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991.
Mori T Kasamatsu S Mosdzianowski C Welch MJ Yonekura Y Fujibayashi Y 《Nuclear medicine and biology》2006,33(2):281-286
16 alpha-[(18)F]fluoro-17beta-estradiol ([(18)F]FES) is a radiotracer for imaging estrogen receptors by positron emission tomography. We developed a clinically applicable automatic preparation system for [(18)F]FES by modifying a cassette-type [(18)F]fluorodeoxyglucose synthesizer. Two milligrams of 3-O-methoxymethyl-16,17-O-sulfuryl-16-epiestriol in acetonitrile was heated at 105 degrees C for 10 min with dried [(18)F]fluoride. The resultant solution was evaporated and hydrolyzed with 0.2 N HCl in 90% acetonitrile/water at 95 degrees C for 10 min under pressurized condition. The neutralization was carried out with 2.8% NaHCO(3), and then the high-performance liquid chromatography (HPLC) purification was performed. The desired radioactive fraction was collected and the solvent was replaced by 10 ml of saline, and then passed through a 0.22-microm filter into a pyrogen-free vial as the final product. The HPLC purification data demonstrated that [(18)F]FES was synthesized with a yield of 76.4+/-1.9% (n=5). The yield as the final product for clinical use was 42.4+/-3.2% (n=5, decay corrected). The total preparation time was 88.2+/-6.4 min, including the HPLC purification and the solvent replacement process. The radiochemical purity of the final product was >99%, and the specific activity was more than 111 GBq/micromol. The final product was stable for more than 6 h in saline containing sodium ascorbate. This new preparation system enables us to produce [(18)F]FES safe for clinical use with high and reproducible yield. 相似文献
992.
Wanaporn Yimchuen Tetsuya Kadonosono Yumi Ota Shinichi Sato Maika Kitazawa Tadashi Shiozawa Takahiro Kuchimaru Masumi Taki Yuji Ito Hiroyuki Nakamura Shinae Kizaka-Kondoh 《RSC advances》2020,10(26):15154
Tumor-binding peptides such as human epidermal growth factor receptor 2 (HER2)-binding peptides are attractive therapeutic and diagnostic options for cancer. However, the HER2-binding peptides (HBPs) developed thus far are susceptible to proteolysis and lose their affinity to HER2 in vivo. In this report, a method to create a HER2-binding fluctuation-regulated affinity protein (HBP-FLAP) consisting of a fibronectin type III domain (FN3) scaffold with a structurally immobilized HBP is presented. HBPs were selected by phage-library screening and grafted onto FN3 to create FN3-HBPs, and the HBP-FLAP with the highest affinity (HBP sequence: YCAHNM) was identified after affinity maturation of the grafted HBP. HBP-FLAP containing the YCAHNM peptide showed increased proteolysis-resistance, binding to HER2 with a dissociation constant (KD) of 58 nM in ELISA and 287 nM in biolayer interferometry and specifically detects HER2-expressing cancer cells. In addition, HBP-FLAP clearly delineated HER2-expressing tumors with a half-life of 6 h after intravenous injection into tumor-bearing mice. FN3-based FLAP is an excellent platform for developing target-binding small proteins for clinical applications.A HER2-binding protein, HBP-FLAP, developed by peptide immobilization specifically binds to HER2 and has improved resistance to proteases. 相似文献
993.
994.
Sensitivities to various epidermal growth factor receptor‐tyrosine kinase inhibitors of uncommon epidermal growth factor receptor mutations L861Q and S768I: What is the optimal epidermal growth factor receptor‐tyrosine kinase inhibitor? 下载免费PDF全文
Eri Banno Yosuke Togashi Yu Nakamura Masato Chiba Yoshihisa Kobayashi Hidetoshi Hayashi Masato Terashima Marco A. de Velasco Kazuko Sakai Yoshihiko Fujita Tetsuya Mitsudomi Kazuto Nishio 《Cancer science》2016,107(8):1134-1140
Most patients with non‐small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor (EGFR) mutations, such as deletions in exon 19 or the L858R mutation in exon 21, respond dramatically to EGFR tyrosine kinase inhibitors (EGFR‐TKI), and their sensitivities to various EGFR‐TKI have been well characterized. Our previous article showed the in vitro sensitivities of EGFR exon 18 mutations to EGFR‐TKI, but little information regarding the sensitivities of other uncommon EGFR mutations is available. First, stable transfectant Ba/F3 cell lines harboring EGFR L858R (Ba/F3‐L858R), L861Q (Ba/F3‐L861Q) or S768I (Ba/F3‐S768I) mutations were created and their drug sensitivities to various EGFR‐TKI were examined. Both the Ba/F3‐L861Q and Ba/F3‐S768I cell lines were less sensitive to erlotinib, compared with the Ba/F3‐L858R cell line, but their sensitivities to afatinib were similar to that of the Ba/F3‐L858R cell line. The Ba/F3‐L861Q cell line was similarly sensitive and the Ba/F3‐S768I cell line was less sensitive to osimertinib, compared with the Ba/F3‐L858R cell line. The results of western blot analyses were consistent with these sensitivities. Next, similar experiments were also performed using the KYSE270 (L861Q) and KYSE 450 (S768I) cell lines, and their results were compatible with those of the transfectant Ba/F3 cell lines. Our findings suggest that NSCLC harboring the EGFR L861Q mutation might be sensitive to afatinib or osimertinib and that NSCLC harboring the EGFR S768I mutation might be sensitive to afatinib. Overall, afatinib might be the optimal EGFR‐TKI against these uncommon EGFR mutations. 相似文献
995.
Yoshiro Okubo Hans Olsson Hiroshi Ito Mirijam Lofti Tetsuya Suhara Christer Halldin Lars Farde 《NeuroImage》1999,10(6):666
The Computerized Brain Atlas (CBA) transforms PET images of individual subjects into a standard brain anatomy. We have previously applied this to PET images with [11C]raclopride and confirmed that the D2 dopamine receptors in the striatum can be evaluated accurately with a standard brain anatomy. There is growing evidence that extrastriatal D2 receptors, in spite of their low density, have pathophysiological significance for schizophrenia. We used the CBA to explore the extrastriatal distribution of D2 receptors in 13 healthy subjects using [11C]FLB 457, a substituted benzamide with very high affinity for D2 and D3 receptors. There was good agreement between the specific binding ratios from CBA quantification of standardized images and those from region-of-interest analyses of original images. The highest levels of binding were observed in the putamen and caudate nucleus, followed by the globus pallidus and nucleus accumbens. Besides the basal ganglia, the hypothalamus and nucleus ruber also showed high levels of binding. Intermediate levels were found in the substantia nigra, nucleus subthalami, amygdala, and thalamus. Interestingly, there was very heterogeneous binding among the thalamic nuclei. The anterior and mediodorsal nuclei showed relatively high binding. The cerebral cortices showed lower levels with significant regional differences. Binding was highest in the temporal cortex and hippocampus followed by the anterior cingulate gyrus, and the parietal and frontal cortices, but was lowest in the occipital cortex. The use of CBA for analysis of [11C]FLB 457 binding makes it possible to build a normal database for the extrastriatal D2 receptors in the living human brain. The heterogeneous distribution of D2 receptors provides an attractive opportunity for new research on the pathophysiology and drug treatment of schizophrenia. 相似文献
996.
997.
Ling Jin Eiichi Arai Shinichi Anzai Tetsunori Kimura Tetsuya Tsuchida Koji Nagata Michio Shimizu 《Pathology international》2010,60(2):65-70
Recently, dermoscopic visualization has been improved, allowing for the identification of malignant melanoma (MM) of the sole in situ. When the parallel ridge pattern is evident on dermoscopy, the proliferation of solitarily arranged melanocytes in the crista profunda intermedia should be examined histologically, since this may be a clue to the early diagnosis of MM in situ. We reviewed 145 Japanese cases of melanocytic nevus on the sole, and investigated several useful histological features for the diagnosis of MM in situ using a recent proposal as well as several standard histological criteria of MM in situ. Five cases were considered to be an early‐stage MM in situ out of 145 cases previously diagnosed as melanocytic nevi of the sole. These cases showed several specific features, including solitarily arranged melanocytes or melanocyte nests comprising fewer than four cells. Our findings indicate that early‐stage MM of the sole in situ can be diagnosed by using new dermoscopy‐related histological findings. They are (i) irregular distribution of solitary melanocytes at the crista profunda intermedia with or without small nests (up to three melanocytes) on the slope of rete ridges; and (ii) larger melanocytes with a halo around the nucleus. 相似文献
998.
Kouji Kawai Tetsuya Sakairi Shuichi Harada Junko Shinozuka Mika Ide Hiroko Sato Masaharu Tanaka Wataru Toriumi Eisuke Kume 《Experimental and toxicologic pathology》2012,64(4):333-338
SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks. SHR/NDcp rats receiving the normal diet displayed obesity, hypertension, hyperlipidemia, and mild elevation of blood glucose and HbA1c levels. Urinary glucose excretion was noted in only 1 out of 6 animals. Histologically, macro- and micro-vesicular steatosis in the liver, glomerular and tubular damages in the kidney and islet hyperplasia mainly of beta cells in the pancreas were characteristically noted. In SHR/NDcp rats fed the diabetogenic diet, obesity was more severe, with higher blood glucose and HbA1c levels, increased numbers of animals with urinary glucose excretion, and more pronounced hepatic steatosis and renal tubular changes. However, elevation of blood glucose levels and urinary glucose excretion proved transient. These observations indicate that the diabetic state and associated histopathological alterations in SHR/NDcp rats are exacerbated by feeding a diabetogenic diet, but the effects are limited. Elevated islet function with compensative insulin secretion might be related to amelioration of the hyperglycemic state. Further diet modification could be needed to induce a more prominent and persistent diabetic state in SHR/NDcp rats. 相似文献
999.
Yasuaki Ogura Kensuke Fukuchi Hiroki Morimoto Tsurumi Yuki Masaki Otsuka Takatoshi Shimauchi Tetsuya Honda Yoshiki Tokura 《The Journal of dermatology》2022,49(1):124-132
Mamushi bites cause swelling and pain that extend from the bitten site. The coagulopathic, anti-coagulopathic, and vasculopathic actions of mamushi venom result in various laboratory abnormalities, occasionally with muscular, renal, and other organ damage. We investigated the serum biomarkers that were associated with the pathogenesis of mamushi bites, focusing on markers related to tissue-damage and neutrophil activation. Twenty patients (one case of grade 2, 13 cases of grade 3, and six cases of grade 4 of severity) seen by us in one summer season were enrolled. Peripheral blood samples were taken from the patients on day 0, day 2, and day 7 after mamushi bites. In addition to routine blood examination, serum samples were subjected to enzyme-linked immunosorbent assay for citrullinated histone H3 (CitH3), interleukin (IL)-8, IL-17A, IL-22, vascular endothelial growth factor (VEGF), high mobility group box protein 1 (HMGB1), tumor necrosis factor (TNF)-α, and IL-33. Creatinine kinase (CK) values significantly correlated with prothrombin time (PT) levels, suggesting that muscular damage is associated with exaggerated coagulation and fibrinolysis. In the vast majority of patients, HMGB1, TNF-α, and IL-33 were under detection levels. Neutrophil counts did not correlate with PT or CK, indicating that the coagulation disorder and muscular damage were virtually independent of the neutrophil activation. The neutrophil number significantly correlated with CitH3, a representative marker of neutrophil extracellular traps. Moreover, there were significant correlations between neutrophil number, CitH3, IL-8, IL-22, and VEGF. Our study suggests that there are two major cascades in mamushi bites. One is an already characterized venom effect on coagulation, vessels, and muscles. In the other novel cascade, we propose that neutrophil activation with IL-8 leads to the production of IL-22 and VEGF. This sequential event may contribute to both vascular damage and repair. 相似文献
1000.
Comparison of Fine-Tuned Deep Convolutional Neural Networks for the Automated Classification of Lung Cancer Cytology Images with Integration of Additional Classifiers 下载免费PDF全文
Tetsuya TsukamotoAtsushi TeramotoAyumi YamadaYuka Kiriyama Eiko SakuraiAyano MichibaKazuyoshi ImaizumiHiroshi Fujita 《Asian Pacific journal of cancer prevention》2022,23(4):1315-1324
Objective: It is essential to accurately diagnose and classify histological subtypes into adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small cell lung carcinoma (SCLC) for the appropriate treatment of lung cancer patients. However, improving the accuracy and stability of diagnosis is challenging, especially for non-small cell carcinomas. The purpose of this study was to compare multiple deep convolutional neural network (DCNN) technique with subsequent additional classifiers in terms of accuracy and characteristics in each histology. Methods: Lung cancer cytological images were classified into ADC, SCC, and SCLC with four fine-tuned DCNN models consisting of AlexNet, GoogLeNet (Inception V3), VGG16 and ResNet50 pretrained by natural images in ImageNet database. For more precise classification, the figures of 3 histological probabilities were further applied to subsequent machine learning classifiers using Naïve Bayes (NB), Support vector machine (SVM), Random forest (RF), and Neural network (NN). Results: The classification accuracies of the AlexNet, GoogLeNet, VGG16 and ResNet50 were 74.0%, 66.8%, 76.8% and 74.0%, respectively. Well differentiated typical morphologies were tended to be correctly judged by all four architectures. However, poorly differentiated non-small cell carcinomas lacking typical structures were inclined to be misrecognized in some DCNNs. Regarding the histological types, ADC were best judged by AlexNet and SCC by VGG16. Subsequent machine learning classifiers of NB, SVV, RF, and NN improved overall accuracies to 75.1%, 77.5%, 78.2%, and 78.9%, respectively. Conclusion: Fine-tuning DCNNs in combination with additional classifiers improved classification of cytological diagnosis of lung cancer, although classification bias could be indicated among DCNN architectures. 相似文献