[The importance of DNA-cytometry for the prediction of nasopharyngeal malignancy].

The method of DNA-cytometry was applied to examine patients presenting with nasopharyngeal malignancy. The results obtained in laboratory studies were compared with clinical observations and data of medical histories. It was shown that diploid and aneuploid nasopharyngeal tumours are represented in an equal proportion. The number of the latter tumours increased with the progress of the neoplastic process. The diploid and aneuploid tumours were characterized by the equally frequent occurrence of metastasis. The survivorship rate of patients presenting with diploid tumours during the first year after the onset of the disease was significantly higher than in the patients having aneuploid nasopharyngeal cancer. The results of the study indicate that DNA-ploidy can not be used as a predictor of the development of the neoplastic process in patients with nasopharyngeal cancer, nor does it have a predictive value for the evaluation of the efficacy of chemo/radiotherapy. Nevertheless, the data obtained may be useful for the selection of patients for the more intensive adjuvant therapy.

[The experience in the use of DNA flow cytometry to predict the natural history of malignant neoplasms]. / Opyt primeneniia protochnoi DNK-tsitometrii dlia prognozirovaniia techeniia zlokachestvennykh novoobrazovanii.

The aim is to study the pattern of a cell population (ploidy) and to evaluate the latter's significance in the prognosis of different carcinomas. A total of 467 patients with primary carcinomas of the breast (n = 177), lung (n = 88), head and neck (n = 140), and colon and rectum (n = 62) were examined. All the patients underwent surgery alone or in combination with radiotherapy (X-ray)/chemotherapy. A follow-up lasted 6 to 120 months. DNA was measured in the operative tumor tissue specimens by using an ICP-22 flow cytometer. Diploid and aneuploid cancers occurred in 20.4-53.6 and 43.6-79.6% of cases, respectively. The frequency of recurrences was mainly associated with aneuploidy and it was more than thrice higher than that with diploidy (21.0-43.2 versus 4.5-14.4%). Five-year survival was twice worse in patients with aneuploid tumors than in those with diploid ones. The survival rates after one operation, preoperative, and postoperative radiation therapy was greater in patients with diploid tumors than in patients with aneuploid ones. Thus, DNA-ploidy of the study neoplasms is of high informative value in predicting the course of a tumorous process and in choosing treatment policy on an individual basis.

[DNA flow cytometry in the prognostication of certain malignant neoformations]. / Protochnaia DNK-tsitometriia v prognozirovanii techeniia nekotorykh zlokachestvennykh novoobrazovanii.

The study has been concerned with DNA ploidy and its significance for prognosis of different neoplasms. The investigation included 314 patients: primary cancer of the lung (96), head and neck (146) and large bowel (72). Patients received surgery alone or surgery plus either radiotherapy or chemotherapy; they were followed up for 6-20 months. DNA levels were assayed in resected material using an ICP-22 flow cytometer. Diploid and aneuploid cancers were detected in 20.4-53.6 and 43.6-79.6%, respectively. The recurrence rates in cases of aneuploid cancers were more than 3 times those of diploidy (21.0-43.2 and 4.5-14.5%, respectively). Overall 5-year survival in diploid patients was twice that in aneuploid ones. Similarly, survival after surgery alone, preoperative chemotherapy and postoperative radiotherapy among diploid patients was longer than in aneuploid ones. Hence, DNA ploidy examination of tumors is of great informative value in prognosing tumor process and working out individually-tailored approach to treatment.

[Effects of biorhythm regulator melatonin on DNA synthesis in short-term cultures of human malignant tumors]. / Deistvie reguliatora bioritmov melatonina na sintez DNK v kratkosrochnykh kul'turakh zlokachestvennykh opukholei cheloveka.

The cytotoxic action of melatonin on DNA synthesis was studied in short-term human tumor tissue cultures. Twenty tumors (ovarian, renal, colorectal, gastric, skin, testicular, thyroid, adrenal gland, endometrial, cervical uterus ones, and melanoma) were isolated from patients at surgery. The effect of melatonin (concentrations of 5 x 10(-5) M to 5 x 10(-13) M on the level of 3H-thymidine incorporation into tumor tissue DNA (4-hour exposure) was evaluated. After exposure, 3H-thymidine was added to the medium for an hour. The quantity of DNA was determined in the hydrolysate by spectrometry; the level of 3H-thymidine incorporation into DNA was radiometrically evaluated by a scintillation counter. The quantity corresponding to 3H-thymidine incorporation per unit of DNA was determined. The control group and the melatonin-treated groups were compared by ANOVA. Melatonin inhibited DNA synthesis in 11 (55%) of the 20 tumors and was ineffective in 9 (45%) of the 20 ones. Melatonin-sensitive tumors were as follows: endometrial CA (33% vs 75% inhibition, p < 0.01), gastric CA (71% inhibition, p < 0.05), adrenal gland CA (38% inhibition, p < 0.01). Ovarian, cervical, skin CA and melanoma were unresponsive to melatonin. Renal cell CA, colonic and rectal CA were sensitive in some cases. In sensitive tumors, melatonin was effective even at concentrations of 5 x 10(-13) M to 5 x 10(-7) M. Thus, melatonin has an oncostatic effect on some human tumors in vitro occasionally at physiological concentrations.

Synthesis of phosphoramide mustard analogues of daunomycin and carminomycin.

New phosphoramide mustards (6-8) have been prepared from the antibiotics 2 and 3, and from 5. The mixture of cyclophosphamides could be separated by preparative layer and column chromatography. The assignments of configuration to the isomeric phosphoramidates was based on the magnetic anisotropy of the P = O bond. The synthesized compounds 6a,b-8a,b (mixture of isomers) were tested for inhibitory activity on the [3H]-thymidine incorporation into the DNA of tumor cells, using ovarian carcinoma cell line.

[The effect of an injection of N-methylformamide into mice on the cell cycle and cell morphology of ascitic hepatoma 22A]. / Vliianie in''ektsii mysham N-metilformamida na kletochnyi tsikl i morfologiiu kletok astsitnoi gepatomy 22A.

A cell differentiating agent N-methylformamide (MF) was studied for its antitumor activity against a murine ascitic hepatoma 22A. After a 48 hour NMF administration (i/p) the tumor cell number was monitored; the distribution of these cells in the cell cycle was registered by flow cytometry, ultrastructural changes were studied by electron microscope. The polar solvent MF inhibited tumor growth, reduced mitotic activity, and nuclear/cytoplasmic ratio, led to structural complication of endoplasmic reticulum and mitochondria. The analysis of these events is suggestive that in consequence of MF effect on tumor cells, proportion of G0/G1 and M cells was decreased, while the proportion of S and G2 cells was increased.

[Morphological and biological features of squamous cell carcinoma of the larynx]. / Morfologicheskie i biologicheskie osobennosti ploskokletochnogo raka gortani.

The study of morphological and biological criteria of laryngeal squamous cell carcinoma in 81 patients proved essential in the disease prognosis. In grade I malignancy 90 +/- 6.7% of patients were 3 years free of recurrences and metastases, in grade 11 - 76 +/- 8.6%, in grade III - 50 +/- 15.8%. Aneuploid laryngeal tumors produced recurrences 6 times more frequently than diploid ones. 3-year recurrence--and metastases-free survival was reported in 88.7 +/- 6.3% of patients with diploid and 59.3 +/- 7.7%. 7% with aneuploid tumors (p < 0.05).

[DNA ploidy of tumor cells in prognostication of the course of malignant neoformations]. / Ploidnost' DNK opukholevykh kletok v prognozirovanii techeniia zlokachestvennykh novoobrazovanii.

DNA flow cytometry (FCM) was used for the clinical prognosis in patients undergone surgical removal of a tumor. The relationship between the structure of the tumor cell population (ploidy) and the frequency, time of a relapse onset (recurrence, metastasis), and the survival length were analyzed. All the patients had presurgical treatment (chemo- and/or radiotherapy). The patients were followed up for 5 to 9 years after surgery. The groups under study included 177 cases of breast cancer, 81 cases of larynx cancer, and 62 cases of colon cancer. Among the patients, the onset of a relapse was earlier and occurred more frequently in cases of aneuploid tumors among the patients regardless of the tumor type. In patients with aneuploid tumors, the most unfavorable prognosis was inherent in the hyperdiploid and multiclonal ones. The probability of 5-year survival for patients with aneuploid tumors appeared to be 20-30% lower than that in cases of diploid ones.

[The effect of cryo- and cryoelectrotherapy on regional hemodynamics in coxarthrosis patients]. / Vliianie krio- i krioélektroterapii na regional'nuiu gemodinamiku u bol'nykh koksartrozom.

Physiotherapy (cryo-, cryoelectrotherapy or sinusoidal modulated currents) and therapeutic exercise were included in the course of rehabilitation given to 110 coxitis patients. Less pronounced reduction in microcirculation in the cooled tissue was registered in the exposure to a single cryoelectrotherapy procedure than to a single cryotherapy one, activation of the blood flow that followed was more intensive. Positive trends in the local and peripheral circulation were more evident after cryo- or cryoelectrotherapy.

[Effect of ribonuclease on cell cycle dynamics in tumor cells in vitro and in vivo]. / Vliianie ribonukleaz na dinamiku kletochnogo tsikla opukholevykh kletok in vitro i in vivo.

The effects of RNAase from Bacteroides intermedius and pancreatic RNAase on the dynamics of cellular cycle phases were studied in the cells of ascitic lympholeukemia NK/Ly in vivo and in vitro, in the cells of the human ovary carcinoma CaOv and in the cells of ascitic leukemia P388 in vivo. It was shown that both the RNAases induced cell accumulation (blocking) in the G2/M phase of a cellular cycle with simultaneous certain depletion of the proportion of DNA-synthesizing cells (S-phase). In in vitro experiments, there was a higher efficiency of pancreatic RNAase. In animal experiments, RNAase from B. intermedius was more efficient. The likely target of the in vitro and in vivo effects of the enzymes on the cellular cycle dynamics and biological activity are discussed.

[Stress and blood circulation in man]. / Stress i krovoobrashchenie cheloveka.

This paper presents the results of studying stress effects on the heart, systemic circulation and cerebral circulation by various methods (ECG, Doppler technique, isotopes, etc). Patterns of circulation changes in response to mental stresses have been identified and variations in circulation regulation as a function of stress enhancement have been revealed. Cerebral circulation changes produced by heavy mental work under stressful conditions are described (increase of blood flow velocity in carotid arteries and of tone of cerebral arteries of large and medium caliber, change in reactivity of anastomoses between branches of the internal and external carotid arteries, patterns of increase and decrease of blood flow in the gray matter of the brain cortex). During prolonged bed rest the type of stressor changes in blood circulation becomes modified and susceptibility to hypertensive states developed. In the course of stressor reactions circulation parameters vary substantially. In this situation changes in systemic circulation are closely related to emotional responses and those in cerebral circulation--to adaptive processes supporting mental activities.

[Effects of organic fluorosilicone compounds on the development of tumors in mice]. / Vliianie ftorkremniiorganicheskikh soedinenii na razvitie nekotorykh opukholei u myshei.

The influence of new synthesized fluoro-silicium-organic complexes on the virus-induced Rauscher leukosis and cell-transferred MX-11 mouse sarcoma was studied. We also studied the cytotoxic effects of these complexes in vitro in the human CaOv cells. Two complexes from seven studied were cytotoxic for CaOv cells. Five complexes from seven studied diminished the mortality of animals with MX-11 tumors on the 27-th day of observation, but the total life duration of the animals in the experimental group was the same as in controls. One complex from seven studied increased the life duration of mice with MX-11 tumors. No effects were noted in relation to mice virus-induced Rauscher leukosis.

[The effect of picolinic acid and iron ions on the proliferation of SPEV cells]. / Vliianie pikolinovoi kisloty i ionov zheleza na proliferatsiiu kletok SPEV.

The effect of picolinic acid (PA) on SPEV cell proliferation is found to be different from that on normal and virus transformed NRC cells, and on spontaneously transformed CHO cells. It is shown that SPEV cells are arrested by PA at the end of G1-phase and at the beginning of S-phase and probably in G2-phase of the cell cycle. Ferrous ions remove the G1/S block induced by PA to permit the cell transfer through S-phase. On the one hand, PA chelates ferrous ions from the cells, and on the other one it inhibits the replicative DNA synthesis. It can be suggested that PA may arrest the SPEV cell growth affecting the iron-depend stable radical formation which is introduced into the active centre of ribonucleotiDE reduCTase. This results in the lower enzyme activity.

[The action of amino acid di[2-haloethyl]hydrazides on DNA synthesis in normal and tumor cells and on the cell cycle kinetics in mice with melanoma B-16]. / Deistvie di-[2-galoétil]gidrazidov aminokislot na sintez DNK v normal'nykh i opukholevykh kletkakh i kinetiku kletochnogo tsikla u myshei s melanomoi B-16.

A comparative study was carried out with two alkylating agents IMB-MM and IMB-97 which are di-(2-halogenoethyl) hydrazides of amino acid derivatives. They have been found to exert a high activity towards wide spectrum of experimental tumours. Both agents caused inhibition of incorporation of 3H-thymidine into DNA of melanoma B16, marrow, intestinal mucosa, spleen and liver cells of mice with tumours. A maximal inhibition of DNA synthesis in all tissues was observed 24 h after the single doses of drugs. However 96 h later this effect was removed excluding the tumour cells. The cytofluorimetric study have shown that IMB-MM, like sarcolysine, caused an accumulation of tumour cells in G2/M phase of cell cycle, while IMB-97 increased accumulation of S-phase cells. The difference in phase sensitivity of tumour cells towards IMB-MM and IMB-97 is due to the differences in aminoacid carriers of di-(2-halogenethyl) hydrazide groups.

[The structure of HeLa cell population after exposure to methylnitrosourea at different phases of culture growth]. / Issledovanie struktury populiatsii kletok HeLa posle vozdeistviia metilnitrozomocheviny v raznye periody rosta kul'tury.

To study the methylnitrosourea (MNU) effect on the HeLa cells culture at different stages of its growth the method of subcultivation, i. e. dissemination of cells immediately after the MNU effect, has been used followed by the study of the growth pattern of the reinoculated culture. When dissemination was carried out on the 4th, 7th and 10th day of the culture growth after the action of MNU, the highest growth inhibition effect was observed at the late stationary growth stage of the culture (the 10th day). The study of the population structure of such a culture by the method of batch cytofluorimetry has shown that MNU exerts a cytotoxic effect on cells: there is a shift in cell distribution according to the DNA content towards 4c typical of the G2/M-period of the cell cycle.

[Biochemical and functional characteristics of thymus and spleen lymphocytes in C3HA mice during the growth of hepatoma 22 and after immunization with sheep erythrocytes]. / Biokhimicheskaia i funktsional'naia kharakteristika limfotsitov timusa i selezenki myshei C3HA pri roste gepatomy 22 i posle immunizatsii éritrotsitami barana.

Activities of key enzymes of purine metabolism [adenosine deaminase (AD); purine nucleoside phosphorylase (PNP); 5'-nucleotidase] were studied; changes in DNA content, nucleus ploidity in thymocytes, T- and B-lymphocytes in the C3HA mouse spleen during solid 22 hepatoma growth and after the immunization were monitored. Immunological properties of lymphocytes were also investigated measuring antibody formation and the reaction of blasttransformation in response to phytohemagglutinin, concanavalin A and lipopolysaccharide. Within the first 48 hrs after the tumor implantation and immunization certain nonspecific biochemical mechanisms of lymphocytes activation (elevated AD activity, decreased activity of 5'-nucleotidase, augmented intracellular DNA levels, polyploidity) were revealed. As the solid 22 hepatoma reached the maximum growth rate specific alterations in the activities of the purine metabolism key enzymes were observed reflecting the response of thymus and spleen lymphocytes to the presence of the malignant tumor.

[Synthesis and properties of an acyclic analog of 9-deazainosine and related compounds]. / Sintez i svoistva atsiklicheskogo analoga 9-dezazainozina i rodstvennykh soedinenii.

An acyclic analogue of 9-deazainosine, 9-(2-hydroxyethoxymethyl)-9-deazahypoxanthine, and related compounds have been synthesized starting from 9-(hydroxyethyl)-9-deazahypoxanthine. The acyclo-9-deazainosine exhibited some cytotoxic activity.