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MDR1 promoter metilasyonu temozolomid direncini etkiler mi? Glioblastomlu hastalarda klinik çalışma

Yıl 2022, Cilt 15, Sayı 3, 547 - 554, 01.07.2022
https://doi.org/10.31362/patd.1013078

Öz

Amaç: Çoklu ilaç direnci 1 (MDR1) gen ekspresyonu ve epigenetik durumu, glioblastomun (GB) kemoterapötik direncinde önemli bir faktör olabilir. Bu çalışmanın amacı, MDR1 promoter metilasyon durumunun, hastanın sağkalımı, kemoterapi direnci ve hastalığın tekrarlaması ile ilgili olarak GB tümör dokusu üzerindeki etkisini analiz etmektir.
Gereç ve yöntem: …. Üniversitesi Tıp Fakültesi Beyin Cerrahisi Anabilim Dalı'nda GB tanısı ile ameliyat edilen 36 hastanın verileri incelendi. Hastaların klinik bilgileri ve tümör dokularının MDR1 metilasyon durumu, hastanın sağkalımı, kemoterapi direnci ve tümör nüksü üzerindeki etkilerine yönelik karşılaştırıldı.
Bulgular: MDR1’nin metile olduğu GB'li hastalarda istatistiksel olarak anlamlı (p<0,001) daha kısa sağkalım süreleri saptandı. Metile tümör dokusu olan hastaların %25'inde ve hemi-metile tümör dokusu olan hastaların %39,3'ünde erken rekürrens saptandı.
Sonuç: GB'li tüm hastalarda standart kemoterapötikleri kullanmak yerine, GB'nin genetik heterojenliği nedeniyle tümörün epigenomik özellikleri ve ekspresyon durumu dikkate alınarak dokuya özgü ilaçlar seçilmelidir. Bu, literatürdeki MDR1 promoter metilasyonu ile GB'nin klinik verileri arasındaki ilişkiyi gösteren ilk çalışmadır.

Kaynakça

  • 1. Krakstad C, Chekenya M. Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics. Mol Cancer. 2010;9:135.
  • 2. Adamson C, Kanu OO, Mehta AI, et al. Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009;Aug;18(8):1061-83.
  • 3. Rosell R, de Las Peñas R, Balaña C, et al. Translational research in glioblastoma multiforme: molecular criteria for patient selection. Future Oncol. 2008;Apr;4(2):219-28.
  • 4. Endicott JA, Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem. 1989;58:137-71.
  • 5. Kartner N, Riordan JR, Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science Sep. 1983; 23;221(4617):1285-8.
  • 6. Feun LG, Savaraj N, Landy HJ. Drug resistance in brain tumors. J Neurooncol. 1994;20(2):165-76.
  • 7. Schaich M, Kestel L, Pfirrmann M, et al. A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients. Ann Oncol 2009;Jan;20(1):175-81.
  • 8. Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013;Nov 10;31(32):4085-91.
  • 9. Khasraw M, Lassman AB. Advances in the treatment of malignant gliomas. Curr Oncol Rep. 2010; Jan;12(1):26-33.
  • 10. Tahara T, Shibata T, Yamashita H, et al. Promoter methylation status of multidrug resistance 1 (MDR1) gene in noncancerous gastric mucosa correlates with Helicobacter Pylori infection and gastric cancer occurrence. Cancer Invest. 2010;Aug;28(7):711-6.
  • 11. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene. 2003;Oct 20;22(47):7468-85.
  • 12. Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB. Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990;Jan 5;265(1):506-14.
  • 13. Takanishi K, Miyazaki M, Ohtsuka M, Nakajima N. Inverse relationship between P-glycoprotein expression and its proliferative activity in hepatocellular carcinoma. Oncology. 1997;May-Jun;54(3):231-7.
  • 14. Scotlandi K, Manara MC, Serra M, et al. The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells. Oncogene. 1999;Jan 21;18(3):739-46.
  • 15. Goldstein LJ, Galski H, Fojo A, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst. 1989;Jan 18;81(2):116-24.
  • 16. Pastan I, Gottesman M. Multiple-drug resistance in human cancer. N Engl J Med. 1987;May 28;316(22):1388-93.
  • 17. Matsumoto T, Tani E, Kaba K, et al. Amplification and expression of a multidrug resistance gene in human glioma cell lines. J Neurosurg. 1990;Jan;72(1):96-101.
  • 18. Podolski-Renić A, Jadranin M, Stanković T, et al. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. Cancer Chemother Pharmacol. 2013;Sep;72(3):683-97.
  • 19. Qiu YY, Mirkin BL, Dwivedi RS. MDR1 hypermethylation contributes to the progression of neuroblastoma. Mol Cell Biochem. 2007;Jul;301(1-2):131-5.
  • 20. Yegnasubramanian S, Kowalski J, Gonzalgo ML, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004;Mar 15;64(6):1975-86.
  • 21. Bastian PJ, Palapattu GS, Yegnasubramanian S, et al. CpG island hypermethylation profile in the serum of men with clinically localized and hormone refractory metastatic prostate cancer. J Urol. 2008;Feb;179(2):529-34; discussion 534-5.
  • 22. Ellinger J, Bastian PJ, Jurgan T, et al. CpG island hypermethylation at multiple gene sites in diagnosis and prognosis of prostate cancer. Urology. 2008;Jan;71(1):161-7.
  • 23. von Bossanyi P, Diete S, Dietzmann K, Warich-Kirches M, Kirches E. Immunohistochemical expression of P-glycoprotein and glutathione S-transferases in cerebral gliomas and response to chemotherapy. Acta Neuropathol. 1997;Dec;94(6):605-11.
  • 24. Yokogami K, Kawano H, Moriyama T, et al. Application of SPET using technetium-99m sestamibi in brain tumours and comparison with expression of the MDR-1 gene: is it possible to predict the response to chemotherapy in patients with gliomas by means of 99mTc-sestamibi SPET? Eur J Nucl Med. 1998;Apr;25(4):401-9.
  • 25. Abe T, Mori T, Wakabayashi Y, et al. Expression of multidrug resistance protein gene in patients with glioma after chemotherapy. J Neurooncol. 1998;Oct;40(1):11-8.

Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma

Yıl 2022, Cilt 15, Sayı 3, 547 - 554, 01.07.2022
https://doi.org/10.31362/patd.1013078

Öz

Purpose: The multidrug resistance 1 (MDR1) gene expression and its epigenetic status may be an important factor in the chemotherapeutic resistance of glioblastoma (GB). The aim of this study was to analyze the effect of the MDR1 promoter methylation status on GB tumor tissue related with patient survival, chemotherapy resistance, and recurrence of the disease.
Materials and methods: Thirty-six patients underwent surgery for GB at the Neurosurgery Department of Ankara University School of Medicine. The patients’ clinical information and the MDR1 methylation status of the tumor tissues was compared to determine the effects on patient survival, chemotherapy resistance, and tumor recurrence.
Results: Patients with MDR1 methylated GB had statistically significantly (p<0.001) shorter survival times. Early recurrence was detected in 25% of the patients with unmethylated tumor tissues and in 39.3% with hemimethylated tumor tissues.
Conclusion: Instead of using the standard chemotherapeutics in all the patients with GB, tissue-specific medications must be chosen while taking into consideration the epigenomic characteristics and expression status of the tumor because of the genetic heterogeneity of GB. This is the first study to show the association between MDR1 promoter methylation and the clinical data of GB in the literature.

Kaynakça

  • 1. Krakstad C, Chekenya M. Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics. Mol Cancer. 2010;9:135.
  • 2. Adamson C, Kanu OO, Mehta AI, et al. Glioblastoma multiforme: a review of where we have been and where we are going. Expert Opin Investig Drugs. 2009;Aug;18(8):1061-83.
  • 3. Rosell R, de Las Peñas R, Balaña C, et al. Translational research in glioblastoma multiforme: molecular criteria for patient selection. Future Oncol. 2008;Apr;4(2):219-28.
  • 4. Endicott JA, Ling V. The biochemistry of P-glycoprotein-mediated multidrug resistance. Annu Rev Biochem. 1989;58:137-71.
  • 5. Kartner N, Riordan JR, Ling V. Cell surface P-glycoprotein associated with multidrug resistance in mammalian cell lines. Science Sep. 1983; 23;221(4617):1285-8.
  • 6. Feun LG, Savaraj N, Landy HJ. Drug resistance in brain tumors. J Neurooncol. 1994;20(2):165-76.
  • 7. Schaich M, Kestel L, Pfirrmann M, et al. A MDR1 (ABCB1) gene single nucleotide polymorphism predicts outcome of temozolomide treatment in glioblastoma patients. Ann Oncol 2009;Jan;20(1):175-81.
  • 8. Gilbert MR, Wang M, Aldape KD, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol. 2013;Nov 10;31(32):4085-91.
  • 9. Khasraw M, Lassman AB. Advances in the treatment of malignant gliomas. Curr Oncol Rep. 2010; Jan;12(1):26-33.
  • 10. Tahara T, Shibata T, Yamashita H, et al. Promoter methylation status of multidrug resistance 1 (MDR1) gene in noncancerous gastric mucosa correlates with Helicobacter Pylori infection and gastric cancer occurrence. Cancer Invest. 2010;Aug;28(7):711-6.
  • 11. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene. 2003;Oct 20;22(47):7468-85.
  • 12. Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB. Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990;Jan 5;265(1):506-14.
  • 13. Takanishi K, Miyazaki M, Ohtsuka M, Nakajima N. Inverse relationship between P-glycoprotein expression and its proliferative activity in hepatocellular carcinoma. Oncology. 1997;May-Jun;54(3):231-7.
  • 14. Scotlandi K, Manara MC, Serra M, et al. The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells. Oncogene. 1999;Jan 21;18(3):739-46.
  • 15. Goldstein LJ, Galski H, Fojo A, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst. 1989;Jan 18;81(2):116-24.
  • 16. Pastan I, Gottesman M. Multiple-drug resistance in human cancer. N Engl J Med. 1987;May 28;316(22):1388-93.
  • 17. Matsumoto T, Tani E, Kaba K, et al. Amplification and expression of a multidrug resistance gene in human glioma cell lines. J Neurosurg. 1990;Jan;72(1):96-101.
  • 18. Podolski-Renić A, Jadranin M, Stanković T, et al. Molecular and cytogenetic changes in multi-drug resistant cancer cells and their influence on new compounds testing. Cancer Chemother Pharmacol. 2013;Sep;72(3):683-97.
  • 19. Qiu YY, Mirkin BL, Dwivedi RS. MDR1 hypermethylation contributes to the progression of neuroblastoma. Mol Cell Biochem. 2007;Jul;301(1-2):131-5.
  • 20. Yegnasubramanian S, Kowalski J, Gonzalgo ML, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004;Mar 15;64(6):1975-86.
  • 21. Bastian PJ, Palapattu GS, Yegnasubramanian S, et al. CpG island hypermethylation profile in the serum of men with clinically localized and hormone refractory metastatic prostate cancer. J Urol. 2008;Feb;179(2):529-34; discussion 534-5.
  • 22. Ellinger J, Bastian PJ, Jurgan T, et al. CpG island hypermethylation at multiple gene sites in diagnosis and prognosis of prostate cancer. Urology. 2008;Jan;71(1):161-7.
  • 23. von Bossanyi P, Diete S, Dietzmann K, Warich-Kirches M, Kirches E. Immunohistochemical expression of P-glycoprotein and glutathione S-transferases in cerebral gliomas and response to chemotherapy. Acta Neuropathol. 1997;Dec;94(6):605-11.
  • 24. Yokogami K, Kawano H, Moriyama T, et al. Application of SPET using technetium-99m sestamibi in brain tumours and comparison with expression of the MDR-1 gene: is it possible to predict the response to chemotherapy in patients with gliomas by means of 99mTc-sestamibi SPET? Eur J Nucl Med. 1998;Apr;25(4):401-9.
  • 25. Abe T, Mori T, Wakabayashi Y, et al. Expression of multidrug resistance protein gene in patients with glioma after chemotherapy. J Neurooncol. 1998;Oct;40(1):11-8.

Ayrıntılar

Birincil Dil İngilizce
Konular Cerrahi
Yayınlanma Tarihi Ekim 2022
Bölüm Araştırma Makalesi
Yazarlar

Yahya Efe GÜNER> (Sorumlu Yazar)
YÜKSEK İHTİSAS ÜNİVERSİTESİ
0000-0001-9660-5941
Türkiye


Eyüp BAYATLİ Bu kişi benim
ANKARA ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0001-6246-4247
Türkiye


Aslıhan KURT>
ONDOKUZ MAYIS ÜNİVERSİTESİ
0000-0002-9323-0993
Türkiye


Derya GÖKMEN>
ANKARA ÜNİVERSİTESİ, ANKARA TIP FAKÜLTESİ
0000-0001-6266-3035
Türkiye


Veysel YÜKSEK>
YÜZÜNCÜ YIL ÜNİVERSİTESİ
0000-0003-0361-2275
Türkiye


Filiz TAŞPINAR Bu kişi benim
AKSARAY ÜNİVERSİTESİ
0000-0003-3780-4021
Türkiye


Bora TETİK>
İNÖNÜ ÜNİVERSİTESİ
0000-0001-7696-7785
Türkiye


Mehmet TAŞPINAR>
AKSARAY ÜNİVERSİTESİ
0000-0002-7598-2665
Türkiye


Hasan Çağlar UĞUR Bu kişi benim
ANKARA ÜNİVERSİTESİ, TIP FAKÜLTESİ
0000-0003-3728-4599
Türkiye

Destekleyen Kurum Yok
Proje Numarası Yok
Teşekkür This study was partially presented as a poster at the Personalized Medicine Conference set for May 18-20, 2016 in Tübingen, Germany
Yayımlanma Tarihi 1 Temmuz 2022
Kabul Tarihi 21 Şubat 2022
Yayınlandığı Sayı Yıl 2022, Cilt 15, Sayı 3

Kaynak Göster

Bibtex @araştırma makalesi { patd1013078, journal = {Pamukkale Tıp Dergisi}, eissn = {1308-0865}, address = {Pamukkale Üniversitesi Tıp Fakültesi Eğitim Blokları Kınıklı kampüsü 20070 Kınıklı, Denizli}, publisher = {Pamukkale Üniversitesi}, year = {2022}, volume = {15}, number = {3}, pages = {547 - 554}, doi = {10.31362/patd.1013078}, title = {Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma}, key = {cite}, author = {Güner, Yahya Efe and Bayatli, Eyüp and Kurt, Aslıhan and Gökmen, Derya and Yüksek, Veysel and Taşpınar, Filiz and Tetik, Bora and Taşpınar, Mehmet and Uğur, Hasan Çağlar} }
APA Güner, Y. E. , Bayatli, E. , Kurt, A. , Gökmen, D. , Yüksek, V. , Taşpınar, F. , Tetik, B. , Taşpınar, M. & Uğur, H. Ç. (2022). Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma . Pamukkale Tıp Dergisi , 15 (3) , 547-554 . DOI: 10.31362/patd.1013078
MLA Güner, Y. E. , Bayatli, E. , Kurt, A. , Gökmen, D. , Yüksek, V. , Taşpınar, F. , Tetik, B. , Taşpınar, M. , Uğur, H. Ç. "Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma" . Pamukkale Tıp Dergisi 15 (2022 ): 547-554 <https://dergipark.org.tr/tr/pub/patd/issue/68347/1013078>
Chicago Güner, Y. E. , Bayatli, E. , Kurt, A. , Gökmen, D. , Yüksek, V. , Taşpınar, F. , Tetik, B. , Taşpınar, M. , Uğur, H. Ç. "Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma". Pamukkale Tıp Dergisi 15 (2022 ): 547-554
RIS TY - JOUR T1 - Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma AU - Yahya Efe Güner , Eyüp Bayatli , Aslıhan Kurt , Derya Gökmen , Veysel Yüksek , Filiz Taşpınar , Bora Tetik , Mehmet Taşpınar , Hasan Çağlar Uğur Y1 - 2022 PY - 2022 N1 - doi: 10.31362/patd.1013078 DO - 10.31362/patd.1013078 T2 - Pamukkale Tıp Dergisi JF - Journal JO - JOR SP - 547 EP - 554 VL - 15 IS - 3 SN - -1308-0865 M3 - doi: 10.31362/patd.1013078 UR - https://doi.org/10.31362/patd.1013078 Y2 - 2022 ER -
EndNote %0 Pamukkale Tıp Dergisi Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma %A Yahya Efe Güner , Eyüp Bayatli , Aslıhan Kurt , Derya Gökmen , Veysel Yüksek , Filiz Taşpınar , Bora Tetik , Mehmet Taşpınar , Hasan Çağlar Uğur %T Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma %D 2022 %J Pamukkale Tıp Dergisi %P -1308-0865 %V 15 %N 3 %R doi: 10.31362/patd.1013078 %U 10.31362/patd.1013078
ISNAD Güner, Yahya Efe , Bayatli, Eyüp , Kurt, Aslıhan , Gökmen, Derya , Yüksek, Veysel , Taşpınar, Filiz , Tetik, Bora , Taşpınar, Mehmet , Uğur, Hasan Çağlar . "Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma". Pamukkale Tıp Dergisi 15 / 3 (Temmuz 2022): 547-554 . https://doi.org/10.31362/patd.1013078
AMA Güner Y. E. , Bayatli E. , Kurt A. , Gökmen D. , Yüksek V. , Taşpınar F. , Tetik B. , Taşpınar M. , Uğur H. Ç. Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma. Pam Tıp Derg. 2022; 15(3): 547-554.
Vancouver Güner Y. E. , Bayatli E. , Kurt A. , Gökmen D. , Yüksek V. , Taşpınar F. , Tetik B. , Taşpınar M. , Uğur H. Ç. Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma. Pamukkale Tıp Dergisi. 2022; 15(3): 547-554.
IEEE Y. E. Güner , E. Bayatli , A. Kurt , D. Gökmen , V. Yüksek , F. Taşpınar , B. Tetik , M. Taşpınar ve H. Ç. Uğur , "Does MDR1 promoter methylation affect temozolomide resistance? A clinical study in patients with glioblastoma", Pamukkale Tıp Dergisi, c. 15, sayı. 3, ss. 547-554, Tem. 2022, doi:10.31362/patd.1013078
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