Expression and significance of CDX2, FXR, and TGR5 in esophageal cancer.

This study explored the expression and significance of three critical morphogenesis genes in normal esophagus, reflux esophagitis (RE), Barrett's esophagus (BE), esophageal adenocarcinoma (EA), and esophageal squamous cell carcinoma (ESCC). Esophageal tissue samples and tissue microarrays were used. CDX2, FXR, and TGR5 protein expression were measured by immunohistochemistry in normal esophageal, RE, BE, EA, and ESCC tissues. All 3 proteins had markedly changed expression during the progression of EA. The expressions of CDX2 and FXR were positively correlated in EA. In addition, TGR5 expression was positively correlated with CDX2 in RE and BE. The expressions of CDX2 and FXR were also positively correlated in ESCC. Although CDX2, FXR, and TGR5 were upregulated in ESCC, these factors might not be markers for the prognosis of ESCC. These results suggested that CDX2, FXR, and TGR5 might play different roles in EA and ESCC. They may represent novel therapeutic targets for patients with these cancers.

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; the HDDT group) 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-to-treat (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, and -9.73% in the PP analysis) was greater than the predefined non-inferiority margin of -10%, 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.

Long Non-Coding RNAs: Potential Biomarkers and Targets for Hepatocellular Carcinoma Therapy and Diagnosis.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Increasing studies showed that long non-coding RNAs (lncRNAs), a novel class of RNAs that are greater than 200 nucleotides in length but lack the ability to encode proteins, exert crucial roles in the occurrence and progression of HCC. LncRNAs promote the proliferation, migration, invasion, autophagy, and apoptosis of tumor cells by regulating downstream target gene expression and cancer-related signaling pathways. Meanwhile, lncRNA can be used as biomarkers to predict the efficacy of HCC treatment strategies, such as surgery, radiotherapy, chemotherapy, and immunotherapy, and as a potential individualized tool for HCC diagnosis and treatment. In this review, we overview up-to-date findings on lncRNAs as potential biomarkers for HCC surgery, radiotherapy, chemotherapy resistance, target therapy, and immunotherapy, and discuss the potential clinical application of lncRNA as tools for HCC diagnosis and treatment.

Alterations in Intestinal Microbiota Composition in Mice Treated With Vitamin D3 or Cathelicidin.

Gut microbiota is a complex aggregation of microbial organisms, which offers diverse protective benefits to the host. Dysbiosis of intestinal microbiota is frequently associated with many diseases. Vitamin D3 (VD), which was originally associated with bone health, also possesses antimicrobial activities and can act through antimicrobial peptide. Cathelicidin is a type of antimicrobial peptide in host to maintain the balance of gut microbiome. Our current study sought to evaluate the protective effect of VD and cathelicidin in mice intestines by administration of VD or mCRAMP-encoding L. lactis. We herein provided a comprehensive profile of the impact of VD and mCRAMP on gut microbiota using 16S rRNA sequencing, followed by bioinformatics and statistical analysis. Our results revealed an increased richness of bacterial community in mice intestines due to VD administration. Moreover, we showed a beneficial effect of VD and mCRAMP by enhancing the colonization of bacterial taxa that are associated with protective effects to the host but repressing the propagation of bacterial taxa that are associated with harmful effects to the host. Various metabolic pathways related to amino acid and lipid metabolism were affected in this process. We further established a bacterial panel as a reliable biomarker to evaluate the efficacy of remodeling the mice gut microbiota by VD and mCRAMP administration. The uncovered effects will deepen the comprehension about the antibacterial mechanisms of VD and mCRAMP and provide new insights for therapeutic implication of them.

Overexpression of NAD(P)H: Quinone Oxidoreductase 1 Inhibits Hepatocellular Carcinoma Cell Proliferation and Induced Apoptosis by Activating AMPK/PGC-1α Pathway.

Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis. The apoptosis-associated gene Bax, Bcl-2, and caspase-3 expression was also measured, with western blot results showing that NQO1 overexpression inhibits Bcl-2 expression and promotes Bax and caspase-3 expression, whereas NQO1 silencing plays a contrasting role. In addition, NQO1 activated AMP-activated protein kinase (AMPK) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and the AMPK inhibitor compound C blocked NQO1-induced PGC-1α activation. Furthermore, the AMPK inhibitor compound C or PGC-1α siRNA partially abolished NQO1-induced cell apoptosis and proliferation inhibition in HCC cells. Taken together, our results demonstrate that NQO1 overexpression induces HCC cell apoptosis and proliferation inhibition through the AMPK/PGC-1α pathway.

Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase.

BACKGROUND: Ginsenoside Rh2 (GRh2) is the main bioactive component in American ginseng, a commonly used herb, and its antitumor activity had been studied in previous studies. PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), a serine/threonine protein kinase, is highly expressed in HCT116 colorectal cancer cells. METHODS: We examined the effect of GRh2 on HCT116 cells ex vivo. Next, we performed in vitro binding assay and in vitro kinase assay to search for the target of GRh2. Furthermore, we elucidated the underlying molecular mechanisms for the antitumor effect of GRh2 ex vivo and in vivo. RESULTS: The results of our in vitro studies indicated that GRh2 can directly bind with PBK/TOPK and GRh2 also can directly inhibit PBK/TOPK activity. Ex vivo studies showed that GRh2 significantly induced cell death in HCT116 colorectal cancer cells. Further mechanistic study demonstrated that these compounds inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 (ERK1/2) and (H3) in HCT116 colorectal cancer cells. In vivo studies showed GRh2 inhibited the growth of xenograft tumors of HCT116 cells and inhibited the phosphorylation levels of the extracellular regulated protein kinases 1/2 and histone H3. CONCLUSION: The results indicate that GRh2 exerts promising antitumor effect that is specific to human HCT116 colorectal cancer cells through inhibiting the activity of PBK/TOPK.

Detection of serum gastric cancer-associated MG7-Ag from gastric cancer patients using a sensitive and convenient ELISA method.

PURPOSE: To seek a high sensitive and convenient method for early diagnosis of gastric cancer by testing MG7-Ag in serum of gastric cancer patients and some other control groups using a convenient ELISA method. EXPERIMENT DESIGN: The expression of serum MG7-Ag was detected in 116 preoperative gastric cancer patients, 63 postoperative gastric cancer patients, 78 precancerous lesion patients, 50 healthy blood donors and patients of other cancers by a convenient ELISA method. For comparison, serum CEA, CA 50, CA 19-9 and TAG-72 were also detected in preoperative gastric cancer patients. Meanwhile, the expression of MG7-Ag was detected by immunohistochemical analysis in the groups of patients with gastric cancer or precancerous lesion mentioned above. RESULTS: The positive rate of Mg7-Ag determined by ELISA was 83. 6% of preoperative gastric cancer patients, 54.8% of lung cancer patients, 45.5% of rectal cancer patients, 17.6% of colonic cancer patients, 14.2% of breast cancer patients, 47.6% of postoperative gastric cancer patients, 12.8% of precancerous lesions patients and 0% of healthy blood donors, respectively. The sensitivity of ELISA (83.6%) was found to be similar with that of immunohistochemistry (94%, p > 0. 01), while the false positive rate was lower (12.8% vs. 51.3%). MG7-Ag expression level in gastric cancer was correlated with tumor differentiation (p < 0. 01) and pathological stage (p < 0. 01). CONCLUSION: This ELISA method may be a non-invasive candidate method for screening of large population with high risk of gastric cancer.

[Expression and significance of glypican-3 in colorectal cancer].

OBJECTIVE: To investigate the expression and significance of Glypican-3 in colorectal cancer. METHODS: Immunohistochemistry was used to detect the expression of Glypican-3 in 200 specimens of colorectal cancer and adjacent non-cancerous tissues resected during operation. RESULTS: Glypican-3 immunoreactivity was recognized in both the cytoplasm and cellular membrane. The Glypican-3 positive expression rate in the tumor samples was 66.0% (132/200), significantly higher than that in the adjacent nontumor tissues (24%, 48/200, P = 0.019). The Glypican-3 expression rate was significantly correlated with the carcinoma invasion (P = 0.023) and lymph node metastasis (P = 0.015), but not associated with gender, age, tumor size, and differentiation grade (all P > 0.05). CONCLUSION: Over-expression of Glypican-3 may play an important role in the genesis and development of colorectal cancer, and may be used as a new biological parameter in predicting invasion and metastasis of colorectal carcinoma.