Prospects in the application of ultrasensitive chromosomal aneuploidy detection in precancerous lesions of gastric cancer

Gastric cancer(GC)is a prevalent malignant tumor within the digestive system,with over 40%of new cases and deaths related to GC globally occurring in China.Despite advancements in treatment modalities,such as surgery supplemented by adjuvant radiotherapy or chemotherapeutic agents,the prognosis for GC remains poor.New targeted therapies and immunotherapies are currently under invest-igation,but no significant breakthroughs have been achieved.Studies have indicated that GC is a heterogeneous disease,encompassing multiple subtypes with distinct biological characteristics and roles.Consequently,personalized treatment based on clinical features,pathologic typing,and molecular typing is crucial for the diagnosis and management of precancerous lesions of gastric cancer(PLGC).Current research has categorized GC into four subtypes:Epstein-Barr virus-positive,microsatellite instability,genome stability,and chromosome instability(CIN).Technologies such as multi-omics analysis and gene sequencing are being employed to identify more suitable novel testing methods in these areas.Among these,ultrasensitive chromosomal aneuploidy detection(UCAD)can detect CIN at a genome-wide level in subjects using low-depth whole genome sequencing technology,in conjunction with bioinformatics analysis,to achieve qualitative and quantitative detection of chromosomal stability.This editorial reviews recent research advancements in UCAD technology for the diagnosis and management of PLGC.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Xiaojianzhong decoction prevents gastric precancerous lesions in rats by inhibiting autophagy and glycolysis in gastric mucosal cells

BACKGROUND Gastric precancerous lesions(GPL)precede the development of gastric cancer(GC).They are characterized by gastric mucosal intestinal metaplasia and dysplasia caused by various factors such as inflammation,bacterial infection,and injury.Abnormalities in autophagy and glycolysis affect GPL progression,and their effective regulation can aid in GPL treatment and GC prevention.Xiaojianzhong decoction(XJZ)is a classic compound for the treatment of digestive system diseases in ancient China which can inhibit the progression of GPL.However,its specific mechanism of action is still unclear.AIM To investigate the therapeutic effects of XJZ decoction on a rat GPL model and the mechanisms underlying its effects on autophagy and glycolysis regulation in GPLs.METHODS Wistar rats were randomly divided into six groups of five rats each and all groups except the control group were subjected to GPL model construction for 18 wk.The rats’body weight was monitored every 2 wk starting from the beginning of modeling.Gastric histopathology was examined using hematoxylin-eosin staining and Alcian blue-periodic acid-Schiff staining.Autophagy was observed using transmission electron microscopy.The expressions of autophagy,hypoxia,and glycolysis related proteins in gastric mucosa were detected using immunohistochemistry and immunofluorescence.The expressions of the following proteins in gastric tissues:B cell lymphoma/Leukemia-2 and adenovirus E1B19000 interacting protein 3(Bnip-3),microtubule associated protein 1 light chain 3(LC-3),moesin-like BCL2-interacting protein 1(Beclin-1),phosphatidylinositol 3-kimase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),p53,AMP-activated protein kinase(AMPK),and Unc-51 like kinase 1(ULK1)were detected using western blot.The relative expressions of autophagy,hypoxia,and glycolysis related mRNA in gastric tissues was detected using reverse transcription-polymerase chain reaction.RESULTS Treatment with XJZ increased the rats’body weight and improved GPL-related histopathological manifestations.It also decreased autophagosome and autolysosome formation in gastric tissues and reduced Bnip-3,Beclin-1,and LC-3II expressions,resulting in inhibition of autophagy.Moreover,XJZ down-regulated glycolysis-related monocarboxylate transporter(MCT1),MCT4,and CD147 expressions.XJZ prevented the increase of autophagy level by decreasing gastric mucosal hypoxia,activating the PI3K/AKT/mTOR pathway,inhibiting the p53/AMPK pathway activation and ULK1 Ser-317 and Ser-555 phosphorylation.In addition,XJZ improved abnormal gastric mucosal glucose metabolism by ameliorating gastric mucosal hypoxia and inhibiting ULK1 expression.CONCLUSION This study demonstrates that XJZ may inhibit autophagy and glycolysis in GPL gastric mucosal cells by improving gastric mucosal hypoxia and regulating PI3K/AKT/mTOR and p53/AMPK/ULK1 signaling pathways,providing a feasible strategy for the GPL treatment.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study

BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.

Detection of Human Papillomavirus DNA and E6/E7 mRNA from HPV Genotypes 16, 18, 31 and 33 in Histologically Confirmed Cases of Cervical Cancer and Precancerous Lesions in Burkina Faso

Introduction: Cervical cancer, caused by persistent high-risk human papillomavirus (HPV) infection, remains a global public health problem. The cellular transformation and maintenance of the malignant phenotype of these HPVs are attributed to the viral oncoproteins E6 and E7. Objective: This study aims to detect the presence of human papillomavirus DNA and E6/E7 oncoprotein mRNA of HPV genotypes 16, 18, 31 and 33 in cases of cervical cancer and precancerous lesions, histologically confirmed in Burkina Faso. Methods: This descriptive cross-sectional study focused on cases of cervical cancer and high-grade intraepithelial neoplasia (CIN) and was conducted from June to December 2022. One hundred (100) samples of fixed and paraffin-embedded tissues were collected from the pathological anatomy and cytology laboratories of hospitals in the capital of Burkina Faso. High-risk human papillomavirus (HR-HPV) DNA was detected using multiplex real-time PCR, while the presence of E6 and E7 mRNA in cervical cancer and high-grade CIN samples was determined using real-time Reverse Transcriptase-PCR (RT-PCR) with TaqMan probes. Results: The mean age of women diagnosed with cervical cancer and high-grade CIN was 50.81 ± 13.65 years, ranging from 22 to 82 years. Cervical cancer and high-grade CIN were positive for at least one high-risk human papillomavirus (HR-HPV) in 80% of cases. The most prevalent genotypes observed were HPV16, 18, 31, and 33, collectively accounting for 70.08% of cases. Of the 89 samples that tested positive for HR-HPV genotypes 16, 18, 31, and 33, 88 (98.88%;95% CI: [94.58 - 99.94]) were also positive for the presence of mRNA encoding the E6 and E7 oncoproteins of HPV16, 18, 31, and 33. Conclusion: In the presence of HPV DNA, testing for E6 and E7 oncoprotein mRNA could serve as a promising biomarker and valuable tool for improved assessment of the progression to cervical cancer.

Significance and relationship between Cripto-1 and p-STAT3 expression in gastric cancer and precancerous lesions

AIM:To explore the relationship between Cripto-1 (CR-1) and tyrosine phosphorylation STAT3 (p-STAT3) expressions in gastric cancer (GC) and gastric carcinogensis and metastasis.METHODS: The PV9000 immunohistochemical method was used to detect the expression of CR-1 and p-STAT3 in 178 cases of GC, 95 matched normal gastric mucosa, 40 chronic atrophic gastritis (CAG), 48 intestinal meta-plasia (IM) and 25 dysplasia (DYS). RESULTS: The positive rates of CR-1 and p-STAT3 expression were significantly higher in CAG (65.0% and 60.0%), in IM (83.3% and 77.1%), DYS (80.0% and 68%) and GC (71.3% and 60.1%) than in normal gastric mucosa (43.2% and 41.1%, P < 0.05), respectively. The expressions of CR-1 and p-STAT3 (78.3% and 66.7%) were signifi cantly higher in GC with lymphnode metastasis than in those without metastasis (53.1% and 42.9%, P < 0.05). CR-1 expression was also related to histological and Lauren's types of GC (P < 0.001). Furthermore, there was positive relation-ship between CR-1 and p-STAT3 expressions in GC (rk = 0.189, P = 0.002).CONCLUSION: The up-regulation of CR-1 and p-STAT3 may play important roles in gastric carcinogenesis and lymph node metastasis. CR-1 and p-STAT3 expression in GC was positively correlated, and the relevant molecular mechanism requires further investigations.

Diagnostic performance of narrow-band imaging international colorectal endoscopic and Japanese narrow-band imaging expert team classification systems for colorectal cancer and precancerous lesions

BACKGROUND In recent years,two new narrow-band imaging(NBI)classifications have been proposed:The NBI international colorectal endoscopic(NICE)classification and Japanese NBI expert team(JNET)classification.Most validation studies of the two new NBI classifications were conducted in classification setting units by experienced endoscopists,and the application of use in different centers among endoscopists with different endoscopy skills remains unknown.AIM To evaluate clinical application and possible problems of NICE and JNET classification for the differential diagnosis of colorectal cancer and precancerous lesions.METHODS Six endoscopists with varying levels of experience participated in this study.Eighty-seven consecutive patients with a total of 125 lesions were photographed during non-magnifying conventional white-light colonoscopy,non-magnifying NBI,and magnifying NBI.The three groups of endoscopic pictures of each lesion were evaluated by the six endoscopists in randomized order using the NICE and JENT classifications separately.Then we calculated the six endoscopists’sensitivity,specificity,accuracy,positive predictive value,and negative predictive value for each category of the two classifications.RESULTS The sensitivity,specificity,and accuracy of JNET classification type 1 and 3 were similar to NICE classification type 1 and 3 in both the highly experienced endoscopist(HEE)and less-experienced endoscopist(LEE)groups.The specificity of JNET classification type 1 and 3 and NICE classification type 3 in both the HEE and LEE groups was>95%,and the overall interobserver agreement was good in both groups.The sensitivity of NICE classification type 3 lesions for diagnosis of SM-d carcinoma in the HEE group was significantly superior to that in the LEE group(91.7%vs 83.3%;P=0.042).The sensitivity of JNET classification type 2B lesions for the diagnosis of high-grade dysplasia or superficial submucosal invasive carcinoma in the HEE and LEE groups was 53.8%and 51.3%,respectively.Compared with other types of JNET classification,the diagnostic ability of type 2B was the weakest.CONCLUSION The treatment strategy of the two classification type 1 and 3 lesions can be based on the results of endoscopic examination.JNET type 2B lesions need further examination.

Deep learning for diagnosis of precancerous lesions in upper gastrointestinal endoscopy:A review

Upper gastrointestinal(GI)cancers are the leading cause of cancer-related deaths worldwide.Early identification of precancerous lesions has been shown to minimize the incidence of GI cancers and substantiate the vital role of screening endoscopy.However,unlike GI cancers,precancerous lesions in the upper GI tract can be subtle and difficult to detect.Artificial intelligence techniques,especially deep learning algorithms with convolutional neural networks,might help endoscopists identify the precancerous lesions and reduce interobserver variability.In this review,a systematic literature search was undertaken of the Web of Science,PubMed,Cochrane Library and Embase,with an emphasis on the deep learning-based diagnosis of precancerous lesions in the upper GI tract.The status of deep learning algorithms in upper GI precancerous lesions has been systematically summarized.The challenges and recommendations targeting this field are comprehensively analyzed for future research.

Inverse relations between Helicobacter pylori infection and risk of esophageal precancerous lesions in drinkers and peanut consumption

BACKGROUND Helicobacter pylori(H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma(ESCC) remains a topic of much debate.AIM To evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection.METHODS Two hundred patients with esophageal precancerous lesions(EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection.RESULTS A total of 47(23.5%) EPL cases and 58(29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio(OR) = 0.32, 95% confidence interval(95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection(OR = 0.39, 95%CI: 0.20-0.74).CONCLUSION Our study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.

Gastric mucosal precancerous lesions in Helicobacter pyloriinfected pediatric patients in central China:A single-center,retrospective investigation

BACKGROUND Helicobacter pylori(H.pylori)infects about 50%of the world population and is the major cause of chronic gastritis,peptic ulcers,and gastric cancer.Chronic H.pylori infection induces gastric mucosal precancerous lesions mostly in adulthood,and it is debatable whether these pathological conditions can occur in childhood and adolescents as well.Since this is a critical issue to determine if intervention should be offered for this population group,we investigated the gastric mucosal precancerous lesions in pediatric patients in an area in central China with a high prevalence of H.pylori and gastric cancer.AIM To investigate the relationship of H.pylori infection and gastric mucosal precancerous lesions in children and adolescents in central China.METHODS We screened 4258 ward-admitted children and adolescent patients with upper gastrointestinal symptoms,and finally enrolled 1015 pediatric patients with H.pylori infection and endoscopic and histological data.H.pylori infection status was determined by rapid urease test and histopathological examination.Both clinical and pathological data were collected and analyzed retrospectively.Occurrence of gastric mucosal precancerous lesions,inflammatory activity and degree of inflammatory cell infiltration between H.pylori-positive and-negative groups were compared.RESULTS Among the 1015 eligible children and adolescents,the overall H.pylori infection rate was 84.14%(854/1015).The infection rate increased with age.The incidence of gastric mucosal precancerous lesions in H.pylori-infected children was 4.33%(37/854),which included atrophic gastritis(17 cases),intestinal metaplasia(11 cases)and dysplasia(9 cases).In H.pylori-negative patients,only 1 atrophic gastritis case[0.62%,(1/161)]was found(P<0.05).Active inflammation in H.pyloriinfected patients was significantly higher than that in non-infected patients,and the H.pyloriinfected group showed more severe lymphocyte and neutrophil granulocyte infiltration(P<0.001).In addition,endoscopy revealed that the most common findings in H.pylori-positive patients were antral nodularity,but in H.pylori-negative patients only superficial gastritis was observed.CONCLUSION In children and adolescents,gastric mucosal precancerous lesions occurred in 4.33%of H.pyloriinfected patients in central China.These cases included atrophic gastritis,intestinal metaplasia,and dysplasia.The data revealed an obvious critical issue requiring future investigation and intervention for this population group.

Association between interleukin-21 gene rs907715 polymorphism and gastric precancerous lesions in a Chinese population

BACKGROUND The single nucleotide polymorphisms of interleukin-21(IL-21)gene were confirmed to be related to various diseases,but no studies have examined the possible role of IL-21 single nucleotide polymorphisms(SNPs)(rs907715,rs2221903,and rs12508721)in gastric precancerous lesions.AIM To explore the associations between SNPs of IL-21 gene(rs907715,rs2221903,and rs12508721)and gastric precancerous lesions in a Chinese population.METHODS Three SNPs of IL-21 were genotyped using polymerase chain reaction–ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China.Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis,atrophic gastritis,and intestinal metaplasia.Descriptive statistic and logistic regression were used for data analyses.RESULTS IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls(OR=1.59,95%CI:1.06-2.38,P=0.013;OR=1.28,95%CI:1.01-2.22,P=0.044,respectively)after adjusting for confounding factors.For SNP rs907715 in intestinal metaplasia patients,significant differences between cases and controls were observed in the frequencies of genotype CC and C(OR=1.92,95%CI:1.24-2.98,P=0.004;OR=1.53,95%CI:1.04-2.24,P=0.028,respectively);for non-atrophic gastritis and atrophic gastritis patients,the CC and C genotypes showed no significant association with risk in all models.No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study.In the haplotype analysis,the TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)were more frequent in the case group than control group(P<0.05).CONCLUSION Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions.The TC haplotype(rs907715 and rs12508721)and TT haplotype(rs2221903 and rs907715)increased the risk of gastric precancerous lesions.If confirmed,these findings will shed light on the etiology of precancerous lesions.

THE EXPRESSION OF BCL-2 AND BAX PROTEINS IN GASTRIC CARCINOMA AND PRECANCEROUS LESIONS

Objective To investigate the variance of expression of bcl-2 and bax genes in the genesis or gastric carcinoma as well as their relationship. Methods Thirty-five cases of early-stage gastric carcinoma and Twenty-four cases ot chronic atrophic gastritis were studied by immunohistochemical method. Results There were no statistical differences of bcl-2 expression levels between gastric carcinoma and atypical hyperplasia or paracancerous intestinal- epithelial metaplasia(IEM) (P>0.05).There were statistical differences of bcl-2 expression between normal epithe- lial tissues (or non-cancerous IEM) and the other three groups(P<0.05), but no statistical difference between the normal epithelial and the non-cancerous IEM group was observed(P>0.05). The expressions or bax protein were found in the normal epithelial and the other groups in varying degrees,but there were no statistical differences be- tween either two of the groups (P>0.05). The bcl-2/bax ratio was higher in early-stage gastric carcinoma,atypical hy- perplasia and paracancerous intestinal-metaplasia than in the non-cancerous intestinal-metaplasia (P<0.05) and nor- mal epithelial tissues(P<0.01). Conclusion The abnormal expression of bcl-2 protein and bax protein,especially the increased bcl-2/bax ratio, probably play an important role in the course of carcinogenesis or gastric carcinoma.

Treatment of Precancerous Lesions of the Cervix of the Uterus by Leep: Experience of the Principal Clinic of the Togolese Association of Family Well-Being Planning Center (ATBEF)

Objectives: Describe the socio-demographic characteristics, describe the main indications for LEEP and present the main complications. Methodology: This was a cross-sectional and descriptive study with consecutive recruitment of the study population through cervical cancer screening campaigns throughout the country during the period July 1, 2017 to April 30, 2019. Included were all patients eligible for LEEP and having benefited from this therapeutic method during our study period. Data were collected from a registry and recorded on a questionnaire developed for this study. These data were analyzed using Epi info 3.5.1 software. The following parameters were studied: patient age, indication for LEEP, intraoperative and postoperative complications, histological examination of the specimens, and postoperative surveillance and screening follow-up one year after LEEP. Results: During the study period, 12,595 women were screened for precancerous cervical lesions. A total of 474 women had precancerous lesions. Of these women, 227 had undergone loop resection, a rate of 47.9%. The main indications for LEEP were extensive lesions (68.7%), lesions penetrating the internal cervical os (12.8%). Incidents occurred in 7.5% of patients during the procedure. Post-operative complications occurred in 14.7% of cases. Conclusion: LEEP is a better way to treat precancerous lesions but is not well known by medical staff. The equipment of health facilities and the training of medical staff will make it possible to popularize the practice throughout the country. This extension will contribute to the fight against cervical cancer.

Differential methylation landscape of pancreatic ductal adenocarcinoma and its precancerous lesions

Background:Pancreatic cancer is one of the most lethal diseases with an incidence almost equal to the mortality.In addition to having genetic causes,cancer can also be considered an epigenetic disease.DNA methylation is the premier epigenetic modification and patterns of aberrant DNA methylation are recognized to be a common hallmark of human tumor.In the multistage carcinogenesis of pancreas starting from precancerous lesions to pancreatic ductal adenocarcinoma(PDAC),the epigenetic changes play a significant role.Data sources:Relevant studies for this review were derived via an extensive literature search in Pub Med via using various keywords such as pancreatic ductal adenocarcinoma,precancerous lesions,methylation profile,epigenetic biomarkers that are relevant directly or closely associated with the concerned area of our interest.The literature search was intensively done considering a time frame of 20 years(1998–2018).Result:In this review we have highlighted the hypermethylation and hypomethylation of the precancerous PDAC lesions(pancreatic intra-epithelial neoplasia,intraductal papillary mucinous neoplasm,mucinous cystic neoplasm and chronic pancreatitis)and PDAC along with the potential biomarkers.We have also achieved the early epigenetic driver that leads to progression from precancerous lesions to PDAC.A bunch of epigenetic driver genes leads to progression of precancerous lesions to PDAC(pp ENK,APC,p14/5/16/17,h MLH1 and MGMT)are also documented.We summarized the importance of these observations in therapeutics and diagnosis of PDAC hence identifying the potential use of epigenetic biomarkers in epigenetic targeted therapy.Epigenetic inactivation occurs by hypermethylation of Cp G islands in the promoter regions of tumor suppressor genes.We listed all hyper-and hypomethylation of Cp G islands of several genes in PDAC including its precancerous lesions.Conclusions:The concept of the review would help to understand their biological effects,and to determine whether they may be successfully combined with other epigenetic drugs.However,we need to continue our research to develop more specific DNA-demethylating agents,which are the targets for hypermethylated Cp G methylation sites.

Promotive action of 2-acetylaminofluorene on hepatic precancerous lesions initiated by diethylnitrosamine in rats:Molecular study

BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.

Review on the progress of treating gastric precancerous lesions with traditional Chinese medicine based on regulatory genes

In recent years,the incidence of Precancerous lesions of gastric cancer(PLGC)has gradually increased,and it is difficult to be cured and easy to recur.Traditional Chinese Medicine(TCM)emphasizes the prevention before the disease.The regulation of PLGC related tumor genes by Chinese medicine has become a research hotspot.This paper summarized PLGC related proto-oncogenes,tumor suppressor genes and apoptosis related genes,and discussed the mechanism of Chinese Medicine Therapy PLGC from the perspective of gene expression,providing new ideas and methods for clinical treatment of PLGC.

Clinical Effect and Tolerance Analysis of Photodynamic/Electroion in the Treatment of Skin Cancer and Precancerous Lesions

The study was dedicated to explore the clinical efficacy and tolerability of photodynamic/electroion therapy of skin cancer and precancerous lesions.Firstly,a total of 60 patients with skin cancer and precancerous lesions,who were admitted to the Dermatology Department of the Fifth Affiliated Hospital of Zhengzhou University from November 2013 to November 2016,were selected and divided into observation group and control group according to the random number table,with 30 patients in each group.Observation group adopted the photodynamic/electroion therapy,and control group adopted photodynamic therapy(PDT).Two groups of patients were last follow-up to December 2018,and loss of follow-up and death were taken as the end point events of follow-up.The frequency of treatment,clinical efficacy and severity of adverse reactions of the two groups were calculated,and Kaplan-Meier curves were plotted to compare the progression free survival(PFS)of the two groups.The results showed that the number of treatment times per capita in the observation group was 3.6±1.1 times,which was lower than that of in the control group(4.1±1.1 times),but the difference was not statistically significant(t=1.760,P=0.083).The total effective rate in the observation group(100.00%)was higher than that of in the control group(80.00%),and the difference was significant(P<0.05).In addition,during the treatment,both groups had adverse reactions such as burning,pain,redness,swelling and exudation of different degrees,but there was no significant difference in the severity score of adverse reactions(P>0.05).There was no statistically significant difference in the follow-up time and PFS between the two groups(P>0.05),but the recurrence rate of the observation group was significantly lower than that of the control group(P<0.05).Therefore,the clinical efficacy of photodynamic/electroion treatment in patients with skin cancer and precancerous lesions was superior to that of PDT alone,which increased the risk of tolerance.So,it is worthy of clinical promotion.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.

Correlation of HPV infection with TLRs pathway activation and downstream gene expression in cervical precancerous lesions

Objective: To study the correlation of HPV infection with TLRs pathway activation and downstream gene expression in cervical precancerous lesions. Methods: Cervical precancerous lesion tissues from surgical resection or cone biopsy in Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University between June 2014 and May 2017 were collected and divided into HR-HPV positive group and HR-HPV negative group according to the condition of high-risk HPV infection;normal cervical tissues surgically removed due to fibroid in Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University during the same period were collected as the control group. The contents of TLRs pathway molecules as well as the expression of apoptosis-related genes and invasion-related genes in the cervical precancerous lesion tissues and normal cervical tissues were determined. Results:TLR2, TLR3, TLR4, TLR9 and NF-κB contents as well as CyclinD1, PCNA, iNOS, Gal-9, N-cadherin, HIF-1α and VEGF mRNA expression in HR-HPV positive group and HR-HPV negative group were significantly higher than those in control group whereas p53, Beclin1, LC3-II and SFRP2 mRNA expression were significantly lower than those in control group, and TLR2, TLR3, TLR4, TLR9 and NF-κB contents as well as CyclinD1, PCNA, iNOS, Gal-9, N-cadherin, HIF-1α and VEGF mRNA expression in HR-HPV positive group were significantly higher than those in HR-HPV negative group whereas p53, Beclin1, LC3-II and SFRP2 mRNA expression were significantly lower than those in HR-HPV negative group. Conclusion: HPV infection in cervical precancerous lesions can regulate downstream apoptosis and invasion gene expression by activating multiple TLRs pathways.

Screening for Precancerous Cervical Lesions in Women of Reproductive Age in the Kara Region of Togo in 2022

Introduction: Worldwide, cervical cancer is the 4th most common cancer in women and is a public health problem. The objective of this study was to estimate the prevalence of precancerous cervical lesions and to describe its associated factors among women of reproductive age in the Kara region of Togo. Methods: A cross-sectional study was conducted from March 6 to 14, 2022 in 11 health centers in Kara. Data were collected using a standardized questionnaire and screening for precancerous cervical lesions was performed by visual inspection of the cervix, after application of 5% acetic acid and Lugol’s. Logistic regression analysis was performed to describe factors associated with precancerous lesions. Results: A total of 728 women with a median age of 36, interquartile range [31 - 41] were enrolled. The prevalence of precancerous cervical lesions was 3.9%, 95% confidence interval (95% CI: [2.6 - 5.4]. Factors associated with the presence of precancerous lesions were age at first sexual intercourse ≥ 18 years (adjusted odds ratio (aOR = 3.67;95% CI [1.17 - 18.4]) and being a sex worker (aOR = 8.14;95% CI [1.96 - 27.1]). HIV infection was not associated with the presence of precancerous lesions. Conclusion: The results of this study underscore the importance of intensifying cervical cancer screening efforts in resource-limited countries for better management. These efforts should prioritize vulnerable populations such as female sex workers.