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Objective: Dysregulated microRNA signatures in different cancer types are being uncovered continually implying their significance in cancer pathogenesis. miR-1267 was not previously associated with RCC. In this study, it is aimed to obtain the expression profile of miR-1267 in patients with ccRCC and its correlation with patient parameters. Methods: Kidney Cancer cDNA Array consisting of cDNA samples obtained from healthy kidney tissues of 4 healthy individuals and tumoral kidney tissues of 5 Stage I, 5 Stage II, 3 Stage III and 2 Stage IV ccRCC patients was used. Hsa-miR-1267 and SNORD48 (as housekeeping gene) expressions were analyzed. miR-1267 expression was statistically correlated with the clinical parameters of patients. miRGator 3.0 database was used to compare miR-1267 expression patterns of different urological cancer types. Results: The expression of miR-1267 was significantly higher in male than female (p=0.027). Also, there were statistically significant increase in miR-1267 expression in stage IV when compared to stage I (p0.05). Conclusion: miR-1267 could have oncogenic function, have predictive value for RCC development and be predictive about aggressiveness in ccRCC.

Gunes, Sezgin/0000-0002-3103-6482 WOS: 000465264700013 PubMed: 30862152 Background/aim: This study aimed to comparatively analyze the expression levels of the SLC1A1 gene in renal specimens from tumors and adjacent healthy kidney tissues of patients with clear cell renal cell carcinoma (ccRCC). Material and methods: Nineteen patients diagnosed with ccRCC were included in the study. The expression levels of the SLC1A1 and GAPDH genes were measured in tumor and fonnalin-fixed paraffin-embedded (FFPE) tissue specimens from the adjacent healthy kidney of each subject. Via the GEPIA database, the distribution of SLC1A1 gene expressions in ccRCC and healthy kidney tissues was obtained. The relative expression of SLC1A1 was evaluated for the association with the clinical parameters of the patients. Results: The expression of the SLC1A1 gene was significantly higher in males than females (P = 0.029). Also, there were statistically significant associations between stages II-IV and Fuhrman grades 2-4 with respect to SLC1A1 gene expression (P < 0.001 for both). Moreover, low levels of red blood cell and hemoglobin counts were significantly associated with the SLC1A1 expression (P < 0.001 and P = 0.005, respectively). The expression of the SLC1A1 gene in tumor tissues increased approximately 3 times compared with normal kidney tissues (P < 0.05). According to the GEPIA database, SLC1A1 gene expression is significantly higher in ccRCC patients than healthy persons (P = 0.01). Conclusion: The change in the expression of SLC1A1 may be crucial for ccRCC pathophysiology.

Tam Metin / Full Text Erkek infertilitesi heterojen ve multifaktöriyel etiyolojili bir bozukluktur. Son yıllarda yapılan bazı çalışmalar erkek infertilitesinin yalnızca sperm üretimindeki bir bozukluktan kaynaklanmadığı, bazı olgularda diyabet, kardiyovasküler hastalıklar ve kanser gibi sistemik bir bozukluğun bir parçası olabileceğini göstermektedir. Spermatogenez sürecindeki çok sayıdaki mitoz ve mayoz bölünmeler ve bazı çevresel faktörler, mutasyon/mutasyonlara neden olabilir ve kansere yol açabilir. Bu nedenlerle, erkek infertilitesi aslında kanser için bir erken belirteç olabilir. Bu derlemede erkek infertiltesi ve kanser arasındaki ortak genomik bulgular değerlendirildi. Male infertility is a highly heterogeneous disorder with multifactorial aetiology. Recent data have demonstrated that male infertility is not only an aberration in sperm production; however, infertility might be a part of various systemic diseases including diabetes, cardiovascular and cancer in some cases of infertility. High number of cell division by mitosis and meiosis during spermatogenesis and various environmental factors may lead to mutation/mutations result in cancer. Therefore, infertility might be an early marker for male infertility. This study reviews common genomic data regarding cancer and male infertility.

WOS: 000537582600001 PubMed: 32496656 There are many unknown aspects of the pathogenesis of renal cell carcinoma (RCC). The aim of the current study was to define new RCC-related genes and measure their associations with RCC and clinical parameters, especially platelet/lymphocyte ratio which may be an independent predictor of prognosis in patients with RCC and other forms of cancer. Via in silico analysis upon RCC-specific deleted genes in chromosome 3, four possible ceRNAs (ATXN3, ABI2, GOLGB1 and SMAD2) were identified. Then, the expression levels of these genes in tumour and adjacent healthy kidney tissues of 19 RCC patients were determined by real-time PCR. ATXN3 and GOLGB1 gene expression levels increased but ABI2 gene expression level decreased in tumour kidney tissues when compared to normal ones. ATXN3, ABI2 and GOLGB1 gene expression levels were significantly higher in Fuhrman grade 4 than other grades (P < .001). ABI2 gene expression levels were significantly associated with higher platelet/lymphocyte ratio of the patients with RCC (P < .05). ATXN3, ABI2 and GOLGB1 may predict higher RCC grades. Also, ABI2 may regulate platelet/lymphocyte ratio which may be an independent predictor of RCC and other forms of cancer. Scientific Research Projects Commission of Ondokuz Mayis UniversityOndokuz Mayis University [TIP.1904.18.002] This study has been financed by Scientific Research Projects Commission of Ondokuz Mayis University (project number: PYO. TIP.1904.18.002)

Standard cancer therapies for solid malignancies, such as chemotherapy and radiotherapy, are not target specific against cancer cells and are often not fully efficacious. Chemotherapy and radiotherapy may cause side effects, and the need to develop additional strategies for cancer treatment is urgent. MicroRNAs (miRNAs) are small non-coding RNAs with heterogeneous functions and have been described in almost every known cancer model. Besides their basic tumor-suppressive and oncogenic functions, they also have the potential to modulate chemotherapy and radiotherapy and to be manipulated with chemical compounds to make them chemically suitable for efficient delivery to cancer cells. It has been suggested that the level of expression of specific miRNAs could increase treatment efficacy by determining the stage of chemotherapy/radiotherapy sensitivity. Application of miRNAs alone or in combination with standard therapeutic strategies may significantly improve the success of cancer treatments in the future.

Objectives: The objective of this study is to define novel biomarkers for gastric neoplasm (GN) via in silico analysis that takes GN-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containing T-UCR among them and potentiates their relevance with GN. Based on this study we can plan new in vitro and in vivo studies. Methods: Four miRNAs of which clinical relevances with GN were proved experimentally were exported via mirTarbase. Using the ComiR database, 1008 genes targeted by these 4 miRNAs simultaneously were identified. Genes containing T-UCR and showing potential ceRNA activity were extracted. Among GN-associated ceRNAs including T-UCR, we identified genes with significant expression differences between GN and normal stomach tissue using the GEPIA database. The statistical evaluation of the association of NFAT5 and CLK3 genes with GN was performed by Spearman correlation test in GEPIA database. Results: GN-associated ceRNAs cross-matching with genes including T-UCR in their exonic regions were NFAT5 and CLK3. We identified genes with significant expression differences between GN and normal stomach tissues among GN-associated ceRNAs including T-UCR. According to this analysis, only NFAT5 gene was significantly higher expressed in GN than in normal stomach tissue while the other didn’t show any significant differential expression pattern. NFAT5 and CLK3 genes were found to be significantly correlated with GN (p

Gunes, Sezgin/0000-0002-3103-6482; us altay, diler/0000-0002-0465-8403; abur, ummet/0000-0002-4811-9321 WOS: 000495590600059 PubMed: 31342295 Truncated KIT (tr-KIT) is an alternative variant of c-KIT protein. Previous studies have clearly documented that c-KIT was associated with various oncogenic processes in RCC. However, the biological significance of tr-KIT in RCC development and progression remains unclear. So, it was aimed to investigate the possible association between RCC and tr-KIT which is thought to activate some oncogenic pathways. In this study, Kidney Cancer cDNA Array containing a total of 48 cDNA samples from the normal kidney tissues of 9 healthy subjects and kidney tumor tissues of 10 stage-1, 5 stage-2, 13 stage-3 and 11 stage-4 RCC patients was used for gene expression analysis. Real-Time PCR method was used to measure tr-KIT/c-KIT expression ratios. tr-KIT/c-KIT expression ratio was compared between tumor and normal samples, and statistically correlated with the clinical parameters of RCC patients. tr-KIT/c-KIT expression ratio was approximately 4-times higher in tumor samples than control ones (p = 0.001). Also, tr-KIT/c-KIT expression ratio was approximately two, three and six times higher in Fuhrman nuclear grades 2, 3 and 4 than normal, respectively (p = 0.009). Moreover, clear cell and papillary RCC has a significantly higher level of tr-KIT/c-KIT expression ratio than chromophobe RCC (p = 0.016). In the current study, it was stated for the first time that tr-KIT/c-KIT expression ratio was up-regulated in RCC tissues, and high tr-KIT/c-KIT expression ratio was correlated with more aggressive clinical features and poor patient prognosis. Our results suggest that increased tr-KIT/c-KIT expression ratio might be useful as a prognostic marker for RCC patients. Scientific & Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [118S162] This study was funded by The Scientific & Technological Research Council of Turkey (TUBITAK) (Grant No: 118S162).

Objective: The objective of this study is to define novel biomarkers for Prostate Cancer (PCa) via in silico analysis that takes PCa-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containing Transcribed Ultra Conserved Region (T-UCR) among them and potentiates their relevance with PCa. Methods: Thirty-four miRNAs of which clinical relevances with PCa were proved experimentally were exported via miRWalk database.Using the ComiR database, 859 genes targeted by these 34 miRNAs simultaneously were identified. Genes with ComiR score above 0.911 were taken into account. Genes containing T-UCR and showing potential ceRNA activity were extracted. Among PCa-associated ceRNAs including T-UCR, we identified genes with significant expression differences between PCa and normal prostate tissue using the GEPIA database. The statistical evaluation of the association of NFAT5 and PTBP2 genes with PCa was performed by Spearman correlation test in GEPIA database. Results: PCa-associated ceRNAs cross-matching with genes including T-UCR in their exonic regions were NFAT5, CLK3, PTBP2, CPEB4, MIPOL1 and TCF4. We identified genes with significant expression differences between PCa and normal prostate tissues among PCa-associated ceRNAs including T-UCR. According to this analysis, NFAT5 and PTBP2 genes were significantly less expressed in PCa than in normal prostate tissue while the others didn’t show any significant differential expression pattern. NFAT5 and PTBP2 genes were found to be significantly associated with PCa (p=0.000012; R=0.72). Conclusion: All in all, this is the study associating NFAT5 and PTBP2 genes with PCa and giving them tumor suppressive potential for PCa. Still, larger and more comprehensive studies are needed on this issue.

Background: Inhibitor of growth (ING) tumor suppressor gene family has been discovered over the past decade and five different genes have been identified from ING1 to ING5. They have some functions like cell transcription regulation, cell cycle control, DNA repair and apoptosis. Because of the fact that ING3 gene expression has not been studied in breast cancer so far, we aimed to determine whether there was a relationship between ING3 gene expression and breast cancer prognostic factors. Methods: 46 female breast cancer patients in different stages were enrolled to our study. ING3 gene expressions obtained from tumoral and healthy breast tissue samples of patients were evaluated together with pathological and histological parameters. Results: The median age of the patients was 49 years. ING3 expression rate has been significantly higher in the tumor tissue compared to normal tissue and was statistically significant (p=0.001). In estrogen receptor (ER) and progesterone receptor (PR) positive patients, gene expression ratio was significantly higher than negative ones (p 0.05). Conclusions: This study was the first study on ING3 gene expression in breast cancer. ING3 gene expression has been shown to be associated with the receptor positivity and advanced stage disease. Further studies should be conducted on the prognostic significance of ING3 gene in breast cancer. Citation Format: Kalender ME, Cakir M, Ergun S, Oztuzcu S, Cengiz B, Ulasli M, Sevinc A, Camci C. Expression and role of ING3 gene in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-08.

MicroRNAs (miRNAs) are important factors during tumorigenesis by affecting posttranscriptional gene expression. miRNA 204 (miR-204) is a miRNA frequently investigated in different types of cancers. According to literature, autophagy has dual roles in cancer, acting as both a tumor suppressor and cell survival agent. Also, the current data suggests that autophagy is activated in human colorectal cancer cells and enhances the aggressiveness of human colorectal cancer cells. So, our aim is to investigate potential effect of miR-204-5p on colorectal cancer by associating its expression with autophagy-related targets of miR-204-5p. This is the first miRNA study conducted on patients with colorectal cancer and healthy subjects and also to search the relation of miR-204-5p with clinicopathological factors and survival. Sixty-six patients with colorectal cancer and healthy subjects without any known chronic disease were enrolled into our study. Total miRNA was isolated from paraffin-embedded tissues of all patients' cancerous and normal tissues, and healthy subjects. cDNAs were obtained from this miRNAs by reverse transcriptase method, and miR-204-5p relative expression levels were detected by qRT-PCR method. Patients were divided into two groups according to median relative expression levels of miR-204-5p, as low- and high-expression group. Relation of miR-204-5p with clinicopathological factors and overall survival was also investigated. Medians of miR-204-5p relative expression levels in cancerous and normal tissues of patients were found as 0.00235 and 0.00376, respectively. The difference between two groups was not statistically significant (p = 0.11). Nonetheless, median of miR-204-5p relative expression levels in healthy subjects were found as 0.00135, and the difference between patient with cancer and healthy subjects and between normal tissues of patients and healthy subjects were statistically significant (p = 0.021 and p = 0.0005, respectively). There were 32 patients (48.5 %) showing high expression and 34 patients (51.5 %) showing low expression according to miR-204-5p relative expression levels. There were no statistically significant relation between clinicopathologic features and miR-204-5p relative expression levels. We also investigated the relation between miR-204-5p relative expression levels and overall survival, and no statistically significant relation was found between them (p = 0.462). The absence of any significant difference between tumor and non-tumor samples, low sample size, and performance at just one center are the limitations of our study. In opposition to literature, miR-204-5p is overexpressed in colorectal cancer patients as compared with healthy subjects and this situation is not associated with clinicopathological factors and overall survival. This may be explained by the fact that miR-204-5p increases in colorectal cancer cases in order to inhibit increased activity of LC3B-II in autophagy and Bcl2 against apoptosis posttranscriptionally and to take role as tumor suppressor.

Colorectal cancer (CRC) develops as a multi-step process which results from gradual accumulation of mutations in proto-oncogenes, tumor suppressor, and DNA repair genes. Mortality rate of CRC is very high. Therefore, development of alternative diagnostic methods which can be used in the early diagnosis is crucial. ATP2B4 gene encodes one of the four isoforms of p-type ATPase PMCA enzyme and bears critical importance in maintaining the balance of intracellular calcium homeostasis by providing the export of calcium ions out of the cell. ATP5B encodes a subunit of the mitochondrial ATP synthase which is an f-type ATPase. In this study, the relationship between ATP2B4 and ATP5B genes and CRC regarding gene expression was investigated. Study groups were constructed from a number of 50 patients (25 males, 25 females) with the mean age of 55.68 ± 9.4 and the gene expression levels in the healthy and cancerous tissues of the patients were compared by using semi-quantitative PCR and Real-Time PCR methods. As a result, in patients with rectum tumors, there was a significant relationship between ATP2B4 gene expression and the tumor location and in patients younger than 45 years, ATP5B gene expressions were detected significantly higher in tumor tissues by using RT-PCR. However, no significant relationship was detected in terms of expression differences of ATP2B4 and ATP5B genes between cancerous and healthy tissues of the CRC patients. ATP2B4 and ATP5B genes might have indirect associations in CRC pathogenesis and the investigation of their interactions with DNA repair and other related genes may help in understanding of CRC formation.

Background Urotensin-II (U-II) is a peptide recognized by its potent vasoconstrictor activity in many vascular events, however the role of urotensin-II in migraine has not been considered yet. The molecular mechanisms and genetics of migraine have not been fully clarified yet, but it is well-known that vascular changes considerably contribute in pathophysiology of migraine and also its complications. The aim of this study was to analyze the plasma U-II levels along with genotype distributions and allele frequencies for UTS2 Thr21Met and Ser89Asn polymorphisms among the patients with migraine without aura (MWoA). Methods One hundred eighty-six patients with MWoA and 171 healthy individuals were included in this study. Plasma U-II levels were measured in attack free period. The genotype and allele frequencies for the Thr21Met (T21M) and Ser89Asn (S89N) polymorphisms in the UTS2 gene were analyzed. Results Plasma U-II levels were significantly higher in MWoA patients (p = 0.002). We detected a significant association between the T21M polymorphism in the UTS2 gene and migraine (53.8 % in patients, 40.4 % in controls, p = 0.035), but not with S89N polymorphism (p = 0.620). A significant relationship was found between U-II levels and MIDAS score (β = 0.508, p = 0.001). Conclusion Our study suggests that U-II may play a role in migraine pathogenesis; also Thr21Met polymorphism was associated with the risk of migraine disease. Further studies are needed for considering the role of U-II in migraine pathophysiology and for deciding if UTS2 gene may be a novel candidate gene in migraine cases.

It is known that high-dose radiation has an effect on tissue healing, but tissue healing does not occur when low dose radiation is applied. To clarify this issue, we compare the treatment success of low dose radiation with programmed cell death mechanisms on wounded tissue. In this study, we aimed to investigate the interactions of low and high-dose radiation using an autophagic mechanism. We included 35 adult Wistar-Albino rats in this study. All animals were injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tips of 18-gauge needles were used to develop a superficial scratching on the left cheek pouch mucosa by dragging in a linear movement on third and fifth days. After mucositis formation was clinically detected, animals were divided into five groups (n = 7). Different wavelengths of laser irradiations (1064 nm, Fidelis Plus, Fotona, Slovenia; 980 nm, FOX laser, A.R.C., Germany; 810 nm, Fotona XD, Fotona, Slovenia; 660 nm, HELBO, Medizintechnik GmbH, Wels, Austria) were performed on four groups once daily for 4 days. The laser irradiation was not performed on the control group. To get the tissue from the left cheek at the end of fourth day from all animals, oval excisional biopsy was performed. Molecular analysis assessments of pathological and normal tissue taken were performed. For this purpose, the expression analysis of autophagy genes was performed. The results were evaluated by normalization and statistics analysis. We found that Ulk1, Beclin1, and Atg5 expression levels were increased in the rats when the Nd:YAG laser was applied. This increase showed that a 1064-nm laser is needed to activate the autophagic mechanism. However, in the diode applications, we found that Beclin1, Atg10, Atg5, and Atg7 expressions numerically decreased. Atg5 is responsible for the elongation of autophagosome. Becn1 is a control gene in the control mechanism of autophagy. The reduction of the expression of these genes leads us to think that it may depend on the effect of drug (5-FU) used to form model. Expressions of therapeutic genes increase to ensure hemostasis, but in our study, expressions were found to decrease. More detailed studies are needed.

Competing endogenous RNAs (ceRNAs) are RNA transcripts which can communicate with each other by decreasing targeting concentration of micro-RNA (miRNA) with the derepression of other messenger RNAs (mRNAs) having the common miRNA response elements (MREs). Oncocers are ceRNAs taking crucial roles in oncogenic pathways processed in many types of cancer, and this study analyzes oncocer-mediated cross-talk by sponging microRNAs (miRNAs) in these pathways. While doing this, breast, liver, colon, prostate, gastric, lung, endometrium, thyroid and epithelial cancers and melanoma, rhabdomyosarcoma, glioblastoma, acute promyelocytic leukemia, retinoblastoma, and neuroblastoma were analyzed with respect to ceRNA-based carcinogenesis. This study defines, firstly, oncocers in the literature and contains all oncocer-related findings found up to now. Therefore, it will help to increase our comprehension about oncocer-mediated mechanisms. Via this study, a novel perspective would be produced to make clear cancer mechanisms and suggest novel approaches to regulate ceRNA networks via miRNA competition for cancer therapeutics. Graphical Abstract Multiple RNA transcripts have common MREs for the similar miRNA in their 3'-untranslated regions (3'-UTRs). Upregulation of ceRNAs rises the abundance of specific MREs and shifts the miRNA pool distribution, as a result, leading to the increased expression of target mRNA. The depot of genomic mutations and epigenetic alterations changing gene function and expression causes cancers. Herewith, genome-based somatic base-pair mutations, DNA copy number alterations, chromosomal translocation, also transcript fusions, alternative splicing are usually seen in cancer situations. Consequently, such cases causing changed UTR expression in transcripts influence the levels of MRE or present new MREs into the cells. Alterations in MREs of ceRNAs affect the capability of a specific mRNA transcript to attach or titrate miRNAs. As a result, the disturbed ceRNA network can lead to diseases and cancers. As a new term in RNA world, oncocers-the name for ceRNAs taking crucial roles in oncogenic pathways-are processed in many types of cancer, and oncocer-mediated cross-talk are analyzed by sponging miRNAs in these pathways.

The most common malignancy in women is breast cancer. Drug resistance in the treatment of cancer still remains a major clinical concern. Resistance to tamoxifen is seen in half of the recurrences in breast cancer. The antiestrogen tamoxifen gains agonistic property by transactivating ER alpha. PAK1-mediated phosphorylation of serine 305 (S305) of ER alpha leads to resistance to tamoxifen. In our study, PAK1-induced suggestive tamoxifen resistance was designed. According to our hypothesis, phosphorylation of ER alpha-S305 by PAK1 may be reversed by PAK1 transcriptional inhibition by miR-221-3p due to miR-221-3p targeting the 3' UTR of PAK1. For this purpose, we used Real-time PCR (qRT-PCR) to measure the expression level of miR-221-3p in ER-positive breast cancer cell lines (ZR-75-1, MCF7) and breast epithelial cell line, hTERT-HME1, as control in the laboratory incur department. The increase in the expression of PAK1 depending on miR-221-3p may be related to ZR-75-1 cell line which has invasive characteristic but other two ER+ cancer cell lines, MCF7 and HCC1500, have milder cancer severity. miR-221-3p may have a role on regulation of PAK1 expression because miR-221-3p expression level decreases while PAK1 expression level increases in SKBR3 cell line. miR-221-3p and PAK1 expressions in MDA-MB-231 cell line are higher than that of hTERT-HME1 cell line. This may mean that miR-221-3p has no regulatory effect on of PAK1 expression in this cell line. According to these results, miR-221-3p may give crucial information about molecular mechanism of the disease upon PAK1 activity or different mechanisms with respect to histopathology and severity of breast cancer. (C) 2014 Elsevier B.V. All rights reserved.

Background and objective: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyper inflammatory disease. It is difficult to differentiate between primary and secondary HLH based on clinical findings at the onset of disease. We aimed to find parameters that can help to differentiate primary and secondary HLH at initial diagnosis especially for physicians working in developing countries.Patient and Method: We retrospectively analyzed data of 38 HLH patients who were admitted to the Pediatric Hematology Department of Gaziantep University between January 2009 and December 2013.Results: Of 38 patients, 20 were defined as primary and 18 were secondary HLH. The average age of primary and secondary HLH patients was 31±9 and 81±14 months, respectively (p=0.03). We found consanguinity rates significantly higher in primary HLH patients compared to secondary HLH patients (p=0.03). We found that total and direct bilirubin levels significantly increased in primary HLH patients compared to secondary HLH patients (p=0.006, p=0.044). Also, CRP levels were found markedly increased in secondary HLH patients compared to primary ones (p=0.017).Conclusion: We showed that cholestasis and hyperbilurubinemia findings of HLH patients at the initial diagnosis should be considered in favor of primary HLH and increased level of CRP should be considered in favor of secondary HLH.

Caspases are important initiators and most well-known finishers of apoptosis. By changing the death propagation homeostatic equilibrium, their different expression patterns might trigger the progression of hazardous diseases like cancer. miR-221 is an oncogenic miRNA. It is known to have both anti-angiogenic and angiogenic effect. The aim of this work was to compare the expression levels of miR-221 and its target caspase-3 in different cancer cell lines and to find out a relationship between these two. We also tried to establish a prominent relationship between miR-221 and its role in apoptosis by studying their expression levels. Our results indicate that expression of caspase-3 is quite lower as compared to miR-221 expression in all of the selected cancer cell lines. As a result, we conclude that miR-221 may have a crucial role in repressing the expression of caspase-3 which may contribute to a lower apoptotic rate, thus supporting the selection of more aggressive cancer cells. To our knowledge, this is the first study related to the expression levels of caspase-3 and miR-221 in different cell lines at the same time. We expect that our study might pave the way for better understanding the role of miR-221 in apoptotic regulation of caspase-3.

Beta (β)-thalassemia is the most frequently observed hereditary blood disorder in the world. It is characterized by deficiency of hemoglobin β-globin gene and is also a profoundly heterogeneous both at the molecular and clinical level. In the case of β-thalassemia, there is reduced (β+ type) or absent (βo type) synthesis of the beta chains of hemoglobin. β-Thalassemia clinically occurs in three main forms: major, intermedia and minor according to requirement of transfusion. The objective of this study was to evaluate β-thalassemia mutations in 89 patients ranging from 2 months to 16 years of age, who enrolled to Medical School Research and Training Hospital, Gaziantep University. The direct DNA sequence analysis was performed for mutation scanning of β-globin gene. 89 children with β-Thalassemia including all types were analyzed, 16 different β-thalassemia mutations were detected. We have also identified a novel mutation (HBB.c.-80delT, rs397509430) in the promoter region (−30 TATA box) of β-globin gene, and clinical data of patient having novel mutation was given. The β-Thalassemia mutations were determined as β-Thalassemia major type in 42 patients (47.19 %), β-Thalassemia intermedia in 4 (4.49 %), β-Thalassemia minor in 43, (48.31 %) patients. The most frequent mutation was IVS I-110 G>A, followed by IVS I-1 G>A, IVS I-6 T>C, IVS II-1 G>A, respectively.

HER2/ErbB2, a known proto-oncogene (also known as HER2, neu), is among the most practiced molecules in the cancer area. Human epidermal growth factor receptor 2 (HER2) is over expressed in approximately 20-30 % of breast cancer tumors and also in a lot of other human cancer types. It is known to be related to the aggressiveness of the disease, increased mortality and higher relapse ratio. The unusual HER2 overexpression is associated with more severe disease characteristics in several cancers. In recent past, there have been remarkable advances in understanding the role of the HER2 gene in cancers. Caspases are well renowned proteases that act as essential initiators and executioners of the apoptotic process. The primary function of HER2 is suppressing apoptosis to enhance cell survival and eventually giving rise to uncontrolled proliferation and tumor growth. The objective of this work was to study the expression levels of HER2 and apoptosis related factors CASP-3 and CASP-8 in several breast and other cancer cell lines and finally to find a meaningful correlation between all these. We summed up by obtaining an increase in expression of HER2 in all cancer cell lines as compared to that of CASP-3 and CASP-8. In summary we conclude that HER2 promotes cell survival by inhibiting apoptosis i.e. by downregulating CASP-3 and CASP-8. This is a novel study comprising the expression study of HER2 and different caspases in different cancer cell lines simultaneously. It is thus expected that this study will aid in better establishment of correlation between HER2 and caspases in different malignancies.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening hyper inflammatory disease. Micro RNAs (miRNA) are about 22 nucleotide-long, small RNAs encoded with genes, and they have regulatory functions in immune response. Objective: To determine the miRNA expression levels of 11 secondary HLH patients, we evaluated the associations of miRNA levels with pathogenesis, clinical presentation, and prognosis of the disease. Patients and Methods: Patients who were diagnosed with secondary HLH from January 2011 to December 2012 were included in this study. We profiled the expressions of 379 miRNAs in plasma of both HLH patients and healthy controls. Patients were evaluated regarding with age, clinical findings, miRNA expresions, laboratory data, treatment, and prognosis, by using descriptive statistics. Results: A total of 11 secondary HLH patients and 11 healthy children were included in this study. miR-205-5p was expressed in all case and controls and expression level of miR-205-5p was found 6.21 fold higher than control group (p=0.01). We detected the second highest expression percent in miR-194-5p with 81% of cases and controls. Expression level of miR-194-5p was found to have 163 fold higher than controls (p= 0.009). miR-30c-5p showed 77% expression percent in cases and controls together. The expression level of this miRNA was detected 9 fold decreased in HLH patients compared to healthy children (p= 0.031). Conclusion: We showed that miR-205-5p, miR-194-5p and miR-30c-5p could be useful plasma biomarkers for HLH. Further research is needed in larger and homogenous study groups, especially for these miRNAs as biomarkers for HLH.

MiRNAs are negative regulators of protein coding genes. Cancer cell survival, metastasis, differentiation and tumor progression have been regulated by a lot of miRNAs having very important functions. Recently, miR-122-5p was proved to play a tumor suppressor role in breast cancer. Apoptosis which takes a crucial act to conserve homeostasis in tissue is the most frequent type of cell death in multicellular living systems. Defects in the regulation of cell death via apoptosis have been associated with many disorders such as cancer. Previous studies suggest that trastuzumab, which shows its activity through its antibody characteristics affecting the immunological control of neoplastic HER2+ breast cancer cells, exhibits an anti-proliferative effect in HER2+ breast cancer cells by triggering caspase-dependent apoptosis. So, we aimed to analyze advancing of apoptosis by miR-122-5p in combination with trastuzumab in the SKBR3 (HER2+) cell line. For this purpose, we firstly transfected SKBR3 cells with miR-122-5p mimic, inhibitor and miRNA negative control for 48 hours. Afterwards, 0.5 µM trastuzumab was administered to miRNA transfected and non-transfected SKBR3 cells for 24 hours. AnnexinV and 7AAD emissions were detected in the FL1 and FL2 channels of a FACSCalibur flow cytometer (Becton-Dickinson, USA), respectively. The data were analyzed using CellQuest program from Becton-Dickinson. We revealed significantly more apoptotic cells upon miR-122-5p administration in combination with trastuzumab and also less apoptotic cells upon miR-122-5p interference with inhibitor miRNA in combination with trastuzumab. The number of apoptotis cells were 34.9 %, 38.9 %, 48.8 % and 27.7 % in trastuzumab, trastuzumab + miR-122-5p-NC, trastuzumab + miR-122-5p-mimic and trastuzumab + miR-122-5p-inhibitor administrations, respectively. All in all, the apoptosis advancing effect of miR-122-5p treatment in combination with trastuzumab may provide new therapeutic treatment choices for HER2+ breast cancer cases. Disclosure All authors have declared no conflicts of interest.