Enhancing the safety of ovarian cortex autotransplantation: cancer cells are purged completely from human ovarian tissue fragments by pharmacological inhibition of YAP/TAZ oncoproteins

2018 ◽  
Vol 34 (3) ◽  
pp. 506-518 ◽  
Author(s):  
Callista L Mulder ◽  
Lotte L Eijkenboom ◽  
Catharina C M Beerendonk ◽  
Didi D M Braat ◽  
Ronald Peek
Keyword(s):  
Cancer Cells ◽  
Ovarian Tissue ◽  
Pharmacological Inhibition ◽  
Ovarian Cortex ◽  
Human Ovarian Tissue

scholarly journals Safety of Ovarian Tissue Autotransplantation for Cancer Patients

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Laurence Bockstaele ◽  
Sophie Tsepelidis ◽  
Julie Dechene ◽  
Yvon Englert ◽  
Isabelle Demeestere
Keyword(s):  
Cancer Cells ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Young Women ◽  
Premature Ovarian Failure ◽  
Ovarian Tissue ◽  
Malignant Cells ◽  
Cancer Treatments ◽  
Ovarian Cortex ◽  
Human Ovarian Tissue

Cancer treatments can induce premature ovarian failure in almost half of young women suffering from invasive neoplasia. Cryopreservation of ovarian cortex and subsequent autotransplantation of frozen-thawed tissue have emerged as promising alternatives to conventional fertility preservation technologies. However, human ovarian tissue is generally harvested before the administration of gonadotoxic treatment and could be contaminated with malignant cells. The safety of autotransplantation of ovarian cortex remains a major concern for fertility preservation units worldwide. This paper discusses the main tools for detecting disseminated cancer cells currently available, their limitations, and clinical relevance.

O-191 Assessing the use of tumour-specific DARPin-toxin fusion proteins for ex vivo purging of cancer metastases from human ovarian cortex tissue fragments before autotransplantation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Eijkenboom ◽  
V Palacio-Castañeda ◽  
F A Groenman ◽  
D D M Braat ◽  
C C M Beerendonk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Fusion Proteins ◽  
Breast Cancer Cells ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
In Vitro Growth ◽  
Ovarian Cortex ◽  
Positive Breast Cancer

Abstract Study question Is it possible to eradicate cancer cells from ovarian cortex by using tumour-specific designed ankyrin repeat protein (DARPin)-toxin fusion proteins, without compromising the ovarian tissue? Summary answer Purging ovarian cortex ex vivo from experimentally induced breast cancer tumour foci is possible by tumour-targeted DARPin-toxin fusion proteins trough inhibition of protein synthesis. What is known already Ovarian tissue cryopreservation and autotransplantation is a successful technique for fertility restoration in cancer patients. The procedure is not without risk since malignant cells may still be present in the graft. Procedures to detect cancer cells render the tissue fragment useless for autotransplantation. Strategies to circumvent this problem such as in vitro maturation of follicles or the construction of artificial ovaries are pursued but are still experimental. Alternatively, we have shown ex vivo purging of ovarian cortex is possible by elimination of rhabdomyosarcoma after treatment with verteporfin. This allows treatment of cortex fragments before autotransplantation without compromising ovarian tissue integrity. Study design, size, duration Human ovarian cortex fragments harbouring breast cancer tumour foci were exposed for 24 h to DARPins fused to the translocation and catalytic domain of Pseudomonas aeruginosa exotoxin A (DARPin-toxin fusion proteins) targeting EpCAM or HER2. After treatment with the DARPin-toxin fusion proteins the tissue was cultured for an additional 6 days to allow any remaining tumour cells to form foci. In addition, the functional integrity of the ovarian tissue was analysed after purging. Participants/materials, setting, methods Breast cancer cell lines expressing different levels of EpCAM and HER2 were introduced in human ovarian tissue to form tumour foci. After purging with DARPin-toxin fusion proteins, the presence of any remaining cancer cells in the tissue was analysed with (immuno)histochemistry and RT-qPCR. Possible detrimental effects on the viability of ovarian cortex and follicles were determined by (immuno)histology, a follicular viability assay and an assay to determine the in vitro growth capacity of small follicles. Main results and the role of chance Ovarian cortex harbouring EpCAM-positive breast cancer cells showed a significant decrease in the number of tumour foci after treatment with the EpCAM-targeted DARPin-toxin fusion proteins. Although exposure to the EpCAM-specific DARPin had no effect on morphology or viability of follicles, a decrease in oocyte viability after in vitro growth experiments was observed, presumably due to low level expression of EpCAM on oocytes. In contrast to the EpCAM-specific DARPin-toxin fusion protein, the DARPin-toxin fusion protein targeting HER2 had no detrimental effects on morphology, viability or in vitro growth of follicles while foci of HER2-positive breast cancer cells were severely affected as indicated by the presence of apoptotic bodies, tumour cell remnants and the absence of viable tumour cells. The histological results after purging with the HER2-specific DARPin-toxin fusions proteins were confirmed by RT-qPCR, showing a decrease to basal levels of HER2 mRNA in the ovarian cortex tissue. Limitations, reasons for caution The effect of DARPin-toxin fusion proteins depends heavily on the expression of their target on the cancer cell. The target protein should not be expressed by ovarian cortex as this may lead to tissue damage. The functional integrity of ovarian cortex after the treatment requires further investigation in vivo. Wider implications of the findings Purging metastases from ovarian cortex without harming ovarian tissue is possible by targeting tumour specific surface expressed antigens with DARPin-toxin fusion proteins. Purging ovarian cortex tissue with DARPin-toxin fusion proteins provides a feasible therapeutic strategy to prevent reintroduction of cancer by autotransplantation in case of malignancies expressing tumour-specific surface markers. Trial registration number not applicable

Banking of human ovarian tissue potentially contaminated by cancer cells: experimental model for study of cryo-stability of these cells

2019 ◽  
Vol 21 (1) ◽  
pp. 57-63
Author(s):  
Vladimir Isachenko ◽  
Xinxin Du ◽  
Evgenia Isachenko ◽  
Plamen Todorov ◽  
Peter Mallmann ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Experimental Model ◽  
Ovarian Tissue ◽  
Human Ovarian Tissue

Ovarian tissue cryopreservation and transplantation in patients with central nervous system tumours

2021 ◽  
Author(s):  
Thu Yen Thi Nguyen ◽  
Luciana Cacciottola ◽  
Alessandra Camboni ◽  
Joachim Ravau ◽  
Michel De Vos ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cancer Cells ◽  
Ovarian Tissue ◽  
Neuron Specific Enolase ◽  
Ovarian Tissue Cryopreservation ◽  
Malignant Cells ◽  
Ovarian Cortex ◽  
Cns Tumours ◽  
Tissue Cryopreservation

Abstract STUDY QUESTION Is there a possibility of reseeding cancer cells potentially present in frozen ovarian tissue from patients with central nervous system (CNS) tumours? SUMMARY ANSWER Malignancy reseeding in cryopreserved ovarian tissue from 20 patients with CNS tumours was not detected by histology, immunohistochemistry (IHC), molecular biology or xenotransplantation. WHAT IS KNOWN ALREADY Ovarian metastasis potential has been documented in patients with leukaemia, borderline ovarian tumours, advanced breast cancer and Ewing sarcoma. However, data on the safety of transplanting frozen-thawed ovarian tissue from cancer patients with CNS tumours are still lacking. STUDY DESIGN, SIZE, DURATION This prospective experimental study was conducted in an academic gynaecology research laboratory using cryopreserved ovarian cortex from 20 patients suffering from CNS tumours. Long-term (5 months) xenografting was performed in immunodeficient mice. PARTICIPANTS/MATERIALS, SETTING, METHODS Subjects enrolled in the study were suffering from one of six types of CNS tumours including medulloblastoma, ependymoma, primitive neuroectodermal tumours, astrocytoma, glioblastoma and germinoma. The presence of malignant cells was investigated with disease-specific markers for each patient in cryopreserved and xenografted ovarian tissue by histology, IHC via expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) for quantification of GFAP and ENO2 gene amplification. MAIN RESULTS AND THE ROLE OF CHANCE Serial sections of cryopreserved and xenografted ovarian tissue from 20 patients showed no malignant cells by histology. All samples were negative for NSE and GFAP, although these neural markers were expressed extensively in the patients’ primary tumours. Analysis by RT-ddPCR revealed no cancer cells detected in cryopreserved and xenografted ovarian fragments from subjects with astrocytoma, ependymoma, glioblastoma or medulloblastoma. Taken together, the study found no evidence of malignancy seeding in frozen-thawed and xenotransplanted ovarian tissue from patients affected by CNS cancers. LIMITATIONS, REASONS FOR CAUTION This analysis cannot guarantee complete elimination of disseminated disease from all cryopreserved ovarian cortex, since we are unable to examine the fragments used for transplantation. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to be conducted in patients with CNS cancers undergoing ovarian tissue cryopreservation and transplantation, and clearly demonstrates no tumour seeding in their frozen-thawed and xenografted tissue. This information is vital for doctors to provide patients with meaningful and accurate advice on the possibilities and risks of ovarian tissue reimplantation. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique–the Excellence of Science (FNRS–EOS), number 30443682 awarded to M.-M.D. and T.Y.T.N., FNRS grant number 5/4/150/5 and FNRS-PDR Convention grant number T.0077.14 awarded to M.-M.D., grant 2018-042 from the Foundation Against Cancer awarded to A.C., and private donations (Ferrero, de Spoelberch). The authors declare no competing financial interests. TRIAL REGISTRATION NUMBER N/A.

A new in vitro model for pre-transplantation diagnosis of frozen/thawed human ovarian tissue

2011 ◽  
Vol 71 (05) ◽  
Author(s):  
M Salama ◽  
K Winkler ◽  
KF Murach ◽  
S Hofer ◽  
L Wildt ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Ovarian Tissue ◽  
Human Ovarian Tissue ◽  
Vitro Model

scholarly journals THE CONVERSION OF TESTOSTERONE-3-C14 TO C14-ESTRADIOL-17β BY HUMAN OVARIAN TISSUE

1956 ◽  
Vol 221 (2) ◽  
pp. 931-941
Author(s):  
Billy Baggett ◽  
Lewis L. Engel ◽  
Kenneth Savard ◽  
Ralph I. Dorfman
Keyword(s):  
Ovarian Tissue ◽  
Human Ovarian Tissue ◽  
Estradiol 17Β

ORIGINAL ARTICLE: Development of Human Graafian Follicles Following Transplantation of Human Ovarian Tissue into NOD/SCID/γcnull Mice

2008 ◽  
Vol 60 (6) ◽  
pp. 534-540 ◽  
Author(s):  
Yukihiro Terada ◽  
Yumi Terunuma-Sato ◽  
Tomoko Kakoi-Yoshimoto ◽  
Hisataka Hasegawa ◽  
Tomohisa Ugajin ◽  
...  
Keyword(s):  
Ovarian Tissue ◽  
Human Ovarian Tissue

Both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model

2010 ◽  
Vol 93 (5) ◽  
pp. 1676-1685 ◽  
Author(s):  
Anne-Sophie Van Eyck ◽  
Caroline Bouzin ◽  
Olivier Feron ◽  
Lydia Romeu ◽  
Anne Van Langendonckt ◽  
...  
Keyword(s):  
Murine Model ◽  
Ovarian Tissue ◽  
Human Ovarian Tissue

Direct metabolism of 7α-3H-dehydroepiandrosteron-35S-sulphate in human ovarian tissue

1967 ◽  
Vol 23 (10) ◽  
pp. 851-852 ◽  
Author(s):  
P. Knapstein ◽  
F. Wendlberger ◽  
G. W. Oertel
Keyword(s):  
Ovarian Tissue ◽  
Human Ovarian Tissue
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