metallothionein and Intestinal-Neoplasms

Metallothioneins (MTs) were reported to be associated with many kinds of tumors' prognosis, although MTs expression varied greatly among tumors. To assess the prognostic value of Metallothioneins (MTs) in different kinds of tumors, comprehensive literature search was conducted to perform a meta-analysis.. Eligible studies were identified by PubMed, MEDLINE, Web of Science (WOS), the Cochrane Library of Systematic Reviews, EMBASE, China National Knowledge Infrastructure (CNKI), WANFANG database and SinoMed database up to December 2017, which was designed to assess the prognostic value of MTs in different kinds of tumors. The main endpoint events were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and its variance were retrieved from the original studies directly or calculated using Engauge Digitizer version 4.1. Random or fixed effects model meta-analysis was employed depending on the heterogeneity. Publication bias was evaluated by funnel plots, Begg and Egger tests.. A total of 22 studies were enrolled in this meta-analysis, including 2843 tumor tissues (1517 were MTs negative/low, and 1326 were MTs high). Results showed that there was significant association between MTs expression and tumors' OS (HR = 1.60; 95%CI 1.34∼1.92, P < .00001). Subgroup analysis showed that high level of MTs expression was associated with prolonged OS in liver cancer (HR = 0.65, 95%CI 0.48∼0.89, P = .007), but it was on the contrary in the tumor of ovary (HR = 1.47, 95%CI 1.01∼2.14, P = .04), bladder (HR = 1.71, 95%CI 1.21∼2.42, P = .002), intestine (HR = 3.13, 95%CI 1.97∼4.97, P < .00001), kidney (HR = 3.31, 95%CI 1.61∼6.79, P = .001). However, there was no significant association between MTs expression and OS in breast (HR = 1.02, 95%CI 0.69∼1.51, P = .93).. MTs could be taken as a potential prognostic biomarker for tumors, and uniqueness of MTs prognostic value in liver cancer deserved further study.

Topics: Biomarkers, Tumor; Case-Control Studies; Disease-Free Survival; Female; Humans; Intestinal Neoplasms; Kaplan-Meier Estimate; Kidney Neoplasms; Liver Neoplasms; Male; Metallothionein; Neoplasms; Ovarian Neoplasms; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Urinary Bladder Neoplasms

Intestinal epithelial cells (IECs) regulate intestinal immune cells, particularly development of T-helper 17 (Th17) cells. Deregulation of this process leads to intestinal inflammation and tumorigenesis, via unknown mechanisms. TANK-binding kinase 1 (TBK1) is expressed by IECs and cells in the innate immune system. We studied the functions of TBK1 in the intestinal immune response and tumorigenesis in mice.. We performed studies of wild-type mice, mice with conditional disruption of Tbk1 (Tbk1. Compared to Apc. Expression of TBK1 by IECs suppresses expression of MT1 and prevents expression of IL1β by macrophages and differentiation of Th17 cells, to prevent inflammation and tumorigenesis. Strategies to block this pathway might be developed for colorectal tumorigenesis.

Topics: Adenomatous Polyposis Coli; Animals; Cell Differentiation; Cell Transformation, Neoplastic; Cells, Cultured; Coculture Techniques; Disease Models, Animal; Epithelial Cells; Genes, APC; Humans; Immunity, Innate; Immunity, Mucosal; Interleukin-17; Interleukin-1beta; Intestinal Mucosa; Intestinal Neoplasms; Macrophages; Metallothionein; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Protein Serine-Threonine Kinases; Th17 Cells

Tumour growth and expansion are the result of proliferative activity and the capacity to eliminate cells by apoptosis and/or necrosis. The present study was aimed at comparing the apoptosis and proliferation intensity in cells of adenocarcinomas of the large intestine with the expression of metallothionein (MT), the grade of the tumour and the depth to which the tumour infiltrated the intestinal wall. The TUNEL technique and immunocytochemical reactions (expression of caspase-3, Ki-67, MT) were used to detect apoptosis. The results demonstrated augmented levels of all the variables examined, positively correlated with grade of malignancy, G, and with the depth of intestinal wall infiltration by the tumour cells. The testing of apoptosis, proliferation and MT expression may prove useful in the appraisal of the growth and progression of primary adenocarcinomas in the large intestine.

Topics: Adenocarcinoma; Apoptosis; Caspase 3; Caspases; Cell Division; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Intestinal Neoplasms; Ki-67 Antigen; Metallothionein; Neoplasm Invasiveness

Differential display is a valuable tool for the identification of differentially expressed genes in human carcinogenesis and development. The search for differentially expressed genes in gastric cancer and its premalignant lesions may help to define molecular alterations in the gastric mucosa that may precede the development of gastric cancer. Using the differential display technique, we identified a cDNA fragment, encoding metallothionein (MT) IIa mRNA. We performed immunohistochemical analysis using a monoclonal antibody directed against human MT and tissues obtained from 34 patients with gastric cancer and 20 healthy individuals to determine the expression and localization of MT in gastric cancer and its associated premalignant lesions and to correlate our findings with histomorphological features and Helicobacter pylori status. In addition, MT expression was assessed in gastric tissues obtained from patients with gastric cancer and first-degree relatives of patients with gastric cancers and healthy individuals using reverse transcription-PCR analysis. Northern blot analysis confirmed the overexpression of MT IIa in gastric cancer. In the normal gastric tissues, no MT immunoreactivity was observed at the superficial gastric epithelium toward the top of gastric glands. However, MT immunoreactivity was detected at the foveolar neck of the gastric glands. Immunohistochemical analysis revealed an intense MT immunoreactivity in gastric cancer cells, independent of tumor stage, grade of differentiation, or tumor type. Furthermore, areas of dysplasia and intestinal metaplasia also exhibited intense MT immunoreactivity. Reverse transcription-PCR analysis of gastric biopsies obtained from first-degree relatives of patients with gastric cancer revealed the frequent expression of MT Ia in this high-risk group as compared with healthy subjects (P < 0.01). The overexpression of MT in gastric cancer and the expression of MT in intestinal metaplasia and dysplasia, as well as the expression of MT in the gastric mucosa of first-degree relatives of patients with gastric cancer, point to a role for MT in the early process of malignant transformation of the gastric mucosa.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Gastric Mucosa; Humans; Intestinal Neoplasms; Male; Metallothionein; Metaplasia; Middle Aged; Precancerous Conditions; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms

Antibody to rat liver metallothionein prepared by the method of Brady and Kafka (1979) was used to localise immunoreactive metallothionein using a sensitive DNP hapten sandwich technique applied to formalin fixed wax embedded tissues. Rat tissues examined were liver, kidney and small intestine, taken from normal animals, from animals fasted after receiving either an oral dose of water, or 1 ml zinc acetate solution either orally or by intraperitoneal injection, (3-4 mg Zn++/Kg body weight). Human tissues examined were 6 histologically normal liver biopsies and small intestine including histologically normal jejunal biopsies and samples of ileum obtained at operation. Pathological tissue including liver from cases of Indian childhood cirrhosis with copper retention and ileum from cases of inflammatory bowel disease were also examined. Immunoreactive metallothionein (IMT) was found in both rat and human liver localised in the hepatocyte cytoplasm, nucleus, sinusoids and canaliculi. In some livers IMT was found in the portal and hepatic veins. In the small intestine the IMT was localised consistently in the enterocyte cytoplasm and nucleus, and in the basement membrane region. The rat kidney IMT was localised in the cytoplasm of the distal convoluted tubules the collecting tubules and the ducts of Bellini. The distribution of IMT in rat tissues showed changes associated with fasting, stress and zinc administration. In man, inflammatory bowel disease appeared to decrease the intestinal IMT and no significant difference was seen when patients had received steroid therapy. The greatest amounts of IMT were seen in the control group of patients. The distribution of IMT in human liver in Indian childhood cirrhosis did not correspond with that of copper associated protein.

Topics: Animals; Basement Membrane; Cell Nucleus; Crohn Disease; Cytoplasm; Dinitrophenols; Fasting; Histocytochemistry; Humans; Immunoenzyme Techniques; Intestinal Diseases; Intestinal Neoplasms; Intestine, Small; Kidney; Liver; Liver Cirrhosis; Metallothionein; Rats; Tissue Distribution