bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐1β upregulates functional expression of neurokinin‐1 receptor (NK‐1R) via NF‐κB in astrocytes
Authors: Guo Chang‐Jiang , Douglas Steven D. , Gao Zhiyong , Wolf Bryan A. , Grinspan Judith , Lai Jian‐Ping , Riedel Eric , Ho Wen‐Zhe 
Published: June 2004

AbstractCytokines and neuropeptides are modulators of neuroimmunoregulation in the central nervous system (CNS). The interaction of these modulators may have important implications in CNS diseases. We investigated whether interleukin‐1β (IL‐1β) modulates the expression of neurokinin‐1 receptor (NK‐1R), the primary receptor for substance P (SP), a potent neuropeptide in the CNS. IL‐1β upregulated NK‐1R expression in human astroglioma cells (U87 MG) and primary rat astrocytes at both mRNA and protein levels. IL‐1β treatment of U87 MG cells and primary rat astrocytes led to an increase in cytosolic Ca2+ in response to SP stimulation, indicating that IL‐1β‐induced NK‐1R is functional. CP‐96,345, a specific non‐peptide NK‐1R antagonist, inhibited SP‐induced rise of [Ca2+]i in the astroglioma cells. Investigation of the mechanism responsible for IL‐1β action revealed that IL‐1β has the ability of activating nuclear factor‐κb (NF‐κB). Caffeic acid phenethyl ester (CAPE), a specific inhibitor of NF‐κB activation, not only abrogated IL‐1β‐induced NF‐κB promoter activation, but also blocked IL‐1β‐mediated induction of NK‐1R gene expression. These findings provide additional evidence that there is a biological interaction between IL‐1β and the neuropeptide SP in the CNS, which may have important implications in the inflammatory diseases in the CNS. © 2004 Wiley‐Liss, Inc.
Astroglial glutamine transport by system N is upregulated by glutamate
Authors: Bröer Angelika , Deitmer Joachim W. , Bröer Stefan 
Published: June 2004

AbstractRelease of glutamine from astrocytes is an essential step of the glutamate‐glutamine cycle, and hence for the maintenance of neuronal glutamate and γ‐aminobutyric acid (GABA) pools. The glutamine transporter SNAT3 (SN1) has recently been identified as one of the major mediators of glutamine efflux from astrocytes. We investigated the regulation of SNAT3 mediated glutamine transport in cultured astrocytes. Incubation of primary astrocyte cultures with physiological concentrations of glutamate resulted in a rapid, about twofold, upregulation of SNAT3‐mediated transport activity. The effect was not mediated by glutamate receptors but required uptake of glutamate into astrocytes. Both net uptake and net efflux increased after treatment of cells with glutamate, excluding an acceleration of the transport by way of an exchange mechanism. Elevated intracellular glutamate most likely reduces the Kmof SNAT3 for its substrate glutamine. The results suggest that astrocytes respond actively to the release of glutamate by increasing glutamine release and thereby may modulate glutamatergic neurotransmission. © 2004 Wiley‐Liss, Inc.
Spatiotemporal wavelet resampling for functional neuroimaging data
Authors: Breakspear Michael , Brammer Michael J. , Bullmore Ed T. , Das Pritha , Williams Leanne M. 
Published: June 2004

AbstractThe study of dynamic interdependences between brain regions is currently a very active research field. For any connectivity study, it is important to determine whether correlations between two selected brain regions are statistically significant or only chance effects due to non‐specific correlations present throughout the data. In this report, we present a wavelet‐based non‐parametric technique for testing the null hypothesis that the correlations are typical of the data set and not unique to the regions of interest. This is achieved through spatiotemporal resampling of the data in the wavelet domain. Two functional MRI data sets were analysed: (1) Data from 8 healthy human subjects viewing a checkerboard image, and (2) “Null” data obtained from 3 healthy human subjects, resting with eyes closed. It was demonstrated that constrained resampling of the data in the wavelet domain allows construction of bootstrapped data with four essential properties: (1) Spatial and temporal correlations within and between slices are preserved, (2) The irregular geometry of the intracranial images is maintained, (3) There is adequate type I error control, and (4) Expected experiment‐induced correlations are identified. The limitations and possible extensions of the proposed technique are discussed. Hum. Brain Mapp. 23:1–25, 2004. © 2004 Wiley‐Liss, Inc.
A novel DNA methyltransferase I–derived peptide eluted from soluble HLA‐A*0201 induces peptide‐specific, tumor‐directed cytotoxic T cells
Authors: Berg Martina , Barnea Eilon , Admon Arie , Zavazava Nicholas 
Published: June 2004

AbstractMHC peptides derived from tumor‐associated antigens (TAAs) can serve as the basis for the development of immunotherapeutics to treat human malignancies. Previously, we identified novel HLA‐A*0201 (HLA‐A2)–restricted peptides recovered from soluble HLA molecules secreted by human tumor cell lines, transfected with truncated genes of HLA‐A2 and HLA‐B7. Here, 4 candidate peptides eluted from soluble HLA‐A2 were selected on the basis of their precursor proteins being TAAs. Peptide p1028 (GLIEKNIEL), derived from DNA methyltransferase I (DNMT‐1), which is overexpressed in various human tumors, showed the highest affinity to HLA‐A2 and was relatively abundant in the sMHC/peptide complexes of all transfected breast, ovarian and prostate cancer cell lines. Peptide p1028‐specific CTLs were generated in vitro and shown to efficiently lyse not only target cells pulsed with the peptide but also HLA‐A2‐positive breast cancer cell lines MDA‐231 and MCF‐7. The peptide induced IFN‐γ production in CTLs, which were selectively stained by a p1028 tetramer. Since DNMT‐1 is a widely expressed tumor‐associated enzyme, the novel DNMT‐1‐derived, HLA‐A2‐restricted peptide GLIEKNIEL identified here may provide a suitable candidate for a therapeutic cancer vaccine. © 2004 Wiley‐Liss, Inc.
Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: Results from a multicenter study in India
Authors: Sankaranarayanan Rengaswamy , Chatterji Ramdas , Shastri Surendra S. , Wesley Ramani S. , Basu Partha , Mahe Cédric , Muwonge Richard , Seigneurin Daniel , Somanathan Thara , Roy Chinmoy , Kelkar Rohini , Chinoy Roshini , Dinshaw Ketayun , Mandal Ranajit , Amin Geethanjali , Goswami Smriti , Pal Smarajit , Patil Sharmila , Dhakad Namrata , Frappart Lucien , Fontaniere Bernard ,   IARC Multicenter Study Group on Cervical Cancer Prevention in India
Published: June 2004

AbstractThe knowledge that cervical neoplasia are caused by human papillomavirus (HPV) infection has led to the evaluation of its role in screening. We evaluated the accuracy of HPV testing by Hybrid capture II (HC II) method in detecting cervical intraepithelial neoplasia grade 2 and 3 (CIN 2 and 3) lesions in 4 cross‐sectional studies with common protocol and questionnaire in 3 different locations (Kolkata, Mumbai and Trivandrum) in India. These studies involved 18,085 women aged 25–65 years. The reference standard for final diagnosis was a combination of colposcopy/biopsy. All women were investigated with colposcopy and 3,116 received directed biopsy. The sensitivity of HPV testing for detecting CIN 2–3 lesions varied from 45.7% to 80.9% across the study sites; the specificity varied from 91.7% to 94.6% and the positive predictive value from 6.7% to 13.7%. Retesting of 298 randomly chosen denatured samples in France revealed an agreement rate of 85.9% and a κ‐value of 0.72. Although HPV testing seems to be a promising approach for cervical cancer prevention, a large range in sensitivity was observed in our study, possibly due to variations in the quality of specimen collection and reference standards. A higher sensitivity was associated with the center performing the test well. Further developments in terms of more reproducible, less expensive and less sophisticated testing are essential to make the test feasible and effective in low‐resource settings. © 2004 Wiley‐Liss, Inc.
Immunohistochemical investigation of SV40 large T antigen in Hodgkin and non‐Hodgkin's lymphoma
Authors: Brousset Pierre , de Araujo Valquiria , Gascoyne Randy D. 
Published: June 2004

AbstractDNA sequences from simian virus 40 (SV40) have been detected in various human tumors, including non‐Hodgkin's lymphomas (NHLs), by highly sensitive PCR techniques. However, there is a strong debate as to whether SV40 is present in lymphoma cells. Using immunohistochemistry and tissue microarrays, we investigated a series of French and Canadian cases of Hodgkin's lymphomas (HLs) and NHLs and tried to detect the SV40 large T antigen using routine paraffin sections with standard and highly sensitive catalyzed system amplification methods. None of the cases of HLs (n = 250) or NHLs (n = 232) were found to contain a single large T antigen‐positive cell, whereas 2 positive controls were repeatedly stained. Therefore, our results do not support the hypothesis that SV40 is implicated in the etiology of human lymphomas. © 2004 Wiley‐Liss, Inc.
Global gene expression profiles of human head and neck squamous carcinoma cell lines
Authors: Jeon Geoung A. , Lee Ju‐Seog , Patel Vyomesh , Gutkind J. Silvio , Thorgeirsson Snorri S. , Kim Eun Cheol , Chu In‐Sun , Amornphimoltham Panomwat , Park Myung Hee 
Published: June 2004

AbstractFor genomewide monitoring and identification of biomarkers of head and neck squamous cell carcinoma (HNSCC), we have conducted a systematic characterization of gene expression profiles, using human cDNA microarrays containing 9K clones, in 25 HNSCC cell lines and 1 immortalized human oral keratinocyte cell line. We used normal human oral keratinocytes (NHOKs) as a reference. Our study showed that genes primarily involved in cell cycle regulation, oncogenesis, cell proliferation, differentiation, apoptosis and cell adhesion were widely altered in the 26 cell lines. Upregulated genes included known oncogenes, protein kinases, DNA‐binding proteins and cell cycle regulators, while those commonly downregulated included differentiation markers, cell adhesion proteins, extracellular matrix proteins, structural proteins (keratins) and protease inhibitor proteins. Compared to NHOK, we observed a striking reduction in the expression of genes involved in terminal differentiation, suggesting that a loss in this process is an important signature of HNSCC. In addition, hierarchical clustering analysis as well as principal component analysis revealed 2 distinctive subtypes of gene expression patterns among the 26 cell lines, reflecting a degree of heterogeneity in HNSCC. By applying significance analysis of microarrays, 128 genes were selected for being distinctively expressed between the 2 groups. Genes differentially expressed in the 2 subgroups include cell proliferation‐related genes, IGFBP6, EGFR and VEGFC; tumor suppression and apoptosis‐related genes such as Tp53, Tp63; as well as cell cycle regulators such as CCND1 and CCND2 (cyclins D1 and D2), suggesting that the 2 subgroups might have undergone different pathways of carcinogenesis. Published 2004 Wiley‐Liss, Inc.
Anti‐tumor activity of a combination of plasminogen activator and captopril in a human melanoma xenograft model
Authors: de Groot‐Besseling Renate R.J. , Ruers Theo J.M. , van Kraats Annemieke A. , Poelen Geert J.M. , Ruiter Dirk J. , de Waal Robert M.W. , Westphal Johan R. 
Published: June 2004

AbstractAngiostatin, a proteolytic fragment of plasminogen consisting of the first 3 or 4 kringle domains, reduces tumor growth by specifically inhibiting tumor angiogenesis. Angiostatin is generated in vitro in a 2‐step process. First, plasminogen is converted to plasmin by plasminogen activators. Next, plasmin excises the angiostatin fragment from plasminogen, a process requiring molecules that are able to donate a free sulfhydryl group. In this study, we investigated whether stimulation of in vivo angiostatin generation by administration of plasminogen activator and a free sulfhydryl group donor (FSD) has anti‐tumor activity. First, we determined the optimal conditions for in vitro angiostatin generation by incubating murine plasma with different concentrations of plasminogen activator and/or the FSD captopril. Angiostatin generation was monitored by western blot analysis. Our results were extrapolated to the in vivo situation by administering the optimal dose of tissue‐type plasminogen activator (tPA, i.v. injection 3 times/week) and captopril (in drinking water) to mice and analyzing the presence of angiostatin in the circulation. Angiostatin was readily detectable in mice receiving both tPA and captopril, but not in mice receiving either one of the agents. Finally, the anti‐tumor activity of the tPA/captopril treatment was tested in a human melanoma xenograft model. Administration of tPA alone had only a marginal effect on tumor growth. Captopril alone reduced tumor growth by about 60%, whereas treatment with both captopril and tPA resulted in 83% inhibition of tumor growth. © 2004 Wiley‐Liss, Inc.
Vegetable, fruit and meat consumption and potential risk modifying genes in relation to colorectal cancer
Authors: Turner Faye , Smith Gillian , Sachse Christoph , Lightfoot Tracy , Garner R. Colin , Wolf C. Roland , Forman David , Bishop D. Timothy , Barrett Jennifer H. ,   on behalf of the Colorectal Cancer Study Group
Published: June 2004

AbstractEpidemiological evidence shows high red meat consumption to increase the risk of colorectal cancer, while the consumption of fruit and vegetables has been shown to be protective. Many genes have been identified that encode for enzymes involved in the metabolism of dietary carcinogens or anti‐carcinogens. A study of 500 incident colorectal cancer cases and population controls, matched for age, sex and general practitioner, was conducted in the United Kingdom to investigate whether 6 such genes (CYP1A1, GSTT1, GSTM1, GSTP1, EPHX1 and NQO1) modify the relationship between diet and disease risk. Usual diet was estimated using a detailed questionnaire administered by interview. Fruit and vegetable consumption were both found to protect against colorectal cancer, while overall meat and red meat consumption were found to increase risk. There was some evidence of interaction between GSTT1 and vegetable consumption (p=0.006, not adjusted for multiple tests) but no evidence of interaction with GSTM1. The protective effect of vegetables was only seen in those with deficient or intermediate GSTT1 predicted phenotype [OR 0.3, 95% confidence interval (0.1, 0.6), and OR 0.6 (0.4, 0.96), OR 1.4 (0.3, 2.4) for those with fast phenotype], and a similar result was observed for cruciferous vegetables. There was also weak evidence of interaction between red meat intake and GSTT1 (p=0.06), GSTP1 (p=0.16, with p=0.02 after adjustment for potential confounders) and NQO1 predicted phenotype (p=0.01). Because of the multiple hypotheses tested in our study, these findings require independent confirmation. © 2004 Wiley‐Liss, Inc.
Efficacy of transferrin‐conjugated paclitaxel‐loaded nanoparticles in a murine model of prostate cancer
Authors: Sahoo Sanjeeb K. , Ma Wenxue , Labhasetwar Vinod 
Published: June 2004

AbstractChemotherapy remains the preferred choice of treatment for prostate cancer but modest drug response and significant toxicity by conventional methods of administration limit their efficacy. In our study, we determined the efficacy of paclitaxel (Tx)‐loaded biodegradable nanoparticles (NPs) on tumor inhibition. We hypothesized that NPs following conjugation to transferrin (Tf) ligand (NPs‐Tf) would enhance the therapeutic efficacy of the encapsulated drug. The antiproliferative activity of NPs was determined in human prostate cancer cell line (PC3) and their effect on tumor inhibition in a murine model of prostate cancer. NPs (∼ 220 nm in diameter, 5.4% w/w drug loading) under in vitro conditions exhibited sustained release of the encapsulated drug (60% release in 60 days). The IC50 (concentration of drug for 50% inhibition of cell growth) of the drug with Tf‐conjugated NPs (Tx‐NPs‐Tf) was about 5‐fold lower than that with unconjugated NPs (Tx‐NPs) or drug in solution. Animals that received a single‐dose intratumoral injection of Tx‐NPs‐Tf (Tx dose = 24 mg/kg) demonstrated complete tumor regression and greater survival rate than those that received either Tx‐NPs or Tx‐Cremophor® EL formulation. In conclusion, sustained release NPs demonstrated greater antitumor activity following their conjugation to Tf ligand. © 2004 Wiley‐Liss, Inc.
Effect of tetravalent bispecific CD19×CD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells
Authors: Reusch Uwe , Le Gall Fabrice , Hensel Manfred , Moldenhauer Gerhard , Ho Anthony D. , Little Melvyn , Kipriyanov Sergey M. 
Published: June 2004

AbstractTo develop an effective antitumor immunotherapy for B‐lineage non‐Hodgkin's lymphoma, we constructed a tetravalent tandem diabody (tanDb) specific for both human CD19 (B‐cell marker) and CD3 (T‐cell antigen). Here, we report the effective killing of malignant primary B cells from patients with B‐cell chronic lymphocytic leukemia (B‐CLL) by autologous T cells induced by tanDb at very low E:T ratios. Mononuclear cells from patients with B‐CLL were cultured with bispecific antibody fragments in either the presence or absence of monospecific anti‐CD28 antibody. Use of tetravalent tanDbs caused almost quantitative elimination of malignant B cells from the blood samples of 19 patients and some cytotoxic activity in 3 of 23 analyzed cases. In contrast, the structurally similar but bivalent diabody and single‐chain diabody demonstrated nearly no antitumor activity in an autologous system. tanDb‐induced activation and proliferation of T cells occurred only in the presence of CD19+ target cells. Expression of the B7‐1 (CD80) and B7‐2 (CD86) molecules on the surface of leukemia cells made unnecessary the additional CD28‐costimulation of T cells. When only a few tanDb molecules were present, the effect of CD28 costimulation on T‐cell activation was more pronounced. Depending on the patient sample, we observed a 10‐ to 1,000‐fold decrease of the half‐maximal concentrations of tanDb for cell lysis. Upon CD28 crosslinking by agonistic MAb, specific tumor cell lysis was found at tanDb concentrations as low as 0.5 pM. These data demonstrate that the tetravalent CD19×CD3 tanDb might be a promising tool for the immunotherapy of human B‐cell leukemias and lymphomas. © 2004 Wiley‐Liss, Inc.
Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization
Authors: Keshavan Pavitra , Schwemberger Sandy J. , Smith Darcey L.H. , Babcock George F. , Zucker Stephen D. 
Published: June 2004

AbstractBilirubin is the principal end product of heme degradation. Prompted by epidemiologic analyses demonstrating an inverse correlation between serum bilirubin levels and cancer mortality, we examined the effect(s) of bilirubin on the growth and survival of colon adenocarcinoma cells. Adenocarcinoma cell monolayers were treated with bilirubin over a range of bilirubin:BSA molar ratios (0–0.6), and viability was assessed colorimetrically. Apoptosis was characterized by TUNEL assay, annexin V staining and caspase‐3 activation. The mechanism(s) by which bilirubin induces apoptosis was investigated by Western blotting for cytochrome c release, assaying for caspase‐8 and caspase‐9 activation and for mitochondrial depolarization by JC‐1 staining. The direct effect of bilirubin on the membrane potential of isolated mitochondria was evaluated using light‐scattering and fluorescence techniques. Bilirubin decreased the viability of all colon cancer cell lines tested in a dose‐dependent manner. Cells exhibited substantial apoptosis when exposed to bilirubin concentrations ranging 0–50 μM, as demonstrated by an 8‐ to 10‐fold increase in TUNEL and annexin V staining and in caspase‐3 activity. Bilirubin treatment evokes specific activation of caspase‐9, enhances cytochrome c release into the cytoplasm and triggers the mitochondrial permeability transition in colon cancer monolayers. Additionally, bilirubin directly induces the depolarization of isolated rat liver mitochondria, an effect that is not inhibited by cyclosporin A. Bilirubin stimulates apoptosis of colon adenocarcinoma cells in vitro through activation of the mitochondrial pathway, apparently by directly dissipating mitochondrial membrane potential. As this effect is triggered at concentrations normally present in the intestinal lumen, we postulate a physiologic role for bilirubin in modulating colon tumorigenesis. © 2004 Wiley‐Liss, Inc.
An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder
Authors: Chen Taiping , Jackson Chad , Costello Ben , Singer Natalie , Colligan Bruce , Douglass Larry , Pemberton Jackson , Deddens James , Graff Jeremy R. , Carter Julia H. 
Published: June 2004

AbstractTGF‐β signaling is frequently perturbed in many human cancers, including renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs) of the bladder. Genetic alterations of the TGF‐β type 1 receptor (TGFBR1) may contribute to these perturbations. We therefore examined variations in the TGFBR1 gene by PCR, SSCP and RFLP in carcinomas of the urinary system and in tissues from noncancer, age‐matched controls. A G→A variant 24 bp downstream of the exon/intron 7 boundary of the TGFBR1 gene (Int7G24A) was evident in patients with RCC (46.5%, n = 86) and bladder and upper urinary tract TCC (49.2%, n = 65) significantly more frequently than in age‐matched controls (28.3%, n = 113, p < 0.002 by χ2 test). Moreover, 8 homozygous variant carriers were found in the cancer groups, whereas not a single homozygous variant carrier was found in the control group. The Int7G24A allele (both heterozygous G/A and homozygous A/A carriers) was associated with increased RCC incidence (OR = 2.20, 95% CI 1.22–3.96) and TCC incidence (OR = 2.45, 95% CI 1.89–3.16). One somatic mutation of serine to phenylalanine at codon 57 of the TGFBR1 gene was confirmed in an upper urinary tract TCC. In conclusion, the Int7G24A variant in the TGFBR1 gene is significantly more frequent in patients with RCC and TCC than normal age‐matched controls, suggesting that it may represent a risk factor for the development of kidney and bladder carcinomas. © 2004 Wiley‐Liss, Inc.
High‐density methylation of p14ARF and p16INK4A in Epstein‐Barr virus–associated gastric carcinoma
Authors: Sakuma Kazuya , Chong Ja‐Mun , Sudo Makoto , Ushiku Tetsuo , Inoue Yoko , Shibahara Junji , Uozaki Hiroshi , Nagai Hideo , Fukayama Masashi 
Published: June 2004

AbstractPromoter hypermethylation of various tumor‐related genes is extremely frequent in gastric carcinoma (GC) associated with Epstein‐Barr virus (EBV). To investigate the significance of the promoter methylation in this type of GC, we examined the methylation densities of the promoter regions of p14ARF and p16INK4A in EBV‐associated (n = 7) and EBV‐negative (n = 14) GC. Bisulfite sequencing demonstrated a high frequency of concurrent methylation of p14ARF and p16INK4A promoter regions in EBVaGC. Methylation was observed in all 29 CpG sites of p14ARF and all 16 sites of p16INK4A with equally high densities. In EBV‐negative GC, the methylation profiles differed between the 2 genes. Promoter methylation was sporadic and variable in p14ARF, and only the last position of CpG in p14ARF was methylated at high frequency. High‐density methylation in p16INK4A was observed in a subset of GC, but the first position of CpG was never methylated in EBV‐negative GC. These findings suggest the presence of mechanisms of de novo and maintenance methylation specific to EBVaGC that might be associated with EBV infection. © 2004 Wiley‐Liss, Inc.