Myxoma virüslerin multipl myelomda otofajik etkilerinin incelenmesi
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Tekirdağ Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
MM (Multipl Myelom) tüm hematolojik maligniteler içinde ikinci sıklıkta rastlanan ve plazma hücrelerini etkileyen malign bir hastalıktır. MM un tedavisinde son yıllarda ortaya çıkan gelişmeler, yeni ilaç ve tedavi protokollerine yol açarak MM da küre yönelik tedavi araştırmaları son yıllarda hız kazanmıştır. Bu amaçla Multipl Myelomda etkinliği bilinen bir onkolitik virüs olan Myxomavirüslerin antimyelom etkinliklerinde Otofajin etkileri araştırılması amaçlanmıştır. Bununla birlikte özellikle kanserde birbirlerine etkileyen yolaklar olan otofaji ve Apoptoz ilişkisini değerlendirmek için apoptoz göstergesi olan Bcl-2 de yine farklı virüs dozlarında analiz edildi. Bu amaçla İnsan kökenli U-266 ve fare kökenli MOPC 315 Myelom hücre hatlarında MYXV'nin farklı dozları kullanılarak otofaji göstergeleri olarak Atg-5, p-62, Beclin-1, LC-IIIB kullanılırken ,apoptoz amacı ile Bcl-2'i inceledik. Bu tez çalışmasında hem U266 hem de MPOC hücre hatları kullanıldı. Analizler ELİZA ile değerlendirildi. Otofajide otofogozomların görüntülenmesi için Elektron Mikroskobu kullanıldı. Çalışmanın sonucunda özellikle 15 MOI gibi yüksek virüs içeren gruplarda ATG 5 ve Beclin-1 artışlarının otofajinin erken aşaması olan ilk 24 saatte U-266 ve MOPC-315 hücre hatlarında arttığını saptadık.Otofajiyi Elektron Mikroskobunda otofogozomlar olarak gösterdik. Otofajinin geç dönem göstergesi oln LCIIIB artışını da 48 saatte saptadık yine Elektron Mikroskopla geç otofaji döneminde otofogozomları tespit ettik. Apoptoz markeri olarak kullanılan Bcl-2 artışını hatlarda saptamadık. Bu marker apaptoz otofaji ilişkisi açısından incelendi. Ancak daha fazla apoptoz göstergesi kullanılarak bu ilişkinin farklı çalışmalarala değerlendirilmesi gerekebilir. Sonuç olarak MM da antimyelom etkinliği bilinen MYXV ile otofaji ilişkisi açısından yapılmış ilk çalışma olan bu tezde virüsün otofajiyi etkin şekilde kullandığını saptadık
MM (Multiple Myeloma) is the second most common malignant disease among all hematological malignancies and affects plasma cells. Recent developments in the treatment of MM have led to new drugs and treatment protocols, and researches on cure for MM have gained momentum in recent years. For this purpose, it was aimed to investigate the autophagy effects on the antimyeloma activities of Myxomaviruses, which is an oncolytic virus known to be effective in Multiple Myeloma. In addition, Bcl-2, which is an apoptosis indicator, was also analyzed at different virus doses to evaluate the relationship between autophagy and apoptosis, which are pathways that affect each other especially in cancer. For this purpose, we examined Bcl-2 for apoptosis while using Atg-5, p-62, Beclin-1, LC-IIIB as autophagy markers by using different doses of MYXV in human U-266 and mouse MOPC 315 Myeloma cell lines. . In this thesis study, both U266 and MPOC cell lines were used. Analyzes were evaluated with ELISA. Electron Microscopy was used to visualize autophagosomes in autophagy. As a result of the study, we determined that ATG 5 and Beclin-1 increases were increased in U-266 and MOPC-315 cell lines in the first 24 hours, which is the early stage of autophagy, especially in groups containing high virus such as 15 MOI. We showed autophagy as autophagosomes in Electron Microscopy. We detected the increase in LCIIIB, which is a late indicator of autophagy, in 48 hours. Again, we detected autophagosomes in the late autophagy period with Electron Microscopy. We did not detect the increase in Bcl-2, which is used as a marker of apoptosis, in the lines. This marker was examined in terms of apoptosis autophagy relationship. However, this relationship may need to be evaluated in different studies by using more apoptosis indicators. As a result, in this thesis, which is the first study conducted in terms of autophagy relationship with MYXV, whose antimyeloma activity is known in MM, we determined that the virus uses autophagy effectively.
MM (Multiple Myeloma) is the second most common malignant disease among all hematological malignancies and affects plasma cells. Recent developments in the treatment of MM have led to new drugs and treatment protocols, and researches on cure for MM have gained momentum in recent years. For this purpose, it was aimed to investigate the autophagy effects on the antimyeloma activities of Myxomaviruses, which is an oncolytic virus known to be effective in Multiple Myeloma. In addition, Bcl-2, which is an apoptosis indicator, was also analyzed at different virus doses to evaluate the relationship between autophagy and apoptosis, which are pathways that affect each other especially in cancer. For this purpose, we examined Bcl-2 for apoptosis while using Atg-5, p-62, Beclin-1, LC-IIIB as autophagy markers by using different doses of MYXV in human U-266 and mouse MOPC 315 Myeloma cell lines. . In this thesis study, both U266 and MPOC cell lines were used. Analyzes were evaluated with ELISA. Electron Microscopy was used to visualize autophagosomes in autophagy. As a result of the study, we determined that ATG 5 and Beclin-1 increases were increased in U-266 and MOPC-315 cell lines in the first 24 hours, which is the early stage of autophagy, especially in groups containing high virus such as 15 MOI. We showed autophagy as autophagosomes in Electron Microscopy. We detected the increase in LCIIIB, which is a late indicator of autophagy, in 48 hours. Again, we detected autophagosomes in the late autophagy period with Electron Microscopy. We did not detect the increase in Bcl-2, which is used as a marker of apoptosis, in the lines. This marker was examined in terms of apoptosis autophagy relationship. However, this relationship may need to be evaluated in different studies by using more apoptosis indicators. As a result, in this thesis, which is the first study conducted in terms of autophagy relationship with MYXV, whose antimyeloma activity is known in MM, we determined that the virus uses autophagy effectively.
Açıklama
Sağlık Bilimleri Enstitüsü, Tümör Biyolojisi ve İmmünolojisi Ana Bilim Dalı
Anahtar Kelimeler
Hematoloji, Hematology ; Tıbbi Biyoloji