bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coupling of Mutated Met Variants to DNA Repair via Abl and Rad51
Authors: Ganapathipillai Suganthini S. , Medová Michaela , Aebersold Daniel M. , Manley Paul W. , Berthou Sylvie , Streit Bruno , Blank-Liss Wieslawa , Greiner Richard H. , Rothen-Rutishauser Barbara , Zimmer Yitzhak 
Published: July 2008

Abstract
Abnormal activation of DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems is a compelling likelihood with significant implications in both cancer biology and treatment. Here, we show that due to a potential substrate switch, mutated variants of the receptor for hepatocyte growth factor Met, but not the wild-type form of the receptor, directly couple to the Abl tyrosine kinase and the Rad51 recombinase, two key signaling elements of homologous recombination–based DNA repair. Treatment of cells that express the mutated receptor variants with the Met inhibitor SU11274 leads, in a mutant-dependent manner, to a reduction of tyrosine phosphorylated levels of Abl and Rad51, impairs radiation-induced nuclear translocation of Rad51, and acts as a radiosensitizer together with the p53 inhibitor pifithrin-α by increasing cellular double-strand DNA break levels following exposure to ionizing radiation. Finally, we propose that in order to overcome a mutation-dependent resistance to SU11274, this aberrant molecular axis may alternatively be targeted with the Abl inhibitor, nilotinib. [Cancer Res 2008;68(14):5769–77]
Conditional Loss of Uterine Pten Unfailingly and Rapidly Induces Endometrial Cancer in Mice
Authors: Daikoku Takiko , Hirota Yasushi , Tranguch Susanne , Joshi Ayesha R. , DeMayo Francesco J. , Lydon John P. , Ellenson Lora H. , Dey Sudhansu K. 
Published: July 2008

Abstract
Etiology of endometrial cancer (EMC) is not fully understood. Animal models with rapidly and spontaneously developing EMC will help explore mechanisms of cancer initiation and progression. Pten+/− mice are currently being used as a model to study EMC. These females develop atypical endometrial hyperplasia of which ∼20% progresses to EMC. In addition, tumors develop in other organs, complicating the use of this model to specifically study EMC. Here, we show that conditional deletion of endometrial Pten results in EMC in all female mice as early as age 1 month with myometrial invasion occurring by 3 months. In contrast, conditional deletion of endometrial p53 had no phenotype within this time frame. Whereas mice with endometrial Pten deletion had a life span of ∼5 months, mice with combined deletion of endometrial Pten and p53 had a shorter life span with an exacerbated disease state. Such rapid development of EMC from homozygous loss of endometrial Pten suggests that this organ is very sensitive to this tumor suppressor gene for tumor development. All lesions at early stages exhibited elevated Cox-2 and phospho-Akt levels, hallmarks of solid tumors. More interestingly, levels of two microRNAs miR-199a* and miR-101a that posttranscriptionally inhibit Cox-2 expression were down-regulated in tumors in parallel with Cox-2 up-regulation. This mouse model in which the loxP-Cre system has been used to delete endometrial Pten and/or p53 allows us to study in detail the initiation and progression of EMC. These mouse models have the added advantage because they mimic several features of human EMC. [Cancer Res 2008;68(14):5619–27]
An Object Lesson: Source Determines the Relations That Trait Anxiety, Prostate Cancer Worry, and Screening Fear Hold with Prostate Screening Frequency
Authors: Consedine Nathan S. , Adjei Brenda A. , Ramirez Paul M. , McKiernan James M. 
Published: July 2008

AbstractFears regarding prostate cancer and the associated screening are widespread. However, the relations between anxiety, cancer worry, and screening fear and screening behavior are complex, because anxieties stemming from different sources have different effects on behavior. In differentiating among anxieties from different sources (trait anxiety, cancer worry, and screening fear), we expected that cancer worry would be associated with more frequent screening, whereas fear of screening would be associated with less frequent screening. Hypotheses were tested in a sample of 533 men (ages 45-70 years) recruited using a stratified cluster-sampling plan. Men provided information on demographic and structural variables (age, education, income, marital status, physician discussion of risk and screening, access, and insurance) and completed a set of anxiety measures (trait anxiety, cancer worry, and screening fear). As expected, two-step multiple regressions controlling for demographics, health insurance status, physician discussion, and health-care system barriers showed that prostate-specific antigen and digital rectal examination frequencies had unique associations with cancer worry and screening fear. Specifically, whereas cancer worry was associated with more frequent screening, fear of screening was associated with less frequent screening at least for digital rectal examination; trait anxiety was inconsistently related to screening. Data are discussed in terms of their implications for male screening and the understanding of how anxiety motivates health behaviors. It is suggested that understanding the source of anxiety and the manner in which health behaviors such as cancer screenings may enhance or reduce felt anxiety is a likely key to understanding the associations between anxiety and behavioral outcomes. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1631–9)
Increases in Serum Estrone Sulfate Level Are Associated with Increased Mammographic Density during Menopausal Hormone Therapy
Authors: Crandall Carolyn J. , Guan Min , Laughlin Gail A. , Ursin Giske A. , Stanczyk Frank Z. , Ingles Sue A. , Barrett-Connor Elizabeth , Greendale Gail A. 
Published: July 2008

Abstract
Background: Menopausal hormone therapy increases mammographic density. We determined whether increases in serum estrone sulfate (E1S) levels during menopausal hormone therapy predict increased mammographic density.
Methods: We measured percent mammographic density and serum E1S levels in 428 participants of the Postmenopausal Estrogen/Progestin Interventions study who were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical MPA (10 mg days 1-12 per 28-day cycle), or CEE + cyclical micronized progesterone (10 mg days 1-12). Serum E1S levels were determined by RIA. Information about covariates was determined by annual questionnaire. Using linear regression, we determined the association between change in E1S level from baseline to 12 months and change in percent mammographic density (by semiquantitative interactive threshold method).
Results: After controlling for baseline mammographic density, age, body mass index, alcohol intake, parity, smoking, ethnicity, physical activity, and age at first pregnancy, mammographic density increased by 1.3% for every 1 ng/mL increase in E1S level (P &lt; 0.0001). The association between change in E1S level and change in mammographic density differed by treatment group (greater effect in CEE + cyclical MPA group versus CEE group; P = 0.05). After controlling for treatment group, change in the ratio of E1S to E1 was also positively associated with change in mammographic density.
Conclusions: Increases in serum E1S levels during menopausal hormone therapy are associated with increases in mammographic density. The relative contribution of E1S and E1 to stimulation of breast tissue awaits further elucidation. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1674–81)
A Systematic Review of the Prevalence and Attribution of Human Papillomavirus Types among Cervical, Vaginal, and Vulvar Precancers and Cancers in the United States
Authors: Insinga Ralph P. , Liaw Kai-Li , Johnson Lisa G. , Madeleine Margaret M. 
Published: July 2008

Abstract
Objectives: To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers.
Methods: U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for ≥10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types.
Results: Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%).
Conclusions: The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1611–22)
High Excretion of Etheno Adducts in Liver Fluke–Infected Patients: Protection by Praziquantel against DNA Damage
Authors: Dechakhamphu Somkid , Yongvanit Puangrat , Nair Jagadeesan , Pinlaor Somchai , Sitthithaworn Paiboon , Bartsch Helmut 
Published: July 2008

Abstract
Chronic infection by Opisthorchis viverrini (OV) is a strong risk factor for developing cholangiocarcinoma (CCA). To clarify the involvement of oxidative stress and lipid peroxidation (LPO)–derived DNA damage, the excretion of LPO-derived etheno DNA adducts was measured in urine samples collected from healthy volunteers and OV-infected Thai subjects. 1,N6-etheno-2′-deoxyadenosine (εdA) and 3,N4-etheno-2′-deoxycytidine (εdC) levels were quantified by immunoprecipitation/high-performance liquid chromatography/fluorescence detection and 32P-postlabeling TLC. Excreted etheno adduct levels were related to indicators of inflammatory conditions [malondialdehyde (MDA) and nitrate/nitrite levels in urine and plasma alkaline phosphatase (ALP) activity]. Mean εdA and εdC levels were 3 to 4 times higher in urine of OV-infected patients; MDA, nitrate/nitrite, and ALP were also increased up to 2-fold. MDA and ALP were positively related to εdA excretion. Two months after a single dose of the antiparasitic drug Praziquantel, εdA and εdC concentrations in urine of OV-infected subjects were decreased; MDA, nitrate/nitrite, and ALP were concomitantly lowered. We conclude that chronic OV infection through oxidative/nitrative stress leads to increased urinary excretion of the etheno-bridged deoxyribonucleosides, reflecting high LPO-derived DNA damage in vivo. These promutagenic DNA etheno adducts in bile duct epithelial cells may increase the risk of OV-infected patients to later develop CCA. Urinary εdA and εdC levels should be explored (a) as noninvasive risk markers for developing opisthorchiasis-related CCA and (b) as promising biomarkers to assess the efficacy of preventive and therapeutic interventions. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1658–64)
Expression of Aurora A (but Not Aurora B) Is Predictive of Survival in Breast Cancer
Authors: Nadler Yasmine , Camp Robert L. , Schwartz Candice , Rimm David L. , Kluger Harriet M. , Kluger Yuval 
Published: July 2008

AbstractPurpose: The cell cycle mediators Aurora A and B are targets of drugs currently in clinical development. As with other targeted therapies in breast cancer, response to therapy might be associated with target expression in tumors. We therefore assessed expression of Aurora A and B in breast tumors and studied associations with clinical/pathologic variables.Experimental Design: Tissue microarrays containing primary specimens from 638 patients with 15-year follow-up were employed to assess expression of Aurora A and B using our automated quantitative analysis method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot and measured Aurora A and B expression within the mask using Cy5-conjugated antibodies.Results: Aurora A and B expression was variable in primary breast tumors. High Aurora A expression was strongly associated with decreased survival (P = 0.0005). On multivariable analysis, it remained an independent prognostic marker. High Aurora A expression was associated with high nuclear grade and high HER-2/neu and progesterone receptor expression. Aurora B expression was not associated with survival.Conclusions: Aurora A expression defines a population of patients with decreased survival, whereas Aurora B expression does not, suggesting that Aurora A might be the preferred drug target in breast cancer. Aurora A expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted treatment. Prospective studies are needed to confirm the prognostic role of Aurora A as well as the predictive role of Aurora A expression in patients treated with Aurora A inhibitors.
A Novel Breast Cancer–Associated BRIP1 (FANCJ/BACH1) Germ-line Mutation Impairs Protein Stability and Function
Authors: De Nicolo Arcangela , Tancredi Mariella , Lombardi Grazia , Flemma Cristina Chantal , Barbuti Serena , Di Cristofano Claudio , Sobhian Bijan , Bevilacqua Generoso , Drapkin Ronny , Caligo Maria Adelaide 
Published: July 2008

Abstract
Purpose: BRCA1-interacting protein 1 (BRIP1; FANCJ/BACH1), which encodes a DNA helicase that interacts with BRCA1, has been suggested to be a low-penetrance breast cancer predisposing gene. We aimed to assess whether BRIP1 mutations contribute to breast cancer susceptibility in our population and, if so, to investigate the effect of such mutation(s) on BRIP1 function.
Experimental Design: A series of 49 breast/ovarian cancer families, devoid of a BRCA1/BRCA2 mutation, were screened for BRIP1 mutations. Functional analyses, including coimmunoprecipitation and stability assays, were employed to further characterize a previously unreported variant.
Results: Five sequence alterations were identified, of which four had been already described. Herein, we report a novel BRIP1 germ-line mutation identified in a woman with early-onset breast cancer. The mutation consists of a 4-nucleotide deletion (c.2992-2995delAAGA) in BRIP1 exon 20 that causes a shift in the reading frame, disrupts the BRCA1-binding domain of BRIP1, and creates a premature stop codon. Functional analysis of the recombinant mutant protein in transfected cells showed that the truncation interferes with the stability of the protein and with its ability to interact with BRCA1. Loss of the wild-type BRIP1 allele with retention of the mutated one was observed in the patient's breast tumor tissue.
Conclusions: These results, by showing that the newly identified BRIP1 c.2992-2995delAAGA mutation is associated with instability and functional impairment of the encoded protein, provide further evidence of a breast cancer–related role for BRIP1.
A High-End Virtual Reality Setup for the Study of Mental Rotations
Authors: Lehmann Alexandre , Vidal Manuel , Bülthoff Heinrich H. 
Published: July 2008

Mental rotation is the capacity to predict the orientation of an object or the layout of a scene after a change in viewpoint. Previous studies have shown that the cognitive cost of mental rotations is reduced when the viewpoint change results from the observer's motion rather than the object or spatial layout's rotation. The classical interpretation for these findings involves the use of automatic updating mechanisms triggered during self-motion. Nevertheless, little is known about how this process is triggered and particularly how sensory cues combine in order to facilitate mental rotations. The previously existing setups, either real or virtual, did not allow disentangling the different sensory contributions, which motivated the development of a new high-end virtual reality platform overcoming these technical limitations. In the present paper we will start by a didactic review of the literature on mental rotations and expose the current technical limitations. Then we will fully describe the experimental platform that was developed at the Max Planck Institute for Biological Cybernetics in Tübingen. The setup consisted of a cabin mounted on the top of a six degree-of-freedom Stewart platform inside of which was an adjustable seat, a physical table with a screen embedded, and a large projection screen. A 5-PC cluster running Virtools was used to drive the platform and render the two passive stereovision scenes that were displayed on the table and background screens. Finally, we will present the experiment using this setup that allowed replicating the classical advantage found for a moving observer, which validates our setup. We will conclude by discussing the experimental validation and the advantages of such a setup.
Truth and Memory: Narrating Viet Nam
Authors: Li-Lian Sharon Seah 
Published: July 2008

AbstractIn the quest for "truths" and "untruths", popular discourse and state memorial practices try to stake a claim on individual and collective memories. This article attempts to unpack narratives and the memories contained within; through an analysis of state memorialization - its monuments and museums - it probes the problematics of "truth" and veracity. We begin, then, to question the constructions of taken-for-granted "truths", history and memory. In the struggle for "reality", it becomes increasingly clear that "Others" are marked out and this poses a problem for Vietnam's past, present and future social dynamics.
Textual Construction of a Nation: The Use of Merger and Separation
Authors: Istiaisyah bte Hussin Dayang 
Published: July 2008

AbstractHistory is not neutral. It is rendered ideological by the very act of being conveyed in a narrative form, for language is both the purveyor of meaning and the principle locus of ideology. This paper explores the idea of history as discourse, and its deployment in the cultural-symbolic construction of the Singapore nation. To this end, I have chosen to analyse a key moment for Singapore history, the years 1963-65, when Singapore was first merged with the nation of Malaysia, and then separated from it. The way that these events are described in official histories is used by the government of Singapore to justify its policy of multiracialism, which also serves as a legitimating device confirming the state in its political and ideological hegemony. I have examined the events through analysis of local newspapers, The Straits Times and Berita Harian, to see in what ways their reporting may have helped to mould popular understandings of what was happening.
The Past in the Present: Memories of the 1964 'Racial Riots' in Singapore
Authors: Cheng Adeline Low Hwee 
Published: July 2008

AbstractThe 1964 racial riots are a prominent event in Singapore's history. They are often cited officially but rarely discussed by the Singapore community. This paper examines the riots from the perspective of a sociology of collective memories. A comparison of official and popular memories reveals a number of contrasts in the interpretations placed on these events by different groups. An official interpretation of the memory of the riots is disseminated to the younger generation through the media and education, and used to justify and legitimize the ideology of multiracialism and its social policies. Older people's memories give rise to more varied interpretations. Although the riots occurred more than thirty years ago, they have not been forgotten. The past still lives in the present because it serves a purpose and has implications for the next generation.
War and Violence, History and Memory: The Philippine Experience of the Second World War
Authors: José Ricardo T. 
Published: July 2008

AbstractThe subject of War and Memory in the Philippines remains a sensitive topic in the Philippines today. Many controversial issues about the Second World War remain subjects of debate, among them collaboration with the Japanese; Japanese war responsibility; American responsibility for the failed defense of the Philippines, and others. In one sense, the war in the Philippines has left an ambiguous legacy which leads to conflicting war memories and commemorations, particularly in the light of present conditions and evolving relationships with the other countries involved.
Remembering, Misremembering and Forgetting: The Struggle over "Serangan Oemoem 1 Maret 1949" in Yogyakarta, Indonesia
Authors:   Heddy Shri Ahimsa Putra
Published: July 2008

AbstractThis paper concerns a question of memory relating to an event that took place towards the end of the Indonesian war of Independence (1945-49). The event is the Serangan Oemum 1 Maret 1949, or "General Attack of 1 March, 1949", when Indonesian freedom-fighters launched an all-out attack on Dutch positions in Yogyakarta and drove them from the city. Who was the originator of this plan? The matter became a national controversy since it involved two prominent persons: the late Sultan of Yogya, and former President Soeharto. While Soeharto was in power, his own account of the event became the focus of elaborate annual commemorations; but since his fall, historians have thrown into question his account of his own role in the episode.
Chinese-Educated Intellectuals in Singapore: Marginality, Memory and Modernity
Authors: Kian-Woon Kwok 
Published: July 2008

AbstractThis paper will first provide a historical and sociological overview of the "Chinese community" and the "Chinese-educated" in Singapore, after which I shall turn to the personal experience of marginalization on the part of older Chinese-educated intellectuals. I then focus on the social memory of Nanyang University as a means in which such marginalization is contested. In conclusion, I highlight the efforts of younger Chinese-educated intellectuals in responding to the condition of marginality by taking on contemporary issues, rather than by refighting old battles, in effect returning Chinese-language discourse to issues of modernity - this time set in a radically changed environment from that of earlier decades.
Problems Associated with Transnational Sociological Research Collaboration in Cambodia
Authors:   Chou Meng Tarr
Published: July 2008

AbstractIn this paper the focus will be the following applied social research projects I have been involved with - (1) role of rural women in the rehabilitation of local irrigation systems; (2) a study of contextual factors affecting risk-related sexual behaviour among young people between the ages of 15 and 25; (3) participatory action research project looking at problems of natural resource management; (4) sociological study of an urban wastewater project in a provincial town still affected by forms of low level insurgency - to illustrate the problems associated not simply with the research process but with the nature of collaborative research itself. However, an underlying purpose of this paper is not to argue against international collaboration on a range of research-based problems, but how we can better communicate the nature of our research and enhance its credibility. Living and working in a society like Cambodia that has yet to develop a critical academic culture of interest, relevance and utility to the international scholarly community, particularly in the field of sociology, is an issue that will be confronted in this paper.