Amaç: Malign plevral mezotelyoma (MPM) gelişiminde hücre çoğalması, protein sentezi, enerji üretimi, hücre iskeletinin yeniden düzenlenmesi ve anjiyogenezde önemli rolleri olan çeşitli sinyal yolaklarının etkisi olduğu düşünülmektedir. Ayrıca, son yıllarda histon modifikasyonlarını da içine alan epigenetik değişikliklerin kanser gelişiminde etkisi olduğu gösterilmiştir. Bu değişikliklerin MPM'nin ortaya çıkmasına neden olabileceği düşünülmektedir. Günümüzde, MPM tedavisi için klasik kemoterapi ajanlarının yeni moleküller ile birlikte kullanılması araştırılarak, daha etkili tedavi seçenekleri belirlenmeye çalışılmaktadır. Bu moleküllerden bir tanesi de histon asetil transferaz (HAT) inhibitörü olan anakardik asittir (AA). Çalışmamızda MPM hücre hattında (MSTO-211H: bifazik), AA ile sisplatinin (CDDP) tek başına ve birlikte kullanılmasının, cMYC, NFKΒ, FOXO3A ve BCL2L1 genlerinin mRNA düzeyindeki ifadeleri üzerine olan etkilerini belirlemeyi amaçladık. Gereç ve Yöntemler: Sisplatin ve AA'nın hücre canlılığı üzerine etkisini belirlemek için 3-(4,5-dimetiltiazol-2-yl)-2,5-difeniltettrazoliyum bromür testi uygulandı. Hücre canlılığı testinin sonucunda seçilen uygun dozlar hücrelere uygulandıktan sonra RNA izolasyonu yapıldı. İzole edilen RNA'lardan kantitatif gerçek zamanlı polimeraz zincir reaksiyonu (qPCR) yöntemiyle cMYC, NFKΒ, FOXO3A ve BCL2L1 genlerinin mRNA düzeyindeki ifadeleri belirlendi. Bulgular: MSTO-211H hücrelerine CDDP'nin 10 μM'ın üzerinde uygulanan dozlarının etkili olduğu belirlendi. Hücre canlılığının AA+CDDP uygulanan grupta, CDDP'nin tek başına uygulandığı gruba oranla daha düşük olduğu belirlendi. MSTO-211H hücrelerine AA ön uygulaması, tek başına CDDP uygulamasına oranla araştırdığımız genlerin mRNA'larının ekspresyon düzeylerinin anlamlı derecede azalmasına neden olduğu saptandı. Sonuç: Elde ettiğimiz veriler, AA ön uygulamasının hücreleri klasik kemoterapi ajanı olan CDDP'ye daha duyarlı hale getirerek etkili bir hücresel ölüm cevabına neden olacağını göstermektedir. Bu preklinik çalışma, MPM gelişiminde epigenetik değişimlerin önemini vurgulamaktadır.
Long non‑coding RNAs (lncRNAs) are molecules that are >200 base pairs long and do not encode a protein. However, they perform important roles in regulating gene expression. Recent studies have revealed that the changes in the expressions of lncRNAs serve a role in the development and metastases of a number of types of cancer. A number of studies have been published on the association of SOX2 overlapping transcript (SOX2OT), differentiation antagonizing non‑protein coding RNA (DANCR) and tissue differentiation‑induced non‑coding RNA (TINCR) expression with various types of cancer. However, researchers have not yet studied their roles in papillary thyroid cancer or at least, those roles are not clarified. The aim of the present study was to investigate the expression and clinical significance of SOX2OT, DANCR and TINCR in papillary thyroid cancer (PTC). A total of 102 patients with PTC were included in the present study. Reverse transcription‑quantitative PCR method was used to determine the relative gene expression levels of lncRNAs and then the relationship between expressions of lncRNAs and clinical characteristics of the subjects was analyzed in detail. Expression levels of SOX2OT (P=0.016) and DANCR (P=0.017) increased in the tumor samples in contrast to the normal tissues. No significant difference was observed in the expression level of TINCR (P=0.298). In addition, SOX2OT expression was associated with micro carcinoma (P<0.001), tumor size (P=0.010) and primary tumor (P=0.006), while DANCR expression was associated with age (P=0.030) and micro carcinoma (P=0.004). The findings of the present study indicated that DANCR may contribute to the development of PTC while SOX2OT may contribute to both the development and progression of PTC.
The activation of the phosphatidylinositol-3 kinase/v‑akt murine thymoma viral oncogene homolog (Akt) and mitogen activated protein kinase kinase/extracellular signal‑regulated kinase (ERK) pathways are implicated in the majority of cancers. Selective inhibition of Akt and ERK represents a potential approach for cancer therapy. Therefore, the present study aimed to investigate the apoptotic and anti‑proliferative effects of the novel and selective Akt inhibitor 4‑amino‑5,8‑dihydro‑5‑oxo‑8-β-D-ribofuranosyl-pyrido[2,3-d]pyrimidine-6‑carboxamide (API‑1) and selective ERK1/2 inhibitor FR180204 (FR) alone and in combination on colorectal cancer (CRC) cells (DLD‑1 and LoVo). In addition, the effects of API‑1 and FR on Akt and ERK signaling pathways were also investigated. The effects of the agents on DLD‑1 and LoVo cells were evaluated in terms of cell viability, cytotoxicity, DNA synthesis rate, DNA fragmentation and caspase‑3 activity levels. In addition, quantitative reverse transcription‑polymerase chain reaction and western blot analysis were performed to examine relevant mRNA and protein levels. The present study observed that the combination of FR with API‑1 resulted in significant apoptosis and cytotoxicity compared with any single agent alone in a time‑dependent manner in these cells. Also, treatment with FR and API‑1 in combination decreased the expression levels of B‑cell lymphoma‑2 (BCL2), Bcl‑2‑like 1, cyclin D1 and cMYC, and increased the expression levels of BCL2‑associated X protein and BCL2 antagonist/killer via phosphorylated Akt and phosphorylated ERK1/2 downregulation. The combination of Akt and ERK1/2 inhibitors resulted in enhanced apoptotic and anti‑proliferative effects against CRC cells. The present study hypothesizes that the combination of FR and API‑1 in CRC cells may contribute toward potential anti‑carcinogenic effects. Additional analyses using other cancer cell lines and animal models are required to confirm these findings in vitro and in vivo.
Thyroid cancers (TCs) are the most common endocrine malignancies. There were two problems with the current cancer chemotherapy: the ineffectiveness of treatment due to resistance to cancer cell, and the toxic effect on normal cells.This study was aimed to determine the effects of thymoquinone (TQ) and genistein (Gen) phytotherapeutics on telomerase activity, angiogenesis, and apoptosis in follicular and anaplastic thyroid cancer cells (TCCs).Cell viability, caspase-3 (CASP-3) activity, and messenger RNA (mRNA) expression levels of human telomerase reverse transcriptase (hTERT), phosphatase and tensin homolog (PTEN), nuclear factor-kappa B (NF-kB), cyclin-dependent kinase inhibitor 1 (p21), and vascular endothelial growth factor-A (VEGF-A) genes were analyzed.It was found that TQ and Gen treatment on TCCs caused a statistically significant decrease of cell viability, and mRNA expression levels of hTERT, VEGF-A, and NF-kB genes, but a statistically significant increase of PTEN and p21 mRNA expression levels. In addition, TQ and Gen treatment also caused a statistically significant increase active CASP-3 protein level in TCCs. Moreover, our results demonstrated that, when compared with follicular TCCs, anaplastic TCCs were more sensitive to the treatment of TQ and Gen.Based on these results, two agents can be good options as potential phytochemotherapeutics against TCCs.
Amac: Anjiyotensin donusturucu enzim (ACE) ve Anjiyotensinojen (AGT) renin-anjiyotensin sisteminin anahtar bilesenleridir. ACE I/D ve AGT M235T polimorfizmleri genellikle konvansiyonel PZR teknigi ile saptanmaktadir. Fakat son zamanlarda hizli genotiplendirme tekniginin gelistirilmesi ile bu polimorfizmlerin belirlenmesi kolaylasmistir. Calismamizda ACE I/D ve M235T polimorfizmlerinin belirlenmesinde Eszamanli ve konvansiyonel PZR yontemlerini karsilastirmayi amacladik. Yontem: ACE I/D ve AGT M235T polimorfizmleri konvansiyonel ve Eszamanli PZR teknikleri ile calisildi ve bu tekniklerin avantajlari ve dezavantajlari belirlendi. Bulgular: Bulgularimiza gore konvansiyonel PZR ile I/D polimorfizminin yanlis genotiplendirme orani % 6 belirlendi. Bu nedenle hatali genotiplendirmeden kacinmak icin tum DD genotipli orneklere ikinci bir PZR daha uygulandi (Insersiyon spesifik PZR). DNA ornekleri ayni zamanda Eszamanli PZR ile de analiz edildi. Son olarak konvansiyonel PZR ve Eszamanli PZR sonuclari karsilastirildi. Tum genotipler Eszamanli PZR ile tek seferde dogru olarak saptandi. Ayrica M235T polimorfizmi de PCR-RFLP ve Eszamanli PZR teknikleri ile analiz edildi. Iki teknigin sonuclari arasida herhangi bir farklilik gozlemedi. Ancak PCR-RFLP yonteminde tamamlanmamis enzim kesimi gibi olasi problemler yanlis genotiplendirmeye neden olabilmektedir. Sonuc: Ozetle ACE I/D ve M235T polimorfizmlerinin hizli genotipleme teknigi olan Eszamanli PZR ile belirlenmesi guvenilirlik ve zaman kaybi yonunden laboratuvar arastirmalari ve tani icin uygun bir secenek sunmaktadir. Anahtar Kelimeler: ACE, AGT, Eszamanli PZR, Polimorfizm, PZR
Aim: Diabetes mellitus (DM) is an important health problem with an increasing incidence worldwide and causes many complications. Diabetic retinopathy (DR) is one of the most serious complications of DM. Polymorphisms of the AKR1B1 gene, which encodes an aldose reductase enzyme, have been associated with development of DM and DR in some studies. The current study aims to investigate the relationship of AKR1B1 rs759853 polymorphism with type 2 DM (T2DM), DR and DR severity in the Turkish population. Materials and Methods: A total of 437 individuals, including 141 T2DM patients without DR, 125 T2DM patients with DR, and 171 healthy controls, were included in the study. Genotyping was performed using PCR-RFLP method.Results: An association between T allele / TT genotype and increased risk of proliferative diabetic retinopathy (PDR) was detected. In the logistic regression analysis in which other risk factors were included, rs759853 polymorphism and diabetes duration were found to be associated with the PDR development. There was no significant relationship between the AKR1B1 rs759853 variation and the development of T2DM and DR. Conclusion: Obtained data showed that AKR1B1 rs759853 polymorphism is not associated with the development of T2DM and DR in the Turkish patients, but TT genotype and diabetes duration are independent risk factors for the development of PDR.
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