Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Phase I:Decitabine by Hepatic Arterial Infusion(HAI) in Unresectable Liver Metastases Colorectal Cancer (CRC)

ABSTRACT: Despite the advances in the medical treatment of unresectable liver metastases from colorectal cancer there is currently no curative treatment option available for these patients. Decitabine is a cytidine analog with proven anti-neoplastic activity in patients with acute myeloid leukemia and myelodysplastic syndromes. Decitabine causes demethylation of the DNA strands of replicating cells. Hereby decitabine treatment demethylates the promoter regions of tumor suppressor- and cancer testis antigen encoding genes leading to expression of these genes by the cancer cells. The hepatic arterial route for administration of cytotoxic drugs has been widely explored in treatment of colorectal cancer liver metastases because these metastases depend for their blood flow from this artery (as opposed to the normal liver tissue that is mainly dependent from the portal vein). By investigating the administration of decitabine by hepatic arterial infusion the investigators intend to explore the potential advantage of minimizing the systemic exposure (and toxicity) and maximizing the concentration of decitabine within the liver metastasis. The primary objective of this phase I will be to establish the recommended dose for decitabine by HAI for further use in phase II trials. The most important secondary objective will be to document the effect of decitabine by HAI on the expression of cancer testis antigens by the colorectal cancer cells, serving as a reference for potential further exploration of decitabine by HAI in combination with cancer immunotherapy

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

PROVIDER: 2180208 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Testing Pump Chemotherapy in Addition to Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone for Patients With Unresectable Colorectal Liver Metastases: The PUMP Trial

Project description:This phase III trial compares hepatic arterial infusion (HAI) (pump chemotherapy) in addition to standard of care chemotherapy versus standard of care chemotherapy alone in treating patients with colorectal cancer that has spread to the liver (liver metastases) and cannot be removed by surgery (unresectable). HAI uses a catheter to carry a tumor-killing chemotherapy drug called floxuridine directly into the liver. HAI is already approved by the Food and Drug Administration (FDA) for use in metastatic colorectal cancer to the liver, but it is only available at a small number of hospitals, and most of the time it is not used until standard chemotherapy stops working. Standard chemotherapy drugs work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding HAI to standard chemotherapy may be effective in shrinking or stabilizing unresectable colorectal liver metastases.

| 60395 | ecrin-mdr-crc

Specific extracellular matrix remodeling signature of colon hepatic metastases

Project description:To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment. 57 samples of patients with stage IV colorectal cancer. We compared using Affymetrix chips gene expression profiles between primary tumors and hepatic metastases

2013-09-01 | E-GEOD-49355 | biostudies-arrayexpress

Specific extracellular matrix remodeling signature of colon hepatic metastases [HG-U133B]

2014-10-15 | E-GEOD-62321 | biostudies-arrayexpress

FUDR/Oxaliplatin HAI Plus Irinotecan vs. FOLFOXIRI Chemotherapy in Treating Initially Unresectable CRCLM

Project description:The aim of the trial is to compare the objective response rates of FUDR/Oxaliplatin HAI plus CPT-11 and FOLFOXIRI chemotherapy in patients with initially non-resectable metastatic colorectal cancer liver metastases. The patients will be treated with systemic FOLFOXIRI chemotherapy or FUDR/Oxaliplatin hepatic arterial infusion with CPT-11 systemic chemotherapy.

| 2284699 | ecrin-mdr-crc

Specific extracellular matrix remodeling signature of colon hepatic metastases [HG-U133B]

2014-10-15 | GSE62321 | GEO

Specific extracellular matrix remodeling signature of colon hepatic metastases [HG-U133A]

2013-09-01 | GSE49355 | GEO

Single cell transcriptomes of hepatic immune cells from mice with and without colorectal cancer liver metastasis

Project description:Metastasis is the primary cause of cancer mortality. Cancer frequently metastasizes to the liver. We report that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. Mechanistically, liver metastases siphon activated CD8+ T cells from systemic circulation. Within the liver, activated antigen-specific Fas+CD8+ T cells undergo apoptosis following their interaction with FasL+CD11b+F4/80+ monocyte-derived macrophages. Consequently, liver metastases create a systemic immune desert in both preclinical models and patients. Liver-directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T-cell survival, and reduces hepatic siphoning. Thus, liver metastases co-opt host peripheral tolerance mechanisms to cause acquired immunotherapy resistance through CD8+ T-cell deletion and the combination of liver-directed radiotherapy and immunotherapy is a novel therapeutic strategy to promote systemic anti-tumour immunity.

2020-10-02 | GSE157600 | GEO

Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases

Project description:Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble, high molecular weight proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the extracellular matrix from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of differentially expressed proteins significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the extracellular matrix component. One of the proteins upregulated in liver metastatic ECM, Annexin A1, was not previously studied in the context of cancer-associated matrisome. Here we show that Annexin A1 was markedly upregulated in colon cancer cell lines compared to cancer cells of other origin, and also overrepresented in human primary colorectal lesions as well as hepatic metastases in comparison with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes Annexin A1 as a putative target for this disease.

2020-05-26 | PXD013350 | Pride

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

Oxaliplatin and Capecitabine With or Without an Hepatic Arterial Infusion With Floxuridine in Treating Patients Who Are Undergoing Surgery and/or Ablation for Liver Metastases Due to Colorectal Cancer

Project description:RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, capecitabine, and floxuridine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hepatic arterial infusion uses a catheter to carry tumor-killing substances, such as chemotherapy, directly into the liver. Giving chemotherapy in different ways may kill more tumor cells. It is not yet known whether giving oxaliplatin and capecitabine together with an hepatic arterial infusion with floxuridine is more effective than giving oxaliplatin and capecitabine alone in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer. PURPOSE: This randomized phase III trial is studying oxaliplatin, capecitabine, and an hepatic arterial infusion with floxuridine to see how well they work compared to oxaliplatin and capecitabine in treating patients who are undergoing surgery and/or ablation for liver metastases due to colorectal cancer.

| 2024624 | ecrin-mdr-crc

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data