Spices are defined as any aromatic condiment of plant origin used to alter the flavor and aroma of foods. Besides flavor and aroma, many spices have antioxidant activity, mainly related to the presence in cloves of ph...Spices are defined as any aromatic condiment of plant origin used to alter the flavor and aroma of foods. Besides flavor and aroma, many spices have antioxidant activity, mainly related to the presence in cloves of phenolic compounds, such as flavonoids, terpenoids and eugenol. In turn, the most common uses of gum arabic are in the form of powder for addition to soft drink syrups, cuisine and baked goods, specifically to stabilize the texture of products, increase the viscosity of liquids and promote the leavening of baked products (e.g., cakes). Both eugenol, extracted from cloves, and gum arabic, extracted from the hardened sap of two species of the Acacia tree, are dietary constituents routinely consumed virtually throughout the world. Both of them are also widely used medicinally to inhibit oxidative stress and genotoxicity. The prevention arm of the study included groups: Ia, IIa, IIIa, Iva, V, VI, VII, VIII. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA, EUG, or 10% GA + EUG by gavage. The treatment arm of the study included groups Ib, IIb, IIIb e IVb, IX, X, XI, XII). Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG by gavage. The novelty of this study is the investigation of their use alone and together for the prevention and treatment of experimental colorectal carcinogenesis induced by dimethylhydrazine. Our results show that the combined use of 10% gum arabic and eugenol was effective, with antioxidant action in the colon, as well as reducing oxidative stress in all colon segments and preventing and treating genotoxicity in all colon segments. Furthermore, their joint administration reduced the number of aberrant crypts and the number of aberrant crypt foci (ACF) in the distal segment and entire colon, as well as the number of ACF with at least 5 crypts in the entire colon. Thus, our results also demonstrate the synergistic effects of 10% gum arabic together with eugenol (from cloves), with antioxidant, antigenotoxic and anticarcinogenic actions (prevention and treatment) at the doses and durations studied, in the colon of rats submitted to colorectal carcinogenesis induced by dimethylhydrazine.展开更多
Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity...Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.展开更多
Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of bioc...Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of biochemical and molecular pathways:thymine dimer formation,DNA damage,oxidative stress,inflammatory responses,and altered cell signaling,eventually resulting in tumor formation.The increased skin cancer rates urge researchers to develop more efficient drugs,but synthetic chemotherapeutic drugs have more contrary effects and drug resistance issues,which have been reported recently.The current review focuses on the relationship between microbes and cancer.Human skin acts as a barrier against the external environment and serves as a protective shield for its inhabitant microbiota,collectively called skin microbes.The gut microbiome plays a vital role in cancer therapy.Production of short-chain fatty acids(SCFAs)such as butyrate,acetate,and propionate by intestinal microbes has anti-cancer properties against various cancer cell lines.Yet,the knowledge of SCFAs produced by skin microbes remains yet to be elucidated exhaustively.In this review,we strive to summarize the findings of studies performed to date regarding the anti-cancer properties of SCFA against various cancer cell lines and provide insight into future directions in the skin microbiome field.展开更多
Oral submucosal fibrosis(OSF)is a chronic,progressive and insidious oral mucosal disease.Its development is highly associated with areca chewing and eventually evolves into oral squamous cell carcinoma(OSCC),which is ...Oral submucosal fibrosis(OSF)is a chronic,progressive and insidious oral mucosal disease.Its development is highly associated with areca chewing and eventually evolves into oral squamous cell carcinoma(OSCC),which is currently recognized as a precancerous state by the International Center for Research on Cancer(IARC).Due to the extremely complex carcinogenesis process of OSF,the carcinogenesis mechanism is not clear,and most scholars believe that the disease is the result of multiple factors.Therefore,this paper mainly summarized the latest research on the molecular mechanism of OSF canceration,aiming at understanding the law of OSF canceration and providing theoretical reference for early detection,diagnosis and treatment of OSF canceration.展开更多
AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained fr...AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.展开更多
Epigenetic alterations contribute significantly to the development and progression of gastric cancer,one of the leading causes of cancer death worldwide.Epigenetics refers to the number of modifications of the chromat...Epigenetic alterations contribute significantly to the development and progression of gastric cancer,one of the leading causes of cancer death worldwide.Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA,and these changes lead to transcriptional activation or silencing of the gene.Over the years,the study of epigenetic processes has increased,and novel therapeutic approaches that target DNA methylation and histone modifications have emerged.A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment.Here,we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome.展开更多
AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/D...AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/DSS to develop the ulcerative colitis(UC) carcinogenesis model. Mice were treated with 5-ASA(75 mg/kg/d), VSL#3(1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months(five days/week). The tumor load was compared in each group, and tumor necrosis factor(TNF-α) and interleukin(IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16 s rDNA sequencing method.RESULTS VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Al oprevotel a in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.展开更多
Inflammation is a primary defense process against various extracellular stimuli,such as viruses,pathogens,foods,and environmental pollutants.When cells respond to stimuli for short periods of time,it results in acute ...Inflammation is a primary defense process against various extracellular stimuli,such as viruses,pathogens,foods,and environmental pollutants.When cells respond to stimuli for short periods of time,it results in acute or physiological inflammation.However,if the stimulation is sustained for longer time or a pathological state occurs,it is known as chronic or pathological inflammation.Several studies have shown that tumorigenesis in the gastrointestinal (GI) tract is closely associated with chronic inflammation,for which abnormal cellular alterations that accompany chronic inflammation such as oxidative stresses,gene mutations,epigenetic changes,and inflammatory cytokines,are shared with carcinogenic processes,which forms a critical cross-link between chronic inflammation and carcinogenesis.Transforming growth factor (TGF)-β is a multi-potent cytokine that plays an important role in regulation of cell growth,apoptosis and differentiation.Most importantly,TGF-β is a strong anti-inflammatory cytokine that regulates the development of effector cells.TGF-β has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth,but on the other hand,many GI cancers originate from uncontrolled cell growth and differentiation by genetic loss of TGF-β signaling molecules or perturbation of TGF-β adaptors.Once a tumor has developed,TGF-β exerts a promoting effect on the tumor itself and stromal cells to enhance cell growth,alter the responsiveness of tumor cells to stimulate invasion and metastasis,and inhibited immune surveillance.Therefore,novel development of therapeutic agents to inhibit TGF-β-induced progression of tumor and to retain its growth inhibitory activities,in addition to anti-inflammatory actions,could be useful in oncology.In this review,we discuss the role of TGF-β in inflammation and carcinogenesis of the GI tract related to abnormal TGF-β signaling.展开更多
The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving p...The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving polymorphonuclear leukocytes (PMNL),as a major actor in digestive carcinogenesis,the different cellular and molecular events occurring in this process are still not completely understood.The transepithelial migration of PMNL,which is the ultimate step of the afflux of PMNL into the digestive mucosa,is a complex phenomenon involving sequential interaction of molecules expressed both on PMNL and on digestive epithelial cells.Chronic inflammatory areas rich in PMNL [so-called (chronic active inflammation)] and iterative transepithelial migration of PMNL certainly evoke intracellular signals,which lead toward progressive transformation of epithelia.Among these different signals,the mutagenic effect of reactive oxygen species and nitrates,the activation of the nuclear factor-κB pathway,and the modulation of expression of certain microRNA are key actors.Following the initiation of carcinogenesis,PMNL are involved in the progression and invasion of digestive carcinomas,with which they interact.It is noteworthy that different subpopulations of PMNL,which can have some opposite effects on tumor growth,in association with different levels of transforming growth factor-β and with the number of CD8 positive T lymphocytes,could be present during the development of digestive carcinoma.Other factors that involve PMNL,such as massive elastase release,and the production of angiogenic factors,can participate in the progression of neoplastic cells through tissues.PMNL may play a major role in the onset of metastases,since they allow the tumor cells to cross the endothelial barrier and to migrate into the blood stream.Finally,PMNL play a role,alone or in association with other cell parameters,in the initiation,promotion,progression and dissemination of digestive carcinomas.This review focuses on the main currently accepted cellular and molecular mechanisms that involve PMNL as key actors in digestive carcinogenesis.展开更多
Pancreaticobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. In PBM, since the pancreatic duct and bile duct converge outside the duodenal wall beyond the influence of the sphincter of Oddi, pa...Pancreaticobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. In PBM, since the pancreatic duct and bile duct converge outside the duodenal wall beyond the influence of the sphincter of Oddi, pancreatic juice and bile are constantly mixed, producing a variety of harmful substances. Because of this, the biliary mucosa is repeatedly damaged and repaired, which causes an acceleration of cell proliferative activity and multiple gene mutations. Histological changes such as hyperplasia, metaplasia, and dysplasia ultimately result in a high incidence of carcinogenesis. In a nationwide survey by the Japanese Study Group on PBM, coexisting biliary tract cancer was detected in 278 of the 1627 registered cases of PBM (17.1%). Of these cases, in those with dilatation of the extrahepatic bile duct, cancer was often detected not only in the gallbladder but also in the bile ducts. More than 90% of cancer cases without dilatation of the extrahepatic bile duct develop in the gallbladder. Standard treatment for PBM is a cholecystectomy and resection of the extrahepatic bile duct. However, cholecystectomy alone is performed at nearly half of institutions in Japan. Conversely, reports of carcinogenesis in the remnant bile duct or pancreas after diversion surgery are steadily increasing. One of the causes for this is believed to be an accumulation of gene mutations which were present before surgery. Anticancer drugs are ineffective in preventing such carcinogenesis following surgery, thus the postoperative administration of chemopreventive agents may be necessary.展开更多
Colorectal cancer(CRC)is a very common malignancy in the Western World and despite advances in surgery,chemotherapy and screening,it is still the second leading cause of cancer deaths in this part of the world.Numerou...Colorectal cancer(CRC)is a very common malignancy in the Western World and despite advances in surgery,chemotherapy and screening,it is still the second leading cause of cancer deaths in this part of the world.Numerous factors are found important in the development of CRC including colonocyte metbolism,high risk luminal environment,inflammation,as well as lifestyle factors such as diet,tobacco,and alchohol consumption.In recent years focus has turned towards the genetics and molecular biology of CRC and several interesting and promising correlations and pathways have been discovered.The major genetic pathways of CRC are the Chromosome Instability Pathway representing the pathway of sporadic CRC through the K-ras,APC,and P53 mutations,and the Microsatellite Instability Pathway representing the pathway of he re di t ar y non-polyposis c olon c anc e r t hrough mutations in mismatch repair genes.To identify early cancers,screening programs have been initiated,and the leading strategy has been the use of faecal occult blood testing followed by colonoscopy in positive cases.Regarding the treatment of colorectal cancer,significant advances have been made in the recent decade.The molecular targets of CRC include at least two important cell surface receptors:the epidermal growth factorreceptor and the vascular endothelial growth factor receptor.The genetic and molecular knowledge of CRC has widen the scientific and clinical perspectives of diagnosing and treatment.However,despite significant advances in the understanding and treatment of CRC,results from targeted therapy are still not convincing.Future studies will determine the role for this new treatment modality.展开更多
Current proposed mechanisms implicate both early and latent Epstein-Barr virus(EBV)infection in the carcinogenic cascade,whereas epidemiological studies have always associated nasopharyngeal carcinoma(NPC)with early c...Current proposed mechanisms implicate both early and latent Epstein-Barr virus(EBV)infection in the carcinogenic cascade,whereas epidemiological studies have always associated nasopharyngeal carcinoma(NPC)with early childhood EBV infection and with chronic ear,nose,and sinus conditions.Moreover,most patients with NPC present with IgA antibody titers to EBV capsid antigen(VCA-lgA),which can precede actual tumor presentation by several years.If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis,one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection.It is perhaps possible that EBV resides within the salivary glands,instead of the epithelium,during latency.This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis,the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene(EDAR),EDARV370A.Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain,but in patients with infectious mononucleosis,EBV has been isolated in this anatomical organ.The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus.Adding to the fact that the fossa of Rosen Muller contains a transformative zone active only in the first decade of life,one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.展开更多
Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the...Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.展开更多
Hepatocellular carcinoma(HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm fo...Hepatocellular carcinoma(HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.展开更多
AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2(e EF1A2) on hepatocellular carcinoma(HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying mechanisms.METHODS: e E...AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2(e EF1A2) on hepatocellular carcinoma(HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying mechanisms.METHODS: e EF1A2 levels were detected in 62 HCC tissue samples and paired pericarcinomatous specimens, and the human HCC cell lines SK-HEP-1, Hep G2 and BEF-7402, by real-time PCR and immunohistochemistry. Experimental groups included e EF1A2 silencing in BEL-7402 cells with lentivirus e EF1A2-sh RNA(KD group) and e EF1A2 overexpression in SK-HEP-1 cells with e EF1A2 plasmid(OE group). Non-transfected cells(control group) and lentivirusbased empty vector transfected cells(NC group) were considered control groups. Cell proliferation(MTT and colony formation assays), apoptosis(Annexin V-APC assay), cell cycle(DNA ploidy assay), and migration and invasion(Transwell assays) were assessed. Protein levels of PI3K/Akt/NF-κB signaling effectors were evaluated by Western blot.RESULTS: e EF1A2 m RNA and protein levels were significantly higher in HCC cancer tissue samples than in paired pericarcinomatous and normal specimens. SK-HEP-1 cells showed lower e EF1A2 m RNA levels; Hep G2 and BEL-7402 cells showed higher e EF1A2 m RNA levels, with BEL-7402 cells displaying the highest amount. Efficient e EF1A2 silencing resulted in reduced cell proliferation, migration and invasion, increased apoptosis, and induced cell cycle arrest. The PI3K/Akt/NF-κB signaling pathway was notably inhibited. Inversely, e EF1A2 overexpression resulted in promoted cell proliferation, migration and invasion.CONCLUSION: e EF1A2, highly expressed in HCC, is a potential oncogene. Its silencing significantly decreases HCC tumorigenesis, likely by inhibiting PI3K/Akt/NF-κB signaling.展开更多
AIM: To investigate the expression profiles of hsa-mi R-29 c and hsa-mi R-135 b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-mi R-29 c and hsa...AIM: To investigate the expression profiles of hsa-mi R-29 c and hsa-mi R-135 b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-mi R-29 c and hsa-mi R-135 b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinaltype gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-mi R-29 c and hsa-mi R-135 b expression profiles in the grouped samples was evaluated by ANOVA and Student's t-test tests. The results were adjusted for multiple testing by using Bonferroni's correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-mi R-29 c and hsa-mi R-135 b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-mi R-29 c and hsa-mi R-135 b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis.RESULTS: The expression levels of hsa-mi R-29 c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-mi R-29 c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This micro RNA(mi RNA) has a good discriminatory accuracy between normal gastric samples and(1) intestinal-type gastric adenocarcinoma; and(2) intestinal metaplasia, and regulates the DMNT3 A oncogene. hsa-mi R-135 b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-mi R-135 b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This mi RNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes.CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-mi R-29 c and hsa-mi R-135 b are promising biomarkers of gastric carcinogenesis.展开更多
Each year there will be an estimated 2.1 million new lung cancer cases and 1.8 million lung cancer deaths worldwide.Tobacco smoke is the No.1 risk factors of lung cancer,accounting for>85%lung cancer deaths.Air pol...Each year there will be an estimated 2.1 million new lung cancer cases and 1.8 million lung cancer deaths worldwide.Tobacco smoke is the No.1 risk factors of lung cancer,accounting for>85%lung cancer deaths.Air pollution,or haze,comprises ambient air pollution and household air pollution,which are reported to cause 252,000 and 304,000 lung cancer deaths each year,respectively.Tobacco smoke and haze(hereafter,smohaze)contain fine particles originated from insufficient combustion of biomass or coal,have quite similar carcinogens,and cause similar diseases.Smohaze exert hazardous effects on exposed populations,including induction of a large amount of mutations in the genome,alternative splicing of mRNAs,abnormalities in epigenomics,initiation of tumor-promoting chronic inflammation,and facilitating immune escape of transformed cells.Tackling smohaze and development of multi-targets-based preventive and therapeutic approaches targeting smohaze-induced carcinogenesis are the key to conquer lung cancer in the future.展开更多
Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut micro...Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer.Some gut bacteria,such as Fusobacterium nucleatum,Escherichia coli,Clostridium difficile,Peptostreptococcus,and enterotoxigenic Bacteroides fragilis,could be implicated in colorectal carcinogenesis through different mechanisms,including the maintenance of a chronic inflammatory state,production of bioactive tumorigenic metabolites,and DNA damage.Studies using the adenomatous polyposis coliMin/+mouse model,which resembles FAP in most respects,have shown that specific changes in the intestinal microbial community could influence a multistep progression,the intestinal“adenoma-carcinoma sequence”,which involves mucosal barrier injury,low-grade inflammation,activation of the Wnt pathway.Therefore,modulation of gut microbiota might represent a novel therapeutic target for patients with FAP.Administration of probiotics,prebiotics,antibiotics,and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP.The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.展开更多
文摘Spices are defined as any aromatic condiment of plant origin used to alter the flavor and aroma of foods. Besides flavor and aroma, many spices have antioxidant activity, mainly related to the presence in cloves of phenolic compounds, such as flavonoids, terpenoids and eugenol. In turn, the most common uses of gum arabic are in the form of powder for addition to soft drink syrups, cuisine and baked goods, specifically to stabilize the texture of products, increase the viscosity of liquids and promote the leavening of baked products (e.g., cakes). Both eugenol, extracted from cloves, and gum arabic, extracted from the hardened sap of two species of the Acacia tree, are dietary constituents routinely consumed virtually throughout the world. Both of them are also widely used medicinally to inhibit oxidative stress and genotoxicity. The prevention arm of the study included groups: Ia, IIa, IIIa, Iva, V, VI, VII, VIII. Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the same period and for an additional 9 weeks, the animals received either water, 10% GA, EUG, or 10% GA + EUG by gavage. The treatment arm of the study included groups Ib, IIb, IIIb e IVb, IX, X, XI, XII). Once a week for 20 weeks, the controls received saline s.c. while the experimental groups received DMH at 20 mg/kg s.c. During the subsequent 9 weeks, the animals received either water, 10% GA, EUG or 10% GA + EUG by gavage. The novelty of this study is the investigation of their use alone and together for the prevention and treatment of experimental colorectal carcinogenesis induced by dimethylhydrazine. Our results show that the combined use of 10% gum arabic and eugenol was effective, with antioxidant action in the colon, as well as reducing oxidative stress in all colon segments and preventing and treating genotoxicity in all colon segments. Furthermore, their joint administration reduced the number of aberrant crypts and the number of aberrant crypt foci (ACF) in the distal segment and entire colon, as well as the number of ACF with at least 5 crypts in the entire colon. Thus, our results also demonstrate the synergistic effects of 10% gum arabic together with eugenol (from cloves), with antioxidant, antigenotoxic and anticarcinogenic actions (prevention and treatment) at the doses and durations studied, in the colon of rats submitted to colorectal carcinogenesis induced by dimethylhydrazine.
基金supported by National Natural Science Foundation of China(92059102 and 81630080)the National Key Research and Development Plan of China(2018YFC1704106).
文摘Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.
文摘Solar ultraviolet B(UVB)radiation is a major skin cancer-causing agent.Initiation,promotion,and progression are the diverse phases of UVB-induced carcinogenesis.Exposure to UVB causes abnormalities in a series of biochemical and molecular pathways:thymine dimer formation,DNA damage,oxidative stress,inflammatory responses,and altered cell signaling,eventually resulting in tumor formation.The increased skin cancer rates urge researchers to develop more efficient drugs,but synthetic chemotherapeutic drugs have more contrary effects and drug resistance issues,which have been reported recently.The current review focuses on the relationship between microbes and cancer.Human skin acts as a barrier against the external environment and serves as a protective shield for its inhabitant microbiota,collectively called skin microbes.The gut microbiome plays a vital role in cancer therapy.Production of short-chain fatty acids(SCFAs)such as butyrate,acetate,and propionate by intestinal microbes has anti-cancer properties against various cancer cell lines.Yet,the knowledge of SCFAs produced by skin microbes remains yet to be elucidated exhaustively.In this review,we strive to summarize the findings of studies performed to date regarding the anti-cancer properties of SCFA against various cancer cell lines and provide insight into future directions in the skin microbiome field.
基金National Natural Science Foundation of China(No.81960199)Major Science and Technology Plan and Key R&D Plan Project of Hainan Province(No.ZDYF2021SHFZ114)Hainan Provincial Department of Health Project(No.22A200001)。
文摘Oral submucosal fibrosis(OSF)is a chronic,progressive and insidious oral mucosal disease.Its development is highly associated with areca chewing and eventually evolves into oral squamous cell carcinoma(OSCC),which is currently recognized as a precancerous state by the International Center for Research on Cancer(IARC).Due to the extremely complex carcinogenesis process of OSF,the carcinogenesis mechanism is not clear,and most scholars believe that the disease is the result of multiple factors.Therefore,this paper mainly summarized the latest research on the molecular mechanism of OSF canceration,aiming at understanding the law of OSF canceration and providing theoretical reference for early detection,diagnosis and treatment of OSF canceration.
基金Supported by National Natural Science Foundation of China,No.81072692Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.10KJB320007
文摘AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
基金Supported by Sao Paulo State Research Foundation (FAPESP),No. 2009/07145-9 and 2010/11174-1National Counsel of Technological and Scientific Development (CNPq)Coordination for the Improvement of Higher Level Personnel (CAPES)
文摘Epigenetic alterations contribute significantly to the development and progression of gastric cancer,one of the leading causes of cancer death worldwide.Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA,and these changes lead to transcriptional activation or silencing of the gene.Over the years,the study of epigenetic processes has increased,and novel therapeutic approaches that target DNA methylation and histone modifications have emerged.A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment.Here,we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome.
基金Supported by the National Natural Science Foundation of China,No.81370500 and No.81770559
文摘AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/DSS to develop the ulcerative colitis(UC) carcinogenesis model. Mice were treated with 5-ASA(75 mg/kg/d), VSL#3(1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months(five days/week). The tumor load was compared in each group, and tumor necrosis factor(TNF-α) and interleukin(IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16 s rDNA sequencing method.RESULTS VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Al oprevotel a in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.
基金Supported by The Korea Science and Engineering Foundation (KOSEF)grant funded by the Korea government (MOST),No.20090081756
文摘Inflammation is a primary defense process against various extracellular stimuli,such as viruses,pathogens,foods,and environmental pollutants.When cells respond to stimuli for short periods of time,it results in acute or physiological inflammation.However,if the stimulation is sustained for longer time or a pathological state occurs,it is known as chronic or pathological inflammation.Several studies have shown that tumorigenesis in the gastrointestinal (GI) tract is closely associated with chronic inflammation,for which abnormal cellular alterations that accompany chronic inflammation such as oxidative stresses,gene mutations,epigenetic changes,and inflammatory cytokines,are shared with carcinogenic processes,which forms a critical cross-link between chronic inflammation and carcinogenesis.Transforming growth factor (TGF)-β is a multi-potent cytokine that plays an important role in regulation of cell growth,apoptosis and differentiation.Most importantly,TGF-β is a strong anti-inflammatory cytokine that regulates the development of effector cells.TGF-β has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth,but on the other hand,many GI cancers originate from uncontrolled cell growth and differentiation by genetic loss of TGF-β signaling molecules or perturbation of TGF-β adaptors.Once a tumor has developed,TGF-β exerts a promoting effect on the tumor itself and stromal cells to enhance cell growth,alter the responsiveness of tumor cells to stimulate invasion and metastasis,and inhibited immune surveillance.Therefore,novel development of therapeutic agents to inhibit TGF-β-induced progression of tumor and to retain its growth inhibitory activities,in addition to anti-inflammatory actions,could be useful in oncology.In this review,we discuss the role of TGF-β in inflammation and carcinogenesis of the GI tract related to abnormal TGF-β signaling.
文摘The role of chronic inflammation,acting as an independent factor,on the onset of gastrointestinal carcinogenesis is now well accepted.However,even if there is an increase in the number of elements directly involving polymorphonuclear leukocytes (PMNL),as a major actor in digestive carcinogenesis,the different cellular and molecular events occurring in this process are still not completely understood.The transepithelial migration of PMNL,which is the ultimate step of the afflux of PMNL into the digestive mucosa,is a complex phenomenon involving sequential interaction of molecules expressed both on PMNL and on digestive epithelial cells.Chronic inflammatory areas rich in PMNL [so-called (chronic active inflammation)] and iterative transepithelial migration of PMNL certainly evoke intracellular signals,which lead toward progressive transformation of epithelia.Among these different signals,the mutagenic effect of reactive oxygen species and nitrates,the activation of the nuclear factor-κB pathway,and the modulation of expression of certain microRNA are key actors.Following the initiation of carcinogenesis,PMNL are involved in the progression and invasion of digestive carcinomas,with which they interact.It is noteworthy that different subpopulations of PMNL,which can have some opposite effects on tumor growth,in association with different levels of transforming growth factor-β and with the number of CD8 positive T lymphocytes,could be present during the development of digestive carcinoma.Other factors that involve PMNL,such as massive elastase release,and the production of angiogenic factors,can participate in the progression of neoplastic cells through tissues.PMNL may play a major role in the onset of metastases,since they allow the tumor cells to cross the endothelial barrier and to migrate into the blood stream.Finally,PMNL play a role,alone or in association with other cell parameters,in the initiation,promotion,progression and dissemination of digestive carcinomas.This review focuses on the main currently accepted cellular and molecular mechanisms that involve PMNL as key actors in digestive carcinogenesis.
文摘Pancreaticobiliary maljunction (PBM) is a high risk factor for biliary tract cancer. In PBM, since the pancreatic duct and bile duct converge outside the duodenal wall beyond the influence of the sphincter of Oddi, pancreatic juice and bile are constantly mixed, producing a variety of harmful substances. Because of this, the biliary mucosa is repeatedly damaged and repaired, which causes an acceleration of cell proliferative activity and multiple gene mutations. Histological changes such as hyperplasia, metaplasia, and dysplasia ultimately result in a high incidence of carcinogenesis. In a nationwide survey by the Japanese Study Group on PBM, coexisting biliary tract cancer was detected in 278 of the 1627 registered cases of PBM (17.1%). Of these cases, in those with dilatation of the extrahepatic bile duct, cancer was often detected not only in the gallbladder but also in the bile ducts. More than 90% of cancer cases without dilatation of the extrahepatic bile duct develop in the gallbladder. Standard treatment for PBM is a cholecystectomy and resection of the extrahepatic bile duct. However, cholecystectomy alone is performed at nearly half of institutions in Japan. Conversely, reports of carcinogenesis in the remnant bile duct or pancreas after diversion surgery are steadily increasing. One of the causes for this is believed to be an accumulation of gene mutations which were present before surgery. Anticancer drugs are ineffective in preventing such carcinogenesis following surgery, thus the postoperative administration of chemopreventive agents may be necessary.
文摘Colorectal cancer(CRC)is a very common malignancy in the Western World and despite advances in surgery,chemotherapy and screening,it is still the second leading cause of cancer deaths in this part of the world.Numerous factors are found important in the development of CRC including colonocyte metbolism,high risk luminal environment,inflammation,as well as lifestyle factors such as diet,tobacco,and alchohol consumption.In recent years focus has turned towards the genetics and molecular biology of CRC and several interesting and promising correlations and pathways have been discovered.The major genetic pathways of CRC are the Chromosome Instability Pathway representing the pathway of sporadic CRC through the K-ras,APC,and P53 mutations,and the Microsatellite Instability Pathway representing the pathway of he re di t ar y non-polyposis c olon c anc e r t hrough mutations in mismatch repair genes.To identify early cancers,screening programs have been initiated,and the leading strategy has been the use of faecal occult blood testing followed by colonoscopy in positive cases.Regarding the treatment of colorectal cancer,significant advances have been made in the recent decade.The molecular targets of CRC include at least two important cell surface receptors:the epidermal growth factorreceptor and the vascular endothelial growth factor receptor.The genetic and molecular knowledge of CRC has widen the scientific and clinical perspectives of diagnosing and treatment.However,despite significant advances in the understanding and treatment of CRC,results from targeted therapy are still not convincing.Future studies will determine the role for this new treatment modality.
文摘Current proposed mechanisms implicate both early and latent Epstein-Barr virus(EBV)infection in the carcinogenic cascade,whereas epidemiological studies have always associated nasopharyngeal carcinoma(NPC)with early childhood EBV infection and with chronic ear,nose,and sinus conditions.Moreover,most patients with NPC present with IgA antibody titers to EBV capsid antigen(VCA-lgA),which can precede actual tumor presentation by several years.If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis,one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection.It is perhaps possible that EBV resides within the salivary glands,instead of the epithelium,during latency.This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased susceptibility to NPC and immature salivary gland morphogenesis,the latter of which is influenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene(EDAR),EDARV370A.Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain,but in patients with infectious mononucleosis,EBV has been isolated in this anatomical organ.The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus.Adding to the fact that the fossa of Rosen Muller contains a transformative zone active only in the first decade of life,one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.
文摘Serrated adenocarcinoma is a recently described subset of colorectal cancer(CRC),which account for about10%of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC.Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps(HPs),sessile serrated adenoma(SSA),traditional serrated adenoma(TSA)and mixed polyps.HPs are the most common serrated polyp followed by SSA and TSA.This distinct histogenesis is believed to have a major influence in prevention strategies,patient prognosis and therapeutic impact.Genetically,serrated polyps exhibited also a distinct pattern,with KRAS and BRAF having an important contribution to its development.Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype.In the present review we will address the current knowledge of serrated polyps,clinical pathological features and will update the most recent findings of its molecular pathways.The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development.
文摘Hepatocellular carcinoma(HCC) is now the second leading cause of cancer-related deaths globally and many patients have incurable disease. HCC predominantly occurs in the setting of liver cirrhosis and is a paradigm for inflammation-induced cancer. The causes of chronic liver disease promote the development of transformed or premalignant hepatocytes and predisposes to the development of HCC. For HCC to grow and progress it is now clear that it requires an immunosuppressive niche within the fibrogenic microenvironment of cirrhosis. The rationale for targeting this immunosuppression is supported by responses seen in recent trials with checkpoint inhibitors. With the impact of immunotherapy, HCC progression may be delayed and long term durable responses may be seen. This makes the management of the underlying liver cirrhosis in HCC even more crucial as studies demonstrate that measures of liver function are a major prognostic factor in HCC. In this review, we discuss the development of cancer in the setting of liver inflammation and fibrosis, reviewing the microenvironment that leads to this tumourigenic climate and the implications this has for patient management.
基金Supported by the Middle-Young Age Backbone Talent Cultivation Program of Fujian Health System,No.2013-ZQNJC-2Key Projects of Science and Technology Plan of Fujian Province,No.2014Y0009
文摘AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2(e EF1A2) on hepatocellular carcinoma(HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying mechanisms.METHODS: e EF1A2 levels were detected in 62 HCC tissue samples and paired pericarcinomatous specimens, and the human HCC cell lines SK-HEP-1, Hep G2 and BEF-7402, by real-time PCR and immunohistochemistry. Experimental groups included e EF1A2 silencing in BEL-7402 cells with lentivirus e EF1A2-sh RNA(KD group) and e EF1A2 overexpression in SK-HEP-1 cells with e EF1A2 plasmid(OE group). Non-transfected cells(control group) and lentivirusbased empty vector transfected cells(NC group) were considered control groups. Cell proliferation(MTT and colony formation assays), apoptosis(Annexin V-APC assay), cell cycle(DNA ploidy assay), and migration and invasion(Transwell assays) were assessed. Protein levels of PI3K/Akt/NF-κB signaling effectors were evaluated by Western blot.RESULTS: e EF1A2 m RNA and protein levels were significantly higher in HCC cancer tissue samples than in paired pericarcinomatous and normal specimens. SK-HEP-1 cells showed lower e EF1A2 m RNA levels; Hep G2 and BEL-7402 cells showed higher e EF1A2 m RNA levels, with BEL-7402 cells displaying the highest amount. Efficient e EF1A2 silencing resulted in reduced cell proliferation, migration and invasion, increased apoptosis, and induced cell cycle arrest. The PI3K/Akt/NF-κB signaling pathway was notably inhibited. Inversely, e EF1A2 overexpression resulted in promoted cell proliferation, migration and invasion.CONCLUSION: e EF1A2, highly expressed in HCC, is a potential oncogene. Its silencing significantly decreases HCC tumorigenesis, likely by inhibiting PI3K/Akt/NF-κB signaling.
基金Supported by Conselho Nacional de Desenvolvimento Científico e TecnológicoFundacao Amazonia Paraense de Amparo a PesquisaCoordenacao de Aperfeicoamento de Pessoal de Nível Superior/Bio Computacional,No.3381/2013
文摘AIM: To investigate the expression profiles of hsa-mi R-29 c and hsa-mi R-135 b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers. METHODS: The expression levels of hsa-mi R-29 c and hsa-mi R-135 b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinaltype gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-mi R-29 c and hsa-mi R-135 b expression profiles in the grouped samples was evaluated by ANOVA and Student's t-test tests. The results were adjusted for multiple testing by using Bonferroni's correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-mi R-29 c and hsa-mi R-135 b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-mi R-29 c and hsa-mi R-135 b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis.RESULTS: The expression levels of hsa-mi R-29 c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-mi R-29 c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This micro RNA(mi RNA) has a good discriminatory accuracy between normal gastric samples and(1) intestinal-type gastric adenocarcinoma; and(2) intestinal metaplasia, and regulates the DMNT3 A oncogene. hsa-mi R-135 b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-mi R-135 b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This mi RNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes.CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-mi R-29 c and hsa-mi R-135 b are promising biomarkers of gastric carcinogenesis.
基金supported by the National Key Research and Development Program of China (Grant No. 2016YFC0905501)the National Natural Science Funds for Distinguished Young Scholar (Grant No. 81425025)+3 种基金the Key Project of the National Natural Science Foundation of China (Grant No. 81830093)the CAMS Innovation Fund for Medical Sciences (Grant No. CIFMS 2019-I2M-1-003)the National Natural Science Foundation of China (Grant No. 81672765)
文摘Each year there will be an estimated 2.1 million new lung cancer cases and 1.8 million lung cancer deaths worldwide.Tobacco smoke is the No.1 risk factors of lung cancer,accounting for>85%lung cancer deaths.Air pollution,or haze,comprises ambient air pollution and household air pollution,which are reported to cause 252,000 and 304,000 lung cancer deaths each year,respectively.Tobacco smoke and haze(hereafter,smohaze)contain fine particles originated from insufficient combustion of biomass or coal,have quite similar carcinogens,and cause similar diseases.Smohaze exert hazardous effects on exposed populations,including induction of a large amount of mutations in the genome,alternative splicing of mRNAs,abnormalities in epigenomics,initiation of tumor-promoting chronic inflammation,and facilitating immune escape of transformed cells.Tackling smohaze and development of multi-targets-based preventive and therapeutic approaches targeting smohaze-induced carcinogenesis are the key to conquer lung cancer in the future.
文摘Patients with familial adenomatous polyposis(FAP),an autosomal dominant hereditary colorectal cancer syndrome,have a lifetime risk of developing cancer of nearly 100%.Recent studies have pointed out that the gut microbiota could play a crucial role in the development of colorectal adenomas and the consequent progression to colorectal cancer.Some gut bacteria,such as Fusobacterium nucleatum,Escherichia coli,Clostridium difficile,Peptostreptococcus,and enterotoxigenic Bacteroides fragilis,could be implicated in colorectal carcinogenesis through different mechanisms,including the maintenance of a chronic inflammatory state,production of bioactive tumorigenic metabolites,and DNA damage.Studies using the adenomatous polyposis coliMin/+mouse model,which resembles FAP in most respects,have shown that specific changes in the intestinal microbial community could influence a multistep progression,the intestinal“adenoma-carcinoma sequence”,which involves mucosal barrier injury,low-grade inflammation,activation of the Wnt pathway.Therefore,modulation of gut microbiota might represent a novel therapeutic target for patients with FAP.Administration of probiotics,prebiotics,antibiotics,and nonsteroidal anti-inflammatory drugs could potentially prevent the progression of the adenoma-carcinoma sequence in FAP.The aim of this review was to summarize the best available knowledge on the role of gut microbiota in colorectal carcinogenesis in patients with FAP.
