Japanese Journal of Clinical Oncology

Figure 1. Professor Shigetaka Asano.

According to Associate Professor Kenzabro Tani, who is in charge of the clinical trial, the first patient is a 60–year–old male with renal cell carcinoma and will be followed by four other patients with the same cancer. The strategy is an immune gene therapy originally proposed by Dr Richard Mulligan’s group: a surgically resected renal tumor is put into a culture, and the cells are transduced ex vivo with a retrovirus vector harboring a GM–CSF (granulocyte–macrophage colony stimulating factor) expression unit. The GM–CSF–transduced renal cancer cells are then irradiated and transplanted in the patients as a ‘tumor vaccine’ eight weeks later. GM–CSF appears to have multiple functions to enhance tumor immunity, including potentiation of antigen presentation by dendritic cells. The retrovirus vector is provided by CellGenesys, Inc., USA, and the safety of the transduced cells will be checked by MA BioServices, Inc., USA.

As many as 3000 patients worldwide have already entered about 300 gene therapy or gene marking clinical protocols, 70% of which have targeted cancer. However, in Japan, this will be only the second case, the first having been a boy with ADA (adenosine deaminase) deficiency who was treated from 1995 to 1997 at Hokkaido University. It is very important to note that almost all of the current protocols for cancer gene therapy are at the phase I or phase I/II stage of clinical study. ‘The principal aim of these studies is the evaluation of the safety, rather than the efficacy, of the protocol’, Dr Asano said.

The IMSUT Hospital is also well–known for the lead role it has played in the establishment of the bone marrow transplantation system in Japan. Although a relatively ‘classic’ tumor vaccine strategy has been chosen for the first cancer gene therapy clinical trial in Japan, the combination of the group’s clinical expertise in cell and molecular technologies is expected to provide a strong power base for future cell/gene therapy in this country.

Teruhiko Yoshida, M.D.

The 30th Meeting of the International Society of Paediatric Oncology

The 30th Meeting of the International Society of Paediatric Oncology (SIOP) was held in Yokohama on October 4-8, 1998. It is the first time that Asia has been chosen to host a SIOP meeting, and 1000 physicians, nurses and parents gathered from 60 countries. This meeting consisted of 3 categories: scientific program, nurses program and parents program. The main topics in the scientific program were neuroblastoma and the role of surgery in paediatric oncology.

Several subjects about neuroblastoma, including oncogene, neurotropin receptors, cell death, international neuroblastoma pathology classification, spontaneous maturation, risk groups and treatment strategy, were discussed with such distinguished guest speakers as Dr G.M. Brodeur of the Children’s Hospital of Philadelphia, USA, Dr A. Nakagawa of Chiba Cancer Center Research Institute, Japan, Dr H. Shimada of Children’s Hospital Los Angeles, USA, Dr L. Robinson of University of Minnesota, USA, Dr S. Cohn of Children’s Memorial Hospital and Northwestern University, Chicago, USA, and Dr I.M. Ambros of Children’s Cancer Research Institute, Austria. The round table discussion on neuroblastoma mass screening attracted a great deal of attention. Dr T. Sawada of Kyoto Prefectural University of Medicine, Japan, reported an outstandingly favorable prognosis (97% of 5–year survival) of 1400 cases detected from 11 284 837 screened over 11 years in Japan. Similar preliminary results were reported from France, Northern England, Austria and Germany. However, the result of Quebec neuroblastoma screening on population based mortality reported by Dr W.G. Woods of Montreal Children’s Hospital, Canada, was that screening for neuroblastoma markedly increases the incidence in infants under one year of age without decreasing the incidence of unfavorable advanced stage disease in older children ironically.

The special multidisciplinary seminar on surgery was focused on reconstruction following resection for malignancy.

In parents program, two subjects ‘Issues facing long term survivors’ and ‘Psychosocial support for bereaved families’ were discussed.

M. Ohira

Report from the 36th Annual Meeting of the Japanese Society of Clinical Oncology

The 36th Annual Meeting of the Japanese Society of Clinical Oncology took place on October 7-9, 1998 in Fukuoka. The main theme of this meeting was ‘combined modality therapy of cancer therapy’. There were over 1000 reports from various fields of oncology.

The Presidential Symposium, entitled ‘The strategy of ovarian cancer treatment for the 21st century’ started with a speech by the President of the meeting Dr Michiaki Yakushiji, Kurume University. He showed progress in the ovarian cancer treatment during the last quarter of the 20th century and emphasized the importance of a multidisciplinary approach for the treatment of ovarian cancer and accumulation of evidence from high quality clinical trials to improve the survival and quality of life of ovarian cancer towards the next century.

A topic featured at the Symposium was ‘Cancer clinical trial’ and suggested meaningful perspectives for development of cancer therapy in Japan. Speakers at the symposium included experts in the field of industrial companies, oncologists and Pharmaceuticals and Medical Devices Evaluation Center. Dr Shunsuke Ono of Evaluation Center, emphasized the advancement of quality of clinical trials after enforcement of the ICH–GCP guideline. Dr Masanori Shimoyama of National Aichi Hospital indicated that what we need to develop cancer clinical trials in Japan were the construction of infrastructure, especially Clinical Research Coordinator (CRC), medical oncologists, biostatistician, a statistical center and an audit system. There seems to be an increasing number of reports from good clinical trials. Clinical trial is indispensable for developing clinical oncology and resolution of practical ‘uncertainty’, and it is hoped that it will spread more widely into Japanese society.

Compiled and edited by N. Katsumata

Awards

Dr Takashi Sugimura was awarded the Grand Cordon of the Orders of the Sacred Treasure

November 3 is a national holiday called ‘Culture Day’ in Japan. The date is originally Emperor Meiji’s birthday and now many cultural events take place to celebrate the Culture Day. On this day, decorations are awarded to those who have made extraordinary contributions to develop the Japanese culture of various fields during one’s life time. This year, Dr Takashi Sugimura, President Emeritus of the National Cancer Center, received the Grand Cordon of the Orders of the Sacred Treasure. He has received many distinct awards, including the Order of Cultural Merits in 1976 and the Japan Prize in 1997.

This award it a great honor not only to himself but also to the National Cancer Center.

Figure 2. Dr Takashi Sugimura and the Grand Cordon of the Orders of the Sacred Treasure.

Cancer Statistics Digest

The trends of smoking prevalence in Japan are displayed for different 10–year age groups of males and females separately. The data of age–specific smoking prevalence were provided by Japan Tobacco, Inc., the former Japan Tobacco Monopoly Bureau. The present report depends on this data, because no other data are available for the period 1965 to 1996. For males, decreasing trends are observed in all age groups with similar magnitude (a). For females, on the other hand, the smoking prevalence among 40s, 50s and 60 or over shows decreasing trends, whereas that among 20s and 30s shows increasing trends (b).

S. Yamamoto and N. Yamaguchi

(a) Males

(b) Females

Source: Statistics and Information Department, Ministry of Health and Welfare, Japan

Viewing the News from Abroad

Tamoxifen for breast cancer prevention

After release of the Breast Cancer Prevention Trial results, which demonstrated a 49% reduction in invasive breast cancer incidence among participants who took tamoxifen, the National Cancer Institute recommended that women at increased risk for this disease could now consider taking tamoxifen to lower their risk (JNCI 1998;90:1371). It was also reported that the Oncologic Drugs Advisory Committee of the Food and Drug Administration recommended the approval of the use of tamoxifen to reduce the risk of breast cancer in women at high risk for the disease in September. The September article of JNCI (JNCI 1998;90:1428-30) dealt with the problems regarding the practical use of this drug for a preventive purpose.

Tamoxifen, an estrogen receptor modulator, is known to have a serious side effect, particularly those inducing endometrial cancer and blood clots in the lung. The important question here is whose risk is high enough to outweigh the risk of such potential side effects. In a situation that breast cancer prevention by tamoxifen is generalized in public, the risk assessment of women might be crucial.

Furthermore, in a recent study, another drug called raloxifen (also an estrogen receptor modulator) was demonstrated to have an effect to reduce breast cancer risk by 70% in post–menopausal women, although this study was originally intended to detect the effect to prevent menopausal osteoporosis. The potential advantage of this drug to tamoxifen was that it was not associated with higher risk of endometrial cancer. Raloxifen is at present respected as a promising drug for breast cancer prevention. However, since the follow–up period is still short, and that the study was designed to study osteoporosis, not breast cancer, the conclusion is yet to be defined.

At present, most people in the oncology community are still being cautious about starting widespread use of tamoxifen for chemoprevention. A number of questions, especially who will best benefit from the preventive use of tamoxifen, must be addressed before use by the general public.

BRCA2 research

Studies on the cancer susceptibility genes, BRCA1 and BRCA2, are rapidly progressing, JNCI October news reported (JNCI 1989;90:1502-5). BRCA2 gene is a breast cancer susceptibility gene which was found together with the BRCA1 gene. The two genes have many similarities: both are extremely large, mutations in each gene result in similar clinical symptoms, both are expressed in most tissues during cell proliferation (peaking at similar phases of the cell cycle), both are nuclear proteins, and both seem to be involved in transcriptional regulation and DNA repair. However, while the localization of protein in the cell, identification of the protein interacting with BRCA1, and making knock–out mouse model were extremely difficult in the BRCA1 gene, the research on the BRCA2 gene quickly progressed.

The direct association of BRCA2 with Rad51, a key protein in both the DNA double–strand break repair pathway and recombination, was found in 1997. Dr Sharan, Frederick, MD, showed that knock–out mouse embryos lacking both functional copies of BRCA2 were sensitive to gamma radiation, known to create double–strand breaks in DNA. Further proof that BRCA2s function is linked to Rad51 was that both are expressed simultaneously in the embryo in rapidly dividing cells and that both Rad51 and BRCA2 knock–out mouse embryos die early during development when the genes are normally expressed. These data suggested strongly that the normal function of BRCA2 is involved in repair of double–strand DNA breaks. Actually the BRCA2–defective human pancreatic cancer cell line was shown to be both deficient in double–strand repair and killed more easily by chemotherapy drugs that cause double–strand DNA breaks. The therapy strategy here is to synthesize a small peptide that will block the interaction BRCA2 and Rad51 proteins (Dr Lee and associates, San Antonio, TX). This block might leave the tumors more susceptible to damage from radiation or drugs causing double stranded DNA breaks.

If progress in the BRCA2 field continues at its present pace, the new rationale for the more effective treatment by radiation should be in relatively soon.

Compiled and edited by H. Asamura

Announcements

VII International Conference on Malignant Lymphoma

Date: June 2-5, 1999
Location: Palazzo dei Congressi, Lugano, Switzerland
Deadlines:
Submission of Abstracts — January 31, 1999
Early Registration — March 31, 1999
Closing Date Registration — May 20, 1999
Further information: Mrs Olga Jackson (Conference Secretariat)
via Fusoni 4, 6900 Lugano, Switzerland
Tel: +41 91 921 45 61
Fax: +41 91 921 45 63
E-mail: lymphcon{at}dial.eunet.ch

Pan–Pacific Lymphoma Conference

Date: July 20-23, 1999
Location: The Hyatt Regency Kauai, Hawaii, USA
Sponsor: The University of Nebraska Medical Center
Further information: Center for Continuing Education
University of Nebraska Medical Center, 985651
Nebraska Medical Center, Omaha, NE 68198–5651, USA
Tel: +1 402 559 4152
Fax: +1 402 559 5915
E-mail: conteduc{at}unmc.edu

To include information of upcoming cancer-related events in the News Section, please send details, including the title, date, place, organization, contact name, address (fax number and e-mail address if any) to the news department of the editorial office of JJCO who also welcome suggestions for news stories. Items in this section are selected for publication and edited by the editorial office at their discretion.

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