Detecting colorectal cancer using electrical impedance spectroscopy: an ex vivo feasibility study

Objective: Colorectal cancer is the fourth most common cancer worldwide, with a lifetime risk of around 20%. Current solutions do not allow clinicians to objectively assess tissue abnormality during endoscopy and perioperatively. A solution capable of objectively assessing samples in real time could greatly improve the treatment process. A solution that can be integrated in minimally invasive diagnostics and management strategies to provide real-time point-of-care information would be greatly transformative. Electrical impedance spectroscopy (EIS) may provide such a solution. In this paper, we present a feasibility study on using EIS in assessing colorectal tissue. Approach: We performed tetrapolar EIS using ZedScan on excised human colorectal tumour tissue and the matched normal colonic mucosa in 22 freshly resected specimens following elective surgery for colorectal cancer. Histopathological examination was used to confirm the final diagnosis. Statistical significance was assessed with Wilcoxon signed rank test. Main results: Tetrapolar EIS could discriminate cancer with statistically significant results when applying frequencies between 305 Hz – 625 kHz (p < 0.05). 300 Ω was set as the transfer impedance threshold to detect cancer. Thus, the area under the corresponding receiver operating characteristic curve for this threshold was 0.7105. Significance: This feasibility study demonstrates that impedance spectra changes in colorectal cancer tissue are detectable and may be statistically significant, suggesting that EIS has the potential to be the core technology in a novel non-invasive point of care test for detecting colorectal cancer. These results warrant further development and increasing the size of the study with a device specificity designed for colorectal cancer

L-glyceraldehyde inhibits neuroblastoma cell growth via a multi-modal mechanism on metabolism and Signaling

Glyceraldehyde (GA) is a three-carbon monosaccharide that can be present in cells as a by-product of fructose metabolism. Bruno Mendel and Otto Warburg showed that the application of GA to cancer cells inhibits glycolysis and their growth. However, the molecular mechanism by which this occurred was not clarified. We describe a novel multi-modal mechanism by which the L-isomer of GA (L-GA) inhibits neuroblastoma cell growth. L-GA induces significant changes in the metabolic profile, promotes oxidative stress and hinders nucleotide biosynthesis. GC-MS and (13)C-labeling was employed to measure the flow of carbon through glycolytic intermediates under L-GA treatment. It was found that L-GA is a potent inhibitor of glycolysis due to its proposed targeting of NAD(H)-dependent reactions. This results in growth inhibition, apoptosis and a redox crisis in neuroblastoma cells. It was confirmed that the redox mechanisms were modulated via L-GA by proteomic analysis. Analysis of nucleotide pools in L-GA-treated cells depicted a previously unreported observation, in which nucleotide biosynthesis is significantly inhibited. The inhibitory action of L-GA was partially relieved with the co-application of the antioxidant N-acetyl-cysteine. We present novel evidence for a simple sugar that inhibits cancer cell proliferation via dysregulating its fragile homeostatic environment

The effects of timing of fine needle aspiration biopsies on gene expression profiles in breast cancers

<p>Abstract</p> <p>Background</p> <p>DNA microarray analysis has great potential to become an important clinical tool to individualize prognostication and treatment for breast cancer patients. However, with any emerging technology, there are many variables one must consider before bringing the technology to the bedside. There are already concerted efforts to standardize protocols and to improve reproducibility of DNA microarray. Our study examines one variable that is often overlooked, the timing of tissue acquisition, which may have a significant impact on the outcomes of DNA microarray analyses especially in studies that compare microarray data based on biospecimens taken <it>in vivo </it>and <it>ex vivo</it>.</p> <p>Methods</p> <p>From 16 patients, we obtained paired fine needle aspiration biopsies (FNABs) of breast cancers taken before (PRE) and after (POST) their surgeries and compared the microarray data to determine the genes that were differentially expressed between the FNABs taken at the two time points. qRT-PCR was used to validate our findings. To examine effects of longer exposure to hypoxia on gene expression, we also compared the gene expression profiles of 10 breast cancers from clinical tissue bank.</p> <p>Results</p> <p>Using hierarchical clustering analysis, 12 genes were found to be differentially expressed between the FNABs taken before and after surgical removal. Remarkably, most of the genes were linked to FOS in an early hypoxia pathway. The gene expression of FOS also increased with longer exposure to hypoxia.</p> <p>Conclusion</p> <p>Our study demonstrated that the timing of fine needle aspiration biopsies can be a confounding factor in microarray data analyses in breast cancer. We have shown that FOS-related genes, which have been implicated in early hypoxia as well as the development of breast cancers, were differentially expressed before and after surgery. Therefore, it is important that future studies take timing of tissue acquisition into account.</p