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Biomedical subjects

N Lang

Publications and source records attributed to N Lang.

At least 19 recordsLinked to original sources

Induction of ovarian tumors by endogenous gonadotropins in rats bearing intrasplenic ovarian grafts.

In this study the role of gonadotropins for the induction of ovarian tumors in rats was examined. The rats were castrated and one ovary was transplanted under the splenic capsule. Rats remained untreated or received a GnRH analog for gonadotropin suppression either immediately, 90 or 180 days after castration. Under these conditions the untreated rats developed ovarian tumors while the treated rats only developed tumors when the stimulation of gonadotropins lasted for more than 90 days. The first appearing tumors were theca cell tumors while during the further course of the experiment the granulosa cell compartment increased; however, no histological signs of malignancy could be detected in these tumors. GnRH analogs could block the induction of granulosa cell tumors when administered 150 days after transplantation. After a period of 210-240 days the tumors grew independently of elevated LH and FSH levels. The causes of this growth autonomy need to be studied further.

Animals

Influence of human luteinizing hormone on cell growth and CA 125 secretion of primary epithelial ovarian carcinomas in vitro.

In the present study, the influence of human luteinizing hormone(hLH) on the growth and the CA 125 secretion of primary ovarian carcinoma cell cultures derived from 11 previously untreated patients was investigated. Two different patterns of in vitro growth of unstimulated ovarian carcinoma cells could be detected: 5 cell cultures in which no changes of cell number were observed during an incubation period of 6 days (group A) and 6 cell cultures which grew without any hormonal support (group B). All tumors of group A showed enhanced cell proliferation when hLH was added to the culture medium, reaching a maximum at dosages of 100 mIU/ml on day 2 after incubation, while such an effect was not observed in group B. In most cases, no positive correlation was found between hLH-induced cell growth and CA 125 release. Our findings demonstrated a dose-dependent hLH-induced stimulation of epithelial ovarian tumors in vitro.

Adenocarcinoma

Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer tissue.

The objective of this study was to test if specific insulin and insulin-like growth factor I (IGF I) receptors are expressed in ovarian cancer tissue. Thirteen tissue specimens from primary ovarian cancers, 1 specimen from a primary peritoneal carcinoma, 10 specimens from metastatic lesions of ovarian carcinomas, and 4 specimens from recurrent ovarian cancers together with 13 normal ovaries were tested for their content of insulin and IGF-I receptors, by the application of specific insulin and IGF-I receptor radioimmunoassays. The insulin receptor (IR) and IGF-I receptor (IGF R) content in the primary tumors varied between 23.8-321.4 and 16.4-554.2 ng/0.1 mg DNA, respectively. Metastatic lesions contained between 12.3 and 226.7 ng IR/0.1 mg DNA and between 7.5 and 459.4 ng IGF R/0.1 mg DNA. In recurrent tumors the receptor concentrations were in the range of 41.5-79.8 and 48.9-160.9 ng/0.1 mg DNA for insulin and IGF-I receptors, respectively. Normal ovarian tissue contained between 12.2 and 150.1 ng IR and between 21.4 and 420.1 ng IGF R per 0.1 mg DNA, respectively. As both insulin and IGF-I receptors are present in ovarian cancer tissue, the effects of insulin and IGF-I as potential growth factors in ovarian cancer should be further investigated.

Adult

In vitro activity of immunoconjugates between cisplatin and an anti-CA125 monoclonal antibody on ovarian cancer cell lines.

Cis-diammine dichloro platinum (II) (CDDP), is a highly potent antineoplastic agent that is used in the treatment of ovarian cancer. However, the clinical use of CDDP is restricted by its severe side effects. In order to reduce these side effects and to enhance its therapeutic efficacy, we developed specific immunoconjugates consisting of the murine monoclonal antibody OC125 and CDDP, using diethylene triamine pentaacetic acid (DTPA) as a linker. The coupling efficiencies of the different preparations synthesized, varied between 1.10 +/- 0.42 and 2.65 +/- 1.60 mol of CDDP per mol of antibody protein. Despite the chemical modification of the antibody molecule, specific binding activity of the OC125-CDDP conjugates toward the CA125 antigen was maintained as was demonstrated by means of immunohisto-/cytochemical staining of frozen sections of ovarian cancer tissue, amniotic epithelium, and the CA125 positive ovarian cancer cell line NIH:OVCAR 3. The antiproliferative activity of the immunoconjugates was tested against the human ovarian cancer cell lines NIH:OVCAR 3 and SKOV 3, applying a kinetic crystal violet microassay. Despite the promising results obtained with the specific immunostaining of the target cells, no significant antiproliferative activity of our immunoconjugates against the cell lines tested was observed. One possible explanation for the lack of antitumor activity could be the fact that CA125 is released in large amounts by the NIH:OVCAR 3 cells. This may have prevented an efficient immunotargeting of the cancer cells by the formation of soluble immune complexes.

Antibodies, Monoclonal

Native gonadotropin-releasing hormone for triggering follicular maturation in polycystic ovary syndrome patients undergoing human menopausal gonadotropin ovulation induction.

OBJECTIVE: To evaluate the role of GnRH administration instead of hCG for triggering follicular maturation in patients with polycystic ovaries (PCO) undergoing hMG ovulation induction when the late follicular 17-beta-E2 levels are > 1,600 pg/mL (> 6,000 pmol/L). DESIGN: Prospective study. SETTING: Infertility outpatient clinic of Rambam Medical Center (general hospital), Haifa, Israel. PATIENTS AND INTERVENTIONS: High serum E2 concentrations from 1,600 to > 3,600 pg/mL (2,800 +/- 68, mean +/- SD [6,000 to > 13,000 pmol/L, 10,279 +/- 2,500]) were experienced in 44 hMG cycles. The number of preovulatory follicles visualized by transvaginal sonography was between 8 and 25. An IV injection of 200 micrograms GnRH was administered for triggering final follicular maturation and ovulation, instead of 10,000 IU IM hCG, usually injected for this purpose, when the E2 levels are < or = 1,600 pg/mL (6,000 pmol/L). Serum E2 and P levels were monitored in the luteal phase. In cycles where E2 decreased to < or = 1,360 pg/mL (5,000 pmol/L), 2,500 IU hCG was administered once or twice at 3-day intervals for luteal support. MAIN OUTCOME MEASURES: Pregnancy and abortion rates and the rate of ovarian hyperstimulation syndrome (OHSS). RESULTS: Ten pregnancies were generated by the hMG and GnRH co-treatment in 32 patients (31.2%), in 44 cycles (23%). Two pregnancies aborted (20%), and eight generated eight healthy neonates. Ovarian hyperstimulation syndrome occurred in two cycles of patients who were both pregnant. All but two of these PCO patients also have undergone 69 hMG and hCG cycles. Only 7 patients conceived (23%) 10 times (10/69, 14.5%); 5 of these pregnancies (50%) were multiple gestations (3 twins, 1 sextuplet, and 1 heptuplet gestation). The pregnancy wastage rate was 30% (3/10). CONCLUSION: The use of native GnRH to trigger ovulation in PCO patients with late follicular E2 levels > 1,600 pg/mL (6,000 pmol/L) appears to be comparable with prior hMG and hCG cycles in terms of pregnancy rate, pregnancy wastage, risk of multiple gestation, and incidence of severe ovarian hyperstimulation. Unlike hMG and GnRH-agonist, which is associated with luteal phase dysfunction, hMG and GnRH offers a preferable alternative due to the ability of hCG luteal support and rescue, providing the E2 levels are not dangerously increased.

Estradiol

Is an increase in CA 125 in breast cancer patients an indicator of pleural metastases?

The retrospective analysis of 250 breast cancer patients with disseminated disease provided evidence that the increase in CA 125 serum levels in these patients was caused by lung metastases or pleural effusions. Seven patients with lung metastases and pleural involvement had elevated CA 125 levels, while in four patients with lung metastases but without pleural effusions CA 125 levels remained normal. In patients with only bone or liver metastases CA 125 levels were usually not elevated. If these results are confirmed, CA 125 would be the first tumour marker in breast cancer whose levels could be associated with one single site of metastases.

Antigens, Tumor-Associated, Carbohydrate

[Indications, technique and results of ultrasound guided punch biopsy in breast diagnosis (n=307)].

From May 1, 1992, to April 30, 1993, we performed 307 ultrasonic guided high-speed punch biopsies. In 119 of the 307 women, we dispensed with further surgical and histological procedures when the tentative diagnosis from complementary mammary diagnostic procedures revealed no pathological findings and concurred with the histological results of the punch biopsy. In 188 women, the biopsy was followed by surgical intervention and correlation of the histological findings. This group of patients showed a sensitivity of 98%, a specificity and positive prognostic value of 100%, and a negative prognostic value of 91%. If we combine the results of the complementary mammary diagnostic (including the punch biopsy), then the sensitivity, specificity, and positive and negative prognostic values for this surgically and histologically confirmed group of patients all reach 100%. In trained hands, the ultrasonic guided high-speed punch is a reliable means of determining the histological nature of lesions detected in ultrasonic scans. This technique has been perfected in our facility. Along with preoperative carcinoma detection, it permits us to avoid unnecessary operations when under defined conditions there are no pathological findings.

Adolescent

[Changes in microcirculatory reactivity in patients with gestosis].

There is increasing evidence in the literature, that the endothelium of the microcirculation as site of production of vasoactive substances (prostacyclin, endothelin and nitric oxide) plays a central role in the pathophysiology of pre-eclampsia. In this investigation, we studied skin microcirculation of the forearm and the volar hand at rest, after a cooling procedure and during reactive hyperemia in 13 patients with pre-eclampsia and 13 healthy pregnant controls. For our measurements we used Laser-Doppler Flowmetry, because this method is non-invasive and of no measurable influence to the microcirculation during measurement. Our main findings were: In pre-eclampsia there is a higher skin vasodilatory reserve during reactive hyperaemia compared to the control group indicating an increased resting vasomotor tone in skin vessels. Vascular reactivity to a vasoconstrictor stimulus (local cooling) was significantly greater in pre-eclamptic patients than in controls. Laser-Doppler Flowmetry is suited to measure alterations in skin vascular reactivity in pre-eclampsia, but there is a wide overlapping range in the results of patients with pre-eclampsia and healthy pregnant controls. A clear distinction between normal pregnancy and pre-eclampsia by Laser Doppler flowmetry is not possible.

Adult

von Willebrand factor: an endothelial marker to monitor in-vitro fertilization patients with ovarian hyperstimulation syndrome.

A retrospective study was conducted to evaluate the possible role of endothelial and extracellular factors in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Plasma changes in von Willebrand-Jürgen factor were correlated with the clinical condition of hyperstimulated patients, since the rise of capillary permeability is the central event in all subsequent morbidity. The corresponding oestradiol levels and ultrasound parameters were assessed. In-vitro fertilization patients designated as 'high responders' and with oestradiol values > 2500 pg/ml and > 8 pre-ovulatory follicles at the time of human chorionic gonadotrophin (HCG) injection were assessed. Among 62 patients, 37 fulfilled these criteria and 18 developed OHSS, indicating the low predictive ability of ultrasound and oestradiol values alone. The remaining 19 patients served as control group. von Willebrand factor-associated antigen in plasma was measured using enzyme-linked immunosorbent assay and ristocetin co-factor activity by an aggregatometric test. Basal values of the two groups of patients did not differ but there were large inter-individual variations. A slight increase occurred in the control group until the day of HCG although individual cycles showed 'no change of pattern' or a 'decreasing tendency' from the start. Some patients allocated to the non-hyperstimulated type showed a steep increase of values followed by a decline. A consistent increase in the OHSS group lasted after embryo transfer even to the late corpus luteum phase. These subtle changes of capillary permeability or damage always preceded the clinical signs, such as ascites, haemoconcentration, hypoproteinaemia and pleural effusion. Mean values differed in the two groups from the day preceding ovum retrieval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Immunohistochemical detection of P-glycoprotein in normal and malignant tissues: a comparative study of three monoclonal antibodies, JSB-1, C 219 and 265/F4, against different epitopes using frozen and paraffin tissue sections.

In this study, the reactivity of three different monoclonal antibodies (MAbs) against the multiple-drug resistance (MDR)-related P-glycoprotein (P-170) were compared with each other using a collection of frozen and paraffin-embedded tumors, normal tissues and metastatic cells of malignant pleural and peritoneal effusions. The MAbs JSB-1, C 219 and 265/F4 were used in an indirect immunoperoxidase technique on frozen material. In addition, MAb C 219 was used on formalin-fixed, paraffin-embedded material from the same tumors, of which frozen sections were studied, and in a retrospective study C 219 was tested on paraffin blocks of the primary tumors that were responsible for the malignant effusions. The results show different staining patterns for all three MAbs to some extent. Results in frozen and paraffin sections obtained with MAb C 219 were comparable. MAb C 219 performs well both in frozen and formalin-fixed, paraffin-embedded material, making it a useful candidate for application in routine laboratory analysis. The retrospective analysis did not show consistency of P-170 expression in the same patients. This leads to the hypothesis that the actual status of P-170 expression in recurrent disease should be obtained before continuing or modifying chemotherapy. Clinical studies aimed at the correlation of immunohistochemistry with therapy response have to evaluate the relevance of P-170 expression in drug resistance of primary and metastatic tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem