bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel panel of protein biomarkers for predicting response to thalidomide‐based therapy in newly diagnosed multiple myeloma patients
Authors: Rajpal Rajesh , Dowling Paul , Meiller Justine , Clarke Colin , Murphy William G. , O'Connor Robert , Kell Malcolm , Mitsiades Constantine , Richardson Paul , Anderson Kenneth C. , Clynes Martin , O'Gorman Peter 
Published: February 2011

AbstractMultiple myeloma (MM) is a heterogeneous group of disorders both genotypically and phenotypically. Response to thalidomide‐based induction therapy in newly diagnosed patients varies significantly in published clinical trials. Proteomic analysis was performed on 39 newly diagnosed MM patients treated with a thalidomide‐based regimen (22 responders; 17 non‐responders) using immunodepletion, 2‐D DIGE analysis and mass spectrometry. Zinc‐α‐2‐glycoprotein (ZAG), vitamin D‐binding protein (VDB), serum amyloid‐A protein (SAA) and β‐2‐microglobulin (B2M) had statistically significant higher concentrations in non‐responders compared to responders, while haptoglobin (Hp) had a lower concentration. ELISAs were used to validate the candidate protein biomarkers using unfractionated serum from 51 newly diagnosed MM patients (29 responders; 22 non‐responders). Using logistic regression, the best possible area under the curve (AUC) was 0.96 using ZAG, VDB and SAA in combination. Leave‐one‐out‐cross‐validation (LOOCV) indicated an overall predictive accuracy of 84% with associated sensitivity and specificity values of 81.8 and 86.2%, respectively. Subsequently, 16 of 22 thalidomide‐refractory patients successfully achieved complete response or very good partial response using second‐line treatment suggesting that the biomarker profile is specific to thalidomide response rather than identifying patients with MM refractory to all therapies. Using a novel panel of predictive biomarkers, the feasibility of predicting response to thalidomide‐based therapy in previously untreated MM has been demonstrated.
Proteomic analysis of heterosis during maize seed germination
Authors: Fu Zhiyuan , Jin Xining , Ding Dong , Li Yongling , Fu Zhongjun , Tang Jihua 
Published: February 2011

AbstractHeterosis is observed for most phenotypic traits and developmental stages in many plants. In this study, the embryos, from germinating seeds after 24 h of soaking, for five elite maize hybrids and their parents were selected to unravel the genetic basis of heterosis using 2‐D proteomic method. In total, 257 (80.06%), 363 (58.74%), 351 (79.95%), 242 (54.50%), and 244 (46.30%) nonadditively expressed proteins were identified in hybrids Zhengdan 958, Nongda 108, Yuyu 22, Xundan 20, and Xundan 18, respectively. The nonadditive proteins were divided into above high‐parent (++; 811, 55.66%), high‐parent (+; 121, 8.30%), partial dominance (+−; 249, 17.09%), low‐parent (−; 30, 2.06%), below low‐parent (− −; 62, 4.26%), and D (different; 184, 12.63%) expression patterns. The observed patterns indicate the important roles of dominance, partial dominance, and overdominance in regulating seed germination in maize. Additionally, 54 different proteins were identified by mass spectrometry and classified into nine functional groups: metabolism (9), cell detoxification (8), unknown functional proteins (8), chaperones (7), signal transduction (6), development process (5), other (5), transporter (3), and stress response (3). Of these, the most interesting are those involved with germination‐related hormone signal transduction and the abscisic acid and gibberellin regulation networks.
Clarifying the signal network of salvianolic acid B using proteomic assay and bioinformatic analysis
Authors: Feng Li‐Xing , Jing Chun‐Jie , Tang Kai‐Lin , Tao Lin , Cao Zhi‐Wei , Wu Wan‐Ying , Guan Shu‐Hong , Jiang Bao‐Hong , Yang Min , Liu Xuan , Guo De‐An 
Published: February 2011

AbstractSalvianolic acid B (SB) is a natural compound with protective effect against ischemia–reperfusion heart injury. However, the signal network of SB including both direct target proteins and downstream signal‐related proteins has not been clarified. In the present study, epidermal growth factor receptor (EGFR) was predicted to be the most possible direct protein target of SB by INVDOCK, a ligand–protein inverse‐docking algorithm. Possible signal‐related proteins of SB in H9C2 cells, including both under normal condition and under ischemia–reperfusion injury, were searched using 2‐DE analysis. Totally, 14 signal‐related proteins were found. Finally, signal network from EGFR to the signal‐related proteins was established using bioinformatic analysis. Interestingly, 9 of the 14 signal‐related proteins could be included in a network together with EGFR through direct interaction or only one intermediate partner. The signal cascade from EGFR to heat shock protein 27 (HSP27) and mitofilin (IMMT, inner membrane mitochondrial protein) might be the most important cascade. The signal network was certified by measuring the binding affinity of SB to EGFR in vitro, the effect of SB on internalization and phosphorylation of EGFR, the effect of SB on viability and proliferation of H9C2 cells, and the expression of inner membrane mitochondrial protein in the presence of EGFR inhibitor AG 1478.
Proteomic profiling of birch (Betula verrucosa) pollen extracts from different origins
Authors: Erler Anja , Hawranek Thomas , Krückemeier Leif , Asam Claudia , Egger Matthias , Ferreira Fátima , Briza Peter 
Published: February 2011

AbstractPollen of the European white birch is a major source of spring pollinosis in Europe. Pollen‐allergy diagnosis and treatment by specific immunotherapy commonly rely on extracts of natural origin. To gain insight into the protein content and its variability, we evaluated the profile of allergenic and non‐allergenic proteins in extracts of pollen from different origins by MS‐based proteomics. Aqueous extracts prepared from commercially available Swedish birch pollen, pollen collected from Austrian trees and a commercial skin prick extract were analyzed by 1‐DE, 2‐DE, immunoblotting and mass spectrometry, resulting in a complete inventory of extractable, disease‐relevant pollen proteins. A main focus of this study was on the isoform distribution of Bet v 1, the major allergen of birch pollen. Using a combination of intact mass determination and peptide sequencing, five isoforms (a, b, d, f and j) were unequivocally identified in Swedish and Austrian birch pollen extracts, while the skin prick extract contained only isoforms a, b and d. Using the same methods as for Bet v 1, divergencies in the sequence of birch profilin (Bet v 2), a plant panallergen, were solved. The molecular characterization of pollen extracts is relevant for standardization and development of new reagents for specific immunotherapy.
2‐D gel electrophoresis‐based proteomic analysis reveals that ormeloxifen induces G0–G1 growth arrest and ERK‐mediated apoptosis in chronic myeloid leukemia cells K562
Authors: Pal Pooja , Kanaujiya Jitendra K. , Lochab Savita , Tripathi Shashi B. , Bhatt Madan L. B. , Singh Pradhyumna K. , Sanyal Sabyasachi , Trivedi Arun K. 
Published: February 2011

AbstractOrmeloxifen is a nonsteroidal selective estrogen receptor modulator (SERM) and has been shown to possess anticancer activities in breast and uterine cancer. Here, we show that ormeloxifen induces apoptosis in dose‐dependent manner in a variety of leukemia cells, more strikingly in K562. 2‐DE‐gel electrophoresis of K562 cells induced with ormeloxifen showed that 57 and 30% of proteins belong to apoptosis and cell‐cycle pathways, respectively. Our data demonstrate that ormeloxifen‐induced apoptosis in K562 cells involves activation of extracellular signal‐regulated kinases (ERKs) and subsequent cytochrome c release, leading to mitochondria‐mediated caspase‐3 activation. Ormeloxifen‐induced apoptosis via ERK activation was drastically inhibited by prior treatment of K562 cells with ERK inhibitor PD98059. Ormeloxifen also inhibits proliferation of K562 cells by blocking them in G0–G1 phase by inhibiting c‐myc promoter via ormeloxifen‐induced MBP‐1 (c‐myc promoter‐binding protein) and upregulation of p21 expression. We further show that ormeloxifen‐induced apoptosis in K562 is translatable to mononuclear cells isolated from chronic myeloid leukemia (CML) patients. Thus, ormeloxifen induces apoptosis in K562 cells via phosphorylation of ERK and arrests them in G0–G1 phase by reciprocal regulation of p21 and c‐myc. Therefore, inclusion of ormeloxifen in the therapy of chronic myeloid leukemia can be of potential utility.
Characterization of Dielectric Barrier Discharge (DBD) on Mouse and Histological Evaluation of the Plasma‐Treated Tissue
Authors: Rajasekaran Priyadarshini , Opländer Christian , Hoffmeister Dennis , Bibinov Nikita , Suschek Christoph Viktor , Wandke Dirk , Awakowicz Peter 
Published: February 2011

AbstractAtmospheric‐pressure dielectric barrier discharge (DBD) in air is investigated for medical applications, especially for skin treatment. When the DBD was tested on mouse skin, a homogeneous discharge accompanied by filamentary microdischarges is observed. For characterization of the homogeneous discharge, averaged plasma parameters (namely electron density and electron velocity distribution function) and gas temperature are determined by optical emission spectroscopy, microphotography and numerical simulation. Chemical kinetics in the active plasma volume and in the afterglow is simulated. Fluxes of biologically useful molecules like nitric oxide (NO) and ozone reaching the treated surface and irradiation by UV photons are determined. Skin biopsy results show that DBD treatment causes no inflammation and no changes in the skin‐collagen.
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Assembly of Standardized Test Specimen for Microbial Quantification of Plasma Sterilization Processes of Fine PTFE Tubes as Used in Thermo Sensitive Medical Devices Like Flexible Endoscopes
Authors: Maucher Tanja , Schnabel Uta , Volkwein Wolfram , Köhnlein Johanna , Winter Jörn , Weltmann Klaus‐Dieter , Trick Iris , Oehr Christian 
Published: February 2011

AbstractFine PTFE tubes are used in high‐end and high cost devices like flexible Endoscopes where no standard sterilization procedure like autoclaving applies due to material properties. The study of innovative decontamination processes like plasma sterilization request appropriate analysis methods in order to verify the process functionality. In a related research project the IGB‐cycle‐method for contamination and recovery of indicator organisms like Bacillus atrophaeus spores was developed. It was possible to proof the IGB‐cycle‐method to be reproducible and reliable using round robin tests between three laboratories that compared their results in reference to a relevant level of contamination and recovery. Of a relevant contamination more than 7 log10 steps of cfu/specimen could be recovered from the tube surface.
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TGF‐β1‐induced EMT of non‐transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug
Authors: Slabáková Eva , Pernicová Zuzana , Slavíčková Eva , Staršíchová Andrea , Kozubík Alois , Souček Karel 
Published: February 2011

AbstractBACKGROUNDEpithelial–mesenchymal transition (EMT) underlying cancer cell invasion and metastasis has been thoroughly studied in prostate cancer. Although EMT markers have been clinically observed in benign prostate hyperplasia, molecular events underlying the onset and progression of EMT in benign prostate cells have not been described.METHODSEMT in BPH‐1 cells was induced by TGF‐β1 treatment and the kinetics of expression of EMT markers, regulators, and selected miRNAs was assessed by western blotting and quantitative RT‐PCR.RESULTSEMT in BPH‐1 cells was accompanied by rapid up‐regulation of SNAI2/Slug and ZEB1 transcription factors, while changes in expression levels of ZEB2 and miR‐200 family members were observed after extended time intervals. Invasive phenotype with EMT hallmarks, characterizing tumorigenic clones derived from BPH‐1 cells, was associated with increased mRNA levels of SNAI2, ZEB1, and ZEB2, but was not associated with significant changes in basal levels of miR‐200 family members. RNA interference revealed that SNAI2/Slug is crucial for TGF‐β1‐induced vimentin up‐regulation and migration of BPH‐1 cells.CONCLUSIONSThis study suggests that in BPH‐1 cells the transcription factor SNAI2/Slug is important for EMT initiation, while the ZEB family of transcription factors in cooperation with the miR‐200 family may oppose the reversal of the EMT phenotype. Prostate 71:1332–1343, 2011. © 2011 Wiley‐Liss, Inc.
Prostate tumor cells with cancer progenitor properties have high telomerase activity and are rapidly killed by telomerase interference
Authors: Xu Tong , He Kaijie , Wang Lina , Goldkorn Amir 
Published: February 2011

AbstractBACKGROUNDCancer progenitor cells (CPCs) have been postulated to promote treatment resistance and disease progression in prostate and other malignancies. We investigated whether the enzyme telomerase, which is active in cancer cells and in normal stem cells, plays an important role in CPC which can be exploited to neutralize these cells.METHODSWe used flow cytometry and assays of gene expression, clonogenicity, and invasiveness to isolate and characterize a putative CPC subpopulation from freshly resected human prostatectomy specimens. Telomerase activity was measured by qPCR‐based Telomeric Repeat Amplification Protocol (TRAP). Telomerase interference was achieved by ectopic expression of a mutated telomerase RNA construct which reprograms telomerase to generate “toxic” uncapped telomeres. Treated cells were assayed for apoptosis, proliferation in culture, and xenograft tumor formation.RESULTSCPC in prostate tumors expressed elevated levels of genes associated with a progenitor phenotype and were highly clonogenic and invasive. Significantly, CPC telomerase activity was 20‐ to 200‐fold higher than in non‐CPC from the same tumors, and CPC were exquisitely sensitive to telomerase interference which induced rapid apoptosis and growth inhibition. Similarly, induction of telomerase interference in highly tumorigenic CPC isolated from a prostate cancer cell line abrogated their ability to form tumor xenografts.CONCLUSIONSHuman prostate tumors contain a CPC subpopulation with markedly elevated telomerase activity which renders them acutely susceptible to telomerase interference. These findings offer the first tumor‐derived and in vivo evidence that telomerase may constitute a CPC “Achilles heel” which may ultimately form the basis for more effective new CPC‐targeting therapies. Prostate 71:1390–1400, 2011. © 2011 Wiley‐Liss, Inc.
Antiandrogenic and growth inhibitory effects of ring‐substituted analogs of 3,3′‐diindolylmethane (Ring‐DIMs) in hormone‐responsive LNCaP human prostate cancer cells
Authors: Abdelbaqi Khalil , Lack Nathan , Guns Emma Tomlinson , Kotha Leela , Safe Stephen , Sanderson J. Thomas 
Published: February 2011

AbstractBACKGROUNDCruciferous vegetables protect against prostate cancer. Indole‐3‐carbinol (I3C) and its major metabolite 3,3′‐diindolylmethane (DIM), exhibit antitumor activities in vitro and in vivo. Several synthetic ring‐substituted dihaloDIMs (ring‐DIMs) appear to have increased anticancer activity.METHODSInhibition of LNCaP prostate cancer cell growth was measured by a WST‐1 cell viability assay. Cytoplasmic and nuclear proteins were analyzed by immunoblotting and immunofluorescence. Androgen receptor (AR) activation was assessed by measuring prostate‐specific antigen (PSA) expression and using LNCaP cells containing human AR and an AR‐dependent probasin promoter‐green fluorescent protein (GFP) construct.RESULTSLike DIM, several ring‐substituted dihaloDIM analogs, namely 4,4′‐dibromo‐, 4,4′‐dichloro‐, 7,7′‐dibromo‐, and 7,7′‐dichloroDIM, significantly inhibited DHT‐stimulated growth of LNCaP cells at concentrations ≥1 µM. We observed structure‐dependent differences for the effects of the ring‐DIMs on AR expression, nuclear AR accumulation and PSA levels in LNCaP cells after 24 hr. Both 4,4′‐ and 7,7′‐dibromoDIM decreased AR protein and mRNA levels, whereas 4,4′‐ and 7,7′‐dichloroDIM had minimal effect. All four dihaloDIMs (10 and 30 µM) significantly decreased PSA protein and mRNA levels. Immuofluorescence studies showed that only the dibromoDIMs increased nuclear localization of AR. All ring‐DIMs caused a concentration‐dependent decrease in fluorescence induced by the synthetic androgen R1881 in LNCaP cells transfected with wild‐type human AR and an androgen‐responsive probasin promoter‐GFP gene construct, with potencies up to 10‐fold greater than that of DIM.CONCLUSIONThe antiandrogenic effects of ring‐DIMs suggest they may form the basis for the development of novel agents against hormone‐sensitive prostate cancer, alone or in combination with other drugs. Prostate 71:1401–1412, 2011. © 2011 Wiley‐Liss, Inc.
The expression of tousled kinases in CaP cell lines and its relation to radiation response and DSB repair
Authors: Ronald Sharon , Sunavala‐Dossabhoy Gulshan , Adams Lisa , Williams Briana , De Benedetti Arrigo 
Published: February 2011

AbstractBACKGROUNDThe Tousled‐like kinases (TLKs) function in processes of chromatin assembly, including replication, transcription, repair, and chromosome segregation. TLK1/1B interacts specifically with the chromatin assembly factor Asf1, a histone H3‐H4 chaperone, and with Rad9, a protein involved in DNA repair, and these interactions are believed to be responsible for the action of TLKs in double‐strand break repair and radioprotection.METHODSWestern blotting and RT‐PCR were used to analyze the expression of TLK1, TLK1B, and TLK2 in a panel of prostate cancer (CaP) cell lines. The pattern of radiotolerance in the cell lines was analyzed in parallel. DU145 and PC‐3 cells were also probed with assays utilizing transfected plasmids that could be cleaved in vivo with adeno‐expressed HO nuclease to assess the potential contribution of TLK1/1B in DSB repair.RESULTSThis is the first report of TLKs' expression in a panel of CaP cell lines and their relationship to radioresistance. Furthermore, expression of TLK1B in non‐expressing PC‐3 cells rendered them highly resistant to radiation, and conversely, knockdown to TLK1/1B in expressing DU145 reduced their radiotolerance.CONCLUSIONSTLKs appear to be intimately linked to the pattern of resistance to DNA damage, and specifically DSBs, a finding that was not reported before for any cell lines, and certainly not systematically for human prostate cell lines. Prostate 71:1367–1373, 2011. © 2011 Wiley‐Liss, Inc.
Blockade of transforming growth factor‐beta (TGFβ) signaling inhibits osteoblastic tumorigenesis by a novel human prostate cancer cell line
Authors: Mishra Sweta , Tang Yuping , Wang Long , deGraffenried Linda , Yeh I‐Tien , Werner Sherry , Troyer Dean , Copland John A. , Sun Lu‐Zhe 
Published: February 2011

AbstractBACKGROUNDThe skeleton is the most common site of prostate cancer metastasis, which often results in osteoblastic lesions. The role of transforming growth factor‐beta (TGFβ) signaling in prostate cancer‐induced osteoblastic metastasis is not clear. We investigated the role of TGFβ signaling in prostate cancer‐induced bone metastasis using a novel human prostate cancer cell line, PacMetUT1.METHODSWe injected PacMetUT1/Luc‐GFP cells in male nude mice by intracardiac and intratibia injections and then investigated the effect of TGFβ signaling abrogation on osteoblastic tumor growth and incidence in vivo by using fluorescence and bioluminescence imaging analysis and quantifying bone and tumor volume by histomorphometry analysis. Osteoclasts were counted using TRAP assay.RESULTSOsteoblastic bone metastasis in skull, rib, and femur was detected after 10–16 weeks of intracardiac injection of the PacMetUT1 cells. Stable knockdown of TGFβ1 with an shRNA resulted in decreased tumor incidence and bone formation when the cells were directly injected into the tibiae. Systemic administration of either a small inhibitor of TGFβ type I receptor kinase or a pan TGFβ binding protein (BGERII) also decreased bone tumor growth and osteoblastic bone formation in vivo after 7 weeks of treatment.CONCLUSIONSOur results for the first time indicate that blockade of TGFβ signaling in the PacMetUT1 model significantly inhibits osteoblastic bone formation and tumor incidence. Thus, TGFβ signaling pathway may be a viable target for the prevention and treatment of prostate cancer‐induced bone metastasis. Prostate 71:1441–1454, 2011. © 2011 Wiley‐Liss, Inc.
Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4‐hydroxy‐tamoxifen in prostatic cancer cell lines
Authors: Barboro Paola , Repaci Erica , Ferrari Nicoletta , Rubagotti Alessandra , Boccardo Francesco , Balbi Cecilia 
Published: February 2011

AbstractBACKGROUNDBicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50% of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4‐hydroxy‐tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma.METHODSNM proteins were analyzed by two‐dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation.RESULTSProteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment.CONCLUSIONThis study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor. Prostate 71:1466–1479, 2011. © 2011 Wiley‐Liss, Inc.