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Overexpression of OGFr Downregulates Ovarian Cancer Cell Proliferation <i>In Vitro</i>and Inhibits Tumorigenesis

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journal of Cancer Therapy 2011年第4期2卷 579-594页

作者： Renee N. Donahue patricia j. mclaughlin Ian S. Zagon 不详

The opioid growth factor (OGF) and its receptor (OGFr) regulate human ovarian cancer cell proliferation through a tonically active inhibitory axis. We investigated the effect of OGFr overexpression on ovarian tumorigenesis. Clonal cell lines of SKOV-3 human ovarian cancer were established to stably overexpress OGFr. shRNA constructs were evaluated for antitumor activity in vitro, as well as in vivo using mouse models of s.c. and i.p. tumor transplantation. The 5 clonal cell lines were characterized by increases in OGFr protein (62% to 245%) and binding capacity (51% - 154%), and decreases (36% - 185%) in cell number, relative to untransfected wild-type (WT) cells and empty vector (EV) transfected clones. Nude mice receiving s.c. injection of 2 overexpressing OGFr cell lines (OGFr-3 and OGFr-22) had reduced tumor incidence, delayed tumor appearance (up to 12 days), and decreased tumor volume (up to 87%) relative to WT and EV controls. Mice injected i.p. with these clonal lines displayed reduced formation of tumor nodules (up to 95%), and depressed tumor weights (up to 99%) compared to WT and EV groups. DNA synthesis, but not cell survival, was depressed in cells and s.c. tumors overexpressing OGFr in comparison to the WT and EV groups. Angiogenesis was reduced up to 86% in clonal tumors compared to WT and EV groups. This preclinical evidence demonstrates that OGFr expression is a molecular determinant of ovarian cancer progression, and has important relevance to understanding the pathogenesis and treatment of this deadly disease.

关键词： Cell Proliferation Opioids [Met5]-Enkephalin OGF OGFr Ovarian Cancer

The Opioid Growth Factor Inhibits Established Ovarian Cancer in Nude Mice and Can Be Combined with Taxol or Cisplatin to Enhance Growth Inhibition

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journal of Cancer Therapy 2011年第2期2卷 110-124页

作者： Renee N. Donahue Ian S. Zagon patricia j. mclaughlin Department of Neural and Behavioral Sciences The Pennsylvania State University College of Medicine Hershey PA

Ovarian cancer is the 5th leading cause of cancer-related mortality in women. Seventy-five percent of ovarian cancer patients present in advanced stages, and receive cytoreductive surgery and adjuvant chemotherapy. However, within 2 years 65% of these patients relapse and thereafter only receive palliative care. Novel therapies based on the biology of these cancers are urgently needed. The opioid growth factor (OGF)-OGF receptor (OGFr) axis is an endogenous opioid system known to inhibit proliferation of human ovarian cancer cells in tissue culture, but does not affect cell survival. The present study determined whether OGF in combination with standard of care chemotherapy, provides an inhibitory effect on the growth of human ovarian cancer cells in vitro. In addition, this investigation assessed whether OGF biotherapy, alone or in combination with taxol or cisplatin, inhibits tumor growth in mice with xenografts of ovarian cancer. The combination of OGF (10–6 M) with taxol (10–9 M or 10–10 M) or cisplatin (0.01 ug/ml or 0.001 ug/ml) markedly reduced cell number and DNA synthesis in vitro to a greater extent than individual compounds. OGF, but not taxol or cisplatin, altered growth in an opioid receptor mediated and reversible manner. Female nu/nu mice inoculated subcutaneously with SKOV-3 cells, and treated with OGF (10 mg/kg) for 5 weeks commencing at the time tumors became measurable, had tumor volumes and weight that were reduced by up to 50% from animals receiving saline. The combination of OGF with taxol (3 mg/kg, weekly) or cisplatin (4 mg/kg, weekly for 2 weeks) for 37 days reduced tumor volumes and weight in contrast to mice receiving individual agents alone. Moreover, OGF treatment in mice receiving cisplatin provided protection against the weight loss associated with cisplatin alone. All treatments suppressed DNA synthesis and angiogenesis, whereas exposure to taxol or cisplatin, but not OGF, induced apoptosis. Additive inhibitory effects on DNA synthesis

关键词： Cell Proliferation [Met5]-Enkephalin Opioid Growth Factor OGFr Ovarian Cancer

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

Acoustic measurements of models of military style supersonic nozzle jets

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Chinese journal of Aeronautics 2014年第1期27卷 23-33页

作者： Ching-Wen Kuo jérémy Veltin Dennis K.mclaughlin Department of Aerospace Engineering The Pennsylvania State UniversityUniversity Park TNO Science and Industry

Modern military aircraft jet engines are designed with variable-geometry nozzles to provide optimal thrust in different operating conditions, depending on the flight envelope. How- ever, acoustic measurements for such nozzles are scarce, due to the cost involved in making full- scale measurements and the lack of details about the exact geometries of these nozzles. Thus the present effort at Pennsylvania State University （PSU） in partnership with GE Aviation and the NASA Glenn Research Center is aiming to study and characterize the acoustic field produced by supersonic jets issuing from converging-diverging military style nozzles, and to identify and test promising noise reduction techniques. An equally important objective is to develop methodology for using data obtained from small- and moderate-scale experiments to reliably predict the full-scale engine noise. The experimental results presented show reasonable agreement between small-scale and medium-scale jets, as well as between heated jets and heat-simulated ones.

关键词： Aeroacoustics Acoustic noise measurement jet noise jets Nozzle Supersonic flow

Intrinsically photosensitive retinal ganglion cells

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Science China(Life Sciences) 2010年第1期53卷 58-67页

作者： Gary E.PICKARD patricia j.SOLLARS School of Veterinary Medicine and Biomedical Sciences University of Nebraska

A new mammalian photoreceptor was recently discovered to reside in the ganglion cell layer of the inner *** intrinsically photosensitive retinal ganglion cells(ipRGCs) express a photopigment,melanopsin,that confers upon them the ability to respond to light in the absence of all rod and cone photoreceptor *** relatively few in number,ipRGCs extend their dendrites across large expanses of the retina making them ideally suited to function as irradiance detectors to assess changes in ambient light *** in ipRGCs appears to be mediated by transient receptor potential channels more closely resembling the phototransduction cascade of invertebrate rather than vertebrate *** convey irradiance information centrally via the optic nerve to influence several *** are the primary retinal input to the hypothalamic suprachiasmatic nucleus(SCN),a circadian oscillator and biological clock,and this input entrains the SCN to the day/night *** contribute irradiance signals that regulate pupil size and they also provide signals that interface with the autonomic nervous system to regulate rhythmic gene activity in major organs of the *** also provide excitatory drive to dopaminergic amacrine cells in the retina,providing a novel basis for the restructuring of retinal circuits by *** we review the ground-breaking discoveries,current progress and directions for future investigation.

关键词： melanopsin circadian rhythms suprachiasmatic nucleus retina pupillary light reflex

Role of ion channels in gastrointestinal cancer

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World journal of Gastroenterology 2019年第38期25卷 5732-5772页

作者： Kyle j Anderson Robert T Cormier patricia M Scott Department of Biomedical Sciences University of Minnesota Medical School

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer *** functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of *** this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and *** members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon ***-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle *** VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC *** have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer ***2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all major GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal *** distinct types of K+channels are found dysregulated in the GI *** are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CR

关键词： Ion channels Gastrointestinal cancer Colorectal cancer Gastric cancer Pancreatic cancer Esophageal cancer Hepatocellular carcinoma Prognostic biomarker Novel therapies Clinical targets

On Systems of Boundary Value Problems for Differential Inclusions

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Acta Mathematica Sinica,English Series 2007年第3期23卷 549-556页

作者： Lynn ERBE Christopher C.TISDELL patricia j.Y.WONG Department of Mathematics The University of Nebraska-LincolnLincolnNE 68588-0130USA School of Mathematics and Statistics The University of New South WalesSydney 2052Australia School of Electrical and Electronic Engineering Nanyang Technological University50 Nanyan9 AvenueSingapore 639798Singapore

Herein we consider the existence of solutions to second-order, two-point boundary value problems （BVPs） for systems of ordinary differential inclusions. Some new Bernstein-Nagumo conditions are presented that ensure a priori bounds on the derivative of solutions to the differential inclusion. These a priori bound results are then applied, in conjunction with appropriate topological methods, to prove some new existence theorems for solutions to systems of BVPs for differential inclusions. The new conditions allow of the treatment of systems of BVPs without growth restrictions.

关键词： boundary value problem, systems of differential inclusions, existence of solutions a priori bounds Bernstein-Nagumo condition

Does the scent of a potential mate prevent the resorption of oocytes by apoptosis in Nauphoeta cinerea？

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Insect Science 2009年第5期16卷 393-398页

作者： Emma L. B. Barrett Allen j. Moore patricia j. Moore Centre for Ecology and Conservation School of Biosciences University of Exeter Cornwall Campus Penryn Cornwall UK

We expect organisms to have evolved mechanisms to gather and use the information available within their environments, to steer resource investment decisions toward the traits that will give the greatest fitness returns. Pheromones are social signals, a common purpose of which is to act as indicators of mate presence. Consequently, pheromones have the potential to act as signals to increase or maintain reproductive investment over that of competing life-history traits. In the cockroach, Nauphoeta cinerea （Oliver）, females pay costs of maintaining investment in reproduction when there are no males, and males produce pheromones that are known to effect female reproductive outcomes. Whether the pheromones have an influence on resource physiology is unknown. We subjected newly eclosed females to either a synthetic blend of male pheromones or control. We dissected females at 7, 12, 17 or 22 days. We measured apoptosis levels and size of all oocytes within the vitellerium, and measured dry fat body mass. Synthetic male pheromone blend did not have an effect on any measure of female reproductive or somatic resource physiology. Although negative results are always problematic, the success of the synthetic pheromone method in the past suggests that females may be insensitive to male pheromones in the pre-oviposition period, and may rely on mating stimulus rather than pheromone as the cue for oocyte maintenance and growth. Previous studies reporting effects of male pheromones on female reproduction suggest that the period of pheromone sensitivity may be between mating and birth.

关键词： apoptosis environment oocyte ovary pheromone predictable trade-off

Celiac disease:Management of persistent symptoms in patients on a gluten-free diet

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World journal of Gastroenterology 2012年第12期18卷 1348-1356页

作者： David H Dewar Suzanne C Donnelly Simon D mclaughlin Matthew W johnson H julia Ellis Paul j Ciclitira King's College London Division of Diabetes and Nutritional SciencesDepartment of GastroenterologyThe Rayne InstituteSt Thomas' HospitalLondon SE1 7EHUnited Kingdom

AIM:To investigate all patients referred to our center with non-responsive celiac disease (NRCD),to establish a cause for their continued ***:We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo *** individuals were investigated to establish the eitiology of their continued *** patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody *** were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion.A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where ***,lactulose hydrogen breath testing,pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms *** clinical progress was followed over a minimum of 2 ***:One hundred and twelve consecutive patients were referred with *** were found not to have celiac disease (CD).Of the remaining 100 patients,45% were not adequately adhering to a strict gluten-free diet,with 24 (53%) found to be inadvertently ingesting gluten,and 21 (47%) admitting *** colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%.Refractory CD was diagnosed in 9%.Three of these were diagnosed with intestinal *** 2 years,78 patients remained well,eight had continuing symptoms,and four had ***:In individuals with NRCD,a remediable cause can be found in 90%:with continued gluten ingestion as the leading *** propose an algorithm for investigation.

关键词： Celiac disease Non-responsive celiac disea-se Refractory celiac disease Gluten Gluten-free diet