Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.     

32nd Annual Meeting of the Scandinavian Society for Psychopharmacology Copenhagen,Denmark April 10–12, 1991 Abstracts

32nd Annual Meeting of the Scandinavian Society for Psychopharmacology Copenhagen, Denmark April 10–12, 1991 Abstracts     

Electron microscopic immunocytochemical evidence for the existence of bidirectional synaptic connections between growth hormone-releasing hormone- and somatostatin-containing neurons in the hypothalamus of the rat

Synaptic contacts between growth hormone-releasing hormone (GHRH)- and somatostatin-containing neurons were demonstrated in the rat hypothalamus by a double-staining immunocytochemical method at the electron microscopic level. Somatostatin-immunoreactive nerve terminals synapse on GHRH-positive dendrites and cell bodies in the arcuate nucleus. A fine network of GHRH-immunopositive nerve terminals was observed at the light microscopic level in the rostral part of the periventricular nucleus and in the dorsal part of the arcuate nucleus around somatostatin-containing neuronal elements. With the electron microscope synaptic contact between GHRH-containing nerve terminals and somatostatin-containing dendrites are demonstrated. The reciprocal innervation between GHRH- and somatostatin-containing neurons that project to the median eminence and regulate growth hormone secretion must allow them to coordinate their activities.     

Cerebrovascular and metabolic perturbations in delayed heavy charged particle radiation injury

Focal heavy charged particle irradiation of the rabbit brain created defined lesions which were observable by nuclear magnetic resonance (NMR) and positron emission tomography (PET) imaging techniques. The lesions appeared approximately 9-11 months after left partial hemibrain irradiation with 30 Gy (230 MeV/u helium ions), and were restricted to the white matter tracts and deep perithalamic and thalamic regions. 82Rubidium PET and Gadolinium DTPA enhanced NMR imaging were used to detect blood-brain barrier perturbations. 18Fluordeoxyglucose PET studies demonstrated widespread decreases in cerebral glucose uptake in the cortex and thalamus of the irradiated hemisphere. NMR and PET imaging results correlated well with histological findings. Rabbits irradiated with 15 Gy did not demonstrate any abnormalities in the brain with sequential NMR scans through 14 months post-irradiation.     

The factor of magnification in mammography

The last generation of mammographic equipment allows mammography to be performed with direct magnification techniques, thanks to such technical features as microfocus, high focus-film distance, high-power generators. The authors compared the diagnostic yield of two different equipment sets, with 1.4x and 2x magnification respectively, and verified the utility of magnification radiography. A significant reduction was obtained in questionable diagnoses (42 to 18) in a group of 63 patients, with no evidence of substantial differences in the diagnostic yield of the images obtained with different magnification ratios. An objective analysis of the system resolution power privileges 2x magnification ratio, which however implies an increase in the average dose to the breast. The use of faster recording systems reduces the dose by 50%, though maintaining good image quality.     

Behavioral treatment of angina-like chest pain in patients with hyperventilation syndrome

The hyperventilation syndrome is present in as many as 50% of patients with non-cardiac chest pain. This study evaluated a behavioral treatment of this disorder in three adult females. They had long histories of chest pain and were documented to be free of coronary artery disease. Each subject met the DSM-III-R diagnostic criteria for an anxiety disorder. Following treatment, all subjects showed a marked decrease in the frequency and intensity of chest pain episodes and in the frequency of shortness of breath episodes. Two subjects maintained their progress at one-year follow-up. The results lend support to the efficacy of controlled breathing and relaxation training for the treatment of hyperventilation-related chest pain and to the inclusion of a hyperventilation provocation test in the diagnosis of the syndrome as well as its role in changing cognitions regarding cardiac status. Also discussed is the rationale for treating hyperventilation related chest pain in a medical care setting.     

Enhanced take of spontaneous murine tumors in mice treated with inhibitors of macrophage and/or NK cell function

Both macrophages and NK cells have been suggested to play a role in recognizing and eliminating early, in situ neoplasms. Therefore we studied the effect of inhibitors of macrophage and/or NK cell function on the take of transplantable spontaneous murine tumors in syngeneic mice. The treatment of animals with trypan blue, a selective inhibitor of macrophage function, decreased considerably the period of latency of BSP3 adenocarcinoma; however, it did not increase the take of SP4, SP82 and SP84 adenocarcinomas. The treatment of recipients with neutral red, a selective inhibitor of NK cell function, enhanced the take of SP4 adenocarcinoma. The treatment of mice with agents depressing both macrophage and NK cell function (silica or carrageenan) decreased the both macrophage and NK cell function (silica or carrageenan) decreased the period of latency and/or increased the take of SP4, SP82 and SP84 adenocarcinomas. Carrageenan or a combined treatment with both trypan blue and neutral red also enhanced the take of BaF1, a benzo(a)pyrene-induced fibrosarcoma. We concluded that both macrophages and NK cells may function as effector cells of an antitumoral surveillance system.