International Journal Of Experimental Pathology[JOURNAL]
Sun
200 papers
Long non-coding RNA GAS5 overexpression inhibits M2-like polarization of tumour-associated macrophages in SMCC-7721 cells by promoting PTEN expression.
Wang X, Li FY, Zhao W … +4 more , Gao ZK, Shen B, Xu H, Cui YF
Int J Exp Pathol · 2020 Dec · PMID 33146930 · Full text
Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differenti...
Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC, si-GAS5, si-PTEN or si-Ctrl. A human liver cancer cell line (SMCC-7721) was incubated with the modified TAM supernatant. Quantitative real-time PCR and Western blot were performed to detect gene and protein expression. The cell proliferation and invasion properties of the SMCC-7721 cells were detected by MTT and Transwell assays. GAS5 is up-regulated in M1 macrophages and down-regulated in M2 macrophages and TAMs. GAS5 overexpression promoted M1-like polarization of TAMs and inhibited M2-like polarization of TAMs. Moreover, GAS5 promoted the expression of PTEN in TAMs. PTEN-silenced TAM supernatant treatment promoted cell proliferative and invasive properties of the SMCC-7721 cells and diminished the effect of GAS5-overexpressed TAM supernatant on the cell proliferation and invasion by SMCC-7721 cells. Our results demostrared that GAS5 overexpression inhibited M2-like polarization of TAMs by enhancing PTEN expression, thereby inhibiting cell proliferation and invasion by SMCC-7721 cells. Thus, our results suggest that GAS5 may be a new therapeutic target for HCC treatment.
TGFBR3 is an independent unfavourable prognostic marker in oesophageal squamous cell cancer and is positively correlated with Ki-67.
Zhang X, Chen Y, Li Z … +2 more , Han X, Liang Y
Int J Exp Pathol · 2020 Dec · PMID 33146446 · Full text
The transforming growth factor beta (TGF-β) superfamily plays an important role in cancer development. One aspect of this is that the transforming growth factor beta receptor III (TGFBR3) is frequently overexpressed in s...
The transforming growth factor beta (TGF-β) superfamily plays an important role in cancer development. One aspect of this is that the transforming growth factor beta receptor III (TGFBR3) is frequently overexpressed in some tumours. However, the role of TGFBR3 in oesophageal squamous cell carcinoma (ESCC) has not been explored as yet. In this study, we aimed to determine the role of TGFBR3 in the development and prognosis of ESCC and the correlation between TGFBR3 expression and Ki-67 and p53. Immunohistochemistry was performed to investigate the expression of TGFBR3 in the tumour tissue microarray consisting of ESCC tissues and matched adjacent normal tissues (n = 80). Only ESCC tissues (n = 20) were also used in our analysis. The association between TGFBR3 expression and clinicopathological characteristics, such as Ki-67 and p53, was analysed by Spearman's rank correlation coefficient analysis. The association between TGFBR3 expression and prognosis of ESCC was analysed using Kaplan-Meier analysis and log-rank tests. The expression levels of TGFBR3 in oesophageal cancer tissues were markedly higher than in matched adjacent normal tissues. Furthermore, TGFBR3 overexpression was significantly associated with tumour-node-metastasis (TNM) stage, lymph node metastasis (N stage) and Ki-67 expression. However, TGFBR3 overexpression was not significantly related to age, sex or p53. In univariate analysis, overall survival of ESCC patients was significantly associated with high TGFBR3 expression, sex, T stage, N stage and TNM stage. Moreover, ESCC patients with high TGFBR3 expression had poorer overall survival than those with low TGFB R3 expression. Our findings showed that TGFBR3 was upregulated in the development of human ESCC and high TGFBR3 expression was associated with high expression of Ki-67 and poor prognosis of ESCC. Therefore, TGFBR3 may be a valuable prognostic marker and a novel therapeutic target for ESCC.
Tempol improves redox status in mdx dystrophic diaphragm muscle.
Hermes TA, Mizobuti DS, da Rocha GL … +5 more , da Silva HNM, Covatti C, Pereira ECL, Ferretti R, Minatel E
Int J Exp Pathol · 2020 Dec · PMID 33098599 · Full text
Oxidative stress is a critical element in relationship to the pathophysiology of Duchenne muscular dystrophy (DMD). In the mice the diaphragm (DIA) is most resembles the dystrophic human pathology. In this study we have...
Oxidative stress is a critical element in relationship to the pathophysiology of Duchenne muscular dystrophy (DMD). In the mice the diaphragm (DIA) is most resembles the dystrophic human pathology. In this study we have evaluated the consequences of a synthetic antioxidant (tempol) on oxidative stress parameters in the DIA muscle of mdx mice. The mdx mice were separated into two groups: mdx, the control group receiving intraperitoneal (i.p.) injections of saline solution (100 µL), and mdxT, the treated group receiving i.p. injections of tempol (100 mg/kg). The tempol-treated group showed reduced oxidative stress markers, decreasing the dihydroethidium reaction (DHE) area; autofluorescent lipofuscin granules; and 4-hydroxynonenal (4-HNE)-protein adduct levels. DIA muscle of mdx mice. At the same time, the manganese-superoxide dismutase 2 (SOD2) levels were increased in the tempol-treated group. In addition, the tempol-treated group showed reduced levels of glutathione-disulphide reductase (GSR), glutathione peroxidase 1 (GPx1) and catalase (CAT) in immunoblots. The tempol-treated group has also shown lower relative gene expression of SOD1, CAT and GPx than the non-treated group. Our data demonstrated that tempol treatment reduced oxidant parameters and increased anti-oxidant SOD2 levels in the DIA muscle of mdx mice, which may contribute to the normalization of the redox homeostasis of dystrophic muscles.
MiR-590-3p regulates cardiomyocyte P19CL6 proliferation, apoptosis and differentiation in vitro by targeting PTPN1 via JNK/STAT/NF-kB pathway.
Wang F, Zhang H, Wang C
Int J Exp Pathol · 2020 Dec · PMID 33058302 · Full text
Cardiomyocyte differentiation is a multi-step process which involves a number of signalling pathways. microRNAs exhibit regulatory functions in various diseases and are involved in the signalling pathways in multiple phy...
Cardiomyocyte differentiation is a multi-step process which involves a number of signalling pathways. microRNAs exhibit regulatory functions in various diseases and are involved in the signalling pathways in multiple physiological processes, but the specific functions of particular mRNAs is often not fully understood. of an example of this is that the role of miR-590-3p in the differentiation of cardiomyocytes remains unclear. In the current study, RT-qPCR was used to determine the expression of miR-590-3p in cardiomyocytes differentiated from the embryonic carcinoma cell line P19CL6. MTT, EdU, caspase-3 activity and flow cytometry assays were performed to examine the influence of miR-590-3p on cell behaviour. A luciferase assay was used to confirm binding between miR-590-3p and PTPN1. Western blotting was used to determine the relationship between the JNK/STAT/NF-kB pathway and PTPN1. The results inferred that miR-590-3p became heavily expressed in differentiated P19CL6. Knockdown miR-590-3p suppressed the cell proliferation while at the same time, accelerated apoptosis. Moreover, PTPN1 was identified as the target of miR-590-3p. More importantly, PTPN1 overexpression activated the JNK/STAT/NF-kB pathway and limited the differentiation of P19CL6. Thus the conclusions from this study are that miR-590-3p has the potential to regulate the proliferation, apoptosis and differentiation of cardiomyocyte P19CL6 in vitro by targeting PTPN1 via the JNK/STAT/NF-kB pathway.
MiR-484 suppressed proliferation, migration, invasion and induced apoptosis of gastric cancer via targeting CCL-18.
Liu J, Li SM
Int J Exp Pathol · 2020 Dec · PMID 32985776 · Full text
Gastric cancer is a common and high-incidence malignant gastro-intestinal cancer that seriously threatens human life. Evidence suggests that microRNAs (miRNAs) play an essential role in regulating the occurrence and deve...
Gastric cancer is a common and high-incidence malignant gastro-intestinal cancer that seriously threatens human life. Evidence suggests that microRNAs (miRNAs) play an essential role in regulating the occurrence and development of gastric cancer, but the possible mechanisms and effects remain to be further explored. In the present study, a new tumour suppresser function of miR-484 was identified in gastric cancer. The expression of miR-484 was obviously decreased, and the expression of CCL-18 was obviously increased in gastric cancer tissues and cell lines. In addition, upregulation of miR-484 suppressed cell proliferation, migration and invasion, and induced cell cycle arrest in G1 phase and cell apoptosis in gastric cancer cells. Besides, miR-484 mimics could block the PI3K/AKT signalling pathway. Moreover, CCL-18 was confirmed as a direct target of miR-484 by binding its 3'-UTR, and over-expression of CCL-18 could restore the effects of miR-484 on the growth and metastasis of gastric cancer. Finally, in vivo experiments showed that over-expression of miR-484 inhibited the subcutaneous tumorigenicity of gastric cancer cells, and the inhibition was blocked after over-expression of CCL-18. To conclude, miR-484 expression was downregulated in gastric cancer tissues and cells and played an anti-cancer role in the occurrence and development of gastric cancer, which may be achieved by inhibiting the expression of transcription factor CCL-18 and blocking the PI3K/AKT pathway.
Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis- and autophagy-associated molecules.
Gebril SM, Ito Y, Shibata MA … +7 more , Maemura K, Abu-Dief EE, Hussein MRA, Abdelaal UM, Elsayed HM, Otsuki Y, Higuchi K
Int J Exp Pathol · 2020 Dec · PMID 32985762 · Full text
In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common comp...
In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6- and 12-hour intervals. Parietal cells (H , K -ATPase β-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context.
An aryl hydrocarbon receptor agonist suppresses the growth of human umbilical vein endothelial cells in vitro: Potent effect with polyunsaturated fatty acids.
Yamaguchi M, Hankinson O
Int J Exp Pathol · 2020 Dec · PMID 32985761 · Full text
Human umbilical vein endothelial cells (HUVECs) are a pivotal component of the hematopoietic microenvironment linked to the modulation of the immune response, inflammation and carcinogenesis. HUVEC expresses the aryl hyd...
Human umbilical vein endothelial cells (HUVECs) are a pivotal component of the hematopoietic microenvironment linked to the modulation of the immune response, inflammation and carcinogenesis. HUVEC expresses the aryl hydrocarbon receptor (AHR), which regulates gene expression by binding to the xenobiotic-responsive element. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent agonist for AHR signalling. Treatment with TCDD (0.1-100 nmol/L) was found to suppress the proliferation and to stimulate the death of HUVEC. TCDD's effects were abolished by culturing with CH223191, an inhibitor of AHR signalling. Mechanistically, TCDD treatment increased the protein levels of cell growth suppressors, including p53, Rb, p21 and regucalcin, and caspase-3 implicated in apoptotic cell death, and decreased the levels of Stat3, mitogen-activated protein kinase (MAPK/Erk1/2) and phospho-MAPK/Erk1/2. Treatment with polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid, eicosapentaenoic acid and arachidonic acid, suppressed the proliferation and stimulated the death of HUVEC in vitro, and decreased the levels of Stat3, MAPK/Erk1/2 and phospho-MAPK/Erk1/2 and increased caspase-3. Notably, the effects of TCDD in suppressing proliferation and stimulating death of HUVEC were modulated by coculturing with PUFAs. These effects were reversed by treatment with CH223191, an inhibitor of AHR. Treatment with both TCDD and PUFAs collaboratively enhanced the levels of AHR, CYP1A1, p53, p21, Rb and regucalcin. Moreover, TCDD suppressed migration with wound healing of HUVEC. Notably, the combination of TCDD and PUFAs revealed potent suppressive effects on angiogenesis of HUVEC, potentially related to disorders of the stromal microenvironment.
Evaluation of the regenerative potential of dentin conditioning and naturally derived scaffold for necrotic immature permanent teeth in a dog model.
El Halaby HM, Abu-Seida AM, Fawzy MI … +2 more , Farid MH, Bastawy HA
Int J Exp Pathol · 2020 Dec · PMID 32985739 · Full text
This study evaluated the outcome of partial exposure of dentin matrix to ethylenediaminetetraacetic acid (EDTA) and application of platelet-rich fibrin (PRF) scaffold on regeneration of necrotic immature permanent teeth...
This study evaluated the outcome of partial exposure of dentin matrix to ethylenediaminetetraacetic acid (EDTA) and application of platelet-rich fibrin (PRF) scaffold on regeneration of necrotic immature permanent teeth in a dog model. The present study was carried out on 216 permanent immature roots in nine mongrel dogs aged 6-9 months. Pulp necrosis and periapical pathosis were induced in 180 roots. These roots were divided into five equal groups (36 roots each) according to the treatment protocol: group I: blood clot; group II: 17% EDTA solution and blood clot; group III: PRF; group IV: 17% EDTA solution and PRF; and group V: without treatment (positive control). The negative control group (group VI) represented 36 untouched normal roots for normal maturation. The groups were followed up for 1, 2 and 3 months (subgroups). Maturation of the roots was monitored by radiography and histopathology. All data were statistically analysed. Group IV exhibited the highest increase in root length and thickness, decrease in apical diameter, the highest score of vital tissue infiltration and least inflammatory scores. There was a significant difference regarding the increase in root length and thickness and decrease in apical diameter in all subgroups of the experimental and negative control groups (P ≤ .05). PRF has a better regenerative potential than the blood clot during treatment of immature permanent teeth with necrotic pulp. Inclusion of 17% EDTA solution as a final irrigation enhances the regenerative potential of both PRF and blood clot.
Megakaryocytes, erythropoietic and granulopoietic cells express CAL2 antibody in myeloproliferative neoplasms carrying CALR gene mutations.
Ali H, Puccio I, Akarca AU … +9 more , Bob R, Pomplun S, Keong Wong W, Gupta R, Sekhar M, Lambert J, Al-Masri H, Stein H, Marafioti T
Int J Exp Pathol · 2021 Feb · PMID 32929772 · Full text
Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the...
Testing for the CALR mutation is included in the updated WHO criteria for essential thrombocythaemia (ET) and primary myelofibrosis (PMF). We report on the application of the CAL2 monoclonal antibody, raised against the mutated CALR gene to myeloid cases. The immunostain was used on 116 acute myeloid leukaemias (AML) and 66 myeloproliferative neoplasms (MPN) or myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). None of AML cases was stained by the CAL2 antibody, while 20/66 MPNs and MDS/MPNs appeared positive. Fourteen of the latter cases were studied by molecular techniques, and all showed aberrations of the CALR gene. In addition, CAL2 positivity was found in some small-sized elements besides megakaryocytes. By double staining, these elements corresponded to small megakaryocytes as well as both erythroid and myeloid precursors. This finding suggests possible occurrence of CALR gene abnormalities in a stem cell.
Effects of low and high doses of fenofibrate on protein, amino acid, and energy metabolism in rat.
Holeček M, Vodeničarovová M
Int J Exp Pathol · 2020 Oct · PMID 32869427 · Full text
A feared adverse effect of dyslipidaemia therapy by fibrates is myopathy. We examined the effect of fenofibrate (FF) on protein and amino acid metabolism. Rats received a low (50 mg/kg, LFFD) or high (300 mg/kg, HFFD) do...
A feared adverse effect of dyslipidaemia therapy by fibrates is myopathy. We examined the effect of fenofibrate (FF) on protein and amino acid metabolism. Rats received a low (50 mg/kg, LFFD) or high (300 mg/kg, HFFD) dose of FF or vehicle daily by oral gavage. Blood plasma, liver, and soleus and extensor digitorum longus muscles were analysed after 10 days. The FF-treated rats developed hepatomegaly associated with increased hepatic carnitine and ATP and AMP concentrations, decreased protein breakdown, and decreased concentrations of DNA and triglycerides. HFFD increased plasma ALT and AST activities. The weight and protein content of muscles in the HFFD group were lower compared with controls. In muscles of the LFFD group there were increased ATP and decreased AMP concentrations; in the HFFD group AMP was increased. In both FF-treated groups there were increased glycine, phenylalanine, and citrulline and decreased arginine and branched-chain keto acids (BCKA) in blood plasma. After HFFD there were decreased levels of branched-chain amino acids (BCAA; valine, leucine and isoleucine), methionine, and lysine and increased homocysteine. Decreased arginine and increased glycine concentrations were found in both muscles in FF-treated animals; in HFFD-treated animals lysine, methionine, and BCAA were decreased. We conclude that FF exerts protein-anabolic effects on the liver and catabolic effects on muscles. HFFD causes signs of hepatotoxicity, impairs energy and protein balance in muscles, and decreases BCAA, methionine, and lysine. It is suggested that increased glycine and decreased lysine and methionine levels are due to activated carnitine synthesis; decreased BCAA and BCKA levels are due to increased BCAA oxidation.
Deleterious effects of Pfaffia glomerata (Spreng.) Pedersen hydroalcoholic extract on the seminiferous epithelium of adult Balb/c mice.
Matta APLF, Leite JPV, Gomes MLM … +4 more , Morais DB, Carvalho FAR, Otoni WC, Matta SLP
Int J Exp Pathol · 2020 Oct · PMID 32869402 · Full text
Several plant species such as Pfaffia glomerata are widely used in traditional Brazilian medicine as stimulants and aphrodisiacs. In this regard, the aim of our study was to explore the effects of the long-term intake of...
Several plant species such as Pfaffia glomerata are widely used in traditional Brazilian medicine as stimulants and aphrodisiacs. In this regard, the aim of our study was to explore the effects of the long-term intake of the hydro-alcoholic root extract of P glomerata on the germ and somatic cells within the seminiferous tubules in adult Balb/c mice. The experimental groups were placed as: controls (water and DMSO), and treated with 300 and 400 mg/kg of the root extract. The number of germ and somatic cells, the proportion of pathological seminiferous tubules, and the germ cell apoptotic levels were evaluated. The volume and proportion of the seminiferous epithelium was decreased after the extract intake due to the increased germ cell apoptotic levels. Vacuolization of Sertoli cell cytoplasm was observed widely in pathological tubules, along with fully disorganized epithelia, showing multinucleated cells, which lead to decreased daily sperm production. Taken together, our results indicate that long-term intake of the P glomerata caused deleterious effects on spermatogenesis by inducing apoptosis and altering the seminiferous tubule's epithelial dynamics.
The cellular origins of cancer with particular reference to the gastrointestinal tract.
Alison MR
Int J Exp Pathol · 2020 Oct · PMID 32794627 · Full text
Stem cells or their closely related committed progenitor cells are the likely founder cells of most neoplasms. In the continually renewing and hierarchically organized epithelia of the oesophagus, stomach and intestine,...
Stem cells or their closely related committed progenitor cells are the likely founder cells of most neoplasms. In the continually renewing and hierarchically organized epithelia of the oesophagus, stomach and intestine, homeostatic stem cells are located at the beginning of the cell flux, in the basal layer of the oesophagus, the isthmic region of gastric oxyntic glands and at the bottom of gastric pyloric-antral glands and colonic crypts. The introduction of mutant oncogenes such as Kras or loss of Tp53 or Apc to specific cell types expressing the likes of Lgr5 and Mist1 can be readily accomplished in genetically engineered mouse models to initiate tumorigenesis. Other origins of cancer are discussed including 'reserve' stem cells that may be activated by damage or through disruption of morphogen gradients along the crypt axis. In the liver and pancreas, with little cell turnover and no obvious stem cell markers, the importance of regenerative hyperplasia associated with chronic inflammation to tumour initiation is vividly apparent, though inflammatory conditions in the renewing populations are also permissive for tumour induction. In the liver, hepatocytes, biliary epithelial cells and hepatic progenitor cells are embryologically related, and all can give rise to hepatocellular carcinoma and cholangiocarcinoma. In the exocrine pancreas, both acinar and ductal cells can give rise to pancreatic ductal adenocarcinoma (PDAC), although the preceding preneoplastic states are quite different: acinar-ductal metaplasia gives rise to pancreatic intraepithelial neoplasia culminating in PDAC, while ducts give rise to PDAC via. mucinous cell metaplasia that may have a polyclonal origin.
A "Western Diet" promotes symptoms of hepatic steatosis in spontaneously hypertensive rats.
Cartland SP, Tamer N, Patil MS … +2 more , Di Bartolo BA, Kavurma MM
Int J Exp Pathol · 2020 Oct · PMID 32783310 · Full text
Systemic hypertension, characterized by elevated blood pressure ≥140/90 mm Hg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non-alcoholic fatty liver disease (NAFLD), wh...
Systemic hypertension, characterized by elevated blood pressure ≥140/90 mm Hg, is a major modifiable risk factor for cardiovascular disease. Hypertension also associates with non-alcoholic fatty liver disease (NAFLD), which is becoming common due to a modern diet and lifestyle. The aim of the present study was to examine whether a high-fat "Western" diet had effects on hypertension and associated NAFLD. Normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were placed on a normal chow or high-fat diet for 8 weeks; blood pressure was measured fortnightly and body weight recorded weekly. As expected, SHR had elevated blood pressure compared to WKY. Diet did not influence blood pressure. Compared to SHR, WKY rats gained more weight, associating with increased white adipose tissue weight. Normotensive rats also had higher plasma cholesterol and triglycerides in response to a "Western" diet, with no changes in plasma glucose levels. Neither strain developed atherosclerosis. Interestingly, high-fat diet-fed SHR had increased liver weight, associating with a significant level of hepatic lipid accumulation not observed in WKY. Further, they exhibited hepatocellular ballooning and increased hepatic inflammation, indicative of steatohepatitis. These findings suggest that a high-fat "Western" diet promotes features of NAFLD in SHR, but not WKY rats. Importantly, the high-fat diet had no effect on blood pressure.
Fatty change of the liver microenvironment influences the metastatic potential of colorectal cancer.
Masaki S, Hashimoto Y, Kunisho S … +2 more , Kimoto A, Kitadai Y
Int J Exp Pathol · 2020 Oct · PMID 32783302 · Full text
Fatty liver is the most common cause of liver disease, and its prevalence has been increasing globally. Colorectal cancer (CRC) accounts for approximately 10% of all cancers and metastasizes most commonly to the liver. P...
Fatty liver is the most common cause of liver disease, and its prevalence has been increasing globally. Colorectal cancer (CRC) accounts for approximately 10% of all cancers and metastasizes most commonly to the liver. Paget's 'Seed and Soil' theory of metastasis proposed that the secondary growth of cancer cells is dependent on the distal organ microenvironment. This implies that the risk of metastasis may change due to changes in the microenvironment of target organs. However, the association between steatosis, fatty change in the liver microenvironment, and liver metastasis has not been clarified. Here, we induced fatty liver conditions in BALB/c mice using a choline-deficient high-fat diet with 0.1% methionine (CDAHFD) and then injected the CT26 cells to produce experimental metastasis. The number of metastatic tumours was significantly increased in mice with severe fatty liver as compared to control mice. The average size of metastatic tumours was smaller in mice with moderate fatty liver than in control mice. The stromal components, including cancer-associated fibroblasts, tumour-associated macrophages and tumour-infiltrating lymphocytes, were also examined. Metastatic tumours in fatty liver showed invasive growth patterns without a fibrotic capsule. Compared to control groups, the polarization of macrophages and subtypes of tumour-infiltrating lymphocytes differed depending on the extent of fatty liver progression. These results indicated that fatty changes in the liver influenced liver metastasis of CRC. Although moderate fatty changes suppress the growth of metastatic tumours in the liver, a severe fatty microenvironment may promote invasion and metastasis through alteration of the tumour microenvironment (TME).
British Society for Matrix Biology Autumn 2019 Meeting: "Cell Adhesion Networks in Health and Disease".
Int J Exp Pathol · 2020 Jun · PMID 32687244 · Full text
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Identification of functional long non-coding RNAs in gastric cancer by bioinformatics analysis.
Li Y, Ma D, Li T … +1 more , Yin Y
Int J Exp Pathol · 2020 Jun · PMID 32608553 · Full text
Long non-coding RNAs (lncRNAs) have been proven to play important roles in various cancers, including gastric cancer (GC). However, detailed knowledge about lncRNAs in GC is limited. Therefore we carried out an in-depth...
Long non-coding RNAs (lncRNAs) have been proven to play important roles in various cancers, including gastric cancer (GC). However, detailed knowledge about lncRNAs in GC is limited. Therefore we carried out an in-depth study of public data and found 83 differently expressed lncRNAs in GC. To further confirm the target genes of these lncRNAs, we constructed a co-expression network between lncRNAs and mRNAs and found three lncRNAs (MBNL1-AS1, HAND2-AS1 and MIR100HG) were at the core of the network. By coalition analysis of clinical information and the three lncRNAs' expression level from The Cancer Genome Atlas (TCGA) and GSE15459 data sets, we found MIR100HG could be a potential prognostic factor. Clinical samples showed patients with higher MIR100HG expression had poorer prognosis, and further experiments demonstrated that MIR100HG was associated with proliferation, migration and invasion of GC cells. Hopefully, MIR100HG might be considered as a novel prognostic factor and biomarker for GC.
Preclinical relevance of probiotics in type 2 diabetes: A systematic review.
Marques AM, Sarandy MM, Novaes RD … +2 more , Gonçalves RV, Freitas MB
Int J Exp Pathol · 2020 Jun · PMID 32608551 · Full text
Type 2 diabetes (T2DM) is among the most prevalent metabolic diseases in the world and may result in several long-term complications. The crosstalk between gut microbiota and host metabolism is closely related to T2DM. C...
Type 2 diabetes (T2DM) is among the most prevalent metabolic diseases in the world and may result in several long-term complications. The crosstalk between gut microbiota and host metabolism is closely related to T2DM. Currently, fragmented data hamper defining the relationship between probiotics and T2DM. This systematic review aimed at investigating the effects of probiotics on T2DM in animal models. We systematically reviewed preclinical evidences using PubMed/MEDLINE and Scopus databases, recovering 24 original articles published until September 27th, 2019. This systematic review was performed according to PRISMA guidelines. We included experimental studies with animal models reporting the effects of probiotics on T2DM. Studies were sorted by characteristics of publications, animal models, performed analyses, probiotic used and interventions. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool. Probiotics improved T2DM in 96% of the studies. Most studies (96%) used Lactobacillus strains, and all of them led to improved glycaemia. All studies used rodents as models, and male animals were preferred over females. Results suggest that probiotics have a beneficial effect in T2DM animals and could be used as a supporting alternative in the disease treatment. Considering a detailed evaluation of the reporting and methodological quality, the current preclinical evidence is at high risk of bias. We hope that our critical analysis will be useful in mitigating the sources of bias in further studies.
Tensin4 (TNS4) is upregulated by Wnt signalling in adenomas in multiple intestinal neoplasia (Min) mice.
Raposo TP, Alfahed A, Nateri AS … +1 more , Ilyas M
Int J Exp Pathol · 2020 Jun · PMID 32567731 · Full text
Apc mice are regarded as a standard animal model of colorectal cancer (CRC). Tensin4 (TNS4 or Cten) is a putative oncogene conferring features of stemness and promoting motility. Our objective was to assess TNS4 expressi...
Apc mice are regarded as a standard animal model of colorectal cancer (CRC). Tensin4 (TNS4 or Cten) is a putative oncogene conferring features of stemness and promoting motility. Our objective was to assess TNS4 expression in intestinal adenomas and determine whether TNS4 is upregulated by Wnt signalling. Apc mice (n = 11) were sacrificed at approximately 120 days old at the onset of anaemia signs. Small intestines were harvested, and Swiss roll preparations were tested for TNS4 expression by immunohistochemistry (IHC). Individual polyps were also separately collected (n = 14) and tested for TNS4 mRNA expression and Kras mutation. The relationship between Wnt signalling and TNS4 expression was tested by Western blotting in the human CRC cell line HCT116 after inhibition of β-catenin activity with MSAB or its increase by transfection with a Flag β-catenin expression vector. Overall, 135/148 (91.2%) of the total intestinal polyps were positive for TNS4 expression by IHC, whilst adjacent normal areas were negative. RT-qPCR analysis showed approximately 5-fold upregulation of TNS4 mRNA in the polyps compared to adjacent normal tissue and no Kras mutations were detected. In HCT116, β-catenin inhibition resulted in reduced TNS4 expression, and conversely, β-catenin overexpression resulted in increased TNS4 expression. In conclusion, this is the first report linking aberrant Wnt signalling to upregulation of TNS4 both during initiation of intestinal adenomas in mice and in in vitro models. The exact contribution of TNS4 to adenoma development remains to be investigated, but the Apc mouse represents a good model to study this.
Association of Abl interactor 2, ABI2, with platelet/lymphocyte ratio in patients with renal cell carcinoma: A pilot study.
Ergun S, Gunes S, Buyukalpelli R … +1 more , Aydin O
Int J Exp Pathol · 2020 Jun · PMID 32496656 · Full text
There are many unknown aspects of the pathogenesis of renal cell carcinoma (RCC). The aim of the current study was to define new RCC-related genes and measure their associations with RCC and clinical parameters, especial...
There are many unknown aspects of the pathogenesis of renal cell carcinoma (RCC). The aim of the current study was to define new RCC-related genes and measure their associations with RCC and clinical parameters, especially platelet/lymphocyte ratio which may be an independent predictor of prognosis in patients with RCC and other forms of cancer. Via in silico analysis upon RCC-specific deleted genes in chromosome 3, four possible ceRNAs (ATXN3, ABI2, GOLGB1 and SMAD2) were identified. Then, the expression levels of these genes in tumour and adjacent healthy kidney tissues of 19 RCC patients were determined by real-time PCR. ATXN3 and GOLGB1 gene expression levels increased but ABI2 gene expression level decreased in tumour kidney tissues when compared to normal ones. ATXN3, ABI2 and GOLGB1 gene expression levels were significantly higher in Fuhrman grade 4 than other grades (P < .001). ABI2 gene expression levels were significantly associated with higher platelet/lymphocyte ratio of the patients with RCC (P < .05). ATXN3, ABI2 and GOLGB1 may predict higher RCC grades. Also, ABI2 may regulate platelet/lymphocyte ratio which may be an independent predictor of RCC and other forms of cancer.
Anti-inflammatory effect of omega unsaturated fatty acids and dialysable leucocyte extracts on collagen-induced arthritis in DBA/1 mice.
Pérez-Martínez PI, Rojas-Espinosa O, Hernández-Chávez VG … +2 more , Arce-Paredes P, Estrada-Parra S
Int J Exp Pathol · 2020 Feb · PMID 32459025 · Full text
Rheumatoid arthritis is a disabling autoimmune disease with a high global prevalence. Treatment with disease-modifying anti-arthritic drugs (DIMARDs) has been routinely used with beneficial effects but with adverse long-...
Rheumatoid arthritis is a disabling autoimmune disease with a high global prevalence. Treatment with disease-modifying anti-arthritic drugs (DIMARDs) has been routinely used with beneficial effects but with adverse long-term consequences; novel targeted biologics and small-molecule inhibitors are promising options. In this study, we investigated whether purified omega unsaturated fatty acids (ω-UFAs) and dialysable leukocyte extracts (DLEs) prevented the development of arthritis in a model of collagen-induced arthritis (CIA) in mice. We also investigated whether the transcription factor NF-κB and the NLRP3 inflammasome were involved in the process and whether their activity was modulated by treatment. The development of arthritis was evaluated for 84 days following treatment with nothing, dexamethasone, DLEs, docosahexaenoic acid, arachidonic acid, and oleic acid. Progression of CIA was monitored by evaluating clinical manifestations, inflammatory changes, and histological alterations in the pads' articular tissues. Both DLEs and ω-UFAs led to an almost complete inhibition of the inflammatory histopathology of CIA and this was concomitant with the inhibition of NF-kB and the inhibition of the activation of NLRP3. These data suggest that ω-UFAs and DLEs might have NF-κB as a common target and that they might be used as ancillary medicines in the treatment of arthritis.
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