Biological functions of lymphatic vessels.

The general functions of lymphatic vessels in fluid transport and immunosurveillance are well recognized. However, accumulating evidence indicates that lymphatic vessels play active and versatile roles in a tissue- and organ-specific manner during homeostasis and in multiple disease processes. This Review discusses recent advances to understand previously unidentified functions of adult mammalian lymphatic vessels, including immunosurveillance and immunomodulation upon pathogen invasion, transport of dietary fat, drainage of cerebrospinal fluid and aqueous humor, possible contributions toward neurodegenerative and neuroinflammatory diseases, and response to anticancer therapies

A novel hexaosmium cluster [Os6(μ-H)(CO)19(μ-CO)(η2-C 6F5NNNC6F5)] formed from an isomeric intermediate [Os6(μ-H)(CO)20(NCMe)2(η 2-C6F5NNNC6F5)] via a capping process

Chemical Communications91075-1076CHCO

Synthesis of 1,3-diaryltriazenido triruthenium and triosmium clusters: Crystal structures of [Ru3(μ-H)(CO)10(μ-C6F 5NNNC6F5)] and [Os3(CO)11Cl(η2-C6F 5NNNC6F5)]

Journal of the Chemical Society - Dalton Transactions81573-158

Reactions of the linear triosmium cluster [Os3H(CO)11(η2-C6F 5NNNC6F5)] with [Os3(CO)12-n(NCMe)n] (n = 1 or 2): Crystal structures of [Os4(μ-H)-(CO)14(η2-C6F 5NNNC6F5)] and [Os5(μ-H)...

Journal of the Chemical Society - Dalton Transactions214083-408

Methylation-dependent regulation of HIF-1α stability restricts retinal and tumour angiogenesis

Hypoxia-inducible factor-1α (HIF-1α) mediates hypoxic responses and regulates gene expression involved in angiogenesis, invasion and metabolism. Among the various HIF-1α posttranslational modifications, HIF-1α methylation and its physiological role have not yet been elucidated. Here we show that HIF-1α is methylated by SET7/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1α methylation is the modulation of HIF-1α stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective Hif1aKA/KA allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1α stabilization. Importantly, S28Y and R30Q mutations of HIF-1α, found in human cancers, are involved in the altered HIF-1α stability. Together, these results demonstrate a role for HIF-1α methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer131311sciescopu

Supplementary Material for: Antiangiogenic Therapy Induces Hepatic Tumor Vascular Network Rearrangement to Receive Perfusion via the Portal Vein and Hepatic Artery

<i>Purpose:</i> Hepatic malignancies can easily develop resistance to antiangiogenic therapy, but the underlying mechanism remains poorly understood. This study explores whether antiangiogenic therapy influences the tumor vascular network and/or the vessels feeding the hepatic tumor. <i>Methods:</i> Mice implanted with Lewis lung carcinoma (LLC) cells were subcutaneously injected 3 times (once every other day starting 1 week after LLC implantation) with either an antiangiogenic agent [vascular endothelial growth factor (VEGF)-Trap] or control agent (bovine serum albumin) at a dose of 25 mg/kg before performing angiography. Hepatic arteriography and portography were performed using a vascular cast method with vascular latex. <i>Results:</i> Arteriography of the control-treated LLC-implanted mice showed marked staining of the mass with a prominent feeding artery, suggesting that the tumor is supplied by arterial perfusion. No significant staining was observed on portography. By contrast, 33% (n = 3/9) of the LLC-implanted mice treated with the antiangiogenic agent VEGF-Trap showed intratumoral staining during portography, indicating that these tumors received perfusion via the portal vein. <i>Conclusion:</i>Antiangiogenic treatment can induce rearrangement of the hepatic tumor vascular network to establish communication with the portal vein. This implies that hepatic tumors can develop resistance to antiangiogenic therapy by maintaining perfusion through portal venous perfusion