Magnifying image-enhanced endoscopy-only mode boosted early cancer diagnostic efficiency: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown. METHODS: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively. RESULTS: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively). CONCLUSIONS: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.).

Anemoside B4 sensitizes human colorectal cancer to fluorouracil-based chemotherapy through src-mediated cell apoptosis.

Currently, 5-Fluorouracil (5-FU) based chemotherapy is the primary option for colorectal cancer after surgery, whereas chemotherapy resistance related mortality is observed in a large proportion of patients. Anemoside B4 (AB4) is a triterpene saponin, which exhibits a considerable activity in oncotherapy. In this study, we explored the efficacy of AB4 in FU-based chemotherapy in colorectal cancer cells and the underlying molecular mechanisms. Our results indicated a significant synergistic activity of AB4 in 5-FU treated colorectal cancer cells. Furthermore, AB4 treatment eliminated colorectal cancer stem cells by promoting apoptotic cell death in 5-FU resistant colorectal cancer cells. Mechanically, AB4 activated caspase-9 pathway in 5-FU resistant colorectal cancer cells. Elevated Src activity induced cell apoptosis and cancer stem cells elimination effects in AB4 treated colorectal cancer cells. In conclusion, AB4 showed promising sensitization effect in the FU-based chemotherapy of colorectal cancer. Our study may pave a way to ameliorate FU-based chemotherapeutic efficiency in colorectal cancer.

Diverse regulatory manners of human telomerase reverse transcriptase.

Human telomerase reverse transcriptase (hTERT) is the core subunit of human telomerase and plays important roles in human cancers. Aberrant expression of hTERT is closely associated with tumorigenesis, cancer cell stemness maintaining, cell proliferation, apoptosis inhibition, senescence evasion and metastasis. The molecular basis of hTERT regulation is highly complicated and consists of various layers. A deep and full-scale comprehension of the regulatory mechanisms of hTERT is pivotal in understanding the pathogenesis and searching for therapeutic approaches. In this review, we summarize the recent advances regarding the diverse regulatory mechanisms of hTERT, including the transcriptional (promoter mutation, promoter region methylation and histone acetylation), post-transcriptional (mRNA alternative splicing and non-coding RNAs) and post-translational levels (phosphorylation and ubiquitination), which may provide novel perspectives for further translational diagnosis or therapeutic strategies targeting hTERT.

Regulation of the master regulator FOXM1 in cancer.

FOXM1 (forkhead box protein M1) is a critical proliferation-associated transcription factor that is widely spatiotemporally expressed during the cell cycle. It is closely involved with the processes of cell proliferation, self-renewal, and tumorigenesis. In most human cancers, FOXM1 is overexpressed, and this indicates a poor prognosis for cancer patients. FOXM1 maintains cancer hallmarks by regulating the expression of target genes at the transcriptional level. Due to its potential role as molecular target in cancer therapy, FOXM1 was named the Molecule of the Year in 2010. However, the mechanism of FOXM1 dysregulation remains indistinct. A comprehensive understanding of FOXM1 regulation will provide novel insight for cancer and other diseases in which FOXM1 plays a major role. Here, we summarize the transcriptional regulation, post-transcriptional regulation and post-translational modifications of FOXM1, which will provide extremely important implications for novel strategies targeting FOXM1.