Abstract: Despite the recent advances in its management using cytoreductive surgery and chemotherapy, ovarian cancer remains the most lethal gynecological malignancy. One possible treatment strategy that may improve patient outcome is the use of monoclonal antibodies (mAb) that selectively target tumor cells expressing tumor-associated antigens, and thus offer potential benefits such as avoiding the cytotoxic side effects in normal tissue caused by traditional chemotherapeutic agents. Based on the promising results of preclinical studies, various mAb are currently being evaluated in patients with ovarian cancer. Some of them have already demonstrated favorable clinical outcomes in phase I/II studies. However, in contrast to its use for hematological malignancies and certain solid malignancies such as breast and colorectal cancer, mAb-based therapy has not been convincingly proven to be clinically effective in patients with ovarian cancer. As the preclinical results of mAb's therapeutic effects on ovarian cancer have been encouraging, further investigations are needed to establish a more effective, specific, and less toxic treatment strategy for this malignancy. ... Read more

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: Age-related Macular Degeneration (AMD) is the major cause of vision loss after age 50 in the United States. Although an important association of the complement cascade with AMD has recently been made, we still do not understand the pathogenesis of the disease. AMD is characterized by loss of the retinal pigment epithelium (RPE) within the macula (i.e., the center of the retina), and in turn, loss of the overlying foveal photoreceptors. Since RPE and photoreceptors can both be generated from stem cells using cell culture, there is hope for future cell replacement therapy. But, aging changes in Bruch's membrane, the scaffold on which the RPE are anchored, may complicate such therapy, and require surgical repair of Bruch's membrane to provide a suitable environment for cell survival and function. We have referred to such a multipronged approach of surgical reconstruction of the macular architecture in conjunction with cell transplantation as Maculoplasty. ... 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: In the past 5 years the management of metastatic renal cell carcinoma has been revolutionized by the advent of anti-angiogenic treatments, particularly the multi-targeted kinase inhibitors. This revolution has put standard and experimental immunotherapy in the shade. However, it is likely that a subset of patients with advanced kidney cancer is still best served by immunotherapy. This article summarizes promising novel immunotherapeutic techniques to identify those patients who will benefit and to optimize outcomes for patients using novel immunotherapeutic approaches. ... Read more

Abstract: Growth of new blood vessels (angiogenesis) is essential for embryo development as well as for wound healing and progression of a number of diseases such as cancer, inflammatory conditions, eye diseases, psoriasis, and rheumatoid arthritis in the adult. Current paradigms explain blood vessel growth entirely by sprouting angiogenesis or by vessel splitting through so called intussusceptive angiogenesis. However, these mechanisms are mainly derived from experiments on the developing embryo while less is known about angiogenesis in the adult during, e.g., wound healing, tumor growth, and inflammation. Recently we showed that blood vessel growth in the adult can be induced and directed by mechanical forces that naturally develop during healing or remodeling of tissues. In contrast to sprouting and intussusception, the new biomechanical hypothesis assumes that functional blood vessels are passively translocated which, if found generic, may drastically change the approach for developing anti- and pro-angiogenic therapies in the treatment of a variety of diseases. ... Read more

Abstract: Scar formation is a dreaded consequence of eye surgery. It is invariably associated with inflammation, angiogenesis and wound healing. There is always a balance in healing the wound with the least scar formation possible. Certain dendrimers (polymers) compounds help keep this balance by reducing inflammation and thus scar formation but leaving the wound healing process largely intact. ... Read more

Other Names: bevacizumab, rhuMAb-VEGF.

Maker: Genentech, Inc.

Disease Treated: Metastatic colorectal cancer.

Approval Status: Approved by the U.S. FDA on February 26, 2004 as a first-line therapy in combination with intravenous 5-fluorouracil-based chemotherapy for the treatment of metastatic colorectal cancer.

Chemical/Biological Nature: AVASTIN is a recombinant humanized monoclonal IgG1 antibody composed of the human antibody framework regions integrated with the complimentarity-determining regions (in contact with its target antigen) of mouse origin. AVASTIN is produced in a Chinese Hamster ovary mammalian cell expression cell culture system.

Administration: AVASTIN with a dose of 5mg/kg body weight is administered by i.v. infusion over a 90-minute period following chemotherapy. ... Read more