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Biomedical subjects

G Emons

Publications and source records attributed to G Emons.

At least 37 records · Page 2Linked to original sources
PubMed2002

Value of sonomorphological criteria of the endometrium in women with postmenopausal bleeding: a multivariate analysis.

OBJECTIVE: This study was performed to examine whether an improvement in the transvaginal sonographic evaluation of the endometrium is possible by the addition of sonomorphological criteria to the measurement of endometrial thickness in women with postmenopausal bleeding. METHODS: Various sonomorphological criteria were analyzed prospectively in 321 patients with postmenopausal bleeding. In a logistic regression model relevant criteria were selected and a diagnostic formula for differentiation of endometrial sonographic findings was derived. RESULTS: The criteria of endometrial structure, endometrial-myometrial border and endometrial thickness were significant for the differentiation of malignancy. These results allowed an estimation of the probability of malignancy for each sonographic endometrial finding. Using the cut-off point of 0.1 for the probability of malignancy, the sensitivity and specificity were 96.8% and 61.9%, respectively, with an accuracy of 72.3%. In contrast, the differentiation by endometrial thickness as the sole criterion (cut-off point > or = 5 mm) achieved a sensitivity of 97.9% and a specificity of 33.2%, with an accuracy of 52.3%. CONCLUSION: A useful diagnostic formula based on sonomorphological and metric criteria for endometrial differentiation was obtained. The specificity and accuracy increased with a minimal loss of sensitivity. However, estimates for sensitivity, specificity, and accuracy may be overoptimistic because they were derived from the same data used for development of the model.

Aged↗
PubMed2002

[Hormonal therapy and chemotherapy of endometrial cancer].

Endometrial cancer is usually diagnosed at an early stage where surgery alone is the adequate therapy. Chemotherapy and hormonal treatment are therefore almost exclusively performed in palliative situations. Hormonal treatment with progestogens (medroxyprogesterone acetate and megestrol acetate) should be the therapy of choice primarily as these drugs are very well tolerated. Tamoxifen and GnRH analogs are further options but are seldom used. The response rates to hormonal treatment are relatively low (max. 25 %) with short remissions in most cases. - So far neither hormonal treatment nor cytotoxic chemotherapy has been shown to have substantial benefits in the adjuvant setting. In some selected high risk cases (serous papillary carcinomas, extra uterine manifestation) adjuvant chemotherapy may be an option following surgery, before or after radiotherapy. Age, general condition and morbidity of the patients need to be considered as limiting factors for chemotherapy. Crucial for the prognosis of all endometrial cancer patients however, is the stage adapted surgery. - Cytotoxic chemotherapy has failed to bring a break through in the therapy of advanced endometrial cancer. Cisplatin plus doxorubicin is the standard combination to date, with anthracyclines being the more important component. In a mono-therapy setting, doxorubicin and epirubicin are well tolerated and convenient in their efficacy. For recurrent and metastatic disease, docetaxel is being evaluated for efficacy and side effects in a multicenter phase II trial.

Antineoplastic Agents, Hormonal↗
PubMed2002

[Diagnosis and therapy of uterine sarcoma].

Radical surgery in stage I and II uterine sarcoma removing all tumor manifestations is the only curative therapy option for early stage disease. Larger tumors (> 4 cm) and the presence of lymph node metastasis correlate with a high local recurrence rate. For these tumors adjuvant radiation and/or adjuvant chemotherapy may be recommended after surgical therapy. Adjuvant therapy however, should preferably be considered for uterine stromal sarcomas and mixed mesodermal tumors. The toxicity of radiation and/or chemotherapy is greater than any possible benefit for patients with leiomysarcomas as these tumors rarely respond to radiation or chemotherapy. For advanced (> stage I and II) and recurrent disease, curative therapy options are not available and palliative therapy for these patients has to take into consideration the negative side effects and weigh up quality of life against an often very limited possible benefit of such therapy.

Female↗
PubMed2002

[Are estrogens carcinogens?].

It is well accepted that unopposed estrogens increase the risk of developing endometrial cancer. A relationship between estrogen exposure and the risk for breast cancer is very probable. In addition, an association of long-term estrogen substitution and ovarian cancer risk has been postulated recently. Estrogens have been considered as typical tumor promotors. Due to their estrogen-receptor-mediated mitogenic activity, these steroids were supposed to increase the statistical probability of spontaneous mutations. Recent experimental findings, however, suggest that estrogen metabolites, in particular 4-hydroxyestrogens are capable of inducing DNA-damage and transforming mutations. The clinical relevance of these genotoxic properties of estrogens remains to be established, but could obtain great importance. First molecular-epidemiologic studies suggest that due to the specific activity of their estrogen metabolizing enzymes some women might produce relevant amounts of mutagenic estrogen metabolites, increasing their risk for breast-, endometrial- or ovarian cancer respectively. These findings might result in novel preventive strategies. The present data do not justify to abandon the practice of hormone replacement therapy with estrogens or estrogens plus progestins in non hysterectomised women. It seems to be wise, however, to restrict hormone replacement therapy to symptomatic women with a clear indication and, according to the actual trend, limit it temporarily.

Breast Neoplasms↗
PubMed2002

Pseudo-meigs syndrome: uterine leiomyoma with bladder attachment associated with ascites and hydrothorax - a rare case of a rare syndrome.

INTRODUCTION: Pseudo-Meigs syndrome is a rare syndrome with pelvic tumors (not ovarian fibromas), which is combined with ascites and hydrothorax. Up to now 23 cases of pseudo-Meigs syndrome associated with uterine leiomyomas are described. We present a further case of a young woman with pseudo-Meigs syndrome combined with bladder attachment and elevated CA-125. CASE REPORT: A 27- year-old woman complained about increasing abdominal volume for about 2 months. Clinical results showed a normal sized uterus with a pedunculated leiomyoma, ascites, and a small pleural effusion. CA-125 levels were approximately more than 50 times higher than normal range. An explorative laparotomy revealed a leiomyoma and ascites. The myoma was attached to the posterior wall of the bladder; the rest of the uterus and both adnexae were normal. An organ-preserving operation was performed. Three months afterwards the patient presented normal clinical and sonographical findings and normal CA-125 serum levels. DISCUSSION: Uterine leiomyoma is only rarely associated with ascites and hydrothorax. Our case is the 24th in literature. Like other authors we could show elevated CA-125 serum levels. Cases of pseudo-Meigs syndrome with penduculated myomas and tight adhesions of neighbouring structures have been described frequently. In our case the bladder was tightly attached, and the vascularisation seemed to come from the uterus and the bladder. This atypical double supply might be in etiological context with the ascites. Pseudo- Meigs syndrome should be considered as a rare differential diagnosis for ascites and pleural effusions.

Adult↗
PubMed2001

Fetal cardiac effects of doxorubicin therapy for carcinoma of the breast during pregnancy: case report and review of the literature.

Cardiotoxicity is a recognized complication of anthracycline drugs given as part of chemotherapy; however, the pre- and postnatal cardiac effects of in utero exposure are not well documented. In this report we present a case of gestational breast cancer with initiation of four cycles of doxorubicin/cyclophosphamide chemotherapy after modified radical mastectomy and axilla dissection during the early second trimester. Serial echocardiographic measurements of the ventricular shortening fraction and biometry of the ventricular cavities were performed. Allowing for the individual variability of these values in the fetus no myocardial dysfunction was observed. The literature was reviewed in an attempt to delineate the possible role of prenatal echocardiography in the diagnosis of doxorubicin-induced cardiotoxicity in the fetus.

Adult↗
PubMed2001

Androblastoma of the ovary: clinical, diagnostic and histopathologic features.

Androblastomas of Sertoli-Leydig cell tumors of the ovaries are classified into the group of sex cord stromal tumors and represent an extremely rare form of tumor (0.2% of all ovarian tumors) in women. Their malignant potential is lower than that of epithelial ovarian cancer. They cause signs of virilization, although these are not obligatory. In many cases secondary amenorrhea is the only symptom of the disease. This leads to an intensive search for the source of the disorder. Frequently only the elevated production of androgens gives a preoperative clue to the tumor type. The recommendation to include the measurement of androgen levels in the routine diagnosis of secondary amenorrhea must therefore be endorsed. The tumors are usually sonographically identifiable; in differential diagnosis, hyperandrogenemia of other origins (e.g., Cushing's disease, adrenal hyperplasia, pituitary adenoma, other causes of ovarian and adrenal androgen hypersecretion, intersexuality, medically induced androgenization) have to be ruled out. In view of the good prognosis, the therapy of choice consists simply in adnexectomy of the affected side. With regular measurement of serum androgen levels an effective control of the course of the disorder is possible. A conclusive pathological diagnosis is difficult as heterologous tumors and mixed tumors exist and, furthermore, other tumor types are capable of imitating Sertoli-Leydig cell tumors.

Androgens↗
PubMed2001

New developments in the treatment of cervical cancer.

Cervical cancer is world-wide the second most frequent cancer found in women and represents 12% of all female malignancies. In fact, it is the most common female cancer in developing countries. There is now sufficient evidence to recommend that women with locally advanced cervical cancer confined to the pelvis receive concurrent pelvic radiation and chemotherapy. New surgical techniques such as laparoscopically assisted radical vaginal hysterectomy and trachelectomy (a fertility-preserving radical operation technique) are being established and have to be evaluated for their long-term safety. Causal treatment by developing multivalent antiviral drugs and vaccines is no longer a pure theoretical approach. Despite these improvements, the early diagnosis by colposcopy and gynaecological cytology remains the safest method to ensure early treatment avoiding death of cervical cancer.

Chemotherapy, Adjuvant↗
PubMed2001

Antiproliferative signaling of luteinizing hormone-releasing hormone in human endometrial and ovarian cancer cells through G protein alpha(I)-mediated activation of phosphotyrosine phosphatase.

The signaling pathway through which LHRH acts in endometrial and ovarian cancers is distinct from that in the anterior pituitary. The LHRH receptor interacts with the mitogenic signal transduction of growth factor receptors, resulting in down-regulation of expression of c-fos and proliferation. Only limited data are available on the cross-talk between LHRH receptor signaling and inhibition of mitogenic signal transduction. The present experiments were performed to analyze in endometrial and ovarian cancer cells: 1) whether mutations or splice variants of the LHRH receptor are responsible for differences in LHRH signaling, 2) the coupling of G protein subtypes to LHRH receptor, 3) the phosphotyrosine phosphatase (PTP) activation counteracting growth factor receptor tyrosine kinase activity. For these studies, the well characterized human Ishikawa and Hec-1A endometrial cancer cell lines and human EFO-21 and EFO-27 ovarian cancer cell lines were used, which express LHRH and its receptor. 1) Sequencing of the complementary DNA of the LHRH receptor from position 31 to position 1204, covering the complete coding region (position 56 to position 1042) showed that there are neither mutations nor splice variants of the LHRH receptor transcript in Ishikawa and Hec-1A endometrial cancer cells or in EFO-21 and EFO-27 ovarian cancer cells. 2) All analyzed cell lines except for the ovarian cancer cell line EFO-27 expressed both G proteins, alpha(i) and alpha(q), as shown by RT-PCR and Western blotting. In the EFO-27 cell line only G protein alpha(i), not G protein alpha(q), expression was found. Cross-linking experiments using disuccinimidyl suberate revealed that in the cell lines expressing G protein alpha(i) and G protein alpha(q), both G proteins coupled to the LHRH receptor. Inhibition of epidermal growth factor (EGF)-induced c-fos expression by LHRH, however, was mediated through pertussis toxin (PTX)-sensitive G protein alpha(i). Moreover, LHRH substantially antagonized the PTX-catalyzed ADP-ribosylation of G protein alpha(i). 3) Using a phosphotyrosine phosphatase assay based on molybdate-malachite green, treatment of quiescent EFO-21 and EFO-27 ovarian cancer cells and quiescent Ishikawa and Hec-1A endometrial cancer cells with 100 nM of the LHRH agonist triptorelin resulted in a 4-fold increase in PTP activity (P < 0.001). This effect was completely blocked by simultaneous treatment with PTX, supporting the concept of mediation through G protein alpha(i). As shown by quantitative Western blotting, EGF-induced tyrosine autophosphorylation of EGF receptors was reduced 45-63% after LHRH (100 nM) treatment (P < 0.001). This effect was completely blocked using the PTP inhibitor vanadate (P < 0.001). These results demonstrate that mutations or splice variants of the LHRH receptor in human endometrial and ovarian cancer cells are not responsible for the different signal transduction compared with that in pituitary gonadotrophs. We provide evidence that the tumor LHRH receptor couples to multiple G proteins, but the antiproliferative signal transduction is mediated through the PTX-sensitive G protein alpha(i). The tumor LHRH receptor activates a PTP counteracting EGF-induced tyrosine autophosphorylation of EGF receptor, resulting in down-regulation of mitogenic signal transduction and cell proliferation.

Adenosine Diphosphate Ribose↗
PubMed2001

Protein kinase C-independent stimulation of activator protein-1 and c-Jun N-terminal kinase activity in human endometrial cancer cells by the LHRH agonist triptorelin.

OBJECTIVE: The expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as a part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumours, including cancers of the endometrium. The signalling pathway through which LHRH acts in endometrial cancer is distinct from that in pituitary gonadotrophs. The LHRH receptor interacts with the mitogenic signal transduction of growth factor receptors via activation of a phosphotyrosine phosphatase, resulting in down-regulation of cancer cell proliferation. In addition, LHRH activates nucleus factor kappaB (NFkappaB) and protects the cancer cells from apoptosis. This study was conducted to investigate additional signalling mechanisms of the LHRH receptor cooperating with NFkappaB in endometrial cancer cells. DESIGN: The LHRH agonist triptorelin-induced activator protein-1 (AP-1) activation was analysed using a pAP-1-SEAP reporter gene assay. Expression of c-jun mRNA was quantified using quantitative reverse transcription (RT)-PCR. c-Jun N-terminal kinase (JNK) activity was measured by quantification of phosphorylated c-Jun protein. RESULTS: Treatment of Ishikawa and Hec-1A human endometrial cancer cells with 100 nM triptorelin resulted in a 3.1-fold and 3.5-fold activation of AP-1 respectively (P<0.05). If the cells had been made quiescent, treatment with triptorelin (100 nM) resulted in a 41.7-fold and 48.6-fold increase of AP-1 activation respectively (P<0.001). This effect was completely blocked by simultaneous treatment with pertussis toxin (PTX). A 17.6-fold and 17.3-fold increase of c-jun mRNA expression respectively (P<0.001) was obtained after 20 min of stimulation with triptorelin (100 nM). Treatment with 1 nM triptorelin resulted in a 12.5-fold or an 11.9-fold increase, and treatment with 10 pM triptorelin resulted in a 6.5-fold or a 5.2-fold increase of maximal c-jun mRNA expression respectively (P<0.001). Maximal c-Jun phosphorylation (68.5-fold and 60.2-fold, respectively, P<0.001) was obtained after 90 min incubation with triptorelin (100 nM). CONCLUSIONS: These results suggest that the LHRH agonist triptorelin stimulates the activity of AP-1 in human endometrial cancer cells mediated through PTX-sensitive G-protein alphai. In addition, triptorelin activates JNK, known to activate AP-1. In earlier investigations we have shown that triptorelin does not activate phospholipase and protein kinase C (PKC) in endometrial cancer cells. In addition, it has been demonstrated that triptorelin inhibits growth factor-induced mitogen activated protein kinase (MAPK, ERK) activity. Thus triptorelin-induced activation of the JNK/AP-1 pathway in endometrial cancer cells is independent of the known AP-1 activators, PKC or MAPK (ERK).

Antineoplastic Agents, Hormonal↗
PubMed2000

The influence of hormone replacement therapy (HRT) on serum leptin concentration in postmenopausal women.

OBJECTIVE: This study aimed to evaluate the influence of hormone replacement therapy (HRT), the estradiol concentration and body mass index (BMI, kg/m(2)) on the serum leptin concentration in postmenopausal women. SUBJECTS AND METHODS: 352 healthy postmenopausal women (mean age, 60.9 +/- 8.5 years) participated in this comparative study. 71 (30%) women (mean age 55.9 +/- 8.3 years) had taken HRT, while 281 (70%) women (mean age, 59.1 +/- 10.6 years) had not. Baseline characteristics -age, weight, height, BMI (greater than or = 25 or <25), follicle stimulating hormone, estradiol, and leptin values-were compared in the two groups. In a second analysis to evaluate the influence of HRT, estradiol concentrations, and BMI on leptin concentrations, these data were analysed in women allocated to one of four groups: (a) postmenopausal women not on HRT with a BMI <25 (n = 130); (b) postmenopausal women not on HRT with a BMI greater than or = 25 (n = 151); (c) postmenopausal women on HRT with a BMI<25 (n = 48); and (d) postmenopausal women on HRT with a BMI greater than or = 25 (n = 23). Leptin concentrations were subsequently analysed in relation to BMI and age and BMI and estradiol concentrations to determine any independent effect of these variables. RESULTS: The women taking HRT had a significantly lower mean age, weight, BMI and follicle stimulating hormone concentration than those who were not taking HRT. Furthermore, they had a higher mean height and serum estradiol value, but a significantly lower serum leptin concentration. After controlling for BMI, neither the use of HRT nor the estradiol concentration was found to be related to the leptin value (group (a) versus (c) and group (b) versus (d)), but there were significant differences in leptin concentrations between HRT users with BMI greater than or = 25 and BMI <25 and between women not taking HRT with BMI greater than or = 25 and BMI <25 (groups (a) versus (b) and (c) versus (d)). Furthermore, women with a BMI greater than or = 25 had significantly higher leptin concentrations than women with a BMI<25, irrespective of the HRT use. CONCLUSIONS: Leptin concentrations are significantly higher in obese postmenopausal women than in their non-obese counterparts. Serum leptin concentrations are not influenced by HRT use or estradiol concentrations. Further studies are needed to elucidate the role of HRT and estrogen on serum leptin concentrations.

Age Distribution↗
PubMed2000

Luteinizing hormone-releasing hormone agonist triptorelin and antagonist cetrorelix inhibit EGF-induced c-fos expression in human gynecological cancers.

OBJECTIVES: Spontaneous and epidermal growth-factor-induced proliferation of human gynecological cancer cell lines is dose- and time-dependently reduced by treatment with the luteinizing hormone-releasing hormone (LHRH) agonist triptorelin and antagonist Cetrorelix. This antiproliferative activity is probably directly mediated through the LHRH receptors expressed by the tumor cells interacting with growth-factor-dependent mitogenic signal transduction. We have examined whether epidermal growth-factor (EGF)-induced expression of the early response gene c-fos is reduced by LHRH analogs. METHODS: Human endometrial (Ishikawa, Hec-1A), ovarian (EFO-21, EFO-27, SK-OV-3), and breast cancer cell lines (MCF-7) were rendered quiescent by incubation (72 h) in the absence of fetal calf serum and phenol red. This was followed by a 15-min incubation in the absence or presence of the LHRH agonist triptorelin (100 nM) or the antagonist Cetrorelix (100 nM) before the cells were stimulated for 10 min with EGF (100 nM). C-fos mRNA expression was determined by semi-quantitative RT-PCR using a synthetic DNA fragment as internal standard. C-Fos protein synthesis was determined by SDS-PAGE and semi-quantitative Western blotting. RESULTS: In cells derived from endometrial and ovarian cancer, maximal c-fos mRNA expression (seven- to ninefold over basal level) was obtained 30 min after EGF stimulation. In the breast cancer cell line MCF-7 this effect was obtained 60 min after EGF treatment. In all of the lines expressing LHRH receptor, EGF-induced c-fos mRNA expression as well as c-Fos protein synthesis was dose-dependently reduced by treatment with LHRH agonists and antagonists. At 100 nM concentrations of the LHRH analogs, c-fos expression was reduced to baseline levels. No effect of LHRH analogs on EGF-induced c-fos expression was observed in the ovarian cancer cell line SK-OV-3, which does not express the LHRH receptor. CONCLUSIONS: These results suggest that the binding of LHRH agonists and antagonists to their receptors inhibits the mitogenic signal transduction pathway of the EGF receptor in endometrial, ovarian, and breast cancer cell lines. The coupling of both signal transduction systems mediates the antiproliferative effect of LHRH analogs.

Antineoplastic Agents, Hormonal↗
PubMed2000

Primary and salvage therapy with LH-RH analogues in ovarian cancer.

The efficacy of modern surgical and chemotherapeutic options for the treatment of ovarian cancer is still unsatisfactory. In spite of the availability of new cytotoxic agents, the majority of ovarian cancer patients will finally die of chemoresistant disease. LH-RH agonists in conventional doses have been shown to induce objective responses in approximately 9% of patients with refractory ovarian cancer and disease stabilization in 26% of these women. As toxicity of LH-RH agonists is low or absent, and since their efficacy is not strikingly inferior to that of experimental chemotherapy, they have a vital indication in the salvage situation. A trial is presently being performed among platinum/taxol-refractory patients, comparing the impact of the LH-RH agonist leuprorelin and that of the cytotoxic agent treosulfane on survival and quality of life. The addition of LH-RH agonists in conventional doses to standard first-line surgical and chemotherapy does not improve relapse-free and overall survival. For many years it has been suggested that LH-RH agonists inhibit proliferation of ovarian cancer by suppressing endogenous gonadotropins, which were considered to be mitogenic in this malignancy. Recent experimental and clinical data have made this hypothesis questionable. In contrast, a large body of experimental evidence has emerged during the past few years indicating that LH-RH agonists and antagonists directly inhibit proliferation of ovarian cancer through LH-RH receptors expressed by 80% of these tumors. To exploit these direct antiproliferative effects of LH-RH analogues, higher tissue concentrations are necessary than those achieved with the conventional doses used today. Alternative routes of administration or higher systemic doses of potent LH-RH antagonists, such as Cetrorelix, might improve the efficacy of this approach. Clinical trials addressing this issue are under way. Finally, the LH-RH receptors expressed by ovarian cancers could be employed for targeted chemotherapy using cytotoxic LH-RH analogues. This approach has been shown to be effective in experimental models and might be tested in clinical trials in the near future.

Animals↗
PubMed2000

Hormonal treatment of endometrial cancer.

In developed western countries endometrial cancer is the most common malignant tumor of the female genital tract. 75% of cases are diagnosed in stage I where cure rates of 75-90% are achieved. In stage II, 5-year survival rates amount only to 50%, in stage III up to 30%, and in stage IV to less than 10%. Despite the preponderance of early stage endometrial cancer, about 20-30% of affected patients will die from this disease. As surgical treatment and/or irradiation are not able to control advanced disease, many investigators have been searching for systemic treatment modalities. Cytotoxic chemotherapy achieves high initial response rates of about 40-60%. Recurrence, however, occurs after a median duration of only a few months. As endometrial cancer develops from hormone dependent cells, endocrine treatment has been the traditional palliative therapy of advanced tumor stages. Several studies to date have failed to demonstrate an efficacy of adjuvant hormonal therapy in cases of high-risk endometrial cancer. For the conservative treatment of precancerous, non-invasive hyperplastic lesions of the endometrium, endocrine therapies have been shown to be efficacious.

Antineoplastic Agents, Hormonal↗
PubMed2000

Assessment by quantitative ultrasonometry of the effects of hormone replacement therapy on bone mass.

OBJECTIVE: This study was undertaken to evaluate the impact of hormone replacement therapy on results of quantitative ultrasonometry of the heel. STUDY DESIGN: A total of 2006 healthy perimenopausal women (mean age, 52.2 (10.3 years) were recruited in 5 German centers: 611 women (30%) had received hormone replacement therapy and 1395 (70%) had not. About 90% of the hormone replacement therapy users were current users, and the rest had stopped <6 months before the study. Speed of sound, broadband ultrasonographic attenuation, and the stiffness index were compared among the following groups: all users and nonusers of hormone replacement therapy, hormone replacement therapy users and nonuser control subjects matched for age and body mass index, and hormone replacement therapy users grouped in relation to the duration of hormone replacement therapy use and age and control subjects matched for body mass index. RESULTS: Women who were using hormone replacement therapy had significantly higher values (P <.001) than did nonusers for all ultrasonographic variables, even after we controlled for age and body mass index. Women who had used hormone replacement therapy for >3 years had significantly higher values (P <.001) than did matched control subjects for all variables. Differences increased with the duration of hormone replacement therapy use. CONCLUSION: Quantitative ultrasonometric measurement at the heel differentiates hormone replacement therapy users from nonusers, reflects duration of hormone replacement therapy use, and could be useful in both clinical trials and patient management.

Age Factors↗
PubMed2000

Luteinizing hormone-releasing hormone induces nuclear factor kappaB-activation and inhibits apoptosis in ovarian cancer cells.

More than 80% of human ovarian cancers express LHRH and its receptor as part of a negative autocrine mechanism of growth control. This study was conducted to investigate whether LHRH affects apoptosis in ovarian cancer. EFO-21 and EFO-27 ovarian cancer cells were treated with LHRH agonist Triptorelin or with cytotoxic agent Doxorubicin in the absence or presence of Triptorelin. Apoptotic cells were quantified by flow cytometry. Expression of nuclear factor kappa B (NFkappaB) was assessed by RT-PCR and immunoblotting. For determination of Triptorelin-induced NFkappaB activation, cells were transfected with a NFkappaB-secreted alkaline phosphatase reporter gene plasmid (pNFkappaB-SEAP) and cultured for 96 h with or without Triptorelin. The causal relation between Triptorelin-induced NFkappaB activation and Triptorelin-induced protection against apoptosis was investigated using SN50, an inhibitor for nuclear translocation of activated NFkappaB. Apoptosis induction by Triptorelin was never observed. Treatment with Doxorubicin (1 nmol/L) for 72 h increased the percentage of apoptotic cells in EFO-21 and EFO-27 ovarian cancer cell lines to 31% or 34%, respectively. In cultures treated simultaneously with Triptorelin (100 nmol/L), the percentage of apoptotic cells was reduced significantly, to 17% or 18%, respectively (P < 0.001). RT-PCR and immunoblotting experiments showed that NFkappaB subunits p50 and p65 were expressed by ovarian cancer cell lines EFO-21 and EFO-27. When EFO-21 or EFO-27 cells were transfected with pNFkappaB-SEAP and subsequently treated with Triptorelin (100 nmol/L), NFkappaB-induced SEAP expression increased 5.3-fold or 4.7-fold, respectively (P < 0.001). Triptorelin-induced reduction of Doxorubicin-induced apoptosis was blocked by SN50-mediated inhibition of NFkappaB translocation into the nucleus. We conclude that LHRH induces activation of NFkappaB and thus reduces Doxorubicin-induced apoptosis in human ovarian cancer cells. This possibility to protect ovarian cancer cells from programmed cell death is an important feature in LHRH signaling in ovarian tumors, apart from the inhibitory interference with the mitogenic pathway.

Apoptosis↗
PubMed2000

Quantitative ultrasound of the os calcis in postmenopausal women with spine and hip fracture.

Quantitative ultrasonometry (QUS) of the os calcis has been shown to predict hip fracture in late postmenopausal women, and vertebral and forearm fracture in early postmenopausal women. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcis were measured using the Achilles ultrasonometer (Lunar, Madison, WI). Osteoporosis risk factors were assessed by a detailed questionnaire. We examined 1314 normal women from age 48 to 79 yr, with a mean age 60 +/- 7.5 yr. In addition, we examined women of similar age, of whom 80 had suffered a hip fracture and 40 a spine fracture. The short-term precision in vivo expressed as the coefficient of variation was 1.2% for BUA, 0.2% for SOS, and 1.3% for SI. A total of 813 women were measured at both the right and left heel. There was high correlation between the two sides (r = 0.80-0.93) (p < 0.001), with no systematic offset. The ultrasound variables decreased significantly (p < 0.001) with age in healthy women; the annual decrease was -0.4% for BUA, -0.07% for SOS, and -0.7% for SI. BUA, SOS and SI discriminated (p < 0.001) between fracture and non-fracture subjects, but the fracture groups were 2 to 4 yr older. The T-score in the controls averaged -2.1 while that in the fracture patients averaged about -3.0. After control for age, years since menopause, and body size, BUA, SOS as well as the SI remained significantly lower (11 to 12% for SI) in women with fracture. The Z-score was -0.8 (p < 0.01) in spine fracture cases, and -0.9 (p < 0.001) in hip fracture patients. QUS provides a gradient of fracture risk comparable to X-ray densitometry of the axial skeleton, and gives comparable Z- and T-scores in younger postmenopausal women. It provides a precise, radiation-free, low-cost, and rapid method for fracture risk assessment in clinical practice.

Aged↗