Background:Despite the well-established benefits in patients with non-valvular atrial fibrillation (NVAF), oral anticoagulants (OAC) have been underused in elderly patients. We investigated the ...characteristics and status of anti-thrombotic therapy in elderly NVAF patients in Japan according to a history of stroke or of transient ischemic attack (TIA).Methods and Results:In a multicenter, prospective, observational study, 32,726 Japanese patients aged ≥75 years with NVAF were enrolled, and divided into 3 groups for the present analysis: 6,543 patients with previous ischemic stroke (IS) or TIA (2,410 women), 275 with previous hemorrhagic stroke (HS; 113 women), and the other 25,908 without previous stroke or TIA (11,470 women). Median CHADS2score was 5 in patients with IS/TIA, 2 in those with HS and 2 in those without stroke/TIA (P<0.05). Anti-thrombotic agents were used in 97.1% of patients with IS/TIA (OAC alone in 73.0%; antiplatelets alone in 3.7%; and both in 23.4%), 90.2% of those with HS (84.7%, 3.2%, and 12.1%, respectively), and 94.1% of those without stroke/TIA (83.4%, 2.7%, and 13.9%, respectively; P<0.05 for any anti-thrombotic choice). Of patients taking OAC, 72.2% received direct OAC (DOAC).Conclusions:In this unique nationwide NVAF registry of >30,000 elderly patients, >90% of patients, even those with HS, received anti-thrombotic therapy, nearly always with OAC. DOAC were the major choice of OAC.
Nanocellular polymer foams have shown significant potential for industrial applications because of their superior thermal, mechanical, and optical properties. Some of these properties may be further ...improved by enhancing the ordering of cell structures. However, it is challenging for conventional foaming methods to control both the cell size and ordering at the nanoscale. Here, we show an innovative method to produce highly ordered nanocellular polymer foams by incorporating the self-assembly of an asymmetric diblock copolymer with the UV-induced chemical foaming technique. The minor domains are designed to generate a gaseous compound from the partial cleavage of the functional group. It is demonstrated that the gas-producing reaction can be accelerated at a temperature low enough to prevent melting of the whole self-assembled template, by mixing a small amount of photoacid generator into the copolymer, followed by UV irradiation. The result is the production of polymer foams with the nanoscale cells highly aligned to the self-assembled domains.
Human epidermal growth factor receptor 2 (HER2) overexpression has been reported in various human cancers. HER2-targeted therapies showed clinical responses in humans with HER2-positive tumors. The ...incidence of canine primary lung cancer (cPLC) is increasing, but there are no effective systemic therapies for dogs with late-stage cPLC. HER2-targeted therapy could be an option for cPLC, but HER2 expression in cPLC remains unknown. We evaluated HER2 expression in cPLC. Immunohistochemical analysis revealed that 3 samples (19%) scored 3+; 8 (50%), 2+; 5 (31%); and 1+ and 0 (0%), 0. Of the cPLC tissues, 69% were HER2 positive (scored ≥2+). These data would lead to further evaluation of the role of HER2 in cPLC as a mechanism of malignancy and therapeutic target.
Controversies exist regarding the aggressive recurrence of glioblastoma after bevacizumab treatment. We analyzed the clinical impact of bevacizumab approval in Japan by evaluating the clinical course ...and relapse pattern in patients with glioblastoma.
We included 100 patients with IDH-wild-type glioblastoma from September 2006 to February 2018 in our institution. The patients were classified into the pre-bevacizumab (n = 51) and post-bevacizumab (n = 49) groups. Overall, progression-free, deterioration-free, and postprogression survivals were compared. We analyzed the relapse pattern of 72 patients, whose radiographic progressions were evaluated.
Significant improvement in progression-free (pre-bevacizumab, 7.5 months; post-bevacizumab, 9.9 months; P = 0.0153) and deterioration-free (pre-bevacizumab, 8.5 months; post-bevacizumab, 13.8 months; P = 0.0046) survivals was seen. These survival prolongations were strongly correlated (r: 0.91, P < 0.0001). The nonenhancing tumor pattern was novel in the post-bevacizumab era (5 of 33). The presence of a nonenhancing tumor did not indicate poor postprogression survival (hazard ratio: 0.82 0.26–2.62, P = 0.7377). The rate of early focal recurrence was significantly lower (P = 0.0155) in the post-bevacizumab (4 of 33) than in the pre-bevacizumab (18 of 39) era. There was a significant decrease in early focal recurrence after approval of bevacizumab in patients with unresectable tumors (P = 0.0110). The treatment era was significantly correlated with a decreased rate of early focal recurrence (P = 0.0021, univariate analysis; P = 0.0144, multivariate analysis).
Approval of first-line bevacizumab in Japan for unresectable tumors may prevent early progression and clinical deterioration of glioblastoma without worsening the clinical course after relapse.
Germ cell tumors constitute a heterogeneous group that displays a broad spectrum of morphology. They often arise in testes; however, extragonadal occurrence, in particular brain, is not uncommon, and ...whether they share a common pathogenesis is unknown. We performed whole exome sequencing in 41 pairs of central nervous system germ cell tumors (CNS GCTs) of various histology and their matched normal tissues. We then performed targeted sequencing of 41 selected genes in a total of 124 CNS GCTs, 65 testicular germ cell tumors (tGCTs) and 8 metastatic GCTs to the CNS. The results showed that mutually exclusive mutations of genes involved in the MAPK pathway were most common (48.4 %), typically in KIT (27.4 %), followed by those in the PI3K pathway (12.9 %), particularly in MTOR (6.5 %), among the 124 CNS GCTs. Pure germinomas and non-germinomatous germ cell tumors (NGGCTs), as well as CNS and testicular GCTs, showed similar mutational profiles, suggesting that GCTs share a common molecular pathogenesis. Mutated MTOR identified in CNS GCTs upregulated phosphorylation of the AKT pathway proteins including AKT and 4EBP1 in nutrient-deprived conditions and enhanced soft-agar colony formation; both events were suppressed in a dose-dependent manner by addition of the MTOR inhibitor pp242. Our findings indicate that the dominant genetic drivers of GCTs regardless of the site of origin are activation of the MAPK and/or PI3K pathways by somatic point mutations. Mutated MTOR represents a potential target for novel targeted therapies for refractory GCTs.
Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor ...receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0–3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored ≥2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.
The structure and properties of lithium salt solutions based on tris(2,2,2-trifluoroethyl)phosphate (TFEP) solvent have been studied to design a safer electrolyte system for large-sized lithium-ion ...battery applications. Influences of the ionic structure on the polarization behavior of the LiCoO
(LCO) positive electrode were investigated. The ionic conductivity and viscosity of the solution consisting of lithium salts dissolved in TFEP, LiX/TFEP (X = PF
, BF
and TFSA) (TFSA = (CF
SO
)
N), were measured. The results suggest that the ion-solvation structure greatly depends on the anionic species in the salt. Spectroscopic measurements also support the conclusion that the Li
-solvation structure varies with the lithium salts. The differences in the ionic structure of LiX/TFEP influence the electrochemical oxidation potential of the solution and the polarization behavior of the LCO electrode. The overvoltage for Li-desertion/insertion from/into LCO in LiX/TFEP, being much higher than that observed in conventional LIB electrolyte solutions, shows the order of BF
< PF
< TFSA. The addition of ethylene carbonate (EC) to LiX/TFEP increases the ionic conductivity, which is probably caused by changes in the Li
-solvation structure in TFEP. The overvoltage for the Li-desertion/insertion of LCO is much lowered by the addition of EC to LiX/TFEP.
Antiproliferative Activity of IL-27 on Melanoma Yoshimoto, Takayuki; Morishima, Noriko; Mizoguchi, Izuru ...
The Journal of immunology (1950),
05/2008, Letnik:
180, Številka:
10
Journal Article
Recenzirano
Odprti dostop
IL-27 is a member of the IL-6/IL-12 family and activates both STAT1 and STAT3 through its receptor, which consists of WSX-1 and gp130. We previously demonstrated that IL-27 has potent antitumor ...activities, which are mediated through CD8(+) T cells, NK cells, or its own antiangiogenic activity. In this study, we demonstrate that IL-27 also possesses a direct antiproliferative activity on melanoma. Although WSX-1 expression was hardly detected in parental mouse melanoma B16F10 cells, IL-27 activated STAT1 and STAT3 and up-regulated MHC class I in B16F10 transfectants expressing wild-type WSX-1. In contrast, IL-27 failed to activate STAT1 and up-regulate MHC class I in those expressing mutant WSX-1, in which the putative STAT1-binding Tyr-609 of the cytoplasmic region was replaced by Phe. IL-27 inhibited the tumor growth of transfectants expressing wild-type WSX-1 in a dose-dependent manner. IL-27 augmented the expression of IFN regulatory factor (IRF)-1 and IRF-8, which possess tumor suppressor activities, in B16F10 transfectants expressing wild-type WSX-1. Down-regulation of IRF-1 but not IRF-8 with small interfering RNA partially blocked the IL-27-induced growth inhibition. A small, but significant, direct antiproliferative effect of IL-27 was also observed in vivo. Moreover, several human melanoma cells were revealed to express both IL-27 receptor subunits, and activation of STAT1 and STAT3 and growth inhibition by IL-27 were detected. These results suggest that IL-27 has an antiproliferative activity on melanomas through WSX-1/STAT1 signaling. Thus, IL-27 may be an attractive candidate as an antitumor agent applicable to cancer immunotherapy.
Background
Nephrectomy is a curative treatment for localized renal cell carcinoma (RCC), but patients with poor prognostic features may experience relapse. Understanding the prognostic impact of ...programmed death-ligand 1 (PD-L1) expression in patients who underwent nephrectomy for RCC may aid in future development of adjuvant therapy.
Methods
Of 770 surgical specimens collected from Japanese patients enrolled in the ARCHERY study, only samples obtained from patients with recurrent RCC after nephrectomy were examined for this secondary analysis. Patients were categorized into low- and high-risk groups based on clinical stage and Fuhrman grade. Time to recurrence (TTR) and overall survival (OS) were analyzed.
Results
Both TTR and OS were shorter in patients with PD-L1-positive than -negative tumors (median TTR 12.1 vs. 21.9 months HR 1.46, 95% CI 1.17, 1.81; median OS, 75.8 vs. 97.7 months HR 1.32, 95% CI 1.00, 1.75). TTR and OS were shorter in high-risk patients with PD-L1-positive than -negative tumors (median TTR 7.6 vs. 15.3 months HR 1.49, 95% CI 1.11, 2.00; median OS, 55.2 vs. 83.5 months HR 1.53, 95% CI 1.06, 2.21) but not in low-risk patients.
Conclusions
This ARCHERY secondary analysis suggests that PD-L1 expression may play a role in predicting OS and risk of recurrence in high-risk patients with localized RCC.
Clinical Trial Registration: UMIN000034131.
In this study, we reclassified 400 consecutive glioma cases including pediatric cases, using the revised 2016 WHO classification with samples collected from the Kyushu University Brain Tumor Bank. ...The
IDH1
/
2, H3F3A
, key genetic markers in the 2016 classification, were analyzed using high-resolution melting, with DNA extracted from frozen tissues. The 1p/19q codeletions were evaluated using a microsatellite-based loss of heterozygosity analysis, with 18 markers, to detect loss of the entire chromosome arm. In the integrated diagnosis, 29 oligodendroglioma cases and 28 anaplastic oligodendroglioma cases were diagnosed as “
IDH
-mutant and 1p/19q-codeleted,” while 2 oligodendroglioma cases and 5 anaplastic oligodendroglioma cases were diagnosed as not otherwise specified (NOS). These “NOS” cases were either
IDH
-mutants or 1p/19q-codeleted, although characteristic oligodendroglial features were evident histologically. Better overall survival of patients with oligodendroglioma correlated with the molecular characteristic of “IDH-mutant and 1p/19q-codeleted,” rather than the WHO grade. Eleven “glioblastoma,
IDH
-wild-type” cases were classified as “1p/19q-codeleted”, however, chromosome 10 loss was also detected in 10 out of 11 cases. The 2016 WHO criteria for glioma classification leads to better diagnosis of patients. However, there are technical pitfalls and problems to be solved in the molecular analysis of routine diagnostics.
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