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08947cam a2200481 i 4500 |
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NSK01000140548 |
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HR-ZaNSK |
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20170228084932.0 |
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960205s1995 ci a m 000 0 hrv |
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|9 (HR-ZaNSK)140699
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|9 (HR-ZaNSK)960205051
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|a (HR-ZaNSK)000140548
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|a HR-ZaNSK
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|c HR-ZaNSK
|e ppiak
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|a hrv
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|a ci
|c hr
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|a 616.5-006-085
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1 |
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|a Bura, Miljenko
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|a Prevencija UV-B karcinogeneze peptidoglikan monomerom (PGM) :
|b doktorska disertacija /
|c Miljenko Bura.
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| 260 |
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|a Zagreb :
|b M. Bura,
|c 1995
|e ([s. l. :
|f s. n.])
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|a 103 lista :
|b table, ilustr. djelomično u bojama, graf. prikazi ;
|c 30 cm.
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|a mentor: Ivi Hršak; Komisija za ocjenu: Matko Marušić, Ivo Bašić, Ivo Hršak; Komisija za obranu: Milan Taradi, Ivo Bašić, Ivo Hršak; datum obrane: 14.12.1995;
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|a Sveučilište u Zagrebu, Medicinski fakultet, Zagreb, 1995
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|a Bibliografija: str. 89-102
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|a Summary
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|a Sažetak: Epidemiološki podaci na ljudima i pokusni nalazi na životinjama pokazuju da UVB zračenje izaziva tumore u koži. Ti se nalazi mogu povezati s imunosupresijom, lokalnom i sistemskom, koja se zapaža poslije UVB zračenja. U ovom su radu opisani pokusi koji su imali za cilj odgovoriti na pitanje može li se stimulacijom imunološkog odgovora pomoću peptidoglikan monomera (PGM) utjecati na pojavu tumora u koži miševa zračenih UVB-om. Radi razjašnjenja dobivenih podataka, ispitali smo, osim praćenja učestalosti malignih te premalignih promjena u koži i sistemske imunosupresije, razinu TNF alfa u serumu, intenzitet imunohistokemijske reakcije c-H-ras i erb B-2 onkoproteina te čimbenika rasta TGF-alfa u koži.
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|a U pokusima smo se koristili miševima soja Balb/c koje smo zračili UVB svjetlom dva puta tjedno (2,0 J/m2/sek) do pojave tumora u kontrolnoj skupini životinja. U tako ozračivanih miševa razvili su se karcinomi i sarkomi (34% životinja) te premaligne lezije (55%). U skupinama koje su počele dobivati imunostimulator PGM (1mg/miš/2 x tjedno), bilo 90 dana prije zračenja, bilo na dan početka zračenja, nije bilo malignih promjena u kožama, a samo smo u 3% životinja našli patomorfološki premaligne promjene.Nasuprot tome, u skupini životinja koja je PGM počela dobivati 90 dana nakon početka zračenja, nisu se ni vrsta ni učestalost promjena u koži gotovo ništa razlikovale od toga u kontrolnih životinja. Imunološku reaktivnost miševa nakon zračenja UVB-om i tretmana PGM-om ispitivali smo u životinja koje su zračene 2 ili 4 mjeseca.
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| 520 |
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|a Samo u miševa koji su bili ozračivani 4 mjeseca, mogli smo utvrditi sistemsku imunosupresiju (smanjen broj stanica slezene koje reagiraju na eritrocite ovce - PFC test). Tretman PGM-om značajno je oporavio imunološku reaktivnost, iako je nije oporavio do razine nezračenih miševa. Intenzitet imunohistokemijske reakcije na onkoprotein c-H-ras u koži miševa izloženih UVB-zrakama bio je različit u odnosu na ekspresiju u koži neozračenih miševa. U koži miševa u kojih je PGM uspješno prevenirao učinak zračenja, intenzitet imunohistokemijske reakcije na onkoprotein c-H-ras bio je u površnom epidermisu isti kao u koži neozračenih miševa. Imunohistokemijska reakcija na onkoprotein erb B-2 bila je različita ako se uspoređuju neozračene kože i kože nakon UVB zračenja. Međutim, nije bilo razlike između miševa koji su primali PGM i onih koji ga nisu primali.
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|a Analiza je pokazala da je u bazalnom sloju kože ozračenih miševa znatno manje TGF-alfa, toga regulatornog hormona rasta, nego u normalnoj koži. Tretman PGM-om nije promijenio intenzitet očitovanja tog čimbenika rasta u pokusnih životinja. U serumu miševa podvrgnutih UVB zračenju tijekom 4 mjeseca, mogli smo dokazati prisutnost TNF-alfa. Međutim, metodom koja je u ovom radu korištena za dokazivanje prisutnosti TNF-alfa (bioesej) nije se mogla otkriti eventualna razlika u količini TNF-alfa između miševa koji su osim UVB-zračenja dobivali PGM i onih koji nisu dobivali PGM. Iz navedenog se može zaključiti da UVB zračenje izaziva očite patološke promjene u ozračivanoj koži.
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|a Pojava tih promjena može se bitno smanjiti kontinuiranim tretmanom bakterijskim imunostimulatorom PGM-om. Ti se učinci mogu korelirati s promjenama u sistemskoj imunološkoj reaktivnosti, kao i s očitovanjem onkoproteina c-H-ras u koži, ali ne i s očitovanjem onkoproteina erb B-2, niti s očitovanjem TGF-alfa čimbenika rasta, niti s razinom TNF alfa u serumu.
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|a Summary: The epidemiological data on humans as well as experimental findings on animals indicate that UVB irradiation induces tumours in the irradiated skin.These findings could be related to the local and systemic immunosuppresion appearing after UVB irradiation.Here we describe experiments conducted with the aim of investigating whether the immunostimulation by bacterial immunostimulator peptidoglycan monomer (PGM) can influence the tumour incidence in the skin of UVB irradiated mice.To explain the results obtained,appart form the follow up of the pathological changes in the skin and systemic immune reactivity in the animals subjected to UVB irradiation and PGM treatment,the level of TNF alpha in the sera and the intensity of immunohistochemical reaction to c-H-ras oncoprotein, erb B-2 oncoprotein and to TGF alpha growth factor were determined.
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|a Balb/c mice were used in these experiments. They were irradiated with UVB lamps (2.0 J/m2/sec) twice a week during 8 months. Classical histological examination of the skin at the end of the obseration period revealed carcinomas and sarcomas (34% of mice) or premalignant lesions (55% of mice). In the groups of animals in which the treatment with PGM (1 mg/mouse/2xweek) started 90 days before UVB irradiation, or on the same day with the beginning of irradiation no malignant changes in the skin were found, and in only 3% of mice premalignant lesions could be seen. On the other hand, in animals in which the treatment with PGM beginned 90 days after irradiation the type and the incidence of pathological changes in the skin did not differ significantly from those in control animals.
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|a The immune reactivity to sheep red blood cells (PFC assay) was determined in the mice 2 and 4 month after UVB irradiation. Systemic immunosuppression was evident only in animals subjected to irradiation during 4 months. Treatment of PGM of these animals could significantly improve their immune reactivity although not restore it to the levels of normal, non-UVB irradiated mice. The intensity of immunohistochemical reaction on c-H-ras oncoprotein was different in the skins of UVB irradiated mice in comparison to nonirradiated animals. Also, the intensity of immunohistochemical reaction to this oncoprotein was different in the skins of animals in which treatment by PGM was effective in reducing immunosuppresion than in the skins of other UVB irradiated mice.
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|a In general, the treatment with PGM reduced the expression of c-H-ras oncoprotein in the skins of UVB irradiated mice. The expression of erb B-2 oncoprotein was different in the irradiated skins in comparison to non-irradiated ones, but there was no significant difference between the findings in the groups of mice treated or not with PGM. In the basal levels of the skins of UVB irradiated mice much less TGF alpha was found then in the same parts of the skin of nonirradiated mice. As with the expression of erb B-2 oncoprotein there was no significant difference found between the groups of animals treated or not with PGM. TNF alpha could be found in the sera of mice irradiated with UVB during 4 months.
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| 520 |
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|a However,by the assay used in these experiments (bioassay on L929 cells) we were not able to find any significant influence of the treatment with PGM on the TNF alpha production in the UVB irradiated mice. It could be concluded that UVB irradiation induces evident premalignant and malignant changes in the irradiated skin. Appearance of these changes could be significantly reduced by continuous treatment with bacterial immunostimulator PGM. These data correlate to the changes in the systemic immune reactivity of the treated animals and also to the expression of c-H-ras oncoprotein in the skin, but not with the expression of erb B-2 oncoprotein, neither to the presence of TGF alpha growth factor or to the presence of TNF alpha in the serum.
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| 650 |
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7 |
|a Koža
|x Karcinom
|x Terapija
|2 nskps
|
| 700 |
1 |
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|a Hršak, Ivo
|4 cns
|4 oth
|
| 700 |
1 |
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|a Marušić, Matko
|4 oth
|
| 700 |
1 |
|
|a Bašić, Ivan,
|c imunolog
|4 oth
|
| 981 |
|
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|p CRO
|r HRB1995
|
| 998 |
|
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|n DCD
|c sbno9802
|c rjkp9803
|c sbni9808
|
| 852 |
4 |
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|j DCD-ZG-14/96
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| 876 |
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|e DCD
|a 14/1996
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| 886 |
0 |
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|2 unimarc
|b 08645iam0 2200409 450
|