Scholars@Duke
Siqing Shan

Siqing Shan

Assistant Professor Emeritus of Radiation Oncology
Radiation Oncology
siqing.shan@duke.edu
PO Box 3085 DUMC, Durham, NC 27710
40 Duke Medicine Circle, Durham, NC 27710

Selected Publications

Nitric oxide loading reduces sickle red cell adhesion and vaso-occlusion in vivo.

Journal Article Blood Adv · September 10, 2019 Sickle red blood cells (SSRBCs) are adherent to the endothelium, activate leukocyte adhesion, and are deficient in bioactive nitric oxide (NO) adducts such as S-nitrosothiols (SNOs), with reduced ability to induce vasodilation in response to hypoxia. All t ... Full text Open Access Link to item Cite

Sevuparin binds to multiple adhesive ligands and reduces sickle red blood cell-induced vaso-occlusion.

Journal Article Br J Haematol · December 2016 Sevuparin is a novel drug candidate in phase II development as a treatment for vaso-occlusive crises (VOC) in patients with sickle cell disease (SCD). As a heparin-derived polysaccharide, sevuparin has been designed to retain anti-adhesive properties, whil ... Full text Link to item Cite

Sevuparin Reduces Adhesion Of Both Sickle Red Cells and Leukocytes To Endothelial Cells In Vitro and Inhibits Vaso-Occlusion In Vivo

Conference Blood · November 15, 2013 AbstractIntroductionSevuparin is a new chemically modified heparin with low anticoagulant activity currently being studied as an adjuv ... Full text Cite

Automated measurement of blood flow velocity and direction and hemoglobin oxygen saturation in the rat lung using intravital microscopy.

Journal Article Am J Physiol Lung Cell Mol Physiol · January 15, 2013 Intravital microscopy of the pulmonary microcirculation in research animals is of great scientific interest for its utility in identifying regional changes in pulmonary microcirculatory blood flow. Although feasibility studies have been reported, the pulmo ... Full text Link to item Cite

The combination of theophylline and endothelin receptor antagonism improves exercise performance of rats under simulated high altitude.

Journal Article J Appl Physiol (1985) · October 15, 2012 Decreased physical performance is a well-known consequence of rapid ascent to high altitude. Hypoxic pulmonary vasoconstriction (HPV) potentially limits cardiac output and systemic blood flow, thus preventing successful adaptation to rapid ascent. We hypot ... Full text Link to item Cite

High-resolution in vivo imaging of fluorescent proteins using window chamber models.

Journal Article Methods Mol Biol · 2012 Fluorescent proteins enable in vivo characterization of a wide and growing array of morphological and functional biomarkers. To fully capitalize on the spatial and temporal information afforded by these reporter proteins, a method for imaging these protein ... Full text Link to item Cite

In vivo optical molecular imaging and analysis in mice using dorsal window chamber models applied to hypoxia, vasculature and fluorescent reporters.

Journal Article Nat Protoc · August 18, 2011 Optical techniques for functional imaging in mice have a number of key advantages over other common imaging modalities such as magnetic resonance imaging, positron emission tomography or computed tomography, including high resolution, low cost and an exten ... Full text Link to item Cite

The pervasive presence of fluctuating oxygenation in tumors.

Journal Article Cancer Res · July 15, 2008 Tumor hypoxia is a persistent obstacle for traditional therapies in solid tumors. Strategies for mitigating the effects of hypoxic tumor cells have been developed under the assumption that chronically hypoxic tumor cells were the central cause of treatment ... Full text Link to item Cite

Bromelain treatment decreases neutrophil migration to sites of inflammation.

Journal Article Clin Immunol · July 2008 Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanism ... Full text Link to item Cite

Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo.

Journal Article Blood · October 1, 2007 Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial alpha ... Full text Link to item Cite

Corneal Angiogenesis Assay

Journal Article · September 27, 2007 New vessel growth in the avascular and transparent cornea occurs under a variety of pathological conditions and is readily distinguishable. Therefore, the corneal neovascularization (CNV) assay has become a widely used in vivo model for angiogenesis resear ... Full text Cite

Angiostatin-like activity of a monoclonal antibody to the catalytic subunit of F1F0 ATP synthase.

Journal Article Cancer Res · May 15, 2007 The antiangiogenic protein angiostatin inhibits ATP synthase on the endothelial cell surface, blocking cellular proliferation. To examine the specificity of this interaction, we generated monoclonal antibodies (mAb) directed against ATP synthase. mAb direc ... Full text Link to item Cite

Preferential extravasation and accumulation of liposomal vincristine in tumor comparing to normal tissue enhances antitumor activity.

Journal Article Cancer Chemother Pharmacol · August 2006 To quantitatively evaluate the extravasation, accumulation and selectivity to tumor tissues of liposomal vincristine (LV), dorsal skin-fold window chambers on athymic mice with or without LX-1, a human small cell lung cancer, xenograft implants and fluores ... Full text Link to item Cite

Quantitative comparison of the inhibitory effects of GW5638 and tamoxifen on angiogenesis in the cornea pocket assay.

Journal Article Angiogenesis · 2006 GW5638 is a novel tissue-selective estrogen receptor (ER) modulator. Structurally, it is a derivative of tamoxifen that is known for its inhibitory effects on angiogenesis in an ER-independent manner. Therefore, it is possible that GW5638 has the same effe ... Full text Link to item Cite

Melanoma, a tumor based on a mutant stem cell?

Journal Article J Invest Dermatol · January 2006 Stem cells play a critical role in normal tissue maintenance, and mutations in these stem cells may give rise to cancer. We hypothesize that melanoma develops from a mutated stem cell and therefore residual stem cell characteristics should be able to be id ... Full text Link to item Cite

Human recombinant erythropoietin (rEpo) has no effect on tumour growth or angiogenesis.

Journal Article Br J Cancer · December 12, 2005 Tumour hypoxia has been shown to increase mutation rate, angiogenesis, and metastatic potential, and decrease response to conventional therapeutics. Improved tumour oxygenation should translate into increased treatment response. Exogenous recombinant eryth ... Full text Link to item Cite

Observation of incipient tumor angiogenesis that is independent of hypoxia and hypoxia inducible factor-1 activation.

Journal Article Cancer Res · July 1, 2005 It is well established that hypoxia potently stimulates tumor angiogenesis by activating hypoxia inducible factor-1 (HIF-1)-induced proangiogenic factors, such as vascular endothelial growth factor. However, very little is known about the role of hypoxia i ... Full text Link to item Cite

Responses of vascular endothelial cells to angiogenic signaling are important for tumor cell survival.

Journal Article FASEB J · February 2004 Neoplastic cells overexpress several angiogenic cytokines, which stimulate neovascularization. Whether the responses of the host endothelial cells to these signaling molecules affect tumor cells during early tumorigenesis has not been investigated. We inve ... Full text Link to item Cite

Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2.

Journal Article Proc Natl Acad Sci U S A · April 29, 2003 Featured Publication Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability. Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangi ... Full text Link to item Cite

A novel rodent mammary window of orthotopic breast cancer for intravital microscopy.

Journal Article Microvasc Res · March 2003 Orthotopic and ectopic organ environments differentially influence tumor growth, metastasis, and sensitivity to therapy. In this study we present a novel rodent mammary window of orthotopic breast cancer, which is amenable to study of microvascular functio ... Full text Link to item Cite

Intravital fluorescence facilitates measurement of multiple physiologic functions and gene expression in tumors of live animals.

Journal Article Dis Markers · 2002 Featured Publication The purpose of this report is to present an overview of the use of fluorescence imaging in vivo, with particular emphasis on oncology. It is important to note, however, that many of the methods described herein have been applied to the study of non-maligna ... Full text Link to item Cite

Mechanisms associated with tumor vascular shut-down induced by combretastatin A-4 phosphate: intravital microscopy and measurement of vascular permeability.

Journal Article Cancer Res · September 1, 2001 Featured Publication The tumor vascular effects of the tubulin destabilizing agent disodium combretastatinA-4 3-O-phosphate (CA-4-P) were investigated in the rat P22 tumor growing in a dorsal skin flap window chamber implanted into BD9 rats. CA-4-P is in clinical trial as a tu ... Link to item Cite

The novel tubulin-binding drug BTO-956 inhibits R3230AC mammary carcinoma growth and angiogenesis in Fischer 344 rats.

Journal Article Clin Cancer Res · August 2001 BTO-956 [methyl-3,5-diiodo-4-(4'-methoxyphenoxy)benzoate], a novel tubulin-binding drug and thyroid hormone analogue, was originally found to inhibit human carcinoma cell proliferation in vitro and to have potent growth delay activity in human breast and o ... Link to item Cite

Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models.

Journal Article Clin Cancer Res · November 2000 Inhibition of tumor angiogenesis is a therapeutic strategy that can inhibit tumor growth and metastases. The aim of this study was to determine whether the estrogen receptor (ER) ligand drug tamoxifen has antiangiogenic effects. We used three different mod ... Link to item Cite

Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models.

Journal Article J Natl Cancer Inst · January 19, 2000 BACKGROUND: There is a paucity of information about events that follow immediately after tumor cells are triggered to initiate the process of angiogenesis (the formation of new blood vessels). Such information is relevant to the issue of when micrometastas ... Full text Link to item Cite

Role of incipient angiogenesis in cancer metastasis.

Journal Article Cancer Metastasis Rev · 2000 Metastasis is the primary cause of mortality in cancer patients. Angiogenesis is intimately involved in metastasis at the site of entry of tumor cells into the vasculature and at the site of eventual metastasis growth. In this commentary, we review current ... Full text Link to item Cite

Inhibition of tumor growth by targeting tumor endothelium using a soluble vascular endothelial growth factor receptor.

Journal Article Cell Growth Differ · January 1998 Featured Publication Vascular endothelial growth factor (VEGF) is a leading candidate for an endogenous mediator of tumor angiogenesis. Recently, two endothelial cell surface receptors, flk-1 and flt-1, have been shown to mediate the angiogenic activities of VEGF. In this stud ... Link to item Cite

Inhibition of tumor angiogenesis using a soluble receptor establishes a role for Tie2 in pathologic vascular growth.

Journal Article J Clin Invest · October 15, 1997 Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium. Disruption of Tie2 function in transgenic mice resulted in embryonic lethality secondary to characteristic vascular defects; similar defects occurred aft ... Full text Link to item Cite

Simultaneous measurement of liposome extravasation and content release in tumors.

Journal Article Microcirculation · March 1997 OBJECTIVE: The success of liposome-based drug delivery systems for tumor targeting relies on maximum extravasation of liposomes into tumor interstitium, as well as optimal release of contents from the liposomes once within the tumor Liposome extravasation ... Full text Link to item Cite

Stroma-free human hemoglobin A decreases R3230Ac rat mammary adenocarcinoma blood flow and oxygen partial pressure.

Journal Article Radiat Res · February 1997 We examined the effect of a nitric oxide (NO) quencher, stroma-free human hemoglobin A (HbA0; 0.01, 0.05, 0.1, 0.2 g/kg), on the blood flow measured using the Doppler flow technique, tumor oxygen pressure (pO2) and the diameter of the arterioles using R323 ... Link to item Cite

Effects of diethylamine/nitric oxide on blood perfusion and oxygenation in the R3230Ac mammary carcinoma.

Journal Article Br J Cancer · 1997 The effects of intravenous diethylamine/nitric oxide (DEA/NO), a short-acting nitric oxide (NO) donor, on systemic haemodynamics, muscle and tumour blood flow (MBF and TBF) and tumour oxygenation were examined in rats bearing subcutaneous R3230Ac carcinoma ... Full text Link to item Cite

Arteriolar oxygenation in tumour and subcutaneous arterioles: effects of inspired air oxygen content.

Journal Article Br J Cancer Suppl · July 1996 Carbogen is thought to be more effective than normobaric oxygen in reducing tumour hypoxia because it may reduce hyperoxic vasoconstriction. In this study, tumour and normal arteriolar diameters were measured simultaneously with perivascular pO2 during air ... Link to item Cite

Arteriolar oxygenation in tumour and subcutaneous arterioles: Effects of inspired air oxygen content

Journal Article British Journal of Cancer · January 1, 1996 Carbogen is thought to be more effective than normobaric oxygen in reducing tumour hypoxia because it may reduce hyperoxic vasoconstriction. In this study, tumour and normal arteriolar diameters were measured simultaneously with perivascular pO2 ... Cite

Nitric oxide synthase inhibition irreversibly decreases perfusion in the R3230Ac rat mammary adenocarcinoma.

Journal Article Br J Cancer · June 1995 We examined the microvascular effects of competitive nitric oxide synthase (NOS) inhibition with NG-monomethyl-L-arginine (MeArg), followed by L-arginine, on R3230Ac mammary adenocarcinoma perfusion. In window preparations containing tumours, superfusion o ... Full text Link to item Cite

Nitric oxide synthase inhibition irreversibly decreases perfusion in the R3230Ac rat mammary adenocarcinoma

Journal Article British Journal of Cancer · January 1, 1995 We examined the microvascular effects of competitive nitric oxide synthase (NOS) inhibition with NG-monomethyl-L-arginine (MeArg), followed by L-arginine, on R3230Ac mammary adenocarcinoma perfusion. In window preparations containing tumours, superfusion o ... Full text Cite

Comparison of the effects of hydralazine on tumor and normal tissue blood perfusion by MRI.

Journal Article Int J Radiat Oncol Biol Phys · June 15, 1994 PURPOSE: The differential effects on blood perfusion of the vasodilator hydralazine (HYD) between tumor and normal muscle have been measured using the dynamic enhanced-magnetic resonance imaging (DE-MRI) technique. METHODS AND MATERIALS: DE-MRI is a noninv ... Full text Link to item Cite