New indicators of pre-ovulatory estrogenization.
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Biomedical subjects
Publications and source records attributed to S Mancuso.
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At the Department of Obstetrics and Gynecology of Catholic University in Rome 1257 pregnancies with vaginal bleeding in the first or second trimesters were ultrasonically observed. Pregnancy was found to be in normal development in 538 cases (42.80%); spontaneous abortion was reported in 688 cases (54.73%) and ectopic pregnancy, confirmed at surgery, in 31 cases (2.47%). The duration of bleeding appeared to have a significant effect on the prognosis of the pregnancy. Bleeding for 4 days or more predicted abortion almost significantly more often than a shorter bleeding episode. The spontaneous abortion rate increased with advancing maternal age and decreased with advancing gestational age. After detection of fetal life signs, the pregnancies ended in later abortion only in 9.29% of the cases. In this case there are no significant differences between normal or abnormal ultrasonic examinations. In our experience the ultrasound scanning, in patients with early pregnancy bleeding, is able to differentiate between live gestation or abortion but cannot predict the future.
Twenty-four patients with immune thrombocytopenic purpura (ITP) were treated with high doses of intravenous immunoglobulin (Ig). Increase in platelets was observed in all the patients. The maximum value was reached between the seventh and the twelfth day of treatment. The mean number of platelets was 18 x 10(9)/l before the treatment and 150 x 10(9)/l after the treatment. The effect was transient; in fact, a fall in the platelets was observed after 18 days of treatment. Our study confirms that high doses Ig is an effective treatment of ITP, but the high cost and the temporary effect limit its use only in those cases in which other treatments are ineffective or contraindicated.
Two hundred three patients (median age 26 years; range 18-45) with untreated multiple and widespread anogenital condyloma were randomly assigned to one of four study arms in order to compare the efficacy, toxicity, and tolerability of recombinant interferon alpha-2b with those of diathermocoagulation. Of 200 evaluable patients, 51 were treated intramuscularly (IM) with 3 x 10(6) U (3 MU)/m2 daily for 3 weeks (total dose 63 MU/m2), 50 received subcutaneous thrice-weekly injections of 3 MU/m2 for 4 weeks (total dose 36 MU/m2), 51 underwent diathermocoagulation, and 48 were not treated and were used as a control group. Six months after the end of treatment, the overall response rate (complete and partial responses) was 70%: 57 and 82% for patients receiving interferon alpha-2b (IM and subcutaneously) and diathermocoagulation, respectively, and 8% for the control group. After 6 months from therapy, no significant differences in complete response were found among the different types of treatment: 20, 20, and 35% for the two interferon groups and the diathermocoagulation group, respectively. Fifteen and two complete responders in the cauterization and interferon groups, respectively, experienced disease recurrence (P less than .01). All patients given interferon therapy complained of flu-like symptoms, which declined progressively after the first week of treatment. Fatigue, lasting as long as patients received interferon, was the most prevalent chronic side effect. We conclude that systemic recombinant interferon alpha-2b is active in treating patients with primary condyloma lesions and does so as well as cauterization.(ABSTRACT TRUNCATED AT 250 WORDS)
We have previously reported the production of a new monoclonal antibody (MAb) (SP-2) recognizing a 90-kDa tumor-associated antigen, termed 90K, which is increased in the serum of many cancer patients. Treatment of CG5 human breast cancer cells with recombinant interferon-alpha 2b (rIFN-alpha 2b) can increase the synthesis and release, in culture medium, of the 90K. The effect of rIFN-alpha 2b was dose-related and occurred at concentrations which did not affect cell proliferation. The increase of 90K expression was due to de novo protein synthesis since cycloheximide, added within 3 hr of the beginning of rIFN-alpha 2b stimulation treatment, completely abolished the effect of rIFN-alpha 2b. The stimulatory effect of rIFN-alpha 2b was already evident after 24 hr treatment. Finally, an increase in serum 90K levels was observed in 3 patients with advanced breast cancer receiving a short course of rIFN-alpha 2b (Intron A). No effect of rIFN-alpha 2b was seen in 3 normal women. The ability of rIFN-alpha 2b to increase the synthesis and release of 90K both in vitro and in vivo may be of clinical importance in the early detection of tumors.
Several immunologic variables were evaluated in 14 patients with untreated primary breast cancer and 20 postmastectomized patients undergoing tamoxifen (TAM) or high-dose medroxyprogesterone acetate (MPA) treatment. Immunologic evaluation in the peripheral blood included lymphocyte count, definition of T-lymphocyte subsets by monoclonal antibodies (OKT3, OKT11, OKT4, and OKT8), and lymphocyte blastogenic response to phytohemagglutinin (PHA) and Concanavalin A (Con A). Moreover, the in vitro effect of TAM and MPA on the blastogenic response of peripheral lymphocytes from normal female subjects was tested. Primary breast cancer patients did not differ from controls in any of the variables tested. Similarly, the immunologic variables of the group treated with TAM were normal, with the exception of a slight reduction of the OKT4+/OKT8+ ratio. In MPA-treated patients, a reduction of the percentage of OKT4+ cells and a decrease of the OKT4+/OKT8+ ratio were observed. Moreover, response to PHA was reduced sharply. However, the addition of interleukin-2 (IL-2) to the culture medium restored PHA response. Likewise, the in vitro addition of MPA to peripheral blood lymphocytes from normal female subjects resulted in a sharp dose-dependent depression of PHA response while TAM was ineffective completely. The inhibitory effect of MPA was not evident when IL-2 was added simultaneously to the culture medium. These results show that the administration of high-dose MPA may alter immunocompetence as defined by T-lymphocyte subsets and response to mitogens. The latter effect may be related to a diminished production of IL-2. In contrast, TAM does not appear to have a significant immunodepressant action either in vitro or in vivo.
A computerized system which simultaneously acquires and quantifies several ultrasonically detected fetal activities, including gross body movements, breathing movements, and eye movements, was developed in order to obtain additional quantitative data on fetal behaviour. Movements were automatically related to fetal heart rate allowing computation of their mean incidence, duration, lag time and percentage time spent moving during different heart rate patterns. The incidence of various behavioural states was also calculated. The study of 15 healthy fetuses near term revealed the existence of statistically significant differences in these parameters between low and high variability patterns of fetal heart rate suggesting a quantitative modulation of fetal movements by behavioural states.
The brain-type (BB) isoenzyme of creatine kinase (CK) has recently been shown to be estrogen-regulated in human breast cancer cells in vitro. In this study we have correlated the presence of CK-BB, evaluated by immunoperoxidase procedures, with the estrogen receptor (ER) content in 35 primary breast cancers. Of 35 tumors examined, 66% revealed moderate to strong CK-BB immunoreactivity. Staining was exclusively located in the cytoplasm of neoplastic cells. A positive relationship was observed between CK-BB positivity and ER content with ER-rich tumors (greater than 50 fmoles/mg protein) showing a more intense immunoreactivity than ER-poor ones. The results indicate that CK-BB is estrogen-regulated in human breast cancer and suggest that evaluation of this enzyme may be of potential value for the detection of hormone responsive tumors.
The antiproliferative effect of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines (CG5, T 47 D, and ZR 75-1) is reported. Both peptides markedly inhibited CG5 cell growth with a maximal inhibition of about 40% as compared with control cells. The antiproliferative effect of somatostatin on T 47 D and ZR 75-1 cells was much less evident. These results suggest that somatostatin is a peptide inhibitory factor for human breast cancer cells. Possible therapeutic implications of these findings are still to be investigated.
An enzyme-linked immuno-absorbent assay has been developed for the detection of a circulating tumor-associated antigen, 90K, recognized by murine monoclonal antibody SP-2 (Iacobelli et al., Cancer Res 46: 3005-3010, 1986). This assay was found to be simple and reproducible. Using this method, 6% of 165 apparently healthy individuals and 15% of 91 patients with benign breast disease showed 90K levels above 1.7 units/ml. Approximately 50% of 129 patients with advanced breast cancer demonstrated serum antigen levels above 1.7 units/ml. All histological types of breast cancer were positive, and no association between the incidence of elevated 90K levels and other prognostic variables could be detected. The titers of 90K were significantly higher in sera from advanced-stage (3 and 4) patients than in those from patients with limited-stage (1 and 2) disease. Elevated 90K levels were also observed in patients with carcinomas of other sites, including gastrointestinal, gynecological, and lung tumors. By means of the immune blotting technique, the antigenic components carrying the determinants in serum and extracts of breast cancer cells have been identified. The levels of 90K did not correlate with those of CA 15-3 or CEA. The measurement of 90K in sera appears to be a useful adjunct to other available assays for the detection and monitoring of breast cancer and other malignant tumors.
Immunoreactive alpha-melanocyte stimulating hormone (IR-alpha-MSH)-like activity was measured by radioimmunoassay (RIA) in at term pregnancy amniotic fluid prior and after adsorption on a Sep-pak C18 cartridge. alpha-MSH activity was 3-4 times lower after Sep-pak purification but, unlike the levels of IR-alpha-MSH in the fluid analyzed in toto, increased linearly with the volume of fluid analyzed. Furthermore, fractionation by high pressure liquid chromatography (HPLC) revealed that IR-alpha-MSH recovered from the Sep-pak was due to several peptides rather than to a single peptide. The most abundant of them (50% of total activity) behaved like authentic des-acetyl-alpha-MSH. Since des-acetyl-alpha-MSH is also the most abundant alpha-MSH-like peptide in the fetal pituitary gland, the present results suggest that the fetal pituitary is a main source of des-acetyl-alpha-MSH in the amniotic fluid.
To determine whether maternal oxygen administration affects fetal hemodynamics, we investigated 10 healthy fetuses and 10 growth-retarded fetuses near term by means of Doppler ultrasonography. The growth-retarded fetuses were characterized by abnormal blood flow velocity waveforms. Velocity waveforms were simultaneously recorded at 5-minute intervals from the fetal descending aorta and internal carotid artery before, during, and after maternal oxygen administered through a face mask that delivered 60% oxygen. The pulsatility index was calculated. During oxygen treatment growth-retarded fetuses showed significant temporary hemodynamic modifications as expressed by changes of pulsatility index values that increased in the internal carotid artery and decreased at the level of the descending aorta. On the other side no changes were found in healthy fetuses. These findings suggest that maternal oxygen administration can modify fetal hemodynamics in cases of growth retardation associated with abnormal blood flow velocity waveforms.
The effect of natural beta-interferon (beta-IFN) on steroid receptor levels and output of prostaglandins (PGs) was investigated in human endometrial cancer. beta-IFN determines in endometrial adenocarcinoma explants an increase of cytosolic estradiol (ER) and progesterone (PR) receptors at concentrations ranging from 10 to 1000 IU/ml of culture medium. Only cases in which there was an enhancement of at least 50% with respect to control values were considered. Low concentrations of beta-IFN (10 IU/ml of culture medium) produce an enhancement of ER in 60% and of PR in 42% of cases, while higher concentrations of beta-IFN (1000 IU/ml of culture medium) produce an enhancement of ER in 32%, and of PR in 82% of cases. Since PGs are involved in proliferation control in a large variety of tumors, we evaluated the ratio between PGF2-alpha and PGE2 levels in culture medium. This ratio increased, in our experimental model, after treatment with 10 and 1000 IU/ml of beta-IFN in 38% and 58% of cases respectively. Our data suggest that beta-IFN could affect cellular hormone sensitivity through a modification of ER and PR and it can also determine a variation of PG output in human endometrial cancer.
Serum levels of CA 15-3 were measured in 778 samples from 270 patients with benign and malignant gynecological conditions. Malignant tumors were present in 180 patients including 58 cases with cancer of the ovary, 47 of the endometrium, 61 of the cervix, and 14 of the vulva. The 90 cases with benign conditions included 24 patients with ovarian tumors, 28 with fibromyomatosis, 18 with endometriosis, and 20 with endometrial hyperplasia. Of 180 cancer patients, CA 15-3 serum levels were elevated (greater than 30 U/ml) in 74 cases (41%) and the frequency of abnormal marker values increased with clinical stage. Of 90 patients with benign conditions, high CA 15-3 levels were found in 5 cases (6%) with benign ovarian tumors. Elevated levels of the marker were most commonly seen in ovarian cancer patients (71%). In endometrial, cervical, and vulvar cancer abnormal CA 15-3 values occurred in 32, 26, and 14%, respectively. In endometrial cancer the percentage of positive marker levels increased with more infiltrating and/or less differentiated tumors. A positive correlation was found between residual tumor after surgery and CA 15-3 levels. Serial measurements in sera of patients who underwent chemotherapy showed a good correlation with response to treatment. CA 15-3 values were correlated with clinical course of disease in 87% of cases.
A prospective longitudinal study determined the physiological patterns of blood flow velocity waveforms in normal and in small-for-gestational-age (SGA) fetuses. Using a Pulsed Doppler Duplex system, 125 normally grown fetuses and 35 SGA fetuses were studied longitudinally at between 27 and 42 weeks gestation. In normal fetuses the ratio between the E velocity (early passive ventricular filling) and the A velocity (active ventricular filling during atrial contraction) increased progressively during pregnancy in both transmitral and transtricuspid waveforms, approaching 1 at term. In SGA fetuses, the E/A ratios did not increase during pregnancy and the values obtained were significantly lower than in normal fetuses. The ratio between the transtricuspid and transmitral mean temporal velocities remained almost constant throughout pregnancy in the normal fetuses with transtricuspid velocity slightly exceeding the transmitral velocity. On the other hand, in SGA fetuses the ratio between the mean temporal velocities was inversed with the transmitral velocity progressively greater than the transtricuspid velocity suggesting the existence of intracardiac haemodynamic changes in these fetuses.
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Serum levels of CA 15-3, an antigen expressed by human breast carcinoma cells, were measured in 58 ovarian cancer patients, 24 patients with benign ovarian tumor and 62 patients with benign gynecological conditions. Abnormally high serum CA 15-3 levels were found in 41 of 58 patients (71%) with ovarian cancer. The percentage of CA 15-3 positivity correlated with tumor stage. Elevated serum CA 15-3 levels were found in 5 of 24 patients (20%) with benign ovarian tumor. None of the patients with benign gynecological conditions had increased serum CA 15-3 levels. Serial measurements showed CA 15-3 concentrations to be correlated with the clinical behavior of disease in 21 of 25 patients (84%). CA 15-3 serum levels were also found to be correlated with findings on second look. These results suggest that CA 15-3 may represent a useful tumor marker in ovarian cancer.