bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlates of Depressive Symptoms in Urban Youth at Risk for Type 2 Diabetes Mellitus
Authors: Jaser Sarah S. , Holl Marita G. , Jefferson Vanessa , Grey Margaret 
Published: May 2009

ABSTRACTBackground:  Rates of overweight in youth have increased at an alarming rate, particularly in minority youth, and depressive symptoms may affect the ability of youth to engage in healthy lifestyle behaviors to manage weight and reduce their risk for health problems. The purpose of this study was to examine the relationships between depressive symptoms, clinical risk factors, and health behaviors and attitudes in a sample of urban youth at risk for type 2 diabetes mellitus (T2DM).Methods:  We obtained self‐report questionnaire data on depressive symptoms and health attitudes and behaviors related to diet and exercise and clinical data on risk markers (eg, fasting insulin) from 198 youth from an urban setting. Seventh‐grade students were eligible if they were at risk for developing T2DM because they had a body mass index (BMI) in the 85th percentile or higher and a family history of diabetes.Results:  Clinically significant levels of depressive symptoms were evident in approximately 21% of the sample, and Hispanic youth reported higher levels of depressive symptoms than black youth. Higher levels of depression were associated with several health behaviors and attitudes, in particular less perceived support for physical activity and poorer self‐efficacy for diet. Depressive symptoms were also related to some clinical risk markers, such as higher BMI and fasting insulin levels.Conclusions:  Because depressive symptoms may affect ability to engage in healthy behavior changes, evaluation and treatment of depressive symptoms should be considered in preventive interventions for youth at risk for T2DM.
Impact of carbohydrate supplementation during endurance training on glycogen storage and performance
Authors: Nybo L. , Pedersen K. , Christensen B. , Aagaard P. , Brandt N. , Kiens B. 
Published: May 2009

AbstractAim:  Glucose ingestion may improve exercise endurance, but it apparently also influences the transcription rate of several metabolic genes and it alters muscle metabolism during an acute exercise bout. Therefore, we investigated how chronic training responses are affected by glucose ingestion.Methods:  In previously untrained males performance and various muscular adaptations were evaluated before and after 8 weeks of supervised endurance training conducted either with (n = 8; CHO group) or without (n = 7; placebo) glucose supplementation.Results:  The two groups achieved similar improvements in maximal oxygen uptake and peak power output during incremental cycling (both parameters elevated by 17% on average) and both groups lost ∼3 kg of fat mass during the 8 weeks of training. An equal reduction in respiratory exchange ratio (0.02 units) during submaximal exercise was observed in both groups. Beta‐hydroxyacyl‐CoA‐dehydrogenase activity was increased in both groups, however, to a larger extent in the placebo group (45 ± 11%) than CHO (23 ± 9%, P < 0.05). GLUT‐4 protein expression increased by 74 ± 14% in the placebo group and 45 ± 14% in CHO (both P < 0.05), while resting muscle glycogen increased (P < 0.05) to a larger extent in the placebo group (96 ± 4%) than CHO (33 ± 2%).Conclusion:  These results show that carbohydrate supplementation consumed during exercise training influences various muscular training adaptations, but improvements in cardiorespiratory fitness and reductions in fat mass are not affected.
The development of MISCANFOR, a new Miscanthus crop growth model: towards more robust yield predictions under different climatic and soil conditions
Authors: HASTINGS ASTLEY , CLIFTON‐BROWN JOHN , WATTENBACH MARTIN , MITCHELL C. PAUL , SMITH PETE 
Published: May 2009

Abstract Miscanthus×giganteus (Greef et Deu.), a perennial rhizomatous grass, native of SE Asia, has been trialed Europe‐wide as a potential bio‐energy crop. Plant growth models have been developed to match previously reported field experiments. These models have been used to extrapolate Miscanthus yields to other environments. Although the models use similar process descriptions, the parameters used to match the experimental data vary from site to site. This paper describes the development of universal process descriptions that use genotype‐specific parameters to predict yields in a wide range of environments. Using these, we develop a new model, MISCANFOR, from an existing model MISCANMOD by improving process descriptions for light interception by the canopy and the impact of temperature and water stress on radiation use efficiency. Genotype‐specific process descriptions for plant growth phase, photo‐period sensitivity, thermal time, temperature dependant radiation‐use efficiency, drought and frost kill predictions, nutrient repartition to the rhizome, and moisture content at harvest are added. Predictions made with MISCANFOR are compared with MISCANMOD for 36 experimental data sets for a wide variety of soils and climatic conditions in Europe. MISCANFOR matches field experiments with an r2=0.84 compared with 0.64 for MISCANMOD, building confidence that the new model will be better able to predict Miscanthus yields for other areas and future IPCC climate scenarios. This model has identified photoperiod sensitivity in addition to drought resistance and frost tolerance as parameters for crop improvement to extend the range of climatic conditions under which this crop can be grown economically.
Cancer mortality and congenital anomalies in a region of Italy with intense environmental pressure due to waste
Authors: Martuzzi M , Mitis F , Bianchi F , Minichilli F , Comba P , Fazzo L 
Published: May 2009

Objectives:Waste management in the Campania region has been characterised, since the 1980s, by widespread uncontrolled and illegal practices of waste dumping, generating concerns over the health implications. The objective of this study was to evaluate possible adverse health effects of such environmental pressure.Methods:The health effects of waste-related environmental exposures in Campania were assessed in a correlation study on nine causes of death (for the years 1994–2001) and 12 types of congenital anomaly (CA) (1996–2002) in 196 municipalities of the provinces of Naples and Caserta. Poisson regression was used to analyse the association between health outcomes and environmental contamination due to waste, as measured through a composite index, adjusting for deprivation.Results:Statistically significant excess relative risks (ERR, %) in high-index compared with low-index (unexposed) municipalities were found for all-cause mortality (9.2 (95% CI 6.5 to 11.9) in men and 12.4 (9.5 to 15.4) in women and liver cancer (19.3 (1.4 to 40.3) in men and 29.1 (7.6 to 54.8) in women). Increased risks were also found for all cancer mortality (both sexes), stomach and lung cancer (in men). Statistically significant ERRs were found for CAs of the internal urogenital system (82.7 (25.6 to 155.7)) and of the central nervous system (83.5 (24.7 to 169.9)).Conclusion:Although the causal nature of the association is uncertain, findings support the hypothesis that waste-related environmental exposures in Campania produce increased risks of mortality and, to a lesser extent, CAs.
Interaction of E-cadherin and PTEN Regulates Morphogenesis and Growth Arrest in Human Mammary Epithelial Cells
Authors: Fournier Marcia V. , Fata Jimmie E. , Martin Katherine J. , Yaswen Paul , Bissell Mina J. 
Published: May 2009

Abstract
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a dual-function phosphatase with tumor suppressor function compromised in a wide spectrum of cancers. Because tissue polarity and architecture are crucial modulators of normal and malignant behavior, we postulated that PTEN may play a role in maintenance of tissue integrity. We used two nonmalignant human mammary epithelial cell lines that form polarized, growth-arrested structures (acini) when cultured in three-dimensional laminin-rich extracellular matrix gels (lrECM). As acini begin to form, PTEN accumulates both in the cytoplasm and at cell-cell contacts where it colocalizes with the E-cadherin/β-catenin complex. Reduction of PTEN levels by shRNA in lrECM prevents formation of organized breast acini and disrupts growth arrest. Importantly, disruption of acinar polarity and cell-cell contact by E-cadherin function–blocking antibodies reduces endogenous PTEN protein levels and inhibits its accumulation at cell-cell contacts. Conversely, in Skbr-3 breast cancer cells lacking endogenous E-cadherin expression, exogenous introduction of E-cadherin gene causes induction of PTEN expression and its accumulation at sites of cell interactions. These studies provide evidence that E-cadherin regulates both the PTEN protein levels and its recruitment to cell-cell junctions in three-dimensional lrECM, indicating a dynamic reciprocity between architectural integrity and the levels and localization of PTEN. This interaction thus seems to be a critical integrator of proliferative and morphogenetic signaling in breast epithelial cells. [Cancer Res 2009;69(10):4545–52]
Epithelial-to-Mesenchymal Transition and Resistance to Ingenol 3-Angelate, a Novel Protein Kinase C Modulator, in Colon Cancer Cells
Authors: Ghoul Aïda , Serova Maria , Astorgues-Xerri Lucile , Bieche Ivan , Bousquet Guilhem , Varna Mariana , Vidaud Michel , Phillips Edelmira , Weill Sophie , Benhadji Karim A. , Lokiec François , Cvitkovic Esteban , Faivre Sandrine , Raymond Eric 
Published: May 2009

Abstract
Acquired resistance to protein kinase C (PKC) modulators may explain the failure of clinical trials in patients with cancer. Herein, we established a human colon cancer cell line resistant to PEP005, a drug that inhibits PKCα and activates PKCδ. Colo205-R cells, selected by stepwise exposure to PEP005, were &gt;300-fold more resistant to PEP005 than parental Colo205-S cells and were cross-resistant to phorbol 12-myristate 13-acetate, bryostatin, bistratene A, and staurosporine. No PKCα or PKCδ mutation was detected in Colo205-S and Colo205-R cells. Changes in Colo205-R cells were reminiscent of the epithelial-to-mesenchymal transition (EMT) phenotype. Accordingly, Colo205-R cells were more invasive than Colo205-S in Matrigel assays and in mouse xenografts. We also found an increased mRNA expression of several EMT genes, such as those encoding for transforming growth factor-β and vimentin, along with a decreased mRNA expression of genes involved in epithelial differentiation, such as CDH1 (E-cadherin), CLDN4 (claudin 4), S100A4, and MUC1, in Colo205-R compared with Colo205-S cells in vitro and in vivo. Interestingly, high expression of ET-1 was shown in Colo205-R cells and correlated with low sensitivity to PEP005 and staurosporine in a panel of 10 human cancer cell lines. Inhibition of the ET-1 receptor ETR-A with bosentan restored the antiproliferative effects of PEP005 in Colo205-R cells and decreased the invasive properties of this cell line. Exogenous exposure to ET-1 and silencing ET-1 expression using small interfering RNA modulated cell signaling in Colo205-S and Colo205-R. In summary, acquired resistance to PEP005 was associated with expression of EMT markers and activates the ET-1/ETR-A cell signaling. [Cancer Res 2009;69(10):4260–69]
The Role of ATF4 Stabilization and Autophagy in Resistance of Breast Cancer Cells Treated with Bortezomib
Authors: Milani Manuela , Rzymski Tomasz , Mellor Howard R. , Pike Luke , Bottini Alberto , Generali Daniele , Harris Adrian L. 
Published: May 2009

Abstract
The ubiquitin-proteasome system plays a key regulatory role in cellular homeostasis. The inhibition of the 26S proteasome by Bortezomib leads to the accumulation of misfolded proteins, resulting in endoplasmic reticulum stress followed by a coordinated cellular response called unfolded protein response (UPR). Endoplasmic reticulum stress is also a potent inducer of macroautophagy. Bortezomib is a selective and potent inhibitor of the 26S proteasome and is approved for the treatment of multiple myeloma. Clinical trials with Bortezomib have shown promising results for some types of cancers, but not for some others, including those of the breast. In this study, we show that Bortezomib induces the UPR and autophagy in MCF7 breast cancer cells. Surprisingly, Bortezomib did not induce phosphorylation of PERK, a key initial step of the UPR. We show that induction of autophagy by Bortezomib is dependent on the proteasomal stabilisation of ATF4 and up-regulation of LC3B by ATF4. We show that ATF4 and LC3B play a critical role in activating autophagy and protecting cells from Bortezomib-induced cell death. Our experiments also reveal that HDAC6 knockdown results in decreased LC3B protein and reduced autophagy. Our work shows that the induction of autophagy through ATF4 may be an important resistance mechanism to Bortezomib treatment in breast cancer, and targeting autophagy may represent a novel approach to sensitize breast cancers to Bortezomib. [Cancer Res 2009;69(10):4415–23]
RETRACTED: A New Class of Quinoline-Based DNA Hypomethylating Agents Reactivates Tumor Suppressor Genes by Blocking DNA Methyltransferase 1 Activity and Inducing Its Degradation
Authors: Datta Jharna , Ghoshal Kalpana , Denny William A. , Gamage Swarna A. , Brooke Darby G. , Phiasivongsa Pasit , Redkar Sanjeev , Jacob Samson T. 
Published: May 2009

Abstract
Reactivation of silenced tumor suppressor genes by 5-azacytidine (Vidaza) and its congener 5-aza-2′-deoxycytidine (decitabine) has provided an alternate approach to cancer therapy. We have shown previously that these drugs selectively and rapidly induce degradation of the maintenance DNA methyltransferase (DNMT) 1 by a proteasomal pathway. Because the toxicity of these compounds is largely due to their incorporation into DNA, it is critical to explore novel, nonnucleoside compounds that can effectively reactivate the silenced genes. Here, we report that a quinoline-based compound, designated SGI-1027, inhibits the activity of DNMT1, DNMT3A, and DNMT3B as well M. SssI with comparable IC50 (6-13 μmol/L) by competing with S-adenosylmethionine in the methylation reaction. Treatment of different cancer cell lines with SGI-1027 resulted in selective degradation of DNMT1 with minimal or no effects on DNMT3A and DNMT3B. At a concentration of 2.5 to 5 μmol/L (similar to that of decitabine), complete degradation of DNMT1 protein was achieved within 24 h without significantly affecting its mRNA level. MG132 blocked SGI-1027–induced depletion of DNMT1, indicating the involvement of proteasomal pathway. Prolonged treatment of RKO cells with SGI-1027 led to demethylation and reexpression of the silenced tumor suppressor genes P16, MLH1, and TIMP3. Further, this compound did not exhibit significant toxicity in a rat hepatoma (H4IIE) cell line. This study provides a novel class of DNA hypomethylating agents that have the potential for use in epigenetic cancer therapy. [Cancer Res 2009;69(10):4277–85]
A Novel Technology for the Imaging of Acidic Prostate Tumors by Positron Emission Tomography
Authors: Vāvere Amy L. , Biddlecombe Gráinne B. , Spees William M. , Garbow Joel R. , Wijesinghe Dayanjali , Andreev Oleg A. , Engelman Donald M. , Reshetnyak Yana K. , Lewis Jason S. 
Published: May 2009

Abstract
Solid tumors often develop an acidic environment due to the Warburg effect. The effectiveness of diagnosis and therapy may therefore be enhanced by the design and use of pH-sensitive agents that target acidic tumors. Recently, a novel technology was introduced to target acidic tumors using pH low insertion peptide (pHLIP), a peptide that inserts across cell membranes as an α-helix when the extracellular pH (pHe) is acidic. In this study, we expanded the application of the pHLIP technology to include positron emission tomography imaging of the acidic environment in prostate tumors using 64Cu conjugated to the pHLIP (64Cu-DOTA-pHLIP). Studies showed that this construct avidly accumulated in LNCaP and PC-3 tumors, with higher uptake and retention in the LNCaP tumors. Uptake correlated with differences in the bulk pHe of PC-3 and LNCaP tumors measured in magnetic resonance spectroscopy experiments by the 31P chemical shift of the pHe marker 3-aminopropylphosphonate. This article introduces a novel class of noninvasive pH-selective positron emission tomography imaging agents and opens new research directions in the diagnosis of acidic solid tumors. [Cancer Res 2009;69(10):4510–6]
Association between Rectal Optical Signatures and Colonic Neoplasia: Potential Applications for Screening
Authors: Roy Hemant K. , Turzhitsky Vladimir , Kim Young , Goldberg Michael J. , Watson Patrice , Rogers Jeremy D. , Gomes Andrew J. , Kromine Alexey , Brand Randall E. , Jameel Mohammed , Bogovejic Andrej , Pradhan Prabhakar , Backman Vadim 
Published: May 2009

Abstract
Field carcinogenesis detection represents a promising means for colorectal cancer (CRC) screening, although current techniques (e.g., flexible sigmoidoscopy) lack the requisite sensitivity. The novel optical technology low-coherence enhanced backscattering (LEBS) spectroscopy, allows identification of microscale architectural consequences of the field carcinogenesis in preclinical CRC models with unprecedented accuracy. To investigate the potential clinical translatability of this approach, we obtained biopsies from the normal-appearing rectal mucosa from patients undergoing colonoscopy (n = 219). LEBS signals were recorded through a bench-top instrument. Four parameters characterizing LEBS signal were linearly combined into a single marker. We found that LEBS signal parameters generally mirrored neoplasia progression from patients with no neoplasia, to 5 to 9 mm adenoma and to advanced adenomas. The composite LEBS marker calculated from the LEBS signal paralleled this risk status (ANOVA P &lt; 0.001). Moreover, this was independent of CRC risk factors, benign colonic findings, or clinically unimportant lesions (diminutive adenomas, hyperplastic polyps). For advanced adenomas, the LEBS marker had a sensitivity of 100%, specificity of 80%, and area under the receiver operator characteristic curve of 0.895. Leave-one-out cross-validation and an independent data set (n = 51) supported the robustness of these findings. In conclusion, we provide the first demonstration that LEBS-detectable alterations in the endoscopically normal rectum were associated with the presence of neoplasia located elsewhere in the colon. This study provides the proof of concept that rectal LEBS analysis may potentially provide a minimally intrusive CRC screening technique. Further studies with an endoscopically compatible fiber optic probe are under way for multicenter clinical validation. [Cancer Res 2009;69(10):4476–83]
From Chronic Feed-Induced Intestinal Inflammation to Adenocarcinoma with Metastases in Salmonid Fish
Authors: Dale Ole B. , Tørud Brit , Kvellestad Agnar , Koppang Hanna S. , Koppang Erling O. 
Published: May 2009

Abstract
Neoplasms in fish normally show poor abilities for metastasis, and there are no reports on intestinal cancer with metastasis to other organs. In aquaculture production, carnivorous salmonids in Northern Europe receive commercial feeds with plant ingredients. Such contents have been shown to cause chronic intestinal inflammation. Inflammation provokes carcinogenesis in the human gut, and here, we report a similar pathologic progression in salmonids. Nine commercially farmed groups of Atlantic salmon and rainbow trout (n = 39,160) and one experimental positive group (n = 789) fed the same commercial feed and two negative control groups (n = 3009) were investigated for the occurrence of intestinal tumors and metastases. Exposure period, gender, and sexual maturation were registered. Autopsy revealed an overall intestinal tumor occurrence of 10.62%, of which liver metastasis varied from 0% to 11.35% between the groups. Intestinal cancer prevalence increased from 0.50% to 14.81% during 4 months of feeding in the experimental group. A significant gender effect was registered in the commercially farmed groups but not in the experimental group. Histologic examination showed adenocarcinomas evolving through progressive epithelial dysplasia associated with severe chronic inflammation. One intestinal tumor was registered in one individual in the negative control groups. This is the first report on feed-induced intestinal carcinogenesis and metastasizing adenocarcinomas in fish fed an approved commercial diet. The pathogenesis was associated with a certain commercial diet provoking the inflammation-dysplasia-carcinoma sequence. The histologic progression was analogous to that of human colorectal cancer associated with inflammatory bowel disease. [Cancer Res 2009;69(10):4355–62]
Prognostic Value of Akt-1 in Human Prostate Cancer: A Computerized Quantitative Assessment with Quantum Dot Technology
Authors: Li Rile , Dai Hong , Wheeler Thomas M. , Sayeeduddin Mohammad , Scardino Peter T. , Frolov Anna , Ayala Gustavo E. 
Published: May 2009

Abstract
Background: Akt/protein kinase B signaling pathway has been implicated in tumorigenesis and progression. Previous studies showed the predictive potential of p-Akt-1, but total Akt-1 could provide more reliable information. We used image deconvolution, nanotechnology (quantum dots), and image analysis to improve Akt-1 quantification.
Design: This tissue microarray study included 840 radical prostatectomy cases. Slides were incubated with primary antibody against nonphosphorylated Akt-1 (Akt-1) followed by biotinylated secondary antibody and then by Qdot655 streptavidin conjugate. Slides were imaged under fluorescence microscopy and spectral deconvolution (Nuance) and quantified using plug-in image analysis software. Average intensity of Akt-1 signal was measured and subject to statistical analysis. Multivariate analysis (Cox regression) was applied to assess the prognostic value of Akt-1 for biochemical recurrence and prostate cancer-specific death. Akt-1 expression was also examined for correlations with Ki-67 index and apoptotic index in our database.
Result: Akt-1 was inversely correlated with apoptotic index (ρ = −0.203; P = 0.004) but not with Ki-67 index. The correlation between Akt and p-Akt is significant but weak (P = 0.0496; R2 = 0.118). On multivariate analysis Akt-1 was independently predictive of biochemical recurrence [hazard ratio, 2.863 (95% confidence interval, 1.127-7.271); P = 0.0270]. Akt-1 level is also predictive of prostate cancer-specific death (P = 0.0376).
Conclusion: High levels of Akt-1, assessed by quantum dots, deconvolution imaging, and image analysis, are associated with a higher risk of biochemical recurrence and prostate cancer-specific death.