bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-26a Inhibits Cell Growth and Tumorigenesis of Nasopharyngeal Carcinoma through Repression of EZH2
Authors: Lu Juan , He Ming-Liang , Wang Lu , Chen Ying , Liu Xiong , Dong Qi , Chen Yang-Chao , Peng Ying , Yao Kai-Tai , Kung Hsiang-Fu , Li Xiang-Ping 
Published: January 2011

AbstractSeveral microRNAs (miRNA) have been implicated in nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in southern China. In this study, we report that microRNA miR-26a iscommonly downregulated in NPC specimens and NPC cell lines with important functional consequences. Ectopic expression of miR-26a dramatically suppressed cell proliferation and colony formation by inducing G1-phase cell-cycle arrest. We found that miR-26a strongly reduced the expression of EZH2 oncogene in NPC cells. Similar to the restoring miR-26 expression, EZH2 downregulation inhibited cell growth and cell-cycle progression, whereas EZH2 overexpression rescued the suppressive effect of miR-26a. Mechanistic investigations revealed that miR-26a suppressed the expression of c-myc, the cyclin D3 and E2, and the cyclin-dependent kinase CDK4 and CDK6 while enhancing the expression of CDK inhibitors p14ARF and p21CIP1 in an EZH2-dependent manner. Interestingly, cyclin D2 was regulated by miR-26a but not by EZH2, revealing cyclin D2 asanother direct yet mechanistically distinct target of miR-26a. In clinical specimens, EZH2 was widely overexpressed and its mRNA levels were inversely correlated with miR-26a expression. Taken together, our results indicate that miR-26a functions as a growth-suppressive miRNA in NPC, and that its suppressive effects are mediated chiefly by repressing EZH2 expression. Cancer Res; 71(1); 225–33. ©2010 AACR.
Identification of New MicroRNAs in Paired Normal and Tumor Breast Tissue Suggests a Dual Role for the ERBB2/Her2 Gene
Authors: Persson Helena , Kvist Anders , Rego Natalia , Staaf Johan , Vallon-Christersson Johan , Luts Lena , Loman Niklas , Jonsson Goran , Naya Hugo , Hoglund Mattias , Borg Ake , Rovira Carlos 
Published: January 2011

Abstract
To comprehensively characterize microRNA (miRNA) expression in breast cancer, we performed the first extensive next-generation sequencing expression analysis of this disease. We sequenced small RNA from tumors with paired samples of normal and tumor-adjacent breast tissue. Our results indicate that tumor identity is achieved mainly by variation in the expression levels of a common set of miRNAs rather than by tissue-specific expression. We also report 361 new, well-supported miRNA precursors. Nearly two-thirds of these new genes were detected in other human tissues and 49% of the miRNAs were found associated with Ago2 in MCF7 cells. Ten percent of the new miRNAs are located in regions with high-level genomic amplifications in breast cancer. A new miRNA is encoded within the ERBB2/Her2 gene and amplification of this gene leads to overexpression of the new miRNA, indicating that this potent oncogene and important clinical marker may have two different biological functions. In summary, our work substantially expands the number of known miRNAs and highlights the complexity of small RNA expression in breast cancer. Cancer Res; 71(1); 78–86. ©2011 AACR.
Endothelial Cell–Specific Deletion of Transcription Factor FoxM1 Increases Urethane-Induced Lung Carcinogenesis
Authors: Balli David , Zhang Yufang , Snyder Jonathan , Kalinichenko Vladimir V. , Kalin Tanya V. 
Published: January 2011

Abstract
Vascular endothelial cells provide essential support to the tumor microenvironment, but little is known about the transcriptional control of endothelial functions during tumorigenesis. Here we define a critical role for the Forkhead transcription factor FoxM1 in modulating the development of tumor-associated endothelial cells. Pulmonary tumorigenesis induced by urethane administration was compared in mice genetically deleted for FoxM1 in endothelial cells (enFoxm1−/− mice). Notably, lung tumor number and size were increased in enFoxm1−/− mice. Increased tumorigenesis was associated with increased proliferation of tumor cells and increased expression of c-Myc and cyclin D1. Furthermore, perivascular infiltration by inflammatory cells was elevated and inflammatory cells in BAL fluid were increased. Expression of Flk-1 (vascular endothelial growth factor receptor 2) and FoxF1, known regulators of pulmonary inflammation, was decreased in enFoxm1−/− mice. siRNA-mediated knockdown of FoxM1 in endothelial cells reduced Flk-1 and FoxF1 expression, which was driven by direct transcriptional induction by FoxM1 as target genes. Endothelial specific deletion of FoxM1 in vivo or in vitro also decreased expression of Sfrp1 (secreted frizzled-related protein 1), a known inhibitor of canonical Wnt signaling, in a manner that was associated with increased Wnt signaling. Taken together, our results suggest that endothelial-specific expression of FoxM1 limits lung inflammation and canonical Wnt signaling in lung epithelial cells, thereby restricting lung tumorigenesis. Cancer Res; 71(1); 40–50. ©2011 AACR.
Molecular Pathobiology of Human Cervical High-Grade Lesions: Paracrine STAT3 Activation in Tumor-Instructed Myeloid Cells Drives Local MMP-9 Expression
Authors: Schröer Nadine , Pahne Jennifer , Walch Barbara , Wickenhauser Claudia , Smola Sigrun 
Published: January 2011

AbstractIn many tumors, the switch from precancerous lesions to malignancy critically relies on expression of the matrix-metalloprotease MMP-9, which is predominantly provided by infiltrating inflammatory cells. Our study defines a novel molecular cascade, how human neoplastic cells instruct tumor-associated myeloid cells to produce MMP-9. In biopsies of human papillomavirus–associated precancerous cervical intraepithelial neoplasia (CIN III lesions), we show broad activation of the transcription factor STAT3 and coexpression of MMP-9 in perivascular inflammatory cells. For the first time, we establish a causative link between tumor-mediated paracrine STAT3 activation and MMP-9 production by human tumor-instructed monocytes, whereas NF-κB activation is dispensable for this response. Our data provide evidence that STAT3 does not directly induce MMP-9 but first leads to a strong production of the monocyte chemoattractant protein-1 (CCL2) in the nanogram range. In a second phase, autocrine stimulation of the CCR2 receptor in the tumor-instructed monocytes amplifies MMP-9 expression via intracellular Ca2+ signaling. These findings elucidate a critical mechanism in the molecular pathobiology of cervical carcinogenesis at the switch to malignancy. Particularly in tumors, which are associated with infectious agents, STAT3-driven inflammation may be pivotal to promote carcinogenesis, while at the same time limit NF-κB–dependent immune responses and thus rejection of the infected preneoplastic cells. The molecular cascade defined in this study provides the basis for a rational design of future adjuvant therapies of cervical precancerous lesions. Cancer Res; 71(1); 87–97. ©2011 AACR. Cancer Res; 71(1); 87–97. ©2011 AACR.
Snail2 is an Essential Mediator of Twist1-Induced Epithelial Mesenchymal Transition and Metastasis
Authors: Casas Esmeralda , Kim Jihoon , Bendesky Andrés , Ohno-Machado Lucila , Wolfe Cecily J. , Yang Jing 
Published: January 2011

Abstract
To metastasize, carcinoma cells must attenuate cell–cell adhesion to disseminate into distant organs. A group of transcription factors, including Twist1, Snail1, Snail2, ZEB1, and ZEB2, have been shown to induce epithelial mesenchymal transition (EMT), thus promoting tumor dissemination. However, it is unknown whether these transcription factors function independently or coordinately to activate the EMT program. Here we report that direct induction of Snail2 is essential for Twist1 to induce EMT. Snail2 knockdown completely blocks the ability of Twist1 to suppress E-cadherin transcription. Twist1 binds to an evolutionarily conserved E-box on the proximate Snail2 promoter to induce its transcription. Snail2 induction is essential for Twist1-induced cell invasion and distant metastasis in mice. In human breast tumors, the expression of Twist1 and Snail2 is highly correlated. Together, our results show that Twist1 needs to induce Snail2 to suppress the epithelial branch of the EMT program and that Twist1 and Snail2 act together to promote EMT and tumor metastasis. Cancer Res; 71(1); 245–54. ©2010 AACR.
Long Intergenic Noncoding RNAs: New Links in Cancer Progression
Authors: Tsai Miao-Chih , Spitale Robert C. , Chang Howard Y. 
Published: January 2011

Abstract
The process of cancer metastasis involves a series of sequential and complex steps. Here we give a perspective on recent results regarding noncoding transcription in cancer progression, focusing on the emerging role of long intergenic noncoding RNAs (lincRNAs). LincRNAs target chromatin modification complexes or RNA-binding proteins to alter gene expression programs. Similarly to miRNAs, lincRNAs exhibit distinct gene expression patterns in primary tumors and metastases. We discuss how lincRNAs can be used for cancer diagnosis and prognosis and serve as potential therapeutic targets. Cancer Res; 71(1); 3–7. ©2011 AACR.
Glioblastoma Recurrence after Cediranib Therapy in Patients: Lack of “Rebound” Revascularization as Mode of Escape
Authors: di Tomaso Emmanuelle , Snuderl Matija , Kamoun Walid S. , Duda Dan G. , Auluck Pavan K. , Fazlollahi Ladan , Andronesi Ovidiu C. , Frosch Matthew P. , Wen Patrick Y. , Plotkin Scott R. , Hedley-Whyte E. Tessa , Sorensen A. Gregory , Batchelor Tracy T. , Jain Rakesh K. 
Published: January 2011

Abstract
Recurrent glioblastomas (rGBM) invariably relapse after initial response to anti-VEGF therapy. There are 2 prevailing hypotheses on how these tumors escape antiangiogenic therapy: switch to VEGF-independent angiogenic pathways and vessel co-option. However, direct evidence in rGBM patients is lacking. Thus, we compared molecular, cellular, and vascular parameters in autopsy tissues from 5 rGBM patients who had been treated with the pan-VEGF receptor tyrosine kinase inhibitor cediranib versus 7 patients who received no therapy or chemoradiation but no antiangiogenic agents. After cediranib treatment, endothelial proliferation and glomeruloid vessels were decreased, and vessel diameters and perimeters were reduced to levels comparable to the unaffected contralateral brain hemisphere. In addition, tumor endothelial cells expressed molecular markers specific to the blood–brain barrier, indicative of a lack of revascularization despite the discontinuation of therapy. Surprisingly, in cediranib-treated GBM, cellular density in the central area of the tumor was lower than in control cases and gradually decreased toward the infiltrating edge, indicative of a change in growth pattern of rGBMs after cediranib treatment, unlike that after chemoradiation. Finally, cediranib-treated GBMs showed high levels of PDGF-C (platelet-derived growth factor C) and c-Met expression and infiltration by myeloid cells, which may potentially contribute to resistance to anti-VEGF therapy. In summary, we show that rGBMs switch their growth pattern after anti-VEGF therapy—characterized by lower tumor cellularity in the central area, decreased pseudopalisading necrosis, and blood vessels with normal molecular expression and morphology—without a second wave of angiogenesis. Cancer Res; 71(1); 19–28. ©2011 AACR.
Dose-Dependent Effects of Focal Fractionated Irradiation on Secondary Malignant Neoplasms in Nf1 Mutant Mice
Authors: Nakamura Jean L. , Phong Connie , Pinarbasi Emile , Kogan Scott C. , Vandenberg Scott , Horvai Andrew E. , Faddegon Bruce A. , Fiedler Dorothea , Shokat Kevan , Houseman Benjamin T. , Chao Richard , Pieper Russell O. , Shannon Kevin 
Published: January 2011

Abstract
Secondary malignant neoplasms (SMN) are increasingly common complications of cancer therapy that have proven difficult to model in mice. Clinical observations suggest that the development of SMN correlates with radiation dose; however, this relationship has not been investigated systematically. We developed a novel procedure for administering fractionated cranial irradiation (CI) and investigated the incidence and spectrum of cancer in control and heterozygous Nf1 mutant mice irradiated to a moderate (15 Gy) or high dose (30 Gy). Heterozygous Nf1 inactivation cooperated with CI to induce solid tumors and myeloid malignancies, with mice developing many of the most common SMNs found in human patients. CI-induced malignancies segregated according to radiation dose as Nf1+/− mice developed predominately hematologic abnormalities after 15 Gy, whereas solid tumors predominated at 30 Gy, suggesting that radiation dose thresholds exist for hematologic and nonhematologic cancers. Genetic and biochemical studies revealed discrete patterns of somatic Nf1 and Trp53 inactivation and we observed hyperactive Ras signaling in many radiation-induced solid tumors. This technique for administering focal fractionated irradiation will facilitate mechanistic and translational studies of SMNs. Cancer Res; 71(1); 106–15. ©2011 AACR.
ShRNA-Targeted MAP4K4 Inhibits Hepatocellular Carcinoma Growth
Authors: Liu An-Wen , Cai Jing , Zhao Xiang-Li , Jiang Ting-Hui , He Tian-Feng , Fu Hua-Qun , Zhu Ming-Hua , Zhang Shu-Hui 
Published: January 2011

Abstract
Purpose: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC).
Experimental Design: MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth in vivo were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways.
Results: MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4 expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression–related signaling pathways including JNK, NFκB, and toll-like receptors were repressed by MAP4K4 downregulation.
Conclusions: MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance. Clin Cancer Res; 17(4); 1–11. ©2010 AACR.
Interpersonal psychotherapy for depression
Authors: Law Roslyn 
Published: January 2011

SummaryInterpersonal psychotherapy is an evidence-based therapy, originally developed to treat major depression. It is cited in numerous good practice guidelines. The biopsychosocial signs of depression are understood in the context of current social and interpersonal stressors, defined in terms of role transitions, disputes, bereavements and sensitivities. In therapy, the patient learns to understand the interactions between symptoms and interpersonal difficulties and the ways in which they are mutually reinforcing. Patients are helped to break this pattern and achieve a reduction in depressive symptoms and improvement in interpersonal functioning through improved communication, expression of affect and proactive engagement with the current interpersonal network. The therapeutic relationship is used as a tool for exploring and modelling external relationships. This article outlines the background to interpersonal psychotherapy, the process of therapy and the expansion of the evidence base.
Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis
Authors: Barbui Corrado , Cipriani Andrea , Patel Vikram , Ayuso-Mateos José L. , van Ommeren Mark 
Published: January 2011

BackgroundDepression is a common condition that has been frequently treated with psychotropics.AimsTo review systematically the evidence of efficacy and acceptability of antidepressant and benzodiazepine treatments for patients with minor depression.MethodA systematic review and meta-analysis of double-blind randomised controlled trials comparing antidepressants or benzodiazepines v. placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company websites. Risk of bias was assessed for the generation of the allocation sequence, allocation concealment, masking, incomplete outcome data, and sponsorship bias.ResultsSix studies met inclusion criteria. Three studies compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid were studied in one study each. No studies compared benzodiazepines with placebo. In terms of failures to respond to treatment (6 studies, 234 patients treated with antidepressants and 234 with placebo) no significant difference between antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81–1.08). In terms of acceptability, data extracted from two studies (93 patients treated with antidepressants and 93 with placebo) showed no statistically significant difference between antidepressants and placebo (RR = 1.06, 95% CI 0.65–1.73). There was no statistically significant between-study heterogeneity for any of the reported analyses.ConclusionsThere is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition.
Impact of compulsory detention under the Mental Health Act 1983 on future visa and insurance applications
Authors: Hurrell Rebecca , Di Mambro Ben J. , Doody Gillian A. 
Published: January 2011

Aims and methodTo assess the extent to which psychiatric history, with specific regard to compulsory psychiatric admission, is questioned in visa, insurance and permit applications. Application forms for the top UK destinations for immigration, work and travel visas, six types of insurance, and driving, sporting and vocational permits were analysed.ResultsPsychiatric history is questioned in some applications across all visa types. Hospital admission, but not compulsory psychiatric admission, is questioned in some immigration visas. Psychiatric history is not questioned in mortgage protection, car or pet insurance but it is questioned in some travel, life and health insurance applications, as is hospital admission. The majority of permit applications questioned psychiatric history and one vocational permit considered compulsory psychiatric admission.Clinical implicationsThe majority of visa, insurance and permit application forms enquire about past medical and psychiatric history. Information concerning detention under the Mental Health Act is very rarely questioned, indicating that a direct link between detention and access restriction is not evident.
Age discrimination in mental health services needs to be understood
Authors: Anderson Dave 
Published: January 2011

SummaryThe ageing population presents a major challenge to health and social care services now and for decades to come. Age discrimination in mental health services is more pronounced than in other areas of healthcare. Legislation, currently being reviewed, which will make unjustified age discrimination unlawful from 2012, has implications for the organisation and delivery of mental healthcare that need to be understood.
Palladium Nanoparticles Supported on Aminopropyl-Functionalized Clay as Efficient Catalysts for Phosphine-Free C–C Bond Formation via Mizoroki–Heck and Suzuki–Miyaura Reactions
Authors: Firouzabadi Habib , Iranpoor Nasser , Ghaderi Arash , Ghavami Maryam , Hoseini S Jafar 
Published: January 2011

Abstract
In this study, we have used palladium nanoparticles supported on aminopropyl-functionalized clay as an efficient catalyst for Mizoroki–Heck and Suzuki–Miyaura reactions. By using this catalyst, the reaction of iodo- and bromoarenes with n-butyl acrylate and styrene proceeded well and smoothly to produce the desired products in good to excellent yields under solvent-free conditions. The catalyst has been recycled for ten runs without much loss of its catalytic activity. Suzuki–Miyaura reaction of structurally different aryl halides (I and Br) with phenylboronic acid by the aid of this catalyst in refluxing water or SDS micellar solution in the absence of any organic co-solvent was also performed well to give the desired biphenyl products in good to excellent yields. Production of the corresponding homocoupled products in negligible amounts was observed in these reactions. In comparison with many other reported palladium-catalyzed Mizoroki–Heck and Suzuki–Miyaura reactions, the Pd-loading of this catalyst is one of the lowest. In the presence of this catalyst, all the reactions proceeded without using any external phosphorus ligands.
Improvement of Carbon-Based Counter Electrode for Dye-Sensitized Solar Cells
Authors: Sakurai Sho , Jiang Hai-qing , Takahashi Masashi , Kobayashi Koichi 
Published: January 2011

Abstract
A ClO4−-doped poly(3,4-ethylenedioxythiophene) (PEDOT)-supported carbon particle (PEDOT–ClO4−/C) composite film electrode was prepared by electrophoretic deposition on transparent conductive oxide glass to improve the performance of carbon-based counter electrodes for dye-sensitized solar cells (DSSC). Evaluation of the electrochemical impedance demonstrated that the PEDOT–ClO4−/C composite film electrode had a lower iodide electrolyte/electrode interfacial resistance than that of a simple carbon particle film electrode. As a result, a DSSC with a PEDOT–ClO4−/C composite film counter electrode had a significantly improved fill factor and photovoltaic conversion efficiency, compared to a cell based on a simple carbon particle film electrode. Furthermore, the photovoltaic conversion efficiency of a DSSC with a PEDOT–ClO4−/C composite film electrode demonstrated approximately 85% of the conversion efficiency of a DSSC with a platinum-sputtered glass counter electrode.
Birmingham hip resurfacing
Authors: Treacy R. B. C. , McBryde C. W. , Shears E. , Pynsent P. B. 
Published: January 2011

We report the survival, radiological and functional outcomes of a single surgeon series of his first 144 consecutive Birmingham hip resurfacing procedures (130 patients) at a minimum of ten years. There were ten revisions during this time. Although no patients were lost to follow-up some did not complete the scoring assessment or undergo radiological assessment at ten years.The ten-year survival for male patients was 98.0% (95% confidence interval 95.2 to 100). The ten-year survival for the total cohort with aseptic revision as the endpoint was 95.5% (95% confidence interval 91.8 to 99.0) and including revisions for sepsis was 93.5% (95% confidence interval 89.2 to 97.6). The median modified Oxford hip score at ten years was 4.2% (interquartile range 0 to 19) and the median University of California, Los Angeles score was 7.0 (interquartile range 5.0 to 8.0).This study confirms the midterm reports that metal-on-metal hip resurfacing using the Birmingham Hip provides a durable alternative to total hip replacement, particularly in younger male patients wishing to maintain a high level of function, with low risk of revision for at least ten years.