Dexrazoxane abrogates acute doxorubicin toxicity in marmoset ovary.

Preservation of ovarian function following chemotherapy for nonovarian cancers is a formidable challenge. For prepubescent girls, the only option to prevent chemotherapy damage to the ovary is ovarian tissue cryopreservation, an experimental procedure requiring invasive surgeries to harvest and reimplant tissue, which carries the risk of cancer reintroduction. Drugs that block the primary mechanism of chemotherapy insult, such as dexrazoxane (Dexra) in the context of anthracycline chemotherapy, provide a novel approach for ovarian protection and have the potential to overcome current limitations to oncofertility treatment. Dexra is a catalytic topoisomerase 2 inhibitor that protects the mouse ovary from acute doxorubicin (DXR) chemotherapy toxicity in vitro by preventing DXR-induced DNA damage and subsequent gammaH2AX activation. To translate acute DXR ovarian insult and Dexra protection from mouse to nonhuman primate, freshly obtained marmoset ovarian tissue was cultured in vitro and treated with vehicle or 20 µM Dexra 1 h prior to 50 nM DXR. Cultured ovarian tissue was harvested at 2, 4, or 24 h post-DXR treatment. Dexra prevented DXR-induced DNA double-strand breaks as quantified by the neutral comet assay. DXR treatment for 24 h increased gammaH2AX phosphorylation, specifically increasing the number of foci-positive granulosa cells in antral follicles, while Dexra pretreatment inhibited DXR-induced gammaH2AX phosphorylation foci formation. Additionally, Dexra pretreatment trended toward attenuating DXR-induced AKT1 phosphorylation and caspase-9 activation as assayed by Western blots of ovarian tissue lysates. The combined findings suggest Dexra prevents primary DXR-induced DNA damage, the subsequent cellular response to DNA damage, and may diminish early apoptotic signaling in marmoset ovarian tissue. This study provides initial translation of Dexra protection against acute ovarian DXR toxicity from mice to marmoset monkey tissue.

Challenges of Fertility Sparing Ovarian Surgery Imposed by Krukenberg Tumors in Pregnancy.

Fertility sparing surgery is advocated for reproductive-age women with benign and borderline ovarian tumors. The hormonal milieu of pregnancy may, however, complicate the decision making process. The patient presented in the third trimester with a rapidly growing tumor that was diagnosed as benign steroid cell tumor by intraoperative frozen section. Fertility-sparing surgery with right oophorectomy and partial left oophorectomy was performed. The final pathology examination demonstrated signet cells staining positive for mucin, which is pathognomonic for Krukenberg tumors. Krukenberg cells were overlooked in the frozen section due to the predominance of hormonally active luteinized ovarian stroma cells. This case highlights the challenges associated with fertility sparing surgery in women presenting with ovarian tumors in pregnancy and the limitations of frozen section in providing an accurate diagnosis.