Ignite Creation Date:
2024-05-06 @ 7:37 PM
Last Modification Date:
2024-10-26 @ 3:10 PM
Study NCT ID:
NCT06071598
Status:
RECRUITING
Last Update Posted:
2023-10-06
First Post:
2023-09-25
Brief Title:
The Role of Lipid Transporter MFSD2A in the Resolution of Colorectal Cancer-associated Inflammation
Sponsor:
IRCCS San Raffaele
Organization:
IRCCS San Raffaele
Study Overview
Official Title:
The Role of Lipid Transporter MFSD2A in the Resolution of Colorectal Cancer-associated Inflammation Implications for New Therapeutic Strategies
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The intrinsic connection between inflammation and tumor promotion is well characterized and is a key pathogenic event in patients with colorectal cancer CRC the second most common cause of tumor-related death in western countries Environmental factors and chronic inflammation represent the major causes of intestinal carcinogenesis In fact patients suffering from inflammatory bowel diseases including Crohns disease and Ulcerative Colitis UC have high risk of developing colitis-associated CRC with poor prognoses Therefore targeting the cancer-associated inflammation may offer new avenues for cancer treatment In fact several anti-inflammatory drugs have been used for prophylaxis and have shown efficacy in contrasting cancer despite various adverse side effects Thus there is an urgent need to discover novel cancer-associated mechanisms to develop alternative therapies that may reduce aberrant inflammatory responses without interfering with physiological defenses against infection and functional anti-tumor immunity A novel approach promoting anti-tumor immunity has been recently proposed after the discovery of potent endogenous specialized pro-resolving mediators SPMs including lipoxins resolvins protectins and maresins mainly derived from omega-3 polyunsaturated fatty acid PUFA docosahexaenoic acid DHA and eicosapentaenoic acid EPA via COX LOX and CYP450 pathways mediated by MFSD2A Due to the potent bioactivity of SPMs in resolving inflammation and because of the correlation between inflammation and cancer the roles of these lipid mediators have attracted great attention for their potential therapeutic role in cancer treatment including CRC Nevertheless the understanding of the endogenous mechanisms that limit the inflammatory response during CRC development is incomplete and requires further investigation
Based on the preliminary results indicating that dysfunctional MFSD2A-dependent pro-resolving pathways may foster CRC development the investigators aim to define the functional role of MFSD2A in orchestrating pro-resolving pathways in the intestinal endothelium of metastatic and not metastatic CRC patients
This is a cross-sectional single-center observational study involving patients with CRC The investigators will enroll 15 patients with colorectal cancer CRC stratified by tumor stage T0 T1-T4 M0 M1 N0 N1 N2 undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center IRCCS Ospedale San Raffaele
Human Intestinal Microvascular Endothelial Cells HIMEC will be generated from each sample of cancer surgical specimens while the healthy cells will be derived from the healthy margins of the colorectal resection of the same CRC patients
MFSD2A will be overexpressed or silenced and the investigators will evaluate its biological effects in both tumor-derived HIMECs and healthy tissue-derived HIMECs through transcriptomics and lipidomics analysis The investigators will also exploit a possible novel therapy based on the delivery of MFSD2A encoding plasmid-conjugated liposomes
Based on the preliminary results indicating that dysfunctional MFSD2A-dependent pro-resolving pathways may foster CRC development the investigators aim to define the functional role of MFSD2A in orchestrating pro-resolving pathways in the intestinal endothelium of metastatic and not metastatic CRC patients
This is a cross-sectional single-center observational study involving patients with CRC The investigators will enroll 15 patients with colorectal cancer CRC stratified by tumor stage T0 T1-T4 M0 M1 N0 N1 N2 undergoing surgery in the Gastroenterology and Digestive Endoscopy unit within Gastro Center IRCCS Ospedale San Raffaele
Human Intestinal Microvascular Endothelial Cells HIMEC will be generated from each sample of cancer surgical specimens while the healthy cells will be derived from the healthy margins of the colorectal resection of the same CRC patients
MFSD2A will be overexpressed or silenced and the investigators will evaluate its biological effects in both tumor-derived HIMECs and healthy tissue-derived HIMECs through transcriptomics and lipidomics analysis The investigators will also exploit a possible novel therapy based on the delivery of MFSD2A encoding plasmid-conjugated liposomes
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None