Time-saving polyp detection in colon capsule endoscopy: evaluation of a novel software algorithm.

BACKGROUND: Colon capsule endoscopy (CCE) is a reliable method to detect colonic polyps in the well-prepared colon. As CCE evaluation can be time consuming, a new software algorithm might aid in reducing evaluation time. OBJECTIVES: The aim of the study was to evaluate whether it is feasible to reliably detect colon polyps in CCE videos with a new software algorithm the "collage mode" (Rapid 8 Software, Covidien/Medtronic®). METHODS: Twenty-nine CCE videos were randomly presented to three experienced and to three inexperienced investigators. Videos were evaluated by applying the collage mode. Investigation time was documented and the results (≥one polyp vs. no polyp) were compared with the findings of two highly experienced central readers who read the CCE videos in the standard mode beforehand. RESULTS: It took a median time of 9.8, 3.5, and 7.5 vs. 4.3, 4.6 and 12.5 min for experienced vs. inexperienced investigators to review the CCE videos. For detecting ≥one polyp vs. no polyp, sensitivity of 93.3%, 73.3%, and 93.3% was observed for the experienced and sensitivity of 46.7%, 33.3%, and 93.3% for the inexperienced CCE readers. CONCLUSION: Collage mode might allow for a quick review of CCE videos with a high polyp detection rate for experienced CCE readers. Future prospective studies should include CCE collage mode for rapid polyp detection to further prove the feasibility of practical colon polyp detection by CCE and possibly support the role of CCE as a screening tool in CRC prevention.

Histone deacetylase 10 promotes autophagy-mediated cell survival.

Tumor cells activate autophagy in response to chemotherapy-induced DNA damage as a survival program to cope with metabolic stress. Here, we provide in vitro and in vivo evidence that histone deacetylase (HDAC)10 promotes autophagy-mediated survival in neuroblastoma cells. We show that both knockdown and inhibition of HDAC10 effectively disrupted autophagy associated with sensitization to cytotoxic drug treatment in a panel of highly malignant V-MYC myelocytomatosis viral-related oncogene, neuroblastoma derived-amplified neuroblastoma cell lines, in contrast to nontransformed cells. HDAC10 depletion in neuroblastoma cells interrupted autophagic flux and induced accumulation of autophagosomes, lysosomes, and a prominent substrate of the autophagic degradation pathway, p62/sequestosome 1. Enforced HDAC10 expression protected neuroblastoma cells against doxorubicin treatment through interaction with heat shock protein 70 family proteins, causing their deacetylation. Conversely, heat shock protein 70/heat shock cognate 70 was acetylated in HDAC10-depleted cells. HDAC10 expression levels in high-risk neuroblastomas correlated with autophagy in gene-set analysis and predicted treatment success in patients with advanced stage 4 neuroblastomas. Our results demonstrate that HDAC10 protects cancer cells from cytotoxic agents by mediating autophagy and identify this HDAC isozyme as a druggable regulator of advanced-stage tumor cell survival. Moreover, these results propose a promising way to considerably improve treatment response in the neuroblastoma patient subgroup with the poorest outcome.

Histone deacetylase 8 in neuroblastoma tumorigenesis.

PURPOSE: The effects of pan-histone deacetylase (HDAC) inhibitors on cancer cells have shown that HDACs are involved in fundamental tumor biological processes such as cell cycle control, differentiation, and apoptosis. However, because of the unselective nature of these compounds, little is known about the contribution of individual HDAC family members to tumorigenesis and progression. The purpose of this study was to evaluate the role of individual HDACs in neuroblastoma tumorigenesis. EXPERIMENTAL DESIGN: We have investigated the mRNA expression of all HDAC1-11 family members in a large cohort of primary neuroblastoma samples covering the full spectrum of the disease. HDACs associated with disease stage and survival were subsequently functionally evaluated in cell culture models. RESULTS: Only HDAC8 expression was significantly correlated with advanced disease and metastasis and down-regulated in stage 4S neuroblastoma associated with spontaneous regression. High HDAC8 expression was associated with poor prognostic markers and poor overall and event-free survival. The knockdown of HDAC8 resulted in the inhibition of proliferation, reduced clonogenic growth, cell cycle arrest, and differentiation in cultured neuroblastoma cells. The treatment of neuroblastoma cell lines as well as short-term-culture neuroblastoma cells with an HDAC8-selective small-molecule inhibitor inhibited cell proliferation and clone formation, induced differentiation, and thus reproduced the HDAC8 knockdown phenotype. Global histone 4 acetylation was not affected by HDAC8 knockdown or by selective inhibitor treatment. CONCLUSIONS: Our data point toward an important role of HDAC8 in neuroblastoma pathogenesis and identify this HDAC family member as a specific drug target for the differentiation therapy of neuroblastoma.