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Karaciğer Hasarının Farklı Basamaklarında ve Hepatoselüler Karsinomda TGF/3R-1 Ekspresyonları

Year 2009, Volume: 42 Issue: 1, 8 - 12, 01.04.2009

Pelin Bağcı Gülşen Özbay

Abstract

Hepatic stellate celi (HSC) is the key fibrogenic celi type in liver. Transforming growth factor-p (TGFp), using mostly trans-forming growth factor-p receptor-1 (TGFpR-1), generated by the activated HSC is the most significant fibrogenic molecule of cirr-hosis. We pianned this study to observe the expressions of TGFpR-1 in different steps of liver injury. We immunostained 65 viral hepatitis, 58 cirrhosis and 21 hepatocellular carcinoma (HCC) cases vvith TGFpR-1 antibody and scored the intensity and the distribution of the stainings. Biostatisticai analysis vvere done to see, if there are any meaningful results betvveen age, sex, etio-logy, hepatic activity index, fibrosis scores; tumor diameter, vascular invasion, multifocality, presence of cirrhosis and receptor expressions. İn the hepatitis group the intensity of TGFpR-1 staining vvas positively correiated vvith the increasing fibrosis score (p< 0.05). İn the cases vvhich cirrhosis vvas inactive, there vvere no TGFfSR-1 expressions. The only positive result in HCC group vvas the inverse correiation betvveen tumor diameter and TGFpR-1 expression. TGFpR-1 is an important mediator in liver vvound healing. But its' effect is important in the early stages of hepatocarcinogenesis. İn complete cirrhosis or HCCs greater than 3 cm, anti-TGFpR strategies vvill not be useful alone.

Keywords

Cirrhosis hepatocellular carcinoma TGFp TGFpR-1.

References

  • Crawford JM. Pathologic basis of disease. Elsevier İne. 7th ed. Liver and biliary tract, 2005:877-927.
  • Farazi PA, DePinho RA. Hepatocellular carcinoma pathoge- nesis: From genes to environment. Nature Revievvs-Cancer 2006:6;674-87.
  • Canbay A, Friedman S, Gores GJ. Apoptosis: The nexus of liver injury and fibrosis. Hepatoiogy 2004;39:273-8.
  • Liu X, Hu H, Yin JQ. Therapeutic strategies against TGF- beta signating pathvvay in hepatic fibrosis. Liver International 2006;26:8-22.
  • Shi YF, Fong CC. Hypoxia induces aetivation of human hepatic stellate cells LX-2 through TGF signaling pathvvay. FEBS tetters 2007;581:203-10.
  • Bissell MD. Chronic iiver injury, TGF-beta, and cancer. Exp Mol Med 2001;33:179-90.
  • Wells RG. TGF-beta signaling pathvvays. Am J Physiol
  • Gastrointest Liver Physiol 2000;279:845-50.
  • Prosser CC, Yen RD, Jian W. Molecular therapy for hepatic injury and fibrosis: Where are we? VVorid J Gastroenterol 2006;12:509-15.
  • Mikula M, Proel V, FischerANM, Mikulits W. Activated hepa­ tic stellate cells induce tumor progression of neoplastic hepatoeytes in a TGF-fi dependent fashion. J Celi Physiol 2006;209:560-7.
  • Paik SY, Park YN, Kim H, Park C. Expression of transfor- ming grovvth factor-pi and transforming growth factor-f receptors in hepatocellular carcinoma and dysplastic nodu- les. Mod Pathol 2003;16:86-96.
  • Ueno T, Hashimoto O. Relation of type II transforming grovvth factor receptor to hepatic fibrosis and hepatocellular carcinoma. IntJ Oncol 2001;18:49-55.
  • Spee B, Arends B, Ingh TSGAM, et al. Transforming grovvth factor p-1 signalling in canine hepatic diseases: New modeis for human fibrotic liver pathoiogies. Liver International 2006;26:716-25. 12

The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*

Year 2009, Volume: 42 Issue: 1, 8 - 12, 01.04.2009

Pelin Bağcı Gülşen Özbay

Abstract

Hepatik yıldızsı hücre (HYH) karaciğerde fibrozisten sorumlu temel hücredir. Transforme edici büyüme faktörü-p (TGFp) ise, aktive HYH'lerden salınan ve çoğunlukla transforme edici büyüme faktörü-p reseptörü-1 (TGFpR-1) üzerinden etkilerini gösteren, siroz gelişiminde fibrozisten sorumlu olan temel moleküldür. Bu çalışma, karaciğer hasarının farklı aşamalarında ve hepatoselüler karsinom (HSK)'da TGFpR-1 ekspresyonlarını değerlendirmek, ve de tedaviye yönelik çıkarımlar yapmak üzere planlanmıştır. Altmış beş viral hepatit, 58 siroz ve 21 HSK olgusu TGFpR-1 primer antikoru ile immünhistokimyasal olarak boyandı. Boyanma yaygınlığı ve yoğunluğu skorlandı. Rutin boyalardaki histolojik aktiviteler ve fibrozis skorları ile immünhistokimyasal boyanma paternleri ve boyanan hücreler karşılaştırıldı. Ardından yaş, cinsiyet, etyoloji, histolojik aktivite indeksleri, fibrozis skorları; tümör çapı, vasküier invazyon, multifokalite ve siroz varlığı ile TGFpR-1 boyanmasındaki yaygınlık ve yoğunluklar arasındaki ilişkileri saptamak üzere biyoistatistiksel çalışmalar uygulandı. Hepatit grubunda TGFpR-1 boyanmasındaki yoğunluk ile fibrozis skorundaki artışın korelasyon gösterdiği saptandı (p< 0.05). inaktif sirozun izlendiği vakalarda TGFpR-1 boyanması görülmedi. HSK grubunda saptanan en önemli bulgu ise; tümör çapı ile TGFpR-1 boyanmaları arasındaki ters korelasyon oldu. TGFp ve reseptörü olan TGFpR-1 karaciğerdeki yara iyileşmesi sürecinde görevli olan en önemli moleküllerdendir. Ancak etkileri hepa-tokarsinogenezin erken dönemlerinde belirgindir. Komplet siroz ve 3 cm ve daha büyük çaplardaki HSK'larda anti-TGFpR stratejilerinin monoterapi şeklinde kullanılması faydalı olmayacaktır.

Keywords

Siroz hepatoselüler karsinoma TGFp TGFpR-1.

References

  • Crawford JM. Pathologic basis of disease. Elsevier İne. 7th ed. Liver and biliary tract, 2005:877-927.
  • Farazi PA, DePinho RA. Hepatocellular carcinoma pathoge- nesis: From genes to environment. Nature Revievvs-Cancer 2006:6;674-87.
  • Canbay A, Friedman S, Gores GJ. Apoptosis: The nexus of liver injury and fibrosis. Hepatoiogy 2004;39:273-8.
  • Liu X, Hu H, Yin JQ. Therapeutic strategies against TGF- beta signating pathvvay in hepatic fibrosis. Liver International 2006;26:8-22.
  • Shi YF, Fong CC. Hypoxia induces aetivation of human hepatic stellate cells LX-2 through TGF signaling pathvvay. FEBS tetters 2007;581:203-10.
  • Bissell MD. Chronic iiver injury, TGF-beta, and cancer. Exp Mol Med 2001;33:179-90.
  • Wells RG. TGF-beta signaling pathvvays. Am J Physiol
  • Gastrointest Liver Physiol 2000;279:845-50.
  • Prosser CC, Yen RD, Jian W. Molecular therapy for hepatic injury and fibrosis: Where are we? VVorid J Gastroenterol 2006;12:509-15.
  • Mikula M, Proel V, FischerANM, Mikulits W. Activated hepa­ tic stellate cells induce tumor progression of neoplastic hepatoeytes in a TGF-fi dependent fashion. J Celi Physiol 2006;209:560-7.
  • Paik SY, Park YN, Kim H, Park C. Expression of transfor- ming grovvth factor-pi and transforming growth factor-f receptors in hepatocellular carcinoma and dysplastic nodu- les. Mod Pathol 2003;16:86-96.
  • Ueno T, Hashimoto O. Relation of type II transforming grovvth factor receptor to hepatic fibrosis and hepatocellular carcinoma. IntJ Oncol 2001;18:49-55.
  • Spee B, Arends B, Ingh TSGAM, et al. Transforming grovvth factor p-1 signalling in canine hepatic diseases: New modeis for human fibrotic liver pathoiogies. Liver International 2006;26:716-25. 12
There are 13 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Pelin Bağcı This is me

Gülşen Özbay This is me

Publication Date April 1, 2009
Published in Issue Year 2009 Volume: 42 Issue: 1

Cite

APA Bağcı, P. ., & Özbay, G. . (2009). The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*. Acta Oncologica Turcica, 42(1), 8-12.
AMA Bağcı P, Özbay G. The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*. Acta Oncologica Turcica. April 2009;42(1):8-12.
Chicago Bağcı, Pelin, and Gülşen Özbay. “The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*”. Acta Oncologica Turcica 42, no. 1 (April 2009): 8-12.
EndNote Bağcı P, Özbay G (April 1, 2009) The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*. Acta Oncologica Turcica 42 1 8–12.
IEEE P. . Bağcı and G. . Özbay, “The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*”, Acta Oncologica Turcica, vol. 42, no. 1, pp. 8–12, 2009.
ISNAD Bağcı, Pelin - Özbay, Gülşen. “The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*”. Acta Oncologica Turcica 42/1 (April 2009), 8-12.
JAMA Bağcı P, Özbay G. The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*. Acta Oncologica Turcica. 2009;42:8–12.
MLA Bağcı, Pelin and Gülşen Özbay. “The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*”. Acta Oncologica Turcica, vol. 42, no. 1, 2009, pp. 8-12.
Vancouver Bağcı P, Özbay G. The TGFpR-1 Expressions in Different Steps of Liver Injury and Hepatocellular Carcinoma*. Acta Oncologica Turcica. 2009;42(1):8-12.