The crosstalk between cellular survival pressures and N6-methyladenosine modification in hepatocellular carcinoma.

BACKGROUND: Within the tumor microenvironment, survival pressures are prevalent with potent drivers of tumor progression, angiogenesis, and therapeutic resistance. N6-methyladenosine (m6A) methylation has been recognized as a critical post-transcriptional mechanism regulating various aspects of mRNA metabolism. Understanding the intricate interplay between survival pressures and m6A modification provides new insights into the molecular mechanisms underlying hepatocellular carcinoma (HCC) progression and highlights the potential for targeting the survival pressures-m6A axis in HCC diagnosis and treatment. DATA SOURCES: A literature search was conducted in PubMed, MEDLINE, and Web of Science for relevant articles published up to April 2024. The keywords used for the search included hepatocellular carcinoma, cellular survival, survival pressure, N6-methyladenosine, tumor microenvironment, stress response, and hypoxia. RESULTS: This review delves into the multifaceted roles of survival pressures and m6A RNA methylation in HCC, highlighting how survival pressures modulate the m6A landscape, the impact of m6A modification on survival pressure-responsive gene expression, and the consequent effects on HCC cell survival, proliferation, metastasis, and resistance to treatment. Furthermore, we explored the therapeutic potential of targeting this crosstalk, proposing strategies that leverage the understanding of survival pressures and m6A RNA methylation mechanisms to develop novel, and more effective treatments for HCC. CONCLUSIONS: The interplay between survival pressures and m6A RNA methylation emerges as a complex regulatory network that influences HCC pathogenesis and progression.

Wingspan stenting with modified predilation for symptomatic middle cerebral artery stenosis.

OBJECTIVES: Our purpose was to assess the feasibility, safety, and effectiveness of a modified predilation for middle cerebral artery (MCA) stenosis. BACKGROUND: Wingspan stenting of MCA remains a technical challenge, and rates of residual stenosis and restenosis must be lowered. METHODS: A series of 48 patients with symptomatic MCA stenosis greater than 50% and refractory to medical therapy underwent Wingspan stenting with different balloon/artery ratios before (group 1, Boston guidelines predilation) or after (group 2, modified predilation) July of 2008. Technical success, periprocedural complications, recurrent symptoms, and restenosis were assessed retrospectively, and risk factors for restenosis were analyzed using logistic regression. RESULTS: Successful stenting occurred in 48 of 49 (98%) lesions. Primary endpoints within 30 days included one (2.12%) minor stroke and two (4.26%) transient ischemic attacks. Stenoses were reduced from 77.11% ± 10.09% to 27.50% ± 6.91% in group 1 versus from 72.56% ± 10.46% to 8.20% ± 5.41% in group 2. A total of 43 patients were followed up for 12.92 ± 5.08 months, and recurrent stroke or transient ischemic attack occurred in two (4.65%) patients. Vessels were followed with transcranial Doppler (43 vessels), angiography (23 vessels), or computed tomographic angiography (one vessel). The restenosis rate was 8 of 18 (44%) in group 1 and 3 of 25 (12%) in group 2. Restenosis was associated with residual stenosis and diabetes. CONCLUSIONS: Wingspan stenting for symptomatic MCA stenosis can be performed with high success and low complication rates, and modified predilation with the Gateway balloon can reduce the rates of residual stenosis and restenosis.

Preliminary evaluation and discussion of the safety of left innominate vein resection.

BACKGROUND: To evaluate the safety of resection of anterior mediastinal lesions involving the left innominate vein (LIV) and analyze the risk factors affecting LIV resection safety. METHODS: Patients who underwent anterior mediastinal lesion and LIV resection from January 2010 to December 2018 in the Department of Thoracic Surgery of Tangdu Hospital, Air Force Medical University, were followed up, and preoperative, intraoperative and postoperative factors were analyzed. RESULTS: Forty-eight patients who underwent anterior mediastinal lesion and LIV resection from January 2010 to December 2018, except for 2 who died of lung infection-induced respiratory failure, were followed up, with an average follow-up time of 32 months (range, 6-72 months). Postoperative: in 31 cases (67.39%), patients did not manifest LIV resection-associated complications; in 15 cases (32.61%), patients manifested mild LIV resection-associated complications; no patient manifested severe LIV resection-associated complications. The average operation time, average blood loss and average hospitalization time were 155.17 min, 324.13 mL and 11.83 days, respectively. Univariate analysis showed that the degree of LIV invasion and surgical approach were risk factors for predicting LIV resection safety. CONCLUSIONS: For anterior mediastinal lesions involving the LIV, LIV resection is a simple, safe and effective surgical procedure.

Knockdown of MALAT1 expression inhibits HUVEC proliferation by upregulation of miR-320a and downregulation of FOXM1 expression.

Regulation of cancer angiogenesis could be a useful strategy in cancer therapy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA), and can induce cancer cell proliferation, while lncRNAs, generally are able to act as microRNA (miRNA) sponges. The latter is a type of competitive endogenous RNA (ceRNA) that regulates expression of the targeting miRNAs and protein-coding genes. This study investigated the proliferative role of MALAT1 in human umbilical vein endothelial cells (HUVECs) and the underlying molecular events. The data showed that knockdown of MALAT1 expression using MALAT1 siRNA inhibited HUVEC proliferation and also significantly decreased levels of FOXM1 mRNA and protein in vitro, while knockdown of FOXM1 expression reduced HUVEC proliferation. Annotation of HUVEC microarray data revealed that seven miRNAs, including miR-320a, were upregulated after knockdown of MALAT1 expression in HUVECs. MALAT1 was shown to reciprocally interact with miR-320a, i.e., expression of one negatively regulated levels of the other, whereas knockdown of MALAT1 expression promoted miR-320a levels. Furthermore, miR-320a could directly target and inhibit FOXM1 expression in HUVECs. Knockdown of MALAT1 expression enhanced miR-320a expression but reduced FOXM1 expression resulting in downregulation of HUVEC proliferation. However, such an effect was inhibited by miR-320a depletion. In conclusion, this study demonstrates that miR-320a plays an important role in mediating the effects of MALAT1 on HUVEC proliferation by suppression of FOXM1 expression. Thus, targeting of this gene pathway could be a novel strategy in cancer therapy.

Prognostic significance of parameters from pretreatment (18)F-FDG PET in hepatocellular carcinoma: a meta-analysis.

PURPOSE: The prognostic value of (18)F-deoxyglucose positron emission tomography ((18)F-FDG PET) on hepatocellular carcinoma (HCC) remains inconclusive. This study aims to investigate the prognostic role of pretreatment (18)F-FDG PET on HCC patients by meta-analysis. METHODS: PubMed, Embase, Cochrane library, and Wanfang databases were searched until June 2015. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were synthesized by Stata 10.0, and the combined results were used as effective values. RESULTS: Twenty-two studies containing a total of 1721 patients were identified. According to random-effect model, meta-analysis results showed that high Tumor SUV/Liver SUV (Tsuv/Lsuv) ratio was significantly associated with poorer overall survival (OS) (HR = 2.04; 95% CI 1.50-2.79; P = 0.000) and poorer disease-free survival (HR = 7.17; 95% CI 3.58-14.36; P = 0.000); and high Tumor SUV (Tsuv) value was also correlated with poor OS (HR = 1.53; 95% CI 1.26-1.87; P = 0.000). Meanwhile, subgroup analysis results showed that the significant association above was not altered by study sample size, parameter cutoff value, analytic method, and follow-up period, but there was no significant association between Tsuv/Lsuv ratio and OS in patients who underwent resection (HR = 1.71; 95% CI 1.00-2.92; P = 0.052). CONCLUSIONS: Both high Tsuv/Lsuv ratio and high Tsuv value are associated with poor prognosis in HCC patients. Therefore, pretreatment (18)F-FDG PET is a useful tool in predicting the prognosis of HCC patients. More studies with explicit treatment modalities are required to investigate the prognostic value of pretreatment (18)F-FDG PET on HCC patients.

Fast-track surgery could improve postoperative recovery in radical total gastrectomy patients.

AIM: To assess the impact of fast-track surgery (FTS) on hospital stay, cost of hospitalization and complications after radical total gastrectomy. METHODS: A randomized, controlled clinical trial was conducted from November 2011 to August 2012 in the Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, the Fourth Military Medical University. A total of 122 gastric cancer patients who met the selection criteria were randomized into FTS and conventional care groups on the first day of hospitalization. All patients received elective standard D2 total gastrectomy. Clinical outcomes, including duration of flatus and defecation, white blood cell count, postoperative pain, duration of postoperative stay, cost of hospitalization and complications were recorded and evaluated. Two specially trained doctors who were blinded to the treatment were in charge of evaluating postoperative outcomes, discharge and follow-up. RESULTS: A total of 119 patients finished the study, including 60 patients in the conventional care group and 59 patients in the FTS group. Two patients were excluded from the FTS group due to withdrawal of consent. One patient was excluded from the conventional care group because of a non-resectable tumor. Compared with the conventional group, FTS shortened the duration of flatus (79.03 ± 20.26 h vs 60.97 ± 24.40 h, P = 0.000) and duration of defecation (93.03 ± 27.95 h vs 68.00 ± 25.42 h, P = 0.000), accelerated the decrease in white blood cell count [P < 0.05 on postoperative day (POD) 3 and 4], alleviated pain in patients after surgery (P < 0.05 on POD 1, 2 and 3), reduced complications (P < 0.05), shortened the duration of postoperative stay (7.10 ± 2.13 d vs 5.68 ± 1.22 d, P = 0.000), reduced the cost of hospitalization (43783.25 ± 8102.36 RMB vs 39597.62 ± 7529.98 RMB, P = 0.005), and promoted recovery of patients. CONCLUSION: FTS could be safely applied in radical total gastrectomy to accelerate clinical recovery of gastric cancer patients.