bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stronger symptoms of depression predict high coronary heart disease mortality in older men and women
Authors: Ahto Merja , Isoaho Raimo , Puolijoki Hannu , Vahlberg Tero , Kivelä Sirkka‐Liisa 
Published: November 2006

AbstractBackgroundMost cohort studies have found depressive symptoms to be associated with increased cardiovascular mortality in the elderly, but follow‐up times have often been short and study populations small.ObjectivesTo describe associations between stronger symptoms of depression and the risk of death from coronary heart disease (CHD) or myocardial infarction (MI) in elderly Finnish subjects free of CHD at the baseline.MethodsThis study is a prospective population‐based epidemiological and clinical twelve‐year follow‐up study in Lieto Health Centre, Finland. The basic population consisted of 1196 elderly (64 years of age or older) persons who lived in the municipality of Lieto in southwestern Finland in 1990. The occurrence of CHD was determined on the basis of electrocardiographic (ECG) findings, Rose questionnaire and the diagnoses in medical records. The persons with CHD were excluded from the study population. Symptoms of depression at the baseline were measured with the Zung Self‐rating Depression Scale (ZSDS). Mortality was followed up for about 12 years.ResultsThe Kaplan‐Meier survival curves showed stronger symptoms of depression to be related to high risks of mortality from CHD or MI among men and women. According to the Cox model for men significant predictors for higher risk of CHD or MI mortality were stronger symptoms of depression, higher age and a large number of medications in use. When women were examined, significant predictors were stronger symptoms of depression and a large number of medications in use.ConclusionsStronger symptoms of depression are an independent risk factor for high CHD or MI mortality in aged Finnish men and women free of CHD at baseline. Copyright © 2006 John Wiley & Sons, Ltd.
Doxycycline induces caspase‐dependent apoptosis in human pancreatic cancer cells
Authors: Mouratidis Petros X.E. , Colston Kay W. , Dalgleish Angus G. 
Published: November 2006

AbstractDoxycycline (DC) belongs to the tetracycline family of antibiotics and has been used clinically for over 5 decades. Despite advances in understanding the molecular pathogenesis of pancreatic cancer, no chemotherapy course has shown significant effectiveness. Hence new treatments are needed. In this study we report the pro‐apoptotic effects of DC in 2 pancreatic adenocarcinoma cell lines, T3M4 and GER. Cell proliferation was measured using the SRB protein dye. Induction of apoptosis was detected using ELISA. Caspase activation was detected using either immunoblotting or a colorimetric assay based on cleavage of caspase‐associated substrates. Expression of proteins and post‐translational modifications were determined using immunoblotting. Treatment of pancreatic cancer cells with DC reduces their proliferation. This reduction is, at least partly, due to increased caspase‐dependent apoptosis involving activation of caspase3, caspase7, caspase8, caspase9, caspase10 and increased levels of FADD. Inhibition of caspase8 or caspase10 but not caspase9 significantly decreases DC‐induced apoptosis in both cell lines. Furthermore treatment of pancreatic cancer cells with DC increases protein levels of Bax and phosphorylation of members of the p38MAPK pathway such as p38MAPK, MKK3/6 and MAPKAPK2. These results provide an insight into mechanisms behind the pro‐apoptotic effects of DC in pancreatic cancer cells. © 2006 Wiley‐Liss, Inc.
The effects of aging on tumor growth and angiogenesis are tumor‐cell dependent
Authors: Reed May J. , Karres Nathan , Eyman Daniel , Cruz Abigail , Brekken Rolf A. , Plymate Stephen 
Published: November 2006

AbstractIt is generally accepted that histologically similar tumors grow more slowly, with less angiogenesis, in aged mice relative to young mice. We subcutaneously implanted TRAMP‐C2 tumor cells, a prostate cancer cell line not previously examined in aging, into syngeneic C57/Bl6 young (4 month) and aged (20 month) mice and compared tumor growth and angiogenesis. Unexpectedly, the prostate tumors grew as fast in aged as in young mice. Angiogenesis in TRAMP‐C2 tumors was robust, with no differences between the young and aged mice in the number of vessels, distribution of vessel sizes or features of vessel maturation. Aged mice had lower levels of serum testosterone than the young mice. VEGF levels were similar in the tumors and sera of the young and aged mice. Comparison with B16/F10 melanoma, a cancer cell line that is representative of previous studies in aged mice, showed that B16/F10 tumors grew minimally in the aged mice. In contrast to the B16/F10, TRAMP‐C2 tumors had an extracellular matrix with significantly higher levels of MMP2 and MMP9 expression and activity. These unique results demonstrate that tumor progression can be as robust in aged tissues as young tissues. The ability of aged mice to grow large, vascularized prostate tumors is associated with high levels of MMP2/9 activity that may produce a permissive environment for tumor growth and angiogenesis. These data demonstrate that tumor‐cell specific features determine the effect of aging on tumor growth and angiogenesis. © 2006 Wiley‐Liss, Inc.
Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer
Authors: Nakahira Shin , Nakamori Shoji , Tsujie Masanori , Takahashi Yuji , Okami Jiro , Yoshioka Shinichi , Yamasaki Makoto , Marubashi Shigeru , Takemasa Ichiro , Miyamoto Atsushi , Takeda Yutaka , Nagano Hiroaki , Dono Keizo , Umeshita Koji , Sakon Masato , Monden Morito 
Published: November 2006

AbstractPancreatic cancer is the most lethal of all solid tumors partially because of its chemoresistance. Although gemcitabine is widely used as a first selected agent for the treatment of this disease despite low response rate, molecular mechanisms of gemcitabine resistance in pancreatic cancer still remain obscure. The aim of this study is to elucidate the mechanisms of gemcitabine resistance. The 81‐fold gemcitabine resistant variant MiaPaCa2‐RG was selected from pancreatic cancer cell line MiaPaCa2. By microarray analysis between MiaPaCa2 and MiaPaCa2‐RG, 43 genes (0.04%) were altered expression of more than 2‐fold. The most upregulated gene in MiaPaCa2‐RG was ribonucleotide reductase M1 subunit (RRM1) with 4.5‐fold up‐regulation. Transfection with RRM1‐specific RNAi suppressed more than 90% of RRM1 mRNA and protein expression. After RRM1‐specific RNAi transfection, gemcitabine chemoresistance of MiaPaCa2‐RG was reduced to the same level of MiaPaCa2. The 18 recurrent pancreatic cancer patients treated by gemcitabine were divided into 2 groups by RRM1 levels. There was a significant association between gemcitabine response and RRM1 expression (p = 0.018). Patients with high RRM1 levels had poor survival after gemcitabine treatment than those with low RRM1 levels (p = 0.016). RRM1 should be a key molecule in gemcitabine resistance in human pancreatic cancer through both in vitro and clinical models. RRM1 may have the potential as predictor and modulator of gemcitabine treatment. © 2006 Wiley‐Liss, Inc.
Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models
Authors: McDowell Heather P. , Meco Daniela , Riccardi Anna , Tanno Barbara , Berardi Anna C. , Raschellà Giuseppe , Riccardi Riccardo , Dominici Carlo 
Published: November 2006

AbstractHigh levels of PDGFR expression in primary rhabdomyosarcoma (RMS) have been associated with disease progression. To date however, there are no reports on the activity of imatinib mesylate, a selective PDGFR inhibitor, in RMS preclinical models. A panel of 5 RMS cell lines was used to investigate the expression of PDGFRα and PDGFRβ, c‐Kit and the multidrug transporter ABCG2 (also inhibited by imatinib). In vitro and in vivo experiments were performed using RD (embryonal) and RH30 (alveolar) cell lines to determine the efficacy of imatinib as single agent and in combination with topotecan (TPT). PDGFRβ was significantly expressed in all cell lines, with the highest levels in RD, while PDGFR α and ABCG2 were significantly expressed only in RH30 and RMZ‐RC2. c‐Kit was not detected. PDGFRβ signaling was active in RD but not in RH30, whilst PDGFRα signaling was not active in either cell lines. Significant ABCG2‐mediated extrusion of Hoechst 33342 was demonstrated in RH30 but not in RD, and was inhibited by imatinib and the specific ABCG2 inhibitor Ko143. In vitro, imatinib was not active as a single agent at therapeutic concentrations, but significantly potentiated TPT antitumor activity in both cell lines. In vivo experiments using tumor xenografts confirmed the synergistic interaction in both cell lines. These results suggest that at least 2 different mechanisms—inhibition of ABCG2 and/or PDGFRβ—are involved in the synergistic interaction between imatinib and TPT, and support the use of this combination for the treatment of high‐risk RMS patients. © 2006 Wiley‐Liss, Inc.
The 6‐maleimidocaproyl hydrazone derivative of doxorubicin (DOXO‐EMCH) is superior to free doxorubicin with respect to cardiotoxicity and mitochondrial damage
Authors: Lebrecht Dirk , Geist Andrea , Ketelsen Uwe‐Peter , Haberstroh Jörg , Setzer Bernhard , Kratz Felix , Walker Ulrich A. 
Published: November 2006

AbstractDoxorubicin causes a chronic cardiomyopathy in which genetic and functional lesions of mitochondria accumulate in the long‐term and explain in part the delayed onset of heart dysfunction. DOXO‐EMCH a 6‐maleimidocaproyl hydrazone derivative of doxorubicin, is an albumin binding prodrug which has entered clinical trials because of its superior antitumor and toxicological profile. In the present work, we examined the chronic cardiotoxicity of DOXO‐EMCH in direct comparison with doxorubicin. Rats (11 weeks of age) were treated with intravenous doxorubicin (0.8 mg/kg weekly for 7 weeks), an equimolar dose of DOXO‐EMCH (1.1 mg/kg), or with 3.3 mg/kg of DOXO‐EMCH. Controls received saline. Animals were euthanized at 48th week. Rats exposed to doxorubicin had a severe clinical, and histopathological cardiomyopathy with depressed myocardial activity of cytochrome c‐oxidase (COX, 26% of controls), reduced expression of the mtDNA‐encoded COX II subunit, decreased mtDNA copy numbers (46% of controls), and high levels of malondialdehyde and superoxide (787% of controls). All parameters were highly correlated with myocardial damage. Both DOXO‐EMCH groups did not differ from controls with regard to clinical symptomatology, mortality and mitochondrial enzymes, although the myocardia of the high‐dose group had slightly increased histopathological abnormalities, depressed mtDNA copies (74% of controls) and elevated superoxide levels (347% of controls). Doxorubicin‐exposed hearts and to a lesser extent the myocardia of both DOXO‐EMCH groups contained mtDNA‐deletions. In summary both DOXO‐EMCH doses were superior over doxorubicin with respect to clinical and histopathological evidence of cardiomyopathy, myocardial COX‐activity, COX II expression, mtDNA‐content, mtDNA mutation loads and superoxide production in rats. © 2006 Wiley‐Liss, Inc.
Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation
Authors: Vangsted Annette , Gimsing Peter , Klausen Tobias W. , Nexø Bjørn A. , Wallin Håkan , Andersen Pernille , Hokland Peter , Lillevang Søren T. , Vogel Ulla 
Published: November 2006

AbstractIndividual variations in the ability to cope with DNA damage by DNA repair may be essential for the response to chemotherapy, since cancer cells from patients with an effective DNA repair may survive treatment. We have studied the effect on time to treatment failure (TTF) and overall survival (OS) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C‐allele of ERCC2 K751Q, the variant T‐allele of XRCC3 T241M and the variant A‐allele of CD3EAP G‐21A had a 1.3‐fold, 1.8‐fold and 1.9‐fold longer TTF, respectively, than homozygous wild type carriers (p = 0.006, p = 0.004, p < 0.001). The polymorphism CD3EAP G‐21A also had significant effect on OS (p < 0.045). The polymorphism ERCC2 K751Q may to be related to sex, since the prolonged TTF was only seen in women (p = 0.001). Carriers of the combination of variant alleles of ERCC2 K751Q and XRCC3 T241M had 2.8‐fold longer TTF (p = 0.0002). This indicates that suboptimal repair of both DNA mechanisms favors prolonged TTF and that polymorphism in ERCC2, XRCC3 and CD3EAP predicts the outcome for patients treated with autologous stem cell transplantation. © 2006 Wiley‐Liss, Inc.
Emmprin in epithelioid sarcoma: Expression in tumor cell membrane and stimulation of MMP‐2 production in tumor‐associated fibroblasts
Authors: Koga Kaori , Nabeshima Kazuki , Aoki Mikiko , Kawakami Takehito , Hamasaki Makoto , Toole Bryan P. , Nakayama Juichiro , Iwasaki Hiroshi 
Published: November 2006

AbstractEmmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMPs). Emmprin and the induced MMPs play a crucial role in tumor progression, invasion and metastasis of human carcinomas (epithelial malignancies). However, only a few reports have addressed its role in soft tissue sarcomas. This study investigated the expression and role of emmprin in epithelioid sarcoma (ES). Immunoblot studies of 2 ES cell lines showed that they express emmprin, and co‐culture of these ES cells with dermal fibroblasts resulted in upregulation of gelatinase A (MMP‐2) in fibroblasts, as shown by zymography, immunoblotting and enzyme immunoassay. This stimulation was inhibited by an activity‐blocking peptide against emmprin and by antiemmprin antibody. In addition, in vivo, immunohistochemical analysis of 5 ES patient cases demonstrated diffuse emmprin expression in ES cells and MMP‐2 expression in both ES cells and peritumoral fibroblasts. The histopathological findings that peritumoral fibroblasts that were not in direct contact with emmprin‐expressing ES cells exhibit upregulated MMP‐2 prompted us to look for a soluble form of emmprin. Soluble full‐length emmprin released from ES cells was detected in conditioned medium and shown to stimulate MMP‐2 production by fibroblasts. In conclusion, emmprin is expressed in ES in both membrane and soluble forms and stimulates MMP‐2 production via interactions with fibroblasts, which could play a role in ES cell stromal invasion and vascular involvement. © 2006 Wiley‐Liss, Inc.
Reproductive risk factors for incident bladder cancer: Iowa Women's Health Study
Authors: Prizment Anna E. , Anderson Kristin E. , Harlow Bernard L. , Folsom Aaron R. 
Published: November 2006

AbstractWe studied the association between reproductive factors and bladder cancer incidence in a prospective cohort study of 37,459 Iowa women aged 55–69 years and initially free from cancer in 1986. Women reported reproductive history and were followed prospectively through 2003. After adjusting for age and smoking, there was an inverse association between age at menopause and incident bladder cancer (n = 192). Compared with menopause at age ≥≥48, the hazard ratio (HR) of bladder cancer was 1.32 (95% CI; 0.90–1.94) for menopause at 43–47, and 1.60 (95% CI; 1.06–2.39) for ≤≤42 (p‐trend = 0.02). The associations were similar for ages at natural and surgical menopause. In addition, women with a history of bilateral oophorectomy had an increased risk of bladder cancer compared with those who did not undergo bilateral oophorectomy: HR = 1.58 (95% CI; 1.12, 2.22). Finally, there was an indication of a positive association between bladder cancer and shorter lifetime years of ovulation (p‐trend = 0.09). There were no associations between incident bladder cancer and age at first birth, number of births, age at menarche, use of hormone replacement therapy or any other reproductive characteristics. This study provides evidence that increased risk of bladder cancer is associated with earlier age at menopause in postmenopausal women. © 2006 Wiley‐Liss, Inc.
Different types of postmenopausal hormone therapy and mammographic density in Norwegian women
Authors: Bremnes Yngve , Ursin Giske , Bjurstam Nils , Lund Eiliv , Gram Inger Torhild 
Published: November 2006

AbstractPostmenopausal hormone therapy (HT) is associated with increased risk of breast cancer. The HTs used in Scandinavia is associated with higher risk estimates than those used in most other countries. Mammographic density is one of the strongest risk factors for breast cancer, and possibly an intermediate marker for breast cancer. We decided to examine the relationship between use of different types of HT and mammographic density in Norwegian women. Altogether, 1,007 postmenopausal participants in the governmental mammographic screening program were asked about current and previous HT use. Mammograms were classified according to percent and absolute mammographic density. Overall, current users of HT had on average 3.6% higher mean percent mammographic density when compared with never users (p < 0.001). After adjustment for age at screening, number of children and BMI in a multivariate model, women using the continuous estradiol (E2) plus norethisterone acetate (NETA) combination had a mean percent mammographic density significantly higher than never users (6.1% absolute difference). Those using the continuous E2 plus NETA combination had an 4.8% (absolute difference) higher mean percent mammographic density after <5 years of use when compared with never users, while the corresponding number for ≥5 years of use was 7% (p‐trend < 0.001). We found similar associations when absolute mammographic density was used as the outcome variable. In summary, our study shows a statistical significant positive dose–response association between current use of the continuous E2 plus NETA combination and both measures of mammographic density. © 2006 Wiley‐Liss, Inc.
Age–period–cohort decomposition of aggregate data: an application to US and Japanese household saving rates
Authors: Fukuda Kosei 
Published: November 2006

AbstractThis paper compares two methods of analyzing aggregate data that is classified by period and age. Because there is a linear relationship among age, period, and cohort, it is not possible to distinguish the separate effects without employing an identifying assumption. The first method, which is applied in the economics literature, assumes that period effects are orthogonal to a linear time trend. The second method, which is applied in the statistics literature, assumes that the effect parameters change gradually. Simulation results suggest that the performances of both methods are comparable. The results of applying the second method to household saving rates suggest that period effects had a negligible influence in the United States but considerable influence in Japan. Copyright © 2006 John Wiley & Sons, Ltd.
Mass spectrometric studies on 4‐aryl‐1‐cyclopropyl‐1,2‐dihydropyridinyl derivatives: an examination of a novel fragmentation pathway
Authors: Bissel Philippe , Geherin Skye , Igarashi Kazuo , Gandour Richard D. , Lazar Iulia M. , Castagnoli Jr Neal 
Published: November 2006

AbstractExamination of the electrospray ionization product ion spectra of 1,2‐dihydropyridinyl and 4‐aryl‐1,2‐dihydropyridinyl derivatives bearing a 1‐cyclopropyl or 1‐trans‐2‐phenylcyclopropyl group has led to the characterization of unexpected fragment ions. For example, the base peak at m/z 156 present in the product ion spectrum of trans‐1‐(2‐phenylcyclopropyl)‐4‐phenyl‐1,2‐dihydropyridine proved not to be the expected 4‐phenylpyridinium species but rather the isomeric 3‐phenyl‐5‐azoniafulvenyl species. The results of studies with a series of structural and isotopically labeled analogs require a novel fragmentation pathway to account for the formation of this and related fragment ions. One possible pathway is based on an initial 1,5‐sigmatropic shift of a cyclopropylmethylene hydrogen atom that is accompanied by opening of the cyclopropyl ring. The resulting eniminium intermediates then fragment to yield the 5‐azoniafulvenyl species. Copyright © 2006 John Wiley & Sons, Ltd.
Methods validation for the determination of trihalomethanes in drinking water
Authors: Culea Monica , Cozar Onuc , Ristoiu Dumitru 
Published: November 2006

AbstractTrihalomethanes (THMs), chlorinated by‐products in drinking water, have been determined by comparing some analytical methods, based on the following techniques: liquid–liquid extraction‐gas chromatography‐mass spectrometry (LLE‐GC‐MS), headspace‐gas chromatography‐mass spectrometry (headspace‐GC‐MS) and purge and trap‐gas chromatography‐mass spectrometry (PT‐GC‐MS). The mass spectrometer was operated in the SIM mode. The quantitative methods were validated and compared to the ability to identify and to measure reliably the yields of the toxic compounds. Good validation parameters were obtained for each method. Copyright © 2006 John Wiley & Sons, Ltd.
Demographic antecedents and performance consequences of structural holes in work teams
Authors: Balkundi Prasad , Kilduff Martin , Barsness Zoe I. , Michael Judd H. 
Published: November 2006

AbstractThis paper addresses two important questions concerning social fragmentation in work teams. First, from where do disconnections between team members, measured in terms of the proportion of structural holes within the work team, derive? Second, what are the consequences for team performance of having more or less structural holes between team members? In answering the first question, the research investigated whether demographic diversity in teams played a role in predicting the proportion of structural holes in team friendship networks. For 19 teams at a wood products company, there were no effects of ethnic and gender diversity on structural hole proportions. However, age diversity significantly reduced the extent of structural ‘holeyness.’ In investigating the second question, two countervailing tendencies were considered. In the absence of structural holes, teams are likely to be at low risk for new ideas. But fragmented teams in which team members are separated by many structural holes are likely to have difficulty coordinating. The researchers demonstrated a curvilinear effect: a moderate level of structural diversity in teams was positively associated with team performance. Thus, the research suggested that it is structural diversity (measured in terms of the proportion of structural holes) rather than demographic diversity that matters in the prediction of team performance. Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis and Optical Properties of Soluble Polyimide/Titania Hybrid Thin Films
Authors: Chang Chih‐Ming , Chang Cheng‐Liang , Chang Chao‐Ching 
Published: November 2006

AbstractSummary: In this study high‐refractive‐index polyimide/titania hybrid optical thin films were successfully prepared using a sol‐gel process combined with spin coating and multistep baking. The hybrid thin films were prepared from a soluble polyimide, a coupling agent, and a titania precursor. Transparent hybrid thin films can be obtained at TiO2 content as high as 40 wt.‐%. The FE‐SEM results suggest that the TiO2 particles in the hybrid thin films have diameters in the nanometer range. The thermal decomposition temperatures of the prepared hybrid materials are above those of the respective polyimide except for the highest TiO2 content hybrids. The refractive indices at 633 nm of the prepared hybrid thin films increase linearly from 1.66 to 1.82 with increasing TiO2 content. The excellent optical transparency, thermal stability, and tunable refractive index provide the potentials of the polyimide/titania hybrid thin films in optical applications.
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