Biomedical subjects

Werner Schmidt

Publications and source records attributed to Werner Schmidt.

36 records · Page 2Linked to original sources

PubMed2004

Serum inhibin A, inhibin B, pro-alphaC, and activin A levels in women with idiopathic premature ovarian failure.

Serum inhibin A, inhibin B, pro-alphaC, and activin A levels in 30 women with idiopathic premature ovarian failure (POF), 30 postmenopausal women, and 30 age-matched fertile women were determined. Women with POF showed low levels of inhibin A and inhibin B, but not of activin A, whereas the levels of pro-alphaC were significantly higher than in postmenopausal women. Thus, the circulating level of pro-alphaC could be a marker for assessing residual ovarian function in women with POF.

Female↗

PubMed2004

Relationship between cytokine concentrations (FGF, sICAM-1 and SCF) in serum, follicular fluid and ICSI outcome.

OBJECTIVE: The aim of this study was (i) to investigate the existence of fibroblast growth factor (FGF), soluble intracellular adhesion molecule-1 (sICAM-1), and stem cell factor (SCF) in serum and human follicular fluid (FF) of intracytoplasmic sperm injection (ICSI) patients, and (ii) to determine the relationship between these parameters and ICSI outcome. MATERIAL AND METHOD: Seventy-five patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) after down-regulation with GnRHa were included in this study. The concentrations of FGF, SCF, and sICAM-1 were measured by using commercially available enzyme-linked immunosorbent assay test kits. RESULTS: The FGF, sICAM-1, and SCF concentrations in the serum of women who become pregnant (group I) were 8.5 +/- 1.5 pg/mL, 235.8 +/- 81.1 ng/mL, and 597.7 +/- 139.9 pg/mL, and the corresponding concentrations of women who did not (group II) were 6.4 +/- 3.6 pg/mL, 230.6 +/- 66.5 ng/mL, and 569.6 +/- 91.4 pg/mL respectively. No significant difference was observed between the two investigated groups with regard to the number of hMG ampoules administered for controlled ovarian hyperstimulation, estradiol concentration on the day of human chorionic gonadotropin (hCG) injection, number of retrieved oocytes and fertilization rate. CONCLUSION: The concentration of FGF, sICAM-1, and SCF did not differ significantly between the two groups in serum or in FF. Besides, the ICSI outcome was not related to their concentrations in serum or FF. Therefore, these parameters could not be used as a prognostic factor in ICSI program.

Adult↗

PubMed2004

Doppler examinations of fetal and uteroplacental blood flow in AGA and IUGR fetuses before and after maternal physical exercise with the bicycle ergometer.

OBJECTIVE: To study changes in uteroplacental and fetal circulation after maternal exercise in appropriate-for-gestational-age fetuses (AGA) and intrauterine-growth-retarded fetuses (IUGR). MATERIALS AND METHOD: 33 women with an uncomplicated course of pregnancy and ten women with IUGR were examined. Physical stress was caused through a bicycle ergometer with 1.25 W/kg maternal weight. Doppler examinations were performed in the umbilical artery, fetal aorta, middle cerebral and in the uterine artery. Fetal heart rate was documented by monitoring. Maternal lactate and glucose levels as well as maternal blood pressure and heart rate were recorded. RESULTS: No significant changes after cycling could be observed in umbilical and uterine vessels either in the normal pregnancies or in pregnancies with IUGR. In contrast, in the fetal aorta an increase of the RI was recorded in both groups (an increase of 16% [P<0.01] and 18% [P<0.05], respectively for AGA and IUGR cases). In cerebral arteries a decrease of the RI was observed after cycling in both groups (a decrease of 24% [P<0.01] and 13% [P<0.05], respectively for AGA and IUGR cases). In AGA fetuses the RI of the aorta and middle cerebral artery returned to pre-test level by the 18th minute of examination. In IUGR fetuses the RI of the aorta and middle cerebral artery did not return to pre-test levels at the end of the test. Fetal heart rate remained unchanged in both groups. Maternal blood pressure and heart rate increased during the exertion phase but returned to initial values at the end of the test. A 21% and 24% (for AGA and IUGR groups respectively) reduction of maternal glucose values after exercise was observed (P<0.001). Lactate values doubled in both groups after exercise (P<0.001). CONCLUSION: From the results obtained we conclude that maternal exercise does not significantly alter uterine and umbilical perfusion in AGA and IUGR pregnancies, suggesting an absence of change in the uterine vascular bed resistance. However, submaximal maternal exercise was followed by fetal cerebral vasodilatation and an increase of resistance in the fetal aorta that was more evident in IUGR fetuses. This might be due to slight fetal hemoglobin desaturation in those cases.

Adult↗

PubMed2003

Identification of an HLA-A*02 restricted immunogenic peptide derived from the cancer testis antigen HOM-MEL-40/SSX2.

HOM-MEL-40/SSX2 is a SEREX-defined cancer testis antigen with frequent expression in various human neoplasms. To search for HLA-A*0201 restricted peptides that induce HOM-MEL-40/SSX2-specific CD8+ responses in breast cancer patients, we used the SYFPEITHI algorithm to identify three HOM-MEL-40/SSX2-derived nonamers with high binding affinity for HLA-A*0201, which has a prevalence of 40% in the Caucasian population. Of the three peptides, p41-49 and p103-111 but not p167-175 had been shown to be processed by the proteasome. Only stimulation with p103-111 induced HOM-MEL-40-specific CTLs in 5/7 patients with HOM-MEL-40/SSX2 positive breast cancers and in 6/11 healthy controls. HLA-A*0201 restriction of p103-111 was demonstrated by blocking with specific antibodies. The natural processing and presentation of p103-111 was demonstrated by the recognition of the HOM-MEL-40/SSX2 positive cell line SK-MEL-37 and of COS7/A2 cells transfected with HOM-MEL-40/SSX2 by p103-111 specific CD8+ cells. No correlation was found between CD8+ T-cell responses against p103-111 and anti-HOM-MEL-40/SSX2 antibody titers in the serum of patients, suggesting that CD8+ and B-cell responses against HOM-MEL-40/SSX2 are regulated independently. p103-111 holds promise as a broadly applicable peptide vaccine for patients with HOM-MEL-40/SSX2 positive neoplasms.

Aged↗

PubMed2003

Analysis of the vitamin D system in cervical carcinomas, breast cancer and ovarian cancer.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the biologically active metabolite of vitamin D and has been shown to regulate the growth of various cell types. There are two principal enzymes involved in the formation of circulating 1,25(OH)2D3 from vitamin D, the vitamin D 25-hydroxylase (25-OHase) and the 1alpha-hydroxylase (1alpha-OHase). Recently, extrarenal activity of 1alpha-OHase has been reported in various cell types. The aim of this study was to analyze expression of VDR and the main enzymes involved in the synthesis and metabolism of calcitriol in gynecological malignancies and corresponding normal tissue. Expression of VDR, 25-OHase, 1alpha-OHase, and 24-OHase was analyzed in breast carcinomas (BC), ovarian cancer (OC), cervix carcinomas (CC) and normal corresponding tissues using real-time PCR and specific hybridization probes as well as using immunohistochemistry. RNA for VDR, 1alpha-OHase, 24-OHase and 25-OHase was up-regulated in breast cervical and ovarian carcinomas as compared to normal tissue. VDR immunoreactivity was increased in breast and ovarian cancer and in cervix carcinomas as compared to normal corresponding tissue. Our findings indicate that cervical carcinomas, breast cancer and ovarian cancer may be considered as potential targets for prevention or therapy with new vitamin D analogs that exert little or no calcemic side effects or by pharmacological modulation of 1,25(OH)2D3 synthesis and metabolism in these tumor cells.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMed2003

Benzophenone synthase and chalcone synthase from Hypericum androsaemum cell cultures: cDNA cloning, functional expression, and site-directed mutagenesis of two polyketide synthases.

Benzophenone derivatives, such as polyprenylated benzoylphloroglucinols and xanthones, are biologically active secondary metabolites. The formation of their C13 skeleton is catalyzed by benzophenone synthase (BPS; EC 2.3.1.151) that has been cloned from cell cultures of Hypericum androsaemum. BPS is a novel member of the superfamily of plant polyketide synthases (PKSs), also termed type III PKSs, with 53-63% amino acid sequence identity. Heterologously expressed BPS was a homodimer with a subunit molecular mass of 42.8 kDa. Its preferred starter substrate was benzoyl-CoA that was stepwise condensed with three malonyl-CoAs to give 2,4,6-trihydroxybenzophenone. BPS did not accept activated cinnamic acids as starter molecules. In contrast, recombinant chalcone synthase (CHS; EC 2.3.1.74) from the same cell cultures preferentially used 4-coumaroyl-CoA and also converted CoA esters of benzoic acids. The enzyme shared 60.1% amino acid sequence identity with BPS. In a phylogenetic tree, the two PKSs occurred in different clusters. One cluster was formed by CHSs including the one from H. androsaemum. BPS grouped together with the PKSs that functionally differ from CHS. Site-directed mutagenesis of amino acids shaping the initiation/elongation cavity of CHS yielded a triple mutant (L263M/F265Y/S338G) that preferred benzoyl-CoA over 4-coumaroyl-CoA.

Acyltransferases↗

PubMed2003

7-Hydroxylated epiandrosterone (7-OH-EPIA) reduces ischaemia-induced neuronal damage both in vivo and in vitro.

Recent evidence suggests that steroids such as oestradiol reduce ischaemia-induced neurodegeneration in both in vitro and in vivo models. A cytochrome P450 enzyme termed cyp7b that 7-hydroxylates many steroids is expressed at high levels in brain, although the role of 7-hydroxylated steroids is unknown. We have tested the hypothesis that the steroid-mediated neuroprotection is dependent on the formation of 7-hydroxy metabolites. Organotypic hippocampal slice cultures were prepared from Wistar rat pups and maintained in vitro for 14 days. Cultures were then exposed to 3 h hypoxia and neuronal damage assessed 24 h later using propidium iodide fluorescence as a marker of cell damage. Neurodegeneration occurred primarily in the CA1 pyramidal cell layer. The steroids oestradiol, dehydroepiandrosterone and epiandrosterone (EPIA) were devoid of neuroprotective efficacy when present at 100 nM pre-, during and post-hypoxia. The 7-hydroxy metabolites of EPIA, 7alpha-OH-EPIA and 7beta-OH-EPIA significantly reduced neurotoxicity at 100 nM and 10 nM. 7beta-OH-EPIA was also neuroprotective in two in vivo rat models of cerebral ischaemia: 0.1 mg/kg 7beta-OH-EPIA significantly reduced hippocampal cell loss in a model of global forebrain ischaemia, whereas 0.03 mg/kg was neuroprotective in a model of focal ischaemia even when administration was delayed until 6 h after the onset of ischaemia. Taken together, these data demonstrate that 7-hydroxylation of steroids confers neuroprotective efficacy, and that 7beta-OH-epiandrosterone represents a novel class of neuroprotective compounds with potential for use in acute neurodegenerative diseases.

Animals↗

PubMed2003

Comparison of perinatal outcome in fetuses with reverse or absent enddiastolic flow in the umbilical artery and/or fetal descending aorta.

OBJECTIVES: To examine the differences of perinatal outcome in fetuses with absent and reversed enddiastolic flow velocity waveforms of the umbilical artery or fetal descending aorta. DESIGN: In a retrospective study, 30 pregnant women with reversed enddiastolic flow in the umbilical artery or fetal aorta (group I) were compared with 30 cases of absent enddiastolic flow (group II). Patients were included in the groups according to the last Doppler finding before delivery. Perinatal and neonatal outcome was correlated with antenatal Doppler flow findings. RESULTS: The mean gestational age at birth was 31 weeks in both groups. Fetuses with reverse flow showed higher perinatal (27% and 7% respectively) and overall mortality (53.3% and 10% respectively) compared to the absent enddiastolic flow group (p < 0.05). All the intrauterine fetal deaths occurred in the reversed flow group (n = 12). The rates of intrauterine growth retardation, oligohydramnios and hypocalcemia were different between the groups (p < 0.05). The cesarean section rate, perinatal and neonatal complications including the incidence of acidosis, the number of cases admitted to neonatal intensive care unit and mean treatment time were not different between the groups. A tendency to higher incidence of neonatal cerebral hemorrhage in reversed flow cases (28%) compared to absent enddiastolic flow cases (17%) was observed, but this was not statistically significant. CONCLUSIONS: The present study suggests that reversed flow should be seen as a particular clinical entity with higher incidences of perinatal and overall mortality, and severe intrauterine growth retardation (< 5. perc) compared to the absent enddiastolic flow group. The optimal timing of delivery in pregnancies complicated by highly pathological Doppler flow findings is only to be resolved in well-designed randomized, multicenter clinical trials.

Aorta, Thoracic↗

PubMed2002

Down-regulation of Rac-1 GTPase by Estrogen.

Rac1 GTPase is essential for the activation of the NAD(P)H oxidase complex and, thereby, regulates the release of reactive oxygen species (ROS) in the vessel wall. 17 beta-estradiol (E2) inhibits vascular ROS production. To elucidate the underlying molecular mechanisms we investigated the potential regulation of Rac1 by E2 in vascular smooth muscle cells. Treatment of vascular smooth muscle cells with angiotensin II as well as overexpression of the constitutively active mutant RacL61 increased ROS release as assessed by dichlorofluorescein fluorescence, whereas inhibition of Rac1 by Clostridium sordellii lethal toxin or overexpression of dominant-negative RacN17 inhibited ROS production. Treatment with E2 (100 nm) completely prevented angiotensin II-induced NAD(P)H oxidase activity and ROS production. E2 time and concentration dependently decreased angiotensin II-induced and basal Rac1 mRNA and protein expression as well as Rac1 activity. Down-regulation of Rac1 expression by E2 was mediated by inhibition of gene transcription (nuclear run-on assays), but E2 had no effect on Rac1 mRNA stability. Regulation of Rac1 was mediated by estrogen receptors since co-incubation with ICI 182.780 prevented down-regulation of Rac1. To test these observations in vivo, ovariectomized spontaneously hypertensive rats were treated with E2 or vehicle. Real-time PCR and Western blotting showed reduction of aortic Rac1 mRNA and protein by 32 and 58%, respectively. Furthermore, down-regulation of Rac1 by E2 was observed in human mononuclear cells of women with elevated E2 levels after controlled ovarian hyperstimulation. Rac1 GTPase gene-transcription and activity is regulated by 17 beta-estradiol, which may be an important molecular mechanism contributing to the cardiovascular effects of estrogens.

Angiotensin II↗

PubMed2002

Proliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemia.

Neurogenesis in the hippocampal dentate area of adult animals is stimulated by neuropathological diseases. We investigated here whether transient global cerebral ischemia in adult gerbils, which causes neurodegeneration selectively in CA1 pyramidal neurons, affects endogenous stem cells in the dentate area as well as CA1 region. The two key findings of this study are that: (1), global ischemia markedly increases neurogenesis in hippocampal subgranular zone from immature neuronal progenitor cells (betaIII-tubulin) to mature neurons (NeuN); and that (2), there is also an appearance of newly born neurons in the degenerated CA1 pyramidal cell layer, as demonstrated by immunofluorescence. These results provide evidence for an increased neurogenesis in the gerbil CA1 pyramidal cell layer four weeks following global cerebral ischemia, which could promote morphological and functional recovery after cerebral ischemia.

Animals↗

PubMed2002

Influence of serotonin-receptor antagonism on mast cell activation during endotoxemia.

INTRODUCTION: Mast cells have been implicated in the aetiology of many diseases and are particularly important in evoking leukocyte-endothelial interactions during endotoxemia. Mast cell activity can be modified by histamine. There are only little data available whether serotonin (5-HT), another amine, is involved in alterations of mast cell activity, too. The aim of the study was to investigate the effects of the 5-HT-receptor antagonists methysergide (5-HT(1/2/7)-receptor antagonist), and ketanserin (5-HT(2A)-receptor antagonist) on mesenteric mast cell activation during endotoxemia. MATERIALS AND METHODS: In male Wistar rats, mast cell activity was determined in the mesentery using intravital microscopy. Rats were randomised in four groups of 12 animals each. Animals underwent laparotomy and the mesentery was exposed beneath an in-vivo videomicroscope. After baseline measurment endotoxemia was induced by continuous intravenous infusion of 2 mg/kg/h endotoxin (ETX group). Animals in the ETX/5-HT(1/2)-ANT group received methysergide (1 mg/kg body weight), animals in the ETX/5-HT(2A)-ANT group received ketanserin (1 mg/kg body weight) additionally prior to laparotomy and to the procedure described above. Animals in saline group served as controls and received equivalent volumes of NaCl 0.9%. Activated mast cells were stained by superfusion of the mesentery with ruthenium red. RESULTS: The relative mast cell activity to baseline value increased significantly in all groups. Values of the ETX-group versus the ETX/5-HT(1/2)-ANT group, the ETX/5-HT(2A)-ANT group, and the saline group were significantly higher at 120 min. CONCLUSIONS: Serotonin receptor antagonism using the 5-HT(1/2/7)-receptor antagonist methysergide or the 5-HT(2A)-receptor antagonist ketanserin reduces endotoxin-induced mast cell activation in-vivo, most probably via the 5-HT(2A)-receptor subtype.

Journal Article↗

PubMed2002

Meckel Gruber syndrome: a first trimester diagnosis of a recurrent case.

We report of a case of Meckel Gruber Syndrome (MGS) in a woman, who suffered previously from a pregnancy with the same disorder. MGS, consisting of an occipital encephalocele, bilateral cystic kidneys and postaxial polydactyly, is a rare autosomal recessive disorder, with a recurrence risk of 25%. With the present technology, a targeted ultrasound in the late embryonic or early fetal stages of pregnancy has the potential to diagnose this syndrome. Clinical screening in further pregnancies is of utmost importance and the management of such cases is presented.

Abnormalities, Multiple↗

PubMed2002

Immunoglobulins and cytokines level in follicular fluid in relation to etiology of infertility and their relevance to IVF outcome.

OBJECTIVE: The aims of the present study were to (i) determine the presence and concentration of albumin fractions (alpha1, alpha2, beta, gamma), immunoglobulins (IgA, IgG, IgM) and cytokines [interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF)] in periovulatory ovarian follicular fluid (FF) of in vitro fertilization (IVF) patients, (ii) examine the relationship between these parameters and the etiology of infertility as well as the IVF outcome and (iii) find out if these parameters in FF could be used as a predictive factor of IVF outcome. DESIGN: The levels of albumin fractions, immunoglobulin and cytokines were measured from women who underwent IVF therapy for various indications and the results were compared between the patient groups and IVF outcome. MATERIALS AND METHODS: Follicular fluid was obtained from 160 IVF patients. A total of 79 patients underwent controlled ovarian hyperstimulations (COH) either with follicle-stimulating hormone (FSH) or HMG. Whereas, the HMG was used for the second set of patients (n=81) - after down regulation with gondotropin-releasing hormone agonists (Gn-RHa) - the protein fractions were determined using electrophoresis separation. Immunoglobulins were measured using a commercial kits and the concentration of cytokines was determined by the highly sensitive enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: The stimulation regimens used have no effect on albumin (alpha1, alpha2, beta, gamma) and immunoglobulin (IgA, IgG, IgM) concentrations, as no significant difference was observed between the two groups. Besides, no specific relationship was found between the concentration of these investigated parameter in FF and etiology of infertility or fertilization, cleavage and pregnancy rate. Besides, there were no significant differences between the groups for any cytokine investigated. Moreover, there were no correlations between the concentration of IL-6, IL-8 and GM-CSF in FF and steroid hormone concentration in the blood at the day of oocytes retrieval or IVF outcome. IN CONCLUSION: Total protein, albumin fraction, immunoglobulins and cytokines level in FF of patients undergoing COH for IVF therapy for various etiology of infertility could not be a useful parameter for predicting IVF outcome.

Adult↗

PubMed2002

Clinical and biophysical aspects of HELLP-syndrome.

OBJECTIVE: The maternal-perinatal outcome and the significance of biophysical parameters in HELPP syndrome patients were evaluated. METHODS: Sixty cases of HELLP syndrome were determined by retrospective analysis. Medical history, correlation of clinical, laboratory findings, records of fetomaternal Doppler studies, Nonstress test and maternal-perinatal outcome data were evaluated. Chi-square test was used for statistical analysis, and p < 0.05 was accepted as the significance level. RESULTS: The incidence of HELLP syndrome in our institution was 1.03%. Mean gestational age at birth was 33.2 weeks, mean birth weight was 1861 +/- 710 g and mean umbilical pH was 7.25 +/- 0.13. Neonatal thrombocytopenia was demonstrable in 38% of neonates. Patients with low antepartal platelets (< 60,000/microliter) had a significantly higher incidence of intrauterine growth retarded fetuses than patients with higher platelet counts (p = 0.002). Doppler flow measurements were performed in 33 patients (55%). In 16 (48.4%) a pathological Doppler flow was documented. Doppler findings demonstrated very high sensitivity (83%) and specificity (80%) in predicting adverse outcome in growth retarded fetuses. In 17 patients (27%) fetal heart rate monitoring had an obvious pathologic pattern. Respiratory distress syndrome (74.4%) was the main indication for NICU admission. Perinatal mortality rate was 8.3% and neonatal mortality rate was 11.6%. Maternal morbidity rate was 30%. The most commonly observed maternal complications were abruptio placentae (n = 8), disseminated intravascular coagulation (n = 3) and severe postpartal bleeding (n = 3). CONCLUSIONS: In HELLP syndrome patients it is very important to closely follow maternal vital signs and fluid intake and output, and to perform fetal status assessment tests. Of the biophysical parameters, Doppler flow measurement is an especially helpful predictor of poor perinatal outcome in growth retarded fetuses in HELLP patients. Patients with very low platelets have a significantly higher risk of intrauterine growth retarded fetuses.

Adult↗

PubMedDate not supplied

Analysis of vitamin D-receptor (VDR) and retinoid X-receptor alpha in breast cancer.

The expression of vitamin D-receptor (VDR) and retinoid X-receptor alpha (RXR-alpha) has been analysed immunohistochemically in benign (n = 62 and n = 5 respectively) and malignant (n = 228 and n = 15 respectively) breast tissue samples using a monoclonal antibody 9A7gamma against VDR and a polyclonal antibody against RXR-alpha. A recently developed immunoreactive scoring method (IRS) was employed. The expression of VDR was detected at the RNA-level using the reverse transcriptase-polymerase chain reaction. A statistically significant higher expression of VDR at the protein level was seen in breast cancer compared with benign breast tissue, whereas at the mRNA level no visible differences in the expression of VDR were found. A higher expression of RXR-alpha was seen in breast cancer compared with benign breast tissue. Our findings indicate that breast tissue may be a new target organ for therapeutically applied vitamin D and retinoid analogues. VDR and RXR-alpha are upregulated at the protein level in breast carcinomas as compared to normal breast tissue, indicating a possibly increased sensitivity to therapeutically applied vitamin D analogues. New vitamin D analogues exerting less calcemic side effects may be promising new drugs for the treatment or chemoprevention of breast carcinomas as well as of precancerous breast lesions. Combination therapies of vitamin D and retinoid analogues with fewer side effects seen promising for the treatment of breast cancer.

Antibodies↗

PubMedDate not supplied

Analysis of 25-hydroxyvitamin D3-1alpha-hydroxylase in cervical tissue.

UNLABELLED: 1,25(OH)2D3 suppresses proliferation and induces differentiation in various cell types, including epithelial cells. Recently, extrarenal activity of 1alpha-hydroxylase for 25(OH)D3 has been reported in various cell types including macrophages, keratinocytes and prostate and colon cancer cells. The aim of this study was to analyze the expression of 1alpha-hydroxylase for 25-hydroxyvitamin D3 in normal cervical samples and in cervical cancer, in order to investigate whether cervical tissue possesses the capacity to produce 1,25(OH)2D3 from 25(OH)D3, indicating that 1,25(OH)2D3 may be a locally produced hormone that controls proliferation in cervical tissue and that alterations in local production of 1,25(OH)2D3 may be involved in tumourigenesis of cervical cancer. MATERIALS AND METHODS: RNA was extracted from normal cervical tissue (n=4), cervical carcinomas (n=8) and HeLa cells using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR. RESULTS: mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in more than 50% of samples analyzed in normal cervical tissue and in cervical cancer with no visible difference between either group. mRNA of 1alpha-hydroxylase for 25-hydroxyvitamin D3 was detected in HeLa cells as well. CONCLUSION: 25(OH)D3-1alpha-hydroxylase is expressed in normal cervical tissue, in cervical cancer and in HeLa cells. Thus, normal cervical and cervical cancer cells seem to be able to synthesize 1alpha, 25(OH)2D3 that may be of significant importance for the growth control in normal and malignant cervical tissue. Normal cervical tissue and cervical cancer cells may be new targets for cancer prevention or cancer treatment with precursors of biologically active vitamin D analogues.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

PubMedDate not supplied

Vitamin D receptor (VDR) expression is not a prognostic factor in cervical cancer.

BACKGROUND: The aim of this study was to analyze whether VDR status is a prognostic factor that may be of importance for the assessment of recurrence in cervical cancer. MATERIALS AND METHODS: VDR-, Ki-67- and p53-status were analyzed immunohistochemically in cervical cancer patients (n=50) and in benign cervical tissue (n=15). The histopathological data of the tumours were evaluated. RNA was extracted from normal cervical tissue (n=4) and cervical carcinomas (n=8) using the method of Chomczynski. RNA was reverse-transcribed and RNA-levels were semiquantitatively detected by PCR. RESULTS: The expression of VDR was significantly increased in cervical cancer compared to normal cervical tissue on the protein-level but not on the RNA-level. No statistically significant correlations were found comparing VDR status with histopathological data (tumour stage, lymph node status, grading, histological tumour type), with the expression of the proliferation marker Ki-67 and of the tumour suppressor gene p53. CONCLUSION: Our findings indicate that VDR protein expression is not a prognostic factor in cervical cancer. The strong I/DR immunoreactivity that we observed in cervical cancer specimens supports the body of evidence that cervical cancer may be a target for therapeutically applied vitamin D analogues.

Adenocarcinoma↗

PubMedDate not supplied

Vitamin D receptor (VDR) expression is not a prognostic factor in breast cancer.

Breast cancer is characterized by its early haematogenous dissemination. Current modalities of risk assessment in lymph node-negative patients, to determine which patients should receive adjuvant chemotherapy, are not effective. The aim of this study was to analyze whether vitamin D receptor (VDR) status is a prognostic factor that may be of importance for the assessment of recurrence in breast cancer. VDR expression was analyzed immunohistochemically in breast cancer patients (n=228). No statistically significant correlations were found comparing VDR expression with histopathological data (tumor stage, lymph node status, grading, histological tumor type), with the expression of estrogen receptors (ER) or progesterone receptors (PR), with the proliferation marker Ki-67, with the tumor suppressor gene p53 or with the S-phase index. Our findings indicate that VDR protein expression is not a prognostic factor in breast cancer. The strong VDR immunoreactivity that we observed in breast cancer specimens supports the body of evidence that breast cancer may be a target for therapeutically applied vitamin D analogues.

Breast Neoplasms↗