tbuckley/cabot-search huggingface dataset:
Abstract 100: Novel selective PI3Kγ inhibitor AZD3458 promotes anti-tumor immune responses and reverts resistance to immunotherapy in checkpoint blockade refractory preclinical models
Authors: Larissa S. Carnevalli, Danielle Carrol, Michele Moschetta, Pablo Morentin Gutierrez, Cristina Gardelli, Molly A. Taylor, Antonio Montoya, Adina Hughes, Matthew King, Teresa Klinowska, Simon T. Barry
Journal: Cancer Research (2019)

Abstract The PI3Kγ isoform is a key regulator of immune cell proliferation, survival, migration and activation. PI3Kγ inhibitors have the potential to treat a variety of diseases including respiratory, inflammatory, metabolic disorders and cancer. In the context of cancer PI3Kγ inhibition re-polarizes macrophages to an immuno-stimulatory phenotype activating a T-cell mediated tumor immune response. Selective PI3Kγ inhibitors have potential as monotherapy and in combination with checkpoint inhibition to overcome resistance and to enhance efficacy of checkpoint inhibitors. AZD3458 is a highly selective PI3Kγ clinical candidate kinase inhibitor with a cellular IC50 of 8nM with a 100-fold selectivity over PI3Kδ. In vitro, AZD3458 inhibits pAKTS308/S473 in human macrophages and mouse CD11b activation at 32nM and 30nM free IC50, respectively. At these concentrations AZD3458 reverses macrophage polarization increasing IL12/IL-10 ratio and does not impact T cell proliferation and function analysed by gene expression profiling, cytokine quantification and flow cytometry. Oral administration of AZD3458 (20mg/Kg BID) remodeled the tumor microenvironment in 4T1 orthotopic breast tumor model. AZD3458 decreased tumor associated macrophages by 20% compared to vehicle and reduced overall protein expression of immunosuppressive markers CD206 and PD-L1 measured by flow cytometry. In addition, AZD3458 reduced MDSC/neutrophil activation and promoted cytotoxic T-cell activation in vivo, measured by GzmB and Perforin mRNA and protein expression. Consistent to the observed tumor remodeling, combination with checkpoint inhibitors α-PD-1 or α-PD-L1 antibodies (10mg/kg 3x week) had greater anti-tumor effects than checkpoint inhibitor alone in 4T1, LLC, CT-26 and MC-38 mouse syngeneic models. These data demonstrate that AZD3458 can reverse myeloid suppressive tumor microenvironment and revert tumor resistance to immunotherapy in myeloid-enriched immunosuppressive tumor types. Citation Format: Larissa S. Carnevalli, Danielle Carrol, Michele Moschetta, Pablo Morentin Gutierrez, Cristina Gardelli, Molly A. Taylor, Antonio Montoya, Adina Hughes, Matthew King, Teresa Klinowska, Simon T. Barry. Novel selective PI3Kγ inhibitor AZD3458 promotes anti-tumor immune responses and reverts resistance to immunotherapy in checkpoint blockade refractory preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 100.
The role of sidedness in second-line therapy for RAS wild-type colorectal cancer: a network meta-analysis (NMA)
Authors: D. Basile, G. Pelizzari, P. Di Nardo, C. Corvaja, E. Ongaro, S. Garattini, L. Gerratana, C. Lisanti, B. Michele, L. Bortot, S. Buriolla, M. Garutti, G. Curtolo, M. Bonotto, L. Da Ros, E. Torrisi, G. Miolo, G. Cardellino, N. Pella, A. Buonadonna, G. Aprile, F. Puglisi
Journal: Annals of Oncology (2019)
A case of reassortant seasonal influenza A(H1N2) virus, Denmark, April 2019
Authors: Ramona Trebbien, Anders Koch, Lene Nielsen, Dår Kristian Kur, Pontus Westerström, Tyra Grove Krause
Journal: Eurosurveillance (2019)

A reassortant influenza A subtype H1N2 virus with gene segments from seasonal A(H1N1)pdm09 virus (HA, MP, NP, NS, PA, PB1 and PB2) and seasonal A(H3N2) virus (NA) was identified in a routine surveillance sample in Denmark. The patient recovered fully. This is the second reassortant influenza A(H1N2) virus identified in Europe in the 2018/19 influenza season, with the first case being detected December 2018 in Sweden.
Efficacy and safety of the randomized, open-label, non-inferiority, phase 3 study of subcutaneous (SC) versus intravenous (IV) daratumumab (DARA) administration in patients (pts) with relapsed or refractory multiple myeloma (RRMM): COLUMBA.
Authors: Maria-Victoria Mateos, Hareth Nahi, Wojciech Legiec, Sebastian Grosicki, Vladimir Vorobyev, Ivan Spicka, Vania TM Hungria, Sibirina Korenkova, Nizar J. Bahlis, Max Flogegard, Joan Blade, Philippe Moreau, Martin Kaiser, Shinsuke Iida, Jacob Laubach, Tahamtan Ahmadi, Dolly A. Parasrampuria, Lixian Peng, Ming Qi, Saad Zafar Usmani
Journal: Journal of Clinical Oncology (2019)

8005 Background: In a phase 1b trial, a SC formulation of DARA with recombinant human hyaluronidase PH20 (rHuPH20; ENHANZE drug delivery technology, Halozyme, Inc.) had adequate PK, low rates of infusion-related reactions (IRRs) and similar efficacy to DARA IV. This phase 3 study compared the efficacy, PK, and safety of DARA SC vs IV in pts with RRMM. Methods: DARA SC (1,800 mg DARA + rHuPH20 [2,000 U/mL]) and DARA IV (16 mg/kg IV) were given weekly for C1-2 (28-day cycles), every 2 weeks for C3-6, and every 4 weeks thereafter. DARA SC (15 mL) was given over 3-5 mins at alternating left/right abdominal sites. Pts (≥18 years) must have received ≥3 prior lines of therapy (LOT), including a PI and an IMiD, or were double refractory. Co-primary endpoints were ORR (analyzed by Farrington-Manning test, with non-inferiority = 60% retention of ORR) and pre-dose C3D1 DARA C trough (non-inferiority = lower bound of 90% CI for the ratio of the geometric means [GM] ≥80%). Results: 522 pts were randomized (n=263 SC; n=259 IV). Median age was 67 yrs. Median baseline body weight was 73 kg. Pts received a median of 4 LOT and 100% had received both PI and IMiD; 17% had high cytogenetic risk at baseline. Median follow-up was 7.5 mos. ORR was 41% for DARA SC and 37% for DARA IV. DARA SC retained at least 89% of the benefit of DARA IV (97.5% confidence). The ratio of GM of C trough for DARA SC over DARA IV was 108% (90% CI, 96%-122%). A significantly lower rate of IRRs was observed with DARA SC vs DARA IV (12.7% vs 34.5%; P&lt;0.0001). Median duration of injection was 5 mins for DARA SC and median duration of infusion was 421/255/205 mins for the first/second/subsequent DARA IV infusions. Median PFS was 5.6 mos DARA SC vs 6.1 mos DARA IV (HR, 0.99; 95% CI, 0.78-1.26). Most common TEAEs (≥15%) were anemia, neutropenia, thrombocytopenia, and diarrhea. Primary reasons for treatment discontinuation included progressive disease (43% SC vs 44% IV) and AEs (7% SC vs 8% IV). Conclusions: Efficacy and PK co-primary endpoints were met, demonstrating non-inferiority of DARA SC to IV. DARA SC significantly decreased IRR rate and administration time, with a comparable safety profile to DARA IV. Clinical trial information: NCT03277105.
Oxaliplatin-based chemotherapy in patients aged at least 75 years with metastatic colorectal cancer: a post-hoc subgroup analysis if three phase II studies
Authors: G. Rosati, S. Cordio, G. Reggiardo, G. Aprile, A. Butera, A. Avallone, A. Tucci, G. Novello, G. Blanco, G. Caputo, D. Bilancia, R. Bordonaro
Journal: Annals of Oncology (2019)
Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study
Authors: Monika Brüggemann, Michaela Kotrová, Henrik Knecht, Jack Bartram, Myriam Boudjogrha, Vojtech Bystry, Grazia Fazio, Eva Froňková, Mathieu Giraud, Andrea Grioni, Jeremy Hancock, Dietrich Herrmann, Cristina Jiménez, Adam Krejci, John Moppett, Tomas Reigl, Mikael Salson, Blanca Scheijen, Martin Schwarz, Simona Songia, Michael Svaton, Jacques J. M. van Dongen, Patrick Villarese, Stephanie Wakeman, Gary Wright, Giovanni Cazzaniga, Frédéric Davi, Ramón García-Sanz, David Gonzalez, Patricia J. T. A. Groenen, Michael Hummel, Elizabeth A. Macintyre, Kostas Stamatopoulos, Christiane Pott, Jan Trka, Nikos Darzentas, Anton W. Langerak
Journal: Leukemia (2019)

Amplicon-based next-generation sequencing (NGS) of immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements for clonality assessment, marker identification and quantification of minimal residual disease (MRD) in lymphoid neoplasms has been the focus of intense research, development and application. However, standardization and validation in a scientifically controlled multicentre setting is still lacking. Therefore, IG/TR assay development and design, including bioinformatics, was performed within the EuroClonality-NGS working group and validated for MRD marker identification in acute lymphoblastic leukaemia (ALL). Five EuroMRD ALL reference laboratories performed IG/TR NGS in 50 diagnostic ALL samples, and compared results with those generated through routine IG/TR Sanger sequencing. A central polytarget quality control (cPT-QC) was used to monitor primer performance, and a central in-tube quality control (cIT-QC) was spiked into each sample as a library-specific quality control and calibrator. NGS identified 259 (average 5.2/sample, range 0-14) clonal sequences vs. Sanger-sequencing 248 (average 5.0/sample, range 0-14). NGS primers covered possible IG/TR rearrangement types more completely compared with local multiplex PCR sets and enabled sequencing of bi-allelic rearrangements and weak PCR products. The cPT-QC showed high reproducibility across all laboratories. These validated and reproducible quality-controlled EuroClonality-NGS assays can be used for standardized NGS-based identification of IG/TR markers in lymphoid malignancies.
ESA use in women with cancer: Consequences of the 2008 FDA clinical alert.
Authors: Kimberly M. Dickinson, Bachir Joseph Sakr
Journal: Journal of Clinical Oncology (2012)

5040 Background: Erythropoietin stimulating agents (ESA) are used clinically as an alternative to blood transfusions in cancer patients suffering from symptoms of anemia. However, more recent randomized controlled trials of ESA usage concluded that its use is associated with an increased risk of tumor progression and death. As a result, in July 2008 the FDA issued a clinical alert restricting the use of ESA. A reduction in the prescribing of ESA was immediately seen but changes in blood transfusion rates have not been examined. Methods: A retrospective chart review was conducted drawing from patients under treatment in the Program in Women’s Oncology at Women and Infant’s Hospital from one year before the clinical alert (August 2007-July 2008) to one year afterward (August 2008-July 2009). The primary outcomes were blood transfusion and ESA administration rates compared across the two time periods. Results: The study population (n=776) included patients with a cancer diagnosis who received chemotherapy during one or both time periods. 165 (21.3%) patients received ESA treatment. The total number of ESA treatments administered in the study period of interest was 1,277, with the majority (60%) given prior to the FDA alert. The mean number of ESA treatments in the first time period was 6.39 per person as compared to 0.61 per person in the second time period. Of the study population, 186 (23.8%) patients received at least one blood transfusion. A total of 463 blood transfusions were administered during the entire study period but a significant difference was not observed in the proportion of those delivered prior to the FDA alert (52%) versus after the FDA alert (48%). The average number of transfusions given in the first time period was 2.34 per person, as compared to 2.17 per person in the second period. Conclusions: Our results indicate that despite a steep decline in the use of ESA for chemotherapy-induced anemia, blood transfusion rates were not significantly different between the two periods. Interestingly, a slight downward trend was observed from before the FDA alert to after the alert. While more work is needed to understand the implications of these findings, it suggests that resource utilization did not increase despite the reduction in ESA use.
Abstract LB-172: Understanding the mechanism underlying vitamin D and prostate cancer: Exploring telomere length
Authors: Jacqueline M. Major, Barry I. Graubard, Stephanie J. Weinstein, Jeeyun Kim, Immaculata De Vivo, Jarmo Virtamo, Sharon A. Savage, Demetrius Albanes
Journal: Cancer Research (2019)

Abstract Background: In an effort to understand the molecular mechanism behind the association between circulating vitamin D and prostate cancer, we measured relative telomere length and 25(OH)D levels in a cohort of older Finnish men. Methods: Using a nested study design, we examined quantitative PCR measured telomere length, season-adjusted serum 25-hydroxyvitamin D [25(OH)D], and subsequent prostate cancer risk in 1000 men (n=500 cases, 500 matched controls) participating in the extension study of the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) Trial. Conditional regression models were used to explore mediation and effect modification of telomere length on the relation between serum 25(OH)D and prostate cancer risk. Results: An increased risk of prostate cancer was observed among men with longer (&amp;gt;median) relative telomere length (OR = 1.41, 95% CI: 1.06 to 1.90; continuous: OR = 2.36, 95%CI: 0.96 to 5.83) as well as men with higher 25(OH)D concentrations (OR = 1.67, 95% CI: 1.08 to 2.57 for highest vs. lowest quintile, P-trend = 0.03). No significant association between 25(OH)D levels and telomere length was observed. A suggested joint effect of 25(OH)D and telomere length on prostate cancer risk was observed. Conclusion: Serum 25(OH)D and relative telomere length are independent predictors of prostate cancer risk in this sample of older male Finnish smokers. No evidence of mediation between circulating vitamin D concentrations and telomere length was observed. Future studies are needed to further clarify the underlying biologic mechanisms of the 25(OH)D-prostate cancer association. Citation Format: Jacqueline M. Major, Barry I. Graubard, Stephanie J. Weinstein, Jeeyun Kim, Immaculata De Vivo, Jarmo Virtamo, Sharon A. Savage, Demetrius Albanes. Understanding the mechanism underlying vitamin D and prostate cancer: Exploring telomere length [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-172.
Abstract 4604: Kidney injury molecule-1 regulates metastasis in renal cell carcinoma
Authors: Jasper C. Lee, Marie A. Sarabusky, Audrey Champagne, Fabrice Lucien, Lakshman Gunaratnam
Journal: Cancer Research (2019)

Abstract Over 30% of patients with renal cell carcinoma (RCC) present with metastases, with median survival of 2 years. Kidney injury molecule 1 (KIM-1) is a cell-surface glycoprotein expressed by &amp;gt;85% of RCC tumours and may serve as an early biomarker for RCC detection. Here we sought to determine if tumour KIM-1 plays a role in RCC cell extravasation and metastasis to lungs. Methods: We overexpressed KIM-1 in Renca cells (murine RCC) using stable transfection of an expression plasmid, or silenced endogenous KIM-1 in human 769-P and 786-O RCC cells using shRNA. We studied extravasation using the chorioallantoic membrane (CAM) model. We injected ~1x105 Renca or 769-P cells into blood vessels of chicken embryos (n=6), and measured percentage of cells that exited the capillary bed into surrounding spaces after 24 hours. To study lung metastasis, we injected ~5x105 Renca or 786-O cells intravenously through the tail vein of syngeneic BALB/c (n=10/group) or immune deficient Rag1-/- [BALB/c] (n=5/group) mice, and manually counted metastatic nodules in excised lungs after 17 days. Finally, we analyzed the publicly available Cancer Genome Atlas Illumina RNA-Seq dataset to determine if KIM-1 mRNA expression predicts overall survival in patients with clear cell RCC. Results: In CAM experiments, extravasation efficiency was significantly decreased in KIM-1pos 769-P cells compared to KIM-1neg 769-P cells (30.08% vs. 47.94%; p=0.0004), and in KIM-1pos Renca cells compared to KIM-1neg Renca cells (47.78% vs 60.73%; p=0.042). BALB/c mice injected with Kim-1pos Renca cells or Kim-1pos 786-O cells had significantly fewer lung metastases compared to mice injected with Kim-1neg Renca cells or Kim-1neg 786-O cells, respectively (257 vs 429, p=0.02; 131 vs 339 p=0.001). The inhibitory effect of KIM-1 expression in Renca and 786-O cells on numbers of lung metastases was similar in Rag1-/- mice, suggesting that the observed effects were not dependent on adaptive immunity. In the TCGA database, patients with the lowest vs. highest tertile of KIM-1 RCC expression has significantly higher mortality (unadjusted HR 1.82, 95% CI 1.23-2.70; p=0.0034). Conclusion: KIM-1 is a negative regulator of cell extravasation and inhibits the development of lung metastases in mice, and KIM-1 expression in human RCC may predict better survival. Deciphering the underlying mechanisms may lead to novel therapies. Citation Format: Jasper C. Lee, Marie A. Sarabusky, Audrey Champagne, Fabrice Lucien, Lakshman Gunaratnam. Kidney injury molecule-1 regulates metastasis in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4604.
Abstract 18033: Stress Analysis of Ascending Thoracic Aortic Aneurysm With Bicuspid Aortic Valves
Authors: Yue Xuan, Zhongjie Wang, Henrik Haraldsson, Michael D Hope, David A Saloner, Julius M Guccione, Liang Ge, Elaine E Tseng
Journal: Circulation (2017)

Introduction: American Heart Association 2016 guidelines recommend elective repair of bicuspid aortic valve associated ascending thoracic aortic aneurysms (BAV-aTAA) at ≥5.5cm. Early BAV-aTAA surge...
<i>MYC</i>Regulates the<i>HIF2α</i>Stemness Pathway via<i>Nanog</i>and<i>Sox2</i>to Maintain Self-Renewal in Cancer Stem Cells versus Non-Stem Cancer Cells
Authors: Bikul Das, Bidisha Pal, Rashmi Bhuyan, Hong Li, Anupam Sarma, Sukanya Gayan, Joyeeta Talukdar, Sorra Sandhya, Seema Bhuyan, Gayatri Gogoi, Arvin M. Gouw, Debabrat Baishya, Jason R. Gotlib, Amal C. Kataki, Dean W. Felsher
Journal: Cancer Research (2019)

Cancer stem cells (CSC) maintain both undifferentiated self-renewing CSCs and differentiated, non-self-renewing non-CSCs through cellular division. However, molecular mechanisms that maintain self-renewal in CSCs versus non-CSCs are not yet clear. Here, we report that in a transgenic mouse model of MYC-induced T-cell leukemia, MYC, maintains self-renewal in Sca1+ CSCs versus Sca-1- non-CSCs. MYC preferentially bound to the promoter and activated hypoxia-inducible factor-2α (HIF2α) in Sca-1+ cells only. Furthermore, the reprogramming factors, Nanog and Sox2, facilitated MYC regulation of HIF2α in Sca-1+ versus Sca-1- cells. Reduced expression of HIF2α inhibited the self-renewal of Sca-1+ cells; this effect was blocked through suppression of ROS by N-acetyl cysteine or the knockdown of p53, Nanog, or Sox2. Similar results were seen in ABCG2+ CSCs versus ABCG2- non-CSCs from primary human T-cell lymphoma. Thus, MYC maintains self-renewal exclusively in CSCs by selectively binding to the promoter and activating the HIF2α stemness pathway. Identification of this stemness pathway as a unique CSC determinant may have significant therapeutic implications. SIGNIFICANCE: These findings show that the HIF2α stemness pathway maintains leukemic stem cells downstream of MYC in human and mouse T-cell leukemias. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/16/4015/F1.large.jpg.
Insulin Delivery: Supercritical Fluid‐Assisted Porous Microspheres for Efficient Delivery of Insulin and Inhalation Therapy of Diabetes (Adv. Healthcare Mater. 12/2019)
Authors: Xiao‐Fen Lin, Ranjith Kumar Kankala, Na Tang, Pei‐Yao Xu, Liu‐Zhi Hao, Da‐Yun Yang, Shi‐Bin Wang, Yu Shrike Zhang, Ai‐Zheng Chen
Journal: Advanced Healthcare Materials (2019)

In article number 1800910 by Yu Shrike Zhang, Ai-Zheng Chen, and co-workers, insulin-loaded poly-l-lactide porous microspheres (INS-PLLA PMs) are fabricated by using supercritical fluid technology, serving as an inhalation delivery system potentially used towards diabetes therapy. The PLLA PMs show negligible toxicity to lung-derived cells, and they are efficiently deposited in the trachea and the bronchi of the superior lobes of the lungs, which exhibit pronounced hypoglycemic activity in induced diabetic rats.
Abstract 2078: Mitochondrial DNA copy number correlates with trifluridine sensitivity of human tumor cell lines
Authors: Takashi Kobunai, Kazuaki Matsuoka, Mamoru Nukatsuka, Hiroshi Tsukihara, Teiji Takechi
Journal: Cancer Research (2019)

Abstract Background: Trifluridine (FTD) is a key component of the novel oral antitumor drug trifluridine/tipiracil, which was approved for the treatment of patients with metastatic colorectal cancer refractory to standard chemotherapies. FTD, an antineoplastic thymidine analogue, is incorporated into the genomic DNA of tumor cells. However no detailed analysis of the relation between mitochondrial DNA (mtDNA) in human tumors and FTD’s cytotoxic effects has been reported yet. In this study, we analyzed mtDNA copy number of 23 human cancer cell lines and its relation with FTD sensitivity. Method: Twenty-three human cancer cell lines, representing the nine main tumor types, were tested for sensitivity to FTD by WST-8 assay. The cell lines included lung (NCI-H226, NCI-H23), colon (COLO 205, HCT 116, HCT-15, SW620), pancreas (PANC-1), breast (Hs 578T, MCF7, MDA-MB-231, T-47D), melanoma (Malme-3M, SK-MEL-28, SK-MEL-5), prostate (DU 145, PC-3), renal (786-O, A-498), leukemia (CCRF-CEM, HL-60, MOLT-4), and ovary (OVCAR-3, SK-OV-3). Genomic DNA was purified using a silica membrane spin column-based centrifugation procedure. The copy number of mtDNA was quantitated by array-based digital PCR and real-time PCR. Furthermore, the mtDNA heterogeneity of each cell line was assessed by deep-sequencing as follows: a DNA panel targeting 222 amplicons covering the entire mitochondrial genome was used for NGS library preparation; NGS libraries were subjected to cluster generation in a flow cell and paired-end sequencing for 300 cycles; and finally, the resulting fastq files were uploaded to mtDNA-server for mapping and heteroplasmy evaluation. Results: The IC50s of FTD ranged from 0.6 uM to 52 uM (Median: 5.6 uM). While cell lines were arbitrarily classified as FTD-high- and FTD-low sensitive cell lines according to their respective IC50 values at median, mtDNA copy numbers of FTD-high sensitive cell lines were significantly lower than those of FTD-low sensitive cell lines (p = 0.01). Median heteroplasmy level and counts were 0.057 and 137, respectively. Interestingly, significant negative correlation was found between mtDNA copy number and heteroplasmy level. (Spearman’s Rho = -0.46, p= 0.02). While 6 out of 23 cell lines were microsatellite instable, MSI status also significantly correlated with mtDNA copy number, FTD-sensitivity, and heteroplasmy level (p&amp;lt; 0.05). Conclusions: Integrated analysis of mtDNA copy number and mutational profiling may be useful to predict FTD sensitivity of cancer cells. Citation Format: Takashi Kobunai, Kazuaki Matsuoka, Mamoru Nukatsuka, Hiroshi Tsukihara, Teiji Takechi. Mitochondrial DNA copy number correlates with trifluridine sensitivity of human tumor cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2078.