bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of pre‐mRNA splicing in cancer
Authors: Kalnin̨a Zane , Zayakin Pawel , Silin̨a Kariīna , Linē Aija 
Published: January 2005

AbstractRecent genomewide analyses of alternative splicing (AS) indicate that up to 70% of human genes may have alternative splice forms, suggesting that AS together with various posttranslational modifications plays a major role in the production of proteome complexity. Splice‐site selection under normal physiological conditions is regulated in the developmental stage in a tissue type‐specific manner by changing the concentrations and the activity of splicing regulatory proteins. Whereas spliceosomal errors resulting in the production of aberrant transcripts rarely occur in normal cells, they seem to be an intrinsic property of cancer cells. Changes in splice‐site selection have been observed in various types of cancer and may affect genes implicated in tumor progression (for example, CD44, MDM2, and FHIT) and in susceptibility to cancer (for example, BRCA1 and APC). Splicing defects can arise from inherited or somatic mutations in cis‐acting regulatory elements (splice donor, acceptor and branch sites, and exonic and intronic splicing enhancers and silencers) or variations in the composition, concentration, localization, and activity of regulatory proteins. This may lead to altered efficiency of splice‐site recognition, resulting in overexpression or down‐regulation of certain splice variants, a switch in splice‐site usage, or failure to recognize splice sites correctly, resulting in cancer‐specific splice forms. At least in some cases, changes in splicing have been shown to play a functionally significant role in tumorigenesis, either by inactivating tumor suppressors or by gain of function of proteins promoting tumor development. Moreover, cancer‐specific splicing events may generate novel epitopes that can be recognized by the host's immune system as cancer specific and may serve as targets for immunotherapy. Thus, the identification of cancer‐specific splice forms provides a novel source for the discovery of diagnostic or prognostic biomarkers and tumor antigens suitable as targets for therapeutic intervention. © 2005 Wiley‐Liss, Inc.
Bile acid deoxycholate induces differential subcellular localisation of the PKC isoenzymes β1, ϵ and δ in colonic epithelial cells in a sodium butyrate insensitive manner
Authors: Looby Eileen , Long Aideen , Kelleher Dermot , Volkov Yuri 
Published: January 2005

AbstractElevated levels of bile acids have been implicated in the abnormal morphogenesis of the colonic epithelium thus contributing to colorectal cancer (CRC). Alternatively sodium butyrate (NaB) produced by anaerobic fermentation of dietary fibre is regarded as being protective against colon cancer. Bile acids such as deoxycholic acid (DCA) are thought to mediate some of their actions by differentially activating protein kinase C (PKC). We examined the effects of DCA on the subcellular localisation of PKC‐β1, ‐ϵ and ‐δ and whether these responses could be modulated by NaB. HCT116 cells endogenously express PKC‐ϵ and ‐δ but not PKC‐β. DCA treatment results in endogenous PKC‐ϵ translocation but not PKC‐δ after 1 hr. To study the subcellular localisation of PKC isoforms in response to DCA in real time, PKC‐β1, PKC‐ϵ and PKC‐δ functionally intact green fluorescent protein (GFP) fusion constructs were used. Stimulation with 300 μM DCA induces rapid translocation of PKC‐β1‐GFP and PKC‐ϵ‐GFP but not PKC‐δ‐GFP from the cytosol to the plasma membrane in 15 min. Interestingly, pretreatment with 4mM NaB does not modify the response of the PKC isoenzymes to DCA as PKC‐β1‐GFP and PKC‐ϵ‐GFP translocates to the plasma membrane in 15 min whereas PKC‐δ‐GFP localisation remains unaltered. Immunofluorescence shows that PKC‐β1‐GFP and PKC‐ϵ‐GFP cells treated with DCA colocalise with the cytoskeletal elements actin and tubulin adjacent to the plasma membrane. Our findings demonstrate that the differential activation of the PKC isoenzymes by DCA may be of critical importance for the functional responses of colonic epithelial cells. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html © 2004 Wiley‐Liss, Inc.
Risk factors of incident melanocytic nevi: A longitudinal study in a cohort of 1,232 young German children
Authors: Bauer Jürgen , Büttner Petra , Wiecker Tine Sander , Luther Heike , Garbe Claus 
Published: January 2005

AbstractThe number of melanocytic nevi is the most important independent risk factor for cutaneous melanoma. Aim of our study was to add information to the controversial discussion on the role of chronic‐moderate and intermittent‐high sun exposure and sunburns for the development of melanocytic nevi by the use of a large longitudinal study. A longitudinal study with a 3‐year follow‐up was conducted in 1,232 young children 2–7 years of age attending 78 public nursery schools in Bochum and Stuttgart, Germany. Total body nevus counts, assessment of pigmentary features and nevus counts on arms of parents were carried out. Parents underwent a standardized interview concerning sun exposure, sunburns and sun‐protective behavior. Applying multiple linear regression analysis higher numbers of incident nevi were associated with host factors like light skin complexion (skin Type II vs. IV, p = 0.022) and freckling of the face (p < 0.001), with parental factors like nevus counts on mothers' (p < 0.001) and fathers' (p = 0.004) arms and at least one parent being of German descent (p = 0.006), and with environmental factors like intermittent‐high sun exposure during holidays (p < 0.001) and chronic‐moderate ultraviolet radiation at home (p = 0.007). Sunburns were a significant risk factor for nevus development (p = 0.005). Total cumulative sun exposure seems to be the crucial environmental risk factor for the development of nevi, whether the child is exposed to chronic‐moderate or intermittent‐high ultraviolet light doses. Public health education should focus primarily on avoiding sun exposure especially in children with fair skin and parents with high nevus counts. © 2004 Wiley‐Liss, Inc.
V3 versican isoform expression alters the phenotype of melanoma cells and their tumorigenic potential
Authors: Serra Montserrat , Miquel Laia , Domenzain Clelia , Docampo María José , Fabra Angels , Wight Thomas N. , Bassols Anna 
Published: January 2005

AbstractVersican is a large chondroitin sulfate proteoglycan produced by several tumor cell types, including malignant melanoma. The expression of increased amounts of versican in the extracellular matrix may play a role in tumor cell growth, adhesion and migration. We have expressed the V3 isoform of versican in human and canine melanoma cell lines. Retroviral overexpression of V3 did not change the morphology of any of the cell lines but markedly reduces cell growth in the V3 versican expressing melanoma cells. The V3‐overexpressing melanoma cells retain their diminished growth potential in vivo because primary tumors arising from these cell lines growth more slowly than their vector only counterparts. This effect was accompanied by increases in cell adhesion on hyaluronan and an enhanced ability to migrate on hyaluronan‐coated transwell chambers. This enhanced migration is blocked when cells are preincubated with soluble hyaluronan, or anti‐CD44 antibodies, suggesting that V3 acts by altering the hyaluronan‐CD44 interaction. Hyaluronan content and CD44 expression are not altered in V3‐overexpressing cells compared to vector‐transduced cells. Our results show that V3 overproduction modulates the in vitro behavior of human and canine melanoma cell lines and reduces their tumorigenicity in vivo. © 2004 Wiley‐Liss, Inc.
Smoking and the risk of endometrial cancer: Results from the Nurses' Health Study
Authors: Viswanathan Akila N. , Feskanich Diane , De Vivo Immaculata , Hunter David J. , Barbieri Robert L. , Rosner Bernard , Colditz Graham A. , Hankinson Susan E. 
Published: January 2005

AbstractAn inverse association between smoking and endometrial cancer has generally been observed, primarily among current smokers. To assess this association, we analyzed data from the prospective Nurses' Health Study. From 1976 to 2000, 702 cases of invasive endometrial cancer were identified during 1.8 million person‐years of follow‐up. Smoking status was assessed in 1976 and updated every 2 years. Cox proportional hazards models were used to calculate multivariate relative risks (RRs), controlling for endometrial cancer risk factors. Compared to never smokers, the multivariate RR of endometrial cancer was significantly lower among both current smokers (RR = 0.63; 95% CI = 0.50–0.79) and past smokers (RR = 0.73; 95% CI = 0.62–0.87). When additionally adjusting for body mass index (BMI), the RR for current smokers was attenuated (RR = 0.72; 95% CI = 0.57–0.90), but the RR for past smokers did not change. Risk was lower among women who smoked 35 or more cigarettes a day (RR = 0.60; 95% CI = 0.39–0.91) and among those who smoked for 40 or more years (RR = 0.63; 95% CI = 0.45–0.87). Tests for trend, which excluded never smokers, were not statistically significant for any of the smoking variables analyzed. These data indicate that both current and past smoking are associated with a lower risk of endometrial cancer. The findings provide insight into disease etiology and suggest that the influence of smoking on endometrial cancer risk occurs even in early adulthood, is long‐lasting, and may not be attributed solely to short‐term hormonal modulation. © 2004 Wiley‐Liss, Inc.
Novel murine B‐cell lymphoma/leukemia model to study BCL2‐driven oncogenesis
Authors: Meijerink Jules P.P. , Van Lieshout Esther M.M. , Beverloo H. Berna , Van Drunen Ellen , Mensink Ewald J.B.M. , Macville Merryn , Pieters Rob 
Published: January 2005

AbstractThe BCL‐2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non‐Hodgkin lymphoma and B‐cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2‐enforced leukemogenesis, we developed a murine B‐cell lymphoma/leukemia model based on the IL‐3‐dependent Balb/C pro‐B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL‐2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL‐2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL‐2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL‐3‐responsive leukemia. Cellular transformation was independent of alterations in c‐Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2‐enforced lymphoma/leukemogenesis. © 2004 Wiley‐Liss, Inc.
CXCR3‐positive B cells found at elevated frequency in the peripheral blood of patients with MALT lymphoma are attracted by MIG and belong to the lymphoma clone
Authors: Suefuji Hiroaki , Ohshima Koichi , Karube Kennosuke , Kawano Riko , Nabeshima Kazuki , Suzumiya Junnji , Hayabuchi Naofumi , Kikuchi Masahiro 
Published: January 2005

AbstractChemokine receptors mediate the migration of lymphocytes through binding of their ligands. CXCR3 is expressed in Th1 T cells; however, CXCR3 was recently reported in B‐cell mucosa‐associated lymphoid tissue (MALT)‐type lymphoma and splenic marginal zone lymphoma. To investigate whether CXCR3‐positive B lymphocytes in peripheral blood (PB) migrate to MALT and spleen, and whether the lymphoma clone is present in PB, we studied 16 cases of MALT lymphoma. In MALT cases, CXCR3‐positive B lymphocytes in PB could migrate to MIG, the CXCR3 ligand. Immunohistochemical analysis showed that MALT lymphoma cells expressed CXCR3, whereas epithelial glands and/or stromal cells expressed MIG. In the PCR analysis for VH gene rearrangements, MALT lymphoma showed monoclonal or oligoclonal bands. In addition, in 8 of 16 MALT cases, the VH gene rearrangement of MALT lymphoma had the same bands as the CXCR3‐positive B lymphocytes in PB. In 4 cases, the same clones of DNA sequences were confirmed in MALT lymphoma and CXCR3‐positive B lymphocytes of PB. The findings support the theory that CXCR3‐positive B lymphocytes in PB of MALT patients belong to the lymphoma clone and migrate to MIG‐expressing mucosa‐associated lymphoid tissue. It seemed to be associated with the dissemination of MALT lymphoma. © 2004 Wiley‐Liss, Inc.
Early diagnosis of breast cancer by hair diffraction
Authors: James Veronica , Corino Gary , Robertson Terry , Dutton Nichole , Halas Danka , Boyd Alexandra , Bentel Jacqueline , Papadimitriou John 
Published: January 2005

AbstractA correlation between the incidence of breast cancer and an observed change in the X‐ray diffraction pattern of hair from the afflicted individuals was first reported in 1999. Since that time, over 500 hair samples have been analyzed in double‐blinded breast cancer studies with no false negatives being detected. To correlate this observed change with the presence of breast cancer, we examined whiskers removed from nude mice prior to and 8 weeks after subcutaneous implantation of a human breast cancer cell line. Here we show that the change observed in human hair was also evident in whiskers and that it appeared soon after cancer cell implantation. © 2004 Wiley‐Liss, Inc.
Anti‐tumor efficacy of the nucleoside analog 1‐(2‐deoxy‐2‐fluoro‐4‐thio‐β‐D‐arabinofuranosyl) cytosine (4′‐thio‐FAC) in human pancreatic and ovarian tumor xenograft models
Authors: Zajchowski Deborah A. , Biroc Sandra L. , Liu Hsaio‐Lai , Chesney Steven K. , Hoffmann Jens , Bauman John , Kirkland Thomas , Subramanyam Babu , Shen Jun , Ho Elena , Tseng Jih‐Lie , Dinter Harald 
Published: January 2005

Abstract1‐(2‐Deoxy‐2‐fluoro‐4‐thio‐β‐D‐arabinofuranosyl) cytosine (4′‐thio‐FAC) is a deoxycytidine analog that has been shown previously to have impressive anti‐proliferative and cytotoxic effects in vitro and in vivo toward colorectal and gastric tumors. In our present studies, the pharmacokinetic behavior in nude mice and the effectiveness of 4′‐thio‐FAC against human pancreatic and ovarian tumor growth were assessed in comparison with standard chemotherapeutic agents. Potent in vitro anti‐proliferative effects were observed against pancreatic (Capan‐1, MIA‐PaCa‐2, BxPC‐3) and ovarian (SK‐OV‐3, OVCAR‐3, ES‐2) cancer cell lines with IC50 of 0.01–0.2 μM. In vivo anti‐tumor activity was evaluated in nude mice bearing subcutaneously (s.c.) implanted human pancreatic tumor xenografts or intraperitoneally (i.p.) disseminated human ovarian xenografted tumors. Oral daily administration of 4′‐thio‐FAC for 8–10 days significantly inhibited the growth of gemcitabine‐resistant BxPC‐3 pancreatic tumors and induced regression of gemcitabine‐refractory Capan‐1 tumors. 4′‐Thio‐FAC was also a highly effective inhibitor of ovarian peritoneal carcinomatosis. In the SK‐OV‐3 and ES‐2 ovarian cancer models, 4′‐thio‐FAC prolonged survival to a greater extent than that observed with gemcitabine. Furthermore, the superiority of 4′‐thio‐FAC to carboplatin and paclitaxel was demonstrated in the ES‐2 clear cell ovarian carcinoma model. Studies provide evidence that 4′‐thio‐FAC is a promising new alternative to gemcitabine and other chemotherapeutic drugs in the treatment of a variety of tumor indications, including pancreatic and ovarian carcinoma. © 2004 Wiley‐Liss, Inc.
Characterization of dinitroporphyrin zinc complexes by electrospray ionization tandem mass spectrometry. Unusual fragmentations of β‐(1,3‐dinitroalkyl) porphyrins
Authors: Silva E. M. P. , Domingues M. R. M. , Barros C. , Faustino M. A. F. , Tomé J. P. C. , Neves M. G. P. M. S. , Tomé A. C. , Santana‐Marques M. G. , Cavaleiro J. A. S. , Ferrer‐Correia A. J. 
Published: January 2005

AbstractThe zinc complexes of diaryl bis(p‐nitrophenyl)porphyrins and β‐(1,3‐dinitroalkyl)tetraphenylporphyrins were studied by electrospray ionization (ESI) tandem mass spectrometry (MS/MS). All porphyrins showed the protonated molecule under ESI conditions. The protonated molecules were induced to fragment and the corresponding ESI tandem mass spectra were analysed. Porphyrins with two p‐nitrophenyl groups showed, as expected, characteristic fragmentations including either loss of one nitro group, as the major fragment of the tandem mass spectra, and loss of both nitro groups. In contrast, MS/MS of the β‐(1,3‐dinitroalkyl)porphyrins provided interesting and unexpected results such as the absence (or in insignificant abundance) of the ions formed by loss of one nitro group. However, these porphyrins show an abundant fragment due to combined loss of the two nitro groups. Also, the typical β‐cleavage of the alkyl chain is not observed per se, only when combined with loss of HNO2 or •NO2. Instead, α‐cleavage, with loss of the β‐pyrrolic substituent, is the most favourable process. Copyright © 2005 John Wiley & Sons, Ltd.
Optimized high power laser mirror design for low quality degradation and beam analysis
Authors: Ach F , Viöl W 
Published: January 2005

The thermally induced deformation of different copper
mirrors for infrared laser beams was simulated using a finite
element method. The deformation is highly dependent on the mirror
design. Several mirror designs with different cooling arrangements
have been simulated.
A mirror design with a set of
straight cooling channels and a stiff body shows the least
deformation. The cooling channel diameter, spacing, surface
distance and overall mirror thickness were varied at this design
and the surface deformation was compared. The mirror design not
only influences the overall expansion of the mirror but also the
shape of the surface deformation.
The optimized mirror
geometry provides small quality degradation at beam guidance and
the possibility of an online beam monitoring method by measurement
of the local surface deformation. The method can serve as a device
for online and beam position detection.
Long‐term botulinum toxin efficacy, safety, and immunogenicity
Authors: Mejia Nicte I. , Vuong Kevin Dat , Jankovic Joseph 
Published: January 2005

AbstractTo determine the long‐term efficacy of botulinum toxin (BTX) treatments, we analyzed longitudinal follow‐up data on 45 patients (32 women; mean age, 68.8 years) currently followed in the Baylor College of Medicine Movement Disorders Clinic, who have received BTX treatments continuously for at least 12 years (mean 15.8 ± 1.5 years). Their mean response rating after the last injection, based one a previously described scale 0‐to‐4 scale (0 = no effect; 4 = marked improvement) was 3.7 ± 0.6 and the mean total duration of response was 15.4 ± 3.4 weeks. Although the latency and total duration of the response to treatment have not changed over time, the peak duration of response (P < 0.005) and dose per visit (P < 0.0001) have increased since the initial visit. Furthermore, global rating (P < 0.02) and peak effect (P < 0.05) have improved. In total, 20 adverse events occurred in 16 of 45 (35.6%) patients after their initial visit and 11 adverse events in 10 of 45 (22.2%) patients at their most recent injection visit. Antibody (Ab) testing was carried out in 22 patients due to nonresponsiveness; blocking Abs were confirmed by the mouse protection assay in 4 of 22 (18%) patients. Of the Ab‐negative patients, 16 resumed responsiveness after dose adjustments and2 persisted as nonrespondents. Except for 1 patient, the 4 Ab‐positive and the 2 clinical nonresponders are being treated with BTX‐B. This longest reported follow‐up of BTX injections confirms the long‐term efficacy and safety of this treatment. © 2005 Movement Disorder Society
A new method for identification of protein (sub)families in a set of proteins based on hydropathy distribution in proteins
Authors: Pánek Josef , Eidhammer Ingvar , Aasland Rein 
Published: January 2005

AbstractStructural similarity among proteins is reflected in the distribution of hydropathicity along the amino acids in the protein sequence. Similarities in the hydropathy distributions are obvious for homologous proteins within a protein family. They also were observed for proteins with related structures, even when sequence similarities were undetectable. Here we present a novel method that employs the hydropathy distribution in proteins for identification of (sub)families in a set of (homologous) proteins. We represent proteins as points in a generalized hydropathy space, represented by vectors of specifically defined features. The features are derived from hydropathy of the individual amino acids. Projection of this space onto principal axes reveals groups of proteins with related hydropathy distributions. The groups identified correspond well to families of structurally and functionally related proteins. We found that this method accurately identifies protein families in a set of proteins, or subfamilies in a set of homologous proteins. Our results show that protein families can be identified by the analysis of hydropathy distribution, without the need for sequence alignment. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Native and modeled disulfide bonds in proteins: Knowledge‐based approaches toward structure prediction of disulfide‐rich polypeptides
Authors: Thangudu Ratna Rajesh , Vinayagam A. , Pugalenthi G. , Manonmani A. , Offmann B. , Sowdhamini R. 
Published: January 2005

AbstractStructure prediction and three‐dimensional modeling of disulfide‐rich systems are challenging due to the limited number of such folds in the structural databank. We exploit the stereochemical compatibility of substructures in known protein structures to accomodate disulfide bonds in predicting the structures of disulfide‐rich polypeptides directly from disulfide connectivity pattern and amino acid sequence in the absence of structural homologs and any other structural information. This knowledge‐based approach is illustrated using structure prediction of 40 nonredundant bioactive disulfide‐rich polypeptides such as toxins, growth factors, and endothelins available in the structural databank. The polypeptide conformation could be predicted in 35 out of 40 nonredundant entries (87%). Nonhomologous templates could be identified and models could be obtained within 2 Å deviation from the query in 29 peptides (72%). This procedure can be accessed from the World Wide Web (http://www.ncbs.res.in/∼faculty/mini/dsdbase/dsdbase.html). Proteins 2005. © 2005 Wiley‐Liss, Inc.