Only complete resection was associated with prolonged survival in recurrent ovarian cancer. The identified criteria panel will be verified in a prospective trial (AGO-DESKTOP II) evaluating whether it will render a useful tool for selecting the right patients for cytoreductive surgery in recurrent ovarian cancer.

IntroductionIn the classical view, activation of factor XII (FXII, Hageman factor) is thought to initiate the intrinsic coagulation pathway by triggering the contact phase system. In this scenario, contact of mammalian plasma with negatively charged surfaces ("contact phase") induces (auto)activation of FXII, possibly due to an allosteric activation and limited proteolysis of the zymogen in the presence of Zn 2+ . The activated serine protease, FXIIa, then cleaves plasma prekallikrein and generates active plasma kallikrein which in turn cleaves and activates FXII to FXIIa, leading to a local burst of protease activity at the surface. At this point, the signaling pathway branches: plasma kallikrein cleaves H-kininogen and liberates bradykinin triggering the NO/cGMP pathway, whereas FXIIa is thought to initiate and enhance fibrin clot formation via factors XI and IX (1, 2). Conversely, activation of FXII may also induce fibrinolysis either directly through the activation of plasminogen or matings of FXII -/-males and FXII -/-females resulted in normal litter sizes demonstrating that total FXII deficiency in FXII -/-females does not affect pregnancy outcome. Also, gross and histological anatomy of FXII -/-mice was indistinguishable from that of their wild-type littermates on both genetic backgrounds. Thus it appears that deficiency of murine FXII does not cause thrombophilia or impaired fibrinolysis in vivo. These results indicate that FXII deficiency does not affect hemostasis in vivo and we anticipate that the FXII -/-mice will be helpful to elucidate the biological role(s) of FXII in health and disease. Keywords Coagulation, factor XII, gene targeting SummaryTo analyze the biological role of factor XII (FXII, Hageman Factor) in vivo, we generated mice deficient for FXII using a gene targeting approach on two distinct genetic backgrounds, i.e. mixed C57Bl/6J X 129X1/SvJ and inbred 129X1/SvJ. Homozygous FXII knockout (FXII -/-) mice showed no FXII plasma activity and had a markedly prolonged activated partial thromboplastin time (aPTT). In contrast, coagulation factors XI, VIII, IX, X,VII,V, II and fibrinogen did not differ between FXII -/-mice and their wild-type littermates. Heterozygous matings segregated according to the Mendelian inheritance indicating that FXII deficiency does not increase fetal loss. Furthermore,

AEZS-108 is a cytotoxic analog designed for receptor-mediated targeted chemotherapy and consists of an LHRH carrier linked to doxorubicin. Preclinical studies demonstrate that the uptake of AEZS-108 is achieved by receptor-mediated endocytosis. Results of Phase I and II clinical trials in patients with gynecological cancers demonstrated anticancer activity without cardiotoxicity even in highly pretreated patients. Phase I/II studies in castration-resistant prostate cancer and chemotherapy refractory bladder cancer are in progress. Targeted chemotherapy with a cytotoxic analog of LHRH, such as AEZS-108, is therefore being considered for Phase III studies in advanced endometrial cancers positive for LHRH receptor. LHRH receptors are also present in human colon cancers, melanomas, lymphomas, and sarcomas, and treatment of these cancers with AEZS-108 should also be undertaken. Before such treatment with AEZS-108 is begun, the status of tumoral LHRH receptors of patients must be determined.

NCT 00567554, www.clinicaltrials.gov.

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