The previously established fact of low activity of Ca, Mg-dependent endonucleolysis of cell nucleus DNA in lymphoproliferative diseases (CME-activity) brought the authors to study intranuclear characteristics of lymphoid cells in childhood acute lymphoblastic leukemia (ALL). The intensity of DNA-endonucleolysis was measured in 0.7% agarose gel using electrophoresis. Peripheral blood and bone marrow samples from 13 untreated ALL patients and 23 children in remission were examined. The age of the patients ranged from 4 to 14 years. CME-activity before treatment appeared to be 2-10 times less than normal in 8 out of 13 patients. In bone marrow cell nuclei CME-activity was universally reduced 3-20-fold. In ALL remission endonuclease activity in blood and bone marrow cells returned to normal.

The results of familial population analysis of stomach cancer and multiple primary malignant tumors (MPMTs) are presented. The data obtained provide evidence for the multifactorial nature of stomach cancer. Hereditary factors accounted for 32% of the general predisposition of individuals to stomach cancer. The age-related character of stomach cancer was established. Genetic heterogeneity of this tumor is suggested by the data obtained. Significant genetic commonness in the inheritance of stomach, colon, Genetic Analysis and Prognosis for Malignant Tumors in breast, endometrial, and ovarian cancer in families of MPMT patients was demonstrated on the basis of the obtained genetic correlations between tumor types in MPMT patients and solitary tumors in members of their families. The greatest genetic load was shown for families of MPMT patients, as compared with families of patients with solitary tumors, the coefficient of MPMT inheritance being equal to 77.4%. The data on the genetic character of stomach cancer and MPMT formed the basis for the identification of criteria for developing methodological approaches to the screening of individuals from risk groups to facilitate early diagnosis and prevention of cancer.

Observation's analysis of 5 children in age from 9 months to 4 years 11 months with tuberous sclerosis was performed. The initial manifestations of disease were following: early children form of epilepsy exactly infantile spasms (West syndrome) appearance, dermal alterations in the form of depigmented spots as well as nonprogressive delay in psychoverbal development. Together with clinical symptoms the main criterion in early form of tuberous sclerosis diagnosis determination turned out to be brain's specific alterations (tubers) which were revealed by computer tomography. The correlation was observed between epileptic seizures polymorphism and frequency as well as brain's morphological alterations. Derivatives of valproic acid were the basic drugs in treatment of epileptic seizures in patients.

Surgical treatment of 258 patients (1st group) with carcinoma of the lung whose hereditary case history was aggravated by the presence of malignant tumors in blood relatives was compared with treatment of 861 patients of the control group (2nd group). Lung cancer patients of the 1st group were less operable than those of the 2nd group, 60.0% and 71.2% (p < 0.001) correspondingly. Resectability was 84.1% and 93.7% (p < 0.001) correspondingly. Totally in early stages (I-II stages) operations were performed only on 118 patients (45.7%) with the aggravated heredity and 536 (62.2%) of patients of the control group (p < 0.001). The symptoms which characterize surgical treatment of lung cancer in patients with the aggravated heredity are much worse as compared with the control group of patients because of the biological features of the tumors characterized by extremely high potential of the regional and remote metastases.

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.

Normalized cDNA library from human erythroleukemia cells has been constructed. For equalizing frequencies of different cDNAs denaturation was carried out followed by partial reassociation. Single-stranded cDNAs separated by hydroxyapatite chromatography were transformed into double-stranded form by PCR and cloned in lambda gt11. Frequencies of 10 control nucleotide sequences were estimated. After normalization frequencies of the abundant sequences decreased. The normalized cDNA library may be used for search of the clones corresponding to the rare mRNAs and for human genome mapping.

A concept is advanced according to which the processes of ageing, non-specific pathology and malignant transformation are caused by mutations of mitochondrial DNA which controls protein synthesis of the oxidation phosphorylation system. A mathematical model is plotted for describing the efficiency of the system of energy supply of mammalian cells as a function of accumulation of mtDNA mutations. It is shown that at a definite degree of heterogeneity of mitochondria population malignant transformation proceeds. Explanations are presented of the existence of a latent period between the effect of cancerogenic agent and occurrence of tumour, mechanism of the realization of remote effects of chronic action of low intensity agents (these explanations are absent in modern theories of cancerogenesis and quantitative radiobiology).

Cell resistance to pharmaceutical agents arises among other causes because of multiple drug resistance induced by P-glycoprotein (P-gp). The analysis of expression of P-gp and differentiation antigens of hemopoietic cells has been made on myeloid cells from 14 patients in CML chronic phase and 25 with CML acceleration and in blast crisis. Surface antigen expression was evaluated at flow cytofluorimetry (FACScan unit). Fluorescent dye rodomin (Rh123) helped examine P-gp functional activity. A close relationship is shown between P-gp expression and CD34 (r = 0.69. p = 0.0004), this giving evidence of these antigens expression on the same cells. In chronic phase P-gp is expressed on a few cells in some patients, its activity being low or absent. The appearance of UIC-2+ cells was unrelated to previous chemotherapy and brought no resistance to treatment. In terminal stage P-gp is expressed in 50% of cases. Functional tests identified the active protein in blast populations with a large number of UIC-2+ cells and in some patients with a small number of cells expressing P-gp. Therefore, comprehensive clinical investigations are needed of multiple drug resistance, though in half of the resistant patients in AML blast crisis P-gp+ cells were not identified suggesting the existence of other mechanisms responsible for resistance to treatment.

Megakaryocytic dysplasia, platelet and megakaryocytic counts were measured in 87 ANLL patients. High megakaryocytic levels were registered in 16.1%, normal in 17.2%, low or negligible in the rest of the examinees. Half of the patients had dysplasia. Thrombocytopenia present in 93% of cases attested to ineffective proliferation of megakaryocytes. Increased number of megakaryocytes with signs of dysplasia occurred more commonly in M0- and M4- variants of ANLL universally in anomalies of chromosome 3 long arm with involvement of q21 and/or q26 segments and occasionally in combination with other chromosome disorders. Megakaryocytosis developed less frequently in patients with ANLL variant M2 with t (8;21) and did not correlate with granulocyte and erythroid cell dysplasia. Pronounced megakaryocytosis in combination with thrombocytosis emerged in 4 patients: 2 of them had typical anomalies of chromosome 3--inv3(q21q26) and dup (3q21q26), 1 had monosomy 7 and 1 normal karyotype. Potential mechanisms responsible for dysplasia of megakaryocytes in ANLL are considered.

A modified system with two pairs of primers is suggested for the analysis of different bcr/abl mRNA variants, using the polymerase chain reaction (PCR) method. It was demonstrated that, with the use of this method, mRNA preparations obtained from bone marrow cells are more informative than those obtained from blood cells. Fresh preparations of thermostable Tth DNA polymerase, which exhibited the reverse transcriptase activity, appeared to be optimal for PCR analysis of the bcr/abl mRNA pattern.