REPORTS ON SEMINARS

(1) Seminar on "Carcinogenesis and Gene Expression in Liver Cell Culture"
This seminar was held in the East-West Center, University of Hawaii, Honolulu, on November 16-18, 1981. The organizers were Dr. Akira Ichihara, Institute for Enzyme Research, School of Medicine, University of Tokushima, Japan, and Dr. Gary M. Willians, Naylor Dana Institute, Valhalla, New York, U.S.A. There were 18 speakers: 9 from Japan, 8 from the U.S.A. and 1 from France. Use of liver cells in culture for cancer research became very popular recently, but there have been only three international meetings on this subject in the last 10 years. Therefore, it was a suitable time to have a meeting of experts from different countries to exchange information.
At this seminar it became clear that there are three kinds of liver cells in culture and the major object of this seminar was to discuss the specificity of each cell population for studies on hepato carcinogenesis.
One cell population is primary cultured parenchymal hepatocytes. These were shown to retain almost all liver functions and to be able to proliferate under certain conditions. The control mechanism of their cell growth could be compared with that of hepatoma cells. It was shown that hepatoma cells contain some growth promoting factors as well as having lost growth inhibitory factors. These cells can also be used to study the metabolism of carcinogens, their binding with DNA and repair of DNA. Their reactions in vitro mimic very well to those in vivo. Primary cultures of human hepatocytes are also available. It was also shown that parenchymal and non-parenchymal cells could be separated and their functional differences were reported. These studies have contributed much information on the mechanism of carcinogenesis of different liver cell types.
The second cell population is hepatoma cell lines derived from highly differentiated hepatomas. Since these cells retain some liver functions, they are useful for studies of particular liver functions and for comparison with normal hepatocytes. The changes in their properties during carcinogenesis have been shown to be immaturation, retrodifferentiation and fetalism. Recent studies have shown that these changes are due to change of gene expression, not to change in the cell population. Cultured liver cells are very useful for such studies.
The third cell population is epithelial liver cells. They can be isolated easily and established as cell lines. However, they show very few characteristics of liver cells and may be derived from bile ductal cells. There is some possibility that these cells can differentiate into parenchymal hepatocytes in vivo. These epithelial cells were also isolated from preneoplastic nodule of liver induced by administration of carcinogens in vivo and they can be transformed in vitro by addition of various carcinogens including promoters.
These studies on liver cells in culture showed that each cell population has their specificity for studies of hepatocarcinogenesis and that there are some relations of cell lineage among these cell populations. Therefore, they are useful to study various stages of hepatocarcinogenesis from very early initiation stage, preneoplastic stage to late stage.

(2) Seminar on "Intestinal Metaplasia and Stomach Cancer"
"The U.S.-Japan Cooperative Seminar on Intestinal Metaplasia and Stomach Cancer" was held from March 23 to March 25, 1982 at the Shimoda Tokyu Hotel in Shimoda, Shizuoka, Japan. The seminar organizers were Dr. Grant N. Stemmermann of the Kuakini Medical Center in Honolulu, Hawaii, and Dr. Takashi Kawachi of the National Cancer Center Research Institute in Chuo-ku, Tokyo. There were 19 speakers: 13 from Japan and 6 from the United States.
At this conference many aspects of intestinal metaplasia (I.M.) were considered. Various scientific disciplines are being used to study this interesting subject, which is no longer only of interest to pathologists.
Agreement could not be obtained on whether I.M. is a precursor lesion for stomach cancer or only an associated condition. Some speakers believed that a definite precursor relationship could be demonstrated, but others believed no close causative relationship existed. Since causes of stomach cancer are complex, it is reasonable to expect that some cancers can be formed by a process not related to I.M. formation. However, the association of I.M. with many stomach cancers appeared to be strong.
At the conference many discussions were held to develop ways of describing various forms of I.M. Besides the usual microscopic procedures and biochemical enzymatic techniques, new methods using stains for specific types of mucins and immunological procedures were described. While these techniques appeared to be useful, no general agreement was reached at the conference as to how they could be used to distinguish between complete I.M. and incomplete I.M. Several researchers had found different types of classification of I.M. with the hope that these classifications could help to indicate which type is most closely associated with stomach cancer.
Several papers were presented describing how mucosal conversion can result from the process of tissue repair in the gall bladder, small intestine and stomach. In this regard, an interesting finding on the relationship between the mesenchymal and epithelial tissue was presented; namely, that stroma can influence and guide the development of epithelial tissues.
Much progress has been made in the detection of I.M. in the human stomach by endoscopy using methylen blue and other dyes. This technique has many useful applications. It may be capable of detecting various types of I.M. and has been used in extensive screening studies of large populations. It is obvious that many more ways can be developed to use this technique in clinical practice and in research.
The conference showed that many investigators are enthusiastically working in different ways to understand the various aspects of I.M. We believe that the conference was an effective catalyst in stimulating ideas in the minds of the participants.
Unfortunately, Dr. Grant N. Stemmermann, the U.S. organizer of this conference could not attend the meeting at the Shimoda Tokyu Hotel because of his illness. Instead, Dr. Howard Mower served as the U.S. organizer during the conference. Dr. Stemmermann's paper was read by his colleague, Dr. Takuji Hayashi.


SEMINAR AGENDA AND PARTICIPANTS

(1) SEMINAR ON CARCINOGENESIS AND GENE EXPRESSION IN LIVER CELL CULTURES
Honolulu, Hawaii, November 16 to November 18, 1981

AGENDA