bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity of physical activity monitors in adults participating in free-living activities
Authors: Berntsen S , Hageberg R , Aandstad A , Mowinckel P , Anderssen S A , Carlsen K-H , Andersen L B 
Published: July 2008

BackgroundFor a given subject, time in moderate to very vigorous intensity physical activity (MVPA) varies substantially among physical activity monitors.ObjectiveIn the present study, the primary objective, whether time in MVPA recorded with SenseWear Pro2Armband (Armband; BodyMedia, Pittsburgh, Pennsylvania, USA), ActiGraph (7164, LLC, Fort Walton Beach, Florida, USA), ikcal (Teltronic AG, Biberist, Switzerland) and ActiReg (PreMed AS, Oslo, Norway) is different compared with indirect calorimetry, was determined. The secondary objective, whether these activity monitors estimate energy expenditure differently compared with indirect calorimetry, was also determined.Material and methodsThe activity monitors and a portable oxygen analyser were worn by 14 men and 6 women for 120 min doing a variety of activities of different intensities. Resting metabolic rate was measured with indirect calorimetry. The cutoff points defining moderate, vigorous and very vigorous intensity were three, six and nine times resting metabolic rate.ResultsTime in MVPA was overestimated by 2.9% and 2.5% by Armband and ActiGraph, respectively, and was underestimated by 11.6% and 98.7% by ikcal and ActiReg, respectively. ActiReg (p = 0.004) and ActiGraph (p = 0.007) underestimated energy expenditure in MVPA, and all monitors underestimated total energy expenditure (by 5% to 21%).ConclusionsRecorded time in MVPA and energy expenditure varies substantially among physical activity monitors. Thus, when comparing physical activity level among studies, it is essential to know the type of physical activity monitor being used.
Elevation of systemic matrix metalloproteinases 2 and 7 and tissue inhibitor of metalloproteinase 2 in patients with a history of Achilles tendon rupture: pilot study
Authors: Pasternak B , Schepull T , Eliasson P , Aspenberg P 
Published: July 2008

ObjectivesIn this study, serum levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) between patients with a history of Achilles tendon rupture and blood donor controls were compared, and their relation to mechanical properties of the tendons during healing were studied.MethodsMore than 3 years after injury, serum levels of MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9 and MMP-13, TIMP-1 and TIMP-2 in eight patients who had Achilles tendon rupture were measured. Twelve blood donors served as controls. During the early phase of healing, the tendon modulus of elasticity was calculated from radiostereometric data and tendon cross-sectional area.ResultsPatients with a history of Achilles tendon rupture had increased levels of MMP-2 (median difference 10%, p=0.01), MMP-7 (median difference 15%, p=0.02) and TIMP-2 (median difference 36%, p=0.02), compared with controls. Levels of MMP-7, measured 3 years after injury, correlated inversely to tendon modulus of elasticity (rs=20.83, p=0.02) and positively to tendon elongation (rs=0.74, p=0.05) during the early phase of healing. There was a trend towards positive correlation between MMP-7 and cross-sectional area during the early phase of healing (rs=0.67, p=0.08).ConclusionsPatients with a history of Achilles tendon rupture appear to have elevated levels of MMP-2, MMP-7 and TIMP-2 in serum. In these pilot data, the view that the MMP–TIMP system is involved in tendinopathy is supported and that disturbances in proteolytic control might be generalised are suggested.
General practitioners’ perceptions and practices of physical activity counselling: changes over the past 10 years
Authors: Buffart L M , van der Ploeg H P , Smith B J , Kurko J , King L , Bauman A E 
Published: July 2008

Objective:In this work, trends in general practitioners’ (GP) knowledge, confidence and practices in promoting physical activity to patients over a 10-year period (1997–2007) were studied.Design:Repeated cross-sectional population surveySetting:General practice in New South Wales (Australia)Participants:646 (40%), 747 (53%) and 511 (64%) GPs that were registered in a selection of urban and rural divisions in New South Wales participated in 2007, 2000 and 1997, respectively.Main outcome measures:Self-report questionnaire on the GP’s knowledge, confidence, role perception, attendance of continuous professional development and counselling practice with regard to promoting physical activity in their patients were the main outcome measures.Results:The majority of GPs felt confident in giving physical activity advice and saw it as their role to do so. The proportion of GPs with high confidence and role perception increased between 1997 and 2000 (p<0.001) but remained unchanged thereafter. In 1997, GPs were 0.54 times less likely (95% CI 0.42 to 0.69, p<0.001) to discuss physical activity with more than 10 patients per week than GPs in 2007. However, the percentage of new patients that were asked about their physical activity did not change over the last decade.Conclusions:Most increases in the proportion of GPs reporting high knowledge, role perception and confidence in giving physical activity advice to patients occurred between 1997 and 2000 and remained unchanged thereafter. In 2007, GPs appeared to give more physical activity advice, but Australian general practice is not yet living up to its potential with regard to physical activity promotion.
Changes in plasma arginine vasopressin concentrations in cyclists participating in a 109-km cycle race
Authors: Hew-Butler T , Dugas J P , Noakes T D , Verbalis J G 
Published: July 2008

ObjectiveTo evaluate the osmotic and non-osmotic regulation of arginine vasopressin (AVP) during endurance cycling.DesignObservational study.Setting109 km cycle race.Participants33 Cyclists.InterventionsNone.Main outcome measurementsPlasma sodium concentration ([Na+]), plasma volume (PV) and plasma arginine vasopressin (AVP) concentration ([AVP]p).ResultsA fourfold increase in [AVP]poccurred despite a 2-mmol l−1decrease in plasma [Na+] combined with only modest (5%) PV contraction. A significant inverse correlation was noted between [AVP]pΔ and urine osmolality Δ (r = −0.41, p<0.05), whereas non-significant inverse correlations were noted between [AVP]pand both plasma [Na+] Δ and % PV Δ. Four cyclists finished the race with asymptomatic hyponatraemia. The only significant difference between the entire cohort with this subset of athletes was postrace plasma [Na+] (137.7 vs 133.5 mmol l−1, p<0.001) and plasma [Na+] Δ (−1.9 vs −5.1 mmol l−1, p<0.05). The mean prerace [AVP]pof these four cyclists was just below the minimum detectable limit (0.3 pg ml−1) and increased marginally (0.4 pg ml−1) despite the decline in plasma [Na+].ConclusionsThe osmotic regulation of [AVP]pduring competitive cycling was overshadowed by non-osmotic AVP secretion. The modest decrease in PV was not the primary non-osmotic stimulus to AVP. Partial suppression of AVP occurred in four (12%) cyclists who developed hyponatraemia during 5 h of riding. Therefore, these results confirm that non-osmotic AVP secretion and exercise-associated hyponatraemia does, in fact, occur in cyclists participating in a 109 km cycle race. However, the stimuli to AVP is likely different between cycling and running.
Cyclin D1b Is Aberrantly Regulated in Response to Therapeutic Challenge and Promotes Resistance to Estrogen Antagonists
Authors: Wang Ying , Dean Jeffry L. , Millar Ewan K.A. , Tran Thai Hong , McNeil Catriona M. , Burd Craig J. , Henshall Susan M. , Utama Fransiscus E. , Witkiewicz Agnieszka , Rui Hallgeir , Sutherland Robert L. , Knudsen Karen E. , Knudsen Erik S. 
Published: July 2008

Abstract
Cyclin D1 is a key mediator of cell cycle progression that is aberrantly regulated in multiple cancers, especially in breast cancers. A number of studies have indicated that a polymorphism in a splice donor site in the cyclin D1 gene is associated with alternative splicing and the production of the alternative cyclin D1b transcript. Furthermore, this polymorphism is selectively associated with disease outcomes. However, relatively little is known regarding the protein product of the alternatively spliced message, cyclin D1b. Using antibodies specific for cyclin D1b, it was found that this protein is readily detectable in a number of cancer cell lines and primary breast cancers. Whereas cyclin D1b interacts with cyclin-dependent kinase 4 (CDK4), it is relatively inefficient at mediating RB phosphorylation and cell cycle progression in model systems due to the lack of exon 5 of cyclin D1–encoded sequences. However, cyclin D1b protein levels are not significantly attenuated by DNA damage or antiestrogen treatment, indicating that the protein may have significant effect on the response to such therapeutic modalities. Whereas enforced expression of cyclin D1b was not sufficient to abrogate DNA damage checkpoint responses, it did efficiently overcome cell cycle arrest mediated by antiestrogen therapeutics. This action of cyclin D1b was not associated with effects on estrogen receptor activity, but was rather dependent on functional association with CDK4. Combined, these studies indicate that the cyclin D1b protein is aberrantly regulated and could contribute to therapeutic failure in the context of ER-positive breast cancer. [Cancer Res 2008;68(14):5628–38]
Hsp90 Inhibition Suppresses Mutant EGFR-T790M Signaling and Overcomes Kinase Inhibitor Resistance
Authors: Shimamura Takeshi , Li Danan , Ji Hongbin , Haringsma Henry J. , Liniker Elizabeth , Borgman Christa L. , Lowell April M. , Minami Yuko , McNamara Kate , Perera Samanthi A. , Zaghlul Sara , Thomas Roman K. , Greulich Heidi , Kobayashi Susumu , Chirieac Lucian R. , Padera Robert F. , Kubo Shigeto , Takahashi Masaya , Tenen Daniel G. , Meyerson Matthew , Wong Kwok-Kin , Shapiro Geoffrey I. 
Published: July 2008

Abstract
The epidermal growth factor receptor (EGFR) secondary kinase domain T790M non–small cell lung cancer (NSCLC) mutation enhances receptor catalytic activity and confers resistance to the reversible tyrosine kinase inhibitors gefitinib and erlotinib. Currently, irreversible inhibitors represent the primary approach in clinical use to circumvent resistance. We show that higher concentrations of the irreversible EGFR inhibitor CL-387,785 are required to inhibit EGFR phosphorylation in T790M-expressing cells compared with EGFR mutant NSCLC cells without T790M. Additionally, CL-387,785 does not fully suppress phosphorylation of other activated receptor tyrosine kinases (RTK) in T790M-expressing cells. These deficiencies result in residual Akt and mammalian target of rapamycin (mTOR) activities. Full suppression of EGFR-mediated signaling in T790M-expressing cells requires the combination of CL-387,785 and rapamycin. In contrast, Hsp90 inhibition overcomes these limitations in vitro and depletes cells of EGFR, other RTKs, and phospho-Akt and inhibits mTOR signaling whether or not T790M is present. EGFR-T790M–expressing cells rendered resistant to CL-387,785 by a kinase switch mechanism retain sensitivity to Hsp90 inhibition. Finally, Hsp90 inhibition causes regression in murine lung adenocarcinomas driven by mutant EGFR (L858R) with or without T790M. However, efficacy in the L858R-T790M model requires a more intense treatment schedule and responses were transient. Nonetheless, these findings suggest that Hsp90 inhibitors may be effective in T790M-expressing cells and offer an alternative therapeutic strategy for this subset of lung cancers. [Cancer Res 2008;68(14):5827–38]
A Special Linker between Macrophage and Hematopoietic Malignant Cells: Membrane Form of Macrophage Colony-Stimulating Factor
Authors: Wang Lin , Zheng Guo-Guang , Ma Cui-Hua , Lin Yong-Min , Zhang Hai-Yan , Ma Yuan-Yuan , Chong Jing-Hui , Wu Ke-Fu 
Published: July 2008

AbstractThe membrane form of macrophage colony–stimulating factor (mM-CSF) is an alternative splicing variant of this cytokine. Although its high expression was detected in hematopoietic malignancies, its physiologic and pathologic roles in hematopoietic system have not been established. In this report, stable transfectant clones expressing mM-CSF (Namalwa-M and Ramos-M) were obtained, which showed reduced proliferation potential in vitro. Moreover, the in vivo study showed that Namalwa-M and Ramos-M exhibited enhanced oncogenicity in tumor size in nude mice model, which could be inhibited by M-CSF monoclonal antibody. A remarkable increase in infiltrating macrophage and the vessel densities was found in tumor tissues formed by lymphoma cell lines that stably expressed mM-CSF, which suggested the involvement of macrophages in this process. The in vitro results using coculture system showed that macrophages could promote Namalwa-M and Ramos-M proliferation and activate extracellular signal-regulated kinase/mitogen-activated protein kinase signal pathway. In addition, the expression of murine origin vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor was elevated in Namalwa-M formed tumor tissues. These results suggested that mM-CSF should be a positive regulator in the development of hematopoietic malignancies by abnormally activating infiltrating macrophages, which in turn promote the malignant development. Thus, mM-CSF may be a critical linker between macrophages and malignant cells in the development of hematopoietic malignancies. [Cancer Res 2008;68(14):5639–47]
Regulatory T Cell–Resistant CD8+ T Cells Induced by Glucocorticoid-Induced Tumor Necrosis Factor Receptor Signaling
Authors: Nishikawa Hiroyoshi , Kato Takuma , Hirayama Michiko , Orito Yuki , Sato Eiichi , Harada Naozumi , Gnjatic Sacha , Old Lloyd J. , Shiku Hiroshi 
Published: July 2008

AbstractWe previously found that a Salmonella typhimurium vector engineered to secrete soluble tumor antigen induces CD4+ T cells resistant to CD4+CD25+ regulatory T cells (Treg) and that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR) signal is involved in the development of this resistance. In this study, we address the potential of incorporating GITR ligand (GITRL) as a way to augment the immunogenicity of cancer vaccines. BALB/c mice were immunized by gene gun with plasmids encoding the mutated extracellular signal-regulated kinase 2 (mERK) with or without plasmids encoding mouse GITRL. Coadministration with GITRL during primary and secondary immunization enhanced the induction of mERK-specific CD8+ T cells. Antibody depletion and minigene analysis suggested that GITRL directly activated CTL epitope-specific CD8+ T cells independently of CD4+ T cells. Immunization with plasmids encoding a CTL epitope and GITRL resulted in strong tumor inhibition in a CD8+ T cell–dependent manner. Furthermore, CTL epitope-specific CD8+ T cells induced by immunization with plasmids encoding CTL epitope coadministered with GITRL were refractory to suppression by CD4+CD25+ Tregs compared with CD8+ T cells induced without GITR signaling. We propose that coadministration of GITR signaling agents with tumor antigens constitutes a promising novel strategy for cancer vaccine development. [Cancer Res 2008;68(14):5948–54]
SerpinB2 Protection of Retinoblastoma Protein from Calpain Enhances Tumor Cell Survival
Authors: Tonnetti Laura , Netzel-Arnett Sarah , Darnell Grant A. , Hayes Tamara , Buzza Marguerite S. , Anglin Ian E. , Suhrbier Andreas , Antalis Toni M. 
Published: July 2008

AbstractThe tumor suppressor retinoblastoma protein (Rb) plays a pivotal role in the regulation of cell proliferation and sensitivity to apoptosis through binding to E2F transcription factors. Loss of Rb in response to genotoxic stress or inflammatory cytokines can enhance cell death, in part, by eliminating Rb-mediated repression of proapoptotic gene transcription. Here we show that calpain cleavage of Rb facilitates Rb loss by proteasome degradation and that this may occur during tumor necrosis factor α–induced apoptosis. The cytoprotective, Rb-binding protein SerpinB2 (plasminogen activator inhibitor type 2) protects Rb from calpain cleavage, increasing Rb levels and enhancing cell survival. Chromatin immunoprecipitation assays show that the increased Rb levels selectively enhance Rb repression of proapoptotic gene transcription. This cytoprotective role of SerpinB2 is illustrated by reduced susceptibility of SerpinB2-deficient mice to multistage skin carcinogenesis, where Rb-dependent cell proliferation competes with apoptosis during initiation of papilloma development. These data identify SerpinB2 as a cell survival factor that modulates Rb repression of proapoptotic signal transduction and define a new posttranslational mechanism for selective regulation of the intracellular levels of Rb. [Cancer Res 2008;68(14):5648–57]
Clinical and Biological Significance of Tissue Transglutaminase in Ovarian Carcinoma
Authors: Hwang Jee Young , Mangala Lingegowda S. , Fok Jansina Y. , Lin Yvonne G. , Merritt William M. , Spannuth Whitney A. , Nick Alpa M. , Fiterman Derek J. , Vivas-Mejia Pablo E. , Deavers Michael T. , Coleman Robert L. , Lopez-Berestein Gabriel , Mehta Kapil , Sood Anil K. 
Published: July 2008

Abstract
Tissue type transglutaminase (TG2) is a unique multifunctional protein that plays a role in many steps in the cancer metastatic cascade. Here, we examined the clinical (n = 93 epithelial ovarian cancers) and biological (in vitro adhesion, invasion, and survival and in vivo therapeutic targeting) significance of TG2 in ovarian cancer. The overexpression of TG2 was associated with significantly worse overall patient survival in both univariate and multivariate analyses. Transfection of TG2 into SKOV3ip1 cells promoted attachment and spreading on fibronectin-coated surfaces and increased the in vitro invasive potential of these cells. Conversely, TG2 silencing with small interfering RNA (siRNA) of HeyA8 cells significantly decreased the invasive potential of the cells and also increased docetaxel-induced cell death. In vivo therapy experiments using chemotherapy-sensitive (HeyA8) and chemotherapy-resistant (HeyA8-MDR and RMG2) models showed significant antitumor activity both with TG2 siRNA-1,2-dioleoyl-sn-glycero-3-phosphatidylcholine alone and in combination with docetaxel chemotherapy. This antitumor activity was related to decreased proliferation and angiogenesis and increased tumor cell apoptosis in vivo. Taken together, these findings indicate that TG2 overexpression is an adverse prognostic factor in ovarian carcinoma and TG2 targeting may be an attractive therapeutic approach. [Cancer Res 2008;68(14):5849–58]
Tripartite Motif Protein 32 Facilitates Cell Growth and Migration via Degradation of Abl-Interactor 2
Authors: Kano Satoshi , Miyajima Naoto , Fukuda Satoshi , Hatakeyama Shigetsugu 
Published: July 2008

Abstract
Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs. [Cancer Res 2008;68(14):5572–80]
The Side Population of Ovarian Cancer Cells Is a Primary Target of IFN-α Antitumor Effects
Authors: Moserle Lidia , Indraccolo Stefano , Ghisi Margherita , Frasson Chiara , Fortunato Elena , Canevari Silvana , Miotti Silvia , Tosello Valeria , Zamarchi Rita , Corradin Alberto , Minuzzo Sonia , Rossi Elisabetta , Basso Giuseppe , Amadori Alberto 
Published: July 2008

AbstractThe side population (SP), recently identified in several normal tissues and in a variety of tumors based on its ability to extrude some fluorescent dyes, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer and found it in 9 of 27 primary tumor samples analyzed, as well as in 4 of 6 cultures from xenotransplants. SP cells from one xenograft bearing a large SP fraction were characterized in detail. SP cells had higher proliferation rates, were much less apoptotic compared with non-SP cells, and generated tumors more rapidly than non-SP cells. We also investigated the effects of IFN-α, a cytokine that has widely been used to treat solid tumors, on epithelial ovarian cancer cells and observed that IFN-α exerted marked antiproliferative and proapoptotic effects on primary cultures containing high numbers of SP cells. In vitro, IFN-α treatment invariably caused a dramatic reduction in SP size in tumor cell lines of different origins; moreover, IFN-α treatment of purified SP cells was associated with a distinctive change in their transcriptional profile. Gene therapy with human IFN-α resulted in regression of established tumors bearing a large SP fraction, which was not observed when tumors bearing low SP levels were treated. These findings could have relevant clinical implications because they imply that tumors bearing large SP numbers, albeit rare, could be sensitive to IFN-α treatment. [Cancer Res 2008;68(14):5658–68]
Cell Competition and Its Possible Relation to Cancer
Authors: Baker Nicholas E. , Li Wei 
Published: July 2008

Abstract
Cell competition can occur when cells of different genotypes share the same developing compartment, with one genotype displacing the other as a result of a proliferative advantage. Studies of cell competition in Drosophila have identified an active process of cell assassination and corpse engulfment, and also roles for Myc and the Warts/Hippo tumor suppressor pathway. Here, we discuss the possible relevance of cell competition to cancer. [Cancer Res 2008;68(14):5505–7]
Identification of c-Cbl as a New Ligase for Insulin-like Growth Factor-I Receptor with Distinct Roles from Mdm2 in Receptor Ubiquitination and Endocytosis
Authors: Sehat Bita , Andersson Sandra , Girnita Leonard , Larsson Olle 
Published: July 2008

Abstract
The insulin-like growth factor receptor (IGF-IR) plays several pivotal roles in cancer. Although most studies on the function of the IGF-IR have been attributed to kinase-dependent signaling, recent findings by our group and others have implicated biological roles mediated by ubiquitination of the receptor. As previously reported, the E3 ligases Mdm2 and Nedd4 mediate IGF-IR ubiquitination. Here we show that c-Cbl is a novel E3 ligase for IGF-IR. On ligand stimulation, both Mdm2 and c-Cbl associate with IGF-IR and mediate receptor polyubiquitination. Whereas Mdm2 catalyzed lysine 63 (K63) chain ubiquitination, c-Cbl modified IGF-IR through K48 chains. Mdm2-mediated ubiquitination occurred when cells were stimulated with a low concentration (5 ng/mL) of IGF-I, whereas c-Cbl required high concentrations (50–100 ng/mL). Mdm2-ubiquitinated IGF-IR was internalized through the clathrin endocytic pathway whereas c-Cbl–ubiquitinated receptors were endocytosed via the caveolin route. Taken together, our results show that c-Cbl constitutes a new ligase responsible for the ubiquitination of IGF-IR and that it complements the action of Mdm2 on ubiquitin lysine residue specificity, responsiveness to IGF-I, and type of endocytic pathway used. The actions and interactions of Mdm2 and c-Cbl in the ubiquitination and endocytosis of IGF-IR may have implications in cancer. In addition, identification and functional characterization of new E3 ligases are important in itself because therapeutic targeting of substrate-specific E3 ligases is likely to represent a critical strategy in future cancer treatment. [Cancer Res 2008;68(14):5669–77]