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Understanding tumor-induced angiogenesis is a challenging problem with important consequences for the diagnosis and treatment of cancer. In this study, we define a novel function for epithelial membrane protein-2 (EMP2) in the control of angiogenesis. EMP2 functions as an oncogene in endometrial cancer, and its expression has been linked to decreased survival. Using endometrial cancer xenografts, modulation of EMP2 expression resulted in profound changes to the tumor microvasculature. Under hypoxic conditions, upregulation of EMP2 promoted vascular endothelial growth factors (VEGF) expression through a HIF-1α-dependent pathway and resulted in successful capillary-like tube formation. In contrast, reduction of EMP2 correlated with reduced HIF-1α and VEGF expression with the net consequence of poorly vascularized tumors in vivo. We have previously shown that targeting of EMP2 using diabodies in endometrial cancer resulted in a reduction of tumor load, and since then we have constructed a fully human EMP2 IgG1. Treatment of endometrial cancer cells with EMP2-IgG1 reduced tumor load with a significant improvement in survival. These results support the role of EMP2 in the control of the tumor microenvironment and confirm the cytotoxic effects observed by EMP2 treatment in vivo.

The annealing behaviors of oxygen vacancies introduced by the epitaxial growth of thin SrTiO3 and Al2O3 films on SrTiO3 substrates were studied by using a monoenergetic positron beam. The films were grown by molecular-beam epitaxy without using an oxidant. The Doppler broadening spectra of the annihilation radiation were measured as a function of the incident positron energy for samples fabricated under various growth conditions. The line-shape parameter S, corresponding to the annihilation of positrons in the substrate, was increased by the film growth, suggesting diffusion of oxygen from the substrate into the film and a resultant introduction of vacancies (mainly oxygen vacancies). A clear correlation between the value of S and the substrate conductivity was obtained. From isochronal annealing experiments, the Al2O3 thin film was found to suppress the penetration of oxygen from the atmosphere for annealing temperatures below 600 °C. Degradation of the film’s oxygen blocking property occurred due to the annealing at 700 °C, and this was attributed to the oxidation of the Al2O3 by the atmosphere and the resultant introduction of vacancy-type defects. [ABSTRACT FROM AUTHOR]

Vacancy-type defects in the CeO[sub 2]/SrTiO[sub 3] structure were studied by means of positron annihilation. Thin CeO[sub 2] films were grown on SrTiO[sub 3] substrates by molecular-beam epitaxy without using an oxidant; oxygen was supplied by diffusion from the substrate (this process is referred to as automatic feeding epitaxy). A preferential epitaxial growth of CeO[sub 2](001) on SrTiO[sub 3](001) was observed, but an increase in the film thickness or annealing in an O[sub 2] atmosphere caused a partial growth of CeO[sub 2](110). The introduction of this phase was found to correlate with the reduction in the concentration of vacancy-type defects. The species of defects introduced into the SrTiO[sub 3] substrate was found to be not only oxygen vacancies but also Sr vacancies or their complexes. We discuss the mechanism that introduced cation vacancies in terms of oxygen nonstoichiometry. We found the trapping rate of positrons by Sr vacancies to depend on the sample temperature. This was associated with the temperature dependence of the dielectric constant near the defects or the presence of shallow trapping centers. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Vacancy-type defects in CeO2/SrTiO3 structure are studied using positron annihilation. The findings show that the value of the S parameter corresponding to the annihilation of positrons in the SrTiO2 substrate is increased by the formation of the CeO2 film.

The growths of BaTiO3 films on interfacial SiO2 were carried out with molecular beam epitaxy (MBE) in various oxygen partial pressures. In the BaTiO3 growth on 2 nm-thick SiO2 film at the oxygen partial pressure of less than 4.8×10−5 Pa, concavities at the BaTiO3 film surface and the Si/SiO2 interface appeared and the Si atoms diffused from the Si substrate to the top BaTiO3 layer. These were observed only after the film growth in the low oxygen pressure and only on ultrathin interfacial SiO2. And the silicide material was formed within the concavity. These results indicate that 2 nm-thick SiO2 film is not enough to the suppression of the reaction of the metal atoms with Si substrate. [Copyright &y& Elsevier]

Vacancy-type defects in SrTiO3 were studied by means of positron annihilation. Thin CeO2 films were grown on SrTiO3 substrates by molecular-beam epitaxy without using an oxidant; oxygen was supplied by diffusion from the substrate. This process is referred as “auto-feeding epitaxy” (AFE). The species of defects introduced into the substrate was found to be not only oxygen vacancies but also Sr-vacancies or their complexes. CeO2 films were grown also on MgO, yttria-stabilized zirconia and sapphire substrates using AFE, and these substrates were characterized by positron annihilation. [Copyright &y& Elsevier]

Ferroptosis is a cell death mechanism mediated by iron-dependent lipid peroxidation. Although ferroptosis has garnered attention as a cancer-suppressing mechanism, there are still limited markers available for identifying ferroptotic cells or assessing their sensitivity to ferroptosis. The study focused on biliverdin, an endogenous reducing substance in cells, and examined the dynamics of intracellular biliverdin during ferroptosis using a biliverdin-binding cyanobacteriochrome. It was found that intracellular biliverdin decreases during ferroptosis and that this decrease is specific to ferroptosis among different forms of cell death. Furthermore, the feasibility of predicting sensitivity to ferroptosis by measuring intracellular biliverdin was demonstrated using a ferroptosis model induced by the re-expression of the transcription factor BACH1. These findings provide further insight into ferroptosis research and are expected to contribute to the development of cancer therapies that exploit ferroptosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society.)

Breast cancer (BC) remains among the most commonly diagnosed cancers in women worldwide. Triple-negative BC (TNBC) is a subset of BC characterized by aggressive behavior, a high risk of distant recurrence, and poor overall survival rates. Chemotherapy is the backbone for treatment in patients with TNBC, but outcomes remain poor compared to other BC subtypes, in part due to the lack of recognized functional targets. In this study, the expression of the tetraspan protein epithelial membrane protein 2 (EMP2) was explored as a predictor of TNBC response to standard chemotherapy. We demonstrate that EMP2 functions as a prognostic biomarker for patients treated with taxane-based chemotherapy, with high expression at both transcriptomic and protein levels following treatment correlating with poor overall survival. Moreover, we show that targeting EMP2 in combination with docetaxel reduces tumor load in syngeneic and xenograft models of TNBC. These results provide support for the prognostic and therapeutic potential of this tetraspan protein, suggesting that anti-EMP2 therapy may be beneficial for the treatment of select chemotherapy-resistant TNBC tumors.

Outbreaks of invasive infections, with high mortality rates, caused by multidrug-resistant Candida auris have been reported worldwide. Although hotspot mutations in FKS1 are an established cause of echinocandin resistance, the actual contribution of these mutations to echinocandin resistance remains unknown. Here, we sequenced the FKS1 gene of a caspofungin-resistant clinical isolate (clade I) and identified a novel resistance mutation (G4061A inducing R1354H). We applied the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system to generate a recovered strain (H1354R) in which only this single nucleotide mutation was reverted to its wild-type sequence. We also generated mutant strains with only the R1354H mutation introduced into C. auris wild-type strains (clade I and II) and analyzed their antifungal susceptibility. Compared to their parental strains, the R1354H mutants exhibited a 4- to 16-fold increase in caspofungin minimum inhibitory concentration (MIC) while the H1354R reverted strain exhibited a 4-fold decrease in caspofungin MIC. In a mouse model of disseminated candidiasis, the in vivo therapeutic effect of caspofungin was more closely related to the FKS1 R1354H mutation and the virulence of the strain than its in vitro MIC. The CRISPR-Cas9 system could thus aid in elucidating the mechanism underlying drug resistance in C. auris .

Objectives: Despite evidence of breast cancer screening efficacy, the screening rate has remained less than 50% in Japan. This study aimed to evaluate the effect of an environmental approach offering on-site mammography in workplaces., Methods: Supermarket stores were randomly assigned into two groups, the intervention group (leaflet and mammography) and the control group (leaflet). From May to July 2018, participants in the intervention group were given a leaflet informing them of the subsidies for breast cancer screening and offered the opportunity to have mammography in their workplaces. Participants in the control group were given the same leaflet, but had to arrange their own screening outside the workplace. The primary outcome was the breast cancer screening rate in 2018. The odds ratio (OR) and 95% confidence interval (CI) for having screening in the intervention group compared with the control group were estimated using multilevel logistic regression., Results: We analyzed data from 1624 participants (mean age 53 years) from 25 supermarket stores (intervention: 8 stores, control: 17 stores). Among participants who had not attended screening in the previous year, the screening rate was 7% in the control group and 53% in the intervention group, with an adjusted OR (95% CI) of 14.22 (8.97-22.54). The effect was greater in those who had never attended screening before., Conclusion: In a worksite-based cluster randomized controlled trial in Japanese supermarket stores, an environmental approach offering mammography in workplaces substantially increased the breast cancer screening rate within 1 year (UMIN000030465)., (© 2023 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Introduction: The purpose of this study was to evaluate balance function before and after total knee arthroplasty (TKA) using Berg balance scale (BBS). The study also aimed to identify factors associated with balance impairment., Materials and Methods: Ninety-three knees in 90 patients were prospectively evaluated using their BBS scores, passive knee extension/flexion angles, Visual analogue scale for pain scores, hip-knee-ankle angles, and knee extensor/flexor muscle strengths before and after TKA. A total BBS score of less than 45 indicates an enhanced risk of multiple falls. Multivariate logistic regression models were performed to elucidate factors associated with post-operative BBS score., Results: A significant difference in mean pre- and post-operative BBS scores were noted (49.3 ± 6.4 vs. 52.2 ± 4.7) (p < 0.05). The percentage of pre- and post-operative BBS scores less than 45 were 20% and 10% (p < 0.05). Rheumatoid Arthritis (RA), lower pre-operative BBS score, and larger post-operative knee flexion contracture were significantly associated with lower post-operative BBS score (p < 0.01). The post-operative knee flexion contracture greater than 10° was significantly associated with substantially high odds of post-operative BBS scores less than 45 (Odds ratio 7.6; 95% confidential interval 1.69-34.17)., Conclusions: While TKA significantly improved BBS scores, 10% of the patients remained at a risk for multiple falls. RA, lower pre-operative BBS score, and post-operative knee flexion contracture greater than 10° retained balance impairment even after TKA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)