エアフィルタアレイによる空気清浄化特性の評価とその応用

13301甲第5597号博士（工学）金沢大学博士論文本文Full 以下に掲載：Aerosol Science ＆ Technology 56 pp.767-774 2022. Taylor & Francis Group LLC. 共著者：Manabu Nishimura, Yajiao Liu, Masao Gen, Takafumi Seto, Yoshio Otan

Structural and Mechanical Properties of the Transparent Dentin Region in the Tooth Root

Dentin is altered in an age-related manner, such that transparent dentin in the tooth root forms during the aging process. Notably, fractures are more likely to occur in aged teeth. However, few studies have examined the mechanical properties of aged dentin. The purpose of this study was to investigate the structural and mechanical properties of the transparent dentin region, by analysis of the mineral density, using micro-computed tomography （micro-CT）, the tensile strength, and nanohardness to understand tooth fracture. As experimental samples, 10 caries-free, human molars were extracted from patients aged >50 years because of periodontal disease. As controls, bovine lower central incisors were extracted immediately after sacrifice from animals estimated at 2–2.5 years of age. Mineral density was quantified with X-ray micro-CT analysis of transparent human dentin and normal bovine dentin. Specimens were prepared from each tooth （human and bovine） and subjected to tensile strength testing; maximum load was used to calculate strength, and mean tensile strength of the specimens was calculated in each group. Finally, the nanohardness and Young’s modulus of intertubular dentin of the upper and apex root regions were investigated. All results were compared by paired Student’s t-test （α=0.05）. The mineral density of transparent dentin was significantly greater than that of normal dentin. Importantly, the tensile strength of the transparent regions was significantly lower than that of the normal regions, whereas the nanohardness and Young’s modulus of transparent intertubular dentin were significantly greater than those of normal intertubular dentin. Fractures of the teeth remain a major problem in clinical practice. Notably, transparent dentin is weaker than normal opaque dentin, which may explain the occurrence of apex root dentin fractures in aged individuals

Vaccination with EphA2-derived T cell-epitopes promotes immunity against both EphA2-expressing and EphA2-negative tumors

BACKGROUND: A novel tyrosine kinase receptor EphA2 is expressed at high levels in advanced and metastatic cancers. We examined whether vaccinations with synthetic mouse EphA2 (mEphA2)-derived peptides that serve as T cell epitopes could induce protective and therapeutic anti-tumor immunity. METHODS: C57BL/6 mice received subcutaneous (s.c.) vaccinations with bone marrow-derived dendritic cells (DCs) pulsed with synthetic peptides recognized by CD8+ (mEphA2(671–679), mEphA2(682–689)) and CD4+ (mEphA2(30–44)) T cells. Splenocytes (SPCs) were harvested from primed mice to assess the induction of cytotoxic T lymphocyte (CTL) responses against syngeneic glioma, sarcoma and melanoma cell lines. The ability of these vaccines to prevent or treat tumor (s.c. injected MCA205 sarcoma or B16 melanoma; i.v. injected B16-BL6) establishment/progression was then assessed. RESULTS: Immunization of C57BL/6 mice with mEphA2-derived peptides induced specific CTL responses in SPCs. Vaccination with mEPhA2 peptides, but not control ovalbumin (OVA) peptides, prevented the establishment or prevented the growth of EphA2+ or EphA2-negative syngeneic tumors in both s.c. and lung metastasis models. CONCLUSIONS: These data indicate that mEphA2 can serve as an attractive target against which to direct anti-tumor immunity. The ability of mEphA2 vaccines to impact EphA2-negative tumors such as the B16 melanoma may suggest that such beneficial immunity may be directed against alternative EphA2+ target cells, such as the tumor-associated vascular endothelial cells

1-year tolvaptan efficacy in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) develops into end-stage kidney disease by 65 years of age in an estimated 45%-70% of patients. Recent trials revealed that tolvaptan inhibits disease progression both in early-stage or late-stage ADPKD ; however, stratified analysis showed a difference of favorable factors correlated with tolvaptan efficacy between early-stage and late-stage ADPKD. Thus, we examined the efficacy of tolvaptan in ADPKD with a wide range of estimated glomerular filtration rates (eGFR). We enrolled 24 patients with eGFR 35.3 (28.0-65.5) ml / min / 1.73m2 and evaluated treatment effect as ΔΔeGFR (ml / min / 1.73m2 / year) or ΔΔtotal kidney volume (TKV) (% / year) that was calculated as post-treatment annual change - pre-treatment annual change. Pre ΔeGFR was significantly low in eGFR responders, defined as ΔΔeGFR > 0 ml / min / 1.73m2 / year. In eGFR responders, pre ΔeGFR, post ΔeGFR, eGFR, TKV, and proteinuria were significantly correlated with ΔΔeGFR. In TKV responders defined as ΔΔTKV > 5 % / year, we identified hypertension history, proteinuria, TKV, and post ΔTKV as significantly correlated factors with ΔΔTKV. In conclusion, pre ΔeGFR may be a predictive factor of therapeutic efficacy on kidney function. Tolvaptan may have greater efficacy in early-stage ADPKD with rapid GFR decline or with well-controlled blood pressure

Differences in serum IL-6 response after 1°C rise in core body temperature in individuals with spinal cord injury and cervical spinal cord injury during local heat stress

Objectives: Passive rise in core body temperature achieved by head-out hot water immersion (HHWI) results in acute increases in serum interleukin (IL)-6 but no change in plasma adrenaline in patients with cervical spinal cord injury (CSCI). The purpose of the present study was to determine the mechanism of heat stress-induced increase in serum IL-6. Setting: A cross-sectional study. Methods: The study subjects were 9 with CSCI, 10 with thoracic and lumbar spinal cord injury (TLSCI) and 8 able-bodied (AB) subjects. Time since injury was 16.4±4.1 years in TLSCI and 16.1±3.4 years in CSCI. Subjects were subjected to lower-body heat stress (LBH) by wearing a hot water-perfused suit until 1°C increase in core temperature. The levels of serum IL-6, plasma adrenaline, tumor necrosis factor (TNF)-α, C-reactive protein (CRP), and counts of blood cells were measured at normothermia and after LBH. Results: Serum IL-6 concentrations increased significantly immediately after LBH in all the three groups. ΔIL-6% was lower in CSCI subjects compared with AB subjects. Plasma adrenaline concentrations significantly increased after LBH in AB and TLSCI subjects, but did not change throughout the study in CSCI subjects. Cardiac output and heart rate increased at the end of LBH in all three groups. Conclusion: Under a similar increase in core temperature, ΔIL-6% was lower in the CSCI group compared with the AB group. These findings suggest that the observed rise in IL-6 during hyperthermia is mediated, at least in part, by plasma adrenaline

Alterations in 18F-FDG accumulation into neck-related muscles after neck dissection for patients with oral cancers

Background: 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) accumulations are commonly seen in the neck-related muscles of the surgical and non-surgical sides after surgery with neck dissection (ND) for oral cancers, which leads to radiologists having difficulty in diagnosing the lesions. To examine the alterations in 18 F-FDG accumulation in neck-related muscles of patients after ND for oral cancer. Material and Methods: 18 F-FDG accumulations on positron emission tomography (PET)-computed tomography (CT) in neck-related muscles were retrospectively analyzed after surgical dissection of cervical lymph nodes in oral cancers. Results: According to the extent of ND of cervical lymph nodes, the rate of patients with 18 F-FDG-PET-positive areas increased in the trapezius, sternocleidomastoid, and posterior neck muscles of the surgical and/or non-surgical sides. In addition, SUVmax of 18 F-FDG-PET-positive areas in the trapezius and sternocleidomastoid muscles were increased according to the extent of the ND. Conclusions: In evaluating 18 F-FDG accumulations after ND for oral cancers, we should pay attention to the 18 F-FDG distributions in neck-related muscles including the non-surgical side as false-positive finding

Success of Crizotinib Combined with Whole-Brain Radiotherapy for Brain Metastases in a Patient with Anaplastic Lymphoma Kinase Rearrangement-Positive Non-Small-Cell Lung Cancer

Although crizotinib shows marked antitumor activity in anaplastic lymphoma kinase (ALK) rearrangement-positive non-small-cell lung cancer (NSCLC) patients, all treated patients ultimately develop resistance to this drug. Isolated central nervous system failure without progression at extracranial sites is a common progression pattern in ALK rearrangement-positive NSCLC patients treated with crizotinib. Here, we report the success of crizotinib combined with whole-brain radiotherapy in an ALK rearrangement-positive NSCLC patient who developed leptomeningeal carcinomatosis and progression of multiple brain metastases. Additionally, we focused on the mechanism involved by examining the plasma and cerebrospinal fluid concentrations of crizotinib in the present case

A randomized phase III study of short-course radiotherapy combined with Temozolomide in elderly patients with newly diagnosed glioblastoma; Japan clinical oncology group study JCOG1910 (AgedGlio-PIII)

BACKGROUND: The current standard treatment for elderly patients with newly diagnosed glioblastoma is surgery followed by short-course radiotherapy with temozolomide. In recent studies, 40 Gy in 15 fractions vs. 60 Gy in 30 fractions, 34 Gy in 10 fractions vs. 60 Gy in 30 fractions, and 40 Gy in 15 fractions vs. 25 Gy in 5 fractions have been reported as non-inferior. The addition of temozolomide increased the survival benefit of radiotherapy with 40 Gy in 15 fractions. However, the optimal regimen for radiotherapy plus concomitant temozolomide remains unresolved. METHODS: This multi-institutional randomized phase III trial was commenced to confirm the non-inferiority of radiotherapy comprising 25 Gy in 5 fractions with concomitant (150 mg/m2/day, 5 days) and adjuvant temozolomide over 40 Gy in 15 fractions with concomitant (75 mg/m2/day, every day from first to last day of radiation) and adjuvant temozolomide in terms of overall survival (OS) in elderly patients with newly diagnosed glioblastoma. A total of 270 patients will be accrued from 51 Japanese institutions in 4 years and follow-up will last 2 years. Patients 71 years of age or older, or 71-75 years old with resection of less than 90% of the contrast-enhanced region, will be registered and randomly assigned to each group with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in April 2020. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in August 2020. DISCUSSION: If the primary endpoint is met, short-course radiotherapy comprising 25 Gy in 5 fractions with concomitant and adjuvant temozolomide will be a standard of care for elderly patients with newly diagnosed glioblastoma. TRIAL REGISTRATION: Registry number: jRCTs031200099 . Date of Registration: 27/Aug/2020. Date of First Participant Enrollment: 4/Sep/2020

Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract

<p>Abstract</p> <p>Background</p> <p>To assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise.</p> <p>Methods</p> <p>We quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan.</p> <p>Results</p> <p>The median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm³(range, 7.17 - 14.3 cm³) and 1.99 for pituitary adenoma, and 6.86 cm³(range 6.05 - 14.6 cm³) and 2.41 for meningioma. PTV volume was 10.1 ± 1.74 cm³for group 1 with a margin of 1 -2 mm around the CTV (n = 3) and 9.28 ± 1.8 cm³(p = 0.51) for group 2 with no margin (n = 7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1 ± 3.26 cm³) than group 2 (6.91 ± 0.7 cm³, p = 0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring.</p> <p>Conclusion</p> <p>Quality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.</p