Inhibition of SENP1 for the Suppression of OS Growth and Metastasis
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|ClinicalTrials.gov Identifier: NCT03798587|
Recruitment Status : Not yet recruiting
First Posted : January 10, 2019
Last Update Posted : January 10, 2019
The aim of this project is to test a new powerful PNA-based SENP1 inhibitor, previously characterized in an in vitro model of OS cell lines.
The most effective PNA, conjugated with a cell-permeable CPP, which is able to inhibit OS cells viability and invasiveness in both normoxia and hypoxia through SENP1-mediated inhibition of HIF1α, ZEB1, and Akt, will be investigated for its ability to penetrate and silence SENP1 expression in ex vivo human OS tissues.
To determine the ability of PNA-CPP to penetrate into an ex vivo tridimensional tissue of OS, derived from wasted biological material obtained during OS eradication surgery, and to exert its biological function of inhibiting SENP1 within the tissue.
|Condition or disease|
|Primary Osteosarcoma of Bone|
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|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||15 participants|
|Target Follow-Up Duration:||1 Day|
|Official Title:||PNA-mediated Inhibition of the SENP1 Molecular Hub as a Potential Therapeutic Approach for the Suppression of Osteosarcoma Growth and Metastasis (PNA-OS)|
|Estimated Study Start Date :||January 2019|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
Patients with age ≥18 years that were/can be recruited within the IRCCS Istituto Ortopedico Galeazzi BioBanca (ethical committee approval n. 29/INT/2017).
Patients with age <18 years: will be additionally recruited besides the IRCCS Istituto Ortopedico Galeazzi BioBanca.
The target group corresponds to patients hospitalized at Istituto Ortopedico Galeazzi, undergoing surgical eradication of primary osteosarcoma.
Patients will be considered eligible for enrollment in the study if able to sign the consent to the procedure after appropriate information from the reference surgeon or signed by parents or legal guardian after appropriate information from the reference surgeon (if age <18).
-Patients not able to sign the Informed Consent.
- Determination of SENP1 expression in OS samples [ Time Frame: 8 months ]OS samples, already existing in the BioBanca as frozen samples preserved in liquid nitrogen at BioRep Service-Provider (BioRep S.r.l. Via Olgettina 60, 20132, Milano), will be used to determine the initial expression levels of SENP1 in OS by RT-qPCR. For this, samples will be homogenized, total RNA will be extracted and RT-qPCR will be performed assaying for SENP1 expression levels.
- Ex vivo analysis of the PNA-R8 silencing ability in osteosarcoma samples. [ Time Frame: 16 months ]Freshly collected OS samples will be preserved in physiological solution until usage. The OS samples will be cut in 3 mm3 pieces, placed in a 24-multiwell culture plate, and cultivated ex vivo as organotypic OS cultures in both normoxia and hypoxia-induced microenvironment under orbital rotation. OS cultures will be treated with senpPNA-R8, and SENP1 expression in naïve and PNA-treated samples will be determined by RT-qPCR and immunohistochemistry in paraffin-embedded sections. The ability of the PNA-R8 to penetrate within the hypoxic core of the OS samples will be assessed: after incubation with scrPNA-R8-Fl, sections will be immediately frozen (-80°C), processed and analyzed by immunofluorescence.
Biospecimen Retention: Samples Without DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03798587
|Contact: Marta Sofia Gomarasca, PhD||+39 026621 ext email@example.com|
|Contact: Elena Cittera, MSc||+39 026621 ext firstname.lastname@example.org|
|IRCCS Istituto Ortopedico Galeazzi||Recruiting|
|Milano, Italy, 20161|
|Contact: Marta Sofia Gomarasca, PhD 0039022261 ext 4068 email@example.com|
|Contact: Elena Cittera, MSc 0039022261 ext 4057 firstname.lastname@example.org|