ABSTRACT
We have administered the glycolysis inhibitors 2-deoxy-D-glucose and 5-thio-D-glucose to C3H/HeJ mice bearing KHT or 16/C transplantable tumors to seek evidence for hypoxic cell toxicity in vivo. The drugs were given (a) with or without insulin, (b) as large single doses or as multiple hourly injections, and (c) alone or immediately after the tumors had received radiation to kill most of the aerobic cell population. Tumor response was assessed by growth delay or by lung colony assay. Limiting toxicity of 2-deoxy-D-glucose and 5-thio-D-glucose was neurological, leading to seizures and/or death, and this toxicity was increased by insulin. The drugs had at most minimal effects on the growth of either untreated or irradiated tumors at maximal tolerated doses. Despite the known selective toxicity of these glucose analogues for hypoxic cells in tissue culture, we have found them to be ineffective in killing hypoxic cells of two murine tumors.
Subject(s)
Adenocarcinoma/drug therapy , Deoxy Sugars/therapeutic use , Deoxyglucose/therapeutic use , Fibrosarcoma/drug therapy , Glucose/analogs & derivatives , Adenocarcinoma/radiotherapy , Animals , Cell Survival/drug effects , Deoxyglucose/toxicity , Fibrosarcoma/radiotherapy , Glucose/therapeutic use , Glucose/toxicity , Hypoxia/drug therapy , Insulin/pharmacology , Male , Mice , Mice, Inbred C3HABSTRACT
Misonidazole (MISO) increased the toxicity of BCNU for hypoxic Chinese Hamster Ovary (CHO) cells in vitro, but had no effect on aerobic toxicity of BCNU. Survival was reduced by up to 10(-3) with an exposure to MISO (ImM x 4 hr) that had no direct toxicity for hypoxic cells. Preincubation of cells with MISO under hypoxic conditions followed by exposure to BCNU in air also resulted in increased toxicity. Related effects were observed when CHO cells were exposed to serum from mice that had received BCNU alone or BCNU + MISO: hypoxic (but not aerobic) cells were more sensitive to serum from mice that had received combined treatment. Studies showed that BCNU was more toxic in serum-free medium and that MISO had little or no effect on BCNU toxicity for hypoxic cells in the absence of serum. High performance liquid chromatography (HPLC) methods showed that BCNU decays with T 1/2 = 0.5 hr in the presence of 10% fetal calf serum and T 1/2 = 1.0 hr in the absence of serum, but the decay curves were not influenced by hypoxia or by MISO. BCNU metabolism to active intermediates is known to be catabolized by albumen. The dependence of the interaction of BCNU and MISO on both serum and hypoxia is consistent with an effect of a hypoxic product of MISO metabolism to delay catabolism or excretion of protein-catalyzed active intermediates of BCNU.
Subject(s)
Carmustine/toxicity , Cell Survival/drug effects , Misonidazole/pharmacology , Nitroimidazoles/pharmacology , Animals , Cells, Cultured , Cricetinae , Cricetulus , Drug Synergism , Female , Hypoxia/physiopathology , Ovary , Oxygen/physiology , Time FactorsSubject(s)
Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Aerobiosis , Anaerobiosis , Animals , Cells, Cultured , Cricetinae , Cricetulus , Doxorubicin/pharmacology , Female , Ovary/cytology , OxygenABSTRACT
The benign cystic ovarian teratoma (dermoid) has distinctive ultrasonic features that differentiate it from other adnexal masses. The most frequent sign is the presence of highly reflective irregular solid components within a fluid-containing adnexal mass. In vitro scans of surgical specimens have shown that the strongly reflective echo pattern is caused by the hair and sebum within the dermoid. Calcium is often sparse or absent. Acoustic shadowing from the hair may totally obscure the back wall of a large, clinically evident mass; hence the term "tip of the iceberg" sign. Recognition of this sign reduces the possibility of a false negative interpretation and confusion with a "bowel gas pattern."
