腫瘤細胞在生長分裂的過程中,，必須經(jīng)由血管透過源源不絕的血液，提供足夠的養(yǎng)份，因此絕大多數(shù)的癌細胞表面,，都存在著吸引血管上皮生長因子 (vascular endothelial growth factor,；簡稱 VEGF)的受體蛋白，因此科學家就利用著這個特點,，設(shè)計出可能成為抗癌武器的新一代藥物,。
這次由美國德州大學 M.D.安德遜癌癥中心的科學家所參與的研究計劃，利用上述癌細胞的特性 開發(fā)出一種融合分子,，據(jù)了解這個分子主要是由一個最小的VEGF蛋白質(zhì),，黏附著稱為 gelonin的毒性分子，研究人員想利用癌細胞會吸附 VEGF蛋白質(zhì)的特性,，將毒性分子拉近,，完成毒殺癌細胞的作用。
參與計劃的科學家,，利用惡名昭彰的前列腺癌細胞 (prostate cancer cells),，注射到實驗動物模型的小鼠骨髓中，再透過上述的融合分子加以治療,，結(jié)果移殖癌細胞的小鼠,，在提供融合分子的實驗組中，居然沒有任何惡性腫瘤的蹤跡,，可見的這個抗癌的融合分子,，確實具有毒殺癌細胞的功效。
英文原文：
‘Trojan Horse’ Technology Destroys Blood Supply to Cancer Tumors in Mice
Researchers at M. D. Anderson and The University of Texas Southwestern Medical Center at Dallas have demonstrated in mice that a new drug formed by linking a vascular endothelial growth factor to a toxin will target and destroy the blood vessels supplying a malignant tumor.
Dr. Michael Rosenblum, professor of medicine at M. D. Anderson, said tests of VEGF121/rGelonin (VEGF/rGel) in mice demonstrated it could selectively destroy blood vessels supplying human solid tumors without harming the vasculature of normal tissue.
“This is like a ‘Trojan horse’ approach to kill the blood vessels that supply solid tumors. We’re using the vascular endothelial growth factor (VEGF) as a carrier to deliver a toxic agent selectively to the tumor’s blood supply – in effect, starving the tumor,” said Dr. Rosenblum, senior author of the study.
The research, which is in the June 11 Proceedings of the National Academy of Sciences, was the result of an ongoing collaboration between UT Southwestern and M. D. Anderson. VEGF/rGel was designed jointly and developed at M. D. Anderson and UT Southwestern.
For the study, mice were injected with human melanoma and human prostate cancer cells. The research showed that tumor growth in the mice that received VEGF/rGel was reduced to 16% of the untreated mice, said Dr. Philip Thorpe, Professor of Pharmacology, who directed tests of VEGF/rGel at UT Southwestern with Dr. Sophia Ran, Assistant Professor of Pharmacology. Both are affiliated with the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.
“The anti-tumor effects of the VEGF/rGel fusion construct against both melanoma and human prostate cancer in mouse models was impressive in magnitude and prolonged,” Dr. Thorpe said. “These studies suggest that VEGF/rGel has potential as an anti-tumor agent for treating cancer patients.”
A clinical trial to test the new technique in patients is expected to begin within the year at M. D. Anderson, Dr. Rosenblum said.
“The significance of this fusion toxin is that it’s not specific to one kind of tumor – it has impressive anti-tumor effects in various kinds of tumors – including melanoma and prostate cancers,” Dr. Rosenblum said. “We need additional research to determine if it is equally effective in other cancers.”
In the mouse study, destruction of the tumor blood vessels was observed as early as 48 hours after administration of the VEGF/rGel. There was no visible damage in any normal organs, including the kidneys, of the treated mice, Dr. Rosenblum said.
VEGF is one of the predominant factors responsible for angiogenesis – the ability of a tumor to create new blood vessels to maintain growth and metastasize.
The researchers chose the genetically engineered toxin gelonin to link to the VEGF “carrier” because it does not appear to be antigenic in human clinical trials conducted thus far at M. D. Anderson, and it does not cause damage to normal blood vessels as do other toxins that have been explored for use in anti-tumor therapies, Dr. Rosenblum said.
Genetically engineered gelonin was developed in a research program at M. D. Anderson, and related intellectual property rights are owned by Research Development Foundation (RDF). RDF is in the process of licensing the gelonin technology for use with various cell-targeting proteins such as growth factors and antibodies.
Therapies that attack tumor blood vessels have recently been a hot area in cancer research because they appear to bypass the major problem with chemotherapy – the tumor cells’ ability to mutate and develop resistance to the drugs.
Other researchers from M. D. Anderson who contributed to the work were Liesbeth M. Veenendaal, Lawrence Cheung, Nora Navone, and Hangqing Jin. The Med. Klinik und Poliklinik der Universität Ulm in Germany also contributed to the research. The work was supported in part by the University of Utrecht and the Dutch Cancer Foundation, Koningen Wilhelmina Funds, the National Institutes of Health and Arcus Therapeutics.
