T. Hawighorst

Universitätsmedizin Göttingen, Göttingen, Lower Saxony, Germany

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Publications (59)176.53 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: Background We have previously reported stromal upregulation of the endogenous angiogenesis inhibitor thrombospondin-2 (TSP-2) during multistep carcinogenesis, and we found accelerated and enhanced skin angiogenesis and carcinogenesis in TSP-2 deficient mice. Goals: To investigate whether enhanced levels of TSP-2 might protect from skin cancer development. Methods We established transgenic mice with targeted overexpression of TSP-2 in the skin and subjected hemizygous TSP-2 transgenic mice and their wild-type littermates to a chemical skin carcinogenesis regimen. Results TSP-2 transgenic mice showed a significantly delayed onset of tumor formation compared to wild-type mice, whereas the ratio of malignant conversion to squamous cell carcinomas was comparable in both genotypes. Computer-assisted morphometric analysis of blood vessels revealed pronounced tumor angiogenesis already in the early stages of carcinogenesis in wild type mice. TSP-2 overexpression significantly reduced tumor blood vessel density in transgenic mice but had no overt effect on LYVE-1 positive lymphatic vessels. The percentage of desmin surrounded, mature tumor-associated blood vessels and the degree of epithelial differentiation remained unaffected. The antiangiogenic effect of transgenic TSP-2 was accompanied by a significantly increased number of apoptotic tumor cells in transgenic mice. Conclusion Our results demonstrate that enhanced levels of TSP-2 in the skin result in reduced susceptibility to chemically-induced skin carcinogenesis and identify TSP-2 as a new target for the prevention of skin cancer.
    No preview · Article · May 2014 · Journal of dermatological science
  • Nina Bock · M. Sigler · LS Meier · G. Emons · T. Hawighorst
    No preview · Article · Feb 2012 · Der Gynäkologe
  • Source
    N. Bock · M. Sigler · L.S. Maier · G. Emons · T. Hawighorst
    [Show abstract] [Hide abstract] ABSTRACT: Kardiologische Erkrankungen in der Schwangerschaft haben großen Einfluss auf die maternale und perinatale Morbidität und Mortalität. Sie führen in westlichen Industrieländern bei 0,2–4% aller Schwangerschaften zu Komplikationen. Die meisten Herzerkrankungen sind kongenitalen Ursprungs, etwa ein Viertel ist erworben. Die Anzahl der Patientinnen mit kardiovaskulären Problemen in der Schwangerschaft nimmt zu. Gründe sind einerseits die verbesserten Behandlungsoptionen bei angeborener Herzerkrankung, wodurch mehr Erkrankte ein reproduktives Alter erreichen, andererseits die steigende Prävalenz an kardiovaskulären Risikofaktoren, wie Diabetes, Übergewicht und Bluthochdruck. Aufgrund der kardiovaskulären Adaptation in der Schwangerschaft entsteht eine zusätzliche kardiale Belastung. Durch eine adäquate interdisziplinäre Betreuung von Risikopatientinnen in einem entsprechenden Zentrum kann die Morbidität und Mortalität, die mit kardiovaskulären Erkrankungen während der Schwangerschaft assoziiert ist, deutlich gesenkt werden.
    Full-text · Article · Feb 2012 · Der Gynäkologe
  • Source
    Antje Schubert · Thomas Hawighorst · Günter Emons · Carsten Gründker
    [Show abstract] [Hide abstract] ABSTRACT: Metastasis to bone is a frequent problem of advanced breast cancer. Particularly breast cancers, which do not express estrogen and progesterone receptors and which have no overexpression/amplification of the HER2-neu gene, so called triple-negative breast cancers, are considered as very aggressive and possess a bad prognosis. About 60% of all human breast cancers and about 74% of triple-negative breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a therapeutic target. Recently, we could show that bone-directed invasion of human breast cancer cells in vitro is time- and dose-dependently reduced by GnRH analogs. In the present study, we have analyzed whether GnRH analogs are able to reduce metastases of triple-negative breast cancers in vivo. In addition, we have evaluated the effects of GnRH analogs on tumor growth. To quantify formation of metastasis by triple-negative MDA-MB-435 and MDA-MB-231 human breast cancers, we used a real-time PCR method based on detection of human-specific alu sequences measuring accurately the amount of human tumor DNA in athymic mouse organs. To analyze tumor growth, the volumes of breast cancer xenotransplants into nude mice were measured. We could demonstrate that GnRH analogs significantly reduced metastasis formation by triple-negative breast cancer in vivo. In addition, we could show that GnRH analogs significantly inhibited the growth of breast cancer into nude mice. Side effects were not detectable. In conclusion, GnRH analogs seem to be suitable drugs for an efficacious therapy for triple-negative, GnRH receptor-positive human breast cancers to prevent metastasis formation.
    Full-text · Article · Dec 2011 · Breast Cancer Research and Treatment
  • Werner Stein · Thomas Hawighorst · Paul Wenzlaff · Günter Emons
    [Show abstract] [Hide abstract] ABSTRACT: To analyze the relationship of the time interval between two deliveries, done by one obstetric team, on the delivery mode of the subsequent birth; to define the length of this interval; and to evaluate this time interval as a risk factor for increased perinatal mortality in a population-based cohort. All singleton deliveries at ≥ 24 weeks' gestation in Lower Saxony, Germany, between 2001 and 2005 (a total of 317,663 deliveries including 402 cases of perinatal mortality) were analyzed. The mode of the previous and the subsequent delivery, the time interval between the two deliveries, the time of birth, the hospital volume, and the existence of an affiliated neonatal ward were investigated. When the first vaginal delivery was <45 min, there was a reduced probability that the subsequent birth would be a cesarean section. In case of a previous cesarean section, the cesarean rate of the following birth was influenced up to 165 min. In a multivariate analysis, vaginal deliveries following an earlier vaginal birth and occurring within <45 min were associated with increased perinatal mortality. Repeated cesarean sections within <165 min were associated with increased perinatal mortality when occurring at night or on weekends. A short time interval between two deliveries in an obstetric unit constitutes an independent risk factor for perinatal mortality.
    No preview · Article · Nov 2011 · Journal of Perinatal Medicine
  • G. Emons · T. Hawighorst · M. Hellriegel
    [Show abstract] [Hide abstract] ABSTRACT: Das Endometriumkarzinom (EC) ist in Deutschland die vierthäufigste Krebsart bei Frauen. Es wird meist in einem frühen Stadium (pT1a, neue Klassifikation) und mit günstiger Histologie (endometrioid, G1, G2) symptomatisch. Hier ist die einfache Hysterektomie mit beidseitiger Adnexexstirpation eine sehr erfolgreiche Therapie. Bei höheren Stadien, höherem Grading und bei Typ-2-Karzinomen (serös, klarzellig) wird die zusätzliche pelvine und paraaortale Lymphonodektomie sowie, zur Verbesserung der lokalen Kontrolle, eine adjuvante Strahlentherapie empfohlen. Oft ist eine vaginale Brachytherapie ausreichend. Bei EC mit hohem Risiko für Fernmetastasen (G3, Typ 2 sowie in den Stadien III und IV) ist eine adjuvante platinhaltige Chemotherapie, ggf. in Kombination mit einer Strahlentherapie, sinnvoll. Diese Empfehlungen müssen jedoch in randomisierten Studien evaluiert werden.
    No preview · Article · Sep 2011 · Der Gynäkologe
  • T Hawighorst · K Frontzek · M Rave-Fränk · A Hille · C Gründker · G Emons
    No preview · Article · Aug 2011 · Geburtshilfe und Frauenheilkunde
  • Source
    [Show abstract] [Hide abstract] ABSTRACT: Thus far the clinical benefits seen in breast cancer patients treated with drugs targeting the vascular endothelial growth factor (VEGF) pathway are only modest. Consequently, additional antiangiogenic approaches for treatment of breast cancer need to be investigated. Thrombospondin-2 (TSP-2) has been shown to inhibit tumor growth and angiogenesis with a greater potency than the related molecule TSP-1. The systemic effects of TSP-2 on tumor metastasis and the underlying molecular mechanisms of the antiangiogenic activity of TSP-2 have remained poorly understood. We generated a recombinant fusion protein consisting of the N-terminal region of TSP-2 and the IgG-Fc1 fragment (N-TSP2-Fc) and could demonstrate that the antiangiogenic activity of N-TSP2-Fc is dependent on the CD36 receptor. We found that N-TSP2-Fc inhibited VEGF-induced tube formation of human dermal microvascular endothelial cells (HDMEC) on matrigel in vitro and that concurrent incubation of anti-CD36 antibody with N-TSP2-Fc resulted in tube formation that was comparable to untreated control. N-TSP2-Fc potently induced apoptosis of HDMEC in vitro in a CD36-dependent manner. Moreover, we could demonstrate a CD36 receptor-mediated loss of mitochondrial membrane potential and activation of caspase-3 in HDMEC in vitro. Daily intraperitoneal injections of N-TSP2-Fc resulted in a significant inhibition of the growth of human MDA-MB-435 and MDA-MB-231 tumor cells grown in the mammary gland of immunodeficient nude mice and in reduced tumor vascularization. Finally, increased serum concentrations of N-TSP2-Fc significantly inhibited regional metastasis to lymph nodes and distant metastasis to lung as shown by quantitative real-time alu PCR. These results identify N-TSP2-Fc as a potent systemic inhibitor of tumor metastasis and provide strong evidence for an important role of the CD36 receptor in mediating the antiangiogenic activity of TSP-2.
    Full-text · Article · Jul 2011 · Breast Cancer Research and Treatment
  • S Wand · R M Waeschle · N Von Ahsen · T Hawighorst · A Bräuer · M Quintel
    [Show abstract] [Hide abstract] ABSTRACT: Acute fatty liver of pregnancy (AFLP) is a rare but serious liver disease and typically occurs during the third trimester. It carries the risk for significant perinatal and maternal mortality. Therefore an early diagnosis and delivery, followed by close monitoring and optimized management of the impaired liver function with all associated problems are necessary to prevent maternal and foetal death. This case report focuses on the management of acute liver failure due to AFLP in a 31 year old women treated in our intensive care unit (ICU) after an emergency C-section.
    No preview · Article · Jun 2011 · Minerva anestesiologica
  • T. Hawighorst · W. Stein · C. Gründker · G. Emons
    [Show abstract] [Hide abstract] ABSTRACT: Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. The formation of new blood vessels is a normal and vital process in growth and development. The switch to the angiogenic phenotype is induced by a change in the balance of positive and negative regulators of angiogenesis. Angiogenesis plays an important role in the regulation of the female menstrual cycle. In prenatal medicine the formation of blood vessels is also significant for implantation and for the development of the placenta. The regulation of angiogenetic processes is defective in many gynecological and obstetric diseases (e.g. ovarian hyperstimulation syndrome, endometriosis and preeclampsia). Angiogenesis also plays an important role in the growth and metastasization of malignant tumors. Inhibition of tumor angiogenesis has become the focus of new treatment strategies. The efficacy of the anti-angiogenic antibody bevacizumab in the treatment of metastatic breast cancer has been demonstrated. This article gives an overview of the role of angiogenesis in the female reproductive system and in gynecological oncology with the main focus on the clinical significance.
    No preview · Article · Jul 2010 · Der Gynäkologe
  • C. Gründker · T. Hawighorst · G. Emons
    [Show abstract] [Hide abstract] ABSTRACT: In den letzten Jahren wurden zahlreiche Hinweise für die Existenz von Stammzellen in Tumoren gefunden. Die Tumorstammzelltheorie besagt, dass Tumoren sich aus einer Subpopulation maligner Zellen entwickeln, die Stammzellcharakteristika aufweisen. Diese Zellen zeigen sowohl Züge von Stammzellen als auch von Tumorzellen. So besitzen sie die Fähigkeit zu Selbsterneuerung, asymmetrischer Zellteilung und unabhängigem Wachstum, zeigen Resistenz gegenüber Apoptoseinduktion, sind tumorigen und haben metastatisches Potenzial. Die Entwicklung aus Tumorstammzellen könnte die Heterogenität von Tumoren eines Gewebes sowie Rezidive nach Therapie erklären. In diesem kurzen Überblicksbeitrag berichten wir über den Fortschritt in der Erforschung von Tumorstammzellen, dabei liegt der Schwerpunkt auf gynäkologische Tumoren einschließlich des Mammakarzinoms. In recent years numerous indications for the existence of stem cells in tumors have been found. The cancer stem cell theory means that cancers develop from a subset of malignant cells which exhibit characteristics of both stem cells and cancer cells. They possess the ability of self-renewal, asymmetric cell division and independent growth, show resistance to induction of apoptosis, tumorigenicity and metastatic potential. The development from cancer stem cells could explain both the heterogeneity of cancers of a tissue and the relapse of tumors after therapy. In this short review we report the progress in the research on cancer stem cells with an emphasis on gynecological tumors and breast cancer. SchlüsselwörterTumorstammzellen-Mammakarzinom-Ovarialkarzinom-Endometriumkarzinom KeywordsTumor stem cells-Breast cancer-Ovarian cancer-Endometrial cancer
    No preview · Article · Jul 2010 · Der Gynäkologe
  • T. Hawighorst · W. Stein · C. Gründker · G. Emons
    No preview · Article · Jan 2010
  • C. Gründker · T. Hawighorst · G. Emons
    No preview · Article · Jan 2010
  • W Stein · F Haller · T Hawighorst · G Emons
    No preview · Article · Dec 2009 · Ultraschall in der Medizin
  • T Hawighorst · F Hussein · C Gründker · G Emons
    No preview · Article · Sep 2009 · Geburtshilfe und Frauenheilkunde
  • G. Emons · T. Hawighorst · M. Hellriegel
    No preview · Article · Sep 2009 · Der Onkologe
  • G. Emons · T. Hawighorst · M. Hellriegel
    [Show abstract] [Hide abstract] ABSTRACT: For fertility-sparing, conservative therapy of low-grade endometrioid endometrial cancer of clinical stage IA, high-dose progestins, given for at least 3–6 months, are the treatment of choice. For adjuvant therapy of surgically treated patients with endometrial cancer that has a high risk of recurrence, endocrine therapies have so far shown no efficacy. Similarly, the available evidence for the efficacy of adjuvant chemotherapies is rather weak. In only one study with well-operated patients with stage III or IV endometrial cancer could it be shown that adjuvant chemotherapy had greater efficacy than percutaneous radiotherapy. For stages I and II, the efficacy of adjuvant chemotherapy (± brachytherapy ± percutaneous radiotherapy) remains to be evaluated. For relapsed or disseminated endometrial cancer that can no longer be controlled by surgical or radiotherapeutic measures, systemic therapy is indicated. For well-differentiated tumors that express estrogen and/or progesterone receptors and that are not immediately life-threatening, high-dose progestins (± tamoxifen) are the treatment of first choice. Only when tumors are resistant to endocrine treatment or are acutely life-threatening should chemotherapy be used. Because multiple drug regimens achieve, at best, only a marginal increase in overall survival but definitely have a marked increase in toxicity, monochemotherapies are preferred in such cases.
    No preview · Article · Sep 2009 · Der Onkologe
  • T. Hawighorst · F. Hussein · C. Gruendker · G. Emons
    No preview · Article · Aug 2009 · Geburtshilfe und Frauenheilkunde
  • G. Emons · M. Hellriegel · T. Hawighorst
    [Show abstract] [Hide abstract] ABSTRACT: Das Endometriumkarzinom wird meist im frühen Stadium symptomatisch und hat eine günstige Prognose. Die traditionelle Therapie bestand in der abdominalen Hysterektomie mit beidseitiger Adnexexstirpation. Hiermit werden die frühen, gut differenzierten Stadien (endometrioid, pT1a, pT1b; G1, G2) wahrscheinlich gut therapiert. Bei höheren Stadien, höherem Grading und vor allem bei den Typ-II-Karzinomen (serös, klarzellig) ist diese Therapie inadäquat. Der Nutzen einer systematischen pelvinen und paraaortalen Lymphonodektomie in dieser Situation muss jedoch prospektiv evaluiert werden. Eine perkutane Strahlentherapie des Beckens verbessert im Stadium I und II zwar die lokale Kontrolle, hat aber keinen positiven Effekt auf das Überleben. Eine vergleichbare Verbesserung der lokalen Kontrolle wird, bei erheblich weniger Nebenwirkungen, auch durch eine Brachytherapie der Scheide erreicht. Eine adjuvante Chemotherapie ist beim Endometriumkarzinom wahrscheinlich wirksam. Der Einsatz einer alleinigen adjuvanten Chemotherapie oder die Kombination mit Brachy- und/oder Teletherapie muss prospektiv evaluiert werden. Most cases of endometrial cancer (EC) become symptomatic at an early stage and have a good prognosis. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early stage, low grade cases (endometrioid, pT1a, pT1b; G1, G2) this is adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell) this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high risk EC, however, remains to be evaluated. External pelvic radiotherapy has been shown to improve local control in stage I and II EC, but has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam therapy remains to be evaluated by prospective trials.
    No preview · Article · Jul 2009 · Der Pathologe
  • G Emons · M Hellriegel · T Hawighorst
    [Show abstract] [Hide abstract] ABSTRACT: Most cases of endometrial cancer (EC) become symptomatic at an early stage and have a good prognosis. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early stage, low grade cases (endometrioid, pT1a, pT1b; G1, G2) this is adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell) this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high risk EC, however, remains to be evaluated. External pelvic radiotherapy has been shown to improve local control in stage I and II EC, but has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam therapy remains to be evaluated by prospective trials.
    No preview · Article · Jul 2009 · Der Pathologe

Publication Stats

2k Citations
176.53 Total Impact Points

Institutions

  • 2012
    • Universitätsmedizin Göttingen
      Göttingen, Lower Saxony, Germany
  • 2008-2009
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany
  • 2001
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2000
    • Massachusetts General Hospital
      • Department of Dermatology
      Boston, Massachusetts, United States