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Background: The progression and metastasis of tumors are typically accompanied by angiogenesis. Crucially, vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a significant role in tumor-associated angiogenesis. In this study, the aim was to investigate the antitumor effect of combining bevacizumab (Bev) with anlotinib (An) on colorectal cancer (CRC). Methods: The CCK-8 assay, EdU assay, and Annexin V staining were conducted to evaluate the proliferation and apoptosis of CRC cells in vitro. The migration capability of CRC cells and HUVECs was assessed using the Transwell assay. Additionally, the tube formation capability of HUVECs was investigated. Furthermore, the antitumor and antiangiogenic effects were evaluated in the BALB/c mice model using immunohistochemistry, TUNEL staining, and 18F-FDG PET/CT imaging. Finally, we analyzed the inhibitory effect of Bev and/or An on related signaling effectors through western blotting. Results: The in vivo CRC mice model revealed that the combination of Bev + An significantly suppressed tumor formation and angiogenesis. Bev + An inhibited tumor glucose metabolism and increased the median survival period in tumor-bearing mice. Mechanistically, the expressions of VEGF, VEGFR2, PDGFR, and FGFR, as well as the phosphorylation levels of AKT, were inhibited after Bev+An treatment. In conclusion, the dual vertical targeting of VEGF and VEGFR in the CRC mice model strongly inhibited tumor growth and angiogenesis, with the suppression of the AKT signaling pathway playing a partial role.

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte’s programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI. [ABSTRACT FROM AUTHOR]

Angiogenesis is involved in the proliferation and metastasis of solid tumours; hence, it is an attractive therapeutic target. However, most patients who undergo anti-angiogenic drug treatment do not achieve complete tumour regression, resulting in drug resistance. The objective of this research is to explore the therapeutic effect of combining bevacizumab (Bev), an anti-vascular endothelial growth factor (VEGF)-A antibody, with apatinib (Apa), a VEGR receptor (VEGFR)-2-targeting tyrosine kinase inhibitor, in non-small cell lung cancer (NSCLC). In vitro, we assessed the influence which Bev + Apa treatment exerts upon the proliferation as well as apoptosis of Lewis lung carcinoma (LLC) cells in virtue of the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide as assay as well as Annexin V staining, respectively. For in vivo assessment, we established a tumour-bearing mouse model with LLC cells and investigated the anti-angiogenic and antitumor effects of Bev + Apa by 18F-FDG PET/CT imaging, immunohistochemistry and TUNEL staining. Bev + Apa treatment significantly inhibited LLC cell growth and proliferation in a larger scale compared to therapy of either of the only agent. Bev + Apa inhibited tumour growth and extended the median survival time of tumour-bearing mice. Mechanistically, Bev + Apa reduced angiogenesis by inhibiting VEGF and VEGFR-2 expression and reducing glucose metabolism in tumour tissues. Thus, Bev and Apa inhibited tumour angiogenesis synergistically, indicating their potential clinical utility for NSCLC treatment. [ABSTRACT FROM AUTHOR]