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A trisomy is a type of aneuploidy characterised by an additional chromosome. The additional chromosome theoretically accepts any kind of changes since it is not necessary for cellular proliferation. This advantage led us to apply two chromosome manipulation methods to autosomal trisomy in chicken DT40 cells. We first corrected chromosome 2 trisomy to disomy by employing counter-selection markers. Upon construction of cells carrying markers targeted in one of the trisomic chromosome 2s, cells that have lost markers integrated in chromosome 2 were subsequently selected. The loss of one of the chromosome 2s had little impacts on the proliferative capacity, indicating unsubstantial role of the additional chromosome 2 in DT40 cells. We next tested large-scale truncations of chromosome 2 to make a mini-chromosome for the assessment of chromosome stability by introducing telomere repeat sequences to delete most of p-arm or q-arm of chromosome 2. The obtained cell lines had 0.7 Mb mini-chromosome, and approximately 0.2% of mini-chromosome was lost per cell division in wild-type background while the rate of chromosome loss was significantly increased by the depletion of DDX11, a cohesin regulatory protein. Collectively, our findings propose that trisomic chromosomes are good targets to make unique artificial chromosomes.

Volcanic eruptions are one of the largest natural disturbances and are followed by the establishment of novel plant and animal communities in terrestrial ecosystems. However, the role of pre‐eruption vegetation in the establishment of arthropod communities after volcanic disturbances is currently unknown. Here, we asked whether the legacy of pre‐eruption vegetation mediates the community structure of ground‐dwelling arthropods after volcanic disturbances. The 2015 eruption in Kuchinoerabu‐jima Island, southwest Japan, caused two types of disturbances [a pyroclastic flow and a lahar (i.e., mudflow)] in three types of forests (broad‐leaved, black pine, and cedar). We hypothesized that pre‐eruption vegetation would influence the community structure of ground‐dwelling arthropods after the disturbance, and we expected that these effects from vegetation would be more prevalent for the less severe disturbances. The total abundance of ground‐dwelling arthropods decreased more in the lahar than the pyroclastic flow, and arthropod species composition showed a greater change after the lahar. These findings suggest that the lahar disturbance was more severe than the pyroclastic disturbance. Contrary to expectations, the difference in the arthropod species composition among the vegetation types was greatest after the lahar. After the pyroclastic flow, leaf litter remained to some degree with all the vegetation types. After the lahar disturbance, however, although the litter in the cedar forests remained, the litter disappeared completely from broad‐leaved and black pine forests. The disappearance of litter from these two forest types after the lahar may be responsible for the greater difference in arthropod species composition among the vegetation types. This study shows that the legacy effects of pre‐eruption vegetation on terrestrial arthropod communities after volcanic disturbance were different depending on the type of disturbance. Focusing on the role of pre‐eruption biotic factors would contribute to a better understanding of the recovery processes of terrestrial ecosystems after large natural disturbances., Our paper found that the legacy of pre‐eruption vegetation influenced the community structure of ground‐dwelling arthropods after volcanic disturbances. Moreover, counterintuitively, these legacy effects of vegetation were more evident for the more severe disturbances. This figure shows how biological legacy of forests remains after receiving the volcanic disturbances.

Background: Demand is growing for remote electrocardiogram (ECG) monitoring systems in the COVID-19 era in Japan. This study describes initial experiences with a small wireless ECG monitoring device and the utility of delivery via the postal service for outpatient care in Japan. Methods and Results: Long-term ECG monitoring following postal delivery of the small ECG device was evaluated in 25 patients. The patients had no difficulties with either the postal delivery or self-fitting and wearing the devices. A median of 57 h monitoring per patient was performed. Arrhythmic events were detected in 8 patients. Most patients were satisfied with both the ECG devices and postal delivery. Conclusions: Postal delivery of ECG devices could be used in clinical practice to achieve less or no in-person contact during the COVID-19 era.

Background Early recurrences of atrial arrhythmias (ERAAs) after ablation may require therapeutic intervention. The optimal medical therapy that prevents ERAAs requires clarification. This study aimed to compare the incidence of ERAAs between patients who received or did not receive bisoprolol transdermal patches (BTPs) at 3 months postablation. Methods This single‐center retrospective study enrolled 203 consecutive patients with paroxysmal atrial fibrillation (AF) who had undergone their first ablation, comprising 59 in the BTP group and 144 in the non‐BTP group. Follow‐up assessments were conducted monthly for 3 months. We evaluated the incidence of ERAAs. Results During the initial 1‐week observational period, the rate of ERAAs was lower in the BTP group (5.0%) than that in the non‐BTP group (18.8%) (P = .013). At 3 months postablation, the rate of ERAAs was lower in the BTP group (6.8%) than that in the non‐BTP group (25.7%) (P = .002). The cumulative freedom from ERAAs was significantly lower in the BTP group than in the non‐BTP group (log‐rank: P = .003). Administering BTPs was an independent factor that protected against ERAAs (odds ratio 0.181, [95% confidence interval 0.059‐0.559], P = .003). Conclusion BTPs may prevent ERAAs after ablation., The patients who were administered bisoprolol transdermal patches (BTPs) immediately after atrial fibrillation (AF) ablation showed significant reductions in the incidence of early recurrence of atrial arrhythmias (ERAAs) compared with the patients who were not administered BTPs. The efficacy of BTPs at preventing ERAAs was confirmed not only immediately after ablation, but also during the short period after AF ablation.

Conferring drought resistant traits to crops is one of the major aims of current breeding programs in response to global climate changes. We previously showed that exogenous application of acetic acid to roots of various plants could induce increased survivability under subsequent drought stress conditions, but details of the metabolism of exogenously applied acetic acid, and the nature of signals induced by its application, have not been unveiled. In this study, we show that rice rapidly induces jasmonate signaling upon application of acetic acid, resulting in physiological changes similar to those seen under drought. The major metabolite of the exogenously applied acetic acid in xylem sap was determined as glutamine—a common and abundant component of xylem sap—indicating that acetic acid is not the direct agent inducing the observed physiological responses in shoots. Expression of drought-responsive genes in shoot under subsequent drought conditions was attenuated by acetic acid treatment. These data suggest that acetic acid activates root-to-shoot jasmonate signals that partially overlap with those induced by drought, thereby conferring an acclimated state on shoots prior to subsequent drought.

Because of their many useful and unique properties, boronic acids are well suited for biomedical applications such as antitumor chemotherapy and boron neutron capture therapy (BNCT). Bortezomib, a boronic acid derivative, has drawn a lot of attention as a potent proteasome inhibitor. Nevertheless, because of rapid excretion and off-target effects, the clinical translation of boronic acid-containing drugs is limited. To this end, we employed a polymeric carrier to stably encapsulate boronic acid-containing drugs and achieve superior pharmacokinetics with an on-target drug release capability. Accordingly, to construct a supramolecular polymeric nanoparticle, we took advantage of the facile, stable, and pH-sensitive conjugation between boronic acids and diethanolamine-installed polymeric carriers. We demonstrated the feasibility of our molecular design by generating and applying bortezomib-loaded nanoparticles to a subcutaneous tumor-bearing mouse model. Stable encapsulation and pH-sensitive release of bortezomib facilitated antitumor efficacy and alleviated hepatotoxicity. We also verified the versatility of our approach through biological evaluations of the nanoparticles encapsulating benzo(b)thiophene-2-boronic acid, phenylboronic acid, and p-phenylene-diboronic acid.

Accumulated studies have revealed that spiders, which are believed to be true predators, also feed on various plant materials such as pollen, nectar, and stigmatic exudate. Hereby, we report observational cases of fermented tree sap feeding by four spider species, namely Sinopoda forcipata (Karsch, 1881) (Sparassidae), Otacilia komurai (Yaginuma, 1952) (Phrurolithidae), Weintrauboa contortipes (Karsch, 1881) (Pimoidae), and Doenitzius cf. peniculus Oi, 1960 (Linyphiidae), in deciduous forests in Japan. This is the first report of spiders feeding on fermented sap, and also the first report of plant material consumption in the families Sparassidae, Phrurolithidae, and Pimoidae.

Vitamin D has an immune-modulating effect, related to the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). However, few studies have focused on the difference between patients with asthma and COPD in the association of circulating vitamin D levels with clinical outcomes. We sought to investigate the associations of circulating vitamin D levels with health-related QOL (HR-QOL), severity, and exacerbations. Subjects included 152 asthma patients and 50 COPD patients. We measured plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3]. HR-QOL was assessed using the EuroQoL 5-Dimension (EQ-5D) and the 12-item Short Form Health Survey (SF-12) scales. Exacerbations were recorded during a one-year follow-up. Associations between plasma 25 (OH)D3 concentrations and outcome variables were evaluated using linear regression. Plasma concentrations of 25(OH)D3 were positively associated with the EQ-5D index value and the SF-12 physical component score in patients with asthma; however, such associations were not observed in patients with COPD. A significant association between severity and plasma concentrations of 25(OH)D3 was found only in patients with COPD. The hazard ratios (95% confidence interval) of plasma 25(OH)D3 concentrations (per 1 ng/mL decrease) for time to first exacerbation was 1.38 (1.10-1.75; p = 0.006) and 0.95 (0.87-1.03; p = 0.179) in patients with COPD and asthma, respectively. Lower concentrations of plasma 25(OH)D3 contributed to lower HR-QOL in patients with asthma, and were associated with severity and risk of future exacerbations in patients with COPD.

Development of pollen, the male gametophyte of flowering plants, is tightly controlled by dynamic changes in gene expression. Recent research to clarify the molecular aspects of pollen development has revealed the involvement of several transcription factors in the induction of gene expression. However, limited information is available about the factors involved in the negative regulation of gene expression to eliminate unnecessary transcripts during pollen development. In this study, we revealed that AtNOT1 is an essential protein for proper pollen development and germination capacity. AtNOT1 is a scaffold protein of the AtCCR4–NOT complex, which includes multiple components related to mRNA turnover control in Arabidopsis. Phenotypic analysis using atnot1 heterozygote mutant pollen showed that the mature mutant pollen failed to germinate and also revealed abnormal localization of nuclei and a specific protein at the tricellular pollen stage. Furthermore, transcriptome analysis of atnot1 heterozygote mutant pollen showed that the downregulation of a large number of transcripts, along with the upregulation of specific transcripts required for pollen tube germination by AtNOT1 during late microgametogenesis, is important for proper pollen development and germination. Overall, our findings provide new insights into the negative regulation of gene expression during pollen development, by showing the severely defective phonotype of atnot1 heterozygote mutant pollen.

Atrial standstill (AS) is a rare condition characterized by the absence of electrical and mechanical atrial activity,1 first described by Cushny.2 The absence of P waves and bradycardia, along with a wide QRS complex, are seen on the electrocardiogram (ECG). The clinical course of AS varies greatly; the timeline can be persistent or transient, and the spatial distribution of the atrial lesion can be diffuse or partial.3, 4 In many cases, the AS appears initially in the right atrium (RA) and progresses to the entire left atrium. It occasionally complicates symptomatic sick sinus syndrome.5 We hereby describe a case of AS where a dual-chamber permanent pacemaker implantation was necessary owing to symptomatic sick sinus syndrome. An electrophysiological study (EPS) revealed inactivity throughout almost the entire RA, with the exception of the coronary sinus (CS). A permanent atrial lead was therefore placed in the CS.

Hemolytic uremic syndrome (HUS) and acute encephalopathy caused by enterohemorrhagic Escherichia coli infection occur commonly in children, whereas adult-onset disease is rare. Here we report the case of a 24-year-old woman who developed acute encephalopathy and recovered without sequelae. She initially developed abdominal pain and diarrhea. On day 6, O-157 Shiga toxin was detected in her stool and she developed HUS. On day 11, acute encephalopathy developed and she required artificial ventilation. She was treated with steroid pulse therapy and plasma exchange (PE) and then discharged on day 53 without any sequelae. Globotriaosylceramide, a Shiga toxin receptor, is more frequently present on the cellular membranes of women than on those of men. Therefore, it is conceivable that adult women are at a higher risk of developing acute encephalopathy than men. Steroid pulse therapy and PE may effectively treat acute encephalopathy by reducing inflammatory cytokine levels in the blood; therefore, these treatments should be proactively considered.

Background: Some of atrial fibrillation (AF) drivers are found in lesser late-gadolinium enhancement (LGE) areas, as well as heterogenous ones. The atrial wall thickness (AWT) has been reported to be important as a possible AF substrate. However, the AWT and degree of LGEs as an AF substrate has not been fully validated in humans. Objective: The purpose of this study was to evaluate the impact of the AWT in lesser LGE areas on AF drivers. Methods: A total of 287 segments in 15 persistent AF patients were assessed. AF drivers were defined as non-passively activated areas (NPAs), where rotational activation was frequently observed, and were detected by the novel real-time phase mapping (ExTRa Mapping). Lesser LGE areas were defined as areas with a volume ratio of the enhancement voxel of

The gnaphosid spider Coillina baka Yin & Peng, 1998, originally described from Yunnan, China is newly recorded from Chin State, Myanmar. While its holotype (male) was the only known record of the spider so far, the female is described and illustrated herein for the first time. The detailed structures of the male palp and female genitalia of this species are depicted, and its possible relationship with some species of Synaphosus Platnick & Shadab, 1980 is briefly discussed.

Solute carrier (SLC) 16A11 has been reported as a risk gene for type 2 diabetes (T2D). However, the physiological function of SLC16A11 has not yet been clarified, and the relationship between SLC16A11 and T2D condition remains unclear. Therefore, we performed an association analysis between the SLC16A11 genotype and T2D pathology. The SLC16A11 genotype was determined by direct sequencing in 85 Japanese patients with T2D. The genotypes were analyzed by Mann-Whitney's U test and Chi-square test. Six single nucleotide polymorphisms (SNPs) were detected in the SLC16A11 gene, and five of them formed a haplotype (5SNP haplotype). The 5SNP haplotype carriers had significantly higher fasting plasma glucose (FPG), total cholesterol (T-CHO), and low-density lipoprotein cholesterol (LDL-C) than the noncarriers. The SLC16A11 genotype affected the values of laboratory parameters for T2D, particularly of blood lipids. The function of SLC16A11 may be related to lipid metabolism.

We report a case of acyclovir encephalopathy in a 77-year-old man who was introduced to peritoneal dialysis three years earlier. He developed herpes zoster and was treated with acyclovir (ACV) at 800 mg daily per oral. Two days later, he developed consciousness disturbance, hallucinations and asterixis. Acyclovir was stopped and continuous ambulatory peritoneal dialysis (CAPD) was switched to hemodialysis, which resulted in the resolution of his symptoms. Because the optimal dose of ACV varies among individuals depending on the bioavailability of ACV and metabolic enzyme activity, ACV encephalopathy can occur even when the acyclovir dose is modified according to the renal function of the affected patient. Because CAPD provides a poorer ACV clearance than hemodialysis, CAPD patients tend to have a higher risk of developing ACV encephalopathy and to recover more slowly. If CAPD patients develop ACV encephalopathy, a temporary change in the type of dialysis to hemodialysis should be considered.

Permanent pacemaker implantation (PPI) following trans catheter aortic replacement (TAVR) is a frequent post interventional complication. Four-dimension computed tomography color map imaging (4D-CTCMI) may be able to show a His bundle and whether severe conduction disturbance occur after TAVR. The

Early recurrences of atrial arrhythmias (ERAA) after atrial fibrillation (AF) ablation may require therapeutic intervention. Optimal medical therapy for the prevention of ERAA, however, remains unclear. The bisoprolol transdermal patch (BTP) which is a novel transdermal β-blocker formulation

The aim of this study is to experimentally evaluate the computed tomography (CT) attenuation of water, saline, iced saline and water ice cubes in order to relate these measurements to low density findings of cadavers on PMCT. Comparing the fluids with the iced materials, the CT number was lower in iced (frozen, with gas) saline (fNaCl) and ice cubes (frozen, without gas) (fH 2 O) than in saline (NaCl) and tap water (H 2 O). The fNaCl, which contained small air bubbles, presented significant lower CT number than fH 2 O. The fNaCl and fH 2 O showed around −80 HU and the values were concordant with the theoretical result. In cases where low density is found when a cadaver is undergoing a CT examination at low temperature, including the freezing effect as a new differential diagnosis could result in more accurate PMCT interpretation.

A serine protease with caspase- and legumain-like activities from basidiocarps of the edible basidiomycete Flammulina velutipes was characterized. The protease was purified to near homogeneity by three steps of chromatography using acetyl-Tyr-Val-Ala-Asp-4-methylcoumaryl-7-amide (Ac-YVAD-MCA) as a substrate. The enzyme was termed FvSerP (F. velutipes serine protease). This enzyme activity was completely inhibited by the caspase-specific inhibitor, Ac-YVAD-CHO, as well as moderately inhibited by serine protease inhibitors. Based on the N-terminal sequence, the cDNA of FvSerP was identified. The deduced protease sequence was a peptide composed of 325 amino acids with a molecular mass of 34.5 kDa. The amino acid sequence of FvSerP showed similarity to neither caspases nor to the plant subtilisin-like serine protease with caspase-like activity called saspase. FvSerP shared identity to the functionally unknown genes from class of Agaricomycetes, with similarity to the peptidase S41 domain of a serine protease. It was thus concluded that this enzyme is likely a novel serine protease with caspase- and legumain-like activities belonging to the peptidase S41 family and distributed in the class Agaricomycetes. This enzyme possibly functions in autolysis, a type of programmed cell death that occurs in the later stages of development of basidiocarps with reference to their enzymatic functions.

Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82-23.79, p = 1.8 x 10-5) and 6.3% of patients with Parkinson's disease (n = 32) (OR = 5.18, 95%CI: 1.1-50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.

e ubiquitin/26S proteasome system (UPS) plays a central role in the degradation of short-lived regulatory proteins that control many cellular events. In this study, the Arabidopsis knockout mutant rpt2a, which contains a defect in the AtRPT2a subunit of the 26S proteasome regulatory particle, showed hypersensitivity to sugars as well as enlarged leaves. When the role of RPT2a in sugar response was examined in further detail it was found that putatively only the AtRPT2a gene of 19S proteasome was markedly transcriptionally promoted by sugar application. Notably, poly-ubiquitinated proteins degraded by the UPS accumulated signi cantly in rpt2a mutant under 6% sucrose conditions compared to wild type. In addition, the AtRPT2a gene in gin2, a glucose insensitive mutant with a defective glucose-sensing hexokinase, was not upregulated by sugar application, indicating that AtRPT2a is involved in hexokinase-dependent sugar response. Taken together, the above ndings indicate that AtRPT2a plays an essential role in the maintenance of proteasome-dependent proteolysis activity in response to sugars.

When Eu2O3 powder compact and film are irradiated with ultraviolet (UV) laser light in a vacuum, their photoluminescence (PL) spectra change from a red sharp-line structure to a white broad band, which can be clearly seen with the naked eye. After removing the UV laser light, the white PL continues for more than several months at room temperature under room light, in spite of any changes of atmosphere. By irradiating with the same UV laser light at room temperature under O2 gas atmosphere, the original red PL state reappears. Such a reversible phenomenon may well yield materials for white-light-emitting devices and erasable optical storage.

Backgrounds and purpose Recently, newly developed drugs such as thalidomide, lenalidomide and bortezomib have significantly improved survival of the patients with multiple myeloma (MM). However, certain group of the patients who have characteristic high-risk cytogenetic changes such as deletion of TP53 tumor suppressor gene revealed significantly shorter survival. In patients with deletion of TP53 gene, the somatic point mutation in the residual TP53 gene has been reported to be rare. Thus, the exact role of alteration of TP53 gene in high-risk myeloma remains unclear. Polymorphism of TP53 gene at codon 72 in exon 4, CGC to CCC transition, leads to arginine (Arg) to proline (Pro) amino-acid substitution. Biological analyses showed that the Arg variant more efficiently induces expression of P21 and apoptosis via Ser-6 and 20 phosphorylation of p53 protein. In contrast the Pro variant is less resistant to MDM-2-mediated degradation and more potently induced cell-cycle arrest and DNA damage repair. Recently, clinical significance of this polymorphism has been extensively studied in solid tumors as well as hematological malignancies including non-Hodgkin lymphoma and leukemia. However, consistent association of the polymorphism with cancer risk has not been elucidated. The purpose of this study is to examine codon 72 polymorphism in patients with refractory multiple myeloma (MM) treated with thalidomide, and to elucidate its association with myeloma risk and outcome of thalidomide-therapy. Patients & methods A total of 37 Japanese patients with refractory or relapsed MM who were treated with thalidomide monotherapy were included in this study. Three cases showed deletion of TP53 gene by fluorescence in situ hybridization (FISH) analyses. The codon 72 polymorphism was evaluated in the rest of 34 patients. Genomic DNA was isolated from bone marrow mononuclear cells. The genomic TP53 gene was amplified by polymerase chain reaction, and the amplified DNAs were directly sequenced. Results Direct DNA sequence showed that the Pro/Pro homozygote was observed in six patients (18%), Pro/Arg heterozygote in 12 (35%) and Arg/Arg homozygote in 16 (47%). There was no significant difference in the frequency of the polymorphism between the 34 Japanese MM patients and the healthy Japanese individuals (P=0.44). Thus, association of codon 72 polymorphism with myeloma risk has failed to be elucidated. The response rate to thalidomide therapy was 33% in the patients with Pro/Pro, 27% in Pro/Arg and 44% in Arg/Arg (P=0.49), respectively. Other clinical backgrounds including age, sex, Durie-Salomon stage, ISS stage, serum creatinine, albumin, b2M, calcium, hemoglobin levels and M-protein type were not correlated with TP53 codon 72 polymorphism, either. Progression free survival (PFS), overall survival (OS) and post-relapse survival were shown in Figure 1. The patients with Pro allele tended to show shorter PFS; 5 weeks for the patients with Pro/Pro versus 32 weeks for those with Pro/Arg plus Arg/Arg (P=0.07) (Figure 1). Overall survival (OS) of the patients with Pro/Pro, Pro/Arg and Arg/Arg allele was 18 weeks, 49 weeks and 133 weeks, respectively (P=0.027). Especially, the patients with Pro/Pro allele revealed significantly shorter OS compared with those with Pro/Arg plus Arg/Arg (18 weeks versus 100 weeks, P=0.023) (Figure 1). Significant difference of OS in patients with Pro/Pro+Pro/Arg vs Arg/Arg (P= 0.032) suggested the dominant effect of Pro allele for poorer prognosis. Post-relapse survival of the patients with Pro/Pro, Pro/Arg and Arg/Arg allele was 11, 42 and 64 weeks, respectively (P=0.054). Post-relapse survival for Pro/Pro versus Pro/Arg plus Arg/Arg were 11 weeks versus 64 weeks (P=0.029). Conclusion These results indicated that codon 72 polymorphism did not correlated with myeloma risk, but significantly associated with therapeutic outcome. Namely, the patients with Pro allele revealed earlier relapse and shorter post-relapse survival, resulted in shorter OS in thalidomide therapy. Further evaluation is needed to clarify whether the codon 72 polymorphism will be a new prognostic marker for the treatment with novel drugs. Disclosures: No relevant conflicts of interest to declare.

Abstract 4076 Purpose: Despite recent advances in the use of newly developed drugs, high-risk multiple myeloma (MM) patients harboring del13q, t(4;14) or del17p revealed significantly shorter survival. To overcome the limitation, we have screened forty synthetic anilinoquinazoline (AQ) derivatives, and found a novel compound, Q15, which significantly inhibited the growth of MM cell lines with high-risk chromosomal abnormalities. The purpose of this study is to examine anti-tumor and anti-osteoclastogenic activities of Q15 and to clarify the possibility of development of new drug effective for high-risk MM and bone diseases. Methods and Results: Forty AQ derivatives were synthesized and screened for anti-proliferative effect on KMS34 cells. Q15 strongly inhibited growth of t(4;14)-positive KMS34 cells and induced apoptosis in much lower concentration (IC50=78nM) compared with gefitinib (IC50=2500nM), a representative AQ. Q15 also inhibited growth of other MM cell lines harboring high-risk chromosomal abnormalities. It was also found that Q15 did not inhibit intracellular tyrosine phosphorylation induced by EGF, FGF-2, HGF and IL-6, suggesting that Q15 showed anti-tumor activity in a different mechanism from that of gefitinib. In vivo anti-myeloma activity was evaluated by intraperitoneal injection of Q15 into KMS34-bearing lcr/SCID mice. Twenty mg/kg Q15 significantly delayed the tumor growth in these mice. Histopathological examinations revealed apoptosis of MM cells in Q15-treated mice. Growth of colony-forming cells was not suppressed by much higher concentrations (25μ M) of Q15 than IC50, suggesting low hematopoietic toxicity of Q15. In pharmacokinetic study using high-performance liquid chromatography (HPLC), the plasma concentration of Q15 in mice reached a maximum (Cmax=4.5μ M) at 1.5hr after injection, and its half life (T1/2) was 4.5hr. In addition, anti-osteoclastogenic activity was also examined by adding Q15 to M-CSF/RANK ligand-induced osteoclastogenic culture of bone marrow mononuclear cells from C57BL/6JJcl mice. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts was reduced in the presence of Q15. Conclusion: Q15, a novel AQ derivative, has anti-MM activity in vivo and is a potentially safe and effective drug for high-risk MM with bone lesions. Disclosures: No relevant conflicts of interest to declare.