SVIBOR - Project code: 1-08-211

MINISTRY OF SCIENCE AND TECHNOLOGY

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Project code: 1-08-211

THE EFFECT OF HYPERTHERMIA CYTOSTATICS AND IRRADIATION ON THE TUMOUR GROWTH

Main researcher: RADAČIĆ, MARKO (39503)

Assistants

Type of research: basic
Duration from: 01/01/91. to 12/31/93.

Papers on project (total): 3

Institution name: Institut "Ruđer Bošković", Zagreb (98)
Department/Institute: Department of Experimental Biology and Medicine
Address: Bijenička 54
City: 10000 - Zagreb, Croatia

Communication: Fax: 385 41 425 497

Summary: The effect of hyperthermia (HT), radiation (R) and cisplatin (CP) have been investigated on the growth of mammary carcinoma in CDF1 and CBA strain of mice. HT was given locally, by tumour-bearing leg emerging into a temperature-controlled cirkulating water bath. The applied temperature was between 41 and 43.5 C for 60 minutes. R was performed by x-ray mashine and given locally to the tumour-bearing leg. CP was given ip. The tumour response to treatment with CP, R and HT was in correlation with the used doses of the each drug. Single treatment with CP increases tumour growth time 1.5 times, while heat (43.5 C/60 min) increases tumour growth time 3 times compared with untreated controls. The effect of R was dose-dependend and TCD50 was 60 Gy for R alone. Combined treatment with CP and heat increases antitumour effect. If CP and heat treatments were separated by 4h (sequential treatment) antitumour effect was only additive. However, when the CP and heat treatments were separated by 15 min time period (simultaneous treatment) antitumour effect was increased giving enhancement ration of 3.0. When R, CP and heat were applied together TCD50 was reduced to 47 Gy. The combined treatment (CP-HT; CP-HT-R) increases not only antitumour effect than also toxic (lethal) effect. When HIDA (100 mg/kg) was given 150 min. before CP and tumours heated 15 min later, the lethal toxicity was significantly reduced. HIDA administered before CP protects against drug-induced toxicity without reducing the drugs antitumour activity, and thus resulting in a significantly improved therapeutic benefit.

Keywords: hyperthermia, irradiation, cytostatics, tumour, mice, tetrahydroindazolone carboxilic acid (HIDA), nephroprotectors

Research goals: To get enough quantitative and qualitative data about hyperthermia (HT), radiation (R) and cisplatin (CP) effect on the tumour growth in mice as a single treatment or in combined treatment protocol. It is expected that combined treatment will be more effective and less toxic. It is known that CP causes kidney damage which can be reduced by CP-antidotes. We will test the tetrahydroindazolone carboxilic acid (HIDA) as a potent nephroprotector. Antitumour effect of HT, R and CP is dose-dependend. The combined treatment (HT-CP; HT-CP-R) gives higher antitumour effect but also toxic effect. The highest antitumour effect, as well as toxic effect was when CP was given 15 min before HT. If all three (R-CP-HT) treatments were given the highest antitumour effect and toxic effect was gained when R was given 4 h before HT and CP 15 min before HT. However, if HIDA (100 mg/kg) was given 2.5 h before CP the toxic effect was almost abolished and antitumour effect unchanged.

COOPERATION - PROJECTS

Name of project: 1-08-211 učinak hipertermije, citostatika i zračenja na rast tumora
Name of institution: Institut Ruđer Bošković
City: 10000 - Zagreb, Croatia

COOPERATION - INSTITUTIONS

Name of institution: Danish Cancer Society Department of Experimental Clinical Oncology
Type of institution: University/Faculty
City: DK-8000 - Aarhus, Danska

Other information about the project.


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