MINUTES OF THE FIFTH ANNUAL JOINT MEETING

Tokyo, Japan
October 31 and November 1, 1978

Program Coordinators: Dr. Haruo Sugano
Dr: Guy R. Newell

AGENDA

October 31
9:30 a.m. OPENING SESSION
Opening Remarks Dr. Haruo Sugano, Chairman JSPS Scientific Group
Remarks Dr. Guy R. Newell, Chairman NCI Scientific Group
Welcoming Remarks Mr. Saburo Kasagi, Executive Director, Japan Society for the Promotion of Science
FIRST SESSION Dr. Haruo Sugano, Chairman
9:50 a.m. Report of the Chemical Carcinogenesis Program Area Dr. I. Bernard Weinstein
Dr. Takashi Sugimura
10:20 a.m. COFFEE BREAK
10:40 a.m. Report of the Cancer Virology Program Area Dr. Yohei Ito
11:10 a.m. Report of the Cancer Immunology Program Area Dr. William Terry
Dr. Yuichi Yamamura
11:40 a.m. Report of the Cancer Chemotherapy Program Area Dr. Stephen K. Carter
Dr. Yoshio Sakurai
12: 10-2:00 p.m. LUNCH
SECOND SESSION Dr. Guy R. Newell, Chairman
2:00 p.m. Report of the Analytical Epidemiology Program Area Dr. Robert W. Miller
Dr. Takeshi Hirayama
2:20 p.m. Report of the Breast Cancer Program Area Dr. Nathaniel I. Berlin
Dr. Haruo Sugano
2:40 p.m. COFFEE BREAK
3:00 p.m. Report of the Cytology Program Area Dr. Chester Herman
Dr. Kiyoji Kimura
3:30 p.m. Report of the Urinary Bladder Cancer Program Area Dr. Ceorge T. Bryan
Dr. Osamu Yoshida
3:50 p.m. Report of the High LET Radiation Therapy Program Area Dr. Glenn E. Sheline
Dr. Akira Tsuya
4:10 p.m. Report of the Lung Cancer Program Area Dr. Oleg S. Selawry
Dr. Yuichi Yamamura
4:30 p.m. Report of the Metastasis Program Area Dr. Philip G. Stansly
Dr. Haruo Sato
5:00 p.m. Adjournment
6:30 p.m. Reception in honor of the American Delegation, hosted by the Japan Society for the Promotion of Science

November 1, 1978
BUSINESS MEETING
9:00 a.m. Report on the Second Joint Steering Committee Meeting June 2 and 3, 1978 Dr. Guy R. Newell
Mr. Kichimasa Soda,
Co-Chairmen
Discussion of Modification and Restructuring of the Program
Review of the Second Progress Report
Preparation of the Final Annual Report
11: 15 a.m. Joint Steering Committee Meeting Dr. Haruo Sugano
Dr. Guy R. Newell
Co-Chairmen
Closing Remarks Dr. Guy R. Newell
Dr. Haruo Sugano
12:30 p.m. Adjournment
Luncheon in honor of the Japanese Delegation hosted by the NCI


MINUTES OF THE FIFTH ANNUAL JOINT MEETING
Tokyo, Japan
October 31 and November 1, 1978

The meeting was called to order at 9:30 a.m. on October 31, 1978, by Dr. Haruo Sugano, Chairman, Japan Society for the Promotion of Science (JSPS) scientific group. Dr. Sugano expressed his pleasure in welcoming all of the participants. He also expressed the appreciation of the Joint Scientific Group to the Drafting Subcommittee for compiling and publishing the Second Progress Report (1976-1977) of the U.S.-Japan Cooperative Cancer Research Program, which was distributed to each of the participants.
Dr. Sugano then introduced the members of the Japanese Delegation. He stated that this meeting culminated the first five years of the Agreement for Cooperation in Cancer Research between the Japan Society for the Promotion of Science and the National Cancer Institute (NCI). He was personally pleased with the excellent results of the past five years of the Program and with the remarkable productivity and cooperation among the Program Coordinators and the numerous participants. From a scientific viewpoint, the Program contents have been excellent and the harvest of information and resulting collaboration have been extremely fruitful. He expressed his heartiest appreciation to the Pro-gram Coordinators for their concerted effort during the past five years of the Program.
Dr. Sugano stated that the Joint Steering Committee met in June 1978, to discuss the restructuring of the Program for its second five-year term. The new proposal for the Program will be presented during the Business Meeting for full discussion by the Joint JSPS-NCI Scientific Group. During this meeting the various program areas will be assessed and reviewed in the context of the past five years of program activities. Future program planning will also be discussed.
Dr. Sugano was delighted to announce that Dr. Takashi Sugimura was named by the Emperor of Japan to receive the august medal of the Order for Cultural Merit on National Culture Day, November 3, 1978, for his contribution in research in biology and medicine. The award is the highest national award given to outstanding scientists and academicians. All the participants joined in congratulating Dr. Sugimura.
Dr. Guy R. Newell, Chairman, NCI Scientific Group, responded by thanking the Japanese Delegation for the warm welcome and expressed his pleasure in visiting Japan again. He especially thanked the Japan Society for the Promotion of Science for the support given to the Program and also for arranging this meeting at the New Otani Hotel.
Dr. Newell extended warmest greetings to the participants from Dr. Arthur C. Upton, Director, NCI, and wished them all a successful and enjoyable meeting. He then introduced the members of the U.S. Delegation.
Dr. Newell extended his personal congratulations, on behalf of the U.S. Delegation, to Dr. Sugimura for the honor bestowed on him by the Emperor of Japan and the Japanese Government.
Mr. Saburo Kasagi, Executive Director, JSPS, delivered a welcoming address to the participants and thanked them for their contributions in establishing an excellent program.
Mr. Kasagi spoke as follows:
"On behalf of the Japan Society for the Pro-motion of Science, I want to thank you for attending the Fifth Annual Joint Meeting of the U.S.-Japan Cooperative Cancer Research Program.
Five years have passed, as you know, since this Program was launched in May 1974, when the representatives of the NCI and the JSPS met in Hawaii and signed the Agreement for Cooperation in Cancer Research between the two sponsoring agencies.
During these five years, joint scientific activities in 11 program areas have been largely developed in the form of scientific seminars, exchange of scientists, and exchange of materials and information. Many scientists of both countries have participated in the Program and con-ducted fruitful research activities.
In particular, I would like to point out that, besides accumulating knowledge on cancer and improvements in techniques resulting from joint scientific activities, the Program has had a great impact among scientists of both countries engaged in cancer research as a whole. Namely, the Program has increased the mutual sharing of each other's knowledge by means of bringing together varying viewpoints and methods from scientists of both countries which have had significant achievements in the field of cancer research. Moreover, the Program has contributed to the advancement of cancer research by means of scientific efforts to gain new knowledge and findings.
I think that we owe much of the success of the Program during the first five years to scientific endeavors and collaborations of the Co-Chairmen, Dr. Newell and Dr. Sugano, the coordinators of the program areas, and participating scientists, as well as Dr. Omata of the NCI. I would like to express our heartiest appreciation to these people.
According to the Agreement for Cooperation in Cancer Research between the NCI and the JSPS, the Agreement will be evaluated for renewal every five years. In this relation I want to report to you that the outline of the Second Five-Year Plan has been prepared by the efforts of the Joint Steering Committee. You will see the outline in the file of documents of this meeting, and the materialization of the plan is now under way.
The JSPS, jointly with the NCI, wants to implement the Second Five-Year Plan based on the achievements of the first five years of the Pro-gram. Your cooperation in this matter will be highly appreciated.
Finally, I would like to tell you about a happy event, and share my delight with you. Dr. Takashi Sugimura, an influential member of the U.S.-Japan Cooperative Cancer Research Pro-gram, will receive the Order for Cultural Merit, the highest national award given this year by the Japanese Government. We would like to share the delight with all of you and to cordially congratulate Dr. Sugimura on the award."
Drs. Sugano and Newell expressed their gratitude to Mr. Kasagi and the JSPS for the sponsorship of the U.S. -Japan Cooperative Cancer Research Program. Dr. Newell also expressed appreciation to Mr. Kichimasa Soda, JSPS, and Dr. Robert R. Omata, NCI, for their contributions to the administration of the Program.
Mr. Soda reported that the Second Progress Report was finished and published with the fine cooperation and work of the Joint Drafting Committee. The members of the committee were Drs. Yoji Ikawa, Takashi Hirayama, Ms. Yuko Kitamura Furukawa, Drs. Chester J. Herman, Glenn E. Sheline, and Robert R. Omata.
Mr. Soda reported that the Japanese Delegation and the JSPS would host a reception on October 31, 1978, at the Kasumigaseki Building in honor of the U.S. Delegation. A motor bus would provide transportation at 6:00 p.m. from the lower lobby of the hotel.
Dr. Omata announced that the Japanese Delegation would be honored at the buffet luncheon in the Sky Lounge at 12:30 p.m. on Wednesday, November 1, hosted by Dr. Newell, on behalf of the National Cancer Institute.
In order to complete all of the business in time, it was agreed that the Wednesday session would commence at 9:00 a.m.

CHEMICAL CARCINOGENESIS PROGRAM AREA
Dr. Sugano, as Chairman of the morning session, called on Drs. I. Bernard Weinstein and Takashi Sugimura to give their presentation for the Chemical Carcinogenesis Program Area.
Dr. Weinstein stated that it was a great pleasure to be in Japan again and to renew acquaintance-ship with the Joint Scientific Group. He was pleased to see Drs. Robert Miller and William Terry again after their visit to the People's Republic of China last Fall.
He reported on the successful meeting of the past year on the "Role of DNA Repair and Misrepair in Radiation and Chemical Carcinogenesis," held in Kyoto, Japan, in December 1977. The subject of the meeting was an in-depth view of DNA repair and misrepair caused by radiation and chemical carcinogens. The meeting was a success with a great deal of exchange of information. The workshop was held jointly with the First Radiation Biology Center International Symposium entitled "Molecular Mechanisms and Genetic Factors in Radiation Carcinogenesis." Summaries of the individual presentations were included in the Annual Report.
A brief report was given on each of the ex-change scientists, sponsored under the Chemical Carcinogenesis Program Area.
The exchange of protease inhibitors provided by Dr. Hamao Umezawa and the JSPS has been an extremely valuable adjunct to the Program. The use of protease inhibitors has opened up and stimulated a new area of research in cell biology and the study of the role of proteases in mutagenesis, carcinogenesis, and tumor promoters. It was agreed that a letter of appreciation from the JSPS and the NCI be sent to Dr. Umezawa for providing the materials and to Dr. Walter Troll for his services in providing samples to American and other foreign investigators interested in the inhibitors as research reagents.
Drs. Sugimura and Weinstein stated that the activities of the past year have been very productive and have established several collaborative studies, as well as stimulating warm and mutualhy beneficial relationships between scientists in Japan and the U.S. Dr. Sugimura made additional comments on the future program plans in the area of carcinogenesis, with a conference on "Carcinogenesis and Tumor-Host Relationshlps" being tentatively scheduled for March, 1979, in Honolulu, Hawaii. Several other proposed meetings or workshops were briefly mentioned. Plans were discussed on the pending exchange of scientists.
Drs. Philip Stansly and Haruo Sato stated that brief reports were very recently given at the Metastasis meeting in Nara, Japan, on the possible role of protease inhibitors in the therapy of micrometastasls. The mechanism of action and a joint study on use of a model system to study the role of protease inhibitors were discussed.

CANCER VIROLOGY PROGRAM AREA
Dr. Yohei Ito was called on to present the report for the Cancer Virology Program Area. Dr. Ito stated that it is most unfortunate that Dr. Robert McAllister was unable to attend the meeting and conveyed Dr. McAllister's sincere regrets and ex-tended his best wishes to the participants.
Dr. Ito presented a brief summary of the activities of the past year and also summarized the main achievements of the Cancer Virology Program Area. There were several recent advances in cancer virology contributed by the participants at the series of workshops and symposia sponsored by the Program. New ideas and information on the role of adenoviruses were exchanged among the scientists from both countries. Several joint projects were initiated in viral genetics, molecular biology of viruses, and transformed cells.
The exchange of leading virologists led to the introduction of new techniques of studying cell transformation, and stimulated the exchange of new data on cell transformation and genetics of viruses. In total, the past five years of cooperation have proved to be extremely informative and productive. Dr. Ito reiterated that excellent opportunities are available to continue the dialogue that has been established and to take full advantage of these past and present contacts. He stated that he is very hopeful that cooperation will continue to flourish during the next five years.

CANCER IMMUNOLOGY PROGRAM AREA
The Chairman called on Drs. William Terry and Yuichi Yamamura to report on the Cancer Immunology Program Area.
They reported that the past year's activities were highly productive. A workshop on the "Immunological Xenogenization of Tumor Cells" held in Sapporo, Hokkaido, June 1978, was an important dividend from the past activities of the Cancer Immunology Program Area, although the workshop was not directly supported under the U.S.-Japan Cooperative Cancer Research Program.
A recent meeting on "Immunology and Cancer" was held in Maui, Hawaii, in September 1978. The main subjects of the meeting were experimental tumor immunology and human tumor immunology. The general discussions were held on broader areas of basic tumor biology and immunology. The proceedings of the meeting will be published in the near future. It was generally agreed that the future direction of this program area will put some stress on basic tumor immunology and cell biology, as well as clinical research.
The accomplishments of the program area during the past five years have been very significant, resulting in the establishment of valuable interaction among the participating scientists and the exchange of new information on immunology and immunotherapy from both countries. The Program Coordinators have acted as effective conduits or sources of information, disseminating the information to scientists of Japan and of the United States.
During the ensuing discussions among the participating members, the subject of preclinical and clinical trials on cancer immunotherapy was brought forward. The Japanese scientists have made considerable advances in investigating the immunopotentiating factors in BCG cell-wall skeleton as well as in cell-wall of Nocardia rubra. There is a great deal of basic immunology and immunochemistry to be accomplished before preclinical and clinical research can be effectively initiated.
It is the hope of the Program Coordinators that greater advances will be made in cancer biology and cancer immunology during the next five years of the Program.

CANCER THERAPY PROGRAM AREA
 Stephen Carter and Yoshio Sakurai were asked to present the report for the Cancer Therapy Program Area.
Dr. Carter began by stating that there are several cooperative projects in clinical research, not supported by the U.S.-Japan Program, but initiated through the contacts and interactions promoted by the U.S.-Japan Cooperative Cancer Research Program. The most prominent project is the Gastric Cancer Therapy Project between a group of Japanese investigators and the Northern California Oncology Group.
It was reported that the presentations given at the symposium on anti-tumor antibiotics held in San Francisco, California, in May 1977 are being published in Recent Results in Cancer Research by Springer-Verlag. Also, the proceedings of the symposium on the methodology of Phase I and Phase II studies held in June 1978 will be published in the new journal Cancer Chemotherapy.
The activities during the past year have been extremely productive, particularly the exchange of information on the new advances in drug therapy using newly developed analogues of bleomycin, fluoridated pyrimidines, and nitrosoureas. There has been extensive exchange of clinical data on new drugs, such as macromycin and bestatin.
The past two years have been particularly informative in studying the treatment of gastric cancer under the Joint U.S.-Japan Cooperative Cancer Research Program. This joint effort has set the stage for other cooperative studies.
The Cancer Therapy Program Area is planning a meeting on recent advances in cancer treatment in San Francisco in May 1979. There has been renewed interest in mitomycin-C and in the advances in uterine cervical cancer treatment. Plans are being made to publish the proceedings.
Drs. Carter and Sakurai stated that excellent communication between clinical investigators from both countries and a tremendous amount of activity and interest have been stimulated by the Program.
Dr. Sakurai reiterated the importance of this Program during the past five years in initiating a number of joint symposia and establishing new cooperative projects. He hoped that the next five years will permit the concentration of effort on several joint projects and will provide impetus in the development of new anticancer drugs. He stated that the original cooperation on screening new drugs between the U.S. and Japan began in 1962 through the efforts of the late Dr. Tomizo Yoshida and Dr. Kenneth Endicott. This current Program has provided the necessary mechanisms for greater cooperation in cancer therapy. Dr. Sakurai hopes that the next five years will provide opportunities to extend the investigations in clinical trials, combined modality, clinical pharmacology, and drug toxicity studies.
The problem of the mutagenicity of anticancer drugs was discussed, particularly the possibility of altering the mutagenicity and toxicity of drugs by structural changes and producing analogues of currently used cancer drugs.

ANALYTICAL EPIDEMIOLOGY PROGRAM AREA
Drs. Robert Miller and Takeshi Hirayama reported that the Analytical Epidemiology Program Area sponsored a very informative and successful conference on "Biostatistics in the Study of Human Cancer" at the Radiation Effects Research Foundation in Hiroshima, Japan, in May 1978. The conference was a bilateral effort to stimulate and encourage the interaction of statisticians and physicians in seeking a fresh view on the use of medical statistics in relation to studying the epidemiology of cancer. About fifty scientists and physicians from both countries attended the conference. The interaction among the participants was excellent. The proceedings of the conference will be published in the near future.
The activities of the past five years of the Pro-gram have been very productive in terms of the exchange of scientists and the extensive exchange of epidemiological, environmental, and demographic information, as well as the exchange of geographic maps on cancer "hot spots." The cooperative studies produced two publications on the "Comparative Epidemiology of Cancer in the U.S. and Japan: Mortality and Morbidity." The Coordinators stated that future plans are to develop further the interactions between biostatisticians and physicians, to study the epidemiology of cancer, and to coordinate closer cooperation between the fields of epidemiology and carcinogenesis. The study of risk factors, particularly the relation of smoking, diet, and environment to cancer, is a very important aspect of the two fields of cancer research.
Dr. Oleg Selawry suggested that the incidence and prevalence of lung cancer could be a good tool for the study of environmental factors. Dr. Hirayama stated that epidemiological studies on the lung cancer cell types can be of great importance in studying risk factors. It was also reported that the National Academy of Sciences (United States) is sponsoring a conference on the toxicology of common substances and the Information from this conference could well provide valuable clues to the relation of dietary and nutritional factors to cancer.
Dr. Weinstein reported that in the United States efforts have been made in evaluating occupational factors. Dr. Hirayama reported that there are several sources of information and statistics in Japan on occupational hazards and cancer. Presently there is a Japanese study on the asbestos problem. In addition, he reported that many mutagenic agents have been found in the environment and that these were being studied. Dr. Miller also reported that suspected carcinogenic factors found in vegetable pickles made in China were obtained and that this material was being investigated by Dr. Sugimura and his group for mutagenicity and carcinogenicity.

BREAST CANCER PROGRAM AREA
Drs. Nathaniel Berlin and Haruo Sugano presented their report on the activities of the Breast Cancer Program Area.
A very successful conference on "Hormone Receptors and Breast Cancer" was held in March 1978 in Hawaii, when over fifteen scientists from Japan and the U.S. discussed the role of hormones and receptors in human breast cancer and basic studies on endocrine therapy in breast cancer. It was evident from the discussions that Japanese scientists have made considerable progress in the hormone receptor field during the past three years since initiating studies on the comparison of population and the incidence of breast cancer in the two countries. The proceedings of the conference were recently published as one of the series in Progress in Cancer Research and Therapy by Raven Press of New York.
During the year, an exchange scientist from the Center for Adult Diseases, Osaka, Japan, visited several American cancer centers to discuss the possibility of organizing a joint workshop on the treatment of breast cancer. It was tentatively agreed to convene the workshop in Japan or in the U.S. sometime during the Spring of 1979.
The past five years of the Program have been extremely effective in exchanging information on the nature of breast cancer in both countries, the difference in the incidence of breast cancer, and the treatment of breast cancer. Also, information was exchanged on the detection and treatment of breast cancer on a national scale in both countries.
Several exchanges of personnel have made it possible to initiate collaborative efforts. It is anticipated that other cooperative projects will be established in the coming years. Leading Japanese scientists will be invited, on a continuing basis, to participate in the NCI sponsored Breast Cancer Task Force and to exchange information.

CYTOLOGY PROGRAM AREA
Drs. Chester Herman and Kiyoji Kimura presented their report for the Cytology Program Area.
They reported that there had been significant accomplishments achieved in automated cytology research since the cooperation was initiated. During the past five years, several joint workshops were organized, and the exchange of scientists proved to be very productive. Through this program, each side was able to gain extensive knowledge of the systems used in automated cytology in both countries. Collaboration in comparing the fluid analytic system versus the image processing system was accomplished. Through the cooperation of individuals and various research centers, research information came to fruition by comparing the same specimens using the different systems.
The capabilities of the image processing system and the flow system have been developing at a rapid pace through this cooperative effort. The technological aspects of automated cytology have reached a stage where the systems could be used for clinical application. Some of the new areas in which the systems may be of considerable utility would be in studies of white blood cells, differential blood counts, cytoplasmic studies of normal and tumor cells, cytotoxicity studies, and cellular immunology.
In the future, collaborative studies on cytology, cancer detection, and diagnosis will continue between the two countries in order to eliminate duplication of effort and waste of resources.

BLADDER CANCER PROGRAM AREA
In giving their report, Drs. Osamu Yoshida and George T. Bryan expressed their gratitude and appreciation to the Joint Scientific Group for the opportunity to work together in developing and coordinating the joint effort between Japan and the U.S. National Bladder Cancer Program. The bladder cancer programs in each country were in different stages of development; however, considerable interest was evident at the outset. The program was able to hasten the merging of the divergent interests in both countries in attempting to encourage urologists and other clinicians to engage in cancer research and basic biomedical research. The NCI sponsored National Bladder Cancer Pro-gram has been very effective and has encouraged Japanese clinicians and researchers to participate in the workshops and conferences organized by the U.S. National Bladder Cancer Program.
As a result of joint participation in the Bladder Cancer Program and the exchange of scientists and information, several cooperative projects have been developed and are strong viable joint pro-grams. The joint meeting in Florida in December 1978 will provide a forum to develop future joint studies. In recent years there has been considerable interest in the possible role of saccharin and nitrosamines in the causation of bladder cancer. These controversial issues will be discussed and future joint studies may be planned.
Dr. Newell congratulated Drs. Yoshida and Bryan for their efforts in developing an excellent program after a late start. The program area progressed very rapidly and he stated that he hoped that the high level of activity will be sustained in the future.
Drs. Bryan and Yoshida reported that there is still much to be learned in the area of bladder cancer, and the difference between the Japanese and American populations should be further explored. The subject of promoters is very important, and they hope to devote more effort to identifying and reclassifying the promoters.

HIGH LET RADIATION THERAPY PROGRAM AREA
Drs. Glenn Sheline and Akira Tsuya reported that the High LET Radiation Therapy Program began in late 1975 and the program has rapidly developed into a very active one. Initially, the joint efforts were concerned with neutron studies and comparative measurements with teams of Japanese and American scientists.
The Program Coordinators reiterated that the joint cooperation was particularly productive with excellent relationships developed through joint investigations on basic and developmental problems. During the past year, the program has dealt with fast neutron radiobiology and radiotherapy. Also, joint studies have been initiated on clinical trials with particulate radiation. New areas of cooperation have been initiated on hypoxic cell radiosensitizers, hyperthermia, and intraoperative radiation therapy. As a result of earlier cooperation on particle radiation, new studies are being developed.
The program area is planning a large meeting in Kyoto in May 1979, in conjunction with the Inter-national Congress on Radiation Research to be held in Japan in May 1979.
In addition to the workshops and seminars sponsored under the program area, several Japanese participants were invited to attend and participate in the meeting of the United States Committee for a Comprehensive Plan for Particle Radiation Therapy held in Philadelphia in June 1978.
The exchange of scientists during the past four years has been particularly effective and productive in terms of the exchange of research information, as well as in conducting joint research studies.

LUNG CANCER PROGRAM AREA
Drs. Yuichi Yamamura and Oleg Selawry presented a brief summary of the joint meeting on "Multidisciplinary Treatment of Lung Cancer" held in February 1978 in Honolulu, Hawaii. The "Morphology of Pulmonary Neoplasms," as described in the Second Edition WHO Report, was discussed by two members of the WHO Committee. Then the subjects of immunotherapy of lung cancer, including microbial cell-wall skeleton vaccine therapy, surgical adjuvant treatment, and the present status of immunotherapy in Japan and the United States were discussed. Multidisciplinary treatment of small cell carcinoma and non-small cell cancer was extensively discussed by the participants. Adjuvant surgical treatment was discussed by two leading surgeons.
Progress of the program area over the past five years was discussed by the Program Coordinators. Initially, meetings were held on staging and morphology to coordinate compatible staging systems. The WHO classification of pulmonary neoplasms was discussed and fully accepted. Sessions on early diagnosis were extremely fruitful with Japanese specialists demonstrating the new fiberoptic bronchoscopes developed by Japanese investigators. Subsequent meetings on the multidisciplinary approach to the treatment of lung cancer have been particularly informative and productive in providing opportunities for clinical investigators from both countries to become aware of the current status of lung cancer treatment.
Plans are being developed to hold a conference on lung cancer treatment in Miami, Florida, in February 1979.
Inasmuch as cooperation has been established during the past years, joint programs will be developed for studying the prevention of lung cancer. Studies on diagnosis based on cell types will be continued. The principles of anti-carcinogenesis, such as the use of retinoic acid analogues and the vaccine produced from microbial cell-wall skeleton, will also be of considerable continuing interest and collaboration.
During the discussion it became evident that lung cancer has been increasing at an alarming rate, not only in the U.S. and Japan, but worldwide. There is growing interest in learning more about the causative factors.

METASTASIS PROGRAM AREA
Drs. Philip Stansly and Haruo Sato presented a report on the meeting on "Experimental Approaches to the Therapy of Micrometastases" which was held in Nara, Japan, just prior to this Joint Review Meeting. Several subjects discussed at the last meeting could lead to several interesting areas of collaboration. Topics were discussed such as the immunologic host factors; properties of metastatic cells, including cell membrane, and the differences in the enzymes in normal and tumor cells; the effect of glucose on potentiating drugs, delivery of antitumor drugs to tumor cells; and studies of models. The discussions were extremely informative and stimulating. The general conclusion of the meeting was that cancer cannot be conquered until the mechanisms of metastasis can be well understood and properly treated. The metastatic process is very important in several types of cancers, such as lung cancer.
There is much interest in metastasis research and more investigations must be accomplished to understand the location of tumor cells, transport lodgment of micrometastatic cells, vascularization of cells and tissue, and the formation of metastatic foci.
The Program Coordinators stated that, since a beginning has been made in the joint effort to study metastasis under the U.S.-Japan Program, interest among investigators should be sustained to maintain the momentum generated under this program.
The first day of the meeting was adjourned at 5:00 p.m. The Chairman announced that the Joint NCI-JSPS Scientific Group would reconvene at 9:00 a.m. on Wednesday, November 1, 1978.
The JSPS hosted a reception at the Tokai University Club at the Kasumigaseki Building beginning at 6:30 p.m.

Business Session
Drs. Haruo Sugano and Guy Newell called the meeting to order at 9:00 a.m.
Dr. Newell expressed the appreciation of the U.S. Delegation to Mr. Saburo Kasagi and the JSPS for hosting the reception at the Tokai University Club on October 31.
The minutes of the Joint Steering Committee Meeting, held in Tokyo on June 2 and 3, 1978, were presented to the Joint NCI-JSPS Scientific Group for discussion.
Dr. Newell stated that the intent of the Joint Steering Committee is to keep many of the present program areas functional as much as possible. The purpose of the new structure is to consolidate the eleven program areas into four large categorical program areas to meet the needs of the changing interests and new research areas now emerging. Under the new structure, Program Coordinators have been named for: (1) Carcinogenesis; (2) Biology and Diagnosis; (3) Treatment; and (4) Interdisciplinary Programs.
1. Carcinogenesis:
Dr. Takashi Sugimura
Dr. I. Bernard Weinstein
2. Biology and Diagnosis:
Dr. Yuichi Yamamura
Dr. William Terry
3. Treatment:
Dr. Yoshio Sakurai
Dr. Stephen Carter
4. Interdisciplinary Programs:
Dr. Haruo Sugano
Dr. Guy Newell
The Interdisciplinary Program and Coordination Area will in essence provide support for general coordination of the total Program and also meet the needs for the development of new areas of cancer research. The area will also provide sup-port for exchanges, workshops, and conferences with strong interdisciplinary orientation or crossing over of two or more fields.
It has been agreed by the JSPS and the NCI that the Joint Steering Committee will act as the Policy making body for the Program. Drs. Newell and Sugano asked for discussion and opinions from the delegations. Mr. Kichimasa Soda stated that the JSPS was generally satisfied with the formation of the Joint Steering Committee and that the new approach or structure would be more flexible and add greater breadth to the Program contents.
Dr. Berlin asked whether the organ site pro-grams would be considered under the Inter-disciplinary Area. He stated that he would strongly recommend that Breast Cancer, Lung Cancer, and Bladder Cancer Programs be continued with other organ sites added as new programs as the needs demand.
Dr. Newell stated that the Joint Steering Committee felt strongly that the current structure of eleven program areas was cumbersome and somewhat restrictive in the attempt to begin new initiatives. He also stated that the new structure will need time to be implemented and that the JSPS needed prior planning for funding from sources within the Japanese Government. There is no wish on the part of the JSPS or the NCI to diminish the activities and the considerable progress that have been supported in the past; however, there will be greater need for forward planning to justify the budgeting and funding processes.
Mr. Soda and Dr. Newell stated that it will be necessary for program organizers and coordinators to submit proposals and plans rather early during the fiscal year. There will be a need for the newly designated Program Coordinators to submit plans for each year's activities, or at least some general outline or ideas.
In order to sponsor seminars, workshops, and conferences, the Program Coordinators will have to be contacted early by those who are planning to submit proposals for funding under the new structure. For instance, if a proposal for a Breast Cancer Treatment Workshop is received, the Joint Steering Committee will decide to have the workshop sup-ported under the Cancer Treatment Program Area. Again, if the Bladder Cancer group wishes to organize a workshop on Etiology, Diagnosis, and Treatment of Bladder Cancer, the proposal will be referred to the Interdisciplinary Program Area.
Mr. Soda stated that there will be additional responsibilities for planning and organization placed on the Program Coordinators: therefore, it will be up to the Program Coordinators not only to provide planning but also to put plans into practice, maintaining contact with the JSPS and the NCI for budget purposes.
Under the current (First Five-Year Program) structure, Dr. Newell stated that subject matters were "locked into" the eleven designated Program Areas and that each of the eleven areas felt there was responsibility to hold one meeting per year. Under the new program structure, it will be easier to combine two program areas (e.g., immunology and cytology) to hold a workshop or a meeting to cover both areas.
Dr. Yoji Ikawa reiterated that under the current system, the program content was distinct and it was the responsibility of the Co-Program Coordinators to plan their respective program area.
Mr. Soda stated that under the new structure there will be Program Coordinators selected for four large program areas instead of eleven program areas. The newly appointed Program Coordinators will have greater responsibility and will need to be more aware of the different research areas.
Dr. Ikawa recommended that for the Japanese the present eleven coordinators could remain as participants and an advisory or program body could meet to advise the JSPS. It was suggested that the four newly appointed Program Coordinators could use other consultants or "principal advisors" on a semi-permanent or ad hoc basis for advice.
Dr. George Bryan asked if the present JSPS-NCI Scientific Group would be dissolved. Dr. Newell stated that it has been in existence for five years and a change was needed and there should also be "turnover" of program areas. Dr. Newell further stated that he and others have been greatly appreciative of everyone's efforts in the past. Mr. Soda joined Dr. Newell in expressing their hopes that the present members of the JSPS-NCI Scientific Group will continue to participate in the Pro-gram as consultants to the new Program Coordinators or as organizers of workshops and conferences. They both praised the work of the present members.
Dr. Yuichi Yamamura asked what will happen to the current plans for meetings. Dr. Newell and Mr. Soda stated that the Program will honor the present commitments already made for the support of exchanges and meetings.
Dr. William Terry asked if the new structuring would increase or diminish funding. Mr. Soda responded by stating that the JSPS has plans for an increase of funds, but he is optimistic of at least a leveling for the present. It has been estimated that the JSPS and the NCI are each providing approximatehy $250,000 per year.
Dr. Oleg Selawry stated that the Program has acted as a catalyst and has stimulated new projects and collaboration. Dr. Bernard Weinstein stated that the Program has provided "seed money" for new exchanges and meetings. Several of the tangible and intangible benefits from the Program were discussed.
Dr. Selawry further stated that the Program Coordinators have established a great deal of mutual respect and trust for each other and smooth cooperation has resulted. He recommended that these intangible investments be preserved in the future.
Dr. Ikawa asked if the new Program Coordinators will include others who have new ideas and new advances. He recommended that each program area should have some type of a "working group" or an "advisory or consulting group."
Dr. Newell stated that all of us associated with the Program, presently and in the future, will need the support of everyone to make the Program functional. The next year will be a transitional period and he would like to see input from anyone who has been participating in the Program.
Dr. Yamamura asked about the opinion of the JSPS. Dr. Sugano stated that the plans are that the term of the present JSPS-NCI Scientific Group will end on March 31, 1979, and the new Program Coordinators will be appointed effective April 1, 1979. Each side will make recommendations for "principal advisor" or "working groups." He stated that the Japanese side has generally agreed to the new structure and that the transition period could create some problems.
Dr. Takashi Sugimura agreed with Dr. Weinstein that the Chemical Carcinogenesis or Carcinogenesis Program Area should be changed to the Etiology Program Area. During the past five years, the Chemical Carcinogenesis Area had covered a rather broad area of cancer research besides chemical carcinogenesis. The new Etiology Program Area will present opportunities to provide coverage for environmental carcinogens, epidemiology, viral oncology, radiation biology, and other research areas.
He further stated that new needs and research advances must be met by a more flexible and broader program structure. There may be some good and some bad experiences, but the Program must be in a position to be more responsive to new demands. He believes that under the new program structure, the JSPS will have more justification to obtain government funds. He further stated that the current Program has been excellent in furthering goodwill, mutual trust and respect, and very smooth collaboration among all the program areas.
Dr. William Terry stated that the Joint Steering Committee has a good mutual agreement in their perception of restructuring the Program, thereby strengthening and improving the Program.
Drs. Ikawa and Weinstein suggested that progress reports from the exchange of scientists would be an excellent device to evaluate the effectiveness of the Program. The report forms will be mailed by the NCI to the Program Coordinators so that they may be integrated into the future annual reports. It was agreed that the draft of the annual report would be compiled by the NCI summarizing the reports presented at this meeting, and that it would be published by the JSPS in the Spring of 1979.
Drs. Newell and Sugano recommended that letters of appreciation be sent from the JSPS and the NCI to Dr. Hamao Umezawa for his contributions to the Program and for the supply of protease inhibitors he provided for research purposes. The inhibitors have added a new area of interest in the field of cellular and molecular biology. Also a letter of appreciation will be sent to Dr. Walter Troll for his services in distributing the protease inhibitors to American and other foreign scientists for research in cell biology.
Drs. Sugano and Newell reported that the Japanese Association for Cancer Research would like to publish a GANN monograph about the U.S.-Japan Cooperative Cancer Research Pro-gram, limited to twenty contributed articles on cancer research. It is planned to be a publication of scientific activities. Dr. Sugano invited all of the Program Coordinators to contribute articles for the publication. The proposed deadline for the manuscripts will be July 1979 for February 1980 publication.
Mr. Justin Bloom, Counselor for Science and Technology, American Embassy, Tokyo, Japan, reported that the Embassy judges the U.S.-Japan Cooperative Cancer Research Program to be one of the best cooperative scientific programs between Japan and the U.S. He stated that many scientists and lay persons do not know of the Program. He suggested that an article about the Program be published in Science or other widely read journals which have worldwide distribution. Dr. Newell reported that a brief article appeared in the Journal of the National Cancer Institute (JNCI) in February 1977.
Dr. Terry asked about the audience for the GANN monograph. Dr. Sugano stated that the monograph content would be targeted to the world scientific community, providing information on the Program as well as documentation of scientific progress and cooperation sponsored under the Pro-gram. Dr. Terry suggested that other participants in the Program, such as exchange scientists and participants at the workshops and seminars who are recognized authorities in their respective fields, should be invited to submit manuscripts. Dr. Sugimura stated that he is inclined to think that most scientists would rather publish primary papers in various journals and consider monographs and review articles as secondary publications. Monographs, in general, contain review articles which are usually of general interest.
Dr. Newell stated that he and Dr. Sugano are extending invitations to all of the Program Coordinators to submit manuscripts for the GANN monograph.
The meeting was adjourned at 10:40 a.m. by the Co-Chairman, with heartiest thanks to all the participants.

Respectfully submitted,

Robert R. Omata, Ph.D.
Executive Secretary
U.S.-Japan Cooperative
Cancer Research Program
National Cancer Institute


MINUTES OF THE JOINT STEERING COMMITTEE MEETINC
Tokyo, Japan November 1, 1978

The Co-Chairmen of the Joint Steering Committee, Drs. Haruo Sugano and Guy Newell, called the meeting to order at 11:05 a.m. The following members and observers were in attendance:

Drs. Haruo Sugano, Yuichi Yamamura, Yoshio Sakurai, Takashi Sugimura, Mr. Saburo Kasagi, Mr. Kichimasa Soda, Drs. Guy Newell, Stephen Carter, William Terry, I. Bernard Weinstein and Robert Omata. The observers were Mr. Nagahide Onozawa, JSPS, and Dr. Donald Henson, NCI.
Drs. Weinstein and Sugimura began the discussion on the four new Program Areas:
1. Carcinogenesis
2. Biology and Diagnosis
3. Treatment
4. Interdisciplinary Program
It was recommended that the Carcinogenesis Program Area be changed to Etiology Program Area and include the sub-areas of: (a) Epidemiology, (b) Chemical and Radiation Carcinogenesis, (c) Viral Carcinogenesis, and (d) Genetics.
The subject of implementation of the newly structured program was brought up for discussion. Initially the Program Area Coordinators should plan for two or three meetings per year for each of the Program Areas. It was the general opinion of the group that there may be some difficulty in program planning for the first year. It will be necessary for each side to invite appropriate consultants or principal advisors for each of the Special Interests under the Program Areas.
Also, the problem of sponsoring a meeting which is among one of the current structures, for in-stance, metastasis, should have to be categorized under Biology and Diagnosis. Other examples are as follows:
1. Lung Cancer Treatment Meeting would be under Treatment Program Area
2. Bladder Cancer Meeting could easily be under Interdisciplinary as organ site and the meeting would deal with the multidisciplinary approach to cancer
3. Breast Cancer Treatment would be under Treatment Program Area.
A proposal for meetings from any scientist or investigator who wishes to organize a meeting under the U.S.-Japan Cooperative Cancer Research Program would have to have a co-organizer from the other side. The proposal could be sent to the Pro-gram Area Coordinator for his country or sent to the JSPS or the Office of International Affairs (OIA), NCI. It would be up to the JSPS or the NCI to notify the Program Coordinators and obtain a review or opinion on the worthiness and/or priority for sponsorship of the meeting under the appropriate program area.
Mr. Soda and Dr. Terry suggested that the responsibility for programming and planning would be that of the Program Coordinators. A procedure for referral by the JSPS and the OIA, NCI, can be established. This was agreed upon.
Dr. Weinstein asked if the organ sites will be limited to only four, such as stomach, lung, breast, and bladder. It was agreed that organ sites would be selected on an ad hoc basis under the Inter-disciplinary Program Area. It was agreed that proposals on organ sites should be left open, depending on the main topic or topics which the organ site proposal would emphasize, such as chemotherapy of bladder cancer. It was generally agreed that topics on organ sites will be considered on a priority basis for support. It was also agreed that the Inter-disciplinary Program Area will act as the "clearing house" for proposals on organ sites and possibly refer the proposal to the appropriate Program Area.
After considerable discussion, Drs. Sakurai and Carter agreed that Clinical Trials should be included under Treatment, in which the following research areas will be included:
Treatment:
1. Chemotherapy
2. Radiation Oncology
3. Immunotherapy
4. Combined Modality
5. Clinical Trials
The subject of selection of Principal Advisors was brought up for discussion. It was generally agreed that the Program Area Coordinators will have the prerogative of establishing ad hoc or semipermanent advisors to form a working group. The coordinators should have the freedom to select advisors on a one-time or continuing basis, according to their needs and requirements. The selection will remain an open policy. Some advisors may be invited on a one-year term basis.
Dr. Terry led a discussion on the possibility of a person, outside of the new structure, proposing a meeting or seminar. It will be possible for a potential proposel or organizer with a new idea to contact one of the advisors for his opinion and then refer the proposal to the Program Coordinator for a decision for support. Dr. Yamamura stated that he favored the procedures to have the Program Coordinators make the decision to support the meeting or exchange of personnel with consultation with an appropriate advisor. This procedure was agreed upon by all the Program Coordinators.
There was full agreement that the following structure of the Program Area will be established in 1979:
I. Etiology
1. Epidemiology
2. Chemical and Radiation Carcinogenesis
3. Viral Carcinogenesis
4. Genetics
II. Biology and Diagnosis
1. Cellular and Molecular Biology
2. Immunology
3. Diagnosis
III, Treatment
1. Chemotherapy
2, Radiation Oncology
3, Immunotherapy
4. Combined Modality
5. Clinical Trials
IV. Interdisciplinary and Program Coordinators
1. Overall coordination of above three program areas
2. Consideration of the new programs or special areas of interest
3. Sponsoring of interdisciplinary sessions
4. Organ sites
It was agreed that the First Joint Steering Committee Meeting be held in San Francisco, California, on May 24 and 25, 1979, following the Chemotherapy Review Meeting on May 21 to 23, 1979.
Finally, Dr. Donald Henson was asked to pre-sent a brief report on the possibility of a collaborative study on "Low Dose Radiation and Breast Cancer" between the National Cancer Institute (NCI) and the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan. If the proposed collaboration is finally approved by the NCI and the RERF, the U.S.-Japan Cooperative Cancer Research Program would provide the "stamp of approval" and provide support for a limited number of personnel exchanges under the Interdisciplinary Program Area.
The meeting was adjourned at 12:30 p.m. The National Cancer Institute hosted the Japanese delegation and other members of the Joint Scientific Groups to a buffet luncheon.

Respectfully submitted,

Robert R. Omata, Ph.D.
Executive Secretary U.S.-Japan Cooperative
Cancer Research Program
National Cancer Institute

PARTICIPANTS AND OBSERVERS

UNITED STATES

Dr. Guy R. Newell
(Chairman)
Deputy Director, NCI

Dr. Nathaniel I. Berlin
Director, Comprehensive Cancer Center
Northwestern University Medical School

Dr. George T. Bryan
Professor, Human Oncology
University of Wisconsin

Dr. Stephen K. Carter
Director, Northern California Cancer Program

Dr. Chester J. Herman
Laboratory of Pathology, Division of Cancer
Biology and Diagnosis, NCI

Dr. Robert W. Miller
Chief, Epidemiology Branch, Division of
Cancer Cause and Prevention, NCI

Dr. Oleg S. Selawry
Deputy Director for Intramural Affairs
Comprehensive Cancer Center
University of Miami School of Medicine

Dr. Glenn E. Sheline
Professor, Division of Radiation Oncology
University of California

Dr. Philip G. Stansly
Program Director for Viral Oncology
Division of Cancer Research Resources and
Centers, NCI

Dr. William D. Terry
Associate Director for Immunology
Division of Cancer Biology and Diagnosis, NCI

Dr. I. Bernard Weinstein
Professor and Director, Division of
Environmental Sciences, Columbia University

Dr. Robert R. Omata
Executive Secretary, U.S.-Japan Cooperative
Cancer Research Program
Office of International Affairs, NCI

Observers

Mr. Justin L. Bloom
Counselor for Scientific and Technological
Affairs, Embassy of the United States of America

Dr. Stuart C. Finch
Vice Chairman and Chief of Research
Radiation Effects Research Foundation

Dr. Donald E. Henson
Special Assistant
Office of International Affairs, NCI

JAPAN

Dr. Haruo Sugano, Chairman
Director, Cancer Institute
Japanese Foundation for Cancer Research

Dr. Takeshi Hirayama
Head, Division of Epidemiology
National Cancer Center Research Institute

Dr. Yoji Ikawa
Head, Laboratory of Viral Oncology
Cancer Institute,
Japanese Foundation for Cancer Research

Dr. Yohei Ito
Professor, Department of Microbiology
School of Medicine, University of Kyoto

Dr. Kiyoji Kimura
Director, Nagoya National Hospital

Dr. Yoshio Sakurai
Director, Cancer Chemotherapy Center
Japanese Foundation for Cancer Research

Dr. Haruo Sato
Professor, Research Institute for Tuberculosis
Leprosy and Cancer, Tohoku University

Dr. Takashi Sugimura
Director, National Cancer Center
Research Institute

Dr. Akira Tsuya
Head, Department of Radiation Therapy
Cancer Institute Hospital
Japanese Foundation for Cancer Research

Dr. Hamao Umezawa
Director, Institute of Microbial Chemistry

Dr. Tadashi Yamamoto
Director, Tokyo Metropolitan Institute of
Medical Science

Dr. Yuichi Yamamura
Professor, Department of Internal Medicine
Osaka University

Dr. Osamu Yoshida
Professor, Department of Urology
School of Medicine, Kyoto University

Dr. Fujio Otani
Counselor for Science and Technology
Minister's Secretariat
Ministry of Health and Welfare
Japanese Government

Mr. Akira Tezuka
Deputy Director-General,
Science and International Affairs Bureau
Ministry of Education, Science and Culture

Observer

Mr. Ikuo Ushio
Deputy Director, International Science Division
Science and International Affairs Bureau
Ministry of Education, Science and Culture
Japanese Government

JSPS

Mr. Saburo Kasagi
Executive Director

Mr. Kichimasa Soda
Head, Program Department

Mr. Nagahide Onozawa
Head, Research Cooperation Division
Program Department

Mr. Iwao Abe
Research Cooperation Division

Mr. Shigeyuki Shimoda
Research Cooperation Division