KDR overexpression

Apatinib has a significant inhibitory effect on small cell lung cancer with high expression of VEGFR2 and may be a treatment for small cell lung cancer patients.

In silico docking study revealed the favorable binding energies of -7.30 kcal/mol and -8.04 kcal/mol for compounds towards Vascular Endothelial Growth Factor Recaptor-2 (VEGFR-2), respectively. In conclusion, we have synthesized antioxidant and anticancer agents that target VEGFR-2 in breast cancer cells.

VEGFR2 and VEGF-C are highly expressed in EGFR-mutant NSCLC cells. Increased expression of VEGFR2 was identified as a significant prognostic factor in patients with EGFR del19 mutation who received osimertinib, whereas co-high expression of VEGFR2 and VEGF-C was a significant predictor for those with EGFR L858R mutation.

The most effective and selective hCA IX and XII inhibitors 8g, 8j and 15b were chosen to be tested for their in vitro inhibitory impact against VEGFR-2 as well as their antiproliferative impact against VEGFR-2 overexpressing MDA-MB-231 and MCF-7 breast cancer cells. Furthermore, molecular docking studies were conducted within the hCA IX, XII, and VEGFR-2 active sites to explain the observed inhibitory results.

VEGFR2 overexpression independently correlated with longer OS or PFS in PM patients, such biomarker deserving prospective evaluation as stratification variable in future clinical trials.

No abstract available

The intense staining of VEGFR2 in UC cells suggested that VEGFR2 may be of prognostic and/or therapeutic value in dogs with UC. Overexpression of VEGFR2 in UC cells validates this receptor as a treatment target in UC.

TGFβ-1 ratio significantly increased following preformed interventions in non-pathologic groups: E (P ≤ 0.001) and NS+E (P ≤ 0.01). IHC and gene assays indicate a favorable and acceptable effect of the designed training protocol besides the treatment with N.sativa nano-drug, by which cancer development could be restricted through recovering the natural balance of angiogenic and angiostatic markers.

We evaluated this using both in vitro and in vivo experiments. The KDR-CAR-T cells targeted and killed KDR-A549 with high efficiency by expressing IFN-γ and releasing granzyme B. The in vivo study showed that KDR-CAR-T cells dramatically inhibited the growth of lung cancer KDR-A549 xenografts in BALB/c-nu mice at day 10. The characterization of T cells modified by KDR-CAR by computational biology and wet-lab experiments suggested its applicability as a new treatment strategy for lung cancer and, potentially, for other vascularized solid tumors.

An increase in VAEs has been documented with ponatinib, nilotinib, and dasatinib but not with imatinib and bosutinib. However, the in-vivo effect of these TKIs on endothelial pathogenesis requires further investigation. Understanding TKI-induced VAE pathogenesis could contribute to the future development of safer next-generation TKIs and could potentially influence TKI-personalized tailoring for CML patients.

VXM01 in combination with avelumab was safe and produced detectable peripheral VEGFR-2-specific immune responses. Three non-resected patients had an objective response, three more patients experienced best response stable disease. For future studies a patient enrichment strategy based on immune biomarkers might be envisaged.

We show that several key immune subsets express VEGFR2, with compensatory changes following VEGF blockade and enrichment within the tissue, highlighting the need to study the direct immunomodulatory role of anti-angiogenic agents in HCC. The expression of PDL1 on CD8 T cells also merits further investigation since this can autoregulate responses through reverse signalling as well as suppressing neighbouring T cells. Access to liver tissue using minimally invasive approaches and specimens from neoadjuvant studies is essential to further our understanding of highly compartmentalised immune responses, including the potential for rescue of exhausted intrahepatic VEGFR2+ and PDL1+ CD8 T cells in HCC.

Our findings indicate that emodin inhibits proliferation and invasion of CRC cells and reduces VEGF secretion and VEGFR1 and VEGFR2 expression by inhibiting ACSL4. This emodin-induced pathway offers insights into the molecular mechanism of its antitumor effect and provides a potential therapeutic strategy for CRC.

Cytotoxicity of immunotoxin was evaluated on the VEGFR-2 positive PC-3 cell line by MTT assay. Overexpression of VEGFR-2 in the PC-3 cell line allowed immunotoxin to recognize them by anti-VEGFR-2 nanobodies. The concentrations above 5 μg/ml represented a significant decrease in cell survival rate in PC-3 cells compared to HEK293 cells (VEGFR-2 negative cells) as controls.VGRNb-DT demonstrated a successful bioconjugation; furthermore, variable concentrations were correlated with cell death in prostate cancer PC-3 cells.

The association of VEGFR2 and HER2 expression in early EC was elucidated. This study shows that the measurement of VEGFR2 expression may be useful in the preoperative assessment of EC and suggests the possibility of anti-HER2 therapy for EC.

Overexpression of VEGFR2 can offset the rescue effect of Apa on PTX-induced drug resistance of MGC803 cells. Taken together, Apa may inhibit PTX resistance of MGC803 cells via the VEGFR2 signaling pathway.

A trend towards longer progression free survival (PFS) was detected univariately for patients with HER2-negative tumors and high expression of VEGFR2, (HR=0.60, p=0.059). VEGFR1 and VEGFR2 seem to have significant prognostic value in BC patients with metastatic disease treated with trastuzumab-based regimens.

5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.

These findings suggest that elevated Topo-II and TS expression may contribute to poor outcomes through protumoral biology in patients with LCNEC, and elevated VEGFR2 expression might negatively impact tumor immune reactions in LCNEC.

These effects were associated with the downregulation of VEGF and VEGFR2 and suppression of the PI3K/AKT signaling pathway. Thus, apatinib inhibited cell migration, invasion and angiogenesis by blocking the VEGF and PI3K/AKT pathways, supporting an effective therapeutic strategy in the treatment of HCC.

Immunohistochemical expression of c-Met, HGF, VEGFR2, and MVD was assessed in tumor specimens of GBM patients treated with bevacizumab, after progression under temozolomide. Concomitant c-Met/VEGFR2 overexpression was associated with worse overall survival (13 months) compared with concomitant c-Met/VEGFR2 negative expression (19 months; p = 0.025). Our data support the hypothesis that c-Met and VEGFR2 overexpression have a role in the development of glioblastoma early resistance and might predict poorer responses to anti-angiogenic therapies.

In a univariate analysis overexpression of VEGFR2 (p <0.0001) and FGFR2 (p = 0.014) had negative influence on cancer-specific survival. Expression of growth factors and tyrosine kinase receptors in the primary tumor cells is strongly interconnected and associated with unfavorable features of RCC.

Anlotinib could exert an antitumor effect on oral cancer cell lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.

Our study suggested that the high expression of VEGFR-2, as well as the VEGFR-2 rs1870377 A > T genetic polymorphism, may be prognostic markers for GC.