[Phase I-II trial of gene therapy with tag-7 modified autologous tumor cells in patients with metastatic solid tumors]. / I-II faza klinicheskoi otsenki éffektivnosti genoterapii na osnove autologichnykh opukholevykh kletok, modifitsirovannykh genom TAG7 u bol'nykh s disseminirovannymi solidnymi opukholiami.

A prospective (phase I-II) trial was undertaken to study the efficacy and toxicity of gene therapy with tag 70-modified autologous tumor cells in 32 patients with metastatic renal cell carcinoma (RC) (5) and melanoma (MBL) (27) treated at the Institute's Clinic (2001-2003). Resected material was reduced to cell culture, which was transfected with tag 70 gene and devitalized by irradiation. Immune blotting was used for gene expression. Clinical and immunological effectiveness was evaluated in 22 patients (MBL--17 and RC--5) who received 1-6 injections (3 on the average). Full course of vaccination was given to 8 (MBL--6 and RC--2). No complete or partial response was reported while least regression (50%) was registered in a case of RC metastatic to the lung. According to CT and ultrasound evidence, stabilization was achieved in 5 (23.8%) (MBL--4 and RC--1). Relapse-free period was 6.5+/-3.5 months beginning from the start of treatment. The vaccine was well tolerated while DHT reaction was observed in 47.6% (10 out of 17) of primary immunized patients. A trend of increased content of T- and B-cells in peripheral blood and intensified functional activity was established.

[Allelic distribution of the CYP1A1 in lung cancer patients, middle-aged tissue donors and in elderly people without cancer]. / Raspredelenie allelei gena CYP1A1 u bol'nykh rakom lëgkogo, donorov srednego vozrasta i pozhilykh liudei bez onkologicheskoi patologii.

The genetic polymorphism of metabolizers of tobacco smoke carcinogens can influence individual susceptibility to lung cancer. The study was concerned with the Mspl-polymorphism of the CYP1A1 gene responsible for encoding aryl hydrocarbon hydroxylase. It also plays a role in the activation of polycyclic aromatic hydrocarbons (PAH). The CYP1A1 alleles and genotype distribution in 146 lung cancer patients was compared with that in 230 healthy donors. Another control group consisted of 259 "cancer-resistant" subjects, i.e. tumor-free smokers and non-smokers aged 75 and more. The CYP1A1 allele incidence (19%) in patients with squamous lung cancer was significantly higher than in the control cohorts (11%) which is consistent with the leading role of PAH in the etiology of this pathology.

[An improved procedure for autologous gene-modified cancer vaccine preparation for active specific immunotherapy of disseminated solid tumors]. / Usovershenstvovanie metoda prigotovleniia autologichnykh modifitsirovannykh protivoopukholevykh vaktsin dlia aktivnoi spetsificheskoi immunoterapii bol'nykh s disseminirovannymi solidnymi opukholiami.

Resected material was used from 108 patients with disseminated skin melanoma and 47 patients suffering metastasized renal tumors to test procedures of tumor cell culture preparation and to search the best parameters. Gene tag 7 transfer, liposome delivery and electroporation were employed to stimulate immunogenic tumor cells. The transfer results were evaluated by expression of beta-galactosidase and EGFP genes whose products were detected microscopically. Transfer efficiency was boosted by 30% due to selecting suitable parameters of tumor cell modification. Maximum effectiveness was attained by individualized choice of the parameters. Yet, undoubtedly, the best way of cell isolation was mechanical fragmentation of tumor. To speed up cell production, DMEM/F12 medium should be recommended. It should contain cattle embryonic serum (20%), conditioned medium of cultured fibroblasts of human embryonic lungs (20%), transferin, insulin and selenium (standard dose).

[Role of DNA diagnosis in modern oncology]. / Rol' DNK-diagnostiki v sovremennoi onkologii.

DNA-diagnosis became to be a mandatory element of the modern oncological care. The molecular-genetic approaches aimed at identifying the high-risk categories in oncology are mostly-renowned. They comprise the diagnosis of the so-called familial cancerous syndromes, the identification of unfavorable normal genome variations (gene polymorphisms) and the detection of a number of oncoviral infections. Laboratory procedures facilitating the individualization of treatment schemes and the monitoring of oncology patients have been widely introduced into clinical practice. The turn between the 20th and 21st centuries was marked by the emergence of principally new DNA-analysis methods designed for a comprehensive and integral genome evaluation. The application of such radically novel techniques in the molecular diagnostics essentially promoted the detection and treatment of neoplasms.

[Clinical and cytogenetic investigation of a family with high predisposition for intestinal polyps]. / Mediko-geneticheskoe i tsitogeneticheskoe issledovanie sem'i s vysokoi predraspolozhennost'iu k polipozu kishechnika.

A medico-genetic investigation of a family, consisting of 25 members, revealed high predisposition to malignant pathology of the gastrointestinal tract: rectal cancer was diagnosed in 2, malignant polyposis of the large intestine--1, diffuse polyposis of the large intestine (DPLI)--3, and uterine fibromyoma--in 1 patient. Six members underwent a cytogenetic examination using the metaphase method for peripheral blood lymphocytes and G-banding of chromosomes. Two patients with DPLI carried 8.7 and 16.7% of hyperaneuploid cells and one--20% of cells with double minute chromosomes (DMS). It is suggested that formation and subsequent significant increase in hyperaneuploid and DMS cells could have been responsible for DPLI development in the family.

[A polymorphism study of the CYP19 gene in endometrial cancer patients]. / Izuchenie polimorfizma gena CYP19 u bol'nykh rakom éndometriia.

A strong connection is known to exist between initiation/promotion of endometrial cancer and excess of estrogens. Therefore, participation of certain alleles of genetic polymorphisms in steroid biosynthesis or metabolism may be responsible for predisposition to the disease. The present study, comparing CYP19 (aromatase) gene polymorphism in 85 patients and 110 healthy females, pointed to a more frequent occurrence of relatively longer alleles (A6 and A7) of the CYP19 gene in the former group. Furthermore, precisely those genotypes co-occurred more frequently with elevated blood levels of estradiol and testosterone in postmenopausal patients. Hence, CYP19 gene polymorphism may be regarded as a factor of genetic risk for endometrial carcinoma.

[Radioimmunoassay of serum pepsinogen I in chronic gastritis and stomach cancer]. / Radioimmunologicheskii analiz syvorotochnogo pepsinogena I u bol'nykh khronicheskim gastritom i rakom zheludka.

Blood serum in stomach cancer and chronic gastritis has been compared. A sharp decrease in pepsinogen 1 level both in cancer and gastritis patients was found as compared with healthy subjects. Pepsinogen 1 level in poorly-differentiated tumor (37.4 ng/ml) was lower than in well-differentiated one (58.2 ng/ml).

[Polymorphism of the GSMT1 gene in lung cancer resistance and susceptibility]. / Polimorfizm gena GSTM1 v gruppakh predraspolozhennosti i rezistentnosti k raku lëgkogo.

The published studies of onco-associated genetic polymorphisms are characterized by insufficient interlaboratory reproducibility. The inconsistency of the results can be partially attributed to some characteristics of patients and control groups, which are used for the comparison of allele frequencies. For instance, many investigations involve so-called "healthy donors" as a standard. However, the efficiency of such a comparison can be questioned; indeed, as an individual life-time risk of malignancy reaches as high as 40-50%, a significant part of "healthy donors" would soon or later become the oncological patients. Here we tested the advantage of using "true" oncologically tolerant individuals as an additional control, e.g. tumor-free people, who succeeded to achieve an elderly age without signs of any neoplastic disease. GSTM1 gene polymorphism was used as a "positive control" for this novel design of molecular epidemiological study, as the GSTM1-null genotype displays slight but reproducible association with lung cancer risk. In the present investigation, GSTM1-deficiency was detected in 45% elderly tumor-free individuals, 55% healthy middle-aged donors, and 59% lung cancer patients. The minimal frequency (43%) of GSTM1(-) genotype was detected in elderly tumor-free smokers, and the maximal one (100%) was found in never-smoking lung cancer patients. Thus, the comparison of lung cancer patients to the "true" oncologically tolerant cohort (elderly tumor-free individuals, especially smokers) revealed more demonstrative deviations for the unfavorable genotype, than the traditional comparative analysis between oncological patients and healthy donors.

[Evaluation of pepsinogen A expression in stomach cancer]. / Analiz ékspressii genov pepsinogena A pri rake zheludka.

The report deals with a molecular-genetic study of human pepsinogen A (PGA) genetic locus. EcoRI, HindIII and BamH 1 restriction endonuclease technique were employed. The investigation involving 58 patients with stomach cancer (SC) and 18 healthy donors failed to identify any significant PGA genetic restructuring in the blood of healthy donors. However, DNA sampled from tumor tissue showed lower expression and deletion of PGA fragments as compared with those of unaltered gastric mucosa in the same patients. Such changes were identified in 27 SC patients.

[L-myc and GSTM1 polymorphism in cerebral glioma]. / Polimorfism genov L-myc i GSTM1 u bol'nykh gliomami golovnogo mozga.

L-MYC and GSTMI polymorphisms were studied in glioma patients. L-MYC allele frequency in patients (L: 61/114 (54%); S: 53/114 (46%)) and controls (L: 108/204 (53%); S: 96/204 (47%)) was identical. S allele was associated with certain unfavourable clinical features of the disease. In particular, its frequency was 26/42 (62%) in relapse vs. 26/68 (38%) in relapse-free disease (p < 0.05). GSTMI "null" genotype was identified in both patients and healthy donors (48%). GSTMI-deficient genotypes were significantly predominant in patients with grade III-IV gliomas as compared with grade I-II tumors (p < 0.05). Patients, but not donors, frequently revealed a combination of SS L-MYC homozygosity and GSTMI (-) variant (p < 0.01) as well as an association of LL L0-MYC homozygosity and GSTMI (+) genotype (p < 0.05).

[Cerebrospinal fluid sorption in patients with heroin addiction]. / Likvorosorbtsiia u bol'nykh geroinovoi narkomaniei.

The sorption of cerebrospinal fluid (CSF) was attempted as a special detoxifying procedure in a group of sixty heroine addicts. CSF contents of cells, total protein, nucleic acids and interleukin-1 (IL-1), as well as acridine orange (AO) binding to CSF cells were determined before and after the procedure. The treatment provided immediate clinical improvement for 70% of the patients. Clinical effect was accompanied by decreased of CSF cells, diminished nucleic acids and protein amounts, along with increased DNA-AO binding and accumulation of IL-l. These data are interpreted in terms of intensive apoptosis of CSF cells and increased acute phase of aseptic inflammation-like events induced by the procedure of liquor sorption.

[Apoptosis: current status of the problem]. / Apoptoz: sovremennoe sostoianie problemy.

Accelerating progress in studying the nature of apoptosis (programmed cell death, PCD) has been observed in recent years. Apoptosis proved to be preprogrammed biological phenomenon with the key role in fundamental processes such as embryogenesis, morphogenesis, and cellular homeostasis. Apoptosis is induced by specific physiological signals as well as by various damaging influences. A complex system of metabolic and genetic control of apoptosis is realized by phylogenetically conserved set of genes with pro- and antiapoptotic activity. Genetic and metabolic disturbances of initiation and/or realization of PCD make substantial contribution to a number of pathologies such as cancer, AIDS, and degenerative processes. Active search for apoptosis-controlling remedies may open new horizons for fighting these widespread diseases.

[Biochemical and immunologic analysis of pepsinogen I in blood serum and mucosa in patients with gastric tumors and non-tumor diseases]. / Biokhimicheskii i immunologicheskii analiz pepsinogena I syvorotki krovi i slizistoi obolochki bol'nykh opukholevymi i neopukholevymi zabolevaniiami zheludka.

The results of the biochemical and immunologic studies of pepsinogen I (PG-I) occurring in the mucosa and blood serum of patients with tumors and non-tumor conditions of the stomach are discussed. Pepsinogen I was identified in human blood serum using rabbit antibodies against PG-I. Sharp drop in blood serum-PG-I level in patients with gastric tumors has been confirmed.