Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer

Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL)-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs) and determined HLA-A24-restricted CTL epitopes

Effects of teaching motor skills to others on the persistence of motor learning

The purpose of this study was to examine the effects of teaching motor skills to others on the survivability of motor learning effects. 20 healthy adults were randomly assigned to two conditions a teaching conditions and reading a magazine condition (control conditions). The number of times of turning was measured before and after each condition. In both conditions, the number of ball rotations and the number of improvements increased 30 minutes after the task was completed compared to before the task. Additionally, the number of improvements in ball rotation was significantly higher in the teaching condition than in the control condition. In the teaching condition, the number of ball turnings significantly increased 30 minutes after the end of the condition compared to before the condition. These results suggested that task for teaching motor skill to others might be useful for improving motor learning

CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi

Background Cation transport regulator 1 (CHAC1), a newly discovered enzyme that degrades glutathione, is induced in Helicobacter pylori (H. pylori)‐infected gastric epithelial cells in culture. The CHAC1‐induced decrease in glutathione leads to an accumulation of reactive oxygen species and somatic mutations in TP53. We evaluated the possible correlation between H. pylori infection and CHAC1 expression in human gastric mucosa. Materials and Methods Both fresh‐frozen and formalin‐fixed paraffin‐embedded tissue samples of gastric mucosa with or without H. pylori infection were obtained from 41 esophageal cancer patients that underwent esophago‐gastrectomy. Fresh samples were used for real‐time polymerase chain reaction for H. pylori DNA and CHAC1 mRNA, and formalin‐fixed samples were used for immunohistochemistry with anti‐CHAC1 and anti‐H. pylori monoclonal antibodies. Double‐enzyme or fluorescence immunohistochemistry and immuno‐electron microscopy were used for further analysis. Results Significant CHAC1 overexpression was detected in H. pylori‐infected parietal cells that expressed the human proton pump/H,K‐ATPase α subunit, whereas a constitutively low level of CHAC1 mRNA expression was observed in the other samples regardless of the H. pylori infection status, reflecting the weak CHAC1 expression detected by immunohistochemistry in the fundic‐gland areas. Immuno‐electron microscopy revealed intact H. pylori cells in the secretory canaliculi of infected parietal cells. Some parietal cells exhibited positive nuclear signals for Ki67 in the neck zone of the gastric fundic‐gland mucosa with H. pylori infection. Conclusion Cation transport regulator 1 overexpression in H. pylori‐infected parietal cells may cause the H. pylori‐induced somatic mutations that contribute to the development of gastric cancer.This work was supported by the Japan Society for the Promotion of Science KAKENHI (16K19077), and by the Practical Research for Innovative Cancer Control from Japan Agency for Medical Research and development, AMED

Growth Inhibition of Re-Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma-Targeted Chemo-Thermo-Immunotherapy

Melanogenesis substrate, N-propionyl-cysteaminylphenol (NPrCAP), is selectively incorporated into melanoma cells and inhibits their growth by producing cytotoxic free radicals. Magnetite nanoparticles also disintegrate cancer cells and generate heat shock protein (HSP) upon exposure to an alternating magnetic field (AMF). This study tested if a chemo-thermo-immunotherapy (CTI therapy) strategy can be developed for better management of melanoma by conjugating NPrCAP on the surface of magnetite nanoparticles (NPrCAP/M). We examined the feasibility of this approach in B16 mouse melanoma and evaluated the impact of exposure temperature, frequency, and interval on the inhibition of re-challenged melanoma growth. The therapeutic protocol against the primary transplanted tumor with or without AMF exposure once a day every other day for a total of three treatments not only inhibited the growth of the primary transplant but also prevented the growth of the secondary, re-challenge transplant. The heat-generated therapeutic effect was more significant at a temperature of 43°C than either 41°C or 46°C. NPrCAP/M with AMF exposure, instead of control magnetite alone or without AMF exposure, resulted in the most significant growth inhibition of the re-challenge tumor and increased the life span of the mice. HSP70 production was greatest at 43°C compared to that with 41°C or 46°C. CD8+T cells were infiltrated at the site of the re-challenge melanoma transplant

Cytometrical analysis of the adverse effects of indican, indoxyl, indigo, and indirubin on rat thymic lymphocytes

Many businesses thrive by producing health supplements from agricultural products, as exemplified by the production of functional (or health) food using plants traditionally cultivated in the rural areas. Dyes, such as indican, indigo, indoxyl, and indirubin, present in dye plants, possess antibacterial, antifungal, and antiproliferative activities. However, these effects may also lead to cytotoxicity. Thus, studies in normal mammalian cells are necessary to identify cytotoxicity and prevent adverse effects of functional foods that contain these dyes. In this study, the effects of indican, indigo, indoxyl, and indirubin were evaluated by flow cytometry using appropriate fluorescent probes in rat thymic lymphocytes. Among the dyes analyzed, indirubin exerted distinct cellular activities. Treatment with indirubin (10–30 μM) increased the population of shrunken dead cells. The side scatter, but not forward scatter, increased in indirubin-treated living cells. It increased the population of annexin V-bound living and dead cells and that of dead cells without annexin V. Indirubin elevated intracellular Ca2+, but not Zn2+ levels. The cellular content of superoxide anions and increased glutathione decreased. Indirubin depolarized the cellular plasma and mitochondrial membranes. It did not potentiate or attenuate the cytotoxicity of A23187 (Ca2+ overload) and H2O2 (oxidative stress). The results suggested that indirubin induces both apoptotic and non-apoptotic cell death. It may be difficult to predict and prevent adverse effects of indirubin due to its diverse activities on normal mammalian cells. Therefore, indirubin should be removed from products that contain dye plant extracts

Herbig Ae/Be Stars in the Magellanic Bridge

We have found Herbig Ae/Be star candidates in the western region of the Magellanic Bridge. Using the near infrared camera SIRIUS and the 1.4 m telescope IRSF, we surveyed about 3.0 deg x 1.3 deg (24 deg < RA < 36 deg, -75 deg < Dec. < -73.7 deg) in the J, H, and Ks bands. On the basis of colors and magnitudes, about 200 Herbig Ae/Be star candidates are selected. Considering the contaminations by miscellaneous sources such as foreground stars and early-type dwarfs in the Magellanic Bridge, we estimate that about 80 (about 40%) of the candidates are likely to be Herbig Ae/Be stars. We also found one concentration of the candidates at the young star cluster NGC 796, strongly suggesting the existence of pre-main-sequence (PMS) stars in the Magellanic Bridge. This is the first detection of PMS star candidates in the Magellanic Bridge, and if they are genuine PMS stars, this could be direct evidence of recent star formation. However, the estimate of the number of Herbig Ae/Be stars depends on the fraction of classical Be stars, and thus a more precise determination of the Be star fraction or observations to differentiate between the Herbig Ae/Be stars and classical Be stars are required.Comment: 22 pages, 6 figures. Accepted for publication in Ap

腰部脊柱管狭窄症患者の脊椎アライメントと大腿四頭筋柔軟性の関係

Several studies have reported that the sagittal vertical axis（SVA）in patients with lumbar spinal stenosis（LSS）is associated with health-related quality of life（QOL）and low back pain. Therefore, it is required to obtain optimal standing spinal alignment. However, the functional factors that increase SVA in LSS patients have not been fully clarified. Therefore, the purpose of this study was to investigate correlations between quadriceps flexibility and spinal sagittal alignment in patients with lumbar spinal stenosis（LSS）. We studied 30 LSS patients（16 males, 14 females, age 65.6±12.1 years）. The quadriceps flexibility was evaluated by measuring the heel-to-buttock distance（HBD）, and the standing spine alignment was evaluated by measuring each parameter from the whole spinal column X-ray sagittal plane image. Each relationship was examined using Spearmanʼs rank correlation coefficient. HBD was positively correlated with SVA（r=0.45, p<0.05）and PT（r=0.39, p<0.05）, respectively. It was suggested that quadriceps flexibility was associated with SVA in LSS patients. In conclusion, improving quadriceps flexibility through preoperative physiotherapy intervention may result in good standing spinal alignment in LSS patients. Randomized controlled trials are needed to determine whether increased quadriceps flexibility in LSS patients improves SVA

N-Propionyl-Cysteaminylphenol-Magnetite Conjugate (NPrCAP/M) Is a Nanoparticle for the Targeted Growth Suppression of Melanoma Cells

A magnetite nanoparticle, NPrCAP/M, was produced for intracellular hyperthermia treatment of melanoma by conjugating N-propionyl-cysteaminylphenol (NPrCAP) with magnetite and used for the study of selective targeting and degradation of melanoma cells. NPrCAP/M, like NPrCAP, was integrated as a substrate in the oxidative reaction by mushroom tyrosinase. Melanoma, but not non-melanoma, cells incorporated larger amounts of iron than magnetite from NPrCAP/M. When mice bearing a B16F1 melanoma and a lymphoma on opposite flanks were given NPrCAP/M, iron was observed only in B16F1 melanoma cells and iron particles (NPrCAP/M) were identified within late-stage melanosomes by electron microscopy. When cells were treated with NPrCAP/M or magnetite and heated to 43°C by an external alternating magnetic field (AMF), melanoma cells were degraded 1.7- to 5.4-fold more significantly by NPrCAP/M than by magnetite. Growth of transplanted B16 melanoma was suppressed effectively by NPrCAP/M-mediated hyperthermia, suggesting a clinical application of NPrCAP/M to lesional therapy for melanoma. Finally, melanoma cells treated with NPrCAP/M plus AMF showed little sub-G1 fraction and no caspase 3 activation, suggesting that the NPrCAP/M-mediated hyperthermia induced non-apoptotic cell death. These results suggest that NPrCAP/M may be useful in targeted therapy for melanoma by inducing non-apoptotic cell death after appropriate heating by the AMF

Editorial: Conflicts

The Editorial Board reflects on the theme of 'conflict', as observed in the work published in this issue, and in the wider world

Newly Diagnosed Atrial Fibrillation in Acute Myocardial Infarction

[Background] It remains controversial whether long‐term clinical impact of newly diagnosed atrial fibrillation (AF) in the acute phase of acute myocardial infarction (AMI) is different from that of prior AF diagnosed before the onset of AMI. [Methods and Results] The current study population from the CREDO‐Kyoto AMI (Coronary Revascularization Demonstrating Outcome Study in Kyoto Acute Myocardial Infarction) Registry Wave‐2 consisted of 6228 patients with AMI who underwent percutaneous coronary intervention. The baseline characteristics and long‐term clinical outcomes were compared according to AF status (newly diagnosed AF: N=489 [7.9%], prior AF: N=589 [9.5%], and no AF: N=5150 [82.7%]). Median follow‐up duration was 5.5 years. Patients with newly diagnosed AF and prior AF had similar baseline characteristics with higher risk profile than those with no AF including older age and more comorbidities. The cumulative 5‐year incidence of all‐cause death was higher in newly diagnosed AF and prior AF than no AF (38.8%, 40.7%, and 18.7%, P<0.001). The adjusted hazard ratios (HRs) for mortality of newly diagnosed AF and prior AF relative to no AF remained significant with similar magnitude (HR, 1.31; 95% CI, 1.12–1.54; P<0.001, and HR, 1.32; 95% CI, 1.14–1.52; P<0.001, respectively). The cumulative 5‐year incidence of stroke decreased in the order of newly diagnosed AF, prior AF and no AF (15.5%, 12.9%, and 6.3%, respectively, P<0.001). The higher adjusted HRs of both newly diagnosed AF and prior AF relative to no AF were significant for stroke, with a greater risk of newly diagnosed AF than that of prior AF (HR, 2.05; 95% CI, 1.56–2.69; P<0.001, and HR, 1.33; 95% CI, 1.00–1.78; P=0.048, respectively). The higher stroke risk of newly diagnosed AF compared with prior AF was largely driven by the greater risk within 30 days. The higher adjusted HRs of newly diagnosed AF and prior AF relative to no AF were significant for heart failure hospitalization (HR, 1.73; 95% CI, 1.35–2.22; P<0.001, and HR, 2.23; 95% CI, 1.82–2.74; P<0.001, respectively) and major bleeding (HR, 1.46; 95% CI, 1.23–1.73; P<0.001, and HR, 1.36; 95% CI, 1.15–1.60; P<0.001, respectively). [Conclusions] Newly diagnosed AF in AMI had risks for mortality, heart failure hospitalization, and major bleeding higher than no AF, and comparable to prior AF. The risk of newly diagnosed AF for stroke might be higher than that of prior AF