semaxanib (SU5416)

This study demonstrates that ANXA3 regulates ERS to drive M1 macrophage polarization and inflammation, which subsequently promotes PASMC function and promotes PAH progression. ANXA3 may serve as a novel immunoinflammatory target and potential therapeutic candidate.

This study emphasizes the METTL3/LHPP/LDHA axis's role in enhancing PASMC proliferation and HPH. LHPP may represent a potential therapeutic target for the treatment of hypoxic pulmonary hypertension.

Although some discrepancies between the structural and functional improvement in tumor vasculatures were observed after PE-SU5416 × 3 and Seq × 3, cancer-associated fibroblasts (CAFs) and collagen levels were significantly reduced after PE-SU5416 × 2, PE-SU5416 × 3, Seq × 2, and Seq × 3, suggesting that a possible decrease in interstitial fluid pressure due to the reduction in CAFs and collagen would have compensated for vascular function. Furthermore, PE-SU5416 × 2, PE-SU5416 × 3, Seq × 2, and Seq × 3 significantly decreased tumor growth factor-β (TGF-β), an activator of CAFs, in tumor tissues, suggesting that the reduction in TGF-β levels by PE-SU5416 suppresses CAF activation.

The present findings demonstrated that CCR2 disruption ameliorated PAH in MCT-treated rats, which was associated with the reversal of dysregulated inflammatory pathways and vascular dysfunction and synergized with tadalafil. These findings suggest that CCR2 may be a therapeutic target in intractable PAH patients with a certain CCR2-related inflammatory phenotype and refractory to conventional pulmonary vasodilators.

In exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, reducing the ratio of BAX to Bcl-2, consistent with apoptosis resistance. These results provide a mechanism by which AQP1 can regulate PASMC fate.

Isatin analogs such as semaxanib and sunitinib were exposed to tyrosine kinase inhibitory properties. The nature of substitution in the N1 region of isatin seems to be able to influence the cytotoxic activity. Based on the obtained results of docking and cytotoxic tests, compound 4d seems to be a good compound for further investigations.

Smooth muscle cell (SMC)-specific HMGB2 knockout or HMGB2-OE (HMGB2 overexpression) mice and HMGB2 silenced rats were used to establish hypoxia+Su5416 (HySu)-induced PH mouse and monocrotaline-induced PH rat models, respectively...Our findings indicate that targeting HMGB2 might be a novel therapeutic strategy for treating PH. Serum HMGB2 levels could serve as a novel biomarker for diagnosing PA hypertension and determining its prognosis.

We discovered that both the mRNA and protein levels of PSEN1 were increased over time in hypoxic rats, monocrotaline (MCT) rats and Su5416/hypoxia (SuHx) mice...PSEN1 can be used as a promising molecular target for treating PAH. PSEN1 inhibitor ELN318463 can prevent and reverse the progression of PH and be developed as a potential anti-PAH drug.

IPC-366 and SUM149 cell lines and xenotransplanted mice were treated with different concentrations of VEGF, SU5416, bevacizumab and celecoxib. In conclusion, sex steroid hormones could regulate the production of angiogenic factors. The intratumoural measurement of sex steroids and growth factors may be useful to develop preventive and individualized therapeutic strategies.

The aim of this study was to evaluate the effect of different anti-angiogenic treatments in the in vitro formation of vascular-like structures as well as cell secretion of different angiogenic and lymphangiogenic factors (VEGFA, VEGFC, VEGFD) and interleukin-8 (IL-8) in culture media.Material and For in vitro tube formation assay, culture human SUM149 cells and canine IPC-366 cells were divided into a control group, treated with DMSO, and 4 experimental groups treated with 1.5 μM of VEGF, SU5416 (anti-VEGFR, VEGF B20-4.1.1 (anti-VEGF) and celecoxib (NSAID), respectively, for 4 h at 37ºC in 5% CO2 conditions. Increased VEGFC levels after celecoxib treatment suggest a switch from a proangiogenic state toward a lymphangiogenic state. Neutralization of VEGF by VEGF B20-4.1.1 enhances the secretion of VEGFA and VEGFC by tumor cells inhibiting angiogenesis and lymphangenesis.

Compared with popular anticancer drugs, the IC of CQDs/CuO was approximately 114-fold and 75-fold lower than the IC of commercial artesunate (ART) and oxaliplatin (OXA)...It also exhibited stronger antiangiogenic effects than commercial antiangiogenic inhibitor (SU5416) through down-regulating the expression of VEGFR2...Therefore, CQDs/CuO selectively mediated of ovarian cancer SKOV3 cells death mainly through decreasing the expression of MMP-2, MMP-9, F-actin, and VEGFR2, meanwhile CQDs/CuO caused apoptosis of SKOV3 via S phase cell cycle arrest. These findings reveal a new application for the use of CQDs/CuO composite as potential therapeutic interventions in ovarian cancer SKOV3 cells.