GENERAL SUMMARY OF THE PROGRAM ACTIVITIES, 1976-1977

The U.S.-Japan Cooperative Cancer Research Program, initiated in May 1974, has achieved noteworthy accomplishments and contributed to the better understanding and the advancement of basic and applied research in oncology during 1976 and 1977.
This bilateral program has been very productive and informative in the dissemination of recent advances in cancer research for the mutual benefit of the cooperating countries. The various program areas have provided excellent opportunities for Japanese and American scientists to engage in informal discussions and to plan collaborative research activities through the media of scientific meetings, seminars, and workshops. Active collaborations have been accomplished through the exchange of scientific personnel, information, and research resources. Some areas of basic and clinical research have been greatly enhanced through cooperative research activities.
The enthusiastic manner in which the Japanese and American scientists have participated in sharing the latest knowledge and advances in cancer research has been particularly impressive. As a result of the meetings and workshops, several joint publications have resulted from the cooperative bilateral programs, which would not have been possible without the interaction between American and Japanese scientists. The interactions have also resulted in the development of high regard and respect among the investigators facilitating more effective communication. Many of the benefits from this bilateral program are intangible; however, the exchange of information and personnel has been highly productive.
Some of the major accomplishments and unique contributions are summarized in this progress report.

Impact of the U.S.-Japan Cooperative Cancer Research Program to Each Country

During the past two years, the Program has had a major impact on scientific research in the cancer field. With the approach to cancer research being fundamentally different in the U.S. and Japan, the Program has encouraged the bringing together of varying viewpoints and methods from scientists in these countries and thereby has opened up a larger area for collaboration.
In the area of cancer virology, the introduction into Japan of new techniques for the study of exogenous and endogenous viral genes and their products has revolutionized fundamental and applied prokaryotic and eukaryotic molecular biology. These techniques include gene splicing, heteroduplex mapping, and analysis of viral transforming proteins.
In the area of cancer epidemiology, the contact between the American and Japanese scientists has initiated a major restructuring of epidemiology in Japan. The development of strong biomathematical and biostatistical inputs to analytical epidemiology has emerged as a redefinition of this scientific discipline.
In cytology, the introduction into Japan of flow analytic and sorting techniques for single cell, and the marked resurgence of interest in sophisticated modern image processing methods into the U.S., would not have occurred without this Program. In chemotherapy, the availability of antitumor antibiotics in the U.S. and the strengthening and redesign of clinical protocols in Japan were made possible under the auspices of this bilateral program.
In the carcinogenesis area, the extensive Japanese experience in environmental chemical carcinogens and mutagens has changed the direction and emphasis of research in the U.S. Conversely, the development of newer and more reliable and rapid carcinogen assay methods, developed in the U.S., has established cooperative research which changed the scope and nature of carcinogen screening in both countries.
Another area in which the Program has had a major impact is in the High LET Radiation Therapy Program where the American and Japanese fast neutron therapy programs have been placed on comparable biological and physical bases permitting comparison of data and development of joint or comparable randomized clinical trials. This program is exploring the relative roles of other high LET particle beams, e.g., pions, the hypoxic cell radiosensitizers, and hyperthermia.

Intensive Comparison of Cancer Patterns in the U.S. and Japan

The comparative epidemiology of cancer patterns in the U.S. and Japan was actively studied in terms of mortality, morbidity (analytical epidemiology group), histology (breast cancer group, urinary bladder cancer group, lung cancer group), and also in terms of host response, e.g., immunological response or estrogen receptors (breast cancer group).

Multidisciplinary Approach to Cancer Research

The Program provides opportunities for scientists in both countries to take multidisciplinary approaches in most of the program areas including chemical carcinogenesis, breast cancer, urinary bladder cancer, analytical epidemiology, high LET radiation therapy, chemotherapy, and cytology. For example, the high LET radiation therapy group brought together physicists, biologists, and clinicians on problems of radiation effect and toxicity. The cytology group brought together engineers, cell biologists, and pathologists to coordinate design of clinically appropriate cell analytic systems. The analytical epidemiology group brought together mathematicians, statisticians, and clinicians for assessment of data collection and analysis.

Research Promotion by Means of Resource Exchange

Research activities in both countries have been significantly stimulated by the exchange of much needed materials and reagents for research, such as protease inhibitors (Chemical Carcinogenesis Program Area), erythropoietin and antisera to type C viruses (Cancer Virology Program Area), BCG cell-wall skeleton (Cancer Immunology Program Area), and promising analogues of Bleomycin (Cancer Chemotherapy Program Area).

Research Promotion by Means of Exchange of Scientists

In each of the program areas, the exchange of scientists was actively planned and implemented. The total number of exchange scientists during 1976 and 1977 was 31 from the United States, and 34 from Japan.

Information Integration by Seminars on Problems of Key Importance

Program coordinators of both countries sponsored series of seminars on urgent problems in cancer research. Details of these seminars are shown in Appendix IV. For example, the “Workshop on Breast Cancer” disclosed entirely new information on estrogen receptor profiles in Japan and the United States.

Introduction of New and Modified Techniques

In some program areas, the exchange of scientists resulted in the introduction of new research techniques to both countries. One such example is the Pienta System of screening carcinogens by cell culture brought to Japan from the U.S. by a Japanese scientist. A scientific group has been formed in Japan under this subject to make full use of this new cell culture system. The introduction of the Ames test for mutagenicity and its subsequent modification by Japanese scientists has greatly affected the testing of potentially carcinogenic substances which are of great concern in both countries. As a result of continued collaboration, modified testing methods have been developed to further improve the reliability of the microbial assay system.

Innovation in Research Facilities and Equipment

As a result of the Program, notable progress was made in both hardware and software necessary for cancer research, diagnosis, and treatment. Examples include the development of instruments for cytology automation, software data processing in several program areas, treatment facilities, and a system using neutron beams (High LET Radiation Therapy Program).

Improvement of Comparability of Research Data

In several program areas, clinical trials were designed to improve comparability of results of cancer research in both countries. For example, uniform protocols in immunotherapy have been designed to ensure maximum comparability and reproducibility. A joint research protocol for gastric carcinoma was formulated by Japanese and American scientists. This has led to the initiation of a joint randomized chemotherapy clinical trial which includes a common treatment arm (cancer therapy group). After the initiation of a clinical trial, accumulation of sufficient research data for valid evaluation requires several years. The results of these studies are anticipated during the second five years of the U.S.-Japan Agreement.

Cancer Prevention Research

In both countries, cancer investigators are facing severe problems in terms of public pressures and demands by the regulatory agencies particularly in the area of carcinogenesis. To meet the demand, several program areas initiated work in cancer prevention. For example, the Chemical Carcinogenesis Program initiated studies on mutagenicity testing of hair dyes, cigarette smoke condensates, and daily foods. An intensive study of the influence of lifestyle, including dietary fat intake, on breast cancer is also being carried out by the Breast Cancer Program Area. These results will be of considerable importance in programs on cancer prevention and cancer control in both countries. Similar studies are in progress in the Lung and Urinary Bladder Cancer Program Areas.

Joint Publications

Joint publications of results of seminars and conferences which highlight the most recent information on basic and applied oncology in selected areas were sponsored in several program areas such as analytical epidemiology, chemical carcinogenesis, breast cancer, and metastasis. These joint publications would not have been possible without the U.S.-Japan Cooperative Cancer Research Program. In addition to these monographs and special journal issues, many individual scientific articles have been published resulting from the collaboration between exchange scientists and their sponsors.

STATUS REPORT OF ACTIVITIES

A summary of the activities of the U.S.-Japan Cooperative Cancer Research Program is presented in the following tables. Table 1 includes the status report for the period April 1, 1976 to March 31, 1977, and Table 2 includes the period April 1, 1977 to March 31, 1978.


Table 1. Summary of Activities April 1, 1976-March 31, 1977

Table 2. Summary of Activities April 1, 1977-March 31, 1978