Ovarian cancer activity of cyclic amine and thiaether metal complexes.

A thiaether metal complex 1-aza-4,7-dithiacyclononane-RhCl3, 2, and cyclic amine metal complexes tacn-CuBr2, 3, and Me3tacn-RuCl3, 4, have been evaluated for anticancer activity against the ovarian cancer cell line NuTu-19 and for cell toxicity against the noncancerous ovarian tissue cell line OVepi. Specifically, metal complex 2 is active when compared to cisplatin at micromolar concentrations using the MTT and cell invasion assay. The in vitro results reported warrant further evaluation of metal complex 2 in living systems.

Control of pulmonary metastases of rat mammary cancer by inhibition of uPA and COX-2, singly and in combination.

Tumor cell metastasis can be suppressed by the attenuation of proteolytic and angiogenic events that are mediated by tumor and endothelial cells. Combinations of specific inhibitors directed to separate stages of the metastatic cascade may improve the potential for adjuvant therapies. Amiloride is an effective plasminogen activator inhibitor, while celecoxib is a cylcooxygenase-2 inhibitor. In vitro invasion assays were used to assess the effect of each inhibitor on the cellular invasion of MATB rat mammary carcinoma cells. Individually, both amiloride and celecoxib impeded cellular invasion in a dose-dependent manner. Combinations consistently exerted a significant inhibitory response (91 to 99%). These inhibitors were administered alone and in combination to evaluate their efficacy in the prevention of pulmonary metastases from a primary rat mammary carcinoma. Amiloride and celecoxib, alone and in combination, consistently showed no effect on the growth of primary tumors. The combined inhibitors were able to reduce significantly the growth of local recurrences following primary tumor excision and metastatic incidence rates. Numbers of pulmonary metastases were reproducibly and significantly decreased with the administration of amiloride and celecoxib, alone and in combination. Celecoxib alone was most effective with a reduction in 98% of the metastases, yet distinctions were observed in the results with respect to the local recurrences, blood levels for the inhibitors and tissue production of prostaglandin E2. These data demonstrate the potential use for celecoxib, alone and in combination with amiloride, in the suppression of metastases.

Does preoperative rofecoxib (Vioxx) decrease postoperative pain with laparoscopic cholecystectomy?

BACKGROUND: A prospective, randomized, double-blinded clinical trial was designed to study the effects of preemptive rofecoxib (Vioxx) analgesia in patients undergoing elective laparoscopic cholecystectomy. METHODS: One hundred-twenty patients were enrolled in the study over a 21-month period, and 116 completed the study. One half of the patients received 50 mg rofecoxib preoperatively and the other half, placebo. Both groups were demographically similar. Medical information, patient and nursing assessments, and surgical data were evaluated. RESULTS: A significant reduction in requirements for postoperative narcotic analgesic dosing was noted in the rofecoxib group. In addition, patients receiving rofecoxib reported significantly less nausea and improvement in their activity level when compared with the control group. No complications were encountered with the preoperative use of rofecoxib. CONCLUSIONS: We conclude that in patients undergoing laparoscopic cholecystectomy, preoperative administration of rofecoxib in selected patients may facilitate postoperative recovery and decrease postoperative narcotic requirements.

Urokinase Plasminogen Activator Receptor (uPAR): A Potential Indicator of Invasion for In Situ Breast Cancer.

Urokinase plasminogen activator (uPA) and its cellular receptor (uPAR) are important mediators in the cellular process of cancer invasion and metastasis. Ductal carcinoma in situ (DCIS) is classified by lack of invasion into the adjacent stroma, yet definitive histologic features have not been identified to indicate the propensity for cellular invasion. Therapy for DCIS remains controversial because of the probability for recurrence. We hypothesized that uPA and uPAR may represent new predictors for recurrence of DCIS. Tissue specimens were obtained from 10 normal, 10 hyperplasia, and 70 patients with DCIS. Representative sections of the regions were mounted and stained by immunohistologic techniques using mouse anti-human uPA and uPAR antibodies. Stain intensities were assessed by densitometry image analysis. Gray scale values for in situ patients were compared to normal averages to determine whether staining intensities were normal or significantly higher (p < 0.05) than normal. DCIS tissues were heterogeneous for stain intensities of uPA and uPAR. Patients with high stain intensities for uPAR (28/70 = 40%) correlated with a higher recurrence rate (15/28 = 54%) than with patients having high stains for uPA (19/70 = 28% with 17/50 = 34% recurrence). In addition, patients with combined high stains for uPA and uPAR (11/19 = 60%) showed a recurrence rate of 55% compared to high uPA/normal uPAR with 0% recurrence. Immunohistologic evaluation of DCIS for uPAR, alone and in combination with uPA, significantly correlates with recurrence of invasive breast carcinoma. Evaluation of uPAR among DCIS lesions may provide a new prognostic indicator for recurrence of breast carcinoma.