bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interference with Activator Protein-2 transcription factors leads to induction of apoptosis and an increase in chemo- and radiation-sensitivity in breast cancer cells
Authors: Thewes Verena , Orso Francesca , Jäger Richard , Eckert Dawid , Schäfer Sabine , Kirfel Gregor , Garbe Stephan , Taverna Daniela , Schorle Hubert 
Published: May 2010

Abstract

Background
Activator Protein-2 (AP-2) transcription factors are critically involved in a variety of fundamental cellular processes such as proliferation, differentiation and apoptosis and have also been implicated in carcinogenesis. Expression of the family members AP-2α and AP-2γ is particularly well documented in malignancies of the female breast. Despite increasing evaluation of single AP-2 isoforms in mammary tumors the functional role of concerted expression of multiple AP-2 isoforms in breast cancer remains to be elucidated. AP-2 proteins can form homo- or heterodimers, and there is growing evidence that the net effect whether a cell will proliferate, undergo apoptosis or differentiate is partly dependent on the balance between different AP-2 isoforms.

Methods
We simultaneously interfered with all AP-2 isoforms expressed in ErbB-2-positive murine N202.1A breast cancer cells by conditionally over-expressing a dominant-negative AP-2 mutant.

Results
We show that interference with AP-2 protein function lead to reduced cell number, induced apoptosis and increased chemo- and radiation-sensitivity. Analysis of global gene expression changes upon interference with AP-2 proteins identified 139 modulated genes (90 up-regulated, 49 down-regulated) compared with control cells. Gene Ontology (GO) investigations for these genes revealed Cell Death and Cell Adhesion and Migration as the main functional categories including 25 and 12 genes, respectively. By using information obtained from Ingenuity Pathway Analysis Systems we were able to present proven or potential connections between AP-2 regulated genes involved in cell death and response to chemo- and radiation therapy, (i.e. Ctgf, Nrp1, Tnfaip3, Gsta3) and AP-2 and other main apoptosis players and to create a unique network.

Conclusions
Expression of AP-2 transcription factors in breast cancer cells supports proliferation and contributes to chemo- and radiation-resistance of tumor cells by impairing the ability to induce apoptosis. Therefore, interference with AP-2 function could increase the sensitivity of tumor cells towards therapeutic intervention.
Gene expression profile and genomic alterations in colonic tumours induced by 1,2-dimethylhydrazine (DMH) in rats
Authors: Femia Angelo Pietro , Luceri Cristina , Toti Simona , Giannini Augusto , Dolara Piero , Caderni Giovanna 
Published: May 2010

AbstractBackgroundAzoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in rats shares many phenotypical similarities with human sporadic colon cancer and is a reliable model for identifying chemopreventive agents. Genetic mutations relevant to human colon cancer have been described in this model, but comprehensive gene expression and genomic analysis have not been reported so far. Therefore, we applied genome-wide technologies to study variations in gene expression and genomic alterations in DMH-induced colon cancer in F344 rats.MethodsFor gene expression analysis, 9 tumours (TUM) and their paired normal mucosa (NM) were hybridized on 4 × 44K Whole rat arrays (Agilent) and selected genes were validated by semi-quantitative RT-PCR. Functional analysis on microarray data was performed by GenMAPP/MappFinder analysis. Array-comparative genomic hybridization (a-CGH) was performed on 10 paired TUM-NM samples hybridized on Rat genome arrays 2 × 105K (Agilent) and the results were analyzed by CGH Analytics (Agilent).ResultsMicroarray gene expression analysis showed thatDefcr4,Igfbp5,Mmp7, Nos2, S100A8andS100A9were among the most up-regulated genes in tumours (Fold Change (FC) compared with NM: 183, 48, 39, 38, 36 and 32, respectively), whileSlc26a3,Mptx,RetlnaandMuc2were strongly down-regulated (FC: -500; -376, -167, -79, respectively). Functional analysis showed that pathways controlling cell cycle, protein synthesis, matrix metalloproteinases, TNFα/NFkB, and inflammatory responses were up-regulated in tumours, while Krebs cycle, the electron transport chain, and fatty acid beta oxidation were down-regulated. a-CGH analysis showed that four TUM out of ten had one or two chromosomal aberrations. Importantly, one sample showed a deletion on chromosome 18 includingApc.ConclusionThe results showed complex gene expression alterations in adenocarcinomas encompassing many altered pathways. While a-CGH analysis showed a low degree of genomic imbalance, it is interesting to note that one of the alterations concernedApc, a key gene in colorectal carcinogenesis. The fact that many of the molecular alterations described in this study are documented in human colon tumours confirms the relevance of DMH-induced cancers as a powerful tool for the study of colon carcinogenesis and chemoprevention.
The association between green space and cause-specific mortality in urban New Zealand: an ecological analysis of green space utility
Authors: Richardson Elizabeth , Pearce Jamie , Mitchell Richard , Day Peter , Kingham Simon 
Published: May 2010

Abstract

Background
There is mounting international evidence that exposure to green environments is associated with health benefits, including lower mortality rates. Consequently, it has been suggested that the uneven distribution of such environments may contribute to health inequalities. Possible causative mechanisms behind the green space and health relationship include the provision of physical activity opportunities, facilitation of social contact and the restorative effects of nature. In the New Zealand context we investigated whether there was a socioeconomic gradient in green space exposure and whether green space exposure was associated with cause-specific mortality (cardiovascular disease and lung cancer). We subsequently asked what is the mechanism(s) by which green space availability may influence mortality outcomes, by contrasting health associations for different types of green space.

Methods
This was an observational study on a population of 1,546,405 living in 1009 small urban areas in New Zealand. A neighbourhood-level classification was developed to distinguish between usable (i.e., visitable) and non-usable green space (i.e., visible but not visitable) in the urban areas. Negative binomial regression models were fitted to examine the association between quartiles of area-level green space availability and risk of mortality from cardiovascular disease (n = 9,484; 1996 - 2005) and from lung cancer (n = 2,603; 1996 - 2005), after control for age, sex, socio-economic deprivation, smoking, air pollution and population density.

Results
Deprived neighbourhoods were relatively disadvantaged in total green space availability (11% less total green space for a one standard deviation increase in NZDep2001 deprivation score, p < 0.001), but had marginally more usable green space (2% more for a one standard deviation increase in deprivation score, p = 0.002). No significant associations between usable or total green space and mortality were observed after adjustment for confounders.

Conclusion
Contrary to expectations we found no evidence that green space influenced cardiovascular disease mortality in New Zealand, suggesting that green space and health relationships may vary according to national, societal or environmental context. Hence we were unable to infer the mechanism in the relationship. Our inability to adjust for individual-level factors with a significant influence on cardiovascular disease and lung cancer mortality risk (e.g., diet and alcohol consumption) will have limited the ability of the analyses to detect green space effects, if present. Additionally, green space variation may have lesser relevance for health in New Zealand because green space is generally more abundant and there is less social and spatial variation in its availability than found in other contexts.
The role of weight status, gender and self-esteem in following a diet among middle-school children in Sicily (Italy)
Authors: Ferrante Margherita , Fiore Maria , Sciacca Gina E , Leon Luca , Sciacca Salvatore , Castaing Marine , Modonutti Gianbattista 
Published: May 2010

AbstractBackgroundWeight-related issues such as obesity, dieting and eating disorders in adolescents are major public health problems. Moreover, undertaking a diet tends to be common among school children and the reasons for doing so are not always related to weight status. The objectives of the study were to evaluate the role of body mass index (BMI), gender and self-esteem in the adoption of a diet in middle-school Sicilian children.MethodsThe survey included middle-school children in some Sicilian provinces. Weight status was determined by sex-specific body mass index for age according to the international BMI cut-off proposed by Cole. Classic chi-square test and linear trend chi-square were used to compare percentages. Univariate and multivariate logistic regressions were computed to study the risk of dieting according to weight status (with the underweight group as the reference group), gender, self-esteem adjusted for province. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) along with associated p-values were furnished.ResultsThe survey showed that 45.2% of the children were of average-weight, 6.6% were underweight, 12.6% were overweight and 2.9% were clinically obese. The missing data were up to 32.8%. Regarding dieting, 26.3% of the children stated that they had been on a diet during the last three months, 56.4% claimed they had not, and 17.2% did not answer. Age was not associated with dieting (p = 0.76). More girls than boys had undertaken a diet (31.4% versus 21.4%, p < 0.0001). Self-esteem had an influence on the choice of following a diet; in fact, 40.8%, 28.5% and 20.9% of the children with negative, normal and positive self-esteem were following a diet (trend p < 0.0001). The multivariate analysis showed that self-esteem seemed to influence more girls than boys (p = 0.06), and stratified analysis by gender indicated that it seemed more influent in girls (p = 0.0008) than in boys (p = 0.01).ConclusionsIn addition to the relation between dieting and BMI, our results highlight the link between dieting, gender and self-esteem. We underline the importance of interventions within the context of health education in order to improve global self-esteem and to encourage proper eating habits to prevent weight-related health problems.
Cyclin K and cyclin D1b are oncogenic in myeloma cells
Authors: Marsaud Véronique , Tchakarska Guergana , Andrieux Geoffroy , Liu Jian-Miao , Dembele Doulaye , Jost Bernard , Wdzieczak-Bakala Joanna , Renoir Jack-Michel , Sola Brigitte 
Published: May 2010

AbstractBackgroundAberrant expression of cyclin D1 is a common feature in multiple myeloma (MM) and always associated with mantle cell lymphoma (MCL).CCND1gene is alternatively spliced to produce two cyclin D1 mRNA isoforms which are translated in two proteins: cyclin D1a and cyclin D1b. Both isoforms are present in MM cell lines and primary cells but their relative role in the tumorigenic process is still elusive.ResultsTo test the tumorigenic potential of cyclin D1bin vivo, we generated cell clones derived from the non-CCND1expressing MM LP-1 cell line, synthesizing either cyclin D1b or cyclin K, a structural homolog and viral oncogenic form of cyclin D1a. Immunocompromised mice injecteds.c. with LP-1K or LP-1D1b cells develop tumors at the site of injection. Genome-wide analysis of LP-1-derived cells indicated that several cellular processes were altered by cyclin D1b and/or cyclin K expression such as cell metabolism, signal transduction, regulation of transcription and translation. Importantly, cyclin K and cyclin D1b have no major action on cell cycle or apoptosis regulatory genes. Moreover, they impact differently cell functions. Cyclin K-expressing cells have lost their migration properties and display enhanced clonogenic capacities. Cyclin D1b promotes tumorigenesis through the stimulation of angiogenesis.ConclusionsOur study indicates that cyclin D1b participates into MM pathogenesisviapreviously unrevealed actions.
A comparative genome analysis of gene expression reveals different regulatory mechanisms between mouse and human embryo pre-implantation development
Authors: He Kan , Zhao Hongbo , Wang Qishan , Pan Yuchun 
Published: May 2010

Abstract

Background
Pre-implantation development is a crucial step in successful implantation and pregnancy in mammals. It has been studied in depth, but mostly in laboratory animal models. Less is known about the regulatory mechanism involved in the pre-implantation development in humans and about the comparative aspects.

Methods
Here, we employed the microarray datasets from the public database library of GEO and applied comparative analysis of genome wide temporal gene expression data based on statistical analysis and functional annotation for both mouse and human, demonstrating the discordance between the regulatory mechanisms of both mouse and human pre-implantation development.

Results
There were differences between mouse and human pre-implantation development both in the global gene expression pattern and in the expression changes of individual genes at each stage, including different major transient waves of transcription profiles and some stage-specific genes and significantly related pathways. There also appeared to be different functional changes from one stage to another between mouse and human.

Conclusions
The analysis presented here lead to interesting and complementary conclusions that the regulatory mechanism of human pre-implantation development is not completely the same as the mouse. Not as the fact that 1-cell to 2-cell stage is important for mouse pre-implantation development, the 4-cell stage and 8-cell stage are both essential for human. Unlike in mouse, of which most of pathways found were related to energy, RNA and protein metabolism, the identified pathways in human were mostly disease-related and associated with human pre-implantation embryonic development. All of these suggest that a further comparative analysis should be required for applying the result of mouse expression data to human research or therapy, particularly in pre-implantation developments. Our study provides several potential targets of genes and pathways for studying the regulatory mechanism of human pre-implantation development using mouse model.
Solid-surface vitrification is an appropriate and convenient method for cryopreservation of isolated rat follicles
Authors: Xing Weijie , Zhou Canquan , Bian Jiang , Montag Markus , Xu Yanwen , Li Yubin , Li Tao 
Published: May 2010

Abstract

Background
Cryopreservation of isolated follicles may be a potential option to restore fertility in young women with cancer, because it can prevent the risks of cancer transmission. Several freezing protocols are available, including slow-rate freezing, open-pulled straws vitrification (OPS) and solid-surface vitrification (SSV, a new freezing technique). The purpose of our study was to investigate the effects of these freezing procedures on viability, ultrastructure and developmental capacity of isolated rat follicles.

Methods
Isolated follicles from female Sprague-Dawley rats were randomly assigned to SSV, OPS and slow-rate freezing groups for cryopreservation. Follicle viability assessment and ultrastructural examination were performed after thawing. In order to study the developmental capacity of thawed follicles, we performed in vitro culture with a three-dimensional (3D) system by alginate hydrogels.

Results
Our results showed that the totally viable rate of follicles vitrified by SSV (64.76%) was slightly higher than that of the OPS group (62.38%) and significantly higher than that of the slow-rate freezing group (52.65%; P < 0.05). The ultrastructural examination revealed that morphological alterations were relatively low in the SSV group compared to the OPS and slow-rate freezing groups. After in vitro culture within a 3D system using alginate hydrogels, we found the highest increase (28.90 ± 2.21 μm) in follicle diameter in follicles from the SSV group. The estradiol level in the SSV group was significantly higher than those in the OPS and slow-rate freezing groups at the end of a 72-hr culture period (P < 0.05).

Conclusions
Our results suggest that the SSV method is an appropriate and convenient method for cryopreservation of isolated rat follicles compared with the conventional slow-rate freezing method and the OPS method.
Ultra-high throughput sequencing-based small RNA discovery and discrete statistical biomarker analysis in a collection of cervical tumours and matched controls
Authors: Witten Daniela , Tibshirani Robert , Gu Sam Guoping , Fire Andrew , Lui Weng-Onn 
Published: May 2010

Abstract

Background
Ultra-high throughput sequencing technologies provide opportunities both for discovery of novel molecular species and for detailed comparisons of gene expression patterns. Small RNA populations are particularly well suited to this analysis, as many different small RNAs can be completely sequenced in a single instrument run.

Results
We prepared small RNA libraries from 29 tumour/normal pairs of human cervical tissue samples. Analysis of the resulting sequences (42 million in total) defined 64 new human microRNA (miRNA) genes. Both arms of the hairpin precursor were observed in twenty-three of the newly identified miRNA candidates. We tested several computational approaches for the analysis of class differences between high throughput sequencing datasets and describe a novel application of a log linear model that has provided the most effective analysis for this data. This method resulted in the identification of 67 miRNAs that were differentially-expressed between the tumour and normal samples at a false discovery rate less than 0.001.

Conclusions
This approach can potentially be applied to any kind of RNA sequencing data for analysing differential sequence representation between biological sample sets.
Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer
Authors: Colleoni Marco , Cole Bernard F. , Viale Giuseppe , Regan Meredith M. , Price Karen N. , Maiorano Eugenio , Mastropasqua Mauro G. , Crivellari Diana , Gelber Richard D. , Goldhirsch Aron , Coates Alan S. , Gusterson Barry A. 
Published: May 2010

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.
Advanced Hepatocellular Carcinoma: Which Staging Systems Best Predict Prognosis?
Authors: Huitzil-Melendez Fidel-David , Capanu Marinela , O'Reilly Eileen M. , Duffy Austin , Gansukh Bolorsukh , Saltz Leonard L. , Abou-Alfa Ghassan K. 
Published: May 2010

Purpose The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival. Patients and Methods Patients with advanced HCC treated over a 5-year period at Memorial Sloan-Kettering Cancer Center were identified from an electronic medical record database. Patients with sufficient data for utilization in all staging systems were included. TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH) systems were ranked on the basis of their accuracy at predicting survival by using concordance index (c-index). Other independent prognostic variables were also identified. Results Overall, 187 eligible patients were identified and were staged by using the seven staging systems. CLIP, CUPI, and GETCH were the three top-ranking staging systems. BCLC and TNM sixth edition lacked any meaningful prognostic discrimination. Performance status, AST, abdominal pain, and esophageal varices improved the discriminatory ability of CLIP. Conclusion In our selected patient population, CLIP, CUPI, and GETCH were the most informative staging systems in predicting survival in patients with advanced HCC. Prospective validation is required to determine if they can be accurately used to stratify patients in clinical trials and to direct the appropriate need for systemic therapy versus best supportive care. BCLC and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data.