Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma.

BACKGROUND: Patients with recurrent glioblastoma have a poor outcome. Data from the phase III registration trial comparing tumour-treating alternating electric fields (TTFields) vs chemotherapy provided a unique opportunity to study dexamethasone effects on patient outcome unencumbered by the confounding immune and myeloablative side effects of chemotherapy. METHODS: Using an unsupervised binary partitioning algorithm, we segregated both cohorts of the trial based on the dexamethasone dose that yielded the greatest statistical difference in overall survival (OS). The results were validated in a separate cohort treated in a single institution with TTFields and their T lymphocytes were correlated with OS. RESULTS: Patients who used dexamethasone doses >4.1 mg per day had a significant reduction in OS when compared with those who used ⩽4.1 mg per day, 4.8 vs 11.0 months respectively (χ(2)=34.6, P<0.0001) in the TTField-treated cohort and 6.0 vs 8.9 months respectively (χ(2)=10.0, P<0.0015) in the chemotherapy-treated cohort. In a single institution validation cohort treated with TTFields, the median OS of patients who used dexamethasone >4.1 mg per day was 3.2 months compared with those who used ⩽4.1 mg per day was 8.7 months (χ(2)=11.1, P=0.0009). There was a significant correlation between OS and T-lymphocyte counts. CONCLUSIONS: Dexamethasone exerted profound effects on both TTFields and chemotherapy efficacy resulting in lower patient OS. Therefore, global immunosuppression by dexamethasone likely interferes with immune functions that are necessary for the treatment of glioblastoma.

Effect of varying the type of fat in a semi-purified AIN-76A diet on cellular proliferation in the mammary gland and intestinal crypts in female Swiss Webster mice.

Young virgin female Swiss Webster mice were fed AIN-76A semi-purified diets containing equal weights of different fats for approximately 30 days. Using [3H]thymidine radioautography, it was established that mice fed 100% lard or high levels of fish oils (menhaden oil or cod liver oil) developed elevated cellular proliferation in the duct cells of the mammary gland and an increased number of labeled cells/crypt in the crypts of the colo-rectum accompanied by an increase in the size of the proliferative compartment. A possible inverse correlation between the level of [3H]thymidine labeling in the mammary gland, but not in the colo-rectum, and the linoleic acid content of individual diets may help to explain the significance of these observations. The effect of adding an antioxidant mixture to these diets was to reduce the excess proliferation induced in the intestinal crypts by lard or fish oil to the level induced by soybean oil, but only partially so in the duct cells of the mammary gland.

Impaired osteoclastic function and linear bone erosion rate in secondary hyperparathyroidism associated with chronic renal failure.

Osteoclastic function, as estimated by the speed with which the haversian cutting cones advance through the compacta of the rib (linear erosion) was found significantly decreased (27.97-SE 0.8 mu/day versus normal 43.61-SE 0.7 mu/day) in dogs rendered chronically uremic (BUN between 36-89 mg/100 ml). The cause of the impairment of osteoclasts' function was tentatively ascribed to the chronic excess of the circulating parathyroid hormone. A decrease in the linear erosion rate, such as observed in this study, will produce predictable morphological changes. As the time necessary to erode a cavity increases, so does the lifespan of cavities, their number and consequently the bone surface area (or in the bone section the perimeter length) covered by Howship's lacunae. Thus, the increased total bone erosion perimeter in secondary hyperparathyroidism associated with moderate uremia does not necessarily reflect an accelerated tissue level erosion rate or even bone loss. As the remodeling sites in both adult man and dog have a similar standard configuration and dimensions, these observations may be extrapolated to disease in man.