Program Reports
SEMINARS


1. BASIC SCIENCE

(1) Telomere, telomerase and cancer
Hawaii: August 3-5, 2002
Organizers: Dr. Jerry SHAY
Dr. Satoru KYO
Participants: US-11
Japan-12

(2) Tumor-specific Delivery:Approaching a Reality
Hawaii: February 12-15, 2003
Organizers: Dr. Esther H. CHANG
Dr. Kazuo MARUYAMA
Participants: US- 8
Japan-10


II. CLINICAL SCIENCE
(3) Hematopoiesis, hemopoietic malignancies and novel therapeutic approaches
Hawaii: February 12-15, 2003
Organizers: Dr. Pier Paolo PANDOLFI
Dr. Hisamaru HIRAI
Participants: US- 10
Japan- 10


III. EPIDEMIOLOGY/BEHAVIORAL SCIENCE
(4) Immigration and Cancer
Gifu (Japan) November 6-8, 2002
Organizers: Dr. Laurence N. KOLONEL
Dr. Hiroyuki SHIMIZU
Participants: US- 7
Japan- 10

(5) Tumor-Associated Mucins and Related Glycoproteins in Metastasis, Tumor-Specific Immunity and Immunotherapy
Hawaii: January 23-27, 2003
Organizers: Dr. Olivera FINN
Dr. Tatsuro IRIMURA
Participants: US- 10
Japan- 11



(1)Telomeres, telomerase and cancers
Period : from August 3th to August 5th 3days
Site: Maui Prince Hotel, Hawaii

Organizer:
Kyo Satoru
Kanazawa Universit School of Medicine
Department of Obstetrics and Gynecology
Lecturer

Shay Jerry
University of Texas, Southwestern University
Cell Biology
Professor


List of Japanese-side Participants

Eiso Hiyama
Associate Prof.
Hiroshima University

Keiko Hiyama
Assistant Prof.
Hiroshima University

Hidetoshi Tahara
Associate Prof.
Hiroshima University

Tohru Kiyono
Director
National Cancer Center

Kazuma Ohyashiki
Prof.
Tokyo Medical School

Junko Ohyashiki
Assistant Prof.
Tokyo Medical School

Tetsuzo Tauchi
Assistant Prof.
Tokyo Medical School

Masaki Inoue
Prof.
Kanazawa University

Yoshinori Yamashita
Director
Kyowa Hakko Kogyo

Kenkichi Masutomi
Research Associate
Dana Farber Cancer Institute

Toshiyoshi Fujiwara
Assistant Prof.
Okayama University

List of US-side Participants

Woodring Wright
Prof.
UT Southwestern Medical Center

Calvin B. Harley
President
Geron Corporation

Kathleen Collins
Prof.
University of California - Berkeley

David Corey
Prof.
UT Southwestern Medical Center

Robert H. Vonderheide
Prof.
University of Pennsylvania School of Medicine

John Jakubczak
Director
Genetic Therapy, Inc

Klaus Damm
Director
Boehringer Ingelheim Pharma KG

Bingliang Fang
Asociate Prof.
MD.Anderson Cancer Center

Anish Majumdar
Researcher
Geron Corporation

David Karpf
Researcher
Geron Corporation

List of Other Country Participants

E, Caso Peláez
Prof.
Laboratorio de Oncología Molecular Aplicada, Spain

Nicol Keith
Prof.
CRC Department of Medical Oncology, England


Itinerary and Topics

Saturday, August 3, 2002.
8:00pm Welcome and meeting plan overview Jerry Shay (UT Southwestern Medical Center)
Satoru Kyo (Kanazawa University)
8:15 - 9:00 Keynote address
Calvin Harley (Geron Corporation)
Therapeutic opportunities of telomerase modulation
9:00 -10:30
Social

Sunday evening, August 4, 2002
7:30 - 7:50 GRN163 - a potent telomerase template antagonist - preclinical update on gliomas, myelomas and lymphomas David Karpf (Geron Corporation)
7:50 - 8:10 Telomerase inhibition and cell death induced by telomerase template antagonist GRN163
Yoshinori Yamashita (Kyowa Hakko Kogyo Co. Ltd)
8:10 - 8:30 Combining gene therapy and telomerase inhibitors Jerry Shay (UT Southwestern Medical Center)
8:30 - 9:00 Discussion
9:00 - 10:30 Social

Monday morning, August 5, 2002
8:00 - 8:20 Telomerase as a new molecular target for cancer diagnosis and therapy Masaki Inoue (Kanazawa University, Japan)
8:20 - 8:40 Replication-competent adenovirus (TRAD) for human cancer therapy: Selective oncolysis by TRAD in telomerase-positive human cancer cells Toshiyoshi Fujiwara (Okayama University, Japan)
8:40 - 9:00 Targeted expression of proapoptotic genes from the hTERT promoter for cancer therapy Bingliang Fang (M.D. Anderson Cancer Center)
9:00 - 9:20 An oncolytic adenovirus dependent on two prevalent alterations in human cancer: Disregulation of the Rb pathway and telomerase John Jakubczak (Genetic Therapy, Inc.)
9:20 - 9:50 Discussion
9:50 - 10:30 Coffee break
10:30 - 10:50 Telomerase as a target for immunotherapy Robert H. Vonderheide (University of Pennsylvania School of Medicine)
10:50 - 11:10 Development of Telomerase based therapeutic vaccines for the treatment of cancer Anish Majumdar (Geron Corporation)
Monday evening, August 5, 2002
7:30 - 7:50 Clinical utility of telomerase in solid tumors Eiso and Keiko Hiyama (Hiroshima University)
7:50 - 8:10
 Diagnostics update of telomeres and telomerase in hematologic neoplasias Junko Ohyashiki (Tokyo Medical University, Japan)
8:10 - 8:30 Identification of serum-anti-human telomerase reverse transcriptase (hTERT) auto-antibodies during progression to hepatocellular carcinoma. Kenkichi Masutomi (Dana-Farber Cancer Institute)
8:30 - 8:50 Role of hTERT gene detection from human body fluids of patients with solid tumors Enrique Caso Pelaez (Ramón y Cajal Hospital, Madrid Spain)
8:50 - 9:30 Discussion/meeting wrap up
9:30 - 11:00pm Social


Scientific Achievements
The major focus of this seminar was how we can apply the knowledge of telomeres and telomerase to cancer diagnosis and therapy. The hot topic was novel anticancer strategy using telomerase inhibitors. A various inhibitors of telomerase have been developed, and the antisense strategies against telomerase RNA as well as telomere structures appeared to be the most promising ones. In fact, striking evidence has been shown that these reagents can inhibit growth of cancer cells following significant telomere shortening. Another exciting topic was telomerase-based immunotherapy against cancers. The catalytic subunit of telomerase, hTERT, was shown to be the good target for the induction of CTL against cancer cells. These novel strategies are currently considered for clinical trials in some institutes of the USA. The molecular mechanisisms of telomerase activation in cancers were also discussed. Transcriptional regulation of hTERT was shown to play the critical roles in hTERT expression in cancers and several novel mechanisms including hypoxia-mediated hTERT induction as well as MAP kinase signaling pathway for hTERT activation were shown. The potential utility of hTERT promoter for cancer gene therapy was also demonstrated. This promoter is highly specific to cancer cells and the target genes driven by this promoter are shown to be expressed only in cancer cells but not normal cells. Replication-competent adenoviral vector system that contain hTERT promoter was introduced by several researchers. This system has extremely potent anti-tumor activity without any significant damage to normal cells. These strategies will be applied as novel techniques for cancer gene therapy in the near future.

Comments and Opinions
This seminar provides us great advantage to our Japanese researchers for scientific communication between Japanese and USA researchers. This kind of closed seminar as well as socials after the presentation were extremely beneficial for us to obtain new information and hot topics about cancer research in the USA. The number of participants were appropriate for closed seminar and to achieve nice discussion. The budget for seminar was also sufficient but will be better if it can be available for any kinds of socials, which are also important for us to get critical information on science.



(2) Hematopoiesis, hemopoietic maligancies and novel therapeutic approaches
Period : from 12 February to 15 February , 4 days
Site : Hawaii (Maui island), USA
Japanese Organizer:
Hisamaru Hirai
University of Tokyo Hospital
Department of Cell Therapy & Transplantation Medicine
Associate Professor

US Organizer :
Pier Paolo Pandolfi
Memorial Sloan-Kettering Cancer Center
Department of Human Genetics and Molecular Biology
Professor

List of Japanese-side Participants:

Toshio Suda
Professor
School of Medicine, Keio University

Toru Nakano
Professor
Research Institute for Microbial Diseases, Osaka University

Masayuki Yamamoto
Professor
Center for TARA, University of Tsukuba

Tsukasa Okuda
Lectuerlar
Kyoto Prefectural University of Medicine

Kinuko Mitani
Professor
Dokkyo University School of Medicine

Takuro Nakamura
Chief
The Cancer Institute, Japanese Foundation for Cancer Research

Kazuo Kitabayashi
Chief
National Cancer Center, Research Institute

Sumiko Watanabe
Associate Professor
Institute of Medical Science, Tokyo University

Toshiya Inaba
Professor
Research Institute for Radiation Biology and Medicine, Hiroshima University

List of US-side Participants:

Leonard Ira Zon
Professor
Harvard Medical School

Riccardo Dalla-Favera
Professor
Columbia University

James N. Ihle
Professor
St Jude Children's Research Hospital

Tom Look
Professor
Dana-Farber Cancer Institute

Gerard Grosveld
Professor
St. Jude Children's Research Hospital

Charles Sawyers
Professor
UCLA

Gary Gilliland
Associate Professor
Harvard

Mike Bishop
Assistant Professor
UCSF

Michael Cleary
Professor
Stanford University

List of Other Country Participants:

Yoshiaki Ito
Professor
Principal Investigator
Institute of Molecular and Cell Biology
Singapore

Itinerary and Topics

Wednesday February 12
Arrival and Hotel check-in

Thursday February 13
Session I. Hematopoiesis / Chairs: Len Zon & Toshio Suda
9:00 - 9:30 GATA-2function in hematopoietic differentiation Toru Nakano
9:30 - 10:00 Induction of hematopoiesis in the zebrafish Len Zon
10:00 - 10:30 Leukemia in GATA-1-knockdown mouse Masayuki Yamamoto
11:00 - 11:30 Hematopoietic stem cells in vascular niche Toshio Suda
11:30 - 12:00 Slugging Away at Cell Death in Acute Leukemia and Normal Hematopoietic Progenitor Cells Tom Look
12:00 - 12:30 Functional regulation of TEL by ERK-induced phosphorylation Kinuko Mitani
Session II. Transcription Factors / Chairs: Gerard Grosveld & Tsukasa Okuda
2:00 - 2:30 Biologic functions mediated by C-terminal subdomains of the leukemia-associated transcription factor, AML1/RUNX1 Tsukasa Okuda
2:30 - 3:00 The roles ofAML1 transcription factor in adult hematopoiesis Hisamaru Hirai
3:00 - 3 :30 TEL genes in leukemia Gerard Grosveld
3:45 - 4:15 Functions ofAML1 transcriptionfactor complexes Issay Kitabayashi
4:15 - 4:45 A role for posttranslational modification in the regulation of AML1 function Mineo Kurokawa

Friday February 14
Session III Hematopoietic Malignancies / Chairs: Michael Cleary & Yoshiaki Ito
9:00 - 9:30 New mouse models for lymphoma Mike Bishop
9:30 - 10:00 Multistep genetic alterations associated with RUNX1/AML1 related leukemia Yoshiaki Ito
10:00 - 10:30 Deconstructing leukemia genetics in the mouse Pier Paolo Pandolfi
11:00 - 11:30 Molecular pathogenesis of B cell lymphoma Riccardo Dalla-Favera
11:30 - 12:00 Identification of cooperative disease genes for NUP98-HOXA9 in myeloid leukemogenesis
Takuro Nakamura
12:00 - 12:30 Role of the epigenetic regulator MLL in myeloid leukemias Michael Cleary
Session IV. Signaling & Therapeutics / Chairs: James N. Ihle & Toshiya Inaba
2:00 - 2:30 Expansion of haematopoietic stem cells by modified cytokine receptor signals Sumiko Watanabe
2:30 - 3:00 Regulation of Cytokine Signaling James N. Ihle
3 :00 - 3 :30 Pathways regulating cytokine-dependent cell survival and their involvement in leukemogenesis Toshiya Inaba
3:45 - 4:15 Genetics of leukemia and myeloproliferative disease: Therapeutic implications Gary Gilliland
4:15 - 4:45 Kinase inhibitors in cancer Charles Sawyers

Saturday, February 15
Session V
9:00 - 12:00 Round table discussion


Scientific Achievements
I. Hematopoiesis
1. GATA-1 and GATA-2 are transcription factors essential for hematopoiesis. Conditional expression of GATA-2 enhanced the production of hematopoietic progenitors. GATA-1 knock-down mice in which expression of GATA-1 is decreased to 5% of wild type mice exhibited a phenotype reminiscent of a myeloproliferative disorder. It was revealed that GATA-1 insufficiency causes deregulated proliferation and immortalization of hematopoietic precursor cells.
2. It was reported that Angiopoietin-1 (Ang-1) and its receptor Tie-2 induce angiogenesis in P-Sp culture. Furthermore, Ang-1 supports cell-matrix adhesion and retains cells in G0 by signaling through Tie-2, resulting in stem cell maintenance.
3. It was shown that Slug, which is upregulated by the E2A-HLF oncoprotein in pro-B cell acute leukemia, functions as an antiapoptotic factor in hematopoietic progenitor cells. Slug(-/-) mice were more radiosensitive than wild-type mice, dying earlier and showing decreases in peripheral blood cell counts, as well as microhemorrhages and disseminated bacterial microabscesses.
II. Transcription factors
1. TEL, a hematopoietic transcription repressor, was revealed to be phosphorylated by extracellular signal regulated kinase (ERK). ERK-induced phsphorylation of TEL impairs repression of transcription, acceleration of erythroid differentiation, and suppression of fibroblast proliferation.
2. AML1 is a transcription factor essential for hematopoiesis. It was revealed that p300, a histone acetyltransferase, acetylates AML1. Acetylation results in the elevated DNA-binding and the enhanced transcriptional activities of AML1. It was also demonstrated that the interaction between AML1 and a transcriptional corepressor mSin3A is disrupted by ERK-mediated phosphorylation, resulting in the enhanced transcriptional activity of AML1.
3. MOZ is involved in some leukemia-associated translocations. It was revealed that MOZ is a part of the AML1 complex and stimulates AML1-mediated transcription. The amount of AML1-MOZ complex increases during the differentiation of M1 myeloid cells into monocytes/macrophages. The MOZ-CBP fusion protein, which is created by the t(8;16) translocation associated with acute monocytic leukemia, inhibits AML1-mediated transcription and differentiation of M1 cells.
4. T lymphocyte-specific AML1 targeting mice were generated by using the Cre-loxP system. It was demonstrated that AML1 plays indispensable roles in early thymocyte development, especially at the double-negative to double-positive transition, by regulating pre-TCR expression and Lck tyrosine kinase activity. VWRP motif located in the carboxyl terminus of AML1 is known to interact with TLE transcriptional corepressor. Knock-in mice that harbor homozygously the AML1 mutant lacking VWRP motif showed significant thymic hypoplasia, indicating an indispensable role for VWRP motif of AML1 in T cell development.
III. Hematopoietic malignancies
1. Haploinsufficiency ofAML1 is related familial platelet disorder with a propensity to acute leukemia in human. Heterozygous knock-out mice of AML1 were analyzed by mating with BXH2 mice that spontaneously develop leukemia at a high frequency. AML1(-/+)/BXH2 mice exhibited a significantly shorter latency for leukemia development. Tracing retrovirus-tagged genes revealed that several genes, such as HoxA4, HoxA9, Sox9, and Nf-1, are highly mutated in these mice.
2. NUP98-HoxA9 chimeric gene is generated by t(7:11) observed in acute myelocytic leukemia. NUP98-HoxA9 transgenic (Tg) mice develop leukemia at a frequency of 10-15%. By mating with BXH2 mice, genes that cooperate with NUP98-HoxA9 were explored and activation of several genes, such as Meis1, Dnalc4, Fgd3, and MN1, were identified.
3. It was reported that PDGFR!!! is fused to FLIP1L1 by deletion of 4q12 in hypereosinophilic syndrome (HES), resulting in activation of PDGFR!!! Activated PDGFR!!! causes HES, which can be effectively treated by imatinib, an inhibitor of PDGFR !!!.
IV. Signal transduction
1 . TACC3 is highly expressed in a cell cycle-dependent manner in hematopoietic lineage cells. It was revealed that TACC3 is a critical component of the centrosome/mitotic spindle apparatus and its absence triggers p53-mediated apoptosis.
2. Bim is a proapoptotic protein, inactivation of which results in elevated proliferation of cells. It was revealed that activated Ras suppressed Bim expression. Tg mice that express Bcr-Abl under tec promoter are known to develop chronic myelogenous leukemia (CML). Using these mice, it was found that Bcr-Abl suppresses Bim expression, indicating a role for Bim in development of CML.
3. Tg mice that express a mutant of granulocyte-macrophage colony stimulating factor (GM-CSF) that transduce signals only through JAK/STAT pathway were generated. These mice exhibited the elevated number of c-Kit+Sca-1+Lin- hematopoietic stem cells, suggesting a role for GM-CSF signaling in stem cell maintenance.
4. It was reported that imatinib resistance of CML were mainly derived from point mutation of abl. It was shown that other Abl inhibitors or Hsp90 inhibitors are effective for imatinib-resistant CML.

Comments and Opinions
The seminar on "Hematopoiesis, hemopoietic malignancies and novel therapeutic approaches." was held under the auspices of National Cancer Institute of US and Japan Society for the Promotion of Science from February 12 to February 15, 2003, at Maui Prince Hotel in Maui island of Hawaii. There were more than 20 American and Japanese scientists who were selected on the basis of their expertise and interests as most likely to contribute to a stimulating and productive environment. Among the topics discussed were: mechanisms of action of the products of chromosomal translocations, cytokine signaling and tyrosine phosphorylation in hematopoietic cells, aberrant transcriptional control, cell cycle alterations, as well as deregulation of apoptotic, differentiation and mitogenic pathways in leukemias and lymphomas. The use of animal models/genetic systems to analyze the biological functions of genes implicated in the development of leukemias and lymphomas was one of the prominent topics. A major purpose of the meeting was to bring together geneticists, biochemists, molecular biologists and clinical investigators. Therefore, the seminar included discussion on emerging genetic and biological technologies as applied to hematological malignancies and a workshop on potential ways to utilize basic informations towards the formulation of novel therapies. Analyses of the mechanisms underlying the development of hematopoietic neoplasms disclosed a unique opportunity for basic scientists with expertise in distinct areas of research to exchange ideas with clinical investigators who are familiar with the phenotypes associated with the various clinical disorders. From the informations exchanged in this seminar, new avenues of research and the development of novel therapeutic strategies in the treatment of hematopoietic malignancies should have emerged. Moreover, it was another objective in this seminar to establish a collaborative research background through sharing scientific tools and materials and active and fruitful discussions among the participants from both countries. In this respect, for instance, Dr. Pandolfi have initiated collaborations/interactions on PML/TEL with Dr. Mitani, PML/AML1 with Dr. Kitabayashi, and PML/EVI-1 with myself. These collaborations will extend our capabilities to translate the basic research products into novel therapeutic modalities in both countries.



(3)Tumor-Associated Mucins and Related Glycoproteins in Metastasis, Tumor-Specific Immunity and Immunotherapy
Period: January 23, 2003-January 27, 2003 (5 days)
Site: Maui Prince Hotel, Hawaii, U.S.A.

Japanese Organizer:
Irimura, Tatsuro
The University of Tokyo
Graduate School of Pharmaceutical Sciences
professor

US Organizer:
Finn, Olivera
University of Pittsburgh School of Medicine/Director, Immunology Program, University of Pittsburg Cancer Institute
Department of Molecular Genetics and Biochemistry
Professor and Chair

List of Japanese-side Participants :

Siguru Yonezawa
Professor
Kagoshima University, Faculty of Medicine

Reiji Kannagi
Department Head
Aichi Cancer Center Research Institute

Kayo Inaba
Professor
Kyoto University, Graduate School of Biological Sciences

Shoko Nishihara
Professor
Soka University, Institute for Life Science

Koichi Honke
Associate Professor
Osaka University, Graduate School of Medicine

Noriko Sorimachi
Associate Professor
Tokyo Medical and Dental University

Koichi Kato
Professor
Nagoya City University, Faculty of Pharmaceutical Sciences

Koichi Furukawa
Professor
Nagoya University School of Medicine

Fumio Ito
Associate Professor
Sapporo Medical University

Kaori Denda-Nagai
Research Associate
The University of Tokyo

List of US-side Participants:

Sandra Gendler
Professor
Mayo Research Institute

Rebecca Hughey
Assistant Professor
University of Pittsburgh

Nissi Varki
Research Pathologist
University of California

Anne Sperling
Assistant Professor
University of Chicago

Emil Unanue
Professor
Washington University

Geoffrey Kansas
Professor
Northwestern University of Medical School

Victor Engelhard
Professor
University of Virginia

Gordon Ross
Professor
UCLA School of Medicine

Kermit Carraway
Professor
University of Miami School of Medicine


Itinerary and Topics

January 24 (Friday)
7:30-8:00 Breakfast
Session 1: "Mucin Biology and Glycobiology"
8:00-8:10 (Opening Remarks) Finn
8:10-8:40 Features regulating human MUC1 processing and membrane trafficking R. Hughey
8:40-9:10 Muc4/Sialomucin Complex in epithelial protection, cell signaling and tumor progression
K. Carraway
9:10-9:40 Muc1 has a role in mammary tumorigenesis S. Gendler
9:40-10:00 Coffee
10:00-10:30 Lectin recognition of mucin glycocodes T. Irimura
10:30-11:00 Drosophila RNAi model system of glycosyltransferases S. Nishihara
11:00-11:30 Regulation of cell proliferation and apoptosis by glycosphingolipids K. Furukawa
12:00 noon to 4:00 p.m. Lunch on your own and beach break
Session 2: "Mucins and Glycans in Cancer Progression"
4:00-4:30 Biological roles of sulfated sugar chains in cancer and inflammation K. Honke
4:30-5:00 Molecular mechanisms involved in the induction of selectin ligand expression in malignant cells R. Kannagi
5:00-5:20 Refreshments
5:20-5:50 Selectin interactions in hematogenous metastasis N. Varki
5:50-6:20 Expression of MUC1 and MUC2 mucins in human neoplasms: its relationship with potential for malignancy S. Yonezawa
6:20-6:50 Anti-Muc-1 antibody in patients with pancreatic cancer F. Ito
7:30 Conference dinner

January 25 (Saturday)
7:30-8:00 Breakfast
Session 3: "Immunological Functions of Glycans"
8:00-8:30 Function of a novel lectin-like inhibitory receptor on macrophage and dendritic cells N. Toyama-Sorimachi
8:30-9:00 Glycosyltransferases, mucins and selectin ligands G. Kansas
9:00-9:30 Vaccine and Monoclonal Antibody Therapy of MUC1 + Tumors G. Ross
9:30-10:00 Coffee
10:30~11:00 Getting Away from it All: The Role of CD43 in T Cell Activation A. Sperling
11:00-11:30 NMR Structural Biology of lgG Glycoproteins K. Kato
11:30-12:00 The Macrophage Galactose-type C-type Lectin on Dendritic Cells K. Denda-Nagai
12:00 to 4:00 p.m. Lunch on your own and beach break
Session 4: "Processing and Presentation and Glycoprotein Antigens"
4:00-4:30 Immune regulation by dendritic cells K. Inaba
4:30-5:00 Presentation of glycopeptides by class II MHC molecules E. Unanue
5:00-5:20 Refreshments
5:20-5:50 Processing and presentation of MUC1 glycopeptides and recognition by glycopeptide-specifc T cells O. Finn
5:50-6:20 Processing of peptide antigens from glycoproteins for presentation by class I MHC molecules V. Engelhard
6:20 Remarks T. Irimura
Dinner on your own

January 26 (Sunday)
7:30-8:00 Breakfast
8:00-11:00 Round Table Session (Chaired by Irimura and Gendler)
11:00 Closing remarks

Scientific Achievements
Tumor-associated mucins and related glycoproteins play an important role in malignant behavior of tumor cells, acting either as adhesion molecules themselves or as inhibitors of cell adhesion through other receptor-ligand interactions. They have a similar dual role in anti-tumor immune responses, acting either as immune targets or as modulators of innate and acquired immune responses against other tumor targets. Full understanding of those functions would provide the basis on which therapeutic approaches directed against these molecules could be applied as innovative cancer therapy.
These molecules have been of intense interest to a number of investigators in Japan and the United States. While cloning of their genes, molecular characterization of the various tumor glycoproteins, cell biological aspects, and their potential as targets for immunotherapy has been the focus of research of the U.S, investigators, the Japanese colleagues have concentrated on the role of glycans on these molecules in the determination of molecular functions and immunogenicity. The number of glycosyltransferase genes cloned in Japan exceeds that cloned in any other country. Based on these previous achievements, Japanese scientists have recently been exploring biological functions of glycans. In this seminar, scientists who have been heavily involved in this field gathered from US and Japan and presented their recent findings and discussed important issues for the future developments in the basic science and in cancer immunotherapy.
Two highly debated areas were biology of mucins in the malignant behavior and handling of glycosylated antigens by the immune system. Researchers who study these glycoproteins in the context of cell migration and antigen processing and presentation, primarily from the U.S., conferred with researchers who study the same glycoproteins in the context of their glycobiology and glycochemistry, primarily from Japan. Questions were raised in the design of immunotherapeutic strategies for cancer using mucins and related glycoproteins.
These issues were also discussed at the roundtable discussion. We came to conclusion that the knowledge of how glycoproteins are handled by the immune system is lacking in immunology in general. The conference will have a strong impact in the future researches by the participants because the group consists of unique mixture of glycobiologists, immunologists, pathologists, and some clinicians.
There were several novel unpublished findings presented and discussed in the meeting. Examples are, functions of cytoplasmic tail of transmembrane mucins, T cell recognition of glycosylated peptides, relationship between mucin glycosylation and clinicopathological features of carcinomas, and biosynthetic regulation of carcinoma associated carbohydrate epitopes.
The sessions were lively and the presentations were excellent. It is worth to report that US participants commented that they were impressed by high performance of Japanese female scientists, because such contributions were relatively limited in the past.