In vitro inducible nitric oxide synthesis inhibitory active constituents from Fraxinus rhynchophylla

Bioassay-guided fractionation of an H2O extract of the barks of Fraxinus rhynchophylla has furnished two inducible nitric oxide synthase (iNOS) inhibitory compounds, ferulaldehyde (1) and scopoletin (3) together with a coumarin, fraxidin (2). Compounds 1 and 3 showed inhibition of nitric oxide (NO) synthesis in a dose-dependent manner by murine macrophage-like RAW 264.7 cells stimulated with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS). The inhibition of NO synthesis of 1 was reflected in the decreased amount of iNOS protein, as determined by Western blotting.     

An antioxidant lignan and other constituents from the root bark of Hibiscus syriacus

A new lignan named as hibiscuside, (+)-pinoresinol 4-O-[beta-glucopyranosyl (1--->2)-alpha-rhamnoside] (1), and a known lignan, syringaresinol (2) were isolated from the root bark of Hibiscus syriacus together with two feruloyltyramines (3,4) and three known isoflavonoids (5,6,7). The structures of these compounds have been established on the basis of their NMR, mass UV spectra. Among these phenolic compounds, 6"-O-acetyldaidzin (5), 6"-O-acetylgenistin (6), and 3-hydroxydaidzein (7) with IC(50) values of 8.2, 10.6, and 4.1 microM, respectively, significantly inhibited lipid peroxidation in rat liver microsomes. Hibiscuside (1), E- and Z-N-feruloyl tyramines (3,4) exhibited moderate antioxidant activity.     

Synthesis of benzo[c]phenanthridine derivatives and theirin vitro antitumor activities

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screenedin vitro antitumor activities against five different cell lines as well as12. Among them the representative cytotoxic results are shown as follows;p-quinone (11) [ED₅₀ (A549=0.22 μg/ml), (HCT15=0.21 μg/ml), fagaridine (1) (HCT 15=0.41 μg/ml), olefin (6) (HCT 15=0.06 μg/ml), acetal (7) (SKMEL-2=0.07 μg/ml), dihydrofagaridne (10) (A549=0. 38 μg/ml), 10-hydroxyfagaridine (12) (A 549=0.45 μg/ml). From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significantin vitro antitumor activity.     

Bioactive suture: a novel immunotherapy for head and neck cancer.

PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.     

The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time.

PURPOSE: We hypothesized that the outcome of liver transplantation in patients with hepatocellular carcinoma (HCC) has improved over the past decade because of the application of published criteria for patient selection. In this study, we compared the outcome of liver transplantation in patients with and without HCC at different time periods using the United Network for Organ Sharing data. PATIENTS AND METHODS: We excluded children, patients with multiple organ transplantation or retransplantation, and those with incomplete survival data. The study period was arbitrarily divided into three time intervals: 1987 to 1991, 1992 to 1996, and 1997 to 2001. RESULTS: During the study period, 985 patients with HCC (HCC group), and 33,339 without HCC underwent liver transplantation (control group). Kaplan-Meier patient and graft survivals were significantly lower for the HCC group compared with the control group. Cox regression analysis (after adjusting for other confounding variables) confirmed a lower patient survival in the HCC group (1-year survival, 77.0% v 86.7%; hazard ratio [HR], 1.7; 95% CI, 1.5 to 2.0; P <.0001) compared with the control group (5-year survival, 48.2% v 74.7%; HR, 2.2; 95% CI, 1.9 to 2.4; P <.0001); HCC was an independent predictor of survival. Kaplan-Meier analysis showed a significant improvement in 5-year patient survival with time in patients with HCC (1987 to 1991, 25.3%; 1992 to 1996, 46.6%; 1997 to 2001, 61.1%; P <.0001). During the same period, there was only minimal improvement in survival among the control group. CONCLUSION: Five-year survival of patients transplanted for HCC is excellent, with a steady improvement in survival over the past decade. It is possible that the published criteria for patient selection may have contributed to the better outcome.     

Growth of Pakistani children in relation to the 1990 growth standards

This study was designed to compare the growth of Pakistani schoolchildren in the UK with the 1990 UK growth standards. Measurements of height, weight, and sitting height were performed on 785 Pakistani schoolchildren aged 5-14 years with the mean values for each age and sex being plotted on the UK growth standards. The results were expressed as SD scores relative to the 1990 reference data. The mean height for the boys was only 0.2 SD scores below the mean for the new growth standards with the mean height for the girls being 0.4 SD scores below the mean. The mean values for weight and body mass index were 0.3 and 0.5 SD scores less than the mean for boys and girls respectively. This study demonstrates that the growth of Pakistani schoolchildren in the UK is comparable to the 1990 UK growth standards with only minor differences. It is not safe to assume that short stature or low body weight in a Pakistani child is due to his or her ethnic background.     

Actual half-life of alpha-fetoprotein as a prognostic tool in pediatric malignant tumors

In a retrospective study, the prognostic value of monitoring the decay of alpha-fetoprotein (AFP) was assessed. Serum AFP was determined serially in 18 children with malignant germ-cell or hepatic tumors: 7 endodermal sinus tumor, 3 embryonal carcinoma, 5 malignant teratoma, 2 hepatoblastomas, and 1 hepatocellular carcinoma. The actual half-life (AHL) of AFP was computed after surgical resection of the tumor. In group 1, which had complete resection and no recurrence during follow-up (n = 13), the AHL of AFP was 4.0 ± 0.9 days. In group 2, which had incomplete resection or recurrence during follow-up (n = 5), the AHL of AFP was 24.8 ± 20 days, significantly longer than that of group 1 (P = 0.0026). The increased AHL of AFP indicated residual active tumor after surgical resection. The AHL of AFP may be more sensitive than serial monitoring of AFP in detecting preclinical recurrence after surgical resection of AFP-secreting tumors. Treatment strategies can be based on AFP clearance, and prospective clinical trials are warranted.