Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288-296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-gamma-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.

Animals↗

PubMedDate not supplied

Deterioration of mechanical properties of the autograft in controlled stress-shielded augmentation procedures. An experimental study with rabbit patellar tendon.

Effects of partial and complete stress shielding on mechanical properties and histology of in situ frozen patellar tendons were studied in 120 mature female Japanese White rabbits that were divided into three groups: completely stress-shielded, partially stress-shielded, and sham-operated groups. In the former two groups, tendon tension was reduced to 0% and about 30% of normal force, respectively, with a polyester artificial ligament. Tensile tests were conducted on patella-patellar tendon-tibia complexes harvested 1, 2, 3, 6, or 12 weeks after surgery. Tensile strength significantly decreased compared with the sham group to 17% and 28% at 3 and 6 weeks, respectively, in the completely stress-shielded group, and to 54% and 63% at 3 and 12 weeks, respectively, in the partially stress-shielded group. Patellar tendon cross-sectional area significantly increased to 156% and 157% at 2 and 3 weeks, respectively, in the completely stress-shielded group and to 133% at 2 weeks in the partially stress-shielded group, compared with the sham group. Stress shielding significantly changed tensile strength, tangent modulus, and cross-sectional area of in situ frozen patellar tendon; these changes depended on degree of stress shielding. Histologic observations indicated that remodeling occurred in the patellar tendon while there were no cells in the fascicle.

Animals↗

PubMedDate not supplied

Forskolin-stimulated adenylylcyclase activity: a marker to assess islet cell viability following cold storage in different solutions and to predict islet cell function following transplantation.

For clinical islet cell transplantation, short-term storage of islet cells is likely to be necessary, and it is imperative that the islet cells be kept as viable as possible during the period. However, there are little data on which preservative solutions are most suitable for the storage of islet cells after isolations or before transplantation. To estimate islet cell viability and transplantation success rate in the present study, adenylylcyclase activity was measured with a rapid new fluorometric assay in rat islet cells prior to transplantation, because cAMP plays an essential role in determining islet beta-cell viability and responsiveness to various hormonal stimuli. Adenylylcyclase activity was measured in islet cells stored for different periods of time 0, 3, 16, 24, 48, 96 h) and in different preservative solutions. Approximately 1,000 islet cells from each preservation group using University of Wisconsin (UW) solution were transplanted to streptozotocin-induced diabetes mellitus (DM) rats. Transplant success was evaluated by measuring blood glucose levels. Preoperative adenylylcyclase activity was compared with posttransplant islet cell function. The adenylylcyclase activity of UW solution was significantly higher than that of Euro-Collins solution and lactate-Ringer's solution through the different preservation time periods. Preoperative adenylylcyclase activity correlated well with posttransplant islet cell function in a rat model of DM. We conclude that adenylylcyclase activity can be used as a marker to assess islet cell viability as well as differences in preservation media and may predict islet cell transplant success.

Adenylyl Cyclases↗

PubMedDate not supplied

Exploration of Vogt-Koyanagi-Harada syndrome by infrared choroidal angiography with indocyanine green.

The choroid affected by the Vogt-Koyanagi-Harada syndrome (VKH) has seldom been explored by indocyanine green choroidal angiography. Five patients with definite diagnosis of VKH underwent this investigation. The first case had the most marked leakage, very similar to that on fluorescein angiography. The right eye of case 2 showed fewer leakage points on ICG than on fluorescein angiography, compared with case 1. The left eye of case 2 did not show any leakage. Cases 3, 4 and 5 yielded segmental hyperfluorescence, distant from the posterior pole, which could not be identified by fluorescein angiography. This might indicate segmental choroiditis. There were two types of hypofluorescent lesions; all the cases except case 2 showed early hypofluorescence. Hypofluorescent areas corresponding to overlying retinal detachment were seen in the right eye of case 4. Multiple spots, late hypofluorescence, about 200 to 500 um in size appeared throughout the posterior pole in four eyes out of ten. In conclusion, indocyanine green choroidal angiography provides a wider variety of pictures than fluorescein angiography.

Adult↗

PubMedDate not supplied

In vivo efficacy and pharmacokinetics of a new hypoxic cell radiosensitizer doranidazole in SUIT-2 human pancreatic cancer xenografted in mouse pancreas.

A new 2-nitroimidazole radiosensitizer doranidazole is now undergoing clinical evaluation in combination with intraoperative radiotherapy for unresectable pancreatic cancer. However, there have been no laboratory data on its effect against pancreatic cancer. This study was undertaken to clarify the efficacy and pharmacokinetics of doranidazole in a human pancreatic cancer SUIT-2 xenografted in the pancreas of nude mice. The tumor-bearing mice were irradiated to the upper abdomen using electron beams with or without prior administration of doranidazole. The tumors were excised 3-6 days later and their weight was measured. Doranidazole given alone had no antitumor effect, but it had radiosensitizing effects when 100, 150, or 200 mg/kg of the drug was combined with single 5 Gy irradiation. The tumor/serum ratios for doranidazole concentration were 0.3-0.4, but the concentrations in the tumor were similar to those in the surrounding normal pancreas. At doses of 100 mg/kg or higher, concentrations of doranidazole in the pancreatic tumor appeared to be sufficient to obtain definite radiosensitization.

Animals↗

PubMedDate not supplied

Plasma soluble Fas ligand concentration: decrease in elderly men and increase in patients with gastric carcinoma.

Fas ligand (FasL), which induces apoptosis against Fas-expressing cells, has been found to be expressed on various cell types including cancer cells. Membrane-bound FasL is cleaved to release soluble FasL (sFasL). Although serum or plasma sFasL concentration has been reported to increase in various diseases, sFasL concentration in healthy normal persons has not been fully studied. There have been few reports on sFasL concentrations in patients with carcinomas. We measured plasma sFasL concentrations using an enzyme-linked immunosorbent assay in 155 healthy volunteers (70 males and 85 females with an average age of 41.5+/-15.4) and 112 patients with gastric carcinoma (76 males and 36 females with an average age of 62.3+/-11.5). A significant negative correlation existed between age and plasma sFasL concentration in healthy volunteers. sFasL concentrations in males were significantly lower than those in females. Plasma sFasL levels were significantly higher in patients with gastric carcinoma than in healthy volunteers when male subjects aged 50 or older were analyzed, although no significant difference existed between the groups in the age bracket of 35 to 49. Male patients aged 50 or older with stage 1B or 2 tumors showed significantly higher plasma sFasL concentrations than those with stage 1A tumors or those with stage 3 or 4 tumors. In conclusion, age- and gender-matched controls should be used when plasma sFasL concentration is investigated. The origin and physiological or clinical significance of plasma sFasL in healthy volunteers and gastric cancer patients remain to be clarified.

Adult↗