Dataset Information

Yttrium-90 Radioembolization + Nivolumab for Liver + Extra-hepatic Metastases From Colorectal Cancer

ABSTRACT: This study has two portions. The main goal of the Phase Ib portion of this research study is to see at what time Yttrium-90 (Y-90) radioembolization therapy and nivolumab can safely be given to patients without having too many side effects. Other purposes of this research study will be to study any tumor responses. The Phase II portion of the study will test how many patients show shrinkage in their tumor with this combination of medicines and what changes occur inside the cancer cells and blood cells after treatment. The study team will pick the part of the study each subject participates in. Y-90 radioembolization therapy is minimally invasive procedure that combines two types of therapy (embolization which blocks certain blood vessels, and radiation therapy, which kills cancer cells) to treat cancer tumors in the liver. This works with tiny glass or resin beads filled with the radioactive isotope yttrium-90 (Y-90). They are placed inside the blood vessels that feed the tumor in the liver. This blocks the supply of blood to the cancer cells and delivers a high dose of radiation to the tumor while sparing normal tissue. Nivolumab is an FDA approved medicine that is used for the treatment of different types of cancers and metastases (second growths from cancer).

DISEASE(S): Metastatic Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2256236 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:The lymphatic vascular system plays important roles in the maintenance of interstitial fluid pressure, the afferent immune response and the absorption of dietary lipids. However, the molecular mechanisms that control lymphatic vessel network maturation and function remain largely unknown. To identify novel players in lymphatic vessel function, we isolated pure populations of lymphatic and blood vascular endothelial cells from mouse intestine using fluorescence-activated high-speed cell sorting and performed transcriptional profiling. We found that the axonal guidance molecules semaphorin 3A (Sema3A) and Sema3D were specifically expressed by lymphatic vessels. Quantitative PCR of ex vivo isolated cells and immunohistochemical analysis confirmed these results. Importantly, we found that the semaphorin receptor neuropilin-1 (Nrp-1) is expressed on the valves of collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1, but not with an antibody that blocks VEGFA binding to Nrp-1, resulted in abnormal development of collecting lymphatic vessels and valves, and aberrant smooth muscle cell coverage. Conversely, Sema3A-deficient mice displayed branching defects of collecting lymphatic vessels as well as impaired valve development. Together, these results reveal an unanticipated role of Sema3A/Nrp-1 signaling in the maturation of the lymphatic vascular network. Colon single-cell suspensions were prepared by a fast protocol that minimizes the RNA degradation. Fluorescence-activated cell sorting (FACS) was used to sort blood vascular endothelial cells (BEC) and lymphatic endothelial cells (LEC). 4 animal-matched pairs of LEC and BEC were chosen based on the quality of extracted and amplified material to provide homogenous groups of biological replicates. This gave 8 samples to analyze. Samples present LEC and BEC isolated from 4 healthy normal mice. The 4 mice used present the 4 biological replicates.

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Yttrium-90 Radioembolization + Nivolumab for Liver + Extra-hepatic Metastases From Colorectal Cancer

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