Risk factors for epilepsy following arterial ischemic stroke childhood: A retrospective cohort study.

AIM: PSE is reported more frequently in childhood than in adults. In this study, we aimed to investigate potential risk factors for the development of post-stroke epilepsy (PSE) in children with arterial ischemic stroke (AIS). MATERIAL METHODS: The current retrospective cohort study included the medical records of 50 pediatric participants (aged 29 days to 18 years) diagnosed with AIS at a university hospital between January 2006 and December 2023. All information of the patients who were followed for at least two years for the development of PSE after AIS was entered into the hospital database and recorded in a pre-designed questionnaire. Acute symptomatic seizures were defined as seizures occurring within 7 days after stroke. Two or more late seizures occurring after the acute period (>7 days) were classified as PSE. The incidence of PSE and potential risk factors were investigated. RESULTS: After AIS, more than half of the patients (58 %) developed acute seizures and almost one-third (38 %) developed PSE. Risk factors associated with the development of PSE, very early seizures (within the first six hours), high stroke severity, cortical lesions, neurological deficits and low serum vitamin D levels were detected (p = 0.05, p = 0.036, p = 0.011, p < 0.001, p < 0.001, respectively). CONCLUSION: Seizures within the first six hours, high stroke severity, and neurological deficits are important risk factors for the development of PSE in children. Knowing the potential risk factors of PSE may be helpful for clinicians to identify high-risk patients. It can also contribute to treatment decision-making and post-discharge follow-up planning.

Comprehensive analysis of splenic artery variations using computed tomography angiography: development of the IPALGEA classification system.

BACKGROUND: The splenic artery, an essential component of abdominal vascular anatomy, exhibits significant variations with clinical implications in surgical and radiological procedures. The lack of a standardized classification system for these variations hinders comparative studies and surgical planning. This study introduces the IPALGEA classification system, based on computed tomography angiography (CTA) findings, to address this gap. METHODS: A retrospective analysis was conducted on 302 patients who underwent CTA at a tertiary university hospital between August 2021 and January 2022. The study focused on the evaluation of splenic artery variations, including the origin, course, terminal branching patterns, and the relationship between the inferior polar artery and the left gastroepiploic artery. The IPALGEA classification was developed to standardize the reporting of these variations. RESULTS: The study highlighted a significant prevalence of splenic artery variations, with the most common pattern being a superior course relative to the pancreas. The IPALGEA classification effectively categorized these variations, emphasizing the relationship between the inferior polar artery and the left gastroepiploic artery. The findings revealed that the bifurcation distance of the celiac trunk varied significantly between genders and that the presence of an inferior polar artery correlated with a shorter hilus distance. CONCLUSION: The IPALGEA classification offers a comprehensive and standardized approach to categorize splenic artery variations. This system enhances our understanding of abdominal vascular anatomy and has significant implications for surgical and radiological procedures, potentially reducing surgical complications and improving patient outcomes.

The role of miR-223 in breast cancer; an integrated analysis.

BACKGROUND: Breast cancer (BRCA) is the most common and leading cause of cancer-related death in women. MicroRNAs (miRNAs) are short non-coding RNA fragments that play a role in regulating gene expression including the cancer-related pathways. Although dysregulation of miR-223 has been demonstrated in recent studies to have prognostic value in various cancers, its diagnostic and prognostic role in BRCA remains unknown. METHODS: The expression and the prognostic value of miR-223 were evaluated using the TCGA data and verified by qRT-PCR. Subsequently, potential oncogenic targets of miR-223 were identified by using three different miRNA target prediction tools and the GEPIA database. In addition to these databases, protein-protein interaction network, molecular functions, prognostic value, and the expression level of miR-223 targets were included by using several other bioinformatics tools and databases; such as, UALCAN, GeneMANIA and Metascape. RESULTS: The bioinformatic results demonstrated that miR-223 downregulated in BRCA and associated with poor prognosis of patients. In vitro experiments validated that miR-223 significantly downregulated in BRCA cells, MCF-7, SK-BR3, MDA-MB-231 and HCC1500, compared to normal breast cell line hTERT-HME1. Furthermore, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3 genes were identified as the potential oncogenic target genes of miR-223 based on their expression and prognosis in BRCA. Additionally, protein-protein interaction network of these target genes was mainly enriched in dynein intermediate chain binding, cell division, regulation of cell cycle process, and positive regulation of cellular component biogenesis. CONCLUSIONS: The results suggests that miR-223 and its targets, ANLN, DYNLT1, LRRC59, SLC12A8 and TPM3, might be reliable potential prognostic biomarkers in BRCA patients.

Sleep quality and depression in mothers of children with epilepsy and its relation to their children's sleep.

OBJECTIVE: This study aimed to evaluate the relationship between sleep disturbances in children with epilepsy (CWE) and maternal sleep quality and depression severity. METHODS: A Cross-sectional study was conducted in pediatric sleep disturbances using questionnaires on mother-reported sleep of CWE [Children's Sleep Habits Questionnaire (CSHQ)], maternal sleep quality [Pittsburgh Sleep Quality Index (PSQI)], and maternal depression status [Self-Rating Depression Scale (SDS)]. 114 dyads consisting of CWE and their mothers were included in this study. RESULTS: Over three-quarters (78.9 %) of mothers reported poor sleep quality (total PSQI score ≥ 5), and nearly a third (29.8 %) met clinical criteria for moderate or severe depression levels. The mothers' total PSQI scores were between 5.93 ±â€¯2.44 (range: 2-16 points). The most affected PSQI subcomponents were sleep latency (AUC = 0.826p < 0.001) and daytime dysfunction (AUC = 0.800p < 0.001). The majority of children (88.6 %) were stated by their mothers to have sleep-related problems. The total CSHQ scores of the children were between 49.06 ±â€¯9.20 (range: 33-86 points). The most affected CSHQ subcomponents were detected sleep anxiety (AUC = 0.856, p < 0.001), bedtime resistance (AUC = 0.818, p < 0.001) and daytime sleepiness (AUC = 0.807, p < 0.001). There was a statistically significant positive correlation between maternal sleep quality and depression severity (rho = 0.842; p < 0.001). A statistically significant positive moderate correlation was detected between sleep problems in CWE and maternal sleep quality and depression severity (rho = 0.406; p < 0.001, rho = 0.399; p < 0.001, respectively). As a result of multiple stepwise logistic regression analysis, the presence of seizures during sleep and generalized epileptiform discharges on electroencephalography were associated risk factors with poor maternal sleep quality (OR:6.6, p = 0.014; OR:11.5, p = 0.018, respectively). A borderline insignificant relationship was observed between a less than 50 % decrease in seizure frequency and the poor maternal sleep quality (OR:20.59p = 0.059). Seizures during sleep was associated risk factor with children's sleep disturbances (OR:7.2, p = 0.02). CONCLUSIONS: Sleep problems in CWE may lead to negative consequences such as sleep quality and/or depression in mothers. Interventions planned to correct sleep disturbances in mothers suggest that children's sleep problems should be optimally managed.

Prediction of Postcoronary Artery Bypass Grafting Atrial Fibrillation: POAFRiskScore Tool.

BACKGROUND: Atrial fibrillation (AF), a condition that might occur after a heart bypass procedure, has caused differing estimates of its occurrence and risk. The current study analyses the possible risk factors of post-coronary artery bypass grafting (post-CABG) AF (postoperative AF [POAF]) and presents a software for preoperative POAF risk prediction. METHODS: This retrospective research was performed on 1,667 patients who underwent CABG surgery using the hospital database. The associations between the variables of the patients and AF risk factors after CABG were examined using multivariable logistic regression (LR) after preprocessing the relevant data. The tool was designed to predict POAF risk using Shiny, an R package, to develop a web-based software. RESULTS: The overall proportion of post-CABG AF was 12.2%. According to the results of univariate tests, in terms of age (p < 0.001), blood urea nitrogen (p = 0.005), platelet (p < 0.001), triglyceride (p = 0.0026), presence of chronic obstructive pulmonary disease (COPD; p = 0.01), and presence of preoperative carotid artery stenosis (PCAS; p < 0.001), there were statistically significant differences between the POAF and non-POAF groups. Multivariable LR analysis disclosed the independent risk factors associated with POAF: PCAS (odds ratio [OR] = 2.360; p = 0.028), COPD (OR = 2.243; p = 0.015), body mass index (OR = 1.090; p = 0.006), age (OR = 1.054, p < 0.001), and platelet (OR = 0.994, p < 0.001). CONCLUSION: The experimental findings from the current research demonstrate that the suggested tool (POAFRiskScore v.1.0) can help clinicians predict POAF risk development in the preoperative period after validated on large sample(s) that can represent the related population(s). Simultaneously, since the updated versions of the proposed tool will be released periodically based on the increases in data dimensions with continuously added new samples and related factors, more robust predictions may be obtained in the subsequent stages of the current study in statistical and clinical terms.

miR-320a promotes p53-dependent apoptosis of prostate cancer cells by negatively regulating TP73-AS1 invitro.

TP73 antisense RNA 1 (TP73-AS1) is an oncogenic long non-coding RNA that is activated in several types of cancers. It has been shown that the activity of TP73-AS1 is controlled by several miRNAs, but post-transcriptional mechanisms that regulate TP73-AS1 activity in prostate cancer remain highly elusive. Accordingly, in the present study, we aimed to determine the miRNAs that are involved in the regulation of TP73-AS1 in prostate cancer and to show the effects of these molecules on the malignant proliferation of prostate cancer cells. Remarkably, colony formation and cell migration were suppressed while cell cycle arrest and apoptosis were induced in prostate cancer cells overexpressing miR-200a and miR-320a. miR-200a and miR-320a were found to be upregulated in TP73-AS1 suppressed prostate cancer cells. Also, TP73-AS1 was shown to be downregulated following miR-200a and miR-320a overexpression. However, overexpression of miR-320a had no significant effect on the expression of TP73. Further analysis revealed that miR-320a induces p53-dependent apoptosis. Consequently, our findings indicate that miR-320a induces p53-dependent apoptosis by negatively regulating TP73-AS1 long non-coding RNA.

Silencing of TP73-AS1 impairs prostate cancer cell proliferation and induces apoptosis via regulation of TP73.

BACKGROUND: Prostate cancer is a malignant disease that severely affects the health and comfort of the male population. The long non-coding RNA TP73-AS1 has been shown to be involved in the malignant transformation of various human cancers. However, whether TP73-AS1 contributes to prostate cancer progression has not been reported yet. Accordingly, here we aimed to report the role of TP73-AS1 in the development and progression of prostate cancer and determine its relationship with TP73. METHODS AND RESULTS: TP73-AS1-specific siRNA oligo duplexes were used to silence TP73-AS1 in DU-145 and PC-3 cells. Results indicated that TP73-AS1 was upregulated whereas TP73 was downregulated in prostate cancer cells compared to normal prostate cells and there was a negative correlation between them. Besides, loss of function experiments of TP73-AS1 in prostate cancer cells strongly induced cellular apoptosis, interfered with the cell cycle progression, and modulated related pro- and anti-apoptotic gene expression. Colony formation and migration capacities of TP73-AS1-silenced prostate cancer cells were also found to be dramatically reduced. CONCLUSIONS: Our findings provide novel evidence that suggests a chief regulatory role for the TP73-TP73-AS1 axis in prostate cancer development and progression, suggesting that the TP73/TP73-AS1 axis can be a promising diagnostic and therapeutic target for prostate cancer.

Comparison of posterior cranial fossa morphometric measurements in Chiari type I patients with and without syrinx cavity on magnetic resonance imaging.

Purpose: To compare the posterior fossa measurements of Chiari type I malformation (CHM1) patients with and without syrinx and with a control group. Material and methods: The patients with syrinx were divided into 2 groupd according to syrinx width/cord width (S/C) ratios: group 1 - S/C ratio < 50%; group 2 - S/C ratio > 50%. The length of the clivus, the AP length of the foramen magnum, the AP length of the posterior fossa, the perpendicular distance between the McRae line and (a) the splenium of corpus callosum, (b) the pons, and (c) the fastigium of the 160 patients and of the 160 control patients were statistically compared. In addition, the measurements of the patients with and without syrinx, according to the S/C ratio, were statistically compared. Results: Syrinx was present in 59 (36.8 %) of the 160 patients. The S/C ratio was < 50% in 30 (50.9 %) of them, and S/C ratio > 50% in 29 (49.1%) of them. All the measurements in the patient group, except of the AP length of the foramen magnum, were statistically significantly lower than in the control group (p = 0.001). There was no significant difference in the measurements of the patients with syrinx group 1 and the patients without syrinx, but the AP length of posterior fossa was statistically significantly lower in the patients with syrinx group 2 than the patients without syrinx (p = 0.03). Conclusion: The S/C ratio can be a guide to the underlying aetiology.

Identification and targeting of novel CDK9 complexes in acute myeloid leukemia.

Aberrant activation of mTOR signaling in acute myeloid leukemia (AML) results in a survival advantage that promotes the malignant phenotype. To improve our understanding of factors that contribute to mammalian target of rapamycin (mTOR) signaling activation and identify novel therapeutic targets, we searched for unique interactors of mTOR complexes through proteomics analyses. We identify cyclin dependent kinase 9 (CDK9) as a novel binding partner of the mTOR complex scaffold protein, mLST8. Our studies demonstrate that CDK9 is present in distinct mTOR-like (CTOR) complexes in the cytoplasm and nucleus. In the nucleus, CDK9 binds to RAPTOR and mLST8, forming CTORC1, to promote transcription of genes important for leukemogenesis. In the cytoplasm, CDK9 binds to RICTOR, SIN1, and mLST8, forming CTORC2, and controls messenger RNA (mRNA) translation through phosphorylation of LARP1 and rpS6. Pharmacological targeting of CTORC complexes results in suppression of growth of primitive human AML progenitors in vitro and elicits strong antileukemic responses in AML xenografts in vivo.

Prevalence and predictors of psychological response during immediate COVID-19 pandemic.

AIM: COVID-19 pandemic has created a serious psychological impact worldwide since it has been declared. This study aims to investigate the level of psychological impacts of the COVID-19 pandemic on the Turkish population and to determine related factors. METHODS: The study was carried out by an online questionnaire using the virtual snowball sampling method. The sociodemographic data were collected on the following subjects: participants' experience on any signs of infection within the last month, the history of COVID-19 contact-treatment-quarantine, level of compliance with precautionary measures, the sources of information and level of knowledge about the pandemic process and their belief levels on the knowledge they acquire. Besides, the questions that take place in the Depression, Anxiety and Stress Scale-21 (DASS-21), and Impact of Events Scale-Revised (IES-R) were asked to participants. RESULTS: Of the 3549 participants, anxiety was found in 15.8%, depression in 22.6%, stress in 12.9%, and psychological trauma in 20.29% based on moderate and above levels. Female gender, young age, higher education level, being single, high monthly income, presence of psychiatric illness, a large number of people living together, having any signs of infection, and contact history with COVID-19 infected person or contaminated object are identified as risk factors that may increase psychological impact. Compliance with the rules was found to reduce the risk of psychological response. CONCLUSIONS: The risk factors for the psychological impact of the COVID-19 pandemic, and acknowledging these factors can help to formulate the interventions to reduce the stress levels of the population.

Interchromosomal effect: Report of a father and son, bearing different translocations of the same chromosome, and a review of the current literature.

Interchromosomal effect is a controversial phenomenon postulating that during gametogenesis of translocation carriers, aside from the unbalanced segregation of chromosomes involved in the translocation, other, structurally normal chromosomes might also be affected and segregated abnormally. Here, we present a balanced reciprocal translocation carrier t(15;20)(q11;p13), and his son, bearing a different translocation of chromosome 15, t(15;Y)(q11;q12). To further elucidate the so-far-controversial interchromosomal effect phenomenon, published original articles and case reports about interchromosomal effect were reviewed. The father was a carrier of t(15;20)(q11;p13). His wife's karyotype was normal. During a pregnancy occurred without any preceding procedure, amniocentesis was recommended to the family and performed. Result of the amniocentesis revealed a different translocation of chromosome 15; t(15;Y)(q11;q12). To our knowledge, this is the first report of two generations within a family, bearing different translocations of a chromosome. On top of all previous studies investigating ICE, our case adds an important finding, showing not only the rate of aneuploidies of structurally normal chromosomes, but also the rate of this 'alternating translocations' might be increased in translocation carriers, and this could be an important clue about interchromosomal effects.

Next-generation screening of a panel of genes associated with periodic fever syndromes in patients with Familial Mediterranean Fever and their clinical characteristics.

Familial Mediterranean Fever (FMF) is a hereditary fever syndrome that primarily affects Mediterranean populations. For the study, total number of 182 patients with FMF disease were enrolled and screening of a panel of genes , called "fever panel" which comprises 17 genes, was performed. The most common mutations in MEFV gene were homozygous M694V missense mutation (4.3%) and R202Q missense mutation (4.9%). The most common heterozygous mutations were R202Q (26.5%), M694V (25.9%) and E148Q (11.9%). Compound heterozygous and homozygous mutations were also detected. Also, different types of mutations were identified in NOD2, CARD14, NLRP12, NLRP3, NLRP7, IL1RN, LPIN2, TNFRSF1A, MVK and PSTPIP1 genes. Two novel missense variations in the MEFV gene, Gln34Pro and Ile247Val, which have not been previously reported in the databases, were identified. Also, Thr91Ile missense variation in the NOD2 gene, Gly461Cys missense variation in NLRP3 and Tyr732Stop nonsense variation in LPIN2 were firstly identified. The results of the current study suggest that in addition to the MEFV gene which has an important roles in FMF, molecular screening of other genes related to other autoinflammatory diseases might provide support in suspected cases and provide detailed information about the course of the disease.

Long noncoding RNA ERICD interacts with ARID3A via E2F1 and regulates migration and proliferation of osteosarcoma cells.

Long noncoding RNA (lncRNA) dysregulation is known to be taking part in majority of cancers, including osteosarcoma. In one of our previous studies, we showed that lncRNA MEG3 is being regulated by microRNA-664a (miR-664a) suppresses the migratory potential of osteosarcoma cells (U-2OS). We now report a novel lncRNA, namely, ERICD, which is linked to the transcription factor AT-rich interaction domain 3A (ARID3A) in U-2OS cells. We show that ARID3A binds to ERICD and indirectly interacts with each other via the E2F transcription factor 1 (E2F1). Furthermore, small interfering RNA (siRNA)-mediated knockdown of ERICD inhibited cell migration, formation of colonies, and proliferation in U-2OS cells. Overexpression of ARID3A inhibited cell migration, colony formation, and proliferation, whereas siRNA-mediated knockdown of ARID3A promoted cell migration, colony formation, and proliferation. Our findings indicate that ARID3A and lncRNA ERICD have plausible tumor suppressive and oncogenic functions, respectively, in osteosarcoma. Our data demonstrate the converse interaction between ARID3A and lncRNA ERICD that target DNA-binding proteins and dysregulation of their expression through E2F1 augments osteosarcoma progression. The cell rescue experiment also indicated E2F1 to be involved in the regulation of ARID3A and ERICD.

Interferon γ (IFNγ) Signaling via Mechanistic Target of Rapamycin Complex 2 (mTORC2) and Regulatory Effects in the Generation of Type II Interferon Biological Responses.

We provide evidence for a unique pathway engaged by the type II IFN receptor, involving mTORC2/AKT-mediated downstream regulation of mTORC1 and effectors. These events are required for formation of the eukaryotic translation initiation factor 4F complex (eIF4F) and initiation of mRNA translation of type II interferon-stimulated genes. Our studies establish that Rictor is essential for the generation of type II IFN-dependent antiviral and antiproliferative responses and that it controls the generation of type II IFN-suppressive effects on normal and malignant hematopoiesis. Together, our findings establish a central role for mTORC2 in IFNγ signaling and type II IFN responses.

Inhibition of miR-664a interferes with the migration of osteosarcoma cells via modulation of MEG3.

Osteosarcoma is the most common primary bone tumor in children and adolescents. Understanding the basic molecular mechanisms in developing cancer can be helpful in developing alternative treatment strategies. The relationship between dysregulated non-coding RNAs' (ncRNA) expression level and osteosarcoma was detected. Among those ncRNAs, the expression levels of miR-664a were detected to be upregulated and MEG3 long non-coding RNA levels were detected to be downregulated in osteosarcoma tissue and cell lines. In this study, miR-664a inhibitor was used in order to investigate the changes in the expression levels of MEG3 gene and miR-664a in osteosarcoma cancer cell line (U2-OS) and human osteoblast cell line (hFOB 1.19). According to our results, the expression level of MEG3 gene was increased while the expression level of miR-664a was decreased, as expected. In addition, changes in expression level of MEG3 and miR-644a interferes with the migration of osteosarcoma cells migration speed of osteosarcoma cells. These results are found to be statistically significant (p < 0.05). As a result of this study, it was shown that the upregulated expression of miR-664a could have an inhibitory effect on MEG3 gene expression and migration of osteosarcoma cells.

Regulatory effects of SKAR in interferon α signaling and its role in the generation of type I IFN responses.

We provide evidence that S6 kinase 1 (S6K1) Aly/REF-like target (SKAR) is engaged in IFN-α signaling and plays a key role in the generation of IFN responses. Our data demonstrate that IFN-α induces phosphorylation of SKAR, which is mediated by either the p90 ribosomal protein S6 kinase (RSK) or p70 S6 kinase (S6K1), in a cell type-specific manner. This type I IFN-inducible phosphorylation of SKAR results in enhanced interaction with the eukaryotic initiation factor (eIF)4G and recruitment of activated RSK1 to 5' cap mRNA. Our studies also establish that SKAR is present in cap-binding CBP80 immune complexes and that this interaction is mediated by eIF4G. We demonstrate that inducible protein expression of key IFN-α-regulated protein products such as ISG15 and p21(WAF1/CIP1) requires SKAR activity. Importantly, our studies define a requirement for SKAR in the generation of IFN-α-dependent inhibitory effects on malignant hematopoietic progenitors from patients with chronic myeloid leukemia or myeloproliferative neoplasms. Taken altogether, these findings establish critical and essential roles for SKAR in the regulation of mRNA translation of IFN-sensitive genes and induction of IFN-α biological responses.

Critical roles for Rictor/Sin1 complexes in interferon-dependent gene transcription and generation of antiproliferative responses.

We provide evidence that type I IFN-induced STAT activation is diminished in cells with targeted disruption of the Rictor gene, whose protein product is a key element of mTOR complex 2. Our studies show that transient or stable knockdown of Rictor or Sin1 results in defects in activation of elements of the STAT pathway and reduced STAT-DNA binding complexes. This leads to decreased expression of several IFN-inducible genes that mediate important biological functions. Our studies also demonstrate that Rictor and Sin1 play essential roles in the generation of the suppressive effects of IFNα on malignant erythroid precursors from patients with myeloproliferative neoplasms. Altogether, these findings provide evidence for critical functions for Rictor/Sin1 complexes in type I IFN signaling and the generation of type I IFN antineoplastic responses.

The role of the UTS2 gene polymorphisms and plasma Urotensin-II levels in breast cancer.

Breast cancer is the most common malignancy predominantly affecting women. To date, numerous numbers of studies were reported novel genetic contributors with diagnostic, prognostic, and therapeutic potential for the breast carcinogenesis. However, the role of urotensin-II in breast carcinogenesis has not been elucidated yet. Urotensin-II is a somatostatin-like cyclic tiny peptide identified by its potent vasoconstrictor activity. Soon after its discovery, its involvement in many disease states as well as its expression in various tissues including the tumors have been demonstrated. Moreover, there is strong evidence that suggest urotensin-II as the significant contributor of angiogenesis as well as cell proliferation and tumor biology. In this study, enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism analysis were used to evaluate plasma levels of urotensin-II and Thr21Met and Ser89Asn polymorphisms of UTS2 gene in breast cancer patients. In the present case-control study, we noticed a significant decrease in the levels of urotensin-II protein in the plasma of the breast cancer patients (p < 0.05). Also, Thr21Met polymorphism in the UTS2 gene was associated with the risk of developing breast cancer (p < 0.0001), whereas the genotype frequency of Ser89Asn was found to be similar in patients and controls (p > 0.05). In addition, we demonstrated the gradual decreasing of urotensin-II protein levels from TT and TM to MM genotypes. In conclusion, these results strongly suggest that urotensin-II could contribute to breast carcinogenesis and Thr21Met polymorphism can be an important risk factor in developing breast tumors.

Loss of heterozygosity of chromosome 13q33-34 region and molecular analysis of ING1 and p53 genes in bladder carcinoma.

Cancer is a consequence of accumulation of genetic and epigenetic alterations in the cell which can lead to activation of oncogenes or inactivation of tumor suppressor genes (TSG). Since members of ING family were discovered as TSGs in different cancer types, it was aimed to analyze the chromosome 13q33-34 region, ING1 and p53 genes in bladder cancer. 30 paired normal and tumor tissues were investigated in terms of microdeletion of chromosome 13q33-34 region, ING1 expression and mutation status of ING1 and p53 genes. Because there is no data available about the transcription factors which bind to ING1 promoter, the promoter sequence was analyzed via Genomatix-MatInspector and TFSEARCH softwares. Used DS markers were D13S285, D13S1315, D13S796, D13S278, D13S158, and D13S779 where loss of heterozygosity (LOH) results were as 23.3, 20, 6.7, 3.3, 6.7, and 0 %, respectively. The highest LOH scores were obtained with markers D13S285 and D13S1315 which are flanking the ING1. Seven of 30 cases showed alteration in expression (p > 0.05). However, no mutation was detected in the exons of ING1. One patient showed a two-nucleotide deletion in p53 gene. However no significant TSG activity of ING1 was observed while higher activity was reported in different cancer types. As for the LOH data 13q33-34 region may contain different candidate TSGs like COL4A1, COL4A2 and SOX1. As a result of computational promoter analysis, some factors like ABL, E2F, HIF1, SOX, P53, BPTF, NRSF, c-Rel and c-ETS were associated with the promoter region. Molecular analysis of ING1 promoter warrants further analysis.

The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer.

MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.