bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Third Glossop Lecture
Authors: Chandler R. J. 
Published: September 2010

The cycle of events and natural processes that affect the geotechnical properties of clay sediments in a depositional basin (the ‘Geotechnical Cycle’) includes: deposition, consolidation/compaction, diagenesis, tectonic disturbance, weathering and erosion. Some of these processes can occur in parallel; their combined effects control the mechanical behaviour of clay sediments. Processes involved in the Geotechnical Cycle are reviewed, using case studies chosen where possible from the London Basin; examples from other depositional basins emphasize the many common elements that control the behaviour of clay sediments.
A simple soil behaviour model (based on the ‘sensitivity framework’) is described that combines the consolidation (geological compaction) and strength behaviour of natural clays, both during loading (deposition) and unloading (erosion). This model enables the mechanical consequences of soil structure (including the effects of diagenesis) to be quantified. Its merits are that it describes real soils, thus aiding ground characterization, and also allows an assessment of such factors as sample disturbance, while providing a realistic and straightforward geotechnical framework.
The effects of tectonic events on the geotechnical behaviour of clays are reviewed in the particular context of flexural slip, and its influence on stability problems.
Uplift, then erosion, results in basin sediments becoming overconsolidated; the history of the London Basin is used to emphasize both what is known and, in particular, what is not known, of these phases of basin history. Following erosion, weathering processes further modify the mechanical properties of clays. The most obvious indicator of weathering is oxidation, with its associated colour changes. The depth of oxidation in the London Clay Formation is reviewed, and shown to relate to topographic position and former groundwater conditions. Finally, the sensitivity framework is used to examine the effects of weathering on the mechanical behaviour of clay, particularly the reduction of yield stress in one‐dimensional compression.
Loss of Osteoclasts Contributes to Development of Osteosarcoma Pulmonary Metastases
Authors: Endo-Munoz Liliana , Cumming Andrew , Rickwood Danny , Wilson Danielle , Cueva Claudia , Ng Charlotte , Strutton Geoffrey , Cassady A. Ian , Evdokiou Andreas , Sommerville Scott , Dickinson Ian , Guminski Alexander , Saunders Nicholas A. 
Published: September 2010

AbstractWe conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone (P &lt; 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2-fold less ACP5/TRAP expression (P &lt; 0.018) than lesions from patients without metastases. In addition, we found a direct correlation (P = 0.0166) between ACP5/TRAP expression and time to metastasis. Therefore, we examined whether metastasis-competent (MC) OS cells could induce loss of ACP5+ osteoclasts and contribute to metastasis. We found that MC OS cell lines can inhibit osteoclastogenesis in vitro and in vivo. In addition, osteoclasts can inhibit the migration of MC OS cells in vitro. Finally, ablation of osteoclasts with zoledronic acid increases the number of metastatic lung lesions in an orthotopic OS model, whereas fulvestrant treatment increases osteoclast numbers and reduces metastatic lesions. These data indicate that the metastatic potential of OS is determined early in tumor development and that loss of osteoclasts in the primary lesion enhances OS metastasis. Cancer Res; 70(18); 7063–72. ©2010 AACR.
Modifying Akt Signaling in B-Cell Chronic Lymphocytic Leukemia Cells
Authors: Hofbauer Sebastian W. , Piñón Josefina D. , Brachtl Gabriele , Haginger Lucia , Wang Wei , Jöhrer Karin , Tinhofer Ingeborg , Hartmann Tanja Nicole , Greil Richard 
Published: September 2010

Abstract
Emerging evidence suggests that the survival of B-cell chronic lymphocytic leukemia (CLL) cells is dependent on microenvironmental influences such as antigenic stimulation and support by stromal cells. Akt, also known as protein kinase B, is a central component in prosurvival signaling downstream of these events. We investigated the role of Akt and its modulation by the protooncogene T-cell leukemia 1a (Tcl1a) in the survival pathways of primary CLL samples and CLL-derived prolymphocytic cell lines MEC-1 and MEC-2. Akt activation was increased by the protective presence of human bone marrow stromal cells and B-cell receptor mimicking signals but antagonized by direct Akt blockade with the novel specific inhibitor AiX, with preferential apoptosis induction in CLL cells with an unmutated immunoglobulin status, which predicts poor clinical outcome. In addition, we found a direct interaction of Akt with Tcl1a in an endogenous coimmunoprecipitation assay. Confirming the critical role of Tcl1a in modulating Akt signaling, Akt activation was enhanced by overexpressing Tcl1a in CLL. In contrast, decreasing Tcl1a levels by small interfering RNA reduced Akt activation in the fludarabine-insensitive CLL cell line MEC-2 and sensitized the malignant cells to fludarabine treatment. In summary, our data reveal a significant role for the Akt-Tcl1a axis in CLL survival and propose a further evaluation of this interplay for targeting chemoresistance phenomena. Cancer Res; 70(18); 7336–44. ©2010 AACR.
The Sympathetic Nervous System Induces a Metastatic Switch in Primary Breast Cancer
Authors: Sloan Erica K. , Priceman Saul J. , Cox Benjamin F. , Yu Stephanie , Pimentel Matthew A. , Tangkanangnukul Veera , Arevalo Jesusa M.G. , Morizono Kouki , Karanikolas Breanne D.W. , Wu Lily , Sood Anil K. , Cole Steven W. 
Published: September 2010

AbstractMetastasis to distant tissues is the chief driver of breast cancer–related mortality, but little is known about the systemic physiologic dynamics that regulate this process. To investigate the role of neuroendocrine activation in cancer progression, we used in vivo bioluminescence imaging to track the development of metastasis in an orthotopic mouse model of breast cancer. Stress-induced neuroendocrine activation had a negligible effect on growth of the primary tumor but induced a 30-fold increase in metastasis to distant tissues including the lymph nodes and lung. These effects were mediated by β-adrenergic signaling, which increased the infiltration of CD11b+F4/80+ macrophages into primary tumor parenchyma and thereby induced a prometastatic gene expression signature accompanied by indications of M2 macrophage differentiation. Pharmacologic activation of β-adrenergic signaling induced similar effects, and treatment of stressed animals with the β-antagonist propranolol reversed the stress-induced macrophage infiltration and inhibited tumor spread to distant tissues. The effects of stress on distant metastasis were also inhibited by in vivo macrophage suppression using the CSF-1 receptor kinase inhibitor GW2580. These findings identify activation of the sympathetic nervous system as a novel neural regulator of breast cancer metastasis and suggest new strategies for antimetastatic therapies that target the β-adrenergic induction of prometastatic gene expression in primary breast cancers. Cancer Res; 70(18); 7042–52. ©2010 AACR.
Chemotherapy-Induced Genotoxic Stress Promotes Sensitivity to Natural Killer Cell Cytotoxicity by Enabling Missing-Self Recognition
Authors: Fine Jason H. , Chen Peter , Mesci Aruz , Allan David S.J. , Gasser Stephan , Raulet David H. , Carlyle James R. 
Published: September 2010

AbstractNatural killer (NK) cells can recognize and kill tumor cells lacking “self” markers, such as class I MHC, but the basis for this recognition is not completely understood. NKR-P1 receptors are members of the C-type lectin-related NK receptor superfamily that are conserved from rodents to humans. Identification of Clr ligands for the NKR-P1 receptors has facilitated functional analysis of MHC-independent target cell recognition by NK cells. One receptor-ligand pair, NKR-P1B:Clr-b, can mediate “missing-self” recognition of tumor and infected cells, but the role of this axis in sensing stressed cells remains unknown. Here, we show that Clr-b is rapidly downregulated in cells undergoing genotoxic and cellular stress at the level of both RNA and surface protein. Stress-mediated loss of Clr-b on leukemia cells enhanced cytotoxicity mediated by NKR-P1B+ NK cells. Notably, Clr-b downregulation was coordinated functionally with stress-mediated upregulation of NKG2D ligands (but not class I MHC). Our findings highlight a unique role for the MHC-independent NKR-P1B:Clr-b missing-self axis in recognition of stressed cells, and provide evidence of two independent levels of Clr-b regulation in stressed cells. Cancer Res; 70(18); 7102–13. ©2010 AACR.
Strategies for Increasing Mammography Screening in Primary Care in Chile: Results of a Randomized Clinical Trial
Authors: Püschel Klaus , Coronado Gloria , Soto Gabriela , Gonzalez Karla , Martinez Javiera , Holte Sarah , Thompson Beti 
Published: September 2010

Abstract
Background: Breast cancer is the cancer with the highest incidence among women in Chile and in many Latin American countries. Breast cancer screening has very low compliance among Chilean women.
Methods: We compared the effects on mammography screening rates of standard care, of a low-intensity intervention based on mail contact, and of a high-intensity intervention based on mail plus telephone or personal contact. A random sample of 500 women with the age of 50 to 70 years registered at a community clinic in Santiago who had not had a mammogram in the past 2 years were randomly assigned to one of the three intervention groups. Six months after randomization, participants were re-evaluated for their compliance with mammography screening. The outcome was measured by self-report and by electronic clinical records. An intention to treat model was used to analyze the results.
Results: Between 92% and 93% of participants completed the study. Based on electronic records, mammography screening rates increased significantly from 6% in the control group to 51.8% in the low-intensity group and 70.1% in the high-intensity group. About 14% of participants in each group received opportunistic advice, 100% of participants in the low- and high-intensity groups received the mail contact, and 50% in the high-intensity group received a telephone or personal contact.
Conclusion: A primary care intervention based on mail or brief personal contact could significantly improve mammogram screening rates.
Impact: A relatively simple intervention could have a strong impact in breast cancer prevention in underserved communities. Cancer Epidemiol Biomarkers Prev; 19(9); 2254–61. ©2010 AACR.
Communication of BRCA Results and Family Testing in 1,103 High-Risk Women
Authors: Cheung Eleanor L. , Olson Ashley D. , Yu Tina M. , Han Pamela Z. , Beattie Mary S. 
Published: September 2010

Abstract
Background: Genetic testing for hereditary cancer risk has implications for individuals and families. This study of women at risk of hereditary breast and ovarian cancer examines communication of BRCA results and subsequent genetic testing in the family.
Methods: We surveyed 1,103 female BRCA testers at two hospitals, querying for communication of results and testing in relatives.
Results: Ninety-seven percent of participants communicated BRCA results with at least one relative. Communication was negatively associated with older age [odds ratio (OR), 0.66 per decade; 95% confidence interval, (95% CI), 0.4–0.9], Asian race (OR, 0.18; 95% CI, 0.06–0.5), and testing at the public hospital versus the cancer center (OR, 0.19; 95% CI, 0.07–0.5). Communication was positively associated with increased knowledge of hereditary breast and ovarian cancer screening and risk reduction recommendations (OR, 1.9; 95% CI, 1.1–3.4) and increased satisfaction with the decision to BRCA test (OR, 2.6; 95% CI, 1.6–4.0). Seventy-five percent of BRCA-positive participants reported that at least one relative pursued genetic testing. Family testing was negatively associated with Asian race (OR, 0.15; 95% CI, 0.02–0.8) and positively associated with increased socioeconomic status (OR, 1.4; 95% CI, 1.1–1.7) and increased satisfaction with decision (OR, 2.1; 95% CI, 1.1–4.1).
Conclusion: Despite high overall rates of communicating BRCA results, underserved and some minority women seem less likely to inform relatives of their BRCA status or have relatives test for a known family mutation. Satisfaction with the decision to BRCA test is positively associated with both outcomes.
Impact: This study identified several novel predictors of family communication and family genetic testing in a large population of high-risk women. This work can inform clinicians interested in improving family communication regarding cancer predisposition testing. Cancer Epidemiol Biomarkers Prev; 19(9); 2211–9. ©2010 AACR.
Seroprevalence of Antibodies against Human Papillomavirus (HPV) Types 16 and 18 in Four Continents: the International Agency for Research on Cancer HPV Prevalence Surveys
Authors: Vaccarella Salvatore , Franceschi Silvia , Clifford Gary M. , Touzé Antoine , Hsu Charles C. , de Sanjosé Silvia , Anh Pham Thi Hoang , Hieu Nguyen Trong , Matos Elena , Shin Hai Rim , Sukvirach Sukhon , Thomas Jaiye O. , Boursaghin Latifa , Gaitan Julien , Snijders Peter J.F. , Meijer Chris J.L.M. , Muñoz Nubia , Herrero Rolando , Coursaget Pierre ,   for the IARC HPV Prevalence Surveys Study Group
Published: September 2010

Abstract
Background: Few human papillomavirus (HPV) seroprevalence studies have been carried out in women from low-resource countries.
Methods: Seroprevalence of antibodies against HPV16 and HPV18 was assessed in 7,074 women ≥15 years of age (median 44 years) from eight world areas. Serum antibodies against HPV16 and HPV18 were tested for using enzyme-linked immunosorbent assay. HPV DNA was assessed using a general primer GP5+/6+–mediated PCR.
Results: HPV16 and HPV18 seroprevalence both ranged from &lt;1% (Hanoi, Vietnam) to ≥25% (Nigeria). Of women who were HPV16 or HPV18 DNA-positive, seropositivity for the same type was 39.8% and 23.2%, respectively. Seropositivity for either type was directly associated with markers of sexual behavior. HPV16 and/or 18 (HPV16/18)–seropositive women had an increased risk of having cytologic abnormalities only if they were also HPV DNA-positive. A high international correlation was found between HPV16/18 seroprevalence and overall HPV DNA prevalence (r = 0.81; P = 0.022). However, HPV16/18 seroprevalence was substantially higher than the corresponding DNA prevalence in all study areas (although to different extents) and, contrary to DNA, tended to increase from young to middle age, and then decline or remain fairly constant. In all study areas, the vast majority of the information on the burden of exposure to HPV16/18 derived from serology.
Conclusions: The correlation between HPV DNA and HPV serology was not very good at an individual woman level, but high at a population level.
Impact: HPV serology is a poor marker of current infection or related lesions, but it can contribute, together with DNA, in evaluating the variations in the burden of HPV infection worldwide. Cancer Epidemiol Biomarkers Prev; 19(9); 2379–88. ©2010 AACR.
Asthma, Asthma Medications, and Prostate Cancer Risk
Authors: Severi Gianluca , Baglietto Laura , Muller David C. , English Dallas R. , Jenkins Mark A. , Abramson Michael J. , Douglass Jo A. , Hopper John L. , Giles Graham G. 
Published: September 2010

Abstract
Background: The aim of this study was to assess whether a history of asthma or the use of asthma medications is associated with prostate cancer risk.
Methods: Of 16,934 men participating in the Melbourne Collaborative Cohort Study, 1,179 were diagnosed with prostate cancer during an average follow-up of 13.4 years to the end of December 2007. Information on asthma history was obtained at baseline interview. Participants were asked to bring their current medications to the study center. The names of the drugs were entered into a form and coded. Asthma medications were categorized into four groups and corresponding hazard ratios (HR) were estimated from Cox regression models adjusted for country of birth.
Results: Asthma was associated with a small increase in prostate cancer risk [HR 1.25; 95% confidence interval (95% CI), 1.05-1.49]. The HRs for use of medications were 1.39 (95% CI, 1.03-1.88) for inhaled glucocorticoids, 1.71 (95% CI, 1.08-2.69) for systemic glucocorticoids, 1.36 (95% CI, 1.05-1.76) for bronchodilators, and 0.78 (95% CI, 0.45-1.35) for antihistamines. The HRs for asthma and asthma medication use changed only slightly after mutual adjustment.
Conclusions: A history of asthma and the use of asthma medications, particularly systemic glucocorticoids, are associated with an increased risk of prostate cancer, although it is difficult to disentangle the effects of asthma medications from those of asthma per se.
Impact: These findings, if confirmed in independent studies, might lead to the identification of new risk factors for prostate cancer. Cancer Epidemiol Biomarkers Prev; 19(9); 2318–24. ©2010 AACR.
ST14Gene Variant and Decreased Matriptase Protein Expression Predict Poor Breast Cancer Survival
Authors: Kauppinen Jaana M. , Kosma Veli-Matti , Soini Ylermi , Sironen Reijo , Nissinen Minna , Nykopp Timo K. , Kärjä Vesa , Eskelinen Matti , Kataja Vesa , Mannermaa Arto 
Published: September 2010

AbstractBackground: Matriptase plays a role in carcinogenesis, but the role of its genetic variation or that of the hepatocyte growth factor activator inhibitor-1 (HAI-1) has not been evaluated. This study aimed to examine the genetic variation of matriptase (ST14 gene) and HAI-1 (SPINT1 gene) in breast cancer risk and prognosis, to assess matriptase and HAI-1 gene and protein expression in breast tumors, and to identify their clinicopathologic correlations and prognostic significance.Methods: Five single nucleotide polymorphisms in ST14 and three in SPINT1 were genotyped in 470 invasive breast cancer cases and 446 healthy controls. Gene expression analysis was done for 40 breast cancer samples. Protein expression was assessed by immunohistochemical analyses in 377 invasive breast tumors. The statistical significance of the associations among genotypes, clinicopathologic variables, and prognosis was assessed.Results: The ST14 single nucleotide polymorphism rs704624 independently predicted breast cancer survival, a poor outcome associated with the minor allele (P = 0.001; risk ratio, 2.221; 95% confidence interval, 1.382-3.568). Moreover, ST14 gene expression levels were lower among the minor allele carriers (P = 0.009), and negative/low matriptase protein expression was independently predictive of poorer survival (P = 0.046; risk ratio, 1.554; 95% confidence interval, 1.008-2.396).Conclusions: The ST14 variant rs704624 and protein expression of matriptase have prognostic significance in breast cancer. This study adds to the evidence for the role of matriptase in breast cancer and has found new evidence for the genotypes having an impact in breast cancer.Impact: This is the first study showing that genetic variation in matriptase has clinical importance. The results encourage further study on the genetic variation affecting protein levels and function in type II transmembrane serine proteases. Cancer Epidemiol Biomarkers Prev; 19(9); 2133–42. ©2010 AACR.
Blood Vitamin D Levels in Relation to Genetic Estimation of African Ancestry
Authors: Signorello Lisa B. , Williams Scott M. , Zheng Wei , Smith Jeffrey R. , Long Jirong , Cai Qiuyin , Hargreaves Margaret K. , Hollis Bruce W. , Blot William J. 
Published: September 2010

Abstract
Background: African-Americans generally have lower circulating levels of 25 hydroxyvitamin D [25(OH)D] than Whites, attributed to skin pigmentation and dietary habits. Little is known about the genetic determinants of 25(OH)D levels nor whether the degree of African ancestry associates with circulating 25(OH)D.
Methods: With the use of a panel of 276 ancestry informative genetic markers, we estimated African and European admixture for a sample of 758 African-American and non-Hispanic White Southern Community Cohort Study participants. For African-Americans, cut points of &lt;85%, 85% to 95%, and ≥95% defined low, medium, and high African ancestry, respectively. We estimated the association between African ancestry and 25(OH)D and also explored whether vitamin D exposure (sunlight, diet) had varying effects on 25(OH)D levels dependent on ancestry level.
Results: The mean serum 25(OH)D levels among Whites and among African-Americans of low, medium, and high African ancestry were 27.2, 19.5, 18.3, and 16.5 ng/mL, respectively. Serum 25(OH)D was estimated to decrease by 1.0 to 1.1 ng/mL per 10% increase in African ancestry. The effect of high vitamin D exposure from sunlight and diet was 46% lower among African-Americans with high African ancestry than among those with low/medium ancestry.
Conclusions: We found novel evidence that the level of African ancestry may play a role in clinical vitamin D status.
Impact: This is the first study to describe how 25(OH)D levels vary in relation to genetic estimation of African ancestry. Further study is warranted to replicate these findings and uncover the potential pathways involved. Cancer Epidemiol Biomarkers Prev; 19(9); 2325–31. ©2010 AACR.