bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of Concern: A small molecule, LLL12 inhibits constitutive STAT3 and IL‐6‐induced STAT3 signaling and exhibits potent growth suppressive activity in human multiple myeloma cells
Authors: Lin Li , Benson Don M. , DeAngelis Stephanie , Bakan Courtney E. , Li Pui‐Kai , Li Chenglong , Lin Jiayuh 
Published: April 2011

AbstractWe characterized the effects of a newly developed signal transducers and activators of transcription 3 (STAT3) inhibitor, LLL12 in multiple myeloma (MM) cells. LLL12 specifically inhibited STAT3 phosphorylation, nuclear localization, DNA binding activity, down‐regulated STAT3 downstream genes, and induced apoptosis in MM cells. Importantly, LLL12 significantly inhibited STAT3 phosphorylation, induced apoptosis in primary MM cells which came from patients that were clinically resistant to lenalidomide and bortezomib. LLL12 is a potent inhibitor of cell proliferation with IC50 values ranging between 0.26 and 1.96 μM in MM and primary MM cells. LLL12 also inhibited STAT3 phosphorylation induced by interleukin‐6 (IL‐6) and interferon‐α but not STAT1, STAT2, STAT4 and STAT6 phosphorylation induced by interferon‐α, interferon‐γ and IL‐4 indicating the selectivity of LLL12 for STAT3. The selectively of LLL12 on STAT3 was further demonstrated on 21 protein kinases, which LLL12 had IC50 values ≥73.92 μM. In addition, the pretreatment of LLL12 blocked the promotion of the cell proliferation and resistance to lenalidomide by IL‐6. Furthermore, LLL12 significantly blocked tumor growth of MM cells in mouse model. Our results indicate that LLL12 blocks constitutive STAT3 and IL‐6 induced STAT3 signaling and may be a potential therapeutic agent for MM.
Down regulation of CSL activity inhibits cell proliferation in prostate and breast cancer cells
Authors: Yong Thomas , Sun Amanda , Henry Michael D. , Meyers Shari , Davis J. Nathan 
Published: April 2011

AbstractThe Notch receptor pathway provides a paradigm for juxtacrine signaling pathways and controls stem cell function, developmental cell fate decisions, and cellular differentiation. The Notch pathway is constitutively activated in human cancers by chromosomal rearrangements, activating point mutations, or altered expression patterns. Therefore, the Notch pathway is the subject of chemotherapeutic intervention in a variety of human cancers. Notch receptor activation results in the gamma‐secretase dependent proteolytic cleavage of the receptor to liberate the Notch intracellular domain that acts to mediate co‐activator recruitment to the DNA binding transcription factor, CSL (CBF‐1/RBP‐Jκ, Su(H), Lag‐1). Therapeutic targeting of the Notch pathway by gamma‐secretase inhibitors prevents NICD production and regulates CSL‐dependent transcriptional activity. To interrogate the loss of CSL activity in breast and prostate cancer cells, we used lentiviral‐based shRNA knockdown of CSL. Knockdown of CSL expression was assessed by decreased DNA binding activity and resulted in decreased cell proliferation. In contrast, gamma‐secretase inhibitor (GSI) treatment of these prostate and breast cancer cell lines resulted in minimal growth effects. PCR profiling of Notch pathway genes identified expression changes in few genes (Delta‐like‐1, Deltex‐1, LMO2, and SH2D1A) after CSL knockdown. Consistent with differential effects of GSI on cell survival, GSI treatment failed to recapitulate the gene expression changes observed after CSL knockdown. Thus, CSL inhibition may provide a more effective mechanism to inhibit Notch‐pathway dependent cancer cell proliferation as compared to GSI treatment. J. Cell. Biochem. 112: 2340–2351, 2011. © 2011 Wiley‐Liss, Inc.
Amelioration of systemic lupus erythematosus by withangulatin A in MRL/lpr mice
Authors: Sun Lijuan , Zhou Lin , Chen Mingcang , Zhong Renqian , Liu Jianwen 
Published: April 2011

AbstractWe have previously reported the anti‐inflammatory potential and the possible underlying mechanisms of Withangulatin A (WA), which is an active component isolated from Physalis angulata L. Here, we demonstrated that WA might improve the life quality, as well as reduced the accumulation of proteinuria symptoms and levels of anti‐double‐stranded DNA antibodies in MRL/lpr mice. Moreover, WA could improve renal histopathologic characteristics of MRL/lpr mice. Intriguingly, expression of B cell‐activating factor (BAFF), BAFF‐R and related gene in the spleen were significantly reduced in 10 mg/kg WA‐treated mice compared with that in 5 mg/kg WA‐treated mice and untreated mice. These findings indicate that WA might have a pleiotropic therapeutic effect through their immunosuppression via inhibiting BAFF signaling, which suggest a potential application of this active constituent in the treatment of SLE. J. Cell. Biochem. 112: 2376–2382, 2011. © 2011 Wiley‐Liss, Inc.
Axin1 expression facilitates cell death induced by aurora kinase inhibition through PARP activation
Authors: Choi Eun‐Jin , Kim Shi‐Mun , Song Ki‐Joon , Lee Jae‐Myun , Kee Sun‐Ho 
Published: April 2011

AbstractAxin, a negative regulator of Wnt signaling, participates in apoptosis, and Axin1 localizes to centrosomes and mitotic spindles, which requires Aurora kinase activity. In this study, Aurora inhibition of Axin1‐expressing cells (L‐Axin) produced polyploid cells, which died within 48 h posttreatment, whereas Axin2‐expressing cells (L‐Axin2) survived the same period. These cell death events showed apoptotic signs, such as chromatin condensation and increased sub‐G1 populations, as well as cell membrane rupture. Further analysis showed that Aurora kinase inhibitor (AKI) treatment of L‐Axin cells induced poly(ADP‐ribose) polymerase (PARP) activation, which increased the poly(ADP‐ribosyl)ation of cellular proteins and reduced cellular ATP content. PARP inhibition reduced a proportion of dead cells, suggesting PARP involvement in AKI‐induced cell death. Also, AKI treatment of L‐Axin cells induced mitochondrial apoptosis‐inducing factor (AIF) release, but not mitochondrial cytochrome c release or caspase‐3 activation. Knockdown of AIF attenuated AKI‐induced cell death in L‐Axin cells. Thus, our results suggest that Axin1 expression renders L929 cells sensitive to Aurora inhibition‐induced cell death in a PARP‐ and AIF‐dependent manner. J. Cell. Biochem. 112: 2392–2402, 2011. © 2011 Wiley‐Liss, Inc.
Hydrogen peroxide induces dimerization of protein kinase G type Iα subunits and increases albumin permeability in cultured rat podocytes
Authors: Piwkowska Agnieszka , Rogacka Dorota , Jankowski Maciej , Kocbuch Katarzyna , Angielski Stefan 
Published: April 2011

AbstractPodocytes help regulate filtration barrier permeability in the kidneys. They express contractile proteins that are characteristic of smooth muscle cells as well as receptors for vasoactive factors such as angiotensin II and atrial natriuretic peptide (ANP). The later one generates intracellular cGMP, with subsequent activation of cGMP‐dependent protein kinase; PKG (isoform PKGIα and PKGIβ). In this study, we asked whether hydrogen peroxide (H2O2), a physiological vasorelaxing factor, affected podocyte permeability and the podoctye PKGIα signaling pathway. Expression of PKGIα was confirmed in cultured rat podocytes using RT‐PCR, immunofluorescence, and Western blotting. Exposure of podocytes to exogenous H2O2 (100 µM) in non‐reducing conditions increased the formation of PKGIα interprotein disulfide bonds, affected the phosphorylation of PKG target proteins, namely MYPT1 (maximal increase of about 57% at 30 min) and MLC (maximal decrease of about 62% at 10 min). Furthermore, H2O2 increased the permeability of a layer of podocytes to albumin: Transmembrane flux for albumin increased five‐fold (106.6 ± 5.2 µg/ml vs. 20.2 ± 2.5 µg/ml, P < 0.05, n = 5), and the PKG inhibitor Rp‐8‐Br‐cGMPS (100 µM) prevented the flux increase. These data suggest that oxidative modulation of PKGIα in podocytes plays an important role in the regulation of filtration barrier permeability. J. Cell. Physiol. 227: 1004–1016, 2012. © 2011 Wiley Periodicals, Inc.
Class III β‐tubulin and the cytoskeletal gateway for drug resistance in ovarian cancer
Authors: De Donato Marta , Mariani Marisa , Petrella Lella , Martinelli Enrica , Zannoni Gian Franco , Vellone Valerio , Ferrandina Gabriella , Shahabi Shohreh , Scambia Giovanni , Ferlini Cristiano 
Published: April 2011

AbstractThe Class III β‐tubulin isotype (βIII‐tubulin) is a predictive biomarker in ovarian cancer and other solid tumor malignancies. We discovered that βIII‐tubulin function is linked to two GTPases: guanylate‐binding protein 1 (GBP1), which activates its function, and GNAI1, which inhibits it. This finding was demonstrated in a panel of ovarian cancer cells resistant to several chemotherapeutic agents. Using a protein microarray, we identified PIM1 as the downstream partner of GBP1, recruited into the cytoskeleton under hypoxic conditions. The clinical value of these observations was tested by performing an archive study of 98 ovarian cancer patients, which demonstrated that the βIII‐tubulin ‐/PIM1‐ cohort responded to treatment, exhibiting long overall survival (OS), while βIII‐tubulin +/PIM+ patients experienced poor outcomes and OS times similar to patients receiving palliation alone. βIII‐tubulin expression is commonly believed responsible for paclitaxel resistance due to its enhancement of the dynamic instability of microtubules, which counteracts the activity of taxanes. In contrast, our research reveals that βIII‐tubulin behaves as a gateway for prosurvival signals, such as PIM1, to move into the cytoskeleton. When cells are exposed to microenvironmental stressors, they activate this pathway by telling the cytoskeleton to incorporate PIM1 through GBP1 and βIII‐tubulin, which ultimately leads to drug resistance. This discovery reveals that βIII‐tubulin does not act alone but requires partners to play its role. The discovery of such protein:protein interactions underlying this prosurvival cascade makes feasible the development of therapeutic approaches using novel compounds that are capable of inhibiting the transmission of prosurvival signals into the cytoskeleton. J. Cell. Physiol. 227: 1034–1041, 2012. © 2011 Wiley Periodicals, Inc.
Pluripotent human stem cells for the treatment of retinal disease
Authors: Rowland Teisha J. , Buchholz David E. , Clegg Dennis O. 
Published: April 2011

AbstractDespite advancements made in our understanding of ocular biology, therapeutic options for many debilitating retinal diseases remain limited. Stem cell‐based therapies are a potential avenue for treatment of retinal disease, and this mini‐review will focus on current research in this area. Cellular therapies to replace retinal pigmented epithelium (RPE) and/or photoreceptors to treat age‐related macular degeneration (AMD), Stargardt's macular dystrophy, and retinitis pigmentosa are currently being developed. Over the past decade, significant advancements have been made using different types of human stem cells with varying capacities to differentiate into these target retinal cell types. We review and evaluate pluripotent stem cells, both human embryonic stem cells and human induced pluripotent stem cells, as well as protocols for differentiation of ocular cells, and culture and transplant techniques that might be used to deliver cells to patients. J. Cell. Physiol. 227: 457–466, 2012. © 2011 Wiley Periodicals, Inc.
Eat‐me signals: Keys to molecular phagocyte biology and “Appetite” control
Authors: Li Wei 
Published: April 2011

AbstractHundreds of billions of cells undergo apoptosis in our body everyday and are removed by immunologically silent phagocytosis to maintain tissue homeostasis. Impairments in phagocytosis result in autoimmune and/or degenerative diseases. Eat‐me signals are the key to the recognition of extracellular cargos and the initiation of the phagocytosis process by activating phagocytic receptors and signaling cascades, and are convenient targets for therapeutic modulation. Despite their importance, eat‐me signals and other phagocytosis players are mostly identified on case‐by‐case basis with daunting challenges. This Commentary focuses on our latest knowledge of the extracellular players, highlights our approaches to systematically map unknown pathways by functional genetic and proteomic technologies, and discusses future direction to unravel the mystery of molecular phagocyte biology. J. Cell. Physiol. 227: 1291–1297, 2012. © 2011 Wiley Periodicals, Inc.
Genotyping of acute hepatitis a virus isolates from China, 2003–2008
Authors: Cao Jingyuan , Bi Shengli , Meng Qingling , Shen Liping , Zheng Huihui , Zhang Yong 
Published: April 2011

AbstractHepatitis A virus (HAV) is usually transmitted by an oral–fecal route and is prevalent not only in developing countries but also in developed countries. In the present study, the phylogenetic characterization of the VP1/2A junction region (321 nucleotides) of China HAV isolates was examined. Anti‐HAV IgM‐positive serum samples were collected from 8 provinces, including 20 cities or counties in China from 2003 to 2008; 337 isolates from 406 HAV patients' serum samples were amplified by RT‐PCR, sequenced at the VP1/2A junction region and aligned with the published sequences from GenBank to establish phylogenetic analysis. All China HAV isolates in this study belonged to genotype I, with 98.8% (333/337) of samples clustering in sub‐genotype IA and 1.2% (4/337) in sub‐genotype IB. In addition, sub‐genotype IA isolates clustered into four groups (92.7–100% nucleotide identity), and the samples collected from all China HAV isolates in this investigation showed 87.5–100% nucleotide identity, but the amino acids in this region were more conserved (95.2–100% identity). Few unique amino acid changes could be deduced (VP1‐253: Glu → Gly; 2A‐34: Pro → Ala; 2A‐33: Leu → Phe). Genetically identical or similar HAV strains existed in some investigated areas in China during different years, suggesting that an indigenous strain has been circulating in those regions. This report provides new data on the genetic relatedness and molecular epidemiology of HAV isolates from China as well as the distribution of sub‐genotype IA and IB in this part of the world. J. Med. Virol. 83:1134–1141, 2011. © 2011 Wiley‐Liss, Inc.
Quantifying osteoarthritic cartilage changes accurately using in vivo microCT arthrography in three etiologically distinct rat models
Authors: Siebelt Michiel , Waarsing Jan H. , Kops Nicole , Piscaer Tom M. , Verhaar Jan A. N. , Oei Edwin H. G. , Weinans Harrie 
Published: April 2011

AbstractIn vivo microCT arthrography (µCTa) can be used to measure both quantity (volumetric) and quality (glycosaminoglycan content) of cartilage. This study investigated the accuracy of four segmentation techniques to isolate cartilage from µCTa datasets and then used the most accurate one to investigate if the µCTa method could show osteoarthritic changes in rat models during longitudinal follow‐up. Volumetric measurements and glycosaminoglycan contents of patellar cartilage from in vivo µCTa‐scans were compared with an ex vivo gold standard µCT‐scan. Cartilage was segmented with three global thresholds and one local threshold algorithm. Comparisons were made for healthy and osteoarthritic cartilage. Next, three rat models were investigated for 24 weeks using µCTa. Osteoarthritis was induced by injection with a chemical (mono‐iodoacetate), a surgical intervention (grooves applied in articular cartilage), and via exercise (strenuous running). After euthanasia, all knee joints were isolated for histology. Local thresholds accurately segmented cartilage from in vivo µCTa scans and best measured cartilage quantity and glycosaminoglycan content. Each of the three osteoarthritic rat models showed a specific pattern of osteoarthritis progression. All µCTa results were comparable to histology. In vivo µCTa is a sensitive technique for imaging cartilage degradation. Local thresholds enhanced the sensitivity of this method and will probably more accurately detect disease‐modulating effects from interventional strategies. The data from rat models may serve as a reference for the time sequence of cartilage degeneration during in vivo testing of new strategies in osteoarthritis treatment. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1788–1794, 2011
Vertebrectomy and expandable cage placement via a one‐stage, one‐position anterolateral retroperitoneal approach in L5 tumors
Authors: Papanastassiou Ioannis D. , Jain Surbhi , Baaj Ali A. , Eleraky Mohammed , Papagelopoulos Panayotis J. , Vrionis Frank D. 
Published: April 2011

AbstractSpinal reconstruction of the L5 vertebrae after tumor resection remains a challenge. Complex resection followed by circumferential fixation in the same setting, or in staged fashion, is often employed. The added operative time associated with this method potentially increases morbidity and mortality in an inherently high‐risk procedure and anatomy in the lumbosacral area makes reconstruction more challenging. The authors describe a technique involving L5 vertebrectomy, placement of an expandable cage, and anterolateral L4‐S1 screw fixation via a one‐stage, one‐position, anterolateral retroperitoneal approach. Two illustrative cases are presented along with the authors overall experience in L5 tumor operations. We believe that this is a feasible reconstructive option after tumor resection in lower lumbar metastatic spine disease. The approach may be also utilized in combined anteroposterior (two‐stage) procedures in primary malignant tumors or oligometastatic disease. J. Surg. Oncol. 2011; 104:552–558. © 2011 Wiley‐Liss, Inc.
Active lymphangiogenesis is a major risk factor for anastomotic leakage following sphincter‐sparing resection of rectal cancer
Authors: Chen Weirong , Li Yanchon , Liao Ziqun , Lin Guangrong , Cai Gaoyang , Lin Kaihuang , Zhan Qinhua , Chen Caoyang 
Published: April 2011

AbstractObjectiveAnastomotic leakage is a major complication of rectal surgery and controversy about its risk factors still exists. The aim of present study was to identify risk factors for anastomotic leakage following sphincter‐sparing resection of rectal cancer, focusing on the role of tissular lymphatic vessel density (LVD) in tumorous margin and distal clearance margin.MethodsIn a 9‐year period, from September 1999 to September 2009, 750 consecutive patients who underwent anterior resection with restoration of the bowel continuity were included. Univariate and multivariate analysis were applied to identify risk facrors for anastomotic leakage.ResultsThe rate of anastomotic leakage was 7.6% (57 of 750 patients). In a multivariate analysis, high LVD in tumorous margin [P = 0.0017; odds ratio (OR) = 5.93; 95% confidence interval (CI) = 2.61–8.514], high LVD in distal clearance margin (P = 0.0011; OR = 6.05; 95% CI = 2.72–10.108) and lower tumor location (P = 0.006; OR = 4.620; 95% CI = 1.76–6.97) were identified as independent factors for anastomotic leakage. A significant LVD correlation was shown by Spearman′s rank test between the tumorous and distal clearance margin (r = 0.796).ConclusionsTissular LVD in tumorous or distal clearance margin and lower tumor location are important risk factors for anastomotic leakage. J. Surg. Oncol. 2011; 104:493–498. © 2011 Wiley‐Liss, Inc.
Theoretical calculations on the mechanisms of the gas‐phase elimination kinetics of 2‐chloro‐1‐phenylethane, 3‐chloro‐1‐phenylpropane, 4‐chloro‐1‐phenylbutane, 5‐chloro‐1‐phenylpentane, and their corresponding chloroalkanes: The effect of the phenyl ring
Authors: Maldonado Alexis , Mora Jose R. , Subero Simon J. , Loroño Marcos , Cordova Tania , Chuchani Gabriel 
Published: April 2011

AbstractThe kinetics and mechanisms of the dehydrochlorination of 2‐chloro‐1‐ phenylethane, 3‐chloro‐1‐phenylpropane, 4‐chloro‐1‐phenylbutane, 5‐chloro‐1‐phenylpentane, and their corresponding chloroalkanes were examined by means of electronic structure calculation using density functional theory methods B3LYP/6–31G(d,p), B3LYP/6–31++G(d,p), MPW1PW91/6–31G(d,p), MPW1PW91/6–31++G(d,p), PBEPBE/6–31G(d,p), and PBEPBE/6–31++G(d,p). The potential energy surface was investigated for the minimum energy path. Calculated enthalpies and energies of activation are in good agreement with experimental values using the MPW1PW91 and B3LYP methods. The transition state of these reactions is a four‐centered cyclic structure. The reported experimental results proposing neighboring group participation by the phenyl group was not supported by theoretical calculations. The rate‐determining process in these reactions is the breaking of ClC bond. The reactions are described as concerted moderately polar and nonsynchronous. © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 292–302, 2011
Kinetics of proton transfer between metasubstituted benzoic acids and the carbinol base of crystal violet in toluene: Specific solvent effect–free metasubstituent effect on the reactivity of benzoic acids
Authors: Gupta Susanta K. Sen , Radha Rani V. 
Published: April 2011

AbstractApolar aprotic solvents are particularly advantageous for investigating the intrinsic metasubstituent effect free from complications of specific solvent effects. A kinetic study for toluene‐phase proton transfers between meta‐Me, F, Cl, Br, I, OMe, OPh, COPh, CF3, CN, NO2, H benzoic acids and Crystal Violet carbinol base has shown the forward rate constant (log k1) the most appropriate reactivity parameter in toluene. log k1 (toluene) as compared to other reported reactivity parameters in benzene or toluene have been found more sensitive to the metasubstituent effect. The regression results of the correlation of log k1 (toluene) of the acids according to the four dual substituent parameter models are statistically significant, and the best result has been obtained using Taft's model. The overall analysis reveals that metasubstituent's effect is exerted by a 65:35 pattern of its field and second‐order resonance effects. The results further demonstrate that a metasubstituent's resonance effect is virtually a relayed universal field/inductive effect. © 2011 Wiley Peiodicals, Inc. Int J Chem Kinet 43: 303–311, 2011
Removal of obstructing T‐tube and stabilization of the airway
Authors: Athavale Sanjay M. , Dang Jennifer , Rangarajan Sanjeet , Garrett Gaelyn 
Published: April 2011

AbstractAlthough they are extremely effective in maintaining tracheal and subglottic patency, T‐tubes themselves can result in airway obstruction from plugging. Many practitioners educate patients on placing a small (5.0) endotracheal tube (ETT) through the tracheal limb of the T‐tube if they develop airway obstruction. Unfortunately, this can be a difficult task to complete during acute airway obstruction. In this article, we describe a simple set of steps for rapid relief of airway obstruction and stabilization of the airway in the event of T‐tube obstruction. This method requires removal of the T‐tube with a Kelly clamp and stabilization of the airway with a tracheostomy tube. Although it is simple, we hope that this technique will prevent morbidity and mortality from acute airway obstructions related to T‐tubes.