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920 result(s) for "Oda, Y"
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Tumour-associated macrophages correlate with poor prognosis in myxoid liposarcoma and promote cell motility and invasion via the HB-EGF-EGFR-PI3K/Akt pathways
Background: Myxoid liposarcoma (MLS) is the second most common subtype of liposarcoma, and metastasis occurs in up to one-third of cases. However, the mechanisms of invasion and metastasis remain unclear. Tumour-associated macrophages (TAMs) have important roles in tumour invasion, metastasis, and/or poor prognosis. The aim of this study was to investigate the relationship between TAMs and MLS. Methods: Using 78 primary MLS samples, the association between clinical prognosis and macrophage infiltration was evaluated by immunochemistry. The effects of macrophages on cell growth, cell motility, and invasion of MLS cell lines were investigated in vitro . In addition, clinicopathological factors were analysed to assess their prognostic implications in MLS. Results: Higher levels of CD68-positive macrophages were associated with poorer overall survival in MLS samples. Macrophage-conditioned medium enhanced MLS cell motility and invasion by activating epidermal growth factor receptor (EGFR), with the key ligand suggested to be heparin-binding EGF-like growth factor (HB-EGF). The phosphoinositide 3-kinase/Akt pathway was mostly involved in HB-EGF-induced cell motility and invasion of MLS. The expression of phosphorylated EGFR in MLS clinical samples was associated with macrophage infiltration. In addition, more significant macrophage infiltration was associated with poor prognosis even in multivariate analysis. Conclusions: Macrophage infiltration in MLS predicts poor prognosis, and the relationship between TAMs and MLS may be a new candidate for therapeutic targets of MLS.
Identification and analysis of CXCR4-positive synovial sarcoma-initiating cells
Synovial sarcoma accounts for almost 10% of all soft tissue sarcomas, and its prognosis is poor with 5-year survival rates at 36%. Thus, new treatments and therapeutic targets for synovial sarcoma are required. Tumor-initiating cells have been defined by the ability for self-renewal and multipotent differentiation, and they exhibit higher tumorigenic capacity, chemoresistance and radiation resistance, expecting to be a new therapeutic target. In synovial sarcoma, the presence of such stemness remains largely unclear; thus, we analyzed whether synovial sarcoma possessed tumor-initiating cells and explored specific markers, and we discovered that synovial sarcoma cell lines possessed heterogeneity by way of containing a sphere-forming subpopulation highly expressing NANOG, OCT4 and SOX2. By expression microarray analysis, CXCR4 was identified to be highly expressed in the sphere subpopulation and correlated with stem-cell-associated markers. Inhibition of CXCR4 suppressed the cell proliferation of synovial sarcoma cell lines in vitro . The tumor-initiating ability of CXCR4-positive cells was demonstrated by xenograft propagation assay. CXCR4-positive cells showed higher tumorigenicity than negative ones and possessed both self-renewal and multipotent differentiation ability. Immunohistochemical analysis of 39 specimens of synovial sarcoma patients revealed that CXCR4 strongly correlated with poor prognosis of synovial sarcoma. Thus, we conclude that CXCR4 is the marker of synovial sarcoma-initiating cells, a new biomarker for prognosis and a new potential therapeutic target.
Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells
Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1 , thymidylate synthetase , S100 calcium binding protein and cyclin B , and downregulated 534 genes, including CXCR4 , N-myc downstream regulated gene 1 , E-cadherin and phospholipase C . Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 ( ABCB1 ) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.
Low toxicity and high surface activity of sophorolipids from Starmerella bombicola in aquatic species: A preliminary study
Aim : This study was carried out to evaluate aquatic toxicity and surface activity of sophorolipids extracted from yeast Starmerella bombicola. Methodology: The half maximal effective concentration (ECJ values of sophorolipids were determined in three aquatic species, and the surface activity of sophorolipids in aqueous solutions was examined at ECS0 concentration. Results : The ECS0 of sophorolipid surfactant >473 mg I'1 was found in alga Pseudokirchneriella subcapitata, a median lethal concentration (LCJ of 64.8 mg I'1 in fish Oryzias latipes, whereas a high ECS0 of 48.2 mg I'1 was noted in crustacean Daphnia magna, respectively. Sophorolipids effectively reduced the aquatic surface tension to 39 mN m'1 in O. latipes and to 41 mN m'1 in D. magna. Interpretation : These results show that sophorolipids from S. bombicola are a promising biosurfactant with an ideal balance of low aquatic toxicity and high surface activity.
Attachment and Mental Health in the COVID-19 Pandemic: Posttraumatic Growth and Religion as Moderators
Consistent with the teachings in various religious traditions of finding meaning amidst suffering, we suspected that Posttraumatic Growth (PTG) would have a buffering effect on attachment insecurity and psychosocial outcomes. We examined the effects of anxious and avoidant attachment, PTG, and religion on psychosocial outcomes (i.e., anxiety, depression, and loneliness). Data from 466 participants recruited from Amazon Mechanical Turk (MTurk) and a college student sample revealed that PTG served as a moderator between anxious attachment and (a) depression and (b) loneliness, and (c) PTG buffered the relationship between anxious attachment and anxiety to a greater extent among Christians, compared to non-Christians. On the other hand, (a) PTG did not moderate the link between attachment avoidance and depression, (b) PTG exacerbated the relationship between attachment avoidance and anxiety, and (c) PTG buffered the association between attachment avoidance and loneliness for non-Christians, but this link was amplified for Christians. We discuss the findings that PTG interacted with religion and offered protective effects for anxious (but not avoidant) attachment. Factors that may have contributed to the difference between the two attachment styles are discussed, along with implications from cultural-religious and adult attachment frameworks.
Y-box binding protein-1 regulates cell proliferation and is associated with clinical outcomes of osteosarcoma
Background: Prognosis of osteosarcoma (OS) with distant metastasis and local recurrence is still poor. Y-box binding protein-1 (YB-1) is a multifunctional protein that can act as a regulator of transcription and translation and its high expression of YB-1 protein was observed in OS, however, the role of YB-1 in OS remains unclear. Methods: Y-box binding protein-1 expression in OS cells was inhibited by specific small interfering RNAs to YB-1 (si-YB-1). The effects of si-YB-1 in cell proliferation and cell cycle transition in OS cells were analysed in vitro and in vivo . The association of nuclear expression of YB-1 and clinical prognosis was also investigated by immunohistochemistry. Results: Proliferation of OS cell was suppressed by si-YB-1 in vivo and in vitro . The expression of cyclin D1 and cyclin A were also decreased by si-YB-1. In addition, si-YB-1 induced G1/S arrest with decreased cyclin D1 and cyclin A in OS cell lines. Direct binding of YB-1 in OS cell lines was also observed. Finally, the nuclear expression of YB-1 was significantly related to the poorer overall survival in OS patients. Conclusion: Y-box binding protein-1 would regulate cell cycle progression at G1/S and tumour growth in human OS cells in vitro and in vivo . Nuclear expression of YB-1 was closely associated with the prognosis of OS, thus, YB-1 simultaneously could be a potent molecular target and prognostic biomarker for OS.
History of Falls and Bedriddenness Ranks are Useful Predictive Factors for in-Hospital Falls: A Single-Center Retrospective Observational Study Using the Saga Fall Risk Model
Introduction: In our former study, we had validated the previously developed predictive model for in-hospital falls (Saga fall risk model) using eight simple factors (age, sex, emergency admission, department of admission, use of hypnotic medications, history of falls, independence of eating, and Bedriddenness ranks [BRs]), proving its high reliability. We found that only admission to the neurosurgery department, history of falls, and BRs had significant relationships with falls. In the present study, we aimed to clarify whether each of these three items had a significant relationship with falls in a different group of patients. Methods: This was a single-center based, retrospective study in an acute care hospital in a rural city of Japan. We enrolled all inpatients aged 20 years or older admitted from April 2015 to March 2018. We randomly selected patients to fulfill the required sample size. We performed multivariable logistic regression analysis using forced entry on the association between falls and each of the eight items in the Saga fall risk model 2. Results: A total of 2932 patients were randomly selected, of whom 95 (3.2%) fell. The median age was 79 years, and 49.9% were men. Multivariable analysis showed that female sex (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.39-0.93, p = 0.022), having a history of falls (OR 1.9, 95% CI 1.16-2.99, p = 0.010), requiring help with eating (OR 1.9, 95% CI 1.12-3.35, p = 0.019), BR of A (OR 6.6, 95% CI 2.82-15.30, p < 0.001), BR of B (OR 7.5, 95% CI 2.95-19.06, p < 0.001), and BR of C (OR 4.1, 95% CI 1.53-11.04, p = 0.005 (were significantly associated with falls. Conclusion: History of falls and BRs were independently associated with in-hospital falls. Keywords: bedridden, Bedriddenness ranks, fall, predictive model, validation, Saga fall risk model 2
Accurate Quantitation of Protein Expression and Site-Specific Phosphorylation
A mass spectrometry-based method is described for simultaneous identification and quantitation of individual proteins and for determining changes in the levels of modifications at specific sites on individual proteins. Accurate quantitation is achieved through the use of wholecell stable isotope labeling. This approach was applied to the detection of abundance differences of proteins present in wild-type versus mutant cell populations and to the identification of in vivo phosphorylation sites in the PAK-related yeast Stc20 protein kinase that depend specifically on the G1 cyclin Cln2. The present method is general and affords a quantitative description of cellular differences at the level of protein expression and modification, thus providing information that is critical to the understanding of complex biological phenomena.
The Administration of Lemborexant at Admission is Not Associated with Inpatient Falls: A Multicenter Retrospective Observational Study
There has been no large-scale investigation into the association between the use of lemborexant, suvorexant, and ramelteon and falls in a large population. This study, serving as a pilot investigation, was aimed at examining the relationship between inpatient falls and various prescribed hypnotic medications at admission. This study was a sub-analysis of a multicenter retrospective observational study conducted over a period of 3 years. The target population comprised patients aged 20 years or above admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals. We extracted data on the types of hypnotic medications prescribed at admission, including lemborexant, suvorexant, ramelteon, benzodiazepines, Z-drugs, and other hypnotics; the occurrence of inpatient falls during the hospital stay; and patients' background information. To determine the outcome of inpatient falls, items with low collinearity were selected and included as covariates in a forced-entry binary logistic regression analysis. Overall, 150,278 patients were included in the analysis, among whom 3,458 experienced falls. The median age of the entire cohort was 70 years, with men constituting 53.1%. Binary logistic regression analysis revealed that the prescription of lemborexant, suvorexant, and ramelteon at admission was not significantly associated with inpatient falls. The administration of lemborexant, suvorexant, and ramelteon at admission may not be associated with inpatient falls.
Molecular evidence that the genes for dioecism and monoecism in Spinacia oleracea L. are located at different loci in a chromosomal region
Spinach (Spinacia oleracea L.) is widely known to be dioecious. However, monoecious plants can also occur in this species. Sex expression in dioecious spinach plants is controlled by a single gene pair termed X and Y. Our previous study showed that a single, incompletely dominant gene, which controls the monoecious condition in spinach line 03-336, should be allelic or linked to X/Y. Here, we developed 19 AFLP markers closely linked to the monoecious gene. The AFLP markers were mapped to a 38.2-cM chromosomal region that included the monoecious gene, which is bracketed between flanking markers with a distance of 7.1 cM. The four AFLP markers developed in our studies were converted into sequence-characterized amplified region (SCAR) markers, which are linked to both the monoecious gene and Y and are common to both populations segregating for the genes. Linkage analysis using the SCAR markers suggested that the monoecious gene (M) and Y are located in different intervals, between different marker pairs. Analysis of populations segregating for both M and Y also directly demonstrates linkage of the genes at a distance of ~12 cM. The data presented in this study may be useful for breeding dioecious and highly male monoecious lines utilized as the pollen parents for hybrid seed production, as well as for studies of the evolutionary history of sexual systems in this species, and can provide a molecular basis for positional cloning of the sex-determining genes.