Kolon Kanserine Yatkınlık ile p53 Geni Kodon 72 ve PAI-1 Geni 4G/5G Polimorfizmleri Arasındaki İlişki

msufbdWe aimed to investigate the relationship between colon cancer and p53 gene codon 72 and PAI-1 gene 4G/5G polymorphism in a Turkish study population. Genomic DNA was extracted from 72 patients with colon cancer and 76 controls. PCR technique was used to amplify extracted DNA with proper primers for each polymorphism. For identifying genotypes PCR products were assessed with UV transilluminator by being exposed to agarose gel electrophoresis. There was no statistical difference between colon cancer patients and controls according to p53 gene codon 72 genotype distribution and allele frequencies (p>0.05). Due to PAI-1 gene 4G/5G genotype distribution 4G4G genotype was frequently higher in colon cancer patients compared to controls  (p<0.05). As a conclusion of our study we may assert that p53 gene codon 72 polymorphism should not be related as a susceptibility factor for colon cancer development in the studied Turkish population while PAI-1 gene 4G/5G polymorphism should be related.Bu çalışmada Türk popülasyonunda kolon kanseri ile p53 geni kodon 72 ve PAI-1 geni 4G/5G polimorfizmleri arasındaki ilişkinin araştırılması amaçlanmıştır. Genomik DNA 72 kolon kanserli hastadan ve 76 kontrol bireyinden izole edilmiştir. Her bir polimorfizm için uygun primerler kullanılarak izolen edilen DNA PCR tekniği kullanılarak amplifiye edilmiştir. PCR ürünleri genotiplerin belirlenmesi için  agaroz jel elektroforezine tabi tutularak  UV translimünatör ile değerlendirilmiştir. p53 geni kodon 72 genotip dağılımı ve allel frekansları incelendiğinde kolon kanserli hastalar ve kontrol bireyleri arasında istatistiksel olarak bir fark belirlenmemiştir (p>0.05). PAI-1 4G/5G genotip dağılımı ve allel frekansları açısından ise 4G4G genotipi kontrol bireylerine göre kolon kanserli hastalarda daha yüksek bulunmuştur (p>0.05). Elde edilen verilere göre çalışmanın yapıldığı Türk popülasyonunda p53 geni kodon 72 polimorfizminin kolon kanseri gelişiminde bir yatkınlık faktörü olamayacağı, PAI-1 4G/5G polimorfizminin ise olabileceği kanısına varılmıştır.35014

Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney

In our previous paper, we demonstrated the ex vivo studies of non-toxic liposome-nanogel systems by which the long-term drug release could be provided from hybrid systems for the 5-fluorouracil (5-FU) drug molecule. The aim of this study was the in vivo magnetic targeting of 5-FU-loaded Fe3O4&nbsp;nanoparticles including DPPC liposome-based PEGylated nanogels (5-FU loaded Fe3O4LPN) to breast cancer tissue and the investigation of the treatment and cytotoxic effects of that hybrid system to the liver and kidney in CD-1 mice using an external magnetic field. The effectiveness of the control, 5-FU group, Fe3O4LPN, and 5-FU-loaded Fe3O4LPN systems was evaluated using histopathology in terms of p53, ESR, PRG and C-erB-2, and qRT-PCR in terms of TYMS, ESR-1, RPG, and EGRF. Also, the cytotoxicity was analyzed by histopathological evaluation of kidney and liver tissues. Caspase-3 and caspase-9 evaluations were performed by qRT-PCR. The creatinine and ALT levels were also evaluated by comparing the blood samples of all groups. A total of 300-nm TEM-sized Fe3O4LNP hybrid system was successfully prepared. That system significantly decreased the TYMS and ESR1 levels after treatment process and increased the levels of p53 expression. The levels of caspase-3 mRNA did not change during the treatment, but the level of caspase-9 mRNA level was significantly decreased. The magnetically targeted liposome-based nanogel hybrid system is promising an effective therapy for the breast tumor with less liver and kidney damage. This Fe3O4LNP hybrid system could be useful for the similar small molecules.</p

The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats

The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, Tadalafil and Sildenafil, on inducible NOS (iNOS), endothelial NOS (eNOS) and p53 genes expressions and apoptosis in ischemia/reperfusion (I/R) induced oxidative injury in rat renal tissue. Eighty Sprague-Dawley rats (300-350 g) were divided into four groups. In ischemia/reperfusion group, rats were subjected to renal ischemia by clamping the left pedicle for 60 min, and then reperfused for 90 min. On the other hand, in other two groups the rats were individually pretreated with Tadalafil and Sildenafil 1 h before the induction of ischemia. Malondialdehyde (MDA) is determined in renal tissue homogenates by high-performance liquid chromatography, the number of apoptotic cell were calculated by TUNEL method and p53 and eNOS expression were detected with immunohistochemistry. On the other hand, myeloperoxidase (MPO) levels were measured by spectrophotometric method and the mRNA level of iNOS in renal tissue was determined by Real-time PCR (RT-PCR). Our results indicate that MDA and MPO levels were increased in the I/R group than those in the control group. Both Tadalafil and Sildenafil treatment decreased the MDA levels in ischemia/reperfusion group, whereas this effect was more potent with Sildenafil. RT-PCR results showed that, iNOS gen expression increased in the I/R group, but decreased in the PDE5 inhibitory drugs treated group. Apoptotic cells, eNOS levels and p53 positive cells were also decreased in PDE5 inhibitory drugs treated group. We suggest that Tadalafil and Sildenafil have beneficial effects against I/R related renal tissue injury and this protective effect is clearer for Sildenafil than Tadalafil

Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer

Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC. Materials and methods: To generate colorectal cancer tumor xenografts, 1 × 107 cells from exponentially growing cultures of HCT-15 cells were injected subcutaneously, at the axillary region of the left and right rear flanks of forty NOD.CB17-Prkdcscid/J (NOD/SCID) female mice. The mice were then monitored for the development of tumors and were randomly divided into five groups when tumor sizes reached a volume of approximately 150 mm3. Mice were used to determine the effectiveness of the gamma-secretase inhibitor (DAPT, Notch inhibitor), the interleukin-1 receptor antagonist (Anakinra) and the leptin receptor antagonist (Allo aca) against tumor growth. The mice were euthanized by CO2 inhalation immediately after the treatments finished, and all efforts were made to minimize suffering. Tumors were excissed for RT-PCR and histological analysis. Results: There is an intact Notch, IL-1, and leptin signaling axis, and in vivo antagonism of Notch, IL-1, and leptin affects mRNA and protein expression of inflammatory and angiogenic molecules. Conclusion: Present data suggest that targeting Notch, IL-1, and leptin may be possesses therapeutic potential in CRC