Mouse models in colon cancer, inferences, and implications.

Mouse models of colorectal cancer (CRC) have been crucial in the identification of the role of genes responsible for the full range of pathology of the human disease and have proved to be dependable for testing anti-cancer drugs. Recent research points toward the relevance of tumor, angiogenic, and immune microenvironments in CRC progression to late-stage disease, as well as the treatment of it. This study examines important mouse models in CRC, discussing inherent strengths and weaknesses disclosed during their construction.

Co-expression patterns explain how a basic transcriptional role for MYC modulates and MAPK pathways in colon and lung adenocarcinomas.

A subset of proliferation genes that are associated with origin licensing, firing, and DNA synthesis has been compared to known drivers of colon (COAD) and lung (LUAD) adenocarcinomas using Spearman's rank correlation coefficients. The frequency with which APC, CTNNB1, KRAS, MYC, Braf, TP53, Rb1, EGFR, and cell cycle components have direct or indirect co-expression with the proliferation factors permits identification of their expression relative to the G1-S phase of the cell cycle. Here, adenomatous polyposis coli (APC), a negative regulator of signaling known to function through MYC, indirectly co-expresses at the same frequency as proliferation genes in both COAD and LUAD, consistent with M phase expression.

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation.

Genes of the pre-replication, pre-initiation and replisome complexes duplicate the genome from many sites once in a normal cell cycle. This study examines complex components in lung adenocarcinoma (LUAD) closely, correlating changes in the genome and transcriptome with proliferation and overall survival. Molecular subtypes (The Cancer Genome Atlas (TCGA), 2014) based on copy number, DNA methylation, and mRNA expression had variable proliferation levels, the highest correlating with decreased survival.

Optical imaging with a novel cathepsin-activatable probe for enhanced detection of colorectal cancer.

We evaluated a cysteine cathepsin-activatable optical imaging probe (LUM015) with improved kinetics relative to larger macromolecules for detection and characterization of colorectal cancer (CRC), and thereby assessed its potential use in fluorescence-guided colonoscopy. We showed that LUM015 is stable in plasma. In-vitro studies demonstrated selectivity of LUM015 for targeting cathepsins; there was robust increase in emitted fluorescence signal from the cathepsin overexpressing HT-29 CRC cells within 1-5 minutes after incubation with LUM015 compared to the cells incubated with combination of LUM015 and a pan-protease inhibitor (as negative control).