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M K Oehler

Publications and source records attributed to M K Oehler.

At least 19 recordsLinked to original sources
PubMed2006

Does retention of the ovaries improve long-term survival after hysterectomy? A gynecological oncological perspective.

Ovarian cancer is, in most cases, a lethal disease as it is virtually impossible to diagnose at an early stage and almost impossible to treat successfully when detected at an advanced stage. In postmenopausal women, there is no prevention for ovarian cancer but oophorectomy. Therefore, from the gynecological oncological perspective, where benign gynecological pathology requires surgery in postmenopausal women, oophorectomy should be the preferred option.

Female↗
PubMed2003

Tissue and plasma expression of the angiogenic peptide adrenomedullin in breast cancer.

Adrenomedullin (ADM) is an angiogenic factor that has also been shown to be a mitogen and a hypoxia survival factor for tumour cells. These properties point to ADM as a potential promoter of human malignancies, but little data are available concerning the expression of ADM in human breast cancer. In the present work, we have examined ADM peptide expression in a series of malignant breast tumours by immunohistochemistry using a newly developed anti-ADM monoclonal antibody. In addition, ADM plasma concentrations in breast cancer patients and healthy controls were determined by radioimmunoassay. Of the examined breast cancer samples, 27/33 (82%) showed a moderate to strong staining intensity. ADM-peptide expression in breast tumours was significantly correlated with axillary lymph node metastasis (P=0.030). Analysis of ADM plasma concentrations showed no significant difference between the circulating ADM levels of breast cancer patients and healthy controls. However, a significant positive correlation was found between tumour size and plasma ADM levels (r=0.641, P=0.017). Moreover, ADM levels in breast cancer patients correlated with the presence of lymph node metastasis (P=0.002). In conclusion, we have shown for the first time that ADM peptide is widely expressed in breast cancer and that the degree of expression is associated with lymph node metastasis. ADM peptide in plasma of breast cancer patients reflects the size of the primary tumour, but is unlikely to be a useful tumour marker for the detection of breast cancer. Plasma ADM might represent an independent predictor of lymph node metastasis. The clinical implications of these findings remain to be evaluated.

Adrenomedullin↗
PubMed2003

Menorrhagia: an update.

Menorrhagia is defined as a 'complaint of heavy cyclical menstrual bleeding occurring over several consecutive cycles'. Objectively it is a total menstrual blood loss equal to or greater than 80 ml per menstruation. It is estimated that approximately 30% of women complain of menorrhagia. Excessive bleeding is the main presenting complaint in women referred to gynecologists and it accounts for two-thirds of all hysterectomies, and most of endoscopic endometrial destructive surgery. Thus, menorrhagia is an important healthcare problem. Its etiology, investigation, medical and surgical management are described. In approximately 50% of cases of menorrhagia no pathology is found at hysterectomy. Abnormal levels of prostaglandins or the fibrinolytic system in the endometrium have been implicated. Effective medical treatments suitable for long-term use include intrauterine progestogens, antifibrinolytic agents (tranexamic acid) and nonsteroidal anti-inflammatory agents (mefenamic acid). Over the past decade there has been increasing use of endometrial destructive techniques as an alternative to hysterectomy. Their further refinement and the advent of fibroid embolization has increased the options available to women.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Wnt-7a is upregulated by norethisterone in human endometrial epithelial cells: a possible mechanism by which progestogens reduce the risk of estrogen-induced endometrial neoplasia.

Progestogens are added to oestrogen in hormone replacement therapy regimens to reduce the risk of endometrial cancer. We have performed in vitro studies analysing gene expression of isolated normal endometrial epithelia cells (NEE) treated with estradiol and the progestogen norethisterone acetate (NETA). We report here for the first time upregulation of the Wnt-7a gene by NETA in estrogen treated NEE. Wnt genes are a large family of developmental genes associated with cellular responses such as oncogenesis. We therefore suggest that upregulation of Wnt-7a may be associated with the antineoplastic effects of progestogens on the endometrium.

Cells, Cultured↗
PubMed2002

Tamoxifen induction of angiogenic factor expression in endometrium.

Tamoxifen is the current therapy of choice for patients with oestrogen receptor positive breast cancer, and it is currently under evaluation as a prophylactic for women at high risk of developing the disease. However, tamoxifen is also known to induce proliferative changes in the endometrium increasing the risk of developing endometrial hyperplasia, polyps and carcinoma. Angiogenesis is an intimate part of this process. For this reason, we have examined the expression of several well characterized angiogenic factors, namely, acidic and basic fibroblast growth factor, thymidine phosphorylase, vascular endothelial growth factor and adrenomedullin in both normal and tamoxifen exposed pre- and postmenopausal endometrium. Vascular density and endothelial proliferation index were also quantified. We found increased expression of acidic and basic fibroblast growth factor and adrenomedullin after treatment with tamoxifen mainly in premenopausal tissue. Vascular density was significantly increased in pre- but not post-menopausal endometrium (P=0.0018) following tamoxifen treatment. These results support the notion that angiogenesis is integral to the response to tamoxifen exposure, and is a potential target with which to block these side effects of tamoxifen.

Adrenomedullin↗
PubMed2002

Protease activated receptor-1 is down regulated by levonorgestrel in endometrial stromal cells.

Progestogens are used clinically for contraception, to control excessive menstrual bleeding and to oppose oestrogen in hormone replacement therapy. The use of intrauterine levonorgestrel (LNG) is however, associated with endometrial atrophy and decidualisation of the stroma. In this study, we aimed to identify genes whose expression is modulated by LNG either alone or in combination with progesterone. Thus endometrial stromal cells were stimulated with progesterone, LNG or LNG and progesterone. Poly-A RNA was isolated and used to probe expression arrays. The expression of a number of genes was altered on exposure to LNG or LNG and progesterone. Alteration of expression patterns was confirmed using semi-quantitative RT-PCR and western blot analysis. In particular, the protease activated receptor-1 (PAR-1) gene that encodes a receptor for thrombin was down regulated. This is the first demonstration that PAR-1 is down regulated by the progestogen LNG in human endometrium. Alteration in the expression levels of this receptor may affect both growth and haemostatic activity within the endometrium and may account for the observed morphological effects seen in users of intrauterine LNG delivery devices.

Down-Regulation↗
PubMed2001

Adrenomedullin inhibits hypoxic cell death by upregulation of Bcl-2 in endometrial cancer cells: a possible promotion mechanism for tumour growth.

Regions of hypoxia are a common feature of solid tumours. When tumour cells are exposed to hypoxic stress, transcription of a battery of genes is initiated. The angiogenic factor adrenomedullin (ADM) is a hypoxia regulated gene. ADM is thought to act through the G protein-coupled receptor calcitonin receptor-like receptor (CRLR), with specificity being conferred by the receptor associated modifying protein 2 (RAMP2). Here we report for the first time that ADM treated or stably transfected Ishikawa cells overexpressing ADM show increased resistance to hypoxia induced apoptosis. These cells also show an upregulation of the oncoprotein Bcl-2, which is protective against hypoxic cell death when transiently transfected into Ishikawa cells. Since Ishikawa cells express the putative ADM-receptor CRLR-RAMP2 the production and secretion of ADM with the consecutive upregulation of Bcl-2 could establish an autocrine/paracrine mechanism rescuing malignant cells from hypoxic cell death. These results, taken together with our previous findings that ADM is an angiogenic factor which is upregulated by the nonsteroidal antiestrogen tamoxifen (TAM) in endometrial cells, implicate this peptide as a promoter of tumour growth and a possible target for anticancer strategies.

Adrenomedullin↗
PubMed2000

Steroids and the endometrium.

Steroids are commonly employed in current clinical practice. The benefits of steroids in hormone replacement therapy, contraception and prevention or treatment of breast cancer are limited by their side effects arising from disorders in endometrial function. These side effects are complex and enclose bleeding problems and endometrial proliferation during hormone replacement therapy and antioestrogen treatment or menstrual disturbances during oral contraception. Numerous reports have identified gene targets influenced by steroids and have implicated these products as contributors to endometrial physiology or pathology. The expression of estrogen and progesterone receptors is regulated by steroids. The new estrogen receptor (ER) subtype ERbeta with different functional characteristics from ERalpha was recently described in endometrium. In addition, there is now increasing evidence that the functionally distinct progesterone receptor (PR) isoforms A and B are differentially expressed in this tissue. The relative proportions of these steroid receptors and their interaction determine the expression of specific genes upon steroidal stimulation. Steroids induce endometrial expression of various growth and angiogenic factors. Dysregulations of this steroid modulated expression is believed to be involved in the pathogenesis of many endometrial diseases. Irregular bleeding induced by steroidal contraception, for example, is thought to involve aberrant endometrial vascular development and expression of angiogenic growth factors. The antioestrogen tamoxifen induces growth factors like vascular endothelial growth factor and adrenomedullin which may be key mediators of endometrial neoplastic effects. This review describes recent advances regarding the mechanism of action of steroids on endometrium. The expression of oestrogen and progesterone receptors as well as steroid hormone dependent growth factors and angiogenic modulators are going to be discussed.

Animals↗
PubMed2000

Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density.

Uterine leiomyomas are the most prevalent benign tumor type in women of reproductive age and are one of the most common indications for hysterectomy. The expression of five angiogenic factors, adrenomedullin (ADM), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived endothelial cell growth factor/thymidine phosphorylase, were examined in 91 uteri collected throughout the menstrual cycle; 52 of which contained leiomyomata, and the remainder were normal controls. The microvascular density and endothelial proliferative indices were then determined for each of the uterine sections. ADM and VEGF were the most widely expressed angiogenic factors in the leiomyomas. Furthermore, the expression of ADM and VEGF in the endometrium and myometrium was up-regulated in leiomyoma-bearing uteri compared with controls. Although acidic fibroblast growth factor and basic fibroblast growth factor were expressed in leiomyomas and endometrium in all of the uterine samples examined, they were only expressed in the myometrium of leiomyomata-bearing uteri. Endothelial proliferation in leiomyomas was statistically greater than that of the myometrium and endometrium, both within and between uteri (P < 0.05). The vascular density in the myometrium but not the endometrium was significantly increased in leiomyoma-containing uteri (P < 0.05). Expression of ADM alone correlated directly with vascular density and endothelial cell proliferation index in leiomyomas and myometrium and may account for the high vascularity found in leiomyomas and the myometrium of leiomyoma-bearing uteri. As such, ADM is identified as a novel target for antiangiogenic therapy of these benign, clinically problematic uterine tumors.

Adrenomedullin↗
PubMed1999

Doppler ultrasonographic evidence of intrapartum brain-sparing effect in fetuses with low oxygen saturation according to pulse oximetry.

OBJECTIVE: This study was undertaken to verify by means of Doppler ultrasonography and simultaneous fetal pulse oximetry the redistribution of fetal blood flow in favor of the brain during intrapartum hypoxemia. STUDY DESIGN: During labor 11 term fetuses with abnormal heart rate patterns and arterial oxygen saturation <30% and 14 control term fetuses with normal oxygen saturation were simultaneously monitored by pulse oximetry and Doppler ultrasonography. The results were compared with the Student t test. RESULTS: The blood flow velocity in the middle cerebral artery was significantly higher in the presence of reduced oxygen saturation, implying lower pulsatility and resistance indices (P <.001). The reduction of blood flow in the umbilical artery was not significant (P =.61). CONCLUSION: Simultaneous intrapartum pulse oximetry and Doppler ultrasonography proved that reduced arterial oxygen saturation (<30%) is associated with profound changes in fetal hemodynamics and could be tolerated for only a limited period, which should be the subject of further studies.

Adult↗
PubMed1999

Risk factors associated with early-onset sepsis in premature infants.

OBJECTIVE: To define perinatal factors associated with early-onset neonatal sepsis. STUDY DESIGN: Maternal and neonatal variables were analysed retrospectively in 343 infants born before 35 weeks using univariate and multivariate statistical analysis. RESULTS: Logistic regression analysis identified risk factors for probable neonatal sepsis: gestational age at delivery (odds ratio 0.9, 95% confidence interval (CI) 0.91-0.96), premature rupture of the membranes (odds ratio 2.9, 95% CI 1.004-8.56), Apgar score after 1 min (odds ratio 0.7, 95% CI 0.53-0.96), and histological chorioamnionitis and/or funisitis (odds ratio 4.1, 95% CI 1.36-12.12). There was a strong association between probable sepsis and intracranial haemorrhage of the infant (odds ratio 4.3, 95% CI 1.07-17.40). Funisitis had a high specificity (91%) and positive predictive value (82%) for the detection of neonatal sepsis < or =32 weeks. CONCLUSIONS: Independent obstetrical risk factors for early-onset neonatal sepsis in premature infants may help to identify newborns who benefit from maternal antibiotic prophylaxis before birth. The histological examination of the umbilical cord can be used as an additional diagnostic test to detect newborns at risk of infection.

Antibiotic Prophylaxis↗
PubMed1999

Comparison of long-term survival of cytomegalovirus promotre versus Rous Sarcoma virus promoter-driven thymidine kinase gene therapy in nude mice bearing human ovarian cancer.

The cytomegalovirus (CMV) promoter is considered one of the strongest positive regulators leading to expression of higher levels of the thymidine kinase (TK) enzyme than the Rous Sarcoma virus (RSV) promoter in vitro and in vivo. Cell killing efficacy of adenovirus-mediated CMV promoter-driven herpes simplex virus (HSV) TK gene therapy has been found to be 2 to 10 times more effective than RSV driven HSV-TK gene therapy in vitro. In this study the impact of CMV- versus RSV-driven HSV-TK gene therapy on long-term survival of nude mice bearing human ovarian cancer has been evaluated using a prospective randomized experimental design. The experiment was designed to show significance of survival differences from a 50% increase of survived days at a p-value of 0.05 with a power of 80%. All treatment groups showed an increase in median survival compared with control groups. Treatment benefit was ADV/CMV-TK vector dose dependent. At a given viral dose, no significant prolongation of survival was observed comparing CMV- and RSV-driven ADV-TK indicating that simply increasing cell killing efficacy in vitro above a minimal threshold level using a stronger promoter may not lead to prolongation of survival in the HSV-TK/GCV system.

Adenoviridae↗
PubMed1999

Regulation of endometrial angiogenesis.

Bleeding problems are the most common reason for discontinuation of hormone replacement therapy. Human endometrium undergoes the unique process of benign angiogenesis under the control of ovarian steroids during reproductive life and it is presumed that similar processes occur when women take hormone replacement therapy. The key players in endometrial growth and angiogenesis are vascular endothelial growth factor, thymidine phosphorylase and adrenomedullin. Regulation of these angiogenic factors is described.

Adrenomedullin↗
PubMed1998

Risk factors associated with preterm (<37+0 weeks) and early preterm birth (<32+0 weeks): univariate and multivariate analysis of 106 345 singleton births from the 1994 statewide perinatal survey of Bavaria.

OBJECTIVE: The study was conducted to identify medical, obstetrical and social risk factors associated with early preterm births (<32+0 gestational weeks). STUDY DESIGN: The Statewide Perinatal Survey of Bavaria is a collection of perinatal data from all Bavarian maternity units using a uniform numbered questionnaire. Data on 106345 singleton births from the 1994 Survey were analysed using univariate and multivariate logistic regression analysis. RESULTS: In the multivariate analysis, early preterm birth was associated with premature rupture of the membranes (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.37-1.86), treatment for infertility (OR 1.7, 95% CI 1.19-2.34), previous induced abortion (OR 1.8, 95% CI 1.57-2.13), maternal age >35 years (OR 1.8, 95% CI 1.47-2.16), premature cervical dilatation (OR 2.3, 95% CI 1.86-2.94), a history of stillbirth (OR 3.2, 95% CI 2.13-4.83), a history of preterm birth (OR 3.3, 95% CI 2.45-4.48), maternal age <18 years (OR 3.4, 95% CI 2.03-5.61), malpresentation (OR 3.9, 95% CI 3.10-4.93), preeclampsia (OR 4.0, 95% CI 3.20-4.94), uterine bleeding (OR 5.0, 95% CI 4.08-6.02), preterm labour (OR 7.0, 95% CI 5.94-8.22), and chorioamnionitis (OR 22.3, 95% CI 17.40-28.66). CONCLUSION: These data identify a subgroup of women at an increased risk for early preterm birth and may benefit from an intensified prenatal care. Risk factors related to the obstetrical history, genital infections, preeclampsia and maternal age are the most relevant for early preterm birth.

Abortion, Induced↗
PubMedDate not supplied

CASA and Ca 125 in diagnosis and follow-up of advanced ovarian cancer.

BACKGROUND: CA 125 is the most important tumor marker in ovarian cancer. Due to its low specificity and the fact that some ovarian malignancies do not produce considerable amounts of CA 125 a combination with the Cancer Associated Serum Antigen (CASA) may reflect more accurately the clinical situation. MATERIALS AND METHODS: CA 125 and CASA determination was performed in sera of 78 patients with advanced ovarian cancer pre- and postoperatively, monthly during chemotherapy and during follow-up care. The cut-off values for CASA were 4 U/ml, for CA 125 35 U/ml and 65 U/ml, respectively. RESULTS: In the detection of advanced ovarian cancer a combination of both tumor markers was superior to the use of either CASA or CA 125 alone. In the follow-up situation CA 125 with the 35 U/ml cut-off showed the highest sensitivity. Both markers had similar prognostic relevance when marker levels three months after surgery were used. CONCLUSION: CA 125 and CASA have similar characteristics in preoperative diagnosis and postoperative follow-up. In clinical situations with inconclusive or negative CA 125 serum values CASA is helpful to improve management of patients with advanced ovarian cancer.

Antigens, Neoplasm↗
PubMedDate not supplied

Diagnostic value of serum VEGF in women with ovarian tumors.

BACKGROUND: Angiogenesis is necessary for growth and invasiveness of malignant tumors. Vascular endothelial growth factor (VEGF) is considered to play a key role in tumor angiogenesis. Few data are available with regard to serum levels of VEGF in patients with ovarian tumors. We investigated the diagnostic value of serum VEGF in patients with ovarian neoplasms. MATERIALS AND METHODS: 61 patients with ovarian neoplasms (41 ovarian carcinomas, 20 cystadenomas) and 20 healthy women were included into the study. VEGF serum concentrations were determined by a commercially available ELISA. RESULTS: Statistical analysis revealed significant differences in VEGF serum values of ovarian cancer patients vs. healthy controls or patients with cystadenomas. No difference could be seen between serum levels of healthy controls and women with benign ovarian tumors. For ovarian cancer patients vs. normal controls a sensitivity of 71% and a specificity of 65% resulted. The sensitivity and specificity of cancer patients vs. patients with benign neoplasms were 71% and 65%, respectively. CONCLUSION: Our results suggest that VEGF has potential as a serum marker with diagnostic relevance in ovarian neoplasms.

Adult↗
PubMedDate not supplied

Prognostic relevance of the endothelial marker CD 34 in ovarian cancer.

BACKGROUND: Tumour angiogenesis and microvessel density are of prognostic significance in several human neoplasia. To investigate how tumour vascularity correlates with disease-free survival microvessel density was assessed in 38 patients with ovarian cancer using the highly specific endothelial marker CD 34. METHODS: Representative specimens were obtained and stained using monoclonal CD 34 antibodies. The microvessels were quantified at 200x and 400x magnification in the most active areas of neovascularisation. Degree of angiogenesis was correlated with histologic tumour type, grading, and tumour stage. Furthermore, survival was calculated using Kaplan-Meier analysis and results again correlated with the microvessel count. RESULTS: No correlation was found between microvessel density, histologic type, grading, and FIGO stage. Patients with a vessel count more than 40 (200x magnification) had a statistically significant lower overall survival (p = 0.022). CONCLUSION: Our results indicate that CD 34 is a useful marker in determining tumour neovascularisation which might be of prognostic relevance in patients with ovarian cancer.

Adult↗