Primary Osteosarcoma in Patients Older than 40 Years of Age

Among the 665 patients who registered at our hospital, we reviewed 39 cases of high grade primary osteosarcoma in patients who were older than 40 yr of age. The aim of this study was to determine if a primary osteosarcoma in older patients has different clinical features, and a poorer prognosis than in younger patients. Two evaluations were performed. In the first, an attempt was made to determine the possible prognostic factors such as gender, location, size, alkaline phosphatase, radiological findings, chemotherapy intensity, chemotherapy-induced tumor necrosis, and surgical margin. The second evaluation involved assessment of whether there were any significant clinical differences between older patients and adolescents. According to the results, a primary osteosarcoma in older patients did not reveal any significant prognostic variables. A primary osteosarcoma in older patients showed a poorer prognosis due to relatively unusual locations, common abnormal radiological findings, and a poor response to chemotherapy. Therefore, careful attention should be paid to making an accurate diagnosis and new strategies for more effective treatment, including chemotherapy, must to be developed in order to achieve long term survival in older patients with osteosarcoma

Safety, tolerability of ES16001, a novel varicella zoster virus reactivation inhibitor, in healthy adults

Purpose Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of Elaeocarpus sylvestris var. ellipticus), a novel inhibitor of varicella zoster virus reactivation in healthy adults. Method Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (n = 32), subjects randomly received a single oral dose of 240, 480, 960, or 1440 mg ES16001 or a placebo. In the MAD study (n = 16), subjects randomly received once daily doses of 480 or 960 mg ES16001 or a placebo for 5 days. The safety and tolerability of the drug were evaluated by monitoring participants treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests. Results In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration. Conclusion ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ. Trial registration: CRIS, KCT0006066. Registered 7 April 2021—Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/19071).This study was funded by Genencell Co. Ltd, Yongin, Korea

SREBP1c-CRY1 signalling represses hepatic glucose production by promoting FOXO1 degradation during refeeding

SREBP1c is a key lipogenic transcription factor activated by insulin in the postprandial state. Although SREBP1c appears to be involved in suppression of hepatic gluconeogenesis, the molecular mechanism is not thoroughly understood. Here we show that CRY1 is activated by insulin-induced SREBP1c and decreases hepatic gluconeogenesis through FOXO1 degradation, at least, at specific circadian time points. SREBP1c−/− and CRY1−/− mice show higher blood glucose than wild-type (WT) mice in pyruvate tolerance tests, accompanied with enhanced expression of PEPCK and G6Pase genes. CRY1 promotes degradation of nuclear FOXO1 by promoting its binding to the ubiquitin E3 ligase MDM2. Although SREBP1c fails to upregulate CRY1 expression in db/db mice, overexpression of CRY1 attenuates hyperglycaemia through reduction of hepatic FOXO1 protein and gluconeogenic gene expression. These data suggest that insulin-activated SREBP1c downregulates gluconeogenesis through CRY1-mediated FOXO1 degradation and that dysregulation of hepatic SREBP1c-CRY1 signalling may contribute to hyperglycaemia in diabetic animals

Characteristics of Ba(Zr0.1Ce0.7Y0.2)O3-δ nano-powders synthesized by different wet-chemical methods for solid oxide fuel cells

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1A6A3A03004416) and (NRF-2015M1A2A2056833).Ba(Zr0.1Ce0.7Y0.2)O3-δ nano-particles were prepared by different wet-chemical synthesis, Pechini (BZCY(P)) and co-precipitation (BZCY(C)), respectively. The BZCY(C) powders have a particle size in range of about 50~150 nm, which is smaller than the BZCY(P) powders with about 500~900 nm. Both the BZCY materials show perovskite structures, but there are impurities in the BZCY (P). Moreover, the electrolyte density was higher in the BZCY (C) than the BZCY (P). The single cells with BZCY (C) electrolytes exhibited about 0.23 W cm−2 at 600 °C and about 0.31 W cm−2 at the same temperature were obtained when the anode-functional layer was introduced between the anode and electrolyte. Thus, the BZCY prepared by carbonate-derived co-precipitation method can be more favorable for high-purity and dense electrolytes in the solid oxide fuel cells than the BZCY prepared by Pechini method.PostprintPeer reviewe

The prognostic factors of recurrent GCT: A cooperative study by the Eastern Asian Musculoskeletal Oncology Group

Background Giant-cell tumor (GCT) of bone is a common primary benign tumor with high local recurrence and potential distant metastasis or malignant transformation. We haveinvestigated the clinical behavior of recurrent GCT of bone in the extremities. Methods We retrospectively reviewed 110 patients with recurrent GCTs of bone in the extremities treated by the Eastern Asian Musculoskeletal Oncology Group. The factors that affected the number of recurrences and distant metastasis were analyzed. Results The median interval between initial surgery and the first recurrence of GCTwas 16 months (2-180 months). All patients received additional surgery for first recurrence. Twenty-five patients had a second recurrence and 6 patients had a third recurrence. The mean interval between theinitial surgery and the first recurrence correlated withthe eventual number of recurrences-14.1 months for the repeated recurrence groups (two and three recurrences) and 28.3 months for the single recurrence group (p = 0.016). Campanacci grade did not correlate with repeated recurrence (p = 0. 446). The venue of the initial surgery did not correlate with recurrence but did affect preservation of the adjacent joint (chi-squared test; p =0.046). Campanacci grade II and III also correlated withsacrifice of the adjacent joint (p = 0.020). The incidence of lung metastasis and malignant transformation were 7.5% (8 out of 107 patients) and 2.7% (3 out of 110 patients), respectively. Repeat recurrence was associated with lung metastasis (p = 0.018). © The Japanese Orthopaedic Association 2011

Haloperidol regulates the phosphorylation level of the MEK-ERK-p90RSK signal pathway via protein phosphatase 2A in the rat frontal cortex

Haloperidol, a classical antipsychotic drug, affects the extracellular signal-regulated kinase (ERK) pathway in the brain. However, findings are inconsistent and the mechanism by which haloperidol regulates ERK is poorly understood. Therefore, we examined the ERK pathway and the related protein phosphatase 2A (PP2A) in detail after haloperidol administration. Haloperidol (0.5 and 1 mg/kg) induced biphasic changes in the phosphorylation level of mitogen-activated protein kinase kinase (MEK), ERK, and p90 ribosomal S6 kinase (p90RSK) without changing Raf-1 phosphorylation. Fifteen minutes after haloperidol administration, MEK-ERK-p90RSK phosphorylation increased, whilst PP2A activity decreased. At 60 min, the reverse was observed and the binding of PP2A to MEK and ERK increased. Higher dosages of haloperidol (2 and 4 mg/kg), affected neither MEK-ERK-p90RSK phosphorylation nor PP2A activity. Accordingly, PP2A regulates acute dose- and time-dependent changes in MEK-ERK-p90RSK phosphorylation after haloperidol treatment. These findings suggest the involvement of a dephosphorylating mechanism in the acute action of haloperidol

Ultraviolet nanoimprinted polymer nanostructure for organic light emitting diode application

Light extraction efficiency of a conventional organic light emitting diode (OLED) remains limited to approximately 20% as most of the emission is trapped in the waveguide and glass modes. An etchless simple method was developed to fabricate two-dimensional nanostructures on glass substrate directly by using ultraviolet (UV) curable polymer resin and UV nanoimprint lithography in order to improve output coupling efficiency of OLEDs. The enhancement of the light extraction was predicted by the three-dimensional finite difference time domain method. OLEDs integrated on nanoimprinted substrates enhanced electroluminance intensity by up to 50% compared to the conventional device

Acetic acid-indigo carmine chromoendoscopy for delineating early gastric cancers: its usefulness according to histological type

<p>Abstract</p> <p>Background</p> <p>Endoscopic treatments, such as endoscopic submucosal dissection (ESD) and laparoscopic gastrectomy, are increasingly used to treat a subset of patients with early gastric cancer (EGC). To achieve successful outcomes, it is very important to accurately determine the lateral extent of the tumor. Therefore, we investigated the diagnostic performance of chromoendoscopy using indigo carmine dye added to acetic acid (AI chromoendoscopy) in delineating differentiated or undifferentiated adenocarcinomas in patients with EGC.</p> <p>Methods</p> <p>We prospectively included 151 lesions of 141 patients that had an endoscopic diagnosis of EGC. All the lesions were examined by conventional endoscopy and AI chromoendoscopy before ESD or laparoscopic gastrectomy. The border clarification between the lesion and the normal mucosa was classified as distinct or indistinct before and after AI chromoendoscopy.</p> <p>Results</p> <p>The borders of the lesions were distinct in 66.9% (101/151) with conventional endoscopy and in 84.1% (127/151) with AI chromoendoscopy (<it>P </it>< 0.001). Compared with conventional endoscopy, AI chromoendoscopy clarified the border in a significantly higher percentage of differentiated adenocarcinomas (74/108 [68.5%] vs 97/108 [89.8%], respectively, <it>P </it>< 0.001). However, the border clarification rate for undifferentiated adenocarcinomas did not differ between conventional endoscopy and AI chromoendoscopy (27/43 [62.8%] vs 30/43 [70.0%], respectively, <it>P </it>= 0.494).</p> <p>Conclusions</p> <p>AI chromoendoscopy is useful in determining the lateral extent of EGCs. However, its usefulness is reduced in undifferentiated adenocarcinomas.</p