Abstract: The idea of promoting angiogenesis in ischemic tissues remains an undisputed therapeutic approach for the treatment of myocardium and skeletal muscles that lack sufficient blood supply. However, clinical experiences from several large trials indicated that delivery of proangiogenic factors to patients suffering from myocardial infarction and leg ischemia has not shown significant benefits. Despite continuous success in various animal disease models, why has this simple principle not shown proof of concept in patients? What has been missing in the trial deign? What are the differences between animal models and patients? What are the optimal components for promoting functional collateral networks? This brief review discusses molecular mechanisms underlying arteriogenesis and proposes novel approaches for improvement of therapeutic outcomes. ... Read more

Abstract: Although thyroid carcinoma usually has an excellent prognosis, the lack of therapeutic options is an issue for patients that develop metastases and are resistant to radioiodine therapy. The development of novel molecular targeted therapies and the characterization of several proteins that have a crucial role in the carcinogenesis process of differentiated thyroid cancer have created an opportunity to design new clinical trials for this setting. Moreover, the encouraging initial results of first clinical trials have accelerated the development of placebo-controlled phase III studies that will assess the role of these new agents in the management of differentiated thyroid cancer. ... Read more

Abstract: Magnetic resonance imaging (MRI) provides essential information on anatomical location and morphology for diagnosis, therapy planning, and treatment evaluation in brain tumors, but lacks biological specificity. "Advanced" quantitative MRI methods yield additional metabolic and physiological indices relevant to tumor growth, vasculature, and ultrastructure; these improve lesion characterization and delineation, and provide potential biomarkers of treatment susceptibility and response. Validation and standardization of relevant parameters is required for use across multiple centers for large scale clinical trials of novel therapeutic regimens and to guide clinical management of individual patients. ... Read more

Abstract: Platelets are key players in hemostasis, but are also involved in fundamental processes of vascular biology such as angiogenesis, tissue regeneration, and tumor metastasis. Microparticles (MP) are small plasma membrane vesicles shed from cells upon their activation or apoptosis. Platelet-derived microparticles (PMP) constitute the majority of the pool of MP circulating in the blood. In this review we will summarize some possible roles of PMP other than participation in blood coagulation. PMP can express and transfer functional receptors from platelet membranes, increase expression of adhesion molecules on cells, stimulate the release of cytokines, activate intracellular signaling pathways, alter vascular reactivity, induce angiogenesis, and are involved in cancer metastasis. The role of PMP in cancer development is unknown but a high PMP level is highly correlated with aggressive tumors and a poor clinical outcome. It has been reported that PMP can stimulate proliferation and adhesion of cancer cells. Given their documented association with pathological conditions, PMP may serve as biomarkers for disease status or as a possible new target for anti-platelet drugs to treat cancer or inflammation. On the other hand, local PMP application may be found useful for developing novel therapeutic strategies targeting angiogenesis-related conditions. ... Read more

Abstract: Pulmonary hypertension is a disease that eventually leads to lung and/or heart failure. Because the causes were largely unknown, it has been called "idiopathic" pulmonary hypertension. Armed with new research tools and technologies, such as genetic and genomic analyses, scientists are now uncovering the causes and pathogenesis of the disease. New understandings of mechanisms of the disease are summarized. ... Read more

On May 19, 2003, Genentech announced that its anti-cancer drug Avastin “markedly” improved overall survival when combined with standard chemotherapy in a phase III clinical trial of colon cancer patients. Details of the trial were made available at the American Society of Clinical Oncology’s (ASCO) Annual Conference held in Chicago in early June (see below), though the few tidbits that were released on May 19 have proven to be especially juicy. Genentech stock was up 45% or an increase of $8.7 billion in market value following the news. The excitement lived on. In the ensuing days, Genentech stock was up ... Read more

Genentech reported on September 10th that its angiogenesis drug Avastin did not improve survival among 462 late stage breast cancer patients who had previously failed all other therapies. Genentech said that Avastin did shrink tumors in some patients but that the shrinkage did not offer survival benefits.

Scientists believe that the concept to choke off the tumor growth by deterring angiogenesis is still a sound approach in fighting cancer. But recently they grew increasingly skeptical whether blocking a single angiogenesis factor would do the trick. Scientists have found that late stage cancer cells, breast cancer in particular, can make as many ... Read more

Avastin is a widely-used, important first-line drug for colorectal cancer and lung cancer. The following lists key aspects of the drug.

Chemical/Biological Nature: Avastin (bevacizumab, rhuMAb-VEGF) is a recombinant humanized monoclonal antibody drug. Only the complementarity-determining regions (CDR) of the antibody are of mouse origin since the antibody was originally produced in mice. In order to reduce the antigenicity of the antibody to patients, all other regions of the antibody are of human origin. CDRs of an antibody make physical contact with the specific antigen and determine the antibody’s specificity.

Maker: Genentech

Diseases Treated: Metastatic colorectal cancer — approved on February 26, 2004; ... Read more