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Objective: Cellular heterogeneity of tumors stems from cell populations expressing a unique set of proteins defective genetic and epigenetic networks. It is shown that versican (VCAN) is upregulated by transforming growth factor-beta (TGF-β1) in several types of cancer cell types. Our prior studies revealed that TGF-β1 expression is elevated in cancer stem cell (CSCs) monolayer cultures and VCAN expression was also significantly increased in spheroid formed CSCs. Methods: Within the scope of these results, it was hypothesized that high TGF-β1 expression in the monolayer might trigger the three-dimensional architectural organization by inducing VCAN expression. This study investigated the expression profiling of VCAN in primary and secondary tumor-derived cell lines and the effect of TGF-β1 signaling in these cells. Results: The findings showed that the VCAN gene expression level in the PC3 human prostate cell line was correlated with VCAN protein expression as analyzed by western blot. There was no inducing or suppressing effect of TGF-β1 on VCAN protein expression. Conclusion: TGF-β1 has neither stimulatory nor inhibitory effects on VCAN expression in prostate cancer cells at the doses used in this study. In the metastatic, high VCAN protein levels were observed while no mRNA was detected which could have resulted from post-transcriptional changes such as increased protein stability and/or expression of different VCAN isoforms that may play an important role in the secondary tumor cells in prostate carcinoma.

Loeys-Dietz syndrome (LDS) is a rare autosomal dominant connective tissue disorder with multisystemic involvement caused by pathogenic genetic variations in the transforming growth factor- β pathway. Here, we report a homozygous case with LDS. A newborn male patient who had congenital diaphragmatic hernia, aortic dilatation and talipes equinovarus was referred to our medical genetics polyclinic. After clinical evaluation, next generation sequencing analysis showed a homozygous c.859C>T pathogenic missense variation [R287W (p.Arg287Trp)] in the SMAD3 gene. It was confirmed that the parents harbor the variant heterozygously. Due to the autosomal dominant inheritance pattern, rarely seen biallelic individuals are expected to have severe clinical conditions. Since there was only one previous report of an individual harboring a homozygous SMAD3 variant in the literature; this case was presented to further enhance our understanding of LDS.

Amaç: Diferansiye tiroit karsinomalarında total tiroidektomi sonrası metastatik odakların tedavisi için radyoaktif I-131 (RAİ) kullanımı standart bir tedavidir. Ancak I-131'in tiroit dışı dokularda yan etkileri bilinmektedir. Montelukast, sisteinil lökotrienlerin CysLT1 reseptörüne bağlanmasını bloke ederek etkisini gösteren lökotrien reseptör antagonistidir. Montelukastın bleomisin ile indüklenmiş akciğer fibrozisinde anti-fibrotik etkisi gösterilmiştir. Biz de çalışmamızda montelukastın RAİ sonrası sıçan akciğerlerinde fibrozisine histopatolojik etkisini inceledik. Yöntem: Otuz Wistar albino sıçan rastgele 10'arlı 3 gruba ayrıldı. Grup 1'e (kontrol grubu) sadece total tiroidektomi uygulandı; grup 2'ye total tiroidektomi sonrası RAİ uygulandı; grup 3'e total tiroidektomi öncesi ve sonrasında montelukast ve RAİ uygulandı. Tüm sıçanlar 12 hafta sonra sakrifiye edildi. Akciğerlerdeki fibrozisin derecesini belirlemek için immünohistokimyasal (İHC) boyama ile TNF-alfa ve TGF-beta doku ekspresyonu skorlanarak değerlendirildi. Bulgular: Grup 2'de TNF-alfa ve TGF-beta doku ekspresyonu grup 1'e göre anlamlı olarak fazla bulundu (p<0,01). Ancak grup 3 ile grup 1 arasında doku ekspresyonu açısından anlamlı fark bulunamadı (p>0,01). Grup 3'te fibrozis, grup 2'ye göre anlamlı olarak daha düşüktü (p<0,01). Sonuç: Çalışmamızda astım ve alerjik rinit gibi hastalıklarda yıllardır güvenle kullanılan anti-enflamatuvar ve antioksidan özelliklere sahip montelukastın RAİ sonrası akciğerlerde izlenebilen fibrozisi azaltarak radyoprotektif etkisi doku ekspresyonu olarak gösterilmiştir. [ABSTRACT FROM AUTHOR]