[Long-term effects of isopropyl unoprostone monotherapy on intraocular pressure and visual field for normal-tension glaucoma and primary open-angle glaucoma patients].

We retrospectively investigated the long-term effects of isopropyl unoprostone monotherapy on intraocular pressure and visual field for normal-tension glaucoma and primary open-angle glaucoma patients. Among 80 eyes of 49 subjects receiving isopropyl unoprostone monotherapy for 2 years or more, 32 eyes of 32 subjects were analyzed because of the good reliability of their visual acuity and visual field (age, 68.1 +/- 10.1 yrs, follow-up period 47.8 +/- 14.7 months). The mean values of intraocular pressure and visual field indices were compared with baseline data before medication. The visual field changes were also analyzed using the Kaplan-Meier life-table method. The mean intraocular pressure decreased for 4 years from 14.7 +/- 4.3 mmHg (mean +/- SD) at baseline, to 12.7 +/- 4.4mmHg at 4 years. The global index of visual field (mean defect, loss variance) did not change significantly during the 4 years. The accumulative probability of survival was 80.7 +/- 8.0% after 4 years when the endpoint was defined as 3dB progression in mean defect. Isopropyl unoprostone might have the possibility of stabilizing the visual field for a long period of time.

Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivo.

Overexpression of the melanoma differentiation associated gene-7 (mda-7) in vitro results in suppression of lung cancer cell proliferation. However, the ability of MDA-7 to suppress lung cancer in vivo has not been previously demonstrated. In this study, we investigated the possibility of inducing overexpression of the mda-7 gene in human non-small cell lung carcinoma cells in vivo and its effects on tumor growth. Adenovirus-mediated overexpression of MDA-7 in p53-wild-type A549 and p53-null H1299 subcutaneous tumors resulted in significant tumor growth inhibition through induction of apoptosis. In addition, decreased CD31/PECAM expression and upregulation of APO2/TRAIL were observed in tumors expressing MDA-7. In vivo studies correlated well with in vitro inhibition of lung tumor cell proliferation and endothelial cell differentiation mediated by Ad-mda7. These data demonstrate that Ad-mda7 functions as a multi-modality anti-cancer agent, possessing both, pro-apoptotic and anti-angiogenic properties. We demonstrate for the first time the potential therapeutic effects of Ad-mda7 in human lung cancer.

Boron trifluoride induced palladium-catalyzed cross-coupling reaction of 1-aryltriazenes with areneboronic acids.

[reaction: see text] Aryltriazenes are directly coupled with areneboronic acids in the presence of a catalytic amount of Pd(2)(dba)(3) and P(tBu)(3) together with 1 equiv of BF(3).OEt(2) in DME to afford the corresponding biaryl products in up to 98% yield. A carbonylative cross-coupling reaction under a carbon monoxide atmosphere is also found to give the corresponding diaryl ketone with a similar catalyst system.

Persistent transgene expression following intravenous administration of a liposomal complex: role of interleukin-10-mediated immune suppression.

Studies conducted in non-tumor-bearing, immunocompetent mice have shown that intravenous administration of liposome-DNA complex elicits an inflammatory response that results in a failure to sustain adequate transgene expression. In the present study, however, we investigated the effects of a cationic liposomal DOTAP:cholesterol (DOTAP:Chol)-DNA complex on cytokine production and transgene expression in both experimental lung tumor-bearing (TB) mice and non-tumor-bearing (NTB) syngeneic mice and nude mice. Intravenous injection of DOTAP:Chol-luciferase (luc) DNA complex resulted in tumor necrosis factor-alpha levels that were 50% lower and interleukin-10 levels that were 50-60% higher in TB mice than in NTB mice. Furthermore, a significant increase in luc expression (P = 0.001) that persisted for 7 days was observed in TB mice. In contrast, luc expression decreased significantly from day 1 to day 2 in NTB mice. Also, luc expression was two- to threefold higher in TB mice that were given multiple injections of DOTAP:Chol-luc complex than in mice who received a single injection. In contrast, luc expression was significantly suppressed following multiple injections in NTB mice (P = 0.01). Further analysis revealed IL-10 protein expression by the tumor cells in TB mice. Injection of anti-IL-10 antibody in TB mice resulted in a significant decrease in luc expression (P = 0.01) compared with that in mice injected with a control antibody. Based on these findings, we conclude that transgene expression persists in TB mice and is partly mediated by IL-10. Additionally, multiple injections of liposome-DNA complex can increase transgene expression in TB mice. These findings have clinical applications in the treatment of cancer.

Increased uptake of liposomal-DNA complexes by lung metastases following intravenous administration.

We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)-DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome-DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome-DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol-DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.