A study of the effectiveness of a carcinostatic and increasing carcinostatic tolerance

1993 Fiscal Year Final Research Report Summary

• Project/Area Number: 04670805
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Tokai Univ.School of Medicine, Dept.surg.II
• Principal Investigator: MITOMI Toshio Tokai Univ.Depart.surg.2, professor school of Med., 医学部・第2外科, 教授 (20055809)
• Co-Investigator(Kenkyū-buntansha): WATANOBE Keiichi Tokai Univ.pathology., proffesor, school Med., 医学部・病理, 教授 (00055865) ; NAKASAKI Hisao Tokai Univ.Depart.surg.2, Assist prof.school of Med., 医学部・第2外科, 助教授 (10056145)
• Project Period (FY): 1992 – 1993
• Keywords: ADM / anti-ADM / anti-carcinostatic / monoclonal antibody

Research Abstract

A STUDY OF THE EFFECTIVENESS OF A CARCINOSTATIC AND INCREASING CARCINOSTATIC TOLERANCE
Summary of the study(for the past fiscal year)
The purpose of the study was threefold :
1.to prepare an antibody anti-carcinostatic
2.to administer the antibody anti-carcinostatic
a)to relieve side effects of the carcinostatic
b)to analyze the potentiation of the carcinostatic effect
3.to prepare a carcinostatic monoclonal antibody
Over the fiscal year, the author concentrated on analyzing the alleviation of carcinostatic related side effects. Two groups of Wistar rats were used for the experiment. One group received ADM only, while the other received ADM followed by an antibody anti-ADM, Heart and bone marrow functions in these two groups were then analyzed and compared. Heart functional disorders in the ADM plus antibody group were reduced, and the bone marrow study showed that leukocyte and thrombocyte levels remained unchanged. Significant easing of carcinostatic-related side effects was observed.
The nex t objective will be to determine the correct dosage of the antibody anti-carcinostatic and the optimal timing for administration. (The antibody was administered 90 minutes after the carcinostatic in this experiment). We also hope to prepare a MoAb and antibodies for other carcinostatics.
We then examined the effectiveness and tolerance levels of a carcinostatic. There is not yet an effective medium for increasing tolerance to carcinostatic drugs. Repeated administration of the carcinostatic at short intervals is the most desirable means of obtaining reasonable increases in tolerance. One way to achieve such repeated administration would be to neutralize the drug's effects, which would allow side effects to be relieved. Thus, we can increase the effectiveness of the drug. Indeed, a more significant anti-cancer effect was observed in the ADM plus antibody group the ADM-alone group.
Finally, a monoclonal antibody was prepared. The author succeeded in obtaining an IgG-type monoclonal antibody which has a specific reaction against the antigen, ADM.This monoclonal antibody should be more specific than polyclonal antibodies used in the past, and the next experiments will focus on increasing the specificity of the new antibody.