128 results on '"Yumiko Hori"'
Search Results
2. Squamous cell carcinoma initially occurring on the tongue dorsum: a case series report with molecular analysis
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Sawako Ono, Katsutoshi Hirose, Shintaro Sukegawa, Kyoichi Obata, Masanori Masui, Kazuaki Hasegawa, Ai Fujimura, Katsumitsu Shimada, Satoko Nakamura, Akari Teramoto, Yumiko Hori, Eiichi Morii, Daisuke Motooka, Takuro Igawa, Takehiro Tanaka, Hitoshi Nagatsuka, Satoru Toyosawa, and Hidetaka Yamamoto
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Squamous cell carcinoma ,Oral squamous cell carcinoma ,Dorsum of the tongue ,TP53 ,p53 ,Next-generation sequencing ,Pathology ,RB1-214 - Abstract
Abstract Background Squamous cell carcinoma (SCC) of the dorsum of the tongue is extremely rare, and it clinically resembles various benign lesions. Somatic mutations in TP53 and some driver genes were implicated in the development of SCC; however, the somatic genetic characteristics of dorsal tongue SCC remain unknown. With a detailed analysis of gene mutations in dorsal tongue SCC, we aimed to better understand its biology. Methods Four cases of SCC initially occurring on the tongue dorsum were evaluated for clinical and histological findings and immunohistochemical expression of p53 and p16. Gene mutations were analyzed using next-generation sequencing with a custom panel of driver genes. Results We retrospectively investigated 557 cases of tongue SCC, and only four cases of SCC initially occurred on the tongue dorsum. The four patients (cases 1–4) were one woman and three men with a mean age of 53.75 years (range: 15–74 years). Histological analysis revealed well-differentiated SCC. Through molecular analysis, we identified pathogenic somatic mutations, namely, TP53 p.C176F (c.527G > T) in case 3 and TP53 p.R282W (c.844 C > T) in case 4. No pathogenic variants were identified in the PI3K/AKT or RAS/RAF pathways. The p53 immunohistochemical examination revealed a wild-type expression pattern in cases 1–3 and strong expression in case 4. The results of p16 immunostaining were negative in all cases. Conclusions We described four previously unreported genetic characteristics of dorsal tongue SCC. Somatic TP53 mutations may contribute to the development of a subset of dorsal tongue SCC; however, more cases with genetic analysis need to be accumulated.
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- 2024
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3. Multiple orthokeratinized odontogenic cysts: clinical, pathological, and genetic characteristics
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Sawako Ono, Katsutoshi Hirose, Shintaro Sukegawa, Satoko Nakamura, Daisuke Motooka, Yuri Iwamoto, Yumiko Hori, Kaori Oya, Yasuo Fukuda, and Satoru Toyosawa
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Orthokeratinized odontogenic cyst ,Odontogenic keratocyst ,Odontogenic cyst ,Odontogenic tumor ,Protein patched homolog 1 ,Pathology ,RB1-214 - Abstract
Abstract Background: Orthokeratinized odontogenic cyst (OOC) is a rare developmental odontogenic cyst of the jaw. It was originally believed to be a variant of odontogenic keratocyst (OKC) but is now considered to be a distinct entity. OOC usually presents as a single lesion and recurs infrequently. On the other hand, OKC often presents with multiple lesions and displays locally aggressive behavior and a high recurrence rate associated with the protein patched homolog 1 (PTCH1) gene mutation. Multiple OOC cases are extremely rare and seem to be aggressive, but their pathogenesis is not fully understood. This study aimed to determine the clinical, pathological, and genetic characteristics of multiple OCC. Methods: Three cases of multiple OOC were evaluated for clinical and histological findings, and immunohistochemical expression of Ki-67 and Bcl-2. Furthermore, PTCH1 mutations were analyzed by next-generation sequencing using a custom panel to cover the entire exon of PTCH1. Results: The three cases of multiple OOC included two men and one woman with a mean age of 25.3 years old (range, 18–38 years old). Each case had two or three OOCs (total of seven OOCs), all of which were simultaneously detected. Of the seven OOCs that manifested as multiple jaw cysts, seven (100%) occurred in the posterior regions, four (57.1%) occurred in the mandible, and four (57.1%) were associated with an impacted tooth. Histological examination revealed cysts lined by orthokeratinized stratified squamous epithelium. Immunohistochemistry showed a low Ki-67 labeling index and no Bcl-2 expression in the seven OOCs. No pathogenic PTCH1 mutations were detected in any of the seven OOCs. None of the patients had any other symptoms or signs of recurrence at the last follow-up (6–60 months). Conclusion: Multiple OOCs appeared to occur more often in younger patients than solitary OOC. Both multiple and solitary OOCs may be related diseases within the entity of odontogenic cysts. Multiple OOCs are clinicopathologically and genetically distinct from OKC.
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- 2022
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4. PIK3CA mutation correlates with mTOR pathway expression but not clinical and pathological features in Fibfibroipose vascular anomaly (FAVA)
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Yumiko Hori, Katsutoshi Hirose, Michio Ozeki, Kenji Hata, Daisuke Motooka, Shinichiro Tahara, Takahiro Matsui, Masaharu Kohara, Hiroki Higashihara, Yusuke Ono, Kaishu Tanaka, Satoru Toyosawa, and Eiichi Morii
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Fibro-adipose vascular anomaly ,FAVA ,PIK3CA ,mTOR ,Vascular anomaly ,Lymphatic malformation ,Pathology ,RB1-214 - Abstract
Abstract Background Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA. Methods We retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway. Results Two PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases. Conclusions There was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.
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- 2022
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5. Nicotinamide N‐methyltransferase is related to MELF pattern invasion in endometrioid carcinoma
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Shinichiro Tahara, Satoshi Nojima, Kenji Ohshima, Yumiko Hori, Kazuaki Sato, Masako Kurashige, Takahiro Matsui, Daisuke Okuzaki, and Eiichi Morii
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endometrioid carcinoma ,invasion ,MELF ,migration ,NNMT ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Grade 1 (G1) endometrioid carcinoma (EC) is relatively a good prognosis. However, in a minority of cases, G1 shows an aggressive histological pattern known as the microcystic, elongated, and fragmented (MELF) pattern. We previously reported that EC with high expression levels of S100A4 and serum deprivation‐response protein (SDPR) was related to MELF pattern invasion. However, the molecular features of the invasive front area of the MELF pattern have not been investigated. In this study, we searched for genes preferentially expressed in the invasive front area of EC with the MELF pattern using laser microdissection and RNA sequencing, and showed that nicotinamide N‐methyltransferase (NNMT) is related to MELF pattern invasiveness. Immunohistochemical analyses confirmed high NNMT expression in the invasive front area of the MELF pattern. Moreover, NNMT promoted migration, invasion, colony formation, epithelial–mesenchymal transition (EMT), and chemoresistance using EC cell lines. We speculate that depletion of NNMT promotes histone methylation and leads to tumor suppression because NNMT consumes S‐adenosyl methionine (SAM), which is an essential methylation cofactor. NNMT knockout cells showed enhanced expression of H3K9me2. RNA sequencing using NNMT knockout cell lines suggested that methylation of H3K9 leads to repression of the transcription of various oncogenic genes. Our findings demonstrate the possibility that NNMT inhibitors, which are expected to be used for the treatment of metabolic disorders, would be effective for the treatment of aggressive EC. This is the first report of gene analyses focusing on the morphological changes associated with MELF pattern invasion of EC.
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- 2021
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6. Fibro-adipose vascular anomaly (FAVA): three case reports with an emphasis on the mammalian target of rapamycin (mTOR) pathway
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Yumiko Hori, Katsutoshi Hirose, Noriko Aramaki-Hattori, Sachi Suzuki, Robert Nakayama, Masanori Inoue, Takahiro Matsui, Masaharu Kohara, Satoru Toyosawa, and Eiichi Morii
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Fibro-adipose vascular anomaly (FAVA) ,PIK3CA ,mTOR ,Vascular anomaly ,Pathology ,RB1-214 - Abstract
Abstract Background Fibro-adipose vascular anomaly (FAVA) is a new entity of vascular anomalies with somatic and mosaic gain-of-function mutations of the phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). PIK3CA mutation excessively activates mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis. Histologically, FAVA is composed of intramuscular fibrous and adipose tissues with venous malformation (VM). Although sirolimus known as a mTOR inhibitor has good response to FAVA, expression pattern of the mTOR pathway was still unclear. Herein, we immunohistochemically investigated three novel FAVA patients with an emphasis on the mTOR pathway (p-S6K1, p-4EBP1 and p-AKT). Case presentation Case 1: A 10-year-old female had complained of pain in the left thigh since she was 6-year-old. Under the clinical diagnosis of VM, she underwent surgical resection for the lesion. Case 2: A 29-year-old female patient had complained of discomfort and mild pain in the left shoulder since she was 18-year-old. After childbirth, she had severe ongoing pain and contracture of the shoulder. Under clinical diagnosis of VM, surgical resection was performed. Case 3: A 53-year-old female had complained of pain and knee restriction after surgical treatment of a knee tumor at the age of 31. Under the clinical diagnosis of atypical lipomatous tumor or high grade liposarcoma, surgical resection was performed. Histologically, all three patients presented with characteristic features of fibrous and adipose tissues with abnormal vessels within the skeletal muscle, leading to diagnosis of FAVA. Although VM has been reported as an important finding in FAVA, immunohistological findings demonstrated that abnormal vessels comprised complex of VM and lymphatic malformation (LM) in all cases. Furthermore, besides vascular malformation, abnormal fibrous and adipose tissues of FAVA expressed mTOR pathway components. Conclusions We presented three new cases of FAVA. Histological and immunohistochemical analyses revealed that VM and LM complex was an important finding in FAVA, and that the mTOR pathway components were expressed in abnormal fibrous tissue, adipose tissue and vascular malformation. These findings suggested that FAVA might be a mesenchymal malformation caused by PI3K/AKT/mTOR pathway.
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- 2020
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7. The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study
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Kosuke Hiramatsu, Yutaka Ueda, Asami Yagi, Akiko Morimoto, Tomomi Egawa-Takata, Satoshi Nakagawa, Eiji Kobayashi, Toshihiro Kimura, Tadashi Kimura, Ryoko Minekawa, Yumiko Hori, Kazuaki Sato, Eiichi Morii, Tomio Nakayama, Yoshimichi Tanaka, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Noriomi Matsumura, Masaki Mandai, Jyunko Saito, Yorihiko Horikoshi, Tetsu Takagi, Takayuki Enomoto, and Kentaro Shimura
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cervical cancer ,hpv vaccine ,cervical intraepithelial neoplasia ,hpv 16 ,hpv 18 ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan – OCEAN (Osaka Clinical resEArch of HPV vacciNe) study – to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old. Among them, 102 participants received HPV/Pap co-test as primary cancer screening at the age of 20–21. We compared the prevalence in two groups (the vaccinated and the unvaccinated group). HPV infection ratio was significantly lower in the vaccinated group compared to the unvaccinated (12.9% vs. 19.7%; p = .04). In particular, HPV 16 and 18 were not detected in the vaccinated group, while 4.9% of participants in the unvaccinated group were infected (p = .001), suggesting that vaccination provided effective protection against high-risk types of HPV. The cross-protection effect of HPV vaccines was also observed against HPV 31, 45, and 52. Although HPV vaccines were not contributed to the reduction of cervical intraepithelial neoplasia 1 (CIN) (p = .28), CIN2 or worse was not observed in vaccinated group. Our research showed that at the age of 20–21, HPV vaccine inhibited the infection of high-risk HPV and had impacted on the development to CIN2 or worse in Japan.
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- 2022
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8. Gastric-Type Adenocarcinoma of the Uterine Cervix Associated with Poor Response to Definitive Radiotherapy
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Airi Kuruma, Michiko Kodama, Yumiko Hori, Kazuaki Sato, Makoto Fujii, Fumiaki Isohashi, Ai Miyoshi, Seiji Mabuchi, Akira Setoguchi, Hiroko Shimura, Takeshi Goto, Aska Toda, Satoshi Nakagawa, Yasuto Kinose, Tsuyoshi Takiuchi, Eiji Kobayashi, Kae Hashimoto, Yutaka Ueda, Kenjiro Sawada, Eiichi Morii, and Tadashi Kimura
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cervical cancer ,gastric-type adenocarcinoma ,definitive radiotherapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
We aimed to evaluate the response to definitive radiotherapy (RT) for cervical cancer based on histological subtypes and investigate prognostic factors in adenocarcinoma (AC). Of the 396 patients treated with definitive RT between January, 2010 and July, 2020, 327 patients met the inclusion criteria, including 275 with squamous cell carcinoma (SCC) and 52 with AC restaged based on the 2018 International Federation of Gynecology and Obstetrics staging system. Patient characteristics, response to RT, and prognoses of SCC and AC were evaluated. The complete response (CR) rates were 92.4% and 53.8% for SCC and AC, respectively (p < 0.05). Three-year overall survival and progression-free survival (PFS) rates of SCC were significantly higher than those of AC (88.6% vs. 74.1%, p < 0.05 and 76.3% vs. 59.3%, p < 0.05, respectively). Among the AC population, univariate and multivariate analyses were performed to examine prognostic factors associated with non-complete response (CR). In the multivariate analysis, gastric-type adenocarcinoma (GAS) was associated with non-CR in AC (adjusted odds ratio, 12.2; 95% confidence interval 1.0–145.6; p < 0.05). The 3-year PFS rate in patients with GAS was significantly lower than that in patients with other histological types of AC (44.4% vs. 66.7%, p < 0.05). Definitive RT for cervical cancer was significantly less effective for AC than for SCC. GAS was the only independent prognostic factor associated with non-CR in AC.
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- 2022
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9. Detection of NRAS mutation in cell-free DNA biological fluids from patients with kaposiform lymphangiomatosis
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Michio Ozeki, Yoko Aoki, Akifumi Nozawa, Shiho Yasue, Saori Endo, Yumiko Hori, Kentaro Matsuoka, Tetsuya Niihori, Ryo Funayama, Matsuyuki Shirota, Keiko Nakayama, and Toshiyuki Fukao
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Vascular anomaly ,Kaposiform lymphangiomatosis ,Neuroblastoma RAS viral oncogene homolog ,Cell-free DNA ,Liquid biopsy ,Medicine - Abstract
Abstract Background Kaposiform lymphangiomatosis (KLA) has recently been distinguished as a novel subtype of generalized lymphatic anomaly (GLA) with foci of spindle endothelial cells. All cases of KLA involve multiple organs and have an unfavorable prognosis. However, the molecular pathogenesis is unknown, and there are no useful biomarkers. In the present study, we performed genetic analysis to elucidate the cause of this disease and detect biomarkers for it. Methods We performed whole-exome sequencing of DNA samples from leukocytes and a biopsy specimen and analyzed cell-free DNA (cfDNA) from plasma and pleural effusion of patients to identify the NRAS c.182A > G (p.Q61R) mutation using the droplet digital polymerase chain reaction (ddPCR). Results All KLA patients (patients 1–5) had invasive and aggressive features (hemorrhagic pleural effusions, coagulation disorder, and thrombocytopenia) and characteristic findings of KLA in their pathological examinations. In whole exome sequencing for patient 1, c.182A > G missense variant (p.Q61R) in NRAS was identified in fresh frozen samples of a mass on the left chest wall at a frequency of 5% of total alleles but not in his blood leukocytes. Furthermore, the same mutation was detected in cfDNA isolated from plasma and pleural effusion by using ddPCR. ddPCR analysis of plasma/pleural effusion samples from an additional four KLA patients showed that the same mutation was detected in isolated cfDNA in three of the four, as well as in a tissue sample from one of the three plasma/effusion-positive patients that had been obtained to confirm the mutation. Conclusion These results provide the first evidence that NRAS oncogenic variant was identified in DNA samples from KLA patients from not only two affected lesions but also plasma and pleural effusion.
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- 2019
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10. Effect of Apple Consumption on Postprandial Blood Glucose Levels in Normal Glucose Tolerance People versus Those with Impaired Glucose Tolerance
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Yutaka Inoue, Lianne Cormanes, Kana Yoshimura, Aiko Sano, Yumiko Hori, Ryuichiro Suzuki, and Ikuo Kanamoto
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apple ,impaired glucose tolerance ,intake timing ,postprandial blood glucose ,Chemical technology ,TP1-1185 - Abstract
The present study investigated the effect of apple consumption on postprandial blood glucose and insulin levels in subjects with normal versus impaired glucose tolerance. The study participants were ten healthy subjects with no glucose intolerance (normal subjects) (mean, 24.4 ± 4.8 years) and nine subjects with impaired glucose tolerance (mean, 45.2 ± 11.1 years, including 2 on insulin therapy). The test meal included white rice (148 g) and a Fuji apple (150 g). The normal subjects were randomly divided into two groups: the apple-first group, wherein the subjects consumed white rice 5 min after consuming the apple, and the rice-first group, wherein the subjects consumed an apple 5 min after consuming the white rice. Blood samples were then taken from both groups for 3 h. In addition, the subjects with impaired glucose tolerance received the same treatment as the normal subjects, with the difference being glucose level monitoring according to the order in which the apples were consumed. In the normal subjects, the Cmax of Δblood glucose and Δinsulin levels were 54.0 ± 5.0 mg/dL and 61.9 ± 7.2 µU/dL versus 46.2 ± 5.9 mg/dL and 49.8 ± 8.5 µU/dL in the rice-first and apple-first groups, respectively. The incremental area under the curve (iAUC) of insulin tended to decrease in the apple-first group. In the impaired glucose tolerance subjects, the Cmax of Δblood glucose was 75.2 ± 7.2 mg/dL in the apple-first group compared to 90.0 ± 10.0 mg/dL in the rice-first group, which was a significant difference (p < 0.05). The iAUC of blood glucose was lower in the apple-first group. Eating an apple before a meal may be a simple and effective strategy for managing the glycaemic response in individuals with impaired glucose tolerance.
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- 2022
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11. Correction: PIK3CA mutation correlates with mTOR pathway expression but not clinical and pathological features in Fibro-adipose vascular anomaly (FAVA)
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Yumiko Hori, Katsutoshi Hirose, Michio Ozeki, Kenji Hata, Daisuke Motooka, Shinichiro Tahara, Takahiro Matsui, Masaharu Kohara, Hiroki Higashihara, Yusuke Ono, Kaishu Tanaka, Satoru Toyosawa, and Eiichi Morii
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Pathology ,RB1-214 - Published
- 2022
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12. A Case of Lymphocytic Myocarditis with Eosinophilic Degranulation Successfully Treated with Steroid Therapy
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Tomoko Inoue, Fusako Sera, Shunsuke Nishimura, Kei Nakamoto, Yasumasa Tsukamoto, Isamu Mizote, Tomohito Ohtani, Shungo Hikoso, Yoshihiko Ikeda, Yumiko Hori, Hatsue Ishibashi-Ueda, Eiichi Morii, Tetsuo Minamino, and Yasushi Sakata
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
A 49-year-old woman was admitted with suspicion of acute myocarditis. On the next day after admission, her serum troponin I level continued to rise, indicating progression of myocardial damage. Moreover, her symptoms persisted, and left ventricular ejection fraction did not improve. Because of a predominant infiltration of lymphocytes in the myocardial specimens, lymphocytic myocarditis was diagnosed. However, a close observation of the specimens revealed eosinophil degranulation. Based on this finding, intravenous steroid therapy was initiated. High-dose methylprednisolone led to rapid and appreciable improvements in symptoms and left ventricular function within 12 hours after the first administration, which was followed by normalization of serum troponin I level. Steroid therapy was switched to oral administration and tapered carefully. There was no recurrence of left ventricular dysfunction or elevation of serum troponin I level. In eosinophilic myocarditis, eosinophil degranulation has been recognized as an important finding associated with progression of inflammation and myocardial damage. However, no attention has been paid to the presence and clinical implications of eosinophil degranulation in lymphocytic myocarditis. This case indicates that eosinophil degranulation in lymphocytic myocarditis may be an important finding associated with a high therapeutic response to steroid therapy.
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- 2020
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13. Detection of Phosphorylated Alpha-Synuclein in the Muscularis Propria of the Gastrointestinal Tract Is a Sensitive Predictor for Parkinson’s Disease
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Goichi Beck, Yumiko Hori, Yoshito Hayashi, Eiichi Morii, Tetsuo Takehara, and Hideki Mochizuki
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Background. Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor impairments, including constipation. Lewy bodies and neurites, the pathological hallmarks of PD, are found in the enteric nervous system (ENS) as well as the central nervous system. Constipation is a well-documented premotor symptom in PD, and recent reports have demonstrated Lewy pathology in gastrointestinal (GI) tissues of PD patients prior to the onset of motor symptoms. Objective. In the present study, we assessed Lewy pathology in the GI tracts of seven PD patients who had undergone a gastrectomy, gastric polypectomy, or colonic polypectomy prior to the onset of motor symptoms in order to assess whether the presence of pathological αSyn in the ENS could be a predictor for PD. Methods. GI tissue samples were collected from control patients and patients with premotor PD. Immunohistochemistry was performed using primary antibodies against α-synuclein (αSyn) and phosphorylated αSyn (pαSyn), after which Lewy pathology in each sample was assessed. Results. In all control and premotor PD patients, accumulation of αSyn was observed in the myenteric plexus in both the stomach and colon. In 82% (18/22) of control patients, mild-to-moderate accumulation of αSyn was observed in the submucosal plexus. However, there was no deposition of pαSyn in the ENS of control patients. In patients with premotor PD, abundant accumulation of αSyn was observed in the myenteric plexus, similar to control patients. On the other hand, pαSyn-positive aggregates were also observed in the nerve fibers in the muscularis propria in all examined patients with premotor PD (100%, 3/3), while the deposition of pαSyn in the submucosal plexus was only observed in one patient (14%, 1/7). Conclusion. Our results suggest that the detection of pαSyn, but not αSyn, especially in the muscularis propria of GI tracts, could be a sensitive prodromal biomarker for PD.
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- 2020
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14. Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study
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Tomomi Egawa-Takata, Yutaka Ueda, Akiko Morimoto, Yusuke Tanaka, Asami Yagi, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Yumiko Hori, Eiichi Morii, Tomio Nakayama, Mikiko Asai-Sato, Etsuko Miyagi, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, and Kentaro Shimura
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cervical cancer screening ,daughter ,leaflet ,mother ,recommendation ,Medicine (General) ,R5-920 - Abstract
Background: In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. Methods: In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. Results: The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). Conclusions: An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters’ screening rate.
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- 2018
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15. Realistic fear of cervical cancer risk in Japan depending on birth year
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Asami Yagi, Yutaka Ueda, Tomomi Egawa-Takata, Yusuke Tanaka, Ruriko Nakae, Akiko Morimoto, Yoshito Terai, Masahide Ohmichi, Tomoyuki Ichimura, Toshiyuki Sumi, Hiromi Murata, Hidetaka Okada, Hidekatsu Nakai, Masaki Mandai, Shinya Matsuzaki, Eiji Kobayashi, Kiyoshi Yoshino, Tadashi Kimura, Junko Saito, Yumiko Hori, Eiichi Morii, Tomio Nakayama, Yukio Suzuki, Yoko Motoki, Akiko Sukegawa, Mikiko Asai-Sato, Etsuko Miyagi, Manako Yamaguchi, Risa Kudo, Sosuke Adachi, Masayuki Sekine, Takayuki Enomoto, Yorihiko Horikoshi, Tetsu Takagi, and Kentaro Shimura
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cervical cancer ,governmental suspension of recommendation ,hpv vaccine ,relative risk ,vaccination rate ,Immunologic diseases. Allergy ,RC581-607 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994–1999 was reduced to 0.56–0.70, however, the rate in those born in 2000–2003 was 0.98–1.0, almost the same risk as before introduction of the vaccine. Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.
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- 2017
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16. Intense fluorodeoxyglucose uptake by a benign sclerosing stromal tumor of the ovary
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Takuji Tomimatsu, Yayoi Fukuda, Kazuya Mimura, Kiyoshi Yoshino, Hiroki Kato, Takahiro Tsuboyama, Yumiko Hori, and Tadashi Kimura
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Gynecology and obstetrics ,RG1-991 - Published
- 2016
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17. Oligosaccharide Sensing Using Fluorophore-Probed Curdlans in Aqueous Media
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Hiroki Kurohara, Yumiko Hori, Munenori Numata, and Gaku Fukuhara
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Polymers and Plastics ,Process Chemistry and Technology ,Organic Chemistry - Published
- 2023
18. A Case of Multifocal Lymphangioendotheliomatosis With Thrombocytopenia and Changes in Coagulopathy
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Daiki Nagao, Michio Ozeki, Akifumi Nozawa, Shiho Yasue, Hideo Sasai, Saori Endo, Takazumi Kato, Yumiko Hori, and Hidenori Ohnishi
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Oncology ,Pediatrics, Perinatology and Child Health ,Hematology - Published
- 2022
19. JCS/JSCVS/JATS/JSVS 2021 Guideline on Implantable Left Ventricular Assist Device for Patients With Advanced Heart Failure
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Minoru, Ono, Osamu, Yamaguchi, Tomohito, Ohtani, Koichiro, Kinugawa, Yoshikatsu, Saiki, Yoshiki, Sawa, Akira, Shiose, Hiroyuki, Tsutsui, Norihide, Fukushima, Goro, Matsumiya, Masanobu, Yanase, Kenji, Yamazaki, Kazuhiro, Yamamoto, Masatoshi, Akiyama, Teruhiko, Imamura, Kiyotaka, Iwasaki, Miyoko, Endo, Yoshihiko, Ohnishi, Takahiro, Okumura, Koichi, Kashiwa, Osamu, Kinoshita, Kaori, Kubota, Osamu, Seguchi, Koichi, Toda, Hiroshi, Nishioka, Tomohiro, Nishinaka, Takashi, Nishimura, Toru, Hashimoto, Masaru, Hatano, Haruhiko, Higashi, Taiki, Higo, Takeo, Fujino, Yumiko, Hori, Toru, Miyoshi, Motoharu, Yamanaka, Takayuki, Ohno, Takeshi, Kimura, Shunei, Kyo, Yasushi, Sakata, and Takeshi, Nakatani
- Subjects
Heart Failure ,Treatment Outcome ,Humans ,Heart-Assist Devices ,General Medicine ,Cardiology and Cardiovascular Medicine ,Defibrillators, Implantable - Published
- 2022
20. Pediatric case of acquired progressive lymphatic anomaly treated with sirolimus
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Sayano Komamizu, Michio Ozeki, Daichi Hayashi, Saori Endo, Yumiko Hori‐Hirose, Satoru Sasaki, and Hidenori Ohnishi
- Subjects
Pediatrics, Perinatology and Child Health - Published
- 2023
21. Consensus Report on Destination Therapy in Japan ― From the DT Committee of the Council for Clinical Use of Ventricular Assist Device Related Academic Societies ―
- Author
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Kaoruko Aita, Teruhiko Imamura, Norihide Fukushima, Miyoko Endo, Koichi Kashiwa, Hiroyuki Kojin, Akira Shiose, Shinichi Nunoda, Koichiro Kinugawa, Yoshiki Sawa, Koichi Toda, Minoru Ono, Yasushi Sakata, Yutaka Tejima, Dai Yumino, Yumiko Hori, and Shogo Oishi
- Subjects
Heart Failure ,Bridge to transplant ,2019-20 coronavirus outbreak ,Consensus ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,COVID-19 ,General Medicine ,medicine.disease ,Japan ,Ventricular assist device ,medicine ,Heart Transplantation ,Humans ,Stage D heart failure ,Heart-Assist Devices ,Medical emergency ,Cardiology and Cardiovascular Medicine ,business ,Pandemics ,End-of-life care ,Destination therapy - Abstract
Destination therapy (DT) is the indication to implant a left ventricular assist device (LVAD) in a patient with stage D heart failure who is not a candidate for heart transplantation. The implantable LVAD has been utilized in Japan since 2011 under the indication of bridge to transplant (BTT). After almost 10 year lag, DT has finally been approved and reimbursed in May 2021 in Japan. To initiate the DT program in Japan, revision of the LVAD indication from BTT is necessary. Also, in-depth discussion of caregiver issues as well as end-of-life care is indispensable. For that purpose, we assembled a DT committee of multidisciplinary members in August 2020, and started monthly discussions via web-based communication during the COVID-19 pandemic. This is a summary of the consensus reached after 6 months' discussion, and we have included as many relevant topics as possible. Clinical application of DT has just started, and we are willing to revise this consensus to meet the forthcoming issues raised during real-world clinical experience.
- Published
- 2021
22. Primary Alveolar Soft Part Sarcoma of Cheek: Report of a Case and Review of the Literature
- Author
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Eiichi Morii, Satoru Toyosawa, Katsutoshi Hirose, Shumei Murakami, Toshihiro Uchihashi, Yuri Iwamoto, Kohei Naniwa, Yumiko Hori, Saori Yamada, Susumu Tanaka, Masaharu Kohara, Yu Usami, Yasuo Fukuda, and Kaori Oya
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Contrast Media ,TFE3 ,Case Reports ,Pathology and Forensic Medicine ,Metastasis ,Diagnosis, Differential ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Alveolar soft part sarcoma ,medicine ,Humans ,business.industry ,Soft tissue sarcoma ,Cheek ,medicine.disease ,Magnetic Resonance Imaging ,Primary Alveolar Soft Part Sarcoma ,Sarcoma, Alveolar Soft Part ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Otorhinolaryngology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,business - Abstract
Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma characterized by an alveolar or organoid arrangement of polygonal tumour cells separated by fibrovascular septa. A specific fusion gene [ASPS critical region 1 (ASPSCR1)—TFE3] was detected in ASPS. Despite being a slow-growing tumour without pain and dysfunction, ASPS is characterized by early metastasis, which leads to poor prognosis. Herein, we report a rare case of primary ASPS of the cheek harbouring ASPSCR1 (exon 7)—TFE3 (exon 5) fusion gene in a 21 year-old woman. This tumour was a well-circumscribed, smooth, round mass that was clinically suspected as a benign tumour. However, histologically, it was observed that the polygonal tumour cells were arranged in solid and alveolar growth patterns. Post-operative examination of the whole body excluded the possibility of metastasis at other sites. Thus, careful immunohistochemical and genetic analyses, as well as whole-body examination, demonstrated that the tumour was a primary ASPS of the cheek.
- Published
- 2021
23. FAM111B enhances proliferation of KRAS‐driven lung adenocarcinoma by degrading p16
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Keisuke Kawasaki, Daisuke Okuzaki, Eiichi Morii, Kenji Ohshima, Yumiko Hori, Sachiko Hijiki, Kansuke Kido, Satoshi Nojima, Masako Kurashige, Hiroki Kiyokawa, Shinichiro Tahara, Takahiro Matsui, and Daisuke Umeda
- Subjects
0301 basic medicine ,Male ,Cancer Research ,proliferation ,Gene Expression ,p16 ,Adenocarcinoma of Lung ,Cell Cycle Proteins ,Biology ,medicine.disease_cause ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Cyclin D ,medicine ,Pathology ,Humans ,Lung cancer ,Cyclin-Dependent Kinase Inhibitor p16 ,Cyclin ,FAM111B ,Aged ,Cell Proliferation ,Aged, 80 and over ,Lung ,Cell Cycle ,Cancer ,Cyclin-Dependent Kinase 4 ,General Medicine ,Original Articles ,Cell cycle ,Middle Aged ,medicine.disease ,lung adenocarcinoma ,Immunohistochemistry ,Tumor Burden ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Cancer research ,Adenocarcinoma ,Original Article ,Female ,KRAS - Abstract
Lung cancer is a common type of cancer that represents a health problem worldwide; lung adenocarcinoma (LUAD) is a major subtype of lung cancer. Although several treatments for LUAD have been developed, the mortality rate remains high because of uncontrollable progression. Further biological and clinicopathological studies are therefore needed. Here, we investigated the role of family with sequence similarity 111 member B (FAM111B), which is highly expressed in papillary‐predominant LUAD; however, its role in cancer is unclear. An immunohistochemical analysis confirmed that papillary‐predominant adenocarcinomas exhibited higher expression of FAM111B, compared with lepidic‐predominant adenocarcinomas. Additionally, FAM111B expression was significantly correlated with clinical progression. In vitro functional analyses using FAM111B‐knockout cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of KRAS‐driven LUAD under serum‐starvation conditions. Furthermore, FAM111B regulated cyclin D1‐CDK4‐dependent cell cycle progression by degradation of p16. In summary, we revealed the clinical importance of FAM111B in human tumor tissues, as well as its function as a degradative enzyme. Therefore, FAM111B has potential as a clinicopathological prognostic marker for LUAD., We screened family with sequence similarity 111 member B (FAM111B), the precise functional role of which in cancers is not clear, as the molecule is highly expressed in papillary‐predominant lung adenocarcinoma. Immunohistochemical analysis confirmed that papillary‐predominant adenocarcinoma had higher expression of FAM111B compared with lepidic‐predominant adenocarcinoma, and FAM111B expression levels were significantly correlated with patients’ clinical progression. In vitro functional analyses using FAM111B‐knockout (FAM111B‐KO) cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of LUAD with the KRAS mutation, specifically under the conditions of serum starvation, and it was revealed that FAM111B negatively regulates CyclinD1‐CDK4‐dependent cell cycle progression by functioning as a degrading enzyme to control p16 expression level.
- Published
- 2020
24. Japanese clinical practice guidelines for vascular anomalies 2017
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Hiroki Nakaoka, Satoshi Hirakawa, Kumiko Chuman, Atsuko Fujikawa, Shunsuke Yuzuriha, Yoshiaki Kinoshita, Shunsuke Sugawara, Akihiro Umezawa, Hideki Mori, Masatoshi Jinnin, Shinichi Watanabe, Junko Ochi, Hidefumi Mimura, Mitsunaga Narushima, Takao Tachibana, Ayato Hayashi, Yumiko Hori, Tadashi Iwanaka, Noriko Aramaki, Eiichi Morii, Naoaki Rikihisa, Satoru Sasaki, Masanori Inoue, Shoji Watanabe, Michio Ozeki, Akihiro Fujino, Keigo Osuga, Kentaro Matsuoka, Shien Seike, Masakazu Kurita, Akira Kuramochi, Yuki Yamamoto, Shunsuke Nosaka, Sadanori Akita, Kosuke Ishikawa, Taiki Nozaki, Masataka Takahashi, Yuki Iwashina, Yoko Aoki, Nobuyuki Takakura, Shigeru Ueno, Kazuki Hashimoto, Yasunari Niimi, Yasunori Arai, Mine Ozaki, Tatsuo Kuroda, and Shuji Nagata
- Subjects
medicine.medical_specialty ,Skin Neoplasms ,Time Factors ,Vascular Malformations ,medicine.medical_treatment ,Vascular malformation ,Dermatology ,030204 cardiovascular system & hematology ,Guideline ,Clinical practice ,Guidelines ,Cochrane Library ,Arteriovenous Malformations ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Pharmacotherapy ,Japan ,030225 pediatrics ,Sclerotherapy ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Vascular Diseases ,Embolization ,Intensive care medicine ,Special Report ,Societies, Medical ,Evidence-Based Medicine ,Lymphangioma ,business.industry ,Age Factors ,General Medicine ,medicine.disease ,Embolization, Therapeutic ,Vascular anomalies ,Clinical Practice ,Radiation therapy ,Treatment Outcome ,Systematic review ,030220 oncology & carcinogenesis ,Pediatrics, Perinatology and Child Health ,Laser Therapy ,Hemangioma ,business - Abstract
The objective was to prepare guidelines to perform the current optimum treatment by organizing effective and efficient treatments of hemangiomas and vascular malformations, confirming the safety, and systematizing treatment, employing evidence-based medicine (EBM) techniques and aimed at improvement of the outcomes. Clinical questions (CQs) were decided based on the important clinical issues. For document retrieval, key words for literature searches were set for each CQ and literature published from 1980 to the end of September 2014 was searched in Pubmed, Cochrane Library, and Japana Centra Revuo Medicina (JCRM). The strengths of evidence and recommendations acquired by systematic reviews were determined following the Medical Information Network Distribution System (MINDS) technique. A total of 33 CQs were used to compile recommendations and the subjects included efficacy of resection, sclerotherapy/embolization, drug therapy, laser therapy, radiotherapy, and other conservative treatment, differences in appropriate treatment due to the location of lesions and among symptoms, appropriate timing of treatment and tests, and pathological diagnosis deciding the diagnosis. Thus, the Japanese Clinical Practice Guidelines for Vascular Anomalies 2017 have been prepared as the evidence-based guidelines for the management of vascular anomalies.
- Published
- 2020
25. Analysis of mTOR pathway expression in lymphatic malformation and related diseases
- Author
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Shinichiro Tahara, Eiichi Morii, Masaharu Kohara, Toshiyuki Fukao, Satoru Toyosawa, Yumiko Hori, Katsutoshi Hirose, Takahiro Matsui, Kentaro Matsuoka, and Michio Ozeki
- Subjects
Adult ,Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Adolescent ,P70-S6 Kinase 1 ,Biology ,Pathology and Forensic Medicine ,Lymphatic System ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Child ,Lymphatic Diseases ,Lymphangiomatosis ,PI3K/AKT/mTOR pathway ,Aged ,TOR Serine-Threonine Kinases ,Infant, Newborn ,Infant ,General Medicine ,Middle Aged ,medicine.disease ,Lymphangiogenesis ,030104 developmental biology ,Lymphatic system ,Kaposiform Hemangioendothelioma ,Child, Preschool ,030220 oncology & carcinogenesis ,Sirolimus ,Immunohistochemistry ,Female ,Signal Transduction ,medicine.drug - Abstract
The mammalian target of rapamycin (mTOR) inhibitor sirolimus is an effective treatment for difficult-to-treat lymphatic anomalies. However, little is known about the expression of mTOR pathway components in lymphatic anomalies. Here we investigated the expression pattern of mTOR pathway components and their phosphorylated forms (mTOR, p-mTOR, 4EBP1, p-4EBP1, S6K1 and p-S6K1) in normal lymphatic vessels and lymphatic anomalies using immunohistochemistry. We studied 18 patients of lymphatic anomalies, including lymphatic malformation (LM, n = 14), Kaposiform lymphangiomatosis (KLA, n = 2) and Kaposiform hemangioendothelioma (KHE, n = 2). Normal lymphatic vessels expressed 4EBP1, S6K1 and p-S6K1, but not p-4EBP1, mTOR or p-mTOR. The mTOR was detected in all lymphatic anomalies, whereas its activation form p-mTOR was detected in half cases of KLA and KHE but not in LM. All lymphatic anomalies expressed S6K1 and its activated form p-S6K1. The expression of 4EBP1 was also found in all lymphatic anomalies, but its activation was detected in approximately half of them. The activation of mTOR was seen in tumor (KLA and KHE) but not in malformation (LM), whereas the activation of S6K1 and 4EBP1 was seen in all and half of lymphatic anomalies, respectively.
- Published
- 2020
26. Mycobacterium kansasii arthritis of the elbow in an immunocompetent patient with a suspected soft-tissue tumor
- Author
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Shigeto Hamaguchi, Hideo Okuno, Eiichi Morii, Hideharu Hagiya, Kazunori Tomono, Hiroyuki Tanaka, Kenichiro Hamada, Yumiko Hori, Hisao Yoshida, and Hideki Yoshikawa
- Subjects
0301 basic medicine ,Microbiology (medical) ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,030106 microbiology ,Elbow ,Arthritis ,Synovectomy ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Ethambutol ,Mycobacterium kansasii ,biology ,business.industry ,Soft tissue ,biology.organism_classification ,medicine.disease ,Infectious Diseases ,medicine.anatomical_structure ,Septic arthritis ,Differential diagnosis ,business ,medicine.drug - Abstract
Mycobacterium kansasii is one of the major non-tuberculous mycobacteria species that typically cause pulmonary diseases. M. kansasii is known to cause septic arthritis as an extrapulmonary disease in immunosuppressed patients or chronic skin disease. Herein, we present a case of M. kansasii arthritis involving the elbow of an immunocompetent patient, which was initially suspected to be a soft-tissue tumor. A 70-year-old man presented with a swollen left elbow that had progressed for 18 months with deteriorating arthralgia and limited range of motion. Magnetic resonance imaging revealed filling of the intra-articular space of the elbow and surrounding of the radial head with a soft tissue mass with mixed signal intensity. Initial incisional biopsy was performed via the lateral approach to the elbow joint, and pathological examination of the mass did not reveal any evidence of malignancy. One year after the first operation, arthroscopic surgery was performed to excise the mass following the recurrence of swelling and limited function of the elbow. Pathological examination of the resected synovium revealed epithelioid granulomas containing a multinucleated giant cell and inflammatory cell infiltration, characteristic of mycobacterial infection. M. kansasii was cultured after 2 weeks of incubation of the synovial sample. He experienced full resolution of the swelling and limited function following a combination of synovectomy and multidrug antimycobacterial treatment (rifampin 600 mg/day, clarithromycin 800 mg/day, and ethambutol 750 mg/day). This case highlights the need to consider this rare infection in the differential diagnosis of intra-articular soft tissue tumor-like lesions even in immunocompetent patients.
- Published
- 2020
27. Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine
- Author
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Jun-ichiro Ikeda, Keisuke Kawasaki, Satoshi Nojima, Eiichi Morii, Daisuke Okuzaki, Yumiko Hori, Yutaka Umakoshi, Masako Kurashige, Eiichiro Fukusaki, Naoki Wada, Moyu Taniguchi, Shinichiro Tahara, and Kenji Ohshima
- Subjects
Chemistry ,Cell growth ,Endocrinology, Diabetes and Metabolism ,Cell Biology ,Colorectal adenoma ,medicine.disease ,Cell biology ,Serine ,Histone H3 ,Cell culture ,Acetylation ,Physiology (medical) ,Serine racemase ,Internal Medicine ,medicine ,Intracellular - Abstract
Serine racemase (SRR) catalyses not only the racemization but also the dehydration of L-serine and D-serine, resulting in the formation of pyruvate and ammonia. Although SRR activity is important in the central nervous system, SRR has not been linked to cancer metabolism before. Here we show that SRR supports proliferation of colorectal-cancer cells. We find that SRR expression is upregulated in colorectal adenoma and adenocarcinoma lesions compared with non-neoplastic mucosa in human colorectal-cancer specimens. SRR-mediated dehydration of serine contributes to the pyruvate pool in colon-cancer cells, enhances proliferation, maintains mitochondrial mass and increases basal reactive oxygen species production, which has anti-apoptotic effects. Moreover, SRR promotes acetylation of histone H3 by maintaining intracellular acetyl-CoA levels. Inhibition of SRR suppresses growth of colorectal tumours in mice and augments the efficacy of 5-fluorouracil treatment. Our findings highlight a previously unknown mechanism through which a racemase supports cancer-cell growth and suggest that SRR might be a molecular target for colorectal-cancer therapy.
- Published
- 2020
28. Effect of Ingestion of Palm Sugar from Cambodia on the Blood Glucose Response in Mice
- Author
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Hiroto Kumakura, Shigenori Kumazawa, Misa Fujinami, Yumiko Hori, Kazuma Yoshizumi, and Takahiro Hosoya
- Subjects
biology ,Palm sugar ,business.industry ,Medicine ,Ingestion ,General Medicine ,Food science ,biology.organism_classification ,business - Published
- 2020
29. The efficacy of human papillomavirus vaccination in young Japanese girls: the interim results of the OCEAN study
- Author
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Eiji Kobayashi, Kentaro Shimura, Satoshi Nakagawa, Yutaka Ueda, Tadashi Kimura, Eiichi Morii, Yoshimichi Tanaka, Hiromi Murata, Hidekatsu Nakai, Noriomi Matsumura, Tomio Nakayama, Tomoyuki Ichimura, Kazuaki Sato, Masahide Ohmichi, Tomomi Egawa-Takata, Akiko Morimoto, Yorihiko Horikoshi, Tetsu Takagi, Kosuke Hiramatsu, Masaki Mandai, Asami Yagi, Takayuki Enomoto, Jyunko Saito, Yoshito Terai, Hidetaka Okada, Toshihiro Kimura, Toshiyuki Sumi, Ryoko Minekawa, and Yumiko Hori
- Subjects
Oncology ,medicine.medical_specialty ,Adolescent ,Immunology ,Uterine Cervical Neoplasms ,Cervical intraepithelial neoplasia ,Japan ,Internal medicine ,Interim ,Humans ,Immunology and Allergy ,Medicine ,Papillomavirus Vaccines ,Prospective Studies ,Human papillomavirus ,Child ,Pharmacology ,Cervical cancer ,Human papillomavirus 18 ,business.industry ,Papillomavirus Infections ,Vaccination ,HPV infection ,virus diseases ,medicine.disease ,female genital diseases and pregnancy complications ,Human papillomavirus vaccination ,Female ,Christian ministry ,business - Abstract
Human papillomavirus (HPV) vaccine has been used to prevent chronic HPV infection, which accounts for cervical cancer. Japanese Ministry of Health, Labor and Welfare (MHLW) conducted an HPV vaccination campaign in 2010 and the Obstetrical Gynecological Society of Osaka initiated a multicenter, prospective cohort study in Osaka, Japan - OCEAN (Osaka Clinical resEArch of HPV vacciNe) study - to investigate the oncogenic HPV prevalence and the long-term protection rate of HPV vaccine. A total of 2814 participants were enrolled on their visit for HPV vaccination between 12 and 18 years old. Among them, 102 participants received HPV/Pap co-test as primary cancer screening at the age of 20-21. We compared the prevalence in two groups (the vaccinated and the unvaccinated group). HPV infection ratio was significantly lower in the vaccinated group compared to the unvaccinated (12.9% vs. 19.7%
- Published
- 2021
30. PIK3CA mutation correlates with mTOR pathway expression but not clinical and pathological features in Fibfibroipose vascular anomaly (FAVA)
- Author
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Yumiko Hori, Katsutoshi Hirose, Michio Ozeki, Kenji Hata, Daisuke Motooka, Shinichiro Tahara, Takahiro Matsui, Masaharu Kohara, Hiroki Higashihara, Yusuke Ono, Kaishu Tanaka, Satoru Toyosawa, and Eiichi Morii
- Subjects
Sirolimus ,Histology ,Class I Phosphatidylinositol 3-Kinases ,Vascular Malformations ,TOR Serine-Threonine Kinases ,Short Report ,Vascular anomaly ,PIK3CA ,General Medicine ,Pathology and Forensic Medicine ,Venous malformation ,Fibro-adipose vascular anomaly ,Mutation ,Pathology ,mTOR ,RB1-214 ,Humans ,Lymphatic malformation ,FAVA ,neoplasms ,Proto-Oncogene Proteins c-akt ,Retrospective Studies - Abstract
Background Fibro-adipose vascular anomaly (FAVA) is a rare and new entity of vascular anomaly. Activating mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene were identified at a frequency of 62.5% in FAVA cases. The PIK3CA mutations excessively activate mammalian target of rapamycin (mTOR) pathway, which promotes angiogenesis and lymphangiogenesis, implying that PIK3CA mutations may act as drivers of FAVAs. This study investigated the correlations between PIK3CA mutational status, clinicopathological features and immunohistochemical expression of the mTOR pathway in a series of FAVA. Methods We retrospectively evaluated the clinical and pathological findings of four FAVA cases. We performed next-generation sequencing (NGS) with a custom panel of genes associated with the mTOR pathway and genes responsible for other vascular anomalies; followed by direct sequencing and immunohistochemical analysis of the mTOR pathway. Results Two PIK3CA-mutation cases and two PIK3CA-wild-type (wt) cases exhibited similar typical clinical features of FAVA. Histological analysis revealed venous malformation, lymphatic malformation, nerves containing enlarged abnormal vessels and fibrofatty tissue were observed regardless of PIK3CA mutational status. In contrast to clinical and histological findings, the immunohistochemical expression of activated AKT and mTOR that are upstream of the mTOR pathway was detected in abnormal vessels of PIK3CA-mutation cases but not in those of PIK3CA-wt cases. However, activated eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1) and ribosomal protein S6 kinase 1 (S6K1), both of which are downstream effectors of the mTOR pathway, were expressed in abnormal vessels of both PIK3CA-mutation and PIK3CA-wt cases. Furthermore, targeting NGS did not find any common genetic mutations involved in the mTOR pathway among PIK3CA-wt cases. Conclusions There was no significant association between the presence of PIK3CA mutations and the clinicopathological features of FAVA, suggesting that the PIK3CA gene is not necessarily involved in the onset of FAVA. FAVAs lacking PIK3CA mutations may be caused by other gene mutations that activate 4EBP1 and S6K1.
- Published
- 2021
31. Nicotinamide N-methyltransferase is related to MELF pattern invasion in endometrioid carcinoma
- Author
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Kenji Ohshima, Satoshi Nojima, Yumiko Hori, Masako Kurashige, Shinichiro Tahara, Takahiro Matsui, Daisuke Okuzaki, Kazuaki Sato, and Eiichi Morii
- Subjects
Cancer Research ,NNMT ,Nicotinamide N-methyltransferase ,Biology ,migration ,Transcription (biology) ,Cell Line, Tumor ,Histone methylation ,Biomarkers, Tumor ,Nicotinamide N-Methyltransferase ,Humans ,Radiology, Nuclear Medicine and imaging ,Neoplasm Invasiveness ,Gene ,RC254-282 ,Research Articles ,Laser capture microdissection ,Cancer Biology ,Carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Methylation ,invasion ,MELF ,Endometrial Neoplasms ,Oncology ,Cancer research ,Immunohistochemistry ,Female ,SDPR ,Signal Transduction ,Research Article ,endometrioid carcinoma - Abstract
Grade 1 (G1) endometrioid carcinoma (EC) is relatively a good prognosis. However, in a minority of cases, G1 shows an aggressive histological pattern known as the microcystic, elongated, and fragmented (MELF) pattern. We previously reported that EC with high expression levels of S100A4 and serum deprivation‐response protein (SDPR) was related to MELF pattern invasion. However, the molecular features of the invasive front area of the MELF pattern have not been investigated. In this study, we searched for genes preferentially expressed in the invasive front area of EC with the MELF pattern using laser microdissection and RNA sequencing, and showed that nicotinamide N‐methyltransferase (NNMT) is related to MELF pattern invasiveness. Immunohistochemical analyses confirmed high NNMT expression in the invasive front area of the MELF pattern. Moreover, NNMT promoted migration, invasion, colony formation, epithelial–mesenchymal transition (EMT), and chemoresistance using EC cell lines. We speculate that depletion of NNMT promotes histone methylation and leads to tumor suppression because NNMT consumes S‐adenosyl methionine (SAM), which is an essential methylation cofactor. NNMT knockout cells showed enhanced expression of H3K9me2. RNA sequencing using NNMT knockout cell lines suggested that methylation of H3K9 leads to repression of the transcription of various oncogenic genes. Our findings demonstrate the possibility that NNMT inhibitors, which are expected to be used for the treatment of metabolic disorders, would be effective for the treatment of aggressive EC. This is the first report of gene analyses focusing on the morphological changes associated with MELF pattern invasion of EC., We searched for genes preferentially expressed in the invasive front area of EC with the MELF pattern using laser microdissection and RNA sequencing. We showed that NNMT is related to MELF pattern invasiveness.
- Published
- 2021
32. An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke
- Author
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Shigeo Murayama, Eiichi Morii, Shintaro Sugiyama, Shuhei Okazaki, Hiroya Mizuno, Hiroki Takai, Satoshi Hattori, Hideki Mochizuki, Takaya Kitano, Manabu Sakaguchi, Tsutomu Sasaki, Yumiko Hori, Hajime Nakamura, Goichi Beck, Takeshi Shimazu, Junichi Iida, Naoki Oyama, Ryo Tamaki, Yoshiki Yagita, Yuki Shimada, Hiroaki Fushimi, Hirotake Nishimura, Hideaki Kanki, Takanori Iwamoto, Shunji Matsubara, Haruhiko Kishima, Taku Hoshi, Jiro Iba, Kenichi Todo, and Masaaki Uno
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Patient characteristics ,030204 cardiovascular system & hematology ,Extracellular Traps ,Histones ,03 medical and health sciences ,0302 clinical medicine ,Reperfusion therapy ,Cerebral embolism ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,cardiovascular diseases ,Thrombus ,Stroke ,Aged ,Ischemic Stroke ,Thrombectomy ,business.industry ,Brain ,Thrombosis ,Hematology ,Neutrophil extracellular traps ,Recovery of Function ,medicine.disease ,Immunohistochemistry ,Mechanical thrombectomy ,Intracranial Embolism ,Ischemic stroke ,Reperfusion ,cardiovascular system ,Cardiology ,Citrullination ,Female ,business ,030217 neurology & neurosurgery ,circulatory and respiratory physiology - Abstract
Background Thrombosis is a dynamic process, and a thrombus undergoes physical and biochemical changes that may alter its response to reperfusion therapy. This study assessed whether thrombus age influenced reperfusion quality and outcomes after mechanical thrombectomy for cerebral embolism. Methods We retrospectively evaluated 185 stroke patients and thrombi that were collected during mechanical thrombectomy at three stroke centers. Thrombi were pathologically classified as fresh or older based on their granulocytes' nuclear morphology and organization. Thrombus components were quantified, and the extent of NETosis (the process of neutrophil extracellular trap formation) was assessed using the density of citrullinated histone H3-positive cells. Baseline patient characteristics, thrombus features, endovascular procedures, and functional outcomes were compared according to thrombus age. Results Fresh thrombi were acquired from 43 patients, and older thrombi were acquired from 142 patients. Older thrombi had a lower erythrocyte content (p Conclusion An older thrombus delays reperfusion after mechanical thrombectomy for ischemic stroke. Adding therapies targeting thrombus maturation may improve the efficacy of mechanical thrombectomy.
- Published
- 2021
33. Prognostic implication of adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide in patients with extraskeletal osteosarcoma
- Author
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Toru Wakamatsu, Ikuo Kudawara, Yoshinori Imura, Shigeki Kakunaga, Takafumi Ueda, Satoshi Takenaka, Yumiko Hori, Norifumi Naka, Hidetatsu Outani, Kenichiro Hamada, and Hideki Yoshikawa
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Extraskeletal Osteosarcoma ,medicine.medical_treatment ,Bone Neoplasms ,Soft Tissue Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Doxorubicin ,Ifosfamide ,Aged ,Retrospective Studies ,Osteosarcoma ,Chemotherapy ,business.industry ,Wide local excision ,Soft tissue sarcoma ,Hematology ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Neoadjuvant Therapy ,Survival Rate ,Regimen ,030104 developmental biology ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Female ,Surgery ,business ,medicine.drug - Abstract
Extraskeletal osteosarcoma (ESOS) is an extremely rare soft tissue sarcoma. Their prognosis remains poor. Our purposes were to identify the effective chemotherapeutic regimen for ESOS. We retrospectively reviewed 16 patients with ESOS treated at the Osaka University Orthopaedic Oncology Group between 1992 and 2012. We extracted the clinical data on patients. Kaplan–Meier method and the log-rank test were used for survival analyses. Median age of the patients was 61.5 years (range 25–79 years). Wide local excision was performed for 11 patients and 9 patients were treated combined with chemotherapy. The 5-year disease-specific survival (DSS) rate was 53.9%. The 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy or not were 66.7% or 25%, respectively (p = 0.0215). Furthermore, the 5-year DSS rates for patients treated with adjuvant/neoadjuvant chemotherapy consisting of doxorubicin and ifosfamide and those treated with other regimens were 100% or 40%, respectively (p = 0.0327). The present study demonstrated that adjuvant/neoadjuvant chemotherapy, especially consisting of doxorubicin and ifosfamide, was potentially efficacious for ESOS. Further prospective study using this multimodality treatment approach to patients with ESOS should be strongly warranted.
- Published
- 2019
34. A fatal case of Exophiala dermatitidis disseminated infection in an allogenic hematopoietic stem cell transplant recipient during micafungin therapy
- Author
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Keigo Kimura, Kazunori Tomono, Atsuko Sunada, Eiichi Morii, Isao Nishi, Tetsuo Maeda, Yumiko Hori, Akiko Ueda, Nori Yoshioka, Hideharu Hagiya, Shinsuke Kusakabe, Keisuke Kawasaki, and Yuzuru Kanakura
- Subjects
Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,Antifungal Agents ,medicine.medical_treatment ,030106 microbiology ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Immunocompromised Host ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,Exophiala ,Humans ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,Fungemia ,Voriconazole ,Peripheral Blood Stem Cell Transplantation ,biology ,business.industry ,Micafungin ,medicine.disease ,biology.organism_classification ,Lymphoproliferative Disorders ,Transplantation ,Phaeohyphomycosis ,Infectious Diseases ,Immunology ,business ,Immunosuppressive Agents ,Exophiala dermatitidis ,medicine.drug - Abstract
Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.
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- 2019
35. Serum deprivation‐response protein regulates aldehyde dehydrogenase 1 through integrin‐linked kinase signaling in endometrioid carcinoma cells
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Masako Kurashige, Jun-ichiro Ikeda, Satoshi Nojima, Eiichi Morii, Daisuke Okuzaki, Yumiko Hori, Naoki Wada, Shinichiro Tahara, Kenji Ohshima, and Yuichi Motoyama
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0301 basic medicine ,Gene isoform ,Cancer Research ,Epithelial-Mesenchymal Transition ,Aldehyde dehydrogenase ,Biology ,integrin‐linked kinase ,Protein Serine-Threonine Kinases ,Aldehyde Dehydrogenase 1 Family ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Pathology ,serum deprivation‐response protein ,Humans ,Integrin-linked kinase ,Neoplasm Invasiveness ,aldehyde dehydrogenase 1 ,Cell Proliferation ,Kinase ,microcystic, elongated and fragmented ,Retinal Dehydrogenase ,General Medicine ,Original Articles ,Aldehyde Dehydrogenase ,Phosphate-Binding Proteins ,Molecular biology ,Endometrial Neoplasms ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Oncology ,Tumor progression ,030220 oncology & carcinogenesis ,biology.protein ,Original Article ,Female ,Stem cell ,SDPR ,Carrier Proteins ,Carcinoma, Endometrioid ,Cavin ,endometrioid carcinoma ,Signal Transduction - Abstract
Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. We reported previously that aldehyde dehydrogenase 1 (ALDH1), a predominant isoform of the ALDH family in mammals and a potential marker of normal and malignant stem cells, is related to the tumorigenic potential of EC. We compared the levels of various proteins in human EC cells with high and low ALDH1 expression using shotgun proteomics and found that serum deprivation-response protein (SDPR) was preferentially expressed in cells with high ALDH1 expression. Also known as cavin-2, SDPR is a member of the cavin protein family, which is required for the formation of caveolae. Using SDPR-knockout EC cells generated using the CRISPR/Cas9 system, we revealed that SDPR was correlated with invasion, migration, epithelial-mesenchymal transition, and colony formation, as well as the expression of ALDH1. RNA sequencing showed that integrin-linked kinase (ILK) signaling is involved in the effect of SDPR on ALDH1. Immunohistochemical analysis revealed that the localization of ILK at the cell cortex was disrupted by SDPR knockout, potentially interfering with ILK signaling. Moreover, immunohistochemical analysis of clinical samples showed that SDPR is related to histological characteristics associated with invasiveness, such as poor differentiation, lymphatic invasion, and the microcystic, elongated, and fragmented histopathological pattern. This is, to our knowledge, the first report that SDPR is related to tumor progression.
- Published
- 2019
36. Abstract MP2: An Older Thrombus Delays Reperfusion in Mechanical Thrombectomy for Ischemic Stroke
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Manabu Sakaguchi, Shuhei Okazaki, Yumiko Hori, Takanori Iwamoto, Hideki Mochizuki, Yoshiki Yagita, Yuki Shimada, Kenichi Todo, Takaya Kitano, Tsutomu Sasaki, Shigeo Murayama, Hajime Nakamura, Hideaki Kanki, Haruhiko Kishima, Goichi Beck, and Eiichi Morii
- Subjects
Advanced and Specialized Nursing ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Thrombolysis ,medicine.disease ,Endovascular therapy ,Thrombosis ,Mechanical thrombectomy ,Embolism ,Internal medicine ,Ischemic stroke ,cardiovascular system ,medicine ,Cardiology ,cardiovascular diseases ,Neurology (clinical) ,Thrombus ,Cardiology and Cardiovascular Medicine ,business ,Stroke - Abstract
Background: Thrombus formation is a dynamic process and the structure of thrombus changes with time. We examined the effect of thrombus age on the quality of reperfusion and prognosis in mechanical thrombectomy for acute ischemic stroke. Methods: We examined 185 patients who underwent mechanical thrombectomy in 3 stroke centers between January 2015 and December 2019, and pathologically evaluated their retrieved thrombi. Thrombi were classified according to histologically accepted definitions as: fresh, with intact granulocytes; and older, with organization or lytic changes characterized by areas of colliquation necrosis and karyorrhexis of granulocytes. The extent of neutrophil extracellular trap formation (NETosis) in thrombi was assessed on the basis of the density of citrullinated histone H3 positive particles. Baseline characteristics, time to successful reperfusion (eTICI 2b or more), thrombus feature, and functional outcome were compared between the patients with fresh and older thrombi. Results: Fresh thrombi were obtained from 43 patients (23%), and older thrombi, from 142 patients (77%). The stroke subtypes and onset-to-puncture time did not significantly differ between the two groups. The erythrocyte content was higher, whereas the density of macrophages and extent of NETosis were lower in the fresh thrombi. Fresh thrombi were associated with shorter time from puncture to recanalization (median, 48 vs. 62 min, P = 0.004; Figure), and fewer passes before reperfusion (median, 1 vs. 2; P < 0.001). In the multivariate analysis, favorable outcome (mRS ≤ 2) was observed more often in patients with fresh thrombi (adjusted OR, 2.76; 95% CI, 1.20-6.32). Conclusions: An older thrombus necessitated longer procedure time and more device passes, which deteriorate the functional outcome of patients with acute ischemic stroke. Thrombus maturation may contribute to resistance to mechanical thrombectomy.
- Published
- 2021
37. Giant cell tumor of bone - Analysis of 213 cases involving extra-craniofacial bones
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Yuko Kuwae, Satoshi Takenaka, Junya Toguchida, Norifumi Naka, Toshiharu Shirai, Yasuaki Nakashima, Yukiko Morinaga, Masayuki Mano, Takeshi Inoue, Masanari Aono, Manabu Hoshi, Eiichi Konishi, Yumiko Hori, Hironori Haga, Shigenori Nagata, Hidetatsu Outani, and Shigeki Kakunaga
- Subjects
0301 basic medicine ,Male ,Pathology ,medicine.medical_treatment ,Gastroenterology ,bone ,Metastasis ,Curettage ,Histones ,0302 clinical medicine ,Japan ,Risk Factors ,Child ,Aged, 80 and over ,Giant Cell Tumor of Bone ,Univariate analysis ,General Medicine ,Middle Aged ,Prognosis ,Denosumab ,risk factor ,030220 oncology & carcinogenesis ,Female ,Original Article ,local recurrence ,Giant-cell tumor of bone ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Bone Neoplasms ,G34W ,Pathology and Forensic Medicine ,03 medical and health sciences ,Young Adult ,statistical analysis ,Internal medicine ,medicine ,Humans ,Craniofacial ,Risk factor ,Pathological ,Aged ,Retrospective Studies ,mitosis ,business.industry ,denosumab ,Original Articles ,medicine.disease ,030104 developmental biology ,Neoplasm Recurrence, Local ,business ,extra‐craniofacial bone - Abstract
We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra‐craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12–80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow‐up period (24–316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence.
- Published
- 2021
38. Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature
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Yumiko Hori, Yuri Iwamoto, Toshihiro Uchihashi, Masaharu Kohara, Eiichi Morii, Satoru Toyosawa, Shumei Murakami, Kaori Oya, Katsutoshi Hirose, Sunao Sato, Yasuo Fukuda, and Yu Usami
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Oncogene Proteins, Fusion ,Chromosomal translocation ,Case Reports ,Biology ,Salivary Glands, Minor ,Pathology and Forensic Medicine ,03 medical and health sciences ,Exon ,0302 clinical medicine ,medicine ,Humans ,Hyalinizing clear cell carcinoma ,EWSR1/ATF1 Fusion Gene ,Salivary gland ,ATF1 ,Palate ,Breakpoint ,Middle Aged ,medicine.disease ,Salivary Gland Neoplasms ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Otorhinolaryngology ,030220 oncology & carcinogenesis ,Clear cell carcinoma ,Female ,Adenocarcinoma, Clear Cell - Abstract
Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported. Although EWSR1 involvement in these cases was confirmed by EWSR1 break-apart FISH indicating the translocation, sequence analysis for EWSR1-ATF1 fusion type has been reported only in three cases of CCC so far. Herein, we report a CCC case with novel EWSR1-ATF1 fusion (EWSR1 exon 15 and ATF1 exon 5) arising in minor salivary gland and review the role of the chimeric variants in some malignancies with EWSR1-ATF1 rearrangement. Current tumor was composed of the small nests of clear tumor cells and hyalized fibrous stroma. Immunohistochemically, the tumor was positive for AE1/AE3, CK5/6 and p63, negative for S100, Melan-A, SMA and CD10. After 8 months of follow-up, there are no evidence of recurrence.
- Published
- 2020
39. A Case of Lymphocytic Myocarditis with Eosinophilic Degranulation Successfully Treated with Steroid Therapy
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Yasushi Sakata, Shunsuke Nishimura, Fusako Sera, Isamu Mizote, Shungo Hikoso, Yumiko Hori, Kei Nakamoto, Hatsue Ishibashi-Ueda, Tomoko Inoue, Eiichi Morii, Yoshihiko Ikeda, Tomohito Ohtani, Tetsuo Minamino, and Yasumasa Tsukamoto
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medicine.medical_specialty ,Inflammation ,Case Report ,030204 cardiovascular system & hematology ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Oral administration ,Internal medicine ,Eosinophilic ,medicine ,Diseases of the circulatory (Cardiovascular) system ,Eosinophil degranulation ,030212 general & internal medicine ,Ejection fraction ,business.industry ,Degranulation ,medicine.disease ,Methylprednisolone ,RC666-701 ,Cardiology ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Infiltration (medical) ,medicine.drug - Abstract
A 49-year-old woman was admitted with suspicion of acute myocarditis. On the next day after admission, her serum troponin I level continued to rise, indicating progression of myocardial damage. Moreover, her symptoms persisted, and left ventricular ejection fraction did not improve. Because of a predominant infiltration of lymphocytes in the myocardial specimens, lymphocytic myocarditis was diagnosed. However, a close observation of the specimens revealed eosinophil degranulation. Based on this finding, intravenous steroid therapy was initiated. High-dose methylprednisolone led to rapid and appreciable improvements in symptoms and left ventricular function within 12 hours after the first administration, which was followed by normalization of serum troponin I level. Steroid therapy was switched to oral administration and tapered carefully. There was no recurrence of left ventricular dysfunction or elevation of serum troponin I level. In eosinophilic myocarditis, eosinophil degranulation has been recognized as an important finding associated with progression of inflammation and myocardial damage. However, no attention has been paid to the presence and clinical implications of eosinophil degranulation in lymphocytic myocarditis. This case indicates that eosinophil degranulation in lymphocytic myocarditis may be an important finding associated with a high therapeutic response to steroid therapy.
- Published
- 2020
40. Motivating Mothers to Recommend Their 20-Year-Old Daughters Receive Cervical Cancer Screening: A Randomized Study
- Author
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Tetsu Takagi, Kiyoshi Yoshino, Masahide Ohmichi, Hidekatsu Nakai, Masayuki Sekine, Eiichi Morii, Yorihiko Horikoshi, Eiji Kobayashi, Asami Yagi, Kentaro Shimura, Mikiko Asai-Sato, Toshiyuki Sumi, Shinya Matsuzaki, Takayuki Enomoto, Tomoyuki Ichimura, Yutaka Ueda, Hiromi Murata, Tomio Nakayama, Yumiko Hori, Yoshito Terai, Hidetaka Okada, Tadashi Kimura, Tomomi Egawa-Takata, Yusuke Tanaka, Junko Saito, Etsuko Miyagi, Akiko Morimoto, and Masaki Mandai
- Subjects
recommendation ,medicine.medical_specialty ,Epidemiology ,media_common.quotation_subject ,cervical cancer screening ,leaflet ,Mothers ,Uterine Cervical Neoplasms ,Health Promotion ,Cervical cancer screening ,law.invention ,Nuclear Family ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Randomized controlled trial ,Japan ,law ,Medicine ,Humans ,030212 general & internal medicine ,Young adult ,Nuclear family ,Early Detection of Cancer ,media_common ,Cancer ,Cervical cancer ,Daughter ,lcsh:R5-920 ,Motivation ,business.industry ,Obstetrics ,mother ,General Medicine ,medicine.disease ,Mother-Child Relations ,Maternal education ,Health promotion ,030220 oncology & carcinogenesis ,daughter ,Original Article ,Female ,Pamphlets ,business ,lcsh:Medicine (General) - Abstract
Background In Japan, the rate of cervical cancer screening is remarkably low, especially among women in their twenties and thirties, when cervical cancer is now increasing dramatically. The aim of this study was to test whether a modified government reminder for 20-year-old women to engage in cervical cancer screening, acting through maternal education and by asking for a maternal recommendation to the daughter to receive the screening, could increase their participation rate. Methods In two Japanese cities, 20-year-old girls who had not received their first cervical cancer screening before October of fiscal year 2014 were randomized into two study arms. One group of 1,274 received only a personalized daughter-directed reminder leaflet for cervical cancer screening. In the second group of 1,274, the daughters and their mothers received a combination package containing the same reminder leaflet as did the first group, plus an additional informational leaflet for the mother, which requested that the mother recommend that her daughter undergo cervical cancer screening. The subsequent post-reminder screening rates of these two study arms were compared. Results The cervical cancer screening rate of 20-year-old women whose mothers received the information leaflet was significantly higher than that for women who received only a leaflet for themselves (11% vs 9%, P = 0.0049). Conclusions An intervention with mothers, by sending them a cervical cancer information leaflet with a request that they recommend that their daughter receive cervical cancer screening, significantly improved their daughters' screening rate.
- Published
- 2018
41. Imaging findings of ovarian dysgerminoma with emphasis on multiplicity and vascular architecture: pathogenic implications
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Mitsuaki Tatsumi, Takahiro Tsuboyama, Masatoshi Hori, Makoto Sakane, Yumiko Hori, Noriyuki Tomiyama, Hiromitsu Onishi, and Takashi Ota
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Adolescent ,Urology ,Contrast Media ,Gonadoblastoma ,Ovary ,Dysgerminoma ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Yolk sac ,Child ,Pathological ,Ovarian Neoplasms ,030219 obstetrics & reproductive medicine ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,Magnetic resonance imaging ,Neoplasms, Germ Cell and Embryonal ,Image Enhancement ,medicine.disease ,Magnetic Resonance Imaging ,Diffusion Magnetic Resonance Imaging ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,Germ cell tumors ,Tomography, X-Ray Computed ,business - Abstract
We report the imaging findings of three ovarian dysgerminomas that coexisted with other germ cell tumors or gonadoblastomas, focusing on the distribution of tumor nests and vascular architecture, which might provide information about the pathogenesis of dysgerminomas. In a 14-year-old female with dysgerminoma and coexisting gonadoblastomas, contrast-enhanced magnetic resonance imaging (MRI) demonstrated a solid mass in the right ovary, which presented as hyperintense lobules on diffusion-weighted imaging separated by fibrovascular septa. Some small nodules were found to exist separately from the lobules (multiplicity) and to include pathological remnants of gonadoblastoma. Large tumor vessels were present at the center of the mass (central blood vessels), which were in direct contact with the ovarian veins and radiated peripherally through the fibrovascular septa. In a 35-year-old female, a mixed germ cell tumor, which was mainly composed of dysgerminoma and yolk sac tumor foci, exhibited the same vascular architecture pattern as the first dysgerminoma on contrast-enhanced computed tomography. In a 10-year-old female with a mixed germ cell tumor, contrast-enhanced MRI revealed an enlarged left ovary, which contained a large heterogeneous mass and multiple tiny nodules (multiplicity). Microscopically, the former corresponded to a yolk sac tumor, and the latter corresponded to a dysgerminoma containing remnants of gonadoblastoma. Based on these cases, the presence of tumor nest multiplicity and central blood vessels might aid the diagnosis of dysgerminoma, and these imaging findings might be indicative of the synchronous development of multiple dysgerminomas from primordial germ cells or gonadoblastomas.
- Published
- 2018
42. CUBIC pathology: three-dimensional imaging for pathological diagnosis
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Atsushi Kumanogoh, Naoto Tsujimura, Hiroki R. Ueda, Yumiko Hori, Satoshi Nojima, Eiichi Morii, Naoki Wada, Masako Kurashige, Hiroyoshi Takemoto, Etsuo A. Susaki, Ko Takachi, Shohei Iijima, Kyotaro Yoshida, Shinichiro Tahara, Yujiro Nakahara, Kenji Ohshima, and Jun-ichiro Ikeda
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pathology ,Biopsy ,H&E stain ,Fluorescent Antibody Technique ,lcsh:Medicine ,Article ,Metastatic carcinoma ,Mice ,03 medical and health sciences ,Imaging, Three-Dimensional ,Image Processing, Computer-Assisted ,medicine ,Atypia ,Animals ,Humans ,lcsh:Science ,Lung ,Lymph node ,Multidisciplinary ,medicine.diagnostic_test ,Clinical pathology ,business.industry ,Carcinoma ,lcsh:R ,medicine.disease ,Immunohistochemistry ,Molecular Imaging ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Lymphatic Metastasis ,Female ,Histopathology ,lcsh:Q ,Lymph Nodes ,Lymph ,business - Abstract
The examination of hematoxylin and eosin (H&E)-stained tissues on glass slides by conventional light microscopy is the foundation for histopathological diagnosis. However, this conventional method has some limitations in x-y axes due to its relatively narrow range of observation area and in z-axis due to its two-dimensionality. In this study, we applied a CUBIC pipeline, which is the most powerful tissue-clearing and three-dimensional (3D)-imaging technique, to clinical pathology. CUBIC was applicable to 3D imaging of both normal and abnormal patient-derived, human lung and lymph node tissues. Notably, the combination of deparaffinization and CUBIC enabled 3D imaging of specimens derived from paraffin-embedded tissue blocks, allowing quantitative evaluation of nuclear and structural atypia of an archival malignant lymphoma tissue. Furthermore, to examine whether CUBIC can be applied to practical use in pathological diagnosis, we performed a histopathological screening of a lymph node metastasis based on CUBIC, which successfully improved the sensitivity in detecting minor metastatic carcinoma nodules in lymph nodes. Collectively, our results indicate that CUBIC significantly contributes to retrospective and prospective clinicopathological diagnosis, which might lead to the establishment of a novel field of medical science based on 3D histopathology.
- Published
- 2017
43. Realistic fear of cervical cancer risk in Japan depending on birth year
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Eiji Kobayashi, Kentaro Shimura, Akiko Sukegawa, Hiromi Murata, Risa Kudo, Yoko Motoki, Mikiko Asai-Sato, Ruriko Nakae, Masahide Ohmichi, Yoshito Terai, Tomomi Egawa-Takata, Masayuki Sekine, Tadashi Kimura, Shinya Matsuzaki, Kiyoshi Yoshino, Hidetaka Okada, Junko Saito, Toshiyuki Sumi, Yukio Suzuki, Yorihiko Horikoshi, Tomoyuki Ichimura, Sosuke Adachi, Yusuke Tanaka, Eiichi Morii, Manako Yamaguchi, Yutaka Ueda, Etsuko Miyagi, Yumiko Hori, Tetsu Takagi, Akiko Morimoto, Masaki Mandai, Tomio Nakayama, Asami Yagi, Hidekatsu Nakai, and Takayuki Enomoto
- Subjects
medicine.medical_specialty ,Vaccination Coverage ,Adolescent ,cervical cancer ,Immunology ,Short Report ,Uterine Cervical Neoplasms ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Japan ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Child ,Adverse effect ,governmental suspension of recommendation ,vaccination rate ,Birth Year ,HPV vaccine ,Pharmacology ,Cervical cancer ,Vaccination rate ,Gynecology ,business.industry ,Papillomavirus Infections ,Age Factors ,HPV infection ,Fear ,medicine.disease ,Vaccination ,relative risk ,Sexual intercourse ,030220 oncology & carcinogenesis ,Relative risk ,Female ,business ,Demography - Abstract
Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk. Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000. Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994–1999 was reduced to 0.56–0.70, however, the rate in those born in 2000–2003 was 0.98–1.0, almost the same risk as before introduction of the vaccine. Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.
- Published
- 2017
44. Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine
- Author
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Kenji, Ohshima, Satoshi, Nojima, Shinichiro, Tahara, Masako, Kurashige, Keisuke, Kawasaki, Yumiko, Hori, Moyu, Taniguchi, Yutaka, Umakoshi, Daisuke, Okuzaki, Naoki, Wada, Jun-Ichiro, Ikeda, Eiichiro, Fukusaki, and Eiichi, Morii
- Subjects
Mice ,Cell Line, Tumor ,Pyruvic Acid ,Racemases and Epimerases ,Serine ,Animals ,Heterografts ,Humans ,Mice, Nude ,RNA, Messenger ,Colorectal Neoplasms ,Cell Proliferation ,Up-Regulation - Abstract
Serine racemase (SRR) catalyses not only the racemization but also the dehydration of L-serine and D-serine, resulting in the formation of pyruvate and ammonia. Although SRR activity is important in the central nervous system, SRR has not been linked to cancer metabolism before. Here we show that SRR supports proliferation of colorectal-cancer cells. We find that SRR expression is upregulated in colorectal adenoma and adenocarcinoma lesions compared with non-neoplastic mucosa in human colorectal-cancer specimens. SRR-mediated dehydration of serine contributes to the pyruvate pool in colon-cancer cells, enhances proliferation, maintains mitochondrial mass and increases basal reactive oxygen species production, which has anti-apoptotic effects. Moreover, SRR promotes acetylation of histone H3 by maintaining intracellular acetyl-CoA levels. Inhibition of SRR suppresses growth of colorectal tumours in mice and augments the efficacy of 5-fluorouracil treatment. Our findings highlight a previously unknown mechanism through which a racemase supports cancer-cell growth and suggest that SRR might be a molecular target for colorectal-cancer therapy.
- Published
- 2019
45. Structural Revision of a Naphthodipyranodione from Gentian Root and its Degradation Pathway from Gentiopicroside
- Author
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Mikio, Fujii, Hidehiro, Ando, Kiju, Konno, Motonori, Fukumura, Yumiko, Hori, Yasuaki, Hirai, and Yoshiteru, Ida
- Subjects
Molecular Structure ,Pyrones ,Iridoid Glucosides ,Gentiana ,Naphthalenes ,Plant Roots - Abstract
Based on NOE experiments, the structure of naphthodipyranodione from Gentianaceae plants was revised to 1,2-dihydro-4H,6H,8H-naphto[1,2-d:4,5- c'd']dipyrano-4,8-dione. Naphthodipyranodione was assumed to be formed by the degradation of gentiopicroside by enzymatic hydrolysis at low water -concentration. The degradation pathway was a unique domino-reaction triggered by enzymatic hydrolysis. Naphthodipyranodione may become an index compound for the drying and/or fermenting procedure of Gentian root.
- Published
- 2018
46. Project conducted in Hirakata to improve cervical cancer screening rates in 20-year-old Japanese: Influencing parents to recommend that their daughters undergo cervical cancer screening
- Author
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Kentaro Shimura, Hiromi Murata, Tetsu Takagi, Eiichi Morii, Takayuki Enomoto, Yusuke Tanaka, Tomoyuki Ichimura, Asami Yagi, Yoshito Terai, Hidekatsu Nakai, Masahide Ohmichi, Eiji Kobayashi, Etsuko Miyagi, Masayuki Sekine, Yorihiko Horikoshi, Risa Kudo, Hidetaka Okada, Junko Saito, Akiko Sukegawa, Tomomi Egawa-Takata, Yukio Suzuki, Shinya Matsuzaki, Masaki Mandai, Kiyoshi Yoshino, Sosuke Adachi, Yoko Motoki, Manako Yamaguchi, Tadashi Kimura, Mikiko Asai-Sato, Toshiyuki Sumi, Tomio Nakayama, Yumiko Hori, and Yutaka Ueda
- Subjects
Cervical cancer ,Daughter ,medicine.medical_specialty ,business.industry ,Obstetrics ,Incidence (epidemiology) ,media_common.quotation_subject ,Obstetrics and Gynecology ,Cervical cancer screening ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Medicine ,030212 general & internal medicine ,Willingness to recommend ,business ,media_common - Abstract
Aim In Japan, the rate of routine cervical cancer screening is quite low, and the incidence of cervical cancer has recently been increasing. Our objective was to investigate ways to effectively influence parental willingness to recommend that their 20-year-old daughters undergo cervical cancer screening. Methods We targeted parents whose 20-year-old daughters were living with them. In fiscal year 2013, as usual, the daughter received a reminder postcard several months after they had received a free coupon for cervical cancer screening. In fiscal year 2014, the targeted parents received a cervical cancer information leaflet, as well as a cartoon about cervical cancer to show to their daughters, with a request that they recommend to their daughter that she undergo cervical cancer screening. The subsequent screening rates for fiscal years 2013 and 2014 were compared. Results The cervical cancer screening rate of 20-year-old women whose parents received the information packet in fiscal year 2014 was significantly higher than for the women who, in fiscal year 2013, received only a simple reminder postcard (P < 0.001). As a result, the total screening rate for 20-year-old women for the whole of the 2014 fiscal year was significantly increased over 2013 (P < 0.001). Conclusion For the first time, we have shown that the parents of 20-year-old daughters can be motivated to recommend that their daughters receive their first cervical cancer screening. This was achieved by sending a cervical cancer information leaflet and a cartoon about cervical cancer for these parents to show to their daughters. This method was significantly effective for improving cervical cancer screening rates.
- Published
- 2016
47. S100A4 accelerates the proliferation and invasion of endometrioid carcinoma and is associated with the ' <scp>MELF</scp> ' pattern
- Author
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Naoki Wada, Yumiko Hori, Shinichiro Tahara, Eiichi Morii, Jun-ichiro Ikeda, Satoshi Nojima, Kenji Ohshima, and Masako Kurashige
- Subjects
0301 basic medicine ,Cancer Research ,MMP2 ,Lymphovascular invasion ,Gene Expression ,Biology ,Gene Knockout Techniques ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Gene expression ,Pathology ,Carcinoma ,medicine ,S100A4 ,Humans ,Neoplasm Invasiveness ,S100 Calcium-Binding Protein A4 ,Protein kinase B ,Cell Proliferation ,Cell growth ,AKT ,Original Articles ,General Medicine ,Aldehyde Dehydrogenase ,medicine.disease ,MELF ,Immunohistochemistry ,Phenotype ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Matrix Metalloproteinase 2 ,Original Article ,Female ,Carcinoma, Endometrioid ,Proto-Oncogene Proteins c-akt ,endometrioid carcinoma ,Protein Binding ,Signal Transduction - Abstract
Endometrioid carcinoma (EC) is one of the most common malignancies of the female genital system. Although the behavior of EC ranges from an excellent prognosis to aggressive disease with a poor outcome, the factors that determine its diversity have not been determined. Here, we show that S100A4, a calcium-binding protein of the EF-hand type, is correlated with the proliferation and invasion ability of EC. We demonstrated previously that EC cells with high aldehyde dehydrogenase (ALDH) activity were more tumorigenic than ALDH-lo cells. Screening by shotgun proteomics demonstrated that the expression level of S100A4 in ALDH-hi EC cells was significantly higher than that in ALDH-lo cells. S100A4-knockout cells generated by the CRISPR/Cas9 system showed reduced proliferation and invasion. These cells showed impaired AKT phosphorylation and matrix metalloproteinase-2 activation, accounting for their impaired proliferation and invasion, respectively. Furthermore, in clinical EC samples, elevated expression of S100A4 was highly related to myometrial and lymphatic invasion in well to moderately differentiated EC. Notably, strong and diffuse expression of S100A4 was observed in tumor tissues with a microcystic, elongated and fragmented ("MELF") pattern, which is associated with a highly invasive EC phenotype. Collectively, our results demonstrate not only that high expression of S100A4 contributes to an aggressive phenotype of EC, but also that its elevated expression is closely related to the MELF histopathological pattern.
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- 2016
48. Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation: Serial Volumetric Intravascular Ultrasound Analysis
- Author
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Tomoyuki Fujita, Junjiro Kobayashi, Kunihiro Nishimura, Takuma Sato, Yoshihiro Murata, Kyoichi Wada, Yoshihiro Miyamoto, Takuya Watanabe, Haruki Sunami, Hatsue Ishibashi-Ueda, Yu Kataoka, Hiroki Hata, Masanobu Yanase, Takeshi Nakatani, Yumiko Hori, Seiko Nakajima, Norihide Fukushima, Kensuke Kuroda, Osamu Seguchi, Norihiro Okada, and Eriko Hisamatsu
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Health Status ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,030230 surgery ,Cardiac allograft vasculopathy ,Coronary Angiography ,Risk Assessment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Imaging, Three-Dimensional ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Intravascular ultrasound ,medicine ,Humans ,Young adult ,Ultrasonography, Interventional ,Retrospective Studies ,Heart transplantation ,Original Clinical Science—General: Outcomes ,Transplantation ,medicine.diagnostic_test ,business.industry ,Incidence (epidemiology) ,Retrospective cohort study ,Middle Aged ,Allografts ,Atherosclerosis ,Plaque, Atherosclerotic ,Tissue Donors ,Surgery ,Treatment Outcome ,Predictive value of tests ,Cardiology ,Disease Progression ,Heart Transplantation ,Female ,business - Abstract
Background The influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear. Methods We performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx. Results Donor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002). Conclusions This volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression., Donor-transmitted atherosclerosis in cardiac transplants, the impact of which is controversial, associates with greater reduction in coronary artery lumen and cardiac allograft vasculopathy at 3 years after transplantation. Supplemental digital content is available in the text.
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- 2016
49. Prognostic significance of a component of the Hippo pathway, TAZ, in human uterine endometrioid adenocarcinoma
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Satoshi Nojima, Jun-ichiro Ikeda, Kiyoshi Yoshino, Maosheng Zhan, Yutaka Ueda, Shin‑Ichiro Tahara, Eiichi Morii, Yumiko Hori, Tadashi Kimura, and Naoki Wada
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Hippo pathway ,Cell ,Biology ,medicine.disease_cause ,Malignancy ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Hippo signaling pathway ,Oncogene ,Articles ,Cell cycle ,medicine.disease ,Molecular medicine ,transcriptional coactivator with PDZ-binding motif ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,immunohistochemistry ,Immunohistochemistry ,prognosis ,Carcinogenesis ,endometrioid adenocarcinoma - Abstract
Transcriptional coactivator with PDZ-binding motif (TAZ) is a crucial component of the Hippo tumor suppressor pathway, interacting with transcriptional factors to regulate cell proliferation, apoptosis and tumorigenesis. TAZ and its paralog, Yes-associated protein (YAP), are activated at high frequencies during the progression towards malignancy in various tumors. Recently, YAP has been identified to modulate oncogenic features in endometrial adenocarcinoma, and it has also been reported that the nuclear expression of YAP is correlated with the poorly-differentiated form of endometrioid adenocarcinoma. In contrast to YAP, no studies have investigated TAZ expression in endometrioid adenocarcinoma. In the present study, TAZ expression was immunohistochemically examined in 55 clinical samples of endometrioid adenocarcinoma, and the clinical implications were evaluated. The results demonstrated that TAZ was located primarily in the cell nuclei, and that high TAZ expression was significantly correlated with high tumor-factor (P=0.024), stage (P=0.041) and histological grade (P=0.001), lymph node metastasis (P=0.046), recurrence (P=0.002) and a poor prognosis (P=0.007). Furthermore, univariate analysis identified that high TAZ expression was a poor prognostic factor for overall and disease-free survival. To the best of our knowledge, the present case is the first to report the clinical implications of TAZ in endometrioid adenocarcinoma of the uterus. TAZ may become a marker of a poor prognosis in endometrioid adenocarcinoma.
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- 2016
50. Pheochromocytoma complicated by cyanotic congenital heart disease: a case report
- Author
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Takaharu Oue, Keiko Yamamoto, Takuo Kubota, Eiichi Morii, Makoto Fujiwara, Noriyuki Namba, Yumiko Hori, Taichi Kitaoka, Kunihiko Takahashi, Takeshi Usui, Shigetoyo Kogaki, and Keiichi Ozono
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medicine.medical_specialty ,Pathology ,endocrine system ,endocrine system diseases ,SDHB ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,cyanotic congenital heart disease ,030209 endocrinology & metabolism ,Case Report ,030204 cardiovascular system & hematology ,Scintigraphy ,Pheochromocytoma ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Tricuspid atresia ,Family history ,neoplasms ,hypoxia-inducible factor ,Cardiac catheterization ,medicine.diagnostic_test ,business.industry ,hypoxia ,medicine.disease ,pheochromocytoma ,Blood pressure ,Pediatrics, Perinatology and Child Health ,Cardiology ,SDHD ,business - Abstract
Coincidental cyanotic congenital heart disease and pheochromocytoma is uncommon, although some cases have been reported. We describe a girl aged 15 yr and 11 mo with pheochromocytoma and tricuspid atresia treated by performing the Fontan surgery. The patient did not have any specific symptoms of syndrome related to pheochromoytoma or a family history of pheochromocytoma. During cardiac catheterization, her blood pressure increased markedly, and an α-blocker was administered. Catecholamine hypersecretion was observed in the blood and urine, and abdominal computed tomography revealed a tumor in the right adrenal gland. Scintigraphy showed marked accumulation of 123I-metaiodobenzylguanidine in the tumor, which led to a diagnosis of pheochromocytoma. We did not detect any germline mutations in the RET, VHL, SDHB, SDHD, TMEM127, or MAX genes. This patient had experienced mild systemic hypoxia since birth, which may have contributed to the development of pheochromocytoma.
- Published
- 2016
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