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ReviewStudy on the pharmacological activities and chemicalstructures of Viburnum dilatatumZhiheng Gao, Yufei Xi, Man Wang, Xiaoxiao Huang*, Shaojiang Song*Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research &Development, Liaoning Province, School of Traditional Chinese Materia Medica, ShenyangPharmaceutical University, Shenyang 110016, ChinaAbstractViburnum dilatatum (jiami in Chinese), belonging to the Caprifollaceae family, is widely distributed in Japan and China. Phytochemical investigations of Viburnum dilatatum (V. dilatatum) have resulted in the isolation of triterpenoids, phenolic glycosides essential oil, norisoprenoids, etc. Research results have shown that the chemical constituents of V. dilatatum possess various pharmacological activities, including antihyperglycemic, antioxidant activity and antiulcer effects. This study reviewed the chemical constituents and pharmacological activities of V. dilatatum to provide practical and useful information for further research and development of this plant.Keywords: Viburnum dilatatum; pharmacological activity; chemical structures1 IntroductionViburnum dilatatum (called jiami in Chinese, gamazumi in Japanese and snowball tree in English), beloinging to family Caprifoliaceae, is a deciduous low tree distributed widely in the hills of northern China and Japan [1]. There are many types of chemical constituents in Viburnum dilatatum (V. dilatatum), including triterpenoids, * Author to whom correspondence should be addressed. Address:School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Rd., Shenyang 110016, China; Tel.: +86-24-43520793 (Xiaoxiao Huang); +86-24-43520707 (ShaojiangSong);E-mail:*******************(XiaoxiaoHuang); ****************(ShaojiangSong).Received: 2021-04-16 Accepted: 2022-08-28phenolic glycosides and norisoprenoids [2-4]. The leaves have been utilized as a traditional Chinese medicine, and phenolic compounds have been reported as the main active chemical component of the leaves. Many researchers have analyzed the functions of these medicinal components and found that these components have good antioxidant antihyperglycemic and antiulcer effects. For example, the gamazumi crude extract obtained from the squeezed juice of the fruit prevented oxidative injury in rats [5]. This review described the chemical structures and pharmacological activities of V. dilatatum, so as to help readers understand comprehensively the research progress of V. dilatatum and provide help for the development of V. dilatatum.2 Chemical constituents and structuresPrevious reports have indicated that the main chemical constituents of V. dilatatum are phenolic glycosides and triterpenoids.2.1 Phenolic glycosidesThirteen phenolic glycosides were isolated and identified from V. dilatatum by extensive spectroscopic methods, namely p -hydroxyphenyl-6-O -trans-caffeoyl-β-D -glucoside (1) [6], p -hydroxyphenyl-6-O -trans-caffeoyl-β-D -alloside (2) [6], 4-allyl-2-methoxyphenyl-6-O -β-D -apiosyl(1→6)-β-D -glucoside (3) [6], 1-(4’-hydroxy-3’-methoxypheny1)-2-[2’’-hydroxy-4’’-(3’’’-hydroxypropyl)]-1,3-propanediol-l-O -β-D -glucopyranoside (erythro isomer) (4-7) [7], neochlorogenic acid methyl ester (8-9) [7], cryptochlorogenic acid methyl ester (10-11) [7], cyanidin-3-sambubioside (Cy-3-sam) (12) [8], cyanidin-3-glucoside (Cy-3-glc) (13) [8], 5-O -caffeoyl-4-methoxyl quinic acid (4-MeO-5-CQA) (14) [8], chlorogenic acid (5-CQA) (15) [8], quercetin (16) [8], 2-(glucopyranosyloxy)-benzyl-3-(glucopyranosyloxy)-benzoate (17) [9] and jiamizioside E (18) [10]. These structures are shown in Fig. 1.Fig. 1 Phenolic glycosides isolated from V . dilatatumContinued fig. 12.2 TriterpenoidsThere were about seventeen triterpenoids isolated and characterized from V. dilatatum , such as viburnols A (19) [11], viburnols B (20) [11], viburnols C (21) [11], viburnols D (22) [11], viburnols E (23) [11], viburnols F (24) [12], viburnols G (25) [12], viburnols H (26) [12], viburnols I (27) [12], viburnols J (28) [12],viburnols K (29) [12], viburnudienone B 2methyl ester (30) [13], viburnenone H 2 (31) [13],v i b u r n e n o n e B 2 m e t h y l e s t e r (32) [13], viburnudienone B 1 methyl ester (33) [13], viburnenone H 1 (34) [13], and viburnenone B 2 methyl ester (35) [13]. The structures are shown in Fig. 2.Continued fig. 23 Pharmacological activities3.1 Antioxidant activityOxidative stress caused by free radicals and their derivatives leads to disturbances in redox homeostasis. Reactive oxygen species (ROS) are not only endogenously produced during intracellular metabolic processes but also generated by exogenous stimuli such as UV radiation, pollutants, smoke and drugs. The cell triggers its defense systems or undergoes apoptosis when intracellular oxidative status increases. It influences numerous cellular processes including core signaling pathways, which are associated with development of systematic and chronic disorders, such as aging and cancer. Therefore, it is critical to remove cellular oxidants and restore redox balance.solution of V. dilatatum (GSS) had strong antioxidant activity in vivo and prevent stress-induced oxidative damage by the XYZ-dish method and the澳electron spin resonance (ESR) method [14]. The experimental result showed that the concentrations of lipid peroxide in plasma, liver and stomach in the GSS group were reduced. Furthermore, the activities of plasma lactic dehydrogenase, amylase and creatine phosphokinase are ordinarily increased by stress. However, these activities in the GSS group decreased to that in the control group. It was concluded that gastric ulcer formation, increase of lipid peroxidation in plasma and tissues and elevation of plasma enzymatic activities were confirmed in rats with water immersion restraint stress. It was also found that intake of GSS could protect the stomach and other tissues from oxidative damage.Kim et al. identified and isolated two major anthocyanins by NMR and LC-ESI-MS/MS, namely, cyanidin 3-sambubioside (I) and kuromanin (II) [15]. By the electron spin resonance method, the superoxide anion radical scavenging activities of I and II were evaluated with the IC 50 values of 17.3 and 69.6 µM, and their activities on hydroxyl radicals were evaluated with the IC 50 values of 4.3 and 53.2 mM. As the positive control, the IC 50 values of ascorbic acid were 74.2 µM on superoxide anion radicals and 3.0 mM on hydroxyl radicals, respectively. The above results suggested that these anthocyanins with radical scavenging properties might be the key compounds contributing to the antioxidant activity and physiological effects of V . dilatatum fruits.Woo et al. determined the free radical scavenging capacity of VD (the leaves of V. dilatatum ) [16]. Anti-oxidant activity of the extracts was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Butylated hydroxytoluene (BHT), a synthetic antioxidant, or α-tocopherol, was used as the positive control in these assays. The experimental result showed that VD inducedincrease in radical scavenging activity. In addition, lipid peroxidation inhibitory activity was determined via measurement of MDA (Malondialdehyde) levels using mouse liver tissue homogenate treated with various concentrations of the extracts. The concentration-dependent decrease in MDA levels observed was consistent with radical scavenging activities of the extracts. To examine whether VD extracts could protect mam-malian cells from oxidative stress, cultures of a human mammary gland-derived epithelial cell line MCF-7 were treated with each extract prior to challenging them with tBHP. The intracellular ROS (Reactive oxygen species) production was determined with the relative intensity of dichlorofluorescein fluorescence. While intracellular ROS formation was significantly promoted by tBHP treatment, the augmented ROS level was significantly reduced after the treatment with VD extracts.3.2 Antihyperglycemic effectIwai et al. used an oral glucose tolerance test on the diabetic rats [17]. They found that the elevation of plasma glucose level after oral administration of 2 g/kg glucose was suppressed by the repeated administration of the freeze-dried powder of V. dilatatum fruit juice (CEV). The α-glucosidase inhibitory activities of isolated compounds from CEV were also measured. Cyanidin 3-sambubioside and 5-caffeoyl quinic acid A showed inhibitory activity. These results suggested that V. dilatatum fruit had the antihyperglycemic effects.4 ConclusionV. dilatatum is distributed widely in the hills of northern China and Japan. Currently, the studies on V. dilatatum have been conducted at home and abroad, but few studies focus on its chemical components and pharmacological activities. Previousphytochemical investigations showed that the constituents of V. dilatatum included triterpenoids, phenolic glycosides, norisoprenoids and other compounds. This study describes thirteen phenolic glycosides and seventeen triterpenoids and their different degrees of antihyperglycemic, antioxidant activity and antiulcer effects, aiming to provide a reference for further studies on V. dilatatum and pharmaceutical development.References[1] Jeffrey B, Harborne A. Colour atlas of medicinal plantsof Japan. Phytochemistry, 1981, 20: 1467.[2] Miyazawa M, Hashidume S, Takahashi T, et al. Aromaevaluation of gamazumi (Viburnum dilatatum) by aroma extract dilution analysis and odour activity value.Phytochem Anal, 2012, 23: 208-213.[3] Kurihara T, Kikuchi M. Studies on the constituentsof flowers. IV. On the components of the flower of Viburnum dilatatum Thunb. J Health Sci, 1975, 95: 1098-1102.[4] Machida K, Kikuchi M. Norisoprenoids from Viburnumdilatatum. Phytochemistry, 1996, 41: 1333-1336. [5] Iwai K, Onodera A, Matsue H. Mechanism of preventiveaction of Viburnum dilatatum Thunb (gamazumi) crude extract on oxidative damage in rats subjected to stress. J Sci Food Agric, 2010, 83: 1593-1599.[6] Machida K, Nakano Y, Kikuchi M. Phenolic glycosidesfrom Viburnum dilatatum. Phytochemistry, 1991, 30: 2013-2014.[7] Machida K, Kikuchi M. Phenolic compounds fromViburnum dilatatum. Phytochemistry, 1992, 31: 3654-3656.[8] Kim MY, Iwai K, Matsue H. Phenolic compositions ofViburnum dilatatum Thunb. fruits and their antiradical properties. J Food Compos Anal, 2005, 18: 789-802. [9] Lu D, Yao S. Phenolic glycoside from the roots ofViburnum dilatatum. Nat Prod Commun, 2009, 4: 945-946.[10] Wu B, Zeng X, Zhang Y. New metabolite fromViburnum dilatatum. Nat Prod Commun, 2010, 5: 1097-1098.[11] Machida K, Kikuchi M. Viburnols: Novel triterpenoidswith a rearranged dammarane skeleton from Viburnum dilatatum. Tetrahedron Lett, 1996, 37: 4157-4160. [12] Machida K, Kikuchi M. Viburnols: Six noveltriterpenoids from Viburnum dilatatum. Tetrahedron Lett, 1997, 38: 571-574.[13] Machida K, Kikuchi M. Studies on the Constituents ofViburnum Species. XIX. Six New Triterpenoids from Viburnum dilatatum Thunb. Chem Pharm Bull, 1999, 47: 692-694.[14] Iwai K, Onodera A, Matsue H, et al. Antioxidant activityand inhibitory effect of Gamazumi (Viburnum dilatatum THUNB.) on oxidative damage induced by water immersion restraint stress in rats. Int J. Food Sci Nutr, 2001, 52: 443-451.[15] Kim MY, Iwai K, Onodera A, et al. Identification andAntiradical Properties of Anthocyanins in Fruits of Viburnum dilatatum Thunb. J Agric Food Chem, 2003, 51: 6173-6177.[16] Woo YJ, Lee HJ, Jeong YS, et al. Antioxidant Potentialof Selected Korean Edible Plant Extracts. Bio Med Res Int, 2017, 2017: 1-9.[17] Iwai K, Kim MY, Akio O, et al. Alpha-glucosidaseinhibitory and antihyperglycemic effects of polyphenols in the fruit of Viburnum dilatatum Thunb. J Agric Food Chem, 2006, 54: 4588-4592.。

effects of the vanilloid agonist olvanil and antagonist capsazepine on rat behaviors

Effects of the vanilloid agonist olvanil and antagonist capsazepineon rat behaviorsJohn W.Kasckow a,b,c,*,James J.Mulchahey b,d ,Thomas D.Geracioti Jr.a,b,caPsychiatry Service (116A),Cincinnati VAMC,3200Vine Street,Cincinnati,OH,USAbDepartment of Psychiatry,School of Medicine,University of Cincinnati,231Albert Sabin Way (ML559)Cincinnati,OH 45267-0559,USAcUniversity of Cincinnati Neurosciences Program,Cincinnati,OH,USA dPhase 2Discovery,Inc.,3130Highland Avenue,Cincinnati,OH,USAAccepted 17October 2003AbstractVanilloid receptors (VR)are molecular integrators of painful chemical and physical stimuli.Olvanil is an agonist of the vanilloid receptor;capsazepine is a competitive VR antagonist.The authors were interested in investigated the effects of these compounds on anxiety-like behaviors in rats using the elevated plus maze.In addition,the authors examined the effects of olvanil on the Porsolt swim test.Doses of 0,0.2,1.0and 5.0mg/kg olvanil,respectively,yielded percent open arm entries at 5min of 25F 10.1,19.3F 7.1,14.9F 5.9and 0F 0.We demonstrated a drug effect by showing that the mean of the 0.2,1and 5mg/kg doses was significantly lower than the 0mg/kg dose at P <.05.In addition,the authors examined the effect of olvanil on the ability of rats to perform in the Porsolt swim test.Float time for rats was tested with 0.1or 2mg/kg olvanil and differences between the float times for the lower and higher doses were significant at P <.05.In addition,the effects of various doses of the vanilloid antagonist capsazepine was examined on elevated plus maze behavior.Doses of 0,1,5and 10mg/kg yielded percent time in the open arms at 5min of 1.46F 1.38,15.05F 10.42,11.54F 10.57,and 14.56F 7.86.The mean of the 1,5and 10mg/kg doses was significantly greater than the percent time in the open arms for the vehicle,consistent with a drug effect.The results suggest that the vanilloid agonists and antagonists may impact on behaviors involving anxiety and affect.However,it cannot be ruled that the findings could be due to nonspecific motor effect.D 2003Elsevier Inc.All rights reserved.Keywords:Capsazepine;Elevated plus maze;Olvanil;Porsolt swim test;Rat1.IntroductionVanilloid receptors are molecular integrators of painful chemical and physical stimuli such as noxious heat (>48j C)and low pH.Heat is known to open the channel pore of the vanilloid receptor 1(VR1).After exposure to these stimuli,VR1receptors become permeable to Na +and Ca 2+ions causing the neurons to depolarize and fire action potentials.Capsaicin and protons lower the heat threshold of the receptor (Piomelli,2001;Szallasi and Blumberg,1999).A variety of agonists and antagonists of the VR1exist.Olvanil is one capsaicin analog,which acts as an agonist atthe vanilloid receptor.Capsazepine is a competitive VR1antagonist.Another capsaicin analogue is 3H-resinferatoxin,which binds to VR1receptors in the central nervous system (CNS).This compound binds to the preoptic area,locus ceruleus,medial hypothalamus,reticular formation and ventral thalamus (Acs et al.,1996).There is evidence that agonists and antagonists of the VR1evoke physiologic responses within the CNS.For instance,both capsaicin and olvanil evoke a concentra-tion-dependent release of calcitonin gene-related peptide;capsazepine inhibits this response (Wardle et al.,1997).Capsaicin has also been shown to stimulate glutamate release from hypothalamic slices and lumbar dorsal horn.This response is calcium dependent and is also inhibited by capsazepine (Sasamura et al.,1998).There are links between VR1and cannabinoid recep-tors.Anandamide transport is apparently inhibited by olvanil given that intracellular accumulation of 3H-anan-damide by human astrocytoma cells is observed following0278-5846/$–see front matter D 2003Elsevier Inc.All rights reserved.doi:10.1016/j.pnpbp.2003.10.007Abbreviations:Vanilloid receptor 1,VR1.*Corresponding author.Department of Psychiatry,School of Medi-cine,University of Cincinnati,231Albert Sabin Way (ML559)Cincinnati,OH 45267-0559,USA.Tel.:+1-513-558-2989;fax:+1-513-558-0264.E-mail address:jkasckow@ (J.W.Kasckow)/locate/pnpbpProgress in Neuro-Psychopharmacology &Biological Psychiatry 28(2004)291–295coincubation with olvanil(Mezey et al.,2000).In addi-tion,as per immunocytochemical and in situ hybridization studies,VR1expressing neurons are located in cortical areas(layers3and5),the limbic system(hippocampus, central amygdala,medial and lateral habenula),striatum, hypothalamus,substantia nigra,reticular formation,locus ceruleus and inferior olive.This would suggest that vanilloid receptors could play a role in modulating the CNS.The effects of vanilloids on behavior have not been studied well.There are studies indicating that motor activity can be suppressed by the activation of vanilloid receptors.For instance,capsaicin and various analogs such as N-linoleoyl-vanilyl-amine(livanil)and N-alpha-linole-noyl-vanilyl-amine(linvanil)inhibit ambulation,stereotyp-ic behavior and activity in the open field test(Di Marzo et al.,2001).The study at hand sought to determine if vanilloid receptor-mediated stimulation or inhibition results in behavioral effects in models of anxiety and depression.The objective of the current study was to evaluate olvanil and capsazepine for their anxiolytic or antidepressant potential utilizing the elevated plus maze and Porsolt swim test.2.Methods2.1.AnimalsSprague–Dawley rats weighing approximately200g were group housed on a12:12-h light–dark cycle(lights on at6:00h and off at18:00h)for7days with food and water available ad libitum.They were housed four per cage at240j C in a humidity-controlled room.3.Experimental procedures3.1.Drug administrationOn the day of experimentation with either the elevated plus maze or Porsolt swim test,rats were injected with olvanil,capsazepine or vehicle intraperitoneally30min before the behavioral tests.Vehicle consisted of sesame oil. Optimal doses of olvanil and capsazepine had been deter-mined based on the degree of sedation achieved;for instance, it was found that intraperitoneal administration of150–400 mg/kg of capsazepine lead to marked sedation and adminis-tration of50mg/kg of olvanil lead to mild sedation.Thus, lower doses were utilized as indicated below.3.2.Behavioral tests and apparatusWe utilized the elevated plus maze initially for our experiments to screen these agents for several reasons. The elevated plus maze has been used in the past to screen for anxiolytic as well as antidepressant medications;it is felt to be relevant to both anxiety and depressive behaviors.The elevated plus maze offers ease of data collection and requires minimal equipment in the form of the test field, behavior recording,and data interpretation.Furthermore, anxiety-like behaviors on the elevated plus-maze are pre-cisely defined in an operational manner.Essentially,all four feet of the rat are either in an open arm or in a closed arm.If a rat receiving some type of treatment spends a significantly greater amount of time in the closed arms of the maze relative to control rats,then the behavior of that rat may be interpreted as anxiety-like.Elevated plus maze testing was performed as follows: based on Lister(1987),a two feet–four arm radial maze consisting of two opposing enclosed arms[30Â30Â5cm (ÂlengthÂwide)]and two opposing exposed arms(30Â5 cm)was constructed and was elevated on a pedestal30cm above the surface of a table and situated in the center of a dimly lit room.Testing was conducted in a quiet,dedicated room that was dimmed to provide22–350lx of illumination on the exposed arms of the maze and less than1lx within the enclosed arms.Animals were placed facing the enclosed arm in the center of the plus maze.Testing took place for5 min following Heinrichs et al.(1992,1994).We assessed time in open arms,number of entries into the open and closed arm as per Windle et al.(1997).All observers were blind to treatment to remove investigator bias.The Porsolt swim test was performed based on Porsolt et al.(1977)and Lopez-Rubalcava and Lucki(2000).Swim sessions were conducted by placing rats in vertical Plexiglas cylinders(heightÂdiameter:40Â18cm)containing15cm of water maintained at25j C.Rats were not able to support themselves by touching the bottom with their feet.An initial pretest was performed in which rats were placed15min in the water,then dried with paper towels for15min and then returned to their home cages.Twenty-four hours later,they were placed in the cylinder again and the amount of swim and float time was determined for5min.Test sessions were videotaped from an overhead view for scoring later.A rat was judged immobile whenever it remained floating pas-sively in the water in a slightly hunched but upright position with its head just above the surface.3.3.Data analysisFor the analysis of elevated plus maze experiments,we expressed the data for each group of animals as percent open arm entries,percent amount of time spent in the open arms and number of closed arm entries.Percent open arm entries was calculated by dividing the number of open arm entries by the total number of entries(open arm entries F closed arm entries)and expressing this as a percentage.In addition, the percent open arm time was calculated by dividing the amount of time in the open arms divided by the total time in both arms(closed and open arm times)and expressed as a percentage.An entry into the closed or open arms wasJ.W.Kasckow et al./Progress in Neuro-Psychopharmacology&Biological Psychiatry28(2004)291–295 292defined as all four feet of the rat being in the respective arm. Data from the Porsolt swim test was expressed as percent float time.Statistical comparisons were performed using a two-way ANOV A followed by planned comparisons with SAS software.Factors analysed included DoseÂDrug effects or drug effects.4.ResultsThe effects of various doses of the vanilloid agonist olvanil on elevated plus maze performance was as follows, Doses of0(n=15),0.2(n=12for this and all subsequent doses), 1.0and 5.0mg/kg olvanil,respectively,yielded percent open arm entries at5min of25F10.1,19.3F7.1, 14.9F5.9and0F0(mean F S.E.;see Fig.1).The percent open arm times at5min were12.9F8.1for the 0mg/kg dose,8.9F4.2for the0.2mg/kg dose,15.2F7.9for the1mg/kg dose and0F0for the5mg/kg olvanil dose.Furthermore,the mean(F S.E.)number of entries into the closed arm at5min were1.7F0.3,3.3F0.8, 2.7F0.3and0.25F0.1for doses of0,0.2,1and5mg/ kg olvanil,respectively.For percent open arm entries,the mean of the0.2,1and5mg/kg doses was significantly lower than the0mg/kg dose at P<.05consistent with the hypothesis that olvanil caused a drug effect on the rat behavior.For this outcome measure,there were no statis-tical differences between the0.2,1and5mg/kg doses and thus a DoseÂDrug effect was not demonstrable.Fig.2represents float time for rats treated with0.1or2 mg/kg olvanil.The left portion of each pair of bars represents float time acquired on the pretest followed24h later by treatment with the indicated dose of olvanil.A dose of0.1 mg/kg olvanil yielded a pretest float time of123.3F12.3s and24h later,the float time was150.1F18.9s.A dose of 2mg/kg olvanil yielded a pretest float time of99.1F11.5s and24h later,the float time was180.7F18.4s.The differ-ences between the float times for the lower and higher doses were significant at P<.05(one-sided t test;n=12per group).The effects of various doses of the vanilloid antagonist capsazepine on elevated plus maze behavior was as follows. Doses of0,1,5and10A g/kg(n=9for each)yielded percent time in the open arms at5min of1.46F1.38, 15.05F10.42,11.54F10.57,and14.56F7.86(see Fig.3).The percent open arm entries at5min were4.2F3.7for the0A g/kg dose,20.7F11.4for the1A g/kg dose,13.9F11.1for the5A g/kg dose and15.7F7.1for the10A g/kg capsazepine dose.Furthermore,the number of entries into the closed arm at5min were3.4F0.5,2.9F0.5, 2.4F0.3and3.1F0.4for doses of0,1,5and10A g/kg capsazepine,respectively.Percent time in the open arms for the mean of the1,5and10A g/kg doses was significantly greater than the percent time in the open arms forthe Fig.1.This figure represents percent open arm entries of rats spent on theelevated plus maze at5min following acute injections of0,0.2,1.0and5.0mg/kg olvanil.The mean value of the percent open arm entries of the0.2,1.0and5.0mg/kg dose was significantly lower relative to the0mg/kg dosebased on P<.05(one-sided test based on planned comparisons;n=9pergroup).Fig.2.This figure represents the float time for rats treated with0.1or2.0mg/kg olvanil.The left portion of each pair of bars represents float timeacquired on the pretest followed24h later by treatment with the indicateddose of olvanil.The differences between the float times for the lower andhigher doses are significant(one-sided t test;n=12pergroup).Fig.3.This figure represents the percent amount of time rats spent in theopen arms at5min following acute administration of capsazepine,1,5or10A g/kg.The mean value of the percent time in the open arms of the threedoses was significantly lower than that obtained with the vehicle based onP<.05based on planned comparisons(two-sided test;n=9per group).J.W.Kasckow et al./Progress in Neuro-Psychopharmacology&Biological Psychiatry28(2004)291–295293vehicle,consistent with a drug effect.We were not,how-ever,able to demonstrate an effect of DoseÂDrug.5.DiscussionThe research literature on endovanilloids has focused predominantly on the role they play in pain perception (Caterina et al.,1997;Di Marzo et al.,2000).Vanilloid receptors have been found to be expressed in various rat brain nuclei,including limbic nuclei.As a result,investi-gators have more recently hypothesised that vanilloids play a role in mediating other behaviors.Recent reports have examined such a possible role.One report indicated that resiniferatoxin,an ultrapotent capsaicin analog can reduce emesis in the ferret(Andrew and Bhandaru,1993).Furthermore,intracerebroventricu-larly administered resiniferatoxin in the musk shrew induced emesis as well as genital grooming(Rudd and Wai,2001).In another report,capsaicin,an agonist of vanilloid receptors,was able to attenuate hyperkinetic activity in a rat model of Huntington’s disease induced by intrastriatal injection of3-nitropropionic acid.The authors in the latter study hypothesized that the mecha-nism of action involved the endovanilloid system interact-ing with either the dopamine or GABA system(Lastres-Becker et al.,2003).In the current study,we have assessed the role of vanilloids in behavioral tests which screen compounds for potential anxiolytic and antidepressant capabilities.Anxiety-like behaviors were measured on the elevated plus maze. There are many other behavioral tests for detecting anxiety-like behaviors(Willner,1991).Each of these have their advantages and limitations in terms of modelling the human condition.When testing olvanil on the elevated plus maze,we demonstrated that the mean of the0.2,1and5mg/kg doses was significantly lower than the0mg/kg dose,consistent with the hypothesis that olvanil may have caused an anxiogenic-like effect.The mean number of entries into the closed arm at5min for the5mg/kg dose of olvanil was low which suggests that a nonspecific effect on motor activity cannot be ruled out.The inability to distinguish between anxiolytic effects and nonspecific motor inhibition is a common challenge when using preclinical animal screening methodology.There are no animal models which can avoid these confounds(Wall and Messier,2001).Our finding that capsazepine was able to increase percent time in the open arms was consistent with our hypothesis that this compound potentially possesses anxiolytic poten-tial.Percent time in the open arms for the mean of the1,5 and10A g/kg doses was significantly greater than the percent time in the open arms for the vehicle.The effects on closed arm entry at all doses were not different suggest-ing that it was less likely that capsazepine had a nonspecific effect on motor performance.We also demonstrated that olvanil appeared to possess potential antidepressant potential given its ability to reduce float time at higher doses relative to lower doses. The Porsolt swim test has been effectively used to screen for antidepressant efficacy.It quantitates the relative time in which a rodent will swim in a water-filled cylinder vs. the time in which the animal will float.Increases in float time are interpreted as cessation of struggling to escape or as giving up(Porsolt et al.,1977).These additional assessments are of benefit since behavioral changes need to be detected reliably via multiple lines of converging evidence.6.ConclusionsBased on the results of these preclinical findings in animals,this family of compounds could possibly have utility in treating anxiety and depression.However,these rodent models are susceptible to multiple interpretations due to potential nonspecific drug effects.Clearly more work is needed to investigate these results further.Additional inves-tigation into their use in anxiety and mood states are warranted.ReferencesAcs,G.,Palkowitz,M.,Blumberg,P.M.,1996.Specific binding of3H-resiniferatoxin binding by human and rat preoptic area,locus ceruleus, medial hypothalamus,reticular formation and ventral thalamus mem-brane preparations.Life Sci.59,1899–1908.Andrews,P.L.,Bhandavi,P.,1993.Resinferatoxin,an ultrapotent capsaicin analogue,has anti-emetic properties in the ferret.Neuropharmacology 32,779–806.Caterina,M.J.,Schumacher,M.A.,Tominaga,M.,Rosen,T.A.,Levine, J.D.,Julius,D.,1997.The capsaicin receptor:a heat activated ion channel in the pain pathway.Nature389(6653),816–824. 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motivation in language learning tesol internation

MOTIVATION IN LANGUAGE LEARNING: SELECTED REFERENCES(last updated 9 May 2013)Ames, C. (1984). Competitive, cooperative, and individualistic goal structures: A cognitive-instructional analysis. In R. E. Ames & C. Ames (Eds.), Research on motivation ineducation (pp. 177-207). New York: Academic Press.Ames, C. (1986). Effective motivation: The contribution of the learning environment. In R. S.Feldman (Ed.), The social psychology of education (pp. 235-256). Cambridge:Cambridge University Press.Amrein, A., & Berliner, D. (2003). The effects of high-stakes testing on student motivation and learning. Educational Leadership, 60(5), 32-38.Bacon, S. M., & Finnemann, M. D. (1990). A study of the attitudes, motives, and strategies of university foreign language students and their disposition to authentic oral and writteninput. Modern Language Journal, 74, 459-473.Bandura, A., & Schunk, D. H. (1981). Cultivating competence, self-efficacy, and intrinsic interest through proximal self-motivation. 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The development and validation of a Portuguese version of the Motivated Strategies for Learning Questionnarie. In Z. Dörnyei & R. Schmidt (Eds.), Motivation and second language acquisition (pp. 257-280).Honolulu, HI: Second Language Teaching & Curriculum Center, University of Hawai‘i Press.Brown, S., Armstrong, S., & Thompson, G. (1998). Motivating students. London: Kogan Page.Chambers, G. (1999). Motivating language learners. Clevedon, UK: Multilingual Matters. Cheng, H-F., & Dörnyei, Z. (2007). The use of motivational strategies in language instruction: The case of EFL teaching in Taiwan. Innovation in language learning and teaching, 1,153-174.Cohen, M., & Dörnyei, Z. (2002). Focus on the language learner: Motivation, styles and strategies. In N. Schmidt (Ed.), An introduction to applied linguistics (pp. 170-190).London, UK: Arnold.Cooper, H., & Tom, D. Y. H. 1984. SES and ethnic differences in achievement motivation. In R.E. Ames & C. 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Ames & C.Ames (Eds.), Motivation in education (pp. 275-310). New York: Academic Press. Deci, E. L., & Ryan, R. M. (1985). Intrinsic motivation and self-determination in human behavior. New York, NY: Plenum.Deci, E. L., & Ryan, R. M. (1991). A motivational approach to self: Integration in personality. In R. A. Dienstbier (Ed.), Perspectives on motivation: Nebraska Symposium on Motivation, 1990 (pp. 237-288). Lincoln, NE: University of Nebraska Press.Deci, E. L., Vallerand, R. J., Pelletier, L. G., & Ryan, R. M. (1991). Motivation and education: The self-determination perspective. Educational Psychologist, 26(3 & 4), 325-346.De Volder, M. L., & Lens, W. (1982). Academic achievement and future time perspective as a cognitive-motivational concept. Journal of Personality and Social Psychology, 44, 20-33Dörnyei, Z. (1990). Conceptualizing motivation in foreign language learning. Language Learning, 40, 45-78.Dörnyei, Z. (1994). Motivation and motivating in the foreign language classroom. Modern Language Journal,78, 273-284.Dörnyei, Z. (1998). Motivation in second and foreign language learning. Language Teaching, 31, 117-135.Dörnyei, Z. (2001). Motivational strategies in the language classroom. Cambridge, UK: Cambridge University Press.Dörnyei, Z. (2001). Teaching and researching motivation. Harlow, UK: Longman.Dörnyei, Z. (2002). The motivational basis of language learning tasks. In P. Robinson (Ed.), Individual differences and instructed language learning (pp. 137-158). Philadelphia, PA: John Benjamins.Dörnyei, Z. (2003). Attitudes, orientations, and motivations in language learning: Advances in theory, research, and applications. Language Learning, 53(Supplement 1), 3-32.Dörnyei, Z. (2007). Creating a motivating classroom environment. In J. Cummins & C. Davison (Eds.), International Handbook of English Language Teaching (Vol. 2) (pp. 719-731).New York, NY: Springer.Dörnyei, Z. (2008). New ways of motivating foreign language learners: Generating vision. 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Working Papers in Applied Linguistics, 4, 43-69.Dörnyei, Z., & Schmidt, R. (Eds.). (2001). Motivation and second language acquisition.Honolulu: National Foreign Language Resource Center/ University of Hawai'i Press.Dörnyei, Z., & Skehan, P. (2003). Individual differences in second language learning. In C. J.Doughty & M. H. Long (Eds.), The handbook of second language acquisition (pp. 589-630). Malden, MA: Blackwell.Dweck, C. S. (1986). Motivational processes affecting learning. American Psychologist, 41, 1040-1048.Ehrman, M. (1996). An exploration of adult language learner motivation, self-efficacy, and anxiety. In R. Oxford (Ed.), Language learning motivation: Pathways to the new century (pp. 81-103). Honolulu, HI: University of Hawai’i Press.Gao, Y., Zhao, Y., Cheng, Y., & Zhou, Y. (2004). Motivation types of Chinese university undergraduates. Asian Journal of English Language Teaching, 14, 45-64.Gardner, R. (1985). Social psychology and second language learning: The role of attitude and motivation. London, UK: Edward Arnold.Gardner, R. (2001). Integrative motivation and second language acquisition. In Z. Dörnyei & R.Schmidt (Eds.), Motivation and language acquisition (pp. 1-19). Honolulu, HI:University of Hawai’i Press.Gardner, R. C. (2000). Correlation, causation, motivation, and second language acquisition.Canadian Psychology, 41, 10-24.Gardner, R. C. (2001). Integrative motivation: Past, present and future. Retrieved from ://publish.uwo.ca/~gardner/docs/GardnerPublicLecture1.pdfGardner, R. (2001). Integrative motivation and second language acquisition. In Z. Dörnyei & R.Schmidt (Eds.), Motivation and language acquisition (pp. 1-19). Honolulu: University of Hawai’i Press.Gardner, R. C. (2005). Integrative motivation and second language acquisition. Retrieved from ://publish.uwo.ca/~gardner/docs/caaltalk5final.pdfGardner, R. C. (2009). Gardner and Lambert (1959): Fifty years and counting. 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(1994). Classroom motivation from an attitudinal perspective. In H. F. J. O'Neil and M. Drillings (Eds.), Motivation: Theory and research (pp. 31-48). Hillsdale, NJ:Lawrence Erlbaum.Guilloteaux, M. J., & Dörnyei, Z. (2008). Motivating language learners: A classroom-oriented investigation of the effects of motivational strategies on student motivation. TESOLQuarterly, 42, 55-77.Hadfield, J. (2013). A second self: Translating motivation theory into practice. In T. Pattison (Ed.), IATEFL 2012: Glasgow Conference Selections (pp. 44-47). Canterbury, UK:IATEFL.Hao, M., Liu, M., & Hao, R. (2004). An empirical study on anxiety and motivation in English asa Foreign Language. Asian Journal of English Language Teaching, 14, 89-104.Hara, C., & Sarver, W. T. (2010). Magic in ESL: An observation of student motivation in an ESL class. In G. Park, H. P. Widodo, & A. Cirocki (Eds.), Observation of teaching:Bridging theory and practice through research on teaching (pp. 141-153). 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Synthesis and characterization of novel systems fo

申请人：Pascal Dumy,Marie-Christine Favrot,Didier Boturyn,Jean-Luc Coll 地址：Allevard FR,Corenc FR,Grenoble FR,Claix FR 国籍：FR,FR,FR,FR 代理机构：DLA Piper LLP (US) 更多信息请下载全文后查看
专利内容由知识产权出版社提供
专利名称：Synthesis and characterization of novel systems for guidance and vectorization of molecules of therapeutic interest towards target cells
发明人：Pascal Dumy,Marie-Christine Favrot,Didier Boturyn,Jean-Luc Coll
申请号：US10528320 申请日：20030919 公开号：US07531622B2 公开日：20090512
摘要：A method for preparing a grafted homodetic cyclopeptide forming a framework that defines a grafted upper face and grafted lower face, including synthesizing a linear peptide from modified or unmodified amino acids, some of which carry orthogonal protective groups; intramolecular cyclizing the resulting protetuting some or all of orthogonal protective groups with a protected precursor; and grafting at least one molecule of interest onto one and/or the other face of the framework via an oxime bond.

三维荧光光谱结合二阶校正法测定保健品中的褪黑素

Ｏ
Ｍ
在生物体内的前体物质是色氨酸，色氨酸在细胞内先经羟基化转化为５一羟基色氨酸，再脱羧转化为血清素，血清素再经 Ⅳ 一乙酰基血清素或５－甲氧基色
Ｓｃｈｅｍｅ１Ｓｔｒｕｃｔｕｒｅｏｆｍｅｌａｔｏｎｉｎ（ＭＴ）
褪黑素（ＭＴ，结构见Ｓｃｈｅｍｅ１）又称松果体素、脑白金或美乐通宁等，化学名称为 Ⅳ 一乙酰基一５－甲氧基色胺，ＭＴ是一种主要由松果体分泌的广泛存在于动植物及微生物体内的内源性吲哚类激素．它
胺最终转化为ＭＴ１ｊ．一旦在体内释放，ＭＴ可以通过不同的受体作用于不同的器官，并直接作用于下丘脑，影响并控制人们的生物钟Ｉ３Ｊ．如果ＭＴ分泌不足或紊乱，可能会出现失眠等与生理规律紊乱相
关的疾病，补充适量ＭＴ可治疗该类疾病Ｊ．目前，欧洲食品安全管理局（ＥＦＡ）已经接受了ＭＴ有益健康的科学证据，认为其能够减缓时差感、减少入睡时间、改善睡眠质量，治疗各种形式的失眠和睡眠障碍等疾病Ｊ．另外，ＭＴ还有许多其它的生理功能，如抗氧化、抗肿瘤、免疫调节剂及神经保护活
性抗衰老等作用．
近年来，ＭＴ已成为国内外的研究热点之一，并取得了一定的进展，但其毒副作用等尚不明确，临
床应用还处于研究阶段 … ．目前，服用ＭＴ是否需要医生的指导仍存在分歧．如ＭＴ在美国已用作膳食

TheNewcastle-OttawaScale（NOS）forAssessingthe…

a) study controls for ___________ (select the most important factor) ♦ b) study controls for any additional factor (This criteria could be modified to
Development: Identifying Items
• Identify ‘high’ quality choices with a ‘star’
• A maximum of one ‘star’ for each item within the ‘Selection’ and ‘Exposure/Outcome’ categories; maximum of two ‘stars’ for ‘Comparability’
2. Representativeness of the cases a) consecutive or obviously representative series of cases ♦ b) potential for selection biases or not stated
3. Selection of Controls a) community controls ♦ b) hospital controls c) no description
Selection
1. Is the case definition adequate? a) yes, with independent validation ♦ b) yes, eg record linkage or based on self reports c) no description
Bias and Confounding

褪黑素与特发性脊柱侧凸

褪黑素与特发性脊柱侧凸南京鼓楼医院脊柱外科朱泽章邱勇朱丽华王斌吕锦瑜俞杨特发性脊柱侧凸最早是19世纪中叶由Bauer[1]提出，1909年Nathan[2]正式使用这一名称，直到1922年才由Whitman[3]给出明确定义，随后被国际脊柱侧凸研究会[4]推广。

特发性脊柱侧凸在临床最为常见，约占全部脊柱侧凸的80％，好发于青少年。

随着对特发性脊柱侧凸生物力学特征的进一步认识及内固定技术的完善，其外科治疗取得了飞快的发展和满意的疗效。

但是特发性脊柱侧凸的发病机理仍然未明，文献报道其发生与遗传、生长发育不对称、结缔组织发育异常、神经--平衡系统功能障碍、内分泌系统异常有关。

近年来，一些学者提出血清褪黑素（Melatonin）水平降低可能是发生特发性脊柱侧凸的重要始动因素，并与侧凸曲线的进展密切相关。

一、褪黑素的分泌节律松果体是从第三脑室后顶部突出的小体，含有大量分泌细胞，一般都认为它是一种内分泌腺。

1958年Lerner首先从松果体中提炼出褪黑素，该激素能使两栖动物皮肤内黑色素细胞颗粒聚集，从而使皮肤颜色变浅，故被命名。

褪黑素化学结构为N-乙酰-5-甲羟色胺，是由色氨酸经4种酶催化后发生一系列反应所合成，具体合成途径为：色氨酸→5-羟色胺酸→5-羟色胺→N-乙酰-5-甲羟色胺→褪色素，其中5-羟色胺是一个重要的中介物质。

在人类生命周期中褪黑素的分泌随年龄增长波动明显：出生后头三个月内，夜间血清褪黑素水平很低，因而24小时内几乎没有波动变化，此后夜间分泌逐渐增加，2岁前达到峰值，然后褪黑素水平稳步下降，成年时褪黑素分泌下降约80％[5]。

每日褪黑素的分泌存在昼低夜高的规律，入睡后6－7小时为分泌高峰，这是因为5-羟色胺-N-乙酰转移酶和5-羟基吲哚-甲基转移酶是褪黑素合成所必须，而这两种酶在无光照时活性最高[6]。

夜间褪黑素分泌可被强光抑制，人类对强度超过150－200lux的光敏感[7]。

大约70％的褪黑素在肝脏代谢为6-羟褪黑素硫酸盐后从尿中排泄。

TARGET目录大全

TARGET国际翻译研究杂志目录Target 1:1（1989） (2)Target 1:2（1989） (3)Target 2:1（1990） (3)Target 2:2（1990） (4)Target 3:1（1991） (5)Target 3:2（1991） (6)Target 4:1（1992） (7)Target 4:2（1992） (9)Target 5:1（1993） (10)Target 5:2（1993） (11)Target 6:1（1994） (12)Target 6:2（1994） (14)Target 7:1（1995） (15)Target 7:2（1995） (16)Target 8:1（1996） (18)Target 8:2（1996） (19)Target 9:1（1997） (20)Target 9:2（1997） (21)Target 10:1（1998） (23)Target 10:2（1998） (25)Target 11:1（1999） (26)Target 11:2（1999） (28)Target 12:1（2000） (29)Target 12:2（2000） (30)Target 13:1（2001） (31)Target 13:2（2001） (32)Target 14:1（2002） (34)Target 14:2（2002） (35)Target 15:1 （2003） (37)Target 15:2（2003） (38)Target 16:1 （2004） (40)Target 16:2（2004） (41)Target 17:1 （2005） (42)Target 17:2（2005） (44)Target 18:1 （2006） (45)Target 18:2 （2006） (46)Target 19:1（2007） (47)Target 19:2（2007） (49)Target 20:1（2008） (50)Target 20:2（2008） (51)Target 21:1（2009） (53)Target 21:2（2009） (54)Target 1:1（1989）On Target's Targets 1 Articles9 In Search of a Target Language: The Politics of Theatre Translation inQuebecAnnie Brisset29 Genre Analysis and the TranslatorCarl James43 Models of the Translation Process: Claim and RealityWolfgang Lörscher69 Wittgenstein, Translation, and SemioticsDinda L. GorléePlato, Bacon and the Puritan Apothecary: The Case of Nicholas95 CulpeperL.G. KellyForum111 Extending the Theory of Translation to Interpretation: Norms as aCase in PointMiriam ShlesingerReview Article117 Bibliographie: Traductions et CulturesJoséLambertReview 123 Paul Chavy. Traducteurs d'autrefois: Moyen âge et RenaissanceReviewed by Theo HermansMary Snell-Hornby (ed.) ZüriLEX '86 ProceedingsReviewed by R.R.K. HartmannTarget 1:2（1989）Articles129 Towards a Multi-facet Concept of Translation BehaviorWolfram WilssTranslation and Original: Similarities and Dissimilarities, I151 Kitty van Leuven-Zwart183 On Aboriginal Sufferance: A Process Model of Poetic TranslatingFrancis R. Jones201 Assessing Acceptability in Translated Children' BooksTiina Puurtinen215 La traduction, les langues et la communication de masse: Lesambiguïtés du discours internationalJoséLambertReview Article239 Verb Metaphors under TranslationGideon TouryReviews 249 James S. Holmes. Translated!: Papers on Literary Translation andTranslation StudiesReviewed by Hendrik van GorpYishai Tobin and Edna Aphek. Word Systems in Modern Hebrew:Implications and ApplicationsReviewed by Hannah Amit-KochaviPaul Nekemann (ed.). Actes du XIe Congrès mondial de la FIT: LaTraduction, notre avenirReviewed by Lieven D’hulstAlan Duff. TranslationReviewed by Francis R. JonesRevue de littérature comparée, numéro spécial: Le Texte étranger.L‘œuvre littéraire en traductionReviewed by Clem RobynsTarget 2:1（1990）Articles1 Typological Aspects of Translating Literary Japanese into German, I:Lexicon and MorphologyGötz WienoldThe Normative Model of Twentieth Century Belles Infidèles:23 Detective Novels in French TranslationClem RobynsA Statistical Method for Translation Quality Assessment43 Shouyi Fan69 Translation and Original: Similarities and Dissimilarities, IIKitty van Leuven-Zwart‗Die Seefahrt an den Nagel hängen‘? Metaphern beim Übersetzen und97 in der ÜbersetzungswissenschaftFrank G. KönigsForumNorms in Interpretation115 Brian HarrisReviews 121 Albrecht Neubert. Text and TranslationReviewed by Christina SchäffnerErika Fischer-Lichte, Fritz Paul Brigitte Schultze Horst Turk, eds.Soziale und theatralische Konventioinen als Problem derDramenübersetzungReviewed by Frank PeetersMary Snell-Hornby Translation Studies: An Integrated ApproachReviewed by Lieven D’hulstTarget 2:2（1990）ArticlesA Theoretical Account of Translation: Without a Translation Theory135 Ernst-August Gutt165 Linguistic Interference in Literary Translations from English intoHebrew of the 1960s and 1970sRachel Weissbrod183 Typological Aspects of Translating Literary Japanese into German, II:Syntax and Narrative TechniqueGötz Wienold199 Surely There Must Exist a Polish Equivalent: On the Inadequacy ofDictionary ExplicationsElżbieta TabakowskaTexttheorie und Translatorisches Handeln 219Hans J. VermeerReviews 243 Harald Kittel, ed. Die literarische Übersetzung: Stand undPerspektiven ihrer ErforschungReviewed by Dirk De GeestReiner Arntz, ed. Textlinguistik und Fachsprache: Akten desInternationalen übersetzungswissenschaftlichen AILA-SymposionsHildesheim, 13.-16 April 1987Reviewed by Wolfgang LörscherValerie Worth. Practising Translation in Renaissance France: TheExample of Étienne DoletReviewed by Paul ChavySherry Simon. L'inscription sociale de la traduction au QuébecReviewed by Clem RobynsNew Books at a Glance 255 Henry G. Schogt. Linguistics, Literary Analysis, and LiteraryTranslationLieven D’hulstMaarten Steenmeijier. De Spaanse en Spaans-Amerikaanse literatuurin Nederland (1946-1985)Ilse LogieTarget 3:1（1991）Articles1 World Knowledge in the Process of TranslationChristina SchäffnerCoincidence in Translation: Glory and Misery Again17 Robert de Beaugrande55 Computer-aided Translation: Where are the Problems?Albrecht Neubert65 Translation Anthologies: An Invitation to the Curious and a CaseStudyHelga Essman and Armin Paul Frank91 Scopos, Loyalty, and Translational ConventionsChristiane NordReviews 111 Candace Séguinot ed. The Translation ProcessReviewed by Hannah Amit-KochaviSusan Bassnett and André Lefevere, eds. Translation, History andCultureReviewed by Theo d’HaenHenri Van Hoof. Traduire l'anglais: Théorie et PratiqueReviewed by Michel BallardDanica Seleskovitch et Marianne Lederer. Pédagogie raisonnée del'interprétationReviewed by Jean DelisleBrian T. Fitch. Beckett and Babel: An Investigation into the Status ofthe Bilingual WorkReviewed by Rainier GrutmanNew Books at a Glance 129 La traduction plurielle. Textes réunis et présentés par Michel BallardLieven D’hulstDaniel Göske. Herman Melville in deutscher SpracheNorbert GreinerKlaus Martens. Die ausgewanderte ―Evangeline‖: Longfellowsepische Idylle im übersetzerischen TransferNorbert GreinerJean Delisle. The Language Alchemists: Société des traducteurs duQuébec (1940-1990)Rainier GrutmanAmparo Hurtado Albir. La notion de fidélité en traductionTarget 3:2（1991）ArticlesA False Opposition in Translation Studies: Theoretical versus/and137 Historical ApproachesDirk Delabastita153 Methodological Aspects of Interpretation (and Translation) ResearchDaniel Gile175 Names and Their Substitutes: Onomastic Observations on Astérix andIts TranslationsSheila Embleton207 Two Traditions of Translating Early Irish LiteratureMaria TymoczkoInstitutional Transmission and Literary Translation: A Sample Case225 Klaus MartensReviews 243 Christiane Nord. Textanalyse und Übersetzen: TheoretischeGrundlagen, Methode und didaktische Anwendung einerübersetzungsrelevanten TextanalyseReviewed by Werner KollerFrederick M. Rener. Interpretatio: Language and Translation fromCicero to TytlerReviewed by Antoine BermanPeter W. Krawutschke, ed. Translator and Interpreter Training andForeign Language PedagogyJean Delisle. Translation: An Interpretive ApproachSonja Tirkkonen-Condit and Stephen Condit, eds. Empirical Studiesin Translation and LinguisticsReviewed by Miriam ShlesingerMary Snell-Hornby and Esther Pöhl, eds. Translation andLexicography: Papers read at the EURALEX Colloquium held atInnsbruck 2-5 July 1987Reviewed by Guy A.J. TopsNew Books at a Glance 261 Bert Westerweel and Theo D'haen, eds. Something Understood:Studies in Anglo-Dutch TranslationDirk DelabastitaMyriam Salama-Carr. La traduction à l'époque abbasside: L'école deHunayn Ibn Ishāq et son importance pour la traductionMichel Ballard261 Andrzej Kątny, Hrsg. Studien zur kontrastiven Linguistik undliterarischen ÜbersetzungGerd FreidhofTarget 4:1（1992）Articles1 The Concept of Function of Translation and Its Application toLiterary TextsRoda P. Roberts17 On Constructing a Transfer Dictionary for Man and MachineJohn Laffling33 Sur le rôle des métaphores en traductologie contemporaineLieven D’hulstFilm (Adaptation) as Translation: Some Methodological Proposals 53Patrick Cattrysse71 Zum Aussagewert motivgeschichtlicher ÜbersetzungsstudienBärbel CzenniaForumNatural Translation: A Reply to Hans P. Krings97 Brian Harris105 Bilinguismus and Übersetzen: Eine Antwort an Brian HarrisHans P. KringsReview ArticleTranslation Theory Revisited111 Raymond van den BroeckReviews 121 Reiner Arntz and Gisela Thome, eds. Übersetzungswissenschaft.Ergebnisse und Perspektiven: Festschrift für Wolfram Wilss zum 65.GeburtstagReviewed by Dirk DelabastitaBasil Hatim and Ian Mason. Discourse and the TranslatorReviewed by Nils Erik EnkvistWolfgang Lörscher. Translation Performance, Translation Process,and Translation StrategiesReviewed by Donald C. KiralyArmin Paul Frank, Hrsg. Die literarische Übersetzung. Der langeSchatten kurzer Geschichten: Amerikanische Kurzprosa in deutschenÜbersetzungenReviewed by Jörn Albrecht and Johannes VolmertPeter Braun, Burkhard Schaeder and Johannes Volmert, eds. Internationalismen: Studien zur interlingualen Lexikologie undLexikographieReviewed by Frank PeetersNew Books at a Glance 139 Jerzy Tomaszczyk and Barbara Lwandowska-Tomaszczyk, eds.Meaning and LexicographyR.R.K. HartmannEija Ventola and Anna Mauranen. Tutkijat ja englanniksikirjoittaminenNils Erik EnkvistMaría Antonia Álvarez Calleja. Estudios de traducción(Inglés-Español): Teoría. Práctica. ApplicationesIlse LogieHenri Van Hoof. Histoire de la traduction en Occident: France,Grande-Bretagne, Allemagne, Russie, Pays-BasLieven D’hulstTarget 4:2（1992）ArticlesGood-bye, Lingua Teutonica? Language, Culture and Science in145 Europe on the Threshold of the 21st CenturyRoland PosnerThe Relations Between Translation and Material Text Transfer171 Anthony Pym191 Translation Policy and Literary/Cultural Changes in Early ModernKorea (1895-1921)Theresa Hyun209 On Two Style Markers of Modern Arabic-Hebrew Prose TranslationsLea Sarig223 The Cloze Technique as a Pedagogical Tool for the Training ofTranslators and InterpretersSylvie LambertReview ArticleA Theoretical Account of Translation: Without Translation Theory?237 Sonja Tirkkonen-ConditReviews 247 J.A. Henderson. Personality and the Linguist: A Comparison of thePersonality Profiles of Professional Translators and ConferenceInterpretersReviewed by Gideon TourySonja Tirkkonen-Condit, ed. Empirical Research in Translation andIntercultural Studies: Selected Papers of the TRANSIF Seminar,Savonlinna 1988Reviewed by Daniel GileAnnie Brisset. Sociocritique de la traduction: Théâtre et altérité auQuébec (1968-1988)Reviewed by Clem RobynsWilliam Luis and Julio Rodríguez-Luis, eds. Translating LatinAmerica: Culture as TextReviewed by Nadia LieNew Books at a Glance 261 Dan Maxwell and Klaus Schubert, eds. Metataxis in Practice:Dependency Syntax for Multilingual Machine TranslationJan DingsPatrice Pavis. Theatre at the Crossroads of Culture261 Sirkku AaltonenTarget 5:1（1993）ArticlesFrom ‗Is‘ to ‗Ought‘: Laws, Norms and Strategies in T ranslation1 StudiesAndrew ChestermanIs There a Special Kind of ―Reading‖ for Translation? An Empirical21 Investigation of Reading in the Translation ProcessGregory M. Shreve, Christina Schäffner,Joseph H. Danks and Jennifer GriffinArab Fatalism and Translation from Arabic into English43 Mohammed Farghal55 Rhetoric and Dutch Translation Theory (1750–1820)Luc Korpel71 Mixed Translation Patterns: The Ladino Translation of Biblical andMishnaic Hebrew VerbsOra (Rodrigue) SchwarzwaldReview Article89 Anthologies et HistoriographeJoséLambertReviews 97 Daniel Gouadec. Le traducteur, la traduction et l'entrepriseReviewed by JoséLambertSusan Bassnett-McGuire. Translation Studies (Revised Edition)Reviewed by John S. DixonGabriele Harhoff. Grenzen der Skopostheorie von Translation undihrer praktischen AnwendbarkeitReviewed by Christiane NordChristian Schmitt, Hrsg. Neue Methoden der SprachmittlungReviewed by Paul KussmaulBarbara Folkart. Le conflit des énonciations: traduction et discoursrapportéReviewed by Reine MaylaertsJelle Stegeman. Übersetzung und Leser: Übersetzung und LeserUntersuchungen zur Übersetzungsäquivalenz dargestellt an derRezeption von Multatulis ‗Max Havelaar‘ und seinen deutschenÜbersetzungenReviewed by Cees KosterSandor Hervey Ian Higgins. Thinking Translation. A Course inTranslation method: French to EnglishReviewed by Hans G. HönigMildred L. Larson, ed. Translation: Theory and Practice. Tension and InterdependenceReviewed by Anthony PymNew Books at a Glance 127 Kitty M. van Leuven Zwart Ton Naaijkens, eds. Translation Studies:The State of the Art. Proceedings of the First James S HolmesSymposium on Translation StudiesMichael SchreiberRainer Schulte John Biguenet, eds. Theories of Translation: AnAnthology of Essays from Dryden to DerridaLieven D’hulstIsabel Pascua Febles and Ana Luisa Peñate Soares. Introducción a losestudios de traducciónAnthony PymTarget 5:2（1993）Articles133 Underpinning Translation TheoryKirsten MalmkjærThe Distinctive Nature of Interpreting Studies149 Heidemarie Salevsky169 The Question of French Dubbing: Towards a Frame for SystematicInvestigationOlivier Goris191 The Grimm Tales in 19th Century DenmarkCay Dollerup215 Das Ende deutscher Romanübersetzungen aus zweiter HandWilhelm GraeberReview ArticleDiscourses on Translation: Recent, Less Recent, and to Come229 AndréLefevereReviews 243 Cay Dollerup and Anne Loddegaard, eds. Teaching Translation andInterpreting: Training, Talent and ExperienceReviewed by Rachel WeissbrodPeter Newmark: About TranslationReviewed by Christina SchäffnerLance Hewson and Jacky Martin. Redefining Translation: TheVariational ApproachReviewed by Michel BallardMarianne Lederer, éd.Études traductologiques en hommage à DanicaSéleskovitchReviewed by Annie BrissetJohn Laffling. Towards High-Precision Machine Translation : Basedon Contrastive TextologyReviewed by Anne-Marie Loffler-LaurianMichel Ballard. De Cicéron à Benjamin: Traducteurs, traductions,réflexionsReviewed by Jean DelisleMats Larsson Från tjeckiska till svenska: Översättningsstrategier förlitterärt talspråkReviewed by Werner KollerJames Hardin, ed. Translation and Translation Theory inSeventeenth-Century GermanyReviewed by Frederick M. RenerNew Books at a Glance 273 Werner Koller. Einführung in die Übersetzungswissenschaft, 4.,Völlig neu bearbeitete AuflageWolfram WilssBrigitte Schultze, Erika Fischer-Lichte, Fritz Paul and Horst Turk,eds.Literatur und Theater. Traditionen und Konventionen als Problem derDramen übersetzungFrank PeetersPhilip C. Stine, ed. Bible Translation and the Spread of the Church:The Last 200 YearsTheo HermansRosa Rabadán. Equivalencia y traducción: Problemática de laequivalencia translémica inglés-españolIlse LogieTarget 6:1（1994）ArticlesSemantic Models and Translating 1Paul KussmaulDid Adapa Indeed Lose His Chance for Eternal Life? A Rationale for15 Translating Ancient Texts into a Modern LanguageShlomo Izre'el43 Twelfth-Century Toledo and Strategies of the Literalist Trojan HorseAnthony PymForum67 Übersetzung * Translation * Traduction: An InternationalEncyclopedia of Translation StudiesReview Article81 Ideological Purity: Machine Translation's Pride or Pitfall?John LafflingReviews 95 Anthony Pym. Translation and Text Transfer: An Essay on thePrinciples of Intercultural CommunicationReviewed by Andrew ChestermanMarcel Thelen and Barbara Lewandowska-Tomaszczyk, eds.Translation and Meaning: Proceedings of the 1990 Maastricht-ŁódźDuo Colloquium I-IIReviewed by Franz PöchhackerHeidemarie Salevsky, Hrsg. Wissenschaftliche Grundlagen derSprachmittlungReviewed by Andreas PoltermannRadegundis Stolze. Hermeneutisches Übersetzen: LinguistischeKategorien des Verstehens und Formulierens beim ÜbersetzenReviewed by Frank G. KönigsRita Copeland. Rhetoric, Hermeneutics and Translation in the MiddleAges: Academic Traditions and Vernacular TextsReviewed by Douglas A. KibbeeCarmela Nocera Avila. Studi sulla traduzione nell'Inghilterra delSeicento e del SettecentoReviewed by Holger KleinChristiane Nord. Einführung in das funktionale Übersetzen: AmBeispiel von Titeln und ÜberschriftenReviewed by Katharina ReissPatrick De Rynck et Andries Welkenhuysen. De Oudheid in hetNederlands: Repertorium en bibliografische gidsReviewed by Arnoud WilsNew Books at a Glance 121 Cecilia Wadensjö. Interpreting as Interaction: OnDialogue-interpreting in Immigration Hearings and MedicalEncountersRuth MorrisCees W. Schoneveld, ed. ‗t Word grooter plas: maar niet zo ‗t was.Nederlandse beschouwingen over vertalen (1670-1760)Patrick De RynckChristiane Beerbom. Modalpartikeln als Übersetzungsproblem: Einekontrastive Studie zum Sprachenpaar Deutsch-SpanischReiner ArntzOther Books Received 127Target 6:2（1994）ArticlesA Framework for Decision-Making in Translation131 Wolfram WilssTranslation Studies in China: Retrospect and Prospect151 Fan ShouyiTranslating Allusions: When Minimum Change Is Not Enough177 Ritva Leppihalme195 Translating Literary Dialogue: A Problem and Its Implications forTranslation into HebrewRina Ben-ShaharReview Article223 Focus on the Pun: Wordplay as a Special Problem in TranslationStudiesDirk DelabastitaReviews 245 Wolfram Wilss. Übersetzungsfertigkeit: Annäherungen an einenkomplexen übersetzungspraktischen BegriffReviewed by John LafflingJean Delisle. La traduction raisonnéeReviewed by Robert LaroseJusta Holz-Mänttäri und Christiane Nord, Hrsg. TRADUCERENAVEM: Festschrift für Katharina Reiβ zum 70. GeburtstagReviewed by Luise Lieflander-KoistinenJohn Newton, ed. Computers in Translation: A Practical AppraisalReviewed by Frank Van EyndeAndré Lefevere, ed. Translation/History/Culture: A SourcebookReviewed by Luc KorpelLuc G. Korpel. Over het nut en de wijze der vertalingen: Nederlandse vertaalreflectie (1750-1820) in een Westeuropees kaderReviewed by Patrick De RynckNew Books at a Glance265 Tejaswini Niranjana. Siting Translation: History, Post-Structuralismand the Colonial ContextGurbhagat SinghWilliam A. Smalley.Translation as Mission: Bible Translation in theModern Missionary MovementAnneke de VriesMichael Hann. The Key to Technical Translation, 1-2Bruce W. Irwin and Erhard EydamClem Robyns, ed. Translation and the (Re)production of Culture:Selected Papers of the CERA Research Seminars in TranslationStudies 1989-1991John S. DixonOther Books Received 273Target 7:1（1995）Mirror Mirror on the Wall: An Introduction1 Daniel GilleArticles7 Stranger in Paradigms: What Lies Ahead for SimultaneousInterpreting Research?Miriam ShlesingerInterpreting Research and the ‗Manipulation School‘ of Translation29 StudiesAnne Schjoldager―Those Who Do…‖: A Profile of Research(ers) in Interpreting47 Franz PöchhackerUne approche asymptotique de la recherche sur l‘interprétation65 Birgit StrolzLa recherche en interprétation dans les pays d‘Europe de l‘Est: un e75 perspective personnelleIvana Čeňková91 Interpretation Research in JapanMasaomi Kondo and Akira Mizuno107 Development of Research Work at SSLM, Trieste (Italy)Laura Gran and Maurizio ViezziA Review of Conference Interpretation: Practice and Training119 Jennifer MackintoshOn The Relevance of Signed Languages to Research in Interpretation135 William P. IshamFidelity Assessment in Consecutive Interpretation: An Experiment151 Daniel Gille165 Interdisciplinary Research — Difficulties and BenefitsIngrid KurzReviews181 Sylvie Lambert and Barbara Moser-Mercer, eds. Bridging the Gap:Emperical Research in Simultaneous InterpretationFranz Pöchhacker181 Franz Pöchhacker. Simultandolmetschen als komplexes HandelnDaniel GilleOther Books Received 189Target 7:2（1995）Articles191 The Concept of Equivalence and the Object of Translation StudiesWerner KollerCorpora in Translation Studies: An Overview and Suggestions for223 Future ResearchMona Baker245 Quantitative and Qualitative Aspects of Corpus Selection inTranslation StudiesLuc van Doorslaer261 Text-Functions in Translation: Titles and Headings as a Case in PointChristiane Nord285 Headlining in Translation: English vs. Greek PressMaria SidiropoulouA Pragmatic Classification of LSP Texts in Science and Technology305 Susanne Göpferich327 Retranslation of Children's Books as Evidence of Changes of NormsMyriam Du-NourForumIntuition in Translation347 Vilen N. KomissarovReviews 355Dinda L. Gorlée. Semiotics and the Problem of TranslationReviewed by Elda WeizmanYves Gambier Jorma Tommola, eds. Translation and Knowledge:SSOTT IV — Scandinavian Symposium on Translation Theory (Turku,4–6.6.1992)Reviewed by Kirsten MalmkjærMary Snell-Hornby, Franz Pöchhacker and Klaus Kaindl, eds.Translation Studies: An InterdisciplineReviewed by Anthony PymRomy Heylen .Translation, Poetics, and the StageReviewed by Sirkku AaltonenCandace Whitman-Linsen. Through the Dubbing Glass: TheSynchronization of American Motion Pictures into German, Frenchand SpanishReviewed by Aline RemaelThomas O. Beebee. Clarissa on the Continent: Translation andSeductionReviewed by Wilhelm GraeberHelga Essmann. Übersetzungsanthologien: Eine Typologie und eine Untersuchung am Beispiel der amerikanischen Versdichtung indeutsch-sprachigen Anthologien, 1920–1960Reviewed by Hannah Amit-KochaviHans J. Vermeer. Skizzen zu einer Geschichte der Translation, Bd:1:Anfäange:von Mesopotamien bis GriechenlandRom und das frühe Christentum bis HieronymusReviewed by Heidemarie SalevskyKitty M. van Leuven-Zwart. Vertaalwetenschap: Ontwikkelingen en perspectievenReviewed by Theo HermansNew Books at a Glance 389 André Lefevere. Translation, Rewriting & the Manipulation ofLiterary FameHannah Amit-KochaviChristine Pagnoulle, éd. Les gens du passageMichel BallardPalma Zlateva Translation as Social Action: Russian and BulgarianPerspectivesAnikóSohárSiegfried Meurer, Hrsg. Die vergessenen Schwestern: FrauengerechteSprache in der BibelübersetzungAnneke de VriesTarget 8:1（1996）Articles1 There Is Always a Teller in a TaleGiuliana SchiaviThe Translator‘s Voice in Translated Narrative23 Theo Hermans49 Directionality in Translation Processes and PracticesSophia S.A. Marmaridou75 Some Thoughts About Think-Aloud ProtocolsCandace SéguinotThe Translation of English Passives into Arabic: An Empirical97 PerspectiveMohammed Farghal and Mohammed O. Al-Shorafat119 Translations, Paratextual Mediation, and Ideological ClosureUrpo KovalaForum149 A Case for Linguistics in Translation TheoryVladimir IvirOn Similarity159 Andrew ChestermanReview Article165 Venuti's VisibilityAnthony PymReviews 179 Elżbieta Tabakowska. Cognitive Linguistics and Poetics ofTranslationReviewed by Vladimir IvirMichel Ballard, dir. La traduction à l‘université: Recherches etpropositions didactiquesReviewed by Robert LaroseHeidrun Gerzymisch-Arbogast. ÜbersetzungswissenschaftlichesPropädeutikumReviewed by Hans G. HönigJuan C. Sager. Language Engineering and Translation: Consequencesof AutomationReviewed by Christina SchäffnerGideon Toury. Descriptive Translation Studies and beyondReviewed by Andrew ChestermanSherry Simon. Le Trafic des langues: Traduction et culture dans lalittérature québécoiseReviewed by Reine MeylaertsRadegundis Stolze. Übersetzungstheorien: Eine EinführungReviewed by Nelleke de Jong-van den BergTarget 8:2（1996）ArticlesLanguage, Translation and the Promotion of National Identity: Two211 Test CasesJudith Woodsworth239 Implicit Information in Literary Translation: A Relevance-TheoreticPerspectiveErnst-August Gutt257 Affective and Attitudinal Factors in Translation ProcessesJohanna LaukkanenA Translator' Reference Needs: Dictionaries or Parallel Texts?275 Ian A. Williams301 Translation of Modifications: About Information, Intention and EffectChunshen ZhuTowards a Model of Translation Proficiency325 Deborah CaoWhat Translators of Plays Think About Their Work341 Marja JänisForum365 Assumed Translation: Continuing the DiscussionVilen N. KomissarovReviews 375 Daniel Gile. Basic Concepts and Models for Interpreter andTranslator TrainingReviewed by Donald C. Kiraly and David B. SawyerJeanne Dancette. Parcours de traduction: étude expérimentale duprocessus de compréhensionReviewed by Wolfgang LörscherGeorges Mounin. Les Belles InfidèlesReviewed by Yves GambierPaul Kussmaul. Training the TranslatorReviewed by Jeanne DancetteHans G. Hönig Konstruktives ÜbersetzenReviewed by Luc van DoorslaerAntoine Berman. Pour une critique des traductions: John DonneReviewed by Reine MeylaertsNew Books at a Glance 395 Deanna L. Hammond, ed. Professional Issues for Translators andInterpretersPeter JansenMichael Schreiber. Übersetzung und Bearbeitung: ZurDifferenzierung und Abgrenzung des ÜbersetzungsbegriffsJuliane HouseAnneke de Vries. Zuiver en onvervalscht?: Een beschrijving voor bijbelvertalingen, ontwikkeld en gedemonstreerd aan de PetrusCanisius VertalingPaul GillaertsOther Books Received 403Target 9:1（1997）ARTICLES‗Acceptability‘ and Language-Specific Preference in the Distribution1 of InformationMonika Doherty25 Translating a Poem, from a Linguistic PerspectiveElżbieta Tabakowska43 Translat ing the Untranslatable: The Translator‘s Aesthetic,Ideological and Political ResponsibilityGillian Lane-Mercier69 Who Verbalises What: A Linguistic Analysis of TAP TextsSonja Tirkkonen-ConditCréativité et traduction85 Michel Ballard111 Cultural Agents and Cultural Interference: The Function of J.H.Campe in an Emerging Jewish CultureZohar ShavitLanguage and Translation in an International Business Context:131 Beyond an Instrumental ApproachChris Steyaert and Maddy JanssensFORUM。

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*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
Seto T, et al. ASCO 2016. Abstract 9012.
53 31 16
Slide credit:
LURET: Efficacy of Vandetanib
Primary analysis: ORR 53% (90% CI: 31% to 74%) for 17 eligible pts
Seto T, et al. ASCO 2016. Abstract 9 data demonstrate activity with vandetanib in RETrearranged advanced NSCLC
– Tumors with CCDC6-RET fusion showed best response to treatment
LURET: Study Design
Pts treated with vandetanib 300 mg PO QD Eligibility criteria
– Advanced nonsquamous NSCLC
– Positive for RET fusion gene on RT-PCR and FISH – ≥ 1 prior chemotherapy regimen – 20 yrs of age or older – ECOG PS 0-2
AEs resulted in discontinuation in 4 pts (21%), dose interruption in 16 pts (84%), and dose reduction in 10 pts (53%)
Slide credit:
Median age, yrs (range)
Female, % ECOG PS 0/1/2, % Never smoker, % Adenocarcinoma histology, % Stage IV disease, % 1/2/≥ 3 prior lines chemotherapy, % Response to first-/second-/third-line therapy, %* RET fusion partners, % KIF5B CCDC6 Unknown
Unknown (n = 3) 67 67 4.7 33
Best efficacy outcomes observed in pts with CCDC6-RET fusions Median DoR: 5.6 mos (range: 1.5-9.1 mos)
– 2 pts with ongoing response for > 1 yr
Go Online for More CCO Coverage of ASCO 2016!
Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in:
Type of RET Fusion Outcome ORR, % DCR, % Median PFS, mos 1-yr OS, %
Overall (N = 19)
47 90 4.7 47
KIF5B-RET (n = 10) 20 90 2.9 42
CCDC6-RET (n = 6) 83 100 8.3 67
Phase II LURET Study: Vandetanib Monotherapy Active in RET-Rearranged Advanced NSCLC
CCO Independent Conference Coverage*
of the 2016 ASCO Annual Meeting, June 3-7, 2016
Primary endpoint: ORR (by IRR committee) Secondary endpoints: DoR, DCR (CR + PR + SD), PFS, OS, safety, response of prior anticancer therapy
Seto T, et al. ASCO 2016. Abstract 9012. Slide credit:
1. Gautschi O, et al. J Thorac Oncol. 2013;8:e43-e44. 2. Falchook GS, et al. J Clin Oncol. 2016;34:e141-e144. 3. Seto T, et al. ASCO 2016. Abstract 9012. Slide credit:
*n = 19/12/8.
59 (41-80)
74 47/42/11 68 100 95 37/21/42 26/25/0
19 pts enrolled (ITT population)
– 2 pts subsequently found ineligible – 17 pts comprise primary efficacy analysis population
QTc prolongation
Anorexia Creatinine increased Vomiting Paronychia Proteinuria
42
32 32 26 26 26
11
5 0 0 0 5

Only 1 grade 4 AE (QTc prolongation); no grade 5 AEs
Seto T, et al. ASCO 2016. Abstract 9012. Slide credit:
LURET: Treatment-Related AEs
Treatment-Related AEs (≥ 20% Pts), % Hypertension Diarrhea Rash acneiform Dry skin Any Grade 84 79 63 42 Grade ≥ 3 58 11 16 5
This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.
Breast, Genitourinary, and Lung cancers Hematologic malignancies Immunotherapy
/oncology
– Will require nationwide screening programs to identify pts with rare driver mutations
Seto T, et al. ASCO 2016. Abstract 9012. Slide credit:
Tumor shrinkage with vandetanib in pts with RETrearranged NSCLC documented in case reports[1,2] Multicenter, single-arm phase II study evaluated vandetanib efficacy and safety in pts with RETrearranged advanced NSCLC who failed ≥ 1 prior line of chemotherapy[3]
LURET: Baseline Characteristics
1536 pts screened for RET fusions Feb 2013 to March 2015
– 34 pts (2%) RETfusion positive
Baseline Characteristic Pts (N = 19)
No new or unexpected safety signals
– Hypertension constituted most common grade ≥ 3 AE (58%)
Investigators conclude that further evaluation of vandetanib in pts with RET-rearranged advanced NSCLC is warranted
Phase II LURET Study of Vandetanib in RET+ NSCLC: Background
RET gene rearrangements observed in 1% to 2% of NSCLC
Vandetanib: oral TKI
– Inhibits RET, EGFR, and VEGFR activity