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ABSTRACT: OBJECTIVE: To study altered hemopexin concentrations in peritoneal fluid (PF) samples from patients with endometriosis. Recent data implicate a role of altered iron metabolism in endometriosis patients. Hemopexin is the major transport protein for heme. Like iron, heme exposure to the epithelial surface can provoke oxidative stress on the peritoneal epithelium. Therefore, altered hemopexin concentrations and heme scavenging in PF might play a role in the pathophysiology of endometriosis. DESIGN: Prospective explorative study. SETTING: Academic tertiary care center. PATIENT(S): Eighty symptomatic patients scheduled for laparoscopy for the diagnosis and/or therapy of endometriosis. INTERVENTION(S): Aspiration of PF samples during laparoscopy. MAIN OUTCOME MEASURE(S): Hemopexin and heme concentration in PF. RESULT(S): At laparoscopy, 47 of 80 (58.8%) patients exhibited endometriosis, and 33 (41.2%) were proven disease-free (CO). By means of ELISA significantly lower concentrations of hemopexin in the samples from patients with endometriosis (endometriosis 0.377 ± 0.16 mg/mL) compared with controls (disease-free 0.479 ± 0.20 mg/mL) could be demonstrated. Heme levels in the samples were not significantly different between groups (endometriosis 9.130 ± 6.124 μM and disease-free 9.990 ± 4.485 μM). There was no significant correlation between heme and hemopexin levels (Pearson's correlation coefficient r = -0.146). Demographic data between the groups were comparable. CONCLUSION(S): These data provide further evidence that hemopexin is significantly down-regulated in PF samples from patients with endometriosis compared with controls. This study confirms recent findings in two-dimensional gel electrophoresis demonstrating a down-regulation of hemopexin in PF from patients with endometriosis in a larger series of samples.
Fertility and sterility 06/2013; · 3.97 Impact Factor
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Dirk O Bauerschlag,
Felix Hilpert,
Werner Meier,
Jörn Rau,
Ivo Meinhold-Heerlein, Nicolai Maass,
Andreas Dubois,
Jalid Sehouli,
Norbert Arnold,
Christian Schem,
Hans-Heinrich Oberg,
Klaus Baumann
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ABSTRACT: In ovarian cancer, new therapeutic strategies are needed because the vast majority of patients develop a recurrence and resistance to platinum derivates. Attached to the AGO-OVAR2.11 study investigating the multityrosine kinase inhibitor sunitinib in recurrent platinum refractory ovarian cancers, this translational research project assesses the potential value of serum vascular endothelial growth factor (VEGF), soluble VEGF receptor-3 (sVEGFR-3), and angiopoietin-2 (Ang-2) levels for progression-free survival (PFS).
Longitudinal serum samples were taken while the patient was on study drugs. Serum concentration of VEGF, sVEGFR-3, and Ang-2 was determined by ELISA. The slope of the markers was correlated to the PFS.
Patients showing a decrease in VEGF concentration had a median PFS of 10.5 months [confidence interval (CI), 2.89-12.25] compared to 2.9 months (CI, 1.48-5.32) in the case of an increase (P = .17). The stratified log-rank test showed a trend for longer PFS if a decrease of Ang-2 was observed (P = .089). Dichotomized in absolute decrease or increase, the PFS was 8.4 months (CI, 2.89-12.26) versus 2.7 months (CI, 1.05-5.32), respectively. Patients with a reduction of the sVEGFR-3 concentration had a median PFS of 4.76 months (CI 2.86-10.65) versus 8.61 months (CI, 1.05-not estimable) in patients with an increase of sVEGFR-3. This observation was statistically not significant in the log-rank test (P = .81).
Ang-2 could potentially identify a patient population that might have a better PFS when under anti-angiogenic treatment, like the tyrosine kinase inhibitor sunitinib.
Translational oncology 06/2013; 6(3):305-10. · 3.40 Impact Factor
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Dirk Bauerschlag,
Karen Bräutigam,
Roland Moll,
Jalid Sehouli,
Alexander Mustea,
Darius Salehin,
Maryla Krajewska,
John C Reed, Nicolai Maass,
Garret M Hampton,
Ivo Meinhold-Heerlein
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ABSTRACT: PURPOSE: Cancer of the ovary confers the worst prognosis among women with gynecological malignancies, primarily because most ovarian cancers are diagnosed at late stage. Hence, there is a substantial need to develop new diagnostic biomarkers to enable detection of ovarian cancer at earlier stages, which would confer better prognosis. In addition, the identification of druggable targets is of substantial interest to find new therapeutic strategies for ovarian cancer. METHODS: The expression of 22,500 genes in a series of 67 serous papillary carcinomas was compared with 9 crudely enriched normal ovarian tissue samples by RNA hybridization on oligonucleotide microarrays. Multiple genes with near-uniformly expression were elevated in carcinomas of varying grade and malignant potential, including several previously described genes (e.g., MUC-1, CD9, CD24, claudin 3, and mesothelin). We performed immunohistochemical staining with antibodies against several of the proteins encoded by differentially expressed genes in an independent cohort of 71 cases of paraffin-embedded ovarian cancer samples. RESULTS: We found striking differences in EpCAM (p < 0.005), CD9 (p < 0.001), MUC-1 (p < 0.001), and claudin 3 proteins (p < 0.001) but not for mesothelin (p > 0.05) using the Mann-Whitney U test. CONCLUSIONS: Protein expression of a majority of the differentially expressed genes tested was found to be elevated in ovarian carcinomas and, as such, define potential new biomarkers or targets.
Journal of Cancer Research and Clinical Oncology 10/2012; · 2.56 Impact Factor
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Inke Lühr,
Andreas Friedl,
Thorsten Overath,
Andreas Tholey,
Thomas Kunze,
Felix Hilpert,
Susanne Sebens,
Norbert Arnold,
Frank Rösel,
Hans-Heinrich Oberg, Nicolai Maass,
Christoph Mundhenke,
Walter Jonat,
Maret Bauer
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ABSTRACT: Stromal factors play a critical role in the development of the mammary gland. Using a three dimensional-coculture model we demonstrate a significant role for stromal fibroblasts in the regulation of normal mammary epithelial morphogenesis and the control of tumor growth. Both soluble factors secreted by fibroblasts and fibroblast-derived modifications of the matrix compliance contribute to the regulation of epithelial cell morphogenesis. Readjustment of matrix tension by fibroblasts can even induce a phenotypic reversion of breast carcinoma cells. These data offer a basis to develop new strategies for the normalization of the tumor stroma as an innovative target in cancer therapy.
Cancer letters 07/2012; 325(2):175-88. · 4.86 Impact Factor
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ABSTRACT: Primary pulmonary choriocarcinoma is a rare disease with only 31 reported cases in the literature so far. Here, we summarize all published cases, including a recent case of our own clinic. Patients usually presented with symptoms like dyspnea, cough, chest pain, weight loss or hemoptysis. In some cases, the nodule in the lung was found in a routine check-up in asymptomatic patients. In the present case, the patient presented to our clinic because of a positive urine pregnancy test despite taking oral contraceptives. Patients in the analyzed cases were either treated with surgery, chemotherapy, radiotherapy or best supportive care. In the present case, a complete resection of the tumor was possible and the patient has not had any signs of recurrence so far. When looking at the published cases and corresponding outcomes, a slight tendency toward a complete resection followed by chemotherapy or close follow-up examinations seems to give the patients the best survival chances. Nevertheless, the overall prognosis of primary pulmonary choriocarinoma is poor and the 5-year survival rate is below 5%.
Gynecologic and Obstetric Investigation 06/2012; 74(2):171-6. · 1.28 Impact Factor
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ABSTRACT: To address the question of whether the high levels of oxidative modified low-density lipoproteins (oxLDL) in pregnancy are opposed by an appropriate humoral autoimmune response providing anti-oxLDL autoantibodies in maternal serum of healthy women throughout gestation.
Blood was taken from 33 patients at four different time points from early to late gestation and post-partum. OxLDL and anti-oxLDL concentrations were measured by enzyme-linked immunosorbent assays. ANOVA was used for statistical evaluations followed by post hoc test with Bonferoni adjustment.
Oxidized Low Density Lipoprotein concentrations increased while anti-oxLDL levels decreased significantly from early to late gestation. OxLDL was strongly positively correlated with LDL concentration and mildly negatively associated with anti-oxLDL levels. Estimating the status of oxidation by calculating oxLDL/LDL ratio revealed decreasing values with ongoing pregnancy. Multivariate analysis showed that anti-oxLDL levels were dependent on gestational age but neither on oxLDL levels nor on the oxLDL/LDL ratio.
The results indicate that normal pregnancy is a well-balanced state of oxidative and anti-oxidative processes. However, we could not confirm a dependence of anti-oxLDL autoantibodies on oxLDL concentration. Whether or not the humoral immune system is involved in oxidative defence remains to be elucidated.
American Journal Of Reproductive Immunology 05/2012; 68(4):345-52. · 2.17 Impact Factor
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ABSTRACT: Small for gestational age neonates (SGA) could be subdivided into two groups according to the underlying causes leading to low birth weight. Intrauterine growth restriction (IUGR) is a pathologic condition with diminished growth velocity and fetal compromised well-being, while non-growth restricted SGA neonates are constitutionally (genetically determined) small. Antenatal sonographic measurements are used to differentiate these two subgroups. Maternal metabolic changes contribute to the pathogenesis of IUGR. A disturbed lipid metabolism and cholesterol supply might affect the fetus, with consequences for fetal programming of cardiovascular diseases. We evaluated fetal serum lipids and hypothesized a more atherogenic lipoprotein profile in IUGR fetuses.
Umbilical cord serum lipids and oxidative modified, low-density lipoprotein (oxLDL) concentrations were measured by colorimetric enzymatic measurements, or by ELISA. Values of IUGR (n=36) and constitutionally small for gestational age neonates (SGA, n=22) were compared with those of healthy, adequate for gestational age, born neonates (CN, n=97). SAS-statistic software was used and two-way ANOVA was adjusted for gestational age at delivery.
Fetal high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) concentrations were found to be lower in the IUGR compared to the CN and SGA groups (HDL-C: P<0.001, TC: P<0.01). Atherogenic indices, including the oxLDL/LDL-C ratio, were increased in the IUGR compared to the CN group (oxLDL/LDL-C ratio: P<0.001).
Our results support the hypothesis of a disturbed cholesterol supply in IUGR fetuses. Born SGA has been shown to be a risk factor for developing cardiovascular disease later in life. Since HDL-C has anti-inflammatory properties, a reduced HDL-C during fetal development, and an increase in atherogenic indices, might provide a link to this observation in IUGR fetuses.
Journal of Perinatal Medicine 01/2012; 40(3):287-96. · 1.70 Impact Factor
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ABSTRACT: Objective. Case report of a 35-year-old gravida 3, para 2, at 40 + 6 weeks with massive respiratory dysfunction with need of oxygenation, requiring cesarean section. Case Report. Postpartum investigations revealed pathological cardiomegaly with left ventricular failure (NYHAIV). Cardiac biopsy diagnosed postpartum dilatative cardiomyopathy. Despite medication with bromocriptine and levosimendan, cardiac function continued to decrease, requiring surgical intervention and implantation of an intracorporal, left ventricular assist device. Following surgery, cardiac function progressively improved and stabilized. Objective. Peripartum cardiomyopathy (PPCM) is a rare, pregnancy-induced disease and requires an interdisciplinary approach for diagnostics and therapeutical treatment.
Hypertension in Pregnancy 01/2012; 31(4):451-3. · 1.69 Impact Factor
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ABSTRACT: Endometriosis is a common gynaecological disease with clinical symptoms such as chronic pain, infertility and intra-abdominal adhesions. Different theories on the pathogenesis of endometriosis and especially its aggressive subtype with infiltrative growth have been discussed. The objective of this study is to evaluate differences in proliferation and invasive properties of invasive colorectal endometriosis, superficial peritoneal endometriosis and endometrial carcinoma (G1 and G2).
Paraffin embedded tissues of peritoneal endometriosis, endometriosis of the intestine and endometrial carcinoma from 97 patients were stained immunohistochemically to assess differences in expression patterns of matrix metalloproteinases (MMP-2, MMP-9) as markers of invasion and the marker of proliferation PCNA. MMP expression was evaluated using the Immuno Reactive Score (IRS) (combining positive cell ratio and staining intensity) and PCNA expression was assessed as the percentage of positively stained cells in representative areas.
MMP-2, MMP-9 and PCNA showed differential expression patterns in the different tissues examined. MMP-2 and PCNA expression was stronger in invasive colorectal endometriosis than in superficial peritoneal endometriosis (p=0.0394). MMP-9, however, was more frequently expressed in peritoneal endometriosis (59.1%) than in colorectal endometriosis (44.4%). This result did not reach statistical significance. When colorectal endometriosis was compared to low grade endometrial carcinoma, proliferation detected by PCNA was significantly higher in endometriosis (p=0.0008). MMP-2 and MMP-9 showed higher expression in endometrial carcinoma than in endometriosis.
There are obvious differences in expression patterns of MMP-2, MMP-9 and PCNA in different stages of endometriosis and in endometrial cancer. These markers can be helpful to evaluate aggressiveness and invasiveness of endometriosis in different localizations. The results obtained could be of relevance for a better understanding of the pathogenesis of endometriosis and the development of an individual therapy concept.
European journal of obstetrics, gynecology, and reproductive biology 11/2011; 160(1):74-8. · 1.97 Impact Factor
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Gunter von Minckwitz,
Kathrin Schwedler,
Marcus Schmidt,
Jana Barinoff,
Christoph Mundhenke,
Tanja Cufer,
Eduard Maartense,
Felix E de Jongh,
Klaus H Baumann,
Joachim Bischoff,
Nadia Harbeck,
Hans-Joachim Lück, Nicolai Maass,
Christoph Zielinski,
Michael Andersson,
Robert C Stein,
Valentina Nekljudova,
Sibylle Loibl
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ABSTRACT: Continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment. Here, we report the final analysis on overall survival.
Patients with HER2-positive, advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy were prospectively randomised to X (2500mg/m(2) on days 1-14, q3w) or XH (6 (8)mg/kg, q3w). Overall survival was a pre-specified secondary end-point.
Median follow-up at June 2010 was 20.7months. Fifty nine of 74 and 60 of 77 patients died in the X and XH arm, respectively. Median overall survival was 20.6 and 24.9months with X and XH, respectively (HR=0.94 [0.65-1.35]; p=0.73). Performance status and metastatic site were independent prognosticators for overall survival. No difference between treatment arms was observed for patients who achieved clinical response or clinical benefit, respectively. Patients who continued/restarted anti-HER2 treatment (trastuzumab or lapatinib) after 2nd progression (N=52) had a post-progression survival of 18.8 compared with 13.3months for those who did not receive 3rd line treatment with anti-HER2 agents (N=88) (HR 0.63; p=0.02).
Final overall survival analysis of the GBG-26 study did not demonstrate a significant survival benefit for treatment beyond progression with trastuzumab. However, in a post-hoc analysis, patients receiving anti-HER2 treatment as 3rd line therapy showed a better post-progression survival than those not receiving this targeted treatment.
European journal of cancer (Oxford, England: 1990) 07/2011; 47(15):2273-81. · 4.12 Impact Factor
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Dirk O Bauerschlag,
Ole Ammerpohl,
Karen Bräutigam,
Christian Schem,
Qiong Lin,
Marion T Weigel,
Felix Hilpert,
Norbert Arnold, Nicolai Maass,
Ivo Meinhold-Heerlein,
Wolfgang Wagner
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ABSTRACT: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy.
Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in >14,000 genes.
Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of >28 months. Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation.
Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value.
Oncology 05/2011; 80(1-2):12-20. · 2.27 Impact Factor
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ABSTRACT: Endometriosis is determined by local and systemic proinflammatory dysregulation and therefore differential protein expression in peritoneal fluid (PF). Of highest interest is lesion formation and the establishment and persistence of endometriosis. In this study we analyzed well-characterized PF samples of patients with ovarian or peritoneal endometriosis and compared them to control samples. We found 11 proteins differentially regulated, of which some might play a key role in the pathogenesis of endometriosis.
Fertility and sterility 04/2011; 95(8):2764-8. · 3.97 Impact Factor
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ABSTRACT: To evaluate the oxidative state of lipoproteins in pregnancies complicated by intrauterine growth restriction (IUGR) in comparison to preeclampsia (PE) and healthy pregnant control subjects (CN).
Maternal serum of 20 PE, 29 IUGR, and 29 gestational age-matched CN were analyzed. Total cholesterol (TC), low-density lipoprotein (LDL)-bound cholesterol (LDL-C), and oxidized LDL (oxLDL) concentration were measured once between 25 and 34 weeks of gestation. Statistical estimates were performed by Student's t-test.
Serum concentrations of LDL-C and TC were significantly reduced in IUGR [LDL-C: CN - mean = 146 mg/dL, SD = ± 40.1; IUGR - mean = 102 mg/dL, SD = ± 27.3 (p < 0.0001); PE - mean = 130 mg/dL, SD = 38.8 mg/dL; TC: CN - mean = 259/dL, SD = ± 46.8; IUGR - mean = 218 mg/dL, SD = ± 35.0 (p < 0.001); PE - mean = 244 mg/dL, SD = 48.2]. There was no significant difference in oxLDL/LDL-C ratio within the three groups (CN: mean = 0.76, SD = 0.24; IUGR: mean = 0.74, SD = 0.12; PE: mean = 0.77, SD = 0.22).
Our results show a lower maternal LDL-C and TC concentration in IUGR pregnancies. These data contribute to the hypothesis of a decreased cholesterol supply to the fetus in IUGR. However, we could not confirm the hypothesis of an altered oxidative state in neither IUGR nor PE.
Hypertension in Pregnancy 01/2011; 31(1):156-65. · 1.69 Impact Factor
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ABSTRACT: In 2008 and 2009, the authors saw in their institution three women who had undergone oocyte donation and went on to develop severe de novo hypertension before the 26(th) week of gestation, with values above 180/110 mm Hg. Pregnancy was prematurely terminated in these cases because of the acute threat to the mother's life, and none of the three neonates survived. Five further cases with better outcomes were found to have occurred from 2006 to 2010. On the basis of this experience, the authors performed a meta-analysis to determine whether oocyte donation elevates the risk of pregnancy-induced hypertension (PIH). The cases are discussed in detail.
Systematic review of the literature on PIH after oocyte donation, with meta-analysis and calculation of an odds ratio. We also provide a retrospective chart review of our own case series.
28 publications were evaluated. The overall rate of PIH in a total of 2308 deliveries after oocyte donation was 22.6%. With the aid of data from 11 studies, the course of pregnancy in a total of 644 oocyte recipients was compared to that in a control group of 2320 women who were not oocyte recipients. The calculated odds ratio for PIH after oocyte donation, compared to conventional reproductive therapy, was 2.57 (95% CI, 1.91-3.47), while the calculated odds ratio for PIH after oocyte donation, compared to other women in the control group, was 6.60 (95% CI, 4.55-9.57).
The data reveal that oocyte donation confers a considerable risk that the recipient will develop PIH. The very early and severe cases of preeclampsia that we report here are rather atypical; similar cases may have occurred elsewhere without finding their way into the relevant literature. The authors recommend close surveillance of pregnancies following allogenic oocyte transplantation by physicians with special expertise in prenatal medicine.
01/2011; 108(3):23-31. · 2.92 Impact Factor
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ABSTRACT: Paraneoplastic syndromes (PNS) are a heterogeneous group of symptoms which are indirectly caused by primary or metastatic tumor. Paraneoplastic polyneuropathy (PNP) is mostly related to small cell lung cancer (5%), prostate, gastric, and breast cancer. Only sporadic cases have been reported to be associated with endometrial cancer. We present a case of a premenopausal woman with severe vasculitic, asymmetric sensorimotor polyneuropathy that developed in conjunction with an endometrial carcinoma responding to surgical therapy of primary tumor combined to steroid therapy. Neurological symptoms such as asymmetrical sensorimotor deficits and painful paresthesias are suspicious when they occur in otherwise healthy women with no medical history. The phenomenon of a paraneoplastic syndrome can point to an underlying malignancy and can be used as marker of progression or regression of the tumor. Due to the rarity of PNP, there is no standard treatment. Recommended therapy is stage-adjusted treatment of the primary tumor.
Case reports in obstetrics and gynecology. 01/2011; 2011:968756.
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ABSTRACT: Ovarian cancer accounts for the highest mortality among all gynecological cancers, mainly due to the fast developing chemoresistance. The death ligand TRAIL induces apoptosis and is able to sensitize tumor cells to cytostatic drugs without affecting physiological tissue. Combined treatment of TRAIL and the antidiabetic acting PPARγ ligands was shown to induce apoptosis synergistically in different ovarian cancer cell lines.
To investigate feasible TRAIL-dependent inhibition of proliferation and induction of apoptosis in chemoresistant ovarian cancer cell lines, the drug- and TRAIL-sensitive HEY cell line was utilized to develop subclones with selective resistance against cisplatin, etoposide, docetaxel, paclitaxel, gemcitabine and pemetrexed, as well as against TRAIL as control cell line. Expression of the key factors of the TRAIL signaling pathway, TRAIL receptors 1-4, caspase-8, FLIP and XIAP, was analyzed before and after TRAIL treatment by immunoblotting.
Cell proliferation experiments showed TRAIL-dependent inhibition that was further increased by combination treatment with the PPARγ ligands. Simultaneous exposure of TRAIL and the PPARγ ligands also resulted in enhanced induction of apoptosis even in partial TRAIL-resistant HEY cell lines. In the parental HEY cell line, additional treatment with the PPARγ ligands led to an increased protein expression of DR5 and a further decline of XIAP expression.
Therefore, the combinational treatment with TRAIL and PPARγ ligands might be a promising experimental therapy because the PPARγ ligands, especially d15-PGJ(2), sensitize drug-resistant ovarian cancer cells to TRAIL-induced apoptosis.
Journal of Cancer Research and Clinical Oncology 09/2010; 137(5):875-86. · 2.56 Impact Factor
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ABSTRACT: Treatment of ovarian cancer is still challenging especially in recurrent platinum refractory cases. Sunitinib is a multi tyrosine kinase inhibitor targeting receptors for vascular endothelial growth factor and platelet-derived growth factor which play a role in tumor angiogenesis. It has been approved for the treatment of recurrent gastro intestinal stroma tumors and metastatic renal cancer.
In this study, sunitinib was tested for its effectiveness as a single agent in an ovarian cancer xenograft mouse model. Skov3 cells stably expressing firefly luciferase were injected into SCID beige mice. Mice received either 40 mg/kg bodyweight sunitinib or vehicle control. Tumor growth was monitored longitudinally by luciferase signal.
Sunitinib significantly reduced tumor growth (p=0.0052) and peritoneal metastases, and was associated with a significantly reduced microvessel density count (p<0.001).
These results suggest that clinical trials are warranted for the evaluation of sunitinib for treatment of patients with recurrent or advanced ovarian cancer.
Anticancer research 09/2010; 30(9):3355-60. · 1.73 Impact Factor
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ABSTRACT: BACKGROUND: Calpains (CAPN) are intracellular, non-lysosomal cytoplasmic cysteine endopeptidases and they are expressed ubiquitously. Their endogenous specific inhibitor is calpastatin. When calcium is present, calpastatin and calpain attach to each other, inhibiting the protease. The calpain system plays an important role in many processes including apoptosis, necrosis, ischaemia and exocytosis. The role of calpains in pathogenesis or further tumour progression has been proved in related studies. This study focused on the expression of the enzymes calpain 1, calpain 2 and the inhibitor calpastatin in normal and malignant endometrial tissue. MATERIALS AND METHODS: Immunohistochemical stainings were performed on paraffin slices and staining intensity, percentage of positive cells and international ratio score were evaluated. Results and conclusion: The endometrial carcinoma showed a higher expression of calpastatin than benign endometrial tissue.
Anticancer research 07/2010; 30(7):2837-43. · 1.73 Impact Factor
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Marion T Weigel,
Linda Dahmke,
Christian Schem,
Dirk O Bauerschlag,
Katrin Weber,
Peter Niehoff,
Maret Bauer,
Alexander Strauss,
Walter Jonat, Nicolai Maass,
Christoph Mundhenke
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ABSTRACT: Breast cancer treatment is based on a combination of adjuvant chemotherapy followed by radiotherapy effecting intracellular signal transduction. With the tyrosine kinase inhibitors new targeted drugs are available. Imatinib mesylate is a selective inhibitor of bcr-abl, PRGFR alpha, beta and c-kit. The purpose of this study was to determine whether Imatinib has an influence on the effectiveness of radiotherapy in breast cancer cell lines and if a combination of imatinib with standard chemotherapy could lead to increased cytoreduction.
Colony-forming tests of MCF 7 and MDA MB 231 were used to study differences in cell proliferation under incubation with imatinib and radiation. Changes in expression and phosphorylation of target receptors were detected using western blot. Cell proliferation, migration and apoptosis assays were performed combining imatinib with doxorubicin.
The combination of imatinib and radiotherapy showed a significantly stronger inhibition of cell proliferation compared to single radiotherapy. Differences in PDGFR expression could not be detected, but receptor phosphorylation was significantly inhibited when treated with imatinib. Combination of imatinib with standard chemotherapy lead to an additive effect on cell growth inhibition compared to single treatment.
Imatinib treatment combined with radiotherapy leads in breast cancer cell lines to a significant benefit which might be influenced through inhibition of PDGFR phosphorylation. Combining imatinib with chemotherapy enhances cytoreductive effects. Further in vivo studies are needed to evaluate the benefit of Imatinib in combination with radiotherapy and chemotherapy on the treatment of breast cancer.
BMC Cancer 01/2010; 10:412. · 3.01 Impact Factor
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Michael Untch,
Volker Möbus,
Wolfgang Janni, Nicolai Maass,
Corinna Crohns,
Peter Fasching,
Christoph Mundhenke,
Walter Jonat,
Daniel Herr,
Rolf Kreienberg,
Thorsten Kühn
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ABSTRACT: Die neoadjuvante (primäre) systemische Therapie umfasst alle medikamentösen Therapieformen, die nach histologischer Diagnosestellung
eines Mammakarzinoms vor Durchführung der operativen Maßnahmen verabreicht werden.
12/2009: pages 174-197;
