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

Mulder, Callista L; Eijkenboom, Lotte; Beerendonk, C.C.M.; Braat, D.D.M.; Peek, Ron

doi:10.1093/humrep/dey384

Cited by 20 publications

(39 citation statements)

References 70 publications

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“…In the tissue from the third subject, a slight but statistically significant difference in glucose uptake in favour of the GSK1070916 treated tissue was observed (Table 3). In line with previous reports [30,59,68], glucose uptake by ovarian cortex tissue in vitro is variable between subjects ranging from 5.675 to 9.050 nmol/mg tissue/ h.…”

Section: Glucose Uptake Assaysupporting

confidence: 91%

“…In subject 1, there is a slight but statistically significant difference in favour of the tissue treated with 1 μM GSK1070916. *CI, confidence interval To analyse the effect of GSK1070916 on metastasised CML and AML cells, we therefore used an established tumour model based on the micro-injection of cancer cells (both AML and CML cell lines and primary AML cells) into human ovarian cortex tissue followed by several days of culture to allow malignant cells to form small metastases [59,61]. We first opted Fig.…”

Section: Discussionmentioning

confidence: 99%

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Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway

Eijkenboom

Mulder

Reijden

et al. 2021

J Assist Reprod Genet

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Purpose Is it possible to eliminate metastasised chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) cells from ovarian cortex fragments by inhibition of Aurora B/C kinases (AURKB/C) without compromising ovarian tissue or follicles? Methods Human ovarian cortex tissue with experimentally induced tumour foci of CML, AML and primary cells of AML patients were exposed to a 24h treatment with 1 μM GSK1070916, an AURKB/C inhibitor, to eliminate malignant cells by invoking mitotic catastrophe. After treatment, the inhibitor was removed, followed by an additional culture period of 6 days to allow any remaining tumour cells to form new foci. Ovarian tissue integrity after treatment was analysed by four different assays. Appropriate controls were included in all experiments. Results Foci of metastasised CML and AML cells in ovarian cortex tissue were severely affected by a 24h ex vivo treatment with an AURKB/C inhibitor, leading to the formation of multi-nuclear syncytia and large-scale apoptosis. Ovarian tissue morphology and viability was not compromised by the treatment, as no significant difference was observed regarding the percentage of morphologically normal follicles, follicular viability, glucose uptake or in vitro growth of small follicles between ovarian cortex treated with 1 μM GSK1070916 and the control. Conclusion Purging of CML/AML metastases in ovarian cortex is possible by targeting the Mitotic Catastrophe Signalling Pathway using GSK1070916 without affecting the ovarian tissue. This provides a therapeutic strategy to prevent reintroduction of leukaemia and enhances safety of autotransplantation in leukaemia patients currently considered at high risk for ovarian involvement.

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Section: Glucose Uptake Assaysupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway

Eijkenboom

Mulder

Reijden

et al. 2021

J Assist Reprod Genet

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“…Upon cell exposure to VP particularly along with long-term light exposure, the reactive oxygen species would be excessively produced, and resultant byproducts of oxidative metabolism can then interact with membrane phospholipids and proteins that constitute ion transport pathways such as BK Ca channels. Lastly, It will be worthy of being investigated regarding to what extent VP-mediated modifications on membrane ion channels reported herein is closely linked to the inhibition of VAP-TEAD complex followed by changes in proliferation or differentiation of different types of neoplastic or stem cells, given that the fact that such photosensitizers as sensitized photochemical modification in an array of tumors, including pituitary tumors and gliomas, have been widely utilized (Marks et al, 2000; Brown et al, 2004; Solban et al, 2006; Triesscheijn et al, 2006; Cole et al, 2008; Brodowska et al, 2014; Valero et al, 2015; Morishita et al, 2016; Nemes et al, 2016; Chen and Hu, 2017; Baskaran et al, 2018; Liao et al, 2018; Mulder et al, 2018; Chen et al, 2019; Li et al, 2019; Pellosi et al, 2019; Qin et al, 2019; Zhang et al, 2019). Alternatively, the efficacy of VP in inhibiting YAP/TEAD interaction was currently noted to remain debated (Lui et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Yes-associated protein (YAP) has been reported to be a main mediator of the Hippo pathway, which is thought to promote cancer development (Feng et al, 2016; Gibault et al, 2016; Kandoussi et al, 2017; Abe et al, 2018; Chen et al, 2019). A number of recent reports has demonstrated that VP can suppress the aberrant growth in a variety of tumor cell lines, including breast cancer, glioma, ovarian cancer, hepatocellular carcinoma, and retinoblastoma, through an intriguing mechanism linked to specific suppression of YAP-TEAD complex (Valero et al, 2015; Feng et al, 2016; Al-Moujahed et al, 2017; Gibault et al, 2017; Abe et al, 2018; Mulder et al, 2018; Li et al, 2019; Pellosi et al, 2019; Qin et al, 2019; Zhang et al, 2019). This compound has been indeed long supposed to be an inhibitor of YAP-TEAD complex and hence to play the roles in growth inhibition in different types of neoplastic cells including pituitary tumors and gliomas (Feng et al, 2016; Gibault et al, 2016, 2017; Al-Moujahed et al, 2017; Deng et al, 2018; Eales et al, 2018; Liao et al, 2018; Pellosi et al, 2019; Zhang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

Huang

Liu

2019

Front. Chem.

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Verteporfin (VP), a benzoporphyrin derivative, has been clinically tailored as a photosensitizer and recently known to suppress YAP-TEAD complex accompanied by suppression of the growth in an array of neoplastic cells. However, the detailed information is little available regarding possible modifications of it and its related compounds on transmembrane ionic currents, despite its growing use in clinical settings. In this study, from whole cell recordings, VP (0.3–100 μM) increased the amplitude of Ca 2+ -activated K + currents ( I K(Ca) ) in pituitary tumor (GH 3 ) cells in a concentration-dependent manner with an EC 50 value of 2.4 μM. VP-stimulated I K(Ca) in these cells was suppressed by further addition of either paxilline, iberiotoxin, or dithiothreitol, but not by that of tobultamide or TRAM-39. VP at a concentration of 10 μM mildly suppressed the amplitude of delayed-rectifier K + current; however, it had minimal effects on M-type K + current. In cell-attached current recordings, addition of VP to the recording medium enhanced the activity of large-conductance Ca 2+ -activated K + (BK Ca ) channels. In the presence of VP, additional illumination with light intensity of 5.5 mW/cm 2 raised the probability of BK Ca -channel openings further. Addition of VP decreased the peak amplitude of L-type Ca 2+ current together with slowed inactivation time course of the current; however, it failed to modify voltage-gated Na + current. Illumination of GH 3 cells in continued presence of VP also induced a non-selective cation current. Additionally, VP increased the activity of BK Ca channels in human 13-06-MG glioma cells with an EC 50 value of 1.9 μM. Therefore, the effects of VP on ionic currents described herein tend to be upstream of its inhibition of YAP-TEAD complex and they are conceivably likely to contribute to the underlying mechanisms through which it and its structurally similar compounds effect the modifications in functional activities of pituitary or glial neoplastic cells, if the in vivo findings occur.

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“…Some studies have proposed that even if ovarian function is impaired, OT can be cryopreserved after undergoing an initial chemotherapy process to reduce the risk of cancer contamination [ 21 , 92 ]. Reportedly, in vitro incubation with YAP/TAZ inhibitor verteporfin prior to auto-transplantation eliminates rhabdomyosarcoma and leukemia cells that have metastasized to the OT [ 93 ]. These studies strongly recommend the wide screening of tissue samples containing fragments intended for transplantation using both histological examinations and possible molecular biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Current and Future Perspectives for Improving Ovarian Tissue Cryopreservation and Transplantation Outcomes for Cancer Patients

Lee

Özkavukçu

2021

Reprod. Sci.

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Although advances in cancer treatment and early diagnosis have significantly improved cancer survival rates, cancer therapies can cause serious side effects, including ovarian failure and infertility, in women of reproductive age. Infertility following cancer treatment can have significant adverse effects on the quality of life. However, established methods for fertility preservation, including embryo or oocyte cryopreservation, are not always suitable for female cancer patients because of complicated individual conditions and treatment methods. Ovarian tissue cryopreservation and transplantation is a promising option for fertility preservation in pre-pubertal girls and adult patients with cancer who require immediate treatment, or who are not eligible to undergo ovarian stimulation. This review introduces various methods and strategies to improve ovarian tissue cryopreservation and transplantation outcomes, to help patients and clinicians choose the best option when considering the potential complexity of a patient’s situation. Effective multidisciplinary oncofertility strategies, involving the inclusion of a highly skilled and experienced oncofertility team that considers cryopreservation methods, thawing processes and devices, surgical procedures for transplantation, and advances in technologies, are necessary to provide high-quality care to a cancer patient.

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

Cited by 20 publications

References 70 publications

Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway

Purging human ovarian cortex of contaminating leukaemic cells by targeting the mitotic catastrophe signalling pathway

Characterization of Perturbing Actions by Verteporfin, a Benzoporphyrin Photosensitizer, on Membrane Ionic Currents

Current and Future Perspectives for Improving Ovarian Tissue Cryopreservation and Transplantation Outcomes for Cancer Patients

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