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WJH 6^(th) Anniversary Special Issues(2): Hepatocellular carcinoma Mammalian target of rapamycin inhibition in hepatocellular carcinoma

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World Journal of Hepatology 2014年第11期6卷 776-782页

作者： René e Ashworth jennifer Wu Hematology and Medical Oncology Pro-gram NYU School of Medicine Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology NYU School of Medicine Subdivision of GI Oncology Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology

Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.

关键词： Mammalian target of rapamycin hepato-cellular carcinoma Mammalian target of rapamycin complex 1 Mammalian target of rapamycin complex 2 PI3K/AKT/mTOR signaling pathway Sorafenib everoli-mus Sirolimus Liver transplantation CC-223

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Association between high deductible health plan coverage and age at pediatric umbilical hernia repair

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World Journal of Pediatric Surgery 2023年第2期6卷 70-76页

作者： Morgan e Doty Lindsay A Gil jennifer N Cooper The Ohio State University College of Medicine ColumbusOhioUSA Department of Surgery Nationwide Children's HospitalThe Ohio State UniversityColumbusOhioUSA Department of Pediatrics Nationwide Children's HospitalThe Ohio State UniversityColumbusOhioUSA

Background High deductible health plans(HDHPs)are associated with the avoidance of both necessary and unnecessary *** hernia repair(UHR)is a procedure that is frequently unnecessarily performed in young children,contrary to best practice *** hypothesized that children with HDHPs,as compared with other types of commercial health plans,are less likely to undergo UHR before 4 years of age but are also more likely to have UHR delayed beyond 5 years of *** Children aged 0-18 years old residing in metropolitan statistical areas(MSAs)who underwent UHR in 2012-2019 were identified in the IBM Marketscan Commercial Claims and encounters Database.A quasi-experimental study design using MSA/year-level HDHP prevalence among children as an instrumental variable was employed to account for selection bias in HDHP ***-stage least squares regression modeling was used to evaluate the association between HDHP coverage and age at *** A total of 8601 children were included(median age 5 years,IQR 3-7).Univariable analysis revealed no differences between the HDHP and non-HDHP groups in the likelihood of UHR being performed before 4 years of age(27.7%vs 28.7%,p=0.37)or after 5 years of age(39.8%vs 38.9%,p=0.52).Geographical region,metropolitan area size,and year were associated with HDHP *** variable analysis demonstrated no association between HDHP coverage and undergoing UHR atears of age(p=0.76)or>5 years of age(p=0.87).Conclusions HDHP coverage is not associated with age at pediatric *** studies should investigate other means by which UHRs in young children can be avoided.

关键词： pediatric hernia likely

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Phase-selective graphene oxide membranes for advanced microfluidic flow control

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Microsystems & Nanoengineering 2016年第1期2卷 256-262页

作者： jennifer Gaughran David Boyle James Murphy Robert Kelly Jens Ducrée School of Physical Sciences Dublin City UniversityDublin 9Ireland Biomedical Diagnostics Institute Dublin City UniversityDublin 9Ireland

For the first time,we harness the unique phase-selectivity of chip-integrated graphene oxide(GO)membranes to significantly enhance flow control on centrifugal microfluidic *** this paper,we present novel processes for the assembly of these GO membranes into polymeric microfluidic systems and demonstrate that multilayer GO membranes allow the passage of water while blocking pressurized air and organic solutions.

关键词： centrifugal microfluidics flow control graphene oxide membranes solvent selectivity

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Hello, goodbye, and everything in between

Hello, goodbye, and everything in between

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作者： Smith jennifer e.

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Town-scale microbial sewer community and H2S emissions response to common chemical and biological dosing treatments

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Journal of environmental Sciences 2020年第1期32卷 133-148页

作者： elizabeth R.Mathews jennifer L.Wood Dean Phillips Nathan Billington Dean Barnett Ashley e.Franks Department of Physiology Anatomy and MicrobiologyLa Trobe UniversityMelbourneAustralia Centre for Future Landscapes La Trobe UniversityMelbourneAustralia Faculty of Science Engineering and TechnologySwinburne University of TechnologyMelbourneAustralia Western Water SunburyAustralia

Controlling hydrogen sulfide(H2S)odors and emissions using a single,effective treatment across a town-scale sewer network is a challenge faced by many water *** of a sewer diversion provided the opportunity to compare the effectiveness of magnesium hydroxide(Mg(OH)2)and two biological dosing compounds(Bioproducts A and B),with different modes of action(MOA),in a field-test across a large sewer ***(OH)2 increases sewer p H allowing suppression of H2S release into the sewer environment while Bioproduct A acts to disrupt microbial communication through quorum sensing(QS),reducing biofilm *** B reduces H2S odors by scouring the sewer of fats,oils and grease(FOGs),which provide adhesion points for the microbial *** revealed that only Mg(OH)2 altered the microbial community structure and reduced H2S emissions in a live sewer system,whilst Bioproducts A and B did not reduce H2S emissions or have an observable effect on the composition of the microbial community at the dosed *** results recommend in situ testing of dosing treatments before implementation across an operational system.

关键词： Microbially induced concrete corrosion Biological dosing treatments Magnesium hydroxide Hydrogen sulfide Sulfate-reducing bacteria Microbial ecology

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The benefits of being dominant:health correlates of male social rank and age in a marmot

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Current Zoology 2022年第1期68卷 19-26页

作者： Kenta UCHIDA Rachel NG Samuel A.VYDRO jennifer e.SMITH Daniel T.BLUMSTeIN Department of ecology&evolutionary Biology University of CaliforniaLos AngelesCA 90095-1606USA Department of Biology Mills CollegeOaklandCA 94613USA The Rocky Mountain Biological Laboratory Crested ButteCO 81224USA

The benefits of dominance may not come without costs,particularly for *** example,the“immunocompetence handicap hypothesis”states that males with enhanced mating success allocate resources to enhance reproductive output at a cost to their current health,whereas the“resource quality hypothesis”predicts that high-ranking males may benefit from increased reproduction and good *** the predictions from each have been well tested in captive animals and in a variety of highly social primates,fewer studies have been carried out in free-living,facultatively social *** adult male yellow-bellied marmots(Marmota flaviventer),we evaluated predictions of these hypotheses by examining the relationship between social rank and 2 health indicators—fecal glucocorticoid metabolite(FCM)levels,and neutrophil/lymphocyte(N/L)ratios—after accounting for variation explained by age,body mass,and *** found that higher-ranking males tended to have a lower N/L ratio(reflecting good health)than lower-ranking individuals,whereas FCM levels were not significantly related to *** addition,heavier male marmots had lower N/L ratios,whereas body mass was not associated with FCM *** also found that older adult males had lower FCM levels(reflecting less physiological stress)but higher N/L ratios than younger ***,we found that FCM levels decreased as the active season progressed and FCM levels were associated with the time of the ***,our results suggest that socially-dominant male marmots enjoyed better,not worse health in terms of lower N/L ratios.

关键词： immunocompetence handicap hypothesis life history trade-offs N/L ratio physiological stress resource quality hypothesis

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Dental microwear of sympatric rodent species sampled across habitats in southern Africa: Implications for environmental influence

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Integrative Zoology 2016年第2期11卷 111-127页

作者： Jenny H.e.BURGMAN jennifer LeICHLITeR Nico L.AVeNANT Peter S.UNGAR environmental Dynamics Program University of ArkansasFayettevilleArkansasUSA Department of Anthropology University of Colorado BoulderBoulderColoradoUSA National Museum and University of the Free State BloemfonteinSouth Africa Department of Anthropology University of ArkansasFayettevilleArkansasUSA

Dental microwear textures have proven to be a valuable tool for reconstructing the diets of a wide assortment of fossil ***,some studies have recently questioned the efficacy of this approach,suggesting that aspects of habitat unrelated to food preference,especially environmental grit load,might have a confounding effect on microwear patterning that obscures the diet *** we evaluate this hypothesis by examining microwear textures of 3 extant sympatric rodent species that vary in diet breadth and are found in a variety of habitat types:Mastomys coucha,Micaelamys namaquensis and Rhabdomys *** sample each of these species from 3 distinct environmental settings in southern Africa that differ in rainfall and vegetative cover:Nama-Karoo shrublands(semi-desert)and Dry Highveld grasslands in the Free State Province of South Africa,and Afromontane(wet)grasslands in the highlands of *** differences between habitat types are evident for some of the species,inconsistency in the pattern suggests that the microwear signal is driven by variation in foods eaten rather than grit-level per *** is clear that,at least for species and habitats sampled in the current study,environmental grit load does not swamp diet-related microwear signatures.

关键词： diet grit tooth wear

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Seasonal shifts in the solute ion ratios of vadose zone rock moisture from the eel River Critical Zone Observatory

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Acta Geochimica 2017年第3期36卷 385-388页

作者： jennifer L.Druhan Nicole Fernandez Jia Wang William e.Dietrich Daniella Rempe Department of Geology University of Illinois Urbana Champaign Department of earth and Planetary Science University of California Berkeley Jackson School of Geosciences University of Texas at Austin

One of the greatest challenges in critical zone studies is to document the moisture dynamics, water flux,and solute chemistry of the unsaturated, fractured and weathered bedrock that lies between the soil and groundwater table. The central impediment to quantifying this component of the subsurface is the difficulty associated with direct observations. Here, we report solute chemistry as a function of depth collected over a full year across the shale-derived vadose zone of the eel River Critical Zone Observatory using a set of novel sub-horizontal wellbores,referred to as the vadose zone monitoring system. The results of this first geochemical glimpse into the deep vadose zone indicate a dynamic temporal and depth-resolved structure. Major cation concentrations reflect seasonal changes in precipitation and water saturation, and normalized ratios span the full range of values reported for the world's largest rivers.

关键词： Vadose zone Solute ion ratios Critical Zone Observatory Seasonal solute dynamics

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Androgen and estrogen receptors in placental physiology and dysfunction

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Frontiers in Biology 2018年第5期13卷 315-326页

作者： erin S McWhorter jennifer e Russ Quinton A Winger Gerrit J Bouma Department of Biomedical Sciences Animal Reproduction and Biotechnology Laboratory Colorado State University. 1683 Campus deliveryFort Collins CO 80523-1683 USA

BACKGROUND： The placenta is recognized as an endocrine organ, largely due to its secretions of steroid hormones, including progesterone, androgens, and estrogens. Steroid hormones play an essential role in the progression of pregnancy, fetal development, and growth. Furthermore, steroids are necessary for establishment and maintenance of a normal pregnancy, preparing the endometrium for implantation, stimulating endometrial secretions, and regulating uterine blood flow, however the exact mechanism of sex steroid signaling through their receptors in placental function is unknown. OBJeCTIVe： In this review, we will provide an overview of the current knowledge on sex steroid receptors in normal placental development, as well as evidence of abnormal signaling associated with placental dysfunction. MeTHODS： A systematic literature search was performed using the NCBI PubMed search engine, including the following key works： estrogen receptor, androgen receptor, placenta, placental development, cytotrophoblast, and differentiation. ReSULTS： Of the over 700 articles that were returned, 125 studies focused on estrogen and androgen receptors in human placenta development and function during normal and abnormal pregnancy, as well as in rodents and ruminants placentae. CONCLUSION： Receptors for both estrogens and androgens have been localized within the mammalian placenta, but surprisingly little is known about their signaling in trophoblast cell differentiation and function. An emerging picture is developing in which estrogen receptors possibly play role in cytotrophoblast proliferation and extravillous trophoblast invasion, whereas androgen receptors are involved in syncytiotrophoblast differentiation and function.

关键词： Placenta eSR AR preeclampsia IUGR PCOS

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Targeting the JAK/STAT pathway in solid tumors

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 287-304页

作者： Zoya Qureshy Daniel e.Johnson jennifer R.Grandis Department of Otolaryngology-Head and Neck Surgery University of California San FranciscoSan Francisco 94158USA

Aberrant activation of signal transducer and activator of transcription(STAT)proteins is associated with the development and progression of solid ***,as transcription factors,these proteins are difficult to target *** this review,we summarize the role of targeting Janus kinases(JAKs),upstream activators of STATs,as a strategy for decreasing STAT activation in solid *** studies in solid tumor cell line models show that JAK inhibitors decrease STAT activation,cell proliferation,and cell survival;in in vivo models,they also inhibit tumor *** inhibitors,particularly the JAK1/2 inhibitor ruxolitinib,sensitize cell lines and murine models to chemotherapy,immunotherapy,and oncolytic viral *** JAK inhibitors have been or are actively being tested in clinical trials as monotherapy or in combination with other agents in patients with solid tumors;two of these inhibitors are already Food and Drug Administration(FDA)approved for the treatment of myeloproliferative disorders and rheumatoid arthritis,making them attractive agents for use in patients with solid tumors as they are known to be *** JAK inhibitors(two of which are FDA approved for other indications)have exhibited promising anti-cancer effects in preclinical studies;however,clinical studies specifically assessing their activity against the JAK/STAT pathway in solid tumors have not yet been *** summary,JAK inhibition is a viable option for targeting the JAK/STAT pathway in solid tumors and merits further testing in clinical trials.

关键词： Clinical trials Janus kinase/signal transducer and activator of transcription(JAK/STAT)pathway JAK inhibitors solid tumors STAT hyperactivation

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