bluuebunny/crossref_metadata_2025_split huggingface dataset:
There is more to mind reading than having theory of mind concepts: new directions in theory of mind research
Authors: Samson Dana , Apperly Ian A. 
Published: April 2010

AbstractFor more than 30 years, researchers have focused on the important transition that children undergo between the ages of 3 and 5, when they start to solve mind‐reading problems that require reasoning about complex mental states, such as beliefs. The main question for debate has been whether, during that transition, children acquire new concepts about how the mind works (i.e. a more sophisticated ‘theory of mind’) or whether their more general cognitive abilities improve and help them deal with the general task demands. Recently, researchers have started to explore mind‐reading abilities in individuals outside of the classic 3–5 age span, showing early theory of mind abilities in ever‐younger children and infants, but also far from flawless performance in adults. In this article, we show how the results of these two new lines of research converge on the idea that there is more to mind reading than having theory of mind concepts: there are various processes required to efficiently implement theory of mind concepts in our reasoning, and there may be, in fact, multiple mind‐reading routes available. We then highlight the emergent new directions for future research. Copyright © 2010 John Wiley & Sons, Ltd.
Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide: Variation by geographical region, histological type and year of publication
Authors: Li Ni , Franceschi Silvia , Howell‐Jones Rebecca , Snijders Peter J.F. , Clifford Gary M. 
Published: April 2010

AbstractPooled data on human papillomavirus (HPV) type distribution in invasive cervical cancer (ICC) can help to predict the potential impact of HPV type‐specific vaccines and screening tests, and to understand the carcinogenicity of HPV types. We performed a meta‐analysis of HPV type‐specific prevalence data published from 1990 to 2010, including a total of 243 studies and 30,848 ICC. The proportion of ICC associated with HPV16 and/or 18 (HPV16/18) was between 70 and 76% in all world regions except Asia. In Western/Central Asia, 82% of ICC was HPV16/18‐associated compared to only 68% in Eastern Asia. The 12 most common HPV types identified, in order of decreasing prevalence, were HPV16 (57%), 18 (16%), 58, 33, 45, 31, 52, 35, 59, 39, 51 and 56. The prevalence of other types, phylogenetically related to those above, ranged from <0.1% for HPV85 to 0.6% for HPV68. Overall HPV prevalence increased significantly from 85.9% in studies published from 1990 to 1999 to 92.9% in studies published from 2006 to 2010. Prevalence increases were large for multiple infections (from 4.0 to 15.7%) and for HPV16 (from 51.8 to 60.0%, including HPV16 alone or in multiple infections). Smaller but significant increases in prevalence were also seen for HPV39, 53 and 58. A large amount of recently published data has improved the understanding of the contribution of a broad range of HPV types to ICC in different world regions. However, estimating the fraction of ICC attributable to different types is increasingly complicated by the detection of multiple HPV infections in ICC.
PD‐1 and PD‐L1 upregulation promotes CD8+ T‐cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients
Authors: Shi Feng , Shi Ming , Zeng Zhen , Qi Rui‐Zhao , Liu Zhen‐Wen , Zhang Ji‐Yuan , Yang Yong‐Ping , Tien Po , Wang Fu‐Sheng 
Published: April 2010

AbstractProgrammed death 1 (PD‐1) and its ligand (PD‐L1) play pivotal roles in regulating host immune responses. However, the inhibitory effects of this pathway on the function of cytotoxic CD8+ T lymphocytes, the main effector cells in hepatocellular carcinoma (HCC) patients, are not well defined. In this study, we characterized circulating and intratumor PD‐1/PD‐L1 expression and analyzed their association with disease progression in a cohort of hepatitis B virus‐infected patients, including 56 with HCC, 20 with liver cirrhosis (LC) and 20 healthy controls (HC). The frequency of circulating PD‐1+CD8+ T cells increased with disease progression from LC to HCC patients versus HC. Furthermore, tumor‐infiltrating effector CD8+ T cells showed a drastic increase in PD‐1 expression. These increases in circulating and intratumor PD‐1+CD8+ T cells could predict poorer disease progression and postoperative recurrence. Immunohistochemical staining showed that PD‐L1 expressing hepatoma cells and apoptotic infiltrating CD8+ T cells were both enriched in tumor sections. In vitro, CD8+ T cells induced PD‐L1 expression on hepatoma cells in an IFN‐γ–dependent manner, which in turn promoted CD8+ T cells apoptosis, and blocking PD‐L1 reversed this effect. Therefore, this study extends our knowledge of the role of the PD‐1/PD‐L1 pathway in tumor evasion and provides evidence for a new therapeutic target in HCC patients.
Frequent changes in subtelomeric DNA methylation patterns and its relevance to telomere regulation during human hepatocarcinogenesis
Authors: Oh Bong‐Kyeong , Um Tae‐Hee , Choi Gi Hong , Park Young Nyun 
Published: April 2010

AbstractSubtelomeric chromatin modifications are important regulators of telomere length. We examined the subtelomeric DNA methylation status of 7q, 8q, 17q, 18p, 21q and XpYp in 32 pairs of hepatocellular carcinomas (HCCs) and their adjacent non‐HCCs via methylation‐specific PCR (quantified as methylation ratio). In addition, 10q was subjected to bisulfite‐genomic‐sequencing. Telomere length was determined by Southern hybridization. In all cases, the relationship between methylation ratio and telomere length was determined. High levels of methylation ratio were found on chromosomes 7q, 18p and XpYp, whereas 8q 17q and 21q were less methylated in both HCCs and non‐HCCs. Compared to non‐HCCs, HCCs exhibited a higher methylation ratio on 18p and 21q, and a wider distribution of methylation ratio on 7q, 21q and 10q (p < 0.05). The methylation ratio of 18p and of 21q was negatively and positively correlated with telomere length of HCCs, respectively (p < 0.05). We evaluated changes in methylation pattern between non‐HCCs and HCCs. Out of 185 sites, hypermethylation changes from non‐HCC to HCC were found at 47 sites and hypomethylation changes at 31 sites. Changes in methylation pattern were observed at three to four sites among six chromosomal sites in 15 patients (47%). There was a tendency toward hypomethylation changes at 7q (p = 0.013) and hypermethylation changes at 21q (p = 0.057) when telomere lengthened from non‐HCCs to HCCs. In summary, subtelomeric methylation patterns dynamically changed during hepatocarcinogenesis. Subtelomeric methylation at certain regions was related to telomere lengthening or shortening, suggesting an association between subtelomeric chromatin structure and telomere length regulation in human hepatocarcinogenesis.
An ISCOM vaccine combined with a TLR9 agonist breaks immune evasion mediated by regulatory T cells in an orthotopic model of pancreatic carcinoma
Authors: Jacobs Collin , Duewell Peter , Heckelsmiller Klaus , Wei Jiwu , Bauernfeind Franz , Ellermeier Jonathan , Kisser Ulrich , Bauer Christian A. , Dauer Marc , Eigler Andreas , Maraskovsky Eugene , Endres Stefan , Schnurr Max 
Published: April 2010

AbstractVaccines based on immune stimulatory complexes (ISCOM) induce T‐cell responses against tumor antigen (Ag). However, immune responses are impaired in pancreatic cancer patients. We investigated the efficacy of an ISCOM vaccine in a murine pancreatic carcinoma model. Panc02 cells expressing OVA as a model Ag were induced subcutaneously or orthotopically in the pancreas of C57BL/6 mice. Treatment consisted of an OVA containing ISCOM vaccine, either used alone or in combination with the TLR9 agonist CpG. The ISCOM vaccine effectively induced Ag‐specific CTL capable of killing tumor cells. However, in mice with established tumors CTL induction by the vaccine was inefficient and did not affect tumor growth. Lack of efficacy correlated with increased numbers of Treg. Depletion of Treg with anti‐CD25 mAb restored CTL induction and prolonged survival. Adding low‐dose CpG to the ISCOM vaccine reduced Treg numbers, enhanced CTL responses and induced regression of pancreatic tumors in a CD8+ T cell–dependent manner. Mice cured from the primary tumor mounted a memory T‐cell response against wild‐type Panc02 tumors, indicative of epitope spreading. Combining ISCOM vaccines with TLR agonists is a promising strategy for breaking tumor immune evasion and deserves further evaluation for the treatment of pancreatic carcinoma.
Autoregulation of phospholipase D activity is coupled to selective induction of phospholipase D1 expression to promote invasion of breast cancer cells
Authors: Kang Dong Woo , Park Mi Hee , Lee Young Jun , Kim Hyung Sik , Lindsley Craig W. , Alex Brown H. , Min Do Sik 
Published: April 2010

AbstractPhospholipase D (PLD) is an important signaling enzyme implicated in the control of many biological processes, including cell proliferation and survival. Despite the importance of the duration and amplitude of PLD signaling in carcinogenesis, mechanisms that regulate PLD expression remain poorly understood. In our study, we define the regulatory components of the machinery that specifies selective PLD1 inductionviasignals propagated through PLD activity. We demonstrate for the first time that establishment of a positive feedback loop that is dependent on enzymatic activity originating from both PLD1 and PLD2 isozymes enhances selective expression of PLD1, but not PLD2. Phosphatidic acid, the product of PLD activity, leads to an increase in the Ras‐ERK/PI3K‐NFκB signaling cascade and enhances binding of NFκB to the PLD1 promoter, consequently inducing selective PLD1 expression in SK‐BR3 breast cancer cells. Moreover, selective PLD inhibitor suppressed epidermal growth factor‐induced matrix metalloproteinase upregulation and invasion by inhibiting PLD1 expression. In conclusion, we propose that autoregulation of PLD activity might be coupled to induction of PLD1 expression, and thereby play a role in carcinogenesis.
Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium
Authors: Lurie Galina , Wilkens Lynne R. , Thompson Pamela J. , Carney Michael E. , Palmieri Rachel T. , Pharoah Paul D. P. , Song Honglin , Hogdall Estrid , Kjaer Susanne Kruger , DiCioccio Richard A. , McGuire Valerie , Whittemore Alice S. , Gayther Simon A. , Gentry‐Maharaj Aleksandra , Menon Usha , Ramus Susan J. , Goodman Marc T. ,   on behalf of the Ovarian Cancer Association Consortium
Published: April 2010

AbstractThe association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non‐Hispanic cases and 3479 controls in a pooled analysis of five population‐based case–control studies within the Ovarian Cancer Association Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Carriers of the rare T allele were at increased risk of ovarian carcinoma compared to women with the CC genotype in all studies combined; each copy of the T allele was associated with a modest 9% increased risk (OR = 1.09; 95% CI: 1.01–1.19; p = 0.04). No significant heterogeneity among studies was observed (p = 0.37) and, after excluding the dataset from the Hawaii study, the risk association for rs2228570 among replication studies was unchanged (OR = 1.09; 95% CI: 1.00–1.19; p = 0.06). A stronger association of rs2228570 with risk was observed among younger women (aged < 50 years versus 50 years or older) (p = 0.04). In all studies combined, the increased risk per copy of the T allele among younger women was 24% (OR = 1.24; 95% CI: 1.04–1.47; p = 0.02). This association remained statistically significant after excluding the Hawaii data (OR = 1.20; 95% CI: 1.01–1.43; p = 0.04). No heterogeneity of the association was observed by stage (p = 0.46), tumor histology (p = 0.98), or time between diagnosis and interview (p = 0.94). This pooled analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility.
TIMP‐3 promotes apoptosis in nonadherent small cell lung carcinoma cells lacking functional death receptor pathway
Authors: Kallio Janne P. , Hopkins‐Donaldson Sally , Baker Andrew H. , Kähäri Veli‐Matti 
Published: April 2010

AbstractTissue inhibitor of metalloproteinases‐3 (TIMP‐3) has previously been identified as a tumor suppressor for adherent malignant and normal cells. TIMP‐3 inhibits adhesion of cells to extracellular matrix and promotes apoptosis through death receptor‐activated, caspase‐8‐mediated pathway. Here, we have studied the effect of adenovirally mediated overexpression of TIMP‐3 on small cell lung cancer (SCLC) cell lines SW2 and N417, which grow in suspension and lack functional caspase‐8. The results show that adenoviral delivery of TIMP‐3 promotes apoptotic cell death in SCLC cells in the absence of caspase‐8 activation. These results suggest TIMP‐3 as a promising therapeutic anticancer protein also in nonadherent malignant cells lacking functional death receptor signaling.
Time‐domain in vivo near infrared fluorescence imaging for evaluation of matriptase as a potential target for the development of novel, inhibitor‐based tumor therapies
Authors: Napp Joanna , Dullin Christian , Müller Friedemann , Uhland Kerstin , Petri Jean Bernhard , van de Locht Andreas , Steinmetzer Torsten , Alves Frauke 
Published: April 2010

AbstractProteolytic enzymes expressed on the surface of tumor cells, and thus easily accessible to external interventions, represent useful targets for anticancer and antimetastatic therapies. In our study, we thoroughly evaluated matriptase, a trypsin‐like transmembrane serine protease, as potential target for novel inhibitor‐based tumor therapies. We applied time‐domain near infrared fluorescence (NIRF) imaging to characterize expression and activity of matriptase in vivo in an orthotopic AsPC‐1 pancreatic tumor model in nude mice. We show strong and tumor‐specific binding of intravenously injected Cy5.5 labeled antimatriptase antibody (MT‐Ab*Cy5.5) only to primary AsPC‐1 tumors and their metastases over time within living mice, taking into account fluorescence intensities and fluorescence lifetimes of the applied probes. Specific binding of MT‐Ab*Cy5.5 to tumor sites was confirmed by ex vivo NIRF imaging of tumor tissue, NIRF microscopy and by coregistration of the in vivo acquired NIRF intensity maps to anatomical structures visualized by flat‐panel volume computed tomography (fpVCT) in living mice. Moreover, using an activatable synthetic substrate S*DY‐681 we could clearly demonstrate that matriptase is proteolytically active in vitro as well as in vivo in tumor‐bearing mice, and that application of synthetic active‐site inhibitors having high affinity and selectivity toward matriptase can efficiently inhibit its proteolytic activity for at least 24 hr. We thus successfully applied NIRF imaging in combination with fpVCT to characterize matriptase as a promising molecular target for inhibitor‐based cancer therapies.
PET imaging of tumor angiogenesis in mice with VEGF‐A–targeted 86Y‐CHX‐A″‐DTPA‐bevacizumab
Authors: Nayak Tapan K. , Garmestani Kayhan , Baidoo Kwamena E. , Milenic Diane E. , Brechbiel Martin W. 
Published: April 2010

AbstractBevacizumab is a humanized monoclonal antibody that binds to tumor‐secreted vascular endothelial growth factor (VEGF)‐A and inhibits tumor angiogenesis. In 2004, the antibody was approved by the US Food and Drug Administration (FDA) for the treatment of metastatic colorectal carcinoma in combination with chemotherapy. This report describes the preclinical evaluation of a radioimmunoconjugate, 86Y‐CHX‐A″‐DTPA‐bevacizumab, for potential use in Positron Emission Tomography (PET) imaging of VEGF‐A tumor angiogenesis and as a surrogate marker for 90Y‐based radioimmunotherapy. Bevacizumab was conjugated to CHX‐A″‐DTPA and radiolabeled with 86Y. In vivo biodistribution and PET imaging studies were performed on mice bearing VEGF‐A–secreting human colorectal (LS‐174T), human ovarian (SKOV‐3) and VEGF‐A–negative human mesothelioma (MSTO‐211H) xenografts. Biodistribution and PET imaging studies demonstrated highly specific tumor uptake of the radioimmunoconjugate. In mice bearing VEGF‐A–secreting LS‐174T, SKOV‐3 and VEGF‐A–negative MSTO‐211H tumors, the tumor uptake at 3 days postinjection was 13.6 ± 1.5, 17.4 ± 1.7 and 6.8 ± 0.7 % ID/g, respectively. The corresponding tumor uptake in mice coinjected with 0.05 mg cold bevacizumab were 5.8 ± 1.3, 8.9 ± 1.9 and 7.4 ± 1.0 % ID/g, respectively at the same time point, demonstrating specific blockage of the target in VEGF‐A–secreting tumors. The LS‐174T and SKOV3 tumors were clearly visualized by PET imaging after injecting 1.8–2.0 MBq 86Y‐CHX‐A″‐DTPA‐bevacizumab. Organ uptake quantified by PET closely correlated (r2 = 0.87, p = 0.64, n = 18) to values determined by biodistribution studies. This preclinical study demonstrates the potential of the radioimmunoconjugate, 86Y‐CHX‐A″‐DTPA‐bevacizumab, for noninvasive assessment of the VEGF‐A tumor angiogenesis status and as a surrogate marker for 90Y‐CHX‐A″‐DTPA‐bevacizumab radioimmunotherapy.
Curcumin enhances dasatinib‐induced inhibition of growth and transformation of colon cancer cells
Authors: Nautiyal Jyoti , Banerjee Sanjeev , Kanwar Shailender S. , Yu Yingjie , Patel Bhaumik B , Sarkar Fazlul H. , Majumdar Adhip P.N. 
Published: April 2010

AbstractColorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF‐1R as well as c‐Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS‐354825; Bristol‐Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a nontoxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter, we utilized C57BL/6 APCMin+/− mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: (i) colony formation, (ii) invasion through extracellular matrix and (iii) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT‐116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in ApcMin+/− mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer.
Epstein‐Barr virus‐encoded EBNA‐5 forms trimolecular protein complexes with MDM2 and p53 and inhibits the transactivating function of p53
Authors: Kashuba Elena , Yurchenko Mariya , Yenamandra Surya Pavan , Snopok Boris , Szekely Laszlo , Bercovich Beatrice , Ciechanover Aaron , Klein George 
Published: April 2010

AbstractWe report that MDM2, a negative regulator of p53, can bind to EBNA‐5. Using GST pull‐down assay, immunoprecipitation, surface plasmon resonance and immunostaining of lymphoblastoid cells, we found that trimolecular complexes are formed between EBNA‐5, MDM2 and p53, where MDM2 serves as a bridge. The EBNA‐5 binding to MDM2 counteracted destabilizing effect of the latter on the p53. In ubiquitination and degradation assays in vitro, EBNA‐5 inhibited p53 polyubiquitination (but not monoubiquitination) in a concentration‐dependent manner. This resembles the effect of p14ARF on p53. Moreover, EBNA‐5 was found to inhibit the degradation of p53 in vitro. High levels of p53 expression were maintained in LCLs. The binding of EBNA‐5 to MDM2 also could impair the functional activity of p53. The p53‐dependent genes P21 and VDR were not induced in EBV‐infected, in contrast to mitogen‐activated cells. This may explain the tolerance of established LCLs to high levels of p53 without undergoing apoptosis.
Assessment of isorhamnetin 3‐O‐neohesperidoside from Acacia salicina: protective effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and nifuroxazide
Authors: Bouhlel Ines , Limem Ilef , Skandrani Ines , Nefatti Aicha , Ghedira Kamel , Dijoux‐Franca Marie‐Genevieve , Leila Chekir‐Ghedira 
Published: April 2010

AbstractAntioxidant activity of isorhamnetin 3‐O‐neohesperidoside, isolated from the leaves of Acacia salicina, was determined by the ability of this compound to inhibit xanthine oxidase activity and to scavenge the free radical 2,2′‐azino‐bis (3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS.−) diammonium salt. Antigenotoxic activity was assessed using the SOS chromotest assay. This compound has the ability to scavenge the ABTS.+ radical by a hydrogen donating mechanism. We also envisaged the study of the antioxidant effect of this compound by the enzymatic xanthine/xanthine oxidase (X/XOD) assay. Results indicated that isorhamnetin 3‐O‐neohesperidoside was a potent inhibitor of xanthine oxidase and superoxide anion scavengers. Moreover, this compound induced an inhibitory activity against nifuroxazide and aflatoxine B1 (AFB1) induced genotoxicity. Taken together, these observations provide evidence that isorhamnetin 3‐O‐neohesperidoside isolated from the leaves of A. salicina is able to protect cells against the consequences of oxidative stress. Copyright © 2010 John Wiley & Sons, Ltd.
Bilateral round ligament varicosities mimicking an inguinal hernia in pregnancy: Case report
Authors: Kahriman Guven , Donmez Halil , Mavili Ertugrul , Ozcan Nevzat 
Published: April 2010

AbstractA 22‐year‐old pregnant woman presented with a painful swelling in the right groin. Sonography was performed to confirm a presumptive diagnosis of inguinal hernia based on physical examination. Gray‐scale sonography examination revealed bilateral inguinal cystic lesion expanding with the Valsalva maneuver. Color Doppler imaging demonstrated multiple prominent vessels with retrograde venous flow during Valsalva maneuver. Bilateral round ligament varicosities were diagnosed and inguinal hernia was excluded by sonographic findings. Round ligament varicosities should be considered in the differential diagnosis of groin swelling during pregnancy. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:512–514, 2010
Sonographic appearance of a metastasis to the breast from a cerebellar medulloblastoma
Authors: Ternier Frédéric , Hadjaj Djamal , Jacquemier Jocelyne 
Published: April 2010

AbstractWe present the case of a 29‐year‐old woman with a medulloblastoma of the cerebellum who developed a breast mass during the course of her disease. Core biopsy of the breast lesion revealed a metastatic medulloblastoma. Development of metastasis to the breast from medulloblastoma is very rare and the prognosis for such patients is poor. It is important to distinguish primary breast cancer from metastasis to the breast, because the therapeutic options as well as the prognosis are very different. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010