can lead to women internalizing the thin ideal, which results in incorporating societal standards of thinness into belief systems. Internalization of the thin-ideal is associated with numerous detrimental effects on women, including decreased levels of self-esteem and increased levels of body-focused anxiety, negative emotions and disordered eating. The present study utilized a sample of women (N = 208) aged between 18 and 67 years (m = 29.44, SD = 13.08) to examine the relationship between internalization of the thin- ideal, body-focused anxiety, body mass index (BmI), and dieting frequency. Correlational, regression and mediation analyses conducted on the data showed that internalization of the thin-ideal, BmI and dieting frequency significantly contributed to body-focused anxiety in women. In addition, body-focused anxiety fully mediated the relationship between internalization of the thin-ideal and dieting frequency among women. BmI did not moderate the relationship between internalization of the thin-ideal and body-focused, indicating that women who internalize the thin-ideal are less vulnerable to dieting unless experiencing body-focused anxiety. The results of the current study enhance our understanding of the relationship between internalization of the thin-ideal, body-focused anxiety, BmI, and dieting frequency among women. Clinical implications will be discussed.

关键词： Body-focused Anxiety Internalization of the Thin-ideal BmI Dieting

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Vascularized omental tissue transfer for the treatment of lymphedema:a review

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Plastic and Aesthetic Research 2023年第1期10卷 46-55页

作者： rachel Skladman William R.moritz Elijah J.Tenenbaum Joani m.Christensen Justin m.Sacks Division of Plastic and Reconstructive Surgery Washington University School of MedicineSt.LouisMO 63108USA

Lymphedema is a debilitating disorder caused by impaired drainage of the lymphatic *** the Western world,lymphedema most often arises secondary to the treatment of *** with lymphedema experience progressive swelling,pain,numbness,and tingling,and decreased quality of *** with persistent symptoms may be subject to chronic *** advent of microsurgery has enabled clinicians to transplant donor lymph nodes and their blood supply from a healthy site to the affected area in a procedure known as vascularized lymph node transplant(VLNT).One donor region is the *** omental lymph node transfer(VOLT)has been shown to decrease limb volume,circumference,and subjective symptoms of *** immunologic properties of the omentum make it a particularly useful lymph node donor site for patients with lymphedemarelated *** omentum may be harvested laparoscopically,with robotic assistance,or through a small laparotomy *** this review,we describe the relevant anatomy and history of VOLT as well as operative *** risks,benefits,and relevant outcome studies will be *** applications of robotic surgery to VOLT will be addressed.

关键词： Lymphedema VOLT VLNT laparoscopy laparotomy gastroepiploic vessels cellulitis

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The Origin of modern East Asians

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人类学学报 2013年第4期32卷 377-398页

作者： milford H Wolpoff rachel Caspari Department of Anthropology University of Michigan Ann Arbor M148109 USA T Department Sociology Anthropology and Social Work Central Michigan University Mount Pleasant M148859 USA

With the development of paleogenetics in the past decade, it has become evident that modern humans do not have a phylogenetic origin in the appearance of a new species Homo sapiens; therefore, anatomical, behavioral and genetic aspects of modernity are not the consequence of the same, single event. In this paper, we examine the evidence for anatomical, behavioral and genetic modernity in East Asia. In each case, modernity can be understood as part of a multiregional evolutionary process, rather than as an entity. Although these three aspects of modernity are somewhat independent, each evolving at different times, they are linked through demographic changes that began in the late Pleistocene - increased survivorship and population expansions that changed the course of human evolution.

关键词：人口变化社会学化石遗传学进化过程

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Assessment of Genetic Stability Among In Vitro Plants of Arachis retusa Using RAPD and AFLP markers for Germplasm Preservation

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Journal of Integrative Plant Biology 2007年第3期49卷 307-312页

作者： rachel Fatima Gagliardi Luiz Ricardo Hanai Georgia Pacheco Carlos Alberto Oliveira Leonardo Alves Carneiro José Francisco montenegro Valls Elisabeth mansur maria Lucia Carneiro Vieira Laboratório de micropropagacao e Transformacao de Plantas Universidade do Estado do Rio de Janeiro postal code 20550-013 Maracana Rio de Janeiro Brazil Departamento de Genética - Escola Superior de Agricultura Luiz de Queiroz Universidade de Sao Paulo postal code 13418-900 Piracicaba Brazil Embrapa Recursos Genéticos e Biotecnologia postal code 70770-901 Brasilia Brazil

Arachis retusa Krapov. et W. C. Gregory et Valls is endemic in the West-central region of Brazil, occurring In areas endangered by human actions. The establishment of in vitro preservation methods for wild species of Arachis is an alternative to seed banks for germplasm storage, multiplication and distribution. The risk of genetic changes Induced by tissue culture and the monitoring of the genetic stability of the biological material before, during and after storage must be considered In the context of conservation. Random amplified polymorphlc ONA （RAPO） and amplified fragment length polymorphism （AFLP） fingerprinting were used to evaluate the genetic stability of in vitro plants originated from cotyledons and embryo axes of A. retusa. Cotyledons originated shoots through direct organogenesls and embryo axes displayed muItishoot formation Induced by 110 mmol/L and 8.8 mmol/L BAP, respectively. Ninety genomlc regions （loci） generated from RAPO and 372 from AFLP analyses were evaluated. All amplified fragments detected by both techniques in plants derived from the two explant types were monomorphic. The results Indicate that the recovered shoots are genetically stable at the assessed genomic regions.

关键词： amplified fragment length polymorphism Arachis retusa in vitro preservation micropropagation random amplifiedpolymorphic DNA somaclonal variation

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methods for extracellular vesicle isolation from cancer cells

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Cancer Drug Resistance 2020年第3期3卷 371-384页

作者： Israa Salem Nicole m.Naranjo Amrita Singh rachel DeRita Shiv Ram Krishn Luca S.Sirman Fabio Quaglia Alexander Duffy Nicholas Bowler Aejaz Sayeed Lucia R.Languino Department of Cancer Biology Sidney Kimmel Cancer CenterThomas Jefferson UniversityPhiladelphiaPA 19107USA. Astellas Institute for Regenerative medicine MarlboroughMA 01752USA. School of Veterinary medicine University of PennsylvaniaPhiladelphiaPA 19104USA. Baruch S.Blumberg Institute DoylestownPA 18902USA.

Cells are known to release different types of vesicles such as small extracellular vesicles(sEVs)and large extracellular vesicles(LEVs).sEVs and LEVs play important roles in intercellular communication,pre-metastatic niche formation,and disease progression;both can be detected cell culture media and biological *** and LEVs contain a variety of protein and RNA cargo,and they are believed to impact many biological functions of the recipient cells upon their internalization or binding to cell surface *** has recently been established that standard isolation techniques,such as differential ultracentrifugation,yield a mixed population of ***,density gradient ultracentrifugation has been reported to allow the isolation of sEVs without cellular ***,we describe the most common methods used to isolate sEVs from cell culture medium,mouse and human plasma,and a new technique for isolating sEVs from tissues as *** article also provides detailed procedures to isolate LEVs.

关键词： Extracellular vesicles differential ultracentrifugation iodixanol density gradient cell culture medium plasma tissue

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