scholarly journals Proteomic indicators of oxidation and hydration state in colorectal cancer

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2238 ◽  
Author(s):  
Jeffrey M. Dick
Keyword(s):  
Colorectal Cancer ◽  
Essential Feature ◽  
Microbial Community Composition ◽  
Compositional Analysis ◽  
Clinical Samples ◽  
Systematic Change ◽  
Bacterial Genomes ◽  
Healthy Donors ◽  
Relative Potential ◽  
Related Proteins

New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer. Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue (${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$) is computed by writing the overall formation reactions of proteins from basis species. Using results reported in proteomic studies of clinical samples, many datasets exhibit higher meanZCor ${\overline{n}}_{{\mathrm{H}}_{2}\mathrm{O}}$ of proteins in carcinoma or adenoma compared to normal tissue. In contrast, average protein compositions in bacterial genomes often have lowerZCfor bacteria enriched in fecal samples from cancer patients compared to healthy donors. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H2O and fugacity of O2that reflect the compositional differences. The compositional analysis suggests that a systematic change in chemical composition is an essential feature of cancer proteomes, and the thermodynamic descriptions show that the observed proteomic transformations in host tissue could be promoted by relatively high microenvironmental oxidation and hydration states.

scholarly journals Proteomic indicators of oxidation and hydration state in colorectal cancer

2016 ◽  
Author(s):  
Jeffrey M. Dick
Keyword(s):  
Colorectal Cancer ◽  
Microbial Community ◽  
Essential Feature ◽  
Microbial Community Composition ◽  
Compositional Analysis ◽  
Community Profiling ◽  
Systematic Shift ◽  
Relative Potential ◽  
Related Proteins ◽  
Chemical Formulas

ABSTRACTNew integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer (CRC). Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (ZC) can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue is computed by writing the overall formation reactions of proteins from basis species. Using reported results from clinical proteomic studies and microbial community profiling, many datasets exhibit higher mean ZC or of proteins in carcinoma or adenoma compared to normal tissue. Microbial protein compositions have lower ZC in bacteria enriched in fecal samples from cancer patients. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H2O and fugacity of O2 that reflect the compositional differences. The compositional analysis suggests that a systematic shift in chemical composition is an essential feature of the cancer proteome, and the thermodynamic descriptions show that the observed proteomic transformations could be promoted by microenvironments shifted toward more oxidizing conditions and increased hydration levels.

scholarly journals Integrated Microfluidic Device for Enrichment and Identification of Circulating Tumor Cells from the Blood of Patients with Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Wentao Su ◽  
Hao Yu ◽  
Lei Jiang ◽  
Wenwen Chen ◽  
Hongjing Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Microfluidic Device ◽  
Whole Blood ◽  
Circulating Tumor Cell ◽  
Clinical Samples ◽  
Leukocyte Depletion ◽  
Healthy Donors ◽  
Integrated Device ◽  
Optimized Conditions

Integrated device with high purity for circulating tumor cell (CTC) identification has been regarded as a key goal to make CTC analysis a “bench-to-bedside” technology. Here, we have developed a novel integrated microfluidic device that can enrich and identify the CTCs from the blood of patients with colorectal cancer. To enrich CTCs from whole blood, microfabricated trapping chambers were included in the miniaturized device, allowing for the isolation of tumor cells based on differences in size and deformability between tumor and normal blood cells. Microvalves were also introduced sequentially in the device, enabling automatic CTC enrichment as well as immunostaining reagent delivery. Under optimized conditions, the whole blood spiked with caco-2 cells passing through the microfluidic device after leukocyte depletion and approximately 73% of caco-2 cells were identified by epithelial cell adhesion molecule (EpCAM) staining. In clinical samples, CTCs were detectable from all patients with advanced colorectal cancer within 3 h. In contrast, the number of CTCs captured on the device from the blood of healthy donors was significantly lower than that from the patients, suggesting the utilization of the integrated device for further molecular analyses of CTCs.

scholarly journals Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2718
Author(s):  
María González-González ◽  
José María Sayagués ◽  
Luis Muñoz-Bellvís ◽  
Carlos Eduardo Pedreira ◽  
Marcello L. R. de Campos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Utility ◽  
Genetic Alterations ◽  
Western World ◽  
Sporadic Colorectal Cancer ◽  
Protein Arrays ◽  
Humoral Immune ◽  
Cellular Processes ◽  
Healthy Donors ◽  
Associated Proteins

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

scholarly journals Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xiaoli Ren ◽  
Jianbiao Xiao ◽  
Wanning Zhang ◽  
Feifei Wang ◽  
Yongrong Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Suppressor Cells ◽  
Metastatic Progression ◽  
Ht29 Cells ◽  
Metastatic Cells ◽  
Long Time ◽  
Mice Liver ◽  
Short Time ◽  
Related Proteins

AbstractIn colorectal cancer (CRC), overt metastases often appear after years of latency. But the signals that cause micro-metastatic cells to remain indolent, thereby enabling them to survive for extended periods of time, are unclear. Immunofluorescence and co-immunoprecipitation assays were used to explore the co-localization of CCL7 and CCR2. Immunohistochemical (IHC) assays were employed to detect the characters of metastatic HT29 cells in mice liver. Flow cytometry assays were performed to detect the immune cells. Bruberin vivo MS FX Pro Imager was used to observe the liver metastasis of CRC in mice. Quantitative real-time PCR (qRT-PCR) and western blot were employed to detect the expressions of related proteins. Trace RNA sequencing was employed to identify differentially expressed genes in MDSCs from liver micro-M and macro-M of CRC in mice. Here, we firstly constructed the vitro dormant cell models and metastatic dormant animal models of colorectal cancer. Then we found that myeloid-derived suppressor cells (MDSCs) were increased significantly from liver micro-metastases to macro-metastases of CRC in mice. Moreover, monocytic MDSCs (Mo-MDSC) significantly promoted the dormant activation of micro-metastatic cells compared to polymorphonuclear MDSCs (PMN-MDSC). Mechanistically, CCL7 secreted by Mo-MDSCs bound with membrane protein CCR2 of micro-metastatic cells and then stimulated the JAK/STAT3 pathway to activate the dormant cells. Low-dose administration of CCL7 and MDSCs inhibitors in vivo could significantly maintain the CRC metastatic cells dormant status for a long time to reduce metastasis or recurrence after radical operation. Clinically, the level of CCL7 in blood was positively related to the number of Mo-MDSCs in CCR patients, and highly linked with the short-time recurrence and distant metastasis. CCL7 secreted by Mo-MDSCs plays an important role in initiating the outgrowth of metastatic latent CRC cells. Inhibition of CCL7 might provide a potential therapeutic strategy for the prevention of metastasis recurrence.

scholarly journals Immunomagnetic sequential ultrafiltration (iSUF) platform for enrichment and purification of extracellular vesicles from biofluids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingjing Zhang ◽  
Luong T. H. Nguyen ◽  
Richard Hickey ◽  
Nicole Walters ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Culture Media ◽  
Metastatic Breast ◽  
Clinical Samples ◽  
Clinical Use ◽  
Immunomagnetic Beads ◽  
Liquid Biopsies ◽  
Cell Culture Media ◽  
Non Invasive ◽  
Healthy Donors

AbstractExtracellular vesicles (EVs) derived from tumor cells have the potential to provide a much-needed source of non-invasive molecular biomarkers for liquid biopsies. However, current methods for EV isolation have limited specificity towards tumor-derived EVs that limit their clinical use. Here, we present an approach called immunomagnetic sequential ultrafiltration (iSUF) that consists of sequential stages of purification and enrichment of EVs in approximately 2 h. In iSUF, EVs present in different volumes of biofluids (0.5–100 mL) can be significantly enriched (up to 1000 times), with up to 99% removal of contaminating proteins (e.g., albumin). The EV recovery rate by iSUF for cell culture media (CCM), serum, and urine corresponded to 98.0% ± 3.6%, 96.0% ± 2.0% and 94.0% ± 1.9%, respectively (p > 0.05). The final step of iSUF enables the separation of tumor-specific EVs by incorporating immunomagnetic beads to target EV subpopulations. Serum from a cohort of clinical samples from metastatic breast cancer (BC) patients and healthy donors were processed by the iSUF platform and the isolated EVs from patients showed significantly higher expression levels of BC biomarkers (i.e., HER2, CD24, and miR21).

scholarly journals Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Mirna Expression ◽  
Gut Microbiome ◽  
Noncoding Rna ◽  
Microbial Community Composition ◽  
Host Cells ◽  
Microbiome Composition ◽  
Small Noncoding Rna

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.

scholarly journals A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Qian Liu ◽  
Lijuan Guo ◽  
Hongyan Qi ◽  
Meng Lou ◽  
Rui Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Ectopic Expression ◽  
Building Blocks ◽  
Small Subunit ◽  
S Phase ◽  
Clinical Samples ◽  
Dependent Manner

AbstractRibonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.

scholarly journals Autophagy-related Proteins as a Prognostic Factor of Patients With Colorectal Cancer

2019 ◽  
Vol 42 (10) ◽  
pp. 767-776 ◽  
Author(s):  
Evangelos Koustas ◽  
Panagiotis Sarantis ◽  
Stamatios Theoharis ◽  
Angelica A. Saetta ◽  
Ilenia Chatziandreou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Related Proteins

scholarly journals CircHMGCS1 is upregulated in colorectal cancer and promotes proliferation of colorectal cancer cells by targeting microRNA-503-5p

2019 ◽  
Vol 17 ◽  
pp. 205873921986955 ◽  
Author(s):  
Jingqing Dong ◽  
Jun Li ◽  
Jihui Luo ◽  
Weiqiang Wu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Clinical Parameter ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Apoptosis Pathway ◽  
Colorectal Cancer Cells ◽  
And Migration ◽  
Related Proteins

This study aims to explore the regulatory mechanism of circHMGCS1/microRNA-503-5p (miR-503-5p) axis during colorectal cancer (CRC) development and progression. Real-time quantitative polymerase chain reaction (RT-qPCR) was applied to evaluate the expression of circHMGCS1 and miR-503-5p in CRC samples and their adjacent non-tumor specimen. Then, cell proliferation and cell apoptosis and migration and invasion of circHMGCS1-knocked down cells were further detected, using cell counting kit-8 (CCK-8), flow cytometry, Transwell assay, and western blotting assays. CircHMGCS1 was found to be significantly upregulated in CRC, and its high expression was closely correlated with the poor clinical parameter. In addition, the knockdown of circHMGCS1 could significantly inhibit CRC cells’ growth promoting apoptosis, as suggested by the expression of apoptosis pathway-related proteins, which changed consistently. Furthermore, miR-503-5p inhibitors were able to reverse the suppression of cell proliferation induced by silencing circHMGCS1. Therefore, circHMGCS1 might serve as a promising bio-marker and treatment target for CRC.

scholarly journals Andrographolide enhanced radiosensitivity by downregulating glycolysis via the inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 colorectal cancer cells

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094616 ◽  
Author(s):  
Xiaofei Li ◽  
Ruifang Tian ◽  
Lan Liu ◽  
Lihui Wang ◽  
Dong He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Survival ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Glycolytic Activity ◽  
Related Proteins ◽  
Hct116 Cells

Objective Radiotherapy plays an important role in the treatment of colorectal cancer (CRC). However, some patients benefit minimally from radiotherapy because of radioresistance. This study investigated the effects of andrographolide on radiosensitivity in HCT116 CRC cells and examined its mechanism of action. Methods Cell survival, proliferation, apoptosis, and migration were evaluated using MTT, colony formation, flow cytometry, and Transwell cell invasion assays, respectively. Glycolysis-related indicators were measured to examine cell glycolytic activity. The expression of related proteins was detected by western blotting. Results After andrographolide treatment, the expression of phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway-related proteins, glycolytic activity, and cell survival and invasion rates were decreased in HCT116 cells. Andrographolide plus irradiation increased apoptosis and decreased survival, invasion, and colony formation compared with the effects of irradiation alone. Conclusion Andrographolide enhanced radiosensitivity by downregulating glycolysis via inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 cells.

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