bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMI and Lipid Levels in Mexican American Children Diagnosed with Type 2 Diabetes
Authors: Fortmeier‐Saucier Linda , Savrin Carol , Heinzer Marjorie , Hudak Christine 
Published: September 2008

ABSTRACT Purpose: The purpose of this study was to determine potential associations between obesity as measured by body mass index (BMI) and lipid values in Mexican American (MA) children diagnosed with type 2 diabetes. Background: Obesity in children is considered to be an emerging epidemic that is accompanied by an increase in prevalence of type 2 diabetes. Literature shows that there is a direct and strong relationship between abnormal lipid levels and obesity in Caucasian and African American children without type 2 diabetes. However, it was unknown whether Mexican American children diagnosed with type 2 diabetes have abnormal lipid levels. Method: A retrospective medical‐record review was conducted on paediatric patients who received medical care from a military medical centre in the Southwest region of the United States. A convenience sample of records was used to study the relationship between obesity as measured by BMI and lipid levels in 49 Mexican American children diagnosed with type 2 diabetes. Total cholesterol, high‐density lipoprotein (HDL), low‐density lipoprotein (LDL), triglycerides (TG), and BMI were reviewed. Data were analysed using descriptive and logistic regression statistics. Findings: Ninety percent of the sample was obese and 75% had two or more abnormal lipid values. Abnormal levels of total cholesterol, HDL, and triglycerides were found to be statistically significant. Conclusions: The main findings indicate that MA children diagnosed with type 2 diabetes had significant associations between obesity as measured by BMI and abnormal total cholesterol, HDL, and triglyceride levels. As the BMI increased, the probability of abnormal total cholesterol and triglyceride levels increased. Similarly, as the BMI increased, the probability of abnormal HDL values increased. Mexican American children in this study had obesity levels similar to those in a study by the National Center for Health Statistics. In this study a step has been taken toward understanding a physiologic marker for cardiovascular disease in children.
The Emotional Impact of Obesity on Children
Authors: Cornette Robert 
Published: September 2008

ABSTRACT Background: Childhood overweight and obesity has become a global epidemic affecting children of all ages and ethnic and socioeconomic backgrounds. While the physical and financial consequences are well documented, little research is available on the emotional effect of overweight and obesity on children and adolescents. Objectives: To assess the emotional effect of overweight and obesity on a child's self‐esteem and self‐concept. Search Strategy: The following databases were searched: CINAHL, Clinical Pharmacology, Health Source–Nursing and Academic Edition, MEDLINE, Pre‐CINAHL, Psychological and Behavioral Sciences Collection, PsycINFO, and Sociological Collection, along with the Cochrane Library, Joanna Briggs Institute, National Institute of Health (NIH), and Centers for Disease Control and Prevention (CDC). Selection Criteria Included: Studies published from January 1995 to December 2005 whose primary aim was to investigate psychological impact of being overweight or obese on children and adolescents of both genders and all ethnic, cultural, and socioeconomic backgrounds. Studies of 50 or more participants with outcomes that included an assessment tool of psychological measurement and weight or body mass index (BMI), and were in English or translated to English were considered. Findings: All participants reported some level of psychosocial impact from being overweight or obese. Younger children, girls, and those with little control over eating suffered the greatest consequences. Conclusions: Evidence to determine the emotional impact of being overweight in children and adolescents is limited. There is even less research focused on the efforts to address the problem of low self‐esteem, depression, and other emotional consequences. More attention should be focused on the emotional effect of childhood overweight and obesity in order to provide more holistic care for this pediatric population.
Probability risk assessment of landslides: A case study at Finneidfjord
Authors: Cassidy Mark J. , Uzielli Marco , Lacasse Suzanne 
Published: September 2008

Probabilistic risk assessments are increasingly being considered the most appropriate framework for engineers to systematically base decisions on hazard mitigation issues. This paper aims to show the advantages of a quantitative risk assessment by application to a historical case study. The generalized integrated risk assessment framework has been applied retrospectively to a submarine landslide that occurred in 1996 near the village of Finneidfjord in northern Norway. Over 1 million cubic metres of predominantly quick clay was displaced. Even though it was triggered underwater on the embankment of the Sørfjord, the retrogressive nature of the slide resulted in it encroaching 100–150 m inland. The triggering mechanism is believed to have been the placement of fill, from a nearby tunnelling project, on the foreshore of the embankment. This paper is a retrospective quantitative evaluation of the risk to the neighbouring houses, the persons in those houses, and the persons in open spaces caused by the placement of increasing levels of embankment fill. A probabilistic approach, making use of second-moment modelling and first-order second-moment approximation is adopted. It aims to demonstrate the advantages of this type of risk assessment in understanding complex and integrated hazards, particularly those in populated environments.
Truncated ETV1, Fused to Novel Tissue-Specific Genes, and Full-Length ETV1 in Prostate Cancer
Authors: Hermans Karin G. , van der Korput Hetty A. , van Marion Ronald , van de Wijngaart Dennis J. , Ziel-van der Made Angelique , Dits Natasja F. , Boormans Joost L. , van der Kwast Theo H. , van Dekken Herman , Bangma Chris H. , Korsten Hanneke , Kraaij Robert , Jenster Guido , Trapman Jan 
Published: September 2008

Abstract
In this study, we describe the properties of novel ETV1 fusion genes, encoding N-truncated ETV1 (dETV1), and of full-length ETV1, overexpressed in clinical prostate cancer. We detected overexpression of novel ETV1 fusion genes or of full-length ETV1 in 10% of prostate cancers. Novel ETV1 fusion partners included FOXP1, an EST (EST14), and an endogenous retroviral repeat sequence (HERVK17). Like TMPRSS2, EST14 and HERVK17 were prostate-specific and androgen-regulated expressed. This unique expression pattern of most ETV1 fusion partners seems an important determinant in prostate cancer development. In transient reporter assays, full-length ETV1 was a strong transactivator, whereas dETV1 was not. However, several of the biological properties of dETV1 and full-length ETV1 were identical. On stable overexpression, both induced migration and invasion of immortalized nontumorigenic PNT2C2 prostate epithelial cells. In contrast to dETV1, full-length ETV1 also induced anchorage-independent growth of these cells. PNT2C2 cells stably transfected with dETV1 or full-length ETV1 expression constructs showed small differences in induced expression of target genes. Many genes involved in tumor invasion/metastasis, including uPA/uPAR and MMPs, were up-regulated in both cell types. Integrin β3 (ITGB3) was clearly up-regulated by full-length ETV1 but much less by dETV1. Based on the present data and on previous findings, a novel concept of the role of dETV1 and of full-length ETV1 overexpression in prostate cancer is proposed. [Cancer Res 2008;68(18):7541–9]
Flt-1 Signaling in Macrophages Promotes Glioma Growth In vivo
Authors: Kerber Mark , Reiss Yvonne , Wickersheim Anke , Jugold Manfred , Kiessling Fabian , Heil Matthias , Tchaikovski Vadim , Waltenberger Johannes , Shibuya Masabumi , Plate Karl H. , Machein Marcia Regina 
Published: September 2008

Abstract
Several lines of evidence indicate that Flt-1, a fms-like tyrosine kinase receptor, which binds to vascular endothelial growth factor (VEGF)-A, VEGF-B, and PlGF, is a positive regulator of angiogenesis in the context of tumor growth and metastasis. However, the molecular basis of its action is still not clear. Besides endothelial cells, Flt-1 is also expressed by other different cell types, including myeloid hematopoeitic cells (monocytes and macrophages). To examine the functions of Flt-1 expressed by bone marrow–derived myeloid cells in supporting tumor growth and angiogenesis, Flt-1 tyrosine kinase–deficient (Flt-1 TK−/−) bone marrow cells were transplanted into lethally irradiated syngeneic recipients. After hematopoietic reconstitution, we orthotopically implanted syngeneic wild-type glioma cells or glioma cells overexpressing either VEGF164 or PlGF-2. Loss of Flt-1 signaling in bone marrow–derived myeloid cells led to a significant decrease in tumor volume and vascularization in gliomas. VEGF but not PlGF overexpressed by glioma cells restored the tumor growth rate in Flt-1 TK−/− bone marrow chimera. VEGF and PlGF overexpression by tumor cells induced an accumulation of bone marrow–derived myeloid cells into tumor tissue. This infiltration was decreased in tumors grown in Flt-1 TK−/− bone marrow chimeras. When investigating chemokines and growth factors involved in myeloid cell recruitment, we determined elevated SDF-1/CXCL12 levels in VEGF- and PlGF-overexpressing tumors. Collectively, these results suggest that Flt-1 signaling in myeloid cells is essential to amplify the angiogenic response and to promote glioma growth. [Cancer Res 2008;68(18):7342–51]
Targeting V600EB-Raf and Akt3 Using Nanoliposomal-Small Interfering RNA Inhibits Cutaneous Melanocytic Lesion Development
Authors: Tran Melissa A. , Gowda Raghavendra , Sharma Arati , Park Eun-Joo , Adair James , Kester Mark , Smith Nadine Barrie , Robertson Gavin P. 
Published: September 2008

Abstract
Most events promoting early melanoma development are yet to be identified, but deregulation of the B-Raf and Akt3 signaling cascades is an important regulator of this process. Approximately 90% of normal moles and ∼60% of early invasive cutaneous melanomas contain a T1799A B-Raf mutation (V600EB-Raf), leading to 10 times higher enzyme activity and constitutive activation of the mitogen-activated protein kinase pathway. Furthermore, ∼70% of melanomas have elevated Akt3 signaling due to increased gene copy number and PTEN loss. Therefore, targeting V600EB-Raf and Akt3 signaling is necessary to prevent or treat cutaneous melanocytic lesions. Agents specifically targeting these proteins are needed, having fewer side effects than those inhibiting both normal and mutant B-Raf protein or targeting all three Akt isoforms. In this study, a unique nanoliposomal-ultrasound–mediated approach has been developed for delivering small interfering RNA (siRNA) specifically targeting V600EB-Raf and Akt3 into melanocytic tumors present in skin to retard melanoma development. Novel cationic nanoliposomes stably encapsulate siRNA targeting V600EB-Raf or Akt3, providing protection from degradation and facilitating entry into melanoma cells to decrease expression of these proteins. Low-frequency ultrasound using a lightweight four-cymbal transducer array enables penetration of nanoliposomal-siRNA complex throughout the epidermal and dermal layers of laboratory-generated or animal skin. Nanoliposomal-mediated siRNA targeting of V600EB-Raf and Akt3 led to a cooperatively acting ∼65% decrease in early or invasive cutaneous melanoma compared with inhibition of each singly with negligible associated systemic toxicity. Thus, cationic nanoliposomes loaded with siRNA targeting V600EB-Raf and Akt3 provide an effective approach for targeted inhibition of early or invasive cutaneous melanomas. [Cancer Res 2008;68(18):7638–49]
RhoC Promotes Metastasis via Activation of the Pyk2 Pathway in Prostate Cancer
Authors: Iiizumi Megumi , Bandyopadhyay Sucharita , Pai Sudha K. , Watabe Misako , Hirota Shigeru , Hosobe Sadahiro , Tsukada Taisei , Miura Kunio , Saito Ken , Furuta Eiji , Liu Wen , Xing Fei , Okuda Hiroshi , Kobayashi Aya , Watabe Kounosuke 
Published: September 2008

Abstract
RhoC is a member of the Ras-homologous family of genes which have been implicated in tumorigenesis and tumor progression. However, the exact role of RhoC is controversial and is yet to be clarified. We have examined the effect of RhoC on prostate tumor cells and found that RhoC had no effect on cell proliferation in vitro or on tumor growth in mice. However, RhoC significantly enhanced the metastatic ability of the tumor cells in these animals, suggesting that RhoC affects only the metastasis but not the growth of prostate tumor cells. The results of our immunohistochemical analyses on tumor specimens from 63 patients with prostate cancer indicate that RhoC expression had no significant correlation with Gleason grade. However, the expression of RhoC showed significant positive correlation with both lymph node and distant metastasis, and it was inversely correlated with patient survival. We also found that RhoC significantly augmented the invasion and motility of prostate tumor cells by activating matrix metalloproteinases 2 and 9 (MMP2 and MMP9) in vitro. The results of our antibody array analysis for signal molecules revealed that RhoC significantly activated kinases including mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK), Akt, and Pyk2. Inhibition of Pyk2 kinase blocked the RhoC-dependent activation of FAK, MAPK, and Akt, followed by the suppression of MMP2 and MMP9. Inhibitors of both MAPK and Akt also significantly blocked the activities of these MMPs. Therefore, our results indicate that RhoC promotes tumor metastasis in prostate cancer by sequential activation of Pyk2, FAK, MAPK, and Akt followed by the up-regulation of MMP2 and MMP9, which results in the stimulation of invasiveness of tumor cells. [Cancer Res 2008;68(18):7613–20]
Knockdown of the Transforming Growth Factor-β Type III Receptor Impairs Motility and Invasion of Metastatic Cancer Cells
Authors: Criswell Tracy L. , Dumont Nancy , Barnett Joey V. , Arteaga Carlos L. 
Published: September 2008

Abstract
The transforming growth factor-β (TGF-β) signaling pathway plays dual roles in epithelial cell tumorigenesis. TGF-β is initially growth inhibitory, but as tumorigenesis progresses, TGF-β becomes prometastatic. Although the role of the types I and II TGF-β receptors is fairly well established, the role of the ubiquitously expressed TGF-β type III receptor (TβRIII) in tumorigenesis is less defined. To examine the role of TβRIII in breast cancer cells, we stably expressed short hairpin RNAs specific to TβRIII in MDA-231 human breast cancer cells and mouse mammary carcinoma cells expressing the polyomavirus middle T oncogene (PMTLuc). MDA-231 and PMTLuc cells with down-regulated TβRIII expression (231-kd; PMTLuc-kd) exhibited decreased growth rate, motility, and invasion into Matrigel, as well as an increase in apoptosis, compared with control cells. MDA-231 xenografts established in nude mice metastasized, whereas tumors made by 231-kd cells did not. Nuclear factor-κB (NF-κB) activity, which is known to regulate cell growth and motility, was lower in the MDA-231 and PMTLuc knockdown cells compared with control cells. Transfection of an expression vector encoding constitutively active IKK2 into the 231-kd cells restored the ability of TβRIII-deficient cells to invade Matrigel and decreased their basal level of apoptosis. These data indicate that TβRIII differentially regulates cell growth, motility, and invasion in tumorigenic MDA-231 and PMTLuc cells and that these growth changes occur through the modulation of NF-κB activity. [Cancer Res 2008;68(18):7304–12]
Nkx3-1 and LEF-1 Function as Transcriptional Inhibitors of Estrogen Receptor Activity
Authors: Holmes Kelly A. , Song Jun S. , Liu Xiaole S. , Brown Myles , Carroll Jason S. 
Published: September 2008

Abstract
Estrogen receptor (ER)-associated cofactors and cooperating transcription factors are one of the primary components determining transcriptional activity of estrogen target genes and may constitute potential therapeutic targets. Recent mapping of ER-binding sites on a genome-wide scale has provided insight into novel cooperating factors based on the enrichment of transcription factor motifs within the ER-binding sites. We have used the ER-binding sites in combination with sequence conservation to identify the statistical enrichment of Nkx and LEF motifs. We find that Nkx3-1 and LEF-1 bind to several ER cis-regulatory elements in vivo, but they both function as transcriptional repressors of estrogen signaling. We show that Nkx3-1 and LEF-1 can inhibit ER binding to chromatin, suggesting competition for common chromatin-binding regions. These data provide insight into the role of Nkx3-1 and LEF-1 as potential regulators of the hormone response in breast cancer. [Cancer Res 2008;68(18):7380–5]
The Cytoplasmic Deacetylase HDAC6 Is Required for Efficient Oncogenic Tumorigenesis
Authors: Lee Yi-Shan , Lim Kian-Huat , Guo Xing , Kawaguchi Yoshiharu , Gao Yasheng , Barrientos Tomasa , Ordentlich Peter , Wang Xiao-Fan , Counter Christopher M. , Yao Tso-Pang 
Published: September 2008

Abstract
Histone deacetylase inhibitors (HDACI) are promising antitumor agents. Although transcriptional deregulation is thought to be the main mechanism underlying their therapeutic effects, the exact mechanism and targets by which HDACIs achieve their antitumor effects remain poorly understood. It is not known whether any of the HDAC members support robust tumor growth. In this report, we show that HDAC6, a cytoplasmic-localized and cytoskeleton-associated deacetylase, is required for efficient oncogenic transformation and tumor formation. We found that HDAC6 expression is induced upon oncogenic Ras transformation. Fibroblasts deficient in HDAC6 are more resistant to both oncogenic Ras and ErbB2-dependent transformation, indicating a critical role for HDAC6 in oncogene-induced transformation. Supporting this hypothesis, inactivation of HDAC6 in several cancer cell lines reduces anchorage-independent growth and the ability to form tumors in mice. The loss of anchorage-independent growth is associated with increased anoikis and defects in AKT and extracellular signal-regulated kinase activation upon loss of adhesion. Lastly, HDAC6-null mice are more resistant to chemical carcinogen-induced skin tumors. Our results provide the first experimental evidence that a specific HDAC member is required for efficient oncogenic transformation and indicate that HDAC6 is an important component underlying the antitumor effects of HDACIs. [Cancer Res 2008;68(18):7561–9]
Kaiso Contributes to DNA Methylation-Dependent Silencing of Tumor Suppressor Genes in Colon Cancer Cell Lines
Authors: Lopes Eloisi C. , Valls Ester , Figueroa Maria E. , Mazur Alexander , Meng Fan-Guo , Chiosis Gabriela , Laird Peter W. , Schreiber-Agus Nicole , Greally John M. , Prokhortchouk Egor , Melnick Ari 
Published: September 2008

Abstract
Aberrant CpG methylation of tumor suppressor gene regulatory elements is associated with transcriptional silencing and contributes to malignant transformation of different tissues. It is presumed that methylated DNA sequences recruit repressor machinery to actively shutdown gene expression. The Kaiso protein is a transcriptional repressor expressed in human and murine colorectal tumors that can bind to methylated clusters of CpG dinucleotides. We show here that Kaiso represses methylated tumor suppressor genes and can bind in a methylation-dependent manner to the CDKN2A in human colon cancer cell lines. The contribution of Kaiso to epigenetic silencing was underlined by the fact that Kaiso depletion induced tumor suppressor gene expression without affecting DNA methylation levels. As a consequence, colon cancer cells became susceptible to cell cycle arrest and cell death mediated by chemotherapy. The data suggest that Kaiso is a methylation-dependent “opportunistic” oncogene that silences tumor suppressor genes when they become hypermethylated. Because Kaiso inactivation sensitized colon cancer cell lines to chemotherapy, it is possible that therapeutic targeting of Kaiso could improve the efficacy of current treatment regimens. [Cancer Res 2008;68(18):7258–63]
Cytoglobin, the Newest Member of the Globin Family, Functions as a Tumor Suppressor Gene
Authors: Shivapurkar Narayan , Stastny Victor , Okumura Naoki , Girard Luc , Xie Yang , Prinsen Clemens , Thunnissen Frederik B. , Wistuba Ignacio I. , Czerniak Bogdan , Frenkel Eugene , Roth Jack A. , Liloglou Triantafillos , Xinarianos George , Field John K. , Minna John D. , Gazdar Adi F. 
Published: September 2008

Abstract
Cytoglobin (CYGB) is a recently discovered vertebrate globin distantly related to myoglobin with unknown function. CYGB is assigned to chromosomal region 17q25, which is frequently lost in multiple malignancies. Previous studies failed to detect evidence for mutations in the CYGB gene. Recent studies provided preliminary evidence for increased methylation of the gene in lung cancer. Our study was aimed at investigating the role of CYGB as a tumor suppressor gene. By nested methylation-specific DNA sequencing analysis of lung and breast cancer cell lines and bronchial and mammary epithelial cell lines, we identified that methylation of a 110-bp CpG-rich segment of the CYGB promoter was correlated with gene silencing. We specifically targeted this sequence and developed a quantitative methylation-specific PCR assay, suitable for high-throughput analysis. We showed that the tumor specificity of CYGB methylation in discriminating patients with and without lung cancer, using biopsies and sputum samples. We further showed the tumor specificity of this assay with multiple other epithelial and hematologic malignancies. To show tumor suppressor activity of CYGB, we performed the following: (a) RNA interference–mediated knockdown of CYGB gene on colony formation in a CYGB expression–positive lung cancer cell line, resulting in increased colony formation; (b) enforced gene expression in CYGB expression–negative lung and breast cancer cell lines, reducing colony formation; and (c) identification of potential proximate targets down-stream of the CYGB genes. Our data constitute the first direct functional evidence for CYGB, the newest member of the globin family, as a tumor suppressor gene. [Cancer Res 2008;68(18):7448–56]