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Cryopreservation of ovarian tissue for fertility preservation should preferably be performed before the start of anti-cancer therapy. For many patients, however, ovarian tissue preservation is offered after some form of gonadotoxic medication has already been administered. Further, in cases of recurrent malignancies the ovarian tissue may not have been cryopreserved after the initial diagnosis. In this case study, we analyzed the viability of ovarian tissue collected for fertility preservation purposes from a 10-year-old Ewing sarcoma patient after chemotherapy. [ABSTRACT FROM AUTHOR]

The article discusses the safety issues involved in the autotransplantation or cryopreservation of ovarian tissues in cancer survivors. The author cites various studies in which there were no certainty over the risks of cancer cell detection in patients with ovarian cancer, leukemia, Ewing sarcoma and breast cancer. The possibility of an oncological relapse after cancer cell reintroduction via transplantation should cautions both patients and physicians.

Background: Upregulation of endogenous angiostatin levels may constitute a novel antiangiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs). Next, plasmin excises angiostatin from other plasmin molecules, a process requiring a donor of a free sulfhydryl group. In previous studies, it has been demonstrated that administration of PA in combination with the free sulfhydryl donor (FSD) agents captopril or N-acetyl cysteine, resulted in angiostatin generation, and anti-angiogenic and anti-tumour activity in murine models. Methods: In this study we have investigated the angiostatin generating capacities of several FSDs. D-penicillamine proved to be most efficient in supporting the conversion of plasminogen to angiostatin in vitro. Next, from the optimal concentrations of tPA and D-penicillamine in vitro, equivalent dosages were administered to healthy Balb/c mice to explore upregulation of circulating angiostatin levels. Finally, anti-tumor effects of treatment with tPA and D-penicillamine were determined in a human melanoma xenograft model. Results: Surprisingly, we found that despite the superior angiostatin generating capacity of Dpenicillamine in vitro, both in vivo angiostatin generation and anti-tumour effects of tPA/Dpenicillamine treatment were impaired compared to our previous studies with tPA and captopril. Conclusion: Our results indicate that selecting the most appropriate free sulfhydryl donor for anti-angiogenic therapy in a (pre)clinical setting should be performed by in vivo rather than by in vitro studies. We conclude that D-penicillamine is not suitable for this type of therapy. [ABSTRACT FROM AUTHOR]

Angiostatin, a proteolytic fragment of plasminogen consisting of the first 3 or 4 kringle domains, reduces tumor growth by specifically inhibiting tumor angiogenesis. Angiostatin is generated in vitro in a 2-step process. First, plasminogen is converted to plasmin by plasminogen activators. Next, plasmin excises the angiostatin fragment from plasminogen, a process requiring molecules that are able to donate a free sulfhydryl group. In this study, we investigated whether stimulation of in vivo angiostatin generation by administration of plasminogen activator and a free sulfhydryl group donor (FSD) has anti-tumor activity. First, we determined the optimal conditions for in vitro angiostatin generation by incubating murine plasma with different concentrations of plasminogen activator and/or the FSD captopril. Angiostatin generation was monitored by western blot analysis. Our results were extrapolated to the in vivo situation by administering the optimal dose of tissue-type plasminogen activator (tPA, i.v. injection 3 times/week) and captopril (in drinking water) to mice and analyzing the presence of angiostatin in the circulation. Angiostatin was readily detectable in mice receiving both tPA and captopril, but not in mice receiving either one of the agents. Finally, the anti-tumor activity of the tPA/captopril treatment was tested in a human melanoma xenograft model. Administration of tPA alone had only a marginal effect on tumor growth. Captopril alone reduced tumor growth by about 60%, whereas treatment with both captopril and tPA resulted in 83% inhibition of tumor growth. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]