bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Inactivation Implies Independent Functions for Insulin-like Growth Factor Binding Protein (IGFBP)-Related Protein 1 and the Related IGFBPL1 in Inhibiting Breast Cancer Phenotypes
Authors: Smith Paul , Nicholson Linda J. , Syed Nelofer , Payne Annette , Hiller Louise , Garrone Ornella , Occelli Marcella , Gasco Milena , Crook Tim 
Published: July 2007

Abstract
Purpose: To analyze epigenetic regulation of two related genes, insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) and IGFBPL1, and its significance as a determinant of clinical phenotypes in human breast cancer.
Experimental Design: We have investigated the expression and epigenetic regulation of IGFBP-rP1 and IGFBPL1 in human breast cancer cell lines and primary and metastatic carcinomas.
Results: Expression of IGFBP-rP1 and IGFBPL1 is down-regulated in breast cancer cell lines. Aberrant methylation in the CpG islands of each gene correlates well with loss of expression at the mRNA level. Analysis of methylation in DNA isolated from human primary breast tumors showed that methylation in either gene was associated with a worse overall survival (OS; P = 0.008) and disease-free survival (DFS) following surgery (P = 0.04) and worse DFS following adjuvant chemotherapy (P = 0.01). Methylation of IGFBP-rP1 alone was associated with a trend toward decreased OS (P = 0.10) and decreased DFS (P = 0.25). Methylation in IGFBPL1 was clearly associated with worse OS (P = 0.001) and DFS (P &lt; 0.0001). Methylation in either IGFBP-rP1 or IGFBPL1 was significantly associated with nodal disease (P &lt; 0.001).
Conclusions: Expression of IGFBP-rP1 and IGFBPL1 is regulated by aberrant hypermethylation in breast cancer, implying that inactivation of these genes is involved in the pathogenesis of this malignancy. Analysis of methylation of these genes may have utility in prediction of clinical phenotypes, such as nodal disease and response to chemotherapy.
The Convergent Development of Molecular-Targeted Drugs for Cancer Treatment and Prevention
Authors: Lippman Scott M. , Heymach John V. 
Published: July 2007

Abstract
Advances in our understanding of multistep and field carcinogenesis are erasing the clear demarcation of intraepithelial neoplasia from invasive neoplasia. The growing ability to define a very high risk of cancer is forging important commonalities between prevention and therapy, such as in potential prognostic/predictive markers, agents, and side effects that patients would be willing to tolerate, and the logistics of definitive trials. The emergence of promising new molecular-targeted agents and new technologies for screening and early detection provides new opportunities for applying clinical trial designs that integrate therapy and prevention end points. Such trials may be used to facilitate targeted drug development and help identify strategies for both cancer prevention and advanced cancer therapy. These several advances are creating a convergence of cancer therapy with cancer prevention that promises to streamline the development of targeted drugs and improve the control of major cancers.
BRCA Mutations in Women with Ductal Carcinoma In situ
Authors: Smith Karen Lisa , Adank Muriel , Kauff Noah , Lafaro Kelly , Boyd Jeff , Lee Johanna B. , Hudis Clifford , Offit Kenneth , Robson Mark 
Published: July 2007

Abstract
Purpose: The strength of the association between ductal carcinoma in situ (DCIS) and BRCA mutations has not been defined.
Experimental Design: Mutation frequency was compared in three groups: (1) a prevalent series of women with DCIS, (2) an incident series of women with DCIS, and (3) a clinic-based series of women with DCIS referred for hereditary cancer risk assessment. In groups 1 and 2, limited to Ashkenazi Jewish (AJ) cases, mutation frequency was compared with that in age-matched AJ controls with invasive breast cancer (IBC).
Results: In group 1, 3 of 62 (4.8%) women with DCIS and 15 of 130 (11.5%) controls with IBC had BRCA mutations. In group 2, 0 of 58 (0%) women with DCIS and 6 of 116 (5.2%) controls with IBC had BRCA mutations [combined odds ratios (OR) in groups 1 and 2: 3.64, 95% confidence interval (95% CI), 1.06-12.46; P = 0.04]. In group 3, deleterious mutations were identified in 10 of 79 (12.7%) probands with DCIS, similar to the frequency in IBC probands. In group 3, mutations were associated with family history of ovarian cancer (OR, 13.35; 95% CI, 2.48-71.94; P = 0.003) or early onset breast cancer (OR, 16.23; 95% CI, 1.68-157.01; P = 0.02) but not with AJ ethnicity or age at diagnosis.
Conclusions:BRCA mutations were less frequent in women with DCIS not selected for family history or age at diagnosis than in women with IBC. Nonetheless, mutations were found in a significant proportion of women with DCIS who presented for hereditary risk assessment.
Protein Expression Profiling and Molecular Classification of Gastric Cancer by the Tissue Array Method
Authors: Lee Hye Seung , Cho Sung-Bum , Lee Hee Eun , Kim Min A , Kim Ji Hun , Park Do Joong , Kim Ju Han , Yang Han-Kwang , Lee Byung Lan , Kim Woo Ho 
Published: July 2007

AbstractPurpose: Gastric cancer is heterogeneous clinically and histologically, and prognosis prediction by tumor grade or type is difficult. Although previous studies have suggested that frozen tissue–based molecular classifications effectively predict prognosis, prognostic classification on formalin-fixed tissue is needed, especially in early gastric cancer.Experimental Design: We immunostained 659 consecutive gastric cancers using 56 tumor-associated antibodies and the tissue array method. Hierarchical cluster analyses were done before and after feature selection. To optimize classifier number and prediction accuracy for prognosis, a supervised analysis using a support vector machine algorithm was used.Results: Of 56 gene products, 27 survival-associated proteins were selected (feature selection), and hierarchical clustering identified two clusters: cluster 1 and cluster 2. Cluster 1 cancers were more likely to have intestinal type, earlier stage, and better prognosis than cluster 2 (P &lt; 0.05). In 187 early gastric cancers (pT1), cluster 2 was associated with the presence of metastatic lymph nodes (P = 0.026). Kaplan-Meier survival curves stratified by pathologic tumor-lymph node metastasis revealed that cluster 2 was associated with poor prognosis in stage I or II cancer (P &lt; 0.05). Support vector machines and genetic algorithms selected nine classifiers from the whole data set, another nine classifiers for stage I and II, and eight classifiers for stage III and IV. The prediction accuracies for patient outcome were 73.1%, 88.1%, and 76%, respectively.Conclusions: Protein expression profiling using the tissue array method provided a useful means for the molecular classification of gastric cancer into survival-predictive subgroups. The molecular classification predicted lymph node metastasis and prognosis in early stage gastric cancer.
Dual Targeting of Endothelial Cells and Pericytes in Antivascular Therapy for Ovarian Carcinoma
Authors: Lu Chunhua , Kamat Aparna A. , Lin Yvonne G. , Merritt William M. , Landen Charles N. , Kim Tae Jin , Spannuth Whitney , Arumugam Thiru , Han Liz Y. , Jennings Nicholas B. , Logsdon Craig , Jaffe Robert B. , Coleman Robert L. , Sood Anil K. 
Published: July 2007

Abstract
Purpose: Pericytes are known to provide a survival advantage for endothelial cells. We hypothesize that strategies aimed at dual targeting of tumor-associated endothelial cells and pericytes will be highly efficacious.
Experimental Design: Paclitaxel-sensitive (HeyA8 and SKOV3ip1) or paclitaxel-resistant (HeyA8-MDR) orthotopic tumors in mice were examined for therapeutic efficacy by targeting the endothelial cells (using a vascular endothelial growth factor receptor inhibitor, AEE788) and pericytes (using STI571) alone or in combination. Additional therapy and survival studies in combination with paclitaxel were also done. Following therapy, tumors were examined for endothelial cell apoptosis, pericyte coverage, microvessel density, and proliferation.
Results: AEE788 inhibited tumor growth by 45% and 59% in the HeyA8 and SKOV3ip1 models, respectively, whereas STI571 alone was not effective. AEE788 plus STI571 resulted in 69% to 84% inhibition of tumor growth in both models. Moreover, combination of these agents with paclitaxel was even more effective, resulting in up to 98% inhibition of tumor growth. The triple combination was even effective in the HeyA8-MDR model. Remarkably, this triple combination also resulted in improved survival compared with all other groups (P &lt; 0.001) and caused regression of formed tumors. Pericyte coverage was significantly decreased in the STI571 treatment groups, and microvessel density was significantly reduced in the AEE788 treatment groups. AEE788 induced endothelial cell apoptosis, which was further enhanced by the addition of STI571.
Conclusions: Strategies targeting both endothelial cells and pericytes are highly effective for in vivo treatment of ovarian carcinoma. This antiangiogenic effect may be partially due to decreased pericyte coverage, thus increasing the sensitivity of tumor vasculature to therapy. These encouraging data support the development of clinical trials based on this strategy.
Prognostic Significance of Nuclear ING3 Expression in Human Cutaneous Melanoma
Authors: Wang Yemin , Dai Derek L. , Martinka Magdalena , Li Gang 
Published: July 2007

Abstract
Purpose: The novel tumor-suppressor ING3 has been shown to modulate transcription, cell cycle control, and apoptosis. Our previous study showed that ING3 promotes UV-induced apoptosis via the Fas/caspase-8–dependent pathway in melanoma cells. To investigate the putative role of ING3 in the development of melanoma, we examined the expression of ING3 in melanocytic lesions at different stages and analyzed the correlation between ING3 expression and clinicopathologic variables and patient survival.
Experimental Design: Using tissue microarray and immunohistochemistry, we evaluated nuclear and cytoplasmic ING3 staining in 58 dysplastic nevi, 114 primary melanomas, and 50 metastatic melanomas.
Results: Nuclear ING3 expression was remarkably reduced in malignant melanomas compared with dysplastic nevi (P &lt; 0.001), which was significantly correlated with the increased ING3 level in cytoplasm (P &lt; 0.05). Furthermore, the reduced nuclear ING3 expression was significantly correlated with a poorer disease-specific 5-year survival of patients with primary melanoma, especially for the high-risk melanomas (thickness ≥2.0 mm) with the survival rate reducing from 93% for patients with strong nuclear ING3 staining in their tumor biopsies to 44% for those with negative-to-moderate nuclear ING3 staining (P = 0.004). Strikingly, our multivariate Cox regression analysis revealed that reduced nuclear ING3 expression is an independent prognostic factor to predict patient outcome in primary melanomas (P = 0.038).
Conclusions: Our data indicate that ING3 may be an important marker for human melanoma progression and prognosis as well as a potential therapeutic target.
Evaluation of MM5 Optically Thin Clouds over Europe in Fall Using ICESat Lidar Spaceborne Observations
Authors: Chepfer H. , Chiriaco M. , Vautard R. , Spinhirne J. 
Published: July 2007

Abstract
The description of clouds in mesoscale models has progressed significantly during recent years by improving microphysical schemes with more physical parameterizations deduced from observations. Recently, the first lidar in space, the Ice, Cloud, and Land Elevation Satellite (ICESat)/Geosciences Laser Altimeter System, has collected a valuable dataset that improves the knowledge of occurrence and macrophysical properties of clouds, and particularly high-altitude clouds, which are usually optically thin. This study evaluates the capability of the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) to reproduce optically thin clouds using the ICESat October–November 2003 dataset. Initial and boundary conditions are prescribed from NCEP products and MM5 run over the European continent with a 40-km spatial resolution. Spaceborne lidar profiles are diagnosed from model outputs and compared with the observed ones at the same location and time. One month of simulations–observations comparisons shows that the model correctly reproduces cloud structures on average, but underestimates the thinnest clouds (by 0%–20%) and overestimates less thin clouds in the upper troposphere (altitude &gt;6 km). The total low-level water cloud amount (altitude &lt;6 km) appears fairly well reproduced, although the masking effect of higher clouds does not allow for a firm conclusion. The clouds are rarely simulated and observed simultaneously, 50% for high clouds and 20% for low clouds. The lack of high-altitude very thin clouds is possibly due to dry biases in the upper-troposphere humidity fields used to force the model. The overestimation of optically less thin cloud may be due to an overestimation of the cloud lifetime or water vapor supersaturation around ice clouds that is not taken into account in the model. When the upper troposphere and low warm clouds appear in the model at the same time and location as in the observations, they are optically too thick, likely because their water/ice content and particle concentration are overestimated simultaneously.
Regional Climate Model–Simulated Timing and Character of Seasonal Rains in South America
Authors: Rauscher Sara A. , Seth Anji , Liebmann Brant , Qian Jian-Hua , Camargo Suzana J. 
Published: July 2007

Abstract
The potential of an experimental nested prediction system to improve the simulation of subseasonal rainfall statistics including daily precipitation intensity, rainy season onset and withdrawal, and the frequency and duration of dry spells is evaluated by examining a four-member ensemble of regional climate model simulations performed for the period 1982–2002 over South America. The study employs the International Centre for Theoretical Physics (ICTP) regional climate model, version 3 (RegCM3), driven with the NCEP–NCAR reanalysis and the European Centre–Hamburg GCM, version 4.5. Statistics were examined for five regions: the northern Amazon, southern Amazon, the monsoon region, Northeast Brazil, and southeastern South America. RegCM3 and the GCM are able to replicate the distribution of daily rainfall intensity in most regions. The analysis of the rainy season timing shows the observed onset occurring first over the monsoon region and then spreading northward into the southern Amazon, in contrast to some previous studies. Correlations between the onset and withdrawal date and SSTs reveal a strong relationship between the withdrawal date in the monsoon region and SSTs in the equatorial Pacific, with above-average SSTs associated with late withdrawal. Over Northeast Brazil, the regional model errors are smaller than those shown by the GCM, and the strong interannual variability in the timing of the rainy season is better simulated by RegCM3. However, the regional model displays an early bias in onset and withdrawal over the southern Amazon and the monsoon regions. Both RegCM3 and the GCM tend to underestimate (overestimate) the frequency of shorter (longer) dry spells, although the differences in dry spell frequency during warm and cold ENSO events are well simulated. The results presented here show that there is potential for added value from the regional model in simulating subseasonal statistics; however, improvements in the physical parameterizations are needed for this tropical region.
Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates
Authors: Kaur Kulwant , Chowdhury Shimul , Greenspan Neil S. , Schreiber John R. 
Published: July 2007

AbstractNeonates have an increased rate of infection with encapsulated bacteria compared with older children and adults because of diminished antibody responses to T-independent (TI) antigens such as bacterial polysaccharides. Because the interactions of tumor necrosis factor (TNF) family ligands BAFF and APRIL with the TNF family receptors (TNFRs) TACI, BCMA, and BAFF-R are crucial to TI antibody responses, we measured the expression of these receptors on adult and cord blood–derived term and preterm neonatal B cells. Preterm neonatal B cells expressed less TACI, BCMA, and BAFF-R compared with adult B cells and had significantly less proliferation compared with adult B cells after stimulation with human recombinant BAFF and anti-IgM in an assay in which TACI-Fc fusion protein inhibits B-cell proliferation. In addition, neonatal dendritic cells had diminished expression of B7–1, B7–2, and CD40 compared with adult cells. Finally, neonatal B cells, particularly preterm B cells, exhibited markedly decreased production of IgG and IgA in response to CD40L and IL-10. Overall, this study shows that maturational delay in TNFR expression particularly by preterm neonatal B cells may interfere with effective antibody responses to TI antigens, cognate T- and B-cell interactions and normal isotype switching.
Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes
Authors: Mohamedali Azim , Gäken Joop , Twine Natalie A. , Ingram Wendy , Westwood Nigel , Lea Nicholas C. , Hayden Janet , Donaldson Nora , Aul Carlo , Gattermann Norbert , Giagounidis Aristotle , Germing Ulrich , List Alan F. , Mufti Ghulam J. 
Published: July 2007

AbstractLow-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q− syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q− syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions.
Ancestral European roots of Helicobacter pylori in India
Authors: Devi S Manjulata , Ahmed Irshad , Francalacci Paolo , Hussain M Abid , Akhter Yusuf , Alvi Ayesha , Sechi Leonardo A , Mégraud Francis , Ahmed Niyaz 
Published: July 2007

Abstract

Background
The human gastric pathogen Helicobacter pylori is co-evolved with its host and therefore, origins and expansion of multiple populations and sub populations of H. pylori mirror ancient human migrations. Ancestral origins of H. pylori in the vast Indian subcontinent are debatable. It is not clear how different waves of human migrations in South Asia shaped the population structure of H. pylori. We tried to address these issues through mapping genetic origins of present day H. pylori in India and their genomic comparison with hundreds of isolates from different geographic regions.

Results
We attempted to dissect genetic identity of strains by multilocus sequence typing (MLST) of the 7 housekeeping genes (atp A, efp, ure I, ppa, mut Y, trp C, yph C) and phylogeographic analysis of haplotypes using MEGA and NETWORK software while incorporating DNA sequences and genotyping data of whole cag pathogenicity-islands (cag PAI). The distribution of cag PAI genes within these strains was analyzed by using PCR and the geographic type of cag A phosphorylation motif EPIYA was determined by gene sequencing. All the isolates analyzed revealed European ancestry and belonged to H. pylori sub-population, hpEurope. The cag PAI harbored by Indian strains revealed European features upon PCR based analysis and whole PAI sequencing.

Conclusion
These observations suggest that H. pylori strains in India share ancestral origins with their European counterparts. Further, non-existence of other sub-populations such as hpAfrica and hpEastAsia, at least in our collection of isolates, suggest that the hpEurope strains enjoyed a special fitness advantage in Indian stomachs to out-compete any endogenous strains. These results also might support hypotheses related to gene flow in India through Indo-Aryans and arrival of Neolithic practices and languages from the Fertile Crescent.
Prevalence, awareness and control of diabetes in the Seychelles and relationship with excess body weight
Authors: Faeh David , William Julita , Tappy Luc , Ravussin Eric , Bovet Pascal 
Published: July 2007

Abstract

Background
The evidence for a "diabesity" epidemic is accumulating worldwide but population-based data are still scarce in the African region. We assessed the prevalence, awareness and control of diabetes (DM) in the Seychelles, a rapidly developing country in the African region. We also examined the relationship between body mass index, fasting serum insulin and DM.

Methods
Examination survey in a sample representative of the entire population aged 25–64 of the Seychelles, attended by 1255 persons (participation rate of 80.2%). An oral glucose tolerance test (OGTT) was performed in individuals with fasting blood glucose between 5.6 and 6.9 mmol/l. Diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined along criteria of the ADA. Prevalence estimates were standardized for age.

Results
The prevalence of DM was 11.5% and 54% of persons with DM were aware of having DM. Less than a quarter of all diabetic persons under treatment were well controlled for glycemia (HbA1c), blood pressure or LDL-cholesterol. The prevalence of IGT and IFG were respectively 10.4% and 24.2%. The prevalence of excess weight (BMI ≥ 25 kg/m2) and obesity (BMI ≥ 30 kg/m2) was respectively 60.1% and 25.0%. Half of all DM cases in the population could be attributed to excess weight.

Conclusion
We found a high prevalence of DM and pre-diabetes in a rapidly developing country in the African region. The strong association between overweight and DM emphasizes the importance of weight control measures to reduce the incidence of DM in the population. High rates of diabetic persons not aware of having DM in the population and insufficient cardiometabolic control among persons treated for DM stress the need for intensifying health care for diabetes.