TuLip : Role of the Tumor Environment in Cancer-related Fat Loss

Study Overview
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Brief Summary
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Cancer cachexia is defined as a weight loss of more than 5% over the last 6 months, a loss of body fat and muscle atrophy. It is found in 80% of patients with advanced cancer. In this context, white adipose tissue is a particularly interesting target since its depletion precedes the loss of muscle mass, and is sufficient to induce a decrease in the response to anti-cancer treatments and in the survival of patients. This cachexia is associated with advanced tumors that present acidosis and metastasis. In this clinical study the investigators would like explore the acid environment effect on the human adipose tissue depletion and more specifically on adipocyte lipolysis. The main objective of the TuLip clinical study is therefore to validate in human subcutaneous and visceral adipocytes that factors secreted by tumor cells cultivated in acid tumor environment stimulate the release of lipids from adipose tissue. Adipocytes retrieves from this study will also be used to validate identified potential lipolytic factors derived from these cells.

Detailed Description
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This study is a monocentric clinical study. Patients with BMI < 30 kg/m2 will be recruited in the context of programmed abdominal surgery. In this context, subcutaneous and visceral adipose tissue pieces (1-2 cm3) will be collected to explore the lypolytic response of adipocytes ex-vivo to factors secreted by human cancer cell lines.

Official Title
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Study of the Tumor-adipose Tissue Dialogue: Role of Tumor Acidosis in the Induction of Adipocyte Lipolysis

Conditions
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Cancer, Cachexia, Adipose Tissue

Intervention / Treatment
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* Procedure: Nissen Fundoplication, cholecystectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Programmed surgeries in the abdominal area in the Department of Surgery and Transplantation at Cliniques Universitaires Saint-Luc under the supervision of Prof. Dr. Benoit Navez. Hospitalization in the context of surgery Caucasian Age between 18 and 60 years (included). Body mass index less than 30 and greater than or equal to 18.5 Programmed Nissen fundoplication (to treat hiatal hernia and gastroesophageal reflux) or cholecystectomy (to treat vesicular lithiasis). Adults capable of expressing their wishes. Understanding French Exclusion Criteria: Body mass index below 18.5 and above 30. Patients with cancer, infection, autoimmune or inflammatory disease, metabolic syndrome. Patients with beta-blockers, hypoglycemics, anti-diabetics, hypolipidemics. Adults unable to express their will. Not understanding French Patients participating in a clinical trial for a drug treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Collection of subcutaneous and visceral adipose tissue from patients with BMI < 30 kg/m2
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with BMI < 30 kg/m2<br>Collection of subcutaneous and visceral adipose tissue pieces of 1-2 cm3 during abdominal surgery procedures | Procedure: Nissen Fundoplication, cholecystectomy<br>* Collection of adipose tissue pieces in the context of programmed abdominal surgery to treat to treat hiatal hernia, gastroesophageal reflux or vesicular lithiasis. During the surgery treatment, adipose tissue of 1-2 cm3 will be collected for the protocol by laparoscopy by the surgeon in charge of the procedures.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the lipolytic response of adipocytes isolated from human visceral and subcutaneous adipose tissue to factors derived from cancer cells in acid environment by the glycerol measurement | Measure ex-vivo of the lipolysis of subcutaneous and visceral adipocytes in the presence of factors derived from cancer cells. The lipolysis will be assessed by the measure of glycerol (in mol/L) released by adipocytes. | Up to 100 days after the adipose tissue collection | 
| Evaluation of the lipolytic response of adipocytes isolated from human visceral and subcutaneous adipose tissue to factors derived from cancer cells in acid environment by the fatty acid measurement. | Measure ex-vivo of the lipolysis of subcutaneous and visceral adipocytes in the presence of factors derived from cancer cells. The lipolysis will be assessed by the measure of free fatty acids (in mol/L) released by adipocytes. | Up to 100 days after the adipose tissue collection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by western-blot | Protein analyses by western-blot (arbitrary units). | Up to 2 years after the adipose tissue collection | 
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by ELISA | Protein analyses by ELISA (mol/L or g/L). | Up to 2 years after the adipose tissue collection | 
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by proteomic analyses | Protein analyses via proteomic analyses (relative units). | Up to 2 years after the adipose tissue collection | 
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by biochemical analyses | Biochemical analyses (biochemical kits) | Up to 2 years after the adipose tissue collection | 
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by metabolomic analyses | Metabolomic analyses (arbitrary units or mol/L) | Up to 2 years after the adipose tissue collection | 
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by RNA sequencing | Measurement of gene expression by RNA sequencing (in counts) of RNA extracted from these ex-vivo cultured human adipocytes. | Up to 2 years after the adipose tissue collection | 
| Evaluation of the lipid metabolism, of adipocytes isolated from human visceral and subcutaneous adipose tissues to factors derived from cancer cells in acid environment, by RT-qPCR | Measurement of gene expression by RT-qPCR (in relative units) of RNA extracted from these ex-vivo cultured human adipocytes. | Up to 2 years after the adipose tissue collection |