ABSTRACT
TNFerade is a radioinducible adenoviral vector expressing tumor necrosis factor-alpha (TNF-alpha) (Ad.Egr-TNF) currently in a phase III trial for inoperable pancreatic cancer. We studied B16-F1 melanoma tumors in TNF receptor wild-type (C57BL/6) and deficient (TNFR1,2-/- and TNFR1-/-) mice. Ad.Egr-TNF+IR inhibited tumor growth compared with IR in C57BL/6 but not in receptor-deficient mice. Tumors resistant to TNF-alpha were also sensitive to Ad.Egr-TNF+IR in C57BL/6 mice. Ad.Egr-TNF+IR produced an increase in tumor-associated endothelial cell apoptosis not observed in receptor-deficient animals. Also, B16-F1 tumors in mice with germline deletions of TNFR1,2, TNFR1 or TNF-alpha, or in mice receiving anti-TNF-alpha exhibited radiosensitivity. These results show that tumor-associated endothelium is the principal target for Ad.Egr-TNF radiosensitization and implicate TNF-alpha signaling in tumor radiosensitivity.
Subject(s)
Genetic Therapy/methods , Melanoma, Experimental/therapy , Radiation-Sensitizing Agents , Tumor Necrosis Factor-alpha/metabolism , X-Ray Therapy , Animals , Apoptosis/drug effects , Cell Line, Tumor , Endothelial Cells/drug effects , Endothelial Cells/physiology , Etanercept , Humans , Immunoglobulin G/pharmacology , Immunosuppressive Agents/pharmacology , Mice , Neoplasm Transplantation , Receptors, Tumor Necrosis Factor , Receptors, Tumor Necrosis Factor, Type I/deficiency , Receptors, Tumor Necrosis Factor, Type II/deficiency , Tumor Necrosis Factor-alpha/antagonists & inhibitorsABSTRACT
Although there is anecdotal evidence of balloon tamponade for posthysteroscopic acute uterine bleeding, a literature review disclosed no articles describing complications of the technique. In our patient, balloon tamponade for acute posthysteroscopic bleeding resulted in disseminated intravascular coagulation. In a second woman the procedure was successful.
Subject(s)
Balloon Occlusion , Catheterization/adverse effects , Disseminated Intravascular Coagulation/etiology , Hysteroscopy/adverse effects , Menorrhagia/surgery , Uterine Hemorrhage/therapy , Blood Transfusion , Catheterization/methods , Disseminated Intravascular Coagulation/therapy , Female , Follow-Up Studies , Humans , Hysteroscopy/methods , Menorrhagia/diagnosis , Middle Aged , Treatment Outcome , Uterine Hemorrhage/diagnosisABSTRACT
The denitrification of nitrites and nitrates (1000 mg N/l) in medium containing methanol as a source of organic carbon was studied. Continuous cultures of mixed population of autochtonic microflora from bottom sludge of nitrogenous wastewater reservoir were set up in a chemostat-type column and packed bed reactor. The efficiency of denitrification of nitrates in packed bed reactor was 506.7 mg N/l/h whereas denitrification of nitrites was from 8.7 to 16.0 mg N/l/h depending on the granulation of the filing material. In the latter case 83% nitrogen was removed from the medium. One of the factors causing low efficiency of denitrification of nitrites is excessive alkalization of the medium in the bed. The use of a three-step bed with adjusted pH resulted in complete denitrification of nitrites with efficiency 60 mg N/l/h. The bacteria inside the bed were dominated by Paracoccus denitrificans and by Pseudomonas aeruginosa when nitrates were present. The sensitivity of P. denitrificans to high concentrations of nitrites seems to be the second factor contributing to low efficiency of denitrification with methanol as organic substrate.
