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The favorable impact of PIK3cA mutations on survival: an analysis of 2587 patients with breast cancer

chinese Journal of cancer 2012年第7期31卷 327-334页

作者： Amaury G. Dumont sarah N.Dumont Jonathan c. Trent Department of Experimental Pediatrics University of Texas-MD Anderson Cancer CenterHouston Texas United States Division of Hematology and Oncology University of Miami-Sylvester Comprehensive Cancer CenterMiami Florida United States

The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3cA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3cA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3cA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3cA mutation have a better clinical outcome than those with a wild-type PIK3cA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3cA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3cA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3cA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3cA mutations is critical for the development of optimally personalized therapeutics against breast can

关键词：肿瘤患者乳腺癌突变转基因小鼠肌动蛋白细胞骨架磷脂酰肌醇-3 信号通路乳腺肿瘤

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Blue emitting exciplex for yellow and white organic light‑emitting diodes

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Frontiers of Optoelectronics 2023年第4期16卷 191-203页

作者： Kavya Rajeev c.K.Vipin Anjali K.Sajeev Atul Shukla sarah K.M.McGregor Shih‑chun Lo Ebinazar B.Namdas K.N.Narayanan Unni centre for Sustainable Energy Technologies CSIR-National Institute for Interdisciplinary Science and TechnologyThiruvananthapuram 695019India Academy of Scientifc and Innovative Research(AcSIR) Ghaziabad 201002India centre for Organic Photonics&Electronics The University of QueenslandBrisbaneQLD 4072Australia School of Mathematics and Physics The University of QueenslandBrisbaneQLD 4072Australia School of chemistry and Molecular Biosciences The University of QueenslandBrisbaneQLD 4072Australia

White organic light-emitting diodes(WOLEDs)have several desirable features,but their commercialization is hindered by the poor stability of blue light emitters and high production costs due to complicated device ***,we investigate a standard blue emitting hole transporting material(HTM)N,N'-bis(naphthalen-1-yl)-N,N'-bis(phenyl)benzidine(NPB)and its exciplex emission upon combining with a suitable electron transporting material(ETM),3-(biphenyl-4-yl)-5-(4-tert-butylphenyl)-4-phenyl-4H-1,2,4-triazole(TAZ).Blue and yellow OLEDs with simple device structures are developed by using a blend layer,NPB:TAZ,as a blue emitter as well as a host for yellow phosphorescent dopant iridium(III)bis(4-phenylthieno[3,2-c]pyridinato-N,c2')acetylacetonate(PO-01).Strategic device design then exploits the ambipolar charge transport properties of tetracene as a spacer layer to connect these blue and yellow emitting *** tetracene-linked device demonstrates more promising results compared to those using a conventional charge generation layer(cGL).Judicious choice of the spacer prevents exciton difusion from the blue emitter unit,yet facilitates charge carrier transport to the yellow emitter unit to enable additional exciplex *** complementary behavior of the spacer improves the blue emission properties concomitantly yielding reasonable yellow *** overall white light emission properties are enhanced,achieving cIE coordinates(0.36,0.39)and color temperature(4643 K)similar to *** intermolecular exciplex emission in OLEDs simplifes the device architecture via its dual functionality as a host and as an emitter.

关键词： Organic light-emitting diodes Dual functional exciplex Spacers Device design strategy Blue exciplex Yellow OLEDs White light emission

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Prevalence of occult hepatitis B virus infection in haemodialysis patients from central Greece

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World Journal of Gastroenterology 2010年第2期16卷 225-231页

作者： Paraskevi Mina sarah P Georgiadou christos Rizos George N Dalekos Eirini I Rigopoulou Department of Medicine and Research Laboratory of Internal Medicine Medical School University of Thessaly41110 LarissaThessalyGreece Research Group of Investigational Medicine Institute of Biomedical Research and TechnologyCentre for Research and Technology-Thessaly(CE.RE.TE.TH)41222 LarissaThessalyGreece RE.TE.TH)41222 LarissaThessalyGreece Research Group of Investigational Medicine Institute of Biomedical Research and TechnologyCentre for Research and Technology-Thessaly(CE.RE.TE.TH)41222 LarissaThessalyGreece

AIM:To assess the hepatitis B virus(HBV)-DNA and the prevalence of occult HBV infection in end-stage renal failure(ESRF)patients from central Greece. METHODS:Sera from 366 ESRF patients attending five out of six dialysis units from central Greece were investigated for HBV-DNA by real-time polymerase chain *** serum samples with repeatedly detectable HBV-DNA were considered *** antibodies to hepatitis c virus(anti-HcV)were tested by a third generation enzyme linked immunosorbent assay(ELISA),while IgG antibodies to hepatitis E virus (anti-HEV)were tested by two commercially available ***:HBV-DNA was detected in 15/366 patient (4.1%)and HBsAg in 20/366(5.5%).The prevalenc of occult HBV infection was 0.9%(3/346 HBsAg negative patients).Occult HBV was not associate with a specific marker of HBV infection or anti-HcV o anti-HEV *** was no significant differenc in HBV-DNA titres,demographic and biochemica features,between patients with occult HBV infectio and those with HBsAg-positive chronic HBV infection. cONcLUSION:In central Greece,4%of ESRF patient had detectable HBV-DNA,though in this setting,th prevalence of occult HBV seems to be very low(0.9%).

关键词： Hepatitis B virus-DNA Occult hepatitis B virus infection Haemodialysis Hepatitis B Real-time polymerase chain reaction

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combining spawn egg counts,individual photo-ID and genetic fingerprinting to estimate the population size and sex ratio of an endangered amphibian

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Integrative Zoology 2021年第2期16卷 240-254页

作者： Marina REYNE sarah HELYAR Aurélie AUBRY Mark EMMERSON Ferdia MARNELL Neil REID School of Biological Sciences Queen’s University BelfastBelfastUK Institute of Global Food Security(IGFS) Queen’s University BelfastBelfastUK Agri-Food&Biosciences Institute(AFBI) HillsboroughUK National Parks&Wildlife Service(NPWS) DublinIreland

According to the International Union for conservation of Nature Red List,41%of the world’s amphibian species are threatened with extinction,making them more threatened than any other vertebrate group *** the global amphibian crisis,comprehensive understanding of demographics and population trends of declining and threatened species is essential for effective management and conservation *** egg spawns is widely used to assess population abundance in pond breeding ***,it is unknown how such counts translate into robust population size *** monitored the breeding activity of the Natterjack toad(Epidalea calamita),combining egg string counts and individual photo-identification with capture-Mark-Recapture population size and operational sex ratio *** Natterjack toads were identified by the pattern of natural markings with repeated ID of the same individual confirmed for 10%of the samples using genetic *** identified 647 unique individuals within a closed study population at caherdaniel,co *** estimates derived from egg string counts estimated a breeding population of 368 females(95%cI 353–384)and capture-Mark-Recapture estimated a breeding population of 1698 males(95%cI 1000–2397).The female:male sex ratio was conservatively estimated at 1:5(95%cI 1:3–1:6)where 62%±6%of females were assumed to *** substantially departed from any priori assumption of 1:1 which could have underestimated the breeding population by up to 72%.Where amphibian absolute population size estimation is necessary,methods should include empirical survey data on operational sex ratios and not rely on assumptions or those derived from the literature which may be highly population and/or context-dependent.

关键词： Epidalea calamita genetic fingerprinting Mark-Recapture Natterjack toad photo-identification

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Effects of progesterone on T-type-ca^(2+)-channel expression in Purkinje cells

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Neural Regeneration Research 2022年第11期17卷 2465-2471页

作者： Annika Eickhoff Jonas Tjaden sarah Stahlke Matthias Vorgerd Verena Theis Veronika Matschke carsten Theiss Department of cytology Institute of AnatomyRuhr-University BochumBochumGermany Department of Neurology Neuromuscular Center RuhrgebietUniversity Hospital BergmannsheilRuhr-Universität BochumBochumGermany

Plasticity of cerebellar Purkinje cells(Pc)is influenced by progeste rone via the classical progeste rone receptors PR-A and PR-B by stimulating dendritogenesis,spinogenesis,and synaptogenesis in these *** Pc cultures were used to analyze progeste rone effects at a molecular level on the voltage-gated T-type-ca^(2+)-channels ca_(v)3.1,ca_(v)3.2,and ca_(v)3.3 as they helped determine neuronal plasticity by regulating ca^(2+)-influx in neuronal *** results showed direct effects of progesterone on the mRNA expression of T-type-ca^(2+)-channels,as well as on the protein kinases A and c being involved in downstream signaling pathways that play an important role in neuronal *** the mRNA expression studies of T-type-ca^(2+)-channels and protein kinases of the signaling cascade,laser microdissection and purified Pc cultures of diffe rent maturation stages were *** staining was also performed to characte rize the localization of T-type-ca^(2+)-channels in *** rimental progesterone treatment was performed on the purified Pc culture for 24 and 48 *** results show that progesterone increases the expression of ca_(v)3.1 and ca_(v)3.3 and associated protein kinases A and cin Pc at the mRNA level within 48 hours after treatment at *** effects extend the current knowledge of the function of progesterone in the central nervous system and provide an explanatory approach for its influence on neuronal plasticity.

关键词： ca_(v)3.1 ca_(v)3.2 ca_(v)3.3 neuronal plasticity progesterone protein kinase A protein kinase c Purkinje cells rat cerebellum T-type-ca^(2+)-channels

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Early development and the point of no return in pikeperch( Sander lucioperca L.) larvae

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chinese Journal of Oceanology and Limnology 2017年第6期35卷 1493-1500页

作者：许郑超李彩娟凌去非 GAUGHAN sarah 王国成韩晓飞 School of Biology and Basic Medical Sciences Soochow University Department of Biology & School of Interdisciplinary Informatics University of Nebraska at Omaha

The objectives of the present study were to evaluate the yolk-sac and oil globule absorption and point of no return （PNR） ofpikeperch （Sander lucioperca L.） larvae. Artificial propagation ofpikeperch was performed at （15±2）℃. Yolk-sac absorption, oil globule absorption, larval growth and the first initial feeding rate were observed to analyze the early growth and to determine the PNR of pikeperch larvae. The total length of newly hatched （0 day after hatching, DAH） pikeperch larvae was （4.25±0.22） mm and the volume of the yolk-sac and the oil globule was （0.30±0.12）mm^3 and （5.14±2.28） 10-2 mm^3 respectively. The yolk-sac and the oil globule were exhausted at 11 DAH and 14 DAH, respectively. Pikeperch larvae began feeding at 8 DAH with an initial feeding rate about 10.0%. From 9 to 14 DAH, the initial feeding rate increased rapidly, and reached its highest （about 82.7%） at 14 DAH. It declined thereafter, 48.9% at 15 DAH and 35.6% at 16 DAH, thus the pikeperch larvae reached PNR by 15-16 DAH. The appropriate first feeding time for the pikeperch larvae is 11-12 DAH, when the initial feeding rate is higher than half of the maximum initial feeding rate.

关键词： growth initial feeding rate pikeperch (Sander lucioperca) larvae Point of No Return

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Novel frameshift mutation in the SAcS gene causing spastic ataxia of charlevoix-saguenay in a consanguineous family from the Arabian Peninsula:A case report and review of literature

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World Journal of clinical cases 2020年第8期8卷 1477-1488页

作者： Abdullah Al-Ajmi sarah Shamsah Aleksandar Janicijevic Michayla Williams Fahd Al-Mulla Neurology Unit Al-Jahra HospitalJahra City 13110Kuwait Faculty of Allied Health Sciences Kuwait UniversityKuwait City 13110Kuwait Department of Radiology Al-Jahra HospitalJahra City 13110Kuwait Department of Genetics Genatak Center for Genomic MedicineKuwait City 12000Kuwait

BAcKGROUND Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula,although the consanguineous marriage rate is very *** report the first family from the Arabian Peninsula harboring a novel frameshift mutation in the SAcS *** SUMMARY A 33-year-old man presented to our neurology clinic with balance problems and weakness of distal upper and lower *** was previously clinically diagnosed with Friedreich's ***,the severity of polyneuropathy and the electrodiagnostic studies(EDX)findings are atypical features of Friedreich’s ataxia,and the deterioration was attributed to diabetic *** examination of other family members identified cerebellar ataxia,lower-limb pyramidal signs,peripheral neuropathy,and magnetic resonance imaging findings characterized by pontine linear *** testing for Friedreich’s ataxia did not yield a *** exome sequencing identified a novel frameshift germline mutation in the SAcS gene termed c.5824_5827delTAcT using the transcript NM_014363.5,which is predicted to cause premature termination of the sacsin protein at amino acid position 1942(***1942Metfs*9)and disrupts the sacsin SRR3 and domains downstream from *** mutation segregated with the disease in the *** Our data add to the spectrum of mutations in the SAcS gene and argues for a need to implement suitably integrated clinical and diagnostic services,including next generation sequencing technology,to better classify ataxia in this area of the world.

关键词： Ataxia Autosomal recessive spastic ataxia of charlevoix-saguenay Sacsin SAcS mutation Arabia Next generation sequencing case report

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Differences in neuroplasticity after spinal cord injury in varying animal models and humans

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Neural Regeneration Research 2019年第1期14卷 7-19页

作者： Mallory E.Filipp Benjamin J.Travis Stefanie S.Henry Emma c.Idzikowski sarah A.Magnuson Megan YF Loh Daniel J.Hellenbrand Amgad S.Hanna Department of Neurological Surgery University of Wisconsin

Rats have been the primary model to study the process and underlying mechanisms of recovery after spinal cord injury. Two weeks after a severe spinal cord contusion, rats can regain weight-bearing abilities without therapeutic interventions, as assessed by the Basso, Beattie and Bresnahan locomotor scale. However, many human patients suffer from permanent loss of motor function following spinal cord injury. While rats are the most understood animal model, major differences in sensorimotor pathways between quadrupeds and bipeds need to be considered. Understanding the major differences between the sensorimotor pathways of rats, non-human primates, and humans is a start to improving targets for treatments of human spinal cord injury. This review will discuss the neuroplasticity of the brain and spinal cord after spinal cord injury in rats, non-human primates, and humans. A brief overview of emerging interventions to induce plasticity in humans with spinal cord injury will also be discussed.

关键词： recovery regeneration spinal cord injury plasticity axons animal studies locomotor training functional recovery

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Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

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Nano Research 2018年第10期11卷 5584-5595页

作者： Jonathan Wang christopher Poon Deborah chin sarah Milkowski Vivian Lu Kenneth R. Hallows Eun Ji chung Department of Biomedical Engineering University of Southern California Los Angeles CA 90089 USA Division of Nephrology and Hypertension Department of Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA USc/UKRO Kidney Research center Keck School of Medicine University of Southern California Los Angeles CA 90033 USA Norris comprehensive cancer center University of Southern California Los Angeles CA 90033 USA Department of Stem cell Biology and Regenerative Medicine University of Southern California Los Angeles CA 90033 USA Mork Family Department of chemical Engineering and Materials Science University of Southern California Los Angeles CA 90089 USA

One in three Americans is at risk for developing chronic kidney disease （cKD） and end-stage renal disease （ESRD）, leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel kidney-targeting multimodal micelle （KM） system for drug delivery applications. SpecificaU~ we incorporated the kidney-targeting peptide （Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid）3-Lysine）（（KKEEE）3K） into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted （NT） control upon intravenous injection in wild-type c57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen （BUN） and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of （KKEEE）BK in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in cKD.

关键词： micelle kidney disease renal targeting biodistribution nanoparticle

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Lipid droplets as metabolic determinants for stemness and chemoresistance in cancer

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World Journal of Stem cells 2021年第9期13卷 1307-1317页

作者： Alba Royo-Garcia sarah courtois Beatriz Parejo-Alonso Pilar Espiau-Romera Patricia Sancho Hospital Universitario Miguel Servet IIS AragónZaragoza 50009Spain

Previously regarded as simple fat storage particles,new evidence suggests thatlipid droplets(LDs)are dynamic and functional organelles involved in keycellular processes such as membrane biosynthesis,lipid metabolism,cellsignalling and ***,an increased LD content is one of the mostapparent features resulting from lipid metabolism reprogramming necessary tosupport the basic functions of cancer *** have been associated to differentcellular processes involved in cancer progression and aggressiveness,such astumorigenicity,invasion and metastasis,as well as ***,all of these processes are controlled by a subpopulation of highly aggressivetumoral cells named cancer stem cells(cScs),suggesting that LDs may befundamental elements for stemness in *** the key role of cScs onchemoresistance and disease relapse,main factors of therapy failure,the design ofnovel therapeutic approaches targeting these cells may be the only chance forlong-term survival in cancer *** this sense,their biology and functionalproperties render LDs excellent candidates for target discovery and design ofcombined therapeutic *** this review,we summarise the currentknowledge identifying LDs and cScs as main contributors to cancer aggressiveness,metastasis and chemoresistance.

关键词： Lipids Lipid droplets Lipid metabolism Stemness cancer stem cells chemoresistance

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