B Rack

Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

Are you B Rack?

Claim your profile

Publications (172)291.78 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Breast, ovarian and endometrial cancers cause significant morbidity and mortality. Despite the presence of existing screening, diagnostic and treatment modalities, they continue to pose considerable unsolved challenges. Overdiagnosis is a growing problem in breast cancer screening and neither screening nor early diagnosis of ovarian or endometrial cancer is currently possible. Moreover, treatment of the diversity of these cancers presenting in the clinic is not sufficiently personalized at present. Recent technological advances, including reduced representation bisulfite sequencing, methylation arrays, digital PCR, next-generation sequencing and advanced statistical data analysis, enable the analysis of methylation patterns in cell-free tumor DNA in serum/plasma. Ongoing work is bringing these methods together for the analysis of samples from large clinical trials, which have been collected well in advance of cancer diagnosis. These efforts pave the way for the development of a noninvasive method that would enable us to overcome existing challenges to personalized medicine.
    Epigenomics 06/2014; 6(3):311-327. · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer. CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0-54). Kaplan-Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided. Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) CONCLUSIONS: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.
    CancerSpectrum Knowledge Environment 05/2014; · 14.07 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch(R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. CellSearch(R) images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2- vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (kappa) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median kappa of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and <3CTCs (median 87%, range 66 to 95%) compared to M0 and >=3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2- vs HER2+), the median agreement was 87% (range 51 to 95%) with a median kappa of 0.74 (range 0.25 to 0.90). The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.
    Breast cancer research: BCR 04/2014; 16(2):R43. · 5.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
    BioMed Research International 04/2014; · 2.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In clinical practice imaging technologies such as computed tomography (CT), positron emission tomography (PET)/CT and magnetic resonance imaging (MRI) are well-established methods for monitoring metastatic breast cancer (MBC) patients and for assessing therapeutic efficacy. However, several weeks of treatment are required before these technologies can offer any reliable information on effective disease regression, and, in the meanwhile, the patients are exposed to potentially unnecessary therapy. Circulating tumor cells (CTCs) have been shown to be powerful prognostic and predictive markers and provide clinicians with valuable information. However, in one clinical trial, an early change of chemotherapy based on CTC detection did not result in improved survival. Currently, CTC detection outside clinical trials should be limited to selected clinical situations, i.e. increased treatment toxicity or as risk estimation.
    Breast Care 02/2014; 9(1):16-21. · 0.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
    BioMed research international. 01/2014; 2014:491459.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tumor xenografts in immunodeficient mice, while routinely used in cancer research, preclude studying interactions of immune and cancer cells or, if humanized by allogeneic immune cells, are of limited use for tumor-immunological questions. Here, we explore a novel way to generate cancer models with an autologous humanized immune system. We demonstrate that hematopoietic stem and progenitor cells (HSPCs) from bone marrow aspirates of non-metastasized carcinoma patients, which are taken at specialized centers for diagnostic purposes, can be used to generate a human immune system in NOD-scid IL2rγ(null) (NSG) and HLA-I expressing NSG mice (NSG-HLA-A2/HHD) comprising both, lymphoid and myeloid cell lineages. Using NSG-HLA-A2/HHD mice, we show that responsive and self-tolerant human T cells develop and human antigen presenting cells can activate human T cells. As critical factors we identified the low potential of bone marrow HSPCs to engraft, generally low HSPC numbers in patient-derived bone marrow samples, cryopreservation and routes of cell administration. We provide here an optimized protocol that uses a minimum number of HSPCs, preselects high-quality bone marrow samples defined by the number of initially isolated leukocytes and intra-femoral or intra-venous injection. In conclusion, the use of diagnostic bone marrow aspirates from non-metastasized carcinoma patients for the immunological humanization of immunodeficient mice is feasible and opens the chance for individualized analyses of anti-tumoral T cell responses.
    PLoS ONE 01/2014; 9(5):e97860. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Triple negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study (GWAS) of TN breast cancer (stage 1: 1,529 TN cases, 3,399 controls; stage 2: 2,148 cases, 1,309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (p<5x10(-8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the SNPs analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (p<0.05). Associations with TN breast cancer were confirmed for ten loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (p<0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 (rs12525163 Odds Ratio (OR)=1.15, p=4.9x10(-4)) and 19p13.1 (rs1864112 OR=0.84, p=1.8x10(-9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR=4.03, 95% CI 3.46-4.70, p=4.8x10(-69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
    Carcinogenesis 12/2013; · 5.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of breast cancer patients is associated with poor outcome. The aim of our study was to evaluate the impact of BM status on survival in a large cohort of cervical cancer patients. 325 patients with cervical cancer were included into this prospective two-center study (University Hospitals Tuebingen, Munich, Germany). BM was collected preoperatively. DTCs were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. DTCs were detected in 22% of all BM aspirates. The number of CK-positive cells ranged from 1 to 93 per 2 × 10(6) mononuclear cells. 18% of patients with T1 stage presented with DTCs in BM compared to 30% in T2 and 45% in T3/4 patients. Among nodal negative patients 18% had tumor cells in BM compared to 32% of nodal positive patients. Positive DTC status was associated with tumor size (p = 0.007) and nodal status (p = 0.009) but not with grading (p = 0.426). DTC status did not correlate with overall or disease-free survival. In the univariate analysis, tumor stage, nodal status, resection status and grading correlated with OS and DFS. In the multivariate analysis, only tumor stage and nodal status were independent predictors of OS and tumor stage, nodal status and grading of DFS. Tumor cell dissemination into bone marrow is thus a common phenomenon in cervical cancer and correlates with higher tumor load but lacks prognostic relevance. Alternative detection methods may be needed to establish prognostic potential. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 08/2013; · 6.20 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, beta-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types. A retrospective analysis was performed on the expression of MUC1, beta-catenin and E-cadherin by immunohistochemistry on tumor tissues of a series of 112 breast cancer patients (total collective) treated in Munich between 2000 and 2002. By matched-pair analysis, 46 patients were entered into two comparable groups of 23 patients after categorizing them as having multicentric/multifocal or unifocal breast cancer. Matching criteria were tumor size, histology grade and lymph node status; based on these criteria, patients were distributed equally between the two groups (p = 1.000 each). Data were analyzed with the Kruskal-Wallis and the Mann--Whitney tests. In the matched groups, we found a significantly down-regulated expression of E-cadherin in multicentric/multifocal breast cancer compared to unifocal disease (p = 0.024). The total collective showed even higher significance with a value of p < 0.0001. In contrast, no significant differences were observed in the expression of beta-catenin between multicentric/multifocal and unifocal tumors (p = 0.636 and p = 0.914, respectively). When comparing the expression of MUC1, E-cadherin and beta-catenin within the unifocal group, we found a significant positive correlation between E-cadherin and beta-catenin (p = 0.003). In the multicentric/multifocal group we observed, in contrast to the unifocal group, a significant decrease of MUC1 expression with increased grading (p = 0.027). This study demonstrates that multicentric/multifocal and unifocal breast cancers with identical TNM-staging clearly differ in the expression level of E-cadherin. We suggest that the down-regulation of E-cadherin in multicentric/multifocal breast cancer is causally connected with the worse prognosis of this tumor type.
    BMC Cancer 07/2013; 13(1):361. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVE: Detection of disseminated tumor cells (DTCs) in the bone marrow (BM) of patients with breast cancer is associated with poor outcomes. Recent studies demonstrated that DTCs may serve as a prognostic factor in ovarian cancer. The aim of this 3-center study was to evaluate the impact of BM status on survival in a large cohort of patients with ovarian cancer. MATERIALS AND METHODS: Four hundred ninety-five patients with primary ovarian cancer were included in this 3-center prospective study. Bone marrow aspirates were collected intraoperatively from the iliac crest. Disseminated tumor cells were identified by antibody staining and by cytomorphology. Clinical outcome was correlated with the presence of DTCs. RESULTS: Disseminated tumor cells were detected in 27% of all BM aspirates. The number of cytokeratin-positive cells ranged from 1 to 42 per 2 × 10 mononuclear cells. Disseminated tumor cell status did correlate with histologic subtype but not with any of the other established clinicopathologic factors. The overall survival was significantly shorter among DTC-positive patients compared to DTC-negative patients (51 months; 95% confidence interval, 37-65 months vs 33 months; 95% confidence interval, 23-43 months; P = 0.023). In the multivariate analysis, BM status, International Federation of Gynecology and Obstetrics stage, nodal status, resection status, and age were independent predictors of reduced overall survival, whereas only BM status, International Federation of Gynecology and Obstetrics stage, and resection status independently predicted progression-free survival. CONCLUSIONS: Tumor cell dissemination into the BM is a common phenomenon in ovarian cancer. Disseminated tumor cell detection has the potential to become an important biomarker for prognostication and disease monitoring in patients with ovarian cancer.
    International Journal of Gynecological Cancer 06/2013; 23(5):839-845. · 1.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Biomarkers uPA/PAI-1 as recommended by ASCO and AGO are used in primary breast cancer to avoid unnecessary CTX in medium risk-recurrence patients. This study verified how many CTX cycles and CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. A prospective, non-interventional, multi-center study was performed among six Certified Breast Centers to analyze application of uPA/PAI-1 and consecutive decision-making. CTX avoided were identified and direct costs for CTX, CTX-related concomitant medication and febrile neutropenia (FN) prophylaxis with G-CSF calculated. In n = 93 breast cancers n = 35 CTX (37.6%) with 210 CTX cycles were avoided according to uPA/PAI-1 test result. uPA/PAI-1 testing saved direct medication costs for CTX of 177,453 €, CTX-related concomitant medication of 27,482 € and FN prophylaxis of 20,599 €, overall 225,534 €. At test costs at 287.50 € uPA/PAI-1 testing resulted in additional costs of 26,737.50 €. uPA/PAI-1 has proven to be cost-effective at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. These results support decision-making for cost-effective diagnostics and therapy in breast cancer.
    Breast (Edinburgh, Scotland) 05/2013; · 2.09 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Disseminated tumor cells are found in the bone marrow of patients with epithelial carcinoma and are correlated with a poor prognosis of the disease. Their detection is a technical challenge. This report describes a model system for the detection of cancer cells by co-immunostaining of Thomsen-Friedenreich and Her-2 antigens. Methods & results: Small numbers of cancer cells from different cancer cell lines were mixed with blood samples of healthy donors. Cytospins were prepared and double immunostaining against Thomsen-Friedenreich antigen and Her-2 was carried out by fluorochrome-coupled antibodies. Quantification of Thomsen-Friedenreich and/or Her-2-positive cells was performed with an epifluorescence microscope. On average, 83% of cancer cells were recovered by this method. Conclusion: Immunostaining is a useful method for the detection of cancer cells in blood samples. Results of this model system will be transferred to bone marrow patient samples to prove the benefits for detection of disseminated tumor cells.
    Future Oncology 05/2013; 9(5):747-52. · 3.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSEWe aimed to determine the prognosis of patients with breast cancer diagnosed during pregnancy (BCP). PATIENTS AND METHODS In this cohort study, a multicentric registry of patients with BCP (from Cancer in Pregnancy, Leuven, Belgium, and GBG 29/BIG 02-03) compiled pro- and retrospectively between 2003 and 2011 was compared with patients who did not have associated pregnancies, using an age limit of 45 years. Patients with a diagnosis postpartum were excluded. The main analysis was performed using Cox proportional hazards regression of disease-free survival (DFS) and overall survival (OS) on exposure (pregnant or not), adjusting for age, stage, grade, hormone receptor status, human epidermal growth factor 2 status, histology, type of chemotherapy, use of trastuzumab, radiotherapy, and hormone therapy.ResultsThe registry contained 447 women with BCP, mainly originating from Germany and Belgium, of whom 311 (69.6%) were eligible for analysis. The nonpregnant group consisted of 865 women. Median age was 33 years for the pregnant and 41 years for the nonpregnant patients. Median follow-up was 61 months. The hazard ratio of pregnancy was 1.34 (95% CI, 0.93 to 1.91; P = .14) for DFS and 1.19 (95% CI, 0.73 to 1.93; P = .51) for OS. Cox regression estimated that the 5-year DFS rate for pregnant patients would have increased from 65% to 71% if these patients had not been pregnant. Likewise, the 5-year OS rate would have increased from 78% to 81%. CONCLUSION The results show similar OS for patients diagnosed with BCP compared with nonpregnant patients. This information is important when patients are counseled and supports the option to start treatment with continuation of pregnancy.
    Journal of Clinical Oncology 04/2013; · 18.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: The detection of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients is an independent prognostic factor. In recent years, the focus of research was on finding methods for the detection of circulating tumor cells (CTC) in peripheral blood (PB). In this study, we investigated the presence of DTC-BM and CTC by simultaneous examinations in 202 patients at different stages of the disease. METHODS: Immunocytochemical examination of DTC-BM (10-20 ml of BM) with the anti-cytokeratin (CK) antibody A45B/B3 followed a standardized protocol. Analysis of PB (7.5 ml) for the presence of CTC was performed with the CellSearch Analyzer system (Veridex, Raritan, NJ, USA). RESULTS: Overall, DTC-BM were detected in 57/202 (28.2 %, 1->1,000 DTC) and CTC in 41/202 (20.3 %, 1-411 CTC) patients. Congruence of findings was 71.3 % (144/202, p = .002). In 147 pts with primary diagnosis, congruence of results was 69.4 % (102/147). There was no significant correlation between DTC or CTC and the established pathological factors. After a median follow-up time of 34 months (0-82), presence of CTC was borderline significant for tumor-associated death (p = .060). For 41 patients at recurrence-free follow-up, congruence of results was 75.6 % (31/41, p = .018). In this group, there was a patient with both the highest DTC (>1,000) and CTC (411) count, and she presented with distant metastases 3 months later and had died 5 months after that. Of 14 patients with metastatic disease, 9 showed both DTC and CTC (overall congruence 78.6 %, p = .176). CONCLUSION: There was significant congruence between DTC and CTC, which even increased in patients at follow-up and in those with metastases. Repeated CTC examinations could be a valuable tool for monitoring patients or the effectiveness of therapies.
    Journal of Cancer Research and Clinical Oncology 03/2013; · 2.91 Impact Factor
  • Breast Care 03/2013; 8(1):77-83. · 0.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: To explore circulating tumor cell (CTCs) counts in different stages of prostate cancer (PC) in association with tumor burden, metastatic pattern and conventional serum biomarkers. Overall survival (OS) analyses were conducted with respect to optimized CTC cutoff levels. METHODS: Circulating tumor cell counts were assessed in healthy controls (n = 15) as well as in locally advanced high risk (LAPC, n = 20), metastatic castration resistant (mCRPC, n = 40) and taxane-refractory (mTRPC, n = 15) PC patients. CTCs were detected using the CellSearch™ System. RESULTS: In metastatic PC (mPC), CTC counts were significantly increased compared to LAPC (p < 0.001). In LAPC, CTCs were at control level (p = 0.66). Patients with both bone and visceral lesions revealed the highest median CTC count (p = 0.004), whereas patients with sole soft tissue metastases displayed CTC counts comparable to controls (p = 0.16). No correlation was observed between CTC counts and osseous tumor burden assessed by bone lesion count (p = 0.54) or bone scan index (p = 0.81). CTC counts revealed a positive correlation with alkaline phosphatase (p < 0.001) and lactate dehydrogenase (p < 0.001) as well as a negative association with hemoglobin (p = 0.004) and PSA-doubling time (p = 0.01). Kaplan-Meier analyses demonstrated a cohort adjusted cutoff level of 3 CTCs with a shorter OS in case of ≥3 CTCs compared to <3 CTCs (p = 0.001), a cutoff level applicable in mCRPC (p = 0.003) but not in mTRPC patients (p = 0.054). CONCLUSIONS: Circulating tumor cell counts are applicable as a prognostic molecular marker, especially in mCRPC patients harboring bone metastases with or without visceral metastases. For clinical practice, mPC patients with elevated CTC counts in combination with short PSA-DT, high alkaline phosphatase and lactate dehydrogenase levels as well as low hemoglobin levels are at high risk of disease progression and limited OS.
    Journal of Cancer Research and Clinical Oncology 01/2013; · 2.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circulating tumour cells were detected and quantified by real-time polymerase chain reaction (PCR) in peripheral blood, based on the fact that the expression of certain genes is upregulated in tumour tissues in comparison to surrounding blood cells. Calibration curves showing gene expression as functions of the number of tumour cells within a blood sample were prepared. Blood samples were therefore spiked with cells of breast cancer cell lines, RNA was extracted, transcribed to complementary DNA (cDNA) and used in real-time PCR reaction on the Cytokeratins (CK) 8, 18 and 19. Calibration curves were generated by Microsoft™ Excel®. Relative quantification curves of gene expression in different breast cancer cell lines showed no unitary tendencies. The oscillations in the relative quantification curves of gene expression suggested an occurrence of immunological effects, leading to an apparent agglutination of added tumour cells together with the blood cells of the sample. Thus, strategies to obtain evaluable results should be considered.
    Biomedical reports. 01/2013; 1(2):231-234.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The SUCCESS-A trial is a prospective, multicenter, phase III clinical trial for high-risk primary breast cancer. It compares disease-free survival after randomization in patients treated with fluorouracil, epirubicin and cyclophosphamide followed by 3 cycles of docetaxel (FEC-D) with that of patients treated with 3 cycles of FEC followed by 3 cycles of gemcitabine and docetaxel (FEC-DG). After a second randomization patients were treated with zoledronate for 2 or 5 years. A total of 251 centers took part in the trial and 3754 patients were recruited over a period of 18 months which ended in March 2007. In a questionnaire-based survey we investigated the impact of enrollment in the trial on patient care, the choice of chemotherapy protocol and access to current oncologic information as well as overall satisfaction in the respective centers. Analysis of the 78 questionnaires returned showed that 40 % of the centers had never previously enrolled patients with these indications in clinical studies. Prior to participating in the study, 4 % of the centers prescribed CMF or other protocols in patients with high-primary breast cancer risk, 46 % administered anthracycline-based chemotherapy and 50 % gave taxane-based chemotherapy. Around half of the participating centers noted that intensity of care and overall quality of care became even better and that access to breast cancer-specific information improved through participation in the trial. After their experience with the SUCCESS-A trial, all of the centers stated that they were prepared to enroll patients in clinical phase III trials again in the future. These data indicate that both patients and physicians benefit from clinical trials, as enrollment improves treatment strategies and individual patient care, irrespective of study endpoints.
    Geburtshilfe und Frauenheilkunde 01/2013; 73(1):63-69. · 0.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Trophoblasttumoren stellen eine heterogene Gruppe von Tumoren dar. Zu dem Formenkreis zählen unter anderem die Partialmole, die komplette Blasenmole, die invasive Blasenmole, das Chorionkarzinom, der Plazentabett – Tumor und der epitheloide Trophoblasttumor. Die vier zuletzt genannten Krankheitsbilder gehören zu den gestationsbedingten trophoblastären Neoplasien (GTN).In der vorliegenden Arbeit wird eine Übersicht über Symptome, Diagnostik und Therapie der Blasenmole und der GTN gegeben.Die häufigsten klinischen Symptome sind die vaginale Blutung sowie eine deutlich erhöhte Konzentration an humanem Choriongonadotropin (HCG). Daneben kann ein intensiv wachsender Uterus zur Diagnosestellung führen. Seltener treten Beschwerden aufgrund einer bereits stattgefundenen Metastasierung auf.Goldstandard sind die Vaginalsonographie sowie die Bestimmung des HCG. Eine histologische Sicherung ist erforderlich. Bei der Diagnose einer GTN ist ein Staging zur Detektion von Metastasen erforderlich.Die Therapie der Wahl bei der partiellen oder kompletten Blasenmole ist die operative Intervention. Bevorzugt werden sollte die Saugkürettage, da sie mit der geringsten Perforationsgefahr einhergeht. Bei den gestationsbedingten trophoblastären Neoplasien richtet sich die Therapie nach dem Stadium der Erkrankung. Je nach Stadium wird eine Mono- oder eine Polychemotherapie verabreicht.Auch wenn die Inzidenz der Trophoblasterkrankungen gering ist, kann diese Erkrankung mit einer relevanten maternalen Morbidität assoziiert sein. Aus diesem Grund ist eine frühzeitige Diagnosestellung und eine stadiengerechte Therapie von entscheidender Bedeutung für die Prognose.
    Der Gynäkologe 01/2013; 46(11).

Publication Stats

1k Citations
291.78 Total Impact Points

Institutions

  • 2009–2013
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2012
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 2001–2012
    • Ludwig-Maximilian-University of Munich
      • Clinic and Polyclinic for Obstetrics and Gynecology
      München, Bavaria, Germany
  • 2011
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 2010–2011
    • Technische Universität München
      München, Bavaria, Germany
    • University of Tuebingen
      • Department of Gynecology and Obstetrics
      Tübingen, Baden-Wuerttemberg, Germany
  • 2007–2011
    • University of Hamburg
      • Department of Tumor Biology
      Hamburg, Hamburg, Germany
  • 2008
    • University Hospital München
      München, Bavaria, Germany