Successful adenovirus-mediated gene transfer in an in vivo model of human malignant mesothelioma

Bystander effect of purine nucleoside analogues in HSV-1tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues

“…[10][11][12] Therefore, the success of the combined gene/chemotherapeutic approach heavily depends on the so-called bystander effect, 1 ie the killing of nontransfected bystander tumor cells by drug metabolites formed in nearby tk gene-transfected cells. Indeed, complete tumor eradication has been demonstrated even when as few as 10% of the tumor cell inoculum is transfected with the herpes tk gene.…”

Re-expression of p16INK4a in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor regression

“…Viral vector was diluted in 1 ml of sterile 16PBS and injected directly into the abdominal cavity of the mice. Injections consisted of 1610 11 PFU per injection for both vectors (Smythe et al, 1994). An identical schedule to the previously described experiment was used, consisting of six treatments over 2 weeks, with the mice being sacri®ced 2 weeks later.…”

“…An identical schedule to the previously described experiment was used, consisting of six treatments over 2 weeks, with the mice being sacri®ced 2 weeks later. Intraperitoneal tumors were graded in accordance with the size and location as previously described by others (Smythe et al, 1994), with four regions (pancreas/stomach, retroperitoneo-diaphragm, mesenteric, and hepatic-portal) chosen to grade the presence and size of tumors. The presence of a tumor between 1 and 5 mm was given a score of 1.…”

“…Clinical trials with gene based therapies in mesothelioma have already began using the novel and interesting concept of targeting tumors with gene products that confer selective toxicity on recipient tumor cells to an administered drug (Treat et al, 1996). Successful gene transfer in malignant pleural e usions has already been demonstrated in this disease in animal models using adenoviral vectors (Smythe et al, 1994). In view of the near absolute lack of e ective treatment for this disease, we have sought to develop reexpression of p16 INK4a in mesothelioma as a potential gene based treatment of this disease.…”

Gene therapy of established mesothelioma xenografts with recombinant p16INK4a adenovirus

“…12 The titer used in these injections was the minimum previously demonstrated to result in gene product expression in murine mesothelioma intraperitoneal xenografts. 13 Injections began after a fixed period for the development of intraperitoneal tumors, which varied depending upon the growth rate of the tumors derived from the various cell lines ( Fig 1) . Once treatments started, injections were delivered three times a week for the remainder of the animal's life.…”