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Intra-arterial infusion chemotherapy on unresectable hepatocellular carcinoma under occlusion of hepatic arterial flow.

Intra-arterial infusion chemotherapy (IAIC) by occluding hepatic arterial flow augments intrahepatic drug concentrations, resulting in response rates higher than those with conventional infusion methods. We recently developed an intra-hepatic artery catheter and device attached with an implantable double-lumen reservoir that can be used for repeated IAIC in outpatient clinics. Eight patients with unresectable hepatocellular carcinoma were treated by infusion of anticancer drugs using this method. The catheter was inserted into the hepatic artery under laparotomy. The occlusion balloon was attached to the common hepatic artery, and catheters were connected to the subcutaneous double-lumen reservoir. Approximately 0.5 ml of distilled water was injected through the one port of the double-lumen reservoir to inflate the balloon, which compressed the artery within the cylinder-like occluder. 4'-O-tetrahydropyranyladriamycin (THP-ADM) was used as the anticancer agent, and two patients received combined administration with carboplatin. Three to seven repeated infusions were possible without any severe side effects. This treatment was also easy to perform in the outpatient clinic. Six of the eight patients survived for more than 2 years, an improvement over the survival rates obtained in a previous conventional IAIC group. We conclude that IAIC with THP-ADM for unresectable hepatocellular carcinoma under occluding blood flow using our device is more convenient and more effective than other available methods.

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Endothelial and glial cell interaction in diabetic retinopathy via the function of vascular endothelial growth factor (VEGF).

VEGF, which is also known as vascular permeability factor (VPF), is a recently identified specific mitogen for endothelial cells, and has been paid much attention for the critical participation in the physiological and pathological angiogenesis/vasculogenesis in retinas. To investigate whether retinal glial cells (RGCs) synthesize VEGF under hypoxic state (2%) in vitro and in retinas in vivo of streptozotocin-induced diabetic rats, VEGF mRNA and activity expressed by cultured RGCs were assessed with Northern blot analysis and in vitro angiogenesis assay, and the in vivo expression of VEGF mRNA and protein was examined in diabetic retinas by in situ hybridization and immunohistochemistry using rabbit anti-IgG against human VEGF. Cultured RGCs synthesized and released VEGF and this VEGF production was markedly enhanced by hypoxia through the activation of AP-1 promotor gene. However, the expression of bFGF mRNA by RGCs was not enhanced under the hypoxic condition. Retinal capillary endothelial cells (RECs) expressed flt-1 mRNA. Therefore, conditioned media harvested from RGCs under hypoxic condition significantly accelerated not only thymidine incorporation by RECs but also in vitro angiogenesis, namely, the formation of capillary-like tubes by RECs in type I collagen gels. In normal rat retinas astrocytes located just beneath the inner limiting membrane revealed immunohistochemically the weak expression of VEGF, while in diabetic retinas six months after the streptozotocin treatment, the enhanced expression of VEGF mRNA and protein mainly by glial cells such as Muller cells and astrocytes, was confirmed by immunohistochemistry and in situ hybridization. These diabetic retinas were associated with the hyperpermeability of albumin, but not angiogenic retinopathy. These findings indicate that VEGF expressed by RGCs under hypoxia or diabetic condition plays an integral role in the maintenance of retinal circulation via the VEGF-VEGF receptor (flt-1) interaction.

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