Hexokinase isoenzymes in the diagnosis of gastric and esophageal neoplasms.

Using a method of electrophoretic separation on agar gel, the hexokinase (HK) isoenzymes were determined in biopsies from patients with gastric and esophageal cancer and nonmalignant diseases (gastric benign tumors and gastritis) as well as in biopsies from healthy people. In the malignant neoplasms studied, a significant elevation of HK-II and the appearance of additional anodal bands (HK-IIf and HK-III) have been demonstrated. As a rule, the HK isoenzyme spectrum in gastric polyps was similar to that of normal mucosa and characterized by a predominance of HK-I. Changes in the HK isoenzyme composition in gastric mucosa with intestinal metaplasia were expressed in lesser degree but had similar cancerous tendency. The HK isoenzyme analysis in biopsy samples may be used for differential diagnosis of malignant and benign tumors, and/or as definite diagnostic implication of an early sign of malignancy in the study of premalignant lesions.

Trepanobiopsy as a tool for the study of the influence of presurgical treatment on the steroid receptor status of advanced breast cancer.

Estrogen, progesterone and glucocorticoid receptors were determined in samples obtained by trepanobiopsy before treatment and in surgical material following chemo- or radiotherapy in 131 Stage III a, b, c breast cancer patients. The levels and distribution of the receptors in bioptates coincided with the data obtained earlier for the surgical material from patients, who didn't receive presurgical therapy. It is concluded that breast tumor trepanobioptates may be used for the determination of tumor receptor status. Radiotherapy affected the level and frequency of occurrence of steroid hormone receptors. The degree of variations depended on the dosage of irradiation and after exposure period. After presurgical chemotherapy the percent of receptor-positive tumors increased.

[Creatine kinase and its isoenzymes in breast tumor tissue]. / Kreatinkinaza i ee izofermenty v tkani opukholei molochnoi zhelezy.

The activity and isoenzyme spectrum of creatine kinase (CK) were studied in cytosole fraction 60 of the mammary gland carcinoma (MGC) and in the corresponding unchanged tissues. The values of the CK activity in MGC were found to be highly different (0.05-14.6 unit/g of tissue). The correlation of CK activity in MGC with the menstrual function was revealed. Enhancement in the CK activity is due to an increase in the BB-isoenzyme activity and an appearance of atypical supplementary MM1-isoenzyme is, possibly, of mitochondrial origin. These isoenzymes may be nonspecific markers of malignancy and may be used for diagnosis of mammary gland carcinoma.

[The capacity of glucocorticoid receptors for activation as a possible criterion of the hormonal sensitivity of human tumors]. / Soposobnost' retseptorov gliukokortikoidov k aktivatsii kak vozmozhnyi kriterii gormonal'noi chuvstvitel'nosti opukholei cheloveka.

For the functional activity evaluation of glucocorticoid receptors (GR) a specific method for their activated form determination was developed on the experimental model of the rat liver. The method is based on the interaction of GR with DNA-cellulose. It has been shown that 26-41% of the total rat liver GR are able of undergoing activation and being bound to DNA-cellulose. Activated GR were studied in 88 renal tumours and in 37 melanomas. 20% of renal tumours and 33% of melanomas contain GR which are not able to undergo activation. The number of activated GR in most cases is much lower than the total GR number. There is no direct correlation between the concentrations of total and activated GR, as well as between the total GR content and the percent of activated forms in the whole receptor pool. It appears that the study of activated GR may give more reliable information about the hormone sensitivity of tumours than the determination of the total receptor content.

[Testosterone stimulation of the growth of a human osteogenic sarcoma strain transplanted into athymic rats]. / Stimuliatsiia testosteronom rosta shtamma osteogennoi sarkomy cheloveka, transplantirovannogo bestimusnym krysam.

Intraperitoneal testosterone administration stimulated the growth of subcutaneously transplanted cell line of human osteogenic sarcoma in nude rats but did not provoke tumour metastasizing to other organs and tissues. The specific connection of androgens with receptor proteins in the cytosol fraction was not found in the studied osteogenic sarcomas, whereas cytoplasmic estrogen receptors were revealed in all tumours. It is supposed that the mechanism of the stimulating effect of androgens on the tumour growth is mediated through other biologic systems being not related to androgen receptors.

[Changes in the content and composition of gangliosides of tumors as affected by chemotherapeutic agents]. / Izmenenie soderzhaniia i sostava gangliozidov opukholei pri deistvii khimioterapevticheskikh preparatov.

The lipid-bound sialic acid (LSA) levels increased in the metastasizing Lewis lung carcinoma (3LL) and significantly decreased in blood plasma of the tumour-bearing mice after cyclophosphamide treatment correlating with the drug therapeutic effect. 5-fluorouracil that was less active in the used therapeutic doses did not cause similar changes in the LSA levels. No correlation was found between the LSA levels in adenocarcinoma 755 and the drug antitumour activity. It was observed that the content of hematoside, GM1 and GD1b sharply increases and GD3 and GD1a levels significantly decrease under the cyclophosphamide treatment of the Lewis tumour.

[Ganglioside content and profile in the ovarian tumor tissues and in the biological body fluids of patients]. / Soderzhanie i profil' gangliozidov v tkaniakh opukholei iaichnikov i biologicheskikh zhidkostiakh organizma bol'nykh.

Lipid-bound sialic acid (LSA) content and ganglioside composition in resected tumours and body fluids of patients with benign ovarian tumours, borderline ovarian tumours, ovarian cancer and also in unaltered ovaries of patients with uterine cancer were examined. LSA levels in tissues and relation of the main gangliosides GD3/GM3 progressively decreased from unaltered ovaries to ovarian cancer. Distribution of gangliosides GD3 and GM3 in the borderline tumours was not uniform. Absolute content of GD3 increased more than twice in profuse growth from the inner surface and decreased almost three times in the cyst capsule as compared to the intact tumour. Ganglioside GD3 content decreased in malignant ovarian tumours but increased in ascitic fluid of cancer patients as compared to GM3. These results suggest that ganglioside GD3 is shed more intensively in the borderline ovarian tumours.

[Secretion of type-E prostaglandin by tumor cells of different degrees of malignancy when in contact with effectors of natural resistance]. / Sekretsiia prostaglandina tipa E opukholevymi kletkami raznoi stepeni zlokachestvennosti pri ikh kontakte s éffektorami estestvennoi rezistentnosti.

It was demonstrated that short-term contact of highly malignant tumour cells with NK-cells, neutrophils and macrophages induced rapid PGE secretion into the culture medium. PGE is detected in the culture fluids by the biological test based on inhibition of cytotoxic activity of NK-cells in standard cytotoxic tests. In the direct radioimmunoassay no PGE release was detected when low malignant tumour cells contact with effector cells of natural resistance system as well as after malignant tumour cell pretreatment with indomethacin. There was no increase in PGE secretion by the malignant tumour cells after their in vitro contact with red cells, normal hamster embryo cells and tumour cells of different origin.

[Genetic analysis of precancer-cancer of the stomach system. II. Lactate dehydrogenase in families of the patients: is it a marker of hereditary predisposition?]. / Geneticheskii analiz sistemy "predrak-rak" zheludka. Soobshchenie II. Laktatdegidrogenaza v sem'iakh porazhennykh: marker nasledstvennogo predraspolozheniia?

The possibility of using the LDH as a marker of hereditary predisposition to the stomach cancer was analysed by using the genetical correlational analysis. The LDH isoenzymes in the gastric body were studied in 56 pedigrees. Similar LDH alterations were detected in relatives with cancer and precancer (ulcer disease, atrophic gastritis). Relatives with no such pathology had LDH isoenzymes, similar to the control individuals. High and significant coefficients of phenotypic and environmental correlation of LDH and predisposition to the stomach cancer were obtained. The coefficient of genetic correlation was not significant. The problem of the origin of these LDH variances is discussed. The preliminary conclusion is that the LDH isoenzyme changes revealed in patients with stomach cancer appear as a consequence of the disease, and cannot be used as the marker of hereditary predisposition.

[The effect of steroid hormones and tamoxifen on the rate of phospholipid turnover in the cells of uterine and breast tumors]. / Vliianie steroidnykh gormonov i tamoksifena na skorost' obrashcheniia fosfolipidov v kletkakh opukholei matki i molochnoi zhelezy.

The cycle of phospholipid turnover has been found to be under the negative control of hormonal cytostatics (progesterone) and under the positive control of proliferation stimulants (17 beta-estradiol, epidermal growth factor). Specific changes in the synthesis of phospholipids are shown when tamoxiphen, an antiestrogen and an inhibitor of protein kinase C, was used. The findings suggest that changes in the turnover rate of phospholipids are one of the key stages of steroid action on target cells and may be regarded as an additional criterion of tumor genetic sensibility.

[A comparative immunohistochemical and biochemical study of estrogen receptors in breast cancer]. / Sravnitel'noe immunogistokhimicheskoe i biokhimicheskoe izuchenie retseptorov éstrogenov v rake molochnykh zhelez.

The authors review the results of a comparative study of 25 mammary carcinomas, examined by the immunohistochemical method (IHM) with the use of ER-D5 monoclonal antibodies (Amersham) and by the cytosol receptor protein binding of a labeled ligand followed by the unbound hormone adsorption on dexteran-coated coal (DCM). Pap test with the above antibodies has been employed in immunohistochemical studies. The IHM has been highly specific. The results coincided in 21 of the 25 cases (83.3%). The reaction has been heterogenous in the same tumor. Quantitative values obtained by the two methods coincided in many cases. The IHM may have a wide practical application, provided the reagents are available, for it does not require sophisticated equipment and is simple to perform.

[Relation of steroid receptors, tumor ploidy, and cell proliferation in various histologic types of breast cancer]. / Vzaimootnosheniia mezhdu retseptorami steroidnykh gormonov, ploidnost'iu opukholi i pokazateliami kletochnoi proliferatsii pri razlichnykh histologicheskikh variantakh raka molochnoi zhelezy.

The receptor status of the tumors examined in 74 patients with breast cancer was found to correlate with its ploidy and proliferative activity as evidenced by flow cytometry and it failed to correlate with a histological tumor type and metastatic involvement of regional lymph nodes. In terms of DNA content, the receptor-positive tumors were more frequently diploid, the receptor-negative ones were aneuploid. The proliferation index (PI) for the receptor-negative tumors was significantly higher than that for the receptor-positive ones. The diploid tumors showed lower proliferative activity than the aneuploid ones. Among the aneuploid tumors, PI for infiltrative lobular cancer was significantly lower than that for infiltrative duct cancer. Early in invasion, duct carcinoma was predominantly diploid, of grade I-IIA malignancy and more infrequently metastasized into regional lymph nodes. Grade IIB-III malignant tumors were chiefly aneuploid and more frequently metastasized into regional lymph nodes.

[Beta-endorphin levels in patients with pain syndromes in the areas of the face and head]. / Issledovanie urovnia beta-éndorfina u bo'lnykh s bolevymi sindromami v oblasti litsa i golovy.

Blood plasma beta-endorphin concentrations were measured in 87 patients with various facial and head pain syndromes: trigeminal neuralgia or neuropathy Horner syndrome and migraine, facial autonomic pains. beta-endorphin concentrations were measured before and after treatment. In the groups under investigation, the neuropeptide showed opposite changes in plasma levels after the therapy depending on the type of the syndrome.

[Relationship between androgen and estrogen receptors and clinico-morphological characteristics of prostatic cancer]. / Vzaimosviaz' mezhdu retseptorami androgenov, éstrogenov i kliniko-morfologicheskoi kharakteristikoi raka predstatel'noi zhelezy.

The paper presents the results of studies on cytoplasmic receptors of androgens (AR) and estrogens (ER) in tumors of 50 patients with prostate carcinoma with respect to age, histological structure and degree of tumor differentiation, and stage of the disease. The study showed the majority of tumors in patients not previously treated with estrogens to contain one or both types of receptors. In prostate carcinoma AR were found more frequently and both receptors were present twice as frequently in elderly as compared to senile patients. In the latter, adenocarcinomas containing only ER were predominant. AR could be detected more frequently in highly differentiated than in poorly differentiated tumors. ER did not correlate with the histological structure and degree of differentiation of the tumor. A negative correlation was observed between the stage of the tumor progression and the presence of AR in prostate carcinoma. AR and ER were seldom found in tumors of the patients treated with estrogens for a long time. Among 13 patients who died from advanced tumor, no AR were found in 12 tumors, both receptors were present in 1 tumor, and ER alone in 5 tumors.

[Relation between estrogen receptors and the clinical morphological characteristics of primary breast cancer]. / O sviazi mezhdu retseptorami éstrogenov i kliniko-morfologicheskoi kharaktaeristikoi pervichnogo raka molochnoi zhelezy.

Clinico-morphological and biochemical analysis of 139 observations of primary mammary gland carcinomas showed the majority of the tumors to be receptor-positive (72%), the tumors with estradiol receptors (ER) being prevalent in the group of patients with menopause (81%). Correlation of the presence of ER with the histological form of carcinoma and degree of its malignancy revealed no relationship between these parameters. In the group of ER-containing tumors, high and poorly differentiated forms of carcinoma were found with similar frequency. Among 8 observations of progressing disease 7 tumors contained ER and were of the II and III degree of malignancy. Thus, the leading factors in the prognosis are still clinical and morphological data on the degree of tumor spread irrespective of the ER presence in it. Further studies will demonstrate more clearly the clinical significance of ER presence in the tumor in patients with mammary gland carcinoma.

[Serum lipids in epithelial ovarian tumor patients]. / Lipidy syvorotki krovi u bol'nykh épitelial'nymi opukholiami iaichnikov.

The report deals with the studies of lipid profile of blood serum and alpha-lipoproteins in 59 cases of epithelial ovarian tumors as well as the effects of surgery and chemotherapy on the serum levels of major lipids. Triglyceride and phospholipid levels In the serum of cancer patients appeared to be much higher than in healthy controls. Serum lipid distribution patterns were normal in patients with benign tumors of ovaries. Serum levels of total cholesterol and alpha-lipoprotein phospholipids in cancer patients were much lower than in healthy controls thus pointing to a considerably decreased level of this fraction of lipoproteins. Surgery was shown to be followed by a noticeable rise in triglyceride levels and a decrease in serum phospholipid concentration in cancer patients. Post-operative polychemotherapy was followed by reversed changes in triglyceride and phospholipid concentrations. It was found that polychemotherapy is not an important factor affecting the serum level of alpha-lipoproteins in untreated patients.

[The membrane sialoglycolipids of tumor cells and the metastasis of bone tumors]. / Sialoglikolipidy membran opukholevykh kletok i metastazirovanie opukholei kostei.

Level and profile of gangliosides were studied in osteogenic and chondrosarcoma cells. Level of lipid-binding sialic acids in bone- and cartilage-producing tumors proved different. Most osteogenic sarcoma samples showed higher level of lipid-binding sialic acids as compared to chondrosarcoma. In the latter tumor, level of lipid-binding sialic acids was related to grade of tumor cell differentiation, peak levels being observed in undifferentiated neoplasms as compared to those showing grade I-II cell anaplasia. Chondro- and osteogenic sarcoma revealed different profiles of sialoglycolipids, particularly, due to markedly reduced set of gangliosides and nearly complete loss of polysialogangliosides in the latter tumor.

[Ganglioside (GD3) in serum of cancer patients]. / Gangliozid (GD3) v syvorotke krovi rakovykh bol'nykh.

Gangliosides were studied in blood serum of healthy volunteers and of patients with cancer of mammary gland and stomach. Blood serum of the majority of patients with cancer and only 15% of healthy persons were shown to contain ganglioside GD3 which was detected in blood of patients with some other tumors.

[Enzyme and isoenzyme activity in patients with malignant tumors of the oral mucosa]. / Issledovanie aktivnosti fermentov i izofermentov u bol'nykh so zlokachestvennymi opukholiami slizistoi obolochki polosti rta.

The activity and isoenzyme profile of lactate dehydrogenase (LDH), alkaline and acid phosphatase were studied in tumors of the tongue, cheek, oral floor, soft palate and palatine tonsils (n = 100), leukoplakia (n = 7) and in the oral mucosa at corresponding sites in healthy subjects (n = 66), to develop tests for early detection, monitoring and prognosis of oral cancer. Levels of alpha-amylase and acid phosphatase were measured in saliva and blood serum of patients with oral cancer and healthy subjects. The activity of LDH and alkaline and acid phosphatase in oral malignancies were 1.5-6 times that in normal mucosa, depending on tumor site. Changes in LDH isoenzyme profile consisted in an increased level of M-subunits (LDH-4 and 5) and a decreased concentration of N-subunits (LDH-1 and 2). With regards to acid phosphatase, an increase in the activity of its tartrate-inhibited fraction was observed. An increase in LDH and alkaline phosphatase activity was registered for oral precancer (leukoplakia), too, although it was less pronounced than in cancer. Changes in LDH isoenzyme profile matched those in cancer patients. A significant increase in the activity of alpha-amylase, acid phosphatase and the latter's tartrate-inhibited fraction was registered in saliva of oral cancer patients (86-96%). The credibility of enzyme activity measurement in saliva for evaluation of response and prognosis is discussed.

[Lysosomal proteolytic enzymes in the processes of melanoma invasion and metastasis]. / Lizosomal'nye proteoliticheskie fermenty v protsessakh invazii i metastazirovaniia melanom.

Spectrofluorimetry was used to study the activity of lysosomal and membrane-binding endopeptidases such as cathepsins B (CB), D (CD) and L (CL) in 72 patients with skin malignant melanoma. Lysosomal endopeptidases were measured separately in the primary tumor, normal skin adjacent to tumor and intact and metastatic lymph nodes. The activity of lysosomal CB in the primary tumor was higher than in the adjacent normal skin. The peak activity of membrane-binding KB was established in metastatic lymph nodes. A significant increase in the activity of lysosomal KB was observed in involved regional lymph nodes as compared to intact ones. The activity of membrane-binding KB in metastatic lymph nodes was 6 times that in metastasis-free ones. A significant increase in the activity of lysosomal KD was established in primary melanoma nodes compared to adjacent normal skin as well as in metastatic lymph nodes compared to intact ones. Preoperative chemo- and radiation therapy was followed by a decrease in lysosomal KB and KL activity in metastatic lymph nodes which, however, did not reach the level established for intact lymph nodes. The pathogenetic role of proteolytic endopeptidases in invasion and dissemination of malignant melanoma is discussed as well as the value of their level measurement for assessing metastatic potential of tumor and prognosis of disease on the basis of tumor site, degree of invasion regional lymph node status.