bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organ‐specific profiles of genetic changes in cancers caused by activation‐induced cytidine deaminase expression
Authors: Morisawa Toshiyuki , Marusawa Hiroyuki , Ueda Yoshihide , Iwai Akio , Okazaki Il‐mi , Honjo Tasuku , Chiba Tsutomu 
Published: September 2008

AbstractVarious molecular changes characterizing organ‐specific carcinogenesis have been identified in human tumors; however, the molecular mechanisms of the genomic changes specific for each cancer are not well defined. A transgenic (Tg) mouse model with constitutive expression of the nucleotide‐editing enzyme, activation‐induced cytidine deaminase (AID), develops tumors in various organs as a result of the mutagenic activities of AID. This phenotypic character of AID Tg mice allowed us to analyze the organ‐specific genetic changes in tumor‐related genes commonly triggered by AID‐mediated mutagenesis. Among the 80 AID Tg mice analyzed, 11 mice developed hepatocellular carcinomas, and 7 developed lung cancers. In addition, 1 developed the gastric cancer and 3 developed gastric adenomas. Organ‐specific preferences for nucleotide changes were observed in some of the tumor‐related genes in each epithelial tissue of the AID Tg mice. Of note, the c‐myc and K‐ras genes were the preferential targets of the mutagenic activity of AID in lung and stomach cancers, respectively, whereas mutations in the p53 and β‐catenin genes were commonly observed in all 3 organs. Quantitative RT‐PCR analyses revealed that alpha‐fetoprotein, insulin‐like growth factor2 and cyclin D1 genes were specifically upregulated in HCC, whereas upregulation of the matrix metalloproteinase7 gene was more marked in lung cancer. Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ‐specific genetic diversity in oncogenic pathways during cancer development. © 2008 Wiley‐Liss, Inc.
Dietary intakes of ω‐6 and ω‐3 polyunsaturated fatty acids and the risk of breast cancer
Authors: Thiébaut Anne C.M. , Chajès Véronique , Gerber Mariette , Boutron‐Ruault Marie‐Christine , Joulin Virginie , Lenoir Gilbert , Berrino Franco , Riboli Elio , Bénichou Jacques , Clavel‐Chapelon Françoise 
Published: September 2008

AbstractExperimental studies suggest detrimental effects of ω‐6 polyunsaturated fatty acids (PUFA), and beneficial effects of ω‐3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow‐up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with α‐linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between ω‐6 and long‐chain ω‐3 PUFAs, with breast cancer risk inversely related to long‐chain ω‐3 PUFAs in women belonging to the highest quintile of ω‐6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk. © 2008 Wiley‐Liss, Inc.
EBAG9 is a tumor‐promoting and prognostic factor for bladder cancer
Authors: Kumagai Jinpei , Urano Tomohiko , Ogushi Tetsuo , Takahashi Satoru , Horie‐Inoue Kuniko , Fujimura Tetsuya , Azuma Kotaro , Muramatsu Masami , Ouchi Yasuyoshi , Kitamura Tadaichi , Inoue Satoshi 
Published: September 2008

AbstractUpregulation of EBAG9 expression has been observed in several malignant tumors such as advanced breast and prostate cancers, indicating that EBAG9 may contribute to tumor proliferation. In the present study, we assess the role of EBAG9 in bladder cancer. We generated human bladder cancer EJ cells stably expressing FLAG‐tagged EBAG9 (EJ‐EBAG9) or empty vector (EJ‐vector), and investigated whether EBAG9 overexpression modulates cell growth and migration in vitro as well as the in vivo tumor formation of EJ transfectants in xenograft models of BALB/c nude mice. EBAG9 overexpression promoted EJ cell migration, while the effect of EBAG9 to cultured cell growth was rather minimal. Tumorigenic experiments in nude mice showed that the size of EJ‐EBAG9‐derived tumors was significantly larger than EJ‐vector‐derived tumors. Loss‐of‐function study for EBAG9 using small interfering RNA (siRNA) in xenografts with parental EJ cells showed that the intra‐tumoral injection of EBAG9 siRNA markedly reduced the EJ tumor formation compared with control siRNA. Furthermore, immunohistochemical study for EBAG9 expression was performed in 60 pathological bladder cancer specimens. Intense and diffuse cytoplasmic immunostaining was observed in 45% of the bladder cancer cases. Positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients (p = 0.0001) and it was an independent prognostic predictor for disease‐specific survival in multivariate analysis (p = 0.003). Our results indicate that EBAG9 would be a crucial regulator of tumor progression and a potential prognostic marker for bladder cancer. © 2008 Wiley‐Liss, Inc.
A prospective investigation of serum 25‐hydroxyvitamin D and risk of lymphoid cancers
Authors: Lim Unhee , Freedman D. Michal , Hollis Bruce W. , Horst Ronald L. , Purdue Mark P. , Chatterjee Nilanjan , Weinstein Stephanie J. , Morton Lindsay M. , Schatzkin Arthur , Virtamo Jarmo , Linet Martha S. , Hartge Patricia , Albanes Demetrius 
Published: September 2008

AbstractStudies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non‐Hodgkin lymphoma (NHL). Ultraviolet radiation‐derived vitamin D may be protective against lymphomagenesis. We examined the relationship between prediagnostic serum 25‐hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case–control study nested within the Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study cohort (1985–2002) of 29,133 Finnish male smokers (ages 50–69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth‐year and month of fasting blood draw at baseline. In conditional logistic regression models for 10 nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (n = 208) or multiple myeloma (n = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D‐NHL association, however, differed by follow‐up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short‐term risk of NHL. © 2008 Wiley‐Liss, Inc.
The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer
Authors: Weberpals Johanne , Garbuio Kyla , O'Brien Anna , Clark‐Knowles Katherine , Doucette Steve , Antoniouk Olga , Goss Glenwood , Dimitroulakos Jim 
Published: September 2008

AbstractThis study compares Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) expression as predictive markers and evaluates the in vitro enhancement of platinum sensitivity using targeted agents in sporadic ovarian cancer (OC). A retrospective study was performed of advanced stage OC patients receiving platinum‐based chemotherapy. BRCA1 and ERCC1 mRNA expression was determined from frozen tissue of 51 patients. Median overall survival (OS) was longer for patients with lower BRCA1 vs. higher BRCA1 (46 vs.33 months, p = 0.03). High BRCA1 was predictive of poorer OS specifically in patients with residual disease (RD) <2 cm (p = 0.03). There was a non‐significant association for patients with lower ERCC1 and RD <2 cm in favor of improved OS and time to progression. Patients who expressed higher levels of both BRCA1 and ERCC1 mRNA had a shorter OS compared to patients with lower levels of either or both transcript (33 vs.46 months, p = 0.04). When Cox proportional modeling was used by representing BRCA1 and ERCC1 mRNA expression as a continuous variable, both emerge as potential predictors of survival. OC cell lines were exposed to chemotherapy in combination with DNA repair pathway inhibitors and cell viability was assessed. In vitro histone deacetylase (HDAC) inhibition increased the sensitivity of A2780s/cp cells to cisplatin and carboplatin but not to taxol, coincident with a significant decrease in BRCA1 and ERCC1 expression, suggesting that this compound directly targets DNA repair. In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro. © 2008 Wiley‐Liss, Inc.
Expression of the putative tumor suppressor genePTPN13/PTPL1is an independent prognostic marker for overall survival in breast cancer
Authors: Révillion Françoise , Puech Carole , Rabenoelina Fanja , Chalbos Dany , Peyrat Jean‐Philippe , Freiss Gilles 
Published: September 2008

AbstractAlthough it is well established that some protein tyrosine kinases have a prognostic value in breast cancer, the involvement of protein tyrosine phosphatases (PTPs) is poorly substantiated for breast tumors. Three of these enzymes (PTP‐gamma, LAR, and PTPL1) are already known to be regulated by estrogens or their antagonists in human breast cancer cells. We used a real‐time reverse transcriptase polymerase chain reaction method to test the expression levels of PTP‐gamma, LAR and its neuronal isoform, and PTPL1 in a training set of RNA from 59 breast tumors. We sought correlations between levels of these molecular markers, current tumor markers, and survival. We then quantified the expression level of the selected phosphatase in 232 additional samples, resulting in a testing set of 291 breast tumor RNAs from patients with a median follow‐up of 6.4 years. The Spearman nonparametric test revealed correlations between PTPL1 expression and differentiation markers. Cox univariate analysis of the overall survival studies demonstrated that PTPL1 is a prognostic factor [risk ratio (RR) = 0.45], together with the progesterone receptor (PR) (RR = 0.52) and node involvement (RR = 1.58). In multivariate analyses, PTPL1 and PR retained their prognostic value (RRs of 0.48 and 0.55, respectively). This study demonstrates for the first time that PTPL1 expression level is an independent prognostic indicator of favorable outcome for patients with breast cancer. In conjunction with our mechanistic studies, this finding identifies PTPL1 as an important regulatory element of human breast tumor aggressiveness and sensitivity to treatments such as antiestrogens and antiaromatase. © 2008 Wiley‐Liss, Inc.
Overexpression of PLK1 is associated with poor survival by inhibiting apoptosis via enhancement of survivin level in esophageal squamous cell carcinoma
Authors: Feng Yan‐Bin , Lin De‐Chen , Shi Zhi‐Zhou , Wang Xiao‐Chun , Shen Xiao‐Ming , Zhang Yu , Du Xiao‐Li , Luo Man‐Li , Xu Xin , Han Ya‐Ling , Cai Yan , Zhang Zi‐Qiang , Zhan Qi‐Min , Wang Ming‐Rong 
Published: September 2008

AbstractPLK1 is essential for the maintenance of genomic stability during mitosis. In our study, we found that overexpression of PLK1 was an independent prognostic factor (RR = 4.253, p = 0.020) and significantly correlated with survivin, an antiapoptotic protein, in esophageal squamous cell carcinoma (ESCC). Reverse transcription‐polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed upregulation of PLK1 mRNA and amplification of PLK1 gene, respectively. Depletion of PLK1 activated the intrinsic apoptotic pathway, which was substantiated by loss of mitochondrial membrane potential, reduction of Mcl‐1 and Bcl‐2 as well as activation of caspase‐9. Coimmunoprecipitation and confocal microscopy displayed that PLK1 was associated with survivin and PLK1 depletion led to downregulation of survivin. Cotransfection of survivin constructs could partially reverse PLK1‐depletion‐induced apoptosis. These data suggest that PLK1 might be a useful prognostic marker and a potential therapeutic target for ESCC. Survivin is probably involved in antiapoptotic function of PLK1. © 2008 Wiley‐Liss, Inc.
Inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase by flavonoids: A quantitative structure‐activity relationship study
Authors: Ogunbayo Oluseye A. , Harris Robert M. , Waring Rosemary H. , Kirk Christopher J. , Michelangeli Francesco 
Published: September 2008

AbstractFlavonoids are commonly found in fruit and vegetables and have been shown to reach concentrations of several micromolars in human blood plasma. Flavonoids are also believed to have cancer chemoprotective properties. One hypothesis is that flavonoids are able to initiate apoptosis, especially in cancer cells, via a Ca2+‐dependent mitochondrial pathway. This pathway can be activated through an exaggerated elevation of cytosolic [Ca2+], and sarcoplasmic/endoplasmic reticulum Ca2+‐ATPases (SERCA) play an essential role in ameliorating such changes. In this study, we demonstrate that flavonoids (especially flavones) can inhibit the activity of Ca2+‐ATPases isoforms SERCA1A and SERCA2B in the micromolar concentration range. Of the 25 flavonoids tested, 3,6‐dihydroxyflavone (IC50, 4.6 μM) and 3,3′,4′,5,7‐pentahydroxyflavone (quercetin) (IC50, 8.9 μM) were the most potent inhibitors. We show that polyhydroxylation of the flavones are important for inhibition, with hydroxylation at position 3 (for SERCA1A) and position 6 (for SERCA2B) being particularly relevant. © 2008 IUBMB IUBMB Life, 60(12): 853–858, 2008
Activation of HIF‐1α in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway
Authors: Dayan Frédéric , Bilton Rebecca L. , Laferrière Julie , Trottier Eric , Roux Danièle , Pouyssegur Jacques , Mazure Nathalie. M. 
Published: September 2008

AbstractAccumulation of HIF‐1α during normoxic conditions at high cell density has previously been shown to occur and can be used to stabilize HIF‐1α protein in the absence of a specific anaerobic chamber. However, the impact and origin of this pool of HIF‐1α, obtained under normoxia, has been underestimated. In this study, we have systematically compared the related pools of HIF‐1α stabilized in normoxia by high cell density to those obtained at low density in hypoxia. At first glance, these two stimuli appear to have similar outcomes: HIF‐1α stabilization and induction of HIF‐1‐dependent genes. However, upon careful analysis, we observed that molecular mechanisms involved are different. We clearly demonstrate that density‐dependant HIF‐1α accumulation during normoxia is due to the cells high consumption of oxygen, as demonstrated by using a respiration inhibitor (oligomycin) and respiratory‐defective mutant cells (GSK3). Finally and most importantly, our data indicate that a decrease in AKT activity followed by a total decrease in p70S6K phosphorylation reflecting a decrease in mTOR activity occurs during high oxygen consumption, resulting from high cell density. In contrast, hypoxia, even at severe low O2 levels, only slightly impacts upon the mTOR pathway under low cell density conditions. Thus, activation of HIF‐1α in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway whereas HIF‐1α activation obtained in high confluency is totally dependent on mTOR pathway as rapamycin totally impaired (i) HIF‐1α stabilization and (ii) mRNA levels of CA9 and BNIP3, two HIF‐target genes. J. Cell. Physiol. 218: 167–174, 2009. © 2008 Wiley‐Liss, Inc.
Skin toxicity caused by EGFR antagonists—An autoinflammatory condition triggered by deregulated IL‐1 signaling?
Authors: Rodeck Ulrich 
Published: September 2008

AbstractAcneiform skin eruptions associated with sterile inflammation frequently accompany pharmacological inhibition of signaling through the epidermal growth factor receptor (EGFR) in cancer patients. Here we discuss possible pathogenic mechanisms for this phenomenon linked to control of inflammatory mediators by EGFR blockade in keratinocytes of the outer root sheath of the hair follicle. This discussion is focused on the putative role of EGFR activation in restraining interleukin (IL)‐1‐dependent inflammatory networks at the hair follicle. J. Cell. Physiol. 218: 32–34, 2009. © 2008 Wiley‐Liss, Inc.
Blockade of sphingosine‐1‐phosphate reduces macrophage influx and retinal and choroidal neovascularization
Authors: Xie Bing , Shen Jikui , Dong Aling , Rashid Aymen , Stoller Glenn , Campochiaro Peter A. 
Published: September 2008

AbstractSphingosine‐1‐phosphate (S1P) is a bioactive lipid molecule that stimulates endothelial cell migration, proliferation, and survival in vitro, and tumor angiogenesis in vivo. In this study, we used a humanized monoclonal antibody (sonepcizumab) that selectively binds S1P to investigate its role in retinal and choroidal neovascularization (NV). Intraocular injection of sonepcizumab significantly reduced macrophage influx into ischemic retina and strongly suppressed retinal NV in mice with oxygen‐induced ischemic retinopathy. In mice with laser‐induced rupture sites in Bruch's membrane, intraocular injection of sonepcizumab significantly reduced the area of choroidal NV and concomitantly reduced fluorescein leakage from the remaining choroidal NV. Four weeks after intraocular injection of up to 1.8 mg of the sonepcizumab in non‐human primates, electroretinograms and fluorescein angiograms were normal, and light microscopy of ocular sections showed no evidence of structural damage. These data show for the first time that S1P stimulates both choroidal and retinal NV and suggest that sonepcizumab could be considered for evaluation in patients with choroidal or retinal NV. J. Cell. Physiol. 218: 192–198, 2009. © 2008 Wiley‐Liss, Inc.
Cloning, sequencing and analysis of dnaK ‐dnaJ gene cluster of Bacillus megaterium
Authors: Bao Fangming , Gong Lei , Shao Weilan 
Published: September 2008

AbstractThe DNA fragment of heat shock genes (hrcA‐grpE‐dnaK‐dnaJ) containing complete hrcA‐grpE‐dnaK operon and the transcription unit of dnaJ was cloned, sequensed and analyzed from Bacillus megaterium RF5. The sequence of hrcA, grpE and dnaJ were first time reported, and their coding products exibit 60%, 63% and 81% of identities to the homologs of B. subtilis. A σA‐type promoter of Gram‐positive bacteria (PA1) and a terminator were located upstream of the hrcA and downstream of dnaK, and a Controlling inverted repeat of chaperone expression element (CIRCE) was identified between PA1 and hrcA. Another σA‐type promoter (PA2) and a terminator were found upstream and downstream of dnaJ, indicating B. megaterium has a transcription unit containing a single gene dnaJ. The structure of dnaJ transcription unit is more similar to that of Listeria monocytogenes than other species of Bacillus. A partial protein‐based phylogenetic tree, derived from Gram‐positive bacteria using HrcA sequence, indicated a closer phylogenetic relationship between B. megaterium and Geobacillus species than other two Bacillus species. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fermentation of cocoa beans: influence of microbial activities and polyphenol concentrations on the flavour of chocolate
Authors: Camu Nicholas , De Winter Tom , Addo Solomon K , Takrama Jemmy S , Bernaert Herwig , De Vuyst Luc 
Published: September 2008

AbstractBACKGROUND: Spontaneous cocoa bean fermentation is characterised by a succession of microbial activities. Cocoa flavour precursors are developed during fermentation and drying of cocoa beans. Polyphenols and alkaloids contribute to astringency and bitterness of cocoa and chocolate.RESULTS: Population dynamics, metabolite target analyses, and chocolate production were performed for seven independent spontaneous cocoa bean heap fermentations in Ghana. Although the same micro‐organisms were involved in these heaps, carried out at different farms or in different seasons, heap temperatures and microbial metabolite concentrations were different. This could be due to heterogeneity and size of the heaps, but was mainly ascribed to microbial variability. Indeed, differences in microbial activity could be linked with the flavour of chocolates made from the corresponding dried, fermented cocoa beans. Whereas the polyphenol and alkaloid contents of cocoa beans were crop‐ and heap‐dependent, epicatechin and theobromine levels decreased during fermentation due to diffusion out of the bean cotyledons and polyphenol oxidation and condensation. Residual levels were responsible for the degree of bitterness of the final chocolates.CONCLUSION: Differences in microbial activities between different heap fermentations can result in dried fermented cocoa beans and chocolates with different flavour characteristics. Hence, fermentation control may direct the flavour of chocolate. Copyright © 2008 Society of Chemical Industry
Revalorisation of vine trimming wastes using Lactobacillus acidophilus and Debaryomyces hansenii
Authors: Portilla Oscar M , Rivas Beatriz , Torrado Ana , Moldes Ana B , Domínguez José M 
Published: September 2008

AbstractBACKGROUND: Mild acid treatments of vine‐shoot trimmings result in the hydrolysis of hemicellulosic sugars that can be utilised by Lactobacillus acidophilus CECT‐4179 (ATCC 832) and Debaryomyces hansenii NRRL Y‐7426 as carbon sources to obtain food additives. Since the high content of glucose in these hydrolysates reduces the effective bioconversion of xylose into xylitol by D. hansenii, the use of Lactobacillus acidophilus, one of the main probiotic species, allows this problem to be solved by the selective consumption of glucose. In order to use both sugars (glucose and xylose), hemicellulosic vine‐shoot trimming hydrolysates can be sequentially fermented by both micro‐organisms.RESULTS: It was found that, in the first step, L. acidophilus generated almost exclusively lactic acid (32.7 g of lactic acid L−1, QLA = 1.363 g L−1 h−1, YLA/S = 0.72 g g−1) by homofermentative degradation of sugars (mainly glucose), and in the second step, the remaining hemicellulosic sugars were transformed primarily into xylitol by Debaryomyces hansenii (31.3 g of xylitol L−1, QXylitol = 0.708 g L−1 h−1, YXylitol/S = 0.66 g g−1). Furthermore, L. acidophilus proved to be a strong cell‐bounded biosurfactant producer. Cell extracts were able to reduce the surface tension (ST) of PBS in 18 mN m−1 units. Lactobacillus acidophilus cells showed no difference in viability before or after PBS extraction of biosurfactants, achieving values of 0.9 × 109 colony‐forming units (CFU) mL−1 in both cases.CONCLUSIONS: These results have made a serious contribution to the re‐evaluation of a useless and pollutant residue, producing a wide range of natural food additives. Copyright © 2008 Society of Chemical Industry