bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract SY10-01: How aneuploidy drives cancer
Authors: Davoli Teresa , Uno Hajima , Xu Andrew , Mengwasser Kristen , Sack Laura , Park Peter J. , Elledge Stephen J. 
Published: July 2016

Abstract
Aneuploidy has been recognized as a hallmark of cancer for over 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. We developed Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing &gt;8200 tumor-normal pairs we provide statistical evidence suggesting many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. These genes represent the vast majority of cancer drivers and the genetic networks they drive are a focus of future cancer system biological approaches to cancer research. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and the potency of TSGs (STOP genes), OGs and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. We are now assessing how aneuploidy drives cancer and the potency with which it does so. We have found that aneuploidy predicts survival better than mutational drivers and as well as existing clinical parameters in many cases. We have also discovered that different classes of aneuploidy drive transcriptional programs for two hallmarks of cancer and will present data supporting these observations and their implications.
Citation Format: Teresa Davoli, Hajima Uno, Andrew Xu, Kristen Mengwasser, Laura Sack, Peter J. Park, Stephen J. Elledge. How aneuploidy drives cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY10-01.
Abstract SY12-01: PI 3-kinase and cancer metabolism
Authors: Cantley Lewis C. 
Published: July 2016

Abstract
In general cancer cells produce higher levels of reactive oxygen species (ROS) than normal cells due to increased rates of metabolism and defective mitochondria. In order to survive under conditions of high ROS, cancer cells typically turn on pathways for generating NADPH and glutathione to bring ROS levels back to homeostasis. Activating mutations in PIK3CA or loss of PTEN or activating mutations in KRAS can stimulate glucose uptake and metabolism and pathways for generating NADPH and glutathione to suppress ROS. A detailed understanding of the biochemical mechanisms by which cancer cells suppress excess ROS may suggest new therapies for inducing synthetic lethality in tumors that evolve in specific mutational backgrounds. Our research using human cancer cell lines and genetically engineered mouse models suggests new approaches for killing cancer cells by targeting metabolic pathways for ROS suppression that allow cancer cells to survive.
Citation Format: Lewis C. Cantley. PI 3-kinase and cancer metabolism. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY12-01.
Abstract SY15-01: SWI/SNF (BAF) complex mutations in cancer: Mechanisms and vulnerabilities
Authors: Roberts. Charles W.M. 
Published: July 2016

Abstract
Data emerging over the last several years implicate the SWI/SNF (BAF) chromatin remodeling complex as a major tumor suppressor as frequent inactivating mutations in at least nine different SWI/SNF subunits, collectively identified in twenty percent of all cancers. These include recurrent mutations of ARID1A (BAF250a) in ovarian, endometrioid, bladder, stomach, colorectal and pancreatic cancers and neuroblastoma; of the BRG1 (SMARCA4) subunit in medulloblastomas and non-small cell lung cancers; of the PBRM1 (BAF180) subunit in renal carcinomas; of the ARID2 subunit in hepatocellular, lung, and pancreas carcinomas as well as melanomas; of the BRD7 subunit in breast cancers. The SWI/SNF complex includes both core and lineage-specific subunits and utilizes the energy of ATP to modulate chromatin structure and regulate transcription.
My laboratory began studying the SWI/SNF complex when SNF5 (SMARCB1/INI1/BAF47) became the first SWI/SNF subunit linked to tumor suppression over fifteen years ago when it was found to be biallelically inactivated in nearly all cases of a highly aggressive type of pediatric cancer called malignant rhabdoid tumor (MRT). Despite the extremely aggressive and lethal nature of MRT we have shown that these cancers are diploid and have remarkably simple genomes. We now study the complex using mouse models, cell lines and primary human tumor samples. Insights into the normal function of SWI/SNF complexes, the mechanisms by which mutation of the complexes drive cancer formation, and potential therapeutic vulnerabilities created by mutation of the complex will be presented including our recent efforts that identify EZH2 and polycomb complexes as potential therapeutic vulnerabilities in these cancers.
Citation Format: Charles W.M. Roberts. SWI/SNF (BAF) complex mutations in cancer: Mechanisms and vulnerabilities. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY15-01.
Abstract SY15-02: Identification of novel oncogenic mechanisms in brain tumors with quiet genomes through mapping the enhancer landscape
Authors: Erkek Serap , Pajtler Kristian W. , Johann Pascal D. , Northcott Paul A. , Chavez Lukas , Kool Marcel , Pfister Stefan M. 
Published: July 2016

Abstract
Malignant pediatric brain tumors, including ependymoma, medulloblastoma and atypical teratoid/rhabdoid tumors, frequently demonstrate a very “quiet” genome with very few nonsynonyomous single nucleotide variants or indels and a stable copy number profile. The recent advance of integrative genomics approaches from primary tumor tissue including whole-genome sequencing, RNA sequencing, whole-genome bisulfite sequencing, and ChIP sequencing for core histone marks and important transcription factors and chromatin configuration have enabled the discovery of new tumor-driving pathways and potentially druggable alterations in these cancers with quiet genomes. This knowledge after functional validation in vitro and in vivo provides critical insight in the search for the cell of origin in these tumors, the understanding of underlying pathomechanisms, and the identification of new treatment options.
Citation Format: Serap Erkek, Kristian W. Pajtler, Pascal D. Johann, Paul A. Northcott, Lukas Chavez, Marcel Kool, Stefan M. Pfister. Identification of novel oncogenic mechanisms in brain tumors with quiet genomes through mapping the enhancer landscape. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY15-02.
Abstract SY18-02: Immunogenomics and precision cancer medicine
Authors: Van Allen Eliezer 
Published: July 2016

Abstract
The expansion of precision cancer medicine through robust interrogation of cancer genomes at the point of care has enhanced patient stratification and treatment selection strategies in numerous cancer types. In parallel, the rise of multiple immunotherapies, such as immune checkpoint blockade, has significantly improved clinical outcomes for multiple patient populations. The intersection of clinical cancer genomics and immuno-oncology has created an opportunity to learn how the tumor and germline genomes impact immune checkpoint blockade response, and how the immune system can be leveraged with knowledge of the cancer genome to more effectively stratify patients and tailor immune-specific therapies. Here, we describe the landscape of genomic correlates of immune checkpoint blockade, and examine how emerging genomic studies of immunotherapy responders and non-responders may inform patient selection strategies for clinical trial design. Furthermore, we explore how knowledge of the cancer genome and prioritization of neoantigens that arise from somatic mutations may impact personalized cancer vaccine development. Finally, we examine emerging data on genomic resistance to immunotherapies and the implications for combination treatment strategies. Broadly, the convergence of comprehensive clinical genomics and immuno-oncology treatment strategies may inform precision medicine for immunotherapies across cancer types.
Citation Format: Eliezer Van Allen. Immunogenomics and precision cancer medicine. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY18-02.
Abstract SY28-01: Immunotherapy in combination with neoadjuvant therapy and immune-related adverse events
Authors: Smyth Mark J. , Liu Jing , Blake Stephen J. , Teng. Michele WL 
Published: July 2016

Abstract
Immunotherapy has recently entered a renaissance phase with the approval of multiple agents for the treatment of cancer. Immunotherapy stands ready to join traditional modalities, including surgery, chemotherapy, radiation, and hormone therapy, as a pillar of cancer treatment. Although immunotherapy has begun to have success in advanced cancer treatment, its scheduling and efficacy with conventional therapies, such as surgery, has not been systematically examined. Here, we have used two models of spontaneously metastatic breast cancers in mice to compare the therapeutic power of neoadjuvant versus adjuvant immunotherapies in the context of primary tumor resection. Therapies, including Treg depletion, anti-PD-1 or anti-PD1/anti-CD137 combinations were evaluated. Elevated and sustained peripheral tumor-specific immune responses underpinned the outcome, and blood sampling of tumor-specific CD8+ T cells immediately prior to and post surgery may provide a predictor of outcome. New combination immunotherapies are displaying both efficacy and immune-related adverse events (irAEs) in humans. Prolonged T regulatory cell (Treg) depletion in tumor bearing Foxp3-DTR mice using diphtheria toxin (DT) mirrored the spectrum of antitumor responses and severity of irAEs that can occur in ipilimumab/nivolumab treated patients, while transient Treg depletion and anti-CTLA-4/PD-1 therapy had equivalent effects in mice, lowering the immune tolerance threshold and allowing irAEs to be more easily provoked following treatment with additional immunomodulatory antibodies. This platform has been used to compare a number of promising immunotherapies.
Citation Format: Mark J. Smyth, Jing Liu, Stephen J. Blake, Michele WL Teng. Immunotherapy in combination with neoadjuvant therapy and immune-related adverse events. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY28-01.
Abstract SY31-03: The future of combinations of immunomodulators with local radiation: toward a personalized immunotherapy approach
Authors: Demaria Sandra 
Published: July 2016

Abstract
We have shown in multiple preclinical tumor models that ionizing radiation therapy can convert tumors refractory to immune checkpoint inhibitors and other immune modulators into responsive ones. Importantly, the elicited antitumor T cells rejected not only the irradiated tumor but also nonirradiated spontaneous metastases or synchronous palpable tumors (abscopal effect), demonstrating the potential of radiation to generate systemically effective antitumor immune responses.
Investigations into the mechanisms underlying a successful response have highlighted a complex interaction between radiation and anti-CTLA-4 occurring at the priming and effector phase of the antitumor immune response. These data support a model whereby the irradiated tumor becomes a “live attenuated vaccine” resulting in marked expansion of a limited number of distinct T-cell clones within the tumor.
Our data also suggest that generation of an in situ tumor vaccine by radiation is regulated by the intrinsic tumor immunogenicity, the host immune system, and the radiation regimen employed. The interaction of these three compartments determines the levels of immune modulating mediators in the tumor microenvironment, including interferon type I, transforming growth factor-b, and adenosine, which in turn control the number and state of activation of intratumoral dendritic cells, and the magnitude of the induced T-cell response. Thus, while radiation offers the promise of a simple treatment to achieve individualized vaccination against each patient's own tumor, success is likely to be achieved by a personalized combination of the most effective radiation regimen and immune modulator(s).
We have recently shown in non-small cell lung cancer patients with chemotherapy-refractory metastatic disease that the synergy of radiotherapy and anti-CTLA-4 can be translated in the clinic (NCT02221739). Analysis of tumor and peripheral blood from responding and non-responding patients are beginning to provide clues to potential biomarkers and underlying mechanisms of response. Overall, local radiotherapy is showing the potential to be an ideal partner for immunotherapy. Because of its universal use in cancer treatment it is tempting to test standard of care radiotherapy in combination with any immunotherapy. However, rational use of radiation regimens and targeting of specific immune suppressive factors preexisting or elicited by radiation in a given tumor will be needed to truly reveal radiation's role in personalized immunotherapy.
Citation Format: Sandra Demaria. The future of combinations of immunomodulators with local radiation: toward a personalized immunotherapy approach. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY31-03.
Abstract SY42-01: Emerging epigenetic targets in high-risk pediatric solid tumors
Authors: Stegmaier Kimberly 
Published: July 2016

Abstract
Pediatric cancers are typically characterized by simple genomes and key initiating events driven by aberrancy of a transcription factor or chromatin modifier. One such example is the most common extracranial solid tumor in children, neuroblastoma. Amplification of the transcription factor encoding gene MYCN is present in ∼50% of high-risk neuroblastomas, representing the best-characterized genetic marker of poor survival in these pediatric patients. We have focused on the discovery of new therapeutic strategies to targeting this recalcitrant subtype of neuroblastoma using chemical and functional genomic approaches. First, we identified BET bromodomain inhibitors as highly active in MYCN-amplified neuroblastoma in an unbiased screen of 673 diverse cancer cell lines and validated this finding using genetic suppression with shRNA and chemical inhibition with multiple BET inhibitors. Mechanistically, BET inhibitors suppress the MYCN transcriptional program and the expression of MYCN itself. Extending these studies in vivo, both to patient derived xenografts (PDX) and to genetically engineered mouse (GEM) models of MYCN-driven neuroblastoma, we demonstrated remarkable efficacy. However, this single agent approach was not curative, suggesting the need for combination therapies. In order to address this issue, we performed both gain-of-function (ORF) and loss-of-function (CRISPR/Cas9) screening of neuroblastoma cell lines treated with BET bromodomain inhibitors at an IC90 to identify potential mechanisms of resistance to treatment and to nominate targetable pathways for combination therapy. Three key pathways emerging at the intersection of these screens are under evaluation and will be presented. In parallel, we have performed a genome-wide CRISPR screen in a panel of 8 neuroblastoma cell lines, 7 of which are MYCN amplified, to identify new dependencies. In comparing neuroblastoma cell lines to over 70 non-neuroblastoma cancer cell lines, several known neuroblastoma dependencies were confirmed, including MYCN, ALK, and PHOX2B. Importantly, novel dependencies were revealed. Validated new dependencies will also be the topic of this presentation.
Citation Format: Kimberly Stegmaier. Emerging epigenetic targets in high-risk pediatric solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY42-01.
Abstract SY44-02: ECM remodeling at the pre-metastatic niche
Authors: Erler Janine T. 
Published: July 2016

Abstract
The extracellular matrix (ECM) is one of the most important regulators of cellular and tissue function in the body. The ECM is known to play a critical role in driving cancer progression, and yet we lack knowledge of how ECM is altered during tumour progression to promote cancer metastasis. We have found that an enzyme secreted by tumor and stromal cells called lysyl oxidase (LOX) is responsible for altering the ECM at primary and metastatic sites to greatly enhance metastasis. LOX is an amine oxidase that catalyses the crosslinking of collagens and elastin in the ECM. LOX activity alters the structural and biochemical properties of the ECM, to drive cell proliferation, invasion and angiogenesis. Importantly, LOX modifies pre-metastatic tissue microenvironments prior to tumor cell arrival, enhancing metastatic colonisation and outgrowth. We are expanding our studies to further investigate how ECM is remodeled during cancer progression and how this impacts on cell behavior to drive metastasis.
Citation Format: Janine T. Erler. ECM remodeling at the pre-metastatic niche. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr SY44-02.
A first note on foliicolous lichens of Assam, India
Authors: Gupta Pooja , Sinha G. P. 
Published: July 2016

A first note on foliicolous lichens of Assam enumerating 26 species belonging to 15 genera and eight families are provided. Four species viz., Bacidina apiahica, Byssoloma chlorinum, Calopadia fusca and Strigula nitidula are reported for the first time from Assam. A number of rare species are present, including Aulaxina uniseptata, Calenia aspidota and Psorotheciopsis patellarioides.
Neuropsychiatric manifestations of Parkinson’s disease
Authors: Molina Ruiz Rosa M , Evans Andrew H , Velakoulis Dennis , Looi Jeffrey CL 
Published: July 2016

Objective: This clinical update review focuses on the classification and description of common neuropsychiatric manifestations in Parkinson’s disease (PD). Method: We conducted a systematic search of the literature using Pubmed and selected the most recent and relevant papers for this review. Results: Neuropsychiatric manifestations in PD are are very frequent and may arise from an abnormal psychopathological response to the disease, neurobiological changes related to the disease itself, complications of treatments or a combination of all of these. Conclusions: Neuropsychiatric symptoms may precede the motor clinical presentation of PD. Early recognition is essential.
Ergonomics and Prevention of Injuries From Needles Sticks and Sharps in the OR
Authors: Kalaga Pramila , Balters Marcus , Crowley Lynn , Paulsen Lisa , Erkes Laura Peet , Boes Emily , Patterson Emalee , Carr Jill , Forse Armour , Alsagar Barb , Culbertson Sandy , Kayl Matt , Jessen Christopher , Wright Christine , Myers Janel 
Published: July 2016

Aim: Implement ergonomic process improvement within the OR, to decrease incidence of injuries from sharps and needle sticks among the OR teams. Method: A pre and post intervention design was adopted. The number of reported incidents related to needle sticks and sharps over a seven month period prior to the implementation of the ergonomic process improvement(January to July 2014) and over a seven month period following implementation(January to July 2015), were compared. A participatory approach was adopted, for conducting the study and the study team included an ergonomist, surgery educators, two surgeons, operations leader, department manager, team lead, risk manager and two pre-med students functioning as study assistants. Ergonomics training for the prevention of injuries from sharps and needle sticks was developed, which incorporated physical, cognitive and teamwork measures alongside the prevention measures outlined by AORN and evidence based measures identified following a literature review. The Surgery Educator, the Ergonomist and an Attending Surgeon, participated in delivering the ergonomics injury prevention training. The management, including the Team Lead and OR Manager participated in supporting and facilitating the implementation of the injury prevention measures, where possible, such as double gloving; safe passing zones; verbal feedback; silence or task related communications only during critical phases, etc. Results: A significant difference was found in the frequency of the overall sharps and needle stick related incidents over the pre and post implementation time periods of interest(Wilcoxon Signed Rank test - significant at p≤ 0.05 level, where the W-value is 2 and the critical value for W with N=6 is 2). 63.51% decrease in incidence rate was found among the OR staff, and 44.25% decrease in incidence rate was found among students and residents, pre and post implementation. Overall, a 55% decrease was found in the incident rate of events related to sharps and needle sticks among the OR teams(experts and novices combined), over the first seven months of implementing the ergonomic process improvement. Conclusion Within the complex task and team work environments of the operating room in teaching hospitals, ergonomics and human factors fundamentals related to individual task performance, team work and work design could help improve the effectiveness of the safety measures.