Colorectal cancer (CRC) cell lines are widely used pre-clinical model systems. Comprehensive insights into their molecular characteristics may improve model selection for biomedical studies.
We have ...performed DNA, RNA and protein profiling of 34 cell lines, including (i) targeted deep sequencing (n = 612 genes) to detect single nucleotide variants and insertions/deletions; (ii) high resolution DNA copy number profiling; (iii) gene expression profiling at exon resolution; (iv) small RNA expression profiling by deep sequencing; and (v) protein expression analysis (n = 297 proteins) by reverse phase protein microarrays.
The cell lines were stratified according to the key molecular subtypes of CRC and data were integrated at two or more levels by computational analyses. We confirm that the frequencies and patterns of DNA aberrations are associated with genomic instability phenotypes and that the cell lines recapitulate the genomic profiles of primary carcinomas. Intrinsic expression subgroups are distinct from genomic subtypes, but consistent at the gene-, microRNA- and protein-level and dominated by two distinct clusters; colon-like cell lines characterized by expression of gastro-intestinal differentiation markers and undifferentiated cell lines showing upregulation of epithelial-mesenchymal transition and TGFβ signatures. This sample split was concordant with the gene expression-based consensus molecular subtypes of primary tumors. Approximately ¼ of the genes had consistent regulation at the DNA copy number and gene expression level, while expression of gene-protein pairs in general was strongly correlated. Consistent high-level DNA copy number amplification and outlier gene- and protein- expression was found for several oncogenes in individual cell lines, including MYC and ERBB2.
This study expands the view of CRC cell lines as accurate molecular models of primary carcinomas, and we present integrated multi-level molecular data of 34 widely used cell lines in easily accessible formats, providing a resource for preclinical studies in CRC.
Drug resistance is a major cause of the inefficacy of conventional cancer therapies, and often accompanied by severe side effects. Thus, there is an urgent need to develop novel drugs with low ...cytotoxicity, high selectivity and minimal acquired chemical resistance. Peptide-based drugs (less than 0.5 kDa) have emerged as a potential approach to address these issues due to their high specificity and potent anticancer activity. In this study, we developed a support vector machine model (SVM) to detect the potential anticancer properties of novel peptides by scanning the American University in Cairo (AUC) Red Sea metagenomics library. We identified a novel 37-mer antimicrobial peptide through SVM pipeline analysis and characterized its anticancer potential through in silico cross-examination. The peptide sequence was further modified to enhance its anticancer activity, analyzed for gene ontology, and subsequently synthesized. To evaluate the anticancer properties of the modified 37-mer peptide, we assessed its effect on the viability and morphology of SNU449, HepG2, SKOV3, and HeLa cells, using an MTT assay. Additionally, we evaluated the migration capabilities of SNU449 and SKOV3 cells using a scratch-wound healing assay. The targeted selectivity of the modified peptide was examined by evaluating its hemolytic activity on human erythrocytes. Treatment with the peptide significantly reduced cell viability and had a critical impact on the morphology of hepatocellular carcinoma (SNU449 and HepG2), and ovarian cancer (SKOV3) cells, with a marginal effect on cervical cancer cell lines (HeLa). The viability of a human fibroblast cell line (1Br-hTERT) was also significantly reduced by peptide treatment, as were the proliferation and migration abilities of SNU449 and SKOV3 cells. The annexin V assay revealed programmed cell death (apoptosis) as one of the potential cellular death pathways in SNU449 cells upon peptide treatment. Finally, the peptide exhibited antimicrobial effects on both gram-positive and gram-negative bacterial strains. The findings presented here suggest the potential of our novel peptide as a potent anticancer and antimicrobial agent.
An efficient PET-based probe, in which the ferrocene quencher and the naphthalimide fluorophore are linked by a disulfide bond, has been developed. This probe can be activated by GSH with ...fluorescence a turn-on response for blocking the PET process. In addition, it was successfully applied for distinguishing cancer cells from normal cells.
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An efficient PET-based probe, in which the ferrocene quencher and the naphthalimide fluorophore are linked by a disulfide bond, has been developed. This probe can be activated by GSH with fluorescence a turn-on response for blocking the PET process. In addition, it was successfully applied for distinguishing cancer cells from normal cells
In recent years there has been a growing interest among cancer biologists in cancer metabolism. This Review summarizes past and recent advances in our understanding of the reprogramming of glucose ...metabolism in cancer cells, which is mediated by oncogenic drivers and by the undifferentiated character of cancer cells. The reprogrammed glucose metabolism in cancer cells is required to fulfil anabolic demands. This Review discusses the possibility of exploiting the reprogrammed glucose metabolism for therapeutic approaches that selectively target cancer cells.
The purpose of this study was to determine the role of HYP-PDT and its cytotoxic and immunomodulatory efficacy in the treatment of colorectal cancer.
SW480 and SW620 cells were properly prepared and ...then treated with HYP-PDT. After HYP-PDT treatment, changes in the concentrations of GM-CSF, MIF, VCAM-1, ICAM-1 and IL-2, IL-4, IL6 were analyzed using Bioplex method.
For SW480 cells: after HYP-PDT, there was a marked decrease in the secretion of GM-CSF, MIF, VCAM-1 and ICAM-1. The applied HYP-PDT showed no effect on the secretion of IL-2, IL-4 and IL-6 by the cell lines.
HYP-PDT shows immunomodulatory potential in in vitro experiments.
The purpose of this study was to determine the role of HYP-PDT and its cytotoxic and immunomodulatory efficacy in the treatment of oral cancer.
SCC-25(oral squamous cell carcinoma) and HGF-1 (gingiva ...fibroblasts) cells were properly prepared and then treated with HYP-PDT. After HYP-PDT treatment, changes in the concentrations of sTNF-R1, sTNF-R2 and sCD30 were analyzed using Bioplex method.
For SCC-25 cells: after HYP-PDT, there was a marked increase in the secretion of sTNF-R1 and sCD30 and no change in concentration of sTNF-R2. The applied HYP-PDT showed no effect on the secretion of sTNF-R1, sTNF-R2 and sCD30 by the HGF-1 cell line.
HYP-PDT shows immunomodulatory potential in in vitro experiments.
Local anesthetics are widely used during clinical cancer surgeries. Studies have suggested that the use and the type of anesthesia affect cancer outcomes. In vivo studies and clinical data show that ...the use of local anesthetics is potentially beneficial for cancer treatment. However, the effect of the use of local anesthetics on the survival rate of cancer patients following surgery is controversial and, so far, little is known about the direct effects of local anesthetics on cancer cells. This work reviews and summarizes the published literature regarding the preclinical research methods and findings on the influence of local anesthetics on cancer cells. We hope that a thorough understanding of this subject will help to define optimal anesthetic regimens that lead to better outcomes for clinical cancer patients.
•Nanomedicine is a promising strategy for target-specific delivery of therapeutics.•Stimuli-responsive nanocarriers enhance tissue specificity.•Advances in nanotechnology improve translation of ...stimuli-responsive nanocarriers.
Nanoscale drug delivery systems or nanocarriers have shown tremendous promise in the target-specific delivery of therapeutics as well as diagnostic agents. Additional properties can be introduced into nanocarriers to enhance the bioavailability and targeting efficiency of the transported drugs at diseased sites. Such nanocarriers are usually incorporated with stimuli-responsive components that can be triggered by specific stimuli (e.g., temperature, pH, or enzymes) and further induced by certain biological responses, such as enzyme hydrolysis and molecular conformational changes, leading to the controlled release of the transported molecules at targeted sites. In this review, we discuss various stimuli-responsive nanoscale delivery systems and summarize the current perspectives as well as challenges facing the successful translation of these innovative stimuli-responsive nanocarriers from the bench to the bedside.
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