• Colorectal cancer
• Diagnostic value
• Growth differentiation factor 15
• High sensitivity
• Time-resolved fluorescence immunoassay

• Humans
• Growth Differentiation Factor 15/blood
• Colorectal Neoplasms/blood
• Colorectal Neoplasms/diagnosis
• Fluoroimmunoassay/methods
• Male
• Female
• Middle Aged
• Biomarkers, Tumor/blood
• Aged

• Biological mass spectrometry
• Colorectal cancer
• Glycan bioinformatics software
• Glycan biomarkers
• Glycan pretreatment

• Colorectal Neoplasms/diagnosis
• Humans
• Glycosylation
• Biomarkers, Tumor/analysis
• Polysaccharides/analysis
• Mass Spectrometry/methods
• Early Detection of Cancer/methods

• National Natural Science Foundation of China
• Natural Science Foundation of Sichuan Province
• National Key Research and Development Program of China

• Cooperating cancer driver genes
• Hypergraph random walk
• Individual patients
• Personalized cancer driver genes
• Personalized hypergraph

• Humans
• Algorithms
• Neoplasms/genetics
• Computational Biology/methods
• Mutation
• Precision Medicine/methods
• Databases, Genetic
• Gene Expression Regulation, Neoplastic
• Signal Transduction/genetics
• Gene Regulatory Networks
• Gene Expression Profiling/methods

• cancer biomarkers
• cancer screening
• diagnostics
• epidemiology
• personalized approach
• prognosis

• Humans
• Precision Medicine/methods
• Prospective Studies
• Biomarkers
• Neoplasms/diagnosis
• Neoplasms/therapy
• Biomarkers, Tumor
• Prognosis

• biomarkers
• endoscopy
• gastric cancer
• gastroenterology
• metabolomics
• screening

• Humans
• Glycosylation
• Artificial Intelligence
• Colorectal Neoplasms/pathology
• Adenoma/diagnosis
• Adenoma/pathology
• Precancerous Conditions/pathology

• colorectal cancer
• policy intervention
• potential impact fraction
• processed meat
• red meat

• Male
• Female
• Humans
• Incidence
• Risk Factors
• Meat Products
• Colorectal Neoplasms/epidemiology
• Meat
• Red Meat
• Germany/epidemiology

• Cell-cell interaction
• Drosophila
• Tumorigenesis
• Tumour microenvironment
• Tumour progression

Colorectal cancer (CRC) and breast cancer are leading causes of death globally, due to significant challenges in detection and management. The late-stage diagnosis and treatment failures require the discovery of potential anticancer agents to achieve a satisfactory therapeutic effect. We have previously reported a series of plastoquinone analogues to understand their cytotoxic profile. Among these derivatives, three of them (AQ-11, AQ-12, and AQ-15) were selected by the National Cancer Institute (NCI) to evaluate their in vitro antiproliferative activity against a panel of 60 human tumor cell lines. AQ-12 exhibited significant antiproliferative activity against HCT-116 CRC and MCF-7 breast cancer cells at a single dose and further five doses. MTT assay was also performed for AQ-12 at different concentrations against these two cells, implying that AQ-12 exerted notable cytotoxicity toward HCT-116 (IC₅₀ = 5.11 ± 2.14 μM) and MCF-7 (IC₅₀ = 6.06 ± 3.09 μM) cells in comparison with cisplatin (IC₅₀ = 23.68 ± 6.81 μM and 19.67 ± 5.94 μM, respectively). This compound also augmented apoptosis in HCT-116 (62.30%) and MCF-7 (64.60%) cells comparable to cisplatin (67.30% and 78.80%, respectively). Molecular docking studies showed that AQ-12 bound to DNA, forming hydrogen bonding through the quinone scaffold. In silico pharmacokinetic determinants indicated that AQ-12 demonstrated drug-likeness with a remarkable pharmacokinetic profile for future mechanistic anti-CRC and anti-breast cancer activity studies.

• DNA binding
• NCI-60
• apoptosis
• breast cancer
• colorectal cancer
• cytotoxicity
• growth inhibition
• pharmacokinetic determinants
• plastoquinone

Digestive system tumors have a poor prognosis due to complex anatomy, insidious onset, challenges in early diagnosis, and chemoresistance. Epidemiological statistics has verified that digestive system tumors rank first in tumor-related death. Although a great number of studies are devoted to the molecular biological mechanism, early diagnostic markers, and application of new targeted drugs in digestive system tumors, the therapeutic effect is still not satisfactory. Epigenomic alterations including histone modification and chromatin remodeling are present in human cancers and are now known to cooperate with genetic changes to drive the cancer phenotype. Chromatin is the carrier of genetic information and consists of DNA, histones, non-histone proteins, and a small amount of RNA. Chromatin and nucleosomes control the stability of the eukaryotic genome and regulate DNA processes such as transcription, replication, and repair. The dynamic structure of chromatin plays a key role in this regulatory function. Structural fluctuations expose internal DNA and thus provide access to the nuclear machinery. The dynamic changes are affected by various complexes and epigenetic modifications. Variation of chromatin dynamics produces early and superior regulation of the expression of related genes and downstream pathways, thereby controlling tumor development. Intervention at the chromatin level can change the process of cancer earlier and is a feasible option for future tumor diagnosis and treatment. In this review, we introduced chromatin dynamics including chromatin remodeling, histone modifications, and chromatin accessibility, and current research on chromatin regulation in digestive system tumors was also summarized.

• National Natural Science Foundation of China
• Chinese Academy of Medical Sciences Initiative for Innovative Medicine

• Colorectal cancer
• NF-κB pathway
• dietary antioxidant capacity
• systemic inflammatory response
• transcription factors.

• Area coverage
• Capsule endoscopy
• Deep reinforcement learning
• Disease classification
• Synthetic data generation

Actinoporins are the most abundant group of sea anemone cytolytic toxins. Their membranolytic activity is of high interest for the development of novel anticancer drugs. However, to date the activity of actinoporins in malignant cells has been poorly studied. Here, we report on recombinant analog of Hct-S3 (rHct-S3), belonging to the combinatory library of Heteractis crispa actinoporins. rHct-S3 exhibited cytotoxic activity against breast MDA-MB-231 (IC₅₀ = 7.3 µM), colorectal HT-29 (IC₅₀ = 6.8 µM), and melanoma SK-MEL-28 (IC₅₀ = 8.3 µM) cancer cells. The actinoporin effectively prevented epidermal growth factor -induced neoplastic transformation of JB6 Cl41 cells by 34% ± 0.2 and decreased colony formation of HT-29 cells by 47% ± 0.9, MDA-MB-231 cells by 37% ± 1.2, and SK-MEL-28 cells by 34% ± 3.6. Moreover, rHct-S3 decreased proliferation and suppressed migration of colorectal carcinoma cells by 31% ± 5.0 and 99% ± 6.4, respectively. The potent anti-migratory activity was proposed to mediate by decreased matrix metalloproteinases-2 and -9 expression. In addition, rHct-S3 induced programmed cell death by cleavage of caspase-3 and poly (ADP-ribose) polymerase, as well as regulation of Bax and Bcl-2. Our results indicate rHct-S3 to be a promising anticancer drug with a high anti-migratory potential.

• Heteractis crispa
• actinoporin
• anti-migratory activity
• anticancer activity
• sea anemone

• Animals
• Antineoplastic Agents/pharmacology
• Breast Neoplasms/drug therapy
• Breast Neoplasms/pathology
• Caspase 3/metabolism
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Cell Transformation, Neoplastic/drug effects
• Cnidarian Venoms/pharmacology
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/pathology
• Female
• HT29 Cells
• Humans
• Matrix Metalloproteinase 2/biosynthesis
• Matrix Metalloproteinase 9/biosynthesis
• Melanoma/drug therapy
• Melanoma/pathology
• Poly(ADP-ribose) Polymerases/metabolism
• Sea Anemones/metabolism

• Carcinogenesis
• Colorectal cancer
• Fusobacterium nucleatum
• Microbioma

• Colorectal cancer (CRC)
• clinical index
• gene mutation
• nomogram model
• stage III/IV

• COVID-19
• breast
• cancer
• cervical
• colorectal
• home
• screening

Globally, colorectal cancer (CRC) is a leading cause of cancer deaths and chemotherapy, in combination with radiotherapy when appropriate, is used to treat the majority of CRC patients. However, the acquisition or development of drug resistance can decrease, or even abolish, the efficacy of chemotherapy. ATP-binding cassette (ABC) transporters, particularly, the ABCB1 and ABCG2 transporter, are mediators of multidrug resistance (MDR) in certain types of cancer cells. The aim of our in vitro study was to determine if poziotinib can overcome MDR to certain chemotherapeutic drugs in colon cancer cells. Our results indicated that in MDR CRC cell lines, poziotinib inhibits the transport function of the ABCB1 and ABCG2 transporters, increasing the intracellular accumulation of certain anticancer drugs, and thus, their efficacy. Furthermore, poziotinib decreased the expression of the ABCG2 protein. Therefore, if our results can be translated to humans, they suggest that using poziotinib in combination with certain anticancer drugs may be of therapeutic benefit in colorectal cancer patients.

Colorectal cancer (CRC) is a leading cause of cancer deaths in the United States. Currently, chemotherapy is a first-line treatment for CRC. However, one major drawback of chemotherapy is the emergence of multidrug resistance (MDR). It has been well-established that the overexpression of the ABCB1 and/or ABCG2 transporters can produce MDR in cancer cells. In this study, we report that in vitro, poziotinib can antagonize both ABCB1- and ABCG2-mediated MDR at 0.1–0.6 μM in the human colon cancer cell lines, SW620/Ad300 and S1-M1-80. Mechanistic studies indicated that poziotinib increases the intracellular accumulation of the ABCB1 transporter substrates, paclitaxel and doxorubicin, and the ABCG2 transporter substrates, mitoxantrone and SN-38, by inhibiting their substrate efflux function. Accumulation assay results suggested that poziotinib binds reversibly to the ABCG2 and ABCB1 transporter. Furthermore, western blot experiments indicated that poziotinib, at 0.6 μM, significantly downregulates the expression of the ABCG2 but not the ABCB1 transporter protein, suggesting that the ABCG2 reversal effect produced by poziotinib is due to transporter downregulation and inhibition of substrate efflux. Poziotinib concentration-dependently stimulated the ATPase activity of both ABCB1 and ABCG2, with EC₅₀ values of 0.02 μM and 0.21 μM, respectively, suggesting that it interacts with the drug-substrate binding site. Molecular docking analysis indicated that poziotinib binds to the ABCB1 (−6.6 kcal/mol) and ABCG2 (−10.1 kcal/mol) drug-substrate binding site. In summary, our novel results show that poziotinib interacts with the ABCB1 and ABCG2 transporter, suggesting that poziotinib may increase the efficacy of certain chemotherapeutic drugs used in treating MDR CRC.

• ABCB1
• ABCG2
• EGFR inhibitor
• colorectal cancer
• multidrug resistance
• poziotinib

• Carboxylic acid metabolome
• Characteristic fragment ions
• Colorectal cancer
• Metabolic flux
• Potential biomarkers

Digestive cancers are the leading cause of cancer-related death worldwide and have high risks of morbidity and mortality. Histone methylation, which is mediated mainly by lysine methyltransferases, lysine demethylases, and protein arginine methyltransferases, has emerged as an essential mechanism regulating pathological processes in digestive cancers. Under certain conditions, aberrant expression of these modifiers leads to abnormal histone methylation or demethylation in the corresponding cancer-related genes, which contributes to different processes and phenotypes, such as carcinogenesis, proliferation, metabolic reprogramming, epithelial–mesenchymal transition, invasion, and migration, during digestive cancer development. In this review, we focus on the association between histone methylation regulation and the development of digestive cancers, including gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer, as well as on its clinical application prospects, aiming to provide a new perspective on the management of digestive cancers.

• Colorectal adenomas
• Colorectal cancer
• Itch
• Notch-1
• Numb
• Siah-1

• Aged
• Biomarkers, Tumor/genetics
• Colorectal Neoplasms/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Lymphatic Metastasis
• Male
• Middle Aged
• Prognosis
• Receptor, Notch1
• Signal Transduction

• genetic alterations
• genetic heterogeneity
• genome profile
• liver metastasis
• sporadic colorectal cancer

• Animals
• Biomarkers, Tumor/genetics
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Gene Expression Profiling/methods
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/secondary
• Mutation

• biosensors
• colorectal cancer
• gold nanoparticles
• microRNA detection in inflammation
• nanosensors
• nanotechnology

• ABC transporter
• Colon cancer
• Drug resistance
• IRE1α

• Mesenchymal stem cells
• TGF-β1
• co-culture
• p53
• tumor microenvironment

• MassARRAY
• colorectal cancer
• risk-stratifying algorithm
• stool DNA

• Bacteria/isolation & purification
• Bacteria/metabolism
• Biomarkers/metabolism
• Feces/chemistry
• Feces/microbiology
• Gastrointestinal Diseases/diagnosis
• Gastrointestinal Diseases/pathology
• Humans
• Microfluidics/methods
• Microscopy, Fluorescence
• Miniaturization
• Point-of-Care Systems
• Transducers

• R44 HL126441 NHLBI NIH HHS

• bacterial enterotoxins
• campylobacter jejuni
• colon carcinogenesis
• infective colitis

• apoptosis
• colorectal cancer
• cyclin-dependent kinase 1
• metastasis
• microRNA-769
• proliferation

• CD8
• colorectal cancer
• dedicator of cytokinesis 2
• infiltration

Accumulated studies have strongly implicated aberrantly expressed microRNAs (miRNAs) in carcinogenesis and cancer progression of various cancers, including colorectal cancer (CRC). Hence, a comprehensive study of miRNAs and their association with CRC may be a promising therapeutic method for patients with this malignancy. MicroRNA-744 (miR-744) is abnormally expressed in several types of human cancer. Thus far, little is known about the expression, biological roles, and exact mechanisms of miR-744 in CRC. Thus, the present study measured the expression level of miR-744 and investigated its roles and associated molecular mechanisms in CRC. This study demonstrated that miR-744 expression was significantly underexpressed in CRC tissues and cell lines. Low miR-744 expression was positively associated with lymphatic metastasis and TNM stage. Functional experiments revealed that miR-744 overexpression obviously inhibited the proliferation and invasion of CRC cells. Furthermore, Notch1 was identified as a direct target of miR-744 in CRC. Moreover, the inhibition of Notch1 phenocopied the inhibitory effects of miR-744 overexpression on CRC cells. Restored Notch1 expression markedly rescued the tumor-suppressive effects of miR-744 overexpression on CRC cells. Overall, miR-744 exhibits an essential role in CRC progression, and the miR-744/Notch1 axis may provide novel insights into future treatments for patients with CRC.

The pursuit of novel and effective biomarkers is essential in the struggle against cancer, which is a leading cause of mortality worldwide. Here we discuss the relative advantages and disadvantages of the most frequently used proteomics techniques, concentrating on the latest advances and application of tissue and plasma proteomics for novel cancer biomarker discovery.

Cancer is caused by the accumulation of multiple genetic mutations, but their cooperative effects are poorly understood. Using a genome-wide analysis of all the somatic mutations in colorectal cancer patients in a large-scale molecular interaction network, here we find that a giant cluster of mutation-propagating modules in the network undergoes a percolation transition, a sudden critical transition from scattered small modules to a large connected cluster, during colorectal tumorigenesis. Such a large cluster ultimately results in a giant percolated cluster, which is accompanied by phenotypic changes corresponding to cancer hallmarks. Moreover, we find that the most commonly observed sequence of driver mutations in colorectal cancer has been optimized to maximize the giant percolated cluster. Our network-level percolation study shows that the cooperative effect rather than any single dominance of multiple somatic mutations is crucial in colorectal tumorigenesis.

Cancer is caused by accumulating genetic mutations. Here, the authors investigate the cooperative effect of these mutations in colorectal cancer patients and identify a giant cluster of mutation-propagating modules that undergoes percolation transition during tumorigenesis.

• crc
• plasma
• biomarker
• mir-29a
• mir-31
• mir-200b
• mir-203

• Adult
• Aged
• Aged, 80 and over
• Area Under Curve
• Biomarkers, Tumor/blood
• Carcinoma/blood
• Carcinoma/diagnosis
• Carcinoma/genetics
• Carcinoma/surgery
• Colorectal Neoplasms/blood
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/surgery
• Early Detection of Cancer
• Female
• Humans
• Male
• MicroRNAs/blood
• Middle Aged
• Neoplasm Recurrence, Local/blood
• Neoplasm Recurrence, Local/diagnosis
• Neoplasm Recurrence, Local/genetics
• Postoperative Period
• Preoperative Period
• Prognosis
• Proportional Hazards Models
• Real-Time Polymerase Chain Reaction
• Risk Assessment
• Young Adult

• P30 CA015704 NCI NIH HHS
• P01 CA077852 NCI NIH HHS
• U54 CA143862 NCI NIH HHS
• U24 CA074794 NCI NIH HHS
• U01 CA206110 NCI NIH HHS
• R01 CA112516 NCI NIH HHS
• R01 CA207371 NCI NIH HHS
• R01 CA114467 NCI NIH HHS
• R03 CA165153 NCI NIH HHS
• R01 CA120523 NCI NIH HHS
• U01 CA152756 NCI NIH HHS
• R01 CA194663 NCI NIH HHS

Studies on gut microbiota regarding colorectal carcinogenesis, including sessile serrated adenoma (SSA), have been scarce. The aim of this study is to investigate the role of mucosa-associated gut microbiota in the colorectal carcinogenesis.

We collected biopsy samples of normal rectal mucosa during colonoscopy from healthy control and patients with conventional adenoma, SSA, and colorectal cancer (CRC), respectively (n = 6). Pyrosequencing for 16S rRNA gene of bacteria was performed to compare gut microbiota.

The most abundant phylum in total samples was Proteobacteria (55.6%), followed by Firmicutes (27.4%) and Bacteroidetes (11.6%). There was no significant difference in relative abundance of the phylum level among the four groups. Fusobacterium nucleatum, known to be frequently detected during colorectal carcinogenesis, was found in only one sample of patient with SSA. The rarefaction curves showed that the diversity of mucosal communities of patients with CRC is the lowest among the four groups and the diversity of mucosal communities of patients with SSA is higher than that of healthy control. Among the four groups, Shannon’s and Simpson’s index for diversity was the lowest and the highest in the patients with CRC, respectively; it did not reach statistical significance. The proportion of genus Pseudomonas was very high in the samples of patients with stage II–IV CRC compared with those with stage I CRC (59.3% vs. 0.3%, P = 0.064).

Our study suggests no significant role of mucosa-associated gut microbiota in the colorectal carcinogenesis. Further study for many samples or using fecal material could be helpful.

• Colon adenoma
• Colon cancer
• Colonic neoplasms
• Microbiota
• Sessile serrated adenoma

• Jagged1
• Notch1
• cell metastasis
• colorectal cancer
• microRNAs

• Colorectal cancer
• biomarkers
• genetic and epigenetic markers
• prognostic and predictive markers
• screening markers

• BRAF serine/threonine kinase proto-oncogene
• Kirsten rat sarcoma viral oncogene homolog
• colorectal cancer
• exosome
• mutation

• LGG
• gut microbiota
• intestinal polyposis
• metagenomics
• probiotics