Comparative effectiveness between two types of head-mounted magnification modes using a smartphone-based virtual display.

SIGNIFICANCE: This work shows the benefits of using two different magnification strategies to improve the reading ability of low-vision patients using a head-mounted technology. PURPOSE: The aim of this study was to conduct a comparative clinical trial evaluating the effectiveness of two magnification strategies in a head-mounted virtual reality display. METHODS: Eighty-eight eligible low-vision subjects were randomized into two arms: (1) the full-field magnification display or (2) the virtual bioptic telescope mode. Subjects completed baseline testing and received training on how to use the device properly and then took the device home for a 2- to 4-week intervention period. An adaptive rating scale questionnaire (Activity Inventory) was administered before and after the intervention (home trial) period to measure the effect of the system. A Simulator Sickness Questionnaire was also administered. Baseline and follow-up results were analyzed using Rasch analysis to assess overall effectiveness of each magnification mode for various functional domain categories. RESULTS: Both magnification modes showed a positive effect for reading, visual information, and the overall goals functional domain categories, with only reading reaching statistical significance after correction for multiple comparisons. However, there were no significant between-group differences between the two modes. The results of the Simulator Sickness Questionnaire showed that the magnification modes of the head-mounted display device were overall well tolerated among low-vision users. CONCLUSIONS: Both the full-field and virtual bioptic magnification strategies were effective in significantly improving functional vision outcomes for self-reported reading ability.

Knockdown of TFAP2E results in rapid G2/M transition in oral squamous cell carcinoma cells.

TFAP2E is a member of the activator protein-2 transcription factor family and acts as a tumor suppressor in several types of cancer. Downregulation of TFAP2E expression is significantly associated with a shorter overall survival period in patients with oral squamous cell carcinoma (OSCC). To evaluate the molecular mechanisms by which TFAP2E suppresses the development or progression of OSCC, the present study investigated the effects of TFAP2E downregulation on OSCC-derived Ca9-22 and HSC-4 cells. The present study demonstrated that small interfering RNA mediated-knockdown of TFAP2E accelerated the proliferation of these OSCC cell lines compared with that in the control group, as determined by the standard water-soluble tetrazolium salt-8 assay. To analyze the cell cycle progression rate, the cell cycle distribution patterns of TFAP2E-knockdown and control cells cultured in the presence of nocodazole, which prevents the completion of mitosis, were analyzed by fluorescence-activated cell sorting at different time points. When analyzing cellular DNA contents, no major differences in cell cycle profiles were observed; however, the rate of increase in cells positive for histone H3 Serine 28 phosphorylation, a standard molecular marker of early M phase, was significantly higher in TFAP2E-knockdown cells than in the control cells. Collectively, these results suggested that TFAP2E may attenuate the proliferation of OSCC cells by regulating G2/M transition.

Application of Rasch Analysis to Timed Instrumental Activities of Daily Living in Low Vision: A Validation Study.

SIGNIFICANCE: This work validates Rasch analysis of a performance-based low vision outcome measure evaluated in patients' own homes to ensure real-world relevance. Inclusion of sources of variance from the patient's home environment in functional outcome measures introduced nonuniform variance in measurements but did not preclude estimation of valid measures. PURPOSE: This study aimed to validate Rasch analysis of a performance-based outcome measure with real-world relevance. METHODS: Low vision patients (N = 161) receiving services from an occupational therapist performed Timed Instrumental Activity of Daily Living (TIADL) tasks in their homes. Rasch analysis was applied to error count and performance time data. Internal validity was assessed with evaluations of the accuracy and precision of estimated measures. External validity was assessed by comparing TIADL measures with measures estimated from the Activity Inventory (i.e., from self-reported difficulty ratings). RESULTS: Task measures were well targeted to person measures estimated from task performance time but were poorly targeted for measures estimated from task performance errors, for which most task trials (72%) were performed without error at baseline. Error-based person measures had larger standard errors with a smaller pseudo- R2 than time-based person or task measures and error-based task measures. Person measure infits for time- and error-based estimates conformed to expected values. The linear regressions between time-based person and task measures and corresponding error-based estimates had slopes of approximately 0.5, an observation consistent with larger estimation error variance for error-based measures than for time-based measures. Time-based TIADL person measures ( x ) and Activity Inventory person measures (estimated from all items, y ) were colinear but weakly correlated ( R = 0.19). CONCLUSIONS: Functional ability measures estimated from performance times of instrumental activity of daily living tasks in patients' homes demonstrate good internal and external validity. The ceiling effect from the infrequency of task performance errors in our data set limits use of TIADL error data to measure rehabilitation outcomes.

Tension force causes cell cycle arrest at G2/M phase in osteocyte-like cell line MLO-Y4.

Bone remodelling is the process of bone resorption and formation, necessary to maintain bone structure or for adaptation to new conditions. Mechanical loadings, such as exercise, weight bearing and orthodontic force, play important roles in bone remodelling. During the remodelling process, osteocytes play crucial roles as mechanosensors to regulate osteoblasts and osteoclasts. However, the precise molecular mechanisms by which the mechanical stimuli affect the function of osteocytes remain unclear. In the present study, we analysed viability, cell cycle distribution and gene expression pattern of murine osteocyte-like MLO-Y4 cells exposed to tension force (TF). Cells were subjected to TF with 18% elongation at 6 cycles/min for 24 h using Flexcer Strain Unit (FX-3000). We found that TF stimulation induced cell cycle arrest at G2/M phase but not cell death in MLO-Y4 cells. Differentially expressed genes (DEGs) between TF-stimulated and unstimulated cells were identified by microarray analysis, and a marked increase in glutathione-S-transferase α (GSTA) family gene expression was observed in TF-stimulated cells. Enrichment analysis for the DEGs revealed that Gene Ontology (GO) terms and Kyoto Encyclopedia Genes and Genomes (KEGG) pathways related to the stress response were significantly enriched among the upregulated genes following TF. Consistent with these results, the production of reactive oxygen species (ROS) was elevated in TF-stimulated cells. Activation of the tumour suppressor p53, and upregulation of its downstream target GADD45A, were also observed in the stimulated cells. As GADD45A has been implicated in the promotion of G2/M cell cycle arrest, these observations may suggest that TF stress leads to G2/M arrest at least in part in a p53-dependent manner.

Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist, combined with hyperbaric oxygen therapy.

BACKGROUND: Radiotherapy is an important treatment option for central nervous system malignancies. However, cranial radiation induces hippocampal dysfunction and white matter injury; this leads to cognitive dysfunction, and results in a reduced quality of life in patients. Excitatory glutamate signaling through N-methyl-d-aspartate receptors (NMDARs) plays a central role both in hippocampal neurogenesis and in the myelination of oligodendrocytes in the cerebrum. METHODS: We provide a method for quantifying neurogenesis in human subjects in live brain during cancer therapy. Neuroimaging using originally created behavioral tasks was employed to examine human hippocampal memory pathway in patients with brain disorders. RESULTS: Treatment with memantine, a non-competitive NMDAR antagonist, reversed impairment in hippocampal pattern separation networks as detected by functional magnetic resonance imaging. Hyperbaric preconditioning of the patients just before radiotherapy with memantine mostly reversed white matter injury as detected by whole brain analysis with Tract-Based Spatial Statics. Neuromodulation combined with the administration of hyperbaric oxygen therapy and memantine during radiotherapy facilitated the restoration of hippocampal function and white matter integrity, and improved higher cognitive function in patients receiving cranial radiation. CONCLUSIONS: The method described herein, for diagnosis of hippocampal dysfunction, and therapeutic intervention can be utilized to restore some of the cognitive decline experienced by patients who have received cranial radiation. The underlying mechanism of restoration is the production of new neurons, which enhances functionality in pattern separation networks in the hippocampi, resulting in an increase in cognitive score, and restoration of microstructural integrity of white matter tracts revealed by Tract-Based Spatial Statics Analysis.

Antitumor effects of pyrrole-imidazole polyamide modified with alkylating agent on prostate cancer cells.

Androgens and androgen receptor (AR) have a central role in prostate cancer progression by regulating its downstream signaling. Although androgen depletion therapy (ADT) is the primary treatment for most prostate cancers, they acquires resistance to ADT and become castration resistant prostate cancers (CRPC). AR complex formation with multiple transcription factors is important for enhancer activity and transcriptional regulation, which can contribute to cancer progression and resistance to ADT. We previously demonstrated that OCT1 collaborates with AR in prostate cancer, and that a pyrrole-imidazole (PI) polyamide (PIP) targeting OCT1 inhibits cell and castration-resistant tumor growth (Obinata D et al. Oncogene 2016). PIP can bind to DNA non-covalently without a drug delivery system unlike most DNA targeted therapeutics. In the present study, we developed a PIP modified with a DNA alkylating agent, chlorambucil (ChB) (OCT1-PIP-ChB). Then its effect on the growth of prostate cancer LNCaP, 22Rv1, and PC3 cells, pancreatic cancer BxPC3 cells, and colon cancer HCT116 cells, as well as non-cancerous MCF-10A epithelial cells, were analyzed. It was shown that the IC50s of OCT1-PIP-ChB for 22Rv1 and LNCaP were markedly lower compared to other cells, including non-cancerous MCF-10A cells. Comprehensive gene expression analysis of CRPC model 22Rv1 cells treated with IC50 concentrations of OCT1-PIP-ChB revealed that the gene group involved in DNA double-strand break repair was the most enriched among gene sets repressed by OCT1-PIP-ChB treatment. Importantly, in vivo study using 22Rv1 xenografts, we showed that OCT1-PIP-ChB significantly reduced tumor growth compared to the control group without showing obvious adverse effects. Thus, the PIP combined with ChB can exert a significant inhibitory effect on prostate cancer cell proliferation and castration-resistant tumor growth, suggesting a potential role as a therapeutic agent.

Altered Calcium Permeability of AMPA Receptor Drives NMDA Receptor Inhibition in the Hippocampus of Murine Obesity Models.

Evidence has accumulated that higher consumption of high-fat diets (HFDs) during the juvenile/adolescent period induces altered hippocampal function and morphology; however, the mechanism behind this phenomenon remains elusive. Using high-resolution structural imaging combined with molecular and functional interrogation, a murine model of obesity treated with HFDs for 12 weeks after weaning mice was shown to change in the glutamate-mediated intracellular calcium signaling and activity, including further selective reduction of gray matter volume in the hippocampus associated with memory recall disturbance. Dysregulation of intracellular calcium concentrations was restored by a non-competitive α-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antagonist, followed by normalization of hippocampal volume and memory recall ability, indicating that AMPARs may serve as an attractive therapeutic target for obesity-associated cognitive decline.

miRNA­218 targets multiple oncogenes and is a therapeutic target for osteosarcoma.

Survivin is overexpressed in various cancers and is correlated with treatment resistance and prognosis. MicroRNAs (miRNAs) directly regulate several target genes and are potential therapeutic agents for various cancers. The present study evaluated multiple gene targets of miR­218, including survivin, in osteosarcoma and compared the anti­tumor effects of miR­218 with those of YM155, an anti­survivin agent. It assessed the expression levels of miR­218 and survivin in osteosarcoma and osteoblast cell lines, as well as the proliferative, migratory and invasive capacities of cells following treatment with miR­218 or YM155. The form of cell death was assessed using fluorescence­activated cell sorting analysis to examine the expression of invasion ability­related genes. Osteosarcoma cell lines were subcutaneously injected into immunodeficient mice; the mice were then treated with miR­218 or YM155 to assess the anti­tumor effects of these agents. The results showed that miR­218 was downregulated, whereas survivin was overexpressed in the osteosarcoma cell line compared with normal osteoblast cells. The expression of survivin was suppressed upon overexpression of miR­218 (miR­218 group) or administration of YM155 (YM155 group), leading to apoptosis and inhibition of osteosarcoma cell proliferation. Invasion and migration abilities were inhibited in the miR­218 group, but not in the YM155 group. In the animal model, both the miR­218 and YM155 groups showed a reduced tumor volume and decreased survivin expression. In osteosarcoma, miR­218 showed a wider range of therapeutic efficacy compared with YM155, suggesting that miR­218 should be evaluated as a treatment target.

Exosomal miR-214-3p as a potential novel biomarker for rhabdoid tumor of the kidney.

PURPOSE: Rhabdoid tumor of the kidney (RTK) is a rare, highly aggressive pediatric renal tumor. No specific biomarkers are available for detection of RTK, and the initial differential diagnosis from other pediatric abdominal tumors, including neuroblastoma (NB), is difficult. Exosomal miRNAs are novel cancer biomarkers that can be detected in biological fluids. We explored candidate RTK-specific exosomal miRNAs as novel biomarkers of RTK. METHODS: Exosomal miRNAs were collected from conditioned media of human RTK-derived cell lines, a human embryonic renal cell line, and human NB-derived cell lines. miRNA sequencing (miRNA-Seq) was performed to detect candidate RTK-specific exosomal miRNAs. The exosomal miRNA expression in conditioned media of tumor cell lines and serum from RTK xenograft-bearing mice was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The expression of exosomal miR-214-3p detected by miRNA-Seq was highest in RTK-derived cell lines. Exosomal miR-214-3p expression level determined by qRT-PCR was significantly higher in RTK-derived cell lines than in the human embryonic renal cell line or NB-derived cell lines. Furthermore, the serum exosomal miR-214-3p expression level was significantly higher in RTK xenograft mice than controls. CONCLUSION: Our data indicated that exosomal miR-214-3p has potential as a novel biomarker of RTK.

Improving the Efficacy of EGFR Inhibitors by Topical Treatment of Cutaneous Squamous Cell Carcinoma with miR-634 Ointment.

For cutaneous squamous cell carcinoma (cSCC), topical treatment is an essential option for patients who are not candidates for, or who refuse, surgery. Epidermal growth factor receptor (EGFR) plays a key role in the development of cSCC, but EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib, have shown only partial clinical benefit in this disease. Thus, there is an unmet need to develop novel strategies for improving the efficacy of TKIs in cSCC. We previously demonstrated that the tumor-suppressive microRNA (miRNA) miR-634 functions as a negative modulator of the cytoprotective cancer cell survival processes and is a useful anticancer therapeutic agent. In the present study, we found that topical application of an ointment containing miR-634 inhibited in vivo tumor growth without toxicity in a cSCC xenograft mouse model and a 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced papilloma mouse model. Functional validation revealed that miR-634 overexpression reduced glutaminolysis by directly targeting ASCT2, a glutamine transporter. Furthermore, overexpression of miR-634 synergistically enhanced TKI-induced cytotoxicity by triggering severe energetic stress in vitro and in vivo. Thus, we propose that topical treatment with miR-634 ointment is a useful strategy for improving for EGFR TKI-based therapy for cSCC.

Knockdown of E2F5 induces cell death via the TP53­dependent pathway in breast cancer cells carrying wild­type TP53.

E2F transcription factor 5 (E2F5) is a member of the E2F family of transcription factors, which are involved in regulation of various cellular processes, including cellular proliferation, apoptosis, differentiation and DNA damage response. Previously, we reported that E2F5 was aberrantly overexpressed in estrogen receptor (ER)­negative breast cancer, especially in triple­negative breast cancer (TNBC). In the present study, it was revealed that E2F5 gene silencing caused a significant reduction in the proliferation rate of breast cancer MCF7 (ER­positive luminal­type) and MDA­MB­231 (TNBC­type) cells. Additional experiments demonstrated that E2F5 knockdown triggered cell death of MCF7 cells but not MDA­MB­231 cells. As MCF7 and MDA­MB­231 cells carry wild­type and mutant TP53, respectively, and BT474 (ER­negative, HER2­positive type) carrying mutant TP53 exhibited similar results to MDA­MB­231, the possible effects of E2F5 gene depletion on cell death­related TP53­target gene expression were examined. Real­time RT­qPCR analysis revealed that knockdown of E2F5 in MCF7 cells stimulated cell death­related transcription of TP53­target genes such as BAX, NOXA and PUMA. For MDA­MB­231 and BT474 cells, E2F5 gene silencing revealed marginal effects on the expression of TP53 target genes. In addition, silencing of TP53 abrogated the effect of E2F5 silencing in MCF7 cells. Collectively, the present results indicated that E2F5 participated in the carcinogenesis of breast cancer carrying wild­type TP53 through suppression of TP53, while E2F5 had a pro­proliferative but not anti­apoptotic effect on breast cancer with TP53 mutation.

Effects of Pyrrole-Imidazole Polyamides Targeting Human TGF-ß1 on the Malignant Phenotypes of Liver Cancer Cells.

Synthetic pyrrole-imidazole (PI) polyamides bind to the minor groove of double-helical DNA with high affinity and specificity, and inhibit the transcription of corresponding genes. In liver cancer, transforming growth factor (TGF)-ß expression is correlated with tumor grade, and high-grade liver cancer tissues express epithelial-mesenchymal transition markers. TGF-ß1 was reported to be involved in cancer development by transforming precancer cells to cancer stem cells (CSCs). This study aimed to evaluate the effects of TGF-ß1-targeting PI polyamide on the growth of liver cancer cells and CSCs and their TGF-ß1 expression. We analyzed TGF-ß1 expression level after the administration of GB1101, a PI polyamide that targets human TGF-ß1 promoter, and examined its effects on cell proliferation, invasiveness, and TGF-ß1 mRNA expression level. GB1101 treatment dose-dependently decreased TGF-ß1 mRNA levels in HepG2 and HLF cells, and inhibited HepG2 colony formation associated with downregulation of TGF-ß1 mRNA. Although GB1101 did not substantially inhibit the proliferation of HepG2 cells compared to untreated control cells, GB1101 significantly suppressed the invasion of HLF cells, which displayed high expression of CD44, a marker for CSCs. Furthermore, GB1101 significantly inhibited HLF cell sphere formation by inhibiting TGF-ß1 expression, in addition to suppressing the proliferation of HLE and HLF cells. Taken together, GB1101 reduced TGF-ß1 expression in liver cancer cells and suppressed cell invasion; therefore, GB1101 is a novel candidate drug for the treatment of liver cancer.

Polyethylene glycol derivative 9bw suppresses growth of neuroblastoma cells by inhibiting oxidative phosphorylation.

Neuroblastoma (NB) is a childhood malignancy originating from the sympathetic nervous system, and accounts for approximately 15% of all pediatric cancer-related deaths. As the 5-y survival rate of patients with high-risk NB is <50%, novel therapeutic strategies for NB patients are urgently required. Nonaethylene glycol mono('4-iodo-4-biphenyl)ester (9bw) is a polyethylene glycol derivative, synthesized by modifying a compound originally extracted from filamentous bacteria. Although 9bw shows remarkable inhibition of tumor cell growth, the underlying mechanisms remain unclear. Here, we examined the efficacy of 9bw on human NB-derived cells, and investigated the molecular mechanisms underlying the cytotoxic effects of 9bw on these cells. Our results indicated that 9bw induced cell death in NB cells by decreasing the production of ATP. Metabolome analysis and measurement of oxygen consumption indicated that 9bw markedly suppressed oxidative phosphorylation (OXPHOS). Further analyses indicated that 9bw inhibited the activity of mitochondrial respiratory complex I. Moreover, we showed that 9bw inhibited growth of NB in vivo. Based on the results of the present study, 9bw is a good candidate as a novel agent for treatment of NB.

Amyloid precursor protein, an androgen-regulated gene, is targeted by RNA-binding protein PSF/SFPQ in neuronal cells.

Amyloid precursor protein (APP) is a representative gene related to Alzheimer's disease (AD). Androgens function by binding to the androgen receptor (AR). Both androgen and RNA-binding protein PSF play a role in the pathology of AD. However, the involvement of AR and PSF in APP regulation in neuron has not been investigated. Here, we explored the regulatory mechanism of APP expression by AR and PSF using neuron-derived cells. We demonstrated that androgen up-regulates the production of APP at the mRNA and protein levels. This induction is enhanced by AR over-expression and inhibited by its silencing. One candidate AR-binding region was identified in the intron region of APP and validated its activity as AR-dependent enhancer by the luciferase assay. Furthermore, the public transcriptome data of brain tissues of mice indicated that APP is regulated by PSF post-transcriptionally. We observed a decreased expression of APP after PSF knockdown and interaction of PSF with the APP transcript. Moreover, we revealed that silencing of PSF inhibited the stability of the APP mRNA. Thus, these results presented a new regulatory mechanism of APP expression by androgen through AR-mediated transcription and PSF at the post-transcriptional level that might be associated with the occurrence of AD.

Identification of new octamer transcription factor 1-target genes upregulated in castration-resistant prostate cancer.

Octamer transcription factor 1 (OCT1) is an androgen receptor (AR)-interacting partner and regulates the expression of target genes in prostate cancer cells. However, the function of OCT1 in castration-resistant prostate cancer (CRPC) is not fully understood. In the present study, we used 22Rv1 cells as AR-positive CRPC model cells to analyze the role of OCT1 in CRPC. We showed that OCT1 knockdown suppressed cell proliferation and migration of 22Rv1 cells. Using microarray analysis, we identified four AR and OCT1-target genes, disks large-associated protein 5 (DLGAP5), kinesin family member 15 (KIF15), non-SMC condensin I complex subunit G (NCAPG), and NDC80 kinetochore complex component (NUF2) in 22Rv1 cells. We observed that knockdown of DLGAP5 and NUF2 suppresses growth and migration of 22Rv1 cells. Furthermore, immunohistochemical analysis showed that positive expression of DLGAP5 in prostate cancer specimens is related to poor cancer-specific survival rates of patients. Notably, enhanced expression of DLGAP5 was observed in CRPC tissues of patients. Thus, our findings suggest that these four genes regulated by the AR/OCT1 complex could have an important role in CRPC progression.

Forced expression of NR4A3 induced the differentiation of human neuroblastoma-derived NB1 cells.

Nuclear receptor subfamily 4, group A, member 3 (NR4A3) is a member of the NR4A subgroup of orphan nuclear receptors, implicated in the regulation of diverse biological functions, including metabolism, angiogenesis, inflammation, cell proliferation, and apoptosis. Although many reports have suggested the involvement of NR4A3 in the development and/or progression of tumors, its role varies among tumor types. Previously, we reported that DNA hypomethylation at NR4A3 exon 3 is associated with lower survival rate of neuroblastoma (NB) patients. As hypomethylation of this region results in reduced expression of NR4A3, our observations suggested that NR4A3 functions as a tumor suppressor in NB. However, the exact mechanisms underlying its functions have not been clarified. In the present study, we analyzed public databases and showed that reduced NR4A3 expression was associated with shorter survival period of NB in two out of three datasets. An in vitro study revealed that forced expression of NR4A3 in human NB-derived cell line NB1 resulted in elongation of neurites along with overexpression of GAP43, one of the differentiation markers of NB. On the other hand, siRNA-mediated knockdown of NR4A3 suppressed the expression level of GAP43. Interestingly, the forced expression of NR4A3 induced only the GAP43 but not the other molecules involved in NB cell differentiation, such as MYCN, TRKA, and PHOX2B. These results indicated that NR4A3 directly activates the expression of GAP43 and induces differentiated phenotypes of NB cells, without affecting the upstream signals regulating GAP43 expression and NB differentiation.

Silencing of EPHB2 promotes the epithelial-mesenchymal transition of skin squamous cell carcinoma-derived A431 cells.

Erythropoietin-producing hepatocellular (Eph) receptors and their ligand ephrins serve crucial roles in the interactions among epithelial cells. Eph receptor/ephrin signaling regulates cell functions, including proliferation, differentiation and migration, via these cell-cell interactions. We reported previously that EPHB2, a member of the Eph receptor family, was highly expressed in chemically induced cutaneous squamous cell carcinoma (cSCC) tissues in mice. Although the higher expression level of EPHB2 has been observed in various human cancers, its roles in the development and progression of cancers are still unclear. In the present study, the functional implications of EPHB2 in the acquisition of malignant phenotypes of cSCC cells was investigated. Silencing of EPHB2 in the human cSCC cell line A431 induced epithelial-mesenchymal transition (EMT)-like morphological changes accompanied by a significant upregulation of epithelial-mesenchymal transition-associated genes such as zinc finger E-box binding homeobox 1/2. In addition, silencing of EPHB2 suppressed anchorage-independent cell growth under 3D culture conditions. Consistent with these observations, EPHB2 exhibited higher levels of expression in tumor spheres formed under 3D culture conditions than in cells cultured in adherent form, and the expression pattern of EMT markers indicated that EMT was suppressed in tumor spheres. The results of the present study indicated that EPHB2 serves a pivotal role in promoting the anchorage-independent growth of A431 cells through the suppression of EMT.

Preliminary Evaluation of Two Digital Image Processing Strategies for Head-Mounted Magnification for Low Vision Patients.

PURPOSE: In an observational clinical outcome study, we tested the effectiveness and use of the combination of two innovative approaches to magnification: a virtual bioptic telescope and a virtual projection screen, implemented with digital image processing in a head-mounted display (HMD) equipped with a high-resolution video camera and head trackers. METHODS: We recruited 30 participants with best-corrected visual acuity <20/100 in the better-seeing eye and bilateral central scotomas. Participants were trained on the HMD system, then completed a 7- to 10-day in-home trial. The Activity Inventory was administered before and after the home trial to measure the effect of system use on self-reported visual function. A simulator sickness questionnaire (SSQ) and a system-use survey were administered. Rasch analysis was used to assess outcomes. RESULTS: Significant improvements were seen in functional ability measures estimated from goal difficulty ratings (Cohen's d = 0.79, P < 0.001), and reading (d = 1.28, P < 0.001) and visual information (d = 1.11, P < 0.001) tasks. There was no improvement in patient-reported visual motor function or mobility. One participant had moderately severe discomfort symptoms after SSQ item calibration. The average patient rating of the system's use was 7.14/10. CONCLUSIONS: Use of the system resulted in functional vision improvements in reading and visual information processing. Lack of improvement in mobility and visual motor function is most likely due to limited field of view, poor depth perception, and lack of binocular disparity. TRANSLATIONAL RELEVANCE: We determine if these new image processing approaches to magnification are beneficial to low vision patients performing everyday activities.

Mapping of new skin tumor susceptibility loci by a phenotype-driven congenic approach.

As cancer susceptibility varies among mouse strains, mouse models are powerful tools for the identification of genes responsible for cancer development. Several cancer susceptibility loci have been mapped by genetic analysis using cancer-resistant and cancer-susceptible mouse strains. However, only a few corresponding genes for these loci have been identified, because most of the cancer susceptibility loci are low-penetrance alleles. We reported previously that wild-derived PWK mice showed no tumor development on treatment with the two-stage skin carcinogenesis protocol [induced by 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)], and that this phenotype is dominant-resistant when crossed with the highly susceptible strain FVB. From the analysis of the F1 backcross generation between PWK and FVB, we have mapped the new significant locus Skts-fp1 on chromosome 4. In the present study, congenic strains were generated with the PWK resistance allele in the FVB background using a phenotype-driven approach, and sought to narrow down the candidate loci and find the responsible gene(s). One of the resistant mice in the N6 generation carried the remaining PWK allele on chromosomes 4, 7 and 11, and an association study using the progeny of this mouse suggested that the locus on chromosome 11 may affect the cancer susceptibility locus on chromosome 7. On the other hand, no skin tumor susceptibility locus was mapped on chromosome 11 as examined in N2 progeny. These findings suggest that there is at least one tumor-resistance gene on chromosome 7, the function of which could be regulated by gene(s) located on chromosome 11.