TANG Zhaoyou
Tang zhaoyou is an internationally renowned liver cancer researcher and the founder for early diagnosis and treatment of hepatocellular carcinoma. He is also one of the first academicians of Chinese Academy of Engineering, Division of Medicine and Health, honorary fellow of American Surgical Association, and honorary member of Japan Surgical Society. He is currently the chairman, professor ofsurgical oncology, and PhD supervisor of Liver Cancer Institute, Zhongshan Hospital, Fudan University. He had been council member of International Union against Cancer (UICC), Hepatoma Professional Committee chairman of the Chinese Anti-Cancer Association, vice presidentoftheChinese Medical Association, and presidentofShanghai Medical University.
He first systematically proposed the conceptof“subclinical hepatocellular carcinoma” and is the chief editor of “Subclinical Hepatocellular Carcinoma” (in English). Hans Popper, the founder of modern hepatology, praised this study by “this concept represents major progress in the understanding, and particularly the management, of hepatocellular carcinoma”. The study of small liver cancer doubled the 5-year survival rate of the patients underwent curative surgery, and promoted the transformation of hepatocellular carcinoma treatment from “incurable disease” to “part-can-be-cured disease”. In recent years, he further carried out “the metastasis and recurrence research of hepatocellular carcinoma”. Then he established the first human liver cancer nude mice model with high metastastic potential and cell lines with different metastatic potentials and targets and successfully used it to study themetastasis of hepatocellular carcinoma. He had been twice the Liver Cancer Conference chairman of the International Cancer Congress, more than 90 times been the invited speaker at international conferences, 7 times as the chairman hosted Shanghai International SymposiumonLiver Cancer and Hepatitis. He is also the editorial board member of 11 international journals and the editor-in-chief of two journals in Asia-Pacific Region. He edited 9 monographs and participated in editing other 16 international monographs. He published 288 articles, which were cited for 6759 times; in liver cancer area, this achievement ranked No. 3 worldwide (No. 1 on the mainland, China). He was honored with a gold medal of “Early Treatment and Early Cure” from USA in 1979. In addition, he got first prize National Science and Technology Progress Award for twice, the third prize for twice, Ho Leung Ho Lee Science and Technology Progress Award, Chinese MedicalScience Award, China Engineering Science and TechnologyAward, Wu Jieping Medical Prize, BethuneMedal, "May 1" Labor Medals, and Shanghai Science and TechnologyHero. Until now, he has 59 PhD students graduated, and four of them got National Excellent Doctoral Dissertation Award.
Studies on early diagnosis, early treatment, and metastasis of hepatocellular carcinoma
Abstract
The pioneering work in the early diagnosis and treatment of liver cancer (hepatocellular carcinoma)
Although α-fetoprotein was firstly discovered abroad, its value in early diagnosis of liver cancer was not determined. Tang developed the concept of “asymptomatic subclinical liver cancer”, diagnosed liver cancer by dynamic analyze of serum AFP for the first time, and limited liver resection was advocated to minimize the risk of surgery for small liver cancer in a cirrhotic liver. All these innovations doubled the 5-year survival rates of the patients under curative surgery. He is also the chief editor of “Subclinical Hepatocellular Carcinoma” (in English). Because this project provided a convenient and cost-effective methods in clinical practice, it won a National Science and Technology Progress Award (first prize).
Establishment of the first human liver cancer nude mice model with high metastatic potential and the development of cell lines with different metastatic potentials and targets
With the purpose of further improvement of the curative effects, Tang developed a research platform for the study of liver cancer metastasis, which is the first model of metastatic model worldwide. In view of thesis that soil (tumor microenvironment) may influence the the biologic features of seed (tumor cell), he developed 3 new technologies to create a metastatic model system which was used worldwide. Based on this model, interferon-α was found, which could increase patients’ survival after curative surgery. And this project won another National Science and Technology Progress Award (first prize).
Inflammation/immune microenvironment plays important role in liver cancer metastasis
This finding indicated that the microenvironment should be taken into consideration in the designing the potential interventions of liver cancer metastasis. This project won a National Prize for Natural Sciences (second prize).
The development of the concept “asymptomatic subclinical liver cancer”; diagnosis of subclinical liver cancer by the dynamic analyze of serum α-fetoprotein changes; using limited liver resection in clinical practice which could lowered the mortality of surgery; using re-resection to treat the metastasis and recurrence in the symptomless subclinical period.
By developing the “seed and soil” hypothesis and based on the theory that “modulating the soil could affect the characteristics of the seed”, Tang established the first human liver cancer nude mice model with high metastatic potential and cell lines with different metastatic potentials and targets. In this project, three new methods were used including: in vivo screening with lung colonies; culture in vivo and in vitro alternatively; organ-directed (ie, lung, lymph node) stepwise screening.
He and colleagues also revealed that peritumoral microenvironment of liver tissue played an important role in cancer metastasis for the first time. This study indicated that microenvironment could be a new promising target in the intervention of metastasis.
Tang’s study mainly focused on how to improve curative effect of liver cancer and the key issues involved including (1) early diagnosis and treatment, which have doubled patients’ survival rates after surgery, and (2) cancer metastasis, the achievements of which are emerging.
1) By integration foreign technology (α-fetoprotein) and three clinical innovations and verification the effects in clinical settings (surgery and follow-up), a convenient and cost-effective method was established, which increased the clinical effects substantially. This method is unique to China.
2) In the project of the establishment and application of human liver cancer nude mice model, Tang highlighted often neglected effects that soil (microenvironment) acted upon the biological features of soil (tumor cell). With the using of 3 new technologies, this platform was established which could be used in the study of the mechanism of metastasis and in the identifications of anti-metastasis drugs. And this platform was also unique to China.
3) Tang and his colleagues found that the non-cancerous inflammation/immune microenvironment plays an important role in cancer metastasis, which indicated that besides tumor cells should be targeted, the tumor microenvironment should also be taken into consideration in the prevention and treatment of metastasis.
The study of small liver cancer doubled the 5-year survival rate of the patients underwent curative surgery. A group of patients with long-term survival were emerging from then on. Hans Popper, the founder of modern hepatology, praised this study by “this concept represents major progress in the understanding, and particularly the management, of hepatocellular carcinoma”, and this project was honored with a gold medal of “Early treatment and Early Cure” from USA.
The high metastatic model was used in screening for anti-metastasis compounds. Among these compounds, anti-metastatic effect of interferon-α was found and being confirmed by clinical trails. The model has been demanded for 162 times from worldwide. US National Cancer Institute stated that “this is the first model that provides a useful tool both in studying the mechanism of HCC metastasis and in identifying potential therapeutic compounds of metastasis that is mostly relevant to human HCC”. Our work was also commented on a top journal as following: the findings support the hypotheses that cancer and stromal cells collaborate with surrounding uninvolved tissue in cancer development…provide new insights into the biology of cancer.
