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| Name | Class |
|---|---|
| Dutch Cancer Society | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cross-sectional study: | Experimental | Testicular cancer survivors who were treated between 2000 and 2005 or between 2006 and 2012 with cisplatin-combination chemotherapy and who were extensively phenotypically mapped within two longitudinal trials (15,16) will be invited to participate in a single cross-sectional follow-up study visit 5-20 years after chemotherapy. |
|
| Longitudinal study - chemotherapy group | Experimental | Patients with metastasized testicular cancer who are about to start with cisplatin-combination chemotherapy will be invited in the longitudinal part of this study. Study participation involves four study visits: Visit 1: before start of chemotherapy Visit 2:before third cycle of chemotherapy Visit 3: one month after completion of chemotherapy Visit 4: one year after start of chemotherapy |
|
| Longitudinal study - stage I control group | Other | Patients with stage I testicular cancer will serve as control group with three study visits: Visit 1: at time of orchidectomy Visit 2: one month Visit 3: one year after orchidectomy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Skin biopsy | Diagnostic Test | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cellular senescence | The change in the amount of senescent cells in skin and fat tissue (defined as % of cells in which nucleus is stained positive for P16, P21 and yH2Ax) | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Senescence-associated secretory phenotype (SASP) | Change in levels of the cytokines: IL-6, IL-8, VEGF | 1 year |
| Pulse-wave velocity | Presence or development of the early ageing phenotype will be assessed measuring vascular damage: change in vascular stiffness (pulse-wave velocity, PWV). |
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Inclusion Criteria:
In order to be eligible to participate in the cross-sectional part of this study, a subject must meet all of the following criteria:
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:
Stage I control-group:
Exclusion Criteria:
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)
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| J. A. Gietema, prof. | Contact | +31 50 361 2821 | j.a.gietema@umcg.nl |
| Name | Affiliation | Role |
|---|---|---|
| J. A. Gietema, Prof. | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Recruiting | Groningen | 9713 GZ | Netherlands |
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| ID | Term |
|---|---|
| D013736 | Testicular Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005834 | Genital Neoplasms, Male |
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A study will be performed consisting of two cohorts. Cross-sectional study Testicular cancer survivors treated between 2000 and 2005 or between 2006 and 2012 with cisplatin-combination chemotherapy and were extensively phenotypically mapped within two longitudinal trials will be invited to participate in a single cross-sectional follow-up study visit 5-20 years after chemotherapy.
Longitudinal study
Patients with metastasized testicular cancer who are about to start with cisplatin-combination chemotherapy will be invited. Study participation involves four study visits:
Visit 1: before start of chemotherapy Visit 2: before third cycle of chemotherapy Visit 3: one month after completion of chemotherapy Visit 4: one year after start of chemotherapy
Patients with stage I testicular cancer will serve as control group with three study visits:
Visit 1: at time of orchidectomy Visit 2: one month after orchidectomy Visit 3: one year after orchidectomy
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| Subcutaneous fat biopsy | Diagnostic Test | 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. |
|
| 1 year |
| Platinum levels | Changes in circulating platinum levels and the amount of platinum depositions in skin and fat tissure will be assessed. | 1 year |
| Adipocytokines 1 | Changes in levels of leptin and PAI-1 (ug/L) | 1 year |
| Adipocytokines 2 | Changes in levels of adiponectin (ug/mL) | 1 year |
| D014565 |
| Urogenital Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D004700 | Endocrine System Diseases |
| D013733 | Testicular Diseases |
| D006058 | Gonadal Disorders |