Search

Diet-based chemoprevention of cancer has emerged as an interesting approach to evade the disease or even target its early phases, reducing its incidence or slowing down tumor progression. In its basis in the essential role of angiogenesis for tumor growth and metastasis, angioprevention proposes the use of inhibitors of angiogenesis in cancer prevention. The anti-angiogenic potential exhibited by many natural compounds contained in many Mediterranean diet constituents makes this dietary pattern especially interesting as a source of chemopreventive agents, defined within the angioprevention strategy. In this review, we focus on natural bioactive compounds derived from the main foods included in the Mediterranean diet that display anti-angiogenic activity, as well as their possible use as angiopreventive agents.

Vascular-disrupting strategies impair a tumor's blood vessel network, which is essential for tumor progression and metastasis. Vascular-disrupting agents (VDAs) cause a rapid and selective vascular shutdown in tumors to produce extensive secondary neoplastic cell death due to ischemia. A lead agent in this therapeutic strategy is the tubulin depolymerizing agent combretastatin-A4 phosphate (CA4P). Used alone, CA4P induces extensive necrosis in a wide variety of preclinical cancer models and significant blood flow reductions in the patient tumors. Preclinical and clinical data further indicate that CA4P can effectively be combined with chemotherapy or radiotherapy. Finally, the potential of combining VDAs with antiangiogenic therapies has shown considerable promise in preclinical models and such combinations are now beginning to be evaluated in patients.

Endostatin, a fragment of the C-terminal domain of mouse collagen XVIII, is a recently demonstrated endogenous inhibitor of tumor angiogenesis. Although endostatin can be detected in blood and urine of tumor-bearing as well as normal mice, the exact localization of the endogenous protein and its related peptides in tumor tissues is unknown. We used immunohistochemistry and immunoblotting to identify endostatin tissue location and staining patterns in tumor, as well as to determine the differences in the levels of endostatin expression between tumor cells (in vitro) and tumor tissues (in vivo). Using a specific polyclonal antibody against murine endostatin, we quantitatively determined the levels of endostatin in five murine mammary tumors and the KHT sarcoma by Western blotting. The staining patterns for this protein in tumor sections were examined histologically by immunohistochemistry. Our results show that: (1) Endogenous endostatin and its related peptides are widely distributed in all in vivo tumor types tested, but not in most of the cultured tumor cell lines. (2) Endogenous endostatin stained most tumor stromal components, including vessel walls, basement membranes, extracellular spaces, and tumor cells. (3) Staining patterns and localization of endostatin and thrombospondin-1 were similar in these tumor sections.

Beer is a complex alcoholic beverage made from barley (malt), hop, water and yeast. Phenolic constituents of beer are derived from malt (70-80%) and hop (20-30%). Structural classes include simple phenols, benzoic- and cinnamic acid derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins, (prenylated) chalcones and flavonoids as well as alpha- and iso-alpha-acids derived from hop. Compounds belonging to different structural classes have distinct profiles of biological activity in in vitro test systems, and in combination might lead to enhanced effects. Scientific evidence has accumulated over the past 10 years pointing to the cancer preventive potential of selected hop-derived beer constituents, i.e., prenylflavonoids including xanthohumol and isoxanthohumol, and hop bitter acids. Chemopreventive activities observed with these compounds relevant to inhibition of carcinogenesis at the initiation, promotion and progression phases, as well as results from in vivo studies on metabolism, bioavailability and efficacy are summarised in this review.

Early clinical development of novel antiangiogenesis agents is hampered by the fact that classic response end points are unlikely to be relevant and there is a lack of validated surrogate markers of efficacy. Toxicity-based decisions for dose setting and tumor size measurements by standard imaging probably are not be applicable. Because these agents modify a multitude of biologic processes that may cause early measurable effects, there is great interest in developing imaging tests that are sensitive to changes in tissue function. This article discusses the development of such "functional" clinical imaging and attempts to address the questions that are being asked of imaging departments by oncologists and pharmaceutical companies.

The aim of this study was to determine the presence of angiostatin in ascitic and pleural effusions from cancer patients, as well as of metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA), both involved in angiostatin generation in in vitro models. Ascitic fluids, pleural exudates, and sera from 21 cancer patients were analyzed for the presence of angiostatin by western blot, whereas gelatinases MMP-2 and MMP-9, and uPA were evaluated by zymography. Our study revealed elevated levels of angiostatin in effusions of cancer patients, contrasting with mostly intermediate levels in less than half of their sera, and undetectable levels in normal sera. Despite the observation of enhanced levels of HMW-uPA and MMP-2 in malignant effusions from cancer patients, their analysis in individual samples showed no association between angiostatin presence and the enzymes, suggesting that the latter would not play an unimportant role, if any, in in vivo generation of angiostatin.