Recently, it has been found that inappropriate expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In this study, we demonstrated that the expression of miRNAs (miRs) ‐143 ...and ‐145, the levels of which were previously shown to be reduced in colon cancers and various kinds of established cancer cell lines, was also decreased in most of the B‐cell malignancies examined, including chronic lymphocytic leukemias (CLL), B‐cell lymphomas, Epstein‐Barr virus (EBV)‐transformed B‐cell lines, and Burkitt lymphoma cell lines. All samples from 13 CLL patients and eight of nine B‐cell lymphoma ones tested exhibited an extremely low expression of miRs‐143 and ‐145. The expression levels of miRs‐143 and ‐145 were consistently low in human Burkitt lymphoma cell lines and were inversely associated with the cell proliferation observed in the EBV‐transformed B‐cell lines. Moreover, the introduction of either precursor or mature miR‐143 and ‐145 into Raji cells resulted in a significant growth inhibition that occurred in a dose‐dependent manner and the target gene of miRNA‐143 was determined to be ERK5, as previously reported in human colon cancer DLD‐1 cells. Taken together, these findings suggest that miRs‐143 and ‐145 may be useful as biomarkers that differentiate B‐cell malignant cells from normal cells and contribute to carcinogenesis in B‐cell malignancies by a newly defined mechanism. (Cancer Sci 2007; 98: 1914–1920)
•Low-cycle fatigue performance of welded joints.•Effect of the weld toe profile and material heterogeneity.•Description of inelastic deformation through cycles.•Characterized the mechanical ...properties of base metal and HAZ.•DIC characterization of strain distribution.•Validation against experimental data.
A previous experimental study by the authors clearly indicated that, due to the delay of the crack initiation, the butt-welded joint with smoother weld toe profile and harder weld metal had a longer low-cycle fatigue life. In the present study, supplementary numerical studies considering weld geometries and inhomogeneous mechanical properties are executed. Monotonic tensile and strain-controlled low-cycle fatigue tests on the reheated round bars are firstly conducted to characterize the mechanical properties for different zones of the butt-welded joints. The test results are used to calibrate the material constitutive model, which is then embedded into three-dimensional finite element models to investigate the low-cycle fatigue behavior of the butt-welded joints. The numerical results suggest the necessity of considering the effects of inhomogeneous material properties when evaluating the low-cycle fatigue of welded joints. It is also confirmed that decreasing weld toe stress concentration and simultaneously increasing weld metal strength can maximally increase the low-cycle fatigue life of welded joints compared to the individual changes for either one. These findings are expected to provide some insights into the low-cycle fatigue life improvement of welded joints.
TAFRO syndrome is a systemic inflammatory disorder characterized by thrombocytopenia, anasarca including pleural effusion and ascites, fever, renal insufficiency, and organomegaly including ...hepatosplenomegaly and lymphadenopathy. Its onset may be acute or sub-acute, but its etiology is undetermined. Although several clinical and pathological characteristics of TAFRO syndrome resemble those of multicentric Castleman disease (MCD), other specific features can differentiate between them. Some TAFRO syndrome patients have been successfully treated with glucocorticoids and/or immunosuppressants, including cyclosporin A, tocilizumab and rituximab, whereas others are refractory to treatment, and eventually succumb to the disease. Early and reliable diagnoses and early treatments with appropriate agents are essential to enhancing patient survival. The present article reports the 2015 updated diagnostic criteria, disease severity classification and treatment strategy for TAFRO syndrome, as formulated by Japanese research teams. These criteria and classification have been applied and retrospectively validated on clinicopathologic data of 28 patients with this and similar conditions (e.g. MCD with serositis and thrombocytopenia).
This study investigates energy harvesting by a deionized (DI) water droplet flow on an epitaxial graphene film on a SiC substrate. We obtain an epitaxial single-crystal graphene film by annealing a ...4H-SiC substrate. Energy harvesting of the solution droplet flow on the graphene surface has been investigated by using NaCl or HCl solutions. This study validates the voltage generated from the DI water flow on the epitaxial graphene film. The maximum generated voltage was as high as 100 mV, which was a quite large value compared with the previous reports. Furthermore, we measure the dependence of flow direction on electrode configuration. The generated voltages are independent of the electrode configuration, indicating that the DI water flow direction is not influenced by the voltage generation for the single-crystal epitaxial graphene film. Based on these results, the origin of the voltage generation on the epitaxial graphene film is not only an outcome of the fluctuation of the electrical-double layer, resulting in the breaking of the uniform balance of the surface charges, but also other factors such as the charges in the DI water or frictional electrification. In addition, the buffer layer has no effect on the epitaxial graphene film on the SiC substrate.
Recently, a unique clinicopathologic variant of multicentric Castleman's disease (MCD) has been identified in Japan. This disease is characterized by a constellation of symptoms, as listed in the ...title, and multiple lymphadenopathy of mild degree with a pathologic diagnosis of atypical CD, often posing diagnostic and therapeutic problems for pathologists and hematologists, respectively. These findings suggest that this disease represents a novel clinical entity belonging to systemic inflammatory disorders with a background of immunological abnormality beyond the ordinal spectrum of MCD. To define this disorder more clearly, Japanese participants presented clinicopathologic data at the Fukushima and Nagoya meetings. Many of the patients presented by the participants were significantly accompanied by a combination of thrombocytopenia, ascites (anasarca), pleural effusions, microcytic anemia, fever, myelofibrosis, renal dysfunction, and organomegaly (TAFRO). Multiple lymphadenopathies were generally of mild degree, less than 1.5 cm in diameter, and consistently featured the histopathology of mixed- or less hyaline vascular-type CD. Autoantibodies were often detected. However, this disease did not fulfill the diagnostic criteria for well-known autoimmune diseases including systemic lupus erythematosus. Castleman-Kojima disease and TAFRO syndrome (the favored clinical term) were proposed for this disease. The patients were sensitive to steroid and anti-interleukin-6 receptor antibody (tocilizumab), but some exhibited a deteriorated clinical course despite the treatment. The participants proposed a future nationwide survey and a Japanese consortium to facilitate further clinical and therapeutic studies of this novel disease. J Clin Exp Hematop 53(1): 57-61, 2013
Introduction The objectives of this study are twofold. The first is to identify potential green infrastructure construction sites by building rooftops and sidewalks. The second is to analyze internal ...flooding for a wide range of drainage areas and to quantitatively evaluate the effectiveness of stormwater runoff control. Methods The target area has approximately 600 ha with a runoff coefficient of 0.71. Using Arc GIS Desktop 10.8.1, this study has identified green roofs and bioswales that would be highly beneficial in capturing large amounts of rainfall. In addition, Info Works ICM was used for the inundation analysis, which can simultaneously calculate the flow in sewer pipelines and above-ground inundation flow. Runoff coefficients were calculated for each land use using the urban land use subdivision mesh data with 100 m unit. This study targeted a 10-year probability rainfall (total rainfall: 86.3 mm, maximum hourly rainfall: 52.3 mm/h, duration: 3 h) with a middle concentrated rainfall waveform obtained from past experiments in the d4PDF database of ensemble climate prediction contributing to global warming. Results The amount of land availability for green roofs and bioswales was about 1 and 0.1% of the drainage area, respectively. The runoff coefficients for green roofs only, bioswales only, with and without introduction of both green roofs and bioswales were 70.34, 70.87, 70.28, and 70.93%, respectively. The difference in runoff coefficients was about 0.65 percentage points even when both were constructed. As a result of inundation analysis, the reduction was 2.5% for the maximum waterlogged area, 1.5% for the flooded area, and 0.7% for the average depth of waterlogging divided by the maximum waterlogged area. The construction of green roofs and bioswales in the same area or downstream of the area shows little mitigation effect when flooding occurs in an area near the downstream end of the sewer network. Discussion Although this study has mainly discussed the stormwater runoff control aspect, the most important feature of green infrastructure is its multifunctionality. In terms of utilizing and promoting green infrastructure, it is important to visualize its multifaceted effects and share them with many stakeholders.
Summary Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of non-Hodgkin lymphoma according to the current WHO classification. This rare form of B-cell lymphoma is characterised ...by selective growth of tumour cells in the lumina of small vessels of various organs. Strange characteristics of IVLBCL, including the absence of marked lymphoadenopathy and the usually aggressive clinical behaviour, result in the delay of timely and accurate diagnosis and fatal complications. Thus, the prognosis of IVLBCL is extremely poor. The success achieved with the anti-CD20 chimeric monoclonal antibody, rituximab, represents an important milestone in the clinical practice of B-cell lymphoma. An advantage of adding rituximab to conventional chemotherapies has been shown, in the process of increasing our understanding of the clinical and pathological manifestations for IVLBCL. This Review describes the cutting edge of research on IVLBCL, and discusses the unsolved issues from biological and clinical perspectives to provide a better understanding of this rare lymphoma.
We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics and predictive biomarkers of tirabrutinib, a second‐generation, enhanced‐selectivity Bruton's tyrosine kinase inhibitor in ...Japanese patients with relapsed/refractory B‐cell non−Hodgkin lymphoma (B‐cell NHL) and chronic lymphocytic leukemia (CLL). This was an open‐label, multicenter, phase I study. Seventeen patients (male N = 8) with a median age of 70 years were enrolled in 4 dose cohorts (160 mg once daily N = 3, 320 mg once daily N = 3, 480 mg once daily N = 4 and 300 mg twice daily N = 7); 4 patients had continued tirabrutinib administration as of 4 January 2018. The maximum tolerated dose was not reached. Pneumonitis (N = 1) was the dose‐limiting toxicity for 300 mg twice daily. Common adverse events (AEs) were rash (35.3%) and vomiting (29.4%). Eight patients (47.1%) developed grade ≥3 AEs: neutropenia (23.5%), anemia (11.8%) and leukopenia (11.8%) were frequent. The overall response rate (≥PR) was 76.5% (13/17 patients), including 4 DLBCL patients with no CD79A/B or MYD88 mutations, and 1 CLL patient with a TP53 mutation, providing promising data for future developments. Of 16 patients with measurable lesions during the screening period, 12 showed ≥50% reductions in tumor diameter. In many patients, the tumor size decreased soon after beginning treatment. The maximum serum concentration for tirabrutinib was 611, 1220, 1280 and 886 ng/mL on Day 1 and 484, 971 1940, and 961 ng/mL on Day 28 for Cohorts 1‐4, respectively. Tirabrutinib pharmacokinetics were linear, with little accumulation following multiple doses. Tirabrutinib was well tolerated and showed promising efficacy for B‐cell NHL/CLL.
This was an open‐label, multicenter, phase I study of tirabrutinib in 17 Japanese patients with relapsed or refractory B‐cell non−Hodgkin lymphoma and chronic lymphocytic leukemia. Patients were enrolled in 4 dose cohorts (160 mg QD N = 3, 320 mg QD N = 3, 480 mg QD N = 4 and 300 mg BID N = 7), and tirabrutinib was observed to have linear pharmacokinetics with little accumulation following multiple doses. The most common AE were rash (35.3%) and vomiting (29.4%). The overall response rate was 76.5% (13/17 patients) and the tumor diameter in 12 of 16 patients revealed ≥50% reductions, with 8 patients showing early response within 1 month after beginning treatment among 13 responders who achieved partial response or better; therefore, tirabrutinib was well tolerated and showed promising efficacy.
Background. There is no standard management of reactivation of hepatitis B virus (HBV) infection in HBV-resolved patients without hepatitis B surface antigen (HBsAg), but with antibodies against ...hepatitis B core antigen and/or antibodies against HBsAg (anti-HBs). Methods. We conducted a prospective observational study to evaluate the occurrence of HBV reactivation by serial monthly monitoring of HBV DNA and to establish preemptive therapy guided by this monitoring in B-cell non-Hodgkin lymphoma (B-NHL) treated with rituximab plus corticosteroid-containing chemotherapy (R-steroid-chemo). The primary endpoint was the incidence of HBV reactivation defined as quantifiable HBV DNA levels of ≥11 1U/mL. Results. With a median HBV DNA follow-up of 562 days. HBV reactivation was observed in 21 of the 269 analyzed patients. The incidence of HBV reactivation at 1.5 years was 8.3% (95% confidence interval, 5.5–12.4). No hepatitis due to HBV reactivation was observed in patients who received antiviral treatment when HBV DNA levels were between 11 and 432 IU/mL. An anti-HBs titer of <10 mIU/mL and detectable HBV DNA remaining below the level of quantification at baseline were independent risk factors for HBV reactivation (hazard ratio, 20.6 and 56.2, respectively; P<.001). Even in 6 patients with a rapid increase of HBV due to mutations, the monthly HBV DNA monitoring was effective at preventing HBV-related hepatitis. Conclusions. Monthly monitoring of HBV DNA is useful for preventing HBV reactivation–related hepatitis among B-NHL patients with resolved HBV infection following R-steroid-chemo (UMIN000001299).
To explore a more effective treatment for localized nasal natural killer (NK)/T-cell lymphoma, we conducted a phase I/II study of concurrent chemoradiotherapy.
Treatments comprised concurrent ...radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC). Patients with a newly diagnosed stage IE or contiguous IIE disease with cervical node involvement and a performance status (PS) of 0 to 2 were eligible for enrollment. The primary end point of the phase II portion was a 2-year overall survival in patients treated with the recommended dose.
Of the 33 patients enrolled, 10 patients were enrolled in the phase I portion and a two thirds dose of DeVIC was established as the recommended dose. Twenty-seven patients (range, 21 to 68; median, 56 years) treated with the recommended dose showed the following clinical features: male:female, 17:10; stage IE, 18; stage IIE, 9; B symptoms present, 10; elevated serum lactate dehydrogenase, 5; and PS 2, 2. With a median follow-up of 32 months, the 2-year overall survival was 78% (95% CI, 57% to 89%). This compared favorably with the historical control of radiotherapy alone (45%). Of the 26 patients assessable for a response, 20 (77%) achieved a complete response, with one partial response. The overall response rate was 81%. The most common grade 3 nonhematologic toxicity was mucositis related to radiation (30%). No treatment-related deaths were observed.
Concurrent chemoradiotherapy using multidrug resistance-nonrelated agents and etoposide is a safe and effective treatment for localized nasal NK/T-cell lymphoma and warrants further investigation.
PDF
