Drug-tolerant persister cells in cancer: the cutting edges and future directions.

Drug-tolerant persister (DTP) cell populations were originally discovered in antibiotic-resistant bacterial biofilms. Similar populations with comparable features have since been identified among cancer cells and have been linked with treatment resistance that lacks an underlying genomic alteration. Research over the past decade has improved our understanding of the biological roles of DTP cells in cancer, although clinical knowledge of the role of these cells in treatment resistance remains limited. Nonetheless, targeting this population is anticipated to provide new treatment opportunities. In this Perspective, we aim to provide a clear definition of the DTP phenotype, discuss the underlying characteristics of these cells, their biomarkers and vulnerabilities, and encourage further research on DTP cells that might improve our understanding and enable the development of more effective anticancer therapies.

Spatial patterns of the cap-binding complex eIF4F in human melanoma cells.

As a central node of protein synthesis, the cap-binding complex, eukaryotic translation initiation factor 4 F (eIF4F), is involved in cell homeostasis, development and tumorigenesis. A large body of literature exists on the regulation and function of eIF4F in cancer cells, however the intracellular localization patterns of this complex are largely unknown. Since different subsets of mRNAs are translated in distinct subcellular compartments, understanding the distribution of translation initiation factors in the cell is of major interest. Here, we developed an in situ detection method for eIF4F at the single cell level. By using an image-based spot feature analysis pipeline as well as supervised machine learning, we identify five distinct spatial patterns of the eIF4F translation initiation complex in human melanoma cells. The quantity of eIF4F complex per cell correlated with the global mRNA translation activity, and its variation is dynamically regulated by cell state or extracellular stimuli. In contrast, the spatial patterns of eIF4F complexes at the single cell level could distinguish melanoma cells harboring different oncogenic driver mutations. This suggests that different tumorigenic contexts differentially regulate the subcellular localization of mRNA translation, with specific localization of eIF4F potentially associated with melanoma cell chemoresistance.

Risk factors for acute exacerbation of interstitial lung disease following lung cancer resection: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to investigate the risk factors for acute exacerbation (AE) of interstitial lung disease (ILD) following lung cancer resection. METHODS: We performed a literature screening on the databases including PubMed, Embase, Ovid MEDLINE® and the Web of Science for related studies published up to January 2021. Eligible studies were included and data on risk factors related to postoperative AE were extracted. All analyses were performed with random-effect model. RESULTS: A total of 12 studies of 2655 lung cancer patients with ILD were included in this article. The meta-analysis indicated that male [odds ratios (ORs) = 1.78, 95% confidence interval (CI): 1.02-3.11, P = 0.041], usually interstitial pneumonia pattern on CT (OR = 1.52, 95% CI: 1.06-2.17, P = 0.021), Krebs von den Lungen-6 [standardized mean difference (SMD) = 0.50, 95% CI: 0.06-0.94, P = 0.027], white blood cell (SMD = 0.53, 95% CI: 0.12-0.93, P = 0.010), lactate dehydrogenase (SMD = 0.47, 95% CI: 0.04-0.90, P = 0.032), partial pressure of oxygen (weighted mean difference = -3.09, 95% CI: -5.99 to -0.19, P = 0.037), surgery procedure (OR = 2.31, 95% CI: 1.42-3.77, P < 0.001) and operation time (weighted mean difference = 28.26, 95% CI: 1.13-55.39, P = 0.041) were risk factors for AE of ILD following lung cancer resection. CONCLUSIONS: We found that males, usually interstitial pneumonia pattern on CT, higher levels of Krebs von den Lungen-6, lactate dehydrogenase, white blood cell, lower partial pressure of oxygen, greater scope of operation and longer operation time were risk factors for AE of ILD following lung cancer resection. Patients with these risk factors should be more prudently selected for surgical treatment and be monitored more carefully after surgery.

Beta-Blocker Landiolol Hydrochloride in Preventing Atrial Fibrillation Following Cardiothoracic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The purpose of this article was to assess the benefit of perioperative administration of the intravenous beta-blocker landiolol hydrochloride in preventing atrial fibrillation (AF) after cardiothoracic surgery. METHODS: We performed a systematic search in PubMed, Web of Science, CNKI, and OVID to identify randomized controlled trials (RCTs) and cohorts up to January 2021. Data regarding postoperative atrial fibrillation (POAF) and safety outcomes were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using the Mantel-Haenszel method. Meanwhile, subgroup analyses were conducted according to surgery type including lung cancer surgery, esophageal cancer surgery, and cardiac surgery. RESULTS: Seventeen eligible articles involving 1349 patients within 13 RCTs and four cohorts were included in our meta-analysis. Compared with control group, landiolol administration was associated with a significant reduction of the occurrence of AF after cardiothoracic surgery (OR = 0.32, 95% CI 0.23-0.43, P <0.00001). In addition, the results demonstrated that perioperative administration of landiolol hydrochloride minimized the occurrence of postoperative complications (OR = 0.48, 95% CI 0.33-0.70, P = 0.0002). Funnel plots indicated no obvious publication bias. CONCLUSIONS: Considering this analysis, landiolol was effective in the prevention of AF after cardiothoracic surgery and did not increase the risk of major postoperative complications.

Upregulated N-cadherin expression is associated with poor prognosis in epithelial-derived solid tumours: A meta-analysis.

BACKGROUND: N-cadherin is an important molecular in epithelial-mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N-cadherin in solid malignancies remains controversially. MATERIALS AND METHODS: The Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role. RESULTS: Involving 36 studies with 5705 patients were performed to investigate relationships between N-cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N-cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N-cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N-cadherin was correlated with poor prognosis of 3-year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5-year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test). CONCLUSIONS: Taken together, upregulation of N-cadherin is associated with more aggressive behaviours of epithelial-derived solid malignancies and can be regarded as a predictor of poor survival.

Prognostic role of Gli1 expression in breast cancer: a meta-analysis.

Glioma-associated oncogene 1 (Gli1) is a critical transcriptional factor of Sonic hedgehog pathway which has been proved to participate in the initiation and progression of tumor in mammalians. However, its clinical value in breast cancer remains unknown. Thus, a meta-analysis was performed to clarify the association of Gli1 over-expression, clinic-pathological characteristics, molecular subtypes and prognosis in breast cancer. According to included criteria, 13 eligible studies containing 2816 patients all around the world were selected in this study. Our results indicated no significant association of Gli1 expression and histological grade (RR = 1.20, 95% CI: [0.98, 1.47]), T stage (RR = 1.05, 95% CI: [0.87, 1.27]), clinical stage (RR = 1.04, 95% CI: [0.93, 1.18]) and lymph node metastasis (RR = 1.12, 95% CI: [0.92, 1.37]). In addition, pooled RR showed no correlation of Gli1 expression and progesterone receptor (PR) (RR = 0.92, 95% CI: [0.70, 1.21]), estrogen receptor (ER) (RR = 1.03, 95% CI: [0.74, 1.42]), human epidermal growth factor receptor 2 (HER-2) (RR = 1.12, 95% CI: [0.90, 1.39]). Nonetheless, up-regulated Gli1 expression predicts shorter disease-free survival (DFS) (HR = 1.38, 95% CI: [1.05, 1.81]), 3-year survival (HR = 1.74, 95% CI: [1.28, 2.36]), 5-year survival (HR = 2.04, 95% CI: [1.62, 2.57]) and overall survival (OS) (HR = 2.05, 95% CI: [1.60, 2.64]). In conclusion, over-expression of Gli1 tends to progressive stages and is related to unfavorable prognosis of breast cancer, which may become a potential prognosis indicator and therapy target in breast cancer.