bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of HER2 pre‐mRNA alternative splicing and its effects on breast cancer cells
Authors: Wan Jing , Sazani Peter , Kole Ryszard 
Published: October 2008

AbstractThe oncogene HER2 is overexpressed in a variety of human tumors, providing a target for anti‐cancer molecular therapies. Here, we employed a 2′‐O‐methoxyethyl (MOE) splice switching oligonucleotide, SSO111, to induce skipping of exon 15 in HER2 pre‐mRNA, leading to significant downregulation of full‐length HER2 mRNA, and simultaneous upregulation of Δ15HER2 mRNA. SSO111 treatment of SK‐BR‐3 cells, which highly overexpress HER2, led to inhibition of cell proliferation and induction of apoptosis. The novel Δ15HER2 mRNA encodes a soluble, secreted form of the receptor. Treating SK‐BR‐3 cells with exogenous Δ15HER2 protein reduced membrane‐bound HER2 and decreased HER3 transphosphorylation. Δ15HER2 protein thus has similar activity to an autoinhibitory, natural splice variant of HER2, Herstatin, and to the breast cancer drug Herceptin. Both SSO111 and Δ15HER2 may be potential candidates for the development of novel HER2‐targeted cancer therapeutics. © 2008 Wiley‐Liss, Inc.
Hypertension is an independent predictor of survival disparity between African‐American and white breast cancer patients
Authors: Braithwaite Dejana , Tammemagi C. Martin , Moore Dan H. , Ozanne Elissa M. , Hiatt Robert A. , Belkora Jeff , West Dee W. , Satariano William A. , Liebman Michael , Esserman Laura 
Published: October 2008

AbstractThe objective of this study was to determine whether comorbidity, or pre‐existing conditions, can account for some of the disparity in survival between African‐American and white breast cancer patients. A historical cohort study was conducted of 416 African‐American and 838 white women diagnosed with breast cancer between 1973 and 1986, and followed through 1999 in the Kaiser Permanente Northern California Medical Care Program. Information on comorbidity, tumor characteristics and breast cancer treatment was obtained from medical records, and Surveillance, Epidemiology and End Results, Northern California Cancer Center Registry. Associations between comorbidity and survival were analyzed with multiple Cox proportional hazards regression. Over a mean follow‐up of 9 years, African Americans had higher overall crude mortality than whites: 165 (39.7%) versus 279 (33.3%), respectively. When age, race, tumor characteristics and breast cancer treatment were controlled, the presence of hypertension was associated with all cause survival [hazard ratio (HR) = 1.33, 95% confidence intervals (CI) 1.07–1.67] and it accounted for 30% of racial disparity in this outcome. Hypertension‐augmented Charlson Comorbidity Index was a significant predictor of survival from all causes (HR = 1.32, 95%CI 1.18–1.49), competing causes (HR = 1.52, 95%CI 1.32–1.76) and breast cancer specific causes (HR = 1.18, 95%CI 1.03–1.35). In conclusion, hypertension has prognostic significance in relation to survival disparity between African‐American and white breast cancer patients. If our findings are replicated in contemporary cohorts, it may be necessary to include hypertension in the Charlson Comorbidity Index and other comorbidity measures. © 2008 Wiley‐Liss, Inc.
How different are luminal A and basal breast cancers?
Authors: Bertucci François , Finetti Pascal , Cervera Nathalie , Charafe‐Jauffret Emmanuelle , Buttarelli Max , Jacquemier Jocelyne , Chaffanet Max , Maraninchi Dominique , Viens Patrice , Birnbaum Daniel 
Published: October 2008

AbstractHeterogeneity of breast cancer makes its evolution difficult to predict, and its treatment far from being optimal. At least 5 main molecular subtypes exist. Two major subtypes are luminal A and basal subtypes, which have opposite features, notably survival. To characterize these 2 subtypes better, with the hope of better understanding their different biology and clinical outcome, we have profiled a series of 138 tumours (80 luminal A and 58 basal) using Affymetrix whole‐genome DNA microarrays. We have identified 5,621 probe sets as differentially expressed between the 2 subtypes in our series. These differences were validated in 6 independent public series (more than 600 tumours) profiled using different DNA microarrays platforms. Analysis of functions and pathways related to these probe sets, and the extent of the observed differences, confirmed that the 2 subtypes represent very distinct entities. Genes associated with proliferation, cell cycle, cell motility, angiogenesis, and NFkB signalling were overexpressed in basal tumours. Genes involved in fatty acid metabolism, TGFB signalling, and oestrogen receptor (ER) signalling were overexpressed in luminal A samples. Half of the genes overexpressed in luminal tumours contained ER‐binding sites. The number of differentially expressed genes was as high as the set of genes discriminating 2 cancers of different anatomical origin (breast and colon) or discriminating acute myeloid and lymphoid leukaemia. We provide a comprehensive list of genes/pathways that define potential diagnostic, prognostic and therapeutic targets for these 2 subtypes, which should be treated differently given the profound differences observed at the molecular level. © 2008 Wiley‐Liss, Inc.
N6‐isopentenyladenosine inhibits cell proliferation and induces apoptosis in a human colon cancer cell line DLD1
Authors: Laezza Chiara , Caruso Maria Gabriella , Gentile Teresa , Notarnicola Maria , Malfitano Anna Maria , Di Matola Tiziana , Messa Caterina , Gazzerro Patrizia , Bifulco Maurizio 
Published: October 2008

AbstractN6‐isopentenyladenosine (i6A) is a modified nucleoside with a pentaatomic isopentenyl derived from mevalonate that induces inhibition of tumor cell proliferation and apoptosis in several tumor cell lines. In this study, we reported that N6‐isopentenyladenosine inhibited the proliferation and promotes apoptosis in DLD1 human colon cancer cells. It suppressed the proliferation of cells through inhibition of DNA synthesis, causing a cell cycle arrest that correlated with a decrease in the levels of cyclin E, cyclin A and cyclin D1 and with a concomitant increase in the levels of cyclin‐dependent kinase inhibitor p21waf and p27kip1. Moreover, it induced apoptosis through an increase in the number of annexin V‐positive cells, a downregulation of antiapoptotic products and caspase‐3 activation. The apoptotic effects of N6‐isopentenyladenosine were accompanied by sustained phosphorylation and activation of c‐jun N‐terminal kinase (JNK) that induced phosphorylation of c‐jun. Overall, our data show that JNK, could play an important role in i6A‐mediated apoptosis in DLD1 human colon cancer cells © 2008 Wiley‐Liss, Inc.
Global expression profiling of sex cord stromal tumors from Men1 heterozygous mice identifies altered TGF‐β signaling, decreased Gata6 and increased Csf1r expression
Authors: Mould Arne W. , Duncan Russell , Serewko‐Auret Magdalena , Loffler Kelly A. , Biondi Christine , Gartside Michael , Kay Graham F. , Hayward Nicholas K. 
Published: October 2008

AbstractHeterozygous disruption of the Men1 gene predisposes mice to the development of multiple endocrine tumors, accurately mimicking the human MEN1 cancer predisposition syndrome. Additionally, Men1+/– mice frequently develop sex cord adenomas. The mechanism underlying the susceptibility of these mice to sex cord tumor development has not been fully determined, but data suggest it may involve transcriptional regulation of key growth promoting/repressing genes. To identify potential menin‐regulated genes that may be important for tumor suppression in sex cord cells, we compared the global gene expression profiles of testis and ovary adenomas with other endocrine tumors of the pancreas and pituitary from Men1 heterozygous mice and with control tissues. Gonadal tumors clustered separately from pancreas and pituitary tumors with only a few genes (e.g., Cdkn2c) commonly dysregulated in all tumor types. Testis and ovary tumors displayed a higher level of transcriptional similarity to each other than they did to their respective control tissues. Among genes that had decreased expression in tumors was significant over‐representation of genes associated with the TGF‐β, hedgehog and Wnt signaling, indicating that loss of menin function affects these pathways at the level of transcription. Aberrant protein expression in Leydig and granulosa cells of 2 transcriptionally dysregulated gene products, Gata6 and Csf1r were confirmed by immunohistochemistry. We propose that sex cord tumor susceptibility in Men1+/– mice involves deregulated cell proliferation due to dysregulation of multiple cell growth regulating genes including: reduced Cdkn2c transcription, loss of TGF‐β pathway tumor suppressor function (e.g., Gata6) and transcriptional activation of Csf1r. © 2008 Wiley‐Liss, Inc.
Chromosomes 6 and 18 induce neoplastic suppression in epithelial ovarian cancer cells
Authors: Dafou Dimitra , Ramus Susan J. , Choi Ken , Grun Barbara , Trott Deborah A. , Newbold Robert F. , Jacobs Ian J. , Jones Christopher , Gayther Simon A. 
Published: October 2008

AbstractMetaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OCs). Therefore we used microcell‐mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into 2 epithelial OC cell lines (TOV112D and TOV21G). The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in 1 cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CGH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. A 36 MB deletion on chromosome 6 in 2 hybrids from 1 cell line mapped the candidate region proximal to 6q15 and distal to 6q22.2; and an ∼10 MB candidate region spanning the centromere on chromosome 18 was identified in 2 hybrids from the other cell line. These data support reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome 18 has been reported. This suggests that these chromosomes may harbour tumour suppressor‐“like” genes. The future identification of these genes may have a significant impact on the understanding and treatment of the disease and the identification of novel therapeutic targets. © 2008 Wiley‐Liss, Inc.
Physical activity, sedentary behavior, and endometrial cancer risk in the NIH‐AARP Diet and Health Study
Authors: Gierach Gretchen L. , Chang Shih‐Chen , Brinton Louise A. , Lacey James V. , Hollenbeck Albert R. , Schatzkin Arthur , Leitzmann Michael F. 
Published: October 2008

AbstractConsistent with a strong hormonal etiology, endometrial cancer is thought to be influenced by both obesity and physical activity. Although obesity has been consistently related to risk, associations with physical activity have been inconclusive. We examined relationships of activity patterns with endometrial cancer incidence in the NIH‐AARP Diet and Health Study cohort, which included 109,621 women, ages 50–71, without cancer history, who in 1995–1996 completed a mailed baseline questionnaire capturing daily routine and vigorous (defined as any period of ≥20 min of activity at work or home causing increases in breathing, heart rate, or sweating) physical activity. A second questionnaire, completed by 70,351 women, in 1996–1997 collected additional physical activity information. State cancer registry linkage identified 1,052 primary incident endometrial cancers from baseline through December 31, 2003. In multivariate proportional hazards models, vigorous activity was inversely associated with endometrial cancer in a dose‐response manner (p for trend = 0.02) (relative risk (RR) for ≥5 times/week vs. never/rarely = 0.77, 95% confidence interval (CI): 0.63–0.95); this association was more pronounced among overweight and obese women (body mass index ≥25; RR = 0.61, 95% CI: 0.47–0.79) than among lean women (body mass index <25; RR = 0.76, 95% CI: 0.52–1.10; p for interaction = 0.12). Although we observed no associations with light/moderate, daily routine or occupational physical activities, risk did increase with number of hours of daily sitting (p for trend = 0.02). Associations with vigorous activities, which may interact with body mass index, suggest directions for future research to clarify underlying biologic mechanisms, including those relating to hormonal alterations. © 2008 Wiley‐Liss, Inc.
Characteristic gene expression in stromal cells of gastric cancers among atomic‐bomb survivors
Authors: Oue Naohide , Sentani Kazuhiro , Sakamoto Naoya , Motoshita Junichi , Nishisaka Takashi , Fukuhara Toshiyuki , Matsuura Hiroo , Sasaki Hiroki , Nakachi Kei , Yasui Wataru 
Published: October 2008

AbstractTo elucidate the mechanism of radiation‐induced cancers, molecular analysis of cancers in atomic‐bomb survivors is important. In our study, we developed a custom oligonucleotide array of 208 genes. We analyzed gene expression profiles of gastric cancers (GCs) from atomic‐bomb survivors and identified 9 genes with significantly lower expression in GCs from exposed patients than in GCs from nonexposed patients. Among these 9 genes, expression of versican and osteonectin was investigated in greater detail using immunohistochemistry in 116 GCs from 64 exposed and 52 nonexposed patients who developed GC after the bombing. In the Stage I/II GCs, the clinicopathologic, phenotypic and proliferative characteristics of GCs from exposed and nonexposed patients did not differ significantly; however, versican and osteonectin were expressed at much lower levels in the area of tumor‐associated stroma of exposed patients than in nonexposed patients (p = 0.026 and p = 0.024, respectively). These results suggest that the characteristics of tumor‐associated stromal cells differ between GCs from exposed and nonexposed patients. © 2008 Wiley‐Liss, Inc.
Interest rate transmission in the UK: a comparative analysis across financial firms and products
Authors: Fuertes Ana‐Maria , Heffernan Shelagh A. 
Published: October 2008

AbstractThis paper differentiates itself from the existing literature by testing for heterogeneities in the interest rate transmission mechanism using a large sample of 662 monthly retail rate histories (1993–2004) on seven key deposit and loan products. Error correction models are estimated to analyse the long‐run pass‐through, the long‐run mark‐up and the short‐run speed of adjustment. The prediction that the official and retail rates move together in the long run is supported by the data. The evidence suggests weak between‐product heterogeneity but notable differences were found between financial firms in the way they adjust their rates, which could hinder the achievement of monetary policy objectives. Consumer responses to official rate changes could therefore be more phased and intricate than hitherto believed. Heterogeneity in adjustment is found to be linked to menu costs and key financial ratios under managerial control. Copyright © 2008 John Wiley & Sons, Ltd.
International value versus growth: evidence from stochastic dominance analysis
Authors: Abhyankar Abhay , Ho Keng‐Yu , Zhao Huainan 
Published: October 2008

AbstractWe investigate the value versus growth investment strategies from the perspective of stochastic dominance analysis. Using G7 country data on value and growth stocks, we find that value stocks stochastically dominate growth stocks only for the US, Canada, and Japan, while there are no significant stochastic dominance relationships between value and growth portfolios for the UK, France, Germany, and Italy. Our results imply that the value premium may be country and sample specific. Copyright © 2008 John Wiley & Sons, Ltd.
The euro as a reserve currency: a challenge to the pre‐eminence of the US dollar?
Authors: Galati Gabriele , Wooldridge Philip 
Published: October 2008

AbstractWell‐developed financial markets are a necessary condition for a currency to play a role as a reserve currency. The introduction of the euro greatly improved the functioning of euro financial markets. This paper investigates whether euro financial markets have developed sufficiently to facilitate the emergence of the euro as a reserve currency on par with the US dollar. We find that the liquidity and breadth of euro financial markets are fast approaching those of dollar markets, and as a result the euro is eroding some of the advantages that have historically supported the pre‐eminence of the US dollar as a reserve currency. This strengthens the incentive for monetary authorities to reconsider the currency composition of their reserves. Nevertheless, the introduction of the euro has not yet resulted in a significant change in the currency composition of official reserve holdings. The US dollar has maintained its place as the dominant reserve currency, supported perhaps by the edge that dollar financial markets still have over euro markets in terms of size, credit quality, and liquidity, as well as inertia in the use of international currencies. Copyright © 2008 John Wiley & Sons, Ltd.
Announcement effects on exchange rates
Authors: Bask Mikael 
Published: October 2008

AbstractAn asset pricing model for exchange rate determination is presented, where technical analysis in currency trade is incorporated in the form of a moving average technique. As a result, the model has jmax+1 rational expectations equilibria (REE), where jmax is large, since jmax past exchange rates affect the current rate due to technical analysis. There is, however, a unique REE that is economically relevant, and focusing on this REE, it is shown that the exchange rate is much more sensitive to a change in money supply than when technical analysis is absent in currency trade. This result is important since it sheds light on the so‐called exchange rate disconnect puzzle in international finance. Copyright © 2008 John Wiley & Sons, Ltd.
Substrate rigidity regulates Ca2+ oscillation via RhoA pathway in stem cells
Authors: Kim Tae‐Jin , Seong Jihye , Ouyang Mingxing , Sun Jie , Lu Shaoying , Hong Jun Pyu , Wang Ning , Wang Yingxiao 
Published: October 2008

AbstractSubstrate rigidity plays crucial roles in regulating cellular functions, such as cell spreading, traction forces, and stem cell differentiation. However, it is not clear how substrate rigidity influences early cell signaling events such as calcium in living cells. Using highly sensitive Ca2+ biosensors based on fluorescence resonance energy transfer (FRET), we investigated the molecular mechanism by which substrate rigidity affects calcium signaling in human mesenchymal stem cells (HMSCs). Spontaneous Ca2+ oscillations were observed inside the cytoplasm and the endoplasmic reticulum (ER) using the FRET biosensors targeted at subcellular locations in cells plated on rigid dishes. Lowering the substrate stiffness to 1 kPa significantly inhibited both the magnitudes and frequencies of the cytoplasmic Ca2+ oscillation in comparison to stiffer or rigid substrate. This Ca2+ oscillation was shown to be dependent on ROCK, a downstream effector molecule of RhoA, but independent of actin filaments, microtubules, myosin light chain kinase, or myosin activity. Lysophosphatidic acid, which activates RhoA, also inhibited the frequency of the Ca2+ oscillation. Consistently, either a constitutive active mutant of RhoA (RhoA‐V14) or a dominant negative mutant of RhoA (RhoA‐N19) inhibited the Ca2+ oscillation. Further experiments revealed that HMSCs cultured on gels with low elastic moduli displayed low RhoA activities. Therefore, our results demonstrate that RhoA and its downstream molecule ROCK may mediate the substrate rigidity‐regulated Ca2+ oscillation, which determines the physiological functions of HMSCs. J. Cell. Physiol. 218: 285–293, 2009. © 2008 Wiley‐Liss, Inc.
Model cell culture system for defining the molecular and biochemical events mediating terminal differentiation of human melanoma cells
Authors: Staudt Michelle R. , DePass Anthony L. , Sarkar Devanand , Fisher Paul B. 
Published: October 2008

AbstractCancer cells are commonly less differentiated than their normal progenitors; a phenotype that correlates with loss of specialized functions and an increased capability to self‐renew. Melanoma is an ideal model to analyze cancer progression and differentiation since a well‐characterized process of step‐wise tumor progression has been defined. Our lab previously described a combinatorial in vitro treatment protocol to induce terminal differentiation of human melanoma cells using a low dose of the PKC activator Mezerein (Mez) combined with interferon‐β (IFN‐β), which also activates IFN‐stimulated gene expression in addition to the re‐differentiation program. In principle, using an alternate way to induce terminal differentiation not including IFN‐β would be more compatible with gene expression profiling. A higher concentration of Mez alone induced terminal differentiation of HO‐1 human melanoma cells as measured by morphological, growth and biochemical assays. Pre‐treatment with the PKC inhibitor GF109203x blocked changes associated with differentiation and inhibited the ability of Mez to force irreversible/terminal differentiation. By combining this efficient method of inducing terminal differentiation with microarray analyses we now identify potential regulators of this process and demonstrate utility of this novel in vitro model in which to study the molecular determinants and mechanisms of human melanoma differentiation. J. Cell. Physiol. 218: 304–314, 2009. © 2008 Wiley‐Liss, Inc.
Kinetic resolution of 1‐phenylethanol integrated with separation of substrates and products by a supported ionic liquid membrane
Authors: Hernández‐Fernández F. J. , de los Ríos A. P. , Tomás‐Alonso F. , Gómez D. , Víllora G. 
Published: October 2008

AbstractBACKGROUND: In the present study, the kinetic resolution of rac‐1‐phenylethanol by transesterification with several vinyl esters catalysed by a commercial immobilized Candida antarctica lipase B (Novozym 435) was carried out in n‐hexane at different water contents. The subtrates and products involved in the kinetic resolution were separated using a membrane bioreactor containing a supported liquid membrane based on the ionic liquid 1‐butyl‐3‐methylimidazolium tetrafluoroborate [bmim+][BF4−].RESULTS: Variables affecting the kinetic resolution performance of the enzyme were studied. First, the influence of water content of the medium on the synthetic activity, selectivity and enantioselectivity of the enzyme was analysed in order to establish the optimal amount of water. The use of vinyl esters of different alkyl chain length (vinyl propionate, vinyl butyrate and vinyl laurate) as acyl donors to kinetic resolution was studied. Finally, the integrated reaction/separation process for the resolution of rac‐1‐phenylethanol was carried out in the optimal conditions found.CONCLUSION: These investigations demonstrate that the coupling of lipase enantioselectivity with the selective separation of supported liquid membranes based on ionic liquids provides a promising basis for practical production of enantiomerically pure or enriched compounds. Copyright © 2008 Society of Chemical Industry