W Jonat

University Medical Center Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany

Are you W Jonat?

Claim your profile

Publications (456)944.49 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Imatinib is a tyrosine kinase inhibitor of BCR-ABL, ABL, PDGFR-α and -β, KIT, and DDR. In solid tumors, it inhibits proliferation and invasiveness and facilitates higher intratumoral cytotoxic drug concentrations. Vinorelbine has good tolerability and efficacy in metastatic breast cancer (MBC). This study evaluates the safety and efficacy of imatinib and vinorelbine in combination. Methods: In a prospective, open-label, phase I/II trial, 400 mg imatinib p.o. daily (corrected from 600 mg) was combined with an escalating dose of vinorelbine i.v. weekly in four dose levels of 10, 15, 20, and 25 mg/m(2) (each n ≥ 5) to treat patients with MBC (expressing PDGFR-α and/or -β, and/or KIT). The last patient of each level was treated for >28 days, before enrolment for the next dose level started. Study endpoints were feasibility and tolerability, incidence of hematological and nonhematological toxicity, and clinical efficacy (data cutoff: November 18, 2011). A total of 33 patients have been enrolled, and all dose levels have been fully recruited. One patient is still on study medication. A translational subprotocol is ongoing. Results: All 33 included patients are evaluable for safety (32 within the ITT population). Eleven patients were excluded early from the study (progressive disease, toxicity, and withdrawal of consent). Twenty-two patients participated in the study for >28 days ('ITT >28'). Within the ITT population, the response rate [complete response (CR) and partial response (PR)] was 9.4% (n = 3), the clinical benefit rate (CBR; CR+PR+stable disease) 50% (n = 16), and the median time to progression (TTP) 155 days. A total of 21.3% of the patients were on study medication for >6 months, and 15.2% for >12 months (mean 140 days, range 15-643). Within 'ITT >28', the response rate was 13.6%, CBR 72.7%, and median TTP 176 days. The response was independent of the receptor status (PDGFR-α, -β, and KIT). Toxicities were as follows (safety population): 21.6% severe leukopenia, 9.1% severe neutropenia (with 1 febrile neutropenia), 1 case of bowel perforation, 36% diarrhea (3% severe), 84.8% nausea (severe 15.2%), 48.5% vomiting (severe 9.1%), 27.3% infections (severe 6.1%), 12.1% peripheral neuropathy (severe 9.1%), and 36.4% dyspnea (3% severe). Four patients on trial died (nondrug-related). Conclusion: The combination of imatinib and vinorelbine in MBC appeared to be feasible and tolerable. A CBR of 50% (ITT) in pretreated patients suggests that this combination may be active. Although toxicities were frequent, they appeared to be manageable. © 2014 S. Karger AG, Basel.
    Oncology 08/2014; 87(5):300-310. · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Nilotinib is a selective tyrosine kinase inhibitor of c-Kit, Abl and platelet-derived growth factor receptor-α/β. To evaluate nilotinib's potential use as a treatment of human ovarian cancer, we tested nilotinib's preclinical activity in ovarian cancer cell lines with different tyrosine kinase expression patterns. Methods: The effects of nilotinib on ovarian cancer cell growth were studied alone and in combination with carboplatin and paclitaxel. Proapoptotic and antimigratory effects were examined using TUNEL and migration assays. Results: Nilotinib alone and in combination with carboplatin and paclitaxel significantly inhibited cell growth in PDGFR-α-positive ovarian cancer cell lines. The combination of nilotinib with carboplatin and paclitaxel showed synergistic effects on cell proliferation. Nilotinib treatment led to the inhibition of cell migration alone and in combination with carboplatin and paclitaxel. Apoptosis induction occurred in response to nilotinib that increased in combination with carboplatin. Conclusions: Nilotinib may be a feasible targeted therapy option for the treatment of ovarian cancer. © 2014 S. Karger AG, Basel.
    Oncology 08/2014; 87(4):232-245. · 2.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Fibroblast growth factor-2 (FGF-2) supports tumor progression in breast cancer. FGF-2 signaling is modulated by heparan sulfate proteoglycans, such as syndecan-1 (CD138). The exact role of CD138 in ductal carcinoma in situ of the breast (DCIS) is still uncertain. Differential expression depending on grading could suggest a role for syndecan-1 during growth and tumor progression. Materials and Methods: Samples of 127 cases of breast DCIS associated with follow-up data were included. CD138 staining intensity, number of positive cells, intracellular and tissue localization were examined. Results: Median follow-up was 45.4 months and median recurrence-free survival (RFS) 86 months. Age, menopausal status and previous hormone replacement therapy had no significant influence on RFS. Smoking significantly influenced RFS (p=0.008). Endocrine therapy or radiotherapy did not improve RFS. Grading was not correlated with CD138 staining intensity, but was significantly associated with the percentage of CD138-positive cells (low-vs. high-grade, p=0.043). Estrogen receptor (ER) expression did not influence staining intensity of CD138 (p=0.247), but negatively correlated with the proportion of CD138-positive cells (p=0.032). Progesterone receptor (PR) expression significantly influenced the intensity of staining (p=0.010) and the percentage of CD138-positive cells (p=0.004); both were increased in PR-negative cases. CD138 staining intensity and percentage of positive cells did not correlate with RFS. Nuclear grade and syndecan-1 staining localization were significantly associated (p=0.001). ER-positive, and PR-positive DCIS more often exhibited membrane-bound syndecan-1 than ER- or PR-negative cases (p=0.001). Nuclear grade and tissue localization of CD138 correlated significantly (p=0.005). PR influenced CD138 tissue distribution, while ER did not. Syndecan-1 localization did not statistically impact RFS. Conclusion: In DCIS of different nuclear grades, tissue localization of syndecan-1 is significantly divergent, suggesting a specific effect on biology and progression of DCIS.
    Anticancer research 07/2014; 34(7):3607-16. · 1.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: For patients undergoing vulva surgery the quality of life (QoL) is generally accepted as an important outcome parameter in addition to long-term survival, mortality and complication rates. Less radical operative treatment can reduce morbidity and thereby improve quality of life. This study focuses on outcome in terms of QoL in patients comparing wide local excision (WLE) with radical vulvectomy and waiver of lymphonodectomy (LNE) with inguinofemoral lymphonodectomy. In a retrospective single-center study from 2000 to 2010, 199 patients underwent surgery for vulvar cancer. To assess QoL, the EORTC QLQ-C30 and a tumor-specific module questionnaire were sent to all patients in the follow-up period. Women who underwent WLE have a superior QoL with regard to global health status and physical, role, emotional and cognitive functioning than those who underwent radical vulvectomy. Less radical surgery also implies less fatigue, nausea/vomiting, pain, insomnia, appetite loss, diarrhea and financial difficulties. After radical vulvectomy 89% of patients have sexual complications. Radical operative treatment, such as radical vulvectomy, causes deterioration in the QoL of these patients. An individualized, less radical surgery must be the aim in the treatment of vulvar cancer.
    European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 04/2014; · 2.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective To investigate trends in the performance of hysterectomy at a single certified endoscopic teaching center. Methods Data were collected retrospectively from 953 patients who underwent hysterectomy between 2002 and 2010 for benign indications at UKSH, Germany. Preoperative risk scores were assigned to patients. Results The most frequent indications for hysterectomy were uterine myoma, adenomyosis, prolapse, endometrial hyperplasia, menstrual disorders, and endometriosis. The shortest operating time was recorded for vaginal hysterectomy (VH) and the longest for laparoscopically assisted VH (LAVH). The average uterine weight was highest for abdominal hysterectomy (AH) and lowest for VH. The major postoperative complication rate was 11.8% for laparoscopic supracervical hysterectomy (LSH) and 23.5% for AH. The highest intraoperative complication rate occurred with AH (46.4%) and the lowest with total laparoscopic hysterectomy (TLH; 3.6%). The minor postoperative complication rate was 5.9%. The mean preoperative score was 1.09 ± 1.51 for AH, 0.75 ± 0.96 for VH, 1.04 ± 1.30 for LSH, 1.0 ± 1.40 for LAVH, and 1.38 ± 1.52 for TLH. Conclusion Laparoscopic hysterectomies have become more common and were associated with decreased complication rates, despite the higher preoperative risk score of these patients.
    International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 01/2014; · 1.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Today, laparoscopic intrafascial hysterectomy and laparoscopic supracervical hysterectomy are well-accepted techniques. With our multimodal concept of laparoscopic hysterectomy for benign indications, preservation of the pelvic floor as well as reconstruction of pelvic floor structures and pre-existing prolapse situations can be achieved. The multimodal concept consists of 3 steps: 1. Intrafascial hysterectomy with preservation of existing structures A. Technique 1: Primary uterine artery ligation B. Technique 2: Classic intrafascial hysterectomy 2. A technique for the stable fixation of the vaginal or cervical stump 3. A new method of pectopexy to correct a pre-existing descensus situation Results and Conclustion: This well-balanced concept can be used by advanced endoscopic gynecologic surgeons as well as by novices in our field.
    JSLS : Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons. 01/2014; 18(1):89-101.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Liver transplantation currently represents the only curative treatment for Wilson's disease. A lifelong immunosuppressive therapy is mandatory. In spite of increased maternal and fetal risks, pregnancies after liver transplantation have been reported with favorable perinatal outcomes. Hypoplastic left heart syndrome is a spectrum of congenital heart defects that results in the inability to support the systemic circulation. Although its etiology remains elusive, the prognosis of this previously fatal condition has dramatically improved over the last 2 decades mainly due to advances in prenatal diagnosis, surgical technique and perioperative care. We present a case of a Caucasian 26-year-old woman, gravida 2, para 1 at 36+0 weeks of gestation who had received a liver transplantation due to Wilson's disease and subsequently delivered a child with hypoplastic left heart syndrome. This coincidence of medical conditions has not been described in the literature so far and its implications for mother and child as well as the pathophysiological mechanisms are discussed on the basis of a literature review.
    Journal of Medical Case Reports 12/2013; 7(1):276.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Implantation of the zygote outside the uterine cavity occurs in 2% of all pregnancies. The product of conception can be removed safely by laparoscopic surgery and be submitted for histological examination. The rate of ectopic pregnancies has increased from 0.5% in 1970 to 2% today. The prevalence of ectopic pregnancy in all women presenting to an emergency department with first-trimester bleeding, lower abdominal pain, or a combination of the 2 is between 6% and 16%. Designation: Workup of all localizations of ectopic pregnancies at a university department of obstetrics and gynecology. Methods: Comparison of diagnostic and therapeutic modalities from the surgical laparoscopic approach to nonsurgical, medical options. Findings: Surgical treatment: Tubal pregnancies: (1) to preserve tubal function, salpingotomy, partial salpingectomy followed by laparoscopic anastomosis, or fimbrial milking is performed. (2) Tubectomy or salpingectomy is performed only in severely damaged or ruptured tubes or if the patient does not desire further pregnancies. Nontubal ectopic pregnancies (ovarian pregnancy, ectopic abdominal pregnancy, interstitial or cornual pregnancy/rudimentary horn, intraligamental and cervical pregnancies) all require their own specific treatment. Medical treatment: The predominant drug is methotrexate, but other systemic drugs, such as actinomycin D, prostaglandins, and RU 486, can also be applied. Complications: Tubal rupture is a complication of late diagnosed tubal pregnancy that is more difficult to treat conservatively and often indicates tubectomy or segmental resection. In 5% to 15% of treated ectopic pregnancy cases, remnant conception product parts may require a final methotrexate injection. Conclusions: This article is a review to aid clinical diagnosis of ectopic pregnancies that now can be diagnosed earlier and treated effectively by laparoscopic surgery.
    Obstetrical & gynecological survey 08/2013; 68(8):571-81. · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Local treatment of breast cancer with tumor-free surgical margins is the standard procedure in the treatment of T1 and small T2 breast cancers. Surgery is followed by radiation therapy, and adjuvant systemic therapy is offered depending on primary tumor characteristics, such as tumor size, grade of differentiation, number of involved axillary lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and the expression of the human epidermal growth factor 2 (HER2) receptor. Although this approach implies a higher risk of ipsilateral breast tumor recurrence, the total risk of recurrence is low (1% per year), with rates of overall survival similar to that after radical procedures. The most peripheral part of epithelial tumors, the tumor margin, is the part which is most likely to remain in loco after surgical resection. Thus, understanding the biology of the invasion front is important as these tumor cells have been reported to lose epithelial properties, such as cohesiveness and keratin expression, and to acquire features of mesenchymal cells. The parallel appearance of tumor cells in different states of cell dedifferentiation implicates a dynamic equilibrium that is determined by the induction of epithelial-mesenchymal transition (EMT). EMT has been suggested to be of prime importance for tissue and vessel invasion. Furthermore, features of EMT are associated with the activity of tumor stem cells (TSC). TSC exist in breast cancer and their appearance varies depending on the used marker profile. Consequently, intratumoral heterogeneity is reflected by the grade of EMT activation. A specific function at the invasion front is hypothesized but has not yet been proven. Nevertheless, the molecular differentiation between the tumor center and the invasion front enhances the importance of tumor-free surgical margins.
    Minerva ginecologica 08/2013; 65(4):363-383.
  • [Show abstract] [Hide abstract]
    ABSTRACT: For better selection of oocytes and embryos, preimplantation genetic screening (PGS) was introduced. As from the beginning of IVF, morphology was used as selection criteria; we investigated the combination of both. If there was a correlation between phenotype and genotype, invasive PGS might be replaced. Therefore, 104 cycles with PGS were done by biopsy of the first polar body and FISH with five chromosomes. Morphology of the oocyte was recorded digitally and noted for 12 categories in 4-13 values; evaluation of the chromosomes was noted for five chromosomes in five values. Morphology and genetics were correlated to each other. Correlations between morphology and genetics for day 0 were found: oocytes with an irregular or dark zona are less probable to have a normal chromosome 13 (80 vs. 53 %, p = 0.001). A medium amount of detritus in the perivitelline space makes it more probable to have a normal chromosome 18 (94 vs. 78 %, p = 0.001). A halo in the cytoplasm makes it less probable to be euploid for chromosome 22 (56 vs. 75 %, p = 0.018). For day 1, pattern "1, 2, 3 and fine" in the pronuclei makes it more probable to be euploid for chromosome 22 (78 vs. 63 %, p = 0.002). There are correlations between the oocyte genome and its morphology also on day 0. These correlations are not sufficient to replace PGS.
    Archives of Gynecology 07/2013; · 0.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Preimplantation genetic screening wants to improve artificial reproductive technologies, primarily by raising the rates of pregnancy, implantation and birth. We investigated if embryos derived from oocytes detected euploid for five chromosomes implant better than those which were biopsied but where the genetic detection failed. They were nevertheless transferred, thus serving as a sham control. From 2004 to 2008 we performed 104 cycles of PGS with laser biopsy of the first polar body and FISH with five chromosomes. It was offered to all patients with eight or more oocytes, free of charge. The average female age was 36 years. If no euploid oocytes were available, not detected oocytes were transferred. In 104 cycles 99 embryo transfers (95 %) were performed, resulting in 28 pregnancies (27 %), 20 births (71 %) and 8 miscarriages (29 %). The implantation rate in the euploid group was 19 vs. 13 % in the not detected group (n.s.). This trend was the same independent of age and embryo morphology. The pregnancy rate does not differ significantly from the national average. The trend in better implantation rates of euploid oocytes justifies a continuation of studies in this matter.
    Archives of Gynecology 07/2013; · 0.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The progesterone-receptor (PR) antagonists onapristone (type I) and mifepristone (type II) showed modest activity in hormone-receptor-positive breast cancer; however, onapristone in particular was associated with hepatotoxicity. Lonaprisan is a novel, type III PR antagonist that was well tolerated in phase I studies. This randomized, open-label, phase II study evaluated the efficacy and tolerability of lonaprisan as second-line endocrine therapy in postmenopausal women with stage IV, PR-positive, HER2-negative, metastatic breast cancer. Patients received once-daily lonaprisan 25 mg (n = 34) or 100 mg (n = 34). The primary objective was not met (≥35% clinical benefit rate: complete/partial responses at any time until month 6 or stable disease [SD] for ≥6 months from start of treatment). There were no complete/partial responses. In the 25 mg and 100 mg groups, 6 of 29 patients (21%) and 2 of 29 patients (7%), respectively, had SD ≥6 months. Overall, 61 of 68 patients (90%) had ≥1 adverse event (AE), the most frequent (≥10% overall) being fatigue, hot flush, dyspnoea, nausea, asthenia, headache, constipation, vomiting, and decreased appetite; 33 patients had serious AEs. Lonaprisan showed limited efficacy as second-line endocrine therapy in postmenopausal women with PR-positive metastatic breast cancer.
    Annals of Oncology 06/2013; · 7.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland. The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year's St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.
    Breast Care 06/2013; 8(3):221-9. · 0.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Objective: We investigated the prognostic relevance of ultrasound visibility of distendend jugular lymphatic sacs (JLS) in fetuses with aberrant karyotypes in First-trimester-screening. Furthermore we tried to differentiate between increased nuchal translucency (NT) and cystic hygroma colli. Methods: We performed a retrospective single center study in 1874 patients presenting for First-trimester-screening between 2009 and 2013. All fetuses with an abnormal risk calculation and NT> 2.5 mm (95th percentile) were reviewed for ultrasound visibility of JLS. A group of 30 fetuses with normal risk calculation served as control. Karyotyping was performed by chorionic-villi-sampling or amniocentesis, respectively. Results: In a total of 2030 fetuses 70 (3.44%) with pathologic first-trimester-screening results showed either aberrant karyotypes or severe ultrasound pathologies. Main aberrant karyotypes were trisomy 21 (25), trisomy 18 (16), trisomy 13(6), Monosomy X (4), 47, XYY or 47,XXX (3) and Noonan`syndrome (2). Distended JLS were visible in 47% of all cases. Statistical anaylsis found a significant correlation between NT and JLS size for the fetuses with trisomies 21, 18 and 13 (r = 0,53, P < 0.002) Cystic hygroma colli was present in all Turner and Noonan syndromes. Conclusions: Distended JLS have a strong correlation with abnormal karyotypes and increased nuchal translucency. Karyotyping should be offered in these cases.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 05/2013; · 1.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die individualisierte Therapie des Mammakarzinoms hat in den vergangenen Jahren große Fortschritte gemacht. Neben der Chemotherapie sind zielgerichtete Therapien, beispielsweise die Blockade des HER2-Rezeptor-Signaltransduktionsweges, wesentliche Bestandteile einer erfolgreichen Therapie. Dennoch werden immer noch viele Patientinnen einer Chemotherapie unterzogen, von der sie vielleicht gar nicht profitieren. Die Abgrenzung zwischen einem hohen und niedrigen Rezidivrisiko ist mit den klassischen histologischen Parametern zwar möglich, doch die Gruppe der Patientinnen mit intermediärem Risiko ist unakzeptabel groß. Für dieses Kollektiv ist der Nutzen einer Chemotherapie nicht immer eindeutig erkennbar. Im Einzelfall muss auch hier immer die Frage gestellt werden, wann das individuelle Rezidivrisiko so groß ist, daß eine Chemotherapie gerechtfertigt ist. In dieser Übersichtsarbeit stellen wir die Klassifikation der intrinsischen Subtypen des Mammakarzinoms vor und beschreiben die Einsatzgebiete der zurzeit kommerziell verfügbaren molekularen Tests zur Prädiktion eines Therapieansprechens und Prognose des Mammakarzinoms.
    Der Gynäkologe 05/2013; 46(6).
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: STUDY OBJECTIVE: To evaluate 3 therapy strategies: hormone therapy, surgery, and combined treatment. DESIGN: Prospective, randomized, controlled study (Canadian Task Force classification I). SETTING: University-based teaching hospital. PATIENTS: Four hundred fifty patients with genital endometriosis, aged 18 to 44 years, before first laparoscopy. INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatment groups: hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focussed on the endometriosis stage, recurrence of symptoms, and pregnancy rate. MEASUREMENTS AND MAIN RESULTS: All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of ≥50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options. CONCLUSION: In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery. The highest cure rate (Endoscopic Endometriosis Classification stage 0) for endometriosis was also achieved in the combined treatment group.
    Journal of Minimally Invasive Gynecology 04/2013; · 1.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background/Aim: The tumor microenvironment plays a major role in tumor growth and progression. Its manipulation can lead to a reversion of the malignant phenotype. Here we explored the ability of normal mammary fibroblasts (HMFs) to induce reversion of the malignant phenotype of primary breast carcinoma cells (PBCs) in a three-dimensional (3D) context. PBCs were isolated from 13 primary breast carcinomas and cultured in 3D collagen-I gels as mono- or co-culture with HMFs. In five co-cultures, PBCs exhibited reversion of their malignant phenotype, whereas PBCs in matched monocultures exhibited disorganized growth. Reversion, defined as the restoration of the complete baso-apical polarity axis, was confirmed with established polarity markers. Secretion of the tissue-specific glycoprotein MAM-6 into the acinar lumens and deposition of basement membrane indicated functional differentiation. Gene expression analysis revealed a set of differentially regulated genes which possibly affect the reversion process. These included MAL, ELF5, MAP6, ZMYND11 and SQLE. These findings highlight the significant role of fibroblasts in regulating the carcinoma phenotype.
    Anticancer research 04/2013; 33(4):1525-36. · 1.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: A substantial number of breast cancer patients are identified as being at high risk of developing metastatic disease. With increasing number of targeted therapeutics entering clinical trials, chronic administration of these agents may be a feasible approach for the prevention of metastases within this subgroup of patients. In this preclinical study we examined whether Sunitinib, a multi-tyrosine kinase inhibitor which has anti-angiogenic and anti-resorptive activity, is effective in the prevention of bone metastases. METHOD: Sunitinib was administered daily with the first dose commencing prior to tumor cell inoculation. Intracardiac injection was performed with MDA-MB23 bone-seeking cells, which were stably transfected with DsRed2. In vivo plain radiography and fluorescent imaging (Berthold NightOwl) was used in the analysis of bone metastases. Histomorphometry was used for the quantification of TRAP+ cells from bone sections and immunohistochemistry was performed using an antibody reactive to CD34 for quantification of microvessel density. RESULTS: Preventive dosing administration of Sunitinib does not inhibit colonization of tumor cells to bone or reduce the size of osteolytic lesions. There was a decrease in the number of TRAP+ cells with Sunitinib treatment but this did not reach significance. Sunitinib inhibited tumor growth as determined by imaging of fluorescent tumor area. Immunohistochemical analyses of microvessel density revealed a concomitant decrease in the number of tumor blood vessels. CONCLUSIONS: The findings suggest that Sunitinib can be used as a therapeutic agent for the treatment of bone metastases but as a single agent it is not effective in terms of prevention. Therefore a combination approach with other cytostatic drugs should be pursued.
    BMC Cancer 01/2013; 13(1):32. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Breast cancer screening programs have been established worldwide and early detection of breast cancer has increased steadily. The most common way to confirm dignity of non-palpable and sonographically-occult suspicious findings on mammography is the stereotactically-guided vacuum-assisted breast biopsyPurposeTo compare two stereotactically guided vacuum-assisted breast biopsy systems measuring time effectiveness and quality of harvested material in clinical practice.Material and Methods One hundred and forty-six patients presenting with suspicious microcalcifications on mammography were included in the study. Biopsies were carried out with either the Mammotome(®) system (11-gauge and 8-gauge) or the ATEC(®) system (12-gauge and 9-gauge). Lesions with a diameter <15 mm on mammography were biopsied with 11-gauge or 12-gauge devices whereas lesions >15 mm were targeted with 8-gauge and 9-gauge. Mammotome(®) system 8-gauge device was used in 34 patients, the 11-gauge system in 37 patients. The ATEC(®) system 9-gauge system was used in 37 patients and 12-gauge in 38 patients. Time was taken, focusing on preparing the system, time of collecting the samples, preparing the samples, and cleaning the site. During the biopsies 24 samples were taken. The histologic quality of the tissue samples was judged by a pathologist in a blinded fashion according to a specimen grading classification concerning tissue fragmentation, artefacts, and the adequacy of the tissue for diagnosis.ResultsThe median overall time for the Mammotome(®) system was 879 s (11-gauge) and 934 s (8-gauge) and for the ATEC(®) system 671 s (12-gauge) and 673 s (9-gauge). The ATEC(®) system displays a significantly shorter overall time for small and large biopsy devices (U-test, P < 0.001). Concerning the mean time difference of the overall time comparing small and large systems the ATEC(®) system was 267.6 s faster using the small and 244.8 s faster using the large system. Comparing the histologic quality of tissue samples the Mammotome(®) system shows significantly higher values for the large and the small system (Chi-square test, P < 0.001).Conclusion Both biopsy systems meet all requirements for daily practice and confirm the diagnosis of suspicious microcalcifications. The ATEC(®) system was observed to be faster but this difference of about 250 s might not be relevant in daily practice. The Mammotome(®) system provides a better histologic quality of tissue samples.
    Acta Radiologica 01/2013; · 1.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die Angiogenese bezeichnet die Neubildung von Blutgefäßen, die durch Sprossungs- oder Spaltungsvorgänge des Gefäßsystems entstehen. Solide Tumoren sind in ihrem Wachstum von einem sie umgebenden mitwachsenden Kapillarnetz abhängig, das den Tumor mit Nährstoffen und Sauerstoff versorgt. Die pathophysiologische Rolle der Angiogenese ist für viele benigne (Endometriose, Menorrhagie, Leiomyomatose, ovarielles Überstimulationssyndrom, Präeklampsie und plazentares Hypoperfusionssyndrom) und maligne (vor allem das metastasierte und therapierefraktäre Mammakarzinom, das Ovarialkarzinom, das Tubenkarzinom sowie das primäre peritoneale Karzinom) gynäkologischen Erkrankungen nachgewiesen. Angiogeneseabhängige Erkrankungen können mit Hilfe antiangiogenetisch wirksamer Therapeutika behandelt werden. Aufgrund der substantiellen Nebenwirkungen dieser oft nur in Kombination mit einer klassischen Chemotherapie wirksamen Medikamente ist der Einsatz etablierter Angiogeneseinhibitoren ausgewählten, meist malignen Ekrankungsbildern vorbehalten. Zu diesen zählen vor allem das metastasierte und therapierefraktäre Mammakarzinom, das Ovarialkarzinom, das Tubenkarzinom und das primäre peritoneale Karzinom. Die Arbeit gewährt einen Überblick über den Kenntnisstand in der antiangiogenetischen Behandlung in der Gynäkologie und über potenzielle weitere Einsatzmöglichkeiten neuer Medikamente in diesem Zusammenhang.
    Der Gynäkologe 01/2013; 46(1).

Publication Stats

5k Citations
944.49 Total Impact Points


  • 2006–2014
    • University Medical Center Schleswig-Holstein
      • Department of Pediatrics
      Kiel, Schleswig-Holstein, Germany
    • German Breast Group
      Neulsenburg, Hesse, Germany
  • 2004–2013
    • Universitätsklinikum Schleswig - Holstein
      • Klinik für Gynäkologie und Geburtshilfe (Kiel)
      Kiel, Schleswig-Holstein, Germany
  • 1997–2013
    • Christian-Albrechts-Universität zu Kiel
      • • Institute of Phytopathology
      • • Department of Gynecology
      Kiel, Schleswig-Holstein, Germany
  • 2009
    • Asklepios Klinik Barmbek
      Hamburg, Hamburg, Germany
    • Klinikum Frankfurt (Oder) GmbH
      Frankfort on the Oder, Brandenburg, Germany
    • University Hospital RWTH Aachen
      Aachen, North Rhine-Westphalia, Germany
  • 2005–2008
    • HELIOS Klinik Kiel
      Kiel, Schleswig-Holstein, Germany
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
    • Bayerisches Landesamt für Umwelt
      Augsberg, Bavaria, Germany
    • University Hospital München
      München, Bavaria, Germany
  • 2003–2008
    • Goethe-Universität Frankfurt am Main
      • Department of Gynecology and Obstetrics
      Frankfurt am Main, Hesse, Germany
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdam, North Holland, Netherlands
  • 1975–2008
    • University of Hamburg
      • • Department of Stem Cell Transplantation
      • • Center for Internal Medicine
      • • Department of Human Genetics
      Hamburg, Hamburg, Germany
  • 1975–2006
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 1981–2004
    • West Georgia Obstetrics and Gynecology
      Georgetown, Georgia, United States
  • 2002–2003
    • Technische Universität München
      München, Bavaria, Germany
  • 2001
    • Keio University
      • Department of Surgery
      Tokyo, Tokyo-to, Japan
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 1998
    • Deutsche Gesellschaft für Gynäkologie und Geburtshilfe e.V.
      Kiel, Schleswig-Holstein, Germany
  • 1989
    • Eppendorf Deutschland
      Hamburg, Hamburg, Germany
    • Hochschule Hannover
      Hanover, Lower Saxony, Germany
  • 1985
    • Philipps University of Marburg
      Marburg, Hesse, Germany
  • 1981–1985
    • Hochschule Bremen
      Bremen, Bremen, Germany