bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gap Junction–Mediated Import of MicroRNA from Bone Marrow Stromal Cells Can Elicit Cell Cycle Quiescence in Breast Cancer Cells
Authors: Lim Philip K. , Bliss Sarah A. , Patel Shyam A. , Taborga Marcelo , Dave Meneka A. , Gregory Larissa A. , Greco Steven J. , Bryan Margarette , Patel Prem S. , Rameshwar Pranela 
Published: February 2011

Abstract
Bone marrow (BM) metastasis of breast cancer (BC) can recur even decades after initial diagnosis and treatment, implying the long-term survival of disseminated cancer cells in a dormant state. Here we investigated the role of microRNAs (miRNA) transmitted from BM stroma to BC cells via gap junctions and exosomes in tumor cell quiescence. MDA-MB-231 and T47D BC cells arrest in G0 phase of the cell cycle when cocultured with BM stroma. Analyses of miRNA expression profiles identified numerous miRNAs implicated in cell proliferation including miR-127, -197, -222, and -223 targeting CXCL12. Subsequently, we showed that these CXCL12-specific miRNAs are transported from BM stroma to BC cells via gap junctions, leading to reduced CXCL12 levels and decreased proliferation. Stroma-derived exosomes containing miRNAs also contributed to BC cell quiescence, although to a lesser degree than miRNAs transmitted via gap junctions. This study shows that the transfer of miRNAs from BM stroma to BC cells might play a role in the dormancy of BM metastases. Cancer Res; 71(5); 1550–60. ©2011 AACR.
Systematic Analysis of MicroRNAs Targeting the Androgen Receptor in Prostate Cancer Cells
Authors: Östling Päivi , Leivonen Suvi-Katri , Aakula Anna , Kohonen Pekka , Mäkelä Rami , Hagman Zandra , Edsjö Anders , Kangaspeska Sara , Edgren Henrik , Nicorici Daniel , Bjartell Anders , Ceder Yvonne , Perälä Merja , Kallioniemi Olli 
Published: February 2011

Abstract
Androgen receptor (AR) is expressed in all stages of prostate cancer progression, including in castration-resistant tumors. Eliminating AR function continues to represent a focus of therapeutic investigation, but AR regulatory mechanisms remain poorly understood. To systematically characterize mechanisms involving microRNAs (miRNAs), we conducted a gain-of function screen of 1129 miRNA molecules in a panel of human prostate cancer cell lines and quantified changes in AR protein content using protein lysate microarrays. In this way, we defined 71 unique miRNAs that influenced the level of AR in human prostate cancer cells. RNA sequencing data revealed that the 3′UTR of AR (and other genes) is much longer than currently used in miRNA target prediction programs. Our own analyses predicted that most of the miRNA regulation of AR would target an extended 6 kb 3′UTR. 3′UTR-binding assays validated 13 miRNAs that are able to regulate this long AR 3′UTR (miR-135b, miR-185, miR-297, miR-299-3p, miR-34a, miR-34c, miR-371–3p, miR-421, miR-449a, miR-449b, miR-634, miR-654–5p, and miR-9). Fifteen AR downregulating miRNAs decreased androgen-induced proliferation of prostate cancer cells. In particular, analysis of clinical prostate cancers confirmed a negative correlation of miR-34a and miR-34c expression with AR levels. Our findings establish that miRNAs interacting with the long 3′UTR of the AR gene are important regulators of AR protein levels, with implications for developing new therapeutic strategies to inhibit AR function and androgen-dependent cell growth. Cancer Res; 71(5); 1956–67. ©2011 AACR.
Integrative Genomics Identifies Molecular Alterations that Challenge the Linear Model of Melanoma Progression
Authors: Rose Amy E. , Poliseno Laura , Wang Jinhua , Clark Michael , Pearlman Alexander , Wang Guimin , Vega y Saenz de Miera Eleazar C. , Medicherla Ratna , Christos Paul J. , Shapiro Richard , Pavlick Anna , Darvishian Farbod , Zavadil Jiri , Polsky David , Hernando Eva , Ostrer Harry , Osman Iman 
Published: February 2011

Abstract
Superficial spreading melanoma (SSM) and nodular melanoma (NM) are believed to represent sequential phases of linear progression from radial to vertical growth. Several lines of clinical, pathologic, and epidemiologic evidence suggest, however, that SSM and NM might be the result of independent pathways of tumor development. We utilized an integrative genomic approach that combines single nucleotide polymorphism array (6.0; Affymetrix) with gene expression array (U133A 2.0; Affymetrix) to examine molecular differences between SSM and NM. Pathway analysis of the most differentially expressed genes between SSM and NM (N = 114) revealed significant differences related to metabolic processes. We identified 8 genes (DIS3, FGFR1OP, G3BP2, GALNT7, MTAP, SEC23IP, USO1, and ZNF668) in which NM/SSM-specific copy number alterations correlated with differential gene expression (P &lt; 0.05; Spearman's rank). SSM-specific genomic deletions in G3BP2, MTAP, and SEC23IP were independently verified in two external data sets. Forced overexpression of metabolism-related gene MTAP (methylthioadenosine phosphorylase) in SSM resulted in reduced cell growth. The differential expression of another metabolic-related gene, aldehyde dehydrogenase 7A1 (ALDH7A1), was validated at the protein level by using tissue microarrays of human melanoma. In addition, we show that the decreased ALDH7A1 expression in SSM may be the result of epigenetic modifications. Our data reveal recurrent genomic deletions in SSM not present in NM, which challenge the linear model of melanoma progression. Furthermore, our data suggest a role for altered regulation of metabolism-related genes as a possible cause of the different clinical behavior of SSM and NM. Cancer Res; 71(7); 2561–71. ©2011 AACR.
TLR3 as a Biomarker for the Therapeutic Efficacy of Double-stranded RNA in Breast Cancer
Authors: Salaun Bruno , Zitvogel Laurence , Asselin-Paturel Carine , Morel Yannis , Chemin Karine , Dubois Clarisse , Massacrier Catherine , Conforti Rosa , Chenard Marie Pierre , Sabourin Jean-Christophe , Goubar Aicha , Lebecque Serge , Pierres Michel , Rimoldi Donata , Romero Pedro , Andre Fabrice 
Published: February 2011

AbstractThe discovery of a targeted therapeutic compound along with its companion predictive biomarker is a major goal of clinical development for a personalized anticancer therapy to date. Here we present evidence of the predictive value of TLR3 expression by tumor cells for the efficacy of Poly (A:U) dsRNA in 194 breast cancer patients enrolled in a randomized clinical trial. Adjuvant treatment with double-stranded RNA (dsRNA) was associated with a significant decrease in the risk of metastatic relapse in TLR3 positive but not in TLR3-negative breast cancers. Moreover, we show the functional relevance of TLR3 expression by human tumor cells for the antitumor effects mediated by dsRNA in several preclinical mouse models carried out in immunocompromised animals. These 2 independent lines of evidence relied upon the generation of a novel tool, an anti-TLR3 antibody (40F9.6) validated for routine detection of TLR3 expression on paraffin-embedded tissues. Altogether, these data suggest that dsRNA mediates its therapeutic effect through TLR3 expressed on tumor cells, and could therefore represent an effective targeted treatment in patients with TLR3-positive cancers. Cancer Res; 71(5); 1607–14. ©2011 AACR.
Human Monoclonal Antibodies to Sialyl-Lewisa (CA19.9) with Potent CDC, ADCC, and Antitumor Activity
Authors: Sawada Ritsuko , Sun Shu-Man , Wu Xiaohong , Hong Feng , Ragupathi Govind , Livingston Philip O. , Scholz Wolfgang W. 
Published: February 2011

Abstract
Purpose: The carbohydrate antigen sialyl-Lewisa (sLea), also known as CA19.9, is widely expressed on epithelial tumors of the gastrointestinal tract and breast and on small-cell lung cancers. Since overexpression of sLea appears to be a key event in invasion and metastasis of many tumors and results in susceptibility to antibody-mediated lysis, sLea is an attractive molecular target for tumor therapy.
Experimental Design: We generated and characterized fully human monoclonal antibodies (mAb) from blood lymphocytes from individuals immunized with a sLea–KLH vaccine.
Results: Several mAbs were selected based on ELISA and FACS including two mAbs with high affinity for sLea (5B1 and 7E3, binding affinities 0.14 and 0.04 nmol/L, respectively) and further characterized. Both antibodies were specific for Neu5Acα2–3Galβ1–3(Fucα1–4)GlcNAcβ as determined by glycan array analysis. Complement-dependent cytotoxicity against DMS-79 cells was higher (EC50 0.1 μg/mL vs. 1.7 μg/mL) for r7E3 (IgM) than for r5B1 (IgG1). In addition, r5B1 antibodies showed high level of antibody-dependent cell-mediated cytotoxicity activity on DMS-79 cells with human NK cells or peripheral blood mononuclear cells. To evaluate in vivo efficacy, the antibodies were tested in a xenograft model with Colo205 tumor cells engrafted into SCID (severe combined immunodeficient mice) mice. Treatment during the first 21 days with four doses of r5B1 (100 μg per dose) doubled the median survival time to 207 days, and three of five animals survived with six doses.
Conclusion: On the basis of the potential of sLea as a target for immune attack and their affinity, specificity, and effector functions, 5B1and 7E3 may have clinical utility. Clin Cancer Res; 17(5); 1024–32. ©2011 AACR.
Inhibition of Prostate Cancer Osteoblastic Progression with VEGF121/rGel, a Single Agent Targeting Osteoblasts, Osteoclasts, and Tumor Neovasculature
Authors: Mohamedali Khalid A. , Li Zhi Gang , Starbuck Michael W. , Wan Xinhai , Yang Jun , Kim Sehoon , Zhang Wendy , Rosenblum Michael G. , Navone Nora M. 
Published: February 2011

Abstract
Purpose: A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF121/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa.
Experimental Design: Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF121/rGel.
Results: VEGF121/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF121/rGel internalization into osteoblasts was VEGF121 receptor driven. Furthermore, VEGF121/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF121/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomographic analysis revealed that VEGF121/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non–tumor-bearing) femurs. VEGF121/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF121/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF121/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation.
Conclusions: Targeting VEGF receptor (VEGFR)-1- or VEGFR-2–expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. Clin Cancer Res; 17(8); 2328–38. ©2011 AACR.
HuR-Mediated Control of C/EBPβ mRNA Stability and Translation in ALK-Positive Anaplastic Large Cell Lymphomas
Authors: Bergalet Julie , Fawal Mohamad , Lopez Celine , Desjobert Cecile , Lamant Laurence , Delsol Georges , Morello Dominique , Espinos Estelle 
Published: February 2011

Abstract
The CCAAT/enhancer-binding protein β (C/EBPβ) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK+). Although ALK-mediated C/EBPβ transcriptional activation has been reported, C/EBPβ mRNA possesses U- and AU-rich domains in its 3′-untranslated region (3′-UTR) that might be privileged targets for posttranscriptional control in ALK+ ALCLs. The purpose of this study was to explore this possibility. By using human ALCL-derived cells and a murine model of ALK-transformed cells, we show that the AU-binding protein HuR binds to the 3′-UTR of C/EBPβ mRNA, as previously reported in adipocytes, and that NPM-ALK enhances this interaction. Interaction between HuR and C/EBPβ mRNA impacts on C/EBPβ gene expression at both the mRNA and protein levels. Indeed, C/EBPβ mRNA stability following HuR silencing is reduced and reaches the value observed in ALK-inactivated cells. Remarkably, HuR expression is not modified by NPM-ALK, but its association with actively translating polysomes is dramatically increased in ALK+ cells. HuR/polysomes association diminishes when NPM-ALK activity is inhibited and is accompanied by a concomitant decrease of C/EBPβ mRNA translation. Finally, we show that HuR and NPM-ALK colocalized in cytoplasmic granules and HuR is phosphroylated on tyrosine residues in ALK+ ALCL cells. Our study thus demonstrates that C/EBPβ is indeed regulated at the posttranscriptional level by HuR in ALK+ cells, leading us to propose that part of NPM-ALK oncogenic properties relies on its ability to modify HuR properties in the cytoplasm and hence to alter expression of key actors of transformation. Mol Cancer Res; 9(4); 485–96. ©2011 AACR.
Myocardial Perfusion Imaging After Coronary Artery Bypass Surgery Using Cardiovascular Magnetic Resonance
Authors: Arnold J. Ranjit , Francis Jane M. , Karamitsos Theodoros D. , Lim Chris C. , van Gaal William J. , Testa Luca , Bhamra-Ariza Paul , Selvanayagam Joseph B. , Sayeed Rana , Westaby Stephen , Banning Adrian P. , Neubauer Stefan , Jerosch-Herold Michael 
Published: February 2011

Background—
Absolute quantification of perfusion with cardiovascular magnetic resonance has not previously been applied in patients with coronary artery bypass grafting (CABG). Owing to increased contrast bolus dispersion due to the greater distance of travel through a bypass graft, this approach may result in systematic underestimation of myocardial blood flow (MBF). As resting MBF remains normal in segments supplied by noncritical coronary stenosis (<85%), measurement of perfusion in such territories may be utilized to reveal systematic error in the quantification of MBF. The objective of this study was to test whether absolute quantification of perfusion with cardiovascular magnetic resonance systematically underestimates MBF in segments subtended by bypass grafts.

Methods and Results—

The study population comprised 28 patients undergoing elective CABG for treatment of multivessel coronary artery disease. Eligible patients had angiographic evidence of at least 1 myocardial segment subtended by a noncritically stenosed coronary artery (<85%). Subjects were studied at 1.5 T, with evaluation of resting MBF using model-independent deconvolution. Analyses were confined to myocardial segments subtended by native coronary arteries with <85% stenosis at baseline, and MBF was compared in grafted and ungrafted segments before and after revascularization. A total of 249 segments were subtended by coronary arteries with <85% stenosis at baseline. After revascularization, there was no significant difference in MBF in ungrafted (0.82±0.19 mL/min/g) versus grafted segments (0.82±0.15 mL/min/g,
P
=0.57). In the latter, MBF after revascularization did not change significantly from baseline (0.86±0.20 mL/min/g,
P
=0.82).

Conclusions—
Model-independent deconvolution analysis does not systematically underestimate blood flow in graft-subtended territories, justifying the use of this methodology to evaluate myocardial perfusion in patients with CABG.
A Method for Forecasting Cloud Condensation Nuclei Using Predictions of Aerosol Physical and Chemical Properties from WRF/Chem
Authors: Ward Daniel , Cotton William 
Published: February 2011

AbstractModel investigations of aerosol–cloud interactions across spatial scales are necessary to advance basic understanding of aerosol impacts on climate and the hydrological cycle. Yet these interactions are complex, involving numerous physical and chemical processes. Models capable of combining aerosol dynamics and chemistry with detailed cloud microphysics are recent developments. In this study, predictions of aerosol characteristics from the Weather Research and Forecasting Model with Chemistry (WRF/Chem) are integrated into the Regional Atmospheric Modeling System microphysics package to form the basis of a coupled model that is capable of predicting the evolution of atmospheric aerosols from gas-phase emissions to droplet activation. The new integrated system is evaluated against measurements of cloud condensation nuclei (CCN) from a land-based field campaign and an aircraft-based field campaign in Colorado. The model results show the ability to capture vertical variations in CCN number concentration within an anthropogenic pollution plume. In a remote continental location the model-forecast CCN number concentration exhibits a positive bias that is attributable in part to an overprediction of the aerosol hygroscopicity that results from an underprediction in the organic aerosol mass fraction. In general, the new system for predicting CCN from forecast aerosol fields improves on the existing scheme in which aerosol quantities were user prescribed.
Evaluation of the Efficacy and Tolerance of a Topical Gel With 4% Quassia Extract in the Treatment of Rosacea
Authors: Ferrari Alicia , Diehl Christian 
Published: February 2011

Background: There are various treatment options available for rosacea, depending on the subtype, but treatment is still generally unsatisfactory. Some studies have reported antiparasitic and anti‐inflammatory properties of Quassia amara.Aim: To check the efficacy and safety of a topical gel with 4% Quassia amara extract in the treatment of various grades of rosacea.Methods: A group of 30 patients with various grades of rosacea (I‐IV) were investigated in a single‐center, open‐label study. They were treated with a topical gel with 4% Quassia amara extract for 6 weeks. Response was evaluated by the flushing, erythema, telangiectasia, papules, and pustules scores. At the end of therapy, overall improvement, safety, and tolerability were assessed.Results: Twenty‐seven of 30 patients (90%) completed the study. The treatment resulted to be very effective, and the results achieved were in line with those published with topical metronidazole and azelaic acid. Safety and tolerability were excellent.Conclusion: Topical quassia extract could be a new, efficient, and safe weapon in the armamentarium for the management of rosacea.)
En Balance Participants Decrease Dietary Fat and Cholesterol Intake as Part of a Culturally Sensitive Hispanic Diabetes Education Program
Authors: Salto Lorena M. , Cordero-MacIntyre Zaida , Beeson Lawrence , Schulz Eloy , Firek Anthony , De Leon Marino 
Published: February 2011

Purpose The purpose of this study was to assess dietary intake habits of Mexican American Hispanic adults participating in the En Balance diabetes education program. Methods En Balance is a 3-month culturally sensitive diabetes education intervention for Spanish-speaking Hispanics. Of the 46 participants enrolled, 39 mainly Mexican American Hispanic adults with type 2 diabetes completed the En Balance program. Participants lived in the Riverside and San Bernardino counties of California, and all participants completed the program by June 2008. Dietary intake was assessed at baseline and at 3 months using the validated Southwest Food Frequency Questionnaire. Results Clinically important decreases in glycemic control and serum lipid levels were observed at the end of the 3-month program. The baseline diet was characterized by a high intake of energy (2478 ± 1140 kcal), total fat (87 ± 44 g/day), saturated fat (28 ± 15 g/day), dietary cholesterol (338 ± 217 mg/day), and sodium (4236 ± 2055 mg/ day). At 3 months, the En Balance group mean intake of dietary fat (P = .045) and dietary cholesterol ( P = .033) decreased significantly. Low dietary intakes of docosahexaenoic acid, eicosapentaenoic acid, and vitamin E were also observed in these adults with type 2 diabetes. Conclusions The En Balance program improved glycemic control and lipid profiles in a group of Hispanic diabetic participants. En Balance also promoted decreases in dietary fat and dietary cholesterol intake.
PARP-1 inhibition prevents CNS migration of dendritic cells during EAE, suppressing the encephalitogenic response and relapse severity
Authors: Cavone Leonardo , Aldinucci Alessandra , Ballerini Clara , Biagioli Tiziana , Moroni Flavio , Chiarugi Alberto 
Published: February 2011

Background: Pharmacological inhibitors of poly(ADP-ribose) polymerase-1 (PARP-1) are currently evaluated in clinical trials for various malignancies but, interestingly, also proved of remarkable efficacy in preclinical models of autoimmune disorders including experimental autoimmune encephalomyelitis (EAE). Objectives: The objectives of the study were to determine molecular mechanisms underlying suppression of the encephalitogenic response by these drugs; likewise, whether clinically-relevant post-treatment paradigms with PARP-1 inhibitors could prevent EAE relapses. Methods: Adopted both in vitro techniques (bone marrow-derived cultured DC) as well as in vivo models of chronic or relapsing–remitting (RR) EAE. Results: We report that two structurally unrelated PARP-1 inhibitors negatively regulated NFκB activation, as well as maturation, cytokine production and APC function of cultured mouse bone marrow-derived dendritic cells (DCs). PARP-1 inhibitors also reduced the number and APC function of DCs migrating in the draining lymph nodes of ovalbumin-immunized mice. In C57Bl mice with chronic EAE or SJL mice with RR EAE, pharmacological inhibition of PARP-1 reduced CNS DC migration and demyelination as well as neurological impairment to an extent similar to that achieved with the potent immunosuppressant cyclosporine A. Remarkably, PARP-1 inhibitors injected after the first phase of disease reduced relapse incidence and severity, as well as the spinal cord number of autoreactive Th17 cells. Under this clinically-relevant treatment paradigm, PARP inhibitors also suppressed epitope spreading of the encephalitogenic response. Conclusions: Overall, data underscore the potential relevance of PARP-1 inhibitors to MS therapy and suppression of autoimmunity.