Angiogenesis May Be Fatal
Angiogenesis inhibitors are drugs or dietary components that restrain the growth of new blood vessels. As such, they prevent the development of tumor by obstructing its blood supply. Through this process, angiogenesis inhibitors have gained the reputation as effective cancer fighters. Furthermore, such inhibitors also fight cancers with fewer side effects as compared to the popular chemotherapy treatment. However, a new study conducted by researchers at UCLA’s Jonsson Cancer Center discovered that such method of blocking blood supply may result to serious and potentially deadly side effects.
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A number of newly developed angiogenesis inhibitors act by blocking vascular endothelial growth factor (VEGF). VEGF is an essential signaling protein that stimulates the growth of new blood vessels. For example, an approved angiogenesis inhibitor for colon and lung cancers, called Avastin, restrains VEGF that is signaling from outside of the cell.
Researchers at UCLA want to find out what would happen if VEGF signaling was blocked from within endothelial cells, which is a mechanism used by some small molecule drugs that are still being currently tested in late phase clinical trials. Conducting the research on laboratory mice, the scientists came up with an unexpected and sobering result. When VEGF signaling was blocked from within endothelial cells, more than half of the mice suffered from heart attacks and fatal strokes. These findings were reported by Luisa Iruela-Arispe, a professor of molecular, cell, and developmental biology and director of the Cancer Cell Biology program at UCLA’s Jonsson Cancer Center. She is also a past president of the North American Vascular Biology Organization and a national expert on angiogenesis.
Iruela-Arispe remarked that the results were extremely surprising. She then cautioned on the use of angiogenesis inhibitors in patients for very long periods of time. She further warns on the usage of inhibitors that block VEGF signaling from inside the cells. Aside from reporting on the results, she also further stated that blood clot-related side effects have developed in about five percent of patients taking Avastin. She further voiced her concern that the effects of long term Avastin use is still unclear since was only approved three years ago.
The laboratory mice that were used in the study were developed by Iruela-Arispe to have VEGF missing in the endothelial cells. Endothelial cells are cells that cover the inside of blood vessels. Such cells coat the circulatory system from the heart to the smallest capillary. Endothelial cells form a boundary between the circulating blood and the vessel wall. As such, they reduce friction between the blood vessels and the flow of blood.
Going back to the study, Iruela-Arispe and her team did not anticipate to see a great extent of effects since the amount of VEGF produced inside endothelial cells was al lot lesser compared to the levels of VEGF produced outside the cells. However, the results surprised the researches because fifty five percent of the laboratory mice died by 25 weeks of age, which is an equivalent of thirty in human age. The other mice that survived grew into old age but were very ill.
