Molecular Pathways Involved in the Pathogenesis and Behavior of Mesenchymal Phosphaturic Tumors Causing Oncogenic Osteomalacia

NCT ID: NCT02331966

Last Updated: 2015-01-06

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 10 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2017-03-31

Brief Summary

The tumors that cause oncogenic osteomalacia (TIO) express and release in the circulation phosphaturic factors such as fibroblast growth factor-23 (FGF-23) that decrease renal phosphate absorption through acting in the proximal renal tubule and decreasing Type 2a and 2c sodium-phosphate co-transporter. They typically follow a benign clinical course and even in the rare malignant cases, local recurrence occurs in less than 5% and distant metastasis are very uncommon.

In this study we aim to investigate the role of other molecular pathways such as ERK1, ERK2, mTOR, EGFR, MEK1, MEK2, VEGFR3, AKT1, AKT2, IGFR-1, IGFR-2, PDGFRA, PDGFRB, cMET, FGFR2, apart from FGF23, KLOTHO and PHEX, in the behavior of histopathologically benign mesenchymal phosphaturic tumors.

Detailed Description

Study Protocol Cell Culture Bone marrow and tissue samples will be obtained from the patients after they will give their written informed consent. Material will be maintained in RPMI culture medium (Sigma, R0883, Germany). Peripheral blood mononuclear cells (PBMCs) from healthy donors will be used as control. For detection of cancer cells in our samples we perform flow cytometry using EpCAM magnetic beads (39-EPC-50; Gentaur), and the negative selection cells (non-cancerous) are isolated and then cultured in a 25-cm2 flask (5520100; Orange Scientific) with RPMI-1640 medium (R6504; Sigma).

Molecular analysis RNA is extracted from cell cultures using RNeasy Mini Kit (74105; Qiagen, Hilden; Germany). iScript cDNA synthesis kit (1708891; Bio-Rad, CA; USA), is used for cDNA synthesis and Real-time polymerase chain reaction (PCR), is performed using the iTaq Universal SYBR Green Supermix (1725124; Bio-Rad). Specific primers for each marker and for an endogenous control gene (18S rRNA) is designed using Genamic Expression 1.1 software. A universal Reference RNA consisting of 10 human cancer cell lines (740000-41; Agilent) as well as human genomic DNA (G304A; Promega) will be used in quantitative PCR (qPCR) reactions Statistical analysis The qPCR results will be tested according to the Kolmogorov-Smirnov test; All the reactions (molecular assays, flow cytometry) are performed in triplicates. A p value <0.05 is considered significant.

Conditions

Tumor Induced Oncogenic Osteomalacia

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

Patients with tumor induced osteomalacia

Exclusion Criteria

None

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AHEPA University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Maria Yavropoulou

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria P. Yavropoulou, M.D

Role: PRINCIPAL_INVESTIGATOR

AHEPA University Hospital

Locations

1st Department of Internal Medicine AHEPA University Hospital

Thessaloniki, , Greece

Site Status: RECRUITING

Countries

Greece

Central Contacts

Michael Daniilidis, M.D

Role: CONTACT

daniilidis@gmail.com

00302310993202

John G. Yovos, M.D

Role: CONTACT

giovos@med.auth.gr

00302310994607

Facility Contacts

Michael Daniilidis, M.D

Role: primary

daniilidis@gmail.com

00302310993202

John G. Yovos, M.D

Role: backup

giovos@med.auth.gr

00302310994607

Other Identifiers

51741

Identifier Type: -

Identifier Source: org_study_id