: Interleukin-6 is dysregulated in multiple pathological conditions, e.g., cancer and inflammatory diseases.
View Article and Find Full Text PDFMicrobiota and luminal components may affect epithelial integrity and thus participate in the pathophysiology of colon cancer (CC) and inflammatory bowel disease (IBD). Therefore, we aimed to determine the effects of fecal luminal factors derived from patients with CC and ulcerative colitis (UC) on the colonic epithelium using a standardized colon-derived two-dimensional epithelial monolayer. The complex primary human stem cell-derived intestinal epithelium model, termed RepliGut Planar, was expanded and passaged in a two-dimensional culture which underwent stimulation for 48 h with fecal supernatants (FS) from CC patients ( = 6), UC patients with active disease ( = 6), and healthy subjects (HS) ( = 6).
View Article and Find Full Text PDFObjectives: Colorectal cancer (CRC) is one of the most prevalent cancer types worldwide, exhibiting significant variance in incidence rates across different ethnicities and geographical regions. Notably, there is a rising incidence of CRC among younger adults, particularly evident in advanced stages, with a more pronounced trend observed in developing nations. Epigenetic alterations potentially play a role in the early onset of CRC and could elucidate interpopulation disparities.
View Article and Find Full Text PDFBackground: Colorectal cancer (CRC) is known to present a distinct microbiome profile compared to healthy mucosa. Non-targeted deep-sequencing strategies enable nowadays full microbiome characterization up to species level.
Aim: We aimed to analyze both bacterial and viral communities in CRC using these strategies.
The incidence of left-sided colon and rectal cancer in young people are increasing worldwide, but its causes are poorly understood. It is not clear if the tumor microenvironment is dependent on age of onset, and little is known about the composition of tumor-infiltrating T cells in early-onset colorectal cancer (EOCRC). To address this, we investigated T-cell subsets and performed gene expression immune profiling in sporadic EOCRC tumors and matched average-onset colorectal cancer (AOCRC) tumors.
View Article and Find Full Text PDFThe combination of 5-fluorouracil (5-FU) and leucovorin (LV) forms the chemotherapy backbone for patients with colorectal cancer. However, the LV administration is often standardized and not based on robust scientific data. To address these issues, a randomized pharmacokinetics study was performed in patients with colon cancer.
View Article and Find Full Text PDFPrevious in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC ( = 6), UC ( = 6), IBS ( = 6) and healthy subjects ( = 6).
View Article and Find Full Text PDFBackground: Tumor-associated macrophages (TAM) are known to facilitate colorectal cancer (CRC) growth. High macrophage infiltration in thymidine phosphorylase (TYMP) expressing CRC may correspond to poor prognosis. The prognostic impact of the expression CD163, a receptor associated with TAM, and TYMP in stroma, respectively, tumor tissue is not yet established.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
September 2022
Purpose: Loss of expression of DLG2 has been identified in a number of cancers to contribute to the disease by resulting in increased tumor cell proliferation and poor survival. In light of the previous evidence that DLG2 alters the cell cycle and affects proliferation, combined with indications that DLG2 is involved in NLRP3 inflammasome axis we speculated that DLG2 has an immune function. So far, there is no data that clearly elucidates this role, and this study was designed to investigate DLG2 in inflammatory colon disease and in colon cancer as well as its impact on inflammasome induction.
View Article and Find Full Text PDFAlthough mouse models of CRC treatments have demonstrated robust immune activation, it remains unclear to what extent CRC patients' APCs and TILs interact to fuel or quench treatment-induced immune responses. Our ex vivo characterization of tumor and adjacent colon cell suspensions suggest that contrasting environments in these tissues promoted inversed expression of T cell co-stimulatory CD80, and co-inhibitory programmed death (PD)-ligand1 (PD-L1) on intratumoral vs. colonic APCs.
View Article and Find Full Text PDFBackground: Intratumoral regulatory T cells (Treg) in colon cancer are a heterogeneous cell population, with potential impact on patient outcome. Generally, a high Treg infiltration has been correlated to a worse patient outcome, but it is still unclear how the composition of different Treg subsets affects patient relapse and survival. In this study, we used mass and flow cytometry to characterize Treg in colon tumors and corresponding unaffected tissue, followed by a correlation to clinical parameters and patient outcome.
View Article and Find Full Text PDFCancer Chemother Pharmacol
October 2021
Purpose: The aim was to investigate the pharmacokinetics of preoperatively administered intraperitoneal (IP) 5-FU in patients with resectable pancreatic ductal adenocarcinoma (PDAC) by analyzing levels of 5-FU and target metabolites in peritoneal fluid, plasma, liver, lymph nodes, pancreatic tumour, and pancreatic tissue. These results were correlated to expression of genes encoding enzymes of the 5-FU pathway and cell membrane transporters of 5-FU and FdUMP.
Methods: Twenty-two patients with PDAC were treated with IP 5-FU before surgery.
Mucosal-associated invariant T (MAIT) cells are unconventional T cells recognizing microbial metabolites, presented by the invariant MR1 protein. Upon activation, MAIT cells rapidly secrete cytokines and exert cytotoxic functions, and may thus be highly relevant also in tumor immunity. MAIT cells accumulate in colon tumors, but in contrast to other cytotoxic T cell subsets, their presence in tumors has been associated with worse patient outcome.
View Article and Find Full Text PDFBackground: Colorectal cancer is the second most common cause of cancer-related death worldwide and standardized therapies often fail to treat the more aggressive and progressive types of colorectal cancer. Tumor cell heterogeneity and influence from the surrounding tumor microenvironment (TME) contribute to the complexity of the disease and large variability in clinical outcomes.
Methods: To model the heterogeneous nature of colorectal cancer, we used patient-derived scaffolds (PDS), which were obtained via decellularization of surgically resected tumor material, as a growth substrate for standardized cell lines.
Purpose: The aim was to explore the correlation between increasing doses of [6R]-5,10-methylenetetrahydrofolate (arfolitixorin) and plasma concentrations of deoxyuridine (dUr) in patients with metastatic colorectal cancer (mCRC), subjected to 5-fluorouracil (5-FU)-based chemotherapy. The aim was further to investigate the possibility to predict toxicity and clinical response during treatment using gender, age, and plasma dUr as explanatory variables.
Methods: Thirty-three patients from the ISO-CC-005 phase I/IIa study, which investigated safety and tolerability of arfolitixorin at four dose levels, were included.
Background: Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.
Methods: SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology.
5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy.
View Article and Find Full Text PDFPurpose: The aim of study was to investigate the relationship between folate concentration and expression of folate-associated genes in tumour, mucosa and plasma of patients with colorectal cancer, after intraoperative administration of bolus leucovorin (LV).
Methods: Eighty patients were randomized into four groups to receive 0, 60, 200, or 500 mg/m LV, respectively. Tissue and plasma folate concentrations were assessed by LC-MS/MS.
: Class IA phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is an integral mediator of insulin signaling. The p110 catalytic and p85 regulatory subunits of PI3K are the products of separate genes, and while they come together to make the active heterodimer, they have opposing roles in insulin signaling and action. Deletion of hepatic p110α results in an impaired insulin signal and severe insulin resistance, whereas deletion of hepatic p85α results in improved insulin sensitivity due to sustained levels of phosphatidylinositol (3,4,5)-trisphosphate.
View Article and Find Full Text PDFBackground: Colorectal cancer is being diagnosed more frequently in the young and it presents in an advanced stage. In TNM staging, stage depends on tumor size and number of positive nodes, which depend on location of tumor as well as the extent of dissection.The lymph node ratio is regarded as a more reliable marker for prognosis.
View Article and Find Full Text PDFAccurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation.
View Article and Find Full Text PDFGenome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry.
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