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22
result(s) for
"Ishihara, Hiromasa"
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Head and Neck Cancer Immunotherapy: Overcoming Limitations and Enhancing Efficacy
by
Shibata, Hirofumi
,
Kuroki, Masashi
,
Ishihara, Hiromasa
in
Antigens
,
Cancer immunotherapy
,
Cancer therapies
2025
Head and neck cancers (HNCs) are a heterogeneous group of malignancies, including head and neck squamous cell carcinoma (HNSCC), thyroid carcinoma, and salivary gland carcinoma. Despite multidisciplinary treatment approaches, outcomes for advanced HNCs remain poor. Among these, HNSCC has been the most extensively studied in the field of immunotherapy. Immune checkpoint inhibitors (ICIs), particularly anti‐PD‐1 antibodies, have demonstrated survival benefits in R/M HNSCC, but response rates remain modest at 15%–20%, highlighting the need for more effective strategies. Recent advances include the use of neoadjuvant and adjuvant immunotherapy in locally advanced HNSCC, which may improve pathological response rates and long‐term survival. Additionally, novel immunotherapeutic approaches such as tumor antigen‐targeted cancer vaccines and T‐cell receptor‐engineered T‐cell (TCR‐T) therapy are emerging. These strategies aim to enhance tumor‐specific immunity, especially in tumors lacking targetable driver mutations. The tumor microenvironment (TME) in HNSCC plays a pivotal role in modulating immune response and therapeutic efficacy. Immunomodulatory agents such as HDAC inhibitors, TLR agonists, and VEGF inhibitors have shown promise in enhancing ICI responsiveness by altering the immunosuppressive TME. Moreover, the identification of predictive biomarkers, including PD‐L1 expression, tumor mutational burden, and tertiary lymphoid structures, is crucial for patient selection and response prediction. This review provides a comprehensive overview of the current landscape and future directions of immunotherapy for HNCs, with a particular focus on HNSCC. We highlight ongoing clinical challenges and discuss emerging strategies aimed at overcoming resistance and improving clinical outcomes. ICI‐included therapies are standard for R/M HNSCC patients. In particular, neoadjuvant ICI therapy shows promising clinical results even in nontreated resectable HNSCC patients. In addition, cancer vaccine, immune cell‐based therapy, immunomodulation therapy, and TME targeting therapy may combine with ICI.
Journal Article
Changes in serum DAMPs and cytokines/chemokines during near‐infrared photoimmunotherapy for patients with head and neck cancer
2024
Background Near‐infrared photoimmunotherapy (NIR‐PIT) for head and neck cancer is a recently developed therapy. However, there is limited data on patients receiving NIR‐PIT in real clinical settings. Methods Seven NIR‐PIT sessions were administered to five patients with head and neck squamous cell carcinoma (HNSCC). Serum damage‐associated molecular patterns (DAMPs) (HMGB1 and Hsp70 levels), and cytokine and chemokine production, were compared before and after NIR‐PIT. Results The serum concentration of HMGB1 increased after NIR‐PIT (p = 0.031, Wilcoxon test) in all patients except one who did not achieve a clinical response. Chemokines MIP‐1α (CCL3) and MIP‐1β (CCL4) increased significantly 1–3 days after treatment (CCL3, p = 0.0036; CCL4, p = 0.0016, Wilcoxon test). A low pre‐treatment neutrophil‐to‐lymphocyte ratio (NLR) was associated with a better response to therapy and survival. Conclusions The release of DAMPs, and cytokine/chemokine production, were detected in the patients' peripheral blood. The baseline NLR may predict patient outcomes in response to NIR‐PIT.
Journal Article
Clinical Impact of Nivolumab in Sinonasal Mucosal Melanoma: A 14-Year Single-Center Retrospective Study and Comprehensive Literature Review
2026
Background: Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy often resected with postoperative irradiation, with some evidence supporting the use of immune checkpoint inhibitors (ICIs). This study explores the potential efficacy and safety of nivolumab in 16 patients with SNMM, and reviews the literature of ICI use in it. Methods: We retrospectively analyzed 16 patients who had pathologically confirmed SNMM treated at Gifu University Hospital over a 14-year period between 2010 and 2024, of whom 11 received nivolumab. Clinical characteristics, treatment modalities, immune-related adverse events (irAEs), progression-free survival (PFS), and overall survival (OS) were examined. Kaplan–Meier and log-rank tests were used for survival analysis. A comprehensive literature review was done regarding ICI in SNMM. Results: Among the 16 patients, 11 received nivolumab and five did not. The nivolumab group showed longer median survival (median OS 26 mo vs. 8 mo; p = 0.00056) and a median PFS of 13 mo vs. 3 mo, p = 0.00175. In recurrent cases, nivolumab was associated with longer median OS (23 mo vs. 9 mo, p = 0.015) and PFS (11 mo vs. 3 mo, p = 0.019). irAEs occurred in four out of eleven of these cases, leading to nivolumab discontinuation; however, three of these four patients maintained durable disease control. A literature review identified generally favorable outcomes for ICIs in SNMM, although results were varied due to small sample sizes and heterogeneous treatment settings. Conclusions: Nivolumab was associated with longer survival in this small cohort in patients with SNMM, including those who discontinued therapy due to irAEs. Our data supports recent meta-analyses demonstrating a benefit of ICIs in SNMM.
Journal Article
MRI findings of epithelial–myoepithelial carcinoma of the parotid gland with radiologic–pathologic correlation
by
Kobayashi, Kazuhiro
,
Miyazaki, Tatsuhiko
,
Matsuo, Masayuki
in
Carcinoma
,
Diffusion coefficient
,
Exocrine glands
2022
PurposeThis study aimed to describe the MRI findings of epithelial-myoepithelial carcinoma (EMC) of the parotid gland.Materials and methodsSeven patients (four males and three females) aged 40–86 years (mean age, 64 years) with histologically proven EMC of the parotid gland who underwent surgical resection after preoperative MRI were enrolled. MRI images were retrospectively reviewed and contrasted with pathological findings.ResultsFive patients (71%) had predominantly solid lesions, and two (29%) had predominantly cystic lesions. All seven lesions had well-demarcated margins and capsules without the invasion of adjacent structures. The capsules were incomplete in five lesions (71%) and complete in two (29%). Four lesions (57%) exhibited a multinodular structure with internal septa. Cystic components were observed in three lesions (43%). On T1-weighted images, the solid components were frequently homogeneous (5/7, 71%), and demonstrated isointensity in five lesions (71%) and hypointensity in two (29%) relative to the spinal cord. On T2-weighted images, the solid components were usually heterogeneous (6/7, 86%), and demonstrated hyperintensity in five lesions (71%) and isointensity in two (29%) relative to the spinal cord. The mean apparent diffusion coefficient value of the solid components was 0.967 × 10−3 mm2/s.ConclusionParotid gland EMCs usually appeared as predominantly solid lesions with well-demarcated margins and capsules. A multinodular structure with internal septa was characteristics of EMCs.
Journal Article
Efficacy of optical frequency domain imaging in detecting peripheral artery disease: the result of a multi-center, open-label, single-arm study
by
Nakano, Shinsuke
,
Shite, Junya
,
Kawamori, Hiroyuki
in
Adverse events
,
Angioplasty
,
Biomedical Engineering and Bioengineering
2021
Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (
p
= 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practice
Trial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025,
https://jrct.niph.go.jp/latest-detail/jRCT2052190025
).
Journal Article
Elevation of pro-inflammatory cytokine levels following anti-resorptive drug treatment is required for osteonecrosis development in infectious osteomyelitis
2017
Various conditions, including bacterial infection, can promote osteonecrosis. For example, following invasive dental therapy with anti-bone resorptive agents, some patients develop osteonecrosis in the jaw; however, pathological mechanisms underlying these outcomes remain unknown. Here, we show that administration of anti-resorptive agents such as the bisphosphonate alendronate accelerates osteonecrosis promoted by infectious osteomyelitis. Potent suppression of bone turnover by these types of agents is considered critical for osteonecrosis development; however, using mouse models we found that acceleration of bone turnover by teriparatide injection did not prevent osteonecrosis but rather converted osteoclast progenitors to macrophages expressing inflammatory cytokines, which were required for osteonecrosis development. In fact, we demonstrate that TNFα-, IL-1α/β- or IL-6-deficient mice as well as wild-type mice administered a TNFα-inhibitor were significantly resistant to development of osteonecrosis accompanying infectious myelitis, even under bisphosphonate treatment. Our data provide new insight into mechanisms underlying osteonecrosis and suggest new ways to prevent it.
Journal Article
Protein intake in inhabitants with regular exercise is associated with sleep quality: Results of the Shika study
2021
Although associations between sleep quality and environmental factors and nutrient intake have been reported, interactions between these factors have not been elucidated in detail. Therefore, this cross-sectional study examined the effects of regular exercise and nutrient intake on sleep quality using the Pittsburgh Sleep Quality Index (PSQI), which is the most frequently used index for sleep evaluation.
The participants included 378 individuals aged 40 years or older living in Shika Town, Ishikawa Prefecture. Of these individuals, 185 met the inclusion criteria. The participants completed a self-administered questionnaire assessing lifestyle habits and frequency and duration of exercise, the PSQI, and the brief-type self-administered diet history questionnaire (BDHQ) on nutrient intake.
A two-way analysis of covariance on regular exercise and PSQI scores indicated that protein intake (17.13% of energy) was significantly higher in the regular exercise and PSQI ≤10 groups than in the non-regular exercise or PSQI ≥11 groups (p = 0.002). In a multiple logistic regression analysis with PSQI scores (≤10 and ≥11), protein intake was a significant independent variable in any of the models adjusted for confounding factors such as age, sex, body mass index, current smoker, and current drinker (OR: 1.357, 95% CI: 1.081, 1.704, p = 0.009) in the regular exercise group but not in the non-regular exercise group.Conclusions We identified a positive relationship between sleep quality and protein intake in the regular exercise group. These findings suggest that regular exercise at least twice a week for 30 minutes or longer combined with high protein intake contributes to good sleep quality.
Journal Article
Current Distribution Characteristics on Transposed Four-Parallel Conductors in Three-phase REBCO Armature Coils under Rotating Magnetic Field
by
Inoue, Tomohiro
,
Kimura, Yudai
,
Yoshida, Kohei
in
Alternating current
,
Conductors
,
Critical current (superconductivity)
2026
The armature of a fully superconducting synchronous motor for electric aircraft requires a current capacity exceeding the critical current of a single REBa2Cu3Oy superconducting tape. Therefore, the armature coils must be composed of multi-tape parallel conductors. In parallel conductors, inductance imbalance among tapes can lead to nonuniform current distribution. To address this issue, transposition techniques that change the stacking order of tapes during winding have been proposed to achieve uniform current distribution. Previous studies proposed the concept of uniform current between groups (CUCG), the transposition concept applicable to 2n (n = 1, 2, 3 and so on) parallel conductors. In an actual motor environment, circulating currents induced by the magnetic field of rotor were found to significantly influence current distribution. The previously proposed transposition structure does not take this effect into account. In this study, the transposition structure based on CUCG was modified to suppress both tape inductance imbalance and circulating currents. Experimental results confirmed that the inductance balance among tapes is achieved under three-phase AC excitation. Furthermore, the analytical results confirmed that a uniform current is shared even during field rotation. This indicates the potential effectiveness of the proposed transposition structure in practical motor environments.
Journal Article
Long-term outcome and chimerism in patients with Wiskott–Aldrich syndrome treated by hematopoietic cell transplantation: a retrospective nationwide survey
2019
We analyzed the outcomes of allogeneic stem cell transplantation (SCT) and risk factors for chimerism in 108 patients with Wiskott–Aldrich syndrome (WAS) who were registered with The Japan Society for Hematopoietic Cell Transplantation between January 1985 and December 2016. A preparative conditioning regimen consisting of myeloablative conditioning (MAC) was provided to 76 patients, and reduced-intensity conditioning was provided to 30 patients. Fifty-one patients received prophylaxis against graft-versus-host disease (GVHD) with cyclosporine, and 51 patients received tacrolimus (Tac). Chimerism analyses had been performed in 91 patients. Neutrophil engraftment was achieved in 91 patients (84.3%). The engraftment rate was significantly higher in patients who received Tac for GVHD prophylaxis (p = 0.028). Overall survival rate (OS) was significantly higher in patients with complete chimerism than in patients with mixed chimerism (88.2 ± 6.1% and 66.7 ± 9.9%, respectively, p = 0.003). Multivariate analysis showed that the rate of complete chimerism in patients who received MAC including cyclophosphamide (CY) at a dose of 200 mg/kg was significantly higher (p = 0.021) than that in patients who received other conditioning. Thus, MAC including CY at a dose of 200 mg/kg and Tac for GVHD prophylaxis were optimal conditions of SCT for patients with WAS under existing study.
Journal Article
Vericiguat and hypotension in patients with heart failure and reduced ejection fraction: VERIFY-HF registry
2026
•This study investigated the associations between patient characteristics, hypotension, and outcomes after initiating vericiguat in patients with heart failure and reduced ejection fraction (HFrEF).•Although symptomatic or asymptomatic hypotension was relatively common within 90 days of starting vericiguat (25.3%), drug discontinuation due to hypotension was infrequent (only 4.4%), suggesting that these complications might not be mainly attributable to vericiguat.•Patients experiencing hypotension had a greater subsequent risk of HF outcomes, but this association likely reflect their baseline vulnerability.
Real-world characteristics and outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. We investigated patient characteristics, hypotension—the most relevant clinical event—, and outcomes after initiating vericiguat in patients with HFrEF.
In this nationwide, multicentre retrospective study involving 22 hospitals in Japan, we examined symptomatic or asymptomatic hypotension and drug discontinuation within 90 days after initiation of vericiguat in patients with left ventricular ejection fraction <45%. The association between hypotension and HF outcomes was also examined.
Among the 799 patients with HFrEF, the mean age was 69.6 years, and 218 (27.3%) were female. Of them, 316 (39.5%) had New York Heart Association classification III or IV, and 329 (41.8%) had systolic blood pressure (sBP) <100 mm Hg. Hypotension was observed in 25.3% of patients within 90 days, with asymptomatic hypotension being the most common (17.9%). By contrast, drug discontinuation related to hypotension was less frequent (4.4%). After adjustment, sBP <100 mm Hg, low body mass index, and in-hospital vericiguat initiation were associated with the incidence of hypotension within 90 days. Patients who experienced hypotension had a greater risk of cardiovascular death or HF hospitalization than those who did not (P = .01).
Although hypotension was relatively common soon after starting vericiguat, they were not often associated with drug discontinuation. Patients experiencing hypotension had a greater risk of HF outcomes, but this would be primarily associated with their vulnerability, given the infrequent discontinuation.
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Journal Article