Anti-cancer effects and mechanism of actions of aspirin-like drugs in the treatment of gliomas

In the past two decades only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action. Aspirin is one of the most widely used drugs, successfully taken as an analgesic, antipyretic, anti-inflammatory agent and for prevention of strokes and ischemic diseases. The effects on cell viability, proliferation, apoptosis and migration of aspirin and aspirin derivatives were tested on primary glioblastoma cell cultures, BTNW911 and BTNW 914, and the well-established cell lines, SVG-p12, 1321N1, GOS-3, U87 MG, using the PrestoBlue assay, CFDA-SE, PI/annexin V, and live imaging receptively. The effects on cell viability following 24 and 48 hour incubation of four aspirin derivatives (PN508, PN517, PN526 and PN529) were compared to cisplatin, aspirin and di-aspirin, establishing IC50 values, showing PN517 to be the most potent analogue, and in some cases greater efficacy than cisplatin. Aspirin analogues showed greatest efficacy in the first 24 hours, while cisplatin increased in efficacy with time showing a lower IC50 value in all cell lines at 48 hours. Cell proliferation was assessed over 3 to 10 days, with each treatment decreasing proliferation and the largest effect of PN517 found in BTNW914 cells. PN517 treatment decreased the population of G0/G1 phase cells in cell cycle analysis, decreased cyclin D1 and EGFR activation, and total EGFR expression. Apoptosis was induced by PN517 in a concentration and time dependent manner in both the cell lines and short term cultures, with activation of both intrinsic and extrinsic pathways. Finally, PN517 reduced migration in both the Boyden chamber and scratch assays, but did not inhibit invasion. In conclusion, these data support the further development of PN517 as a novel therapeutic drug for the treatment of glioma

The role of morpho-phonological salience in tense marking: a comparison between Greek and Cypriot-Greek SLI children*

The current study investigates past formation in Standard Greek (SG) and Cypriot Greek (CYG) measuring the associated morphophonological salience and its effects on SLI grammars. Elicited production of real and pseudo verbs was carried out with SLI and TD groups from each variety. Results show that phonological salience of past formation affects SLI but not TD performance. Between varieties, the GR/SLI group performs better than CYG/SLI group with real verbs. We attribute this finding to the difference in the status of the augment in each variety

Investigating Use of a Parent Report Tool to Measure Vocabulary Development in Deaf Greek-speaking Children with Cochlear Implants

Objective: There are very few measures of language development in spoken Greek that can be used with young deaf children. This study investigated the use of Cyprus Lexical List (CYLEX), a receptive and expressive vocabulary assessment based on parent report that has recently been adapted to Standard Greek, to measure the vocabulary development of deaf Greek-speaking children with cochlear implants. Design: A Standard Greek version of CYLEX was used to collect data on receptive and expressive vocabulary development from parents of thirteen deaf children with cochlear implants aged between 21 and 71 months. These data were compared with data collected previously from typically developing hearing Greek-speaking children. Results: Use of the test by parents of deaf children was found to be reliable. No correlation was found between children's vocabulary scores and chronological age. A positive correlation was however found between children's post-implant age and expressive vocabulary. The vocabulary skills of implanted children with a mean post-implant age of 20 months were not significantly different from those of typically developing hearing children of similar chronological age. Conclusion: CYLEX is a reliable and useful tool for exploring vocabulary development with this clinical group. Findings confirm the results of other studies in indicating that the vocabulary size of implanted pre-school-aged deaf children is related to the amount of time that children have used their implant, rather than chronological age

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Promoting Speech Intelligibility in Autism Spectrum Disorder through the Implementation of Phonologically Similar Stimuli

Objectives: The study focused on promoting expressive phonological skills in 1 Greek-speaking child with autism spectrum disorder (ASD) and comorbid speech sound disorder (SSD). Based on the phonological neighborhood density framework, it was hypothesized that the experimental manipulation through clinical implementation of phonologically overlapping stimuli would yield positive expressive phonology gains relevant to ASD. Participant and Methods: A multiple-baseline single-subject design was implemented. Three baseline sessions measured expressive phonology variables. Sixteen biweekly 30-min intervention sessions were carried out for a period of 2 months. Dependent variables included phonetic inventory size, proportion of consonants correct, occurrences of phonological processes, and percentage of whole word matches elicited via specific word probe stimuli. The Intelligibility in Context Scale was completed by the child’s teacher prior to the initiation of intervention and at a follow-up session. Experimental stimuli were grouped together in phonologically dense cohorts. Results: Comparison between pre-test and post-test measures revealed expressive phonology gains across all measured variables. Follow-up session results showed generalization of expressive phonology gains on untreated targets. Conclusions: Significant expressive phonology gains were achieved through the implementation of phonologically similar word stimuli within a systematic intervention protocol with the implementation of specific word-level variables. The findings supported this treatment approach for a child with ASD and SSD, while providing evidence for the phonological density advantage from a cross-linguistic perspective