Jun 20, 2017
Antitumor activity of indenoisoquinoline inhibitors of topoisomerase 1 (TOP1) via apoptosis and autophagocytosis pathways in animal models.
R. J. Kinders, A. B. Dull, D. Wilsker, A. LeBlanc, C. Mazcko, M. G. Hollingshead, R. E. Parchment, J. H. Doroshow , Journal of Clinical Oncology , DOI: 10.1200/JCO.2017.35.15_suppl.11588
Background: We performed pharmacodynamic biomarker analysis for response to a panel of three indenoisoquinolines (LMP776, LMP400 and NSC706744, J. Med. Chem. 49:7740, 2006) that have demonstrated anti-tumor activity in dogs. In preclinical xenograft models treated with indenoisoquinolines, we observed that gH2AX was not a useful biomarker for the biological activity...
May 29, 2017
Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression
N. Kramer, J. Schmöllerl, C. Unger, H. Nivarthi, A. Rudisch, D. Unterleuthner, M. Scherzer, A. Riedl, M. Artaker, I. Crncec, D. Lenhardt, T. Schwarz, B. Prieler, X. Han, M. Hengstschläger, J. Schüler, R. Eferl, R. Moriggl, W. Sommergruber, H. Dolznig , Oncogene , DOI: 10.1038/onc.2017.144
The canonical WNT signaling pathway is crucial for intestinal stem cell renewal and aberrant WNT signaling is an early event in colorectal cancer (CRC) development. Here, we show for the first time that WNT2 is one of the most significantly induced genes in CRC stroma as compared to normal stroma....
May 22, 2017
Prolonged exposure to extracellular lumican restrains pancreatic adenocarcinoma growth
X. Li, Y. Kang, D. Roife, Y. Lee, M. Pratt, M. R. Perez, B. Dai, E. J. Koay, J. B. Fleming , Oncogene , DOI: 10.1038/onc.2017.125
We previously demonstrated that pancreatic stellate cells within pancreatic ductal adenocarcinoma (PDAC) stroma secrete lumican and its presence is associated with prolonged survival of patients with localized PDAC. Here, we observed that extracellular lumican decreases PDAC tumour cell growth in xenograft and syngeneic orthotopic animal models, and induces growth inhibition...
May 20, 2017
Mutually exclusive expression of CD73 and PDL1 in tumors from patients (pt) with NSCLC, gastroesophageal (GE) and urothelial bladder carcinoma (UBC).
P. Martin, A. Spitzmueller, S. Wu, M. Widmaier, R. Korn, S. Althammer, J. Zha, B. W. Higgs, Z. Cooper, K. Steele , Journal of Clinical Oncology , DOI: 10.1200/JCO.2017.35.15_suppl.3079
Background: Tumors use multiple means of immune evasion, notably the programmed death-1 (PD1)/PDL1 pathway. Anti-PD1/PDL1 therapy induces anti-tumor activity and has improved pt outcomes. Activation of the immunosuppressive CD39/CD73/adenosine pathway might play a role in pts who do not benefit from anti-PD1/PDL1 therapies. We evaluated expression of CD73 and PDL1...
May 20, 2017
Immune cell profiling of melanoma metastases from patients treated with TriMixDC-MEL dendritic cell therapy in combination with ipilimumab.
K. Schats, E. A. Van Vre, I. Debyser, A. Vandenbroeck, Y. Jansen, T. Seremet, K. Marien, E. Fransen, D. Schrijvers, W. Van Criekinge, K. Thielemans, B. Neyns, I. De Meester, M. Kockx , Journal of Clinical Oncology , DOI: 10.1200/JCO.2017.35.15_suppl.e21030
Background: Ipilimumab has proven clinical benefit in a subset of melanoma patients. Previously a high rate of durable complete response was shown with the combination of ipilumumab and TriMixDC-MEL therapy (Wilgenhof et al. JCO 2016). Methods: Melanoma metastases were collected from patients, before initiation of combined ipilimumab and dendritic cell...