Targeted delivery of a phosphopeptide prodrug inhibits the proliferation of a human glioma cell line

Peptides are ideal candidates for developing therapeutics. Polo-like kinase 1 is an important regulatory protein in the cell cycle and contains a C-terminal polo-box domain, which is the hallmark of this protein family. We developed a peptide inhibitor of polo-like kinase 1 that targets its polo-box domain. This new phosphopeptide, cRGDyK-S-S-CPLHSpT, preferentially penetrates the cancer cell membrane mediated by the integrin receptor, which is expressed at high levels by cancer cells. In the present study, using high performance liquid chromatography and mass spectroscopy, we determined the stability of cRGDyK-S-S-CPLHSpT and its cleavage by glutathione under typical conditions for cell culture. We further assessed the ability of the peptide to inhibit the proliferation of the U87MG glioma cell line. The phosphorylated peptide was stable, and the disulfide bond of cRGDyK-S-S-CPLHSpT was cleaved in 50 mM glutathione. This peptide inhibited the growth of cancer cells and changed their morphology. Therefore, we conclude that the phosphopeptide shows promise as a prodrug and has a high potential to act as an anticancer agent by inhibiting polo-like kinase 1 by binding its polo-box domain. These findings indicate the therapeutic potential of PLHSpT and peptides similarly targeted to surface receptors of cancer cells and to the functional domains of regulatory proteins.     

Sequence polymorphisms in ribosomal RNA genes and variations in chromosomal loci of Oenothera odorata and O. laciniata

Numerous studies on Oenothera species have been investigated for the physiological and ecological characteristics. However, no such an information based on molecular cytogenetic has yet been introduced, in turn, is very essential for identifying sequence polymorphisms of rRNA genes with their loci on mitotic phases for further biological researches. In this study, sequence variations of rRNA genes in Oenothera odorata and O. laciniata were examined to identify informative factors as unique or repeat sequences in intra- and inter-specific variations. Intra-specific variation revealed that the sequences of the rRNA genes including the spacer regions were highly conserved revealing only a few variations. From the inter-specific variation, spacer regions of species were completely different as (1) non-homologous sequences in NTS and (2) different type repeat sequences in ITS 1, 2 and 5.8S rRNA, whereas the remaining coding regions were highly conserved. FISH was carried out on mitotic phases using the 5S rDNA of the analyzed sequences. From the interphase and metaphase chromosomes of the examined species, two loci of 5S rDNA in O. odorata and four loci in O. laciniata were confirmed on the telomeric region of the short arm. Due to the small size and unclear centromere of the chromosomes, karyotype could not be completed. However, we confirmed that the chromosomes are organized by meta- and acrocentric chromosomes and the chromosomes with identified loci were assumed to be paired by the location of loci at the telomeric region on the short arm with relative lengths.     

Development and Validation of a Smartphone Addiction Scale (SAS)

Objective

The aim of this study was to develop a self-diagnostic scale that could distinguish smartphone addicts based on the Korean self-diagnostic program for Internet addiction (K-scale) and the smartphone''s own features. In addition, the reliability and validity of the smartphone addiction scale (SAS) was demonstrated.

Methods

A total of 197 participants were selected from Nov. 2011 to Jan. 2012 to accomplish a set of questionnaires, including SAS, K-scale, modified Kimberly Young Internet addiction test (Y-scale), visual analogue scale (VAS), and substance dependence and abuse diagnosis of DSM-IV. There were 64 males and 133 females, with ages ranging from 18 to 53 years (M = 26.06; SD = 5.96). Factor analysis, internal-consistency test, t-test, ANOVA, and correlation analysis were conducted to verify the reliability and validity of SAS.

Results

Based on the factor analysis results, the subscale “disturbance of reality testing” was removed, and six factors were left. The internal consistency and concurrent validity of SAS were verified (Cronbach''s alpha = 0.967). SAS and its subscales were significantly correlated with K-scale and Y-scale. The VAS of each factor also showed a significant correlation with each subscale. In addition, differences were found in the job (p<0.05), education (p<0.05), and self-reported smartphone addiction scores (p<0.001) in SAS.

Conclusions

This study developed the first scale of the smartphone addiction aspect of the diagnostic manual. This scale was proven to be relatively reliable and valid.     

Light Transmission and Preference of Eye Patches for Occlusion Treatment

Purpose

To investigate light transmission and preference for six eye patches for occlusion therapy.

Methods

Six patches were examined, including; Ortopad Fun Pack, Ortopad Flesh, Kawamoto A-1, Kawamoto A-2, 3M Opticlude, and Everade Eye Guard. The size and the presence of a light blocking pad of patches were investigated. The amount of light transmitted through the patches was evaluated, using a digital light meter and a model eye, in three different environments; indoors with fluorescent light, outdoors on a sunny day, and strong light from illuminator. After patching the normal eye, the flash visual evoked potential (VEP) was measured. Thirty patients with amblyopia or horizontal strabismus, who received occlusion therapy as initial treatment, were included. After using all six patches, patients completed a 7-item questionnaire regarding the patch preference for size, color and shape, adhesive power, pain with removal, skin irritation after removing patch, parent’s preference and overall opinion.

Results

All patches had a light-blocking pad, except the 3M Nexcare. Ortopad had the strongest light blocking power in the three environments, and the 3M Nexcare had the weakest power. In flash VEP, Ortopad and Kawamoto patches showed flat, but 3M Nexcare and Everade Eye Guard showed normal response. There were significant preferential differences among the patches in all the items of the questionnaire (P<0.05). In comparison between the patches respectively, 3M Nexcare received the lowest satisfaction in pain when removing a patch and skin irritation after removing a patch. Kawamoto A-2 received the lowest score in the overall satisfaction.

Conclusions

We found differences in the light-blocking power and in the preference of the various patches for the occlusion treatment. This is a pilot study regarding only characteristics and preferences of patches. Further clinical studies regarding the relationship between characteristics or preferences of patches and outcomes of occlusion treatment are needed.     

Competitive Advantage in Intercollegiate Athletics: Role of Intangible Resources

The present research explored the dynamics of competitive advantages in intercollegiate athletics by investigating the contribution of intangible resources (i.e., athletic and academic reputations) on the generation of more tangible resources (i.e., human and financial resources), which in turn influence the athletic performance (i.e., winning record) and academic performance (i.e., graduation rates), and gender equity. The research was based entirely on archival data of 324 NCAA Division I member institutions. The results of the SEM supported the study’s basic arguments that tangible resources are the sources of competitive advantages in Division I intercollegiate athletics, and that intangible resources contribute to the generation of tangible resources.     

TrkB Promotes Breast Cancer Metastasis via Suppression of Runx3 and Keap1 Expression

In metastatic breast cancer, the acquisition of malignant traits has been associated with the increased rate of cell growth and division, mobility, resistance to chemotherapy, and invasiveness. While screening for the key regulators of cancer metastasis, we observed that neurotrophin receptor TrkB is frequently overexpressed in breast cancer patients and breast cancer cell lines. Additionally, we demonstrate that TrkB expression and clinical breast tumor pathological phenotypes show significant correlation. Moreover, TrkB expression was significantly upregulated in basal-like, claudin-low, and metaplastic breast cancers from a published microarray database and in patients with triple-negative breast cancer, which is associated with a higher risk of invasive recurrence. Interestingly, we identified a new TrkB-regulated functional network that is important for the tumorigenicity and metastasis of breast cancer. We demonstrated that TrkB plays a key role in regulation of the tumor suppressors Runx3 and Keap1. A markedly increased expression of Runx3 and Keap1 was observed upon knockdown of TrkB, treatment with a TrkB inhibitor, and in TrkB kinase dead mutants. Additionally, the inhibition of PI3K/AKT activation significantly induced Runx3 and Keap1 expression. Furthermore, we showed that TrkB enhances metastatic potential and induces proliferation. These observations suggest that TrkB plays a key role in tumorigenicity and metastasis of breast cancer cells through suppression of Runx3 or Keap1 and that it is a promising target for future intervention strategies for preventing tumor metastasis and cancer chemoprevention.     

Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3

The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer.