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109
result(s) for
"Takagi, Shinsuke"
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Effects of Clay Nanosheets on the Photostability of Cationic Porphyrin
by
Kyosuke Arakawa
,
Tetsuya Shimada
,
Yugo Hirade
in
absorption spectroscopy
,
Adsorption
,
Chemical reactions
2024
The photodecomposition behavior of cationic porphyrin ZnTMAP4+ (zinc tetrakis-(N,N,N-trimethylanilinium-4-yl) porphyrin) in water and complexed with clay nanosheets was investigated by light irradiation to the Soret band of ZnTMAP4+. The decomposition of ZnTMAP4+ was observed by UV–visible absorption spectroscopy. While the decomposition quantum yield (ϕdec) was 3.4 × 10−4 in water, that was 9.4 × 10−7 on the exfoliated clay nanosheets. It was revealed that the photostability of ZnTMAP4+ was stabilized by the complex formation with clay. When ZnTMAP4+ was intercalated between the stacked clay nanosheets, ϕdec was further decreased to 4.9 × 10−7. The photostability increased by 361 times and 693 times for the exfoliated and stacked state, respectively. These results indicate that the flat clay surface has the potential to control intra- and intermolecular photochemical reactions.
Journal Article
Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML
by
Ishikawa, Fumihiko
,
Wake, Atsushi
,
Takagi, Shinsuke
in
631/61/2320
,
631/67/71
,
692/699/67/1990/283/1897
2010
In acute myeloid leukemia, a sub-population of quiescent cancer cells, called leukemia stem cells, is thought to be responsible for chemotherapy resistance and eventual recurrence of the disease. Saito
et al
. show that treatment with granulocyte colony-stimulating factor can overcome resistance to standard therapy by inducing cell cycle entry of the leukemia stem cells.
Cancer stem cells have been proposed to be important for initiation, maintenance and recurrence of various malignancies, including acute myeloid leukemia (AML)
1
,
2
,
3
. We have previously reported
4
that CD34
+
CD38
−
human primary AML stem cells residing in the endosteal region of the bone marrow are relatively chemotherapy resistant. Using a NOD/SCID/IL2rγ
null
mouse model of human AML, we now show that the AML stem cells in the endosteal region are cell cycle quiescent and that these stem cells can be induced to enter the cell cycle by treatment with granulocyte colony-stimulating factor (G-CSF). In combination with cell cycle-dependent chemotherapy, G-CSF treatment significantly enhances induction of apoptosis and elimination of human primary AML stem cells
in vivo
. The combination therapy leads to significantly increased survival of secondary recipients after transplantation of leukemia cells compared with chemotherapy alone.
Journal Article
Clinical characteristics and drug susceptibility patterns of Corynebacterium species in bacteremic patients with hematological disorders
by
Abe, Masahiro
,
Kimura Muneyoshi
,
Otsuka Yoshihito
in
Amides
,
Antibiotics
,
Antiinfectives and antibacterials
2021
The aim of this study was to clarify the clinical and microbiological characteristics of Corynebacterium bacteremia in hematological patients. We retrospectively reviewed the medical records of patients with Corynebacterium bacteremia from April 2013 to June 2018. The causative Corynebacterium species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Drug susceptibility tests were performed using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. In total, 147 cases of Corynebacterium bacteremia were identified during the study period. Corynebacterium striatum was the most frequent pathogen. Catheter-related bloodstream infection was diagnosed in 19.7% of all patients, and moderate/severe oral or severe gastrointestinal mucosal impairment was detected in 19.7%. Polymicrobial infection was found in about 20% of cases, with Enterococcus faecium being the most frequent isolate. The overall 30-day mortality was 34.7% (51/147). Multivariate analysis showed that E. faecium co-infection (odds ratio (OR) 9.3; 95% confidence interval (CI) 2.1–40), systemic corticosteroids (OR 3.6; 95% CI 1.4–8.9), other immunosuppressive drugs (OR 0.32; 95% CI 0.13–0.76), and a Pitt bacteremia score ≥4 (OR 12; 95% CI 3.9–40) were significant risk factors for overall 30-day mortality. The drug susceptibility rates for beta-lactam antimicrobial agents were quite low. All isolates were susceptible to glycopeptides and linezolid. However, some C. striatum isolates were resistant to daptomycin. Corynebacterium bacteremia can occur in the presence of several types of mucosal impairment. Our drug susceptibility data indicate that Corynebacterium bacteremia in hematological patients could be treated by glycopeptides or linezolid.
Journal Article
The impact of graft cell source on bloodstream infection in the first 100 days after allogeneic hematopoietic cell transplantation
2021
Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0–46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40–2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14–2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.
Journal Article
Differential impact of allogeneic stem-cell transplantation on large B-cell lymphomas and peripheral T-cell lymphomas
by
Asano-Mori, Yuki
,
Yamamoto, Go
,
Wake, Atsushi
in
Allogeneic stem cell transplantation
,
Cord blood transplantation
,
Graft versus host disease
2026
Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one of the standard treatments for relapsed/refractory (r/r) non-Hodgkin lymphoma, but benefits across large B-cell lymphoma (LBCL) and nodal peripheral T-cell lymphoma (PTCL) subtypes remain unclear. This single-center retrospective study evaluated outcomes after the first allo-HSCT in 92 adults with r/r aggressive lymphoma (59 and 33 patients with LBCLs and PTCLs, respectively) treated during 2011–2023. The patients’ median age was 51 years; 58.7% had active disease at transplant, and 77.2% received cord blood grafts. With a median follow-up of 7.6 years among survivors, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 31.6% and 27.9%, respectively. Furthermore, the non-relapse mortality (NRM) and relapse/progression rates were 30.8% and 41.3%, respectively. Compared with patients with LBCLs, those with PTCLs showed superior 5-year outcomes (OS: 47.7% vs. 22.4%,
P
= 0.03; PFS: 39.7% vs. 21.0%,
P
= 0.04) and lower relapse rates (26.9% vs. 49.5%,
P
= 0.02), with similar NRM and acute graft-versus-host disease rates. Multivariable models showed that PTCL histology was an independent predictor of improved OS and PFS. These findings suggest that allo-HSCT confers greater long-term benefits in patients with PTCL, supporting its role as an effective option in this subgroup.
Journal Article
Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis
2021
The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum β-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.
Journal Article
CXCR4 induces memory formation over exhaustion in CAR-T cells to achieve durable leukemia targeting
2026
Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of B-cell malignancies, but its success in acute myeloid leukemia (AML) remains limited. Durable responses depend on the formation of long-lived memory T cells, whereas T cell exhaustion contributes to non-response and relapse. In patients with AML who achieved remission after cord blood transplantation, we here first observe enrichment of memory T cells with high expression of the chemokine receptor CXCR4. Next, we show that engineering CAR-T cells to co-express CXCR4 enhances their persistence and anti-leukemic activity in patient-derived xenograft models. Using single-cell profiling and metabolic analysis, we find that CXCR4 promotes memory-associated transcriptional programs, reduces exhaustion, and supports oxidative metabolism. These effects are observed with CAR-T cells targeting CD25 or CD96 as AML-associated targets. Our results indicate that CXCR4 strengthens CAR-T cell memory and durability, offering a strategy to improve immunotherapy outcomes in AML and beyond.
CAR-T cell efficacy is often limited by the inability to maintain a memory T cell program. Here, the authors show that intrinsic CXCR4 expression enhances CAR-T cell persistence and memory differentiation in acute myeloid leukemia.
Journal Article
Clinical and microbiological characteristics of bacterial meningitis in umbilical cord blood transplantation recipients
2022
Bacterial meningitis is a rare but severe infectious complication after hematopoietic stem cell transplantation. However, its clinical features were previously not clear. We reviewed the cases of 7 patients diagnosed with bacterial meningitis with a positive cerebrospinal fluid culture among 1147 patients who underwent cord blood transplantation (CBT) at our institution between September 2007 and September 2020. The diagnosis was made on day + 5– + 45, and 5 patients developed bacterial meningitis before neutrophil engraftment. The causative organisms were all Gram-positive cocci: Enterococcus faecium and Enterococcus gallinarum (2 patients each), and Staphylococcus haemolyticus, Streptococcus mitis/oralis, and Rothia mucilaginosa (1 patient each). Six patients developed bacterial meningitis secondary to prior or concomitant bacteremia caused by the same bacterium. Five patients had received anti-MRSA agents at onset: vancomycin in 3, teicoplanin in 1, and daptomycin in 1. After diagnosis of bacterial meningitis, linezolid was eventually used for 6 patients. Two patients with E. gallinarum were alive at day + 1380 and + 157 after CBT, respectively, whereas 5 patients died 17–53 (median 43) days after the onset of bacterial meningitis. Breakthrough meningitis in CBT can occur even during the use of anti-MRSA drugs, and intensive antibiotic treatment is necessary.
Journal Article
Preparation and Catalytic Properties of Gold Single‐Atom and Cluster Catalysts Utilizing Nanoparticulate Mg‐Al Layered Double Hydroxides
by
Nakayama, Akihiro
,
Sakaguchi, Norihito
,
Aono, Chika
in
Alcohol oxidation
,
Au cluster
,
Au single atom
2025
Au single atoms and clusters were stabilized on Mg−Al layered double hydroxide nanoparticles (LDH NPs), and the obtained Au@LDH NPs were supported on SiO2 and CeO2. After hydrogen reduction, Au single atoms were found together with Au clusters on LDH/SiO2. In contrast to Au single‐atom catalysts which are deposited in metal vacancies of oxide supports, the LDH NPs stabilize very small Au species despite the absence of metal vacancies. The obtained Au(0)@LDH/SiO2 catalyzed aerobic oxidation of alcohols, and Au single atoms maintained after the reaction. Given that only Au NPs were observed on bulk LDH, the abundant surface OH group of LDH NPs would contribute to stabilize Au, resulting in higher activity than Au/LDH‐bulk. After calcination to transform LDH to mixed metal oxide (MMO), the obtained Au(0)@MMO/SiO2 also exhibited high catalytic activity. Moreover, Au(0)@LDH/CeO2 exhibited higher activity and excellent selectivity for hydrogenation of 4‐nitrostyrene to 4‐aminostyrene than conventional Au catalysts such as Au/CeO2 and Au/TiO2. We demonstrated that Au size can be minimized using LDH NPs, exhibiting high catalytic performance. The basic surface OH groups of LDH would be also beneficial for deprotonation of alcohols and heterolytic dissociation of H2 in the catalytic reactions. Au single atoms and clusters were stabilized on Mg−Al layered double hydroxide nanoparticles (LDH NPs) supported on SiO2 and CeO2. The catalysts exhibited excellent activity for aerobic oxidation of alcohols and selective hydrogenation of 4‐nitrostyrene to 4‐aminostyrene. The surface OH groups of LDH NPs worked efficiently for both stabilizing Au and for the catalytic reactions as basic sites.
Journal Article