Cancer treatment and the ovary - The effects of chemotherapy and radiation
ABSTRACT Certain chemotherapeutic drugs ("alkylators") and radiation therapy are toxic to the ovaries, leading to both loss of sex steroid hormone production and infertility. Higher doses and older age at treatment are both associated with greater damage. Even patients with spontaneous menstrual cycles have evidence of decreased ovarian potential. Adolescents who are treated for cancer with these agents should be counseled about future fertility risks.
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- "Disease, senescence and radio-and chemotherapy for cancer treatment can result in the complete loss of female reproductive capacity and premature ovarian failure, especially when alkylating drugs and pelvic radiation are involved (Larsen et al., 2003; Wallace and Thomson, 2003; Agarwal and Chang, 2007; Cohen, 2008; Oktem and Oktay, 2009). In order to preserve fertility, there is a demand to improve cryopreservation and follicle culture, and assess safety of cryopreservation for oocyte health and genomic integrity (Gook and Edgar, 2007; Amorim et al., 2009; Smitz et al., 2010). "
ABSTRACT: Cryopreservation of follicles for culture and oocyte growth and maturation in vitro provides an option to increase the number of fertilizable oocytes and restore fertility in cases where transplantation of ovarian tissue poses a risk for malignant cell contamination. Vitrification for cryopreservation is fast and avoids ice crystal formation. However, the influences of exposure to high concentrations of cryoprotectants on follicle development, oocyte growth and maturation, and particularly, on the DNA integrity and methylation imprinting has not been studied systematically. Follicle survival and development, DNA damage, oocyte growth patterns, maturation, spindle formation and chromosomal constitution were studied after Cryo-Top vitrification of mouse pre-antral follicles cultured to the antral stage and induced to ovulate in vitro. Methylation of differentially methylated regions (DMRs) of two maternally (Snrpn and Igf2r) and one paternally (H19) imprinted genes was studied by bisulfite pyrosequencing. Vitrification results in partial or total loss of oocyte-granulosa cell apposition and actin-rich transzonal projections, a transient increase in DNA breaks and a delay in follicle development. However, the oocyte growth pattern, maturation, spindle and chromosomal constitution are not significantly different between the vitrified and the control groups. Vitrification is not associated with elevated levels of imprinting mutations (aberrant methylation of the entire DMR), although the distribution of sporadic CpG methylation errors in the Snrpn DMR appears to differ slightly between control and vitrified oocytes. DNA breaks appear to be rapidly repaired and vitrification of oocytes inside pre-antral follicles by the Cryo-Top method does not appear to increase risks of abnormal imprinting or disturbances in spindle formation and chromosome segregation.Human Reproduction 10/2010; 25(12):3025-42. DOI:10.1093/humrep/deq278 · 4.59 Impact Factor
- Cancer 01/1964; 16(12):1578-83. DOI:10.1002/1097-0142(196312)16:12<1578::AID-CNCR2820161209>3.0.CO;2-K · 4.90 Impact Factor
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ABSTRACT: A majority of ovarian cancer metastases result from the shedding of malignant cells from the primary tumor into the abdominal cavity. Free-floating cancer cells in serous effusions of late-stage ovarian cancer patients may spread to internal organs, making effective treatment extremely difficult. Selective removal of ovarian cancer cells from serous fluids may abate metastasis and improve long-term prognoses. We have already shown that superparamagnetic nanoparticles conjugated to an ephrin-A1 mimetic peptide with a high affinity for the EphA2 receptor can be used to capture and remove cultured human ovarian cancer cells from the peritoneal of experimental mice. Here we demonstrate the potential clinical utility of the methodology by in vitro capture and isolation of cancer cells from the ascites fluid of ovarian cancer patients. FROM THE CLINICAL EDITOR: Ovarian cancer metastases usually are the result of shedding of malignant cells from the primary tumor into the abdominal cavity. In this paper, a novel nanotechnology-based method is demonstrated for the in vitro capture and isolation of cancer cells from the ascites fluid of ovarian cancer patients.Nanomedicine: nanotechnology, biology, and medicine 12/2009; 6(3):399-408. DOI:10.1016/j.nano.2009.11.003 · 5.98 Impact Factor