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.

[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.

[Biochemical methods and their place in prognosis and evaluation of the effectiveness of treatment of small cell lung cancer]. / Biokhimicheskie metody i ikh mesto v prognozirovanii i otsenke éffektivnosti lecheniia melkokletochnogo raka legkogo.

The blood plasma levels of ACTH, CEA, calcitonin, parathyrin, hydrocortisone, serotonin, and histamine were measured radioimmunologically in 58 cases of small cell lung cancer prior to treatment. Elevated concentrations of CEA (61%) and ACTH (44%) were relatively frequent. Blood plasma--ACTH level in cases of expanded small cell lung cancer was higher than in healthy subjects and patients with localized tumor. A correlation was found between cancer patients survival time and the basal levels of CEA, ACTH and calcitonin. Polyamines were assayed in diurnal urine of 24 cancer patients prior to treatment and during chemotherapy. The mean level of putrescine before treatment was much in excess of normal value. Responders to treatment revealed a considerable rise in spermidine excretion within the first 10 days after treatment. In non-responders, spermidine excretion remained at the same level.

[Glucocorticoid receptors and the histological structure of breast cancer]. / Retseptory gliukokortikoidov i gistologicheskoe stroenie raka molochnoi zhelezy.

Glucocorticoid receptors (GR) were studied in tumor cytosols from 140 breast cancer patients. The level of GR depended upon tumor histology. The highest GR level was found in medullary cancer, while the lowest--in a mucinous one. The GR level in ductal-invasive cancer was significantly higher than in the lobular infiltrative type. The frequency of GR in tumors of the 1st grade of malignancy was significantly lower than in those of the 2nd and 3rd grade of malignancy. The 1st grade of malignancy tumors which contained GR had estrogen and progesterone receptors, too. The increasing malignancy was matched by the rising percentage of such tumors which was as high as 47% among 3rd grade of malignancy tumors.

[Electron microscopic and biochemical characteristics of the hormonal activity of small-cell lung cancer]. / Elektronno-mikroskopicheskaia i biokhimicheskaia kharakteristika gormonal'noi aktivnosti melkokletochnogo raka legkogo.

An electron microscopic study of small-cell carcinoma of the human lung showed that tumors identified by light microscopy as small-cell lung cancer were, in actual fact, histologically heterogenous, ranging from those free from any signs of specific cell differentiation, neoplasms with endocrine differentiation, squamous cell cancer, adenocarcinomas to tumors with mixed cell differentiation. Elevated blood-ACTH concentrations occur in patients with tumors which do not incorporate cells with endocrine differentiation. In such cases, activation of ACTH synthesis may be due to hyperfunction and hyperplasia of apudocytes (elements of a diffuse endocrine system--the APUD system) of the lung or other organs in response to tumor growth.

[Prognostic value of the level of steroid hormone receptors in cancer of the large intestine]. / Prognosticheskoe znachenie urovnia retseptorov steroidnykh gormonov pri rake tolstoi kishki.

Clinical course of 77 surgical cases of cancer of the large bowel was evaluated versus levels of estrogen, androgen, progesterone and glucocorticoid hormone receptors. Within the follow-up period (range 6-41 months), 7 (9%) patients died of tumor progression, 16 (21%) developed recurrence or metastases, while the rest 54 (70%) cases continued in remission. Patients with steroid hormone receptor-positive tumors revealed more favorable clinical course as well as longer disease-free and overall survival than cases of receptor-negative cancer. Estrogen receptor status was found to be of the highest prognostic value in terms of clinical course and survival, as compared to all other hormone receptors studied.

[The importance of determining androgen receptors in malignant breast tumors]. / Znachenie opredeleniia retseptorov androgenov v zlokachestvennykh opukholiakh molochnoi zhelezy.

Androgen receptor (AR) level was studied in 254 untreated cases of breast cancer. The occurrence and mean level of AR did not depend upon stage of disease or reproductive status. However, distribution of AR was determined by histologic pattern and grade of malignancy. Increase in degree of anaplasia of ductal invasive carcinoma was matched by decrease in its AR-positive fraction from 75 to 20%. Recurrence-free survival in surgically treated p T1-2 No Mo patients did not depend upon AR status of tumor. In cases of p T1-2 No Mo AR-positive malignancy, recurrences or metastases occurred 2.2 times as rarely when surgery was followed by endocrine therapy. However, in patients with AR-negative tumors (same stage), the best results were obtained with postoperative chemo- and chemoradiation treatment.

[Bioelectric activity of the brain and glucocorticoid production in patients with hematologic malignancies]. / Bioélektricheskaia aktivnost' golovnogo mozga i produktsiia gliukokortikoidov u bol'nykh opukholiami sistemy krovi.

A parallel study of bioelectrical activity of the brain and urine excretion of 17-hydroxycorticosteroids was carried out in 107 patients with various malignant tumors of hemopoietic tissue before, during and after treatment. In all of them, electroencephalography showed excitation of the hypothalamus, the central component of the hypothalamo-pituitary-adrenal system. Moreover, the patients revealed a significant increase in the excretion of 17-hydroxycorticosteroids that pointed to the activation of the peripheral component--the adrenal cortex. Activation of both central and peripheral components suggests that its intermediate component--the pituitary--is activated in patients with hemopoietic system neoplasms, too.

[Prognostic significance of the glucocorticoid receptor level in the bone marrow blast cells of children with leukemias]. / Prognosticheskoe znachenie urovnia retseptorov gliukokortikoidov v blastnykh kletkakh kostnogo mozga detei, bol'nykh leikozami.

Glucocorticoid receptor (GR) levels of bone marrow blast cells were measured in 29 pediatric patients suffering different forms of acute leukemia. A decrease in GR level was registered immediately after prednisolone treatment. Differences in cell GR levels in patients with lymphoblastic and myeloblastic leukemia were not significant. The level of GR of bone marrow blast cells was found to be of prognostic significance in acute lymphoblastic leukemia: 4 out of 5 patients with GR levels under 3,000 sights per cell relapsed within 5-7 months of follow-up whereas all 7 cases with higher levels continue in remission. No correlation between GR level and prognosis was established in 5 patients with various forms of acute myeloblastic leukemia.

[Steroid hormone receptors in lung cancer tissue]. / Retseptory steroidnykh gormonov v tkani raka legkogo.

Receptors to estrogens (ER), progesterone (PR), glucocorticoids (GR) and androgens (AR) were assayed in 44 lung cancer patients to evaluate hormonal sensitivity of tumor. In 30 cases, active forms of GR were additionally measured by DNA-cellulose adsorption method. GR appeared to be most frequent (65%). Tumors contained PR and ER in 22% and 16% respectively, but failed to reveal AR. A correlation was established between stage and GR positivity, with 83 +/- 8% of GR-positive tumors observed at stage T1-3N0M0 as compared to 50 +/- 12% at stage T1-3N 1-2M0 (P less than or equal to 0.05). As few as 55% (11 out of 20) of GR-positive tumors revealed receptors capable of activation and interaction with DNA-cellulose. These tumors alone, one third of tumors studied, are likely to respond to glucocorticoid treatment.

[Effect of L-ascorbic and D-isoascorbic acids on induced formation of tyrosine aminotransferase in rat liver]. / Vliianie L-askorbinoovoi i D-izoaskorbinovoi kislot na indutsirovannoe obrazovanie tirozin-aminotransferazy v pecheni krys.

Administration of ascorbic acid at moderate doses/0.05-0.1 g per kg of body mass/was shown to induce tyrosine transaminase in liver tissue of intact rats. The enzyme induction depended on the state of adrenal glands and was inhibited by actinomycin D. As distinct from the native form of L-ascorbic acid moderate doses of D-isoascorbic acid did not induce the enzyme in rat liver tissue; these data suggest the relative biological inactivity of D-isoascorbic acid.

[Change in the level of steroid hormone receptors in the tumors of patients with breast cancer complicated by liver and bile duct diseases]. / Izmenenie soderzhaniia retseptorov steroidnykh gormonov v opukholiakh bol'nykh rakom molochnoi zhelezy s zabolevaniiami pecheni i zhelchnykh putei.

Estrogen, progesterone and glucocorticoid receptor levels were assayed in cytosols of primary tumor in 132 patients with breast cancer. Concomitant diseases of the liver and bile ducts were detected in 13 of them. Patients with concomitant hepatic pathology showed a relatively lower percentage of tumors bearing receptors of the above steroid hormones. This was matched by a significant reduction in the level of progesterone receptors. The frequency of identification of receptors of both estrogens and progesterone in tumor in cases of concomitant hepatic pathology was three times less than in those free from it.

[Cytoplasmatic receptors of steroid hormones in malignant epithelial ovarian tumors]. / Tsitoplazmaticheskie retseptory steroidnykh gormonov v zlokachestvennykh épitelial'nykh opukholiakh iaichnikov.

The levels of estrogen, progesterone, androgen and glucocorticoid receptors were assayed in 70 malignant epithelial tumors of human ovaries. The percentage of progesterone, androgen and glucocorticoid receptor-positive tumors was significantly higher in reproductive patients than in menopausal ones. Well-differentiated serous cystadenocarcinomas showed a higher level of progesterone receptors than those characterized by poor differentiation of cells. It was found that steroid hormone receptor profile of primary tumor may be determined in its metastases into the greater omentum whenever tumor cannot be removed. In cases of preoperative chemotherapy, the percentage of receptor-positive ovarian tumors was lower.

[Effect of different types of treatment on the levels of steroid hormone receptors in breast tumors]. / Vliianie razlichnykh vidov lecheniia na urovni retseptorov steroidnykh gormonov v opukholiakh molochnoi zhelezy.

The levels of estrogen, progesterone and glucocorticoid receptors were assayed in samples obtained by trepanobiopsy before surgery and in resected material following chemo- and radiation therapy of 94 patients with stage IIIa, b, and c breast cancer. The biopsy levels and distribution of receptors were shown to be in agreement with those in the resected material from patients with malignancies of the same stage who, however, did not receive preoperative combined therapy. It is inferred that breast tumor biopsies may be used to determine receptor status. Radiation therapy was found to influence the level of steroid hormone receptors, the effect being determined by dosage and after exposure period.

[Cytoplasmic receptors of steroid hormones and clinico-morphological characteristics of skin melanoma]. / Tsitoplazmaticheskie retseptory steroidnykh gormonov i kliniko-morfologicheskie osobennosti melanomy kozhy.

Receptors of estrogens (ER), progesterone (PR), glucocorticoids (GR) and androgens (AR) were assayed in samples obtained from 142 patients with malignant melanoma. GR were observed most often (57% of cases), the percentage being significantly lower for ER (25%) and PR (18%) and extremely low for AR (4%). The occurrence of GR was significantly higher in metastasis to lymph nodes (69%) and soft tissue (67%) as compared to primary tumor (39%). It was higher in acro-lentiginous melanoma (83%) than in superficially extending (30%) or nodular one (33%). GR occurrence rose with the increase in level of invasion (from 30% for level III to 71% for level V) and tumor thickness. In application of adjuvant chemotherapy, patients with GR--negative tumors tended to survive better than those with GR--positive tumors whereas in the chemotherapy-naive group, GR--positive tumors carried better prognosis.

[Content of 17 beta éstradiol, progesterone and glucocorticoid receptors in patients with benign breast diseases]. / Soderzhanie retseptorov éstradiola-17 beta, progesterona i gliukokortikoidov u bol'nykh dobrokachestvennymi zabolevaniiami molochnoi zhelezy.

The levels of estradiol-17 beta, progesterone and glucocorticoids were assayed in tumor tissues from 41 patients with benign breast tumors. Histologically, 21 tumors were identified as fibroadenomas of various types, 14--as fibrous-cystic non-proliferative mastopathy and 6--proliferative mastopathy. Tumor tissue contained estradiol receptors in 51% of cases, all three types of receptors--in 7% and none of the receptors was found in 29% of tumors. The levels of estrogen and glucocorticoids in cases of benign tumors were lower than those in cancer patients. However, in proliferative fibrous-cystic mastopathy group, estrogen receptor level was higher than in the other two groups.

[Cytoplasmic steroid hormone receptors in primary breast tumors]. / Tsitoplazmaticheskie retseptory steroidnykh gormonov v pervichnykh opukholiakh molochnoi zhelezy.

Receptors of steroid hormones (estrogens, progesterone and glucocorticoids) were studied in 148 patients with primary tumors of the mammary gland at different stages. All three types of receptors were found in 40% of patients. Receptor levels were compared versus menstrual status, histological pattern of tumor and preliminary chemo-hormonotherapy. It was established that estrogen and progesterone levels depend on menstrual status. No significant correlation was found between the degree of tumor cell differentiation and level of estrogen receptors. A retrospective assessment of estrogen receptor level and chemo-hormonotherapy results in 74 premenopausal patients with stage II tumor is given.

[Prognostic importance of determining steroid hormone receptors in breast tumors]. / Prognosticheskoe znachenie opredeleniia retseptorov steroidnykh gormonov v opukholiakh molochnoi zhelezy.

The levels of receptors of estrogens, progesterone and glucocorticoids were measured in the cytosols of 400 breast tumors at early (242) and advanced (158) stage of development. No significant differences were found in the receptor status of tumor in cases of early and advanced stage, untreated before surgery. Preoperative chemo- and chemohormonotherapy resulted in a lower percentage of tumors containing all three types of receptors and a higher percentage of tumors in which neither of the three types of receptors were found. Radiation therapy produced a similar effect. Relapse was observed in 53 cases (13%) during a follow-up from 2 months to 3 years. Patients with tumors which contained estrogen receptors revealed a tendency for increased free interval, as compared with those in which receptors were not identified. This tendency was particularly pronounced in cases of advanced tumor, untreated before surgery.

[Prognostic importance of the tumor receptor status in patients with ovarian cancer]. / Prognosticheskoe znachenie retseptornogo statusa opukholi u bol'nykh rakom iaichnikov.

Estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid (GR) receptor levels were assayed in 70 malignant epithelial ovarian tumors from untreated patients and in 23 malignancies from those receiving preoperative chemotherapy. Both PR+ and AR+ frequency and their mean levels in tumor were found to be relatively lower after preoperative chemotherapy. The prognostic significance of receptor status in tumor was identified: the efficacy of combined chemotherapy in PR- and RA- tumor patients was much lower as compared with PR+ and RA+ tumors; a 2-year recurrence-free survival of 12.5% and median duration of remission of 6 months were observed in the former group, while in the latter the disease-free survival rate was as high as 66.7%, and a median duration of remission had not been reached at 24 months of follow-up.

[Surgical stress in pediatric oncology]. / Operatsionnyi stress v detskoi onkologii.

Hormonal-metabolic examination was performed in 150 children suffering nephroblastoma and retroperitoneal tumors to outline features of surgical stress in pediatric cancer patients. Surgical trauma causes hyperglycemia associated with relatively low level of insulin and elevated concentration of somatotropin in blood. A reverse correlation was established between pre- and intraoperative values of many hormonal-metabolic parameters. Surgical stress results in cytolysis, protein catabolism and an increase in endogenous intoxication. Retabolil, eleuterococcus, gordox and preoperative infusion of glucose and neohemodes can be used for prevention of surgical stress.