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Identification of anticancer drugs to radiosensitise BRAF-wild-type and mutant colorectal cancer

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Cancer Biology & Medicine 2019年第2期16卷 234-246页

作者： rebecca Carter Azadeh Cheraghchi-Bashi Adam Westhorpe Sheng Yu Yasmin Shanneik elena Seraia Djamila Ouaret Yasuhiro Inoue Catherine Koch Jenny Wilding Daniel ebner Anderson J. Ryan Francesca M. Buffa Ricky A. Sharma NIHR University College London Hospitals Biomedical Research Centre/ UCL Cancer Institute University College London London WC1E 6DD UK NIHR Oxford Biomedical Research Centre Department of Oncology University of Oxford Oxford 0X1 2JD UK Computational Biology and Integrative Genomics University of Oxford Oxford 0X1 2JD UK NDM Research Building Nuffield Department of Medicine University of Oxford Oxford 0X1 2JD UK Weatherall Institute of Molecular Medicine John Radcliffe Hospital University of Oxford Oxford 0X1 2JD UK Mie University Graduate School of Medicine Department of Gastrointestinal and Pediatric Surgery Division of Reparative Medicine Institute of Life Sciences Edobashi 2-174 Tsu Japan Departme nt of Biology Massachusetts In stitute of Tech no logy Cambridge Massachusetts 02142 USA Target Discovery Institute National Phenotypic Screening Centre Nuffield Department of Medicine University of OxfordOxford 0X1 2JD UK CRUK & MRC Oxford Institute for Radiation Oncology University of Oxford Oxford 0X1 2JD UK

Objective: Patients with BRAF-mutant colorectal cancer(CRC) have a poor prognosis. Molecular status is not currently used to select which drug to use in combination with radiotherapy. Our aim was to identify drugs that radiosensitise CRC cells with known BRAF ***: We screened 298 oncological drugs with and without ionising radiation in colorectal cancer cells isogenic for BRAF. Hits from rank product analysis were validated in a 16-cell line panel of human CRC cell lines, using clonogenic survival assays and xenograft models in ***: Most consistently identified hits were drugs targeting cell growth/proliferation or DNA damage repair. The most effective class of drugs that radiosensitised wild-type and mutant cell lines was PARP inhibitors. In clonogenic survival assays, talazoparib produced a radiation enhancement ratio of 1.9 in DLD1(BRAF-wildtype) cells and 1.8 in RKO(BRAF V600 e) cells. In DLD1 xenografts, talazoparib significantly increased the inhibitory effect of radiation on tumour growth(P ≤ 0.01).Conclusions: Our method for screening large drug libraries for radiosensitisation has identified PARP inhibitors as promising radiosensitisers of colorectal cancer cells with wild-type and mutant BRAF backgrounds.

关键词： Radiosensitizer colorectal cancer PARP inhibitor radiotherapy

Young Child-Rearing Latina Cancer Survivors Living in the US-Mexico Border Region: A Qualitative Study

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Journal of Cancer Therapy 2021年第4期12卷 174-185页

作者： Clara L. Reyes rebecca L. Palacios Karoline Sondgeroth ernesto A. Moralez Department of Public Health Sciences New Mexico State University Las Cruces NM USA Department of Public Health St. Lawrence University Canton NY USA

Background: Despite increasing cancer incidence among young Latinas (Objective: The purpose of this study was to explore how young, child-rearing Latinas described their challenges, strengths, and social support sources for coping with cancer in the US-Mexico border region. Methods: Nine Latinas that had been diagnosed with cancer, had at least one child 5 to 13 years old, and lived in one of two targeted border counties participated in audio-recorded, semi-structured focus groups (n = 6) or interviews (n = 3) in their preferred language (i.e., English or Spanish). Interview recordings were transcribed and inductively coded using methods based on grounded theory. Results: Three major themes emerged. First, in reporting their physical and emotional struggles with cancer as the most difficult time of their lives, participants described feeling alone as they navigated treatment side effects and continued fear of cancer. Second, they explained figuring out how to live day-by-day, reporting the negative impact of cancer on their families and on their ability to maintain their roles as mothers. Third, they highlighted factors that gave them the strength to fight and carry on, emphasizing their children and their inner strength. Conclusions: Even with a supportive family, young Latina mothers felt alone as they navigated cancer (i.e., treatment, fear, and impact on their families) and as they worked to garner the strength to overcome the stress of cancer. Interventions for young Latina survivors sho

关键词： Cancer Survivorship Latinas Coping Family US-Mexico Border

effect of a region-wide incorporation of an algorithm based on the 2012 international consensus guideline on the practice pattern for the management of pancreatic cystic neoplasms in an integrated health system

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World Journal of Clinical Cases 2018年第13期6卷 624-631页

作者： Andrew Khoi Nguyen Agathon Girgis Timnit Tekeste Karen Chang Mopelola Adeyemo Armen eskandari emilio Alonso Priyanka Yaramada Charles Chaya Albert Ko edmund Burke Isaiah Roggow rebecca Butler Aniket Kawatkar Brian S Lim School of Medicine University of California Department of Gastroenterology Kaiser Permanente Riverside Medical Center Department of Surgery Kaiser Permanente Riverside Medical Center Department of Research and evaluation Southern California Permanente Medical Group

AIM To examine the practice pattern in Kaiser Permanente Southern California(KPSC), i.e., gastroenterology(GI)/surgery referrals and endoscopic ultrasound(eUS), for pancreatic cystic neoplasms(PCNs) after the regionwide dissemination of the PCN management *** Retrospective review was performed; patients with PCN diagnosis given between April 2012 and April 2015(18 mo before and after the publication of the algorithm) in KPSC(integrated health system with 15 hospitals and 202 medical offices in Southern California) were ***2558(1157 pre-and 1401 post-algorithm) received a new diagnosis of PCN in the study period. There was no difference in the mean cyst size(pre-19.1 mm vs post-18.5 mm, P = 0.119). A smaller percentage of PCNs resulted in eUS after the implementation of the algorithm(pre-45.5% vs post-34.8%, P er proportion of patients were referred for GI(pre-65.2% vs post-53.3%, P ery consultations(pre-24.8% vs post-16%, P er the implementation. There was no significant change in operations for PCNs. Cost of diagnostic care was reduced after the implementation by 24%, 18%, and 36% for eUS, GI, and surgery consultations, respectively, with total cost saving of 24%.CONCLUSION In the current healthcare climate, there is increased need to optimize resource utilization. Dissemination of an algorithm for PCN management in an integrated health system resulted in fewer eUS and GI/surgery referrals, likely by aiding the physicians ordering imaging studies in the decision making for the management of PCNs. This translated to cost saving of 24%, 18%, and 36% for eUS, GI, and surgical consultations, respectively, with total diagnostic cost saving of 24%.

关键词： Pancreatic cyst Algorithm incorporation Pancreas Optimization of resource utilization Fukuoka criteria Sendai criteria Pancreatic cancer Intraductal papillary mucinous neoplasm Practice management Algorithm

Art系列微距第一镜适马镜头深度测评 70mm F2.8 DG MACRO|Art

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摄影之友 2019年第5期 98-99页

作者： rebecca(文/图) 不详

性能参数镜头构成:10组13片视角:34.3°光圈叶片数:9片(圆形光圈)最小光圈:F22最短拍摄距离:25.8cm放大倍率:1:1滤镜直径:(?)49mm最大直径×长度:(?)70.8mm×105.8mm重量:515g亮点01兼容索尼e卡口全幅无反相机此镜头提供索尼e卡口版本,... 详细信息

性能参数镜头构成:10组13片视角:34.3°光圈叶片数:9片(圆形光圈)最小光圈:F22最短拍摄距离:25.8cm放大倍率:1:1滤镜直径:(?)49mm最大直径×长度:(?)70.8mm×105.8mm重量:515g亮点01兼容索尼e卡口全幅无反相机此镜头提供索尼e卡口版本,与其他卡口版本拥有相同的光学系统。无需使用MC-11,即可直接使用在索尼e卡口全幅无反相机上,兼容防抖、镜头畸变校正等机身功能,同时还支持索尼机身的连续自动对焦功能。

关键词：微距镜头 Art F2.8 DG MACRO|Art 增距镜自动对焦 DG

<i>In vitro</i>Bile Acid Binding of Mustard Greens, Kale, Broccoli, Cabbage and Green Bell Pepper Improves with Sautéing Compared with Raw or Other Methods of Preparation

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Food and Nutrition Sciences 2012年第7期3卷 951-958页

作者： Talwinder S. Kahlon rebecca R. Milczarek Mei-Chin M. Chiu Western Regional Research Center United States Department of Agriculture - Agricultural Research Service 800 Buchanan St Albany CA 94710

Bile acid binding potential of foods and food fractions has been related to lowering the risk of heart disease and that of cancer. Steam cooking has been observed to significantly improve bile acid binding of green/leafy vegetables. It was hypothesized that other cooking methods could further improve the bile acid binding of various vegetables. Sautée cooking resulted in in vitro bile acid binding measured on a dry matter basis relative to cholestyramine of 14% for mustard greens and kale, 9% for broccoli, 8% for collard greens, 6% for cabbage, and 5% for green bell pepper. These results point to the significantly different (P ≤ 0.05) health promoting potential of mustard greens = kale > broccoli > collard greens > cabbage > green bell pepper. Sautéing significantly improved in vitro bile acid binding of mustard greens, kale, broccoli, cabbage and green bell pepper compared with steaming, boiling or raw (uncooked). Collard greens exhibited significantly higher bile acid binding by steaming compared with sautéing, boiling or raw. Data suggest that the cooking method with most heath promoting potential for mustard greens, kale, broccoli, cabbage and green bell pepper should be sautéing. Steaming should be used for collard greens as the cooking method. These green/leafy vegetables, when consumed regularly after sautéing, would promote a healthy lifestyle and have the potential to lower the risk of premature degenerative diseases.

关键词： In vitro Bile Acid Binding Mustard Greens Kale Broccoli Cabbage Green Bell Pepper and Collard Greens Sautéing Steaming Boiling

无反标变全能王适马镜头镜头体验 24-70mm F2.8 DG DN|Art

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摄影之友 2020年第5期 104-105页

作者： rebecca(图/文) 不详

适马24-70 mm F2.8 DG DN|Art镜头重点参数镜头结构:15组19片视角:84.1-34.3光圈叶片数:11片(圆形光圈)最小光圈:F22最近对焦距离:18-38cm最大放大倍率:广角端1:2.9–长焦端1:4.5滤镜口径:82mm最大直径x长度:φ87.8mm×124.9mm(e卡口)重... 详细信息

适马24-70 mm F2.8 DG DN|Art镜头重点参数镜头结构:15组19片视角:84.1-34.3光圈叶片数:11片(圆形光圈)最小光圈:F22最近对焦距离:18-38cm最大放大倍率:广角端1:2.9–长焦端1:4.5滤镜口径:82mm最大直径x长度:φ87.8mm×124.9mm(e卡口)重量:830g(e卡口)。

关键词：放大倍率镜头结构光圈广角端全能王最大直径

CONSIDeRATIONS WHeN SPeCIFYING LITHIUM ADMIXTUReS TO MITIGATe THe RISK OF ASR

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CONSIDERATIONS WHEN SPECIFYING LITHIUM ADMIXTURES TO MITIGAT...

The Potential Risk Associated with Foodborne Pathogens in Watersheds: <i>Salmonellap</i>spp. in Dairy Cattle

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作者： rebecca L Hooper Philip J Nixon Michael D A Thomas Scott Wilson Pavement engineering 9/10 Faraday BuildingNottingham Science and Technology ParkUniversity BoulevardNottinghamNG7 2QPUK. Building Research establishment Garston WatfordWD25 9XXUK. Department of Civil engineering Head HallUniversity of New BrunswickFrederictonNBE3B 5A3Canada.

＜正＞ Based on research conducted at the Building Research establishment （BRe） and work from across the globe, theUK has established recommended addition levels of lithium admixtures as one method to minimize the risk ofdeleterious alkali-silica reaction （ASR）.These addition levels allow increases in the permitted alkali content of concrete mixtures beyond that previouslyrecommended in the UK, and allow for combinations of lithium admixtures with pulverized-fuel ash （pfa） alsoknown as fly ash, a supplementary cementitious material or Type Ⅱ*** the impossibility of testing every lithium admixture addition level in combination with every alkali contentconcrete mixture, the recommendations are based on a pragmatic approach to safe specification. Thisspecification process includes interpolation of threshold levels and determination of an appropriate margin ofsafety based on concrete batching practices in the UK and embodied in european *** paper provides an overview of the use of lithium salts to mitigate deleterious ASR and provides furtherresearch evidence to validate the findings of previous authors. The paper explains the research basis for the UKrecommendations and describes the approach to the safe specification of lithium admixtures. Theserecommendations were published in BRe Information paper IP 1/02, and are now included in the 2004 edition ofBRe Digest 330, and referenced in the British Standard, BS 8500.

关键词： Lithium Specification Pulverized-fuel ash Fly ash.

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Journal of Water Resource and Protection 2015年第6期7卷 476-484页

作者： rebecca Bordonaro Patrick L. McDonough Yung-Fu Chang Hussni O. Mohammed Section of epidemiology Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca NY USA

Salmonella spp. is one of the most important food- and waterborne pathogens implicated in human and animal disease. A repeat cross-sectional study was performed to assess the occurrence of Salmonella in dairy herds in a watershed and determine the factors that play a role in the likelihood of perpetuation of this organism among animals on these farms. A convenience sample of herds in the Delaware County watershed was selected based on farmers’ willingness to participate. Fecal samples were collected per rectum from a representative sample of cattle in these herds and tested for the presence of Salmonella using a combination of culturing and molecular detection methods. The significance of association between the putative risk factors and the likelihood of Salmonella spp. was evaluated using the logistic regression analysis. A total of 34 dairy farms were enrolled in the study and 1987 samples were collected coinciding with seasonal variation. Salmonella spp. was detected in 44% (15/34) of the herds in the study population (i.e., from at least one animal in these herds). However, only a small fraction of the entire sampling population (1.7%) was found to be shedding Salmonella. Risk factors that were found to be associated with the presence of the pathogen on the farm in the final multivariable model included concrete flooring for calves, prevention of calf access to the dam, and the lack of a designated calving pen. Two serovars, Salmonella enterica serovar Infantis and Salmonella enterica serovar Oranienburg, were identified among the isolates recovered in this study. Our study demonstrated that there was a potential risk of watershed degradation from Salmonella associated with cattle.

关键词： Salmonellap Risk Dairy Cows Watershed Polymerase Chain Reaction (PCR)

Renal stem cell reprogramming: Prospects in regenerative medicine

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World Journal of Stem Cells 2014年第4期6卷 458-466页

作者： elvin e Morales rebecca A Wingert Department of Biological Sciences and Center for Zebrafish Research University of Notre DameNotre DameIN 46556United States

Stem cell therapy is a promising future enterprise for renal replacement in patients with acute and chronic kidney disease, conditions which affect millions worldwide and currently require patients to undergo lifelong medical treatments through dialysis and/or organ transplant. Reprogramming differentiated renal cells harvested from the patient back into a pluripotent state would decrease the risk of tissue rejection and provide a virtually unlimited supply of cells for regenerative medicine treatments, making it an exciting area of current research in nephrology. Among the major hurdles that need to be overcome before stem cell therapy for the kidney can be applied in a clinical setting are ensuring the fidelity and relative safety of the reprogrammed cells, as well as achieving feasible efficiency in the reprogramming processes that are utilized. Further, improved knowledge about the genetic control of renal lineage development is vital to identifying predictable and efficient reprogramming approaches, such as the expression of key modulators or the regulation of geneactivity through small molecule mimetics. Here, we discuss several recent advances in induced pluripotent stem cell technologies. We also explore strategies that have been successful in renal progenitor generation, and explore what these methods might mean for the development of cell-based regenerative therapies for kidney disease.

关键词： Kidney Regeneration Induced pluripotent stem cell Reprogramming Differentiation Stem cell Renal progenitor