SVIBOR - Project code: 3-01-079

MINISTRY OF SCIENCE AND TECHNOLOGY

Strossmayerov trg 4, HR - 10000 ZAGREB
tel.: +385 1 459 44 44, fax: +385 1 459 44 69
E-mail: ured@znanost.hr

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Project code: 3-01-079


The role of prostaglandins in the growth of malignant tumors


Main researcher: ČULO, FILIP (8565)


Assistants
Type of research: basic
Duration from: 01/01/91. to 12/31/93.
Papers on project (total): 47
Papers on project quoted in Current Contents: 18
Institution name: Medicinski fakultet, Zagreb (108)
Department/Institute: Department of Physiology and Immunology
Address: Šalata 3b
City: 10000 - Zagreb, Croatia
Communication
Phone: 385 (0)41 466 945
Fax: 385 (0)41 424 001
Summary: Data in literature and own results show that prostaglandins E (PGE1 and PGE2) facilitate the growth of some malignant tumors. Our results have shown that production of PGE2 by planocellular carcinoma of larynx and hypopharynks correlate positively with the incidence of tumor recurrences and inversely with the patient's survival. This correlation was not found with the carcinomas of gastrointestinal tract. In further work, the production of PGE2, PGI2 and tromboxan A2 (TxA2) was determined in paralell in samples of tumors ex vivo. We found that production of individual and total prostanoids varied among patients, but it did not correlate with clinical stage of tumors. We are trying to establish if there is any correlation between the rate of synthesis of particular or total prostanoids with incidence of tumor recurrences and survivval of patients. The samples of mouse tumors produce different total amounts of PGs and different prophiles of individual PGs ex vivo. Cell lines of these tumors produce in vitro mainly PGE2, small amounts of PGI2 and do not produce TxA2. Inhibitory effect of IMC on growth of tumors in vivo correlates with the production of total PGs ex vivo and production PGE2 ex vivo and in vitro. Neither PGE2 nor indomethacin (IMC) have any effect on growth of tumor cells in vitro. Inhibitory effect of IMC in vivo is more pronunced in normal than in immunodeficient mice, indicating that antitumor effect of inhibitors of PG synthesis is based on modulation of host immunological reaction.

Keywords: head and neck carcinoma, squamous carcinoma, prostaglandins, indomethacin

Research goals: The purpose of our investigations is: a) to find out if there isa correlation between production of PGE and progression ofmalignant tumors b) to find out whether the tumors of the samehistological origin produce different types and amount ofprostaglandins. c) whether the tumors which produce high amountof PGE produce different amount of other prostaglandins (PGF2,PGI2 or tromboxan), d) whether the tumors which produce highamount of PGE are more sensitive to IMC in vivo than tumors which produce normal amount of PGE, f) to find out whether PGEand IMC affect tumor growth directly by modulation ofimmunologic reaction and what is the cellular or molecularmechanisms of this action and, g) , based on above findings, toselect patients for treatment with prostaglandin synthesisinhibitors in vivo. The expected results: To explain themechanism of promotive and inhibitory effect of PGE andIMC, respectively, on growth of malignant tumors. Our previousresults have shown that there exist inverse relationship betweenPGE level in blood in patients with squamous carcinoma of larynxand hypopharynx and survival time of patients. We have shown thatonly about 1/3 to 1/2 patients with squomous carcinoma of larynxan hypopharinx produce significantly higher amount of PGE thannormal mucosa. A some data show that tromoxan A2 (TxA2)accelerate tumor growth. Therefore, it appears necessary tomeasure, in parallel with PGE, the production of thisprostanoide in the same tumor samples (ex vivo). Also it will betested whether PGE and IMC enhance or inhibit, respectively, thegrowth of tumor lines in vitro. The inhibitory effect of IMC ongrowth of mouse tumors in normal and immunodeficient animals willbe tested.

COOPERATION - INSTITUTIONS


  1. Name of institution: INSERM U313, Groupe Pitie-Salpetriere, 911 Bd de l Hopital, 75013
    Type of institution: University/Faculty
    City: Paris, Francuska
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