bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Victim to Victimhood: Truth Commissions and Trials as Rituals of Political Transition and Individual Healing
Authors: Humphrey Michael 
Published: February 2009

The victim has been put at the centre of states' post‐atrocity strategies to reform governance, rehabilitate state authority and promote reconciliation. This paper explores the role of the victim in the truth commissions and trials aimed at reconciliation and justice and their experiences of the outcomes. The successor state's focus on recovering victims after mass atrocity ritually inverts the former regime's project of producing them. In both truth commissions and trials the state seeks to manipulate the ‘spectacle’ of the victim's pain and suffering to publicly project the power of the state for different ends. Whereas the repressive state seeks to deepen the effects of violence as a strategy of rule, the successor state seeks to reverse the social and political effects of violence. These strategies of transitional justice have sought to reverse the effects of exclusion, to reverse the direction of state power from producing victims towards redeeming victims, from injuring to healing.Because of the problems of mass criminality and widespread impunity, truth commissions have become widely adopted in preference to trials as a bureaucratic response to bureaucratic murder. They set about producing a ‘democratising truth’ through a process of public inquiry located outside the state in the people. On the whole, the process, the public testimony and the witnessing has been better received than the product, the reports and the reparations. By contrast, trials seek to produce a societal consensus based on the recovery of the law. But in both cases the victim is redeemed through the individualising discourse of law or the polarising logic of trials which establishes the guilty and innocent. The truth of atrocity is found in affirming gross human rights abuses in victims, in transacted violence rather than the deeper structures of violence. Thus, victimhood is built on a universalising human rights discourse which overly individualises the origins of atrocity.
Identification of Cancer Stem Cells in Ewing's Sarcoma
Authors: Suvà Mario-Luca , Riggi Nicolò , Stehle Jean-Christophe , Baumer Karine , Tercier Stéphane , Joseph Jean-Marc , Suvà Domizio , Clément Virginie , Provero Paolo , Cironi Luisa , Osterheld Maria-Chiara , Guillou Louis , Stamenkovic Ivan 
Published: February 2009

Abstract
Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESFT), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in nonobese diabetic/severe combined immunodeficiency mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic, and chondrogenic lineages. Quantitative real-time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133− counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells and demonstration of their MSC properties, a critical step towards a better biological understanding and rational therapeutic targeting of these tumors. [Cancer Res 2009;69(5):1776–81]
Vascular Cell Adhesion Molecule-1 Is a Regulator of Ovarian Cancer Peritoneal Metastasis
Authors: Slack-Davis Jill K. , Atkins Kristen A. , Harrer Christine , Hershey E. Daniel , Conaway Mark 
Published: February 2009

AbstractOvarian cancers metastasize by attaching to and invading through the mesothelium, a single layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5-year survival &lt;25%). Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface receptor that mediates leukocyte attachment and extravasation across endothelial and mesothelial monolayers at sites of inflammation. Membranous VCAM-1 expression was observed on the mesothelium of 13 of 14 women with ovarian cancer compared with 6 of 15 who were cancer-free. Using a cell culture model system of mesothelial invasion, highly tumorigenic SKOV-3 and ES-2 cells were 2.5 to 3 times more efficient in transmigration through the mesothelial monolayer compared with poorly tumorigenic OVCAR-3 cells. Blocking antibodies to, or small interfering RNA knockdown of, VCAM-1 or its ligand α4β1 integrin significantly decreased, but did not completely inhibit, transmigration of SKOV-3 cells through mesothelial monolayers. Furthermore, using a mouse model of ovarian cancer metastasis, treatment with VCAM-1 function-blocking antibodies decreased tumor burden and increased survival. Together, these observations implicate VCAM-1-α4β1 integrin interactions in the regulation of ovarian cancer cell mesothelial invasion and metastatic progression and offer the possibility of novel therapeutic targets. [Cancer Res 2009;69(4):1469–76]
Serum Vitamin D and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial
Authors: Stolzenberg-Solomon Rachael Z. , Hayes Richard B. , Horst Ron L. , Anderson Kristin E. , Hollis Bruce W. , Silverman Debra T. 
Published: February 2009

Abstract
Experimental evidence suggests that vitamin D has anticarcinogenic properties; however, a nested case-control study conducted in a population of male Finnish smokers found that higher 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status as determined by the sun and diet, was associated with a significant 3-fold increased risk for pancreatic cancer. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic serum 25(OH)D concentrations were associated with pancreatic cancer risk. Between 1994 and 2006, 184 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n = 368) who were alive at the time the case was diagnosed were selected for each case and matched by age, race, sex, and calendar date of blood draw (to control for seasonal variation). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression, adjusting for smoking and body mass index. Vitamin D concentrations were not associated with pancreatic cancer overall (highest versus lowest quintile, &gt;82.3 versus &lt;45.9 nmol/L: OR, 1.45; 95% CI, 0.66–3.15; P trend = 0.49). However, positive associations were observed among subjects with low estimated annual residential solar UBV exposure, but not among those with moderate to high annual exposure (P interaction = 0.015). We did not confirm the previous strong positive association between 25(OH)D and pancreatic cancer; however, the increased risk among participants with low residential UVB exposure is similar. [Cancer Res 2009;69(4):1439–47
Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis
Authors: Devy Laetitia , Huang Lili , Naa Laurent , Yanamandra Niranjan , Pieters Henk , Frans Nicolas , Chang Edward , Tao Qingfeng , Vanhove Marc , Lejeune Annabelle , van Gool Reinoud , Sexton Daniel J. , Kuang Guannan , Rank Douglas , Hogan Shannon , Pazmany Csaba , Ma Yu Lu , Schoonbroodt Sonia , Nixon Andrew E. , Ladner Robert C. , Hoet Rene , Henderikx Paula , TenHoor Chris , Rabbani Shafaat A. , Valentino Maria Luisa , Wood Clive R. , Dransfield Daniel T. 
Published: February 2009

Abstract
Inhibition of specific matrix metalloproteinases (MMP) is an attractive noncytotoxic approach to cancer therapy. MMP-14, a membrane-bound zinc endopeptidase, has been proposed to play a central role in tumor growth, invasion, and neovascularization. Besides cleaving matrix proteins, MMP-14 activates proMMP-2 leading to an amplification of pericellular proteolytic activity. To examine the contribution of MMP-14 to tumor growth and angiogenesis, we used DX-2400, a highly selective fully human MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocked proMMP-2 processing on tumor and endothelial cells, inhibited angiogenesis, and slowed tumor progression and formation of metastatic lesions. The combination of potency, selectivity, and robust in vivo activity shows the potential of a selective MMP-14 inhibitor for the treatment of solid tumors. [Cancer Res 2009;69(4):1517–26]
Integral Role of Transcription Factor 8 in the Negative Regulation of Tumor Angiogenesis
Authors: Inuzuka Takayuki , Tsuda Masumi , Tanaka Shinya , Kawaguchi Hideaki , Higashi Yujiro , Ohba Yusuke 
Published: February 2009

Abstract
Angiogenesis is involved in various physiologic and pathological conditions, including tumor growth, and is tightly regulated by the orchestration of proangiogenic and antiangiogenic factors. Inhibition of vascular endothelial growth factor (VEGF), the best-established antiangiogenic treatment in cancer, has shown some effectiveness; however, the identification of novel regulators, whose function is independent of VEGF, is required to achieve better outcomes. Here, we show that transcription factor 8 (TCF8) is up-regulated in endothelial cells during angiogenesis, acting as a negative regulator. Furthermore, TCF8 is specifically expressed in the endothelium of tumor vessels. Tcf8-heterozygous knockout mice are more permissive than wild-type mice to the formation of tumor blood vessels in s.c. implanted melanoma, which seems to contribute to the more aggressive growth and the lung metastases of the tumor in mutant mice. Suppression of TCF8 facilitates angiogenesis in both in vitro and ex vivo models, and displays comprehensive cellular phenotypes, including enhanced cell invasion, impaired cell adhesion, and increased cell monolayer permeability due to, at least partly, MMP1 overexpression, attenuation of focal adhesion formation, and insufficient VE-cadherin recruitment, respectively. Taken together, our findings define a novel, integral role for TCF8 in the regulation of pathologic angiogenesis, and propose TCF8 as a target for therapeutic intervention in cancer. [Cancer Res 2009;69(4):1678–84]
Reactivation of Suppressed RhoB is a Critical Step for the Inhibition of Anaplastic Thyroid Cancer Growth
Authors: Marlow Laura A. , Reynolds Lisa A. , Cleland Alan S. , Cooper Simon J. , Gumz Michelle L. , Kurakata Shinichi , Fujiwara Kosaku , Zhang Ying , Sebo Thomas , Grant Clive , McIver Bryan , Wadsworth J. Trad , Radisky Derek C. , Smallridge Robert C. , Copland John A. 
Published: February 2009

Abstract
Anaplastic thyroid carcinoma (ATC) is a highly aggressive form of the disease for which new therapeutic options are desperately needed. Previously, we showed that the high-affinity peroxisome proliferator–activated receptor γ (PPARγ) agonist, RS5444, inhibits cell proliferation of ATC cells via induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). We show here that up-regulation of RhoB is a critical step in PPARγ-mediated activation of p21-induced cell stasis. Using multiple independently derived ATC cell lines, we found that treatment with RS5444 leads to the up-regulation of RhoB and subsequent activation of p21, and that silencing of RhoB by RNAi blocks the ability of RS5444 to induce p21 and to inhibit cell proliferation. Our results show that transcriptional regulation of RhoB by the nuclear transcription factor PPARγ is responsible for the induction of p21 mRNA and protein. We further implicate RhoB as a key signaling effector for the growth inhibition of ATC, as treatment with a histone deacetylase inhibitor shown to increase RhoB expression in lung cancer cells caused the up-regulation of RhoB in ATC cells accompanied by increased expression of p21 and inhibition of cell proliferation; this effect occurred even in ATC cells that were unresponsive to RS5444 due to a lack of expression of PPARγ. Our results implicate RhoB as a novel intermediate in critical signaling pathways and as an additional target for therapeutic intervention in ATC. [Cancer Res 2009;69(4):1536–44]
Predicting Relapse in Favorable Histology Wilms Tumor Using Gene Expression Analysis: A Report from the Renal Tumor Committee of the Children's Oncology Group
Authors: Huang Chiang-Ching , Gadd Samantha , Breslow Norman , Cutcliffe Colleen , Sredni Simone T. , Helenowski Irene B. , Dome Jeffrey S. , Grundy Paul E. , Green Daniel M. , Fritsch Michael K. , Perlman Elizabeth J. 
Published: February 2009

AbstractPurpose: The past two decades has seen significant improvement in the overall survival of patients with favorable histology Wilms tumor (FHWT); however, this progress has reached a plateau. Further improvements may rely on the ability to better stratify patients by risk of relapse. This study determines the feasibility and potential clinical utility of classifiers of relapse based on global gene expression analysis.Experimental Design: Two hundred fifty FHWT of all stages enriched for relapses treated on National Wilms Tumor Study-5 passed quality variables and were suitable for analysis using oligonucleotide arrays. Relapse risk stratification used support vector machine; 2- and 10-fold cross-validations were applied.Results: The number of genes associated with relapse was less than that predicted by chance alone for 106 patients (32 relapses) with stages I and II FHWT treated with chemotherapy, and no further analyses were done. This number was greater than expected by chance for 76 local stage III patients. Cross-validation including an additional 68 local stage III patients (total 144 patients, 53 relapses) showed that classifiers for relapse composed of 50 genes were associated with a median sensitivity of 47% and specificity of 70%.Conclusions: This study shows the feasibility and modest accuracy of stratifying local stage III FHWT using a classifier of &lt;50 genes. Validation using an independent patient population is needed. Analysis of genes differentially expressed in relapse patients revealed apoptosis, Wnt signaling, insulin-like growth factor pathway, and epigenetic modification to be mechanisms important in relapse. Potential therapeutic targets include FRAP/MTOR and CD40.
Interruption of RNA processing machinery by a small compound, 1-[(4-chlorophenyl)methyl]-1H-indole-3-carboxaldehyde (oncrasin-1)
Authors: Guo Wei , Wu Shuhong , Wang Li , Wang Rui-yu , Wei Xiaoli , Liu Jinsong , Fang Bingliang 
Published: February 2009

Abstract
Protein kinase Cι (PKCι) is activated by oncogenic Ras proteins and is required for K-Ras–induced transformation and colonic carcinogenesis in vivo. However, the role of PKCι in signal transduction and oncogenesis is not clear. We recently identified a small molecule, designated 1-[(4-chlorophenyl)methyl]-1H-indole-3-carboxaldehyde (oncrasin-1), that can selectively kill K-Ras mutant cancer cells and induce abnormal nuclear aggregation of PKCι in sensitive cells but not in resistant cells. To determine the causes and biological consequences of PKCι aggregates in the nucleus, we analyzed the effect of oncrasin-1 on proteins involved in DNA repair and RNA processing. Our results showed that oncrasin-1 treatment led to coaggregation of PKCι and splicing factors into megaspliceosomes but had no obvious effects on the DNA repair molecule Rad51. Moreover, oncrasin-1 treatment suppressed the phosphorylation of the largest subunit of RNA polymerase II and the expression of intronless reporter genes in sensitive cells but not in resistant cells, suggesting that suppression of RNA transcription is a major effect of oncrasin-1 treatment. Studies with cultured cells or with recombinant proteins showed that oncrasin-1 can disrupt the interaction of PKCι and cyclin-dependent protein kinase 9/cyclin T1 complex, which is known to phosphorylate the largest subunit of RNA polymerase II and is required for RNA transcription. Together, our results suggest that oncrasin-1 suppresses the function of RNA processing machinery and that PKCι might be involved in the biological function of RNA processing complexes. [Mol Cancer Ther 2009;8(2):441–8]
Anastellin, the Angiostatic Fibronectin Peptide, Is a Selective Inhibitor of Lysophospholipid Signaling
Authors: Ambesi Anthony , McKeown-Longo Paula J. 
Published: February 2009

Abstract
Angiogenesis is regulated by integrin-dependent cell adhesion and the activation of specific cell surface receptors on vascular endothelial cells by angiogenic factors. Lysophosphatidic acid (LPA) and sphingosine-1 phosphate (S1P) are bioactive lysophospholipids that activate G protein–coupled receptors that stimulate phosphatidylinositol 3-kinase (PI3K), Ras, and Rho effector pathways involved in vascular cell survival, proliferation, adhesion, and migration. Previous studies have shown that anastellin, a fragment of the first type III module of fibronectin, functions as an antiangiogenic peptide suppressing tumor growth and metastasis. We have previously shown that anastellin blocks serum-dependent proliferation of microvessel endothelial cells (MVEC) by affecting extracellular signal-regulated kinase (ERK)–dependent G1-S transition. However, the mechanism by which anastellin regulates endothelial cell function remains unclear. In the present study, we mapped several lysophospholipid-mediated signaling pathways in MVEC and examined the effects of anastellin on LPA- and S1P-induced MVEC proliferation, migration, and cytoskeletal organization. Both LPA and S1P activated PI3K, Ras/ERK, and Rho/Rho kinase pathways, leading to migration, G1-S cell cycle progression, and stress fiber formation, respectively. Stimulation of proliferation by LPA/S1P occurred through a Gi-dependent Ras/ERK pathway, which was independent of growth factor receptors and PI3K and Rho/Rho kinase signaling. Although LPA and S1P activated both PI3K/Akt and Ras/ERK signaling through Gi, anastellin inhibited only the Ras/ERK pathway. Stress fiber formation in response to LPA was dependent on Rho/Rho kinase but independent of Gi and unaffected by anastellin. These results suggest that lysophospholipid mediators of Gi activation leading to PI3K/Akt and Ras/ERK signaling bifurcate downstream of Gi and that anastellin selectively inhibits the Ras/ERK arm of the pathway. (Mol Cancer Res 2009;7(2):255–65)
KRAS2 Mutations in Human Pancreatic Acinar-Ductal Metaplastic Lesions Are Limited to Those with PanIN: Implications for the Human Pancreatic Cancer Cell of Origin
Authors: Shi Chanjuan , Hong Seung-Mo , Lim Phillip , Kamiyama Hirohiko , Khan Mehtab , Anders Robert A. , Goggins Michael , Hruban Ralph H. , Eshleman James R. 
Published: February 2009

Abstract
Pancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma of the pancreas. Observations made in genetically engineered mouse models suggest that the acinar/centroacinar compartment can give rise to ductal neoplasia. To integrate findings in mice and men, we examined human acinar cells, acinar-ductal metaplasia (ADM) lesions, and PanINs for KRAS2 gene mutations. Surgically resected pancreata were screened for foci of ADM with or without an associated PanIN lesion. Stromal cells, acinar cells, ADMs, and PanINs were separately isolated using laser capture microdissection. KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue. Twelve of these 31 foci of ADM occurred in isolation, whereas 19 were in the same lobules as a PanIN lesion. All 31 microdissected foci of acinar cells were KRAS2 gene wild-type, as were all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations were present in 14 of 19 (74%) PanIN lesions and in 12 of the 19 (63%) foci of ADM associated with these PanINs. All ADM lesions with a KRAS2 gene mutation harbored the identical KRAS2 gene mutation found in their associated PanIN lesions. Ductal neoplasms of the human pancreas, as defined by KRAS2 gene mutations, do not appear to arise from acinar cells. Isolated AMD lesions are genetically distinct from those associated with PanINs, and the latter may represent retrograde extension of the neoplastic PanIN cells or less likely are precursors to PanIN. (Mol Cancer Res 2009;7(2):230–6)
Yin Yang 1 Regulates the Expression of Snail through a Distal Enhancer
Authors: Palmer Matthew B. , Majumder Parimal , Cooper John C. , Yoon Hyesuk , Wade Paul A. , Boss Jeremy M. 
Published: February 2009

Abstract
Expression of the Snail gene is required for the epithelial-mesenchymal transitions that accompany mammalian gastrulation, neural crest migration, and organ formation. Pathologic expression of Snail contributes to the migratory capacity of invasive tumors, including melanomas. To investigate the mechanism of Snail up-regulation in human melanoma cells, a conserved enhancer located 3′ of the Snail gene was analyzed. An overlapping Ets and yin yang 1 (YY1) consensus sequence, in addition to a SOX consensus sequence, was required for full enhancer activity. Proteins specifically binding these sequences were detected by electrophoretic mobility shift assay. The Ets/YY1 binding activity was purified by DNA-affinity chromatography and identified as YY1. Although ubiquitously expressed, YY1 was bound at the Snail 3′ enhancer in vivo in Snail-expressing cells but not in cells that did not express Snail. Knockdown of YY1 in A375 cells led to decreased Snail expression. These results identify a role for YY1 in regulating transcription of Snail in melanoma cells through binding to the Snail 3′ enhancer. (Mol Cancer Res 2009;7(2):221–9)