Abstract Library

#2834 Tumor-Promoting Effects of the Transcriptional Regulator CUX1 in PanNET

Introduction: Previously, we identified CUX1 as mediator of metastatic behaviour and poor differentiation in human insulinomas. CUX1 mediated tumor-promoting functions via enhancing proliferation, resistance to apoptosis and angiogenesis in-vitro and in-vivo.

Conference: 17th Annual ENETSConcerence (2020)

Presenting Author: Weißbach J

Authors: Weißbach J, Schmitz R, Haybäck J, Perren A, Blank A,

Keywords: CUX1, RIP1Tag2, DAPK1, Apoptosis, Tumor Progression,

#2280 The BON-SSTR2 Chicken Chorioallantoic Membrane (CAM) Model for the Analysis of Lu-17-DOTATOC Sensitizing Agents

Introduction: Peptide radioreceptor therapy (PRRT) is a promising therapy option for SSTR2-positive pancreatic neuroendocrine neoplasms (NEN). However, therapeutic effects are often not satisfying concerning sensitivity to PRRT. We hypothesize that the slow proliferation of NENs provides sufficient time for the repair of beta-particle induced-DNA damage. The ubiquitin-proteasome-system is involved in DNA damage repair and affected by the proteasome inhibitor bortezomib (Velcade®). The inhibition of DNA damage repair during PRRT may be an option to improve therapy response in NEN. We have recently demonstrated the damage repair inhibitory and pro-apoptotic effect of bortezomib in NEN in vitro (Briest et al., in revision).

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Briest F

Authors: Briest F, Grötzinger C, Exner S, Sedding D, Baum R,

Keywords: peptide radioreceptor therapy, Lu-177-DOTATOC, PRRT, bortezomib, in vivo model, SPECT/CT Imaging, chicken CAM model, Sensitizer, DNA damage repair,

#1546 O6-Methylguanine DNA Methyltransferase (MGMT) Expression by Immunochemistry May Help Predict Response to Streptozotocin-based Chemotherapy in Pancreatic Neuroendocrine Tumours

Introduction: Streptozotocin (STZ) is an alkylating agent inducing DNA damage mainly repaired by MGMT. STZ-based chemotherapy is the first line treatment of non-resectable well-differentiated PNET. As for temozolomide, tumour MGMT deficiency may predict the efficacy of STZ in PNET.

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author: Hentic O

Authors: Hentic O, Cros J, Zappa M, Rebours V, Muller N,

Keywords: MGMT, Streptozotocin, PFS ,

#616 Assessment of DNA Double-Strand Breaks in Blood Lymphocytes after Whole-Body Radiation Exposure in Patients with Neuroendocrine Tumors Undergoing 177Lu-Octreotate Therapy

Introduction: Peptide receptor radionuclide therapy using somatostatin receptor-binding peptides, such as 177Lu-Octreotate (LuTate), has been clinically proven to be effective in treating patients with inoperable neuroendocrine tumors. Despite the rather high radiation exposure, only few side effects have been reported. However, blood cells are very sensitive to radiation. Therefore, it is important to determine how much radiation they received. Recently, the detection by immunofluorescence of the phosphorylation of the histone variant H2AX (γ‐H2AX) has been established as a reliable and sensitive technique to monitor DNA double-strand breaks (DSBs) in blood lymphocytes.

Conference: 10th Annual ENETSConcerence (2013)

Presenting Author: Denoyer D

Authors: Denoyer D, Martin O, Jackson P, Johnston V, Hicks R,

Keywords: 177Lu-Octreotate, γ‐H2AX, DNA damage,

#55 Metronomic combination therapy including temozolamide, bevacizumab and somatostatin analogue for the treatment of malignant gastroenteropancreatic neuroendocrine tumors

Introduction: Malignant gastroenteropancreatic neuroendocrine tumors (GEPNETS), mainly carcinoids, are not considered to be particularly chemotherapy-sensitive to conventional chemotherapeutic schemes. Long-standing evidence suggests these tumors to be highly vascularised and responsive to antiangiogenic strategies. Newest reports demonstrate benefit by the use of temozolamide, an oral alkylating agent similar to intravenous dacarbazine. The DNA repair enzyme O6-alkylguanine–DNA alkyltransferase (AGAT) confers cancer cell resistance to O6-alkylating agents such as temozolamide through its ability to remove methyl/alkyl groups from the O6-position of guanine, thus correcting drug-induced DNA damage.

Conference: 7th Annual ENETSConcerence (2010)

Presenting Author:

Authors: Koumarianou A, Zilos A, Syrios J, Kanakis G, Antoniou S,

Keywords: GEPNETs, temozolamide, bevacizumab, somatostatin analogue,