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Trial of Preoperative Hepatic and Regional Arterial Chemotherapy (PHRAC) to Prevent Postoperative Liver Metastasis of Colorectal Cancer

ABSTRACT: The purpose of this study is to investigate whether preoperative hepatic and regional arterial chemotherapy are able to prevent liver metastasis and improve overall survival in patients receiving curative colorectal cancer resection.

DISEASE(S): Neoplasm Metastasis,Colorectal Neoplasms,Neoplasms

PROVIDER: 2052795 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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A prospective, multicenter, randomized controlled clinical trial of preoperative regional arterial infusion chemotherapy and systemic intravenous chemotherapy for locally advanced colorectal cancer

Project description:Interventions: Control Group (A Group):Systemic intra-venous chemotherapy;Experimental group (B Group):Regional arterial perfusion chemotherapy Primary outcome(s): downstaging rate Study Design: Parallel

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Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combination With Chemotherapy With/Without Bevacizumab for Hepatic Metastases From Colorectal Cancer

Project description:The purpose of this study is to determine whether the addition of bevacizumab, to hepatic arterial therapy with floxuridine (FUDR) and dexamethasone (Dex) (regional chemotherapy), and either oxaliplatin or CPT-11, plus 5-fluorouracil and leucovorin (systemic chemotherapy) will increase disease free survival in patients who have undergone liver resection. The patient will be randomized (a computer generated decision as in the flip of a coin) to receive, or not to receive bevacizumab in addition to regional and systemic chemotherapy.

| 2019516 | ecrin-mdr-crc

Hepatic perilipin 5 is required for fasting-induced autophagy to prevent fatty acid-induced inflammation

Project description:Hepatic perilipin 5 is required for fasting-induced autophagy to prevent fatty acid-induced inflammation.

2019-11-07 | GSE140024 | GEO

Preoperative Hepatic Arterial Infusion Chemotherapy

Project description:To assess the feasibility and results of liver resection after preoperative hepatic artery infusion (HAI) chemotherapy with FUDR.

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Hepatic Arterial Infusion of Melphalan With Hepatic Perfusion in Treating Patients With Unresectable Liver Cancer

Project description:RATIONALE: Hepatic arterial infusion uses a catheter to deliver anticancer substances directly into the liver. Drugs used in chemotherapy, such as melphalan, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs in different ways may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving an hepatic arterial infusion of melphalan together with hepatic perfusion works in treating patients with unresectable liver cancer.

| 2011729 | ecrin-mdr-crc

Hepatic Arterial Chemotherapy With Raltitrexed and Oxaliplatin Versus Standard Chemotherapy in Unresectable Liver Metastases From Colorectal Cancer After Conventional Chemotherapy Failure

Project description:Standard treatment of metastatic colorectal cancers relies on fluoropyrimidines, irinotecan alone or in association with fluoropyrimidines, oxaliplatin in association with fluoropyrimidines, bevacizumab and anti EGFR antibodies. After failure of classical regimen the national reference frame on the basis of phase II study proposes an association of fluoropyrimidine and mitomycin. These treatments give response rates of 10-20% with progression free survivals from 2 to 3 months. Hepatic intra-arterial chemotherapy is logical in the case of isolated hepatic metastases nonaccessible to curative resection: 1) hepatic metastases are vascularized by hepatic arterial system in contrast to nontumoral hepatic parenchyma; 2) arterial perfusion of oxaliplatin leads to a strong extraction by the liver during the first passage, a high intra-tumoral concentration and a low systemic concentration. So oxaliplatin is a drug of choice for arterial treatment but combination with fluoropyrimidines is impossible because of need for prolonged perfusion. Floxuridin is not available in France. Raltitrexed, a definitive inhibitor of the thymidylate synthase, does not require a prolonged perfusion and could be a good substitute.In a previous pilot study we demonstrated the feasibility, safety and efficacy of combination of raltitrexed and oxaliplatin arterial perfusion. Now we propose a phase II randomized clinical trial to evaluate the efficacy of hepatic arterial infusion of raltitrexed and oxaliplatin association versus standard chemotherapy for patients with metastases of colorectal origin restricted to the liver after failure of conventional chemotherapy.

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Transcription profiling of pig aortic endothelial cells to investigate the impact of gender, high fat/high cholesterol diet and regional hemodynamics on gene expression

Project description:Atherosclerosis preferentially develops in susceptible regions of the arterial system that are defined by the regional vascular hemodynamics. Previous work in adult castrate male pigs revealed the coexistence of pro- and anti-atherosclerotic profiles in endothelial cell gene expression in disturbed flow regions of arteries in the absence of risk factors for atherogenesis. This study investigates the impact of gender, high fat/high cholesterol diet and regional hemodynamics on arterial endothelial cell gene expression profiles in sexually mature intact pigs.

2007-12-15 | E-CBIL-41 | biostudies-arrayexpress

Hepatic Arterial Infusion With Floxuridine and Systemic Irinotecan After Surgery in Treating Patients With Hepatic (Liver) Metastases From Colorectal Cancer

Project description:RATIONALE: Drugs used in chemotherapy such as floxuridine and irinotecan use different ways to stop tumor cells from dividing so they stop growing or die. Hepatic arterial infusion uses a catheter to deliver chemotherapy directly to the liver. Combining more than one drug and giving them in different ways may kill any tumor cells remaining after surgery. PURPOSE: Phase II trial to study the effectiveness of systemic irinotecan and hepatic arterial infusion with floxuridine after surgery in treating patients who have hepatic (liver) metastases from colorectal cancer.

| 2009478 | ecrin-mdr-crc

Regional CNS immune fingerprint in chronic peripheral inflammation

Project description:Rheumatoid arthritis (RA) is linked to depression and dementia in later life by inflammatory involvement of the central nervous system (CNS). Regional heterogeneity of brain immunophenotypes was described under homeostasis, but a topographical resolution of CNS immune responses in chronic peripheral inflammatory diseases like RA is missing. We demonstrate regional heterogeneity of CNS susceptibility to chronic peripheral inflammation in the human tumor necrosis factor α transgenic (TNFtg) mouse model of RA. TNFtg mice showed myeloid cell infiltration, microglial activation, and a mutual transcriptomic fingerprint of neuroinflammation in the cortex, striatum, and thalamus. Immune responses were minimal in the hippocampus and cerebellum. We demonstrate regional CNS immune responses to chronic peripheral inflammation, sparing the hippocampus and cerebellum and reversible by peripheral anti-inflammatory treatment. Targeting microenvironmental susceptibility or resilience of brain regions will help to prevent and treat RA-related neuropsychiatric comorbidity. RNA-sequencing was performed from five brain regions (cortex, striatum, thalamus, hippocampus, and cerebellum) from C57Bl6/J wild type mice and TNFtg mice (strain Tg197; kindly provided by George Kollias (Fleming Institute, Vari, Greece).

2018-10-22 | E-MTAB-7279 | biostudies-arrayexpress

Pre-treatment of Interferon-α stimulates DHX58 to prevent hepatic ferroptosis

Project description:Characterized by lethal iron accumulation and lipid peroxidation, ferroptosis plays critical roles in liver injury, especially caused by ischemia/reperfusion (I/R) of hepatic inflow occlusion during liver operation. However, the lack of effective and safe clinical precautionary measure is still the main problem in preventing hepatic ferroptosis. Here, we found that the excessive production of reactive oxygen species could decrease the expression of Interferon (IFN)-stimulated gene DExH-box helicase 58 (DHX58) in hepatocytes, and then promote hepatic ferroptosis, while pre-treatment using IFN-α increased DHX58 expression and prevented ferroptosis during I/R injury. Mechanistically, DHX58 with RNA-binding activity could constitutively associate the mRNA of glutathione peroxidase 4 (GPX4), a crucial ferroptosis suppressor, and then recruit the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in m6A-dependent manner, thus enhancing GPX4 protein level and preventing hepatic ferroptosis. Therefore, we provide mechanistic evidence for the IFN-stimulated DHX58 in promoting the translation of m6A-modified Gpx4 mRNA, and suggest the promising clinical potential of IFN-α pre-treatment in the prevention of hepatic ferroptosis.

2024-05-24 | PXD042083 | Pride

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