ig 315 ne F immunomodulation by the Viscum album L. || preparation Isorel® and its antitumorous effects ot e ” durin, N. Zarkovic, S. Borovic! and D. Kissel Introduction | ag Tver the last 50 years there has been increasing interest inthe use of different 5 extracts of mistletoe plants (Viscum aléumn L.) to tumorous patients (72, 17). [Numerous data point © a cytotoxic action of these extracts against different tumor call lines and, on the other hand, to their immunomodulatory effects in the organism (2, 11). The antitumor activities of mistletoe preparations could, thus, be ascribed to the combination of immunomodulating effects on the ‘organism and cytotoxicity against the tumor. This could support their thera- peutical application, because numerous antitumor drugs, or treatments, alongside thair antitumor action, could have side effects, particularly pro- nounced immunosuppression (18). Nowadays several mistletoe preparations are used as complementary treatment in tumorous patients. Isorel (,.Nov pharm’, Austria) is one of these preparations. In our previous results it was shown that the application of Isorel could stimulate foreign skin rejection and increase the number of plaque-forming cells (PFC) against sheep erythrocytes in mice, but only if proper time and dose were used (10). Further, the appli- cation of Isorel to fibrosarcoma bearing mice significantly increased the ef- fectiveness of local tumor irradiation (10). Due to repeated doses of Isorel used during patients’ treatment we determined the influence of its different doses, applied as single or multiple injections, on normal or tumorous mice and the results will be presented here. Further, the results ofthe effectiveness of the drug used alone, or in the combination with surgery or chemotherapy, on tumorous mice will be presented also, Visewm album L. extract Original preparation ofthe fresh mistletoe plant grown on apple tee - Isorel M, (Novipharm GmbH, Portschach, Austria) was used (10). For all the ex- periments pecformed, the dose of the preparation used will be presented as mg ofthe fresh plant (planta tora) per body weight (ka) ofthe animals treated eS TTP RT316 a7 Experimental procedures and the results obtained 100 ‘The influence of Vise normal and tumorous m a Caan be cells (SRBC) and z ig antibodies again: 5. s determined four days - bn ie | 1 separate exper steers make noel ate i (5-18 mm) were treated la [Dvr we ncion | SRBC injection. Secret Fo tnmune mod tho en rues pr groups spective mean) of the activated B-c ‘munised with sheep erythrocytes are *<0.05, Mann Whitney ‘As presented in cereased with increasing Isorel dose. sed PEC mum bor in the mice bearing ig. 2).318 319 Antitumorous activity of the Visewm album L preparation given alone or in combined cancer therapy 22 Since the use of very high dosage of the Viscum album extract (14 = 1400 ses mglkg) gave pr ing effects, as described in the previ- gs 5 ous cf particularly immunosuppression after multiple injections, further BE 8 task was to test the impact of such treatment on the growth of the tumor. For eee that purpose murine mammary car g2 3 Ss 8 | extract for two weeks, starting with the first day after tumor S| iq y 2 os 2 jon. As can be seen from Figure 3, tumors developed both in the 2 28 2 2 752 gg = £98 2 1 = PRE: soo E ysd2 22 8 E : PPE 58 og aie 2 gg a 7 ERE p= See. ne fb , £88 ¢ tafe 2885 é S2pE B28 Figs 1 of the murine mammary carcinoma growth nthe hind ib of 2 £ Seee syngeneic mice treated with the Viscum afbumL. extract. Mean values = 3,28 Bead er group (N=5, SD<20 per cent of the respective mean) of the solid tu- £ HES 852% ‘mot volume are presented. i sng gop MSintcant (Ped 0s Mann Whine test to the cor 2 exes eveo gee Isore! (140 mg/kg) was further applied to CBA/Zgr mice bearing trans- f planted mammary carcinoma starting from the first day following palliative sues sosoum-uou rare ag 8919) Sn 3a ene & surgical removal of the tumor implanted into the hind limb. As presented on320 Surgery + trote extracts have already fou the therapy of cancer pat m procedures. are Acknowledgments ‘The authors would Hir(1 for her paper, unune react References (1995) 505-507 and humoral adju- 1979) 309-3 joncr: how apoptosis controls 7 (1995) 694-703 ra Viscum album preparation, jak M,, Hc Z. Anticumorous and immiano- L preparation Isorel. Oncology $0 (1993) Hs Studies on eytotoxie and ef D, Jurin M., Zarkovie N.: Uoer die kombinierte Tumortherapie.- Eine Studie ber die wirksamkeit von Viscum album. Dtsch, Zsche. 22,1990) 134-136 15. Kjaer MN MiM4, Ritz J.: Biology and clinical relevance of human natural killer Blood 76 (1990) 2421 G., Dekker A 1 Texbook 0 nesi U. Oxford 7 (1995) 704-710 nak M, Grainca S., Jurin M. 'N., Trbojevie-Cepe M Ile Z, Hs Comparison of the effects of high a 325 Comparison of the antitumorous effects of Viscum album lectins and the plain or fra‘ fresh plant preparation Isorel® nai N. Zarkovic, M. Jurin, W. Dittrich, M. Hartieb, 8, Sladoljev and D. Kissel Introduction ory. There are numerous plant prepara ined therapy of cancer, for which the active principle has ied, Among these preparations of particular interest are mistle- patholo; cytotoxic action of 14, 19). Moreover, reparations in vivo might ig the cytotoxic activity of y of the mistletoe preparations tumor eells and the enhancement of the immune host cells) gives a support for use ofthese so shown for ie prepara- 1 which was used Different he active components from the earch on the active compone determination of some new phytotherapes agents. The major reason why no particular and defined pihytotherapeutic agent was isolated from mistletoe so Far seems to be the common opinion that hypothesis