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Neurosurgical Development over 55 Years: A Story from Soochow University Jun Dong, Hua Chen, Qing Lan, Qiang Huang
H
ua Chen won the Young Neurosurgeons Award (YNSA) at the Fifteenth World Federation of Neurosurgical Societies (WFNS) World Congress, which was the fourth time for our team at Soochow University, the only institutional winner of the WFNS YNSA in Mainland China to achieve such an honor since the Ninth WFNS World Congress in 1989. So far, 5 young Chinese neurosurgeons have won the award, including George K.C. Wong of The Chinese University of Hong Kong, who also won the Fifteenth WFNS YNSA. There are altogether 46 individuals who have won this award, among whom 10.9% are Chinese. We at Soochow University feel deeply proud and cannot help asking how we have achieved this honor. The answer lies in our development over the last 55 years. INTRODUCING STATE-OF-THE-ART TECHNOLOGIES The Neurosurgical Department of Soochow University (formerly the Neurosurgical Department of Soochow Medical School) was established under the leadership of YaoDong Bao as a department dedicated to diagnosis and treatment of common injuries and tumors of the central nervous system. In 1972, Ziwei Du returned to China from Keio University in Japan. He worked in the Neurosurgery Department of Soochow Medical School and applied clinically the operating microscope and microsurgical instruments he brought back from Japan. Our department won the Scientific and Technical Progress Award at the National Science and Technology Conference in 1978 as the first department capable of microscopically conducting cerebral aneurysm clipping, intracranial arteriovenous malformation resection, microvascular decompression for trigeminal neuralgia, and superficial temporal arteryemiddle cerebral artery anastomosis. At that time in China, some neurosurgeons in other institutions employed oldfashioned methods to treat ruptured aneurysms by thread-knotting the intracranial aneurysm neck and trigeminal neuralgia by resecting the sensory root of the semilunar ganglion. FILLING IN THE DOMESTIC GAP When Ziwei Du returned to China, he brought with him a complete set of equipment and reagents for cell culture and started the
Key words Education - Training - Young Neurosurgeons Award -
Abbreviations and Acronyms GSCs: Glioma stem cells WFNS: World Federation of Neurosurgical Societies YNSA: Young Neurosurgeons Award
first round of research on human glioma culture in vitro in Mainland China. In 1984, after 12 years of diligent work, we finally established the first human glioma cell line SHG-44 (currently preserved in the Cell Bank Institute of Cell Biology of the Chinese Academy of Sciences for use by institutions) from the forty-fourth human glioblastoma multiforme sample in China. We implanted SHG-44 in nude mice from the Animal Center of Fujita Health University in Japan to establish human glioma model NHG-1 and obtained the first monoclonal antibody cell strain SZ39 of human glioma hybridoma by using NHG-1 in China. The monoclonal antibody was labeled with radioactive iodine 131 and sulfur 35 for biological targeted experimental diagnosis and treatment research (7, 9, 19). On this basis, we revealed the chromosomal character of glioma in the Chinese population (12) and proved that hexamethylene bisacetamide and dimethylformamide had significant induced differentiation function for SHG-44 in vitro (10, 11). All of these were unprecedented findings reported in China. MOVING TOWARD INTERNATIONAL FRONTIERS In the 21st century, particular emphasis of our research has been on biological characteristics of glioma stem cells (GSCs). First, we established 3 strains of GSCs named after Soochow University— SU1, SU2, and SU3 (8). In a comparative study of induced differentiation of GSCs and neural stem cells, we found GSCs could not reach terminal differentiation and would dedifferentiate with the absence of differentiation inducer. We put forward the opinion that differentiated GSCs could return to stem cell status under favorable conditions for the first time in the international community (21). Our study showed that GSCs, despite their ability to dedifferentiate, could transdifferentiate into endotheliumlike cells under hypoxic conditions (23); we further found that GSCs played a major role in the tissue remodeling of gliomas, especially in the formation of blood vessels of tumors in nude mice (5, 6). The digital version of our findings was published earlier than the 2 articles concurrently published in Nature by Wang (18) and RicciVtiani (16); their research is more widely accepted as being more intensive than ours.
Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China To whom correspondence should be addressed: Qiang Huang, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2014) 81, 3/4:464-467. http://dx.doi.org/10.1016/j.wneu.2014.01.002 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
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We comprehensively analyzed our findings about the roles of GSCs in gliomagenesis and progression (4), which led us to investigate the tumor microenvironment and the roles of host in establishing the tumor microenvironment. We then built a genetically modified human glioma nude mice model of SU3-RFPGFP double fluorescence trace (3). Despite the presence of fused cells expressing both red fluorescent protein and green fluorescent protein in transplanted tumor tissues, there were malignantly transformed host stromal cells cloned from tumor tissues. Malignant transformation of host cells was also observed in vitro and could be attributed to a cell fusion mechanism, which is now being analyzed further.
CULTIVATING OUTSTANDING YOUNG NEUROSURGEONS The Johns Hopkins University has been endeavoring to become a research-based university since its foundation and is dedicated to cultivating interdisciplinary talents who are both clinical surgeons and scientists. Madjid Samii systematically illustrated the fact that both clinical skills and scientific thinking should be practiced during the cultivation of outstanding young neurosurgeons at the Fifteenth WFNS World Congress. In review, we found that the glioma research team led by Ziwei Du also followed this developmental pattern. The supervisor of Ziwei Du—Tatsuyuki Kudo, the founder of the Neurosurgical Department at Keio University and one of the discoverers of moyamoya disease—advocated combining clinical practice, research, and teaching to cultivate young neurosurgeons, from which Du benefited a great deal. After returning to China, Du dispatched his students Qiang Huang and Dai Zhou to study with Tetsuo Kanno at Fujita Health University Hospital in Japan for more than 1 year. Huang and Zhou continued their research on gliomas and cerebrovascular diseases after returning to China and became neurosurgical professors and chairmen of the second and first affiliated hospitals, respectively, of Soochow University. They both subsequently followed the same pattern; Huang’s students Qing Lan, Jun Dong, and Quanbin Zhang studied with Axel Perneczky at Mainz University in Germany, with Kiyoshi Matsumoto at Showa University in Japan, with Takashi Kawase at Keio University in Japan, and with Robert Arceci at The Johns Hopkins University in the United States. Both Qing Lan and Jun Dong are currently professors and doctoral supervisors, and Quanbin Zhang is an associate professor and master supervisor. Qing Lan is department director and the authority on keyhole neurosurgery in China (14, 15). Annual training of the neurosurgical keyhole approach has been offered 13 times since 2001, making a great contribution to the promotion of the neurosurgical keyhole approach in China. Another member of our team, Zhongping Chen, also followed this pattern. After obtaining a Doctor of Medicine degree, he pursued clinical and basic research on the central nervous system at McGill University in 1993 (13, 20). After returning to China in 1999, he worked at Sun Yat-sen University Cancer Center in Guangzhou and is now department director, professor, doctoral supervisor, former President of the Chinese Society of Neurooncology, editor-in-chief of Chinese Journal of Neuro-Oncology, and a leading expert in the glioma field of China (Figure 1).
WORLD NEUROSURGERY 81 [3/4]: 464-467, MARCH/APRIL 2014
Figure 1. Three generations of professors on our glioma research team. Ziwei Du (born 1931) (A) is the supervisor of Qiang Huang (born 1936) (B) and Zhongping Chen (born 1957) (C). Qiang Huang is the teacher of Qing Lan (born 1964) (D) and Jun Dong (born 1971) (E).
Under the guidance of Du and Huang, 4 young neurosurgeons have won the WFNS YNSA. These individuals are working even harder at their posts with the encouragement of the award. JianHong Zhu was the winner of the Ninth WFNS YNSA; his award-winning article is entitled “Preclinical Trials with Monoclonal Antibody-Adriamycin Immunoconjugates for the Targeting Chemotherapy of Human Brain Gliomas” (Figure 2A). He is currently the Yangtze River Scholar of the Ministry of Education; vice-chairman of the state key laboratory of medical neurobiology of Fudan University; and a professor at Huashan Hospital who is dedicated to research on biology of neural stem cells, repairing of neural injury, and central nervous system tumors. His work on tracking neural stem cells in patients with brain trauma was published in The New England Journal of Medicine (26). His research on brain tumor antiangiogenic gene therapy was judged the best paper at the International Conference on Gene Therapy of Cancer in 1999. He is treasurer of the
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Figure 2. (A) JianHong Zhu, winner of Ninth World Federation of Neurosurgical Societies Young Neurosurgeons Award. (B) XiaoNan Li, winner of Eleventh World Federation of Neurosurgical Societies Young Neurosurgeons Award. (C) YaoDong Zhao, winner of Fourteenth World Federation of Neurosurgical Societies Young Neurosurgeons Award. (D) Hua Chen, winner of Fifteenth World Federation of Neurosurgical Societies Young Neurosurgeons Award.
Asian Australasian Society of Neurological Surgeons, leading scientist of “973” Major Scientific Research Project, vice-chairman of the Neuro-oncology Committee of the Chinese Anti-Cancer Association, editor of Regenerative Medicine and Reviews on Clinical Trials, and deputy editor-in-chief of Chinese Journal of Neuro-Oncology.
REFERENCES 1. Chen H, Dong J, Huang Q: Xenograft model of human brain tumor. In: Abujamra AL, ed. Brain Tumors—Current and Emerging Therapeutic Strategies. Rijeka, Croatia: InTech; 2011:3-20. 2. Chen H, Huang Q, Dong J, Zhai DZ, Wang AD, Lan Q: Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo. BMC Cancer 8:29, 2008. 3. Dong J, Dai XL, Lu ZH, Fei XF, Chen H, Zhang QB, Zhao YD, Wang ZM, Wang AD, Lan Q, Huang Q: Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling. Chin Med J (Engl) 125:4349-4354, 2012.
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XiaoNan Li was winner of the Eleventh WFNS YNSA; his awardwinning article is entitled “Growth-Inhibitory and DifferentiationInducing Activity of Dimethylformamide in Cultured Human Malignant Glioma Cells” (Figure 2B). He is now associate professor at Texas Children’s Cancer and Hematology Centers where he established the first array of brain tumor models of up to 30 different pathologic types and for the first time proved that tumor stem cells could be preserved for a long time in animal models established on the basis of primary tumor. He has published more than 60 articles in academic journals including Stem Cells, Proceedings of the National Academy of Sciences of the United States of America, Clinic Cancer Research, and Cancer Research (17, 22). YaoDong Zhao was winner of the Fourteenth WFNS YNSA; his award-winning article is entitled “Autophagy Impairment Inhibits Differentiation of Glioma” (Figure 2C). He is now associate professor of the Neurosurgical Department of Shanghai 10th People’s Hospital Affiliated Tongji University and associate researcher at Tongji University in Shanghai. He published 7 articles collected by the Science Citation Index in the field of GSCs (24, 25). Zhao also won the Hoshino Award at the Third Quadrennial Meeting of the World Federation of Neuro-Oncology in 2009. In 2012, Zhao won the I. A. Raja Award at the Ninth Asian Congress of Neurological Surgeons in Turkey. With the financial support of the National Natural Science Foundation (Grant No. 81101909), he is currently continuing his research on mechanisms of transdifferentiation of GSCs into endotheliumlike cells under hypoxic conditions, which was discovered by him. Hua Chen was winner of the Fifteenth WFNS YNSA; his awardwinning article is entitled “Glioma Stem Cells Induce Host Cells Canceration by Cell Fusion: Evidence and Thinking from Cell Sociology” (Figure 2D). He now works in the Neurosurgical Department of Nanjing–Hospital-Affiliated Nanjing Medical University (Nanjing First Hospital) and continues basic and clinical research on human gliomas. He proved the significant role of cell division cycle 2 in glioma progression with gene knockdown technology (2). With the financial support of the National Natural Science Foundation (Grant No. 81302180), he currently is conducting further research into the role of host bone marrowederived cells in the glioma microenvironment by using self-made double color fluorescent glioma models (1).
4. Dong J, Huang Q: Targeting glioma stem cells: enough to terminate gliomagenesis? Chin Med J (Engl) 124:2756-2763, 2011. 5. Dong J, Zhang Q, Huang Q, Chen H, Shen Y, Fei X, Zhang T, Diao Y, Wu Z, Qin Z, Lan Q, Gu X: Glioma stem cells involved in tumor tissue remodeling in a xenograft model. J Neurosurg 113: 249-260, 2010. 6. Dong J, Zhao Y, Huang Q, Fei X, Diao Y, Shen Y, Xiao H, Zhang T, Lan Q, Gu X: Glioma stem/ progenitor cells contribute to neovascularization via transdifferentiation. Stem Cell Rev 7:141-152, 2011. 7. Huang Q, He G, Lan Q, Li X, Qian Z, Chen J, Lu Z, Du Z: Target imaging diagnosis of human brain glioma. Clinical analysis of 40 cases. Chin Med J (Engl) 109:93-96, 1996.
8. Huang Q, Zhang QB, Dong J, Wu YY, Shen YT, Zhao YD, Zhu YD, Diao Y, Wang AD, Lan Q: Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the primary tumor, and both can be maintained long-term in vitro. BMC Cancer 8:304, 2008. 9. Lan Q, Huang Q, Bao S: Preclinical evaluation of SPECT imaging with 131I-labeled monoclonal antibody SZ39 in nude mice bearing human glioma xenografts. J Neuroimaging 6:131-135, 1996. 10. Li XN, Du ZW, Huang Q: Modulation effects of hexamethylene bisacetamide on growth and differentiation of cultured human malignant glioma cells. J Neurosurg 84:831-838, 1996. 11. Li XN, Du ZW, Huang Q, Wu JQ: Growthinhibitory and differentiation-inducing activity of dimethylformamide in cultured human malignant
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glioma cells. Neurosurgery 40:1250-1258 [discussion 1258-1259], 1997. 12. Li XN, Huang Q, Du ZW: Methodologic study of direct preparation for chromosome analysis of human solid brain tumors. Cancer Genet Cytogenet 58:160-164, 1992. 13. Liu XM, Zhang QP, Mu YG, Zhang XH, Sai K, Pang JC, Ng HK, Chen ZP: Clinical significance of vasculogenic mimicry in human gliomas. J Neurooncol 105:173-179, 2011. 14. Ma Y, Lan Q: Supraorbital keyhole approach to upper basilar artery aneurysms via the opticocarotid window: a cadaveric anatomic study and preliminary application. Minim Invasive Neurosurg 54:228-235, 2011. 15. Ma Y, Lan Q: An anatomic study of the occipital transtentorial keyhole approach. World Neurosurg 80:183-189, 2013. 16. Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, Maira G, Parati EA, Stassi G, Larocca LM, De Maria R: Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468:824-828, 2010. 17. Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT, Antalffy BC, Baxter P, Perlaky L, Yang J, Dauser RC, Chintagumpala M, Blaney SM,
NEUROSURGERY AT SOOCHOW UNIVERSITY
Lau CC, Li XN: Direct orthotopic transplantation of fresh surgical specimen preserves CD133þ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 26: 1414-1424, 2008. 18. Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C, Tabar V: Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468: 829-833, 2010. 19. Yang WL, Du ZW, Huang Q: Localization of 131Ilabelled anti-glioma monoclonal antibody SZ-39 in human brain tumor transplanted in nude mice. Chin Med J (Engl) 101:919-922, 1988.
orthotopic xenograft mouse models of medulloblastoma. Neuro Oncol 14:574-583, 2012. 23. Zhao Y, Dong J, Huang Q, Lou M, Wang A, Lan Q: Endothelial cell transdifferentiation of human glioma stem progenitor cells in vitro. Brain Res Bull 82:308-312, 2010. 24. Zhao Y, Huang Q, Wang A, Dong J, Lan Q: Mutation of PTEN in glioma stem/progenitor cells: a case report. Cancer Genet Cytogenet 195: 183-185, 2009. 25. Zhao Y, Huang Q, Yang J, Lou M, Wang A, Dong J, Qin Z, Zhang T: Autophagy impairment inhibits differentiation of glioma stem/progenitor cells. Brain Res 1313:250-258, 2010.
20. Yue WY, Yu SH, Zhao SG, Chen ZP: Molecular markers relating to malignant progression in Grade II astrocytoma. J Neurosurg 110:709-714, 2009.
26. Zhu J, Zhou L, XingWu F: Tracking neural stem cells in patients with brain trauma. N Engl J Med 355:2376-2378, 2006.
21. Zhang QB, Ji XY, Huang Q, Dong J, Zhu YD, Lan Q: Differentiation profile of brain tumor stem cells: a comparative study with neural stem cells. Cell Res 16:909-915, 2006.
Citation: World Neurosurg. (2014) 81, 3/4:464-467. http://dx.doi.org/10.1016/j.wneu.2014.01.002
22. Zhao X, Liu Z, Yu L, Zhang Y, Baxter P, Voicu H, Gurusiddappa S, Luan J, Su JM, Leung HC, Li XN: Global gene expression profiling confirms the molecular fidelity of primary tumor-based
WORLD NEUROSURGERY 81 [3/4]: 464-467, MARCH/APRIL 2014
Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
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Neurosurgical Development over 55 Years: A Story from Soochow University Jun Dong, Hua Chen, Qing Lan, Qiang Huang
H
ua Chen won the Young Neurosurgeons Award (YNSA) at the Fifteenth World Federation of Neurosurgical Societies (WFNS) World Congress, which was the fourth time for our team at Soochow University, the only institutional winner of the WFNS YNSA in Mainland China to achieve such an honor since the Ninth WFNS World Congress in 1989. So far, 5 young Chinese neurosurgeons have won the award, including George K.C. Wong of The Chinese University of Hong Kong, who also won the Fifteenth WFNS YNSA. There are altogether 46 individuals who have won this award, among whom 10.9% are Chinese. We at Soochow University feel deeply proud and cannot help asking how we have achieved this honor. The answer lies in our development over the last 55 years. INTRODUCING STATE-OF-THE-ART TECHNOLOGIES The Neurosurgical Department of Soochow University (formerly the Neurosurgical Department of Soochow Medical School) was established under the leadership of YaoDong Bao as a department dedicated to diagnosis and treatment of common injuries and tumors of the central nervous system. In 1972, Ziwei Du returned to China from Keio University in Japan. He worked in the Neurosurgery Department of Soochow Medical School and applied clinically the operating microscope and microsurgical instruments he brought back from Japan. Our department won the Scientific and Technical Progress Award at the National Science and Technology Conference in 1978 as the first department capable of microscopically conducting cerebral aneurysm clipping, intracranial arteriovenous malformation resection, microvascular decompression for trigeminal neuralgia, and superficial temporal arteryemiddle cerebral artery anastomosis. At that time in China, some neurosurgeons in other institutions employed oldfashioned methods to treat ruptured aneurysms by thread-knotting the intracranial aneurysm neck and trigeminal neuralgia by resecting the sensory root of the semilunar ganglion. FILLING IN THE DOMESTIC GAP When Ziwei Du returned to China, he brought with him a complete set of equipment and reagents for cell culture and started the
Key words Education - Training - Young Neurosurgeons Award -
Abbreviations and Acronyms GSCs: Glioma stem cells WFNS: World Federation of Neurosurgical Societies YNSA: Young Neurosurgeons Award
first round of research on human glioma culture in vitro in Mainland China. In 1984, after 12 years of diligent work, we finally established the first human glioma cell line SHG-44 (currently preserved in the Cell Bank Institute of Cell Biology of the Chinese Academy of Sciences for use by institutions) from the forty-fourth human glioblastoma multiforme sample in China. We implanted SHG-44 in nude mice from the Animal Center of Fujita Health University in Japan to establish human glioma model NHG-1 and obtained the first monoclonal antibody cell strain SZ39 of human glioma hybridoma by using NHG-1 in China. The monoclonal antibody was labeled with radioactive iodine 131 and sulfur 35 for biological targeted experimental diagnosis and treatment research (7, 9, 19). On this basis, we revealed the chromosomal character of glioma in the Chinese population (12) and proved that hexamethylene bisacetamide and dimethylformamide had significant induced differentiation function for SHG-44 in vitro (10, 11). All of these were unprecedented findings reported in China. MOVING TOWARD INTERNATIONAL FRONTIERS In the 21st century, particular emphasis of our research has been on biological characteristics of glioma stem cells (GSCs). First, we established 3 strains of GSCs named after Soochow University— SU1, SU2, and SU3 (8). In a comparative study of induced differentiation of GSCs and neural stem cells, we found GSCs could not reach terminal differentiation and would dedifferentiate with the absence of differentiation inducer. We put forward the opinion that differentiated GSCs could return to stem cell status under favorable conditions for the first time in the international community (21). Our study showed that GSCs, despite their ability to dedifferentiate, could transdifferentiate into endotheliumlike cells under hypoxic conditions (23); we further found that GSCs played a major role in the tissue remodeling of gliomas, especially in the formation of blood vessels of tumors in nude mice (5, 6). The digital version of our findings was published earlier than the 2 articles concurrently published in Nature by Wang (18) and RicciVtiani (16); their research is more widely accepted as being more intensive than ours.
Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China To whom correspondence should be addressed: Qiang Huang, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2014) 81, 3/4:464-467. http://dx.doi.org/10.1016/j.wneu.2014.01.002 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.
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We comprehensively analyzed our findings about the roles of GSCs in gliomagenesis and progression (4), which led us to investigate the tumor microenvironment and the roles of host in establishing the tumor microenvironment. We then built a genetically modified human glioma nude mice model of SU3-RFPGFP double fluorescence trace (3). Despite the presence of fused cells expressing both red fluorescent protein and green fluorescent protein in transplanted tumor tissues, there were malignantly transformed host stromal cells cloned from tumor tissues. Malignant transformation of host cells was also observed in vitro and could be attributed to a cell fusion mechanism, which is now being analyzed further.
CULTIVATING OUTSTANDING YOUNG NEUROSURGEONS The Johns Hopkins University has been endeavoring to become a research-based university since its foundation and is dedicated to cultivating interdisciplinary talents who are both clinical surgeons and scientists. Madjid Samii systematically illustrated the fact that both clinical skills and scientific thinking should be practiced during the cultivation of outstanding young neurosurgeons at the Fifteenth WFNS World Congress. In review, we found that the glioma research team led by Ziwei Du also followed this developmental pattern. The supervisor of Ziwei Du—Tatsuyuki Kudo, the founder of the Neurosurgical Department at Keio University and one of the discoverers of moyamoya disease—advocated combining clinical practice, research, and teaching to cultivate young neurosurgeons, from which Du benefited a great deal. After returning to China, Du dispatched his students Qiang Huang and Dai Zhou to study with Tetsuo Kanno at Fujita Health University Hospital in Japan for more than 1 year. Huang and Zhou continued their research on gliomas and cerebrovascular diseases after returning to China and became neurosurgical professors and chairmen of the second and first affiliated hospitals, respectively, of Soochow University. They both subsequently followed the same pattern; Huang’s students Qing Lan, Jun Dong, and Quanbin Zhang studied with Axel Perneczky at Mainz University in Germany, with Kiyoshi Matsumoto at Showa University in Japan, with Takashi Kawase at Keio University in Japan, and with Robert Arceci at The Johns Hopkins University in the United States. Both Qing Lan and Jun Dong are currently professors and doctoral supervisors, and Quanbin Zhang is an associate professor and master supervisor. Qing Lan is department director and the authority on keyhole neurosurgery in China (14, 15). Annual training of the neurosurgical keyhole approach has been offered 13 times since 2001, making a great contribution to the promotion of the neurosurgical keyhole approach in China. Another member of our team, Zhongping Chen, also followed this pattern. After obtaining a Doctor of Medicine degree, he pursued clinical and basic research on the central nervous system at McGill University in 1993 (13, 20). After returning to China in 1999, he worked at Sun Yat-sen University Cancer Center in Guangzhou and is now department director, professor, doctoral supervisor, former President of the Chinese Society of Neurooncology, editor-in-chief of Chinese Journal of Neuro-Oncology, and a leading expert in the glioma field of China (Figure 1).
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Figure 1. Three generations of professors on our glioma research team. Ziwei Du (born 1931) (A) is the supervisor of Qiang Huang (born 1936) (B) and Zhongping Chen (born 1957) (C). Qiang Huang is the teacher of Qing Lan (born 1964) (D) and Jun Dong (born 1971) (E).
Under the guidance of Du and Huang, 4 young neurosurgeons have won the WFNS YNSA. These individuals are working even harder at their posts with the encouragement of the award. JianHong Zhu was the winner of the Ninth WFNS YNSA; his award-winning article is entitled “Preclinical Trials with Monoclonal Antibody-Adriamycin Immunoconjugates for the Targeting Chemotherapy of Human Brain Gliomas” (Figure 2A). He is currently the Yangtze River Scholar of the Ministry of Education; vice-chairman of the state key laboratory of medical neurobiology of Fudan University; and a professor at Huashan Hospital who is dedicated to research on biology of neural stem cells, repairing of neural injury, and central nervous system tumors. His work on tracking neural stem cells in patients with brain trauma was published in The New England Journal of Medicine (26). His research on brain tumor antiangiogenic gene therapy was judged the best paper at the International Conference on Gene Therapy of Cancer in 1999. He is treasurer of the
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Figure 2. (A) JianHong Zhu, winner of Ninth World Federation of Neurosurgical Societies Young Neurosurgeons Award. (B) XiaoNan Li, winner of Eleventh World Federation of Neurosurgical Societies Young Neurosurgeons Award. (C) YaoDong Zhao, winner of Fourteenth World Federation of Neurosurgical Societies Young Neurosurgeons Award. (D) Hua Chen, winner of Fifteenth World Federation of Neurosurgical Societies Young Neurosurgeons Award.
Asian Australasian Society of Neurological Surgeons, leading scientist of “973” Major Scientific Research Project, vice-chairman of the Neuro-oncology Committee of the Chinese Anti-Cancer Association, editor of Regenerative Medicine and Reviews on Clinical Trials, and deputy editor-in-chief of Chinese Journal of Neuro-Oncology.
REFERENCES 1. Chen H, Dong J, Huang Q: Xenograft model of human brain tumor. In: Abujamra AL, ed. Brain Tumors—Current and Emerging Therapeutic Strategies. Rijeka, Croatia: InTech; 2011:3-20. 2. Chen H, Huang Q, Dong J, Zhai DZ, Wang AD, Lan Q: Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo. BMC Cancer 8:29, 2008. 3. Dong J, Dai XL, Lu ZH, Fei XF, Chen H, Zhang QB, Zhao YD, Wang ZM, Wang AD, Lan Q, Huang Q: Incubation and application of transgenic green fluorescent nude mice in visualization studies on glioma tissue remodeling. Chin Med J (Engl) 125:4349-4354, 2012.
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XiaoNan Li was winner of the Eleventh WFNS YNSA; his awardwinning article is entitled “Growth-Inhibitory and DifferentiationInducing Activity of Dimethylformamide in Cultured Human Malignant Glioma Cells” (Figure 2B). He is now associate professor at Texas Children’s Cancer and Hematology Centers where he established the first array of brain tumor models of up to 30 different pathologic types and for the first time proved that tumor stem cells could be preserved for a long time in animal models established on the basis of primary tumor. He has published more than 60 articles in academic journals including Stem Cells, Proceedings of the National Academy of Sciences of the United States of America, Clinic Cancer Research, and Cancer Research (17, 22). YaoDong Zhao was winner of the Fourteenth WFNS YNSA; his award-winning article is entitled “Autophagy Impairment Inhibits Differentiation of Glioma” (Figure 2C). He is now associate professor of the Neurosurgical Department of Shanghai 10th People’s Hospital Affiliated Tongji University and associate researcher at Tongji University in Shanghai. He published 7 articles collected by the Science Citation Index in the field of GSCs (24, 25). Zhao also won the Hoshino Award at the Third Quadrennial Meeting of the World Federation of Neuro-Oncology in 2009. In 2012, Zhao won the I. A. Raja Award at the Ninth Asian Congress of Neurological Surgeons in Turkey. With the financial support of the National Natural Science Foundation (Grant No. 81101909), he is currently continuing his research on mechanisms of transdifferentiation of GSCs into endotheliumlike cells under hypoxic conditions, which was discovered by him. Hua Chen was winner of the Fifteenth WFNS YNSA; his awardwinning article is entitled “Glioma Stem Cells Induce Host Cells Canceration by Cell Fusion: Evidence and Thinking from Cell Sociology” (Figure 2D). He now works in the Neurosurgical Department of Nanjing–Hospital-Affiliated Nanjing Medical University (Nanjing First Hospital) and continues basic and clinical research on human gliomas. He proved the significant role of cell division cycle 2 in glioma progression with gene knockdown technology (2). With the financial support of the National Natural Science Foundation (Grant No. 81302180), he currently is conducting further research into the role of host bone marrowederived cells in the glioma microenvironment by using self-made double color fluorescent glioma models (1).
4. Dong J, Huang Q: Targeting glioma stem cells: enough to terminate gliomagenesis? Chin Med J (Engl) 124:2756-2763, 2011. 5. Dong J, Zhang Q, Huang Q, Chen H, Shen Y, Fei X, Zhang T, Diao Y, Wu Z, Qin Z, Lan Q, Gu X: Glioma stem cells involved in tumor tissue remodeling in a xenograft model. J Neurosurg 113: 249-260, 2010. 6. Dong J, Zhao Y, Huang Q, Fei X, Diao Y, Shen Y, Xiao H, Zhang T, Lan Q, Gu X: Glioma stem/ progenitor cells contribute to neovascularization via transdifferentiation. Stem Cell Rev 7:141-152, 2011. 7. Huang Q, He G, Lan Q, Li X, Qian Z, Chen J, Lu Z, Du Z: Target imaging diagnosis of human brain glioma. Clinical analysis of 40 cases. Chin Med J (Engl) 109:93-96, 1996.
8. Huang Q, Zhang QB, Dong J, Wu YY, Shen YT, Zhao YD, Zhu YD, Diao Y, Wang AD, Lan Q: Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the primary tumor, and both can be maintained long-term in vitro. BMC Cancer 8:304, 2008. 9. Lan Q, Huang Q, Bao S: Preclinical evaluation of SPECT imaging with 131I-labeled monoclonal antibody SZ39 in nude mice bearing human glioma xenografts. J Neuroimaging 6:131-135, 1996. 10. Li XN, Du ZW, Huang Q: Modulation effects of hexamethylene bisacetamide on growth and differentiation of cultured human malignant glioma cells. J Neurosurg 84:831-838, 1996. 11. Li XN, Du ZW, Huang Q, Wu JQ: Growthinhibitory and differentiation-inducing activity of dimethylformamide in cultured human malignant
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glioma cells. Neurosurgery 40:1250-1258 [discussion 1258-1259], 1997. 12. Li XN, Huang Q, Du ZW: Methodologic study of direct preparation for chromosome analysis of human solid brain tumors. Cancer Genet Cytogenet 58:160-164, 1992. 13. Liu XM, Zhang QP, Mu YG, Zhang XH, Sai K, Pang JC, Ng HK, Chen ZP: Clinical significance of vasculogenic mimicry in human gliomas. J Neurooncol 105:173-179, 2011. 14. Ma Y, Lan Q: Supraorbital keyhole approach to upper basilar artery aneurysms via the opticocarotid window: a cadaveric anatomic study and preliminary application. Minim Invasive Neurosurg 54:228-235, 2011. 15. Ma Y, Lan Q: An anatomic study of the occipital transtentorial keyhole approach. World Neurosurg 80:183-189, 2013. 16. Ricci-Vitiani L, Pallini R, Biffoni M, Todaro M, Invernici G, Cenci T, Maira G, Parati EA, Stassi G, Larocca LM, De Maria R: Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells. Nature 468:824-828, 2010. 17. Shu Q, Wong KK, Su JM, Adesina AM, Yu LT, Tsang YT, Antalffy BC, Baxter P, Perlaky L, Yang J, Dauser RC, Chintagumpala M, Blaney SM,
NEUROSURGERY AT SOOCHOW UNIVERSITY
Lau CC, Li XN: Direct orthotopic transplantation of fresh surgical specimen preserves CD133þ tumor cells in clinically relevant mouse models of medulloblastoma and glioma. Stem Cells 26: 1414-1424, 2008. 18. Wang R, Chadalavada K, Wilshire J, Kowalik U, Hovinga KE, Geber A, Fligelman B, Leversha M, Brennan C, Tabar V: Glioblastoma stem-like cells give rise to tumour endothelium. Nature 468: 829-833, 2010. 19. Yang WL, Du ZW, Huang Q: Localization of 131Ilabelled anti-glioma monoclonal antibody SZ-39 in human brain tumor transplanted in nude mice. Chin Med J (Engl) 101:919-922, 1988.
orthotopic xenograft mouse models of medulloblastoma. Neuro Oncol 14:574-583, 2012. 23. Zhao Y, Dong J, Huang Q, Lou M, Wang A, Lan Q: Endothelial cell transdifferentiation of human glioma stem progenitor cells in vitro. Brain Res Bull 82:308-312, 2010. 24. Zhao Y, Huang Q, Wang A, Dong J, Lan Q: Mutation of PTEN in glioma stem/progenitor cells: a case report. Cancer Genet Cytogenet 195: 183-185, 2009. 25. Zhao Y, Huang Q, Yang J, Lou M, Wang A, Dong J, Qin Z, Zhang T: Autophagy impairment inhibits differentiation of glioma stem/progenitor cells. Brain Res 1313:250-258, 2010.
20. Yue WY, Yu SH, Zhao SG, Chen ZP: Molecular markers relating to malignant progression in Grade II astrocytoma. J Neurosurg 110:709-714, 2009.
26. Zhu J, Zhou L, XingWu F: Tracking neural stem cells in patients with brain trauma. N Engl J Med 355:2376-2378, 2006.
21. Zhang QB, Ji XY, Huang Q, Dong J, Zhu YD, Lan Q: Differentiation profile of brain tumor stem cells: a comparative study with neural stem cells. Cell Res 16:909-915, 2006.
Citation: World Neurosurg. (2014) 81, 3/4:464-467. http://dx.doi.org/10.1016/j.wneu.2014.01.002
22. Zhao X, Liu Z, Yu L, Zhang Y, Baxter P, Voicu H, Gurusiddappa S, Luan J, Su JM, Leung HC, Li XN: Global gene expression profiling confirms the molecular fidelity of primary tumor-based
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