ABSTRACT
Ehrlich carcinoma transplanted into preirradiated calf muscle of mice was used as a model for tumor recurrence after unsuccessful radiotherapy. Due to the tumor bed effect (TBE), these grafts grew more slowly than control tumors implanted in the unirradiated tissue. When these tumors achieved the same volume (0.3-0.4 cm3), in 10-11 days for tumors implanted in irradiated tissue and 7-8 days for control tumors, they were treated with radiation, the tumor blood flow inhibitor hydralazine, and hyperthermia, alone or in different combinations. In the case of the trimodality treatment, single irradiation of tumors at a dose of 12.5 Gy was followed 2.5-3 h later by administration of hydralazine (2.5 mg/kg) and local hyperthermia (water bath, 43 degrees C for 30 min). The growth delay induced in the different tumor types by irradiation, hydralazine and hyperthermia, alone or in different combinations, was related to the blood flow measured in the tumors by the 133Xe clearance technique 24-48 h after treatment. It was shown that the reduction of blood flow after treatment with hyperthermia or hydralazine was approximately equal in both types of tumors. However, the combined inhibiting effect of these agents differed in the tumors: It was synergistic in control tumors and close to additive in tumors implanted in irradiated tissue. In terms of the specific tumor growth delay, the latter tumors were slightly more sensitive to hyperthermia, but were more resistant to radiation and thermoradiotherapy compared to control tumors. Hydralazine potentiated the tumoricidal effects of heat alone and heat combined with radiation. The enhancement was more substantial in control tumors compared to tumors implanted in irradiated tissue. A general correlation between the hydralazine-induced enhancement of the effects of heat on tumor blood flow and growth delay was observed. In tumors implanted in irradiated tissue, the inhibition of perfusion after treatment with hydralazine plus hyperthermia was smaller, and presumably a less marked treatment response to these agents (with or without radiation) was therefore achieved as a result in these tumors compared to the control tumors.
Subject(s)
Carcinoma, Ehrlich Tumor/blood supply , Carcinoma, Ehrlich Tumor/therapy , Hydralazine/pharmacology , Hyperthermia, Induced , Vasodilator Agents/pharmacology , Animals , Carcinoma, Ehrlich Tumor/radiotherapy , Cell Division/drug effects , Cell Division/radiation effects , Combined Modality Therapy , Male , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Neoplasm TransplantationSubject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Ehrlich Tumor/metabolism , Hydralazine/therapeutic use , Hyperthermia, Induced , Phosphates/metabolism , Animals , Carcinoma, Ehrlich Tumor/blood supply , Carcinoma, Ehrlich Tumor/therapy , Combined Modality Therapy , Magnetic Resonance Spectroscopy , Mice , Phosphorus IsotopesABSTRACT
In order to study effectiveness of surgical treatment in patients with glaucoma in association with atherosclerosis or diabetes mellitus, remote observations (from 1 to 8 years) were carried out over 216 patients operated at different stages of the glaucomatous process: at the initial stage--104 eyes, at the advanced--87, and the far-advanced--53 eyes. Sinusotrabeculectomy in the author's modification was used: at first the external wall of the Schlemm's canal was removed, then the trabecula was destroyed by a blunt spatula, gradually letting out the chamber aqueous. The observations carried out have shown that surgical treatment of glaucoma in patients with atherosclerosis is more effective at the initial and advanced stages. In patients with glaucoma and diabetes mellitus, surgical treatment was most effective in persons with initial stage of glaucoma. It should be noted here that surgical treatment at initial stage of glaucoma allows to preserve high visual functions for a long period of time. Stabilization of the process in persons operated at the initial stage was achieved in 95-97% of cases. This gives grounds to recommend surgical treatment of glaucoma in patients with atherosclerosis and diabetes mellitus at the initial stage of the glaucomatous process. The fall of intraocular pressure is mainly connected with improvement of the aqueous outflow.
Subject(s)
Arteriosclerosis/surgery , Diabetes Mellitus/surgery , Glaucoma/surgery , Arteriosclerosis/physiopathology , Diabetes Mellitus/physiopathology , Female , Follow-Up Studies , Glaucoma/physiopathology , Humans , Intraocular Pressure , Iris/surgery , Male , Time Factors , Trabeculectomy/methods , Visual AcuityABSTRACT
An electron-affinic compound, AK-2123, and the anti-hypertensive agent, hydralazine, were combined with radiation and hyperthermia for treatment of murine SCC-VII tumours. Hydralazine markedly decreased tumour perfusion while AK-2123 had no influence on it. Hydralazine enhanced the tumouricidal effects of hyperthermia alone and in combination with radiation. AK-2123 provided a radiosensitization which was significant only in tumours irradiated without supplementary hyperthermia. The greatest tumour response was achieved when thermoradiotherapy was combined with hydralazine alone; the additional use of AK-2123 with this treatment combination did not further increase the effect. It is concluded that hydralazine plus heat virtually eliminated a hypoxia-related radioresistance in tumours, thus removing the requirement for AK-2123 administration.