Metastases Of Gastrointestinal Tumors Research Articles

Gut Roseburia is a protective marker for peritoneal metastasis of gastric cancer.

Gastric cancer (GC), particularly for advanced stage of GC, commonly undergoes peritoneal metastasis (PM), which is the leading cause of GC-related death. However, there currently has no reliable biomarker to predict the onset of GCPM. It is well known that the imbalance of gut microbiota contributes to the development and metastasis of gastrointestinal tumors. Unfortunately, little is known about how the alternation in gut microbiota is associated with the onset of GCPM. Our current study analyzed structural characteristics and functional prediction of gut microbiota in GC patients with PM (PM group) and without PM (non-PM group). Fresh fecal samples were collected from a discovery cohort (PM = 38, non-PM = 54) and a validation cohort (PM = 15, non-PM = 21) of GC patients and their 16S ribosomal RNA (16s rRNA) gene amplicons were sequenced, followed by bioinformatics. The results indicated an increase in the biodiversity of gut microbiota in the non-PM group of the discovery cohort, compared with the PM group. Moreover, LEfSe analysis found 31 significantly different microorganisms, of which the Roseburia ranked the fifth in the random forest (RF) model. The characteristics of intestinal microbiota in GCPM patients were changed, and the abundance of Roseburia in gut microbiota from the GCPM patients was reduced and receiver operating characteristic (ROC) analysis revealed that the reduced abundance of gut Roseburia effectively predicted the onset of GCPM. This signature was also observed in the validation cohort. Therefore, Roseburia is a protective microbial marker and the reduced abundance of Roseburia in gut microbiota may help early diagnosis of GCPM.

Advances in the Mechanism of Action of Neutrophil Extracellular Traps in Gastrointestinal Tumors: A Review.

Neutrophils are important immune cells in the body, extremely abundant, phagocytic and bactericidal, and usually involved in the defense against infectious diseases as immune become. However, a new reticulum structure has been discovered: neutrophil extracellular traps (NETs), which consists of various components such as DNA and proteins, etc. Current studies have found that NETs are closely associated with various diseases such as immune diseases, inflammation and tumors, and the study of the development and metastasis of gastrointestinal tumors has become a recent research hotspot. The clinical significance of NETs has been gradually highlighted, especially in the area of immunosuppression. We reviewed a large amount of relevant literature, summarized the latest detection methods of NETs, explored the mechanism of NETs in gastrointestinal tumors and summarized the latest hotspot directions. NETs are involved in the development of gastrointestinal tumors, and are closely related to the proliferation and metastasis of gastrointestinal tumors. Higher levels of NETs are associated with poor prognosis of gastrointestinal tumors, promote local growth of tumors through various pathways, participate in tumor-related systemic injury, and promote tumor growth and metastasis by enhancing the mitochondrial function of tumor cells and awakening dormant tumor cells. NETs are highly expressed in tumors, and tumors and their microenvironment can promote the production of NETs, providing new ideas for the clinical diagnosis and treatment of gastrointestinal tumors. In this paper, we describe the basic information about NETs, explore the research mechanisms related to NETs in gastrointestinal tumors, and prospectively explore the clinical potential of hotspots and inhibitors related to NETs for gastrointestinal tumors, in order to provide new ideas and targets for the diagnosis and treatment of gastrointestinal tumors.

Circular RNAs as the pivotal regulators of epithelial-mesenchymal transition in gastrointestinal tumor cells.

Gastrointestinal (GI) cancers, as the most common human malignancies are always considered one of the most important health challenges in the world. Late diagnosis in advanced tumor stages is one of the main reasons for the high mortality rate and treatment failure in these patients. Therefore, investigating the molecular pathways involved in GI tumor progression is required to introduce the efficient markers for the early tumor diagnosis. Epithelial-mesenchymal transition (EMT) is one of the main cellular mechanisms involved in the GI tumor metastasis. Non-coding RNAs (ncRNAs) are one of the main regulatory factors in EMT process. Circular RNAs (circRNAs) are a group of covalently closed loop ncRNAs that have higher stability in body fluids compared with other ncRNAs. Considering the importance of circRNAs in regulation of EMT process, in the present review we discussed the role of circRNAs in EMT process during GI tumor invasion. It has been reported that circRNAs mainly affect the EMT process through the regulation of EMT-specific transcription factors and signaling pathways such as WNT, PI3K/AKT, TGF-β, and MAPK. This review can be an effective step in introducing a circRNA/EMT based diagnostic panel marker for the early tumor detection among GI cancer patients.

He-Chan Pian inhibits the metastasis of non-small cell lung cancer via the miR-205-5p-mediated regulation of the GREM1/Rap1 signaling pathway

BackgroundHe-Chan Pian (HCP), a traditional Chinese medicinal formula, shows promising efficacy for the treatment of lung cancer. PurposeGremlin (GREM1) plays an important role in gastrointestinal tumor metastasis; however, little is known about its role in lung cancer. We determined the mechanism underlying the protective effect of HCP against metastasis in a mouse model of non-small cell lung cancer (NSCLC) and demonstrated the role of GREM1. MethodsUltra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the herbal components and metabolites from the serum of HCP-treated mice. The tumor, liver, and kidney were examined histologically, and the antitumor effects and toxicity of HCP were evaluated. Levels of epithelial-mesenchymal transition (EMT)-associated transcription factors were measured using western blotting in tumors from five groups (i.e., model, HCP [L], HCP [M], HCP [H], and positive control [cisplatin, DDP]). Differentially expressed proteins and genes were identified using protein chip and sequencing analyzes, respectively. Short hairpin RNAs and overexpression plasmids were introduced into cells to evaluate the effects of GREM1. To evaluate proliferation, migration, and invasion, the expression levels of proteins involved in the Rap1 pathway and EMT were measured in vitro. Xenograft tumors with overexpression-GREM1 (OE-GREM1) in A549 cells were examined for cell proliferation. A dual-luciferase assay was performed to verify the direct interaction of GREM1 with miR-205-5p in lung cancer. ResultsThirty-six ingredients and bioactive constituents detected in the serum of HCP-treated mice were identified as the key compounds involved in the inhibition of tumor growth. Animal experiments revealed that HCP significantly decreased tumor volumes and had no adverse effects on the liver or kidney or side effects. GREM1 upregulation was closely related to tumor metastasis and was regulated by miR-205-5p, as confirmed using a dual-luciferase reporter assay. OE-GREM1 promoted A549 cell migration and invasion, promoted EMT, and increased the expression of Rap1 pathway intermediaries, whereas shGREM1 had the opposite effects. Furthermore, the effects of OE-GREM1 on proliferation in the A549 xenograft mouse model were attenuated, although HCP has an inhibitory effect on tumors. ConclusionOur results suggest that HCP contributes to the inhibition of NSCLC metastasis via the Gremlin/Rap1 signaling pathway regulated by miR-205-5p.

Immunogenic Cell Death In Murine Colon-Carcinoma Cells Following Exposure To Cold Physical Plasma-Treated Saline Solution

Diffuse peritoneal metastasis of gastrointestinal tumors is a life-threatening complication in end-stage tumor patients. Standard of care is hyperthermic intraperitoneal chemotherapy (HIPEC) and/or radiation therapy, both associated with significant side effects [1]. Previous studies have suggested that cold physical plasma may present a new anti-tumor tool with few to none side effects [2]. Moreover, plasma-induced reactive species can be transferred to cell culture medium where they react to more stable entities. We were able to demonstrate that phosphate-buffered saline (PBS) treated with cold physical plasma has toxic effects on mouse carcinoma cells cultured in 2D. We observed a reduced metabolic activities and apoptotic cell death. Morphological alterations, such as spiking of nuclei and changes in the shape of cytofilaments were also visible. Accordingly, treatment increased cell stiffness and reduced cell motility. Cancer cells are able to develop several mechanisms to subvert and avoid immune response. Danger associated molecular patterns (DAMPs) are linked to an immunogenic cell death (ICD) [3]. We observed an upregulation of DAMPs on the cell surface as well as increased concentrations in the cell’s liquid surroundings following incubation with plasma-treated saline. The activation of the immune system for cancer therapy is a promising approach. Animal experiments will show whether plasma-treated saline solution is effective in vivo and could be in principle considered for medical application.

Proteome Characteristics of Non-Alcoholic Steatohepatitis Liver Tissue and Associated Hepatocellular Carcinomas.

To uncover mechanisms of nonalcoholic steatohepatitis (NASH) associated hepatocarcinogenesis, we compared the proteomes of human NASH-associated liver biopsies, resected hepatocellular carcinomas (HCCs) and HCCs of HCV+ patients with normal liver tissue of patients with gastrointestinal tumor metastasis, in formalin-fixed paraffin-embedded samples obtained after surgery in our hospital during the period from 2006 to 2011. In addition, proteome analysis of liver tumors in male STAM NASH-model mice was performed. Similar changes in the proteome spectrum such as overexpression of enzymes involved in lipid, cholesterol and bile acid biosynthesis and examples associated with suppression of fatty acid oxidation and catabolism, alcohol metabolism, mitochondrial function as well as low expression levels of cytokeratins 8 and 18 were observed in both human NASH biopsies and NASH HCCs, but not HCV+ HCCs. Alterations in downstream protein expression pointed to significant activation of transforming growth factor β, SMAD family member 3, β-catenin, Nrf2, SREBP-LXRα and nuclear receptor-interacting protein 1 (NRIP1), and inhibition of PPARs and p53 in human NASH biopsies and/or HCCs, suggesting their involvement in accumulation of lipids, development of fibrosis, oxidative stress, cell proliferation and suppression of apoptosis in NASH hepatocarcinogenesis. In STAM mice, PPARs inhibition was not obvious, while expression of cytokeratins 8 and 18 was elevated, indicative of essential differences between human and mouse NASH pathogenesis.

Clinical Features of Metastatic Hepatic Malignancies.

The liver is a common site for gastrointestinal tumor metastases as it is the first major organ reached by blood draining the portal venous system. With the development of more effective chemotherapeutic agents which may eradicate residual microscopic disease in the liver and help reduce known tumor burden, partial hepatectomy to remove gross metastatic disease will likely become increasingly utilized in the future. This chapter discusses the presentation and clinical factors in liver directed surgical resection.

Correlation between high mobility group box-B1 and gastrointestinal tumors

High mobility group box-B1 (HMGB1)is a non histone DNA-binding protein and extracellular molecule related to damage.Normally it is located inside the cell and exerts a variety of biological effects. It has been demonstrated that the expression of HMGB1 presents in almost all gastrointestinal tumors and is closely correlated with the cell growth, proliferation, invasion and metastasis of gastrointestinal tumors. It has been discovered that HMGB1 inhibitor inhibits growth and metastasis of gastrointestinal tumors, which might become a new approach to the treatment of gastrointestinal tumors. Key words: HMGB1; Gastrointestinal neoplasms

The novel monoclonal antibody MH8-4 inhibiting cell motility recognizes integrin alpha 3: inverse of its expression withmetastases in colon cancer.

The molecular basis of cell motility is obviously highly complex and is considered to be controlled by a number of molecular systems including cell adhesion molecules, their receptors, cytoskeletal components, a junctional unit connecting cytoskeletal components and membrane receptors, and various peptide growth factors. The possible involvement of proteins at the cell surface in controlling cell motility has been systematically investigated. Previously, we have addressed this question using functional monoclonal antibodies (MAbs), which inhibit cell motility as probes. In order to further identify cell surface molecules involved in metastasis of gastrointestinal tumors, the present study utilized an approach based on the selection of a colon cancer cell line RPMI4788, which showed high motility out of a large number of human gastrointestinal tumor cell lines. MAb MH8-4 was established after immunization of mice with RPMI4788 and selected on the basis of inhibition of RPMI4788 cell migration in a transwell penetration assay. MH8-4 inhibited the phagokinetic tract motility of various cancer cell lines. A cDNA cloning revealed that MH8-4 recognized a specific protein structure, integrin alpha 3. In order to determine whether these experimental results are of relevance with respect to actual human gastrointestinal tumors, we investigated integrin alpha 3 expression in 40 colon cancers with distant metastases. Our immunohistochemical study showed that in almost 27.5% of the cases, the metastatic tumors had lower integrin alpha 3 levels than their corresponding primary tumors. Moreover, there were no primary tumors with lower integrin alpha 3 expression than their corresponding metastatic tumors. Our data suggest that low integrin alpha 3 expression may be associated with the metastatic potential of certain colon cancers.

STREAMLINE PHENOMENA IN LIVER METASTASIS OF GASTROINTESTINAL TUMORS - A CLINICAL-STUDY BASED UPON 172 PATIENTS

Location and number of liver metastasis of gastrointestinal tumors were detected preoperatively and intraoperatively. The distribution of the liver segment(s) occupied by metastatic tumors varied significantly (p<0.05). Significantly more frequent distributions were demonstrated in the lateral segment with gastric cancer (p<0.05), in the posterior segment with left colic cancer (p<0.001), in the medial segment with rectal cancer (p<0.01), in the anterior segment with bile duct cancer (p<0.05) and the whole of the liver with pancreatic cancer (p<0.05). Significantly less frequent distribution was demonstrated in the posterior segment with gastric cancer (p<0.01). When the liver was divided into the right and the left halves, the distribution of each half of the liver occupied by metastatic tumors varied significantly (p<0.05). Liver metastases of whole colic cancer were significantly more frequent in the right half of the liver (p<0.05). The results suggest that the tumor distribution in liver metastases of gastrointestinal tumors differ depending upon the primary tumors, basically in accordance with the 'streamline' phenomena.