Fig. 5From: HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiformeA Systemic treatment of U87-MG flank tumours with HTL-001. 100ul of live U87-MG cells (1e6 cells) in 50% matrigel were injected subcutaneously in the right flank of BALB c nude mice (n = 8 per group). When tumours were between 30-60mm3 in size (approx. day 10) the animals received an intraperitoneal injection of HTL-001 at a single site (IP), a maximum of three times in a week (1–2-day part), for four consecutive weeks. HTL-001 treatment resulted in significant disease stability compared to PBS controls, unpaired student t- test P = 0.0052 B Comparing the efficacy of HTL-001 treatment against the CXR9 control in a subcutaneous GL-261 glioblastoma model in mice GL-261 cells were subcutaneously inoculated into the right flanks of 6-week-old C57BL/6 mice. Once the tumour grew to 100 mm3, mice were randomized into groups receiving either CXR9 or HTL-001 (30 mg/kg) by intraperitoneal injection three times a week until the experimental endpoint. Tumour volume was measured every 2–3 days. Tumours treated with HTL-001 were significantly smaller compared to tumours treated with CXR9 (P = 0.001186). C)Tissue was resected from tumours treated with either CXR9 or HTL-001 and sections evaluated. Top left: low power view (magnification 40X) of tumour treated with HTL-001 with large areas of necrosis, as indicted by the arrow. Top right: High power view (magnification X200) of tumour treated with HTL-001 with evidence of apoptosis and necrosis. Bottom left: High power view (magnification X200) of tumour treated with HTL-001 with areas of apoptosis, as indicated by the arrow. Bottom right; Tumour from orthotopic model with adjacent normal brain wherein no effect of treatment can be seen (magnification X40). D) Areas of apoptosis (Ap) and necrosis (Ne) were observed in tumour tissue treated with HTL-001, but not in tissue treated with CXR9. E GL-261 cells were intracranially inoculated by stereotactic injection into 6-week-old C57BL/6 mice. After 7 days, tumour-bearing mice were IP treated with either CXR9 or HTL-001 (30 mg/kg) three times a week until the experimental endpoint. Kaplan–Meier analysis showed that mice treated with HTL-001 survived significantly longer than mice treated with CXR9 (P = 0.0078 via log-rank test). F Tissue was resected from tumours treated with either CXR9 or HTL-001 and evaluated after H&E staining, 40X magnification shown. Top. Tumour from CXR9 control mice showed typical features of GL-261 with dense undifferentiated tumour (T) and areas of spontaneous focal necrosis (FN). Bottom; Tumour from HTL-001 treated mouse showed extensive apoptosis (Ap) and widespread necrosis (WN). G-K) Intravital imaging of peptide accumulation in the brain of NSG mice bearing RFP tumours after systemic delivery. FITC dextran shows perfused blood vessels. 100 ul of HTL-001 Alex 660 peptide (5 mg/ml in PBS) was administrated intraperitoneally on day 2, and the confocal images of same area were acquired on day 3. G Both intraperitoneal and intravenous injection showed efficient delivery of peptide (white) into brain. H The scheme of experimental setup for C. I Time-course imaging showed the accumulation of peptide into tumour. J Inset of Fig.I K Non-tumour area did not show the peptide accumulationBack to article page