bluuebunny/crossref_metadata_2025_split huggingface dataset:
What types of interventions generate inequalities? Evidence from systematic reviews
Authors: Lorenc Theo , Petticrew Mark , Welch Vivian , Tugwell Peter 
Published: August 2012

BackgroundSome effective public health interventions may increase inequalities by disproportionately benefiting less disadvantaged groups (‘intervention-generated inequalities’ or IGIs). There is a need to understand which types of interventions are likely to produce IGIs, and which can reduce inequalities.MethodsWe conducted a rapid overview of systematic reviews to identify evidence on IGIs by socioeconomic status. We included any review of non-healthcare interventions in high-income countries presenting data on differential intervention effects on any health status or health behaviour outcome. Results were synthesised narratively.ResultsThe following intervention types show some evidence of increasing inequalities (IGIs) between socioeconomic status groups: media campaigns; and workplace smoking bans. However, for many intervention types, data on potential IGIs are lacking. By contrast, the following show some evidence of reducing health inequalities: structural workplace interventions; provision of resources; and fiscal interventions, such as tobacco pricing.ConclusionOur findings are consistent with the idea that ‘downstream’ preventive interventions are more likely to increase health inequalities than ‘upstream’ interventions. More consistent reporting of differential intervention effectiveness is required to help build the evidence base on IGIs.
Descriptive clinical and epidemiological characteristics of influenza A H1N1 2009 virus infections in pigs in England
Authors: Williamson S. M. , Tucker A. W. , McCrone I. S. , Bidewell C. A. , Brons N. , Habernoll H. , Essen S. C. , Brown I. H. ,   COSI, Wood J. L. N. 
Published: August 2012

Infection of pigs with influenza A H1N1 2009 virus (A(H1N1)pdm09) was first detected in England in November 2009 following global spread of the virus in the human population. This paper describes clinical and epidemiological findings in the first English pig farms in which A(H1N1)pdm09 influenza virus was detected. These farms showed differences in disease presentation, spread and duration of infection. The factors likely to influence these features are described and relate to whether pigs were housed or outdoors, the age of the pigs, inter‐current disease and the management system of the unit. Infection could be mild or clinically inapparent in breeding pigs with more typical respiratory disease being identified later in their progeny. Mortality was low where disease was uncomplicated by environmental stresses or concurrent infections. Where deaths occurred in pigs infected with A(H1N1)pdm09 influenza, they were mainly due to other infections, including streptococcal disease due to Streptococcus suis infection. This paper demonstrates the ease with which A(H1N1)pdm09 virus was transmitted horizontally and maintained in a pig population.
Description and evaluation of a right flank, mini‐laparotomy approach to canine ovariohysterectomy
Authors: Reece J. F. , Nimesh M. K. , Wyllie R. E. , Jones A. K. , Dennison A. W. 
Published: August 2012

Surgical ovariohysterectomy (OVH) using a right flank approach was performed in 114 bitches as part of the Animal Birth Control (ABC) Programme at Help in Suffering, Jaipur, India. Incision length, duration of surgery and postoperative pain scores were recorded for each animal. The mean weight of the bitches was 13.7 kg, and the mean body condition score was 4.5 on a 1–9 scale. Mean surgical incision length and time were 22 mm and 11 minutes 4 seconds, respectively. It was seen that 86.1 per cent of bitches required no additional postoperative analgesia. These findings compare favourably with other techniques for OVH, including laparoscopic techniques. The surgical approach described may be an alternative for canine OVH, particularly in a shelter setting.
Age-Specific Effectiveness of the Finnish Cervical Cancer Screening Programme
Authors: Lönnberg Stefan , Anttila Ahti , Luostarinen Tapio , Nieminen Pekka 
Published: August 2012

Abstract
Background: There is currently some uncertainty about the effectiveness of screening outside the established core ages of 30 to 60. We audited the screening histories of cervical cancers and conducted a case–control evaluation of the effectiveness of organized screening in different ages.
Methods: Screening histories for 1,546 cervical cancer cases and 9,276 age-matched controls were derived by linkage to the screening register. ORs and 95% confidence intervals (CI) for the association of participation in a program screen and cervical cancer diagnosis in the following screening interval were estimated using conditional logistic regression and corrected for self-selection bias.
Results: Participation in a single screen was associated with a 47% decrease in cervical cancers, but this effect was age-dependent. Screening at 25 showed little or no impact on the risk of cervical cancer in the next interval, whereas screens at 40 to 65 showed protective effects of 51% to 66%.
Conclusions: Program screening at the age of 25 is not associated with a reduced risk of cervical cancer in the following screening interval. Additional analyses are needed that also take opportunistic screening of women during the first rounds of organized screening into consideration. In contrast, screening yields substantial risk reductions in older ages at least up to the age of 60. This study also provides moderate indication of a long-lasting risk reduction associated with screening at the age of 65.
Impact: Cervical cancer screening effectiveness is for the first time evaluated at different ages up to 65 with correction for self-selection bias of participation in organized screening. Cancer Epidemiol Biomarkers Prev; 21(8); 1354–61. ©2012 AACR.
Phase I Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients
Authors: Cohen Ezra E.W. , Wu Kehua , Hartford Christine , Kocherginsky Masha , Eaton Kimberly Napoli , Zha Yuanyuan , Nallari Anitha , Maitland Michael L. , Fox-Kay Kammi , Moshier Kristin , House Larry , Ramirez Jacqueline , Undevia Samir D. , Fleming Gini F. , Gajewski Thomas F. , Ratain Mark J. 
Published: August 2012

Abstract
Purpose: Sirolimus is the eponymous inhibitor of the mTOR; however, only its analogs have been approved as cancer therapies. Nevertheless, sirolimus is readily available, has been well studied in organ transplant patients, and shows efficacy in several preclinical cancer models.
Experimental Design: Three simultaneously conducted phase I studies in advanced cancer patients used an adaptive escalation design to find the dose of oral, weekly sirolimus alone or in combination with either ketoconazole or grapefruit juice that achieves similar blood concentrations as its intravenously administered and approved prodrug, temsirolimus. In addition, the effect of sirolimus on inhibition of p70S6 kinase phosphorylation in peripheral T cells was determined.
Results: Collectively, the three studies enrolled 138 subjects. The most commonly observed toxicities were hyperglycemia, hyperlipidemia, and lymphopenia in 52%, 43%, and 41% of subjects, respectively. The target sirolimus area under the concentration curve (AUC) of 3,810 ng-h/mL was achieved at sirolimus doses of 90, 16, and 25 mg in the sirolimus alone, sirolimus plus ketoconazole, and sirolimus plus grapefruit juice studies, respectively. Ketoconazole and grapefruit juice increased sirolimus AUC approximately 500% and 350%, respectively. Inhibition of p70 S6 kinase phosphorylation was observed at all doses of sirolimus and correlated with blood concentrations. One partial response was observed in a patient with epithelioid hemangioendothelioma.
Conclusion: Sirolimus can be feasibly administered orally, once weekly with a similar toxicity and pharmacokinetic profile compared with other mTOR inhibitors and warrants further evaluation in studies of its comparative effectiveness relative to recently approved sirolimus analogs. Clin Cancer Res; 18(17); 4785–93. ©2012 AACR.
Abstract 1019: CD34+ progenitors resident in the human white adipose tissue promote tumor angiogenesis, growth and metastases in orthotopic models of breast cancer
Authors: Martin-Padura Ines , Gregato Giuliana , Marighetti Paola , Mancuso Patrizia , Calleri Angelica , Corsini Chiara , Lohririwat Visnu , Petit Jean-Yves , Bertolini Francesco 
Published: August 2012

Abstract
Similarly to neoplasia, the human white adipose tissue (WAT) shows in vivo a robust angiogenic switch when the growth rate exceeds a given expansion threshold. Also, anti-angiogenic drugs have been found to inhibit WAT development in postnatal mice. We have recently reported that the human WAT is very rich in CD45-CD34+ progenitors that express high levels of angiogenesis-related genes and can generate in culture endothelial cells and tubes as efficiently as mesenchymal cells (Martin-Padura et al, Cancer Res, in the press). Compared to the bone marrow, WAT contains &gt;250 times more CD45-CD34+ progenitors with endothelial differentiation potential. The co-injection of human WAT-derived CD45-CD34+ progenitors from lipotransfer procedures contributed to tumor vascularization and significantly increased tumor growth and metastases in several orthotopic models of human breast cancer in immunodeficient NSG mice. At variance with human bone marrow-derived CD34+ progenitors, which were found to incorporate only in perivascular sites of tumor vasculature, confocal z-stack studies showed that mature endothelial cells derived from human WAT-CD34+ progenitors lined the lumen of fully functional cancer vessels where red cells were found to circulate. Transwell and 3D time-lapse studies in collagen showed that human WAT cells significantly promoted an EMT switch as well as breast cancer cell directionality, migration and invasion towards a gradient of several different chemo-attractants. Autologous lipotransfer for tissue/organ reconstruction is used in patients who had surgical removal of breast and other types of cancer. We have recently reported a study of 321 consecutive patients operated for primary breast cancer who subsequently underwent a lipotransfer procedure, compared with two matched patients with similar characteristics who did not undergo lipotransfer (Petit et al, Ann Oncol, in the press). In this study, the lipotransfer group exhibited a higher risk of local events compared to the controls when the analysis was limited to intraepithelial neoplasia. A second data revision after prolonged follow-up confirmed this significant difference. The dissection of the different roles of purified populations of WAT-derived progenitors and mature cells seems urgent to clarify which WAT cell populations can be used safely for breast reconstruction in cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1019. doi:1538-7445.AM2012-1019
Abstract 102: Functional characterization of long noncoding RNA SPRY4-IT1 in human melanomas
Authors: Zhao Wei , Mazar Joseph , Perera Ranjan J. 
Published: August 2012

Abstract
Recently, we have reported that long noncoding RNA SPRY4-IT1 (Khaitan et al., Cancer Research 2011) is highly upregulated in human melanomas compared to melanocytes and keratinocytes. The elevated expression of SPRY4-IT1 in melanoma cells compared to melanocytes, its accumulation in cell cytoplasm, and effects on cell dynamics, including increased rate of wound closure upon SPRY4-IT1 overexpression, suggest that the higher expression of SPRY4-IT1 may have an important role in the molecular etiology of human melanoma. We have now engineered melanocytes to ectopically express SPRY4-IT1 and engineered cells were assayed to identify gene and protein expression changes compared to vector only cells. We observed that engineered cells show higher cell proliferation rate compared to vector only cells. Melanoma cells were treated with α-amenitin to identify the half-life of both SPRY4 and SPRY4-IT1, and our results indicate that SPRY4-IT1 has a higher RNA decay compared to its host gene SPRY4. Isolation of monosome and polysome fractions followed by qRT-PCR shows that SPRY4-IT1 is primarily transported in to the polysome fraction. Finally, we have demonstrated that SPRY4-IT1 transcriptional regulation is independent of SPRY4 gene. SPRY4-IT1 molecular function, transcriptional regulation, cellular compartmentalization, interaction with other RNAs and proteins will be discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 102. doi:1538-7445.AM2012-102
Abstract 1020: Recruitment of Tie2-expressing monocytes is associated with the heightened invasive phenotype of gliomas after antiangiogenic therapies
Authors: Gabrusiewicz Konrad R. , Liu Dan , Cortes-Santiago Nahir , Hossain Mohammad B. , Piya Sujan , Conrad Charles , Marini Frank C. , Fueyo Juan , Gomez-Manzano Candelaria 
Published: August 2012

Abstract
Gliomas are highly vascularized tumors, and preclinical data have suggested that glioma growth critically depends on the generation of tumor associated blood vessels. Among multiple factors controlling the complex process of angiogenesis, VEGF (Vascular Endothelial Growth Factor) and its associated signaling cascade are considered of central importance. Glioma cells are a major source of VEGF, and high levels of VEGF generation have been reported to correlate with high grade malignancy and poor prognosis. Antiangiogenic therapy has been recently added to the battery of treatments to newly diagnosed malignant gliomas. However, preclinical data from our laboratory and others, as some clinical results, shown concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness. These results warrant preclinical investigation. Here, we present evidence of accumulation of Tie2-expressing monocytes (TEMs) in the brain tumor/normal interphase regions in tumor-bearing animals treated with anti-VEGF agents. Immunohistochemistry using F4/80 or Iba1 antibodies revealed an increase number of microglia/macrophages in central and peripheral tumoral areas after antiangiogenesis treatment. Moreover, the recruitment of these tumor-associated microglia/macrophages (TAMs) was associated with an overrepresentation of TEMs. Almost 50% of Tie2-positive cells co-localized with microglia/macrophages after bevacizumab or prolonged VEGF-Trap/Aflibercept therapies. To determine the role of TEMs in the invasive phenotype of gliomas upon antiangiogenic therapies, we use monocytes isolated from buffy coats and sorted positively for Tie2 expression, and monocytic cultures polarized to M2 phenotype and forced to express Tie2. We found that TEMs express high level of MMP2, MMP9, CD44, and CXCR4, molecules related with extracellular matrix remodeling, using q-PCR, ELISA, FACS analysis and double immunofluorescence. Gelatin zymography, as well as collagenase assay confirmed the upregulation of MMP-2 and MMP-9 activity. Of interest, knocking down Tie2 by siRNA suppresses MMP9 activity emphasizes a role of Tie2 signaling in the regulation of MMP9. Additionally, in vitro invasion assay showed a pivotal role of TEMs in development of an invasive phenotype in glioma cells. Together, our results suggest a novel mechanism of escape of GBMs to anti-VEGF therapies and the necessity of targeting the TEM population in combination with anti-VEGF therapies to improve clinical outcome.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1020. doi:1538-7445.AM2012-1020
Abstract 1049: DNMT3b increases transformation efficiency and accelerates carcinogen induced transformation of human bronchial epithelial cells
Authors: Teneng Ivo , Telles Carmen S. , Belinsky Steven A. 
Published: August 2012

Abstract
Malignant tumors and cell lines are characterized by increased expression of DNMT1, DNMT3a and DNMT3b. While evidence suggests that DNMT1, DNMT3a and DNMT3b co-operate in methylation and gene silencing during carcinogenesis, very little is known regarding gene targets for DNMT3a and DNMT3b and their impact on the development of adenocarcinoma. We developed an in vitro model using human telomerase/cyclin dependent kinase 4-immortalized human bronchial epithelial cell lines (HBECs) to identify key molecular changes that drive transformation and clonal outgrowth of preneoplastic lung epithelial cells during exposure to tobacco carcinogens. Carcinogen exposure (0.5mM MNU and 0.05µM BPDE) for 12 weeks induced transformation of HBEC2 cells and transformation efficiency was associated with DNA repair capacity. A significant increase in DNMT1 protein was observed during carcinogen exposure while moderate increases in DNMT3a and DNMT3b were observed in transformed cells. Increased DNMT3a and DNMT3b levels have been reported in several cancers. We observed 5-20 fold increased expression of DNMT3a and DNMT3b in tumor derived lung cancer cell lines. Therefore we tested the hypothesis that over expressing DNMT3a and DNMT3b would accelerate transformation by targeting specific genes for methylation and promote full malignancy in carcinogen-treated HBECs. Over expression of DNMT3a or DNMT3b did not affect DNA repair capacity and was not sufficient to drive spontaneous transformation as evidenced by inability to form colonies on soft agar. Transformation efficiency was increased 2-2.5 fold in the two HBEC2 cell lines over expressing DNMT3b after 12 weeks of carcinogen treatment relative to treated parental HBEC2. In addition, after 8 weeks, colony formation was evident in the DNMT3b over expressing, but not in parental HBECs indicating that increased expression of this de novo DNMT accelerates transformation. Over expressing DNMT3a had no effect on carcinogen-induced transformation. Current studies are evaluating global re-programming of the epigenome in transformed clones using the Illumina 450k promoter array and the effect of over expression of DNMT3b on stem cell markers. This study was supported by R01 ES008801 to S.A.B. and 1F32 CA157082 to I.T.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1049. doi:1538-7445.AM2012-1049
Abstract 1064: Sloan-Kettering Institute (Ski) protein plays distant roles in activation of Smad proteins in response to nodal and TGF-β in prostate cancer cells
Authors: Vo BaoHan T. , Cody Bianca , Cao Yang , Khan Shafiq A. , Development Center for Cancer Research and Therapeutic 
Published: August 2012

Abstract
Transforming growth factor-β (TGF-β) acts as a tumor suppressor in the early stages of epithelial cancers by inhibiting proliferation and inducing apoptosis. However, in the later stages of the disease, TGF-β acts as a tumor promoter and is associated with aggressive forms of cancer due to its effects on angiogenesis, immune suppression, and metastasis. Previously, we have demonstrated that Nodal, another member of the TGF-β superfamily and its receptors are expressed in prostate cancer cell lines. Nodal and TGF-β exerted differential effects on prostate cancer cells; both inhibited proliferation in WPE, RWPE1, and DU145 cells while neither had effect on the proliferation of LNCaP and PC3 cells. On the other hand, Nodal and TGF-β induced migration in PC3 cells, but had no effect on cell migration in DU145 cells. Nodal primarily employs Smad2 for intracellular signaling while TGF-β is essential for both Smad2/3 phosphorylations. In the present study, we have determined the expression and role of Ski in Nodal and TGF-β signaling in prostate cancer cells. Ski is a co-repressor of the Smad-mediated TGF-β signaling. Ski was originally classified as an oncogene based on its ability to transform chicken and quail fibroblasts. RT-PCR analysis showed comparable mRNA levels of Ski in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cell lines and Ski protein levels were very low or absent in normal cells. Ski protein levels were also high in prostate cancer tissue samples compared to normal prostate tissues. Treatment with Nodal and TGF-β had no effects on Ski mRNA levels; however, Nodal had no effect on Ski protein levels while TGF-β induced degradation of Ski protein levels mediated by the proteasome pathway. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous of Ski reduced proliferation in DU145 prostate cancer cells and enhanced migration of PC3 cells. We conclude that high level of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad2/3 signaling, but Ski protein levels do not influence Nodal effects.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1064. doi:1538-7445.AM2012-1064