tbuckley/cabot-search huggingface dataset:
EPIG-17HUMAN ES CELLS AS A MODEL FOR MODELING BRAINSTEM GLIOMAS
Authors: Kosuke Funato, Tamara Major, Peter Lewis, C. David Allis, Viviane Tabar
Journal: Neuro-Oncology (2015)

Recent sequencing data demonstrate the presence of novel mutations in the H3.3. histone gene variant in diffuse intrinsic brainstem gliomas of childhood, DIPG. Surgical access to these tumors presents high risks, leading to a paucity of patient specimens and poor understanding of this tumor's biology. We used human embryonic stem cells differentiated into early neural precursors as a system to model the H3.3K27M tumors. We demonstrate in vitro and in vivo the neoplastic transformation of these cells, following expression of the H3.3K27M gene, as well as a combination of PDGFRA and p53. The tumors reproduced the major features of DIPG, and genome-wide analyses indicated a resetting of the transformed precursors to a developmentally more primitive stem cell state, with evidence of major modifications of histone marks at several master regulator genes. Gene expression data from the transformed precursors clustered tightly with patient samples of H3.3K27M mutated gliomas rather than wild type or H3.3G34R/V gliomas. In addition, the tumors formed in animals upon grafting the transformed cells into the pons of immunocompromised mice, demonstrated key histological features of DIPG, including infiltration of the pons, leptomeningeal spread and encasement of the basilar artery. We established a drug screening system based on a competitive assay between the transformed precursors and normal neural precursors. Assays identified a compound targeting the protein menin as an inhibitor of tumor cell growth in vitro and in mice. The drug was validated in cell lines established from DIPG samples. Ongoing work aims to establish efficacy of the drug in a large series as well as its pharmacokinetics and blood brain barrier permeability. In addition, we are investigating the role of menin in enhancing the tumorigenic potential of DIPG. These data highlight a considerable potential for human embryonic stem cell systems as a platform for developing cancer models.
Predicting In-Hospital Mortality in Patients With Acute Myocardial Infarction
Authors: Robert L. McNamara, Kevin F. Kennedy, David J. Cohen, Deborah B. Diercks, Mauro Moscucci, Stephen Ramee, Tracy Y. Wang, Traci Connolly, John A. Spertus
Journal: Journal of the American College of Cardiology (2016)
US Congress fails to agree Zika virus funding before summer break
Authors: Michael McCarthy
Journal: BMJ (2016)

The US Congress adjourned for a seven week summer recess on 14 July without passing additional funding aimed at tackling the Zika virus outbreak, despite warnings from health officials that this would slow research into diagnostic tests and vaccines and hamper prevention efforts.

President Barack Obama requested $1.9bn (£1.4bn; €1.7bn) in emergency funding in late February, but Democrats in the Senate blocked a $1.1bn funding bill twice, after Republicans added provisions that the Democrats said were unacceptable.

These provisions included substantial cuts to other health programs, restrictions on funding …
Abstract 3245: IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity of murine breast and colon carcinomas
Authors: Peter S. Kim, Anna R. Kwilas, Wenxin Xu, Sarah Alter, Emily K. Jeng, Hing C. Wong, Jeffrey Schlom, James W. Hodge
Journal: Cancer Research (2016)

Abstract Interleukin (IL)-15-N72D superagonist-complexed with IL-15RαSushi-Fc fusion protein (IL-15SA/IL-15RαSu-Fc; ALT-803) has been reported to exhibit significant anti-tumor activity in murine myeloma, rat bladder cancer, and murine glioblastoma models. In this study, we examined the immunomodulatory and anti-tumor effects of IL-15SA/IL-15RαSu-Fc in tumor-free and highly metastatic tumor-bearing mice. Here, IL-15SA/IL-15RαSu-Fc significantly expanded NK and CD8+ T cells. In examining natural killer (NK) cell subsets, the greatest significant increase was in highly cytotoxic and migrating (CD11b+, CD27hi; high effector) NK cells, leading to enhanced function on a per-cell basis. CD8+ T cell subset analysis determined that IL-15SA/IL-15RαSu-Fc significantly increased IL-15 responding memory (CD122+, CD44+) CD8+ T cells, in particular those having the innate (NKG2D+, PD1-) phenotype. In 4T1 breast tumor-bearing mice, IL-15SA/IL-15RαSu-Fc induced significant anti-tumor activity against spontaneous pulmonary metastases, depending on CD8+ T and NK cells, and resulting in prolonged survival. Similar anti-tumor activity was seen in the experimental pulmonary metastasis model of CT26 colon carcinoma cells, particularly when IL-15SA/IL-15RαSu-Fc was combined with a cocktail of checkpoint inhibitors, anti-CTLA-4 and anti-PD-L1. Altogether, these studies showed for the first time that IL-15SA/IL-15RαSu-Fc (1) promoted the development of high effector NK cells, (2) enhanced function of NK cells, and (3) played a vital role in reducing tumor metastasis and ultimately survival, especially in combination with checkpoint inhibitors. Citation Format: Peter S. Kim, Anna R. Kwilas, Wenxin Xu, Sarah Alter, Emily K. Jeng, Hing C. Wong, Jeffrey Schlom, James W. Hodge. IL-15 superagonist/IL-15RαSushi-Fc fusion complex (IL-15SA/IL-15RαSu-Fc; ALT-803) markedly enhances specific subpopulations of NK and memory CD8+ T cells, and mediates potent anti-tumor activity of murine breast and colon carcinomas. [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 3245.
Sensitivity to EGFR inhibitors based on location of <i>EGFR</i> exon 20 insertion mutations within the tyrosine kinase domain of EGFR.
Authors: Daniel Botelho Costa, Hiroyuki Yasuda, Natasha J Sng, Wee-Lee Yeo, Lorena Lobo de Figueiredo-Pontes, Daniel G. Tenen, Susumu Kobayashi
Journal: Journal of Clinical Oncology (2012)

7523 Background: Epidermal growth factor receptor (EGFR) mutations (M) define an important subgroup of non-small-cell lung cancer (NSCLC). Most patients whose tumors harbor exon 19 deletions or L858R EGFR M have responses to reversible ATP-mimetic EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib. Exon 20 insertion M comprise ~5% of EGFR M, occur at the N-lobe of EGFR after its C-helix (AA M766), and nearly all NSCLCs with EGFR exon 20 insertion M display lack of responses to EGFR TKIs (Yasuda H. Lancet Oncol 2011). Methods: We have 1) compiled genotype-clinical outcomes of EGFR exon 20 insertion M NSCLCs to EGFR TKIs, 2) generated a comprehensive panel of exon 20 EGFR M constructs using site-directed mutagenesis and introduced them into Ba/F3 cells for in vitro analysis, and 3) compared NSCLC cell lines with EGFR M to a novel malignant pleural effusion-derived cell line. Results: The disease control rate of gefitinib or erlotinib was significantly higher in EGFR exon 20 insertion M located within the C-helix (3/3,100%) when compared to M following the C-helix (1/14, 7%; p=0.00059). The NSCLC with EGFR-A763_Y764insFQEA (located within the C-helix of EGFR) achieved a partial response to erlotinib that lasted 18 months. Most other exon 20 insertion M-positive NSCLCs did not respond (p=0.07). Eight representative exon 20 insertion M were studied (including EGFR-A763_Y764insFQEA, Y764_S765insHH, A767_V769dupASV, D770_N771insNPG, H773_V774insH). All, but A763_Y764insFQEA, were resistant to micromolar concentrations (C) of EGFR TKIs. Ba/F3 cells with EGFR-A763_Y764insFQEA underwent apoptosis upon exposure to nanomolar C of erlotinib. A patient-derived cell line with EGFR-A763_Y764insFQEA had phosphorylated EGFR, ERK and AKT inhibited by nanomolar C of erlotinib. Conclusions: Not all EGFR exon 20 insertion mutations are resistant to EGFR TKIs, and in specific EGFR-A763_Y764insFQEA is an EGFR TKI-sensitive M. This finding has clinical implications for the care of the 10,000 cases of EGFR exon 20 insertion M NSCLC diagnosed yearly and points towards the need to define the molecular mechanisms that underlie differential responses to EGFR TKIs.
Abstract 1359: Design, synthesis and evaluation of fluorinated antifolates for improved selectivity and potency against tumor cells
Authors: Aleem Gangjee, Manasa P. Ravindra, Mike R. Wilson, Adrianne W. Povrik, Lisa P. Hou, Carrie O’Connor, Zhanjun Hou, Larry H. Matherly
Journal: Cancer Research (2016)

Abstract Folates are important single carbon transferring cofactors required for the biosynthesis of purine and pyrimidine nitrogen bases and DNA. Antifolates inhibit synthesis of these nitrogenous bases and function as antineopastic agents. The use of currently marketed antifolates such as methotrexate (MTX and pemetrexed (PMX) is limited by dose-limiting toxicity due to non-selective transport by the ubiquitously expressed reduced folate carrier (RFC). We previously reported a series of 6-substituted pyrrolo[2,3-d]pyrimidine classical antifolates that are selectively transported by folate receptors (FR) and/or by the proton-coupled folate transporter (PCFT) over RFC and inhibit FR/PCFT expressing tumor cells (KB and IGROV1) at sub-nanomolar IC50 values. These antifolates are comparatively more potent and circumvent the important limitation of currently marketed clinical antifolates that lack selective uptake into tumors. As an extension of the SAR, we now report on the role of fluorine atom(s) in improving selectivity as well potency. Fluorine was incorporated into our 6-substituted pyrrolo[2,3-d]pyrimidine antifolates to improve pharmacodynamics by improving binding affinity to target proteins via a number of well documented electrostatic and hydrophobic interactions of fluorine. In addition, fluorines were strategically placed on the side chain of our targeted antifolates for improved potency and selectivity through induced conformational restriction due to a plausible intramolecular fluorine-hydrogen bonding interaction. The fluorinated analogs had IC50s in the subnanomolar range (IC50 = 0.33 to 0.29 nM) for KB tumor cells and nanomolar (IC50 = 2.77 to 3.47 nM) for IGROV-1 cells. In addition, these analogs showed 600- to 1000-fold selectivity for FRα expressing cells over RFC. Protection studies suggest that glycinamide ribonucleotide formyl transferase (GARFTase) is the intracellular targets. In vivo activity was established toward the SKOV3 tumor xenograft model. These preclinical studies suggest that these fluorinated analogs are candidates for possible clinical trial as antitumor agents. Citation Format: Aleem Gangjee, Manasa P. Ravindra, Mike R. Wilson, Adrianne W. Povrik, Lisa P. Hou, Carrie O’Connor, Zhanjun Hou, Larry H. Matherly. Design, synthesis and evaluation of fluorinated antifolates for improved selectivity and potency against tumor cells. [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 1359.
Abstract 5199: An in vivo reporter to quantitatively and temporally analyze the effects of CDK4/6 inhibitor-based therapies in melanoma
Authors: Jessica L. Teh, Timothy Purwin, Evan J. Greenawalt, Inna Chervoneva, Allison Goldberg, Michael E. Davies, Andrew Aplin
Journal: Cancer Research (2016)

Abstract Aberrant cell cycle progression is a hallmark feature of cancer cells. Cyclin-dependent kinase 4 and 6 (CDK4/6) drive progression through the G1 stage of the cell cycle, at least in part, by inactivating the tumor suppressor, retinoblastoma (RB). CDK4/6 are targetable and the selective CDK4/6 inhibitor, palbociclib (IBRANCE/PD-0332991), was recently FDA approved for the treatment of estrogen receptor-positive, HER2-negative advanced breast cancer. In cutaneous melanoma, driver mutations in NRAS and BRAF signal to promote CDK4/6 activation suggesting that inhibitors such as palbociclib are likely to provide therapeutic benefit most likely in combination with BRAF and/or MEK inhibitors that are FDA-approved. However, the determinants of the response to CDK4/6 inhibitors alone and in combination with other targeted inhibitors are poorly defined. Furthermore, in vivo systems to quantitatively and temporally measure the efficacy of CDK4/6 inhibitors and determine the extent that CDK activity is reactivated during acquired resistance are lacking. Here, we describe the heterogeneous effects of CDK4/6 inhibitors, the expression of anti-apoptotic proteins that associate with response to CDK4/6 and MEK inhibitors, and the development of a luciferase-based reporter system to determine the effects of CDK4/6 inhibitors alone and in combination with MEK inhibitors in melanoma xenografts. These findings are likely to inform on-going and future clinical trials utilizing CDK4/6 inhibitors in cutaneous melanoma. Citation Format: Jessica L. Teh, Timothy Purwin, Evan J. Greenawalt, Inna Chervoneva, Allison Goldberg, Michael E. Davies, Andrew Aplin. An in vivo reporter to quantitatively and temporally analyze the effects of CDK4/6 inhibitor-based therapies in melanoma. [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 5199.
Tricuspid Regurgitant Jet Velocity (TRV), Biomarkers of Hemolysis, and Impact of Oxygen Therapy in Children with Sickle Cell Disease (SCD) and Vaso-Occlusive Pain Episodes (VOE)
Authors: Cornelia Latronica, Frans A Kuypers, Howard Rosenfeld, Sandra K Larkin, Stephanie Doniger, Elliott Vichinsky, Claudia R. Morris
Journal: Blood (2012)
Phase I study of intraperitoneal (IP) denileukin diftitox in patients with advanced ovarian cancer (OC)
Authors: L. G. Salazar, R. Swensen, V. Markle, A. Coveler, B. Royer, Y. Dang, M. Slota, J. Childs, D. Wallace, M. L. Disis
Journal: Journal of Clinical Oncology (2008)

3036 Background: CD4+CD25+Foxp3+ regulatory T cells (Tregs) which induce T cell suppression are increased in the ascites and peripheral blood (PB) of OC patients and associated with a poor prognosis. Denileukin diftitox, a diphtheria/IL-2R fusion protein, depletes PB Tregs in humans when given IV and induces an antitumor response in mice. We hypothesized that IP infusion of denileukin diftitox may reverse immune suppression in the peritoneum by depleting local Tregs. A phase I dose-escalation study was initiated to establish the MTD of IP denileukin diftitox, and assess its effect on Tregs in patients with OC. Methods: Up to 18 subjects with refractory OC are enrolled at 3 dose levels, 5, 15, and 25mcg/kg. A treatment cycle consists of IP denileukin diftitox on days 1–3 every 14 days for 4 cycles. The primary endpoint is to establish the MTD. Secondary endpoints include effect on Tregs and cytokines in PB and ascites, and clinical activity. Toxicity is evaluated days 1–3, 8, and 14 of each cycle. Tregs are assessed using RT-PCR and cytokines using LUMINEX at baseline, and after cycles 2 and 4. CA125 is checked serially during treatment. Results: 9 subjects have been enrolled, 3 to Arm 1 and 6 to Arm 2. Median age is 56 years (range, 34–73) and median salvage regimens is 3 (range, 2–7). 3 subjects in Arm 1 and 4/6 subjects in Arm 2 have completed 4 cycles without DLT. In Arm 2, 1 subject had DLT (grade 3 esophagitis) and 1 had disease progression after cycle 1. Toxicity in both Arms was primarily grade 1 and 2. Tregs (reported as relative quantitation level of Foxp3 normalized to CD4) in PB and ascites decreased in 1/3 patients in Arm 1, and 3/4 patients in Arm 2. CA125 decreased in 4/6 subjects in Arm 2 by a median value of 92 (range, 26–200). Cytokine analyses are on-going. Conclusions: Data suggests that IP denileukin diftitox at 5–15 mcg/kg is well tolerated in subjects with refractory OC; and at 15 mcg/kg results in decreased CA125 and Tregs. Accrual to dose level 3 continues. No significant financial relationships to disclose.
Abstract 3401: Impact of VEGF and VEGFR polymorphisms on neuroendocrine tumors of the gastro-entero-pancreatic system (GEPNETs) outcome
Authors: Rossana Berardi, Mariangela Torniai, Silvia Pagliaretta, Silvia Rinaldi, Francesca Morgese, Stefano Partelli, Miriam Caramanti, Azzurra Onofri, Vanessa Polenta, Sonia Pasquini, Massimo Falconi, Stefano Cascinu
Journal: Cancer Research (2016)

Abstract Introduction: Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) are uncommon neoplasms including a wide range of anatomical, clinical, histological and molecular malignant entities. Improving our understanding of the molecular biology of GEP-NETs represents a key challenge in the treatment of these rare tumors. Therefore we aimed to analyze genotypes of VEGF-A, VEGFR2 and Flt4 in GEP-NETs and their potential correlation with the risk of these tumors and/or with the outcome. Methods: The genomic DNA of 28 consecutive patients with GEP-NETs treated at our Institution was extracted from paraffinembedded tissue. We selected polymorphisms in the following genes: VEGF-A (rs2010963G&amp;gt;C, rs699947A&amp;gt;C), VEGFR-2 (rs2305948C&amp;gt;T, rs1870377T&amp;gt;A) and VEGFR-3 (rs307826T&amp;gt;C, rs307821C&amp;gt;A). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. Results: Median age was 58 (range 33-78) and M/F ratio was 1/1. Twenty-one out of the 28 patients had NETs of the pancreas. The allele frequency of VEGFR2 rs2305948C and of VEGFA rs2010963G showed a trend of lower frequency than in general population (82% vs. 92% and 60.3% vs. 68.8%, respectively, p&amp;lt;0.001). The following factors significantly correlated with a poorer overall survival (p&amp;lt;0.05): VEGFA rs699947C, VEGFA rs2010963A, VEGFR-2 rs1870377T/A, VEGFR-2 rs2305948C/T, VEGFR-3 rs307821C and VEGFR-3 rs307826T. Conclusion: Our results suggest, for the first time, that inherited abnormalities in VEGF pathway influence the risk and aggressiveness of GEP-NETs. Within March 2016 final data about all the enrolled 64 patients will be also available. These results should be validated prospectively in order to optimize the diagnosis and treatment of these patients. Citation Format: Rossana Berardi, Mariangela Torniai, Silvia Pagliaretta, Silvia Rinaldi, Francesca Morgese, Stefano Partelli, Miriam Caramanti, Azzurra Onofri, Vanessa Polenta, Sonia Pasquini, Massimo Falconi, Stefano Cascinu. Impact of VEGF and VEGFR polymorphisms on neuroendocrine tumors of the gastro-entero-pancreatic system (GEPNETs) outcome. [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 3401.
Abstract 4706: ABBV-075 exhibits robust in vitro and in vivo activities against the ABC and GCB subtypes of DLBCL
Authors: Xiaoyu Lin, Xiaoli Huang, Aparna Sarthy, Terry Magoc, Daniel Albert, Lloyd Lam, Tamar Uziel, Xin Lu, Mai-Ha Bui, Emily Faivre, Denise Wilcox, Steven Elmore, Keith McDaniel, Warren Kati, Yu Shen
Journal: Cancer Research (2016)

Abstract Diffuse Large B-Cell Lymphoma (DLBCL) consists of activated B-cell-like (ABC), germinal center B cell-like (GCB), and primary mediastinal B cell lymphoma (PMBL) subtypes. Among these, the ABC subtype of DLBCL often harbors mutations that cause abnormal NF-κB activation, which subsequently activates genes important for cell survival and disease progression in ABC DLBCL. The bromodomain and extraterminal domain (BET) protein BRD4 binds acetylated NF-κB and regulates NF-κB dependent transcription. Accordingly, targeting BET family proteins using small molecule inhibitors such as ABBV-075 might provide therapeutic benefit in ABC DLBCL by blocking the NF-κB pathway. In this study, we examined the activity of ABBV-075 in both the ABC and GCB subtypes of DLBCL. As expected, ABBV-075 diminished NF-κB reporter activity, down-regulated NF-κB target genes, inhibited proliferation and survival of ABC DLBCL cells in vitro, and delayed the growth of ABC DLBCL tumors in vivo. Interestingly, ABBV-075 also exhibited robust anti-proliferative activities in GCB DLBCL cells in vitro and inhibited the growth of GCB DLBCL tumors in vivo. Further characterization of the responses of GCB DLBCL cells to ABBV-075 indicated that ABBV-075 induced strong apoptosis in GCB DLBCL cells that are resistant to the Bcl-2 inhibitor venetoclax (ABT-199), but rarely in venetoclax-sensitive GCB DLBCL cell lines. Our results indicate that ABBV-075 could be active against both the ABC and GCB subtypes of DLBCL. The complementary activity of ABBV-075 and ABT-199 further suggests that ABBV-075 maybe an interesting option for ABT-199 resistant/refractory DLBCL patients. Citation Format: Xiaoyu Lin, Xiaoli Huang, Aparna Sarthy, Terry Magoc, Daniel Albert, Lloyd Lam, Tamar Uziel, Xin Lu, Mai-Ha Bui, Emily Faivre, Denise Wilcox, Steven Elmore, Keith McDaniel, Warren Kati, Yu Shen. ABBV-075 exhibits robust in vitro and in vivo activities against the ABC and GCB subtypes of DLBCL. [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 4706.
Abstract 1645: Tumor-associated macrophages enhance DNA damage repair and improve survival of murine breast cancers after irradiation
Authors: Luis A. Soto, Marjan Rafat, Marta Vilalta Colomer, Amato Giaccia, Edward Graves
Journal: Cancer Research (2016)

Abstract Tumor-associated macrophages (TAMs) are known to promote physiological processes that drive tumor progression and survival, including angiogenesis, immunosuppression, and invasion. While most studies on TAMs have focused on the molecular mechanisms by which TAMs drive these processes, less focus has been given to direct effects that TAMs may exert on tumor cells. It is known that monocytes are recruited to tumor sites after radiotherapy and support tumor regrowth. In this study we sought to determine if TAMs are able to exert a direct, protective effect on tumor cells against radiotherapy in vitro. We used murine 4T1 cells, a well-characterized animal model for breast cancer, and murine RAW264.7 macrophages to carry out co-culture experiments. Co-culture of 4T1 cells with RAW264.7 macrophages resulted in increased 4T1 cell survival rates post-irradiation compared to 4T1 cells cultured alone. We further determined that this effect is not contact-dependent but mediated through macrophage secreted factors. Next, we tested whether co-culturing RAW264.7 macrophages with 4T1 cells induced macrophage polarization to an M2/TAM phenotype. Using antibodies against M2 markers and FACS, we found that co-culture of RAW macrophages with 4T1 cells polarizes these macrophages toward an M2 phenotype. We hypothesized that the increased 4T1 cell survival rates were mediated by an enhanced DNA damage repair mechanism induced by TAMs. We tested this via a combination of immunofluorescence against phosphorylated histone H2AX and comet assays. We show that co-culture of 4T1 cells with TAMs after irradiation results in lower 4T1 cell levels of DNA damage and a faster decrease in DNA damage over time compared to 4T1 cells alone. Future work will focus on characterizing the molecular mechanism through which TAMs induce this enhanced DNA damage repair response in 4T1 cells after irradiation and we will test whether such response occurs in vivo after radiotherapy. In conclusion, we show that TAMs confer resistance against ionizing radiation to tumor cells in vitro and that this resistance is driven by an enhanced DNA damage repair mechanism in tumor cells induced by TAM secreted factors. Citation Format: Luis A. Soto, Marjan Rafat, Marta Vilalta Colomer, Amato Giaccia, Edward Graves. Tumor-associated macrophages enhance DNA damage repair and improve survival of murine breast cancers after irradiation. [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 1645.