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Glioblastoma tümörlerinde çoklu ilaç direnci

Yıl 2013, Cilt: 23 Sayı: 4, 133 - 143, 01.01.2013

Öz

Merkezi sinir sisteminin gerek yapı ve fonksiyonunu gerekse patolojisini hücresel düzeyde anlamada nöronal ve glial paradigma olmak üzere iki yaklaşım öne çıkmaktadır. Nöronal paradigma nöronları, glial paradigma ise glia hücrelerini vurgulayarak patolojiyi açıklamakta ve anlamlandırmaktadır. Beyin tümörlerinin en yaygın türlerinden biri olan glioblastoma, konumu, sağ kalım süresinin kısalığı ve ilacın hedef dokuya ulaşabilirliğinin zorluğu noktalarından özgün bir tümördür. Glioblastomalarda kemoterapötik tedavi- de gözlenen ilaç direnci, diğer tümörlerde gözlenen direnç mekanizmalarıyla uyumludur. Bu direnç mekanizmaları, tümör hücreleri- nin ilaca hassasiyetini azaltan kan beyin bariyeri ve membran transport proteinlerine bağlı olarak hücre içine ilaç girişinin azalması, DNA tamir sistemlerindeki adaptif cevap ve hedef molekülün ilaca bağlanma etkinliğinin azaltılması ve ilaçların hedef dokudaki et- kin konsantrasyonunu azaltan mekanizmalar detoksifikasyonda rol alan proteinlerdeki değişimler, tümör mikroçevresinde meydana gelen hipoksik bölgeler olmak üzere iki alt başlıkta incelenebilir. Ayrıca, onkogenlerin aktivasyonu ve apoptozisle ilişkili Bcl-2 ailesi proteinlerinin ifadesindeki düzensizliklerin de ilaç direncinin ortaya çıkışında rol aldığı bilinmektedir. Bu derlemede glioblastoma tümörlerinde görülen çoklu ilaç direncinin olası mekanizmalarını güncel literatür ışığında tanımlanarak sistemik ve bütüncül bir bakış açısı ortaya konulmaya çalışılmıştır

Kaynakça

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Multiple drug resistance in glioblastoma

Yıl 2013, Cilt: 23 Sayı: 4, 133 - 143, 01.01.2013

Öz

In cellular perspective, neuronal and glial paradigms are two prevailing approaches for understanding both structure/function and pathology of central nervous system. Neuronal paradigm explains brain pathology mainly based on neurons, while glial paradigm put more emphasize to glial cells. Glioblastoma, one of the most common brain tumors, is unique due to its location, the shortness of median survival and the difficulty of efficient uptake in target tissue. Drug resistance mechanisms observed in the chemotherapy of glioblastoma are quite similar to the ones of other tumor types. These mechanisms can be investigated under two main groups: one is decreasing the sensitivity of tumor cells to chemotherapeutic agents decreasing of drug uptake into cell by blood brain barrier and membrane transport proteins and the other one is reducing the efficient concentration of the drug in target tissue variabilities in detoxification proteins and hypoxia in the tumor microenvironment . Moreover, activation of oncogenes and abnormalities of expression of Bcl-2 protein family members are mediating players in the development of drug resistance in glioblastoma. In this review, the possible drug resistance mechanisms in glioblastoma were described in the light of recent literature by using systemic and integrative perspective

Kaynakça

  • Weaver J. A new look at ‘‘filler cells’’ in the brain reveals their role in learning. PLoS Biol 2012;10:e1001263.
  • Verkhratsky A and Butt A. Introduction to Glia, in Glial Neuro- biology: A Textbook. 1st ed. Chichester, UK, John Wiley & Sons Ltd, 96-121.
  • Aggarwal S, Yurlova L, Simons M. Central nervous system myelin: structure, synthesis and assembly. Trends Cell Biol 2011;21:585- 93.
  • Harry GJ, Kraft AD. Microglia in the developing brain: a potential target with lifetime effects. Neurotoxicology. 2012;33:191-206.
  • Sevc J, Daxnerová Z, Haňová V, et al. Novel Jiangs on the origin of ependymal cells in the ventricular zone of the rat spinal cord. Acta Histochem 2011;113:156-62.
  • Jiang Y, Uhrbom L. On the origin of glioma. Ups J Med Sci 2012;117:113-121.
  • Herrup K, Yang Y. Cell cycle regulation in the postmitotic neuron: oxymoron or new biology? Nat Rev Neurosci 2007;8:368-378.
  • Nagane M, Huang HJ, Cavenee WK. Causes of drug resistance and novel therapeutic opportunities for the treatment of glioblastoma. Drug Resist Updat 1999;2:30-37.
  • Chen Y, Liu L. Modern methods for delivery of drugs across the blood-brain barrier. Adv Drug Deliv Rev 2012;64:640-665.
  • Pitz MW, Desai A, Grossman SA, et al. Tissue concentration of systemically administered antineoplastic agents in human brain tumors. J Neurooncol 2011;104:629-38.
  • Haar CP, Hebbar P, Wallace GC, et al. Drug resistance in glioblas- toma: a mini review. Neurochem Res 2012;37:1192-200.
  • Potschka H. Targeting regulation of ABC efflux transporters in brain diseases: a novel therapeutic approach. Pharmacol Ther 2010;125:118-27.
  • Bredel M, Zentner J. Brain-tumour drug resistance: the bare essen- tials. Lancet Oncol 2002;3:397-406.
  • Beaulieu E, Demeule M, Ghitescu L, et al. P-glycoprotein is strong- ly expressed in the luminal membranes of the endothelium of blo- od vessels in the brain. Biochem J 1997;326:539-44.
  • Cordon-Cardo C, O’Brien JP, Casals D, et al. Multidrug-resistan- ce gene (P-glycoprotein) is expressed by endothelial cells at blo- od-brain barrier sites. Proc Natl Acad Sci USA. 1989;86:695-8.
  • Goldman B. Multidrug resistance: can new drugs help chemothe- rapy score against cancer? J Natl Cancer Inst 2003;95:255-7.
  • Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cas- sette (ABC) transporter superfamily. J Lipid Res 2001;42:1007-17.
  • Vries NA, Buckle T, Zhao J, et al. Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP. Invest New Drugs 2012;30:443-9.
  • Tsuruo T, Naito M, Tomida A, et al. Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci 2003;94:15-21.
  • Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 1998;95:15665-70.
  • Lu C, Shervington A. Chemoresistance in gliomas. Mol Cell Bioc- hem 2008;312:71-80.
  • Natarajan K, Xie Y, Baer MR, et al. Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Phar- macol 2012;83:1084-103.
  • Vries NA, Zhao J, Kroon E, et al. P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 2007;13:6440-9.
  • Elmeliegy MA, Carcaboso AM, Tagen M, et al. Role of ATP-binding cassette andsolute carrier transporters in erlotinib CNS penetration and intracellular accumulation. Clin Cancer Res 2011;17:89-99.
  • Vries NA, Buckle T, Zhao J, et al. Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transpor- ters P-gp and BCRP. Invest New Drugs 2010;27:31-40.
  • Agarwal S, Sane R, Ohlfest JR, et al. The role of the breast cancer resistance protein (ABCG2) in the distribution of sorafenib to the brain. J Pharmacol Exp Ther 2011;336:223-33.
  • Garwal S, Sane R, Gallardo JL, et al. Distribution of geŞtinib to the brain is limited by P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)-mediated active efflux. J Pharmacol Exp Ther 2011;334:147-55.
  • Zhou L, Schmidt K, Nelson FR, et al. The effect of breast cancer re- sistance protein and P-glycoprotein on the brain penetration of fla- vopiridol, imatinib mesylate (Gleevec), prazosin, and 2-methoxy- 3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic acid (PF-407288) in mice. Drug Metab Dispos 2009;37:946-55.
  • Ballatori N, Hammond CL, Cunningham JB, et al. Molecular mec- hanisms of reduced glutathione transport: role of the MRP/CFTR/ ABCC and OATP/SLC21A families of membrane proteins. Toxi- col Appl Pharmacol 2005;204:238-55.
  • Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a trans-porter gene in a multidrug-resistant human lung cancer cell line. Science 1992;258:1650-4.
  • Benyahia B, Huguet S, Declèves X, et al. Multidrug resistance-as- sociated protein MRP1 expression in human gliomas: chemosen- sitization to vincristine and etoposide by indomethacin in human glioma cell lines overexpressing MRP1. J Neurooncol 2004;66:65- 70.
  • Borst P, Evers R, Kool M, et al. A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 2000;92:1295-302.
  • Leggas M, Adachi M, Scheffer GL, et al. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol Cell Biol 2004;24:7612-21.
  • Abe T, Hasegawa S, Taniguchi K, et al. Possible involvement of multidrug-resistance-associated protein (MRP) gene expression in spontaneous drug resistance to vincristine, etoposide and adri- amycin in human glioma cells. Int J Cancer 1994;58:860-4.
  • Abe T, Mori T, Wakabayashi Y, et al. Expression of multidrug re- sistance protein gene in patients with glioma after chemotherapy. J Neurooncol 1998;40:11-8.
  • Bronger H, König J, Kopplow K, et al. ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Cancer Res 2005;65:11419-28.
  • Sasaki T, Hankins GR, Helm GA. Major vault protein/lung resis- tance-related protein (MVP/LRP) expression in nervous system tumors. Brain Tumor Pathol 2002;19:59-62.
  • Aronica E, Gorter JA, van Vliet EA, et al. Overexpression of the human major vault protein in gangliogliomas. Epilepsia 2003;44:1166-75.
  • Berger W, Spiegl-Kreinecker S, Buchroithner J, et al. Overexpres- sion of the human major vault protein in astrocytic brain tumor cells. Int J Cancer 2001;94:377-82.
  • Silber JR, Bobola MS, Blank A, et al. O(6)-Methylguanine-DNA methyltransferase in glioma therapy: Promise and problems. Bio- chim Biophys Acta 2012;1826:71-82.
  • Hayat MA. Tumors of the central nervous system. Chapter 1, Edi- tor: Hayat MA, Springer, 2011, 3.
  • Friedman HS, McLendon RE, Kerby T, et al. DNA mismatch-repa- ir and O -alkylguanine-DNA-alkyltransferase analysis and respon- se to temodal in newly diagnosed malignant glioma. J Clin Oncol 1998;16:3851–7.
  • Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352: 997-1003.
  • Paz MF, Yaya-Tur R, Rojas-Marcos I, et al. CpG island hypermet- hylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res 2004;10:4933-8.
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Toplam 90 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Derleme
Yazarlar

Emir Bozkurt Bu kişi benim

Harika Atmaca Bu kişi benim

Selim Uzunoğlu Bu kişi benim

Yayımlanma Tarihi 1 Ocak 2013
Yayımlandığı Sayı Yıl 2013 Cilt: 23 Sayı: 4

Kaynak Göster

Vancouver Bozkurt E, Atmaca H, Uzunoğlu S. Glioblastoma tümörlerinde çoklu ilaç direnci. Genel Tıp Derg. 2013;23(4):133-4.