Value of Various Chemokines in the Detection and Follow up of RCC

Study Overview
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Brief Summary
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This study was designed as a pilot study to try and find a Chemokine that may be specific for renal cell carcinoma

Detailed Description
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I n previous studies that were initiated in experimental models of different inflammatory autoimmune diseases and then extended to humans, we have shown that in the course of inflammatory autoimmune diseases, the immune system selectively generates an auto-Ab response to a few inflammatory mediators, mostly chemokines and cytokines, which are thought to participate in promoting the inflammatory process (1-6). For example, we showed that patients suffering from rheumatoid arthritis (RA) but not osteoarthritis display a significant level of neutralizing auto- Abs directed against TNF-a (tumor necrosis factor)(3). These patients did not mount any auto-Ab response either to several key inflammatory chemokines or to regulatory mediators, such as IL-10(interleukin-10) or TGF-b(tumor growth factor)(, or even the chemokine CXCL12(C-X-C motif chemokine 12), which also functions as a regulatory mediator that selects Ag-specific IL-10-producing CD4+(cluster of differentiation 4) T cells (7). Complementary experiments suggested that in experimentally induced RA, these anti-TNF-a auto-Abs participate in the natural regulation of disease and restrain-although they are incapable of totally preventing-its development (3). Nevertheless, their selective amplification by targeted DNA vaccines led to rapid recovery from an ongoing disease (8). These studies also showed that selective breakdown of tolerance to TNF-a is due to its preferential expression at a partially immune-restricted site undergoing a destructive process (3, 8). Very recently, we have shown that type I diabetes mellitus (T1DM) patients preferentially display auto-Ab production to CCL3( Chemokine (C-C motif) ligand 3) and not to several other proinflammatory chemokines (9). It is yet to be proven that this chemokine dominates the chemokine expression at the autoimmune site. Nevertheless, a previous study showing that selective neutralization of CCL3 suppresses T1DM in NOD mice has implications for the important role of this chemokine in this disease (10). Similarly to organ-specific autoimmunity in various cancer diseases, one of which is cancer of the prostate (CaP), key inflammatory chemokines are expressed at the primary tumor site, which also undergoes a destructive process at a restricted site. In a previous study we showed that in primary tumor sections of prostate cancer subjects, CCL2Chemokine (C-C motif) ligand 2) is predominantly expressed at the tumor site over other chemokines that also have been associated with tumor development, including: CXCL12, CXCL10, CXCL8, CCL3,CCL4, and CCL5. Subsequently, the immune response selectivity mounts an Ab-based response to CCL2. These Abs are neutralizing Abs. These findings hold diagnostic and therapeutic implications. Little is known about the possible function of chemokine receptors in the development and progression of renal cell carcinoma (RCC). Few studies exist dealing with gene expression of chemokines in RCC. We therefore suggest a study checking antibody response to a few chemokines

Official Title
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Value of Various Chemokines in the Detection and Follow up of RCC

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Other: patients with renal cell carcinoma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with renal cell carcinoma of one or both kidneys scheduled for surgical resection - Exclusion Criteria: Males with elevated PSA (prostatic specific antigen ) Any other untreated malignancy -

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Renal cell carcinoma<br>Patients with renal cell carcinoma scheduled for partial or radical nephrectomy | Other: patients with renal cell carcinoma<br>* Chemokines that may be elevated in patients with RCC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the titers of chemokines before and after tumor resection |  | before nephrectomy (day of surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCC, Chemokines, nephrectomy, partial nephrectomy