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This study investigated changes in treatment modalities and outcomes of chronic myeloid leukemia in the chronic phase (CP-CML) after the approval of second-generation tyrosine kinase inhibitors (2G-TKIs) for first-line therapy. Patients were grouped into those who underwent TKI therapy up to December 2010 (imatinib era group, n = 185) and after January 2011 (2G-TKI era group, n = 425). All patients in the imatinib era group were initially treated with imatinib, whereas patients in the 2G-TKI era group were mostly treated with dasatinib (55%) or nilotinib (36%). However, outcomes including progression-free survival, overall survival, and CML-related death (CRD) did not differ significantly between groups. When stratified by risk scores, the prognostic performance of the ELTS score was superior to that of the Sokal score. Even though both scoring systems predicted CRD in the imatinib era, only the ELTS score predicted CRD in the 2G-TKI era. Notably, the outcome of patients classified as high-risk by ELTS score was more favorable in the 2G-TKI era group than in the imatinib era group. Thus, expanding treatment options may have improved patient outcomes in CP-CML, particularly in patients classified as high-risk by ELTS score. [ABSTRACT FROM AUTHOR]

ABL1-tyrosine kinase inhibitors (TKIs) are an established treatment choice for patients with chronic myeloid leukemia in the chronic phase (CML-CP). However, effects of TKI dose modification have not been well investigated. In this study, we retrospectively analyzed 178 patients with newly diagnosed CML-CP who were treated with dasatinib or nilotinib, focusing on age and dose effects. Efficacy as measured by cumulative major molecular response (MMR) and molecular response 4.5 rates did not differ significantly between the younger group and elderly group. Elderly patients who started nilotinib at a reduced dose had similar or better efficacy outcomes (including cumulative MMR and continuation ratios) than other groups, and elderly patients who started dasatinib at a reduced dose had the lowest MMR ratio and longest MMR duration. Effects of dose modification based on age and TKI selection can be attributed to flexible management of TKI therapy in real-world practice, but further studies are required to validate the findings of this study. [ABSTRACT FROM AUTHOR]

Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF patients were analyzed. A total of 16 of 23 patients (69.6%) were found to have VB6 deficiency, but VB6 supplementation with pyridoxal phosphate hydrate did not elevate hemoglobin levels in deficient patients. None of the patients presented with vitamin B12, iron, or copper deficiencies. Four patients showed serum folate levels below the lower limit of normal and eight patients showed serum zinc levels below the lower limit of normal; however, these deficiencies were marginal and unlikely to contribute to anemia. Compared to VB6-sufficient patients, VB6-deficient patients showed significantly lower serum folate levels and higher serum copper levels. Studies elucidating the relationship of VB6 deficiency and etiology of PMF/sMF are warranted. [ABSTRACT FROM AUTHOR]

This study investigated the incidence rate and features of vascular adverse events (VAEs) in Japanese patients with chronic myeloid leukemia (CML) who were treated with tyrosine kinase inhibitors (TKIs). The analysis included 369 CML patients in the chronic or accelerated phases, selected from the CML Cooperative Study Group database; 25 events in 23 (6.2%) of these patients were VAEs. At the time of VAE incidence, nine patients were on treatment with imatinib, 12 with nilotinib, three with dasatinib, and one with bosutinib. VAE incidence comprised 13 cases of ischemic heart disease (IHD), eight of cerebral infarction (CI), and four of peripheral arterial occlusive disease (PAOD). IHD incidence rate in the study population was higher than that in the age-matched general population, particularly in nilotinib-treated patients, while CI incidence rate was almost equivalent. Compared with the Suita score, the SCORE chart and the Framingham score risk assessment tools detected more patients with high or very high risk of VAEs. In conclusion, incidence of IHD requires closer monitoring in nilotinib-treated patients. More detailed investigations for determining the most useful tool to predict VAE incidence and long-term analysis of therapy-related VAE cases are needed for improving safety during TKI therapy. [ABSTRACT FROM AUTHOR]

Background: To develop an adhesion system satisfying both constant adhesion strength during use and quick debonding ability during a dismantling process. Methods: Adhesive properties were investigated for the random and block copolymers consisting of 1-isobutoxyethyl acrylate (iBEA), 2-ethylhexyl acrylate (2EHA), and 2-hydroxyethyl acrylate (HEA) as the dismantlable pressure-sensitive adhesives in the presence of a photoacid generator in response to dual external stimuli of photoirradiation and post baking. Results: The use of LED combined with a new photoacid generator SIN-11 was enable us to achieve a rapid dismantling process during UV irradiation within several minutes. The protection of the ester alkyl group in the iBEA repeating unit to give an acrylic acid unit was suppressed by the introduction of isobornyl acrylate (IBoA) as the additional unit into the copolymer of iBEA, 2EHA, and HEA. While IBoA-containing block copolymer showed a constant adhesive strength during photoirradiation as the single external stimulus, deprotection was immediately induced by the subsequent heating, leading to a significant decrease in the adhesive strength. Conclusion: The copolymer including the iBEA and IBoA units was revealed to function as the highly sensitive adhesive materials for dual-locked dismantlable adhesion. [ABSTRACT FROM AUTHOR]

Patients diagnosed with polycythemia vera (PV) or essential thrombocythemia (ET) sometimes suffer transformation of the disease into myelofibrosis (MF), which is associated with a poorer prognosis. This study investigated the prognostic value of the allele burden of JAK2V617F, a somatic driver mutation in these diseases, by comparing the allele burden between formalin-fixed paraffin-embedded bone marrow collected at initial diagnosis and peripheral blood from follow-up visits. Although the annual changes in the JAK2V617F allele burden were comparable between MF-transformed ( n = 11) and untransformed ( n = 23) patients, the burden was significantly increased in MF-transformed patients exhibiting a longer disease duration than untransformed patients. Furthermore, MF transformation was only observed in patients whose JAK2V617F allele burden exceeded the mean values for each disease (PV, 71.7 %; ET, 35.5 %) at initial diagnosis or during follow-up. Finally, we showed that hydroxycarbamide treatment exerted neither a preventive effect on MF transformation nor a suppressive effect on the increased JAK2V617F allele burden. In conclusion, a high JAK2V617F allele burden at initial diagnosis or during follow-up is predictive of MF transformation in PV and ET. Therefore, routine measurement of the JAK2V617F allele burden using an accurate assay system is recommended to predict MF transformation. [ABSTRACT FROM AUTHOR]

We describe the magnetic resonance (MR) imaging findings in a 20-year-old woman with a fibroepithelial polyp of the vulva. Within the lesion, abundant fibrous tissue was visualized as stratiform hypointense areas on T2-weighted magnetic resonance imaging (MRI) scans. At the center of the attachment site, clustered fatty tissue was revealed as linear hyperintense areas on T1-weighted MRI. A mild degree of edematous stroma including less fibrosis and cellularity was demonstrated as hyperintense areas on T2-weighted MRI and hypointense areas on T1-weighted MRI. Although the MRI findings of fibroepithelial polyps of the vulva are often similar to those of aggressive angiomyxoma, angiomyofibroblastoma, and cellular angiofibroma, a fibroepithelial polyp should be considered when radiological images demonstrate the following features: stratiform hypointense areas surrounded by patchy hyperintense areas on T2-weighted MRI and hyperintense areas on T1-weighted MRI. [ABSTRACT FROM AUTHOR]

We investigated the pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine in patients with urogenital cancer to clarify the significance of monitoring of the serum concentration of paclitaxel. Paclitaxel was administered at 175 mg/m2 or 150 mg/m2 to patients with hormone-refractory prostate cancer ( n = 10) or advanced transitional cell carcinoma ( n = 6) along with carboplatin or gemcitabine, respectively. The relationships between pharmacokinetic parameters and hematological adverse effects, as well as pharmacological effects, were examined. The effects of patient characteristics, including single-nucleotide polymorphisms of MDR1(ABCB1), CYP2C8, CYP3A4, and CYP3A5, on the total body clearance of paclitaxel were evaluated. Total body clearance and volume of distribution at a steady-state after the intravenous infusion of paclitaxel were not significantly different between patients with carboplatin or gemcitabine. The percent decreases in neutrophils and platelets for the regimen with gemcitabine were significantly greater than those with carboplatin, and showed a significant positive relationship with the observed concentration at the end of infusion or time above 0.1-µM concentration of paclitaxel. Post-therapy decreases in prostate-specific antigen were not positively correlated with the extent of paclitaxel exposure in the prostate cancer patients. Neither the polymorphisms at exon 26 (C3435T) and at exon 21 (G2677A/T) in MDR1 nor the CYP3A5*1 allele significantly affected the total body clearance of paclitaxel. The hematological side effects of paclitaxel were intensified by gemcitabine, and were correlated with paclitaxel pharmacokinetics. Monitoring of the serum concentration of paclitaxel will facilitate the therapy, with less myelosuppression and without any loss of therapeutic efficacy. [ABSTRACT FROM AUTHOR]

This article discusses surface initiated atom transfer radical polymerization of N-Hydroxysuccinimide Methacrylate from Magnetite Surface as Precursor for Functional Polymer Shell. The article presents charts and diagrams, which discuss the FT-IR spectra of oleic acid stabilized FE3 O4 nanoparticles before (a) and after (b) ligand exchange with BrIBA, FT-IR spectra of Fe3O4 pSucMA (a) and Fe3O4-pTDMA, TEM image of Fe3O4-pSucMA core-shell nanoparticles.

In this study, we consider the control of a liquid droplet movement rolling down on an inclined plate with gravitational force using a micro-wrinkle on a wall. The micro-wrinkle was manufactured by the buckling of a thin polymer film (poly(N-vinylcarbazole), PVK) on a base polymer (poly(vinyl chloride), PVC). The PVC was stretched once and then PVK (~ 100-nm thickness) was spin-coated on the surface of the base polymer at ambient temperature. When the strain was released in a thermostatic chamber heated above the glass transition temperature of PVC, a two-dimensional micro-wrinkle having a wavelength of several micrometers was formed on the surface. The advancing and receding contact angles were measured in directions parallel and perpendicular to the wrinkle. It was observed that there were several degrees of contact angle anisotropy. When the droplet was set on the wrinkle surface inclined at 45° to the gravitational force, the direction of droplet movement could be changed by ~ 20° from the gravitational direction. The deflection angle was estimated from a theoretical model with the principle of minimum work of the contact line. The micro-wrinkle was manufactured by the buckling of a thin polymer film (poly(N-vinylcarbazole), PVK) on a base polymer (poly(vinyl chloride), PVC). It was observed that there were several degrees of contact angle anisotropy dependent on the direction in normal and parallel to the wrinkle. When the droplet was set on the oblique wrinkle, the direction of droplet sliding movement could be changed by ~20° from the gravitational direction in the plane as shown in the figure below. The deflection angle β can be roughly estimated from a theoretical model with the principle of minimum work of the droplet. [ABSTRACT FROM AUTHOR]

Treatment with a tyrosine kinase inhibitor (TKI) is the standard of care for patients with chronic myeloid leukemia (CML). The new-generation TKIs, nilotinib and dasatinib, are found to have deeper and faster treatment response rates compared to imatinib in the first-line setting. However, a direct comparison between nilotinib and dasatinib has never been reported previously. Our study aims to compare the outcomes and molecular responses achieved following the first-line use of these two agents in patients with CML-CP. The database of the CML Cooperative Study Group was reviewed and patients with CML in the chronic phase (CP) who were given nilotinib or dasatinib as first-line therapy were identified. Out of 361 patients with CML-CP enrolled in our database, 58 and 63 had been treated with conventional doses of nilotinib (300 mg twice daily) and dasatinib (100 mg once daily), respectively, as first-line therapy. The patient demographics did not show significant differences between the groups. The event-free survival rates did not differ between these two groups. The major molecular response (MMR) and the deep molecular response (DMR) rates by 6, 12, 18, and 24 months did not differ between groups. Among the three scoring systems, only the Hasford score could predict the achievement of DMR, and all of them failed to predict the achievement of MMR in the entire cohort. Our data suggest that both nilotinib and dasatinib have comparable efficacies and promising outcomes. [ABSTRACT FROM AUTHOR]

Abstract: This study deals with the control of the movement of liquid droplets rolling down an inclined plate based on the differences in the wettability of the plate. We used a photoreactive polymer poly(7-methacryloyloxy coumarin) (PMC) whose molecular structure can be changed reversibly to realize different wettabilities by ultraviolet irradiation. We proposed employing sawtooth patterns at boundaries between areas with different contact angles to control the droplet trajectory. Furthermore, we experimentally observed that the droplet moves along a line inclined to the direction of gravity. The droplet behavior can be analyzed using a theoretical model based on the droplet dynamics wherein the surface tension acting on the contact line and the gravitational force are considered. The theoretical results suggest that inclination from the gravitational direction can be increased if the advancing contact angle is reduced. In the experiments conducted herein, ultrasonic vibration was applied to the inclined plate to reduce the contact angle hysteresis. The results showed that the advancing contact angle actually decreased and that the droplet trajectory was controlled to realize motion along a line with inclination angle almost twice of that realized without vibration.Graphical abstract: A saw-tooth pattern of boundary between the areas with different contact angles was proposed to control the trajectory of a droplet rolling down on an inclined plate. As shown in the right figure, the droplet immediately diverges from the direction of gravity and moves in accordance with the target lines. [ABSTRACT FROM AUTHOR]

We performed a retrospective study to evaluate the incidence of second malignancies (SMs) in chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs). We analyzed data from 339 patients with CML who were extracted from the CML Cooperative Study Group database. The standardized incidence ratio (SIR) was calculated to assess the risk of SMs using data from the Cancer Registries in Japan. The median follow-up was 65 months. SMs developed in 14 patients (4.1%, 10 men, 4 women) after the start of TKIs. The median age was 69 years at the time of the CML diagnosis and 72.5 years at the time of the SM diagnosis. Ten patients were treated with imatinib, three with dasatinib, and one with nilotinib as the initial treatment. The SIR for all malignancies was 1.05 (95% CI 0.50-1.93) for men and 1.08 (95% CI 0.29-2.76) for women. The difference in the overall survival (OS) of patients with or without SMs was not statistically significant (5-year OS: 82.5% vs. 92.9%; p = 0.343). A subgroup analysis of 166 patients treated with second-generation TKIs (92 dasatinib, 74 nilotinib) showed that the SIRs for all malignancies were 1.33 (95% CI 0.36-3.41) for men and 0 for women. In conclusion, the incidence of SMs in CML patients during TKI treatment was the same as that in the general Japanese population. There was no evidence of an increase in the incidence of SMs during second-generation TKI treatment. Furthermore, the occurrence of SMs during TKI treatment did not affect the survival or mortality in our cohort. [ABSTRACT FROM AUTHOR]

ABL1-tyrosine kinase inhibitors (TKIs) have led to dramatic changes in treatment strategies for chronic myeloid leukemia in the chronic phase (CML-CP). However, clinical studies have highlighted increasing numbers of adverse events (AE) with TKIs. Although TKI modification plays a key role in AE management, this process is poorly understood, particularly in terms of the TKI nilotinib. In the present study, we retrospectively analyzed the records of 70 patients with newly diagnosed (ND)-CML-CP who were treated with nilotinib to investigate the drug potency of nilotinib and treatment management. During a median observation period of 3.4 years, 76% of patients continued nilotinib as a first-line treatment. The 1-year and overall major molecular response (MMR) rates and the overall molecular response (MR) 4.5 rate for all patients receiving first-line nilotinib therapy were 70, 84.2, and 50%, respectively. No case progressed to the accelerated or blast phase during the study. To avoid AEs during the early phase, nilotinib doses were reduced to < 600 mg/day in a third of patients (Reduced group); these patients experienced better therapeutic efficacy and a lower rate of AEs relative to those in Standard group (300 mg twice daily). Ten patients who received < 600 mg/day of nilotinib throughout the study had a 1-year MMR rate and overall MR4.5 rate of 90 and 60%, respectively. In summary, our findings indicate that careful management, including dose reduction, can yield better outcomes in patients with ND-CML-CP. [ABSTRACT FROM AUTHOR]