Deficient Pms2, ERCC1, Ku86, CcOI in Field Defects During Progression to Colon Cancer

In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia

Are Surgical Guideline Changes in Diverticulitis Care Associated With Decreased Inpatient Healthcare Expenditure?

Objective:. To examine possible associations in inpatient healthcare expenditure and guideline changes in the surgical management of diverticulitis, in terms of both cost per discharge and total aggregate costs of care. Background:. Medical costs throughout the healthcare system continue to rise due to increased prices for services, increased quantities of high-priced technologies, and an increase in the amount of overall services. Methods:. We used a retrospective case-control design using the Healthcare Cost and Utilization Project National Inpatient Sample to evaluate cost per discharge and total aggregate costs of diverticulitis management between 2004 and 2015. The year 2010 was selected as the transition between the pre and postguideline implementation period. Results:. The sample consisted of 450,122 unweighted (2,227,765 weighted) inpatient discharges for diverticulitis. Before the implementation period, inpatient costs per discharge increased 1.13% in 2015 dollars (95% confidence intervals [CI] 0.76% to 1.49%) per quarter. In the postimplementation period, the costs per discharge decreased 0.27% (95% CI –0.39% to –0.15%) per quarter. In aggregate, costs of care for diverticulitis increased 0.61% (95% CI 0.28% to 0.95%) per quarter prior to the guideline change, and decreased 0.52% (95% CI –0.87% to –0.17) following the guideline change. Conclusions:. This is the first study to investigate any associations between evidence-based guidelines meant to decrease surgical utilization and inpatient healthcare costs. Decreased inpatient costs of diverticulitis management may be associated with guideline changes to reduce surgical intervention for diverticulitis, both in regards to cost per discharge and aggregate costs of care

Dataset for: First experience in clinical application of hyperspectral endoscopy for evaluation of colonic polyps

All code and processed images used to prepare the figures associated with this manuscript. Raw endoscopy videos can be obtained on request from the corresponding author

microRNA-451a regulates colorectal cancer proliferation in response to radiation

Abstract Background Colorectal cancer (CRC) is a leading cause of cancer-related death. The biologic response of CRC to standard of care adjuvant therapies such as chemotherapy and radiation are poorly understood. MicroRNAs (miRs) have been shown to affect CRC progression and metastasis. Therefore, we hypothesized that specific miRs modulate CRC response to chemoradiation. Methods In this study, we used miR expression profiling and discovered a set of microRNAs upregulated rapidly in response to either a single 2 Gy dose fraction or a 10 Gy dose of γ-radiation in mouse colorectal carcinoma models. We used gain and loss-of-function studies in 2D and 3Dcell proliferation assays and colony formation assays to understand the role of the top miR candidate from our profiling. We used Student’s T-tests for simple comparisons and two-factor ANOVA for evaluating significance. Results The most upregulated candidate at early time points in our signature, miR-451a inhibited tumor cell proliferation and attenuated surviving fraction in longer-term cultures. Conversely, inhibition of miR-451a increased proliferation, tumorsphere formation, and surviving fraction of tumor cells. Using a bioinformatics approach, we identified four genes, CAB39, EMSY, MEX3C, and EREG, as targets of miR-451a. Transfection of miR-451a decreased both mRNA and protein levels of these targets. Importantly, we found miR-451a expression was high and CAB39, EMSY levels were low in a small subset of rectal cancer patients who had a partial response to chemoradiation when compared to patients that had no response. Finally, analysis of a TCGA colorectal cancer dataset revealed that CAB39 and EMSY are upregulated at the protein level in a significant number of CRC patients. Higher levels of CAB39 and EMSY correlated with poorer overall survival. Conclusions Taken together, our data indicates miR-451a is induced by radiation and may influence colorectal carcinoma proliferation via CAB39 and EMSY pathways

Cancer and age related colonic crypt deficiencies in cytochrome c oxidase I

AIM: To investigate whether deficiency of expression of cytochrome c oxidase I (CcOI) in colonic crypts is associated with colon cancer

Additional file 1: of microRNA-451a regulates colorectal cancer proliferation in response to radiation

Figure S1 Affymetrix .cel files were uploaded to Partek Genomics Suite 6.6 and normalized using the default parameters of the RMA subroutine (background correction, quantile normalization, median polish summarization) as a single set. All probesets on each array were included in normalization. Following normalization, the log2 transformed signal data set was filtered to exclude all non-human probesets and control probesets. These miRNAs are qualitatively identified as being differentially expressed in both tumor types within a time point in the same direction. (XLSX 1528 kb

Additional file 2: of microRNA-451a regulates colorectal cancer proliferation in response to radiation

Figure S1 Responses of CT26 mouse and HCT-116 human colorectal carcinoma cells to radiation. Figure S2 miR-451a levels in HCT-116 and CT26 cells at different doses of radiation. Figure S3 miR-451a levels in non-transformed primary cells. Figure S4 miR-451a levels in HCT-116 in survival fraction studies. Figure S5 Ectopic expression of miR-451a inhibits proliferation and clonogenic survival of CT26 cells. Figure S6 Inhibition of miR-451a does not affect proliferation of endothelial cells in response radiation. Figure S7 Ectopic expression of miR-451a inhibits of HCT-116 cells in combination with radiation and 5-FU.Figure S8 miR binding site predictions for miR-451a on target mRNAs. Figure S9 Regulation of miR-451a and target genes in human colorectal cancer. (PPTX 1174 kb

Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future DirectionsSummary

In patients with colorectal cancer (CRC) that metastasizes to the liver, there are several key goals for improving outcomes including early detection, effective prognostic indicators of treatment response, and accurate identification of patients at high risk for recurrence. Although new therapeutic regimens developed over the past decade have increased survival, there is substantial room for improvement in selecting targeted treatment regimens for the patients who will derive the most benefit. Recently, there have been exciting developments in identifying high-risk patient cohorts, refinements in the understanding of systemic vs localized drug delivery to metastatic niches, liquid biomarker development, and dramatic advances in tumor immune therapy, all of which promise new and innovative approaches to tackling the problem of detecting and treating the metastatic spread of CRC to the liver. Our multidisciplinary group held a state-of-the-science symposium this past year to review advances in this rapidly evolving field. Herein, we present a discussion around the issues facing treatment of patients with CRC liver metastases, including the relationship of discrete gene signatures with prognosis. We also discuss the latest advances to maximize regional and systemic therapies aimed at decreasing intrahepatic recurrence, review recent insights into the tumor microenvironment, and summarize advances in noninvasive multimodal biomarkers for early detection of primary and recurrent disease. As we continue to advance clinically and technologically in the field of colorectal tumor biology, our goal should be continued refinement of predictive and prognostic studies to decrease recurrence after curative resection and minimize treatment toxicity to patients through a tailored multidisciplinary approach to cancer care. Keywords: Colorectal Cancer Liver Metastasis, Biomarkers, Hepatic Arterial Infusion, High-Risk Colorectal Cancer, Recurrenc