Silencing NIK potentiates anti-VEGF therapy in a novel 3D model of colorectal cancer angiogenesis.

Silencing NIK potentiates anti-VEGF therapy in a novel 3D model of colorectal cancer angiogenesis. Oncotarget. 2018 Jun 19;9(47):28445-28455 Authors: Maracle CX, Jeucken KCM, Helder B, van Gulik TM, Steins A, van Laarhoven HWM, Tas SW Abstract Angiogenesis is essential for colorectal cancer (CRC) progression, as demonstrated by the beneficial clinical effects of therapeutics inhibiting VEGF signaling. However, alternative mechanisms of neovascularization can develop, resulting in treatment failure. Previously we demonstrated NF-κB-inducing kinase (NIK) contributes to pathological angiogenesis. Here, we investigate NIK as a therapeutic target in endothelial cells (EC) in CRC. To determine NIK expression levels in CRC tissues, we immunostained both primary colorectal tumors and tumors metastasized to the liver. Additionally, a 3D tumor-stromal cell interaction model was developed including EC, fibroblasts and CRC cells to study tumor angiogenesis. This model tested efficacy of NIK-targeting siRNA (siNIK) in EC alone or in combination with the anti-VEGF antibody, bevacizumab. Both primary CRC and liver metastases contained blood vessels expressing NIK. In patients receiving chemotherapy plus bevacizumab, immature NIK+ vessels (p
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

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AbstractAll colon cancer patients with lymph node (LN) positive disease are treated with chemotherapy. Patients with node negative disease are usually cured by surgery alone. Yet about 20% of patients develop recurrence within 5  years despite node negative status. This may often be the result of missed micrometastases by conventional examination. Sentinel lymph node (SLN) mapping was developed to find those nodes detected by blue dye which was ultrastaged to detect micrometastases. Consecutive patients, underwent SLN mapp ing with the blue dye with success rate of 99.2%. Average number of LN was 18.3, average number ...
Source: Clinical and Experimental Metastasis - Category: Cancer & Oncology Source Type: research
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Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
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Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
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Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
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