bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2214: Impact of comorbidities at diagnosis on prostate cancer treatment and survival
Authors: Matthes Katarina L. , Limam Manuela , Pestoni Giulia , Held Leonhard , Korol Dimitri , Rohrmann Sabine 
Published: August 2018

Abstract
Background: For Switzerland, it is currently unclear in which way comorbidities influence the choice of primary treatment in prostate cancer (PCa) patients and how comorbidities affect long-term survival of PCa patients. Thus, the aim of this study was to assess the associations of comorbidities with primary treatment of PCa patients and of comorbidities with PCa-specific mortality (PCSM) compared to other-cause mortality (OCM) in Switzerland.
Patients and Methods: We included 1527 men diagnosed with PCa in 2000 and 2001 in the canton of Zurich. Comorbidities at time of diagnosis were based on the Charlson Comorbidity Index (CCI). For each patient, the scores of the respective comorbidities were summed up and classified into three groups: CCI 0 = no comorbidities, CCI 1 = sum of scores equals to 1, CCI 2+ = sum of scores equals to 2 or larger. Multiple imputation methods were applied to missing data for stage, grade and comorbidities. Multinomial logistic regression analyses were used to explore the associations of comorbidities with treatment. Cox regression models were used to estimate all-cause mortality, and Fine and Gray competing risk regression models to estimate sub-distribution hazard ratios for the outcomes PCSM and OCM.
Results: Increasing age was associated with a decreasing probability of receiving curative treatment, whereas an increasing CCI did not influence the treatment decision as strongly as age. The probability of OCM was significantly higher for patients with comorbidities compared to those without comorbidities (CCI 1: 2.07 [95% CI 1.51 - 2.85], CCI 2+: 2.34 [1.59 - 3.44]); this was not observed for PCSM (CCI 1: 0.79 [0.50 - 1.23], CCI 2+: 0.97 [0.59 - 1.59]). In addition, comorbidities had a greater impact on the patients' mortality than age.
Conclusions: The results of the current study suggest that the chronological age is a stronger predictor of treatment choices than comorbidities. This study supports the inclusion of comorbidities in treatment choices in order to offer more appropriate treatment for PCa patients to counteract over- or undertreatment.
Citation Format: Katarina L. Matthes, Manuela Limam, Giulia Pestoni, Leonhard Held, Dimitri Korol, Sabine Rohrmann. Impact of comorbidities at diagnosis on prostate cancer treatment and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2214.
Abstract 2219: Expression of PCNA and MCM2 in ameloblastoma
Authors: Mallipudi Bhavana 
Published: August 2018

Abstract
Background:-Ameloblastoma is an odontogenic neoplasm with the most frequent osseous destructive lesions of the jaws. Ameloblastoma deserves special attention, because of its biological behaviour exhibiting great infiltrative potential, high recurrence rate and capacity to metastasize. The increased proliferation rate in the odontogenic epithelium can be a result of perturbations in the cell cycle regulators and dictates the aggressive behavior of the tumors. Investigating proliferative rates in the epithelial lining of these lesions helps in assessing their biological behaviour. Various cell proliferation markers are used as diagnostic and prognostic tools in oral lesions. Assessing the expression of these markers helps in estimating the proliferative index of the tissues.
Aim:- The aim of this study is to analyze the presence of, Proliferating cell nuclear antigen (PCNA) and the minichromosome maintenance-2 (MCM2) proteins, two well established markers of cell proliferation, in clinically diagnosed cases of ameloblastoma and correlate with aggressiveness and its types (Solid/multicystc{Follicular, plexiform} unicystic).
Materials and method:-14 clinically diagnosed cases of ameloblastomas (10 Solid/multicystic cases{6 cases of Follicular, 4 cases of plexiform} and 4 cases of unicystic) are obtained from the archieves of the Department of Oral and Maxillofacial Pathology to study the expression of MCM2 and PCNA. The data was analysed by Kruskals ANOVA, Mann-Whitney U test and Post hoc analysis.
Results and conclusion:- A Kruskal-Wallis ANOVA was used to detect if there was a significant difference in the expression of MCM2 and PCNA between the three variants of ameloblastoma. There was a significant difference between the three groups for mean percentage expression of MCM2 but there was uniformly higher expression of PCNA in all the three variants. Interestingly, further post hoc analysis revealed that the expression of MCM2 was significantly higher in the follicular variantas compared to the unicystic variant, suggesting that dual staining of MCM2 and PCNA may be a better marker for follicular variant.
Keywords:-Ameloblastoma, MCM2, PCNA.
Citation Format: Bhavana Mallipudi. Expression of PCNA and MCM2 in ameloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2219.
Abstract 2249: PWS: An integrated web service platform enabling precision medicine
Authors: Duan Zhenyu 
Published: August 2018

Abstract
Aiming at providing an integrated platform to accelerate global drug development with personalized medicine, Predicine Web Service (PWS) is built to enable real time project status report, interpretation of clinical impact for genomic aberrations, and novel biomarker discovery with data mining algorithms and analytics.
A large-scale Predicine database is built with KnowledgeBase layer and dynamically growing genomics data layer. The KnowledBase layer integrates genome annotations, ontologies, computed variant impacts, and curated clinical implications. The dynamic genomic data layer is designed to be scalable so that both Predicine patient genomic profiles and public domain genomics data can be imported with standardized data models. A wide range of curated databases and public domain genomics profiles are integrated, including COSMIC, ClinVar, dbSNP, 1000 Genomes, ExAC, CIViC, GeneDrug KnowledgeBase, MSK IMPACT, and TCGA. Data mining algorithm and analytics are developed to enable data driven interpretation and biomarker discovery.
An intuitive web interface is developed for users to select patient space with clinical and genomics criteria, to generate patient reports with ability to drill down to multi-level variant data, and to discover biomarkers leading to hypothesis of novel targets, drug response association, and combination therapy. The project management module securely communicates the status of projects and samples for pharmaceutical companies and other clients. On PWS, private domain patient data can be combined with comprehensive public domain data for comparative and comprehensive global analysis to enable precision medicine.
Citation Format: Zhenyu Duan. PWS: An integrated web service platform enabling precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2249.
Abstract 2257: AGISTM-OncoGxKB: A simple tool for actionable genomic knowledgebase curation and clinical interpretation
Authors: Yu Pengfei , Yan Cheng 
Published: August 2018

Abstract
Nowadays, targeted therapy and immunotherapy have become the mainstream of cancer therapy because of their overall merit over traditional chemotherapy. With the increasing number of drug targets being discovered, cancer patients are more likely to benefit from these advanced therapies. However, the interpretation of actionable variants from patients is still a challenge in cancer clinical sequencing workflows. Here we present OncoGxKB, a crowdsource-based knowledgebase system tailored to provide clinical interpretation of variants in cancer. Based on genetic makeup of patient tumor, OncoGxKB provides actionable therapeutic strategies that maximize treatment efficacy and minimize side effects. The clinical recommendations provided cover targeted therapies, immunotherapies and clinical trials associated with actionable variants. Interpretations are rendered in tiers based on clinical evidence and stratified cancer types, following the newest AMP guideline. The crowdsource-based implementation keeps OncoGxKB comprehensive, updated, transparent and accessible to scientific community. The application programming interface (API) availability can also make the interpretation system be easily adopted to different existing pipelines. OncoGxKB is publicly available at: https://agis.admerahealth.com/OncoGxKB.
Citation Format: Pengfei Yu, Cheng Yan. AGISTM-OncoGxKB: A simple tool for actionable genomic knowledgebase curation and clinical interpretation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2257.
Abstract 2284: Semiautomated MRI segmentation workflow for glioblastoma treated by Tumor Treating Fields
Authors: Timmons Joshua J. , Lok Ed , San Pyay , Bui Kevin , Wong Eric T. 
Published: August 2018

Abstract
Background: Tumor Treating Fields (TTFields) therapy is an approved modality of treatment for glioblastoma. Patient anatomy-based finite element analysis (FEA) has the potential to reveal not only how these fields affect tumor control but also how they can be optimized to improve efficacy. Historically, this has been achieved with manual segmentation by an expert familiar with intracranial neuroanatomic structures, but this method is time-consuming, financially costly, and highly variable between individuals. While the availability of tools for segmenting MRIs obviates some of these obstacles, creating FEA models requires manual adjustments, including removal of disconnected voxels, incorporation of unsegmented structures that may alter the electric field, and addition of 36 electrodes matching those of the transducers on the scalp. Existing approaches are also not scalable to a large number of patient MRI scans.
Methods: Patient anatomy-based FEA models were created by segmenting MRI images—using the NewSegment algorithm from Statistical Paramedic Mapping 8 (SPM8)—into tissue “masks” using ScanIP from Simpleware (Exeter, UK). The electric properties of each tissue were applied to these masks in silico using COMSOL Multiphysics (Burlington, MA). The fidelity of the segmentations was compared using the Dice coefficient, and COMSOL generated electric field maps were compared for models with and without post-processing in ScanIP.
Results: A semiautomated workflow was developed to prepare FEA models for TTFields with fully automated electrode placement. The workflow encompassed image preprocessing, co-registration, segmentation, post-processing and mesh generation in ScanIP. Modified extended tissue probability maps were used to segment cerebellum and orbits in addition to white matter, gray matter, cerebrospinal fluid, skull, and scalp. Further automated post-processing in ScanIP cleaned up disconnected voxels, smoothed surfaces, and layered the masks to prevent erroneous boundary conditions. The Dice coefficient was greater for the model with ScanIP post-processing, as compared to the segmentations resulting from SPM8 NewSegment alone. COMSOL-generated electric field maps also displayed differences when models were generated with post-processing in ScanIP compared to those without.
Conclusions: These software and workflow may be used to accelerate the investigation of TTFields in patients by facilitating the creation of FEA models, like electric field maps, derived from patient MRI.
Citation Format: Joshua J. Timmons, Ed Lok, Pyay San, Kevin Bui, Eric T. Wong. Semiautomated MRI segmentation workflow for glioblastoma treated by Tumor Treating Fields [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2284.
Abstract 2306: Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin/ISO on human bladder cancer cells
Authors: Xu Jiheng , Li Jingxia , Huang Chuanshu , Huang Haishan , Jiang Guosong 
Published: August 2018

Abstract
Our recent studies have demonstrated that Isorhapontigenin (ISO), a new derivative isolated from the Chinese herb Gnetum Cleistostachyum, effectively induces cell-cycle arrest at the G0/G1 phase and inhibits anchorage-independent cell growth through the miR-137/Sp1/cyclin D1 axis in human muscle invasive bladder cancer cells both in vitro and in vivo. Herein, we found that treatment of muscle invasive bladder cancer cells with ISO resulted in a significant upregulation of p27, a key cyclin-dependent kinase inhibitor. Importantly, knockdown of p27 caused a decline in the ISO-induced G0-G1 growth arrest and reversed ISO suppression of anchorage-independent growth in bladder cancer cells. Mechanistic studies revealed that ISO promoted p27 expression at mRNA transcription level through increasing direct binding of FOXO1 to its promoter, while knockdown of FOXO1 attenuated ISO inhibition of cell growth. On the other hand, ISO upregulated the 3'UTR activity of p27, which was accompanied by a reduction of miR-182 expression. In line with these observations, ectopic expression of miR-182 significantly blocked p27 3'UTR activity, whereas mutation of the miR-182 binding site at p27 mRNA 3'UTR effectively reversed this inhibition. Accordingly, ectopic expression of miR-182 also attenuated ISO upregulation of p27 expression and impaired ISO inhibition of cancer cell growth. Our results not only provide novel insight into understanding of the underlying mechanism related to regulation of muscle invasive bladder cancer cell growth, but also identify new roles and mechanisms underlying ISO inhibition of the growth of human bladder cancer cells.
Citation Format: Jiheng Xu, Jingxia Li, Chuanshu Huang, Haishan Huang, Guosong Jiang. Transcriptional and post-transcriptional upregulation of p27 mediates growth inhibition of isorhapontigenin/ISO on human bladder cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2306.
Abstract 2309: Increase in Cdk4 activity during progression of small intestinal neuroedocrine tumors
Authors: Contractor Tanupriya , Harris Chris R. 
Published: August 2018

Abstract
In the USA, there are approximately 5000 new cases of small intestinal neuroendocrine tumors (SINETs) per year, many of which already show liver metastasis upon initial diagnosis. The genetic causes of SINETs have long been a mystery. The only known recurrent mutations are in the Cdkn1b gene, which is mutated in 8% of tumors. Cdkn1b encodes p27kip1, an inhibitor of Cdk4 and Cdk2. We analyzed proteins and genes linked to the function of Cdk4 in a set of early and late SINETs (pathological stages M0 or M1). Amplification of Cdk4 activators (CcnD1, CcnD2, CcnD3), or loss of copy of Cdk4 inhibitors (Cdkn1b as well as Cdkn2a), or mutation of Cdkn1b were uncommon events, but notably occurred almost exclusively in patients with late stage disease. Patients with late stage tumors also had genetic abnormalities in Phlda3, including loss of copy, loss of heterozygosity, or presence of the rs35383942 SNP. Altogether, more than 50 percent of the advanced tumors had one or more of these genetic events, compared to less than 15 percent of the early tumors. Phlda3 is known to affect Akt activity which in turn is known to repress p27kip1 by phosphorylation, and indeed we detected more p27kip1 phosphorylation in late stage tumors. Finally, advanced tumors showed higher expression of Cdk4 and increased phosphorylation of serine-807 or serine-811 of the Rb1 protein. Together, these data argue that there is genetic pressure to increase Cdk4 activity during progression of SINETs, and suggest that patients with advanced SINETs may respond to Cdk4 inhibitors.
Citation Format: Tanupriya Contractor, Chris R. Harris. Increase in Cdk4 activity during progression of small intestinal neuroedocrine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2309.
Abstract 2326: Time-resolved studies of necroptosis reveal distinct regulatory functions for NFκB
Authors: Metzig Marie Oliver , Mitchell Simon , Taylor Brooks , Hoffmann Alexander 
Published: August 2018

Abstract
Resistance to regulated cell death (RCD) is an important hallmark of cancer and reason why chemotherapy fails. Efficient reprogramming of cancer cells requires a molecular and dynamic understanding of regulatory circuits. Research has uncovered several resistance mechanisms for apoptosis with nuclear factor κB (NFκB) as a key inhibitory transcription factor. Targeted induction of necroptosis, which was recently discovered as an alternative form of RCD, could be a promising strategy to overcome apoptosis resistance. However, whether NFκB has a regulatory role in necroptosis is less clear. Here, we develop a molecular and time-resolved understanding of how NFκB regulates necroptosis. We present a real-time experimental system to quantify necroptosis in single cancer cells to study the cytotoxic effect of substances while avoiding the bias of proliferation in endpoint protocols. Using live-cell microscopy, computational cell tracking and automated image analysis we quantitate necroptotic death rates in L929 cells, a murine fibrosarcoma cell line, treated with tumor necrosis factor (TNF). While it is known that L929 cells predominantly respond with necroptosis despite rapid activation of NFκB, our experiments reveal an unsuspected temporal phasing of necroptosis over a time course of 24 hours. By perturbing NFκB activation dynamics using targeted CRISPR/Cas9 of IκB and/or Rel proteins, we find that NFκB has at least two distinct roles regulating early and late phases of TNF-induced necroptosis. Further, we will present our molecular analysis that identified NFκB-responsive candidate genes and mapped them into a functional temporo-spatial context within the NFκB-necroptosis signaling network. Our combined approach may inform novel personalized anticancer strategies to exploit targeted necroptosis while avoiding NFκB-induced drug resistance.
Citation Format: Marie Oliver Metzig, Simon Mitchell, Brooks Taylor, Alexander Hoffmann. Time-resolved studies of necroptosis reveal distinct regulatory functions for NFκB [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2326.
Abstract 2367: Identification of p-AKT as a PD marker for MER kinase in human G361 cells
Authors: Chen Yaoyu 
Published: August 2018

Abstract
Abnormalities in receptor tyrosine kinases (RTKs) have been shown to be involved in a wide range of important biological activities in cancer, including cell proliferation, differentiation and drug resistance. The TAM family of RTKs includes three family members: TYRO3, AXL, and MER. Binding of ligands to the these receptors was reported to lead to activation of the TAM kinases, as well as PI3K/AKT, RAS/RAF/MAPK and JAK/STAT signaling pathways in human cancer cells. Among these three TAM kinases, the MER signaling pathway represents an attractive target for the treatment of human cancers. MER phosphorylation is dependent on the ligand GAS6, however, ligand activated phospho-MER is often not stable and is very difficult to detect without pervanadate pretreatment in human cancer cells and this has been a hurdle for developing a selective MER kinase inhibitor. Therefore, it is important to identify a specific pharmacodynamic marker to monitor MER kinase activity in human cancer cells. Here, we report the development of a phospho-AKT assay for characterization of MER kinase inhibitors in human G361 cells. We profiled the expression of MER among multiple human cancer cells and demonstrated that MER and TYRO3, but not AXL show high levels of protein expression in human G361 melanoma cells. In G361 cells, phospho-AKT is induced by GAS6 treatment and the induction of phospho-AKT can be reversed by AXL/MER tool compounds. To determine the role MER and TYRO3 play in the activation of phospho-AKT, either MER or TYRO3 was selectively depleted by siRNA knockdown. We demonstrate that GAS6 induced phospho-AKT is only dependent on MER kinase, but not TYRO3 in human G361 melanoma cells. In addition, using phospho-AKT as readout, a high-throughput cell-based assay was established in the G361 human melanoma cells for evaluation of compound potency in inhibiting MER pathway activation. Further, we observed a correlation in compound potency between inhibition of phospho-AKT in G-361 cells and phospho-MER in MER-overexpressing BAF3 cells. In summary, we have demonstrated that GAS6 induced phospho-AKT can be a potential pharmacodynamic marker for inhibition of MER kinase and have successfully developed a cell-based functional assay for screening small molecule inhibitors of MER kinase for potential therapeutic utility in treating GAS6/MER-deregulated human cancers.
Citation Format: Yaoyu Chen. Identification of p-AKT as a PD marker for MER kinase in human G361 cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2367.