High-field magnetization and magnetic phase transition in CeOs2Al10

We have studied the magnetization of CeOs2Al10 in high magnetic fields up to 55 T for H // a and constructed the magnetic phase diagram for H // a. The magnetization curve shows a concave H dependence below T_max \sim40 K which is higher than the transition temperature T_0 \sim29 K. The magnetic susceptibility along the a-axis shows a smooth and continuous decrease down to \sim20 K below T_max \sim40 K without showing an anomaly at T_0. From these two results, a Kondo singlet is formed below T_max and coexists with the antiferro magnetic order below T_0. We also propose that the larger suppression of the spin degrees of freedom along the a-axis than along the c-axis below T_max is associated with the origin of the antiferro magnetic component.Comment: 4 pages, 4 figures, to appear in Phys. Rev. B, Rapid Commu

High-field magnetization and magnetic phase transition in CeOs2Al10

We have studied the magnetization of CeOs2Al10 in high magnetic fields up to 55 T for H // a and constructed the magnetic phase diagram for H // a. The magnetization curve shows a concave H dependence below T_max \sim40 K which is higher than the transition temperature T_0 \sim29 K. The magnetic susceptibility along the a-axis shows a smooth and continuous decrease down to \sim20 K below T_max \sim40 K without showing an anomaly at T_0. From these two results, a Kondo singlet is formed below T_max and coexists with the antiferro magnetic order below T_0. We also propose that the larger suppression of the spin degrees of freedom along the a-axis than along the c-axis below T_max is associated with the origin of the antiferro magnetic component.Comment: 4 pages, 4 figures, to appear in Phys. Rev. B, Rapid Commu

Fluorescence in situ hybridization (FISH) analysis of primary ocular adnexal MALT lymphoma

BACKGROUND: It remains unknown whether primary ocular adnexal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a homogeneous entity, as there are few reports of the results of cytogenetic or molecular analyses of these tumors. METHODS: We performed interphase fluorescence in situ hybridization (FISH) analysis to detect translocations and aneuploidy in 34 cases of primary ocular adnexal MALT lymphoma, and reviewed the histopathological findings. Correlations between the results of FISH analysis, the histopathological features and the clinical data were also analyzed. RESULTS: Among the 34 cases, FISH analysis revealed t(14;18)(q32;q21) in one case, trisomy 3 in 21 cases (62%), and trisomy 18 in 16 cases (47%). The cases with trisomy 18 had significantly more prominent lymphoepithelial lesions (LELs) and less nodularity in the tumors. In regard to the clinical correlations, tumors with trisomy 18 were observed predominantly in females and younger patients; also, in the majority of the cases, the tumor was of conjunctival origin. All the cases with recurrence showed trisomy 18 in the tumor. CONCLUSION: Primary ocular adnexal MALT lymphoma is a significantly heterogeneous entity. Cases with trisomy 18 may have unique clinicopathological features

Resminostat in EGFR-mutated lung cancer

Drug-tolerant cells are mediators of acquired resistance. BIM-intron2 deletion polymorphism (BIM-del) is one of the mechanisms underlying the resistance to epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI)-mediated apoptosis that induces drug tolerance. Here, we investigated whether resminostat, a histone deacetylase inhibitor, circumvents BIM-del-associated apoptosis resistance. The human EGFR-mutated non-small cell lung cancer (NSCLC) cell line PC-9 and its homozygous BIM-del-positive variant (PC-9 BIMi2-/-), established by editing with zinc finger nuclease, were used. In comparison with PC-9 cells, PC-9 BIMi2-/- cells were less sensitive to apoptosis mediated by EGFR-TKIs such as gefitinib and osimertinib. The combined use of resminostat and an EGFR-TKI preferentially induced the expression of the pro-apoptotic BIM transcript containing exon 4 rather than that containing exon 3, increased the level of pro-apoptotic BIM protein (BIMEL), and stimulated apoptosis in vitro. In a subcutaneous tumor model derived from PC-9 BIMi2-/- cells, gefitinib monotherapy decreased tumor size but retained residual lesions, indicative of the presence of tolerant cells in tumors. The combined use of resminostat and gefitinib increased BIMEL protein level and induced apoptosis, subsequently leading to the remarkable shrinkage of tumor. These findings suggest the potential of resminostat to circumvent tolerance to EGFR-TKIs associated with BIM deletion polymorphism

Asymptotic analysis of the model for distribution of high-tax payers

The z-transform technique is used to investigate the model for distribution of high-tax payers, which is proposed by two of the authors (K. Y and S. M) and others. Our analysis shows an asymptotic power-law of this model with the exponent -5/2 when a total ``mass'' has a certain critical value. Below the critical value, the system exhibits an ordinary critical behavior, and scaling relations hold. Above the threshold, numerical simulations show that a power-law distribution coexists with a huge ``monopolized'' member. It is argued that these behaviors are observed universally in conserved aggregation processes, by analizing an extended model.Comment: 5pages, 3figure

AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells

A novel EGFR-tyrosine kinase inhibitor (TKI), osimertinib, has marked efficacy in patients with EGFR-mutated lung cancer. However, some patients show intrinsic resistance and an insufficient response to osimertinib. This study showed that osimertinib stimulated AXL by inhibiting a negative feedback loop. Activated AXL was associated with EGFR and HER3 in maintaining cell survival and inducing the emergence of cells tolerant to osimertinib. AXL inhibition reduced the viability of EGFR-mutated lung cancer cells overexpressing AXL that were exposed to osimertinib. The addition of an AXL inhibitor during either the initial or tolerant phases reduced tumor size and delayed tumor re-growth compared to osimertinib alone. AXL was highly expressed in clinical specimens of EGFR-mutated lung cancers and its high expression was associated with a low response rate to EGFR-TKI. These results indicated pivotal roles for AXL and its inhibition in the intrinsic resistance to osimertinib and the emergence of osimertinib-tolerant cells

Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer

Drug tolerance is the basis for acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) including osimertinib, through mechanisms that still remain unclear. Here, we show that while AXL-low expressing EGFR mutated lung cancer (EGFRmut-LC) cells are more sensitive to osimertinib than AXL-high expressing EGFRmut-LC cells, a small population emerge osimertinib tolerance. The tolerance is mediated by the increased expression and phosphorylation of insulin-like growth factor-1 receptor (IGF-1R), caused by the induction of its transcription factor FOXA1. IGF-1R maintains association with EGFR and adaptor proteins, including Gab1 and IRS1, in the presence of osimertinib and restores the survival signal. In AXL-low-expressing EGFRmut-LC cell-derived xenograft and patient-derived xenograft models, transient IGF-1R inhibition combined with continuous osimertinib treatment could eradicate tumors and prevent regrowth even after the cessation of osimertinib. These results indicate that optimal inhibition of tolerant signals combined with osimertinib may dramatically improve the outcome of EGFRmut-LC