bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of exercise training andn-3 fatty acid supplementation on postprandial lipemia
Authors: Thomas Tom R. , Liu Ying , Linden Melissa A. , Rector R. Scott 
Published: May 2007

The effect of combining omega-3 fatty acid (n-3 FA) supplementation and exercise training treatment on postprandial lipemia (PPL) has not been studied. The purpose of this study was to examine the interaction of n-3 FA and exercise training in attenuating PPL after a high-fat meal. Previously sedentary, overweight, subjects (n = 22; 12 women, 10 men, BMI 26.6 ±0.7 kg/m2) were randomly assigned to one of two treatment groups: n-3 FA supplementation alone (FO, n = 10) or n-3 FA supplementation plus exercise training (FO+ExTr, n = 12). Both groups consumed 4 g/d n-3 FA, and one group also exercise trained for 45 min/d, 5d/week of brisk walking and (or) jogging at 60% VO2 max. Before and after 4 weeks of treatment, subjects performed a baseline PPL and a PPL following a single session of exercise (ExPPL). PPL was assessed by triglyceride (TG) area under the curve (AUC) and peak TG response (TGpeak). A two-way analysis of variance (ANOVA) with repeated measures was used to compare results from treatments for baseline and exercise trials. FO alone reduced PPL and Ex PPL, and FO+ExTr attenuated the ExPPL response measured as total AUC and TGpeak. There was no significant main effect for group or group by time interaction for baseline PPL or ExPPL. Fasting high-density lipoprotein cholesterol (HDL-C) and HDL2-C (i.e., subfraction 2) concentrations were significantly increased in the FO+ExTr group after the treatments. These results suggest that n-3 FA supplementation reduced PPL in sedentary subjects. Exercise training has no interference or additive effects with n-3 FA supplementation in attenuating PPL, but combined treatments may be additive in raising high-density lipoprotein cholesterol.
A lifestyle intervention of weight-gain restriction: diet and exercise in obese women with gestational diabetes mellitus
Authors: Artal Raul , Catanzaro Rosemary B. , Gavard Jeffrey A. , Mostello Dorothea J. , Friganza Joann C. 
Published: May 2007

Objective: This study assessed whether a weight-gain restriction regimen, with or without exercise, would impact glycemic control, pregnancy outcome, and total pregnancy weight gain in obese subjects with gestational diabetes mellitus (GDM). A total of 96 subjects with GDM met the inclusion criteria and were sequentially recruited, with 39 subjects self-enrolled in the exercise and diet (ED) group, and the remaining 57 subjects self-enrolled in the diet (D) group owing to contraindications or a lack of personal preference to exercise. All patients were provided a eucaloric or hypocaloric consistent carbohydrate meal plan and instructed in the self-monitoring of blood glucose. In addition, all ED subjects were prescribed an exercise routine equivalent to a 60% symptom-limited VO2max. Subjects were followed at weekly or biweekly office visits. Results showed maternal weight and body mass index (35.2 ± 7.2 (ED) vs. 33.5 ± 9.2 (D)) at study entry as well as number of weeks into the study (7.7 ± 5.7 (ED) vs. 9.4 ± 4.7 (D)) were similar in both the ED and D groups. Weight gain per week was significantly lower in the ED group than in the D group (0.1 ± 0.4 kg vs. 0.3 ± 0.4 kg; p < 0.05). Subjects (either ED or D) who gained weight had a higher percentage of macrosomic infants than those subjects who lost weight or had no weight change during pregnancy. Other pregnancy and fetal outcomes such as complications, gestational age at delivery, and rate of cesarean delivery were similar in both groups. Conclusions of this study were that caloric restriction and exercise result in limited weight gain in obese subjects with GDM, less macrosomic neonates, and no adverse pregnancy outcomes. Pregnancy is an ideal time for behaviour modification, and this intervention may also help promote long-term healthy lifestyle changes.
Responses to acute exercise in type 2 diabetes, with an emphasis on metabolism and interaction with oral hypoglycemic agents and food intake
Authors: Galbo Henrik , Tobin Lillan , van Loon Luc J.C. 
Published: May 2007

In people with type 1 diabetes mellitis (DM), insulin administration, food intake, and exercise have to be carefully matched to avoid either hypo- or hyperglycemia. People with type 2 DM have some insulin secretion, which changes with needs. Accordingly, during exercise, these people do not run the same metabolic risks as people with type 1 DM. However, a contraction-mediated increase in glucose clearance in muscle is intact in type 2 DM. Therefore, , in the postabsorptive state in diet-treated type 2 DM, a marked reduction in hyperglycemia can occur during prolonged moderate exercise. Sulfonylurea drugs augment the rate of decline in plasma glucose, because stimulation of insulin secretion reduces hepatic glucose production. After abstention from sulfonylurea for 5 days, the rate of decrease in plasma glucose with exercise is also enhanced, but from a higher glucose level. In the postabsorptive state, brief vigourous exercise elicits an increase in plasma glucose concentration, reflecting an exaggerated counterregulatory hormone response and glucose production. Moreover, insulin sensitivity is reduced in the early postexercise period. In the postprandial state, both prolonged moderate exercise and intermittent high-intensity exercise markedly decrease meal-induced increases in glucose, insulin, and C-peptide concentrations, whereas glucose appearance in plasma is unchanged. When exercise bouts are isocaloric, responses are identical, indicating that overall energy expenditure, and not peak exercise intensity, is the major determinant of exercise-induced changes in overall glucose homeostasis and insulin secretion in type 2 DM. Neither prolonged moderate nor intermittent high-intensity exercise performed in the postprandial state influences glucose or insulin responses to a subsequent meal. Finally, in people with type 2 DM, after a high-fat meal, prolonged moderate exercise reduces the exaggerated increases in plasma concentrations of triglycerides contained in chylomicrons and very low-density lipoproteins.
Attenuated Expression of Xeroderma Pigmentosum Group C Is Associated with Critical Events in Human Bladder Cancer Carcinogenesis and Progression
Authors: Chen Zhiwen , Yang Jin , Wang Gan , Song Bo , Li Jin , Xu Zhigang 
Published: May 2007

Abstract
Xeroderma pigmentosum group C (XPC) is an important DNA damage recognition protein that binds to damaged DNA at a very early stage during DNA repair. The XPC protein is also involved in DNA damage–induced cell cycle checkpoint regulation and apoptosis. XPC defects are associated with many types of solid tumors. The mechanism of the XPC protein in cancer progression, however, remains unclear. In this report, we showed the strong correlation between bladder cancer progression and attenuated XPC protein expression using tissues derived from patients with bladder cancer. The results obtained from our immunohistochemical studies further revealed a strong correlation of XPC deficiency, p53 mutation, and the degree of malignancy of bladder tumors. In addition, the results obtained from our studies have also shown that HT1197 bladder cancer cells, which carry a low-level XPC protein, exhibited a decreased DNA repair capability and were resistant to cisplatin treatment. When an XPC gene cDNA-expression vector was stably transfected into the HT1197 cells, however, the cisplatin treatment–induced apoptotic cell death was increased. Increased p53 and p73 responses following cisplatin treatment were also observed in HT1197 cells stably transfected with XPC cDNA. Taken together, these results suggest that XPC deficiency is an important contributing factor in bladder tumor progression and bladder cancer cell drug resistance. [Cancer Res 2007;67(10):4578–85]
Angiostatin-Like Activity of a Monoclonal Antibody to the Catalytic Subunit of F1F0 ATP Synthase
Authors: Chi Sulene L. , Wahl Miriam L. , Mowery Yvonne M. , Shan Siqing , Mukhopadhyay Somnath , Hilderbrand Susana C. , Kenan Daniel J. , Lipes Barbara D. , Johnson Carrie E. , Marusich Michael F. , Capaldi Roderick A. , Dewhirst Mark W. , Pizzo Salvatore V. 
Published: May 2007

AbstractThe antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial cell surface, blocking cellular proliferation. To examine the specificity of this interaction, we generated monoclonal antibodies (mAb) directed against ATP synthase. mAb directed against the β-catalytic subunit of ATP synthase (MAb3D5AB1) inhibits the activity of the F1 domain of ATP synthase and recognizes the catalytic β-subunit of ATP synthase. We located the antibody recognition site of MAb3D5AB1 in domains containing the active site of the β-subunit. MAb3D5AB1 also binds to purified Escherichia coli F1 with an affinity 25-fold higher than the affinity of angiostatin for this protein. MAb3D5AB1 inhibits the hydrolytic activity of F1 ATP synthase at lower concentrations than angiostatin. Like angiostatin, MAb3D5AB1 inhibits ATP generation by ATP synthase on the endothelial cell surface in acidic conditions, the typical tumor microenvironment where cell surface ATP synthase exhibits greater activity. MAb3D5AB1 disrupts tube formation and decreases intracellular pH in endothelial cells exposed to low extracellular pH. Neither angiostatin nor MAb3D5AB1 showed an antiangiogenic effect in the corneal neovascularization assay; however, both were effective in the low-pH environment of the chicken chorioallantoic membrane assay. Thus, MAb3D5AB1 shows angiostatin-like properties superior to angiostatin and may be exploited in cancer chemotherapy. [Cancer Res 2007;67(10):4716–24]
Modulation of Intracellular Ceramide Using Polymeric Nanoparticles to Overcome Multidrug Resistance in Cancer
Authors: van Vlerken Lilian E. , Duan Zhenfeng , Seiden Michael V. , Amiji Mansoor M. 
Published: May 2007

Abstract
Although multidrug resistance (MDR) is known to develop through a variety of molecular mechanisms within the tumor cell, many tend to converge toward the alteration of apoptotic signaling. The enzyme glucosylceramide synthase (GCS), responsible for bioactivation of the proapoptotic mediator ceramide to a nonfunctional moiety glucosylceramide, is overexpressed in many MDR tumor types and has been implicated in cell survival in the presence of chemotherapy. The purpose of this study was to investigate the therapeutic strategy of coadministering ceramide with paclitaxel, a commonly used chemotherapeutic agent, in an attempt to restore apoptotic signaling and overcome MDR in the human ovarian cancer cell line SKOV3. Poly(ethylene oxide)-modified poly(epsilon-caprolactone) (PEO-PCL) nanoparticles were used to encapsulate and deliver the therapeutic agents for enhanced efficacy. Results show that indeed the cotherapy eradicates the complete population of MDR cancer cells when they are treated at their IC50 dose of paclitaxel. More interestingly, when the cotherapy was combined with the properties of nanoparticle drug delivery, the MDR cells can be resensitized to a dose of paclitaxel near the IC50 of non-MDR (drug sensitive) cells, indicating a 100-fold increase in chemosensitization via this approach. Molecular analysis of activity verified the hypothesis that the efficacy of this therapeutic approach is indeed due to a restoration in apoptotic signaling, although the beneficial properties of PEO-PCL nanoparticle delivery seemed to enhance the therapeutic success even further, showing the promising potential for the clinical use of this therapeutic strategy to overcome MDR. [Cancer Res 2007;67(10):4843–50]
Repression of Sestrin Family Genes Contributes to Oncogenic Ras-Induced Reactive Oxygen Species Up-regulation and Genetic Instability
Authors: Kopnin Pavel B. , Agapova Larissa S. , Kopnin Boris P. , Chumakov Peter M. 
Published: May 2007

Abstract
Oncogenic mutations within RAS genes and inactivation of p53 are the most common events in cancer. Earlier, we reported that activated Ras contributes to chromosome instability, especially in p53-deficient cells. Here we show that an increase in intracellular reactive oxygen species (ROS) and oxidative DNA damage represents a major mechanism of Ras-induced mutagenesis. Introduction of oncogenic H- or N-Ras caused elevated intracellular ROS, accumulation of 8-oxo-2′-deoxyguanosine, and increased number of chromosome breaks in mitotic cells, which were prevented by antioxidant N-acetyl-l-cysteine. By using Ras mutants that selectively activate either of the three major targets of Ras (Raf, RalGDS, and phosphatidylinositol-3-kinase) as well as dominant-negative Rac1 and RalA mutants and inhibitors of mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinases kinase-1 and p38 MAPKs, we have shown that several Ras effectors independently mediate ROS up-regulation. Introduction of oncogenic RAS resulted in repression of transcription from sestrin family genes SESN1 and SESN3, which encode antioxidant modulators of peroxiredoxins. Inhibition of mRNAs from these genes in control cells by RNA interference substantially increased ROS levels and mutagenesis. Ectopic expression of SESN1 and SESN3 from lentiviral constructs interfered with Ras-induced ROS increase, suggesting their important contribution to the effect. The stability of Ras-induced increase in ROS was dependent on a p53 function: in the p53-positive cells displaying activation of p53 in response to Ras, only transient (4–7 days) elevation of ROS was observed, whereas in the p53-deficient cells the up-regulation was permanent. The reversion to normal ROS levels in the Ras-expressing p53-positive cells correlated with up-regulation of p53-responsive genes, including reactivation of SESN1 gene. Thus, changes in expression of sestrins can represent an important determinant of genetic instability in neoplastic cells showing simultaneous dysfunctions of Ras and p53. [Cancer Res 2007;67(10):4671–8]
SOCS1 Silencing Enhances Antitumor Activity of Type I IFNs by Regulating Apoptosis in Neuroendocrine Tumor Cells
Authors: Zitzmann Kathrin , Brand Stephan , De Toni Enrico N. , Baehs Sebastian , Göke Burkhard , Meinecke Jennifer , Spöttl Gerald , Meyer Heinrich H.H.D. , Auernhammer Christoph J. 
Published: May 2007

Abstract
IFN-α is commonly used for biotherapy of neuroendocrine carcinomas. However, its antitumor efficacy is often limited due to IFN resistance. In this study, we evaluate the role of suppressor of cytokine signaling protein 1 (SOCS1) in modulating the effects of type I IFNs (IFN-α and IFN-β) in human neuroendocrine BON1 and CM tumor cells. In both cell lines, type I IFNs activated signal transducers and activators of transcription (STAT) and significantly decreased cell viability. However, the effects of IFN-β were significantly more pronounced than those of IFN-α and involved the induction of the intrinsic apoptotic pathway as shown by cleavage of caspase-8, Bid, and caspase-9. Stable overexpression of SOCS1 completely abolished the apoptotic effects of both type I IFNs. In contrast, small interfering RNA (siRNA)–mediated silencing of SOCS1 resulted in strongly enhanced type I IFN signaling as shown by increased and prolonged STAT phosphorylation and stronger induction of apoptosis. Silencing of SOCS1 was associated with down-regulation of basal Bcl-2 and Bcl-xL and up-regulation of basal Bak and Bax, suggesting that reduced SOCS1 expression might lower the threshold of susceptibility to type I IFN–mediated apoptosis by decreasing the ratio of antiapoptotic to proapoptotic molecules. In summary, our results indicate an important role of SOCS1 in IFN resistance of neuroendocrine tumor cells, mediated through negative regulation of type I IFN–induced Jak/STAT signaling. Knocking down SOCS1 by siRNA is a promising new approach to enhance the therapeutic potency of type I IFNs in neuroendocrine tumors. [Cancer Res 2007;67(10):5025–32]
Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: A Joint NCI's EDRN and NIST Workshop on Standards, Methods, Assays, Reagents and Tools
Authors: Kagan Jacob , Srivastava Sudhir , Barker Peter E. , Belinsky Steven A. , Cairns Paul 
Published: May 2007

Abstract
The workshop report, entitled Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: A Joint National Cancer Institute's Early Detection Research Network and National Institute of Standards and Technology Workshop, presents a summary of the main issues, current challenges, outcomes, and recommendations toward application of methylated DNA sequences as cancer biomarkers. [Cancer Res 2007;67(10):4545–9]
Scavenger Receptor-A Negatively Regulates Antitumor Immunity
Authors: Wang Xiang-Yang , Facciponte John , Chen Xing , Subjeck John R. , Repasky Elizabeth A. 
Published: May 2007

Abstract
The scavenger receptor-A (SR-A), originally recognized by its ability to internalize modified lipoproteins, has largely been studied in relation to atherosclerosis as well as innate immunity against pathogen infection. SR-A was recently shown to be a receptor on antigen-presenting cell for heat shock protein (HSP) and was implicated in the cross-presentation of HSP-chaperoned antigens. Here, we show that SR-A is not required for antitumor immunity generated by HSP-based (e.g., grp170) vaccine approaches in vivo. The lack of SR-A significantly enhances HSP- or lipopolysaccharide-mediated vaccine activities against poorly immunogenic tumors, indicating that SR-A is able to attenuate immunostimulatory effects of adjuvants or “danger” molecules. The improved antitumor response in SR-A knockout mice is correlated with an increased antigen-specific T-cell response. Moreover, SR-A–deficient dendritic cells are more responsive to inflammatory stimuli and display a more effective antigen-presenting capability compared with wild-type cells. This is the first report illustrating that SR-A negatively regulates antigen-specific antitumor immunity, which has important clinical implications in vaccine design for cancer immunotherapy. [Cancer Res 2007;67(10):4996–5002]
High-Level Expression of Chemokine CXCL16 by Tumor Cells Correlates with a Good Prognosis and Increased Tumor-Infiltrating Lymphocytes in Colorectal Cancer
Authors: Hojo Shozo , Koizumi Keiichi , Tsuneyama Koichi , Arita Yoshihisa , Cui Zhengguo , Shinohara Kanna , Minami Takayuki , Hashimoto Isaya , Nakayama Takashi , Sakurai Hiroaki , Takano Yasuo , Yoshie Osamu , Tsukada Kazuhiro , Saiki Ikuo 
Published: May 2007

AbstractCXCL16 is a new member of the chemokine superfamily, which exists in a transmembrane as well as a soluble form. Its receptor CXCR6 is detected on CD4+ T cells, CD8+ T cells, and natural killer T cells. Here, we report a significant correlation of CXCL16 expression by tumor cells with the infiltration of T cells and prognosis in colorectal cancer (CRC). We first found that CXCL16 expression was consistently up-regulated more in tumor tissues than in normal mucosa derived from the same CRC patients. Four human CRC cell lines also expressed CXCL16 mRNA and secreted soluble CXCL16. We next examined the expression of CXCL16 and infiltration of lymphocytes in CRC specimens (n = 58) by immunohistochemistry. CRC patients with high levels of CXCL16 expression (n = 43) had higher levels of CD4+ and CD8+ tumor-infiltrating lymphocytes (TIL; P &lt; 0.01) than those with low levels of CXCL16 expression (n = 15). Furthermore, the high CXCL16 expression group showed significantly better prognosis than the low CXCL16 expression group (P &lt; 0.05). Collectively, our data suggest that the expression of CXCL16 by tumor cells enhances the recruitment of TILs, thereby bringing about a better prognosis in CRC. Thus, CXCL16 is a new prognostic biomarker and may be useful for the development of a more effective therapeutic strategy for CRC. [Cancer Res 2007;67(10):4725–31]
Extensive Methylation Is Associated with β-Catenin Mutations in Hepatocellular Carcinoma: Evidence for Two Distinct Pathways of Human Hepatocarcinogenesis
Authors: Nishida Naoshi , Nishimura Takafumi , Nagasaka Takeshi , Ikai Iwao , Ajay Goel , Boland C. Richard 
Published: May 2007

Abstract
Hepatocellular carcinoma (HCC) with p53 mutations is usually characterized by extensive chromosomal instability (CIN), whereas those with β-catenin mutations have relatively less CIN and the molecular pathogenesis of these tumors is unknown. Methylation of CpG dinucleotides in the promoters of cancer-related genes is another characteristic feature of HCCs. The aim of this study was to determine the contribution of the methylator phenotype to HCC and its relationship to genomic instability. Fractional allelic loss (FAL) was determined using 400 microsatellite markers in 81 HCCs and 77 corresponding noncancerous livers as a measure of CIN. Methylation of 21 genetic loci was quantitated using combined bisulfite restriction analysis. Using hierarchical clustering analysis based upon the quantification of methylation levels, all HCCs were segregated into two groups characterized by either limited or extensive methylation. Mutations in the β-catenin and p53 genes were determined by DNA sequencing. We found that the methylation levels were significantly higher in the HCCs than in noncancerous livers in 18 of the 21 loci (P values ranged from 0.035 to &lt;0.0001). Among 18 loci, elevated levels of methylation at nine loci were significantly associated with β-catenin mutations (P values ranged from 0.02 to &lt;0.0001). In addition, the presence of β-catenin mutations was associated with HCCs in the extensive methylation group (P &lt; 0.0001), whereas p53 mutations correlated with high FAL scores (P = 0.0036). These data suggest that HCCs can be classified into two distinct categories based upon promoter methylation, CIN, and mutations of cancer-related genes. HCCs with extensive methylation harbor frequent β-catenin mutations, whereas HCCs with high levels of CIN are associated with p53 mutations, suggesting the presence of two independent pathways for the pathogenesis of HCC. [Cancer Res 2007;67(10):4586–94]
Functional Analysis of Human MLH1 Variants Using Yeast and In vitro Mismatch Repair Assays
Authors: Takahashi Masanobu , Shimodaira Hideki , Andreutti-Zaugg Corinne , Iggo Richard , Kolodner Richard D. , Ishioka Chikashi 
Published: May 2007

Abstract
The functional characterization of nonsynonymous single nucleotide polymorphisms in human mismatch repair (MMR) genes has been critical to evaluate their pathogenicity for hereditary nonpolyposis colorectal cancer. We previously established an assay for detecting loss-of-function mutations in the MLH1 gene using a dominant mutator effect of human MLH1 expressed in Saccharomyces cerevisiae. The purpose of this study is to extend the functional analyses of nonsynonymous single nucleotide polymorphisms in the MLH1 gene both in quality and in quantity, and integrate the results to evaluate the variants for pathogenic significance. The 101 MLH1 variants, which covered most of the reported MLH1 nonsynonymous single nucleotide polymorphisms and consisted of one 3-bp deletion, 1 nonsense and 99 missense variants, were examined for the dominant mutator effect by three yeast assays and for the ability of the variant to repair a heteroduplex DNA with mismatch bases by in vitro MMR assay. There was diversity in the dominant mutator effects and the in vitro MMR activities among the variants. The majority of functionally inactive variants were located around the putative ATP-binding pocket of the NH2-terminal domain or the whole region of the COOH-terminal domain. Integrated functional evaluations contribute to a better prediction of the cancer risk in individuals or families carrying MLH1 variants and provide insights into the function-structure relationships in MLH1. [Cancer Res 2007;67(10):4595–604]