Identification of SDPR as a metastasis suppressor in breast cancer

Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. While some progress has been made in the understanding of metastasis, the detailed molecular mechanisms that define the various stages of the process remain elusive. A major rate limiting step in metastasis is the loss of function of metastasis suppressor genes which block a cascade of crucial steps including the loss of adhesion of primary tumor cells, intravasation into the blood and lymphatics with subsequent extravasation at distant sites, and the formation of new colonies. Our examination of gene expression profiles from a breast cancer model system consisting of cell lines with the same genetic lineage representing the benign, carcinoma in situ and the metastatic stages led to the identification of a candidate metastasis suppressor gene, serum deprivation response (SDPR). We observed that stable SDPR over-expression in highly metastatic breast cancer model cell lines significantly suppressed metastatic nodule formation in NOD/SCID mice. Furthermore, meta-analysis of pre-existing gene expression data suggests that the loss of SDPR expression significantly correlated with relapse of breast cancer in patients who underwent therapy. We found that the mechanism of SDPR function involves activation of the p53 pathway and inhibition of ERK and NF-κB signaling pathways. SDPR increased the apoptotic population, hindered growth in 3D cell culture and impaired migration. Moreover, SDPR was suppressed by promoter DNA methylation in metastatic cell line models and its expression was restored by 5-aza-2'-deoxycytidine treatment. Together, our results reveal that SDPR is a novel metastasis suppressor gene with potential value as a target for future therapeutic applications

Morphological Changes of Anterior Cerebral Artery (ACA) in Hydrocephalic Pediatric Patients

How to Cite This Article: Ozturk S, Ayan E, Kaplan M. Morphological Changes of Anterior Cerebral (ACA) Artery in Hydrocephalic Pediatric Patients. Iran J Child Neurol. Winter 2017; 11(1):37-42. AbstractObjectiveThe morphology of anterior cerebral artery (ACA) in patients with hydrocephalus (HCP) was analyzed, and its importance was discussed in maintaining cerebral perfusion.Materials & MethodsA total of 84 cases in 2 groups between 0 and 3 months, followed-up at Firat Universitesi Hastanesi, Beyin Cerrahisi Klinigi, Elazig, Turkiye due to in 2010-2013, were enrolled. Two groups were created for the study. Group 1; patients with HCP and Group 2; as control group without HCP. In both groups, the length of the A2 segment of ACA was measured from its origin to the junction of the genu and body portions of the corpus callosum on T2 mid-sagittal magnetic resonance (MR) scans. For all cases, axial MR imaging scans were used to calculate Evans’ index (EI), and the cases were divided into three groups: Group A, EI ≥50%; Group B, EI of 40-50% and Group C, EI <40%. The two groups (Groups 1 and 2) were compared with respect to ACA length, and the correlation with the EI was quantified. P values below 0.05 were considered statistically significant.ResultsMean length of ACA was 57.3 mm in Group 1 and 37.5 mm in Group 2. EI increased as the length of ACA increased. A statistical comparison of the two groups revealed that the ACA length was significantly greater in Group 1. The relationship between EI and ACA length was statistically significant.ConclusionReducing ventricular size appears to be an important factor in addition to reducing intracranial pressure in an attempt to maintain normal cerebral perfusion(CP).References1. Westra SJ, Lazareff J, Curran JG, Sayre JW, Kawamoto H Jr. Transcranial Doppler ultrasonography to evaluate need for cerebrospinal fluid drainage in hydrocephalic children. J Ultrasound Med 1998; 17): 561-569.2. Kolarovszki B, Zubor P, Kolarovszka H, Benco M, Richterova R, Matasova K. The assessment of intracranial dynamics by transcranial Doppler sonography in perioperative period in paediatric hydrocephalus. Arch Gynecol Obstet 2013; 287: 229-238.3. Tritton DJ. Fluid Mechanics. Physical fluid Dynamics. Tritton, DJ: 2nd ed. Oxford, Clarendon Press 1988; pp:536-540.4. de Oliveira RS, Machado HR. Transcranial color-coded Doppler ultrasonography for evaluation of children with hydrocephalus. Neurosurg Focus 2003; 15: ECP3. 5. Kempley ST, Gamsu HR. Changes in cerebral artery blood flow velocity after intermittent cerebrospinal fluid drainage. Arch Dis Child 1993; 69: 74-76.6. Hanlo PW, Gooskens RH, Nijhuis IJ, Faber JA, Peters RJ, van Huffelen AC and et al. Value of transcranial Doppler indices in predicting raised ICP in infantile hydrocephalus. A study with review of the literature. Childs Nerv Syst 1995; 11: 595-603.7. Nishimaki S, Yoda H, Seki K, Kawakami T, Akamatsu H, Iwasaki Y. Cerebral blood flow velocities in the anterior cerebral arteries and basilar artery in hydrocephalus before and after treatment. Surg Neurol 1990; 34: 373- 377.8. Wang B, Cheng Z, Mu X, Fan B, Guo Z. Preoperative and postoperative transcranial Doppler sonographic evaluations of the cerebral hemodynamics of craniostenosis. J Craniofac Surg 2010; 21: 432-435.9. Bell SR, Vo AH, Armanda RA. Applied neurovascular anatomy of the brain and skull. In: Hurst RW, Rosenwasser RH, editors. Interventional Neuroradiology. New York: Informa; 2008: pp: 22-27.10. Kaplan M, Berilgen MS, Erol FS, Artas H, Serhatlioglu S, Ozveren MF. Relationship between Clinical Grade, Cerebral Blood Flow, and Electroencephalographic Alterations in Patients with Chronic Subdural Hemorrhage. Neurosurgery Q 2006; 16: 157-160.11. Riggo JD, Kolarovszki B, Richterova R, Kolarovszka H, Sutovsky J, Durdikc P. Measurement of the blood flow velocity in the pericallosal artery of children with hydrocephalus by transcranial Doppler ultrasonography-preliminary results. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2007; 151: 285-289.12. Zenger MN, Kabataş S, Zenger S, Cakmakçi H. The value of power Doppler ultrasonography in the differential diagnosis of intracranial extraaxial fluid collections. Diagn Interv Radiol. 2007; 13: 61-63.13. Kaplan M, Erol FS, Bozgeyik Z, Koparan M: The effectiveness of simple drainage technique in improvement of cerebral blood flow in patients with chronic subdural hemorrhage. Turk Neurosurg 2007; 17: 202-206.14. Rozenfeld A. Ultrasound in diagnostics of blood vessels: the role of the assessment of both extra- and intracranial flows by Doppler ultrasonography. Neurol Neurochir Pol 1994; 28: 51-66.15. Miller SP, Cozzio CC, Goldstein RB, Ferriero DM, Partridge JC, Vigneron DB and et al. Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings. AJNR Am J Neuroradiol 2003; 24: 1661-1669

Integrin Signaling in Mammary Epithelial Cells and Breast Cancer

Cells sense and respond to the extracellular matrix (ECM) by way of integrin receptors, which facilitate cell adhesion and intracellular signaling. Advances in understanding the mammary epithelial cell hierarchy are converging with new developments that reveal how integrins regulate the normal mammary gland. But in breast cancer, integrin signaling contributes to the development and progression of tumors. This paper highlights recent studies which examine the role of integrin signaling in mammary epithelial cells and their malignant counterparts

Intraday Price Discovery in Fragmented Markets

For many assets, trading is fragmented across multiple exchanges. Price discovery measures summarize the informativeness of trading on each venue for discovering the asset’s true underlying value. We explore intraday variation in price discovery using a structural model with time-varying parameters that can be estimated with state space techniques. An application to the Expedia stock demonstrates intraday variation, to the extent that the overall dominant trading venue (NASDAQ) does not lead the entire day. Spreads, the number of trades and volatility can explain almost half of the intraday variation in information shares

Why do Pit-Hours outlive the Pit?

__Abstract__ We study why a majority of trades still happen during the pit hours, i.e. when the trading pit is open, even after the pit ceased to be a liquid and informative venue. We investigate the case of 30-year U.S. Treasury futures using a ten-years-long intraday data set which contains the introduction of the CME Globex platform as an example of sophistication in electronic trading. We use a structural model to estimate the time-variation in potential factors of the clustering of trading activity around the pit hours, namely price informativeness, information asymmetry and price impact of trades. We find evidence for a feedback mechanism between trading activity and these factors. Across the sample period, price informativeness during the afterhours is a consistently significant factor attracting trade activity. Information asymmetry has a negative effect on afterhours act ivity, particularly during the crisis years. The negative effect of price impact on afterhours activity ceases to be a significant factor from 2007 on, possibly due to improvements in order execution algorithms and electronic trading facilities

Epicardial fat thickness and cardiovascular involvements.

No Abstrac

Ankle-brachial index in coronary artery disease

Ankle-brachial index in coronary artery diseas