MINUTES

Joint NCI-JSPS Steering Committee U.S.-Japan Cooperative Cancer Research Program
June 10-11, 1980
Nara Hotel, Nara, Japan

The meeting was called to order by the Chairman, Dr. Haruo Sugano. The following persons attended the meeting:

OPENING REMARKS

Dr. Sugano introduced Professor Sogo Okamura, Executive Director, JSPS, and Professor Emeritus, Faculty of Engineering, Tokyo University. Professor Okamura welcomed the American delegation. He then expressed his interest in the functions of the Joint Steering Committee as a policy-making body which also reviews, evaluates, and plans the program of the cooperative activities sponsored under the U.S.-Japan Cooperative Cancer Research Program. He was pleased to learn of the newly structured program starting in April 1979 which will broaden the cooperation to study and exchange information in the following research areas:

1. Environmental and intrinsic factors in carcinogenesis
   
2. Cancer biology, cell biology, and diagnosis
   
3. Clinical studies and the research and treatment of cancer, including radiation oncology and therapeutic methods
   

Professor Okamura hopes that the accumulated knowledge will enhance the effective treatment of cancer and diminish the fear of cancer in the public mind. The new program provides more flexibility in cooperative studies of cancer. He believes that improved coordination and administration will hasten the exchange of information and improve the interaction among the various specialty areas. He was impressed with the multidisciplinary approach in the area of combined modality treatment, the seminar on the epidemiology and basic studies on colon and stomach cancer, and the "Conference on Recent Advances in Cancer Research" to be held in Osaka after the Steering Committee Meeting.
He stated that he was happy to join this meeting being held in Nara (Heijo-kyo), which was the second capital of Japan in 700 A.D. before being moved to Kyoto in late 780 A.D. The site was deeply steeped in the ancient history of Japan and provided a very peaceful environment for this meeting. He wished the Joint Steering Committee a very successful and productive meeting.
Mr. Soda announced that the JSPS will host a dinner for the United States delegation. Dr. Omata stated that the Japanese delegation will be invited to a luncheon before the Joint Steering Committee leaves for Osaka on June 11, 1980.
Dr. Miller expressed his appreciation to Professor Okamura for his kind words. He stated that he was happy to be back in Nara to experience the serene atmosphere of the city and to stay in the beautiful, historic Nara Hotel, which is over 80 years old.
He then briefly discussed the program activities during the past five years and stated that he looked forward to the cooperation in the future. The question was brought up as to how the U.S.-Japan Cooperative Cancer Research Program differed from other bilateral programs. Dr. Miller indicated that there are considerable differences between the countries, not only in language and customs, but also in the types of diseases, composition of the population, incidence of cancer, as well as other differences. He hoped that this and future meetings would be intellectual exercises instead of centered only on administrative and program decisions.

What contributes to the success of a binational program?

Based on these discussions in conjunction with other experience in the binational program, Dr. Miller recorded the following items that help make binational programs successful:

1. Attention to diseases that differ in frequency or nature in the two countries.
   
2. Special techniques or resources available in only one of the countries (e.g., record-linkage through the koseki in Japan or through the VA Follow-up Agency in the United States).
   
3. A special research approach (e.g., observational, as in China).
   
4. Amplification of studies at low cost (e.g., the use of a common arm in clinical trials of chemotherapy in Japan and the United States with an uncommon arm in each country for contrast).
   
5. The availability of informed scientific advisors for making binational agreements. These advisors should know and appreciate the collaborating country.
   
6. Ample opportunity should be provided for brainstorming as contrasted with formal presentations.
   
7. An extra dividend should be sought from each international meeting by timing it to other meetings (big or small), to consultations, or to lectures.
   
8. In forming committees of binational programs, concepts should take priority over traditional designations to permit the greatest possible crossing of disciplines.
   

Mr. Soda made the motion for the adoption of the agenda. The Joint Committee unanimously voted its approval.
The co-chairman, Dr. Robert W. Miller, asked Drs. Weinstein and Sugimura to present the Annual Report for the Etiology Program Area.


ETIOLOGY PROGRAM AREA

Dr. Weinstein expressed his thanks to the JSPS for the fine arrangements for the meeting and also for the excellent cooperation in administering the U.S.-Japan Cooperative Cancer Research Program. He acknowledged the special participation of Drs. T. Benjamin, H. Hanafusa, and W. Nichols, as Principal Advisors for the Etiology Program Area, for their assistance in formulating the program during the year, and for future planning.
The Tokyo "Seminar on the Biochemistry of DNA," was noteworthy. It addressed the question: How does DNA replicate in carcinogenesis or naturally? New data were presented by both sides concerning replication of DNA in vitro, multiple DNA polymerases in mammalian cells, and DNA repair. During the past year, twelve exchange scientists (six Japanese and six Alnericans) were sponsored under the Etiology Program.
The U.S. side was very pleased to receive samples of amino acid pyrolysates, which are highly mutagenic and carcinogenic, from the laboratory of Dr. Sugimura. These new compounds will be distributed to investigators, and it is hoped that they will be used to investigate new avenues in carcinogenic processes.
Dr. Sugimura reported on highlights from the meeting on "Colon and Stomach" Cancer held in Honolulu. The incidence of stomach and colon cancer in Japan and the United States are quite different (i.e., stomach cancer is high in Japan and low in the United States while colon cancer is low in Japan and high in the United States). There are indications that differences in dietary and nutritional patterns have considerable effect on the occurence of these two types of cancer. High-fat and low-fiber intake diet point to the high incidence of colon cancer. There is some evidence that the high content of sodium chloride (table salt) in the Japanese diet may influence the high incidence of stomach cancer. There is a great need for multidisciplinary effort to study the mechanism of carcinogenesis. Dr. Sugimura hoped that the side-by-side comparison of two cancers in the two countries addressed by several disciplines would set a new fashion in the Program. Also, the contribution at the meeting by several young scientists indicated that a special effort should be made to include them in future meetings.
The Program Coordinators agreed that the sharing and exchanging of information and scientific personnel have enhanced collaborative efforts, and the interaction has been very free and open. During the past year, experts from different areas, as well as many young investigators, have brought up new ideas and dicussed common areas of research which were not apparent in the past. It was generally agreed that the newly restructured program has provided opportunities for biochemists, geneticists, epidemiologists, clinicians, virologists, and others to discuss scientific data across disciplinary lines.
It is apparent that the exchange of personnel and seminars proved that the level of expertise in both countries was comparable and, therefore, it has been possible to maximize open discussions and personal interaction, and to sponsor good cooperative activities. The coordinators plan to have two levels of scientists exchanged; senior investigators for short-term visits and young scientists for longer visits. The senior scientists will be able to stimulate interest and to provide new ideas for young investigators to engage in collaborative research studies.
Dr. Carter recommended that agendas of all meetings and seminars be distributed to all members of the Joint Steering Committee so they will be current in their views of the Program and aware of the invited participants. There are times when the other Program Coordinators may be able to attend meetings as observers and participate in seminars. There was full agreement by the Joint Steering Committee.

CANCER BIOLOGY AND DIAGNOSIS PROGRAM AREA

Dr. Yamamura was asked to present the Annual Report for the Cancer Biology and Diagnosis Program Area. Dr. Miller said that Dr. William Terry sent his deepest regrets for being unable to attend this meeting.
Dr. Yamamura reported that the highlight of the past year was the exchange of information in areas oriented toward basic research. The three meetings sponsored during the year were on the "Molecular Genetics of Oncogenic Viruses," "Mechanism of Host Tumor rlrununity and the Theoretical Basis for Tulnor Immunology," and the "Development of New Techniques in Automated Cytology."
Dr. Yamamura reported that the exchange of information in the field of cancer immunology has been enhanced by the U.S.-Japan Cooperative Cancer Research Program. Thus far the emphasis had been on anti-tumor activities of various microbial preparations, such as BCG cell-wall skeleton and other immunopotentiating preparations. More recently collaboration on the studies on the anti-tumor activity of the natural killer (NK) cells and macrophages have been initiated between the Japanese and American investigators.
During the discussions, Drs. Sugano and Miller brought up the cluster of T cell leukemias which has recently occurred in southern Kyushu. This is a newly recognized type of leukemia in adults. Dr. Sugano reported that prognosis was poor. In children the leukemias appear to be similar to other types of lymphomas. He stated that Japanese cancer specialists are now collecting epidemiological data. There is some indication that the T cell leukemia may be genetically linked.
There was also some discussion on the status of automated cytology. It is felt that the technology is presently ahead of the cytology, and there is need to refine the cytological techniques for preparation, classification, and the identification of cell types. It was reported that a cytology meeting will not be held during the coming year, but future meetings should link automation techniques to the biology of the tumor.
A digression about hybridomas led to the suggestion that a conference be held under the Program to address techniques in relation to cancer research (e.g., to develop tumor-specific antibodies).

CANCER TREATMENT PROGRAM AREA

Drs. Carter and Sakurai were asked to present the accomplishments of the Cancer Treatment Program Area. Dr. Carter reported that efforts were made to integrate the activities of the former Cancer Therapy Program Area toward combined modality treatment of cancers. Chemotherapy, radiation oncology, and immunotherapy will be emphasized and the activities will be moving toward disease-oriented studies on lung and breast cancers and towards the multi-disciplinary approach to treatment.
This past year, three meetings were sponsored under the Cancer Treatment Program. The May 1979 meeting in San Francisco reviewed and discussed the continuing collaboration in evaluating the analogues of nitrosoureas, flourinated pyrimidines, anthracyclines, and other anti-tumor drugs. Discussions on better treatment protocols with drug combinations and combined modalitites were held. Also, the exchange of new drugs was reviewed. The collaboration on the drug treatment of gastric cancer was discussed and will be continued between the group of Japanese oncologists and the Northern California Gastric Cancer Group. The nontherapists present asked if in vitro tests of susceptibility to chemo-therapy could be a subject for interdisciplinary attention, specifically, basic laboratory scientists might be encouraged to participate in devising new in vitro sensitivity tests. Also, it was suggested that a search might be made for biological modifiers other than cytotoxic agents for therapy (e.g., modifiers of differentiation such as hormones or growth promoters). The modification of biological response is a major new programmatic area in the United States.
The meeting on "High LET and Allied Areas in Radiology" was held in Kyoto in May 1979. The seminars included discussions on linear accelerator design, particle physics, radiation biology, and therapy. The cooperation in radiation oncology will be broadened to include other aspects of radiation oncology, such as the use of radiosensitizers and hyperthermia.
In January 1980, a meeting on the "Treatment of Lung Cancer by Chemotherapy Combined with Other Modality" was held in Osaka. This meeting was the third in the series on the multidisciplinary approach to treatment of lung cancer. The meeting was successful in discussing the multidisciplinary viewpoints between Japanese and American oncologists. There is good potential for the coordination of collaborative studies with increasing comparability in the staging and treatment of different types of lung cancer.
The Program Coordinators reported that collaborative studies on gastrointestinal cancer and radiation oncology have been progressing very smoothly with several clinical trial studies continuing, particulary in the drug trials. It was emphasized that coordination of the drug trials was very important to study the response and side effects in the treated patients. The status of drug development and the exchange of new analogues are continuing actively. It is anticipated that there will be new cooperative activity in the area of biological response modifiers.
Special features of the Program during the past year included the development of a true collaboration in the gastric cancer study, in which each country used a common treatment arm (chemotherapy) and an experimental arm according to the preference of each national group. The establishment of comparability in high LET physics was also a notable achievement. The meeting was recessed for the luncheon.

INTERDISCIPLINARY PROGRAM AREA

Dr. Sugano reported that the cooperative study between Japanese and American pathologists on the "Status of Breast Cancer among the Survivors of the Atomic Bomb" had been concluded. Initially, the NCI group approached the Radiation Effects Research Foundation (RERF) in Hiroshima, formerly the Atomic Bomb Casualty Commission (ABCC), to study the types of breast cancer among the women survivors of the atomic blast. These studies were an outgrowth of U.S. interests in the effects of low-dose radiation on cancer rates. A group of three American and five Japanese pathologists met to standardize classification and methodology, and to review slides of known cases of breast cancer among the survivors. The studies were completed and the results will be published.
An important by-product observation was made: breast tissue from 56 women who had received 100 rads or more, but had died of cancer other than breast cancer, revealed greater fibrosis and less fat than seen in breast tissue of U.S. women. In the present absence of controls, it could not be determined if the binational difference was due to radiation or aging. The observation indicates how material already on file at RERF can be used for binational studies not necessarily related to radiation.
Dr. Miller stated that Dr. Sugano contributed much time and effort for this collaboration. This study can stimulate additional studies in pathology and epidemiology with well-planned cooperation between teams of experts and can accomplish a great deal. It is possible that other studies on different factors in the etiology of breast and other cancers among survivors receiving high and low levels of radiation may be planned in the future.
Discussions continue on the changing patterns of cancer incidence in Japan. There are strong indications that incidence of breast cancer is increasing with age; that leukemia is high among those exposed in childhood, but generally decreasing in numbers, indicating age dependency; cancer of salivary glands is high, with thyroid and latent cancers increasing among the survivors; and, in general, the incidence of lung cancer is increasing.
The Program Coordinators reported that the "Conference on Recent Advances in Cancer Research", to be held in Osaka following the Joint Steering Committee meeting, was a joint effort under the Interdiciplinary Program Area. It was anticipated that a small but highly specialized audience will be present.
Dr. Sugano asked the coordinators of each of the four program areas to discuss their plans for the period between April 1, 1980, and March 31, 1981 (Japanese Fiscal Year 1980-81).

1. Etiology Program Area
   It was reported that during the coming year, two meetings have been planned. Program agendas are being planned by the meeting organizers.
   - Biochemical Epidemiology
   February 1981--Honolulu, Hawaii
   Organizers: Drs. Susumu Nishimura and Alan Conney
   - Interspecies Correlations in Chemical Carcinogenesis
   March 1981--Tokyo, Japan
   Organizers: Drs. Shozo Takayama and Curtis Harris
   The Etiology Program plans to nominate six Japanese scientists and two or three American investigators as exchange scientists in the areas of viral oncology, biochemistry, and epidemiology.
   
2. Cancer Biology and Diagnosis Program Area
   It was reported that the following meetings will be sponsored under this Program Area:
   - Analysis of the Mechanisms for Induction of Tumor-specific lmmunity and Experimental A roach for Tumor-immunoprophylaxis and Therapy.
   October 1980--Osaka, Japan Organizers: Drs. Toshiyuki Hamaoka and Richard Hodes
   - Carcinoembryonic Proteins--Cellular and Molecular Biology and Application for Early
   Diagnosis of Cancer
   December 1980--San Diego, California
   Organizers: Drs. Hidematsu Hirai and William H. Fishman
   - Genetic and Epigenetic Aspects of Cancer
   - January 1981--Honolulu, Hawaii
   Organizers: Drs. Yoji Ikawa and lra Pastan
   Nominations for exchange scientists include three Japanese and one American.
   
3. Cancer Treatment Program Area
   The following meetings for the Cancer Treatment Program Area have been planned:
   - Development and Evaluation of Cancer Treatment
   June 7-9, 1980--Tokyo, Japan
   Organizers: Drs. Yoshio Sakurai and Stephen Carter
   This meeting was very successful as information on new drugs and treatment regimens were discussed. More information on the anti-tumor effects of aclacinomycin and PEP-bleomycin were exchanged, as well as new analogues of currently used drugs.
   - High LET Radiation and Combined Modalities
   November 1980--Honolulu, Hawaii
   Organizers: Drs. Yoichiro Umegaki and Glenn E. Sheline
   - Treatment of Breast Cancer with Combined Modality
   March 1981--San Antonio, Texas
   Organizers: Drs. Hiroki Koyama and William McGuire
   Under the Exchange of Scientists Program, two American radio-biologists were recently engaged in collaborative studies on biological dosimetry measurements of high-energy particles. Early in 1981, a Japanese oncologist will spend two months at the Memorial Sloan-Kettering Cancer Center in New York.
   
4. Interdisciplinary Program Area
   The following meetings are being organized for this current year:
   - The Conference on Recent Topics in Cancer Research
   June 12-13, 1980--Osaka, Japan
   Organizers: Drs. Haruo Sugano and Robert W. Miller
   This conference is the first of two biennial conferences to be sponsored under the Interdisciplinary Program Area. The conference is being jointly supported by the U.S.-Japan Cooperative Cancer Research Program and the Japanese Cancer Association.
   Difference in Lymphocytic Diseases in Japan and the United States
   March 1981--Honolulu, Hawaii
   Organizers: Drs. Robert W. Miller and Haruo Sugano
   There is increasing information and interest in the difference in lymphocytic diseases in Japan and the United States. The United States has a higher incidence of various types of lymphocytic diseases, such as chronic lymphocytic
   Difference in Lymphocytic Diseases (continued)
   leukemia, lymphosarcoma, and others. Among the Japanese, there is a higher incidence of autoimmune diseases, such as systemic lupus erythematosus, Hashimoto's disease, and possibly T cell lynphomas. The meeting will bring together groups of clinician pathologists and epidemiologists to discuss the factors contributing to these differences.
   It is anticipated that two or three exchange scientists will be sponsored under this program area.
   

Mr. Soda thanked the Program Coordinators for their presentations, and then asked them to consider the general format for the Annual Reports to be submitted to NCI and JSPS in the future. The format was accepted by the full Committee.
The subject of dates for the next Joint Steering Committee meeting was discussed. One possibility discussed was holding the next meeting prior to or after the annual meeting of the American Association for Cancer Research, to be held in late May in Washington, D.C. It was decided that attendance at both meetings would prolong the absence of most of the Program Coordinators from their offices and laboratories. It was tentatively agreed that the Joint Steering Committee should meet in the Washington area one and one-half days during either the first or second week of June 1981.
The meeting was closed with Drs. Sugano and Miller thanking all members for their excellent reports and presentations. The discussions during the meetings were most stimulating and aroused considerable interest on recent advances discussed among the members.

Prepared by:
Robert R. Omata, Ph.D.
Executive Secretary U.S.-Japan Cooperative Cancer Research Program
Office of International Affairs
National Cancer Institute