SUMMARY REPORTS OF EXCHANGE SCIENTISTS
Report for Personnel Exchange under The US-Japan Cooperative Cancer Research Program
Hiroki Koyama, M.D.
Chief, Department of Surgery
The Center for Adult
Diseases, Osaka
1. Field of specialization
Cancer Chemotherapy
2. Subject of research
Chemo-endocrine Therapy for Breast Cancer
3. Period of stay
From November 16 to November 30, 1985 (15 days)
4. Name, position and institution of host scientist
William L. McGuire, M.D.
Chief, Division of Medical Oncology
Professor of Medicine
The University of Texas Health Science Center
5. Itinerary
| Nov. 16 |
Dept. Osaka- Arr. Buffalo |
| Nov. 18-19 |
Visit Drs. T.L. Dao and T, Nemoto
Department of Breast Surgery
Roswell Park Memorial Institute |
| Nov. 20 |
Dept. Buffalo- Arr. Washington, D.C. |
| Nov. 21-22 |
Visit Dr. M.E. Lippman
Head, Medical Breast Cancer Section
Medicine Branch
National Cancer Institute |
| Nov. 23 |
Dept. Washington, D.C.- Arr. San Antonio |
| Nov. 25-26 |
Visit Dr. W.L. McGuire
Chief, Division of Medical Oncology
The University of Texas Health Science Center |
| Nov. 27 |
Dept. San Antonio- Arr. Chicago |
| Nov. 27-28 |
Visit Dr. G.L. Greene
Associate Professor
The Ben May Laboratory
The University of Chicago |
| Nov. 29 |
Dept. Chicago |
| Nov. 30 |
Arr. Osaka |
6. Accomplishment
The main purpose of the present delegation was to learn the current status of chemo-endocrine therapy which attracted much attention in the treatment of breast cancer. The following questions were made to each of the doctors I visited:
(1)Simultaneous administration of chemotherapy and endocrine therapy is really advantageous over chemotherapy alone or endocrine therapy alone?
(2)If the two therapies are to be administered successively, which should be given first?
Dr. Dao and his coworkers (Drs. T. Nemoto and D. Shinha) answered that there was a considerable number of articles showing better results of chemo-endocrine therapy in terms of response rate but none showing definite advantage in terms of survival time after the start of treatment.
They usually started with endocrine therapy for the treatment of fresh patients with recurrences.
Dr. Lippman had the same opinion as Dr. Dao and his colleagues in that there was no positive reason to administer chemotherapy and endocrine therapy at the same time. He aggreed that Tamoxifen (TAM) to be given as an initial therapy for ER-positive patients followed by chemotherapy when the patients becomes refractory to TAM.
He sited the conclusion of the consensus development meeting for adjuvant chemotherapy that had been held in September, 1985. According to this, in premenopausal patients chemotherapy is positively indicated and in postmenopausal patients with ER-positive TAM is indicated. But in postmenopausal patients with ER-negative, no regimen is available at the present time that has proved to be effective.
I presented a lecture on chemo-endocrine therapy for advanced breast cancer at the staff meeting of Dr. McGuire's department, showing the results so far obtained in my institute and in Japan. Discussions were again directed to the problem as to whether mild therapy with single drug or heavy multiple chemo-endocrine therapy should be given as an initial therapy. The same conclusion was reached as obtained in the previous institutions I visited. But for rapidly growing ER-negative tumor they were obliged to give massive poly-chemotherapy since there is no alternatives.
Dr. Greene first succeeded to purify the monoclonal antibody for estrogen receptor. The enzyme-immuno assay(EIA) using this antibody is now taking the place of DCC method for ER determination. He and his coworkers are working on histochemical demonstration of ER by immuno-cytochemical assay(LCA) using frozen sections. Contrary to the expectation, ER localizes exclusively in nucleus, and not in cytoplasm. This new and interesting finding deserves further study. Determination of ER will become much easier and provide more important information for chemo-endocrine therapy not only clinically but also basically.
7. Requests to the scientist exchange program
Incidence and biology of breast cancer are greatly different between the US and Japan. Exchange of scientists is particularly meaningful in this area. I hope more scientists will have such opportunities in future exchange program.
Report on personnel exchange under US-Japan cooperative cancer research program
Takashi Tsuruo, Ph.D.
Chief-in-Research, Cancer Chemotherapy Center
Japanese Foundation for Cancer Research
Toshima, Tokyo 170, Japan
Subject: Basic research for the overcoming of drug resistance
Period: from April 23, 1984 to May 31, 1985
Host Scientist:
Dr. Robert F. Ozols Section
Chief, Medicine' Branch
Division of Cancer Treatment, National Cancer Institute
Bethesda, MD 20205, U.S.A.
| Scheduel: |
|
April 23, 1 984 |
leave Tokyo, arrive Bethesda, MD |
|
April 24, 1984- April 22, 1985 |
Research at NCI |
|
Nov. 1, 1984- Nov. 14, 1984 |
M.D. Anderson Hospital & Tumor Inst. (c/o Dr. I. J. Fidler) seminar & information exchange |
|
Nov. 14, 1984- Nov. 23, 1984 |
UCLA Cancer Center (c/o Dr. M. A. Baluda) seminar & information exchange |
|
April 22, 1985 |
leave Bethesda, arrive Houston |
|
April 23, 1985- May 30, 1985 |
Research at M. D. Anderson Hospital & Tumor Institute (c/o Dr. I. J. Fidler) |
|
May 30, 1985 |
leave Houston and arrive Tokyo on May 31, 1 985 |
Scientific Report
During the stay for one year at the National Cancer Institute, I could collaborate with Dr. Ozols and other scientists at the National Cancer Institute on the problems of anti-tumor drug-resistance from wide points of view. We collaborated on the problems of circumvention of multi-drug resistance of human tumors by calcium channel blockers and buthionine sulfoximine. We developed an approach to study the problems of drug-resistance as well as tumor metastasis by using cell fusion technique. This approach is useful for the studies of mechanisms of drug resistance and tumor metastasis in future.
I believe that an exchange program for one year is suitable for many purposes and the exchange of this time was fruitful for both sides not only for science but also for a good human relationship. The research projects and the publications during the exchange was the followings.
Research Projects
- Biochemical changes of drug resistant human ovarian tumor cells
- Potentiation of vincristine and adriamycin cytotoxicity by calcium channel blockers in human ovarian tumor cells
- Potentiation of adriamycin, melphalan and cisplatin cytotoxicity by buthionine sulfoximine
- Collateral susceptibility of adriamycin-, melphalan- and cisplatin-resistant human ovarian tumor cells to bleomycin
- Separation of adriamycin- and vincristine-resistant phenotypes and genes by cell fusion
Publications
- Louie, K. G., Hamilton, T. C., Winker, M. A., Behrens, B. C., Tsuruo, T., Klecker, R. W., Jr., McKoy, W. M., Grotzinger, K. R., Myers, C. E., Young, R. C. and Ozols, R. F. Adriamycin accumulation and metabolism in Adriamycin-sensitive and resistant human ovarian cancer cell lines. Biochem. Pharmacol., 35: 467-472 ( 1 986).
- Behrens, B. C., Hamilton, T. C., Louie, K. G., Grotzinger, K. R., McKoy, W. M., Tsuruo, T., Young, R. C. and Ozols, R. F. Activity of tricyclic nucleoside 5'-phos-phate in vitro and in vivo models of human ovarian cancer. Cancer Res., submitted.
- Hamilton, T. C., Winker, M. A., Louie, K. G., Betist, G., Behrens, B. C., Tsuruo, T., Grotzinger, K. R., McKoy, W. M., Young, R. C. and Ozols, R. F. Augmentation of Adriamycin, melphalan, and cisplatin cytotoxicity in drug-resistant and Hsensitive human ovarian carcinoma cell lines by buthionine sulfoximine mediated glutathione depletion. Biochem. Pharmacol., 34: 2583-2586 (1985).
- Tsuruo, T., Hamilton, T. C., Louie, K. G., and Ozols, R. F. Collateral susceptibility of Adriamycin-, melphalan-, and cisplatin-resistant human ovarian tumor cells to bleomycin. (in preparation).
- Behrens, B. C., Grotzinger, K. R., Hamilton, T. C., Whong-Peng, J., Batist, G., Louie, K. G., Knutsen, T., Tsuruo, T., McKoy, W. M., Young, R. C. and Ozols, R. F. Cytotoxicity of 3 cisplatin (CP) analogues (CPAs) in a drug sensitive and a new CP resistant human ovarian cancer (OC) cell line. 26th Annual Meeting of the American Association for Cancer Research. Abst. #1032, Houston, Texas, U.S.A., May, 1985.
- Hamilton, T. C., Winker, M. A., Louie, K. G., Batist, G., Fine, R. L., Behens, B. C., Tsuruo, T., Grotzinger, K. R., McKoy, W. M., Young, R. C. and Ozols, R. F. Augumentation of adriamycin (AD), melphalan (ME), and cisplatin (CP) cytotoxicity (CT) by buthionine sulfoximine depletion of glutathione (GSH) in drug (D) resistant (R) human ovarian cancer (OC) cell lines (C1). 26th Annual Meeting of the American Association for Cancer Research. Abst. #1361, Houston, Texas, U.S.A., May, 1985.
REPORT OF THE STUDY
Tsukuba University
Toshio Kitagawa M.D.
Clinical value of particle therapy with proton beams, heavy ion beams and fast neutron beams, and production of practical unit in these particle treatment were investigated successfully with discussion on mainly clinical basis with radiotherapists and radiophysicists at the most active institutions for the particle therapy in the United States of America namely Massachusetts General Hospital in Boston, Memorial Center in New York, Lawrence Berkeley Laboratory in Berkeley, University of Washington Hospital in Seattle. The results of investigation are as follows,
1. Proton beam irradiation could be taken in cancer therapy field as a main particle treatment technique in at least next ten years. Because proton beam treatment is safe and easy to manage with good result and minimal radiation injury and also irradiation unit for clinical purpose may be produced with rather small, compact volume and with reasonable cost for maintenance.
2. Heavy ion beam treatment may obtain better tumor control than proton beams. However, there is still many problems to be investigated in clinical and fundamental basis. And also treatment unit for this particle is difficult to be produced with suitable size to install in ordinary hospital in this moment. Therefore, heavy ion therapy requires more time to be used for practical purpose.
3. Fast neutron therapy has more than ten years history on clinical use. However, treatment unit is to be improved to get reasonable dose distributions to decrease its late radiation injury.