Yüksek insidansa sahip olan Küçük Hücreli Dışı Akciğer Kanseri (KH-DAK) en yüksek mortaliteye sahip kanser alt tipi olarak önemini korumaktadır. Çoğunlukla belirtilerin ileri evrelerde kendini göstermesi tedavi başarısını önemli ölçüde kısıtlamaktadır. Son yıllarda, tümör dokusunda meydana gelen genetik değişiklikler sonucu ortaya çıkan onko-proteinlerin baskılanabilmesi tedavi başarısına önemli katkı sağlamıştır. Tümördeki bu moleküler değişimlerin tespiti kişiye özgü tedavilerin ön plana çıkmasına katkı sağlamıştır. Toplumdan topluma ve kişiden kişiye farklılık gösterebilen bu moleküler değişimlerin tedavi başarısını artırmak amacıyla her ülkedeki sıklık ve korelasyonlarının ortaya konması önem arz etmektedir. Ülkemizde KHDAK onkogen sıklık ve korelasyonlarına dair yeterli veri bulunmamaktadır, tanı ve tedavi batılı toplumlara benzer olduğu varsayılarak düzenlenmektedir. Ülkemize ait verilerin oluşturulması, tanı ve tedavi stratejileri açısından klinisyene fayda sağlaması ve böylece tedavi başarısını artırabilmesi bakımından önemlidir. Bu amaçla çalışmamızda KHDAK tanılı olguların tümör parafin bloklarında onkogen oluşumuna sebep olan ve sık gözlemlenen mutasyonların sıklıklarının ve korelasyonlarının belirlenmesi amaçlanmıştır. Materyal-Metot: Tanısı KHDAK olan toplam 80 hastaya ait parafin blok kesitlerinden genomik DNA izolasyonu yapılmıştır. Ticari mutasyon kitleri (Roche Diagnostics, Amoy Diagnostics) kullanılarak Cobas z (Roche Diagnostics) RT-PCR cihazında Epidermal Büyüme Faktörü Reseptörü (EGFR), Kirsten sıçan sarkoma viral onkogen homoloğu (KRAS), v-Ras Nöroblastom viral onkogen homoloğu (NRAS), v-Raf Murine sarkoma viral onkogen homoloğu (BRAF), Fosfatidil inozitol-3-kinaz katalitik alfa polipertid (PIK3CA), İnsan Epidermal Büyüme Faktör Reseptörü 2 (HER2) mutasyonları araştırılmıştır. Bulgular: 80 olgunun 37'sinde toplam 38 mutasyon saptanmıştır. Olguların 7'sinde EGFR, 23'ünde KRAS, 6'sında PIK3CA, 1'inde BRAF ve 1'inde NRAS mutasyonu saptanmıştır. HER2 mutasyonu hiçbir olguda saptanmamıştır. KRAS mutasyonu bulunan bir olguda PIK3CA mutasyonu birlikteliği saptanmıştır. Sonuç: Sonuçlarımız; Ülkemizde PIK3CA mutasyon sıklığı dışında batılı toplumların mutasyon profiline benzer bir profile sahip olduğumuzu göstermektedir. Elde ettiğimiz PIK3CA mutasyon sıklığı %7,5'tir ve literatürdeki gösterilen %1-4 aralığının üzerindedir. Sonuçlarımız doğrultusunda PIK3CA mutasyonlarının tanı ve tedavide daha fazla dikkate alınmasının tedavi başarısına katkı sağlayabileceğini düşünmekteyiz.
SUMMARY OBJECTIVE: Celiac disease is an autoimmune disease characterized by an abnormal immune response occurring in the small intestine linked to consumption of food containing gluten in individuals with a genetic predisposition. Dysregulation of Wnt signal transduction plays a role in the pathogenesis of many diseases including autoimmune diseases like celiac disease. In this study, the correlation of Wnt pathway gene expressions with each other and the correlation with clinical data were researched in pediatric celiac disease cases grouped according to the Marsh classification. METHODS: Gene expression levels of FZD8 , DVL2 , LRP5 , RHOA , CCND2 , CXADR , and NFATC1 , which are involved in the Wnt pathway, were determined using quantitative real-time polymerase chain reaction in 40 celiac disease and 30 healthy individuals. RESULTS: All cases with the short height symptom were observed to be in Marsh 3b\3c groups (p=0.03). The gene expressions of DVL2 , CCND2 , and NFATC1 were high in the Marsh 3b group, and these genes showed positive correlation with each other (p=0.002). LRP5 and CXADR gene expressions were lower in the Marsh 3b group compared to other Marsh groups, and these genes showed a positive correlation with each other (p=0.003). CCND2 gene expression was associated with Marsh 3b group, diarrhea, and vomiting symptoms. DVL2 gene expression was correlated with Marsh 2 group and constipation symptom (p<0.05). CONCLUSION: Wnt signaling in the early stages of the disease of Marsh 1–2 involves high expression of LRP5 and CXADR genes, while expression of these two genes reduces, and DVL2 , CCND2 , and NFATC1 gene expressions clearly increase with a transduction variation observed from Marsh 3a stage when villous atrophy begins to form. It appears that the Wnt pathway may contribute to disease progression through expression changes.
Celiac disease (CD) is an immune-dependent systemic disorder that occurs in genetically predisposed individuals resulting in damage in the small intestine. It is known that chromatin remodeling, an epigenetic mechanism, is associated with gastrointestinal diseases associated with chronic inflammation. However, no information is available on the link between CD and chromatin remodeling. For this purpose, the expression profiles of chromatin remodeling group genes in children diagnosed with CD according to Marsh classification and HLA profile were evaluated and their relationship with CD was investigated. Endoscopic biopsies embedded in the paraffin block of 40 children with CD diagnosis and 30 healthy children were included in the study. The most common four mutations (DQA1*05, DQB1*02, DQA1*03, and DQB1*03:02) related to CD on human leukocyte antigen (HLA) gene were screened. Intestinal biopsy samples were used for mRNA isolations and cDNA synthesis. Expressions of total seven genes in the chromatin remodeling groups (SWI/SNF Complex Group: ARID1A, Polycomb Group: CTBP1, Nucleosome-Remodeling & Histone Deacetylase (NuRD) Complex Group: MTA1, Chromobox/Heterochromatin Protein 1 (HP1) Homologs Group: CBX3 and CBX7, Homeodomain (PHD) Protein Group: NSD1, Inhibitor of Growth (ING) family group: ING 5) were analyzed by Real-Time qPCR. Data analysis was performed online using the software provided by the manufacturer. Overexpression in ARID1A, CTBP1, and NSD1 genes was detected when the CD group was compared against the control group, however they were not significant (p=0.31, 0.33, and 0.33). When CD group who had diarrhea symptom (typical) were compared to the CD group without diarrhea symptom (atypical), statistically significant under-expression was found in CBX3 and CTBP1 genes (p=0.04 and p=0.004). Statistically significant CTB1 overexpression was detected in Marsh 2 CD cases (p=0.03). In the comparison of HLA DQ2/DQ8 positive CD patient group with the control group, the NSD1, CBX3, and EED (p=0.75, 0.75, and 0.78) genes were over-expressed and the CBX7, MTA1, ARID1A, and CTBP1 genes (p=0.74, 0.75, 0.75, and 0.75) were under-expressed. This is the first study to report that expression of chromatin remodeling genes may have roles in the development and progression of CD. The results of this case-control study are open to confirmation by future studies with larger number of subjects to obtain statistically significant results.
Aim: Acute myeloid leukemia (AML) is a disease characterized by relapse and treatment resistance in most patients. Therefore, there is a need for targeted therapies in AML. Photodynamic therapy (PDT) is a promising alternative for the treatment of malignant tumors. Also, PDT has the potential to be used individually or complementally in the treatment of leukemia. In this study, it was aimed to investigate possible the effect of malachite green (MG)-based PDT on acute myeloid leukemia cells. Materials and Methods: Cells were incubated with 0.19, 0.39, 0.78,1.56, 3.125, and 6.25 µM MG for one hour and irradiated with 46.4 J/cm2 of light. The trypan blue test was used to assess the viability of cells, and the change in mitochondrial activity was determined by MTT. Morphological features were determined by Giemsa staining and scanning electron microscopy. Cell cycle and Annexin V/PI assays (measuring fluorescence emitted by staining reagents) were measured by flow cytometry. Results: With the combination of MG and light, HL60 cell viability was found to be significantly reduced compared to the control group. Giemsa staining and SEM results showed that 3.125 μM MG-based PDT induced various morphological changes in cells typical for apoptosis. Late apoptosis was observed in cells treated with 3.125 μM MG combined PDT according to Annexin/PI staining, further showing that it caused an arrest in the subG1 phase of the cell cycle. Conclusion: MG-based PDT has the potential to inactivate HL60 cells. Thus, MG-based PDT may ensure a promising approach for treating acute myeloid leukemia cells.
The neurobiology of obsessive-compulsive disorder (OCD) is evidenced by a strong demonstration of malfunctions in the serotonergic and dopaminergic system. Recently, glial cell line-derived neurotrophic factor (GDNF) gene polymorphisms have been emphasized in psychiatric diseases and treatment strategies that have been tried to be developed in this regard. In the literature, there are several studies investigating the relationship between GDNF gene polymorphisms and psychiatric diseases excluding OCD. Therefore, this study aimed to compare the symptomatology and GDNF gene polymorphisms in early and late-onset OCD patients. For this purpose, patients diagnosed with OCD according to DSM-V diagnostic criteria in structured clinical interviews were grouped as early and late-onset based on the age of initiation. DNA was isolated from blood samples collected from 140 subjects (70 OCD and 70 healthy controls) in EDTA tubes, and rs2910702, rs3096140, and rs3812047 polymorphisms in GDNF gene were examined by Real-Time PCR. No significant correlation was detected between GDNF and the rs2910702, rs3096140, and rs3812047 polymorphisms in early and late-onset OCD subjects (P>0.05). Failure to detect correlations between OCD and GDNF gene polymorphisms might be due to the variable expression pattern of the GDNF gene in different tissues and pathologies. Therefore, future studies might be improved by including a larger group of patients and examining a wider range of tissues for the expression pattern of GDNF.
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