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Takeshi Nagashima Ken Yamaguchi Kenichi Urakami Yuji Shimoda Sumiko Ohnami Keiichi Ohshima Tomoe Tanabe Akane Naruoka Fukumi Kamada Masakuni Serizawa Keiichi Hatakeyama Kenya Matsumura Shumpei Ohnami Koji Maruyama Tohru Mochizuki Masatoshi Kusuhara Akio Shiomi Yasuhisa Ohde Masanori Terashima Katsuhiko Uesaka Tetsuro Onitsuka Seiichiro Nishimura Yasuyuki Hirashima Nakamasa Hayashi Yoshio Kiyohara Yasuhiro Tsubosa Hirohisa Katagiri Masashi Niwakawa Kaoru Takahashi Hiroya Kashiwagi Masahiro Nakagawa Yuji Ishida Takashi Sugino Mitsuru Takahashi Yasuto Akiyama 《Cancer science》2020,111(2):687-699
This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients. 相似文献
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Yusuke Kagawa Hiromi Furuta Takehiro Uemura Naohiro Watanabe Junichi Shimizu Yoshitsugu Horio Hiroaki Kuroda Yoshitaka Inaba Takeshi Kodaira Katsuhiro Masago Shiro Fujita Akio Niimi Toyoaki Hida 《Cancer science》2020,111(12):4442
Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non‐small‐cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD‐1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty‐eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option. 相似文献
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Akio Akagi Yasushi Iwasaki Akihiro Yamamoto Hiroshi Matsuura Toshimasa Ikeda Maya Mimuro Yuichi Riku Hiroaki Miyahara Tetsuyuki Kitamoto Mari Yoshida 《Neuropathology》2020,40(4):399-406
We report a case of early-phase sporadic Creutzfeldt–Jakob disease (sCJD) complicated by intracerebral hemorrhage (ICH), classified as MM1 + 2C-type based on autopsy. A 61-year-old Japanese man presented to our hospital with speaking difficulties including repeated usage of the same words. He was hospitalized on the seventh day after symptom onset, and diffusion-weighted images on magnetic resonance imaging showed hyperintense regions in the frontal cortex and caudate nucleus. On the 11th day after symptom onset, head computed tomography revealed ICH in the right occipital and parietal lobes. Routine laboratory evaluations and angiography revealed no cause of ICH. Myoclonus of the extremities and drowsiness were observed on the 15th day after symptom onset. He reached the state of akinetic mutism approximately two months after symptom onset. The cerebrospinal fluid test revealed positive real-time quaking-induced conversion and 14-3-3 protein. Electroencephalography revealed periodic sharp wave complexes. A clinical diagnosis of probable Creutzfeldt–Jakob disease was made according to the diagnostic criteria. After a relapse of pneumonia, he passed away on the 103rd day after symptom onset. Postmortem examination revealed ICH in the right posterior cingulate gyrus. No pathological change that might have caused ICH was obtained. Although the effect of sCJD on the onset of ICH is undeniable, the cause of ICH was unknown. Prion protein immunohistochemistry revealed the following results: (1) weak synaptic-type deposits in the tissue rarefacted by ICH; (2) synaptic-type deposits in the cerebral cortex, which showed fine vacuoles; and (3) perivacuolar-type deposits in the inferior temporal gyrus and lingual gyrus, which showed frequent large confluent vacuoles. Although it could be considered MM1-type sCJD clinically, this case was neuropathologically diagnosed as having MM1 + 2C-type sCJD. It was shown that ICH may occur in early-phase sCJD. To improve sCJD prognosis, treatment of complications and careful follow up are important. Furthermore, pathological diagnosis is indispensable for sCJD type diagnosis. 相似文献
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Shoko Sadashima Satoshi O. Suzuki Hironori Haruyama Nobutaka Mukae Yutaka Fujioka Nobuhiro Hata Masahiro Mizoguchi Keisuke Ishimatsu Akio Hiwatashi Toru Iwaki 《Neuropathology》2020,40(6):646-650
Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAFA598T mutation, the first case reported in a glioma. BRAFA598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention. 相似文献
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Koichi Ohata BS Junichi Kitagawa MD PhD Takashi Niwa PhD Tomoyo Takahashi-Yamauchi BS Saki Harada BS Takuro Matsumoto MD PhD Nobuhiko Nakamura MD PhD Hiroshi Nakamura MD Nobuhiro Kanemura MD PhD Masahito Shimizu MD PhD Akio Suzuki PhD 《Journal of clinical pharmacy and therapeutics》2020,45(6):1342-1348
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Natsume N Niimi T Furukawa H Kawai T Ogi N Suzuki Y Kawai T 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2001,91(2):157-161
There have been many reports on congenital anomalies associated with cleft lip and/or palate (CL/CLP) in Japan. However, these reports included data only on patients who came to hospitals; thus the real situation regarding these anomalies remains unclear. Therefore, we surveyed newborns at all delivery facilities in the central area of Japan for the presence of these anomalies, following their progress for 12 consecutive years; at the end of that time, questionnaires were collected and analyzed. In this article, we describe our results. 相似文献
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González-Alva P Tanaka A Oku Y Yoshizawa D Itoh S Sakashita H Ide F Tajima Y Kusama K 《Journal of Oral Science》2008,50(2):205-212
In 2005, the WHO Working Group considered odontogenic keratocyst (OKC) to be a tumor and recommended the term keratocystic odontogenic tumor (KCOT), separating the lesion from the orthokeratinizing variant, which is now considered an odontogenic cyst. We analyzed the clinicopathological features of KCOTs encountered over a period of 28 years at Meikai University Hospital. The diagnosis was confirmed by reevaluation of hematoxylin and eosin-stained slides on the basis of the 2005 WHO Classification. Clinical history was also taken into consideration. A total of 183 KCOTs were found, and the two genders were affected almost evenly (51.3% male; 48.7% female; male to female ratio 1.05 to 1). Patient age at the time of diagnosis ranged from 6 to 78 years, with a peak in the third decade of life (mean age: 32.8 years). The mandible was the site of occurrence of 70.5% of tumors; 16.4% occurred in the maxilla and 13.1% in both. Association with the nevoid basal cell carcinoma syndrome (NBCCS) was found in 6.0% of all tumors, and recurrence was found in 13.1% of patients. We found that tumors that initially appeared in the maxilla alone had a higher recurrence rate than those that first appeared in the mandible alone. Pathological examination of KCOT is important to avoid misdiagnosis and provide appropriate treatment and follow-up. 相似文献