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Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period. [ABSTRACT FROM AUTHOR]

The Bohai Bay Basin, located on the eastern Asian margin, is the second largest oil-production basin in China. It contains numerous depressions and sags, among which Nanpu Sag has become particularly important because of significant oil discoveries in recent years. Geologically and tectonically, however, the rifting mechanism and geodynamic evolution of the basin remain uncertain. This paper uses detailed volcanic and stratigraphic records obtained through extensive drilling and sampling in Nanpu Sag to interpret tectono-stratigraphic sequences and discuss basin dynamic evolution and crust-mantle interactions of the Bohai Bay Basin. Nanpu Sag contains voluminous volcanic rocks of dominantly alkaline basalts. Drill core samples, well logs, and seismic profiles reveal three volcanic cycles between the Eocene and Miocene Epochs. These basalts were created during a transition from garnet- to spinel-peridotite. Five tectono-stratigraphic sequences produced by episodic continental rifting have been identified, each composed of a basal coarse clastic sequence, a lower volcanic sequence, a middle deep-water clastic sequence, and an upper infilling sequence. Tectonically, Nanpu Sag experienced four evolutionary phases. The first three corresponded to three rifting events revealed by cyclic volcanism and sedimentary depositional features. The fourth phase was marked by extreme thermal subsidence and prograding fluvial deposition fallowed by tectonic inversion. A diapiric upper-mantle upwelling model is proposed to explain the dynamics that controlled the multiple rifting processes, the cyclic volcanism, and the periodic tectonic evolution of Nanpu Sag and the greater Bohai Bay Basin. doi: 10.1130/B30041.1

Voltage-gated sodium channels (VGSCs), which are aberrantly expressed in several human cancers, affect cancer cell behavior; however, their role in gastric cancer (GC) and the link between these channels and tumorigenic signaling remain unclear. The aims of this study were to determine the clinicopathological significance and role of the VGSC Nav1.7 in GC progression and to investigate the associated mechanisms. Here, we report that the SCN9A gene encoding Nav1.7 was the most abundantly expressed VGSC subtype in GC tissue samples and two GC cell lines (BGC-823 and MKN-28 cells). SCN9A expression levels were also frequently found to be elevated in GC samples compared to nonmalignant tissues by real-time PCR. In the 319 GC specimens evaluated by immunohistochemistry, Nav1.7 expression was correlated with prognosis, and transporter Na+/H+ exchanger-1 (NHE1) and oncoprotein metastasis-associated in colon cancer-1 (MACC1) expression. Nav1.7 suppression resulted in reduced voltage-gated sodium currents, decreased NHE1 expression, increased extracellular pH and decreased intracellular pH, and ultimately, reduced invasion and proliferation rates of GC cells and growth of GC xenografts in nude mice. Nav1.7 inhibition led to reduced MACC1 expression, while MACC1 inhibition resulted in reduced NHE1 expression in vitro and in vivo. Mechanistically, the suppression of Nav1.7 decreased NF-κB p65 nuclear translocation via p38 activation, thus reducing MACC1 expression. Downregulation of MACC1 decreased c-Jun phosphorylation and subsequently reduced NHE1 expression, whereas the addition of hepatocyte growth factor (HGF), a c-Met physiological ligand, reversed the effect. These results indicate that Nav1.7 promotes GC progression through MACC1-mediated upregulation of NHE1. Therefore, Nav1.7 is a potential prognostic marker and/or therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms., Methods: Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152-3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152-3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo., Results: ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152-3p. JAK1 was identified as a direct target of miR-152-3p, and ALA-PDT was found to regulate the expression levels of miR-152-3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152-3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152-3p/JAK1/STAT1 pathway expression., Conclusions: ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152-3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. No conflicting relationship exists for any author., (Copyright © 2024. Published by Elsevier B.V.)

Background: Glioblastoma is the most common type of malignant tumor of the brain. Despite substantial improvements in therapy, the 5-year survival rate of patients with glioblastoma remains low. Antitumor drug development has encountered considerable obstacles, which can be attributed to metastasis and the blood-brain barrier (BBB). Hesperetin (HSP), derived from citrus fruits, exhibits several biological properties, including anticancer and anti-inflammatory activities. In addition, in vitro models have shown that HSP can easily cross the BBB. The purpose of the present study was to explore the effects and underlying mechanisms of HSP on glioblastoma cells., Methods: GL261 cell were cultured and treated with different dose HSP. The cell viability was assessed with Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis was determined using an Annexin V/propidine iodide (PI) staining and Hoechst staining and detection assay, cell migration and invasion were observed on GL261 cells using Matrigel-coated Transwells and Wound-Healing assay. The expression of proteins was detected by Western blotting., Results: HSP suppressed cell proliferation and could induce apoptosis, the latter of which might be regulated through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor-kappa B (NF-κB) pathways. Furthermore, HSP inhibited cell migration and invasion by downregulating the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited epithelial-mesenchymal transition (EMT) by upregulating the expression of E-cadherin while downregulating N-cadherin and vimentin expression., Conclusions: These findings suggest HSP to be an alternative preventive and therapeutic antiglioblastoma drug that may be especially useful for patients with recurrent glioblastoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-1497/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Voltage-gated sodium channels (VGSCs), which are aberrantly expressed in several human cancers, affect cancer cell behavior; however, their role in gastric cancer (GC) and the link between these channels and tumorigenic signaling remain unclear. The aims of this study were to determine the clinicopathological significance and role of the VGSC Nav 1.7 in GC progression and to investigate the associated mechanisms. Here, we report that the SCN9A gene encoding Nav 1.7 was the most abundantly expressed VGSC subtype in GC tissue samples and two GC cell lines (BGC-823 and MKN-28 cells). SCN9A expression levels were also frequently found to be elevated in GC samples compared to nonmalignant tissues by real-time PCR. In the 319 GC specimens evaluated by immunohistochemistry, Nav 1.7 expression was correlated with prognosis, and transporter Na(+) /H(+) exchanger-1 (NHE1) and oncoprotein metastasis-associated in colon cancer-1 (MACC1) expression. Nav 1.7 suppression resulted in reduced voltage-gated sodium currents, decreased NHE1 expression, increased extracellular pH and decreased intracellular pH, and ultimately, reduced invasion and proliferation rates of GC cells and growth of GC xenografts in nude mice. Nav 1.7 inhibition led to reduced MACC1 expression, while MACC1 inhibition resulted in reduced NHE1 expression in vitro and in vivo. Mechanistically, the suppression of Nav 1.7 decreased NF-κB p65 nuclear translocation via p38 activation, thus reducing MACC1 expression. Downregulation of MACC1 decreased c-Jun phosphorylation and subsequently reduced NHE1 expression, whereas the addition of hepatocyte growth factor (HGF), a c-Met physiological ligand, reversed the effect. These results indicate that Nav 1.7 promotes GC progression through MACC1-mediated upregulation of NHE1. Therefore, Nav 1.7 is a potential prognostic marker and/or therapeutic target for GC., (© 2016 UICC.)