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1.
Clin Radiol ; 79(6): 453-459, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38614869

ABSTRACT

AIM: To evaluate whether deep learning reconstruction (DLR) can accelerate the acquisition of magnetic resonance imaging (MRI) sequences of the knee for clinical use. MATERIALS AND METHODS: Using a 1.5-T MRI scanner, sagittal fat-suppressed T2-weighted imaging (fs-T2WI), coronal proton density-weighted imaging (PDWI), and coronal T1-weighted imaging (T1WI) were performed. DLR was applied to images with a number of signal averages (NSA) of 1 to obtain 1DLR images. Then 1NSA, 1DLR, and 4NSA images were compared subjectively, and by noise (standard deviation of intra-articular water or medial meniscus) and contrast-to-noise ratio between two anatomical structures or between an anatomical structure and intra-articular water. RESULTS: Twenty-seven healthy volunteers (age: 40.6 ± 11.9 years) were enrolled. Three 1DLR image sequences were obtained within 200 s (approximately 12 minutes for 4NSA image). According to objective evaluations, PDWI 1DLR images showed the smallest noise and significantly higher contrast than 1NSA and 4NSA images. For fs-T2WI, smaller noise and higher contrast were observed in the order of 4NSA, 1DLR, and 1NSA images. According to the subjective analysis, structure visibility, image noise, and overall image quality were significantly better for PDWI 1DLR than 1NSA images; moreover, the visibility of the meniscus and bone, image noise, and overall image quality were significantly better for 1DLR than 4NSA images. Fs-T2WI and T1WI 1DLR images showed no difference between 1DLR and 4NSA images. CONCLUSION: Compared to PDWI 4NSA images, PDWI 1DLR images were of higher quality, while the quality of fs-T2WI and T1WI 1DLR images was similar to that of 4NSA images.


Subject(s)
Deep Learning , Knee Joint , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Male , Adult , Female , Knee Joint/diagnostic imaging , Knee Joint/anatomy & histology , Healthy Volunteers , Middle Aged , Signal-To-Noise Ratio , Image Interpretation, Computer-Assisted/methods
3.
Nat Commun ; 13(1): 7193, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36424384

ABSTRACT

The dynamics of a nuclear open quantum system could be revealed in the correlations between the breakup fragments of halo nuclei. The breakup mechanism of a proton halo nuclear system is of particular interest as the Coulomb polarization may play an important role, which, however, remains an open question. Here we use a highly efficient silicon detector array and measure the correlations between the breakup fragments of 8B incident on 120Sn at near-barrier energies. The energy and angular correlations can be explained by a fully quantum mechanical method based on the state-of-the-art continuum discretized coupled channel calculations. The results indicate that, compared to the neutron halo nucleus 6He, 8B presents distinctive reaction dynamics: the dominance of the elastic breakup. This breakup occurs mainly via the short-lived continuum states, almost exhausts the 7Be yield, indicating the effect of Coulomb polarization on the proton halo state. The correlation information reveals that the prompt breakup mechanism dominates, occurring predominantly on the outgoing trajectory. We also show that, as a large environment, the continuum of 8B breakup may not significantly influence elastic scattering and complete fusion.

4.
Rev Sci Instrum ; 93(2): 023301, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35232164

ABSTRACT

In high-frequency pulsed magnets, such as kickers in particle accelerators, it is essential to reduce eddy currents that could be induced in the magnet core during excitation not to distort and attenuate the magnetic field pulse. A novel iron lamination scheme with additional interlaminar insulation is proposed for the magnet core of such pulsed magnets. A laminated steel sheet core is formed by alternately stacking thin steel and insulation sheets. For application to matched kicker magnets for accelerators, test magnets with the new and conventional iron lamination were designed, assembled, and extensively evaluated. The pulsed magnetic field waveforms of two test magnets with the new lamination successfully matched to below 0.1% over the entire pulse duration, which was significantly better than those with the conventional lamination. Among the applications of the developed high-frequency pulsed magnets, beam injection kickers for the coming next generation light sources and future colliders, where suppression of the transient stored-beam oscillation during beam injection is crucial, are considered to be promising.

5.
Int J Oral Maxillofac Surg ; 51(10): 1264-1272, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35125267

ABSTRACT

The aim of this study was to evaluate the therapeutic efficacy and safety of proton beam therapy combined with retrograde intra-arterial infusion chemotherapy in elderly patients with locally advanced oral cancer. Between February 2009 and October 2019, 42 oral cancer patients aged ≥75 years were treated with this therapy. Median age was 80 years (range 75-90 years) and the median follow-up duration was 39 months (range 2-106 months). Of the 42 patients, 34 (81%) were diagnosed with stage IV cancer. The 3-year overall survival, local control, progression-free survival, and disease-specific survival rates were 56%, 69%, 32%, and 67%, respectively. Regarding acute toxicities, grade 3 neutropenia was observed in six patients (14%), anaemia in five (12%), acute kidney injury in one (2%), and oral mucositis in 18 (42%). Late toxicities of grade 3 were observed in seven patients: dysphagia in six (14%) and osteonecrosis of the jaw in one (2%). This study showed that proton beam therapy combined with retrograde intra-arterial infusion chemotherapy was effective for elderly patients with oral cancer, and toxicities were tolerable and manageable. The study findings suggest that this therapy is a potential treatment option for elderly oral cancer patients with difficulty in surgery and systemic chemotherapy.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Proton Therapy , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/therapy , Child , Cisplatin/adverse effects , Humans , Infusions, Intra-Arterial , Mouth Neoplasms/drug therapy , Treatment Outcome
6.
Phys Rev Lett ; 127(17): 172701, 2021 Oct 22.
Article in English | MEDLINE | ID: mdl-34739292

ABSTRACT

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

7.
J Maxillofac Oral Surg ; 20(1): 95-99, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33584049

ABSTRACT

INTRODUCTION: The aim of this study was to compare body weight loss between postoperative intermaxillary fixation with metal wire and elastic traction and to investigate factors related to body weight loss after orthognathic surgery. MATERIALS AND METHODS: Subjects were 59 patients with dentofacial deformity, comprising 31 patients treated with intermaxillary fixation (IMF) and 28 patients treated with elastic traction without IMF (ELT) just after surgery. Body weight loss was measured at 1 week (T1) and 2 weeks (T2) after surgery. Body weight loss was compared between IMF and ELT, and factors related to body weight loss were statistically analyzed. RESULTS: Body weight loss ratio was significantly increased in IMF (2.6%) rather than in ELT (1.4%) at T1, but only tended to be increased in both groups at T2, showing no statistical difference. Body weight loss ratio was significantly increased at T2 compared to T1 in both groups. Body weight loss was significantly greater at T2 than at T1. CONCLUSION: Both IMF and ELT cause body weight loss after orthognathic surgery, but IMF causes body weight loss earlier than ELT and increased early body weight loss increases continuous body weight loss after orthognathic surgery.

8.
J Hazard Mater ; 406: 124314, 2021 03 15.
Article in English | MEDLINE | ID: mdl-33168312

ABSTRACT

The monitoring and removal of abundant heavy metals such as Cu ions are considerable global concerns because of their severe impact on the health of humans and other living organisms. To meet this global challenge, we engineered a novel mesoscopic capture protocol for the highly selective removal and visual monitoring of copper (Cu2+) ions from wide-ranging water sources. The capture hierarchy carriers featured three-dimensional, microsized MgO mesoarchitecture rectangular sheet-like mosaics that were randomly built in horizontal and vertical directions, uniformly arranged sheet faces, corners, and edges, smoothly quadrilateral surface coverage for strong Cu2+-to-ligand binding exposure, and multidiffusible pathways. The Cu2+ ion-selectively active captor surface design was engineered through the simple incorporation/encapsulation of a synthetic molecular chelation agent into hierarchical mesoporous MgO rectangular sheet platforms to produce a selective, visual mesoscopic captor (VMC). The nanoscale VMC dressing of MgO rectangular mosaic hierarchy by molecularly electron-enriched chelates with actively double core bindings of azo- and sulfonamide- groups and hydrophobic dodecyl tail showed potential to selectively trap and efficiently remove ultratrace Cu2+-ions with an extreme removal capability of ~233 mg/g from watery solutions, such as drinking water, hospital effluent, and food-processing wastewater at specific pH values. In addition to the Cu2+ ion-selective removal, the VMC design enabled the continuous visual monitoring of ultratrace Cu2+ ions (~3.35 × 10-8 M) as a consequence of strong chelate-to-Cu2+ binding events among all accumulated matrices in water sources. Our experimental recycle protocol provided evidence of reusability and recyclability of VMC (≥10 cycles). With our mesoscopic capture protocol, the VMC can be a promising candidate for the selective decontamination/removal and sensitive detection of hazardous inorganic pollutants from different water sources with indoor or outdoor applications.


Subject(s)
Copper , Water Pollutants, Chemical , Adsorption , Humans , Hydrogen-Ion Concentration , Ions , Wastewater , Water Pollutants, Chemical/analysis
9.
Rev Sci Instrum ; 91(8): 083505, 2020 Aug 01.
Article in English | MEDLINE | ID: mdl-32872928

ABSTRACT

Two new vertical neutron cameras characterized by high detection efficiency were developed on the Large Helical Device in order to observe poloidal structures of helically trapped beam ions created by the perpendicularly injected positive-ion based neutral beam (P-NB) and are newly operated since 2018. In this work, the neutron fields at the vertical neutron cameras are investigated using the Monte Carlo N-particle transport code to evaluate the performance of its collimators. The results indicate that neutrons are attenuated by the heavy concrete and are well collimated through the collimator to detectors. Neutron spectra at the detector position show over 99% of uncollided 2.45 MeV neutrons. Time evolution of neutron emission profiles during the short pulse of P-NB injection is measured by the vertical neutron cameras. Peaks on the neutron emission profiles corresponding to the helically trapped beam ion are successfully obtained, as designed. The decrease in line integrated neutron flux at the peak positions after the P-NB stops is consistent with the behavior of the total neutron emission rate measured by the neutron flux monitor.

10.
Ann Oncol ; 30(12): 1950-1958, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31566666

ABSTRACT

BACKGROUND: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Biliary Tract Neoplasms/drug therapy , Cisplatin/administration & dosage , Deoxycytidine/analogs & derivatives , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biliary Tract Neoplasms/epidemiology , Biliary Tract Neoplasms/pathology , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Disease-Free Survival , Drug Combinations , Female , Humans , Japan/epidemiology , Male , Middle Aged , Nausea/chemically induced , Nausea/pathology , Oxonic Acid/administration & dosage , Oxonic Acid/adverse effects , Tegafur/administration & dosage , Tegafur/adverse effects , Vomiting/chemically induced , Vomiting/pathology , Gemcitabine
11.
Rev Sci Instrum ; 90(7): 073504, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31370451

ABSTRACT

Negative-ion neutral-beam injection (NNBI) is an important source of heating and current drive for next-step fusion devices where the injected energy can range from hundreds of keV to 1 MeV. Few diagnostics are suitable for phase-space resolved measurements of fast ions with energy in excess of 100 keV. A study to assess the feasibility of fast-ion deuterium-alpha (FIDA) spectroscopy to diagnose high-energy ions produced by NNBI is presented. Case studies with the Large Helical Device (LHD) and JT-60SA illustrate possible solutions for the measurement. The distribution function of fast ions produced by NNBI is calculated for both devices, and the FIDA spectrum is predicted by synthetic diagnostic simulation. Results with 180 keV NNBI in LHD show that, with a judicious choice of viewing geometry, the FIDA intensity is comparable to that obtained with the existing FIDA system. The measurement is more challenging with the 500 keV NNBI in JT-60SA. Simulations predict the FIDA intensity to be about 1% of the background bremsstrahlung, which is small compared to existing FIDA implementations with positive neutral-beam injection where signal levels are an order of magnitude larger. The sampling time required to extract the small FIDA signal is determined using a probabilistic approach. Results indicate that long averaging periods, from ones to tens of seconds, are needed to resolve the FIDA signal in JT-60SA. These long averaging times are suitable in long-pulse (∼100 s), steady-state devices like JT-60SA where an important measurement objective is the spatial profile of the slowing-down distribution of fast ions.

12.
Nat Commun ; 9(1): 1331, 2018 04 06.
Article in English | MEDLINE | ID: mdl-29626213

ABSTRACT

The ability to manipulate acoustic and elastic waveforms in continuous media has attracted significant research interest and is crucial for practical applications ranging from biological imaging to material characterization. Although several spatial focusing techniques have been developed, these systems require sophisticated resonant structures with narrow bandwidth, which limit their practical applications. Here we demonstrate temporal pulse manipulation in a dispersive one-dimensional phononic crystal waveguide, which enables the temporal control of ultrasonic wave propagation. On-chip pulse focusing is realized at a desired time and position with chirped input pulses that agree perfectly with the theoretical prediction. Moreover, traveling four-wave mixing experiments are implemented, providing a platform on which to realize novel nonlinear phenomena in the system. Incorporating this dispersive pulse engineering scheme into nonlinear phononic crystal architecture opens up the possibility of investigating novel phenomena such as phononic solitons.

13.
Int J Oral Maxillofac Surg ; 47(4): 505-510, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29305246

ABSTRACT

The aim of this study was to investigate the incidence of anterior disc displacement without reduction (ADDwoR) of the temporomandibular joint (TMJ) in patients with dentofacial deformity. Eighty-eight female patients (176 joints) with skeletal class III malocclusion and 33 female patients (66 joints) with skeletal class II malocclusion, with or without anterior open bite and asymmetry, were evaluated. Magnetic resonance imaging (MRI) of the TMJ was used to diagnose ADDwoR. A statistical analysis was performed to examine the relationship between ADDwoR and skeletal structure. ADDwoR was present in 37 of the 66 joints (56.1%) in class II compared to 34 of the 176 joints (19.3%) in class III (P<0.05). In class III, ADDwoR was significantly more common in joints with mandibular asymmetry (24/74; 32.4%) than in joints with open bite (9/62; 14.5%) and joints with open bite and without mandibular asymmetry (1/38; 2.6%). In class II, ADDwoR was significantly less common in joints with mandibular asymmetry and without open bite (1/8; 12.5%). ADDwoR was only observed on the deviated side in both class III and class II with mandibular asymmetry. The prevalence of ADDwoR differed according to the dentofacial morphology.


Subject(s)
Malocclusion, Angle Class III/complications , Malocclusion, Angle Class II/complications , Temporomandibular Joint Disc/pathology , Temporomandibular Joint Disorders/epidemiology , Temporomandibular Joint Disorders/etiology , Adolescent , Adult , Female , Humans , Incidence , Magnetic Resonance Imaging , Middle Aged , Prevalence , Temporomandibular Joint Disc/diagnostic imaging , Temporomandibular Joint Disorders/diagnostic imaging
14.
Oncogene ; 37(2): 208-217, 2018 01 11.
Article in English | MEDLINE | ID: mdl-28925391

ABSTRACT

Inhibitors against poly (ADP-ribose) polymerase (PARP) are promising targeted agents currently used to treat BRCA-mutant ovarian cancer and are in clinical trials for other cancer types, including BRCA-mutant breast cancer. To enhance the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi sensitivity is urgently needed. Here, we show enhancer of zeste homolog 2 (EZH2), an enzyme that catalyzes H3 lysine trimethylation and associates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells. Mechanistically, upon oxidative stress or alkylating DNA damage, PARP1 interacts with and attaches poly-ADP-ribose (PAR) chains to EZH2. PARylation of EZH2 by PARP1 then induces PRC2 complex dissociation and EZH2 downregulation, which in turn reduces EZH2-mediated H3 trimethylation. In contrast, inhibition of PARP by PARPi attenuates alkylating DNA damage-induced EZH2 downregulation, thereby promoting EZH2-mediated gene silencing and cancer stem cell property compared with PARPi-untreated cells. Moreover, the addition of an EZH2 inhibitor sensitizes the BRCA-mutant breast cells to PARPi. Thus, these results may provide a rationale for combining PARP and EZH2 inhibition as a therapeutic strategy for BRCA-mutated breast and ovarian cancers.


Subject(s)
Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm , Enhancer of Zeste Homolog 2 Protein/metabolism , Ovarian Neoplasms/drug therapy , Poly (ADP-Ribose) Polymerase-1/metabolism , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , ADP-Ribosylation/drug effects , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , DNA Damage , Down-Regulation , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Enhancer of Zeste Homolog 2 Protein/genetics , Female , Gene Silencing , Humans , Mice , Mice, Nude , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , RNA, Small Interfering/metabolism , Xenograft Model Antitumor Assays
15.
J Oral Rehabil ; 45(3): 235-239, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29284179

ABSTRACT

There is little evidence of sensation in individuals with diabetes mellitus (DM) in the dental research field. We investigated whether pain thresholds (PTs) differ between individuals with and without DM (non-DM; NDM). To this end, we assessed whether PTs obtained from the oral cavity, hands, and feet differed from each other and across groups, and whether PTs differed for the three current frequencies used for testing (2000 Hz, 250 Hz, and 5 Hz). Pain threshold measurements were obtained from the oral mucosa and the tips of the fingers and toes of 56 volunteers, including 21 individuals with DM (12 men and 9 women, average age: 72.1 ± 4.7 years) and 35 NDM individuals (17 males and 18 females, average age: 51.2 ± 23.9 years) using the Neurometer CPT/C® device to deliver electrical stimulation. A single operator obtained PT measurements from around the left greater palatine foramen and from the tip of the left first finger and of the left great toe. Individuals with DM had significantly lower PT values than those without DM. The PT values for the oral cavity, hands, and feet differed significantly from each other (foot > hand, foot > oral cavity, hand > oral cavity). Moreover, there was a significant difference in the PT values for 5 Hz and 2000 Hz, as well as for 250 Hz and 2000 Hz. This study concluded that PT values derived from DM participants are lower than those from NDM participants, although PT measurements varied across regions and with current frequency.


Subject(s)
Diabetes Mellitus/physiopathology , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/physiopathology , Electric Stimulation , Pain Threshold/physiology , Sensory Thresholds/physiology , Aged , Alveolar Process/physiopathology , Dental Health Surveys , Female , Foot/physiopathology , Hand/physiopathology , Humans , Male , Middle Aged , Pain Measurement/methods , Peripheral Nerves/physiopathology , Predictive Value of Tests , Reproducibility of Results
17.
Sci Rep ; 7(1): 12745, 2017 10 06.
Article in English | MEDLINE | ID: mdl-28986526

ABSTRACT

The high-quality-factor mechanical resonator in electromechanical systems has facilitated dynamic control of phonons via parametric nonlinear processes and paved the development of mechanical logic-elements. However, the narrow spectral bandwidth of the resonating element constrains the available nonlinear phenomena thus limiting the functionality of the device as well as the switching speeds. Here we have developed phonon waveguides, with a two-octave-wide phonon transmission band, in which mechanical four-wave-like mixing is demonstrated that enables the frequency of phonon waves to be converted over 1 MHz. We harness this platform to execute multiple binary mechanical logic gates in parallel, via frequency division multiplexing in this broadband, where each gate can be independently reconfigured. The fidelity of the binary gates is verified via temporal measurements yielding eye diagrams which confirm the availability of high speed logic operations. The phonon waveguide architecture thus offers the broadband functionality that is essential to realising mechanical signal processors.

18.
Bone Marrow Transplant ; 52(7): 969-976, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28368379

ABSTRACT

Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-AML/MDS) represent severe late effects in patients receiving hematopoietic cell transplantation (HCT) for lymphoma. The choice between high-dose therapy with autologous HCT and allogeneic HCT with reduced-intensity conditioning remains controversial in patients with relapsed lymphoma. We retrospectively analyzed incidence and risk factors for the development of t-AML/MDS in lymphoma patients treated with autologous or allogeneic HCT. A total of 13 810 lymphoma patients who received autologous (n=9963) or allogeneic (n=3847) HCT between 1985 and 2012 were considered. At a median overall survival (OS) of 52 and 46 months in autologous and allogeneic HCT groups, respectively, lymphoma patients receiving autologous HCT (1.38% at 3 years after autologous HCT) had a significant risk for developing t-AML/MDS compared to allogeneic HCT (0.37% at 3 years after allogeneic HCT, P<0.001). Significant risk factors for the development of t-AML/MDS after autologous and allogeneic HCT were high-stage risk at HCT (P=0.04) or secondary malignancies (P<0.001) and receiving cord blood stem cell (P=0.03) or involved field radiotherapy (P=0.002), respectively. Strategies that carefully select lymphoma patients for autologous HCT, by excluding lymphoma patients with high-stage risk at HCT, may allow the identification of individual lymphoma patients at particular high risk for t-AML/MDS.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/epidemiology , Lymphoma/epidemiology , Lymphoma/therapy , Myelodysplastic Syndromes/epidemiology , Neoplasms, Second Primary/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Allografts , Autografts , Female , Follow-Up Studies , Humans , Male , Middle Aged , Risk Factors
19.
Oncogene ; 36(9): 1265-1275, 2017 03 02.
Article in English | MEDLINE | ID: mdl-27593935

ABSTRACT

The Yes-associated protein (YAP) is an effector that transduces the output of the Hippo pathway to transcriptional modulation. Considering the role of YAP in cancers, this protein has emerged as a key node in malignancy development. In this study, we determined that Aurora A kinase acts as a positive regulator for YAP-mediated transcriptional machinery. Specifically, YAP associates with Aurora A predominantly in the nucleus. Activation of Aurora A can impinge on YAP activity through direct phosphorylation. Moreover, aberrant expression of YAP and Aurora A signaling is highly correlated with triple-negative breast cancer (TNBC). We herein provide evidence to establish the functional relevance of this newly discovered regulatory axis in TNBC.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Aurora Kinase A/metabolism , Biomarkers, Tumor/metabolism , Cell Proliferation , Phosphoproteins/metabolism , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Animals , Apoptosis , Humans , Immunoenzyme Techniques , Mice , NIH 3T3 Cells , Phosphorylation , Signal Transduction , Transcription Factors , YAP-Signaling Proteins
20.
Bone Marrow Transplant ; 52(3): 423-430, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27941766

ABSTRACT

In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Methotrexate/administration & dosage , Mycophenolic Acid/administration & dosage , Adolescent , Adult , Cyclosporine/administration & dosage , Disease-Free Survival , Female , Humans , Incidence , Japan , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Registries , Survival Rate , Tacrolimus/administration & dosage
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