CXCR2-Expressing Tumor Cells Drive Vascular Mimicry in Antiangiogenic Therapy-Resistant Glioblastoma was written by Angara, Kartik;Borin, Thaiz F.;Rashid, Mohammad H.;Lebedyeva, Iryna;Ara, Roxan;Lin, Ping-Chang;Iskander, A. S. M.;Bollag, Roni J.;Achyut, Bhagelu R.;Arbab, Ali S.. And the article was included in Neoplasia (New York, NY, United States) in 2018.Reference of 212141-54-3 This article mentions the following:
BACKGROUND: Glioblastoma (GBM) was shown to relapse faster and displayed therapeutic resistance to antiangiogenic therapies (AATs) through an alternative tumor cell-driven mechanism of neovascularization called vascular mimicry (VM). We identified highly upregulated interleukin 8 (IL-8)-CXCR2 axis in tumor cells in high-grade human glioma and AAT-treated orthotopic GBM tumors. METHODS: Human GBM tissue sections and tissue array were used to ascertain the clin. relevance of CXCR2-pos. tumor cells in the formation of VM. We utilized U251 and U87 human tumor cells to understand VM in an orthotopic GBM model and AAT-mediated enhancement in VM was modeled using vatalanib (anti-VEGFR2) and avastin (anti-VEGF). Later, VM was inhibited by SB225002 (CXCR2 inhibitor) in a preclin. study. RESULTS: Overexpression of IL8 and CXCR2 in human datasets and histol. anal. was identified as a bonafide candidate to validate VM through in vitro and animal model studies. AAT-treated tumors displayed a higher number of CXCR2-pos. GBM-stem cells with endothelial-like phenotypes. Stable knockdown of CXCR2 expression in tumor cells led to decreased tumor growth as well as incomplete VM structures in the animal models. Similar data were obtained following SB225002 treatment. CONCLUSIONS: The present study suggests that tumor cell autonomous IL-8-CXCR2 pathway is instrumental in AAT-mediated resistance and VM formation in GBM. Therefore, CXCR2 can be targeted through SB225002 and can be combined with standard therapies to improve the therapeutic outcomes in clin. trials. In the experiment, the researchers used many compounds, for example, N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3Reference of 212141-54-3).
N-(4-Chlorophenyl)-4-(pyridin-4-ylmethyl)phthalazin-1-amine (cas: 212141-54-3) belongs to phthalazine derivatives.Like many other isomeric benzodiazines, phthalazine derivatives reveal numerous pharmacological and biological activities such as analgesic, anticonvulsant, antitumor, antiproliferative. Both pyridazine and phthalazine give rise to very good TREPR signals in rigid media at low temperatures.Reference of 212141-54-3
Referemce:
Phthalazine – Wikipedia,
Phthalazine | C8H6N2 – PubChem