Senescence and the Early Ageing Phenotype After Chemotherapy for Testicular Cancer: the SEA-CAT Study
University Medical Center Groningen
192 participants
Feb 9, 2019
INTERVENTIONAL
Conditions
Summary
Cisplatin-combination chemotherapy causes inevitably DNA damage by platinum-DNA adduct formation of both tumor cells but also healthy cells. It therefore stands to reason that testicular cancer treatment causes an increased burden of senescent cells, which causes upregulation of the SASP resulting in a pro-inflammatory phenotype. The investigators hypothesize that this may be an important mechanism behind development of late effects and an early ageing phenotype after treatment for testicular cancer.
Eligibility
Inclusion Criteria12
- In order to be eligible to participate in the cross-sectional part of this study, a subject must meet all of the following criteria:
- Diagnosed with metastatic testicular cancer in 1999-2012 (stage II or higher)
- Received first-line cisplatin-based chemotherapy
- Was younger than 50 years of age at start of chemotherapy
- In order to be eligible to participate in the longitudinal part of this study, a subject must meet all of the following criteria:
- Chemotherapy-group:
- Diagnosis of metastatic testicular cancer (stage II or higher)
- Is about to start with first-line cisplatin-based chemotherapy
- Younger than 50 years of age at diagnosis of metastatic testicular cancer
- Stage I control-group:
- Diagnosis of testicular cancer stage I disease
- Younger than 50 years of age at diagnosis of testicular cancer
Exclusion Criteria2
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- \- Not able to provide informed consent (in example in case of mental or psychiatric disability)
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
A 4 mm skin biopsy will be performed at the upper leg of the patient. Before the skin biopsy local anesthesia is applied subcutaneously. In these skin biopsies senescent cells will be detected by p16, p21 and yH2Ax staining. Furthermore, we will measure platinum levels in the skin biopsies.
An abdominal subcutaneous fat biopsy will be performed 7-10 cm on the right side of the umbilicus. Before the fat biopsy local anesthesia is applied subcutaneously. An amount of 30 mg fat tissue will be collected using needle aspiration. In these fat biopsies senescent cells will be detected by p16, p21 and yH2Ax staining. Furthermore, we will measure platinum levels (ICP-MS), adipocytokines (leptin, adiponectin, interleukin-6, PAI-1, TNF-α), p53 activation indirectly by measuring p21 or mdm2 expression using immunohistochemistry, microRNA regulation of insulin signaling in adipose tissue: miR-103, miR-107, miR-29.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT04113122