British Journal of Cancer

FIGURES AND TABLES

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A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

M Guzmán, M J Duarte, C Blázquez, J Ravina, M C Rosa, I Galve-Roperh, C Sánchez, G Velasco and L González-Feria

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Figure 1.

Effect of THC administration on overall survival. (A) Schematic diagram of the clinical protocol. See text for further details. (B) Kaplan–Meier survival curve of the cohort of patients from the surgical operation of tumour relapse. For comparison with survival upon administration of standard chemotherapeutic drugs such as temozolomide and carmustine, see Dinnes et al (2002) and Brem et al (1995), respectively.

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Figure 2.

Effect of THC administration on tumour growth. Tumour growth plots and gadolinium-enhanced T1-weighted magnetic resonance scans after the second surgery in three patients. Arrows indicate the THC administration cycles. (A) Patient 3, scans before and after surgery of tumour relapse as well as after the second, fourth and sixth THC cycle (weeks 4, 18 and 29, respectively). (B) Patient 8, scans before and after surgery of tumour relapse as well as after the THC cycle (week 3) and at week 32. (C) Patient 5, scans before and after surgery of tumour relapse as well as after the fist THC cycle (week 3) and at week 15.

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Figure 3.

Effect of THC administration on tumour cells. (A) Western blot analysis of CB1 and CB2 receptor expression in three different tumour zones of Patient 1 (left panel) and in tumour biopsies of Patient 1 before and after THC treatment (right panel). Optical density values relative to those of loading controls (alpha-tubulin) are given for Patients 1 and 2 in arbitrary units. (B) Immunostaining of CB1 and CB2 receptors (red) in a tumour biopsy of Patient 1. Nuclei are stained in green. (C) Immunostaining of CB1 and CB2 receptors (green) in tumour cells obtained from Patient 1. (D) THC-induced apoptotic death of tumour cells obtained from Patients 1–3. Cells were incubated for 48 h with THC and/or 1.0 mu M SR141716 (SR1) plus 1.0 mu M SR144528 (SR2). Statistical comparison vs vehicle (*) or vs 2.5 mu M THC alone (#) is given. Arrows point to Hoechst-stained fragmented nuclei or to TUNEL-positive nuclei in cells from Patient 1 treated with 2.5 mu M THC. (E, F) Tumour cell proliferation (Ki67 immunostaining, panel E) and tumour vascularisation (CD31 immunostaining, panel F) as determined by confocal microscopy in Patient 1 (circle) and Patient 2 (filled circle) before and after THC treatment. Insets in panel E show higher-magnification micrographs. Cell nuclei are stained in green. Representative micrographs of Patient 1 biopsies are shown.

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