bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smokeless tobacco use and risk of cancer of the pancreas and other organs
Authors: Boffetta Paolo , Aagnes Bjarte , Weiderpass Elisabete , Andersen Aage 
Published: January 2005

AbstractLimited data are available on the carcinogenicity of smokeless tobacco products in organs other than the mouth. Snus is a smokeless tobacco product widely used in Norway. We studied 10,136 Norwegian men enrolled since 1966 in a prospective cohort study, 31.7% of whom were exposed to snus. The relative risk of pancreatic cancer for snus use was 1.67 (95% confidence interval [CI] = 1.12, 2.50); that of oral and pharyngeal cancer was 1.10 (95% CI = 0.50, 2.41), that of esophageal cancer was 1.40 (95% CI = 0.61, 3.24), and that of stomach cancer was 1.11 (95% CI = 0.83, 1.48). The relative risks of cancers of the lung (either all histological types or adenocarcinoma), urinary bladder and kidney were not increased among snus users. The increase in the relative risk of pancreatic cancer was similar in former and current snus users and was restricted to current tobacco smokers. Our study suggests that smokeless tobacco products may be carcinogenic on the pancreas. Tobacco‐specific N‐nitrosamines are plausible candidates for the carcinogenicity of smokeless tobacco products in the pancreas. © 2004 Wiley‐Liss, Inc.
Use of a transgenic mouse model to identify markers of human lung tumors
Authors: Linnerth Nicolle M. , Sirbovan Kelly , Moorehead Roger A. 
Published: January 2005

AbstractLung cancer remains the leading cause of cancer related deaths worldwide. Despite advances in detection technologies, most patients diagnosed with lung cancer already harbor metastatic lesions. Because early detection is one of the primary determinants of patient outcome, a transgenic mouse model of lung cancer was utilized to identify markers of early lung tumors in humans. DNA microarray analysis of lung tumors arising in MMTV‐IGF‐II transgenic mice showed 9 genes consistently elevated in the murine lung tumors. Western blot analyses confirmed that several of these proteins were elevated in the lung tumors and immunohistochemical analyses identified 3 proteins, microsomal glutathione‐S‐transferase 1 (Mgst1), cathepsin H and syndecan 1 as being consistently elevated in the murine lung tumors compared to non‐tumor bearing transgenic lung tissue and normal lung tissue surrounding the tumor. These 3 proteins were also elevated in human lung adenocarcinoma and squamous cell carcinomas. Importantly, the proteins were elevated in early stage, node negative tumors indicating their ability to detect early lung lesions that would be amenable to surgical resection. Therefore, our findings indicate that Mgst1, cathepsin H and syndecan 1 should be further evaluated as markers capable of identifying patients with early stage lung tumors. © 2004 Wiley‐Liss, Inc.
Intrinsic chemotherapy resistance to the tubulin‐binding antimitotic agents in renal cell carcinoma
Authors: Ferguson Roisean E. , Jackson Sharon M. , Stanley Anthea J. , Joyce Adrian D. , Harnden Patricia , Morrison Ewan E. , Patel Poulam M. , Phillips Roger M. , Selby Peter J. , Banks Rosamonde E. 
Published: January 2005

AbstractRenal cancer is one of the most chemoresistant tumor types. Using a panel of 10 established renal cancer cell lines that have not been subjected to prior drug selection, the range of functional resistance phenotypes to the tubulin‐binding agents paclitaxel, vinblastine, vincristine and patupilone (epothilone B, EPO906) was determined, together with expression of P‐glycoprotein (PgP), multidrug resistance associated protein‐2 (MRP2) and major vault protein (MVP) proteins. The IC50 values for vincristine correlated positively with PgP expression (r = 0.73; p = 0.031), with values for paclitaxel and vinblastine just failing to reach significance. A significant positive correlation was observed for sensitivity to paclitaxel and MRP2 expression only (r = 0.8; p = 0.013). MVP expression did not correlate with sensitivity to any of the drugs examined. All cell lines exhibited much greater sensitivity to patupilone, demonstrating for the first time the potential use of patupilone in this cancer. In tissue samples from chemotherapy‐naive renal cell carcinoma (RCC) patients, marked downregulation or absence of PgP in many tumor cells with expression levels more similar to sensitive cell lines rather than the resistant lines was seen. Similarly, MRP2 was absent or only weakly present in tumor cells, whereas MVP was very strongly upregulated in most tumor samples. This study illustrating discrepancies between results exclusively based on studies in cell lines and findings in vivo suggests that the role of PgP and MRP2 in intrinsic resistance in RCC in vivo may be less than expected from the in vitro findings and supports a potential role for MVP on the basis of in vivo expression studies. © 2004 Wiley‐Liss, Inc.
Single‐cell analysis of loss of heterozygosity at the ATM gene locus in Hodgkin and Reed‐Sternberg cells of Hodgkin's lymphoma: ATM loss of heterozygosity is a rare event
Authors: Lespinet Virginie , Terraz Fanny , Recher Christian , Campo Elias , Hall Janet , Delsol Georges , Al Saati Talal 
Published: January 2005

AbstractHodgkin's lymphoma (HL) is a lymphoid malignancy characterized by the presence of rare neoplastic cells, Hodgkin and Reed‐Sternberg (HRS) cells, scattered among a predominant population of inflammatory cells. On the basis of previously reported cytogenetic analyses, the ATM (ataxia‐telangiectasia mutated) gene at 11q22‐23 has been implicated in the etiology of HL. We therefore developed a single‐cell PCR approach to detect ATM loss of heterozygosity (LOH) in HRS cells. Three microsatellites were investigated; 1 localized inside the ATM gene and the remaining 2 in close proximity. In 2 of the 15 lymph node samples, an allelic loss of the ATM gene locus was detected. ATM protein expression was examined in 8 cases (including 1 of the 2 cases with LOH) by immunohistochemistry. In the case associated with an allelic loss, the ATM protein was absent in the HRS cells, whereas in the 7 remaining cases, without detectable LOH at the ATM locus, nuclear ATM expression was observed. In the 2 HL cases with LOH, the ATM gene was sequenced following whole genome amplification of DNA isolated from microdissected HRS cells. In 1 of these 2 cases, a splice site mutation in the second ATM allele was found. This mutation could generate a premature termination codon leading to a marked instability and a rapid degradation of the resulting ATM mRNA transcripts. This latter event could explain the loss of the expression of the ATM protein in HRS cells as detected by immunohistochemistry in this particular case. As previously reported in some B‐cell lymphomas, our results suggest that ATM genetic anomalies could play a role in the pathogenesis of a subset of HL cases. © 2004 Wiley‐Liss, Inc.
Skeletal health in postmenopausal survivors of early breast cancer
Authors: Mackey John R. , Joy Anil A. 
Published: January 2005

AbstractEstrogen plays an important role in the skeletal health of all women. Many therapies used in the treatment of breast cancer reduce estrogen levels and have the potential to affect bone negatively by increasing the risk of osteoporosis and associated bone fractures. The long‐term effects of systemic endocrine therapy on bone, therefore, are an important consideration in the adjuvant setting. Tamoxifen has been shown to have a moderate protective effect on postmenopausal bone due to its partial estrogen agonist activity; however, its long‐term use is potentially associated with negative side effects, such as an increased risk of thromboembolic disease and endometrial cancer. Newer agents, the third‐generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, for example, do not possess estrogen agonist effects and have improved breast cancer outcomes when compared to the standard 5 years of tamoxifen. However, patients treated with adjuvant AIs have been shown to have an increased incidence of osteoporosis and osteoporotic fractures. In order to select the optimal adjuvant therapy for each patient, it is important to assess the overall risk:benefit ratio for each endocrine strategy. All postmenopausal women should follow published guidelines to assess the risk of osteoporosis and, where appropriate, they should receive bone mineral density monitoring. Postmenopausal women with breast cancer who are at increased risk of osteoporotic fracture should be identified and managed with appropriate nonpharmacologic and pharmacologic measures. © 2004 Wiley‐Liss, Inc.
Roles of CXC chemokines and macrophages in the recruitment of inflammatory cells and tumor rejection induced by Fas/Apo‐1 (CD95) ligand‐expressing tumor
Authors: Shimizu Motomu , Yoshimoto Takayuki , Sato Mayumi , Morimoto Junji , Matsuzawa Akio , Takeda Yasutaka 
Published: January 2005

AbstractThe role of CD95 ligand (FasL/Apo‐1L)‐expressing tumors in immunosuppression or immunopotentiation is controversial. CD95L‐transfected tumors induce immunopotentiation after vigorous neutrophil infiltration. Thus, the induction of neutrophil infiltration by CD95L seems to play an important role in tumor rejection. The mechanism by which CD95L‐expressing tumors cause neutrophil infiltration and antitumor immunity has not been well understood. CXC chemokine receptor 2 (CXCR2) knockout (KO) mice are a powerful tool for studying CXC chemokine‐mediated neutrophil infiltration. We investigated the roles of CD95L and chemokines in CD95L‐induced antitumor activity by using CXCR2 KO mice and CD95LcDNA‐transfected MethA (MethA + CD95L) fibrosarcoma. MethA + CD95L cells were completely rejected in wild‐type (WT) and even in KO mice. MethA + CD95L cells injected intraperitoneally (i.p.) induced the recruitment of both neutrophils and macrophages in WT but only macrophages in KO mice, although CXC and CC chemokines were released in both mice. Macrophages incubated with MethA + CD95L cells released CXC and CC chemokines. Macrophages derived from WT and KO but not neutrophils from WT mice induced the recruitment of neutrophils when adoptively i.p. transferred with MethA + CD95L cells into CD95L/CD95‐deficient mice. The different recruitment of inflammatory cells between WT and KO mice was attributed to bone marrow (BM) cells by BM transfer experiment. Our results demonstrated that CXC chemokines are essential for neutrophil recruitment and that macrophages but not neutrophils play a critical role in the CD95L‐induced infiltration of inflammatory cells and the eradication of CD95L‐expressing tumor cells. © 2004 Wiley‐Liss, Inc.
Selective induction of apoptosis through the FADD/caspase‐8 pathway by a p53 c‐terminal peptide in human pre‐malignant and malignant cells
Authors: Li Yin , Mao Yuehua , Rosal Ramon V. , Dinnen Richard D. , Williams Ann C. , Brandt‐Rauf Paul W. , Fine Robert L. 
Published: January 2005

AbstractA p53 C‐terminal peptide (aa 361–382, p53p), fused at its C‐terminus to the minimal carrier peptide of antennapedia (17 aa, Ant; p53p‐Ant), induced rapid apoptosis in human cancer cells, via activation of the Fas pathway. We examined p53p‐Ant mechanism of action, toxicity in various human normal, non‐malignant, pre‐malignant and malignant cancer cells and investigated its biophysical characteristics. p53p‐Ant selectively induced cell death in only pre‐malignant or malignant cells in a p53‐dependent manner and was not toxic to normal and non‐malignant cells. p53p‐Ant was more toxic to the mutant p53 than wild‐type p53 phenotype in H1299 lung cancer cells stably expressing human temperature‐sensitive p53 mutant 143Ala. Surface plasmon resonance (BIACORE) analysis demonstrated that this peptide had higher binding affinity to mutant p53 as compared to wild‐type p53. p53p‐Ant induced‐cell death had the classical morphological characteristics of apoptosis and had no features of necrosis. The mechanism of cell death by p53p‐Ant was through the FADD/caspase‐8‐dependent pathway without the involvement of the TRAIL pathway, Bcl‐2 family and cell cycle changes. Blocking Fas with antibody did not alter the peptide's effect, suggesting that Fas itself did not interact with the peptide. Transfection with a dominant‐negative FADD with a deleted N‐terminus inhibited p53p‐Ant‐induced apoptosis. Its mechanism of action is related to the FADD‐induced pathway without restoration of other p53 functions. p53p‐Ant is a novel anticancer agent with unique selectivity for human cancer cells and could be useful as a prototype for the development of new anti‐cancer agents. © 2004 Wiley‐Liss, Inc.
Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV‐proofer and consensus PCR: A 2‐year follow‐up of women with ASCUS or LSIL pap smear
Authors: Molden Tor , Nygård Jan F. , Kraus Irene , Karlsen Frank , Nygård Mari , Skare Gry Baadstrand , Skomedal Hanne , Thoresen Steinar Ø. , Hagmar Bjørn 
Published: January 2005

AbstractIt has been suggested that human papillomavirus (HPV) testing improves follow‐up of atypical cells of undetermined significance (ASCUS) and low‐grade squamous intraepithelial lesion (LSIL) in cervical cancer screening programs. To evaluate the prognostic value of including HPV testing as an adjunct to cytology, we carried out a 2‐year follow‐up study of 77 women with ASCUS or LSIL Papanicolaou (Pap) smear in the Norwegian Cervical Cancer Screening Program (NCCSP) for detection of histological cervical intraepithelial neoplasia (CIN) 2+. The study includes a comparison between viral mRNA and DNA detection. PreTect HPV‐Proofer was used for HPV E6/E7 mRNA detection from the 5 high‐risk types 16, 18, 31, 33 and 45, and Gp5+/6+ consensus PCR was used for HPV DNA detection. Twice as many women were positive for HPV DNA (54.6%) than for HPV mRNA (23.4%). PreTect HPV‐Proofer and consensus PCR had a sensitivity of 85.7% (95% confidence interval [CI] = 42.1–99.6) for detecting CIN2+ during follow‐up. The specificity was significantly higher for PreTect HPV‐Proofer, 84.9% (95% CI = 73.9–92.5), than for consensus PCR, 50.0% (95% CI = 37.4–62.6). PreTect HPV‐Proofer positive women were 69.8 times (95% CI = 4.3–1137.3) more likely to be diagnosed with CIN2+ within 2 years than PreTect HPV‐Proofer negative women. Consensus PCR‐positive women were 5.7 times (95% CI = 0.6–52.0) more likely to be diagnosed with CIN2+ within 2 years than PCR‐negative women. With equal sensitivity and higher specificity than consensus PCR, the PreTect HPV‐Proofer might offer an improvement for the triage of women with ASCUS or LSIL Pap smear. © 2004 Wiley‐Liss, Inc.
Development and validation of a liquid chromatographic/tandem mass spectrometric assay for the quantitation of nucleoside HIV reverse transcriptase inhibitors in biological matrices
Authors: Compain Séverine , Schlemmer Dimitri , Levi Mikaël , Pruvost Alain , Goujard Cécile , Grassi Jacques , Benech Henri 
Published: January 2005

AbstractBesides liquid chromatographic (LC)/UV methods adapted to therapeutic drug monitoring, there is still a need for more powerful techniques that can be used for pharmacological research and clinical purposes. We developed an LC method coupled with tandem mass spectrometry (MS/MS) to separate, detect and quantify with high sensitivity the nucleoside analogues used in multitherapies (zidovudine, stavudine, zalcitabine, didanosine, lamivudine and abacavir) in plasma and in the intracellular medium. We worked on two essential issues: (i) the need to use two ionization modes in order to achieve the best sensitivity, which leads to the optimization of the chromatographic separation of drugs detected in the positive ionization mode and drugs detected in the negative ionization mode, and (ii) the need to optimize the extraction step in order to enhance sample recovery. The peripheral blood mononuclear cells were lysed in Tris buffer–MeOH. A clean‐up procedure was performed by solid‐phase extraction only for plasma samples. The LC separation was carried out on a Zorbax Stable Bond C18 column followed by MS/MS analysis after electrospray ionization in either the negative or positive mode. The positive ionization mode was applied at the beginning of the run to detect zalcitabine and lamivudine, then the ionization mode was changed to negative for the detection of didanosine, stavudine, internal standard and zidovudine. The calibration range for all the analytes was 0.5–200 ng ml−1. The recoveries were between 64 and 90%, with coefficients of variation (CVs) lower than 15%. The inaccuracy (bias) was ±15% with CVs always lower than 12%. The analytes were stable at room temperature and in the extraction solvent for at least 24 h, after storage at −80 °C for 3 months, after three freeze–thaw cycles and in the injection solvent after 48 h at 4 °C. Together with the measurement of intracellular triphosphorylated metabolites thanks to the powerful plasma and intracellular assay method for intact drugs, it is possible to describe the behaviour of nucleoside analogues against HIV through plasma pharmacokinetics, cell membrane diffusion including drug transport involvement, and also the intracellular metabolism. Copyright © 2005 John Wiley & Sons, Ltd.
Glycan side chains on naturally presented MHC class II ligands
Authors: Dengjel Jörn , Rammensee Hans‐Georg , Stevanovic Stefan 
Published: January 2005

AbstractThe molecular characterization of unknown naturally presented major histocompatibility complex (MHC) class II glycopeptides carrying complex glycans has so far not been achieved, reflecting the different fragmentation characteristics of sugars and peptides in mass spectrometric analysis. Human leukocyte antigen (HLA)‐DR‐bound peptides were isolated by affinity purification, separated via high performance liquid chromatography and analyzed by matrix‐assisted laser desorption/ionization and electrospray ionization mass spectrometry. We were able to identify two naturally processed MHC class II ligands, CD53122–136 and CD53121–136, carrying complex N‐linked glycan side chains by a combination of in‐source and collision‐induced fragmentation on a quadrupole time‐of‐flight tandem mass spectrometer. Copyright © 2005 John Wiley & Sons, Ltd.
New designer drug, 2,5‐dimethoxy‐4‐propylthio‐β‐phenethylamine (2C‐T‐7): studies on its metabolism and toxicological detection in rat urine using gas chromatography/mass spectrometry
Authors: Theobald Denis S. , Fehn Susanna , Maurer Hans H. 
Published: January 2005

AbstractStudies are described on the metabolism and toxicological analysis of the phenethylamine‐derived designer drug 2,5‐dimethoxy‐4‐propylthio‐β‐phenethylamine (2C‐T‐7) in rat urine using gas chromatography/mass spectrometry (GC/MS). The identified metabolites indicated that 2C‐T‐7 was metabolized by hydroxylation of the propyl side chain followed by N‐acetylation and sulfoxidation and also by deamination followed by oxidation to the corresponding acid or by reduction to the corresponding alcohol. To a minor extent, 2C‐T‐7 was also metabolized by S‐dealkylation followed by N‐acetylation, S‐methylation and sulfoxidation. The authors' systematic toxicological analysis (STA) procedure using full‐scan GC/MS after acid hydrolysis, liquid–liquid extraction microwave‐assisted acetylation allowed the detection of an intake of a dose of 2C‐T‐7 in rat urine that corresponds to a common drug users' dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C‐T‐7 in human urine. Copyright © 2005 John Wiley & Sons, Ltd.
Short‐segment nerve conduction studies in the localization of ulnar neuropathy of the elbow: Use of flexor carpi ulnaris recordings
Authors: Lo Y. L. , Leoh T. H. , Xu L. Q. , Nurjannah S. , Dan Y. F. 
Published: January 2005

AbstractShort‐segment nerve conduction studies were performed in 17 limbs with clinical features suggestive of ulnar neuropathy at the elbow. Recording from flexor carpi ulnaris yielded 93% sensitivity, compared with 71.4% when recording from abductor digiti minimi. The rationale underlying the technique is discussed. This approach should be of value as a diagnostic adjunct in technically challenging cases of ulnar neuropathy at the elbow. Muscle Nerve, 2005
Interfacial steady‐state and transient thermal fracture of dissimilar media using the boundary element contact analysis
Authors: Giannopoulos G. I. , Anifantis N. K. 
Published: January 2005

AbstractA boundary element procedure is formulated to treat frictional contact problems of thermally stressed structures. The aim is the computation of steady‐state and time‐dependent thermal stress intensity factors of interfacial cracks in two‐dimensional bimaterial structures when crack closure conditions are present. The effect of friction between the crack faces is taken into consideration. The problems considered are formulated in an incremental and iterative fashion because of their non‐linear nature. Near crack tip singularities of temperature and displacement fields are modelled through appropriate quarter‐point singular elements. Fracture parameters are evaluated from nodal displacements of singular elements utilizing proper formulas. Numerical results are compared with available solutions from the literature, where possible. Good agreement between them can be found. Copyright © 2005 John Wiley & Sons, Ltd.
Mixed finite volume method for nonlinear elliptic problems
Authors: Kim Kwang Y. 
Published: January 2005

AbstractIn this article we construct and analyze a mixed finite volume method for second‐order nonlinear elliptic problems employing H(div; Ω)‐conforming approximations for the vector variable and completely discontinuous approximations for the scalar variable. The main attractive feature of our method is that, although the vector variable is H(div; Ω)‐conforming, one can eliminate it in a local manner to obtain a discontinuous Galerkin method for the scalar variable. Optimal error estimates will be established for both vector and scalar variables. We also present a fully discrete version of this method that is more convenient for computational purposes. © 2005 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Morphology and thermal properties of poly(L‐lactide)/poly(butylene succinate‐co‐butylene adipate) compounded with twice functionalized clay
Authors: Chen Guang‐Xin , Yoon Jin‐San 
Published: January 2005

AbstractPoly(L‐lactide) (PLLA)/poly(butylene succinate‐co‐butylene adipate) (PBSA) blends were compounded with Cloisite 25A® (C25A) and C25A functionalized with epoxy groups, respectively. Epoxy groups on the surface of C25A were introduced by treating C25A with (glycidoxypropyl)trimethoxy silane (GPS) to produce so called Twice Functionalized Organoclay (TFC). Variation of morphology and properties of PLLA/PBSA/C25A composites was investigated before and after the treatment with GPS. The morphological structure of the composites was analyzed by using X‐ray diffractometry (XRD) and transmission electron microscopy (TEM). The silicate layers of PLLA/PBSA/TFC were exfoliated to a larger extent than PLLA/PBSA/C25A. Incorporation of the epoxy groups on C25A improved significantly elongation at break as well as tensile modulus and tensile strength of PLLA/PBSA/C25A. The larger amount of exfoliation of the silicate layers in PLLA/PBSA/TFC as compared with that in PLLA/PBSA/C25A was attributed to the increased interfacial interaction between the polyesters and the clay due to chemical reaction. Thermo gravimetric analysis revealed that both T5%, which was the temperature corresponding to 5% weight loss, and activation energy of thermal decomposition of PLLA/PBSA/TFC were far superior to those of PLLA/PBSA/C25A as well as to those of PLLA/PBSA, indicating that the composites with exfoliated silicate layers were more thermally stable than those with intercalated silicate layers. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 478–487, 2005