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H3K27M diffuse intrinsic pontine gliomas (DIPG) exhibit cellular heterogeneity comprising less-differentiated, stem-like glioma cells that resemble oligodendrocyte precursors (OPC) and more differentiated astrocyte (AC)-like cells. H3K27M DIPG stem-like cells exhibit tumor-seeding capabilities in vivo, a feature lost or greatly diminished in the more differentiated AC-like cells. In this study, we established isogenic in vitro models of DIPG that closely recapitulated the OPC-like and AC-like phenotypes of DIPG cells. Using these tools, we performed transcriptomics, metabolomics, and bioenergetic profiling to identify metabolic programs operative in the different cellular states. From this, we defined new strategies to selectively target metabolic vulnerabilities within the specific tumor populations. Namely, we showed that the AC-like cells exhibited a more mesenchymal phenotype and were thus sensitized to ferroptotic cell death. In contrast, OPC-like cells upregulated cholesterol metabolism and mitochondrial oxidative phosphorylation (OXPHOS) and were accordingly more sensitive to statins and OXPHOS inhibitors. Additionally, statins and OXPHOS inhibitors showed efficacy and extended survival in preclinical orthotopic models established with stem-like H3K27M DIPG cells. Together, this study demonstrates that cellular subtypes within DIPGs harbor distinct metabolic vulnerabilities that can be uniquely and selectively targeted for therapeutic gain.

Background Metabolic programs in cancer cells are influenced by genotype and the tissue of origin. We have previously shown that central carbon metabolism is rewired in pancreatic ductal adenocarcinoma (PDA) to support proliferation through a glutamate oxaloacetate transaminase 1 (GOT1)-dependent pathway. Methods We utilized a doxycycline-inducible shRNA-mediated strategy to knockdown GOT1 in PDA and colorectal cancer (CRC) cell lines and tumor models of similar genotype. These cells were analyzed for the ability to form colonies and tumors to test if tissue type impacted GOT1 dependence. Additionally, the ability of GOT1 to impact the response to chemo- and radiotherapy was assessed. Mechanistically, the associated specimens were examined using a combination of steady-state and stable isotope tracing metabolomics strategies and computational modeling. Statistics were calculated using GraphPad Prism 7. One-way ANOVA was performed for experiments comparing multiple groups with one changing variable. Student’s t test (unpaired, two-tailed) was performed when comparing two groups to each other. Metabolomics data comparing three PDA and three CRC cell lines were analyzed by performing Student’s t test (unpaired, two-tailed) between all PDA metabolites and CRC metabolites. Results While PDA exhibits profound growth inhibition upon GOT1 knockdown, we found CRC to be insensitive. In PDA, but not CRC, GOT1 inhibition disrupted glycolysis, nucleotide metabolism, and redox homeostasis. These insights were leveraged in PDA, where we demonstrate that radiotherapy potently enhanced the effect of GOT1 inhibition on tumor growth. Conclusions Taken together, these results illustrate the role of tissue type in dictating metabolic dependencies and provide new insights for targeting metabolism to treat PDA.

Cancer metabolism is rewired to support cell survival in response to intrinsic and environmental stressors. Identification of strategies to target these adaptions is an area of active research. We previously described a cytosolic aspartate aminotransaminase (GOT1)-driven pathway in pancreatic cancer used to maintain redox balance. Here, we sought to identify metabolic dependencies following GOT1 inhibition to exploit this feature of pancreatic cancer and to provide additional insight into regulation of redox metabolism. Using pharmacological methods, we identify cysteine, glutathione, and lipid antioxidant function as metabolic vulnerabilities following GOT1 withdrawal. We demonstrate that targeting any of these pathways triggers ferroptosis, an oxidative, iron-dependent form of cell death, in GOT1 knockdown cells. Mechanistically, we reveal that GOT1 inhibition represses mitochondrial metabolism and promotes a catabolic state. Consequently, we find that this enhances labile iron availability through autophagy, which potentiates the activity of ferroptotic stimuli. Overall, our study identifies a biochemical connection between GOT1, iron regulation, and ferroptosis., The aspartate aminotransaminase GOT1 is important for maintaining redox balance. Here, the authors show that inhibition of GOT1 in pancreatic cancer cells leads to cell death via ferroptosis.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDA) restricts vascularization and, consequently, access to blood-derived nutrients and oxygen, which impacts tumor growth. Intracellular redox imbalance is another restraint on cellular proliferation, yet it is unknown if the TME contributes to the maintenance of redox homeostasis in PDA cells. Here, we demonstrate that the loss of mitochondrial glutamate-oxaloacetate transaminase 2 (GOT2), a component in the malate-aspartate shuttle, disturbs redox homeostasis and halts proliferation of PDA cells in vitro. In contrast, GOT2 inhibition has no effect on in vivo tumor growth or tumorigenesis in an autochthonous model. We propose that this discrepancy is explained by heterocellular pyruvate exchange from the TME, including from cancer associated fibroblasts. More broadly, pyruvate similarly confers resistance to inhibitors of mitochondrial respiration. Genetic or pharmacologic inhibition of pyruvate uptake or metabolism abrogated pyruvate-mediated alleviation of reductive stress from NADH buildup. In sum, this work describes a potential resistance mechanism mediated by metabolic crosstalk within the pancreatic TME. These findings have important implications for metabolic treatment strategies since several mitochondrial inhibitors are currently in clinical trials for PDA and other cancers.

SummaryPancreatic ductal adenocarcinoma (PDA) is one of the deadliest solid malignancies, with a 5-year survival rate at ten percent. PDA have unique metabolic adaptations in response to cell-intrinsic and environmental stressors, and identifying new strategies to target these adaptions is an area of active research. We previously described a dependency on a cytosolic aspartate aminotransaminase (GOT1)-dependent pathway for NADPH generation. Here, we sought to identify metabolic dependencies induced by GOT1 inhibition that could be exploited to selectively kill PDA. Using pharmacological methods, we identified cysteine, glutathione, and lipid antioxidant function as metabolic vulnerabilities following GOT1 withdrawal. Targeting any of these pathways was synthetic lethal in GOT1 knockdown cells and triggered ferroptosis, an oxidative, non-apoptotic, iron-dependent form of cell death. Mechanistically, GOT1 inhibition promoted the activation of autophagy in response to metabolic stress. This enhanced the availability of labile iron through ferritinophagy, the autolysosome-mediated degradation of ferritin. In sum, our study identifies a novel biochemical connection between GOT1, iron regulation, and ferroptosis, and suggests the rewired malate-aspartate shuttle plays a role in protecting PDA from severe oxidative challenge.HighlightsPDA exhibit varying dependence on GOT1 forin vitroandin vivogrowth.Exogenous cystine, glutathione synthesis, and lipid antioxidant fidelity are essential under GOT1 suppression.GOT1 inhibition sensitizes pancreatic cancer cell lines to ferroptosis.GOT1 inhibition represses anabolic metabolism and promotes the release of iron through autophagy.

BACKGROUND Diffuse Intrinsic Pontine Glioma (DIPG) is a uniformly fatal pediatric brainstem tumor and the leading cause of brain-tumor related deaths in children. It is therefore imperative to identify novel treatment strategies for this aggressive and devastating disease. Metabolic reprogramming in tumors and in the tumor microenvironment contribute to evasion of therapy and tumor recurrence. The goal of this study was to identify and therapeutically target metabolic vulnerabilities in DIPG that mediate aggressiveness and treatment resistance. METHODS DIPG tumors are marked by cellular heterogeneity and are driven by a population of cells with stem cell properties. We took a comprehensive metabolomics and transcriptomic screening approach to determine the operative pathways in the tumor driving stem cell compartment. To demonstrate efficacy and potential therapeutic window of activity, we treated DIPG tumors with clinically available and brain-penetrant inhibitors of the identified dysregulated metabolic pathways. RESULTS Our multi-omics analyses revealed that tumorigenic patient-derived DIPG cells significantly upregulate metabolic programs including cholesterol biosynthesis and mitochondrial oxidative phosphorylation (OXPHOS) compared to DIPG cells that were induced to undergo differentiation (events associated with a loss of tumorigenic capabilities). The therapeutic targeting of DIPG tumors with clinically available and brain penetrant inhibitors of OXPHOS and cholesterol biosynthesis resulted in tumor cell killing and growth inhibition both in vitro and in vivo. Moreover, there was a therapeutic window of activity in tumorigenic DIPG cells compared with differentiated gliomas and non-malignant cells. CONCLUSION Our findings demonstrate that DIPG harbor perturbations in metabolic programs that can be exploited for therapeutic benefits. The results from this study defined the metabolic pathways operative in the tumor-driving population in DIPG and demonstrated efficacy of targeting these pathways.

Esophageal adenocarcinoma (EAC) patients commonly present with advanced stage disease and demonstrate resistance to therapy, with response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for improvement of clinical outcomes. IGFBP2 is a member of the IGFBP family of proteins that has been reported to modulate both IGF and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. In this study, high IGFBP2 expression was observed in a subset of primary EACs and was found to be significantly higher in patients with shorter disease-free intervals as well as in treatment-resistant EACs as compared to chemonaive EACs. Modulation of IGFBP2 expression in EAC cell lines promoted cell proliferation, migration and invasion, implicating a role in the metastatic potential of these cells. Additionally, knockdown of IGFBP2 sensitized EAC cells to cisplatin in a serum-dependent manner. Further in vitro exploration into this chemosensitization implicated both the AKT and ERK pathways. Silencing of IGFBP2 enhanced IGF1-induced immediate activation of AKT and reduced cisplatin-induced ERK activation. Addition of MEK1/2 (selumetinib or trametinib) or AKT (AKT Inhibitor VIII) inhibitors enhanced siIGFBP2-induced sensitization of EAC cells to cisplatin. These results suggest that targeted inhibition of IGFBP2 alone or together with either the MAPK or PI3K/AKT signaling pathway in IGFBP2-overexpressing EAC tumors may be an effective approach for sensitizing resistant EACs to standard neoadjuvant chemotherapy.

While self-efficacy has been widely used to explain and treat various biobehavioral responses, few investigations have examined this concept in the context of sexual response and dysfunction. In this study, the authors constructed a measure of sexual self-efficacy, investigated whether it differentiated men with and without sexual dysfunction, and determined the utility of this construct by exploring its relation to other variables known to be related to erectile dysfunction in a sample of 60 men with erectile dysfunction and 14 functional men visiting a urology clinic. The sexual self-efficacy index differentiated men with and without erectile dysfunction, and general linear modeling showed that the index did indeed relate to other variables known to affect sexual and emotional response during a partnered sexual experience. These findings suggest that, as a unifying construct that predicts cognitive, affective, motivational, and behavioral responses, sexual self-efficacy has the potential to play an important role in the assessment of effective treatments for sexual problems.

Study Type – Therapy (qualitative) Level of Evidence 4 What's known on the subject? and What does the study add? Sexually dysfunctional men report higher negative affect and lower positive affect than sexually functional men. Furthermore, men with sexual problems tend to make internal, self-blaming, attributions for negative sexual events, which can result in a diminished sense of self-efficacy and cause men to expect similar negative outcomes across future sexual situations. This pattern may sustain and actually intensify the sexual problem. This study shows that causal attributions for dysfunctional response influence emotional response to a partnered sexual situation. Specifically, sexually dysfunctional men who attribute their problem to a medical condition do better emotionally than those who attribute the problem to unknown or psychological factors – and this attribution process is a more powerful and reliable predictor of emotional response than the man's actual diagnosed somatic risk for a sexual problem. Furthermore, the study strongly suggests that those men who attribute their problem to a physical/medical issue are able to ‘externalize’ it – needing to assume less responsibility for and/or control over it, thereby reducing their psychological burden. These findings indicate not only that communication between physician and patient regarding the aetiology of a sexual problem may be critically important but also that, at least for some patients, pharmacological treatment should be combined with strategies that promote the development of internal positive self-serving attributions surrounding sexual activity. OBJECTIVE • To investigate factors that influence sexually dysfunctional men's emotional response within a partnered sexual situation, and, most specifically, whether they attribute their dysfunctional response to a specific biomedical cause vs a psychological or unknown cause. PATIENTS AND METHODS • Based on a sample of 59 sexually dysfunctional men visiting a urology clinic, linear regression was used to determine the relationship between patients' attributions and five global affective factors derived through principal components analysis: apprehension, insecure, arousable, affection, and pleasant. • Two other covariates were included: actual (diagnosed) somatic risk as determined by the patient's medical history and clinician's notes, and the patient's self-reported importance of sexual intimacy. RESULTS • Attribution (biomedical vs psychological/unknown) had significant effects on three psycho-affective factors (insecure, arousable, affection); men who attributed their problem to a biomedical cause had higher positive affect and lower insecurity. • Diagnosed somatic risk was significant for insecure and marginally for affection. • Importance of sex was significant on four psycho-affective variables (insecure, arousable, pleasant, affection), with higher endorsement associated with higher insecurity and lower positive affect. CONCLUSIONS • Men who can attribute their sexual dysfunction to a medical condition do much better emotionally (higher positive affect and lower negative affect) than those who attribute the problem to unknown or psychological factors – and this factor is more predictive of their emotionality than the patient's actual somatic risk for sexual dysfunction. • As demonstrated in a previous analysis, higher ratings of the importance of sex independently predicted stronger negative affect for men experiencing sexual problems.

Discharge planning is an integral but ill-defined process in most acute care settings. The time available to a healthcare team to adequately prepare patients for discharge has virtually evaporated with decreasing lengths of hospital stay. A research utilization (RU) team at a tertiary care teaching institution reviewed the literature from 1990 to 2002 in search of a research-based practice regarding staff nurses' roles in the discharge process. Review of the literature revealed varied discharge planning processes using staff nurses, advanced practice nurses, or case managers specifically prepared to implement the discharge planning process. Insufficient evidence was found to support a change from the current staff nurse practice.

// Jules Lin 1 , Amy L. Myers 1 , Zhuwen Wang 1 , Derek J. Nancarrow 1 , Daysha Ferrer-Torres 1 , Amy Handlogten 1 , Kimmy Leverenz 1 , Julia Bao 1 , Dafydd G. Thomas 2 , Thomas D. Wang 3 , Mark B. Orringer 1 , Rishindra M. Reddy 1 , Andrew C. Chang 1 , David G. Beer 1 , Lin Lin 1 1 Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI, USA 2 Department of Pathology, University of Michigan, Ann Arbor, MI, USA 3 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA Correspondence to: Lin Lin, e-mail: linlin@umich.edu David G. Beer, e-mail: dgbeer@umich.edu Keywords: OPN/SPP1 isoforms, co-overexpression, collective function, esophageal adenocarcinoma Received: March 11, 2015 Accepted: May 14, 2015 Published: June 01, 2015 ABSTRACT Esophageal adenocarcinoma (EAC) is often diagnosed at an advanced stage, thus understanding the molecular basis for EAC invasion and metastasis is critical. Here we report that SPP1 /OPN was highly overexpressed in primary EACs and intracellularly localized to tumor cells. We further demonstrate that all known OPN isoforms (OPNa, b, c, 4 and 5) were frequently co-overexpressed in primary EACs. Distinct pro-invasion and dissemination phenotypes of isoform-specific OPNb and OPNc stable transfectants were observed. Expression of OPNb significantly enhanced cell migration and adhesion to laminin. In contrast, OPNc cells showed significantly decreased cell migration yet increased cell detachment. Enhanced invasion, both in vitro and in vivo , was observed for OPNb- but not OPNc-expressing cells. Inhibition of RGD integrins, one family of OPN receptors, attenuated OPNb cell migration, abrogated OPNb cell adhesion and significantly reduced OPNb cell clonogenic survival but did not affect OPNc phenotypes, indicating that OPNb but not OPNc acts through integrin-dependent signaling. Differential expression of vimentin, E-cadherin and β-catenin in OPN stable cells may account for the variation in cell adhesion and detachment between these isoforms. We conclude that while all OPN isoforms are frequently co-overexpressed in primary EACs, isoforms OPNb and OPNc enhance invasion and dissemination through collective yet distinct mechanisms.

Study Type - Therapy (qualitative) Level of Evidence 4 What's known on the subject? and What does the study add? Sexually dysfunctional men report higher negative affect and lower positive affect than sexually functional men. Furthermore, men with sexual problems tend to make internal, self-blaming, attributions for negative sexual events, which can result in a diminished sense of self-efficacy and cause men to expect similar negative outcomes across future sexual situations. This pattern may sustain and actually intensify the sexual problem. This study shows that causal attributions for dysfunctional response influence emotional response to a partnered sexual situation. Specifically, sexually dysfunctional men who attribute their problem to a medical condition do better emotionally than those who attribute the problem to unknown or psychological factors - and this attribution process is a more powerful and reliable predictor of emotional response than the man's actual diagnosed somatic risk for a sexual problem. Furthermore, the study strongly suggests that those men who attribute their problem to a physical/medical issue are able to 'externalize' it - needing to assume less responsibility for and/or control over it, thereby reducing their psychological burden. These findings indicate not only that communication between physician and patient regarding the aetiology of a sexual problem may be critically important but also that, at least for some patients, pharmacological treatment should be combined with strategies that promote the development of internal positive self-serving attributions surrounding sexual activity.To investigate factors that influence sexually dysfunctional men's emotional response within a partnered sexual situation, and, most specifically, whether they attribute their dysfunctional response to a specific biomedical cause vs a psychological or unknown cause.Based on a sample of 59 sexually dysfunctional men visiting a urology clinic, linear regression was used to determine the relationship between patients' attributions and five global affective factors derived through principal components analysis: apprehension, insecure, arousable, affection, and pleasant. Two other covariates were included: actual (diagnosed) somatic risk as determined by the patient's medical history and clinician's notes, and the patient's self-reported importance of sexual intimacy.Attribution (biomedical vs psychological/unknown) had significant effects on three psycho-affective factors (insecure, arousable, affection); men who attributed their problem to a biomedical cause had higher positive affect and lower insecurity. Diagnosed somatic risk was significant for insecure and marginally for affection. Importance of sex was significant on four psycho-affective variables (insecure, arousable, pleasant, affection), with higher endorsement associated with higher insecurity and lower positive affect.Men who can attribute their sexual dysfunction to a medical condition do much better emotionally (higher positive affect and lower negative affect) than those who attribute the problem to unknown or psychological factors - and this factor is more predictive of their emotionality than the patient's actual somatic risk for sexual dysfunction. As demonstrated in a previous analysis, higher ratings of the importance of sex independently predicted stronger negative affect for men experiencing sexual problems.

Despite improved understanding of esophageal adenocarcinoma (EAC) progression and advances in endoscopic surveillance and multimodality treatment, patients commonly present with advanced stage disease and demonstrate resistance to therapy, with complete response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for predicting and overcoming this resistance. IGFBP2 is a member of the IGFBP family of proteins that has been shown to modulate both insulin growth factor (IGF) and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. Because these pathways have been implicated in esophageal cancer growth and progression, we evaluated the functional role of IGFBP2 in EAC tumorigenesis and chemoresistance. High IGFBP2 expression was observed in a subset of EAC patients and was found to be significantly higher in patients with shorter disease-free intervals as well as in treatment-resistant EACs as compared to chemonaive EACs. To evaluate the role of IGFBP2 as a potential modulator of chemoresistance in vitro, IGFBP2-expressing Flo-1 EAC cells were pretreated with siRNA to IGFBP2 while non-expressing OE33 EAC cells were stably-transfected with an IGFBP2 expression construct or pre-treated with exogenous recombinant IGFBP2 followed by 3-day treatment with chemotherapy. All experiments were performed in serum-deprived and serum-replete conditions and were assessed using WST-1 cell proliferation reagent. IGFBP2 siRNA inhibition sensitized Flo-1 cells to cisplatin in the presence of serum but exogenous treatment or ectopic expression of IGFBP2 in OE33 cells did not alter their chemosensitivity. Immunoblot analyses of Flo-1 cells treated with cisplatin showed a dose-dependent reduction in IGFBP2 expression but a dose-dependent induction of ERK and AKT phosphorylation at 24 hours post-treatment. Knockdown of IGFBP2 blocked IGF1 and CDDP-induced ERK activation at 15 minutes and 3-days post-treatment, respectively. In contrast, IGFBP2 knockdown resulted in the activation of AKT and was further enhanced by the addition of IGF1 up to 24 hours post-treatment. In an attempt to augment siIGFBP2-induced CDDP chemosensitization, we pretreated Flo-1 cells with either a MEK1/2 inhibitor, selumetinib or trametinib, or the AKT inhibitor, AKT Inhibitor VIII, in repeat cytotoxicity assays. The MEK1/2 inhibitors increased sensitivity in serum-replete conditions while AKT Inhibitor VIII increased sensitivity in serum-deprived conditions as compared to CDDP alone, IGFBP2 knockdown alone, and the combination of IGFBP2 knockdown and CDDP. These results suggest that targeted modulation of IGFBP2 and either the MAPK or PI3K/AKT signaling pathway in IGFBP2-overexpressing EAC tumors may be an effective approach for sensitizing resistant tumors to standard-of-care chemotherapy treatment options. Citation Format: Amy L. Myers, Lin Lin, Derek J. Nancarrow, Zhuwen Wang, Daysha Ferrer-Torres, David G. Beer, Andrew C. Chang. The functional role of insulin-like growth factor binding protein-2 in esophageal adenocarcinoma chemoresistance. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4440. doi:10.1158/1538-7445.AM2015-4440

Objective: The incidence of esophageal adenocarcinoma (EAC) has increased over 300% in the past decades in western countries. EAC is characterized by an early metastasis, with a 5-year survival rate of only 19%, making the identification of clinically-targetable proteins critical for improving patient outcome. Osteopontin (SPP1/OPN) is a secreted glycosylated phosphoprotein that is found overexpressed in many cancer types including EAC. OPN protein functions in cell adhesion and cell migration by regulating cell-matrix interactions and cellular signaling through binding with integrin and CD44 receptors. However, little is known about the role of OPN in EAC invasion and metastasis. Methods: We analyzed the OPN gene expression in a series of 46 esophageal samples including esophageal Barrett's, low-grade dysplasia, high-grade dysplasia and adenocarcinomas mRNA using Affymetrix U133A arrays. Real-time RT-PCR was performed to validate array results and examine a larger cohort of 130 EAC samples. Tissue microarrays (TMA) were made containing 64 EACs, eight lymph node metastases, eight dysplastic and 11 none dysplastic Barrett's mucosa sections from 59 patients. Primers flanking the potential gene alternative splice regions were designed and the in-frame transcript variants were sequenced. Expression of OPN in EAC cell lines was analyzed using RT-PCR and western blot analysis. Ectopic OPN expression of splice variants and OPN knockdown in EAC cell lines have been performed to examine its roles in tumor invasion and EMT assays. Results: OPN is highly overexpressed in EAC and overexpression of the gene is associated with poorer survival in patients. Three OPN splice variants were identified with their expression either proportionally increased or differentially expressed in the primary EAC and EAC-derived cells. Highly overexpressed OPN is a transcriptional event as no OPN gene amplification was found in the corresponding EACs. In addition, abundant OPN protein was found primarily in tumor cells in the tissue sections using immunohistochemical (IHC)-TMA assays. OPN variants differ in their N-terminal thrombin fragment with either exon 6 or 5 being absent in OPN-b or OPN-c, respectively. We found that EAC cells treated with the medium containing different OPN variants demonstrated distinctive morphological phenotypes. We further identified that OPN variants played different roles in tumor cell proliferation, epithelial-mesenchymal transition (EMT), and chemosensitivity. Conclusion: Upregulation of OPN is predominant event in primary EACs and associated with poorer survival in patients. The alternative splice variants demonstrate differential tumor invasion, EMT transition and chemosensitivity in EAC cells. Citation Format: Zhuwen Wang, Kimmy Leverenz, Dafydd G. Thomas, Amy L. Myers, Andrew C. Chang, Mark B. Orringer, Thomas J. Giordano, Jules Lin, David G. Beer, Lin Lin. Osteopontin (SPP1/OPN) alternative splice variants and metastatic potential in esophageal adenocarcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3879. doi:10.1158/1538-7445.AM2013-3879