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Cellular & Molecular Immunology 2010年第3期7卷 211-220页

作者： Paul l Bollyky Stephen P Evanko rebecca P Wu Susan Potter-Perigo S Alice long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight Benaroya Research Institute SeattleWAUSA

Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and *** hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC *** primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA ***,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA *** effects were seen upon the addition of exogenous Th1 cytokines,Il-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th *** data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell *** also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen *** data point to a pivotal role for HA in DC–T cell interactions at the IS.

关键词： dendritic cell hyaluronan immune synapse pericellular matrix Th1

Ovarian cancer stem cells: Can targeted therapy lead to improved progression-free survival?

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World Journal of Stem Cells 2014年第4期6卷 441-447页

作者： Christen l Walters Haygood rebecca C Arend J Michael Straughn Donald J Buchsbaum Department of Obstetrics and Gynecology University of Alabama at Birmingham Department of Radiation Oncology University of Alabama at BirminghamBirminghamAL 35233United States

Despite significant effort and research funds, epithelial ovarian cancer remains a very deadly disease. There are no effective screening methods that discover early stage disease; the majority of patients are diagnosed with advanced disease. Treatment modalities consist primarily of radical debulking surgery followed by taxane and platinum-based chemotherapy. Newer therapies including limited targeted agents and intraperitoneal delivery of chemotherapeutic drugs have improved disease-free intervals, but failed to yield longlasting cures in most patients. Chemotherapeutic resistance, particularly in the recurrent setting, plagues the disease. Targeting the pathways and mechanisms behind the development of chemoresistance in ovarian cancer could lead to significant improvement in patient outcomes. In many malignancies, including blood and other solid tumors, there is a subgroup of tumor cells, separate from the bulk population, called cancer stem cells(CSCs). These CSCs are thought to be the cause of metastasis, recurrence and resistance. However, todate, ovarian CSCs have been difficult to identify, isolate, and target. It is felt by many investigators that finding a putative ovarian CSC and a chemotherapeutic agent to target it could be the key to a cure for this deadly disease. This review will focus on recent advances in this arena and discuss some of the controversies surrounding the concept.

关键词： Epithelial ovarian cancer Cancer stem cells Chemoresistance Targeted therapy Chemotherapy Recurrent ovarian cancer

Arctic ground squirrel neuronal progenitor cells resist oxygen and glucose deprivation-induced death

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World Journal of Biological Chemistry 2016年第1期7卷 168-177页

作者： Kelly l Drew Matthew Wells rebecca McGee Austin P Ross Judith Kelleher-Andersson Institute of Arctic Biology Univer-sity of Alaska Neuronascent Inc. lifeline Cell Technology

AIM: To investigate the influence of ischemia/reperfusion on arctic ground squirrel(AGS) neuronal progenitor cells(NPCs), we subjected these cultured cells to oxygen and glucose ***: AGS NPCs were expanded and differentiated into NPCs and as an ischemia vulnerable control, commercially available human NPCs(hNPCs) were seeded from thawed NPCs. NPCs, identified by expression of TUJ1 were seen at 14-21 d in vitro(DIV). Cultures were exposed to control conditions, hypoxia, oxygen and glucose deprivation or glucose deprivation alone or following return to normal conditions to model reperfusion. Cell viability and death were assessed from loss of ATP as well as from measures of alamarB lue~ and lactate dehydrogenase in the media and from counts of TUJ1 positive cells using immunocytochemistry. Dividing cells were identified by expression of Ki67 and phenotyped by double labeling with GFAP, MAP2 ab or TUJ1. RESUlTS: We report that when cultured in Neuralife^(TM), AGS cells remain viable out to 21 DIV, continue to express TUJ1 and begin to express MAP2 ab. Viability of hN PCs assessed by fluorescence alamarB lue(arbitrary units) depends on both glucose and oxygen availability [viability of hNPCs after 24 h oxygen glucose deprivation(OGD) with return of oxygen and glucose decreased from 48151 ± 4551 in control cultures to 43481 ± 2413 after OGD, P ll viability assessed by alamar Blue increased from 165305 ± 11719 in control cultures to 196054 ± 13977 after OGD. likewise AGS NPCs recovered ATP(92766 ± 6089 in control and 92907 ± 4290 after modeled reperfusion; arbitrary luminescence units), and doubled in the ratio of TUJ1 expressing neurons to total dividing cells(0.11 ± 0.04 in control cultures vs 0.22 ± 0.2 after modeled reperfusion, P longer time in culture lowered resistance to injury, however, did not impair proliferation of

关键词： Neurogenesis Neuronal progenitor Hypoxia tolerance Hibernation

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

第十二届国际混凝土碱集料反应会议

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)

A Retrospective Study on the Use of High-Dose letrozole while Undergoing Ovarian Stimulation for Oocyte and Embryo Cryopreservation in Cancer Patients

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Advances in Reproductive Sciences 2022年第1期10卷 19-26页

作者： Rahana Harjee Jeffrey roberts University of British Columbia Vancouver Canada Pacific Centre for Reproductive Medicine Burnaby Canada

Objective: To determine the efficacy of letrozole in suppressing estradiol levels during ovarian stimulation in cancer patients. Methods: A retrospective chart review of cancer patients undergoing ovarian stimulation for fertility preservation between 2014-2019 at a private university-affiliated fertility clinic in Canada was conducted. Ovarian stimulation was completed with no letrozole (Group A, n = 10), and adjuvant daily letrozole use at 5.0 (Group B, n = 34) or 7.5 mg (Group C, n = 61). The primary outcomes were peak estradiol levels and oocyte yield. ANOVA with a post hoc two-tailed t-test assuming equal variance was utilized as a statistical method. Result(s): Patient age and AFC count were not different between groups. The yield of mature eggs was not different at each letrozole dose;9.2 ± 6.0, 13.9 ± 6.5 and 12.7 ± 7.2 for Groups A to C respectively (p = 0.18). Mean estradiol levels(pmol/l) were reduced in a dose-dependent manner;7432 ± 4553 for Group A, 2072 ± 1656 for Group B, and 1445 ±1238 for Group C (A vs. C, p vs. C, p Conclusion(s): The use of letrozole during ovarian stimulation for oocyte and embryo cryopreservation in cancer patients can maintain physiologic estradiol levels, while ensuring satisfactory oocyte and embryo yield. letrozole can, therefore, minimize the theoretical risk of stimulating residual and metastatic diseases, while still optimizing future fertility outcomes.

关键词： Ovarian Stimulation Oocyte Preservation Fertility Preservation Cancer

Exportin 1 governs the immunosuppressive functions of myeloid-derived suppressor cells in tumors through ERK1/2 nuclear export

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Cellular & Molecular Immunology 2024年第8期21卷 873-891页

作者： Saeed Daneshmandi Qi Yan Jee Eun Choi Eriko Katsuta Cameron R.MacDonald Mounika Goruganthu Nathan roberts Elizabeth A.Repasky Prashant K.Singh Kristopher Attwood Jianmin Wang Yosef landesman Philip l.McCarthy Hemn Mohammadpour Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Cell Stress Biology Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Oncology Yokohama City UniversityGraduate School of MedicineYokohamaJapan Department of Cancer Genetics&Genomics Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Department of Biostatistics&Bioinformatics Roswell Park Comprehensive Cancer CenterBuffaloNYUSA Karyopharm Therapeutics NewtonMAUSA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNYUSA

Myeloid-derived suppressor cells(MDSCs)are a main driver of immunosuppression in *** the mechanisms that determine the development and immunosuppressive function of these cells could provide new therapeutic targets to improve antitumor ***,using preclinical murine models,we discovered that exportin 1(XPO1)expression is upregulated in tumor MDSCs and that this upregulation is induced by Il-6-induced STAT3 activation during MDSC ***1 blockade transforms MDSCs into T-cell-activating neutrophil-like cells,enhancing the antitumor immune response and restraining tumor ***,XPO1 inhibition leads to the nuclear entrapment of ERK1/2,resulting in the prevention of ERK1/2 phosphorylation following the Il-6-mediated activation of the MAPK signaling ***,XPO1 blockade in human MDSCs induces the formation of neutrophil-like cells with immunostimulatory ***,our findings revealed a critical role for XPO1 in MDSC differentiation and suppressive functions;exploiting these new discoveries revealed new targets for reprogramming immunosuppressive MDSCs to improve cancer therapeutic responses.

关键词： MDSCs Tumor Exportin 1 MAPK pathway

Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-l1 treatment

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Cancer Drug Resistance 2023年第3期6卷 611-641页

作者： Kyra laubach Tolga Turan rebecca Mathew Julie Wilsbacher John Engelhardt Josue Samayoa Computational Oncology AbbVieSouth San FranciscoCA 94080USA Immuno-Oncology AbbVieSouth San FranciscoCA 94080USA Immuno-Oncology AbbVieLake CountyIL 60064USA

The development of immune checkpoint blockade (ICB) therapies has been instrumental in advancing the field of immunotherapy. Despite the prominence of these treatments, many patients exhibit primary or acquired resistance, rendering them ineffective. For example, anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-l1) treatments are widely utilized across a range of cancer indications, but the response rate is only 10%-30%. As such, it is necessary for researchers to identify targets and develop drugs that can be used in combination with existing ICB therapies to overcome resistance. The intersection of cancer, metabolism, and the immune system has gained considerable traction in recent years as a way to comprehensively study the mechanisms that drive oncogenesis, immune evasion, and immunotherapy resistance. As a result, new research is continuously emerging in support of targeting metabolic pathways as an adjuvant to ICB to boost patient response and overcome resistance. Due to the plethora of studies in recent years highlighting this notion, this review will integrate the relevant articles that demonstrate how tumor-derived alterations in energy, amino acid, and lipid metabolism dysregulate anti-tumor immune responses and drive resistance to anti-PD-1/PD-l1 therapy.

关键词： Immunotherapy resistance tumor-immune microenvironment immune checkpoint blockade energy metabolism amino acid metabolism lipid metabolism

Soil Chemical Property Changes over Time from Struvite Compared to Other Fertilizer-Phosphorus Sources in Multiple Soils

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Agricultural Sciences 2023年第10期14卷 1465-1500页

作者： Tatum Simms Kristofor R. Brye Trenton l. roberts lauren F. Greenlee Department of Crop Soil and Environmental Sciences University of Arkansas Fayetteville AR USA Department of Chemical Engineering Pennsylvania State University University Park PA USA

Studies have shown that phosphorus (P) recovered from wastewater as the mineral struvite [MgNH4PO4·6(H2O)] may be a viable alternative fertilizer-P source. This study aimed to compare the effectiveness of electrochemically precipitated struvite (ECST), reclaimed from synthetic wastewater, to other commercial fertilizer-P sources in cultivated soils from Arkansas [AR;silt loam (Sil) and loam (l)], Missouri (MO;Sil), and Nebraska [NE;Sil and sandy loam (Sl)]. A plant-less, moist-soil incubation experiment, including ECST, chemically precipitated struvite (CPST), monoammonium phosphate (MAP), triple superphosphate (TSP), and an unamended control (UC), was conducted to quantify soil pH, nitrate (NO3-N), ammonium (NH4-N), and Mehlich-3 (M3)-P, -Ca, -Mg, and -Fe concentrations at 0.5, 1, 2, 4, and 6 months. All measured soil properties differed (P ·kg-1 for AR-l-TSP after 1 month and NE-Sil-MAP after 6 months, respectively. Soil M3-P ranged from -29.6 mg·kg-1 in the AR-l-UC after 1 month to 429 mg·kg-1 AR-Sil-TSP after 0.5 months. Results showed that, over time, ECST had comparable pH and soil NO3-N, NH4-N, and M3-P, -Ca, -Mg, and -Fe behavior compared to CPST, MAP, and TSP across various soil textures.

关键词： Electrochemically Precipitated Struvite Chemically Precipitated Struvite Soil Incubation Soil Texture

Web-Based Spatial Decision Support System andWatershed Management with a Case Study

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International Journal of Geosciences 2011年第3期2卷 195-203页

作者： Yanli Zhang Ramanathan Sugumaran Matthew McBroom John DeGroote rebecca l Kauten Paul K Barten 不详

In order to maintain a proper balance between development pressure and water resources protection, and also to improve public participation, efficient tools and techniques for soil and water conservation projects are needed. This paper describes the development and application of a web-based watershed management spatial decision support system, WebWMPI. The WebWMPI uses the Watershed Management Priority Indices (WMPI) approach which is a prioritizing method for watershed management planning and it integrates land use/cover, hydrological data, soils, slope, roads, and other spatial data. The land is divided into three categories: Conservation Priority Index (CPI) land, Restoration Priority Index (RPI) land, and Stormwater Management Priority Index (SMPI) land. Within each category, spatial factors are rated based on their influence on water resources and critical areas can be identified for soil conservation, water quality protection and improvement. The WebWMPI has user-friendly client side graphical interfaces which enable the public to interactively run the server side Geographic Information System to evaluate different scenarios for watershed planning and management. The system was applied for Dry Run Creek watershed (Cedar Falls, Iowa, US) as a demonstration and it can be easily used in other watersheds to prioritize crucial areas and to increase public participation for soil and water conservation projects.

关键词： Web-Based SDSS Watershed Management GIS