Effects of Typical Athletic Shoes on Postural Balance According to Foot Type.

BACKGROUND: The effects of shoes and foot type on balance are unclear. We aimed to investigate the differences between static and dynamic balance among three foot types and the changes in postural balance while wearing typical athletic shoes. METHODS: Based on the Foot Posture Index, the feet of 39 participants were classified as pronated, neutral, or supinated by a physiatrist. Static and dynamic balance function were assessed by center of gravity (COG) sway velocity with eyes open and eyes closed and a modified Star Excursion Balance Test in a random order with participants either barefoot or wearing shoes. RESULTS: The COG sway velocity was significantly higher in the supinated foot group than in the neutral foot group (barefoot: eyes open, P = .004, eyes closed, P = .001). Normalized composite reach distance (NCRD) was significantly lower in the pronated and supinated foot groups (barefoot: P = .039, P = .008; shoes: P = .018, P = .018). In all three foot type groups, COG sway velocity was significantly decreased (P < .05) and NCRD was significantly increased (P < .05) while wearing typical athletic shoes. CONCLUSIONS: The medial longitudinal arch of the foot affects postural balance. Typical athletic shoes improve postural balance regardless of foot type. However, the pronated and supinated foot groups still had lower dynamic postural balance compared with the neutral foot group, even when wearing athletic shoes. People with pronated and supinated feet may need additional interventions, such as foot orthoses or balance training.

Secretome analysis of patient-derived GBM tumor spheres identifies midkine as a potent therapeutic target.

Glioblastoma (GBM) is the most lethal primary brain tumor with few treatment options. The survival of glioma-initiating cells (GICs) is one of the major factors contributing to treatment failure. GICs frequently produce and respond to their own growth factors that support cell proliferation and survival. In this study, we aimed to identify critical autocrine factors mediating GIC survival and to evaluate the anti-GBM effect of antagonizing these factors. Proteomic analysis was performed using conditioned media from two different patient-derived GBM tumor spheres under a growth factor-depleted status. Then, the antitumor effects of inhibiting an identified autocrine factor were evaluated by bioinformatic analysis and molecular validation. Proteins secreted by sphere-forming GICs promote cell proliferation/survival and detoxify reactive oxygen species (ROS). Among these proteins, we focused on midkine (MDK) as a clinically significant and pathologically relevant autocrine factor. Antagonizing MDK reduced the survival of GBM tumor spheres through the promotion of cell cycle arrest and the consequent apoptotic cell death caused by oxidative stress-induced DNA damage. We also identified PCBP4, a novel molecular predictor of resistance to anti-MDK treatment. Collectively, our results indicate that MDK inhibition is an important therapeutic option by suppressing GIC survival through the induction of ROS-mediated cell cycle arrest and apoptosis.

Identification of genomic and molecular traits that present therapeutic vulnerability to HGF-targeted therapy in glioblastoma.

BACKGROUND: Cancer is a complex disease with profound genomic alterations and extensive heterogeneity. Recent studies on large-scale genomics have shed light on the impact of core oncogenic pathways, which are frequently dysregulated in a wide spectrum of cancer types. Aberrant activation of the hepatocyte growth factor (HGF) signaling axis has been associated with promoting various oncogenic programs during tumor initiation, progression, and treatment resistance. As a result, HGF-targeted therapy has emerged as an attractive therapeutic approach. However, recent clinical trials involving HGF-targeted therapies have demonstrated rather disappointing results. Thus, an alternative, in-depth assessment of new patient stratification is necessary to shift the current clinical course. METHODS: To address such challenges, we have evaluated the therapeutic efficacy of YYB-101, an HGF-neutralizing antibody, in a series of primary glioblastoma stem cells (GSCs) both in vitro and in vivo. Furthermore, we performed genome and transcriptome analysis to determine genetic and molecular traits that exhibit therapeutic susceptibility to HGF-mediated therapy. RESULTS: We have identified several differentially expressed genes, including MET, KDR, and SOX3, which are associated with tumor invasiveness, malignancy, and unfavorable prognosis in glioblastoma patients. We also demonstrated the HGF-MET signaling axis as a key molecular determinant in GSC invasion, and we discovered that a significant association in HGF expression existed between mesenchymal phenotype and immune cell recruitment. CONCLUSIONS: Upregulation of MET and mesenchymal cellular state are essential in generating HGF-mediated therapeutic responses. Our results provide an important framework for evaluating HGF-targeted therapy in future clinical settings.

Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.

Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscapes of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared with the traditional long-term cultured cancer cell line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. Here, we provide insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors, and the potential repurposing of ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present a potential implementation of PDC-derived drug sensitivities for the prediction of clinical response to targeted therapeutics using retrospective clinical studies.

Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma.

CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio- and chemoresistance in GBM.

Talin1 targeting potentiates anti-angiogenic therapy by attenuating invasion and stem-like features of glioblastoma multiforme.

Glioblastoma multiforme (GBM) possesses florid angiogenesis. However, the anti-angiogenic agent, Bevacizumab, did not improve overall survival of GBM patients. For more durable anti-angiogenic treatment, we interrogated resistant mechanisms of GBM against Bevacizumab. Serial orthotopic transplantation of in vivo Bevacizumab-treated GBM cells provoked complete refractoriness to the anti-angiogenic treatment. These tumors were also highly enriched with malignant phenotypes such as invasiveness, epithelial to mesenchymal transition, and stem-like features. Through transcriptome analysis, we identified that Talin1 (TLN1) significantly increased in the refractory GBMs. Inhibition of TLN1 not only attenuated malignant characteristics of GBM cells but also reversed the resistance to the Bevacizumab treatment. These data implicate TLN1 as a novel therapeutic target for GBM to overcome resistance to anti-angiogenic therapies.

Paraplegia in a Patient With IgG4-Related Sclerosing Disease: A Case Report.

Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic disease, characterized by mass forming inflammatory lesions which respond well to steroid therapy. Pancreas is the most common site of involvement, and other organ involvements are also common. However, there are only a few reports about central nervous system involvement. We report a case of IgG4-related sclerosing disease which involves spinal cord causing paraplegia. A middle-aged female presented with sudden lower limb weakness. Magnetic resonance imaging showed a soft tissue mass which was diffusely compressing spinal cord along the C7 to T5 levels. Intravenous steroid pulse therapy and emergent operation was performed. The immunopathologic findings revealed IgG4-related sclerosing pachymeningitis postoperatively. There was no evidence of other organ involvement. Her neurologic deficit remained unchanged after two months of comprehensive rehabilitation therapy.

Contributing factors analysis for the changes of the gross motor function in children with spastic cerebral palsy after physical therapy.

OBJECTIVE: To investigate the factors which contribute to the improvements of the gross motor function in children with spastic cerebral palsy after physical therapy. METHODS: The subjects were 45 children with spastic cerebral palsy with no previous botulinum toxin injection or operation history within 6 months. They consisted of 24 males (53.3%) and 21 females (46.7%), and the age of the subjects ranged from 2 to 6 years, with the mean age being 41±18 months. The gross motor function was evaluated by Gross Motor Function Measure (GMFM)-88 at the time of admission and discharge, and then, the subtractions were correlated with associated factors. RESULTS: The GMFM-88 was increased by 7.17±3.10 through 52±16 days of physical therapy. The more days of admission, the more improvements of GMFM-88 were attained. The children with initial GMFM-88 values in the middle range showed more improvements in GMFM-88 (p<0.05). The children without dysphagia and children with less spasticity of lower extremities also showed more improvements in GMFM-88 (p<0.05). CONCLUSION: We can predict the improvements of the gross motor function after physical therapy according to the days of admission, initial GMFM-88, dysphagia, and spasticity of lower extremities. Further controlled studies including larger group are necessary.