Regulatory role of exosomes in colorectal cancer progression and potential as biomarkers

Colorectal cancer(CRC)remains an enormous challenge to human health worldwide.Unfortunately,the mechanism underlying CRC progression is not well understood.Mounting evidence has confirmed that exosomes play a vital role in CRC progression,which has attracted extensive attention among researchers.In addition to acting as messengers between CRC cells,exosomes also participate in the CRC immunomodulatory process and reshape immune function.As stable message carriers and liquid biopsy option under development,exosomes are promising biomarkers in the diagnosis or treatment of CRC.In this review we have described and analyzed the biogenesis and release of exosomes and current research on the role of exosomes in immune regulation and metastasis of CRC.Moreover,we have discussed candidate exosomal molecules as potential biomarkers to diagnose CRC,predict CRC progression,or determine CRC chemoresistance,and described the significance of exosomes in the immunotherapy of CRC.This review provides insight to further understand the role of exosomes in CRC progression and identify valuable biomarkers that facilitate the clinical management of CRC patients.

Lamb’s tripe extract and vitamin B12 capsule plus celecoxib reverses intestinal metaplasia and atrophy:A retrospective cohort study

BACKGROUND Chronic atrophic gastritis(AG)with intestinal metaplasia(IM)significantly increases the risk of gastric cancer.Some medicines have showed definite therapeutic effects in AG and IM regression.AIM To validate the efficacy of Lamb’s tripe extract and vitamin B12 capsule(LTEVB12)initial therapy and celecoxib rescue therapy for IM and AG.METHODS A total of 255 patients were included to receive LTEVB12 initial therapy(2 capsules each time,three times daily for 6 mo)in hospital in this study.The patients with failure of IM regression continued to receive celecoxib rescue therapy(200 mg,once daily for 6 mo).After each therapy finished,the patients underwent endoscopy and biopsy examination.The regression efficiency was assessed by the operative link on gastritis assessment(OLGA)and the operative link on the gastric intestinal metaplasia assessment(OLGIM)staging system.Logistic regression analysis was applied to identify factors associated with the curative effect.RESULTS For LTEVB12 initial therapy,the reversal rates of IM and AG were 52.95%and 48.24%,respectively.Analogously,for celecoxib rescue therapy,the effective rates for IM and AG were 56.25%and 51.56%,respectively.The IM regression rate of complete therapy was up to 85.03%.In different OLGA and OLGIM stages of IM patients,therapeutic efficiency showed a significant difference in each group(P<0.05).For both therapies,patients with high stages(III or IV)of both the OLGA and OLGIM evaluation systems showed a higher IM or AG regression rate than those with low stages(I or II).Among patients with high stages(OLGIM III and IV),the IM regression rate was above 70%for each therapy.Eating habits,fresh vegetable intake,and high-salt diet were identified as independent factors for the IM reversal effect of LTEVB12 therapy,especially high-salt diet(odds ratio=1.852,P<0.05).CONCLUSION Monotherapy could reverse IM and AG.LTEVB12 initial therapy and celecoxib rescue therapy significantly increase the regression effect.IM may not be the point of no return among gastric precancerous lesions.

Efficacy and safety of high-dose esomeprazole–amoxicillin dual therapy for Helicobacter pylori rescue treatment:a multicenter,prospective,randomized,controlled trial

Background:High-dose dual therapy(HDDT)with proton pump inhibitors(PPIs)and amoxicillin has attracted widespread attention due to its favorable efficacy in eradicating Helicobacter pylori(H.pylori).This study aimed to compare the efficacy and safety of high-dose PPI-amoxicillin dual therapy and bismuth-containing quadruple therapy for H.pylori rescue treatment.Methods:This was a prospective,randomized,multicenter,non-inferiority trial.Patients recruited from eight centers who had failed previous treatment were randomly(1:1)allocated to two eradication groups:HDDT(esomeprazole 40 mg and amoxicillin 1000 mg three times daily;theHDDTgroup)and bismuth-containing quadruple therapy(esomeprazole 40 mg,bismuth potassium citrate 220 mg,and furazolidone 100 mg twice daily,combined with tetracycline 500 mg three times daily;the tetracycline,furazolidone,esomeprazole,and bismuth[TFEB]group)for 14 days.The primary endpoint was the H.pylori eradication rate.The secondary endpoints were adverse effects,symptom improvement rates,and patient compliance.Results:A total of 658 patients who met the criteria were enrolled in this study.The HDDT group achieved eradication rates of 75.4%(248/329),81.0%(248/306),and 81.3%(248/305)asdetermined by the intention-to-treat(ITT),modified intention-totreat(MITT),and per-protocol(PP)analyses,respectively.The eradication rates were similar to those in the TFEB group:78.1%(257/329),84.2%(257/305),and 85.1%(257/302).The lower 95%confidence interval boundary(9.19%in the ITT analysis,9.21%in the MITT analysis,and9.73%in the PP analysis)was greater than the predefined non-inferiority margin of10%,establishing a non-inferiority of the HDDT group vs.the TFEB group.The incidence of adverse events in the HDDT group was significantly lower than that in the TFEB group(11.1%vs.26.8%,P<0.001).Symptom improvement rates and patients’compliance were similar between the two groups.Conclusions:Fourteen-day HDDT is non-inferior to bismuth-containing quadruple therapy,with fewer adverse effects and good treatment compliance,suggesting HDDT as an alternative for H.pylori rescue treatment in the local region.Trial registration:Clinicaltrials.gov,NCT04678492.

MG7-Ag, hTERT, and TFF2 identified high-risk intestinal metaplasia and constituted a prediction model for gastric cancer

To the Editor:Gastric cancer(GC)ranks third in incidence and mortality both worldwide and in China.[1,2]Intestinal metaplasia(IM)significantly increases risk of GC so that identifying high-risk IM patients who will progress to GC is crucial.Currently,the effect of many risk-stratification methods for gastric precancerous lesions(GPLs)was minimal.Monoclonal gastric cancer 7 antigen(MG7-Ag)combined with cyclooxygenase-2 has been shown earlywarning value for the progression of GPLs.[3]The expression of human telomerase reverse transcriptase(hTERT)was proven to be related to state of cell proliferation in IM tissue.[4]Loss expression of trefoil factor family 2(TFF2)from spasmolytic polypeptideexpressing metaplasia to IM may lead to a hyperproliferation and deleterious mutations.[5]We tried to construct and verify a multimolecular prediction model included MG7-Ag and hTERT and TFF2,which could identify high-risk IM patients and have early-warning value for GC.