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Background The outcome focus for survivors of critical care has shifted from mortality to patient-centered outcomes. Multidimensional outcome assessments performed in critically ill patients typically exclude those with primary neurological injuries. Objective To determine the feasibility of measurements of physical function, cognition, and quality of life in patients requiring neurocritical care. Methods This evaluation of a quality improvement initiative involved all patients admitted to the neuroscience intensive care unit at the University of Cincinnati Medical Center. Interventions Telephone assessments of physical function (Glasgow Outcome Scale-Extended and modified Rankin Scale scores), cognition (modified Telephone Interview for Cognitive Status), and quality of life (5-level EQ-5D) were conducted between 3 and 6 months after admission. Results During the 2-week pilot phase, the authors contacted and completed data entry for all patients admitted to the neuroscience intensive care unit over a 2-week period in approximately 11 hours. During the 18-month implementation phase, the authors followed 1324 patients at a mean (SD) time of 4.4 (0.8) months after admission. Mortality at follow-up was 38.9%; 74.8% of these patients underwent withdrawal of care. The overall loss to follow-up rate was 23.6%. Among all patients contacted, 94% were available by the second attempt to interview them by telephone. Conclusions Obtaining multidimensional outcome assessments by telephone across a diverse population of neurocritically ill patients was feasible and efficient. The sample was similar to those in other cohort studies in the neurocritical care population, and the loss to follow-up rate was comparable with that of the general critical care population.

In this manuscript, we present an experimental setup capable to extract main electrical parameters and thermal effects from semiconductor devices within a range of temperatures from 300 K down to 350 mK. Key aspects of the system such as sample holder design and wire material selection, are discussed. One of the most critical design limitations is the maximum thermal power handling, since at sub-Kelvin temperatures the cooling power is limited by a3He4He fridge. The largest amount of heat transferred into the system comes from the electrical wiring, is reduced by the combined use of Copper and Manganin wires. This way we reach an optimized balance between electrical resistance and heat conduction. Therefore we ensure the DUT reaches the Ultra-Cold Stage (UCS) temperature while the electrical measurements are minimally affected by the electrical resistance. Under this condition the cryogenic system allows a reliable electrical characterization of a 14 nm SOI p-FinFET down to 350 mK.

Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Development Co., Shenzhen, China]), TomoTherapy® (Tomo [Accuray Inc., Sunnyvale, CA]), and CyberKnife® (CK [Accuray Inc.]). All plans were retrospectively reviewed to establish the maximum distance (MaxDis) from the prescription dose to the end of the dural tail and the minimum dose at the dural tail (MinDoseT) at this point. We also established the midpoint distance (MPDis) from the prescription dose to MaxDis and the dose at this point (MPDose). Plans were further distinguished when the physician intended to cover the dural tail versus when not. Patients and tumor response were assessed by imaging and clinical and phone call evaluations. Results Of the 143 patients, 81 were treated using Gamma, 34 using Tomo, and 28 using CK. Eighty patients were eligible for follow-up, of whom 58 (72.5%) had an unmistakable dural tail sign. Median follow-up was 1,118 days (range 189-3,496), mean age was 54.5 (range 19-90), and 61 were women, and 19 were men. Overall tumor volume was 6.5 cc (range 0.2-59); mean tumor volumes by different platforms were 2.4, 9.45, and 8 cc; dose prescribed and mean tumor coverage were 14 Gy and 92%, 14.5 Gy and 95%, and 14 Gy and 95.75% with Gamma, Tomo, and CK, respectively. The dural tail was drawn and planned with an attempt to treat in 18 patients (31%); the mean MaxDis, MinDoseT, MPDis, and MPDose were 9.0 mm, 2 Gy, 4.5 mm, and 10.6 Gy, respectively. At last follow-up, tumor control was achieved in 96% of patients for the whole series, and there were no statistical variations regarding tumor volume, dose, conformality, or control when stereotactic radiosurgery was used to cover the dural tail versus when it was not (p=0.105). One patient experienced a Grade 4 Radiation Therapy Oncology Group toxicity as an adverse radiation effect that required surgery, and 11 (7.6%) experienced a Grade 1 toxicity. Conclusions This is our preliminary report regarding the efficacy of radiosurgery for meningiomas using diverse platforms at three years of follow-up; the results regarding tumor control are in accordance with the published literature as of this writing. A conscious pursuit of the dural tail with the prescription dose has not proven to provide better tumor control than not doing so - even small areas of the tumor uncovered by the prescription dose did not alter tumor control at current follow-up. The doses delivered to these uncovered areas are quite significant; further follow-up is necessary to validate these findings.

INTRODUCTION: A qualitative assessment of discharge resource needs is important for developing evidence-based care improvements in neurocritically ill patients. We hypothesized that standardized, open-ended assessments of patients or caregivers after neurocritical care would result in themes that reflect post-intensive care concerns. METHODS: We conducted a quality improvement initiative at an academic hospital and included all patients admitted to the Neurosciences Intensive Care Unit (NSICU) over an 18-month period. Telephone assessments were made at 3–6 months following admission. Patients or caregivers were asked if they had adequate resources upon discharge and if they had any unanswered questions. The content of responses was reviewed by a neurointensivist and neurocritical care nurse practitioner. A structured codebook was developed, organized into themes, and applied to the responses. RESULTS: 61 patients or caregivers responded regarding access to resources at discharge with 114 individual codable responses. Responses centered around five themes with 23 unique codes: satisfied, needs improvement, dissatisfied, poor post ICU care, and poor health. The most frequently coded responses were that caregivers believed their loved one had experienced an unclear discharge (n=11) or premature discharge (n=12). 204 patients or caregivers responded regarding unanswered questions or additional comments at follow-up, with 516 codable responses. These centered around six themes with 26 unique codes: positive experience, negative experience, neutral experience, medical questions, ongoing medical care or concern, or remembrance of time spent in the ICU. The most frequent response was that caregivers or patients stated that they received good care (n= 115). Multiple concerns were brought up, including lack of follow-up after hospitalization (n=15), and dissatisfaction with post-ICU care (n=15). CONCLUSIONS: Obtaining qualitative responses after discharge provided insight into the transition from critical care. This could form the basis for an intervention to provide a smoother transition from the ICU to the outpatient setting.

The emergence of drug resistance is a major obstacle for the success of targeted therapy in melanoma. Additionally, conventional chemotherapy has not been effective as drug-resistant cells escape lethal DNA damage effects by inducing growth arrest commonly referred to as cellular dormancy. We present a therapeutic strategy termed "targeted chemotherapy" by depleting protein phosphatase 2A (PP2A) or its inhibition using a small molecule inhibitor (1,10-phenanthroline-5,6-dione [phendione]) in drug-resistant melanoma. Targeted chemotherapy induces the DNA damage response without causing DNA breaks or allowing cellular dormancy. Phendione treatment reduces tumor growth of BRAFV600E-driven melanoma patient-derived xenografts (PDX) and diminishes growth of NRASQ61R-driven melanoma, a cancer with no effective therapy. Remarkably, phendione treatment inhibits the acquisition of resistance to BRAF inhibition in BRAFV600E PDX highlighting its effectiveness in combating the advent of drug resistance. ispartof: Genes and Development vol:34 issue:9-10 pages:637-649 ispartof: location:United States status: published

Introduction We report our initial series of patients treated with radiosurgery to the Centromedian (CM) and Parafascicular (Pfc) Complex (CM-Pf) of the contralateral thalamus mainly for trigeminal neuralgia that had failed most known forms of conventional treatments. The coordinates were co-registered to a three-dimensional atlas of the thalamus in order to have a better comprehension of isodose curves distribution. Methods A fully automated rotating gamma ray unit was used to deliver a high dose of radiation (140 Gy) using a 4-mm collimator to the CM-Pf of the contralateral thalamus in 14 patients suffering from refractory trigeminal pain and other complex pain syndromes. The best stereotactic coordinates were plotted in a thalamic three-dimensional atlas space along with isodose curves corresponding to 50% of the dose prescription and the dose gradient. Results From November 2016 to July 2019, 14 patients experiencing severe forms of different pain syndromes were treated, and 10 were eligible for follow-up evaluation. Pain deriving from trigeminal neuralgia was present in the majority (80%) of patients and from other complex pain syndromes in the rest (20%). Median follow-up was 384 days (range: 30-994). The Visual Analogue Scale (VAS) score before treatment was 9 (range: 7-10) and standardized to 10. Before treatment, all the patients had a Barrow Neurological Institute Pain Scale (BNI) of 5 (V). The median years suffering from pain was 4.5 years (range: 1-15), the number of procedures including radiosurgery to the trigeminal nerve before thalamotomy was four (range: 1-10). Most patients (90%) reported some form of relief, the average VAS at the time of response was 3.5 (range: 0-9), and the average time to response was 67.3 days (range: 2-210). The neuromodulation effect of radiation was seen in 60% of patients. The average BNI score at response was 2.7 (range: 1-5). The final VAS score at last follow-up was 5.5 (range: 0-10) in six patients. In four patients (40%), the procedure had failed with a final BNI of IV, and V, three patients (30%) had excellent response (BNI of I), and three patients (30%) had worthwhile results with BNI of IIIa and IIIb. The total success rate (BNI of I to IIIb) was 60%, and the number of patients experiencing more than 50% of pain reduction at final follow-up was five (50%). Excluding both patients that were treated for pain outside of trigeminal neuralgia, 75% of the patients responded. The best coordinates on average were X: 5.5 mm from the thalamic border, Y: 3.7 mm anterior to the posterior commissure, and Z: 3.7 mm from the intercomissural line. There were no complications to report. Conclusion Radiosurgery to the CM-Pf of the thalamus was demonstrated to be a safe and relatively effective alternative to treat refractory trigeminal neuralgia. Further studies are needed to optimize target dimensions based on the three-dimensional studies of isodose curves as well as coordinates. Longer follow-up is necessary to evaluate recurrence rates that could not be reached.

Background Deep brain stimulation and levodopatherapy ameliorate motor manifestations in Parkinson's disease, but their effects on axial signs are not sustained in the long term. Objectives The objective of this study was to investigate the safety and efficacy of spinal cord stimulation on gait disturbance in advanced Parkinson's disease. Methods A total of 4 Parkinson's disease patients who experienced significant postural instability and gait disturbance years after chronic subthalamic stimulation were treated with spinal cord stimulation at 300 Hz. Timed-Up-GO and 20-meter-walk tests, UPDRS III, freezing of gait questionnaire, and quality-of-life scores were measured at 6 months and compared to baseline values. Blinded assessments to measure performance in the Timed-Up-GO and 20-meter-walk tests were carried out during sham stimulation at 300 Hz and 60 Hz. Results Patients treated with spinal cord stimulation had approximately 50% to 65% improvement in gait measurements and 35% to 45% in UPDRS III and quality-of-life scores. During blinded evaluations, significant improvements in the Timed-Up-GO and 20-meter-walk tests were only recorded at 300 Hz. Conclusion Spinal cord stimulation at 300 Hz was well tolerated and led to a significant improvement in gait. © 2016 International Parkinson and Movement Disorder Society.

A gradual decline in insulin response is known to precede the onset of type 1 diabetes (T1D). To track age-related changes in the β-cell function of nonobese diabetic (NOD) mice, the most commonly used animal model for T1D, and to establish differences between those who do and do not become hyperglycemic, we performed a long-term longitudinal oral glucose tolerance test (OGTT) study (10-42 weeks) in combination with immunofluorescence imaging of islet morphology and cell proliferation. We observed a clear biphasic decline in insulin secretion (AUC0-30 min ) even in euglycemic animals. A first phase (10-28 weeks) consisted of a relatively rapid decline and paralleled diabetes development in the same cohort of animals. This was followed by a second phase (29-42 weeks) during which insulin secretion declined much slower while no additional animals became diabetic. Blood glucose profiles showed a corresponding, but less pronounced change: the area under the concentration curve (AUC0-150 min ) increased with age, and fit with a bilinear model indicated a rate-change in the trendline around 28 weeks. In control NOD scids, no such changes were observed. Islet morphology also changed with age as islets become surrounded by mononuclear infiltrates, and, in all mice, islets with immune cell infiltration around them showed increased β-cell proliferation. In conclusion, insulin secretion declines in a biphasic manner in all NOD mice. This trend, as well as increased β-cell proliferation, is present even in the NODs that never become diabetic, whereas, it is absent in control NOD scid mice.

The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.

Fluorescein angiography provides useful images of the retinal vessels in most instances, but choroidal vessel assessment may be hindered because of inherent properties of fluorescein (i.e., rapid difussion through the choriocapillaris and blockage by pigments like xanthophylle, melanin or hemoglobin).

Cervical cancer represents the second most common cancer in women worldwide. About 90% of cervical cancer contain high-risk human papillomavirus (HPV) DNA, most often HPV type 16. Animal models and mostly laboratory mice are excellent for carrying out diverse immunological studies. We transfected a fibroblast cell line, 3T3-A31, with human papillomavirus type 16 genome to develop an in vivo/in vitro malignant transformant model. Isolated clones inoculated to immunocompetent mice displayed a tumorigenic phenotype. Small clusters of metastatic cells were found in the liver of animal 45 days after receiving the inoculum. Integrated viral DNA and expression of E7 viral oncogene from the high-risk HPV-16 were demonstrated both in transfectans and tumor-derived cells. The observed high-grade neovascularization was correlated with the upregulation of vascular endothelial growth factor (VEGF) mRNA on HPV-16 transformed fibroblast cells. These observations emphasize the association between papillomavirus expression and progression to malignancy.

Introduction: We describe for the first time, a novel chromosomal translocation in AML. The cells bearing this translocation proliferated rapidly following stimulation with ATRA in vitro. A 30-year old woman presented with monocytic AML. Karyotype revealed: 46,XX,t(9;11)(p22;q23)[13]/46,XX[7]. Mutational analysis showed an activating mutation in NRAS (c.34G>A; p.G12S). She achieved remission with standard induction therapy followed by cytarabine consolidation in the absence of an optimal donor. Following a disease free interval of 8 months, she relapsed. Karyotype at relapse: 46,XX,t(4;15)(q31;q22),t(9;11)(p22;q23)[20] (Figure 1). Mutational analysis revealed no new mutations. In the setting of chemotherapy refractory disease, she was enrolled on a phase I clinical trial combining escalating doses of TCP (tranylcypromine, Parnate¨) with fixed doses of ATRA (NCT02273102). The patient died from rapid disease progression shortly after her first cycle of therapy. Unexpectedly, we observed a rapid proliferation in the patient's blasts following treatment with ATRA in vitro. We hypothesized that the novel t(4;15) translocation was involved in the regulation of retinoic acid (RA) signaling, and may have contributed to the rapid disease progression observed in this patient when she was treated with ATRA. To this end, we fully characterized the fusion gene and created a cell line bearing the translocation. Using these cells, we will further elucidate the mechanisms accounting for a rare and potentially clinically relevant effect of ATRA, in vitro. Methods: Cytogenetics and molecular-cytogenetic techniques, next generation sequencing (WES), RNA-seq, RT-PCR, and direct Sanger sequencing were used to map the chromosomal translocation. Cell proliferation and Annexin V apoptosis assays were used to test the effects of ATRA and various retinoic acid receptor (RAR) agonists and antagonists in vitro. Cells were treated with ATRA, RARα, and RARγ agonists and antagonists for 72 h and cell proliferation and apoptosis were measured with CellTiter-Glow (Promega)¨ luminescence viability assay and Annexin V/PI staining (FACS), respectively. Results: We mapped the t(4;15)(q31;q22) at the single nucleotide level, and discovered a novel fusion of TMEM154 (4q31.3) and RASGRF1 (15q24.2) genes at both the DNA and RNA level. The fusion protein included exons 1-6 from TMEM154 and exons 15-24 from RASGRF1. RASGRF1 (Ras protein specific nucleotide releasing factor 1) activates Ras by catalyzing the exchange of Ras-bound GDP for GTP. We determined that TMEM154 (transmembrane protein 154) is regulated by RA based on gene expression profiling. This particular translocation appears to result in a proliferative advantage in AML cells treated with RAR agonists such as ATRA, even at physiological levels (10 nM) (Figure 2). In MLL-rearranged cell lines without t(4;15), ATRA has a neutral or anti-proliferative effect, suggesting that the t(4;15) product interacts with the RA pathway to induce proliferation of AML blasts. We hypothesize that by increasing expression of TMEM154-RASGRF1, ATRA drives proliferation through Ras signaling. Of note, RAR antagonists inhibited proliferation and induced cell death (Figure 2). Also, treating the cells with MAP Kinase and Ras inhibitors consistently diminished the proliferative effect of ATRA. Updated studies shedding light on the mechanism of interaction between RA signaling and the TMEM154-RASGRF1 fusion protein will be presented. Conclusions: Our study for the first time identifies t(4;15) as a novel and pathogenic translocation in AML. This rare event may confer a proliferative advantage in the presence of ATRA and caution is advised should patients with this lesion be considered for treatment with ATRA. Figure 1 Conventional karyotyping showing 46,XX,t(4;15)(q31;q22),t(9;11)(p22;q23).Chromosome analysis was performed on 20 G-banded metaphase cells from multiple unstimulated cultures. Both translocations were present in all cells examined. Figure 1. Conventional karyotyping showing 46,XX,t(4;15)(q31;q22),t(9;11)(p22;q23).Chromosome analysis was performed on 20 G-banded metaphase cells from multiple unstimulated cultures. Both translocations were present in all cells examined. Figure 2 ATRA and other RAR agonists increased proliferation in t(4;15) AML cells. Primary cells from a patient with t(4;15) AML were treated with ATRA, RARα (AM80 and 195183), and RARγ (205327) agonists, and RARα (196996), RARγ (205728) and dual (194310) antagonists. Cell proliferation was determined by CellTiter-Glo¨ luminescent cell viability assay (Promega) after 72 h of treatment. Figure 2. ATRA and other RAR agonists increased proliferation in t(4;15) AML cells. Primary cells from a patient with t(4;15) AML were treated with ATRA, RARα (AM80 and 195183), and RARγ (205327) agonists, and RARα (196996), RARγ (205728) and dual (194310) antagonists. Cell proliferation was determined by CellTiter-Glo¨ luminescent cell viability assay (Promega) after 72 h of treatment. Disclosures No relevant conflicts of interest to declare.

We have reported that interferon-alpha inhibits HPV-18 mRNA in HeLa cells. Here we examine mechanisms by which IFN could modulate HPV expression. In northern blot experiments, we observed that interferon-alpha 2b treatment reduced HPV-18 mRNA levels in a time- and dose-dependent manner, with a maximal effect achieved at 48 h. Simultaneously, induction of 2-5A synthetase mRNA was verified as indicative of IFN action. The IFN regulatory effect on HPV-18 mRNA at 48 h required de novo protein synthesis. We performed run-on experiments to determine whether the IFN regulatory effect was at the transcriptional level. HPV-18 endogenous transcription was repressed using 200 and 1000 IU/ml. Interferon treatment did not affect HPV-18 mRNA stability, at least under our experimental conditions. To verify whether HPV-18 enhancer sequences were involved in the interferon effect, we transfected a construct containing the chloramphenicol acetyltransferase driven by the HPV-18 upstream regulatory region. The enzyme activity was unmodified on human keratinocytes and HeLa cells by interferon exposition. Our data demonstrate that interferon-alpha downregulates HPV-18 mRNA levels on HeLa cells by repressing nascent viral transcripts, possibly through regulatory cellular flanking regions.

Breast cancer is the second leading cause of death by cancer in women in the United States. The occurrence of high numbers of macrophages in the tumor stroma has been associated with tumor progression and poor prognosis in breast and other solid malignancies. However, macrophage numbers in tumors have not been validated as a prognostic factor in clinical practice. The present analysis was designed as a pilot study aimed at determining whether the presence of CD68+ macrophages is an independent prognostic factor in small T1 estrogen receptor (ER)+ breast cancers across three different ethnic groups, i.e. African-American, Latina and Caucasian women. A retrospective pilot analysis of 30 T1 breast cancer cases encompassing these three ethnic groups was carried out. African-American and Latina women present with less incidence but more aggressive breast cancer disease and, therefore, proportionally higher death rates. Using immuno-histochemistry, we sought to identify whether there was any association between the presence and density of CD68+ macrophages and standard prognostic markers with overall survival in these groups. Our data revealed that overall survival did not differ significantly for the occurrence or density of CD68+ macrophages in T1 ER+ tumors. There were also no significant differences in overall survival for the occurrence of CD68+ macrophages across ethnicities, although macrophage numbers were significantly higher in tumors from African-American and Latina than in Caucasian patients. Importantly, but not surprisingly, the absence of the progesterone receptor was associated very strongly with decreased overall survival. This pilot project shows that CD68+ macrophages are not pivotal in determining tumor prognosis in early T1 breast cancers. New studies are presently being conducted to assess the value of different macrophage markers and macrophage activation profiles as prognostic factors in breast cancers of different clinical stages, using a larger number of patients among these three different ethnicities.

Breast cancer is the second leading cause of death by cancer in women in the United States. The occurrence of high numbers of macrophages in the tumor stroma has been associated with tumor progression and poor prognosis in breast and other solid malignances. However, macrophage numbers in tumors have not been validated as a prognostic factor in clinical practice. The present analysis was designed as a pilot study aimed at determining whether the presence of CD68+ macrophages is an independent prognostic factor in small T1 ER+ breast cancers across three different ethnic groups, i.e. African American, Latinas and Caucasian women. A retrospective pilot analysis of 30 T1 breast cancers cases encompassing these three ethnic groups was carried out. African American and Latina women present with less incidence but more aggressive breast cancer disease and therefore proportionally higher death rates. Using immunohistochemistry, we sought to find out whether there was any association between the presence and density of CD68+ macrophages and standard prognostic markers with overall survival in these groups. Our data showed that overall survival did not differ significantly for the occurrence or density of CD68+ macrophages in T1 ER+ tumors. There were also no significant differences in overall survival for the occurrence of CD68+ macrophages across ethnicities, although macrophage numbers were significantly higher in tumors from African American and Latinas than in Caucasian patients. Interestingly but not surprisingly, the absence of PR associated very strongly with decreased overall survival. This pilot project shows that CD68+ macrophages are not pivotal in determining tumor prognosis in early T1 breast cancers. New studies are presently being conducted to assess the value of different macrophage markers and macrophage activation profiles as prognostic factors in breast cancers of different clinical stages, using a larger number of patients among these three different ethnicities. Citation Format: Roberto Carrio, Tulay Koru-Sengul, Feng Miao, Stefan Gluck, Omar Lopez, Yamil Selman, Consuelo Alvarez, Clara Milikowski, Carmen Gomez, Merce Jorda, Mehrad Nadji, Marta Torroella-Kouri. Macrophages as independent prognostic factors in small T1 breast cancers. [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 3456. doi:10.1158/1538-7445.AM2013-3456