Delta-Tocotrienol Downregulates Mmp-9 Expression In Nsclc Cells

Lung cancer is the leading cause of cancer death in Unites States. The main types of lung cancer are small cell lung cancer and non small cell lung cancer. NSCLC accounts for about 80% of the cases with less than 15% of patients surviving beyond 5 years. Most common causes of lung cancer are smoking, inhaling asbestos fiber, radon gas, passive smoking, air pollution, familial predisposition, prior history of lung cancer etc. Surgery, chemotherapy, targeted therapy, palliative care are commonly used treatment techniques for lung cancer. Radiation therapy is an important part of lung cancer management. The objective of this study was to investigate if δ-tocotrienol which is an isoform of essential nutrient vitamin E can be successfully used in the treatment of NSCLC. The effect of pure δ-tocotrienol was studied on NSCLC cell lines A549 and H1299. Previously it was proved that Notch-1 pathway could be a therapeutic target for NSCLC and also that pure δ-tocotrienol down regulates Notch-1 via NF -КB. This study mainly focuses on MMP-9 and uPA expression in the NSCLC cell lines via Notch-1 and HES-1. Aggregation and adhesion capability, invasive and migration ability, MMP-9 activity and molecular mechanisms like gene expression and protein expression were evaluated. Different assays like cell aggregation assay, cell adhesion assay, cell invasion assay, wound healing assay, zymogram gel assay, Real-Time PCR analysis, Western Blot analysis were performed for this purpose. A dose dependent decrease was observed in MMP-9 activity confirming its inhibition. Since there is inhibition in cell aggregation, adhesion, invasion, migration, gene and protein expressions, the study suggests that administration with pure δ-tocotrienol could be an effective approach for the treatment of NSCLC

Meeting the Federal Mandates: Research on Effective Reading Instructional Programs and Implications for Classroom Teachers

Both the No Child Left Behind (NCLB) mandate (2001) and the Individuals with Disabilities Education Improvement Act (IDEA) (2004), call for use of scientifically validated reading instructional practices, curricula, and accountability for successful learning outcomes. This paper highlights one of the reading programs identified as scientifically validated by independent research groups and discusses its implications for classroom teachers. On the other hand, we do not embrace the idea that other reading programs are ineffective. We believe that there is no one single method or program to teach all children effectively. However, we believe that use of programs that have been demonstrated as effective through research may reduce the number of children who are atrisk of failing to read competently

Observer recall bias in radiology comparative diagnostic test accuracy research: Systematic review

A review exploring current strategies in reducing observer recall bias in diagnostic test accuracy research comparing different modalities

Preventing Summer Reading Slide: Examining the Effects of Two Computer-Assisted Reading Programs

Students who display reading difficulties/disabilities at the end of third grade are less likely to succeed in content areas and graduate from high school than their reading-proficient peers. Literature suggests that students in rural school districts lag behind their suburban peers in terms of their reading levels and accessibility to resources. Furthermore, students from low socioeconomic status (SES) households and those who have disabilities exhibit greater learning loss during the summer break. This exploratory study examined the effects of two parent-implemented computer-based reading programs on the reading skills of 20 students at-risk for reading failure during a summer break. Parental and students’ perceptions regarding the effectiveness and desirability of the programs were elicited. Results suggested that both programs facilitated gains in phonemic awareness and phonics. Furthermore, students in the Funnix group exhibited large gains in vocabulary and oral reading fluency, and the students in the PLATO group exhibited large gains in comprehension. Most of the students indicated they liked the programs and the programs helped them read. Similarly, most of the parents agreed that the programs were useful, and they were comfortable using the programs. A description of the computer programs, results, implications, and limitations of the study are discussed

Delta-tocotrienol inhibits non-small-cell lung cancer cell invasion via the inhibition of NF-κB, uPA activator, and MMP-9

Lichchavi D Rajasinghe, Rohini H Pindiprolu, Smiti Vaid Gupta Department of Nutrition and Food Science, Wayne State University, Detroit, MI, USA Background: Delta-tocotrienol (δT), an isomer of vitamin E, exhibits anticancer properties in different cancer types including non-small-cell lung cancer (NSCLC). Yet, anti-invasive effects of δT and its underlying cellular mechanism in NSCLC have not been fully explored. Matrix metalloproteinase 9 (MMP-9)-based cell migration and invasion are critical cellular mechanisms in cancer development. The current evidence indicates that MMP-9 is upregulated in most patients, and the inhibition of MMPs is involved in decreasing invasion and metastasis in NSCLC. Therefore, its suppression is a promising strategy for attenuating cell invasion and metastasis processes in NSCLC. Purpose: The aim of this study was to evaluate the possibility of MMP-9 inhibition as the underlying mechanism behind the antimetastatic properties of δT on NSCLC cells. Methods: The effects of δT on cell proliferation, migration, invasion, adhesion, and aggregation capabilities were investigated using different cell-based assays. An inhibitory effect of MMP-9 enzyme activity with δT was also identified using gel zymography. Using real-time PCR and Western blot analysis, a number of cellular proteins, regulatory genes, and miRNA involved in the Notch-1 and urokinase-type plasminogen activator (uPA)-mediated MMP-9 pathways were examined. Results: The study found that δT inhibited cell proliferation, cell migration, invasion, aggregation, and adhesion in a concentration-dependent manner and reduced MMP-9 activities. Real-time PCR and Western blot analysis data revealed that δT increased miR-451 expressions and downregulated Notch-1-mediated nuclear factor-κB (NF-κB), which led to the repressed expression of MMP-9 and uPA proteins. Conclusion: δT attenuated tumor invasion and metastasis by the repression of MMP-9/uPA via downregulation of Notch-1 and NF-κB pathways and upregulation of miR-451. The data suggest that δT may have potential therapeutic benefit against NSCLC metastasis. Keywords: metalloproteinases, miR-451, lung cancer, A549, H1299, metastasis, cell migration, vitamin

Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles

Oxaliplatin is one of the chemotherapeutic agents in the first line therapy for treatment of colorectal cancer. But, limitations of chemotherapy affects the clinical applicability of oxaliplatin depriving its activity at targeted site attributed to the lack of site specificity. This limitation paves the way for undesirable toxic effects to healthy cells resulting in sub-standard drug amount at the tumors obliging for increased dose. The present study emphasizes on formulating gold nanoparticles encapsulating oxaliplatin and later conjugating with anti-DR5 antibody for improved anti-cancer activity in a synergistic and site-specific manner. Oxaliplatin immuno-nanoparticles (Co-Ox-AuNPs) had shown sustained release and confirmed by fluorescence and flow cytometry studies. MTT assay exhibited 3-fold decrease in cell viability of nanoparticles comparable to oxaliplatin. Triple fluorescence method employed in HCT 116 and MCF-7 cells justified its site specificity. Annexin-propidium iodide (PI) and Acridine orange-ethidium bromide assays further supported the apoptotic activity. Moreover, caspase-dependent molecular mechanism behind oxaliplatin induced anti-cancer activity was explored by western blot analysis. Reduction in tumor size and volume in xenograft tumor models justified its in vitro activity. Oxaliplatin side effects were analyzed in mice and were confirmed for their clinical efficacy highlighting our formulation as an alternative to chemotherapy

Using Web-Mediated Experiential Case-Based Instruction to Teach Functional Behavioral Assessment Skills

This article describes three Web-mediated experiential case strategies employed with preservice teachers to facilitate practice of functional behavioral assessment skills. A pre-posttest group experimental design was used to examine the effects of three case-based teaching tactics on students\u27 knowledge and application of information to conduct functional assessments. The results suggested that the three teaching tactics were equally effective in facilitating the application of functional behavioral assessment skills. However, there were some differences in the students\u27 perceptions about the relevance and meaningfulness of their experiences as a means to teach functional assessment skills. Technology issues and other variables that could have influenced the results are discussed