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The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology--to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work,(More)
As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis. Here we show that hypoxia and hypoglycaemia reduce proliferation and increase apoptosis in wild-type (HIF-1alpha+/+)(More)
The recent landmark Phase III clinical trial with a VEGF-specific antibody suggests that antiangiogenic therapy must be combined with cytotoxic therapy for the treatment of solid tumors. However, there are no guidelines for optimal scheduling of these therapies. Here we show that VEGFR2 blockade creates a "normalization window"--a period during which(More)
No growth factors specific for the lymphatic vascular system have yet been described. Vascular endothelial growth factor (VEGF) regulates vascular permeability and angiogenesis, but does not promote lymphangiogenesis. Overexpression of VEGF-C, a ligand of the VEGF receptors VEGFR-3 and VEGFR-2, in the skin of transgenic mice resulted in lymphatic, but not(More)
New vessel formation (angiogenesis) is an essential physiological process for embryologic development, normal growth, and tissue repair. Angiogenesis is tightly regulated at the molecular level. Dysregulation of angiogenesis occurs in various pathologies and is one of the hallmarks of cancer. The imbalance of pro- and anti-angiogenic signaling within tumors(More)
Nitric oxide (NO) and nitric oxide synthases are ubiquitous in malignant tumours and are known to exert both pro- and anti-tumour effects. We summarize our current understanding of the role of NO in tumour progression, especially in relation to angiogenesis and vascular functions. We also discuss potential strategies for cancer treatment that modulate NO(More)
Intravital microscopy coupled with chronic animal window models has provided stunning insight into tumor pathophysiology, including gene expression, angiogenesis, cell adhesion and migration, vascular, interstitial and lymphatic transport, metabolic microenvironment and drug delivery. However, the findings to date have been limited to the tumor surface (<(More)
Intravital multiphoton microscopy has provided powerful mechanistic insights into health and disease and has become a common instrument in the modern biological laboratory. The requisite high numerical aperture and exogenous contrast agents that enable multiphoton microscopy, however, limit the ability to investigate substantial tissue volumes or to probe(More)
A solid tumor forms an organ-like entity comprised of neoplastic cells and non-transformed host stromal cells embedded in an extracellular matrix. Similar to normal tissues, blood vessels nourish cells residing in tumors. However, unlike normal blood vessels, tumor vasculature has abnormal organization, structure, and function. Tumor vessels are leaky and(More)
Hypoxia and acidosis are hallmarks of tumors as well as critical determinants of response to treatments. They can upregulate vascular endothelial growth factor (VEGF) in vitro. However, the relationship between tissue oxygen partial pressure (pO(2))/pH and VEGF transcription in vivo is not known. Thus, we developed a novel in vivo microscopy technique to(More)