Defining Inflammation Related to Peritoneal Carcinomatosis in Women With Ovarian or Colon Cancer.

Study Overview
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Brief Summary
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Inflammation plays an important role in the pathogenesis of peritoneal carcinosis. Patients with elevated levels of different inflammation cytokines show a worse prognosis at the time of diagnosis. In women, ovarian and colon cancer are the main causes of peritoneal carcinosis and a comparison of these two different types of peritoneal invasion have not been conducted yet. We found interesting studying the role of immune response, in particular tumour-associated antigens (TAA) that modulate the metastatic process. We will investigate also mitochondrial defects, such as mutations in mt-DNA, potentially involved in carcinogenesis.

Detailed Description
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At the time of hospitalization all the patients will undergo a complete clinical evaluation with determination of biochemical parameters such as fasting blood glucose, blood count, hs-CRP, AST and ALT, uric acid, creatinine and BUN. An extra blood aliquot will be collected to assess the serum biomarkers under investigation. During surgery two samples of peritoneal tissue macroscopically undamaged will be collected. On those samples will be executed separation of adipocytes cells, RNA and protein extraction for measuring of inflammatory and neoplastic biomarkers, determination of P2X7R-inflammasome activity and mitochondrial DNA analyse.

Official Title
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Molecular Characterisation and Clinical Implications of Inflammation Related to Peritoneal Carcinomatosis in Women With Ovarian or Colon Cancer.

Conditions
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Peritoneal Carcinomatosis, Ovarian Cancer, Colon Cancer

Intervention / Treatment
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* Procedure: Cytoreductive surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histological diagnosis of peritoneal carcinosis secondary to colon cancer or high-grade ovarian cancer patients able to consent Exclusion Criteria: previous malignancies, except for patients with cutaneous basal cell carcinoma, Cervical Intraepithelial Neoplasia (CIN) or melanoma in situ current chemotherapy or radiotherapy current steroid therapy or immunotherapy patients affected by systemic inflammatory disease and/or Inflammatory bowel disease (IBD)

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Ovarian cancer<br>Patients affected by ovarian cancer will be stratified according to BRCA1 and BRCA2 mutational status. | Procedure: Cytoreductive surgery<br>* Partial removal of peritoneal tissue involved by neoplastic invasion<br>* Other names: Debulking;|
| Colon cancer<br>Patients affected by colon cancer will be similarly stratified according to BRAF and KRAS mutational status and to the presence of low-grade or high-grade microsatellite instability (MSI). | Procedure: Cytoreductive surgery<br>* Partial removal of peritoneal tissue involved by neoplastic invasion<br>* Other names: Debulking;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune biomarkers level | Serum level of different immune related biomarkers (such as CD4, CD8, CUZD1, LAG3, PD1, PDL1, IMP1 and p62/IMP2) will be determined using ELISA. | Each patients will be assessed at baseline | 
| Metastatic mediators level | Peritoneal expression of cytokines related to metastatic process (such as IL6, IL2, TNFα, TGFβ1, VEGF, CD68, FGFR1, CCL2/MCP-1, CD73) will be determined using real time-PCR. | Each patients will be assessed at baseline | 
| P2X7R-inflammasome activity | Peritoneal expression of NLRP3-ASC will be determine using RT-PCR | Each patients will be assessed at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peritoneal carcinomatosis, colon cancer, ovarian cancer, P2X7R-inflammasome