Oxidative Stress and Mitochondrial TERT in Papillary Thyroid Cancer.

NCT05752669 | Completed

• 1 other identifier: 05M902
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Oxidative stress (OS) could be involved in the progression of papillary thyroid cancer (PTC). Indeed, thyroid differentiation genes are silenced by a mechanism controlled by NOX4-derived OS. On the other hand, TERT contributes to mitochondrial OS protection, which could increase the resistance of cancer cells to therapeutic agents. The investigators aim to address the role of OS and mitochondrial TERT in the progression and therapeutic resistance of PTC. OS and TERT subcellular localization will be investigated in 150 PTCs and correlated to the genetic and expression profile of the tumors and to the clinical and prognostic features of the patients. Mechanisms implicated in TERT mitochondrial migration and the contribution of mitochondrial TERT to tumor progression will be investigated in cancer cell lines and primary cell cultures. This study will allow to identify OS as a marker of therapeutic resistance in PTC and will open new opportunities for the development of novel treatments targeting ROS generation/TERT nuclear export.

Conditions

Papillary Thyroid Cancer

Outcome Measures

Primary Outcomes (7)

• H202 generation (nmol/mg tissue) in papillary thyroid cancer and in corresponding normal tissues.

  months 1-24

• TERT mitochondrial localization (TERT/VDAC) in papillary thyroid tumors.

  TERT mitochondrial localization will be investigated by Western blot of mitochondrial fractions and normalized to VDAC protein expression.

  months 13-30

• Effect of exogenous oxidative stress (H2O2) and therapeutic agents (BRAF, MEK and Src kinase inhibitors) on TERT nuclear to mitochondrial translocation in thyroid cancer cell lines.

  TERT mitochondrial translocation will be measured by immunofluorescence.

  month 19-30

• Mitochondrial oxidative stress generation in cells lines treated with Src kinase inhibitors.

  Mitochondrial oxidative stress will be measured by immunofluorescence.

  months 25-36

• Proliferation in cells lines treated with Src kinase inhibitors.

  Proliferation will be measured by a colorimetric assay.

  months 25-36

• Apoptosis in cells lines treated with Src kinase inhibitors.

  Apoptosis will be measured by a luminometric assay.

  months 25-36

• Migration in cells lines treated with Src kinase inhibitors.

  Migration will be measured by wound healing assays.

  months 25-36

Secondary Outcomes (2)

• Genetic characterization of tumor tissues.

  months 1-24

• Expression profile of tumor tissues.

  months 1-24

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients operated for papillary thyroid cancer and followed by our Center of Excellence for the Diagnosis and Treatment of Thyroid Tumors.

You may qualify if:

• Patients with papillary thyroid cancer
• Patients whose tumor and contralateral healthy tissues can be collected for the analyses

You may not qualify if:

• patients who did not provide consent
• patients lost at follow-up
• tissues not adequate for the analyses

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• University of Milan: collaborator

Study Sites (1)

Istituto Auxologico Italiano

Milan, Italy

Location

Related Publications (5)

• Muzza M, Colombo C, Cirello V, Perrino M, Vicentini L, Fugazzola L. Oxidative stress and the subcellular localization of the telomerase reverse transcriptase (TERT) in papillary thyroid cancer. Mol Cell Endocrinol. 2016 Aug 15;431:54-61. doi: 10.1016/j.mce.2016.05.005. Epub 2016 May 7.

  PMID: 27164443 BACKGROUND

• Pesenti C, Muzza M, Colombo C, Proverbio MC, Fare C, Ferrero S, Miozzo M, Fugazzola L, Tabano S. MassARRAY-based simultaneous detection of hotspot somatic mutations and recurrent fusion genes in papillary thyroid carcinoma: the PTC-MA assay. Endocrine. 2018 Jul;61(1):36-41. doi: 10.1007/s12020-017-1483-2. Epub 2017 Dec 6.

  PMID: 29214440 BACKGROUND

• Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014 Oct 23;159(3):676-90. doi: 10.1016/j.cell.2014.09.050.

  PMID: 25417114 BACKGROUND

• Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020.

  PMID: 26462967 BACKGROUND

• Coperchini F, Croce L, Denegri M, Awwad O, Ngnitejeu ST, Muzza M, Capelli V, Latrofa F, Persani L, Chiovato L, Rotondi M. The BRAF-inhibitor PLX4720 inhibits CXCL8 secretion in BRAFV600E mutated and normal thyroid cells: a further anti-cancer effect of BRAF-inhibitors. Sci Rep. 2019 Mar 13;9(1):4390. doi: 10.1038/s41598-019-40818-w.

  PMID: 30867499 BACKGROUND

Related Links

• PubMed ID: 27164443
• PubMed ID: 29214440
• PubMed ID: 25417114
• PubMed ID: 26462967
• PubMed ID: 30867499

MeSH Terms

Conditions

Thyroid Cancer, Papillary

Condition Hierarchy (Ancestors)

Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases

Study Officials

• Marina Muzza, PhD

  Istituto Auxologico Italiano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 3, 2023
• Study Start: September 15, 2021
• Primary Completion: May 31, 2025
• Study Completion: May 31, 2025
• Last Updated: August 21, 2025

Record last verified: 2025-08

Locations

IT (1)