Hormonal and cytotoxic chemotherapy for endometrial carcinoma. Steroid receptors in the selection of appropriate therapy.
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Antineoplastic Agents↗
Biomedical subjects
A Kauppila
Publications and source records attributed to A Kauppila.
LH(hCG) receptor in benign and malignant tumors of human ovary.
LH(hCG) receptors were identified with [125I]hCG in 38 benign and 26 malignant ovarian tumors of the human ovary. Eighteen per cent of all the benign and 27% of all the malignant tumors were LH(hCG) receptor-positive. Four of 12 benign serous tumors and 3 of 17 benign mucinous tumors displayed definitive binding of [125I]hCG. Two Brenner tumors failed to bind [125I]hCG. Six of 21 malignant epithelial tumors displayed definitive binding of [125I]hCG. Only one out of 4 malignant granulosa cell tumors bound [125I]hCG, while the other sex cord stromal tumors as well as one dysgerminoma failed to bind [125I]hCG. LH(hCG) receptor content in the benign and malignant receptor-positive tumors was low compared with the normal ovarian tissue. The presence of LH(hCG) receptors in certain benign and malignant ovarian tumors may be a sign of the gonadotropic control of these tumors. The possible applications of these findings for the diagnosis and treatment of human ovarian tumors is discussed.
Adenocarcinoma↗
[Trophoblastic disease in northern Finland].
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Antineoplastic Agents↗
Effect of cytostatics on prostaglandin F2 alpha prostacyclin, and thromboxane in patients with gynecologic malignancies.
Serial measurements of 6-keto-PGF1 alpha (a stable metabolite of prostacyclin), thromboxane B2 (TxB2, a stable metabolite of thromboxane A2), and 13,14-dihydro-15-keto-PGF2 alpha (M-PGF2 alpha, a stable metabolite of prostaglandin F2 alpha) were made from plasma of 9 women with metastatic ovarian or uterine malignancies before and after the combined administration of doxorubicin, cyclophosphamide, 5-fluorouracil, and cis-platinum. Elevated basal levels of TxB2 were detected in all patients, elevated levels of 6-keto-PGF1 alpha in 5 patients and elevated levels of M-PGF2 alpha in 3 patients. The use of chemotherapy was accompanied by a significant increase of 37% (P less than .01) in the M-PGF2 alpha level on the day after treatment and by significant decreases of 30 to 40% (P less than .05) in 6-keto-PGF1 alpha and TxB2 levels, which became apparent immediately after the treatment and persisted for 3 to 5 days. Thus, malignancies may be accompanied by increased production of prostacyclin and thromboxane A2, which can be lowered by cytostatics.
Aged↗
Aryl hydrocarbon hydroxylase induction in maternal and cord blood mitrogen-treated lymphocytes.
The inducibility of aryl hydrocarbon hydroxylase was measured in mitrogen-activated peripheral lymphocytes from smoking and nonsmoking mothers and their newborn infants (cord blood). The mean inducibility ratio in lymphocytes from smoking women was 4.02 and that for nonsmokers 2.87. Benz(a)anthracene-induced and noninduced AHH activities were 3-6 times higher in the lymphocytes from the cord blood than in those from the mothers. The inducibility ratio in the cord blood lymphocytes from the smoking mothers was 3.65 and did not differ significantly from that for the nonsmokers, 3.54. There was a significant correlation in the induction ratio between maternal and cord blood lymphocytes from the nonsmokers, but not in the smokers. Thymidine incorporation was about twice as high on average in the cord blood lymphocytes as in the maternal lymphocytes. The results demonstrate that the extent and distribution of inducibility were very similar in the maternal and cord blood lymphocytes.
Adolescent↗
CRE calculations for different combined radiation therapy schemes of uterine cervical carcinoma.
The CRE concept is not applicable to the assessment of the effect of combined radiotherapy when external and intracavitary radiations are given alternately and with unequal doses. Because of the numerous recurrences, we had to change our radiation treatment schemes for carcinoma cervix uteri, and we attempted, on a theoretical basis, to acquire the same biological effects as Joslin with his own method. In the comparison of different schemes we used as slightly modified approximate CRE and the "nominal dose" presented by Kellerer. In this paper we have presented the treatment schemes we used and the methods for calculating the biological effect in combined treatments. Moreover, we have examined the applicability and compatibility of the above methods in comparing the effects of different combined radiation treatment schemes.
Brachytherapy↗
Therapeutic, clinical and histological factors related to the survival of patients with advanced ovarian carcinoma.
Retrospective evaluation of 137 patients with advanced ovarian carcinoma was attempted 4-12 years after therapy. The operation was radical or almost radical in 56 cases (40.8%). Postoperative treatment consisted of single-drug (N = 53) or multi-drug cytotoxic chemotherapy (N = 53) and irradiation alone (N = 8) or together with cytotoxic chemotherapy (N = 53). Postoperative therapy of any kind was impossible in 23 cases. Nine patients were alive 5 years after therapy. Eight of them had had a clinical stage III (survival rate 7.7%) and one clinical stage IV malignancy (survival rate 3.0%). The extent of the operation was of major importance, 8 out of 9 survivors having undergone a radical operation, which also prolonged the life of the non-survivors. Single drug chemotherapy and combination chemotherapy yielded similar results, 4 and 5 survivors, and 21.1 and 19.6 months as the mean length of survival respectively. None of the patients on postoperative radiotherapy survived. Their mean survival period was 16.6 months. Radiotherapy as an additional measure did not produce any benefit. The prognosis was most favourable for patients with serous cystadenocarcinoma. A poor prognosis was typical of nulliparous women, suggesting that hormones may contribute to the clinical behaviour of this illness.
Adenocarcinoma↗
Treatment of advanced endometrial adenocarcinoma with a combined cytotoxic therapy. Predictive value of cytosol estrogen and progestin receptor levels.
Twenty patients with advanced or recurrent endometrial adenocarcinoma were treated with combination chemotherapy consisting of Adriamycin, cyclophosphamide, 5-fluorouracil, and vincristine at three-week intervals. A minimum of four treatment courses was given in each case. There were five total and five partial responses (50% favorable response rate); progression of the disease was evident in seven cases (35%). Lung metastases responded significantly better (P < 0.01) than other lesions: seven out of nine lung metastases showed an objective remission, whereas only two out of 11 tumors in pelvic, abdominal, or retroperitoneal space responded. The response rate did not correlate with histologic grade of tumor differentiation, or the performance state and age of the patient. Cytosol estrogen and progestin receptor levels were measured in 15 cases from the carcinomatous endometrial tissue prior to therapy. Ten patients with low receptor values (estrogen and/or progestin receptors below 30 fmol/mg cytosol protein) had a significantly (P < 0.025) greater response rate (70%) than did patients with higher receptor values (both receptors above 30 fmol/mg protein, response rate 20%). Determination of only one of the two receptors did not differentiate the patients equally well, although the response rate tended to be better (0.05 < P < 0.1) in patients with a low level of either estrogen or progestin receptor (67% response rate) when compared with a 33% response rate in patients with a high level of the corresponding receptor. Our results suggest that the measurement of cytosol steroid hormone receptors has the potential to serve as a suitable indicator for selection of endocrine or nonhormonal chemotherapy for patients with advanced endometrial adenocarcinoma.
Adenocarcinoma↗
Suppression of threatened premature labor by administration of cortisol and 17 alpha-hydroxyprogesterone caproate: a comparison with ritodrine.
A shift in progesterone-to-estradiol balance to estradiol dominance is assumed to be a prerequisite for regular uterine contractions. To antagonize this effect in premature labor 24 consecutive women were treated with intravenous cortisol for 3 days and with weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate (17 OHP-C). Twenty-four similar patients treated with ritodrine served as a reference group. The delivery was postponed by at least 1 week in 21 patients (87.5%) in the steroid treatment group and in 18 patients (75%) in the ritodrine group. The premature labor lasted for 5.1 +/- 0.4 hours (mean +/- SEM) with steroid therapy and for 2.2 +/- 0.3 hours with ritodrine. In singleton pregnancies the gestational length and birth weight of the newborn infants were greater in the steroid treatment group (N = 23, 39.1 +/- 0.3 weeks, 3,460 +/- 119 gm) than in the ritodrine group (N = 24, 37.7 +/- 0.4 weeks, 3,106 +/- 118 gm). Steroid treatment suppressed serum estradiol concentrations (maximally by 60%) and, to a lesser extent, testosterone, estriol, and progresterone levels (maximally by 30%).
17 alpha-Hydroxyprogesterone Caproate↗
Stable prolactin level after enhanced estradiol production following dehydroepiandrosterone sulfate.
To evaluate whether intravenous injection of dehydroepiandrosterone sulfate (DHEAS), by enhancing estradiol (E2) production, would stimulate prolactin (PRL) secretion in late pregnancy, maternal serum PRL was determined before and 1 to 5 hours after administration of 100 mg of DHEAS in a total of 41 women with normal or complicated late pregnancies (twin pregnancy, pre-eclampsia, intrahepatic cholestasis of pregnancy, diabetes). The basal serum PRL concentration in patients with diabetes was significantly lower than normal. The mean PRL level did not change significantly in any group in spite of the increase in serum E2 levels after the DHEAS injection. The lack of PRL response to a rapid rise in E2 may be due to the maximal inhibition of the PRL-inhibiting factor in the hypothalamus and/or maximal activation of the pituitary lactotrophs occasioned by the high estrogen environment during late pregnancy.
Dehydroepiandrosterone↗
Serum progesterone, estradiol, and estriol before and during induced labor.
To investigate the association of serum levels of progesterone (P), estradiol (E2), and estriol (E3) with the initiation of regular contractions, venous blood samples were taken prior to and 3 hours after the successful induction of labor in 83 parturients by means of low amniotomy and intravenous oxytocin infusion. The serum P level and P/E2 ratio decreased and serum E2 level increased after induction in healthy primigravidas and in parturients with an initial P dominance (serum P/E2 ratio more than 5). There was also a decrease in the serum P level and P/E2 ratio in postterm patients and parturients with a ripe cervical state. Cholestasis of pregnancy was associated with a rise in the serum level of E2 and a decrease in the P/E2 ratio. In an unfavorable cervical state there was a rise in the serum E2 level; patients with an initial E2 dominance (serum P/E2 ratio 5 or less) showed a rise in the serum P level and P/E2 ratio. Healthy multigravidas and patients with pre-eclampsia did not show any hormonal changes. The onset of induced labor seems to be associated with a rise in serum E2 concentration and/or with a drop in P concentration. The increase in serum E2 level is thought to be due to the activation of the anterior pituitary--adrenal axis. The lower P level is supposedly a result of diminished uteroplacental circulation.
Cervix Uteri↗
Comparison of cytosol estrogen and progestin receptor status in malignant and benign tumors and tumor-like lesions of human ovary.
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Adenocarcinoma↗
Surface ultrastructure of human endometrium. Effect of hormonal status and neoplastic progression.
The structure, size and number of uterine endometrial surface epithelial cells and specialized structures, cilia and microvilli were analyzed by light microscopy, transmission and scanning electron microscopy. The purpose was to further our understanding of the biological, morphological and prognostical implications of change in hormonal status and neoplastic progression. The results of this study showed that the quantitative and qualitative alterations followed a similar pattern: the cilia and microvilli were minimally developed in atrophic endometrium, and gradually progressed in size and number in relation to oped in atrophic endometrium, and gradually progressed in size and number in relation to the hormonal cycle and hyperplastic endometrium, unless associated with cellular atypia. Lesions with atypical adenomatous hyperplasia showed irregular and disorganized surface structure, progressively more apparent in specimens from adenocarcinomas. Decreasing degree of differentiation of the tumor and radiation treatment caused a reduction in number and size, as well as derangement in the structure of cilia and microvilli. The results showed the sensitivity of the uterine lining to hormonal changes, the distinction between different types of edometrial hyperplasia and the close interrelationship between atypical adenomatous hyperplasia and early adenocarcinoma, as well as the extent and severity of different clinical entities, including radiation treatment.
Adenocarcinoma↗
Comparison between naproxen tablets and suppositories in primary dysmenorrhea.
Naproxen tablets and suppositories were compared, in the treatment of primary dysmenorrhea, in a double-blind cross-over trial. The results on 32 patients treated during 128 menstruations with either tablets and suppositories were analysed. Both naproxen tablets and suppositories produced a significant but similar overall relief of dysmenorrhea, although the tablets had a better effect in relieving spasmodic pain than the suppositories (p < 0.05). Occasions of failure to obtain relief were not related to the occurrence of vomiting or diarrhea during the trial. Vomiting seems not to be responsible for the therapeutic failures of oral treatments with prostaglandin-synthetase inhibitors in primary dysmenorrhea.
Adolescent↗
Trophoblastic markers in women using intrauterine contraception.
Serum levels of human chorionic gonadotropin (hCG) and pregnancy-specific beta 1-glycoprotein (PSBG) were measured in 214 women using Copper-T200 intrauterine devices (CIUDs). In a cross-sectional study the samples were taken between the 25th and 35th cycle days, 1 sample per cycle. Either trophoblastic marker was detectable in 8 women (3.7%), hCG in 3 (1.4%), PSBG in 7 (3.3%), and both markers together in (0.9%). Normal menstruation-like bleeding ensued in all but 1 woman whose bleeding was delayed by 5 days. Our results suggest that the intrauterine contraceptive device (IUD) prevents pregnancy mainly before significant amounts of trophoblastic products are secreted. Still, the incidence of subclinical abortion based on the demonstration of trophoblastic markers in serum was 7 to 10 times higher than that of established pregnancy in women using a CIUD.
Abortion, Spontaneous↗
Conversion of dehydroepiandrosterone sulphate to oestrogens in intraphepatic cholestasis and other complications of pregnancy.
The aim of the present study was to determine whether pregnancy complications themselves influence the conversion rate of dehydroepiandrosterone sulphate (DHAS) to oestrogens during pregnancy. 100 mg DHAS was given intravenously to seven women with intrahepatic cholestasis of pregnancy, nine women with preeclampsia, nine diabetics, ten with twins and eight women with normal pregnancy between 31--40 weeks of gestation. Serum oestradiol (E2) and oestriol (E3) were measured with specific radioimmunoassays before and 1--5 h after DHAS injections. A significant oestradiol elevation following DHAS was similar in each group. By contrast there was an oestriol elevation (P less than 0.05) only in intrahepatic cholestasis of pregnancy. The results indicate that: (1) pregnancy complication itself does not effect the conversion rate of DHAS to oestradiol, (2) in patients with intrahepatic cholestasis there is a disturbed E3 metabolism which may be due to an increased placental permeability to exogenous DHAS or to a decreased metabolism of E3 by maternal liver.
Cholestasis, Intrahepatic↗
Intra-amniotic or intravenous injection of dehydroepiandrosterone sulphate: simultaneous changes in steroid levels in amniotic fluid and maternal serum.
Levels of unconjugated oestradiol-17 beta (E2) and testosterone (T) and total oestriol (E3) were measured hourly to 6 h after intra-amniotic (i.a.) (100--200 mg) or intravenous (i.v.) (100 mg) injection of dehydroepiandrosterone sulphate (DHEA-S) in a series of twenty-six women with mid-trimester abortion. Amniotic fluid E2 and T levels were elevated significantly 1--6 h after the i.a. injection of DHEA-S, while the E3 level in amniotic fluid did not change. The i.a. administration also induced significant rises in serum E2 and T levels between 1 and 6 h and in the serum E3 level between 2--6 h. The i.v. injection of DHEA-S was accompanied by significantly elevated serum levels of E2 and T, while the E3 concentration remained unchanged. It appears that following maternal i.v. administration or an amniotic fluid injection, DHEA-S is rapidly converted to E2 and T, and these accumulate in both the maternal circulation and the amniotic fluid. E3, however, is formed only after i.a. administration of DHEA-S, and is selectively transported to the maternal blood.
Amnion↗
Luteinizing hormone receptors in ovarian follicles of patients with polycystic ovarian disease.
Wedge resection was performed in 12 patients with polycystic ovarian disease, and cell samples from the cystic follicles were assayed for LH(hCG) receptor using [125I]iodo-hCG as a ligand hormone. Simultaneously to wedge resection, blood samples were taken for serum FSH, LH, 17 beta-estradiol, progesterone, and testosterone RIA measurements. Serum LH was regularly elevated (16.0-57.1 U/liter), whereas FSH (5.2-11.5 U/liter) was within the normal reference range. The LH to FSH ratio was between 2.1-7.8. The 17 beta-estradiol concentrations (0.12-0.23 nmol/liter) were within the normal reference range found during the early follicular phase. Only 3 patients had progesterone levels exceeding the assay sensitivity limit of 0.1 nmol/liter. Ony 3 of the 11 patients assayed for serum testosterone had values exceeding the upper limit of the reference range. Seventy-seven percent of the ovarian follicular samples showed specific binding of [125I]iodo-hCG. The number of receptors in positive samples averaged 0.67 +/- 0.11 fmol/mg homogenate protein, which is clearly lower than that in normal preovulatory follicles. Scatchard analyses revealed a single class of binding sites, with a mean equilibrium association constant of 5.4 X 10(9) M-1 at 37 C. These results suggest that the derangement of follicular development in patients with polycystic ovarian disease probably is not due to the lack of appearance of the LH(hCG) receptor. It is possible that the tonic elevation of serum LH results in a decrease in the number of available receptor sites; this would be one step in the process leading to ovarian changes characteristic of this disease.
Adult↗