SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1) Ohtsura Niwa
Home Institution:
Department of Pathology, Research Institute for Nuclear Medicine and Biology, Hiroshima University

Sponsor and Host Institution:
Dr. Isaiah Fidler, University of Texas
Dates of Visit: September 27th, 1987 to October 10th, 1987

Summary of Activities:
The purpose of the visit is to study current research activities on molecular biology of tumor metastasis in US. During two weeks of the stay, I visited 6 laboratories in 4 cities and gave 3 seminars, met more than 30 scientists working mainly on experimental tumors. Tumor metastasis is determined by the host response to the tumor cells and by the behavior of the cells themselves. Molecular studies on tumor metastasis is mainly on the genes involved in the behavior of the cells. Oncogene expression is studied in many laboratories on highly metastatic as well as on low metastatic tumors. Augmentation of metastasis is noted for H-ras gene transfected tumor cells. Attempts are also made to clone a gene directly responsible for the metastatic behavior of the cells. One such gene is already cloned in Dr. Liotta’s laboratory at NIH. Study on enzymatic activity of a highly metastatic tumor line indicates heparanase activity in tumor cells is an Important determinant of tumor metastasis. Inhibitors of the enzyme suppress experimental metastasis of the same tumor. This line of research leads to the clinical application directly.
The molecular mechanism of tumor metastasis involves complex interaction of the tumor cells and the host environment. Although many laboratories in US and in Japan are now working on the study of the molecular mechanism of tumor metastasis, the genes reparted to be responsible are still small and many are yet to be identified. There is still no clear picture of the molecular processes involved in tumor metastasis. Therefore, molecular biology of tumor metastasis is still in a stage where we have to identify more genes involved in the process. Only after we have enough number of genes identified, we will be able to understand the molecular mechanism of tumor metastasis.



(2) Shuichi Fujimoto
Home Institution:
Chiba Cancer Center Research Institute

Sponsor and Host Institution:
Dr. Robert H. Shoemaker, NCI-Frederick Cancer Research Facility
Dr. Enrico Mihich, Roswell Park Memorial Institute, Grace Cancer Drug Center
Dr. Furanco M. Muggia, University of Southern California Comprehensive Cancer Center, Kenneth Norris Jr. Cancer Hospital & Research Institute
Dates of Visit: October 12, 1987 - November 1, 1987 (three weeks)

Summary of Activities:
In order to discover potent new antitumor agents against solid tumors, we should understand the backgrounds for refractoriness of most solid tumors towards chemotherapy. The major factors will be the retardation of tumor growth rate, the appearance of drug-resistant tumor clones, and the variation of intrinsic sensitivity of individual tumor cells to antitumor agents.
Can the effective antitumor agents against solid tumors which follow the Gomperzian growth pattern be discovered using experimental animal and human tumor cells in vivo and in vitro which follow the exponential growth pattern?
The existence of tumor clones resistant to a single drug may be almost sure, and the probability of existence of doubly-resistant tumor clones appears to be high in tumor cell populations at macrosize. On the other hand, the clinical studies of new antitumor agents are carried out for those patients with tumors which are refractory to some standard chemotherapy either initially or during treatments. Those tumor cells may show the cross resistance or the pleiotropic cross resistance to potential new antitumor agents.
The disease-oriented anticancer drug screening program which is conducted mainly in U.S.A., especially by NCI, is very huge in its scale and functional in its system. It appears rational and practical for drug screening system at the present situations.
However, I believe that there is another type of drug screening system. Since the sensitivity of tumor cells to antitumor agents differs from patients to patients even in the same type of disease, it is no wonder if the experimental animal and human tumor cells may have drug sensitivity which greatly different to those of human solid tumor cells. Therefore, testing the antitumor potential of new drugs using the clinical materials appears to be more desirable, if possible, in order to find the effective drugs towards solid tumors in each field. We are now planning to develop a reliable and more efficient drug sensitivity test system and to introduce this system into drug screening program.



(3) Ryuzo Ueda
Home Institution:
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464, Japan

Sponsor and Host Institution:
Dr. Loyd J. Old, M.D., Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021, U.S.A.
Date of Visit: November 5, 1987-November 25, 1987 (21 days)

Summary of Activities:
The purpose of this visit to USA was to exchange informations regarding the present status of application of mouse and human monoclonal antibodies produced against human tumors for diagnosis and treatment of cancer patients. The following investigators provided me their recent progress in this field: Dr. Old, Dr. Oettgen, Dr. Houghton and Dr. Livingston of Memorial Sloan-Kettering Institute, New York, Dr. Bast and Dr. Peters of Duke University, Durham, and Dr. Herlyn of Wister Institute, Philadelphia.

Detailed subjects
1) Antigens shed by tumor cells were discussed with Dr. Bast and Dr. Herlyn.
2) Radioimmunoimaging were discussed with Dr. Old and Dr. Bast.
3) Immunotherapy of solid tumor discussed with Dr. Houghton, Dr. Old and Dr. Herlyn
4) Anti-idiotype immunization as a treatment of cancer patients was discussed with D Herlyn.
5) Autologous bone marrow transplantation (ABMT) were discussed with Dr. Bast.
6) Present status of human monoclonal antibodies were discussed with Dr. Old.
7) Biological response modifiers in the field of cancer treatment were discussed with D Oettgen.
8) Active immunotherapy against melanoma patients with purified gangliosides were discussed with Dr. Livingston.
Discussion with the doctors mention above gave us valuable practical and basic informations of utilization of immunodiagnosis and immunotherapy with monoclonal antibodies. Through the program, I was able to have chance for collaboration and discussion with leading scientists in the United States. Up to date and new approaches encouraged and improved our research. The collaboration will be continued by exchange materials and methodologies.