[Proliferative activity and the efficacy of radiation therapy in melanoma and squamous-cell keratinizing cancer of the skin]. / Proliferativnaia aktivnost' i éffektivnost' luchevoi terapii melanomy i ploskokletochnogo orogovevaiushchego raka kozhi.

Proliferative activity (growth fraction) of malignant melanoma and keratinizing squamous cell carcinoma of the skin (19 patients) was studied using L. Schiffer's method (1975) modified by R. K. Karakulov (1982) and based on differences in the activity of DNA-polymerase in proliferating cells and cells "beyond the cycle". The number of active DNA-polymerase containing nuclei was determined using tumor cell nuclear DNA as matrices. The results obtained showed that malignant skin melanoma possessed a low proliferative activity (13.4% before radiation exposure). After the delivery of a dose of 30 Gy growth fraction was lowered by 25% (approximately 10%). Squamous cell skin carcinoma possessed a high proliferative activity, its basal value was 39.4%. After a dose of 30 Gy growth fraction was decreased 3-fold (approximately 12.9%). In malignant melanoma there was no correlation between a growth fraction value, the period and stage of disease as well as between a decrease in growth fraction and a degree of tumor regression by the end of irradiation. In skin cancer there was direct correlation between the depth of a growth fraction drop and a degree of tumor regression after a dose of 30 Gy. Therefore one can assume that the determination of a value of proliferative activity of radiosensitive tumors can serve as a criterion of therapeutic efficacy.

[Use of the indicators of the proliferative activity of tumors of the oropharyngeal area as qualitative prognostic criteria of the radiotherapy]. / Ispol'zovanie pokazatelei proliferativnoi aktivnosti opukholei orofaringeal'noi zony v kachestve prognosticheskogo kriteriia luchevoi terapii.

Labeling index (LI) and growth fraction (GF) values were studied over time using biopsy specimens from patients with oropharyngeal cancer. The comparison of laboratory findings with tumor clinical response showed that a significant factor determining the tumor radiation reaction was the degree of LI and GF decrease during radiotherapy rather than their basal values. A favourable prognostic sign was a drop down to 0 or a sharp decrease in LI and GF values indicating a high tumor radiosensitivity, and enabling one to continue radiotherapy according to the radical program. A tumor could be considered radioresistant in case of an increase in LI and GF values by the end of an interval in the middle of a split course. In patients with resectable tumors treatment should end up with an operation; in those with unresectable tumors--it should be followed by combined radiotherapy, with an increased dose of interstitial gamma-therapy.

Studies of metronidazole radiosensitizing effect in radiation treatment of patients with oral cavity cancer.

Clinical observations of 26 patients with tongue, oral cavity and oropharyngeal cancer receiving telegammatherapy by dynamic dose fractionation scheme in combination with metronidazole (MZ) and of 38 patients from control group treated by identical schedule without MZ suggest that MZ favors increasing of the radiation damage in tumors of those sites without changing the character or intensifying early radiation reactions. After oral administration of MZ in single doses of 5-6 g/m2 it reaches its maximum in the blood serum within 2-4 h. When the total dose of 30-60 g of MZ was used, a marked toxic effect manifested by gastrointestinal symptoms was observed in 33.3% of patients. MZ has a negative effect on liver functions, however, changes in biochemical tests illustrating it, are reversible and within the norm. Simultaneous studies of biopsy material from 22 patients (11 from each group) in terms of proliferation activity showed that oral cavity tumors contain a significant portion of proliferating cells which notably decrease in the course of radiation therapy. To a greater extent that decrease is marked after irradiation with MZ.

[Oxygen status and angioarchitectonics of different types of tumors and their changes after radiotherapy]. / Kislorodnyi status i angioarkhitektonika opukholei razlichnykh tipov i ikh izmenenie pri luchevoi terapii.

The study of the oxygen tension and blood supply to the implanted tumors of different histological structures demonstrated a correlation between pO2 and blood supply of sarcoma 37 after a single and fractionated irradiation. As to Lewis carcinoma and B-16 melanoma, the correlation was only found in tumors of a small size: as the tumor grew up to 14-15 mm such a correlation was absent. It was also established that the radiation-induced changes in the vessels and the oxygenation depended upon the histological structure of the tumor.

[Metronidazole: basic experimental results and clinical prospects]. / Metronidazol, osnovnye éksperimental'nye rezul'taty, perspektivy dlia kliniki.

The paper is concerned with the effect of metronidazole, one of the radiosensitizers of hypoxic cells. Analysis of the literature data has shown that at present metronidazole can be used to enhance the sensitivity of hypoxic cells to irradiation, chemotherapeutic drugs and as a cytotoxic agent. These effects are determined by the radiation-chemical mechanism, the toxic effect of recovery products, a decrease in the content of nonprotein sulfhydryl compounds, the suppression of cell regeneration resulting from lethal injuries. The authors' experimental results obtained in 4 murine and human tumors growing in diffusion chambers have shown that the level of radiosensitization does not depend on tumor growth rate and proliferative activity, that it depends on the type of tumors and their individual features and increases with single irradiation as compared to fractional. The degree of chemosensitization also depends, to a great extent, on a tumor type, schemes of drug administration and the type of drugs.

[Effect of combined exposure to an interferon inducer, irradiation and 5-fluorouracil on sarcoma 37 in mice]. / Effekt kombinirovannogo vozdeistviia induktora interferona, oblucheniia i 5-ftoruratsila na sarkomu 37 myshei.

Oral administration of a liposome-encapsulated agent triggering the synthesis of interferon--poly(I) poly (C)--to mice bearing solid sarcoma 37 was followed by (a) production of an interferon which circulates for a longer period after preliminary administration of "empty" liposomes; (b) lengthening of the period of tumor latency; in some cases tumor failed to appear at all; (c) higher efficacy of radiation treatment which was manifested by a higher inhibition of tumor growth or complete regression; (d) increased antitumor effect of 5-fluorouracil, and (e) suppression of proliferative activity of tumor.

[Oxygen status of transplantable murine tumors and its change during radiotherapy]. / Kislorodnyi status perevivnykh opukholei myshei i ego izmenenie pri luchevoi terapii.

The degree of oxygenation in sarcoma 37, Lewis' carcinoma and melanoma B-16 of mice has been shown to depend on a tumor type (the most marked degree in sarcoma 37), it decreases from the periphery and with tumor growth. In single and fractionated irradiation the oxygen tension increases considerably in large size tumors and in the central zones of small size tumors. In melanoma B-16 reoxygenation is insignificant. It is assumed that the oxygen status plays an important role in the radiation response of large size tumors only.

[Cell kinetics of oral cancer during gamma teletherapy in combination with the administration of metronidazole]. / Osobennosti kletochnoi kinetiki raka polosti rta pri distantsionnoi gamma-terapii v sochetanii s vvedeniem metronidazola.

Proceeding from the clinical observation of 11 patients with cancer of the tongue, oral mucosa and stomatopharynx who received gamma-beam therapy according to the scheme of dynamic fractionation combined with metronidazole, it has been concluded that the drug enhances the degree of radiation injury of the above tumors. It is expressed in early time (the 2nd day of treatment) and a low dose level (8 Gy) at which tumor resorption starts and the completeness of gamma-beam therapy in summary doses of 30-60 Gy is revealed (a general index of a clinically complete resorption is 90.8% - 10 out of 11 patients). A simultaneous study of the proliferative activity on the biopsies from the same 11 patients has shown that tumors of the oral cavity contain a considerable amount of nonproliferating cells that reduces in the process of radiotherapy combined with metronidazole. No correlation was found between the initial content of these cells, the degree of its decrease during radiotherapy combined with metronidazole and the completeness of resorption at the end of radiotherapy.

[Experimental approaches in studying the biological properties and radiation sensitivity of human brain tumors]. / Eksperimental'nye podkhody k izucheniiu biologicheskikh svoistv i chuvstvitel'nosti k oblucheniiu opukholei golovnogo mozga cheloveka.

The share of proliferating cells, the tumor growth fraction, was studied in 11 cases of glial tumors of the large hemispheres of man. The individual sensitivity of human glial tumors to irradiation was determined in 7 cases by the method of tumor growth in diffusion chambers. It was established that glioblastomas and dedifferentiated astrocytomas were characterized by a sufficiently high proliferative activity. The duration of the history of the disease and the period free of recurrences correlated with the value of the growth fraction in many cases. Gliomas, even of the same histostructure, differed considerably in the reaction to irradiation in some patients. The sensitivity of tumor cells to irradiation in growth in diffusion chambers does not depend on the proliferative activity of the initial tumors determined on operative material.

Proliferative activity and radiosensitivity of human tumors.

On surgery material and biopsies from human tumors of various types investigation of labeling index and growth fraction in vitro, cell survival and cell population kinetics in diffusion chambers and changes in the cell kinetic parameters after irradiation were performed. The analysis of results obtained using the diffusion chambers and in vitro system demonstrate variability in labeling index within tumors of various type, individual differences and variation within the same tumor. Significant variability of growth fraction in individual tumors was also noted, however, in many instances, the most of cells in tumor were not proliferating. The growth fraction in gliomas and tumors of the floor of mouth was greater in tumors with high labeling index, in patients with a short tumor history and in patients with the short nonrelapse period. In the same groups of tumors changes of labeling index growth fraction during radiotherapy were compared with the therapeutic response of tumors. It can be concluded that the initial parameters of proliferative activity (labeling index and growth fraction) did not determine the radiation response of tumors but the dynamics and the intensity of their changes during the treatment were more informative in this respect. Complete regression of tumor may be expected only with decrease of labeling index and growth fraction.

[Cell proliferation parameters in human rectal tumors and their transformation during fractionated irradiation]. / Parametry proliferatsii kletok opukholei priamoi kishki cheloveka i ikh izmenenie pri fraktsionirovannom obluchenii.

Human rectal adenocarcinoma is characterized by considerable variation in labelling index for different tumors as well as different areas within the same tumor. Therefore, the averaged indices of tumor cell proliferative activity do not mirror the actual heterogeneity of tumor. Conventional schedules of fractionated irradiation resulted in a decreased labelling index and varying response in most cases under study. Following large-dosage fractionated irradiation, labelling index remained unchanged or showed a slight decrease. The rate of DNA synthesis is practically unaffected by the available schedules of fractionated irradiation.