[Monoclonal antibody-based design of antitumor drugs: prerequisites and progress]. / Sozdanie protivoopukholevykh preparatov na osnove monoklonal'nykh antitel: predposylki i dostizheniia.

To obtain monoclonal antibodies (MAb) to tumor-specific antigens is a promising line in the design of antitumor drugs since this makes it possible to provide a strictly selective effect on tumor cells. As of now, thousands of MAbs to different human and animal antigens have been obtained; hundreds of them have shown their promising properties in experimental studies, tens have been tested in clinical trials and about 10 MAb have been already permitted for clinical use in oncological care. The N. N. Blokhin Russian Cancer Research Center (RCRC), Russian Academy of Medical Sciences (RAMS), is one of few Russian research organizations where the technology of MAb production has been successfully introduced and is applied now. By using this technology, RCRC, RAMS, has designed the drugs Imyteran and ATEMA that may be used to treat tumor and other diseases and at present they are under clinical trials. A great variety of MAbs that can potentially replace expensive imported analogues are pre-clinically designed.

[Adaptation of reverse transcriptase polymerase chain reaction for clinical diagnosis of expression of MDR1 gene]. / Adaptatsiia metoda obratnotranskriptaznoi tsepnoi reaktsii dlia klinicheskoi diagnostiki ékspressii gena MDR1.

Chemotherapy of malignant tumors is ineffective usually because of tumor cell resistance to it. Two types of resistance are known: cell resistance to a certain drug and multiple drug resistance (MDR). MDR covers a wide spectrum of drugs with different chemical structure and mechanisms of action. The most frequent cause of MDR is hyperexpression in the plasma membrane of P glycoprotein cells, which is coded for by MDR1 gene realizing active release of many cytotoxic substances from cells (Pgp-MDR). Acquisition of MDR phenotype by patient's cells impedes therapy and is often a poor prognostic sign, and therefore testing of material from cancer patients for MDR phenotype is important for selecting tumor therapy. We adapted the reverse transcriptase polymerase chain reaction (RT-PCR) to evaluating the MDR1 gene expression in peripheral blood cells of patients with hemoblastosis, assessed its sensitivity and specificity, and carried out clinical trials with blood samples from patients with MDR. Comparison of the results of RT-PCR with the findings of other methods used for detection of Pg-MDR showed their good correlation in the majority of cases. These results recommend these method for clinical practice in patients with hemoblastosis.

[Possible markers of the progression and ulcerogenesis of stomach cancer]. / Vozmozhnye markery progressii i ul'tserogeneza raka zheludka.

The stomachs from 40 patients operated on for gastric cancer and chronic ulcer were studied immunohistochemically using antibodies to CEA, galactosyl transferase, pepsinogens A and C, gastrin, alpha 1-antitrypsin. CEA and galactosyl transferase of the cancer parenchyma are shown to mark tumor progression. The ratio of alpha 1-antitrypsin to pepsinogens in gastric epithelium and cancer cells probably plays a role in ulcerogenesis of normal mucosa and tumor tissue. Gastrin in carcinoma tissue is both an ulcerogenesis factor and a marker of tumor progression, an unfavourable prognosis of gastric cancer.

[The duration of courses of manual therapy in vertebrogenic neurological and somatic pathology]. / Prodolzhitel'nost' kurosv manual'noi terapii vertebrogennoi nevrologicheskoi i somaticheskoi patologii.

The authors have developed and validated algorithms, programs, regimens and techniques of manual and instrumental treatment which produced positive effects in 99% of patients with neurological syndromes of spinal affections. The criteria of the treatment discontinuation were alleviation of painful syndrome by 25-50%. This occurred, as a rule, after 3-4 sessions. The course averaged 10 sessions and more. The treatment was discontinued after stabilization of subjective improvement.

Isolation, crystallization and preliminary X-ray diffraction data of human progastricsin.

Human progastricsin, a zymogen of one of the gastric aspartic proteinases, was isolated and crystallized. The crystals belong to the tetragonal space group P4(2)2(1)2, and have unit cell dimensions a = b = 105.5 +/- 0.1 A, c = 70.6 A. The native crystals of progastricsin diffract X-rays at least to 2.5 A and are suitable for a high-resolution X-ray analysis.

[Blood serum galactosyltransferase in oncologic diseases]. / Galaktoziltransferaza syvorotki krovi pri onkologicheskikh zabolevaniiakh.

The paper is concerned with comparative analysis of the results of the determination of activity of galactosyl transferase, CEA and antigen CA-125 in the blood serum of 44 healthy persons, 70 cancer patients and 12 patients with benign diseases. It was shown that a radiometric test for galactosyl transferase in its diagnostic sensitivity was not inferior to CEA in stomach and ovarian tumors and exceeded the test for antigen CA-125 in ovarian cancer. In colon cancer the diagnostic accuracy of the tests for the activity of galactosyl transferase and CEA turned out to be identical. The most reliable diagnostic test in acute lymphoblastic leukemia in children was the test for galactosyl transferase activity.

[Expression and secretion of carcinoembryonic antigen in tumors of the large intestine]. / Ekspressiia i sekretsiia rakovo-émbrional'nogo antigena pri opukholiakh tolstoi kishki.

The correlation between the expression of the carcinoembryonic antigen (CEA) on cell membranes and the intensity of its secretion into the circulation is studied in patients with malignant tumours of the rectum and the transverse colon. With the use of the monoclonal antibodies against CEA and the immunoperoxidase technique on the frozen sections, the localization of the primary tumour, microinvasion and micrometastases in the lymph nodes are shown. The dependence of the serum CEA concentration upon the histologic type of the tumour and the stage of the disease is not established. The trend towards the inverse correlation between the CEA level in the tumour tissue extract and the degree of the tumour cell differentiation is noted. The opinion is expressed of the applicability of the monoclonal antibody anti-CEA-1 for the morphologic differential diagnosis of the colon tumours, the evaluation of the thoroughness of the surgical treatment and for the metastases radioimmunolocalization.

[Immuno-scanning of human colon cancer xenografts using a labeled monoclonal antibody to the carcinoembryonic antigen]. / Immunoskanirovanie ksenotransplantatov raka tolstoi kishki cheloveka s mechenym monoklonal'nym antitelom k rakovo-émbrional'nomu antigenu.

The results of experiments using 131I-labelled monoclonal antibody (131I-MoAb) were described. The experiments were staged on nude male mice with transplanted human colon adenocarcinoma of the 34th generation (RTK-12). Tumor sizes by the time of 131I-MoAb administration varied from 1 to 3 cm. 131I-MoAb specific radioactivity was 456.6 kBq/micrograms in the volume of 0.3 ml. The same amount of 131I-Na was administered to control animals. Scanning on the Scintimat-2F (Siemens) was performed 1, 2, 3 and 4 days after injection of 131I-MoAb. Three days before scanning 0.2% KI was added to the drinking water. Some animals were decapitated on the 2nd-3rd day for radiometry of organs and tissues. After the injection of 131I-MoAb 10-fold less than the CEA serum concentration and with specific radioactivity of 370-444 kBq its tumor accumulation in 48 h was 10-15-fold higher than that in the surrounding tissues resulting in better tumor scans. Intensive dehalogenation of 131I-MoAb in vivo and related 131I accumulation in the thyroid and adrenal glands (in the medullary layer) required the administration of stable iodine not only before but also after injection of the radioactive agent.

[Use of the carcinoembryonic antigen in the gastric juice for diagnosing pretumorous stomach diseases]. / Ispol'zovanie rakovo-émbrional'nogo antigena v zheludochnom soke dlia diagnostiki predopukholevykh zabolevanii zheludka.

Radioimmunologic procedures were employed in comparing the levels of carcino-embryonic antigen in the gastric juice, blood plasma and saliva in cases of stomach cancer, gastritis, polyposis and gastric ulcer. No correlation between the antigen levels in different biological fluids was established. It was found, however, that the assay of carcino-embryonic antigen level in gastric juice may be instrumental in detecting precancerous lesions of the stomach.

[Thyroliberin test in the diagnosis of thyroid cancer]. / Tiroliberinovyi test v diagnostike raka shchitovidnoi zhelezy.

The function of the hypothalamus-pituitary-thyroid system was studied in patients with nodular diseases of the thyroid gland to determine the importance of the thyroliberin test for the diagnosis of thyroid cancer. Patients with thyroid cancer develop profound disturbances in the hypothalamus-pituitary-thyroid system. Unlike benign nodular thyroid diseases, the cancerous process is marked by suppression of the pituitary responsiveness to stimulation with thyroliberin while the degree of thyrotropin level elevation turns out twice as decreased after thyroliberin administration. The thyroliberin test can be used in differential diagnosis of malignant and benign nodular diseases of the thyroid gland. The sensitivity of cancer as regards "the lowered thyrotropin index" calculated as the ratio of stimulated thyrotropin to basal one constitutes 85%, specificity 89.5%.

[Ganglioside and carcinoembryonic antigens in the diagnosis of malignant tumors of the gastrointestinal tract]. / Gangliozidnyi i rakovo-émbrional'nyi antigeny v diagnostike zlokachestvennykh opukholei zheludochno-kishechnogo trakta.

Radioimmunologic procedures were used in a comparative assay of ganglioside and carcinoembryonic antigen levels in the blood plasma of patients with benign and malignant lesions at different sites. Measurements of ganglioside antigen level proved to be an efficient test for differentiating between benign and malignant tumors of the pancreas. However, it cannot be used as an aid to carcinoembryonic antigen test for detection of stomach and rectal cancers or their recurrences and metastases into the liver.

[Thyroid and calcitropic hormone secretion disorders in thyroid cancer]. / Narushenie sekretsii tireoidnykh i kal'tsitropnykh gormonov u bol'nykh rakom shchitovidnoi zhelezy.

Strong positive correlation was found between the level of thyrotropin and calcitonin. In papillary cancer this correlation is strong, in poorly differentiated it decreases, and in follicular cancer it disappears. The ratio of total thyroxine to thyrotropin which is of the least value in papillary cancer, is considerably reduced. The balance of calcitropic hormones is also disturbed at the expense of enhanced calcitonin production. The changes progress in the direction: papillary-follicular-poorly differentiated cancer.

[Blood concentrations of calcitonin, calcium and parathyrin in patients with thyroid diseases]. / Kal'tsitonin, kal'tsii i paratirin v krovi bol'nykh pri zabolevaniiakh shchitovidnoi zhelezy.

The article was written on the basis of clinical data. The relationship between calcitropic hormone levels (calcitonine and parathyrin, containing ionized calcium in the blood of patients with several thyroid diseases) was comparatively analyzed. It was determined that functional-structural reformation of the thyroid, seen in these cases, disturbed the normal hormone balance, followed by affection of calcium metabolism. In thyroid insufficiency (Hashimoto's disease and initial hypothyrosis) the increased thyrotropin secretion is accompanied by an elevation of the calcitonine level The ratio of calcitropic hormones is changed in the direction of relative hypoparathyrinemia. The blood ionized calcium content grows, the total calcium level remaining unchanged. The blood calcitonine concentration decreases in patients with euthyroid goiter in the presence of the normal or reduced thyrotropin level, indicating thyrotropin-calcitonine relationships. Calcitropic hormone ratio tends to relative hyperparathyrinemia.

[Calcitonin and paratirin in nodular pathology of the thyroid gland]. / Kal'tsitonin i paratirin pri uzlovoi patologii shchitovidnoi zhelezy.

The calcitonin-parathyroid hormone secretion (CPS) ratio was studied by means of radioimmunoassay in different cases of nodose thyroid pathology. It was found that functional thyroid reconstruction induces un balance of calcitropic hormones. The development of "hot", functionally active nodes is accompanied by CPS lowering due to disturbed parathyroid hormone secretion. "Cold" nodes produce no disorder in the calcitropic hormone ratio in relative insufficiency of thyroid function. However, a marked shift towards an increase in calcitonin secretion and a decrease in parathyroid hormone level occur in malignant "cold" thyroid nodes. CPS is enhanced in adenocarcinoma and is maximum in medullary cancer.

[Blood plasma content of hormones and carcinoembryonic antigen in tumorous and nontumorous disease of the thyroid]. / Soderzhanie v plazme krovi gormonov i rakovo-émbrional'nogo antigena pri opukholevykh i neopukholevykh zabolevaniiakh shchitovodnoi zhelezy.

Radioimmunological tests for carcinoembryonic antigen, antibodies to thyroglobulin, thyrotropin of pituitary, thyroxin and triiodothyronine were run in healthy subjects and patients suffering from cervical thyroid and extrathyroid neoplasms, e. g. nodular goiter, adenoma, cancer, chronic thyroiditis, lymphadenitis, neurinoma, hemangioma and thyrotoxicosis. The thyroid was scanned with 131I or 99mTcO4 in all cases. Scanning of thyroid in the first stage of screening for malignant tumors because "warm" or "hot" foci in scanograms of cases of malignant nodes are very rare. In patients with "cold" thyroid nodes, detection of thyroglobulin antibodies points to thyroiditis since such antibodies are not found in all other cases. None of the indices showed any differences in cases of nodular goiter and "cold" adenoma. Coefficient sTTH/bTTH (ratio of thyroliberine-stimulated level of pituitary thyrotropin to basal one) is decreased, while coefficient (Formula: see text) and blood plasma level of carcinoembryonic antigen are increased in patients with thyroid cancer as compared with benign tumors.