Effect of Anesthesia and Surgical Stress on the Expression of Programmed Death-1 and Programmed Death-1 Ligand on T Lymphocyte After Breast Cancer Surgeries
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Programmed Cell Death 1
- Sponsor
- Assiut University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- change in level of PD1 and PD1 ligand postoperatively
- Last Updated
- 5 years ago
Overview
Brief Summary
Surgery is first-line treatment for solid tumors. However, surgical trauma-induced physiologic stress has been demonstrated to facilitate metastasis and recurrence in different types of cancer. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.
Detailed Description
The cellular immune response plays a central part in postoperative clearance of tumor cells. T lymphocytes and natural killer (NK) cells are two predominant cytotoxic effector cells that are the major components of antitumor immunity. In mouse models, proliferation of T lymphocytes in response to surgical trauma is defective . Programmed death-1 (PD-1) belongs to the CD28 receptor superfamily. It is an inhibitory receptor, and its expression is upregulated on activated leukocytes, resulting in an inhibited immune response. PD-1 interacts with two ligands: programmed death ligand-1 (PD-L1, also referred to as B7-H1) and programmed death ligand-2 (PD-L2, also known as B7-DC). PD-L2 is expressed mainly on activated dendritic cells (DCs) and macrophages, whereas PD-L1 is distributed widely. In addition to immune cells, some subsets of tumor cells also express PD-L1 to escape from immunosurveillance. It has been reported that the PD-1/PD-L1 pathway could be activated by surgical stress. Hence, we instigate the effect of anesthetic technique on expression of PD1 and PD1 ligand.
Investigators
Shereen Mamdouh
Lecturer of anesthesia, ICU and pain managment
Assiut University
Eligibility Criteria
Inclusion Criteria
- •patients scheduled for breast cancer surgery
Exclusion Criteria
- •compromised immune function (such as infection with the human immunodeficiency virus, immunodeficiency, or treatment with corticosteroids, immunosuppressive drugs, or chemotherapy)
- •ASA \> III
- •age\> 70 years old.
- •patients refusal to the procedure.
- •Infection of the skin at or near site of needle puncture.
- •Coagulopathy .
- •Drug hypersensitivity or allergy to the studied drugs.
- •Central or peripheral neuropthy .
- •Pre-operative opoid consumption ( within 24 hours preoperative )
- •Anomalies of the vertebral column .
Outcomes
Primary Outcomes
change in level of PD1 and PD1 ligand postoperatively
Time Frame: preoerative (day-0),1st day, and 3 rd day after surgery
blood sample will be withdrawn and human peripheral blood monocyte cells (PBMCs) will be separated with a Ficoll-Isopaque density gradient. Flow cytometric analyses will be carried out immediately. For ex vivo experiments, PBMCs will be cultured with Iscove's modified Dulbecco's medium (IMDM) containing 10 % human serum albumin.
Secondary Outcomes
- total request of analgesia(24 hours postoperative)