[Hypophyseal hormones in young patients with breast cancer]. / Gipofizarnye gormony u bolnykh rakom molochnoi zhelezy molodogo vozrasta.

Hypophyseal hormones were studied in comparison with cellular and humoral immunity in young and middle aged females with breast cancer and controls matched by age. No correlation existed between LH concentrations and cellular, humoral immunological parameters in young breast cancer patients. Basal secretion of FSH directly correlated with the activation markers expression (antigens CD30, CD38) only in young patients. Prolactin concentration was negatively related to B-cell marker (mu-chain IgM) and expression of adhesion molecules (antigen CD11b) in the young, while in the middle-aged to mature T-cell levels only (antigen CD3). No age-specific correlations were found between immunological parameters and ACTH basal secretion, except direct relationship with CD11b-positive cells expression in middle-aged subjects.

[Sex steroid hormone receptors in the cytosolic fraction of cancer and leukoplakia of the oral mucosa]. / Retseptory polovykh steroidnykh gormonov v tsitozol'noi fraktsii raka i leikoplakii slizistoi obolochki polosti rta.

The paper deals with the studies of sexual steroidal hormone receptors in the tumor cytosolic fraction in 37 patients with squamous cell carcinoma and in 18 patients from leukoplakia foci in the oral mucosa. One or two types of androgen and estrogen receptors were detected in the tumor cytosolic fraction in most female (75%) and male (62%) patients with squamous cell carcinoma. The detection rate and the mean values of androgen and estrogen receptors in squamous cell carcinoma of the oral mucosa were associated with sex, age, disease stage, type of growth and site of a tumor. Detection and levels of androgen and estrogen receptors in the leukoplakia foci of the oral mucosa depended on the age of patients. Cytoplasmic estrogen receptors (50%) and oral mucosal squamous cell cancer (34.4%) were much more encountered in the foci of leukoplakia and their mean levels tended to increase. The mechanism of action of sexual steroids on normal and tumor target cells, the role of androgens and estrogens in the pathogenesis of oral mucosal carcinoma and leukoplakia, and possible methods of endocrine therapy for these diseases are discussed.

Regulation of phospholipid turnover by steroid hormones in endometrial carcinoma and breast cancer cells.

To study the early effects of steroid hormones on cells we investigated the influence of the sex steroids and tamoxifen on phospholipid turnover in endometrial carcinoma and breast cancer cells. Studies were performed on 19 human uterine adenocarcinomas and 29 breast cancer tumors. Progesterone in a final concentration of 10(-7) mol/l caused a twofold decrease of 32P incorporation into phospholipids (phosphatidylcholine and phosphoinositides) in 85% of the uterine adenocarcinomas where the progesterone receptor (PR) content was more than 100 nmol/kg and only in 30% of the tumors where the PR content was less than 100 nmol/kg. Treatment of the cells with 10(-8) mol/l 17 beta-estradiol or 10(-8) mol/l epidermal growth factor led to an increase in 32P incorporation into phospholipids. Analysis of the hormonal responsiveness of 29 human breast cancers showed that 17 beta-estradiol increased 32P incorporation into phospholipids in 47% of the tumors where the estradiol receptor (ER) content was more than 10 nmol/kg and in 21% of the receptor-negative tumors (ER < 10 nmol/kg) The results show that phospholipid turnover in uterine and breast cells can be regulated by sex steroids. Treatment of the breast cancer cells with the antiestrogen tamoxifen (10(-6) mol/l) led to an increase of 32P incorporation into phosphoinositides and a decrease of 32P incorporation into phosphatidylcholine. Addition of an activator of protein kinase C, i.e. 2 x 10(-7) mol/l 12-0-tetradecanoylphorbol-13-acetate, weakened the inhibitory effect of tamoxifen on phosphatidylcholine turnover. These findings suggest that tamoxifen action can be mediated via an alteration of the growth signal transducing system.

[The effect of progesterone and tamoxifen on EGF-dependent activation of phospholipid turnover in uterine and breast tumor cells]. / Vliianie progesterona i tamoksifena na EFR-zavisimuiu aktivatsiiu obrashcheniia fosfolipidov v kletkakh opukholei matki i molochnoi zhelezy.

The in vitro effects of the epidermal growth factor (EGF) and progesterone on phospholipid turnover in cells of 19 human adenocarcinomas (postsurgical material) have been studied. In 58% of tumours EGF increased the 32P incorporation into two basic cell phospholipids--phosphatidylcholine and phosphoinositides. In EGF-insensitive cells progesterone induced no noticeable changes in the basal level of phospholipid metabolism. However, in 10 out of 11 positively responding to EGF adenocarcinomas progesterone inhibited the EGF-dependent activation of 32P incorporation into the phospholipids already on the 15th min after its addition to the cells. Analysis of effects of EGF and the anti-estrogen drug tamoxifen on phospholipid turnover in 22 human mammary tumours did not reveal any significant differences in tamoxifen effect on tumour cells differing in their sensitivity to EGF. Independently of cell sensitivity to EGF, tamoxifen caused some decrease in the 32P incorporation into phosphatidylcholine but increased the label incorporation into phosphoinositides. Tamoxifen added to tumour cells prestimulated with EGF or 17 beta-estradiol failed to abrogate the effect of these compounds on phospholipid turnover. At the same time, treatment of cells with the protein kinase C activator 12-O-tetradecanoyl-phorbol-13-acetate fully inhibited the effect of tamoxifen on phospholipid metabolism. The results obtained suggest that the EGF-dependent activation of intracellular phospholipid turnover is under the negative control of progesterone. As for tamoxifen, its effect on cells is independent of EGF and consists, apparently, in the inhibition of protein kinase C activity.

[Metal-dependent collagenolytic activity in primary foci and metastatically involved lymph node in melanoma]. / Metallozavisimaia kollagenoliticheskaia aktivnost' v pervichnykh ochagakh i metastaticheski porazhennykh limfaticheskikh uzlakh melanom.

Collagenolytic activity was estimated in primary focuses of melanoma, in preparations of normal skin surrounding the tumor, in benign pigmentary neoplasms (nevus) as well as in normal and metastatic lymph nodes. Both metal-dependent and -independent collagenolytic activity was significantly increased in tumoral tissues as compared with that of healthy tissues. At the same time, the collagenolytic activity was considerably lower in benign pigmentary neoplasms than that of melanoma primary focuses. Importance of the collagenolytic enzymes in the processes of melanoma invasion and metastatic spreading is discussed.

[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.

[The characteristics of prostaglandin E synthesis in epithelial ovarian tumors]. / Osobennosti sinteza prostaglandinov serii E v épitelial'nykh opukholiakh iaichnikov.

Comparative investigation of prostaglandin E (PGE) levels in primary malignant and benign epithelial tumors, metastases, and normal tissue of the ovaries has revealed more significant variations in PGE levels in malignant tumors than in benign ones. PGE content was reliably higher in adenocarcinomas as against benign tumors and normal ovarian tissue. No noticeable differences in PGE levels of benign tumors and normal tissue were revealed. The possibility of using arachidonic acid cyclooxygenase metabolism blockers in therapy of ovarian carcinoma, besides the common methods of treatment, is discussed.

[The prognostic significance of determining androgen receptors in prostatic cancer]. / Prognosticheskoe znachenie opredeleniia retseptorov androgenov pri rake predstatel'noi zhelezy.

The role of androgen receptors (ARs) registration in cytosol tumor fraction has been investigated in 86 new cases of prostatic cancer. The frequency of occurrence and mean ARs levels in the tumor were found dependent on the disease stage and tumor differentiation. Well-differentiated against moderately and poorly differentiated prostatic cancers contain ARs in 73% and 39% of cases, respectively, in concentrations 10-100 fmol/mg protein and 100 fmol/mg protein, respectively. Patients with well-differentiated prostatic cancer at stage T1-4N0M0 and 10-100 fmol/mg protein ARs in the tumor tend to achieve longer remissions compared to patients with ARs-free tumors or tumor comprising ARs in concentrations surpassing 100 fmol/mg protein. No significant correlation exists between remission duration in patients on radiation treatment combined with estrogen therapy and the presence, levels of ARs in the tumor.

[Changes in the concentration of beta-endorphin in the cerebrospinal fluid due to morphine analgesia in incurable oncologic patients]. / Izmeneniia kontsentratsii beta-éndorfina v likvore pod vliianiem spinal'noi analgezii morfinom u inkurabel'nykh onkologicheskikh bol'nykh.

Thirty cancer patients, clinical group IV, have been examined. It has been established that a persistent pain syndrome leads to lowering in beta-endorphin liquor level. Morphine analgesia is followed by beta-endorphin level elevation which directly depends on pain intensity and analgesia efficacy. Determination of changes in beta-endorphin liquor level may serve as a criterion of analgesia efficacy.

[Sex and pituitary hormone secretion in normal-height and tall adolescents with primary osteogenic sarcoma]. / Sekretsiia polovykh i gipofizarnykh gormonov u normoroslykh i vysokoroslykh podrostkov, bol'nykh pervichnoi osteogennoi sarkomoi.

The paper deals with a comparison of basal levels of secretion of total testosterone (T) and estradiol-17 beta (E2), their free and albumin and sex-steroid-binding globulin fractions as well as LH, FSH, prolactin and STH in blood serum of 60 normal height and 60 tall healthy adolescents and those with primary osteogenic sarcoma of bones at different stages of puberty. The study established a significantly higher level of testosterone and free androgen index and a lowered concentration of sex-steroid-binding globulin in blood serum of both normal and tall adolescent patients with osteogenic sarcoma at different stages of puberty. No significant differences were found in said indexes of estrogens between sarcoma patients and a specific group chosen for comparison, as far as physical status is concerned. The role of sex steroid hormones and, particularly, that of androgens in the pathogenetical mechanisms of osteogenic sarcoma growth is discussed.

[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.

[Sex and pituitary hormone secretion in adolescents with osteogenic sarcoma and retarded sexual development]. / Sekretsiia polovykh i gipofizarnykh gormonov u podrostkov, bol'nykh osteogennoi sarkomoi s zaderzhkoi polovogo razvitiia.

Basal levels of secretion of total testosterone, estradiol-17 beta, their free, albumin-binding and sex steroid-binding globulin (SSBG)--binding fractions, luteinizing hormone, follicle-stimulating hormone, prolactin and somatotropic hormone were measured in blood serum in the following groups of adolescents: (1) healthy, (2) suffering primary osteogenic sarcoma of the bone, (3) osteogenic sarcoma patients with pubertal retardation, and (4) pubertal retardation. A significant increase in total testosterone fraction, free androgen index and a decrease in blood SSBG level were established in osteogenic sarcoma patients as compared to corresponding controls, irrespective of pubertal status. No difference in the above indexes for estrogens was established between osteogenic sarcoma patients and controls in both pubertal status subgroups. The role of sex steroid hormones, particularly, androgens in the pathogenesis of osteogenic sarcoma is discussed.

[Estradiol-17beta, sex steroid-binding globulin and the cellular and humoral immunity indices in young women with breast cancer]. / Estradiol-17beta, polovye steroidy sviazyvaiushchii globulin i nekotorye pokazateli kletochnogo i gumoral'nogo immuniteta u molodykh zhenshchin, bol'nykh rakom molochnoi zhelezy.

Blood serum levels of sex steroid-binding globulin (SSBG), free and SSBG- and albumin-binding fractions of estradiol-17 beta as well as some indexes of cellular and humoral immunity were compared in 25 young female patients with stage 1-3 breast cancer and controls. No significant difference in SSBG and free estradiol-17 beta fraction as well as free estrogen index was established between patients and controls. In the patient group, a direct correlation was established between free estradiol-17 beta fraction level and that of mature T-cells expressing CD3 antigen and between SSBG level, on the one hand, and total level of T-cells (CD7 antigen) and that of T-suppressors (CD8 antigen-containing cytotoxic lymphocytes), on the other. An inverse correlation was established in the same group between SSBG level and that of B-cell markers expressing CD3 and 7 antigens and IgM mu-chain. In the follicular and lutein phases of the menstrual cycle, a difference in the degree of correlation between total estradiol-17 beta level and immunologic indexes was established between breast cancer patients and controls.

[Steroid hormone receptors in spontaneous testicular tumors in dogs]. / Retseptory steroidnykh gormonov v spontannykh opukholiakh iaichka u sobak.

Cytoplasmic receptors to androgens (AR), estrogens (ER), progesterone (PR) and glucocorticoids (GR) were studied in tumors and normal tissue of the testis in dogs. Peculiarities of distribution of receptors were assessed versus age and tumor histology. Benign Leydig cell tumors failed to reveal AR and ER. ER were more often detected in benign Sertoli cell tumors. Malignant seminomas and Sertoli cell tumors were characterized by higher occurrence and levels of AR, GR and PR than their benign counterparts. The results obtained can be used in studies of the activity of newly developed hormonal antitumor drugs against testicular tumors in dogs.

[The effect of indomethacin and leukinferon on the thromboxane B2 level in the blood plasma of patients with endometrial cancer in the perioperative period]. / Vliianie indometatsina i leikinferona na uroven' tromboksana B2 v plazme krovi bol'nykh rakom éndometriia v perioperatsionnom periode.

The paper discusses the effect of indomethacin, leukinferon as well as their combined effect on blood thromboxane B2 (TxB2) level in 40 endometrial cancer patients in the perioperative period. Perioperative treatment with indomethacin was followed by a significant decrease in blood TxB2 level before surgery and in the postoperative period. Treatment with leukinferon exerted similar effect which, however, was less pronounced than that of indomethacin. The effect was most apparent when the two drugs were combined. The influence of indomethacin and leukinferon on metabolism of arachidonic acid in tumor cells and those of the immune system of endometrial cancer patients are discussed as well possible role of eicosanoids in the pathogenetic mechanism of growth and dissemination of reproductive tumors.

[The characteristics of eicosanoid synthesis in osteogenic sarcoma in children at puberty]. / Osobennosti sinteza éikozanoidov v osteogennoi sarkome detei v pubertatnom periode.

Levels of prostaglandin E (PGE), prostaglandin F2 alpha, prostacyclin A2, thromboxan B2 and leucotriene B4 assayed radioimmunologically were compared in 42 samples of osteogenic sarcoma and 22 samples of benign tumors and tumor-like lesions from children at the pubertal period. In osteogenic sarcoma samples, PGE and prostaglandin F2 alpha levels were higher than those of thromboxan B2, prostacyclin A2 and leucotriene B4. Osteogenic sarcoma revealed higher levels of the eicosanoids as compared to benign tumors and tumor-like lesions of the bone. An inverse correlation was established between PGE level and time of dissemination of osteogenic sarcoma. The role of eicosanoids in the pathogenesis of growth and dissemination of osteogenic sarcoma is discussed. The use of non-steroid anti-inflammatory drugs in complex treatment of osteogenic sarcoma of children at the pubertal period is suggested.

[Proteolytic lysosomal enzymes in ovarian cancer]. / Proteoliticheskie fermenty lizosom pri rake iaichnikov.

Activity of lysosomal proteinases cathepsins B and D was studied in normal tissues, malignant and benign ovary tumors, in blood sera and ascites fluid of patients with primary ovary cancer. The cathepsin B activity was 12-fold higher in tissues of ovary malignant tumors as compared with that of normal ovary and 6-fold higher -- as compared with tissues of benign tumors. Activation of the enzyme depended directly on the mass of malignant tumors and on the intensity of their penetration into surrounding tissues (uterus, urinary bladder, small pelvic fat) and spreading over peritoneum. Activity of cathepsin D was 2- and 2.6-fold higher in malignant ovary tumors as compared with normal tissue and benign tumors, respectively. The data obtained suggest that estimation of cathepsins B and D activities in bioptic material from ovary tumors might be useful for diagnosis of the disease.

[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.