The administration of an adenoviral thymidine kinase suicide gene to the uterine artery of rabbits does not affect fertility: a safety study of pregnant and nonpregnant rabbits and their offspring

Laurema, Anniina; Riekkinen, Mervi S.; Heikura, Tommi; Vähäkangas, Elisa; Manninen, Hannu; Heinonen, Seppo; Ylä‐Herttuala, Seppo

doi:10.1002/jgm.1230

Cited by 3 publications

(1 citation statement)

References 19 publications

(26 reference statements)

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“…Furthermore, transfection of isolated primary ovarian cells has been shown to be rather difficult because in mature follicles the oocyte is surrounded by the zona pellucida , a glycoprotein layer that presents a barrier for transfection of human oocytes [60]. On the other hand, cell‐line transfection experiments have raised serious questions regarding the regulation of LOX gene expression.…”

Section: Discussionmentioning

confidence: 99%

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

Papachroni

Piperi

Levidou

et al. 2009

J Cellular Molecular Medi

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Connective tissue components – collagen types I, III and IV – surrounding the ovarian follicles undergo drastic changes during ovulation. Abnormal collagen synthesis and increased volume and density of ovarian stroma characterize the polycystic ovary syndrome (PCOS). During the ovulatory process, collagen synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in ovarian follicles. LOX catalyzes collagen and elastin cross-linking and plays essential role in coordinating the control of ovarian extracellular matrix (ECM) during follicular development. We have recently shown accumulation of advanced glycation end products (AGEs), molecules that stimulate ECM production and abnormal collagen cross-linking, in ovarian tissue. However, the possible link between LOX and AGEs-induced signalling in collagen production and stroma formation in ovarian tissue from PCOS remains elusive. The present study investigates the hypothesis of AGE signalling pathway interaction with LOX gene activity in polycystic ovarian (PCO) tissue. We show an increased distribution and co-localization of LOX, collagen type IV and AGE molecules in the PCO tissue compared to control, as well as augmented expression of AGE signalling mediators/effectors, phospho(p)-ERK, phospho(p)-c-Jun and nuclear factor κB (NF-κB) in pathological tissue. Moreover, we demonstrate binding of AGE-induced transcription factors, NF-κB and activator protein-1 (AP-1) on LOX promoter, indicating a possible involvement of AGEs in LOX gene regulation, which may account for the documented increase in LOX mRNA and protein levels compared to control. These findings suggest that deposition of excess collagen in PCO tissue that induces cystogenesis may, in part, be due to AGE-mediated stimulation of LOX activity.

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Section: Discussionmentioning

confidence: 99%

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

Papachroni

Piperi

Levidou

et al. 2009

J Cellular Molecular Medi

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Efficacy and Safety of Clinical-Grade Human Vascular Endothelial Growth Factor-D^ΔNΔC Gene Therapy Containing Residual Replication-Competent Adenoviruses

et al. 2021

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Sitimagene Ceradenovec: A Gene-Based Drug for the Treatment of Operable High-Grade Glioma

et al. 2010

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The field of gene therapy for malignant glioma has made important advances since the first gene transfer studies were performed 20 years ago. Multiple Phase I/II trials and two Phase III trials have been performed and have demonstrated the feasibility and safety of intratumoral vector delivery in the brain. Sitimagene ceradenovec is an adenoviral vector encoding the herpes simplex thymidine kinase gene, developed by Ark Therapeutics Group plc (UK and Finland) for the treatment of patients with operable high-grade glioma. In preclinical and Phase I/II clinical studies, sitimagene ceradenovec exhibited a significant increase in survival. Although the preliminary results of a Phase III clinical study demonstrated a significant positive effect of sitimagene ceradenovec treatment on time to reintervention or death when compared with standard care treatment (hazard ratio: 1.43; 95% CI: 1.06-1.93; p < 0.05), the European Committee for Medicinal Products for Human Use did not consider the data to provide sufficient evidence of clinical benefit. Further clinical evaluation, powered to demonstrate a benefit on a robust end point, is required. This article focuses on sitimagene ceradenovec and provides an overview of the developments in the field of gene therapy for malignant glioma.

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The administration of an adenoviral thymidine kinase suicide gene to the uterine artery of rabbits does not affect fertility: a safety study of pregnant and nonpregnant rabbits and their offspring

Abstract: Although AdvTK gene therapy may initially affect ovarian cells, the influence appears to be transient. However, after direct exposure of the ovarian cells in high concentration of adenoviruses, transmission of a transgene in the offspring cannot be excluded.

Cited by 3 publications

References 19 publications

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

Efficacy and Safety of Clinical-Grade Human Vascular Endothelial Growth Factor-D^ΔNΔC Gene Therapy Containing Residual Replication-Competent Adenoviruses

Sitimagene Ceradenovec: A Gene-Based Drug for the Treatment of Operable High-Grade Glioma

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The administration of an adenoviral thymidine kinase suicide gene to the uterine artery of rabbits does not affect fertility: a safety study of pregnant and nonpregnant rabbits and their offspring

Abstract: Although AdvTK gene therapy may initially affect ovarian cells, the influence appears to be transient. However, after direct exposure of the ovarian cells in high concentration of adenoviruses, transmission of a transgene in the offspring cannot be excluded.

Cited by 3 publications

References 19 publications

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue

Efficacy and Safety of Clinical-Grade Human Vascular Endothelial Growth Factor-DΔNΔC Gene Therapy Containing Residual Replication-Competent Adenoviruses

Sitimagene Ceradenovec: A Gene-Based Drug for the Treatment of Operable High-Grade Glioma

Contact Info

Product

Resources

About

Efficacy and Safety of Clinical-Grade Human Vascular Endothelial Growth Factor-D^ΔNΔC Gene Therapy Containing Residual Replication-Competent Adenoviruses