MicroRNAs (miRNAs) in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer in the world and third leading cause of cancer-related deaths in men and women as well. While early screening procedures and removal of small polyps improve the survival rates among the patients, there is still need for new diagnostic and therapeutic approaches for developing more effective treatments. MicroRNAs (miRNAs) are short noncoding RNA fragments, which involve in posttranscriptional regulation of gene expression, and they are shown to involve in tumorigenesis either targeting oncogenes or tumor suppressor genes. Based on the current studies, miRNAs are now suggested as potential biomarkers for CRC diagnosis, prognosis, and therapeutic responses. In this chapter, the latest findings on the role of miRNA in CRC in many aspects are reviewed: diagnosis (role of circular miRNAs in blood and miRNAs from tissue biopsies and their potential role in pathophysiology and diagnosis of CRC), prognosis (miRNAs related with metastasis, recurrence, and survival rates in CRC), and therapeutic responses (role of miRNAs both in chemotherapies and/or in targeted therapies in CRC). In conclusion, miRNAs are promising molecules for diagnosis, prognosis, and therapeutic responses of CRC

ST sequence miner: visualization and mining of spatio-temporal event sequences

As a promising field of research, event sequence analysis seems to assist in facilitating clear reasoning behind human decisions by mining reality behind the sequential actions. Mining frequent patterns from event sequences has proved to be promising in extracting actionable insights, which plays an important role in many application domains. Much of the related work challenges the problem solely from the temporal perspective omitting the information that could be gained from the spatial part. This could be in part due to the fact that analysis of event sequences with references to both time and space is attributed as a challenging task due to the additional variance in the data introduced by the spatial aspect. We propose a visual analytics approach that incorporates spatio-temporal pattern extraction leveraging an extended sequential pattern mining algorithm and a pattern discovery guidance mechanism operating on geographic query and selection capabilities. As an implementation of our approach, we introduce a visual analytics tool, namely ST Sequence Miner, enabling event pattern exploration in time-location space. We evaluate our approach over a credit card transaction dataset by adopting case study methodology. Our study unveils that patterns mined from event sequences can better explain possible relationships with proper visualization of time-location data

Production of Zinc Borate for Pilot-Scale Equipment and Effects of Reaction Conditions on Yield

In this study, zinc borate (ZB) was synthesized by reacting zinc oxide and boric acid in the presence of standard ZB (w/w, in terms of boric acid) in order to promote crystallization. The effects of seed, H₃BO₃/ZnO (boric acid/zinc oxide) ratio, reaction time, water volume, reaction temperature and cooling temperature on yield were investigated for pilot-scale equipment. The results indicated that the addition of seed (w/w) to a saturated solution of reactants increased the yield of the reaction. The results of reaction yields obtained from either magnetically or mechanically stirred systems were compared. At various reaction times, the optimal yield was 86.78 % in a saturated aqueous solution. The products were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and Thermogravimetric/Differential Thermal Analysis (TG/DTA). The results displayed that ZB was successfully produced under the optimized reaction conditions and the product synthesized had high thermal stability.<p>DOI: <a href="http://dx.doi.org/10.5755/j01.ms.19.2.4432">http://dx.doi.org/10.5755/j01.ms.19.2.4432</a></p

Clinical, Electrodiagnostic, and Genetic Features of Tangier Disease in an Adolescent Girl with Presentation of Peripheral Neuropathy

WOS: 000365348100010PubMed ID: 26479764Tangier disease (TD) is a rare, autosomal recessive inherited disorder caused by a mutation in the adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene, which results in a decrease in plasma high-density lipoprotein (HDL) levels. Peripheral neuropathy can be seen in approximately 50% of patients with TD, which usually occurs after the age of 15 years, and is characterized by relapsing-remitting mono-or polyneuropathy or syringomyelia-like neuropathy. Herein, we report a 16-year-old female patient who was initially diagnosed with peripheral neuropathy at the age of 13 years. Whole exome sequencing was performed, and a nonsense mutation (p.Arg1817X) in ABCA1 was identified. The patient was investigated for systemic findings of TD after the genetic diagnosis was made, and low (<5 mg/dL) levels of HDL cholesterol were detected by lipid electrophoresis. Other family members were reexamined after the diagnosis of the proband, and asymptomatic sister of the proband was diagnosed with TD. We would like to emphasize that TD should be considered in the differential diagnosis of pediatric patients presenting with peripheral neuropathy; furthermore detection of HDL levels by lipid electrophoresis is a simple but indicative diagnostic test

Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome

ABSTRACT Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. Methods: The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. Results: The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion: Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome

Suppression of STAT5A increases chemotherapeutic sensitivity in imatinib-resistant and imatinib-sensitive K562 cells

WOS: 000282895200021PubMed ID: 20849385STAT proteins are cytoplasmic transcription factors that are involved in the regulation of numerous cellular activities such as cell growth, differentiation, and survival. In this study, we aimed to identify the expression pattern of STAT genes in imatinib-sensitive and -resistant K562 cells, and further, to reveal the effects of STAT5A siRNA knockdown on cell growth and apoptosis induction. The XTT cell proliferation assay showed that both sensitive and resistant K562 cells were sensitized to imatinib upon transfection with STAT5A siRNA. Caspase-3 enzyme activity was increased significantly in both cells. These results may open up new opportunities to overcome chemotherapeutic resistance in leukemia.The Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Turkish Society of Hematology [TUBITAK 105S459, THD 200-02/08]This work was supported by The Scientific and Technological Research Council of Turkey and by the Turkish Society of Hematology (TUBITAK 105S459 and THD 200-02/08, respectively, to BK)

Clinical, Electrodiagnostic, and Genetic Features of Tangier Disease in an Adolescent Girl with Presentation of Peripheral Neuropathy

Tangier disease (TD) is a rare, autosomal recessive inherited disorder caused by a mutation in the adenosine triphosphate-binding cassette transporter 1 (ABCA1) gene, which results in a decrease in plasma high-density lipoprotein (HDL) levels. Peripheral neuropathy can be seen in approximately 50% of patients with TD, which usually occurs after the age of 15 years, and is characterized by relapsing-remitting mono-or polyneuropathy or syringomyelia-like neuropathy. Herein, we report a 16-year-old female patient who was initially diagnosed with peripheral neuropathy at the age of 13 years. Whole exome sequencing was performed, and a nonsense mutation (p.Arg1817X) in ABCA1 was identified. The patient was investigated for systemic findings of TD after the genetic diagnosis was made, and low (<5 mg/dL) levels of HDL cholesterol were detected by lipid electrophoresis. Other family members were reexamined after the diagnosis of the proband, and asymptomatic sister of the proband was diagnosed with TD. We would like to emphasize that TD should be considered in the differential diagnosis of pediatric patients presenting with peripheral neuropathy; furthermore detection of HDL levels by lipid electrophoresis is a simple but indicative diagnostic test

Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome

Purpose: Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome.Methods:The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference.Results:The mean ages of the patients in pseudoexfoliation and control groups were 71.7 +/- 7.1 and 67.4 +/- 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Conclusion:Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome

STAT pathway in the regulation of zoledronic acid-induced apoptosis in chronic myeloid leukemia cells

WOS: 000324098000012PubMed ID: 23725755In this study, we aimed to evaluate the cytotoxic and apoptotic effects of zoledronic acid on K562 chronic myeloid leukemia (CML) cells and to examine the roles of STAT genes on zoledronic acid-induced apoptosis. The results showed that zoledronic acid decreased proliferation, and induced apoptosis in K562 cells in a dose- and time-dependent manner. mRNA and protein levels of STAT3, -5A and -5B genes were significantly reduced in zoledronic acid-treated K562 cells. These data indicated that STAT inhibition by zoledronic acid may be therapeutic in CML patients following the confirmation with clinical studies. (C) 2013 Elsevier Masson SAS. All rights reserved

A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP

The fat mass and obesity associated (FTO) gene has previously been associated with a variety of diseases and conditions, notably obesity, acute coronary syndrome and metabolic syndrome. Reports describing mutations in FTO as well as in FTO animal models have further demonstrated a role for FTO in the development of the brain and other organs. Here, we describe a patient born of consanguineous union who presented with microcephaly, developmental delay, behavioral abnormalities, dysmorphic facial features, hypotonia and other various phenotypic abnormalities. Whole-exome sequencing revealed a novel homozygous missense mutation in FTO and a nonsense mutation in the cholesteryl ester transfer protein (CETP). Exome copy number variation analysis revealed no disease-causing large duplications or deletions within coding regions. Patient's, her parents' and non-related control' fibroblasts were analyzed for morphologic defects, abnormal proliferation, apoptosis and transcriptome profile. We have shown that FTO is located in the nucleus of cells from each tested sample. Western blot analysis demonstrated no changes in patient FTO. Quantitative (qPCR) analysis revealed slightly decreased levels of FTO expression in patient cells compared with controls. No morphological or proliferation differences between the patient and control fibroblasts were observed. There is still much to be learned about the molecular mechanisms by which mutations in FTO contribute to such severe phenotypes