bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale for the development of IMC‐3G3, a fully human immunoglobulin G subclass 1 monoclonal antibody targeting the platelet‐derived growth factor receptor α
Authors: Shah Gaurav D. , Loizos Nick , Youssoufian Hagop , Schwartz Jonathan D. , Rowinsky Eric K. 
Published: February 2010

AbstractA large body of evidence suggests that the platelet‐derived growth factor (PDGF) family and associated receptors are potential targets in oncology therapeutic development because of their critical roles in the proliferation and survival of various cancers and in the regulation and growth of the tumor stroma and blood vessels. Several small molecules that nonspecifically target the PDGF signaling axis are in current use or development as anticancer therapies. However, for the majority of these agents, PDGF and its receptors are neither the primary targets nor the principal mediators of anticancer activity. IMC‐3G3, a fully human monoclonal antibody of the immunoglobulin G subclass 1, specifically binds to the human PDGF receptor α (PDGFRα) with high affinity and blocks PDGF ligand binding and PDGFRα activation. The results of preclinical studies and the frequent expression of PDGFRα in many types of cancer and in cancer‐associated stroma support a rationale for the clinical development of IMC‐3G3. Currently, IMC‐3G3 is being evaluated in early clinical development for patients with several types of solid malignancies. Cancer 2010;116(4 suppl):1018–26. © 2010 American Cancer Society.
Toxicity‐reducing potential of extracorporeal affinity adsorption treatment in combination with the auristatin‐conjugated monoclonal antibody BR96 in a syngeneic rat tumor model
Authors: Nilsson Rune , Mårtensson Linda , Eriksson Sophie E. , Sjögren Hans‐Olov , Tennvall Jan 
Published: February 2010

AbstractBACKGROUND:Antibody‐drug conjugates, comprising monoclonal antibodies (MoAbs) that bind to tumor‐associated antigens, display different toxicity profiles compared with radiolabeled MoAbs. Dose‐limiting toxicities may include damage to the liver and myelotoxicity. The drug component is the antimitotic agent auristatin, which is 100‐1000 times more potent than doxorubicin. Consequently, auristatin antibody‐drug conjugates require a high selectivity in tumor targeting to display pronounced activity at well‐tolerated doses. We have evaluated the possibility of increasing the therapeutic index of BR96‐auristatin by combining the administration of conjugates with subsequent extracorporeal affinity adsorption treatment.METHODS:Rats were injected with biotinylated, monomethyl auristatin F (MMAF)‐conjugated monoclonal antibody BR96. The conjugate was then removed from the circulation by extracorporeal affinity adsorption treatment, 24 hours postinjection using an avidin affinity column. By analyzing blood parameters for 100 days, myelotoxicity, hepatotoxicity, and nephrotoxicity were assessed. Body weight, general status, and tumor size were also recorded. The toxicity‐reducing effect of extracorporeal affinity adsorption treatment was evaluated.RESULTS:Extracorporeal affinity adsorption treatment removed 85%‐90% of BR96‐MMAF from the circulation. Early toxicity‐related death was seen in nontumor‐bearing animals that were given MMAF‐conjugated BR96, in contrast to animals that were given a higher amount of BR96‐MMAF with subsequent extracorporeal affinity adsorption treatment, in which all survived 100 days postinjection. Extracorporeal affinity adsorption treatment reduced the loss of body weight, myelotoxicity, and hepatotoxicity.CONCLUSIONS:Extracorporeal affinity adsorption treatment can be used to reduce the toxicity associated with administration of BR96‐MMAF conjugates, making it possible to increase the amount of conjugates administered. The combined treatment will be further optimized in future studies. Cancer 2010;116(4 suppl):1033–42. © 2010 American Cancer Society.
Improved efficacy of α‐particle–targeted radiation therapy
Authors: Milenic Diane E. , Brady Erik D. , Garmestani Kayhan , Albert Paul S. , Abdulla Alia , Brechbiel Martin W. 
Published: February 2010

AbstractBACKGROUND:Human epidermal growth factor receptor–2 (HER‐2) and tumor‐associated glycoprotein 72 (TAG‐72) have proven to be excellent molecular targets for cancer imaging and therapy. Trastuzumab, which binds to HER‐2, is effective in the treatment of disseminated intraperitoneal disease when labeled with 213Bi or 212Pb. 213Bi‐humanized CC49 monoclonal antibody (HuCC49ΔCH2), which binds to TAG‐72, inhibits the growth of subcutaneous xenografts. A next logical step to improve therapeutic benefit would be to target tumors with both molecules simultaneously.METHODS:Athymic mice bearing intraperitoneal human colon carcinoma xenografts were treated with a combination of trastuzumab and HuCC49ΔCH2 labeled with 213Bi administered through an intraperitoneal route. The sequence of administration also was examined.RESULTS:Before combining the 2 monoclonal antibodies, the effective doses of 213Bi‐CC49ΔCH2 and 213Bi‐trastuzumab for the treatment of peritoneal disease were determined to be 500 μCi for each labeled antibody. Treatment with 213Bi‐HuCC49ΔCH2 resulted in a median survival of 45 days and was comparable to the median survival achieved with 213Bi‐trastuzumab. Each combination provided greater therapeutic efficacy than either of the agents given alone. However, the greatest therapeutic benefit was achieved when 213Bi‐HuCC49ΔCH2 and 213Bi‐trastuzumab were coinjected, and a median survival of 147 days was obtained.CONCLUSIONS:Dual targeting of 2 distinct molecules in tumors such as TAG‐72 and HER‐2 with α‐particle radiation resulted in an enhanced, additive, therapeutic benefit. The authors also observed that this radioimmunotherapeutic strategy was well tolerated. Cancer 2010;116(4 suppl):1059–66. Published 2010 by the American Cancer Society.
In vitro evaluation of avidin antibody pretargeting using 211At‐labeled and biotinylated poly‐L‐lysine as effector molecule
Authors: Frost Sofia HL , Jensen Holger , Lindegren Sture 
Published: February 2010

AbstractBACKGROUND:Pretargeting is an approach for enhancing the therapeutic index of radioimmunotherapy by separating the administrations of tumor‐targeting substance and radiolabel. In this study, a pretargeting model system of avidin‐conjugated monoclonal antibody trastuzumab and biotinylated, 211At‐labeled poly‐L‐lysine was constructed and analyzed in vitro.METHODS:Avidin activated by 4‐(N‐maleimidomethyl)cyclohexane‐1‐carboxylic acid 3‐sulfo‐N‐hydroxysuccinimide ester sodium salt (sulfo‐SMCC) and thiolated trastuzumab were incubated overnight at 4°C. The monomeric fraction was extracted using size exclusion fast protein liquid chromatography (FPLC) and further purified on an iminobiotin affinity column. Poly‐L‐lysine was biotinylated with succinimidyl‐6‐(biotinamido)hexanoate (NHS‐LC‐biotin), followed by direct 211At‐labeling with N‐succinimidyl‐3‐(trimethylstannyl)benzoate (m‐MeATE), and succinylation with succinic anhydride. The avidin‐trastuzumab conjugate was characterized by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and FPLC, together with cell‐binding and biotin‐binding analyses. The labeled poly‐L‐lysine conjugate was assessed in terms of radiochemical purity and avidin binding. Furthermore, the full pretargeting system was evaluated in a tumor cell binding assay.RESULTS:The estimated size of the pretargeting molecule was 220 kDa, which corresponds to that of the expected avidin‐trastuzumab monomer. Neither cell‐binding ability (64%) nor biotin‐binding ability (85%‐95%) indicated any severe adverse effects from the chemical modifications. The radiochemical purity of the effector molecule was 92%‐97%, and the avidin binding capacity was 91%‐93%. The complete pretargeting assay resulted in a binding of 75.3 ± 6.2% of added effector molecules to cells.CONCLUSIONS:The high binding of effector molecules to cells demonstrates a proof of concept for the synthesized molecules and pretargeting system, which will be further evaluated in vivo in future studies. Cancer 2010;116(4 suppl):1101–10. © 2010 American Cancer Society.
Low‐Energy‐Barrier Proton Transfer Induced by Electron Attachment to the Guanine⋅⋅⋅Cytosine Base Pair
Authors: Szyperska Anna , Rak Janusz , Leszczynski Jerzy , Li Xiang , Ko Yeon Jae , Wang Haopeng , Bowen Kit H. 
Published: February 2010

AbstractThe photoelectron spectrum of the anion of the guanine⋅⋅⋅cytosine base apair (GC).− is recorded for the first time. The observed variation in the spectral peak‐height ratios with the source conditions suggests the presence of two or more anionic isomers. Two maxima of the broad bands in the photoelectron spectrum were measured at about 1.9 and about 2.6 eV. These values are very well reproduced by the vertical detachment energies of the B3LYP/6‐31++G(d,p) calculated low‐energy anionic structures, which are 1) the Watson–Crick base‐pair anion with proton transferred from N1 of guanine to N3 of cytosine, 2) its analogue in which the proton is transferred from N9 of guanine to N7 of guanine, and 3) the global minimum geometry, which is formed from the latter anion by rotation of guanine about the axis approximately defined by C2 of guanine and C4 of cytosine. Furthermore, a minor difference in the stabilities of the two lowest energy anions explains the experimentally observed source (temperature) dependence of the PES spectrum. A rational procedure, based on the chemistry involved in the formation of anionic dimers, which enables the low‐energy anions populated in the photoelectron spectrum to be identified is proposed. In contrast to the alternative combinatorial approach, which in the studied case would lead to carrying out quantum chemical calculations for 2000–2500 structures, the procedure described here reduces the computational problem to only 15 geometries.
Demand‐specific alteration of medial prefrontal cortex response during an inhibition task in recovered anorexic women
Authors: Oberndorfer Tyson A. , Kaye Walter H. , Simmons Alan N. , Strigo Irina A. , Matthews Scott C. 
Published: February 2010

AbstractObjective:It is well known that individuals with anorexia nervosa (AN) are inhibited and over‐controlled. This study investigated a prefrontal‐cingulate network that is involved in inhibitory control.Method:To avoid the confounds of malnutrition, 12 recovered (RAN) subjects were compared to 12 matched control women (CW) using a validated inhibition task (i.e., a stop signal task) during functional magnetic resonance imaging.Results:Consistent with the a priori hypothesis, RAN subjects showed altered task‐related activation in the medial prefrontal cortex (mPFC), a critical node of the inhibitory control network. Specifically, whereas RAN and CW showed similar mPFC acitivity during trials when inhibitory demand was low (i.e., easy trials), RAN relative to CW showed significantly less mPFC activation as inhibition trials became more difficult (i.e., hard trials), suggesting a demand‐specific modulation of inhibitory control circuitry in RAN.Discussion:These findings support a neural basis for altered impulse control symptoms in AN © © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2011; 44:1–8)
Mediators between perfectionism and eating disorder psychopathology: Shape and weight overvaluation and conditional goal‐setting
Authors: Watson Hunna J. , Raykos Bronwyn C. , Street Helen , Fursland Anthea , Nathan Paula R. 
Published: February 2010

AbstractObjective:To examine mediators of the relationship between perfectionism and eating disorder (ED) psychopathology in a clinical sample.Method:Participants were 201 women with a DSM‐IV diagnosed ED consecutively referred to a specialist outpatient treatment clinic. Participants completed measures of perfectionism, ED psychopathology, shape and weight overvaluation, and conditional goal‐setting (CGS).Results:Evaluation of a multivariate mediator model using Baron and Kenny's (1986) four‐step mediation methodology showed that shape and weight overvaluation and CGS significantly and uniquely mediated the relation between self‐oriented perfectionism (SOP) and restraint, eating concern, shape concern, and weight concern. The mediator model furthered the proportion of explained variance in outcomes beyond the direct effects model by 28–49%.Discussion:The findings support the conclusion that the relationship between SOP and ED psychopathology in women with a clinically diagnosed ED is mediated by shape and weight overvaluation and CGS. © 2010 by Wiley Periodicals, Inc.
Polydipsia and hyponatremia in a woman with anorexia nervosa
Authors: Bahia Amit , Chu Eugene S. , Mehler Philip S. 
Published: February 2010

AbstractObjective:Hyponatremia is infrequently reported in the constellation of metabolic abnormalities in patients with eating disorders. We sought to identify the etiology and describe the management of a patient with anorexia nervosa and hyponatremia.Method:We report the case of a 23‐year‐old woman with anorexia nervosa who suffered with severe hyponatremia.Results:The etiology of hyponatremia in this case, as in most patients with eating disorders, was multifactorial, encompassing both hypovolemic and euvolemic categories of hyponatremia. Multiple impairments in the ability to clear free water are responsible for a heightened risk for hyponatremia in patients with anorexia nervosa.Discussion:This case underscores the importance of careful scrutiny of fluid intake, an awareness of medications that lead to hyponatremia, and the need for regular monitoring of serum electrolytes, even in patients with anorexia nervosa, to allow for an early diagnosis and to assist in the formulation of an effective treatment and prevention strategy. © 2010 by Wiley Periodicals, Inc.
Use of mirtazapine in an adult with refractory anorexia nervosa and comorbid depression: A case report
Authors: Safer Debra L. , Darcy Alison M. , Lock James 
Published: February 2010

AbstractThe objective of this report was to describe an efficacious treatment of an adult with long‐standing anorexia nervosa (AN). A 50‐year‐old woman with an over 7‐year history of AN and comorbid major depression had been treated unsuccessfully with numerous psychotropic medications, manualized cognitive behavior therapy, and an intensive outpatient treatment program before referral. After treatment with mirtazapine, she gained weight and her depression improved. A 9‐month follow‐up revealed a maintenance of these benefits. Mirtazapine may be useful for older, chronically ill patients presenting with AN and comorbid depression. © 2010 by Wiley Periodicals, Inc.
Comparisons over time: Temporal trajectories, social comparison, and self‐evaluation
Authors: Zell Ethan , Alicke Mark D. 
Published: February 2010

AbstractSocial comparison information fluctuates over time. We examined how people evaluate their task performance and ability after receiving test feedback specifying not only that they ranked above or below average, but also that their social status was rising, falling, or remaining constant. Participants' self‐evaluations were more positive when their social standing was rising over time rather than remaining constant. On the other hand, participants whose status was falling did not evaluate themselves less favorably than those with a constant position in the performance distribution. These reactions to performance feedback were observed on self‐evaluations of ability, but not on more even‐handed assessments of performance. Implications for social comparison and self‐evaluation maintenance theories are discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Hillslope scale surface runoff, sediment and nutrient losses associated with tramline wheelings
Authors: Silgram Martyn , Jackson D.R , Bailey Alison , Quinton John , Stevens Carly 
Published: February 2010

AbstractResearch on arable sandy loam and silty clay loam soils on 4° slopes in England has shown that tramlines (i.e. the unseeded wheeling areas used to facilitate spraying operations in cereal crops) can represent the most important pathway for phosphorus and sediment loss from moderately sloping fields. Detailed monitoring over the October–March period in winters 2005–2006 and 2006–2007 included event‐based sampling of surface runoff, suspended and particulate sediment, and dissolved and particulate phosphorus from hillslope segments (each ∼300–800 m2) established in a randomized block design with four replicates of each treatment at each of two sites on lighter and heavier soils. Experimental treatments assessed losses from the cropped area without tramlines, and from the uncropped tramline area, and were compared to losses from tramlines which had been disrupted once in the autumn with a shallow tine. On the lighter soil, the effects of removal or shallow incorporation of straw residues was also determined.Research on both sandy and silty clay loam soils across two winters showed that tramline wheelings represented the dominant pathway for surface runoff and transport of sediment, phosphorus and nitrogen from cereal crops on moderate slopes. Results indicated 5·5–15·8% of rainfall lost as runoff, and losses of 0·8–2·9 kg TP ha−1 and 0·3–4·8 t ha−1 sediment in tramline treatments, compared to only 0·2–1·7% rainfall lost as runoff, and losses of 0·0–0·2 kg TP ha−1 and 0·003–0·3 t ha−1 sediment from treatments without tramlines or those where tramlines had been disrupted. The novel shallow disruption of tramline wheelings using a tine once following the autumn spray operation consistently and dramatically reduced (p < 0·001) surface runoff and loads of sediment, total nitrogen and total phosphorus to levels similar to those measured in cropped areas between tramlines. Results suggest that options for managing tramline wheelings warrant further refinement and evaluation with a view to incorporating them into spatially‐targeted farm‐level management planning using national or catchment‐based agri‐environment policy instruments aimed at reducing diffuse pollution from land to surface water systems. Copyright © 2010 John Wiley & Sons, Ltd.
Emotional imagery: Assessing pleasure and arousal in the brain's reward circuitry
Authors: Costa Vincent D. , Lang Peter J. , Sabatinelli Dean , Versace Francesco , Bradley Margaret M. 
Published: February 2010

AbstractResearch on emotional perception and learning indicates appetitive cues engage nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), whereas amygdala activity is modulated by the emotional intensity of appetitive and aversive cues. This study sought to determine patterns of functional activation and connectivity among these regions during narrative emotional imagery. Using event‐related fMRI, we investigate activation of these structures when participants vividly imagine pleasant, neutral, and unpleasant scenes. Results indicate that pleasant imagery selectively activates NAc and mPFC, whereas amygdala activation was enhanced during both pleasant and unpleasant imagery. NAc and mPFC activity were each correlated with the rated pleasure of the imagined scenes, while amygdala activity was correlated with rated emotional arousal. Functional connectivity of NAc and mPFC was evident throughout imagery, regardless of hedonic content, while correlated activation of the amygdala with NAc and mPFC was specific to imagining pleasant scenes. These findings provide strong evidence that pleasurable text‐driven imagery engages a core appetitive circuit, including NAc, mPFC, and the amygdala. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Attachment style, affective loss and gray matter volume: A voxel‐based morphometry study
Authors: Benetti Stefania , McCrory Eamon , Arulanantham Sobida , De Sanctis Teresa , McGuire Philip , Mechelli Andrea 
Published: February 2010

AbstractEarly patterns of infant attachment have been shown to be an important influence on adult social behavior. Animal studies suggest that patterns of early attachment influence brain development, contributing to permanent alterations in neural structure; however, there are no previous studies investigating whether differences in attachment style are associated with differences in brain structure in humans. In this study, we used Magnetic Resonance Imaging (MRI) and voxel‐based morphometry (VBM) to examine for the first time the association between attachment style, affective loss (for example, death of a loved one) and gray matter volume in a healthy sample of adults (n = 32). Attachment style was assessed on two dimensions (anxious and avoidant) using the ECR‐Revised questionnaire. High attachment‐related anxiety was associated with decreased gray matter in the anterior temporal pole and increased gray matter in the left lateral orbital gyrus. A greater number of affective losses was associated with increased gray matter volume in the cerebellum; in this region, however, the impact of affective losses was significantly moderated by the level of attachment‐related avoidance. These findings indicate that differences in attachment style are associated with differences in the neural structure of regions implicated in emotion regulation. It is hypothesized that early attachment experience may contribute to structural brain differences associated with attachment style in adulthood; furthermore, these findings point to a neuronal mechanism through which attachment style may mediate individual differences in responses to affective loss. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Investigation of a plasmid containing a novel immunotoxin VEGF165‐PE38 gene for antiangiogenic therapy in a malignant glioma model
Authors: Hu Chang‐chen , Ji Hong‐ming , Chen Sheng‐li , Zhang Han‐wei , Wang Bin‐quan , Zhou Li‐yuan , Zhang Zi‐ping , Sun Xin‐lin , Chen Zhen‐zhou , Cai Ying‐qian , Qin Ling‐sha , Lu Li , Jiang Xiao‐dan , Xu Ru‐xiang , Ke Yi‐quan 
Published: February 2010

AbstractInhibition of tumor neovascularization has profound effects on the growth of solid tumors. Our previous studies have shown the effect of VEGF165‐PE38 recombinant immunotoxin on proliferation and apoptosis in human umbilical vein endothelial cells in vitro. In this study, we explored the direct inhibition of angiogenesis in chick chorioallantoic membrane and antiangiogenic therapy in a malignant glioma model. HEK293 cells were transfected with the pVEGF165PE38‐IRES2‐EGFP plasmid. ELISA was used to confirm the expression of VEGF165‐PE38 in the transfected cells. These cells released 1396 ± 131.9 pg VEGF165‐PE38/1×104 cells/48 h into the culture medium and the supernatant was capable of inhibiting the growth of capillary‐like structures in chick chorioallantoic membrane assay. In a murine malignant glioma model, plasmid was directly administered via multiple local intratumoral delivery. After day 16 the tumor volume in mice treated with pVEGF165PE38‐IRES2‐EGFP was significantly lower than that in mice in the control groups. Immunohistochemistry studies showed that the treated group had decreased expression of CD31. Quantitative analysis of microvessel density in the treated group was 1.99 ± 0.69/0.74 mm2, and was significantly lower than that in the control groups (9.33 ± 1.99/0.74 mm2, 8.09 ± 1.39/0.74 mm2 and 8.49 ± 1.69/0.74 mm2). Immunohistochemistry analysis indicated that immunotoxin VEGF165‐PE38 was distributed in the treated group in malignant glioma tissue. Our findings provide evidence that the in vivo production of VEGF165‐PE38 through gene therapy using a eukaryotic expression plasmid had potential antiangiogenic activity in malignant glioma in vivo.