<i>In-vivo</i> efficacy of long-term repetitive intralesional administration of the compound drug (kB1-MGMT-LODN and the carrier) in A375P human melanoma xenografts.

<p>Kaplan Meier survival curve of mice bearing A375P subcutaneous xenograft. IL treatment with either 25 ug of MGMT-kB1-LODN or with control ODN or with vehicle (5% glucose) was started once tumor volume approached 75 mm³ (on day 6 post inoculation) and treatment was repeated every 4 to 5 days for up to 55 days after tumor induction.</p

Interference with NF-kappaB binding to the MGMT-NFkB1 site using LODN (locked modified ODN).

<p>The HEK293T cell line was transiently transfected with either the kB1-MGMT-luc or pNF-kB-Luc reporter gene construct together with NFkappaB/p65. LODN corresponding to the MGMT-kB1 site were added at the indicated concentrations. The CMVβ-galactosidase expression vector (CMVβgal) was included in each transfection to normalize the transfection efficiency. The observed enhancer activity is relative to the corresponding reporter plasmid transfected with NFkappaB/p65. All concentrations of MGMT-kB1 LODN significantly reduced the levels of luciferase expression <i>(p<0.05)</i> compared with cells transfected with control ODN. The control bars indicate the average inhibition of three different concentrations of ODN as indicated for MGMT-kB1 LODN. An asterisk indicates a significant difference of <i>p<0.05</i> and a double asterisk indicates <i>p<0.01</i>.</p

The activity induced by the NF-kappaB sites within the MGMT enhancer and their corresponding mutant sites as measured by luciferase fold induction.

<p>The HEK293T cell line was transiently transfected with a reporter gene construct either alone or with other plasmids as indicated on the graph. The CMVβ-galactosidase expression vector (CMVβgal) was included in each transfection to normalize the transfection efficiency. The observed enhancer activity is relative to the corresponding reporter plasmid transfected alone. An asterisk indicates a significant difference <i>(p<0.05)</i> compared with the control (reporter plasmid transfected alone).</p

The cytotoxic efficacy of MGMT-kB1-LODN treatment given either in sequence with Temozolomide or as a monotherapy in three tumor cell lines.

<p>The effect of combination treatment with MGMT-kB1-decoy LMODNs and TMZ in three tumor cell lines (A) T98G, (B) U87MG and (C) A375P. The cells were transfected with the indicated concentrations of MGMT-kB1-LODN, and 3 hrs later were treated with the indicated doses of TMZ. The percentage of cell survival was evaluated 72 hrs later. (D) The effect of MGMT-kB1-LODN as a monotherapy. Each point represents the average viability percentage ± SEM. (A, B) An asterisk indicates a significant difference of <i>p<0.05</i> and double asterisk indicates <i>p<0.01</i>, between cells treated with MGMT-kB1-LODN and untreated cells. (D) The results are expressed as percentage of cell survival compared with cells treated with control ODN.</p

<i>In-vivo</i> efficacy of the compound drug (kB1-MGMT-LODN and the carrier) with or without temozolomide in A375P human melanoma xenografts.

<p>Athymic nude mice were inoculated subcutaneously with 5*10⁶ tumor cells (A375P) and randomized into treatment groups. (A) a single dose of IP treatment (indicated by red arrows) was administered as follows: 10% DMSO (control) or TMZ at a dose of 100 mg/kg or 200 mg/Kg or 300 mg/kg. (B) Treatment started on day 5 when the tumors grew to an approximate size of 75 mm³. Mice were injected IL (indicated by black arrows) with 25 ug of MGMT-kB1 LODN or with vehicle (5% glucose) on days 5 and 7. On day 6 IP treatments (red arrow) were given with either 100 mg/kg TMZ or with vehicle (10% DMSO). An asterisk indicates a significant difference <i>(p<0.05)</i> between the treated and control group (10% DMSO). Each point represents the average tumor size ± SEM.</p

Anonymized Full data set-CA72-4-111012

<p><strong>endoscopic findings:</strong><br> normal=1, inflammatory=2, mucosal tumor (polyp/carc)=3, 4=other<br> <strong>histological findings:</strong><br> 1=normal, 2=chronic gastritis, 3=acute gastritis, 4=intestinal metaplasia, 5=gastric cancer, 6=other<br> <strong>smoking status:</strong><br> 0=never, 1= active or ex<br> <strong>alcohol intake</strong><br> 0=never, 1= active or ex<br> <strong>Endoscopic evidence of gastric bleeding</strong><br> 0=no, 1=yes<br> <strong>PPI dose</strong><br> muliples of standard dose<br> <strong>Hp-status</strong><br> 0=negative, 1=positive</p