Synthesis of 4‑Ynamides and Cyclization by the Vilsmeier Reagent to Dihydrofuran-2(3<i>H</i>)‑ones

The room-temperature nucleophilic addition of vinyl azides to propargylic alcohols under BF₃·Et₂O catalysis provides an efficient synthesis of 4-ynamides. The procedure is operationally convenient, shows broad substrate scope, and is viable for the synthesis of multifunctional 4-ynamides. Further, a Vilsmeier intramolecular cyclization of 4-ynamides into dihydrofuran-2­(3<i>H</i>)-ones has also been discovered, which represents the first report of alkynes being used as the nucleophiles in Vilsmeier-type reactions

Human tumor xenografts vascularized with mouse endothelial cells is more responsive to a chemotherapeutic and an anti-angiogenesis drug.

<p>Xenograft tumors were engineered in immunodefficient mice by the co-transplantation of human tumor cells and human endothelial cells or human tumor cells and mouse endothelial cells seeded in biodegradable scaffolds measuring 6×6×1 mm. (A) Graph depicting the growth of human xenografts tumors (UM-SCC-17B cells) vascularized with HDMEC or MDMEC. As soon as we observed growth of the tumors beyond the size of the scaffold (<i>i.e.</i> when average tumor volume was 180 mm³), mice began to receive either 4 mg/kg cisplatin (i.p.) every 5 days, or 40 mg/kg sunitinib (o.r.) daily. (B) Fold change difference between the pre-treatment volume of the tumors and the volume of the same tumors after 30 days of treatment with cisplatin or sunitinib. (C) Tumor volume at the end of treatment with cisplatin or sunitinib. (D) Graph depicting the number of microvessels in tumor xenografts vascularized with HDMEC or MDMEC after treatment with cisplatin or sunitinib. Asterisk depicts P<0.05, as compared with controls. Results are representative of 3 independent experiments, n = 8.</p

Human and mouse dermal microvascular endothelial cells have similar angiogenic potential <i>in vitro</i> and <i>in vivo</i>.

<p>(<b>A-D</b>) Representative photomicrographs of human dermal microvascular endothelial cells (HDMEC) and mouse dermal microvascular endothelial cells (MDMEC) stably transduced with GFP under light microscopy (<b>A</b> and <b>B</b>) and fluorescence microscopy (<b>C</b> and <b>D</b>). (<b>E</b> and <b>F</b>) Representative images of capillary sprouts formed by HDMEC (<b>E</b>) and MDMEC (<b>F</b>) on 3-D type I collagen matrices. (<b>G</b> and <b>H</b>) Photomicrographs of representative fields of GFP-immunostaining (red color) used to localize the blood vessels formed by HDMEC (<b>G</b>) and MDMEC (<b>G</b>) 14 days after implantation in immunodefficient mice. (<b>I</b>) The number of microvessels in implants populated with HDMEC or MDMEC. Microvessels were counted in 10 random microscopic fields/scaffold (200×) in 6 scaffolds per group. Results are representative of 3 independent experiments, n = 6.</p

<i>In vitro</i> response of human and mouse endothelial cells to a chemotherapeutic and an anti-angiogenesis drug.

<p>(<b>A</b> and <b>B</b>) The 48-hour cytotoxicity of cisplatin (<b>A</b>) and sunitinib (<b>B</b>) was evaluated by the SRB assay in HDMEC and MDMEC. Results are normalized against vehicle control and initial plating density. (<b>C</b> and <b>D</b>) Fold-change difference in the percentage of apoptotic cells upon treatment with cisplatin (<b>C</b>) or sunitinib (<b>D</b>) for 48 hours. Apoptosis was determined as the percentage of cells in Sub-G₀/G₁ by propidium iodide staining followed by flow cytometry. (<b>E</b> and <b>F</b>) Effect of cisplatin (<b>E</b>) or sunitinib (<b>F</b>) on the cell cycle of HDMEC and MDMEC. Results are representative of 3 independent experiments.</p

Tumor xenografts vascularized with human endothelial cells have similar microvessel density by grow faster than xenografts vascularized with mouse endothelial cells.

<p>(A) Representative photographs of HeLa tumors vascularized with either HDMEC or MDMEC. (B-D) Graphs depicting tumor growth of xenografts of HN12 (B), HeLa (C), UM-SCC-17B (D) vascularized with HDMEC or MDMEC. (E) Graph depicting tumor volume at the end of the experimental period. Asterisk depicts p<0.05. (F and G) Representative photomicrographs of tumors generated with UM-SCC-17B and HDMEC or MDMEC. Immunohistochemistry for GFP was performed to identify GFP-tagged endothelial cells. (H) Microvessel density of xenograft tumors generated with UM-SCC-17B and HDMEC or MDMEC. Results are representative of 3 independent experiments, n = 8.</p