bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A19: Establishment of in vitro and in vivo models of inflammatory myofibroblastic tumor
Authors: Xie Jinhan (Angela) , Mould Emily V. A. , Fordham Ashleigh , Gifford Andrew J. , Trahair Toby , Mackenzie Karen L. 
Published: August 2018

Abstract
Inflammatory myofibroblastic tumors (IMTs) are sarcomas of soft tissue that most commonly arise in children, adolescents, and young adults. If not cured by surgery, IMT has a high propensity for local recurrence as multifocal nodules, and may rapidly progress to fatal disease. Anaplastic Lymphoma Kinase (ALK) driven tumorigenesis is implicated in approximately 50% of IMT cases. IMT patients with ALK rearrangement have been reported to respond to the ALK inhibitor, crizotinib, but with the possibility of relapse with resistant disease. The second-generation ALK inhibitor ceritinib showed improved specificity and potency toward crizotinib-resistant tumors; however, resistant disease may still emerge. Thus, there is an urgent need for identifying alternative treatment options for ALK-driven IMT. In this study, we utilized fresh malignant ascites collected from a 9-year-old boy (IMT-1) with epithelioid inflammatory myofibroblastic sarcoma (eIMS), at diagnosis (IMT-1A) and third relapse (IMT-1D) to establish the in vitro cell culture and in vivo orthotopic patient-derived xenograft (PDX) model. Primary cell cultures were successfully established from both samples with confirmed ALK rearrangement. The PDX was established by intraperitoneal injection of cultured IMT-1D cells into nonobese diabetic severe combined immune-deficient mice with IL-2 receptor gamma chain deficiency (NSG) mice. Within 6-8 weeks of inoculation, 100% of the mice became moribund due to robust multifocal intraperitoneal tumors that grew in close association with abdominal organs, including the pancreas and small bowel. The xenograft recapitulated both morphologic and immunohistochemical features of the tumor within the patient. Positive immunohistochemical staining for ALK in a characteristic perinuclear membrane pattern and ALK gene rearrangement were also demonstrated in tumor cells cultured from peritoneal fluid of the xenografted mice. Our in vitro cultures and in vivo PDX models provide a valuable opportunity to undertake a detailed characterization of ALK-driven IMT at diagnosis and following ceritinib failure. They are ideal models for preclinical evaluation of new therapeutic approaches to the treatment of ALK-driven IMT.
Citation Format: Jinhan (Angela) Xie, Emily V. A. Mould, Ashleigh Fordham, Andrew J. Gifford, Toby Trahair, Karen L. Mackenzie. Establishment of in vitro and in vivo models of inflammatory myofibroblastic tumor [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A19.
Abstract A21: Modeling of oncogenic chromosomal translocations of aggressive fusion-positive sarcomas by CRISPR-Cas9 genomic engineering
Authors: Spraggon Lee , Martelotto Luciano , Hmeljak Julija , Hitchman Tyler , Wang Jiang , Wang Lu , Slotkin Emily , Fan Pang-Dian , Reis-Filho Jorge , Ladanyi Marc 
Published: August 2018

Abstract
A prominent challenge in fusion-positive sarcoma research is that the oncogenic driver is typically a chimeric transcription factor. Although considered the disease-specific molecular drivers, these chimeric transcription factors remain challenging to target pharmacologically. An alternative approach is the elucidation of molecular pathways controlled by the oncogenic transcription factor, with the aim of identifying druggable targets.
However, many fusion-driven sarcomas have a paucity of suitable genetic models, with some lacking any patient-derived cell lines. In the situations where patient-derived cell lines are available, most have been passaged for decades, potentially adding further complexity and bias. Therefore, development of faithful model systems of oncogenic chromosomal translocations is of principal importance for these aggressive translocation-driven pediatric sarcomas.
Here, we describe a novel approach that combines CRISPR-Cas9 genomic editing technology, with homology-directed repair (HDR) to engineer, capture, and modulate the expression of chromosomal translocation products in a human cell line.
We have applied this approach to the genetic modeling of t(11;22)(q24;q12) and t(11;22)(p13;q12), translocation products of the EWSR1 gene and its 3 fusion partners FLI1 and WT1, present in Ewing's sarcoma and desmoplastic small round cell tumor, respectively. Our approach establishes an innovative platform for constructing isogenic and conditionally inducible biologically relevant models for a variety of sarcomas driven by chromosomal translocations.
Citation Format: Lee Spraggon, Luciano Martelotto, Julija Hmeljak, Tyler Hitchman, Jiang Wang, Lu Wang, Emily Slotkin, Pang-Dian Fan, Jorge Reis-Filho, Marc Ladanyi. Modeling of oncogenic chromosomal translocations of aggressive fusion-positive sarcomas by CRISPR-Cas9 genomic engineering [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A21.
Abstract A25: Elephant p53 (EP53) enhances and restores p53-mediated apoptosis in human and canine osteosarcoma
Authors: Abegglen Lisa M. , Toruno Cristhian , Donovan Lauren N. , Robinson Rosann , Goldfeder Mor , Couldwell Genevieve , Kiso Wendy K. , Schmitt Dennis L. , Caulin Aleah F. , Maley Carlo C. , Schroeder Avi , Schiffman Joshua D. 
Published: August 2018

Abstract
Amplification of elephant p53 (EP53) was recently described as a potential mechanism for cancer resistance in elephants. Osteosarcoma is the most common pediatric bone tumor and also occurs frequently in pet dogs. Both human and canine osteosarcoma contain a very high rate of TP53 alterations leading to genomic instability. The purpose of our study was to determine if EP53 could enhance and/or restore p53 function in osteosarcoma and trigger p53-mediated cell death. We expressed various EP53 proteins in canine and human osteosarcoma cell lines (OSCA-40, U-2 OS, and Saos-2) by transfection or viral transduction. Expression of EP53 was confirmed by Western blot. Apoptosis of cells transfected/transduced with EP53 was compared to cells transfected/transduced with negative control vectors. Apoptosis was measured by fluorescence microscopy and caspase activity. We observed a significant increase in caspase activity (normalized to cell viability) of U-2 OS (TP53-wild type) cells expressing EP53 compared to negative control cells (p&lt;0.0001). Saos-2 (TP53-null) and OSCA-40 cells underwent apoptosis as visualized by time-lapse fluorescence microscopy. Experiments to confirm these results with caspase activity assays are currently under way. Increased expression of p21, a direct p53 target, was observed in Saos-2 cells by Western blot. Taken together, our results indicate that EP53 enhances and restores p53-mediated apoptosis in osteosarcoma. These data suggest for the first time that EP53 can function in both human and canine osteosarcoma cells to promote cell death. Efforts to define the mechanism of action of EP53 in osteosarcoma cells are ongoing. Our results support further exploration of EP53-based osteosarcoma therapeutics for both humans and dogs.
Citation Format: Lisa M. Abegglen, Cristhian Toruno, Lauren N. Donovan, Rosann Robinson, Mor Goldfeder, Genevieve Couldwell, Wendy K. Kiso, Dennis L. Schmitt, Aleah F. Caulin, Carlo C. Maley, Avi Schroeder, Joshua D. Schiffman. Elephant p53 (EP53) enhances and restores p53-mediated apoptosis in human and canine osteosarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr A25.
Abstract IA03: Translating genomic risk into an early detection strategy for sarcoma
Authors: Pinese Mark , Ballinger Mandy , Thomas David 
Published: August 2018

Abstract
Sarcomas are a heterogeneous and rare group of cancers that particularly afflict younger populations. We have developed the International Sarcoma Kindred Study (ISKS) to understand the genetic basis of sarcomas as a population. The ISKS has recruited almost 2,300 families from 21 centers in 7 countries, and has clinical information on over 71,000 relatives of affected probands. Using a 72-cancer gene panel, we identified enrichment of monogenic and polygenic variation amongst sarcoma patients, and which correlated with age at first cancer diagnosis. We identified that 6-8% of subjects unselected for family history carried apparently pathogenic alleles in dominant cancer genes, and that 25% of subject carry variants of potential therapeutic significance. The correlation with family patterns or classic cancer phenotypes was inconsistent. However, panel tests are limited by both exonic gene content, and cannot capture many kinds of structural variation. We report here the initial results of whole genome sequencing on over 1,100 sarcoma probands, and case:control and age-of-onset analyses to exhaustively map sarcoma-associated rare and common germline genetic variation.
Citation Format: Mark Pinese, Mandy Ballinger, David Thomas, for the International Sarcoma Kindred Study. Translating genomic risk into an early detection strategy for sarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA03.
Abstract IA16: Natural history of peripheral nerve sheath tumors in NF1: Identification and characterization of malignant precursor lesions
Authors: Widemann Brigitte C. 
Published: August 2018

Abstract
Neurofibromatosis type 1 (NF1) is a common (incidence 1:2,700) inherited disorder characterized by the development of peripheral nerve sheath tumors, including plexiform neurofibromas (PN) and malignant peripheral nerve sheath tumors (MPNST). While PN are histologically benign they can result in substantial morbidity including pain, disfigurement, and neurologic or functional deficits. Importantly, PN are at risk for transformation to MPNST with a lifetime incidence in NF1 of 15.8%.
We are evaluating the natural history of NF1 PN in children enrolled on an NCI natural history study. Patients undergo detailed clinical evaluations and longitudinal evaluation with whole body MRI to assess total body tumor burden.
Our studies confirm that PN grow most rapidly in young children and that substantial PN growth in patients ≥15 years old is infrequent and should raise concern for malignant transformation. We also identified the development of distinct nodular lesions (DNL) on MRI. These lesions appear after early childhood, frequently grow more rapidly than the surrounding PN, show a growth rate independent of age, and are avid for fluorodexyglucose on positron emission tomography. On biopsy, some of these lesions were identified as atypical neurofibromas (ANF), which were recently identified as precursor lesions to MPNST, and are characterized by CDKN2A/B loss.
We have confirmed that patients with ANF are at greater risk for MPNST and are developing strategies for the evaluation and management of patients with ANF. Surgical resection of ANF, when safely feasible, may reduce the risk for MPNST development. We recently identified that MEK inhibition results in shrinkage of most PN and are expanding our efforts to evaluate the effect of MEK inhibition on DNL and ANF.
Citation Format: Brigitte C. Widemann. Natural history of peripheral nerve sheath tumors in NF1: Identification and characterization of malignant precursor lesions [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr IA16.
Abstract PR05: Familial cancer patient specific iPSCs based study of a potential oncogenic factor, sFRP2, in osteosarcoma
Authors: Kim Huen Suk , Yuan Ye X. , Bernitz Jeffrey M. , Gomes Andreia , Schaniel Christopher , Lee Dung-Fang , Lemischka Ihor R. 
Published: August 2018

Abstract
Osteosarcoma (OS), despite being a serious pediatric cancer with the lowest survival rate, is not well studied due to its rare occurrence. For this reason, studying OS in a patient-specific manner is more challenging. In an attempt to establish a method to study OS in a patient-specific manner, we previously generated Li-Fraumeni syndrome (LFS---a germline P53 mutation disease) patient specific iPSCs, and demonstrated that the LFS-iPSC derived mesenchymal stem cells (MSCs) and osteoblasts (OBs) can recapitulate tumorigenic phenotypes in vitro and in vivo (Lee, Kim, et al., Cell 2015). Taking advantage of this new platform, we focused on finding potential therapeutic targets. We found SFRP2 (secreted frizzled related protein 2) to be highly expressed in LFS iPSC-derived MSCs and OBs by global RNA-seq gene expression analysis. Using global transcript profiling of ectopic overexpression (OE) of sFRP2 in wild-type MSCs, we discovered that sFRP2 regulates osteoblast differentiation, cell adhesion, cell proliferation, and apoptosis-related gene sets. Further functional assays revealed that sFRP2 OE contributes to the generation of abnormal osteoblast cells, which are the cause of OS, by suppressing osteogenic alkaline phosphatase activity, mineralization, and osteogenic BMP and WNT signaling. Furthermore, ectopic OE of sFRP2 is associated with LFS mediated tumorigenesis. sFRP2 OE in MSCs and OBs facilitates cell proliferation through cell cycle alteration and increases anchorage independency. In in ovo and in vivo xenograft assays (subcutaneous and intratibial injections), the tumor size is significantly increased in sFRP2 OE group and decreased in knockdown sFRP2 group. Interestingly, we also found that sFRP2 OE augments angiogenesis in vitro and in vivo, suggesting sFRP2 has a role as a paracrine factor. In the future, we will analyze sFRP2 expression levels in human OS tissue samples to determine whether sFRP2 OE has clinical relevance. Conclusively, this study demonstrates that P53 mutation-mediated osteosarcoma exerts oncogenicity through sFRP2 overexpression and that targeting of sFRP2 is a potential therapeutic strategy for OS treatment.
This abstract is also being presented as Poster A22.
Citation Format: Huen Suk Kim, Ye X. Yuan, Jeffrey M. Bernitz, Andreia Gomes, Christopher Schaniel, Dung-Fang Lee, Ihor R. Lemischka. Familial cancer patient specific iPSCs based study of a potential oncogenic factor, sFRP2, in osteosarcoma [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr PR05.
Between Rupture and Continuity
Authors: Rozo Esteban 
Published: August 2018

Abstract
This paper explores the politics of conversion in the Colombian Amazon, comparing missionary narratives of conversion with indigenous accounts of conversion. It shows how conversion to Christianity articulates new meanings of indigeneity today in Amazonia. Using ethnographic evidence, documents and interviews, the paper demonstrates that neither the missionaries nor the indigenous populations view conversion only as rupture. Although they recognize the transformational process involved in conversion, they both emphasize cultural continuity, albeit for different reasons. It also analyses how indigenous pastors and missionaries combine narratives of rupture and narratives of continuity while articulating a new kind of indigeneity (Christian indigeneity), and a specific politics of conversion. In this context, politics of conversion articulates emergent regimes of indigeneity that postulate strong complementarities between Christianity and indigenous values.
Same Memory, Different Memorials
Authors: Loffman Reuben Alexander 
Published: August 2018

Abstract
Recent literature on modern martyrdom and memory has focused on cases in which individual groups remember martyrs’ sacrifices by making similar memorials to them. However, this article argues that even if members of a group agree on a martyr narrative, different memorials with diverse meanings can still be erected in memory of the martyrs concerned. This article supports its argument by exploring the case of twenty members of the Holy Ghost Fathers (Spiritans) who were killed on 1 January 1962 in Kongolo in southeastern Congo-Kinshasa. The memorials dedicated to these Spiritans differ substantively with each other by emphasizing different aspects of sacrifice and memory. This article concludes by arguing that the diversity of memorials involved in this case alerts us to the fact that the traditions associated with martyrdom do not always dominate the public memory of those who sacrifice their lives for a cause.
Cost-minimization analysis of community pharmacy-based point-of-care testing for strep throat in 5 Canadian provinces
Authors: Lathia Nina , Sullivan Karen , Tam Kathy , Brna Margaret , MacNeil Paula , Saltmarche Deb , Agro Karen 
Published: August 2018

Background: Strep throat point-of-care (POC) testing in community pharmacies will enable pharmacist-based care for this condition. Our objective was to conduct an economic evaluation of treating severe sore throat when this service was offered in pharmacies in 5 Canadian provinces. Methods: We conducted 5 separate cost-minimization analyses for the provinces of Alberta, British Columbia, Nova Scotia, Ontario and Saskatchewan, from the public payer perspective, to estimate mean cost per patient of treating severe sore throat in 2 scenarios: 1) physician-based usual care in a family physician’s office, a walk-in clinic or an emergency room (ER) and 2) a new scenario where patients received care described above or in a pharmacy offering strep throat POC testing. One-way sensitivity analyses were conducted to account for model uncertainty. Results: Mean cost per patient for each pathway in the base-case analyses for the 5 provinces ranged from 1) $37.55 to $61.57 for family physician, 2) $37.55 to $61.57 for walk-in clinic, 3) $38.88 to $57.56 for ER and 4) $19.12 to $21.83 for pharmacy, representing savings ranging from $12.47 to $24.36 per patient for the new scenario. Approximate total cost savings range from $1.3 million to $2.6 million per year across the 5 provinces. All sensitivity analyses yielded cost savings for the new scenario. Discussion: Across 5 provinces, strep throat POC testing in pharmacies was cost saving compared to physician-based care. Sensitivity analyses demonstrated the robustness of these results. Conclusions: Funding strep throat POC testing in community pharmacies in these 5 provinces would lead to public health system cost savings and potentially improve patients’ access to care for severe sore throat.
Mainstreaming as rhetoric or reality? Gender and global health at the World Bank
Authors: Winters Janelle , Fernandes Genevie , McGivern Lauren , Sridhar Devi 
Published: August 2018

Background:Over the past decade gender mainstreaming has gained visibility at global health organisations. The World Bank, one of the largest funders of global health activities, released twoWorld Development Reportsshowcasing its gender policies, and recently announced a $1 billion initiative for women’s entrepreneurship. We summarise the development of the Bank’s gender policies and analyse its financing of gender projects in the health sector. This article is intended to provide background for future research on the Bank’s gender and global health portfolio.Methods:First, we constructed a timeline of the Bank’s gender policy development, through a review of published articles, grey literature, and Bank documents and reports. Second, we performed a health-focused analysis of publicly available Bank gender project databases, to track its financing of health sector projects with a gender ‘theme’ from 1985-2017.Results:The Bank’s gender policy developed through four major phases from 1972-2017: ‘women in development’ (WID), institutionalisation of WID, gender mainstreaming, and gender equality through ‘smart economics’. In the more inclusive Bank project database, projects with a gender theme comprised between 1.3% (1985-1989) and 6.2% (2010-2016) of all Bank commitments. Most funding targeted middle-income countries and particular health themes, including communicable diseases and health systems. Major gender-related trust funds were absent from both databases. The Bank reports that 98% of its lending is ‘gender informed’, which indicates that the gender theme used in its publicly available project databases is poorly aligned with its criteria for gender informed projects.Conclusion:The Bank focused most of its health sector gender projects on women’s and girls’ issues. It is increasingly embracing private sector financing of its gender activities, which may impact its poverty alleviation agenda. Measuring the success of gender mainstreaming in global health will require the Bank to release more information about its gender indicators and projects.
The orthographic significance of the Latin name for the “Norfolk Island Hibiscus” (Malvaceae)
Authors: Mabberley David J. 
Published: August 2018

AbstractA consideration of the naming of Hibiscus patersonius (Malvaceae) and similar names leads to the conclusion that such adjectival forms in specific epithets are in accordance with Classical Latin and that their “correction” to other adjectival forms or the genitive form of nouns is disruptive in botanical Latin.