Dataset Information

Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer.

ABSTRACT: BACKGROUND:The lack of predictive biomarkers or test systems contributes to high failure rates of systemic therapy in metastasized colorectal carcinoma, accounting for a still unfavorable prognosis. Here, we present an ex vivo functional assay to measure drug-response based on a tissue slice culture approach. METHODS:Tumor tissue slices of hepatic metastases of nine patients suffering from colorectal carcinoma were cultivated for 72?h and treated with different concentrations of the clinically relevant drugs Oxaliplatin, Cetuximab and Pembrolizumab. Easy to use, objective and automated analysis routines based on the Halo platform were developed to measure changes in proliferative activity and the morphometric make-up of the tumor. Apoptotic indices were assessed semiquantitatively. RESULTS:Untreated tumor tissue slices showed high morphological comparability with the original "in vivo"-tumor, preserving proliferation and stromal-tumor interactions. All but one patients showed a dosage dependent susceptibility to treatment with Oxaliplatin, whereas only two patients showed responses to Cetuximab and Pembrolizumab, respectively. Furthermore, we identified possible non-responders to Cetuximab therapy in absence of RAS-mutations. CONCLUSIONS:This is the first time to demonstrate feasibility of the tissue slice culture approach for metastatic tissue of colorectal carcinoma. An automated readout of proliferation and tumor-morphometry allows for quantification of drug susceptibility. This strongly indicates a potential value of this technique as a patient-specific test-system of targeted therapy in metastatic colorectal cancer. Co-clinical trials are needed to customize for clinical application and to define adequate read-out cut-off values.

SUBMITTER: Martin SZ

PROVIDER: S-EPMC6824140 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer.

Martin Steve Z SZ Wagner Daniel C DC Hörner Nina N Horst David D Lang Hauke H Tagscherer Katrin E KE Roth Wilfried W

BMC cancer 20191101 1

<h4>Background</h4>The lack of predictive biomarkers or test systems contributes to high failure rates of systemic therapy in metastasized colorectal carcinoma, accounting for a still unfavorable prognosis. Here, we present an ex vivo functional assay to measure drug-response based on a tissue slice culture approach.<h4>Methods</h4>Tumor tissue slices of hepatic metastases of nine patients suffering from colorectal carcinoma were cultivated for 72 h and treated with different concentrations of t ...[more]

PMID: 31675944

Similar Datasets

Project description:West Nile virus (WNV) is a neurotropic flavivirus that causes significant neuroinvasive disease involving the brain and/or spinal cord. Experimental mouse models of WNV infection have established the importance of innate and adaptive immune responses in controlling the extent and severity of central nervous system (CNS) disease. However, differentiating between immune responses that are intrinsic to the CNS and those that are dependent on infiltrating inflammatory cells has proven difficult. We used a murine ex vivo spinal cord slice culture (SCSC) model to determine the innate immune processes specific to the CNS during WNV infections. By 7 days after ex vivo infection of SCSCs, the majority of neurons and a substantial percentage of astrocytes were infected with WNV, resulting in apoptotic cell death and astrogliosis. Microglia, the resident immune cells of the CNS, were activated by WNV infection, as exemplified by their amoeboid morphology, the development of filopodia and lamellipodia, and phagocytosis of WNV-infected cells and debris. Microglial cell activation was concomitant with increased expression of proinflammatory cytokines and chemokines, including CXCL10, CXCL1, CCL5, CCL3, CCL2, tumor necrosis factor alpha (TNF-?), TNF-related apoptosis-inducing ligand (TRAIL), and interleukin-6 (IL-6). The application of minocycline, an inhibitor of neuroinflammation, altered the WNV-induced proinflammatory cytokine/chemokine expression profile, with inhibited production of CCL5, CCL2, and IL-6. Our findings establish that CNS-resident cells have the capacity to initiate a robust innate immune response against WNV infection in the absence of infiltrating inflammatory cells and systemic immune responses.There are no specific treatments of proven efficacy available for WNV neuroinvasive disease. A better understanding of the pathogenesis of WNV CNS infection is crucial for the rational development of novel therapies. Development of a spinal cord slice culture (SCSC) model facilitates the study of WNV pathogenesis and allows investigation of the intrinsic immune responses of the CNS. Our studies demonstrate that robust CNS innate immune responses, including microglial activation and proinflammatory cytokine/chemokine production, develop independently of contributions from the peripheral immune system and CNS-infiltrating inflammatory cells.

Dataset Information

Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer.

Publications

Ex vivo tissue slice culture system to measure drug-response rates of hepatic metastatic colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets