SVIBOR - Project code: 1-08-198

MINISTRY OF SCIENCE AND TECHNOLOGY

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Project code: 1-08-198


THE CONTROL OF GROWTH AND DIFFERENTIATION OF NORMAL AND TUMOR CELL


Main researcher: JURIN, MISLAV (19380)


Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/93.
Papers on project (total): 55
Papers on project quoted in Current Contents: 23
Institution name: Institut "Ruđer Bošković", Zagreb (98)
Department/Institute: Department of Experimental Biology and Medicine
Address: Bijenička 54
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)41 461130 425295
Fax: 385 (0)41 425497
E-mail: JURIN@OLIMP.IRB.HR
Summary: SAŽETAK (engl) In transgeneic mice expressing hepatitis B antigen (high expressing lineage 50-4), fed of low or high cadmium diets, there was no difference in the incidence of tumors. However, the tumors were more poorly differentiated in high cadmium diet fed animals. The data indicate to a positive correlation of the endemic hepatitis B and the cadmium intake (estimated from daily dietary intake of foods of plant origin) in the incidence of primary hepatocellular carcinoma in human population. Few hours following allyl alchohol injection necrosis were detected in rats' liver. By using standard methods of histology and autoradiography as well as specific immunohistochemical approaches a pronounced proliferation of hepatocytes throughout the hepatic cords was noticed within 2 to 3 days following initial necrosis. Restitutive proliferation of these periportal necrotic zones appears to be accomplished by proliferation of intraportal (stem?) cells. Further, glutathione-S-transferase-P could be detected in mature hepatocytes as a reflection of the immature (fetal) phenotype in regenerative cells and should not be considered a general marker of initiated or transformed cell during chemical hepatocarcinogenesis. Growth characteristics of several cell lines were changed following the cultivation with 4-hydroxynonenal (HNE) - one of the main "second toxic messengers" of oxygen free radicals. HNE preterated cells of all used cell lines incorporated less radioactive thymidine in the presence of serum than if cultured if cultured under serum-free conditions. Further, HNE precultured cells became less sensitive to further HNE treatment. The treatment of melanoma B16-F10 cells with HNE in vitro or in vivo did not prevent tumor development, but its growth was inhibited and tumorous mice survived longer than their controls. The results obtained suggest that exposing tumor cells to HNE decrease their malignancy and tumor growth dynamics. In continuing the work toward to the identification of molecules involved in the regulation of cell growth and differentiation it was determined that mitogenic signal, induced with fibroblast growth factor, is different in particular cells isolated from rat prostate carcinoma. Signal transmission is using at least two different ways, one of which is protein kinase C independent. In patients suffering from long bones or large joints fractures osteogenesis, i.e. callus formation, is usual. However in the patients where the trauma is combined with severe head injury hypertrophic callus formation and/or heterotopic ossifications are pronounced. Further, in these patients significantly increased concentrations of carboxy terminal propeptide of type I procollagen, alkaline phosphatase and its bone isoenzyme were detected. In all these traumatised patients the levels of basic fibroblast growth factor were increased but the increase was the most pronounced in these with combined trauma. The measurements of these parameters could hav both diagnostic and prognostic values. Glycopeptides isolated from porcine spleen (Polyerga) applied i.p., and polypeptides given per os were very effective in reducing the incidence of experimental lung metastases. The preparation from misteltoe (Isorel) is active on the way that low quantities stimulate and high suppress the immune reactivity of normal or tumor bearing organisms. Further, its antitumorous activity is pronounced if applied alone or in the combination with other approaches as chemotherapy, surgery or radiotherapy. Low power laser stimulate regeneration in the patients with trophic ulcera, modulate experimental wound heeling in mice and could modulate the immune reactivity of the organisms. The use of photoactive components and the light of particular wave length were successfull in controling local tumor growth.

Keywords: malignant tumors, growth regulatory factors, cell differentiation, light power laser, phototherapy

Research goals: rezultati (eng.) 1. Determination of the effect of high cadmium levels in the diet on the development of primary hepatocellular carcinomas (PHC), i.e. its frequency and the degree of differentiation, in transgeneic mice expressing hepatitis B surface antigen. 2. Examination of the involvement of different hepatocyte populations in response to periportal injury induced with allyl alcohol in searching for particular markers characterizing the process and these which can be considered as a general markers of the initiations of chemical hepatocarcinogenesis. 3. Determination of different cells growth in vitro and in vivo under the influence of 4-hydroxynonenal which is one of "second toxic messengers" of oxygen free radicals. 4. Incvestigations of the mechanisms involved in the mitogenic signal transmission in tumorous and normal cells. 5. Correlation of the intensity of regenerative processes of ossification with blood levels of carboxy terminal propeptide of type I procolagen, alkaline phospahatase and its bone isoenzyme in the patients suffering from fractures of long bones or large joints and/or severe head injury respectively. 6. To study the influences of particular plant or animal tissue extracts on tumor cells in vitro and in vivo and on the immune reactivity of an organism. 7. Examination of low power laser influences on regenerating tissues and its possible systemic effects. 8. To introduce an experimmental model for the studies of the influences of fotoactive substances growing tumor. All the goals are generally obtained and the results are publiushed or presented on scientific meetings.

COOPERATION - PROJECTS


  1. Name of project: Analysis of the Systemic Mechanisms involved in the Control of Tissue Regeneration: the Effects of Traumatic Brain Injury on Bone Regeneration and the Role of Humoral Growth Regulating Factors
    Name of institution: Universitat Klinik fur Chirurgie
    City: A-8010 - Graz, Austrija

  2. Name of project: Primjena lasera niske energije u bolesnika s ulcus cruris
    Name of institution: Dom zdravlja Medveščak
    City: 10000 - Zagreb, Croatia

  3. Name of project: Biological properties of Polyerga
    Name of institution: HorFerVit Pharma GmbH
    City: D-2900 - Oldenburg, Njemačka

  4. Name of project: Antitumorous effects of Isorel
    Name of institution: Novipharm GmbH
    City: A-9210 - Portschach, Austrija

  5. Name of project: The influence of growth factors on rat prostate carcinoma cells
    Name of institution: The University of Texas Health Science Center at San Antonio, Medical School, Department of Obstetrics and Gynecology
    City: 78284-7836 - San Antonio, Texas, USA

  6. Name of project: The role of bcl-2 gene in apoptosis during hepatocarcinogenesis
    Name of institution: The University of Texas Houston, Medical School, Department of Pathology and Laboratory Medicine
    City: 77030 - Houston, Texas, USA

  7. Name of project: Primjena fototerapije u liječenju tumorske bolesti
    Name of institution: Klinička bolnica "Sestre milosrdnice"
    City: 10000 - Zagreb, Croatia

  8. Name of project: Lipids and Oxidative Substances in Tumor Progression and Therapy
    Name of institution: Institut fur Biochemie
    City: A-8010 - Graz, Austrija

COOPERATION - INSTITUTIONS


  1. Name of institution: Dom zdravlja Medveščak
    Type of institution: International organization
    City: 10000 - Zagreb, Croatia

  2. Name of institution: Institut fur Biochemie, Karl Franzens Universitet
    Type of institution: University/Faculty
    City: A-8010 - Graz, Austrija

  3. Name of institution: Universitat Klinik fur Chirurgie
    Type of institution: International organization
    City: A-8010 - Graz, Austrija

  4. Name of institution: HorFerVit Pharma GmbH
    Type of institution: State institute
    City: D-2900 - Oldenburg, Njemačka

  5. Name of institution: Novipharm GmbH
    Type of institution: State institute
    City: A-9210 - Portschach, Austrija

  6. Name of institution: The University of Texas, Houston, Medical School, Department of Pathology and Laboratory Medicine
    Type of institution: Economical/Production
    City: 77030 - Houston, Texas, USA

  7. Name of institution: The University of Texas Health Science Center at San Antonio,, Medical School Department of Obstetrics and Gynecology
    Type of institution: University/Faculty
    City: 78284-7836 - San Antonio, Texas, USA

  8. Name of institution: Klinička bolnica "Sestre milosrdnice"
    Type of institution: International organization
    City: 10000 - Zagreb, Croatia
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