In recent years, natural products gained popularity with their anti-inflammatory and antioxidant effects mediated by chemical compounds within their composition. Study results offering them as palliative therapy options in cancer or as anticancer agents with high levels of cytotoxicity brought a new approach to combine cancer treatment protocols with these products. From a different perspective, edible types of these products are suggested in daily diets due to their potential cancer preventive effects. Our preliminary work was on blueberry extracts (Vaccinium myrtillus) as a main representative of these natural products, and the contents of the extracts were analyzed with liquid chromatography tandem mass spectrometry (LC MS/ MS) to reveal the composition and distribution of polyphenolic compounds within. The most abundant polyphenols detected in V. myrtillus extracts were quercetin, kaempferol, and a phenolic acid, gentisic acid (GA). The compounds were further evaluated on treated HCT-116 cells for their potential anticancer effects by measuring total antioxidant status, total oxidant status, and 8hydroxydeoxyguanosine levels for evaluation of oxidative stress and through protein array analysis and flow cytometric analysis for evaluation of apoptosis. In analysis of oxidative stress parameters, reduced total oxidant levels and reduced oxidative stress index levels were found in cells treated with the compounds in comparison with untreated cells. In apoptosis-related protein profiles, at least twofold reduction in various apoptotic proteins was observed after quercetin and kaempferol treatment, whereas a different profile was observed for GA. Overall, results of this study showed that quercetin and kaempferol have strong cytotoxic, antioxidant, and apoptotic effects, although GA is mostly effective as an antioxidant polyphenol on HCT-116 cells.

BCR-ABL oncoprotein stimulates cell proliferation and inhibits apoptosis in chronic myeloid leukemia (CML). For cure, imatinib is a widely used tyrosine kinase inhibitor, but developing chemotherapeutic resistance has to be overcome. In this study, we aimed to determine differing genome-wide microRNA (miRNA) and messenger RNA (mRNA) expression profiles in imatinib resistant (K562/IMA-3 μM) and parental cells by targeting STAT5A via small interfering RNA (siRNA) applications. After determining possible therapeutic miRNAs, we aimed to check their effects upon cell viability and proliferation, apoptosis, and find a possible miRNA::mRNA interaction to discover the molecular basis of imatinib resistance. We detected that miR-2278 and miR-1245b-3p were most significantly regulated miRNAs according to miRNome array. Upregulating miR-2278 expression resulted in the inhibition of resistant leukemic cell proliferation and induced apoptosis, whereas miR1245b-3p did not exhibit therapeutic results. Functional analyses indicated that AKT2, STAM2, and STAT5A mRNAs were functional targets for miR-2278 as mimic transfection decreased their expressions both at transcriptional and translational level, thus highlighting miR-2278 as a tumor suppressor. This study provides new insights in discovering the mechanism of imatinib resistance due to upregulating the tumorsuppressor hsa-miR-2278 which stands for a functional therapeutic approach, inhibited leukemic cell proliferation, induced apoptosis, and regain of chemotherapeutic drug response in CML therapy.

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Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland.More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients' lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not su cient in the treatment of ATC, so alternative therapies are needed. The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, Effect of VPA on miRNAs affecting histone deacetylase were determined by Quantitative RT-PCR. In BRAFV600E / mut SW1736 (SW1736) cell line IC50 dose for VPA found 1.6 mg/ml. in our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes is miR- 323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101-5p increased signi cantly. VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). We got very promising results with VPA.

Previously, we demonstrated that biotransformation of propolis by some special strains of Lactobacillus plantarum might decrease the allergenic molecules in propolis.In this study, we aimed to investigate the effect of biotransformation of propolis on its antioxidant effect and its protective effect against potassium bromate-induced cancer in human colon cell line. Propolis samples were treated with different solutions (ethanol, polyethylene glycol, and water), and ultrasonication was applied at 40 Hz (5, 10, and 15 minutes) in order to facilitate solvation of solid samples. Fermentations were performed by L. plantarum strains (ISLG-2, ATCC-8014, and Visbyvac). The phenolic content of propolis was determined with liquid chromatography-mass spectrometry/mass spectrometry (LCMS/MS). The antioxidant activity (antioxidant enzymes, lipid peroxidation) and apoptosis markers (caspase 3,8,9, cytochrome-c, tumour necrosis factor-related apoptosis-inducing ligand-R1 and R2 [TRAIL], and apoptosis protease activating factor-1 [APAF-1] levels) were determined in CCD 841-human colon cell line after induction of oxidative stress by potassium bromate. All propolis samples in different solvents induced apoptosis and 4 biotransformed (by L. plantarum ISL-2 strain and L. plantarum ATCC 8014 strain) propolis samples with low allergenic molecules demonstrated similar inductions of apoptosis in CCD841 cell line.In conclusion, reduction of allergenic molecules in propolis via biotransformation did not change the antioxidant and protective effects of propolis, and it is suggested as a potential therapeutic molecule in prevention of colon cancer caused by oxidative stress for all patients.Significance of the study: This study is the first investigation that shows protective effect of propolis against potassium bromate toxicity by means of decreasing lipid peroxidation and reversing the main molecule levels in intrinsic and extrinsic pathway of apoptosis. Biotransformed propolis samples by L. plantarum ISL-2 and ATCC 8014 strain with low allergen molecule content has also the same effect in potassium bromate toxicity in CCD841 colon cell. Our data contributed that propolis as a natural

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.

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ObjectivesRituximab is a monoclonal antibody that targets the B-lymphocyte surface antigen CD20. It is used in the treatment of some diseases including B-cell chronic lymphocytic leukemia (B-CLL). There are a lot of data regarding effect of Rituximab on lymphoma cells. But, there is no satisfactory information about the effect of Rituximab on the signaling pathways in leukemia cells. In this study, it was aimed to understand the effect of Rituximab on JAK-STAT and NF-κB signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) and B-CLL.Material and methodsApoptotic effect of Rituximab in the TANOUE (B-ALL) and EHEB (B-CLL) cell lines were evaluated by using the Annexin V method. mRNA expression levels of STAT3 and RelA were analysed by quantitative RT-PCR (Q-PCR). Alterations in STAT3 and RelA protein expressions were detected by using a chromogenic alkaline phosphatase assay after Western Blotting.ResultsRituximab had no apoptotic effect on both cell lines. Complement-mediated cytotoxicity was only detected in EHEB cells. mRNA and protein expressions of STAT3 and RelA genes were decreased following Rituximab treatment.ConclusionOur preliminary results suggest that the use of Rituximab might be effective in B-ALL though both signaling pathways.