Background/Aims: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC), while the effect of cholesterol on CRC metastasis has not been widely studied. Methods: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL) and CRC metastases, and LDL receptor (LDLR) level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD) on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. Results: The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR) expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of “stemness” genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD) significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS)-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS) levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK) signaling pathway. Conclusions: LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored.

Targeting cancer via ROS-based mechanism has been proposed as a radical therapeutic approach. Cancer cells exhibit higher endogenous oxidative stress than normal cells and pharmacological ROS insults via either enhancing ROS production or inhibiting ROS-scavenging activity can selectively kill cancer cells. In this study, we randomly chose 4 cancer cell lines and primary colon or rectal cancer cells from 4 patients to test the hypothesis and obtained following paradoxical results: while piperlongumin (PL) and β-phenylethyl isothiocyanate (PEITC), 2 well-defined ROS-based anticancer agents, induced an increase of cellular ROS and killed effectively the tested cells, lactic acidosis (LA), a common tumor environmental factor that plays multifaceted roles in promoting cancer progression, induced a much higher ROS level in the tested cancer cells than PL and PEITC, but spared them; L-buthionine sulfoximine (L-BSO, 20 μM) depleted cellular GSH more effectively and increased higher ROS level than PL or PEITC but permitted progressive growth of the tested cancer cells. No evident dose-response relationship between cellular ROS level and cytotoxicity was observed. If ROS is the effecter, it should obey the fundamental therapeutic principle – the dose-response relationship. This is a major concern.

Background Cancer stem cells (CSCs) play a critical role in tumor development and progression and are involved in cancer metastasis. The role of reactive oxygen species (ROS) in CSCs and cancer metastasis remains controversial. The aim of the present study was to investigate the correlation between ROS level of CSCs and cancer metastasis and to explore the possible underlying molecular mechanisms. Methods Four different cell lines were used to isolate tumor spheres and to analyze intrinsic properties of tumor sphere cells including proliferation, self-renewal potential, differentiation, drug-resistance and cancer metastasis in vitro and in vivo. ROS assays were used to detect the intracellular ROS level of tumor spheres cells. Gene expression analysis and western blot were used to investigate the underlying mechanisms of ROS in regulating cancer metastasis. Results Tumor spheres possessed the characteristic features of CSCs, and ROS-high tumor spheres (RH-TS) displayed elevated mitochondrial ROS level exclusively drove metastasis formation. The gene expression analysis showed elevated fatty acid β-oxidation, downregulation of epithelial marker upregulation of mesenchymal markers, and the activation of MAP kinase cascades. Furthermore, 14 up-regulated genes in RH-TS cells were associated with reduced overall survival of different cancer patients. Conclusions Our findings demonstrate that CSCs characterized by elevated mitochondrial ROS level potentiate cancer metastasis. Mechanistically, elevated mitochondrial ROS via fatty acid β-oxidation, activates the MAPK cascades, resulting in the epithelial-mesenchymal transition (EMT) process of RH-TS cells, thereby potentiating caner invasion and metastasis. Therefore, targeting mitochondrial ROS might provide a promising approach to prevent and alleviate cancer metastasis induced by RH-TS cells. Electronic supplementary material The online version of this article (10.1186/s13287-019-1265-2) contains supplementary material, which is available to authorized users.

Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis – two tumor microenvironmental factors – could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy.

Background The increasing incidence of inflammatory bowel disease (IBD) has imposed heavy financial burdens for Chinese patients; however, data about their financial status and access to health care are still lacking. This information is important for informing patients with IBD about disease treatment budgets and health care strategies. Objective The aim of this study was to evaluate the economic status and medical care access of patients with IBD through the China Crohn’s & Colitis Foundation web-based platform in China. Methods Our study was performed in 14 IBD centers in mainland China between 2018 and 2019 through WeChat. Participants were asked to complete a 64-item web-based questionnaire. Data were collected by the Wenjuanxing survey program. We mainly focused on income and insurance status, medical costs, and access to health care providers. Respondents were stratified by income and the associations of income with medical costs and emergency visit times were analyzed. Results In this study, 3000 patients with IBD, that is, 1922 patients with Crohn disease, 973 patients with ulcerative colitis, and 105 patients with undetermined colitis were included. During the last 12 months, the mean (SD) direct and indirect costs for per patient with IBD were approximately US $11,668.68 ($7944.44) and US $74.90 ($253.60) in China. The average reimbursement ratios for most outpatient and inpatient costs were less than 50%. However, the income of 85.5% (2565/3000) of the patients was less than ¥10,000 (US $1445) per month. Approximately 96.5% (2894/3000) of the patients were covered by health insurance, but only 24.7% (741/3000) of the patients had private commercial insurance, which has higher imbursement ratios. Nearly 98.0% (2954/3000) of the patients worried about their financial situation. Thus, 79.7% (2392/3000) of the patients with IBD tried to save money for health care and even delayed their medical treatments. About half of the respondents (1282/3000, 42.7%) had no primary care provider, and 52.2% (1567/3000) of the patients had to visit the emergency room 1-4 times per year for the treatment of their IBD. Multivariate analysis revealed that lower income ( P =.001) and higher transportation ( P =.004) and accommodation costs ( P =.001) were significantly associated with the increased number of emergency visits of the patients. Conclusions Chinese patients with IBD have enormous financial burdens and difficulties in accessing health care, which have increased their financial anxiety and inevitably influenced their disease outcomes. Early purchase of private insurance, thereby increasing the reimbursement ratio for medical expenses, and developing the use of telemedicine would be effective strategies for saving on health care costs.