T. Cordes

Universitätsklinikum Schleswig - Holstein, Kiel, Schleswig-Holstein, Germany

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Publications (49)40.46 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Zusammenfassung Die Frage, ob eine ovarielle hormonelle Stimulation mit einem erhöhten Krebsrisiko für gynäkologische Karzinome einhergeht, stellt nach wie vor eine Kontroverse dar. Es gibt Hinweise in Studien, dass Risikofaktoren im Kollektiv infertiler Frauen existieren, die zu einem erhöhten Erkrankungsrisiko für bestimmte Malignome führen. Zu diesen zählen Nulligravidität, lange Stimulationsbehandlungen von Patientinnen mit einer langen Nachbeobachtungszeit sowie häufig durchgeführte Clomifenstimulationen. Außerdem scheint eine leichte Erhöhung von Borderline-Tumorinzidenzen während ovarieller Stimulation vorzuliegen. Die Daten zum Mammakarzinom werden in den einzelnen Untersuchungen sehr heterogen angegeben, während neuere Studien zum Endometriumkarzinom bei Clomifenstimulation durchaus Hinweise auf ein erhöhtes Erkrankungsrisiko zeigen. Die Ergebnisse der einzelnen Studien müssen weiterverfolgt werden, insbesondere, da die Patientinnen, die eine ovarielle Stimulation erhalten haben, erst jetzt den malignomspezifischen Altersgipfel der Karzinomerkrankung erreichen. Es müssen weitere epidemiologische Untersuchungen durchgeführt und die Daten längerer Nachbeobachtungszeiten in laufenden Studien abgewartet werden, um hinsichtlich dieser Fragestellung eindeutigere Aussagen machen zu können.
    Gynäkologische Endokrinologie 09/2014; 5(4).
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    ABSTRACT: PURPOSE: In the GnRH-antagonist protocol, ovarian stimulation with gonadotropins typically commences on cycle day 2 or 3. Initiation of ovarian stimulation with a spontaneously occurring menstruation, however, poses significant organizational challenges for treatment centres and patients alike. It has previously been demonstrated in the context of fertility preservation that initiation of stimulation in the luteal phase is feasible in terms of retrieval of mature oocytes for cryopreservation. Herein, we report the extension of this concept to a routine IVF setting with the aim of establishing an ovarian stimulation protocol, which can be utilized independent of menstruation. Because of asynchrony of endometrium and embryo in such a setting, all fertilized oocytes have to be cryopreserved for a later transfer. METHODS: This was a prospective, case-control study (trial registration: NCT00795041) on the feasibility of starting ovarian stimulation in a GnRH-antagonist protocol in the luteal phase. Inclusion criteria were: IVF or ICSI; 18-36 years; ≤3 previous IVF/ICSI attempts; BMI 20-30 kg/m(2); regular cycle (28-35 days); luteal phase progesterone >7 ng/ml at initiation of stimulation. Exclusion criteria were: PCOS, endometriosis ≥AFS III°, unilateral ovary, expected poor response. Stimulation was performed with highly purified uFSH (Bravelle(®)) 300 IU/day and 0.25 mg/day GnRH-antagonist starting on cycle day 19-21 of a spontaneous menstrual cycle and commencing until hCG administration when three follicles ≥17 mm were present. All 2PN stage oocytes were vitrified for later transfers in programmed cycles. Feasibility was defined as the achievement of ongoing pregnancies progressing beyond the 12th gestational week in at least 2/10 study subjects (primary outcome). Secondary outcomes were gonadotropin consumption per oocyte obtained, stimulation duration, and fertilization rates. Study subjects were matched in a 1:3 ratio with concomitantly treated control cases of similar age, BMI, and duration of infertility who were treated in a conventional GnRH-antagonist protocol with 150-225 rFSH or HP-HMG/day. RESULTS: The study group consisted of ten subjects, mean age 31.4 years, BMI 25.4 kg/m(2), of which one had fertilization failure. Mean stimulation duration was 11.7 (SD 1.6) vs. 9.1 (SD 1.3) days, mean cumulative FSH dose was 3,495.0 (SD 447.5) vs. 2,040.5 (SD 576.2) IU, and mean number of oocytes was 8.8 (SD 5.0) vs. 10.0 (SD 5.4) in study vs. control group, respectively. Per follicle ≥10 mm, the cumulative FSH dose was 274.5 (SD 130.8) IU vs. 245.2 (SD 232.3) IU in study and control groups, respectively. Cumulative ongoing pregnancy rates were 1/10 (10 %) and 6/30 (20.0 %) in study and control group, respectively (difference: 10 %, 95 % confidence interval of the difference: -29.2-22.2 %, p = 0.47). Fertilization rate was similar between groups, with 63.5 % (SD 32.9) in the study and 61.3 % (SD 26.7) in the control group, respectively. Serum estradiol levels were significantly lower on the day of triggering final oocyte maturation with 1,005.3 (SD 336.2) vs. 1,977.4 pg/ml (SD 1,106.5) in study and control group, respectively. Similarly, peak estradiol biosynthesis per growing follicle ≥10 mm was lower in the study group (134 pg/ml, SD 158.4 vs. 186.7 pg/ml, SD 84.7). CONCLUSIONS: Per retrieved oocyte, a nearly threefold higher dose of FSH had to be administered when ovarian stimulation had been initiated in the luteal phase. Furthermore, the present study casts doubt on the efficacy of initiating ovarian stimulation in the luteal phase in terms of pregnancy achievement. Thus, this concept is currently not feasible for routine use, and it should also be explored further before using it at larger scale in the context of emergency stimulation for fertility preservation.
    Archives of Gynecology 04/2013; · 0.91 Impact Factor
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    ABSTRACT: Seit der Geburt des ersten Kindes nach IVF-Therapie im Jahr 1978 hat die Reproduktionsmedizin rasante Fortschritte in den Behandlungsmöglichkeiten von Kinderwunschpaaren gemacht. Zuletzt wurden in Deutschland 75.928 ART-Behandlungen mittels IVF/ICSI dokumentiert mit einer klinischen Schwangerschaftsrate von 28,69%. Obwohl die Methoden der ART kontinuierlich verbessert werden, bleiben Risiken der Behandlung, wie das Überstimulationssyndrom, Komplikationen bei der Eizellentnahme, das Mehrlingsrisiko und eine erhöhte kindliche Fehlbildungsrate, bestehen. Paaren mit der Anlageträgerschaft einer schweren genetischen Erkrankung steht nun auch in Deutschland an ausgewählten Zentren und nach einem positiven Ethikvotum die Möglichkeit einer Präimplantationsdiagnostik zur Verfügung, um die psychischen und physischen Belastungen einer ,,Schwangerschaften auf Probe“ zu vermeiden.
    Der Gynäkologe 01/2013; 46(1).
  • Dr. T. Cordes, K. Diedrich
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    ABSTRACT: Durch die heutzutage deutlich effektivere Therapie von Krebserkrankungen junger Patientinnen und Patienten und die glücklicherweise deutlich gestiegenen Überlebensraten rücken Themen wie der Fertilitätserhalt vor Beginn einer Chemo- oder Strahlentherapie in den Vordergrund. Über die mögliche Nebenwirkung Sterilität müssen die Patienten vor der Behandlung aufgeklärt werden. Da viele junge Patienten in der internistischen Onkologie behandelt werden, ist eine Plattform zur Information und Aufklärung für die Beratung essenziell. In diesem Zusammenhang sind die behandelnden Frauenärzte eine wichtige Instanz, um betroffene Patientinnen, ggf. auch deren Partner, über Therapien und die Möglichkeit des Fertilitätserhaltes zu informieren. So kann der Kontakt zum nächsten beratenden Kinderwunschzentrum hergestellt werden und der Patientin eine sofortige Beratung bei noch nicht abgeschlossenem Kinderwunsch angeboten werden. Ein Gespräch über diese belastende Situation und die vorhersehbaren iatrogen hervorgerufenen Folgeerscheinungen sollte daher mit einer der Patientin nahestehenden Person erfolgen. Optionen vor geplanter zytotoxischer Therapie sind neben den konventionellen reproduktionsmedizinischen Techniken die Gabe von GnRH-Analoga die Oozytenkryokonservierung, die Kryokonservierung von Ovarialgewebe und die In-vitro-Maturation. Der teils noch sehr experimentelle Charakter einzelner Maßnahmen ist bei der individuellen Nutzen-Risiko-Abwägung zu berücksichtigen.
    Der Gynäkologe 12/2012; 45(12).
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    ABSTRACT: The anticarcinogenic potential of vitamin D is attributed to antiproliferative and prodifferentiative effects on cells for a wide variety of carcinomas. The biological effects of 1,25(OH)(2)D (calcitriol) are mediated through a soluble receptor protein termed vitamin D receptor (VDR). However, thus far there have been no studies evaluating the association between VDR expression and vulvar cancer. Using immunohistochemical analysis, VDR expression was evaluated separately in the nucleus, cytoplasm and membrane, in vulvar cancer samples and adjacent non-pathological vulvar tissue from 48 squamous cell carcinoma patients with no prior therapy, and the association between VDR and overall survival was investigated. Overall, among the 48 vulvar cancer cases, nuclear and cytoplasmic VDR expression was present in 47 (97.9%) and 23 (47.9%) cases respectively. The median nuclear VDR expression was significantly higher as compared to the cytoplasmic VDR in the vulvar cancer tissue. No significant correlation between VDR values and the age of the patients was detected. Nuclear and cytoplasmatic VDR in the vulvar cancer tissue were also compared according to the tumor size, and no significant association between mean tumor VDR and tumor size was detected. There was no association between cytoplasmatic VDR expression and OS, but better OS was observed in patients with reduced nuclear VDR expression as compared to those with high VDR expression. VDR may be considered as a useful pathological marker.
    Anticancer research 01/2012; 32(1):283-9. · 1.71 Impact Factor
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    ABSTRACT: Vitamin D and its active form calcitriol have multiple effects in cancer cells, such as anti-proliferative effects, induction of apoptosis and cell cycle arrest. There is a link between vitamin D metabolism and inflammatory processes, which should be considered in cancer therapy. An association between these two types of metabolism is also observed in breast and ovarian cancer. These inflammatory processes are based on an increase of cyclooxygenase-2 (COX-2) activity. The current study aimed to evaluate the expression of prostaglandin-metabolising enzymes COX-2 and 15-hydroxyprostaglandin-dehydrogenase (15-PGDH) along with the vitamin D receptor (VDR) in benign and malignant breast and ovarian tissues. VDR, COX-2, 15-PGDH and prostanoid receptor E2/E4 expression were measured in tissues by western blot analysis. Additionally, plasma 25(OH)(2)D(3) and PGE(2) levels were measured in healthy patients and cancer patients. We detected an elevated COX-2 and inversely a lowered VDR expression in cancer patients compared to healthy women. Breast cancer patients diagnosed during wintertime had a significantly lower serum level of 25(OH)(2)D(3); PGE(2) serum levels were higher in both types of cancer. These results support the idea of a link between prostaglandin and vitamin D metabolism in regards to their influences on breast and ovarian cancer.
    Anticancer research 01/2012; 32(1):351-7. · 1.71 Impact Factor
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    ABSTRACT: Cyclooxygenase-2 (COX-2) is a potential molecular prognostic factor for breast cancer, and calcitriol [1,25(OH)(2)D(3)], the biologically active form of vitamin D, is a promising target in breast cancer therapy. The influence of calcitriol on the proliferation and the effects of calcitriol on the expression of prostaglandin- and vitamin D-metabolising enzymes were examined in benign and malignant breast cells. Calcitriol inhibited the proliferation of MCF-10F and MCF-7 cells but not of invasive MDA-MB-231 cells and reduced the expression of COX-2 and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the benign breast cell line MCF-10F. Furthermore, dysregulation in vitamin D-metabolising proteins was detected, especially in MDA-MB-231 cells. These results suggest dysregulation of vitamin D metabolism and a lack of a possible influence of calcitriol on the metabolism of prostaglandins in the malignant breast cell lines.
    Anticancer research 01/2012; 32(1):359-65. · 1.71 Impact Factor
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    ABSTRACT: Cyclooxygenase-2 (COX-2) plays a crucial role in prognosis of malignancy and has been associated with carcinogenesis, particularly neoangiogenesis and tumor progression. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumour suppressor in cancer. The antiproliferative effects of calcitriol [1,25(OH)(2)D(3)] mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. The expression of prostaglandin (PG)-metabolizing enzymes, vitamin D-metabolising enzymes and VDR were determined in benign and malignant breast cell lines using western blot analysis. We detected an inverse correlation between the two types of metabolism, a reduced VDR expression in the malignant breast cell lines, and therefore an insufficient induction of 24-hydroxylase in the malignant cells. We suggest the possibility of dysregulation of vitamin D-metabolizing enzymes in malignant breast cell lines.
    Anticancer research 01/2012; 32(1):367-72. · 1.71 Impact Factor
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    ABSTRACT: The anticarcinogenic potential of vitamin D 25(OH)D has been attributed to the inhibition of proliferation of cells from different carcinomas. Reduced serum levels of 25(OH)D are associated with an increased incidence of various types of cancer. The influence of serum 25(OH)D on the incidence and outcome of patients with vulvar cancer is unknown. The serum 25(OH)D levels in 24 patients with vulvar cancer and 24 age-matched cancer-free patients was investigated. The blood samples were collected between October 2009 and September 2010 and time of blood collection of each patient and control was matched to avoid seasonal variations between the pairs. The median 25(OH)D serum levels in the under 50 year old group of patients were significantly lower in the vulvar cancer group than the controls. The younger cancer group also had an age-related trend of lower median serum level than the older population. In the control population the trend was vice versa, yet this finding was not statistically significant. Serum 25(OH)D has a possible role in the pathogenesis and progression of vulvar cancer, but further investigations of the association of vitamin D and vulvar cancer as well as regarding its influence on patient survival and quality of life are warranted in the future.
    Anticancer research 01/2012; 32(1):265-70. · 1.71 Impact Factor
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    ABSTRACT: The vitamin D metabolizing enzymes 25-, 1α- and 24-hydroxylase are expressed in malignant cells of the cervix and the ovaries. The aim of this study was to obtain further information about the regulation of the aforementioned enzymes by vitamin D, calcidiol and calcitriol in cervical and ovarian cancer. The human cervical adenocarcinoma cell line HeLa and the human ovarian adenocarcinoma cell line OVCAR-3 were incubated with vitamin D, calcidiol and calcitriol. The influence of vitamin D and its metabolites on the expression of 25-, 1α- and 24-hydroxylase was assessed by real-time RT-PCR. Calcitriol significantly increased the 24-hydroxylase mRNA levels in HeLa and OVCAR-3 cells. The expression of 25- and 1α-hydroxylase was not regulated in a statistically significant manner. These results suggest that in HeLa as well as OVCAR-3 cell lines, the metabolism of vitamin D is regulated via the expression of the catabolizing 24-hydroxylase.
    Anticancer research 11/2010; 30(11):4429-34. · 1.71 Impact Factor
  • Fertility and sterility 09/2010; 94(4):e70; author reply e71-2. · 3.97 Impact Factor
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    ABSTRACT: Die Kinderwunschbehandlung mit der kontrollierten, ovariellen Überstimulation mit Gonadotropinen und GnRH-Analoga ist durch den sog. Lutealphasendefekt gekennzeichnet. Dieser kann durch eine Lutealphasenunterstützung (Lutealphasensupport, LPS) behandelt werden. Der Goldstandard ist eine Unterstützung mit vaginalem oder intramuskulärem Progesteron oder aber auch die Gabe von humanem Choriongonadotropin, wobei das vaginale Progesteron aufgrund der Anwenderfreundlichkeit und des geringeren Risikos von Überstimulationssyndromen von Patientinnen und Behandelnden bevorzugt wird. Die Applikation wird üblicherweise spätestens zum Zeitpunkt des Embryotransfers begonnen, und die Dauer der Anwendung sollte zumindest bis zum Schwangerschaftstest erfolgen. In den meisten Zentren wird die Progesteronverabreichung bei Schwangerschaft bis zum sonographischen Nachweis einer intakten intrauterinen Schwangerschaft ausgedehnt. Die zusätzliche Gabe von Östrogenen, Kortikoiden, ASS oder Heparin zeigt keinen evidenten Vorteil bei der LPS. Controlled ovarian stimulation with gonadotrophins and GnRH analogues causes a luteal phase defect. Support of the luteal phase (LPS) is an integral part of IVF treatment cycles. There is consensus that LPS with progesterone or hCG is mandatory in IVF cycles. Vaginal progesterone is commonly used because of the convenience and a lower risk of ovarian hyperstimulation syndrome. LPS is commonly started on the day of embryo transfer and continued until either the day of pregnancy test or until evidence of heart beat on sonography in the case of pregnancy (6–7weeks of pregnancy). There is no evidence that an addition of estrogens, aspirin, steroids, or heparin will improve pregnancy rates. SchlüsselwörterLutealphasenunterstützung-Progesteron-Adjuvante Therapie-Schwangerschaftsraten-IVF KeywordsLuteal phase support-Progesterone-Adjuvant therapy-Pregnancy rate-IVF
    Gynäkologische Endokrinologie 05/2010; 8(2):117-123.
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    ABSTRACT: In der täglichen Praxis wird dem behandelnden Arzt häufig die Frage nach einem möglicherweise erhöhten Risiko für gynäkologische Malignomerkrankungen nach Kinderwunschbehandlung mit hormoneller Stimulation gestellt. Die Datenlage zeigt Faktoren, die eine Tendenz für ein erhöhtes Erkrankungsrisiko erkennen lassen: Bekannt ist, dass eine Sterilitätsanamnese per se mit einem erhöhten Endometrium- und Ovarialkarzinomrisiko einhergeht, weitere Faktoren für das Endometriumkarzinom sind Nulligravidität und lange Clomifenstimulationen. Bei Kinderwunschpatientinnen scheint eine leicht erhöhte Inzidenz von Borderline-Tumoren des Ovars nach hormoneller Stimulation vorzuliegen, für das Ovarialkarzinom trifft dieses nach aktueller Studienlage nicht zu. Die Daten zum Mammakarzinom sind sehr heterogen, eine Erhöhung des Risikos liegt nach einigen Subgruppenanalysen vor, insgesamt scheint es nach derzeitigem Kenntnisstand jedoch nicht erhöht zu sein. Eine längere Nachbeobachtungszeit muss abgewartet werden, insbesondere bei Patientinnen nach ovarieller Stimulation, da erst in kommenden Jahren die Erkrankungsgipfel der Karzinome bei den Studienteilnehmern erreicht werden. Weitere epidemiologische retrospektive Analysen von verfügbaren Daten sollten in den einzelnen IVF-Registern der Länder durchgeführt werden, um die Erkenntnisse zu untermauern. In daily practice there are frequently indications of a possibly higher risk of gynecologic malignoma following pregnancy treatment with hormonal stimulation. The data indicate a tendency to higher risk of such disease. It is known that a sterility anamnesis correlates to higher risk of endometrial and ovarian cancer. Other factors for endometrial cancer include infertility and long-term clomifen stimulation. For patients wishing pregnancy the incidence of borderline ovarian tumors appears slightly higher following hormonal stimulation. Current studies indicate that this does not apply to ovarian cancer. Data concerning breast cancer are strongly heterogeneous and show increased risk in some subgroup analyses, but at the present this appears to be unproven. Longer observation periods are needed, especially after ovarian stimulation, because the carcinomic disease peak of the study participants will be reached some years from now. More retrospective epidemiologic analyses of the available data should be carried out in national in-vitro-fertilization registers to substantiate present knowledge. SchlüsselwörterKrebs-Assistierte Reproduktion-Clomifen-In-vitro-Fertilisierung KeywordsCancer-Assisted reproduction-Clomifen-In-vitro fertilization
    Der Gynäkologe 01/2010; 43(4):335-340.
  • Gynakologe. 01/2010; 43(4):335-340.
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    ABSTRACT: It is known that 1,25(OH)2D3 can be metabolized to 1,24(OH)2D3 in breast tissue. This tissue-specific expression of 24-OHase may act as a pivotal link between vitamin D status (25(OH)D3 level) and the anticancer effects of 1,25(OH)2D3. Different expressions of the enzymes of vitamin D metabolism are found in breast cancer cells and tissues, and alternative splicing may play a role in biological functions and may cause tissue-specific variations. We describe the expression of vitamin D-1alpha-hydroxylase and vitamin D-24-hydroxylase in benign and malign breast tissues. We estimated that alternative splicing of the enzymes would lead to a catalytically dysfunctional product and may lead to a lower reduction of the target protein. Expression of 1alpha-OHase and 24-OHase RNA and protein was assessed using a real-time polymerase chain reaction (RT-PCR) and on protein level by Western blot in benign and malign breast tissue samples. In breast cancer tissue the expression of 1alpha-OHase and 24-OHase were reduced significantly compared to benign breast tissue. The results described above do not support results of previous studies. Alternative splicing of 1alpha-OHase and 24-OHase may regulate the levels of active enzyme but is more likely due to different cell types in samples with the result of testing a variety of tissue samples not purified benign and malign breast cancer cells. The significance of smaller variants in cells has not been clarified either, but it is known that they are not able to use 25(OH)D3 as a substrate to generate 1,25(OH),D3.
    European journal of gynaecological oncology 01/2010; 31(2):151-5. · 0.58 Impact Factor
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    ABSTRACT: Calcitriol is judged to have a positive effect on control of the immune system, cell growth and differentiation and therefore, the prevention of cancer genesis. The aim of this study was to detect any possible differences in the 25-hydroxyvitamin D-1alpha-hydroxylase (1alphaOHase)-expression between benign and malignant ovarian tissue and cell lines. The analysis was conducted quantitatively, by means of nested "touchdown" PCR and Western blot, and qualitatively, with the use of real-time PCR and Western blot. The gene structure was sequenced. Compared to the benign cell line, the malignant cell lines showed a significantly higher expression of 1alphaOHase at the RNA level. A statistically lower expression of the 1alphaOHase protein was found in the malignant tissue. In the malignant cell lines and tissues, divergent bands were detected, which led to various splice variants on sequencing. Their increased expression in malignancy is possibly bound to the reduction of enzyme activity, which may lead to the genesis of ovarian cancer. In the future, preventive and therapeutic activities may result from these findings.
    Anticancer research 10/2009; 29(9):3627-33. · 1.71 Impact Factor
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    ABSTRACT: Prostaglandins (PGs) within the periovulatory follicle are essential for various female reproductive functions such as follicular development and maturation. In animal models, granulosa cells express the PG synthesizing enzyme cyclooxygenase-2 (COX-2) and the PG inactivating enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH). First references suggest a correlation between vitamin D and prostaglandin metabolism through the impact of 1,25(OH)2D3 (calcitriol) on the expression of COX-2 and 15-PGDH. The expression of COX-2, 15-PGDH and the vitamin D receptor (VDR) in human granulosa cells (COV434, hGC and HGL5), which were originally isolated from different stages of follicular maturation, was determined by real-time PCR (RT-PCR) and Western blot analysis. A positive correlation of COX-2 and VDR protein was found in the COV434 and HGL5 cells and an inverse correlation of 15-PGDH and VDR protein levels in all the investigated cell types. There may be a link between VDR, associated target genes and prostaglandin metabolism in human follicular maturation and luteolysis.
    Anticancer research 10/2009; 29(9):3611-8. · 1.71 Impact Factor
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    ABSTRACT: Calcitriol (1,25-dihydroxyvitamin D3, 1,25(OH)2D3) plays a pivotal role in maintaining calcium and phosphate homeostasis. Aside from that, it supports the native and attenuates the acquired immune system and has positive effects on cell growth, differentiation and the prevention of carcinogenesis. The goal of this study was to detect possible differences in the expression of the calcitriol-degrading enzyme 24-hydroxylase (24-OHase) between malignant and benign ovarian cell lines and tissue. The analyses were based on real-time PCR, nested touchdown PCR and Western blot. When compared to benign granulose GLZ cells, the malignant HGL5 cells showed a significantly higher 24-OHase expression at the protein level (p<0.01). In the malignant ovarian tissue, the expression was significantly higher in RNA (p<0.001), but lower at the protein level (p<0.01). An increased 24-OHase expression could indicate a decrease in available calcitriol.
    Anticancer research 10/2009; 29(9):3635-9. · 1.71 Impact Factor
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    ABSTRACT: Tissue-specific expression of 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) and vitamin D-hydroxylase (24-OHase) may act as the pivotal link between 25-hydroxyvitamin D3 (25(OH)D3) serum levels and the anticancer effects of 1,25-dihydoxyvitamin D3 (1,25(OH)2D3) and alternative splicing of the enzymes may regulate their biological function. The expression of 24-OHase in cells and breast tissue was investigated and its splice variants were detected. The expression of 24-OHase RNA and protein was assessed by RT-PCR followed by Western blot. The expression of 24-OHase was reduced by about 57% in MCF-7 breast cancer cells, compared to MCF-10F benign breast cells. In the Western blot, a signal at 56 kDa was found and further bands were detected at 42 and 44 kDa. In the breast cancer tissue, the expression of 24-OHase was reduced by about 58% compared to benign tissue. However, in the Western blot, only one signal was found in the benign tissue at 56 kDa, while in malignant tissue, a further band was detected at 40 kDa. Alternative splicing of 24-OHase may lead to a catalytically dysfunctional enzyme and may lead to less reduction of the target protein.
    Anticancer research 10/2009; 29(9):3641-5. · 1.71 Impact Factor
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    ABSTRACT: The antiproliferative effects of calcitriol (1,25(OH)2D3) mediated via the vitamin D receptor (VDR), render the biologically active form of vitamin D a promising target in breast cancer therapy. Furthermore, breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression, the prostaglandin E2 (PGE2) synthesizing enzyme. The PGE2 metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumor suppressor in cancer. First references suggest a correlation between vitamin D and prostaglandin metabolism through the impact of 1,25(OH)2D3 on the expression of COX-2 and 15-PGDH. The expression of VDR, COX-2 and 15-PGDH in benign MCF-10F and malignant MCF-7 breast cells was determined by real-time PCR (RT-PCR) and Western blot analysis. Although the RT-PCR data were divergent from those obtained from the Western blot analysis, the COX-2 protein expression was MCF-7 2-fold higher in the MCF-7 compared to the MCF-10F cells. Moreover, a correlation of 15-PGDH to VDR by RT-PCR was found in both cell lines. The VDR protein levels were inversely correlated to the 15-PGDH protein levels and revealed that the MCF-10F cells had the highest VDR expression. A possible link between VDR-associated target genes and prostaglandin metabolism is suggested.
    Anticancer research 10/2009; 29(9):3619-25. · 1.71 Impact Factor

Publication Stats

106 Citations
40.46 Total Impact Points

Institutions

  • 2005–2014
    • Universitätsklinikum Schleswig - Holstein
      • • Klinik für Gynäkologie und Geburtshilfe (Kiel)
      • • Sektion für Gynäkologische Endokrinologie und Reproduktionsmedizin (Lübeck)
      Kiel, Schleswig-Holstein, Germany
  • 2012
    • HELIOS Klinikum Krefeld
      Crefeld, North Rhine-Westphalia, Germany
  • 2006–2012
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
  • 2009
    • Caritas Klinikum Saarbrücken
      Saarbrücken, Saarland, Germany