SUMMARY REPORTS OF EXCHANGE SCIENTISTS

(1)Koji Nanba
Hiroshima University

Sponsor and Host Institutions:
Dr. Eugene Yanagihara Kuakini Medical Center, Honolulu
Dr. Bharat N. Nathwani University of Southern California
Dates of Visit: February 8- March 9, 1986

Summary of Activities:
The purpose of the visit was to study histopathologically malignant lymphomas among Japanese-Americans from the viewpoint of comparative geographic pathology. The computer printout had listed 234 such lymphomas in the Hawaiian Cancer Registry through 1984, but only 154 cases were available for review. They were reclassified according to the Working Formulation. 139 cases were accepted as malignant lymphomas and 15 were rejected because they were not lymphomas or the slides were technically inadequate. Non-Hodgkin's lymphoma was the diagnosis for 133 (96 percent) cases and the remaining six cases had Hodgkin's disease.
Of the 128 cases of non-Hodgkin's lymphoma that were morphologically subclassifiable, 90 were of the B-cell type including 25 follicular lymphomas, of which 22 were of the follicular small-cleaved and follicular mixed types. 24 were of the T-cell type. Thus, at least 80 percent of non-Hodgkin's lymphoma was of the B-cell type. 103 (74 percent) were nodal and 36 were extranodal.
These data indicate that malignant lymphomas among Hawaiian Japanese resemble those of U.S. Caucasians with respect to the relative excess of B-cell non-Hodgkin's lymphoma, including follicular lymphoma and the predominance of nodal lymphomas. Japanese in Hawaii and Japan, however, both have a low frequency of Hodgkin's disease, an observation that suggests a genetic influence. Future collaboration was agreed upon, and the results of the slide review in Hawaii will be presented at the next Cancer Congress in Japan. Publication of a joint paper is planned. In Los Angeles, I engaged in detailed exchanges of opinions with Dr. Nathwani and other investigators.



(2)Aya Hanai
Center for Adult Diseases
Osaka

Sponsor and Host Institution:
Dr. John L. Young, Jr. National Cancer Institute
Dates of Visit: October 20- December 19, 1985

Summary of Activities:
The purpose of my visit was a) to learn about the system and activities of the Surveil-lance Epidemiology and End Results (SEER) Program in the U.S., and b) to studys factors concerning the difference in stomach cancer survival among Whites and Japanese in the U.S. and Japanese in Japan. The center for SEER data is at NCI, and the data are collected at 10 locations in various parts of the U.S. I visited NCI, and the registries in California, Iowa, Connecticut, and Honolulu. I also attended the Annual Meeting of the International Association of Cancer Registries and the 1985 annual meeting of the SEER Program.

Oct. 21 Los Angeles Cancer Surveillance Program: H. Menck, Deputy Director and 3 other members of the registry
a) Studied the system of cancer registration; mainly a data-collection system, data-matching system and the education of abstractors in this non-SEER registry.
b) Discussed the methodology of a case-control study using registry data. Obtained the manual for neighborhood control selection.
c) Discussed the incidence of cancer in Korean and other Asian groups in the USA.
Oct. 22 Kenneth Norris Jr. Cancer Hospital and Research Institute, Univ. of Southern California: B.E. Henderson, Prof., Director.
Discussed epidemiological studies at the Institute and the next symposium on cancer epidemiology in the Pacific Basin.
Oct. 23 California Tumor Registry: D. Austin, Director, V. Gurgin, Assist. Director and 4 other members of CTR.
Investigated registration methods in the SEER registry. The registration network system "CANCUR/NET" between hospital registries and central registry developed by CTR was especially studied.
North California Cancer Program: T. Davis, Director.
Discussed future cancer registration in California. New laws on cancer registration have just been signed by the Governor. Under the new laws cancer will become a reportable in the entire state in 1990. The new registration system and budget were discussed.
Oct. 24 General Tumor Registry, Cancer Research Institute, Univ. of California, C. Zippin, Prof. Director and D. Lum, Assistant Director
a) Studied the training program for cancer registrars: The 2-week, program in S.F. is conducted 3 or 4 times a year for the staffhospital-based as well as population-based cancer registries. 3- or 5-day programs for epidemiology or biostatistics are also prepared. The content and budget of the program were studied.
b) Investigated methodology and results of quality control of SEER registries. Reliability of collected data is important for data-utilizing. Collected instructions for quality control.
Oct. 25 State Health Registry of lowa: D. Isacson, Professor, Univ. of data K. McKeen, Assist. Director, SHIR.
a) Collected the following manuals: Iowa SEER Code Manual and general information on the State Health Registry of lowa.
b) Discussed and collected passive follow-up methods
Oct. 28-Dec.6 Demographic Analysis Section, National Cancer Institute: P. Greenwald, Director, Division of Cancer Prevention and Control E. Sondik, Chief, Surveillance and Operations Research Branch, C.R. Smart, Chief, Community Oncology and Rehabilitation Branch, R.W. Miller, Chief, Clinical Epidemiology Branch, J.D. Boice, Jr., Chief Radiation Epidemiology Branch, J.L. Young Jr., Chief Demo-graphic Analysis Section, and 7 other NCI staff members.
Studied the history, contracts, budget, results of cost analysis, quality control of the SEER Program, roles of central registry of SEER Program, SEER data, data utilization for epidemilogy and for cancer control, related laws, results of a review of the SEER Program, etc.:
Discussed and collected information on: 1. Requirements for new members of SEER Program, 2. Reports for cost analysis of the SEER program, 3. Quality control instruction manual, 4. Self instructional manual for cancer registrars vol. 1-8, 5. Summary staging guide, 6. Reports on SEER Program- importance and recommendations, 7. SEER annual reports, 8. NCI Fact Book for 1983, 9. Report of activities of the Division of Cancer Prevention and Control, 10. Report of activities of the Division of Cancer Epidemiology.
At the Annual Meeting of the American Public Health Association, attended 1) The cancer epidemiology session and 2) The National Death Index Session.
Dec. 9 Connecticut Tumor Registry: J.T. Flannery, Director and 4 other members of CTR. of CTR.
Discussed and collected information on the general system and activities of CTR: data collection, and storage, utilization of data by users outside the registry, multiple primary cancers in Connecticut and Denmark.
Dec.10- Dec.12 Annual Meeting of the International Association of Cancer Registries: The main theme was "multiple cancers".
Attended the meeting and presented "Association of 2nd primary leukemia to the method of treatment for the first primary cancer." Chaired the session, "Multiple Cancer and Computer Methodology."
Dec.13- Dec.14 SEER Program 1 985 Annual Meeting:
Presentation and discussion of the SEER registries' research activities and problems. Attended the meeting. Presented the results of a cooperative study of the difference in stomach cancer survival between Whites and Japanese.
Dec.16- Dec.17 Epidemiology Program, Cancer Research Center of Hawaii, Univ. of Hawaii at Manoa: L.N. Kolonel, Professor, Director, J.H. Hankin, J. LeMarchand and 4 other members of registry.
Discussed dietary study. Population by ethnic group in Hawaii as a denominator, and cooperation in future studies were also discussed.

The Exchange Scientist Program stimulates research in both countries, especially for the developing country. I hope more scientists will have more opportunities to participate in the future exchange program.



(3)Motoharu Seiki
Cancer Institute, Tokyo

Sponsor and Host Institution:
Dr. Kenichi Arai DNAX Research Institute of Molecular and Cellular Biology iralo Alto, CA
Dates of Visit: December 25, 1 985- January 12, 1986

Summary of Activities:
The pX is a unique gene of HTLV-I and is suspected to play an important role in leukemogenesis induced by HTLV-I infection. One pX gene product, p40X-IV, has the function to trans-activate transcription from its own LTR and some other promoters. This trans-activating function is supposed to be related to the transforming activity of HTLV-I by inducing lymphokines and their receptors, which are known to modulate T-cell proliferation, or by activating cellular growth related to genes directly. To confirm this idea, I visited DNAX Research Institute and started a collaboration with scientists there. They have an efficient virus vector system to introduce exogenous genes into T-cells, and quick methods to analyze the altered expression of lymphokines and receptors.

Achievements at DNAX Research Institute:
  1. Recombinant retrovirus vector and EB virus vector having a pX gene were constructed.
  2. A large amount of constructed recombinant plasmids were prepared.
  3. Biological activities of pX gene in the recombinants were confirmed.
  4. Recombinant viruses were successfully recovered after DNA transfection of recombinant plasmid into helper virus-producing cell lines.
  5. Various mouse T-cell clones were infected with recovered recombinant viruses.
  6. A mouse T-cell clone was transfected with recombinant EB virus vector.

Thus, our collaboration has just started and it will take a long time to observe alterations of infected or transfected cells. However, these are inevitable steps for us to identify the cellular target genes which are activated by the pX product and related to leukemogenesis.



(4)Charles E. Rogler
Albert Einstein College of Medicine
New York

Sponsor and Host Institution:
Dr. Okio Hino Cancer Institute, Tokyo
Dates of Visit: November 2- 1 8, 1985

Summary of Activities:

Nov. 6: Gave a seminar at Ehime University School of Medicine on "Chronic HBV Infection and Hepatocellular Carcinoma."
Nov. 7-9 Participated in the Annual Meeting of the Japanese Society of Gastroenterology (Ehime).
Gave a special lecture on "Cellular and Molecular Aspects of Chronic Hepatitis Infection and Hepatocellular Carcinoma."
Served as Commentator at a special symposium on current research in Hepatitis B virus DNA in Japan.
Nov. 11-13 Visited the Cancer Institute, Tokyo- Worked on collaborative research project with Dr. Okio Hino.
Nov. 12 Gave a lecture at the Fall meeting of the Japanese Society of Pathology on "Molecular Aspects of Chronic HBV and WHV Infection and Hepatocellular Carcinoma."
Nov. 13 Gave a lecture at the Cancer Institute, Tokyo, on "Molecular Aspects of Chronic HBV and WHV Infection and Hepatocellular Carcinoma."

Impressions of State of Science in Japan in Hepatitis Research
Japanese scientists are pursuing vigorous studies in many areas of hepatitis research. My primary interactions were with investigators working on molecular aspects of hepatocellular carcinoma. Excellent work is being conducted by Dr. Okio Hino of the Cancer Institute investigating the molecular structure of HBV integrations. Dr. Hino has set up a laboratory to study HBV integrations, and he has sequenced several viral-cell junctions from cloned HBV integrations. He has also subcloned unique cellular sequences flanking HBV integrations and looked for modifications in these sequences in panels of HCC DNA's from many patients. Dr. Hino has made observations indicating that sequences flanking HBV integrations may be amplified in independent tumors. This observation is very exciting and could lead to a major advance in the field of HBLV research. Dr. Hino's research is on the leading edge of HBV research worldwide. Dr. Kobayashi in Dr. Hattori's group in Kanazawa University has developed a woodchuck HCC cell line which is a valuable contribution to the field.
Studies on the mechanism of HBV integration are also being conducted in Dr. Koike's laboratory in the Cancer Institute, Tokyo, using molecular cloning technology. Excellent work is also being conducted on molecular aspects of DHBV infection and HCC in Pekin ducks and Chinese ducks in the laboratories of Dr. Okuda and Dr. Uchida. Many other workers, too numerous to name, are actively pursuing interesting studies of HBV.
Drs. Tomo Kitagawa and Haruo Sugano of the Cancer Institute are leaders in the field of chemical hepatocarcinogenesis. They have developed cell cultures of rat hepatocytes at various stages during hepatocarcinogenesis. Experimental manipulation of these cells with phenobarbital can accelerate the rate of oncogenesis, and the system they have developed can be used to study the mechanism of this promotion. These cells represent a valuable contribution to the field of experimental hepatocarcinogenesis.
In other areas, Dr. Seiki and Yoshida, also of the Cancer Institute have made very significant contributions to HTLV-I research. Their work characterizing the mechanism of control of gene transcription by the pX protein of HTLV-I is on the leading edge of its field.
I was happy to learn that the Japanese government is increasing its support of basic research. This is particularly helpful in the areas in HBV and HTLV-I research. As can be seen by my brief review, I was very impressed with Japanese scientists and their research programs.
The JSPS fellowship program is very valuable. The interactions and collaborations I was able to develop during my stay in Japan were valuable for me and the Japanese scientists involved. Plans for my trip and my Japanese host were excellent.
My general impression was that the Japanese scientists are very hard working, and imaginative in their research. The gracious hospitality I received during my stay gave me a very warm feeling toward Japanese people and customs. I greatly appreciate all the effort my hosts went to make my stay in Japan an enjoyable and productive one.