Metabolism of liriodendrin and syringin by human intestinal bacteria and their relation toin vitro cytotoxicity

When liriodendrin or syringin was incubated for 24 h with human intestinal bacteria, two metabolites, (+)-syringaresinol-beta-D-glucopyranoside and (+)-syringaresinol, from liriodendrin and one metabolite, synapyl alcohol, from syringin were produced. The metabolic time course of liriodendrin was as follows: at early time, liriodendrin was converted to (+)-syringaresinol-beta-D-glucopyranoside, and then (+)-syringaresinol. The in vitro cytotoxicities of these metabolites, (+)-syringaresinol and synapyl alcohol, were superior to those of liriodendrin and syringin.     

Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Effect of DW2282 on the induction of methemoglobinemia, hypoglycemia or WBC count and hematological changes

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl] -4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induce methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it does produce.     

Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus vernicifera stokes)

Cytotoxicities of four urushiols, congeners isolated from the sap of Korean lacquer tree (Rhus vernicifera Stokes), to 29 human cancer cell lines originated from 9 organs were evaluated. Their values of 50% growth inhibition were below 4 microg/ml, and showed cell line specific cytotoxicity. The present result is the first report on the cytotoxicity of urushiols suggesting that they would have an anticancer activity to human cancer cells.     

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.     

Synchronous coexpression of epidermal growth factor receptor and cyclooxygenase-2 in carcinomas of the uterine cervix: a potential predictor of poor survival.

PURPOSE: To evaluate the potential of the new prognostic information gained by analyzing the coexpression of epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in cervical cancer patients. EXPERIMENTAL DESIGN: Sixty-eight patients with International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix, who underwent concurrent chemoradiotherapy between 1993 and 1996, were divided into the following four groups according to their immunoreactivities for EGFR and COX-2 in paraffin-embedded sections: (a). the EGFR-negative/COX-2-negative group (n = 11); (b). the EGFR-negative/COX-2-positive group (n = 8); (c). the EGFR-positive/COX-2-negative group (n = 27); and (d). the EGFR-positive/COX-2-positive group (n = 22). The clinical features, patterns of treatment failure, and survival data in the four groups were compared. RESULTS: Positive immunoreactivity for EGFR and COX-2 was observed in 49 of 68 (72%) and 19 of 68 (28%), respectively. However, no strong correlation was found between the levels of EGFR and COX-2 immunopositivity (R(2) = 0.05, P = 0.07). Patients in the EGFR-positive/COX-2-positive group had a higher likelihood of locoregional recurrence than those in the other three groups (P = 0.02). Of the patients in the four groups, patients positive for both oncoproteins were found to have the worst prognosis with an overall 5-year disease-free survival rate of 55% compared with 91% for the EGFR-negative/COX-2-negative patients, 88% for the EGFR-negative/COX-2-positive patients, and 69% for the EGFR-positive/COX-2-negative patients (P = 0.05, log-rank test). In addition, the synchronous coexpression of the EGFR and COX-2 oncoproteins was found to be an independent prognostic factor by univariate and multivariate analyses (relative risk = 4.0, P = 0.03). CONCLUSIONS: Given these observations, we conclude that the coexpression of EGFR and COX-2 immunoreactivity may be used as a potent molecular risk factor for predicting the poor survival of patients with the International Federation of Gynecology and Obstetrics stage IIB squamous cell carcinoma of the uterine cervix.     

Interfractional variation in position of the uterus during radical radiotherapy for cervical cancer.

BACKGROUND AND PURPOSE: This study was conducted to investigate the positional change of the uterus during radiotherapy which can degrade the accuracy of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: Sixty-six patients received radical radiotherapy for cervical cancer in Samsung Medical Center. For each patient, two MRI scans were taken; one was before beginning radiotherapy and the other was in the third or fourth week of radiotherapy. In T2-weighted MRI images, the positional change of the uterus was quantified by measuring six parameters; the distance from the external uterine opening to the isthmus of the uterus (Dcx), the distance from the isthmus of the uterus to the uterine fundus (Dco), the perpendicular distance of the uterine body to the uterine corpus (Dco-per), the angle between the vertical line and the cervical canal in sagittal images (Acx), the uterine corpus angle from the vertical line in sagittal plan (Aco), the angle between the uterine corpus from an arbitrary bony landmark and a vertical mid line in axial images (Aco-axi) RESULTS: Mean value of change in Dcx+Dco of tumor size during treatment was 8.0 mm in small tumors and 17.9 mm in large tumors. Among 44 anteflexed uterus patients, 5 changed into a retroflexed position. 12 patients (18%) had a greater than 30 degrees variation in any angle. For patients under 60 years, the difference in Acx was statistically significant. CONCLUSIONS: Positional changes of the uterus during radiotherapy should be considered in the treatment planning of 3DCRT or IMRT, particularly in patients under 60 years or those with tumor size greater than 4 cm in diameter.     

Intracerebral clysis in a rat glioma model

OBJECTIVE: Intracerebral clysis (ICC) is a new term we use to describe convection-enhanced microinfusion into the brain. This study establishes baseline parameters for preclinical, in vivo, drug investigations using ICC in a rat glioma model. METHODS: Intracranial pressure was measured, with an intraparenchymal fiber-optic catheter, in male Fischer rats 10, 15, 20, and 25 days after implantation of C6 glioma cells in the right frontal lobe (n = 80) and in control rats without tumor (n = 20), before and during ICC. A 25% albumin solution (100 microl) was infused through an intratumoral catheter at 0.5, 1.0, 2.0, 3.0, and 4.0 microl/min. Infusate distribution was assessed by infusion of fluorescein isothiocyanate-dextran (Mr 20,000), using the aforementioned parameters (n = 36). Brains were sectioned and photographed under ultraviolet light, and distribution was calculated by computer analysis (NIH Image for Macintosh). Safe effective drug distribution was demonstrated by measuring tumor sizes and apoptosis in animals treated with N,N'-bis(2-chloroethyl)-N-nitrosourea via ICC, compared with untreated controls. Magnetic resonance imaging noninvasively confirmed tumor growth before treatment. RESULTS: Intracranial pressure increased with tumor progression, from 5.5 mm Hg at baseline to 12.95 mm Hg on Day 25 after tumor cell implantation. Intracranial pressure during ICC ranged from 5 to 21 mm Hg and was correlated with increasing infusion volumes and increasing rates of infusion. No toxicity was observed, except at the higher ends of the tumor size and volume ranges. Fluorescein isothiocyanate-dextran distribution was greater with larger infusion volumes (30 microl versus 10 microl, n = 8, P < 0.05). No significant differences in distribution were observed when different infusion rates were compared while the volume was kept constant. At tolerated flow rates, the volumes of distribution were sufficient to promote adequate drug delivery to tumors. N,N'-Bis(2-chloroethyl)-N-nitrosourea treatment resulted in significant decreases in tumor size, compared with untreated controls. CONCLUSION: The C6 glioma model can be easily modified to study aspects of interstitial delivery via ICC and the application of ICC to the screening of potential antitumor agents for safety and efficacy.     

The value of intraoperative cystoscopy in urogynecologic and reconstructive pelvic surgery

OBJECTIVE: Our goal was to evaluate the role of intraoperative cystoscopy during surgery for pelvic organ prolapse and urinary incontinence. STUDY DESIGN: Charts of 224 consecutive patients who had intraoperative cystoscopy performed after urogynecologic surgery were reviewed. RESULTS: Nine injuries occurred that were unsuspected before cystoscopy, for an incidence of 4%. Six ureteral ligations occurred, four after Burch cystourethropexy and two after vaginal culdoplasty. Intravesical sutures were noted after two Burch procedures, and another injury occurred with passage of fascia lata through the bladder during a pubovaginal sling procedure. Eight injuries were managed by removal and replacement of the suture or sling with only one requiring ureteroneocystotomy. When patients with injuries were compared with those without, there were no statistical differences in demographic or surgical parameters. CONCLUSIONS: The potential for damage to the lower urinary tract is significant with complex urogynecologic surgery. Because of the increased and delayed morbidity associated with unrecognized injury, intraoperative surveillance cystoscopy should be considered a part of all such procedures.(Am J Obstet Gynecol 1997;177:71)