bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inclusion Body Myositis: A Degenerative Muscle Disease Associated with Intra‐Muscle Fiber Multi‐Protein Aggregates, Proteasome Inhibition, Endoplasmic Reticulum Stress and Decreased Lysosomal Degradation
Authors: Askanas Valerie , Engel W. King , Nogalska Anna 
Published: June 2009

AbstractSporadic inclusion body myositis (s‐IBM), the most common muscle disease of older persons, is of unknown cause, and there is no enduring treatment. Abnormal accumulation of intracellular multi‐protein inclusions is a characteristic feature of the s‐IBM phenotype, and as such s‐IBM can be considered a “conformational disorder,” caused by protein unfolding/misfolding combined with the formation of inclusion bodies. Abnormal intracellular accumulation of unfolded proteins may lead to their aggregation and inclusion body formation.The present article is focusing on the multiple proteins that are accumulated in the form of aggregates within s‐IBM muscle fibers, and it explores the most recent research advances directed toward a better understanding of mechanisms causing their impaired degradation and abnormal aggregation. We illustrate that, among other factors, abnormal misfolding, accumulation and aggregation of proteins are associated with their inadequate disposal—and these factors are combined with, and perhaps provoked by, an aging intracellular milieu. Other concurrent and possibly provocative phenomena known within s‐IBM muscle fibers are: endoplasmic reticulum stress and unfolded protein response, mitochondrial abnormalities, proteasome inhibition, lysosome abnormality and endodissolution. Together, these appear to lead to the s‐IBM‐specific vacuolar degeneration, and muscle fiber atrophy, concluding with muscle fiber death.
Subconjunctival bevacizumab for corneal neovascularization
Authors: Zaki Ahmed A. , Farid Samar F. 
Published: June 2009

Acta Ophthalmol. 2010: 88: 868–871Abstract.Purpose:  This work aimed to study and evaluate the effect of subconjunctival bevacizumab injection in patients with corneal neovascularization (CNV) resulting from different ocular surface disorders.Methods:  Ten eyes with CNV caused by different ocular surface disorders were studied. All eyes had both major and minor vessel CNV caused by factors such as healed corneal ulcers, long‐standing chronic inflammatory diseases and corneal ischaemia (caused by contact lenses). All eyes received a single subconjunctival injection of 2.5 mg (0.1 ml) bevacizumab. Morphological changes in the major and minor vessels were evaluated using slit‐lamp biomicroscopy and corneal photography.Results:  Conspicuous recession of the minor vessels of CNV was observed in all eyes at 2 weeks post‐injection. The extent of CNV of the major vessels was significantly decreased at 2 weeks post‐injection. The level of CNV continued to decrease noticeably for 3 months and then stabilized for the remainder of the 6‐month follow‐up period. Parameters used for evaluation included the total area of CNV, which amounted to 14.0 ± 5.4% of the corneal surface pre‐injection, compared with 9.4 ± 3.9% post‐injection (p < 0.01), reflecting a mean decrease in CNV of 33 ± 8%, and the extent of neovascularization, which decreased from 4.3 ± 1.5 clock hours pre‐injection to 2.4 ± 1.1 clock hours post‐injection (p < 0.01). During the 6‐month follow‐up, none of the 10 eyes showed any complication that could be related to subconjunctival bevacizumab injection.Conclusions:  Bevacizumab can be used safely and effectively for CNV resulting from different ocular surface disorders. It represents an effective treatment for minor vessel neovascularization caused by long‐standing chronic inflammation (e.g. trachoma) or long‐standing corneal ischaemia (e.g. contact lenses), as well as for major vessel neovascularization resulting from different causes. Bevacizumab was well tolerated over the 6‐month follow‐up period.
Life cycle assessment of biofuels from Jatropha curcas in West Africa: a field study
Authors: NDONG ROBERT , MONTREJAUD‐VIGNOLES MIREILLE , SAINT GIRONS OLIVIER , GABRIELLE BENOÎT , PIROT ROLAND , DOMERGUE MARJORIE , SABLAYROLLES CAROLINE 
Published: June 2009

AbstractIn recent years, liquid biofuels for transport have benefited from significant political support due to their potential role in curbing climate change and reducing our dependence on fossil fuels. They may also participate to rural development by providing new markets for agricultural production. However, the growth of energy crops has raised concerns due to their high consumption of conventional fuels, fertilizers and pesticides, their impacts on ecosystems and their competition for arable land with food crops. Low‐input species such as Jatropha curcas, a perennial, inedible crop well adapted to semiarid regions, has received much interest as a new alternative for biofuel production, minimizing adverse effects on the environment and food supply. Here, we used life‐cycle assessment to quantify the benefits of J. curcas biofuel production in West Africa in terms of greenhouse gas emissions and fossil energy use, compared with fossil diesel fuel and other biofuels. Biodiesel from J. curcas has a much higher performance than current biofuels, relative to oil‐derived diesel fuels. Under West Africa conditions, J. curcas biodiesel allows a 72% saving in greenhouse gas emissions compared with conventional diesel fuel, and its energy yield (the ratio of biodiesel energy output to fossil energy input) is 4.7. J. curcas production studied is eco‐compatible for the impacts under consideration and fits into the context of sustainable development.
The burden of smoking-related ill health in the UK
Authors: Allender S , Balakrishnan R , Scarborough P , Webster P , Rayner M 
Published: June 2009

Background:Smoking is one of the biggest avoidable causes of morbidity and mortality in the United Kingdom. This paper quantifies the current health and economic burden of smoking in the UK. It provides comparisons with previous studies of the burden of smoking in the UK and with the costs for other chronic disease risk factors.Methods:A systematic literature review to identify previous estimates of National Health Service costs attributable to smoking was undertaken. Information from the World Health Organization’s Global Burden of Disease Project and routinely collected mortality data were used to calculate mortality due to smoking in the UK. Population-attributable fractions for smoking-related diseases from the Global Burden of Disease Project were applied to NHS cost data to estimate direct financial costs.Results:Previous studies estimated that smoking costs the NHS about £1.4 billion to £1.7 billion in 1991 and has been responsible for about 100 000 deaths per annum over the past 10 years. This paper estimates that the number of deaths attributable to smoking in 2005 was 109 164 (19% of all deaths, 27% deaths in men and 11% of deaths in women). Smoking was directly responsible for 12% of disability adjusted life years lost in 2002 (15.4% in men; 8.5% in women) and the direct cost to the NHS was £5.2 billion in 2005–6.Conclusion:Smoking is still a considerable public health burden in the UK. Accurately establishing the burden in terms of death, disability and financial costs is important for informing national public health policy.
Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1α–Dependent Pathway in Multiple Myeloma
Authors: Zhang Jing , Sattler Martin , Tonon Giovanni , Grabher Clemens , Lababidi Samir , Zimmerhackl Alexander , Raab Marc S. , Vallet Sonia , Zhou Yiming , Cartron Marie-Astrid , Hideshima Teru , Tai Yu-Tzu , Chauhan Dharminder , Anderson Kenneth C. , Podar Klaus 
Published: June 2009

Abstract
Bone marrow angiogenesis is associated with multiple myeloma (MM) progression. Here, we report high constitutive hypoxia-inducible factor-1α (Hif-1α) expression in MM cells, which is associated with oncogenic c-Myc. A drug screen for anti-MM agents that decrease Hif-1α and c-Myc levels identified a variety of compounds, including bortezomib, lenalidomide, enzastaurin, and adaphostin. Functionally, based on transient knockdowns and overexpression, our data delineate a c-Myc/Hif-1α–dependent pathway mediating vascular endothelial growth factor production and secretion. The antiangiogenic activity of our tool compound, adaphostin, was subsequently shown in a zebrafish model and translated into a preclinical in vitro and in vivo model of MM in the bone marrow milieu. Our data, therefore, identify Hif-1α as a novel molecular target in MM and add another facet to anti-MM drug activity. [Cancer Res 2009;69(12):5082–90]
Long-term Cultures of Bone Marrow–Derived Human Mesenchymal Stem Cells Frequently Undergo Spontaneous Malignant Transformation
Authors: Røsland Gro Vatne , Svendsen Agnete , Torsvik Anja , Sobala Ewa , McCormack Emmet , Immervoll Heike , Mysliwietz Josef , Tonn Joerg-Christian , Goldbrunner Roland , Lønning Per Eystein , Bjerkvig Rolf , Schichor Christian 
Published: June 2009

Abstract
Human mesenchymal stem cells (hMSC) aid in tissue maintenance and repair by differentiating into specialized cell types. Due to this ability, hMSC are currently being evaluated for cell-based therapies of tissue injury and degenerative diseases. However, extensive expansion ex vivo is a prerequisite to obtain the cell numbers required for human cell-based therapy protocols. Recent studies indicate that hMSC may contribute to cancer development and progression either by acting as cancer-initiating cells or through interactions with stromal elements. If spontaneous transformation ex vivo occurs, this may jeopardize the use of hMSC as therapeutic tools. Whereas murine MSC readily undergo spontaneous transformation, there are conflicting reports about spontaneous transformation of hMSC. We have addressed this controversy in a two-center study by growing bone marrow–derived hMSC in long-term cultures (5–106 weeks). We report for the first time spontaneous malignant transformation to occur in 45.8% (11 of 24) of these cultures. In comparison with hMSC, the transformed mesenchymal cells (TMC) showed a significantly increased proliferation rate and altered morphology and phenotype. In contrast to hMSC, TMC grew well in soft agar assays and were unable to undergo complete differentiation. Importantly, TMC were highly tumorigenic, causing multiple fast-growing lung deposits when injected into immunodeficient mice. We conclude that spontaneous malignant transformation may represent a biohazard in long-term ex vivo expansion of hMSC. On the other hand, this spontaneous transformation process may represent a unique model for studying molecular pathways initiating malignant transformation of hMSC. [Cancer Res 2009;69(13):5331–9]
ROC1/RBX1 E3 Ubiquitin Ligase Silencing Suppresses Tumor Cell Growth via Sequential Induction of G2-M Arrest, Apoptosis, and Senescence
Authors: Jia Lijun , Soengas Maria S. , Sun Yi 
Published: June 2009

Abstract
Regulator of Cullins-1 (ROC1) or Ring Box Protein-1 (RBX1) is a RING component of SCF (Skp-1, cullins, F-box proteins) E3 ubiquitin ligases, which regulate diverse cellular processes by targeting a variety of substrates for degradation. However, little is known about the role of ROC1 in human cancer. Here, we report that ROC1 is ubiquitously overexpressed in primary human tumor tissues and human cancer cell lines. ROC1 silencing by siRNA significantly inhibited the growth of multiple human cancer cell lines via induction of senescence and apoptosis as well as G2-M arrest. Senescence induction is coupled with DNA damage in p53/p21- and p16/pRB-independent manners. Apoptosis is associated with accumulation of Puma and reduction of Bcl-2, Mcl-1, and survivin; and G2-M arrest is associated with accumulation of 14-3-3σ and elimination of cyclin B1 and Cdc2. In U87 glioblastoma cells, these phenotypic changes occur sequentially upon ROC1 silencing, starting with G2-M arrest, followed by apoptosis and senescence. Thus, ROC1 silencing triggers multiple death and growth arrest pathways to effectively suppress tumor cell growth, suggesting that ROC1 may serve as a potential anticancer target. [Cancer Res 2009;69(12):4974–82]
Harnessing Competing Endocytic Pathways for Overcoming the Tumor-Blood Barrier: Magnetic Resonance Imaging and Near-Infrared Imaging of Bifunctional Contrast Media
Authors: Migalovich Helena Sheikhet , Kalchenko Vyacheslav , Nevo Nava , Meir Gila , Kohen Fortune , Neeman Michal 
Published: June 2009

Abstract
Ovarian cancer is the most lethal gynecologic malignancy, often diagnosed at advanced stage leading to poor prognosis. In the study reported here, magnetic resonance imaging and near-infrared reflectance imaging were applied for in vivo analysis of two competing endocytic pathways affecting retention of bifunctional daidzein-bovine serum albumin (BSA)–based contrast media by human epithelial ovarian carcinoma cells. Suppression of caveolae-mediated uptake using nystatin or by BSA competition significantly enhanced daidzein-BSA-GdDTPA/CyTE777 uptake by tumor cells in vitro. In vivo, perivascular myofibroblasts generated an effective perivascular barrier excluding delivery of BSA-GdDTPA/CyTE777 to tumor cells. The ability to manipulate caveolae-mediated sequestration of albumin by perivascular tumor myofibroblasts allowed us to effectively overcome this tumor-stroma barrier, increasing delivery of daidzein-BSA-GdDTPA/CyTE777 to the tumor cells in tumor xenografts. Thus, both in vitro and in vivo, endocytosis of daidzein-BSA-GdDTPA/CyTE777 by ovarian carcinoma cells was augmented by albumin or by nystatin. In view of the cardinal role of albumin in affecting the availability and pharmacokinetics of drugs, this approach could potentially also facilitate the delivery of therapeutics and contrast media to tumor cells. [Cancer Res 2009;69(13):5610–7]
Subcellular Localization of Cyclic AMP-Responsive Element Binding Protein-Regulated Transcription Coactivator 2 Provides a Link between Obesity and Breast Cancer in Postmenopausal Women
Authors: Brown Kristy A. , McInnes Kerry J. , Hunger Nicole I. , Oakhill Jonathan S. , Steinberg Gregory R. , Simpson Evan R. 
Published: June 2009

Abstract
Epidemiologic evidence supports a correlation between obesity and breast cancer in women. AMP-activated protein kinase plays an important role in energy homeostasis and inhibits the actions of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 (CRTC2). In postmenopausal women, the cyclic AMP-responsive element binding protein-dependent regulation of aromatase is a determinant of breast tumor formation through local production of estrogens. The present work aimed to examine the effect of adipokines on aromatase expression and identify additional mechanisms by which prostaglandin E2 causes increased aromatase expression in human breast adipose stromal cells. Treatment of human adipose stromal cells with forskolin and phorbol 12-myristate 13-acetate (PMA), to mimic prostaglandin E2, resulted in nuclear translocation of CRTC2. Aromatase promoter II (PII) activity assays showed that CRTC2 in addition to forskolin/PMA treatment significantly increased PII-induced activity. CRTC2 binding to PII was examined by chromatin immunoprecipitation, and forskolin/PMA treatment was associated with increased binding to PII. Treatment of human adipose stromal cells with leptin significantly up-regulated aromatase expression associated with nuclear translocation of CRTC2 and increased binding of CRTC2 to PII. Adiponectin treatment significantly decreased forskolin/PMA-stimulated aromatase expression, consistent with the decreased nuclear translocation of CRTC2 and the decreased binding of CRTC2 to PII. The expression and activity of the AMP-activated protein kinase LKB1 was examined and found to be significantly decreased following either forskolin/PMA or leptin treatment. In contrast, adiponectin significantly increased LKB1 expression and activity. In conclusion, the regulation of aromatase by CRTC2, in response to the altered hormonal milieu associated with menopause and obesity, provides a critical link between obesity and breast cancer. [Cancer Res 2009;69(13):5392–9]
Infrequent Detection of Germline Allele-Specific Expression of TGFBR1 in Lymphoblasts and Tissues of Colon Cancer Patients
Authors: Guda Kishore , Natale Leanna , Lutterbaugh James , Wiesner Georgia L. , Lewis Susan , Tanner Stephan M. , Tomsic Jerneja , Valle Laura , de la Chapelle Albert , Elston Robert C. , Willis Joseph , Markowitz Sanford D. 
Published: June 2009

Abstract
Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-β type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (&gt;1.5-fold), and was shown to occur in ∼20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio &lt;0.67 or &gt;1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event. [Cancer Res 2009;69(12):4959–61]
Cancer Genome Sequencing—An Interim Analysis
Authors: Fox Edward J. , Salk Jesse J. , Loeb Lawrence A. 
Published: June 2009

Abstract
With the publishing of the first complete whole genome of a human cancer and its paired normal, we have passed a key milestone in the cancer genome sequencing strategy. The generation of such data will, thanks to technical advances, soon become commonplace. As a significant number of proof-of-concept studies have been published, it is important to analyze now the likely implications of these data and how this information might frame cancer research in the near future. The diversity of genes mutated within individual tumor types, the most striking feature of all studies reported to date, challenges gene-centric models of tumorigenesis. Although cancer genome sequencing will revolutionize certain aspects of personalized care, the value of these studies in facilitating the development of new therapies, their primary goal, seems less promising. Most significantly, however, the cancer genome sequencing strategy, as currently applied, fails to characterize the most relevant genomic features of cancer—the mutational heterogeneity within individual tumors. [Cancer Res 2009;69(12):4948–4950]
Proposal and Validation of Prognostic Scoring Systems for IgG and IgA Monoclonal Gammopathies of Undetermined Significance
Authors: Rossi Francesca , Petrucci Maria Teresa , Guffanti Andrea , Marcheselli Luigi , Rossi Davide , Callea Vincenzo , Vincenzo Federico , De Muro Marianna , Baraldi Alessandra , Villani Oreste , Musto Pellegrino , Bacigalupo Andrea , Gaidano Gianluca , Avvisati Giuseppe , Goldaniga Maria , DePaoli Lorenzo , Baldini Luca 
Published: June 2009

Abstract
Purpose: The presenting clinico-hematologic features of 1,283 patients with IgG and IgA monoclonal gammopathies of undetermined significance (MGUS) were correlated with the frequency of evolution into multiple myeloma (MM).
Experimental Design: Two IgG MGUS populations were evaluated: a training sample (553 patients) and a test sample (378 patients); the IgA MGUS population consisted of 352 patients.
Results: Forty-seven of the 553 training group patients and 22 of 378 test group IgG patients developed MM after a median follow-up of 6.7 and 3.6 years, respectively. Multivariate analysis showed that serum monoclonal component (MC) levels of ≤1.5 g/dL, the absence of light-chain proteinuria and normal serum polyclonal immunoglobulin levels defined a prognostically favorable subset of patients, and could be used to stratify the patients into three groups at different 10-year risk of evolution (hazard ratio, 1.0, 5.04, 11.2; P &lt; 0.001). This scoring system was validated in the test sample. Thirty of the 352 IgA patients developed MM after a median follow-up of 4.8 years, and multivariate analysis showed that hemoglobin levels of &lt;12.5 g/dL and reduced serum polyclonal immunoglobulin correlated with progression. A pooled statistical analysis of all of the patients confirmed the validity of Mayo Clinic risk model showing that IgA class, serum MC levels, and light-chain proteinuria are the most important variables correlated with disease progression.
Conclusions: Using simple variables, we validated a prognostic model for IgG MGUS. Among the IgA cases, the possible prognostic role of hemoglobin emerged in addition to a decrease in normal immunoglobulin levels.
Suppression of Androgen-Independent Prostate Cancer Cell Aggressiveness by FTY720: Validating Runx2 as a Potential Antimetastatic Drug Screening Platform
Authors: Chua Chee-Wai , Chiu Yung-Tuen , Yuen Hiu-Fung , Chan Kwok-Wah , Man Kwan , Wang Xianghong , Ling Ming-Tat , Wong Yong-Chuan 
Published: June 2009

Abstract
Purpose: Previously, FTY720 was found to possess potent anticancer effects on various types of cancer. In the present study, we aimed to first verify the role of Runx2 in prostate cancer progression and metastasis, and, subsequently, assessed if FTY720 could modulate Runx2 expression, thus interfering downstream events regulated by this protein.
Experimental Design: First, the association between Runx2 and prostate cancer progression was assessed using localized prostate cancer specimens and mechanistic investigation of Runx2-induced cancer aggressiveness was then carried out. Subsequently, the effect of FTY720 on Runx2 expression and transcriptional activity was investigated using PC-3 cells, which highly expressed Runx2 protein. Last, the involvement of Runx2 in FTY720-induced anticancer effects was evaluated by modulating Runx2 expression in various prostate cancer cell lines.
Results: Runx2 nuclear expression was found to be up-regulated in prostate cancer and its expression could be used as a predictor of metastasis in prostate cancer. Further mechanistic studies indicated that Runx2 accelerated prostate cancer aggressiveness through promotion of cadherin switching, invasion toward collagen I, and Akt activation. Subsequently, we found that FTY720 treatment down-regulated Runx2 expression and its transcriptional activity, as well as inhibited its regulated downstream events. More importantly, silencing Runx2 in PC-3 enhanced FTY720-induced anticancer effects as well as cell viability inhibition, whereas overexpressing Runx2 in 22Rv1 that expressed very low endogenous Runx2 protein conferred resistance in the same events.
Conclusion: This study provided a novel mechanism for the anticancer effect of FTY720 on advanced prostate cancer, thus highlighting the therapeutic potential of this drug in treating this disease.