Interleukin-8 Producing Malignant Fibrous Histiocytoma with Prolonged Fever

We present a case of malignant fibrous histiocytoma accompanied by prolonged spiking fevers, which disappeared after tumor resection. Sarcoma with fever as a primary symptom is rare. Furthermore, in this case, fever was closely related to the clinical course of the tumor. In order to detect possible production of febriferous substance(s), we used blood and tumor tissue samples to investigate nine candidate cytokines possibly responsible for the fever. Expression of IL-8 mRNA was detected in preoperative peripheral blood mononuclear cells by RT-PCR. Expressions of IL-6, IL-8, IFN-γ and TNF-α mRNAs were also detected in tumor tissue, while IL-1α, IL-1β, IL-2, IL-4 and COX-2 mRNAs were not. We suspected IL-8 to be a causative factor, and examined its localization by immunohistochemical staining, paraffin sections of tumor tissue stained positive for IL-8. Since infiltrating mononuclear cells were positive for IL-8, this may explain the tumor-associated fever. This case involves intratumoral production of IL-8 as a causative factor, and IL-6, IL-8, IFN-γ and TNF-α cytokine production might have resulted from stimulation with a substance(s) derived from tumor tissue, since the fever disappeared postoperatively. To date the patient is alive and in good health for 7 years and 2 months since the surgery

Comprehensive analysis of liver and blood miRNA in precancerous conditions

Streptozotocin administration to mice (STZ-mice) induces type I diabetes and hepatocellular carcinoma (HCC). We attempted to elucidate the carcinogenic mechanism and the miRNA expression status in the liver and blood during the precancerous state. Serum and liver tissues were collected from STZ-mice and non-treated mice (CTL-mice) at 6, 10, and 12 W. The exosome enriched fraction extracted from serum was used. Hepatic histological examination and hepatic and exosomal miRNA expression analysis were serially performed using next-generation sequencing (NGS). Human miRNA expression analysis of chronic hepatitis liver tissue and exosomes, which were collected before starting the antiviral treatment, were also performed. No inflammation or fibrosis was found in the liver of CTL-mice during the observation period. In STZ-mice, regeneration and inflammation of hepatocytes was found at 6 W and nodules of atypical hepatocytes were found at 10 and 12 W. In the liver tissue, during 6–12 W, the expression levels of let-7f-5p, miR-143-3p, 148a-3p, 191-5p, 192-5p, 21a-5p, 22-3p, 26a-5p, and 92a-3p was significantly increased in STZ-mice, and anti-oncogenes of their target gene candidates were down-regulated. miR-122-5p was also significantly down-regulated in STZ-mice. Fifteen exosomal miRNAs were upregulated in STZ-mice. Six miRNAs (let-7f-5p, miR-10b-5p, 143-3p, 191-5p, 21a-5p, and 26a-5p) were upregulated, similarly to human HCC cases. From the precancerous state, aberrant expression of hepatic miRNAs has already occurred, and then, it can promote carcinogenesis. In exosomes, the expression pattern of common miRNAs between mice and humans before carcinogenesis was observed and can be expected to be developed as a cancer predictive marker

Current-induced magnetization switching in MgO barrier magnetic tunnel junctions with CoFeB based synthetic ferrimagnetic free layers

We investigated the effect of using a synthetic ferrimagnetic (SyF) free layer in MgO-based magnetic tunnel junctions (MTJs) on current-induced magnetization switching (CIMS), particularly for application to spin-transfer torque random access memory (SPRAM). The employed SyF free layer had a Co40Fe40B20/ Ru/ Co40Fe40B20 and Co20Fe60B20/Ru/Co20Fe60B20 structures, and the MTJs(100x(150-300) nm^2) were annealed at 300oC. The use of SyF free layer resulted in low intrinsic critical current density (Jc0) without degrading the thermal-stability factor (E/kBT, where E, kB, and T are the energy potential, the Boltzmann constant, and temperature,respectively). When the two CoFeB layers of a strongly antiferromagnetically coupled SyF free layer had the same thickness, Jc0 was reduced to 2-4x10^6 A/cm^2. This low Jc0 may be due to the decreased effective volume under the large spin accumulation at the CoFeB/Ru. The E/kBT was over 60, resulting in a retention time of over ten years and suppression of the write current dispersion for SPRAM. The use of the SyF free layer also resulted in a bistable (parallel/antiparallel) magnetization configuration at zero field, enabling the realization of CIMS without the need to apply external fields to compensate for the offset field.Comment: 6 page

A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding

Phosphoinositides have crucial roles in cellular controls, many of which have been established through the use of small-molecule inhibitors. Here, we describe YM201636, a potent inhibitor of the mammalian class III phosphatidylinositol phosphate kinase PIKfyve, which synthesizes phosphatidylinositol 3,5-bisphosphate. Acute treatment of cells with YM201636 shows that the PIKfyve pathway is involved in the sorting of endosomal transport, with inhibition leading to the accumulation of a late endosomal compartment and blockade of retroviral exit. Inhibitor specificity is shown by the use of short interfering RNA against the target, as well as by rescue with the drug-resistant yeast orthologue Fab1. We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux

NCRT with S-1 plus irinotecan for LALRC

Background and purpose: Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1. Materials and methods: Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45 Gy in 25 fractions. S-1 (80 mg/m2/day) was administered on days 1–5, 8–12, 22–26, and 29–33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60 mg/m2 (level 1). Surgery was performed 6–10 weeks after the chemoradiotherapy. Results: Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80 mg/m2 (level 2), but developed in 3 of the 6 patients who received irinotecan at 90 mg/m2 (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%. Conclusions: Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60 mg/m2

Heliocentric Distance Dependence of Zodiacal Light Observed by Hayabusa2#

Zodiacal light (ZL) is sunlight scattered by interplanetary dust particles (IDPs) at optical wavelengths. The spatial distribution of IDPs in the Solar System may hold an important key to understanding the evolution of the Solar System and material transportation within it. The number density of IDPs can be expressed as $n(r) \sim r^{-\alpha}$, and the exponent $\alpha \sim 1.3$ was obtained by previous observations from interplanetary space by Helios 1/2 and Pioneer 10/11 in the 1970s and 1980s. However, no direct measurements of $\alpha$ based on ZL observations from interplanetary space outside Earth's orbit have been performed since then. Here, we introduce initial results for the radial profile of the ZL at optical wavelengths observed over the range 0.76-1.06 au by ONC-T aboard the Hayabusa2# mission in 2021-2022. The ZL brightness we obtained is well reproduced by a model brightness, although there is a small excess of the observed ZL brightness over the model brightness at around 0.9 au. The radial power-law index we obtained is $\alpha = 1.30 \pm 0.08$, which is consistent with previous results based on ZL observations. The dominant source of uncertainty arises from the uncertainty in estimating the diffuse Galactic light (DGL).Comment: 22 pages, 19 figures, 4 tables, accepted for publication by Earth, Planets and Spac

Integration and Diffusion in Sustainable Development Goals: Learning from the Past, Looking into the Future

One of the next major challenges for research and policy on sustainability is setting the post-2015 Development Agenda. This challenge arises as a direct result of the formal ending of the Millennium Development Goals (MDGs) in 2015 and as an outcome of the 2012 United Nations Conference on Sustainable Development (Rio+20). The post-2015 Development Agenda is expected to include two agendas: one on human well-being to advance the MDG targets and the other on planetary well-being, which requires a safe "operating space" within the Earth\u27s life-support system. In contrast to the MDGs, the Sustainable Development Goals (SDGs) are meant to apply to both developing and developed countries and create a space for development within the stable functioning of the Earth\u27s systems. However, what might this all look like? For answers, this paper reviews the achievements and reflections of the MDGs to date and identifies new challenges entailed in the shift of development goals from "millennium" to "sustainable". While most of the existing studies look at these two sets of issues separately, combining the two reveals two important features of the SDGs. First, SDGs need to integrate both human and planetary well-being in a goal, and second, goals, or sub-goals, need to be formulated at multiple levels, from global to local levels. While the MDGs represented no integrated goals, some of the existing proposals on SDGs include integrated goals. However, our analysis has shown that they do not present the vertical diffusion of goals. Considering both integration and diffusion in the architecture of SDGs is a remaining task

Correction: Kanie, N., et al. Integration and Diffusion in Sustainable Development Goals: Learning from the Past, Looking into the Future. Sustainability 2014, 6, 1761?1775

The authors wish to make the following correction, due to a typographical error, to this paper [1]. On page 1761, the author name “Shunsuke Mangagi” should be “Shunsuke Managi”. [...

Republication: Targeting PI3KC2β Impairs Proliferation and Survival in Acute Leukemia, Brain Tumours and Neuroendocrine Tumours

BACKGROUND Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks. MATERIALS AND METHODS The expression pattern and functions of the class II PI3KC2β isoform were investigated in a panel of tumour samples and cell lines. RESULTS Overexpression of PI3KC2β was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2β or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2β also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents. CONCLUSION Together, these data show that PI3KC2β contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation