80 results on '"Keiko Mitani"'
Search Results
52. A case of bilateral renal cell carcinoma associated with long-term dialysis showing false-positive immunoreactivity for TFE3 as Xp11 translocation renal cell carcinoma
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Aiko, Kurisaki-Arakawa, Tsuyoshi, Saito, Michiko, Takahashi, Keiko, Mitani, Yuki, Fukumura, Yoji, Nagashima, Pedrum, Argani, and Takashi, Yao
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Male ,Chromosomes, Human, X ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Case Report ,Kidney Diseases, Cystic ,Middle Aged ,urologic and male genital diseases ,Immunohistochemistry ,Nephrectomy ,Polymerase Chain Reaction ,Kidney Neoplasms ,Translocation, Genetic ,Predictive Value of Tests ,Renal Dialysis ,Biomarkers, Tumor ,Humans ,False Positive Reactions ,Gene Fusion ,Carcinoma, Renal Cell ,In Situ Hybridization, Fluorescence - Abstract
Renal carcinomas associated with Xp11.2 translocations/transcription factor 3 (TFE3) gene fusion (Xp11 translocation RCC) are a rare subtype of renal cell carcinoma. A middle-aged Japanese man, who had a medical history of dialysis for more than 12 years, had bilateral renal cancers with a background of acquired cystic disease of the kidney and remarkable deposition of calcium oxalate in the tumorous area. The right renal tumor showed papillary architecture of clear cells with diffuse and strong immunoreactivity for TFE3 and focal and weak positivity for cathepsin K, suggesting a possibility of Xp11 translocation RCC. However, RT-PCR failed to detect any type of the reported fusion genes involving TFE3. Thus, the sample was sent for a TFE3 break-apart FISH assay in a renal tumor consultation service, which reported no evidence of TFE3 gene rearrangement. The right renal tumor was finally diagnosed as papillary renal cell carcinoma with cystic change. We report here a case of bilateral renal cell carcinoma in a patient undergoing long-term dialysis, which showed false-positive immunoreactivity for TFE3 immunostaining. Titration of TFE3 immunohistochemical staining (IHC) should be performed and cross-referenced wcith the FISH or RT-PCR results to avoid the misinterpretation of TFE3 IHC results.
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- 2013
53. Galectin-4, a novel predictor for lymph node metastasis in lung adenocarcinoma
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Saiko Kazuno, Keiko Mitani, Reiko Mineki, Takuo Hayashi, Takashi Ueno, Takashi Yao, Shiaki Oh, Tsuyoshi Saito, Kenji Suzuki, Kieko Hara, Kazuya Takamochi, and Tsutomu Fujimura
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Galectin 4 ,lcsh:Medicine ,Adenocarcinoma ,Metastasis ,medicine ,Adenocarcinoma of the lung ,Carcinoma ,Humans ,lcsh:Science ,Lymph node ,Aged ,Retrospective Studies ,Multidisciplinary ,Lung ,business.industry ,lcsh:R ,Cancer ,Middle Aged ,medicine.disease ,Neoplasm Proteins ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Lymphatic Metastasis ,Immunohistochemistry ,lcsh:Q ,Female ,Lymph Nodes ,business ,Follow-Up Studies ,Research Article - Abstract
Metastasis is still a major issue in cancer, and the discovery of biomarkers predicting metastatic capacity is essential for the development of better therapeutic strategies for treating lung adenocarcinoma. By using a proteomic approach, we aimed to identify novel predictors for lymph node metastasis in lung adenocarcinoma. Two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis showed 6 spots differentially expressed between lymph node metastasis-positive and lymph node metastasis-negative groups in a discovery set. Subsequent mass spectrometry showed that 2 of these spots were derived from galectin-4, and western blot analysis confirmed the overexpression of galectin-4 in metastatic samples. The predictive value of galectin-4 was confirmed by immunohistochemical analysis for a validation set consisting of 707 surgically resected specimens of lung adenocarcinomas (stages I to IV). We observed that 148 lung adenocarcinomas (20.9%) expressed galectin-4, which was significantly associated with variables of disease progression such as tumor size (p
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- 2013
54. Amount of CD4+CD25+ regulatory T cells in autoimmune pancreatitis and pilonidal sinus
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Masaru Takase, Hiroshi Abe, Koichi Suda, Akiko Ueda, Keiko Mitani, Abdukadir Imamhasan, Yuki Fukumura, Bunsei Nobukawa, and Takashi Yao
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,chemical and pharmacologic phenomena ,T-Lymphocytes, Regulatory ,Autoimmune Diseases ,Young Adult ,Endocrinology ,Pilonidal Sinus ,Japan ,Internal Medicine ,medicine ,Humans ,IL-2 receptor ,Abscess ,Autoimmune pancreatitis ,Aged ,Hepatology ,Chemistry ,Interleukin-2 Receptor alpha Subunit ,FOXP3 ,hemic and immune systems ,Forkhead Transcription Factors ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Cd4 cd25 ,Microscopy, Fluorescence ,Pancreatitis ,Immunoglobulin G ,Female ,Infiltration (medical) ,Immunostaining ,Biomarkers - Abstract
OBJECTIVES Infiltration of many IgG4-positive plasma cells (G4-Ps) is seen in IgG4-related diseases and in several "non-IgG4-related diseases," such as pilonidal sinus (PS) as well. The involvement of CD4+CD25+ regulatory T cells (CD4CD25 Tregs) in IgG4-related diseases has been reported. To see whether CD4+CD25+ Tregs are involved in autoimmune pancreatitis (AIP)/non-IgG4-related diseases with many G4-Ps, we investigated the amount of G4-Ps and CD4+CD25+ Tregs histologically in AIP/PS. METHODS Four AIP and 10 PS were immunostained with IgG4/Foxp3, a specific marker for CD4+CD25+ Tregs. Double immunohistochemistry and dual fluorescent immunohistochemistry were conducted to see the amount of CD4+CD25+ Tregs. RESULTS All AIP and 30% of PS showed abundant G4-Ps. G4-Ps infiltrated diffusely for all AIPs and in a patchy pattern for PS at the abscess/granulation foci. Foxp3 immunostaining/double immunohistochemistry showed moderate to abundant CD4+CD25+ Tregs in AIP and abscess of PS, but few to moderate in granulation of PS. Dual fluorescent immunohistochemistry also showed many CD4+CD25+ Tregs in AIP. CONCLUSIONS Many CD4+CD25+ Tregs were seen in AIP lesions, abscess of PS, but not in granulation of PS, suggesting that the amount of CD4+CD25+ Tregs sometimes do not synchronize with that of G4-Ps and might relate to the inflammatory activity of both AIP and PS.
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- 2012
55. Uterine angiosarcoma associated with lymphangioleiomyomatosis in a patient with tuberous sclerosis complex: an autopsy case report with immunohistochemical and genetic analysis
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Keiko Mitani, Kengo Koike, Kuniaki Seyama, Satoru Takeda, Tsuyoshi Saito, Daiki Ogishima, Takashi Yao, Takuo Hayashi, Kazuhisa Takahashi, Toshio Kumasaka, and Yasuhisa Terao
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CD31 ,Adult ,Pathology ,medicine.medical_specialty ,Hemangiosarcoma ,Loss of Heterozygosity ,Pathology and Forensic Medicine ,Loss of heterozygosity ,Tuberous sclerosis ,Tuberous Sclerosis ,Tuberous Sclerosis Complex 2 Protein ,Uterine Angiosarcoma ,medicine ,Humans ,Angiosarcoma ,Lymphangioleiomyomatosis ,neoplasms ,business.industry ,Tumor Suppressor Proteins ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,Lymphatic system ,Uterine Neoplasms ,Female ,Autopsy ,TSC2 ,Tumor Suppressor Protein p53 ,business - Abstract
A 41-year-old woman carrying a germline tuberous sclerosis complex 2 (TSC2) mutation, whose regular medical follow-up for tuberous sclerosis complex and tuberous sclerosis complex-associated lymphangioleiomyomatosis had continued for 2 years, had uterine angiosarcoma concomitant with uterine lymphangioleiomyomatosis. Immunohistochemically, the uterine angiosarcoma cells showed an extremely skewed lymphatic differentiation; they were diffusely immunopositive for CD31 but negative for other vascular endothelial markers including factor VIII and CD34 yet strongly immunopositive for lymphatic endothelial markers including D2-40 and Prox-1. Loss of heterozygosity analysis demonstrated that not only lymphangioleiomyomatosis and renal angiomyolipoma but also the uterine angiosarcoma had loss of heterozygosity on TSC2. Furthermore, direct sequencing revealed a TP53 mutation in the uterine angiosarcoma. Collectively, the findings suggest that combined dysfunction of the p53 and TSC2 tumor suppressor proteins may contribute to the development of uterine angiosarcoma in this rare clinical setting.
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- 2012
56. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: a clinicopathologic study of 10 patients
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Masao Watanabe, Toshio Kumasaka, Ryo Konno, Takashi Yao, Yukio Nakatani, Akira Hebisawa, Takashi Oide, Keiko Mitani, Kuniaki Seyama, Takuo Hayashi, Yasuhisa Terao, and Kazuhisa Takahashi
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Adult ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Uterus ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,Tuberous sclerosis ,Adnexa Uteri ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Prevalence ,Humans ,Lymphangioleiomyomatosis ,Aged ,Aged, 80 and over ,Lung ,business.industry ,Myometrium ,Anatomical pathology ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Immunohistochemistry ,Lymphangiogenesis ,Vascular endothelial growth factor ,medicine.anatomical_structure ,chemistry ,Adnexal Diseases ,Uterine Neoplasms ,lipids (amino acids, peptides, and proteins) ,Surgery ,Female ,Anatomy ,business - Abstract
Lymphangioleiomyomatosis (LAM), a systemic disorder affecting almost exclusively young women, is characterized by the abnormal proliferation of smooth muscle-like cells (LAM cells). LAM can occur either in association with the tuberous sclerosis complex (TSC) (TSC-LAM) or without TSC (sporadic LAM). Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signaling pathway dysregulated by a functional loss of TSC genes, but the primary organ of origin remains unclear. Therefore, we performed histologic and immunohistologic analyses of gynecologic organs in 20 patients, half with and the other half without pulmonary LAM, to determine how often LAM involves the uterus. The results showed that 9 of 10 (90%) patients with pulmonary LAM had uterine LAM lesions. In contrast, no patients without pulmonary LAM had so. All uterine LAM lesions were accompanied by LAM lesions in retroperitoneal or pelvic lymph nodes and LAM cell clusters, each enveloped by a monolayer of vascular endothelial growth factor receptor-3-positive lymphatic endothelial cells. Furthermore, when we compared uterine lesions of TSC-LAM with those of sporadic LAM, proliferation of HMB45-positive epithelioid-shaped LAM cells and infiltrates with a tongue-like growth pattern was more prominent in the former, whereas the extent of lymphangiogenesis within the myometrium was greater in the latter. These results indicate that uterine involvement is a common manifestation of LAM, and, possibly, that the uterus or an adjacent locale in the retroperitoneum or pelvic cavity is the primary site of origin of LAM.
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- 2011
57. Complete remission of gastric plasmacytoma following eradication of 'Candidatus Helicobacter heilmannii'
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Tatsuya Yamaguchi, Hiroyuki Ohtsuka, Keiko Mitani, Masahiko Ohtaka, Nobuyuki Enomoto, Akihisa Tatsumi, Tomoyoshi Uetake, Mitsuharu Fukasawa, Tadashi Sato, and Hidenobu Watanabe
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CD20 ,medicine.medical_specialty ,Pathology ,biology ,medicine.diagnostic_test ,business.industry ,Gastroenterology ,General Medicine ,Hepatology ,CD79A ,medicine.disease ,Endoscopy ,Lesion ,Internal medicine ,Biopsy ,biology.protein ,medicine ,Plasmacytoma ,Antibody ,medicine.symptom ,business - Abstract
This is the first case report of gastric plasmacytoma associated with “Candidatus Helicobacter heilmannii” (‘H. heilmannii’) infection. The patient was a 40-year-old woman with epigastric discomfort. Upper gastrointestinal endoscopy demonstrated a white granular lesion on the wall of the gastric body. Histological studies showed numerous eosinophilic globules expanding the lamina propria mucosae. Immunohistochemically, the cells with these globules stained positive for CD138, CD79a, immunoglobulin (Ig) M, and kappa light chain, but negative for CD20, IgG, IgA, and lambda light chain. A diagnosis of plasmacytoma was made. Although a Helicobacter pylori infection was not detected, the patient received H. pylori eradication treatment. Two months after H. pylori eradication treatment, an upper gastrointestinal endoscopy showed a reduction of the white granular lesion. Eighteen months after eradication treatment, endoscopy, endoscopic ultrasonography and histological studies revealed complete remission of the lesion. No relapse has been documented 30 months after the initial diagnosis of plasmacytoma. Retrospectively, analysis of biopsy specimens removed before eradication treatment demonstrated that this patient had ‘H. heilmannii’ infection. Therefore, H. pylori eradication therapy should be considered as a potential first-line therapy for early-stage gastric plasmacytoma with or without H. pylori infection.
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- 2011
58. Oncocytic mucoepidermoid carcinoma of the parotid gland with CRTC1-MAML2 fusion transcript: report of a case with review of literature
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Katsuhisa Ikeda, Shiro Uchida, Keiko Mitani, Tsuyoshi Saito, Takashi Yao, Junkichi Yokoyama, Yuki Fukumura, and Mitsuhisa Fujimaki
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Male ,Pathology ,medicine.medical_specialty ,Translocation, Genetic ,Pathology and Forensic Medicine ,Fusion gene ,Diagnosis, Differential ,Mucoepidermoid carcinoma ,Carcinoma ,medicine ,Humans ,Parotid Gland ,RNA, Messenger ,Crtc1 maml2 ,Oxyphil Cells ,Paraffin Embedding ,business.industry ,Tumor Embolism ,Chromosomes, Human, Pair 11 ,Membrane Proteins ,Nuclear Proteins ,Sequence Analysis, DNA ,Middle Aged ,medicine.disease ,Salivary Gland Neoplasms ,Parotid gland ,DNA-Binding Proteins ,stomatognathic diseases ,medicine.anatomical_structure ,Treatment Outcome ,Fusion transcript ,Superficial Parotidectomy ,Trans-Activators ,Carcinoma, Mucoepidermoid ,Gene Fusion ,business ,Chromosomes, Human, Pair 19 ,Follow-Up Studies ,Transcription Factors - Abstract
Oncocytic mucoepidermoid carcinoma is a very rare variant of mucoepidermoid carcinoma, composed predominantly of oncocytic cells. Most previously reported cases described the difficulty in histologic differentiation from other oncocytic tumors. Here we report a case of oncocytic mucoepidermoid carcinoma of parotid gland diagnosed by the detection of CRTC1-MAML2 fusion. A 53-year-old man had a left superficial parotidectomy conducted for 3-cm-sized mass. The resected tumor was composed almost exclusively of oncocytic tumor cells. With detailed histologic evaluation, scarce vacuolated tumor cells, suggestive of mucous cell of mucoepidermoid carcinoma, and one focus of tumor embolism in a vein were found, suggesting the possibility of oncocytic mucoepidermoid carcinoma. Immunohistochemically, oncocytic cells were diffusely positive for p63. Reverse transcriptase polymerase chain reaction and direct sequencing revealed CRTC1-MAML2 translocation of this tumor. To our knowledge, this report describes the first case of oncocytic mucoepidermoid carcinoma confirmed with CRTC1-MAML2 fusion. Identification of this fusion gene may help in distinguishing oncocytic mucoepidermoid carcinoma from its mimics.
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- 2010
59. Cytologic, immunocytochemical and ultrastructural characterization of lymphangioleiomyomatosis cell clusters in chylous effusions of patients with lymphangioleiomyomatosis
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Koichi Suda, Kuniaki Seyama, Yoko Gunji, Makiko Kunogi, Toshio Kumasaka, Kazuhisa Takahashi, Hiroyuki Takemura, Taeko Akiyoshi, Takuo Hayashi, and Keiko Mitani
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Adult ,medicine.medical_specialty ,Pathology ,Histology ,Immunocytochemistry ,Muscle Proteins ,Pathology and Forensic Medicine ,Antigen ,immune system diseases ,Antigens, Neoplasm ,hemic and lymphatic diseases ,Chylous ascites ,Progesterone receptor ,Medicine ,Humans ,Lymphangioleiomyomatosis ,Chylous Ascites ,business.industry ,Endothelial Cells ,Anatomical pathology ,General Medicine ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Immunohistochemistry ,Staining ,Neoplasm Proteins ,Cancer cell ,lipids (amino acids, peptides, and proteins) ,Female ,business ,Receptors, Progesterone ,Melanoma-Specific Antigens - Abstract
OBJECTIVE To establish the cytologic and immunocytochemical features of lymphangioleiomyomatosis (LAM) cell clusters (LCCs) and to clarify its diagnostic significance for LAM. STUDY DESIGN We evaluated 17 samples of LAM-associated chylous effisions from 13 patients with LAM. We performed Papanicolaou staining and immunocytochemistry for muscular antigens, melanoma-related antigens, female 'hormone receptors and markers for lymphatic endothelial cells (LECs). RESULTS The cytologic features of LCCs were a well-organized, globular cluster consisting of LAM cells enveloped by LECs. The LAM cells were observed to form a tightly cohesive core and had a moderate nuclear/cytoplasmic ratio. These are distinct characteristics from cancer cell clusters. Immunocytochemical examinations revealed the LAM cells to be positive for muscular antigens, melanoma-related antigens and progesterone receptor, but only 2 of 7 specimens were positive for estrogen receptor. The surface monolayer cells were confirmed to be immunopositive for various LEC markers. Ultrastructural study confirmed that LCCs were covered by LECs. CONCLUSION LCCs were detected in all LAM-associated chylous effusion samples. The cytologic and immunocytochemical examinations of chylous effusions are thus considered to have diagnostic significance for LAM that may therefore enable patients to avoid undergoing such invasive tests as lung biopsies.
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- 2009
60. Urothelial carcinoma of the renal pelvis with rhabdoid features
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Takashi Yao, Yuki Fukumura, Toshiharu Matsumoto, Koichi Suda, Yoshiro Sakamoto, Hiroaki Fujii, and Keiko Mitani
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Male ,Pathology ,medicine.medical_specialty ,Esophageal Neoplasms ,CD3 ,Loss of Heterozygosity ,Vimentin ,CD38 ,Pathology and Forensic Medicine ,Lesion ,Loss of heterozygosity ,medicine ,Humans ,Kidney Pelvis ,Aged ,CD20 ,biology ,Carcinoma ,Neoplasms, Second Primary ,General Medicine ,CD79A ,Immunohistochemistry ,Kidney Neoplasms ,medicine.anatomical_structure ,biology.protein ,Carcinoma, Squamous Cell ,medicine.symptom ,Renal pelvis - Abstract
Reported herein is the case of a 70-year-old man with high grade urothelial carcinoma (UC) with rhabdoid features of the renal pelvis. For the most part, the tumor was composed of pleomorphic, non-cohesive round tumor cells with abundant cytoplasm. In situ high-grade UC composed of cohesive tumor cells was seen only in a small portion. Pleomorphic dyscohesive tumor cells often showed rhabdoid features, containing eosinophilic inclusions. These pleomorphic/rhabdoid tumor cells were immunohistochemically positive for vimentin but negative for cytokeratins, CD45, CD20, CD79a, CD3, CD45RO, CD38, and CD138. Loss of heterozygosity (LOH) analysis demonstrated identical allelic losses as well as additional allelic losses for the dyscohesive and cohesive UC lesion, indicating that these two lesions originated from a single clonal lesion.
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- 2009
61. Contribution of TIR domain-containing adapter inducing IFN-beta-mediated IL-18 release to LPS-induced liver injury in mice
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Shizuo Akira, Ryosuke Uchiyama, Keiko Mitani, Jiro Fujimoto, Shuhei Hayashi, Michiko Imamura, Tetsuya Yamamoto, Jürg Tschopp, Nico van Rooijen, Shizue Yumikura-Futatsugi, Kenji Nakanishi, Shun'ichiro Taniguchi, Hiroko Tsutsui, Koubun Yasuda, Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis
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Lipopolysaccharides ,Propionibacterium acnes ,Mice ,Adenosine Triphosphate ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Animals ,Liver injury ,Mice, Knockout ,Toll-like receptor ,Granuloma ,Hepatology ,biology ,Liver Diseases ,Macrophages ,Caspase 1 ,Interleukin-18 ,Interleukin ,Inflammasome ,Interferon-beta ,biology.organism_classification ,medicine.disease ,Molecular biology ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,Adaptor Proteins, Vesicular Transport ,Liver ,TRIF ,Immunology ,Myeloid Differentiation Factor 88 ,TLR4 ,Interleukin 18 ,Female ,Carrier Proteins ,medicine.drug ,Signal Transduction - Abstract
Background/Aims: After treatment with heat-killed Propionibacterium acnes mice show dense hepatic granuloma formation. Such mice develop liver injury in an interleukin (IL)-18-dependent manner after challenge with a sublethal dose LPS. As previously shown, LPS-stimulated Kupffer cells secrete IL-18 depending on caspase-1 and Toll-like receptor (TLR)-4 but independently of its signal adaptor myeloid differentiation factor 88 (MyD88), suggesting importance of another signal adaptor TIR domain-containing adapter inducing IFN-beta (TRIF). Nalp3 inflammasome reportedly controls caspase-1 activation. Here we investigated the roles of MyD88 and TRIF in P. acnes-induced hepatic granuloma formation and LPS-induced caspase-1 activation for IL-18 release. Methods:Mice were sequentially treated with P. acnes and LPS, and their serum IL-18 levels and liver injuries were determined by ELISA and ALT/AST measurement, respectively. Active caspase-1 in LPS-stimulated Kupffer cells was determined by Western blotting. Results: Macrophage-ablated mice lacked P. acnes-induced hepatic granuloma formation and LPS-induced serum IL-18 elevation and liver injury. Myd88(-/-) Kupffer cells, but not Trif(-/-) cells, exhibited normal caspase-1 activation upon TLR4 engagement in vitro. Myd88(-/-) mice failed to develop hepatic granulomas after P. acnes treatment and liver injury induced by LPS challenge. In contrast, Trif(-/-) mice normally formed the hepatic granulomas, but could not release IL-18 or develop the liver injury. Nalp3(-/-) mice showed the same phenotypes of Trif(-/-) mice. Conclusions: Propionibacterium acnes treatment MyD88-dependently induced hepatic granuloma formation. Subsequent LPS TRIF-dependently activated caspase-1 via Nalp3 inflammasome and induced IL-18 release, eventually leading to the liver injury. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved
- Published
- 2009
62. Lymphangioleiomyomatosis
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Kuniaki Seyama, Toshio Kumasaka, Teruhiko Sato, and Keiko Mitani
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- 2009
63. Detection of Epstein-Barr virus-encoded small RNA-expressed myofibroblasts and IgG4-producing plasma cells in sclerosing angiomatoid nodular transformation of the spleen
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Toshiharu Matsumoto, Yuki Fukumura, Nobukawa Bunsei, Hiroshi Abe, Koichi Suda, Toshio Kumasaka, Satoko Kashiwagi, Keiko Abe, Keiko Mitani, and Shigetaka Yamasaki
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Stromal cell ,Anaplastic Lymphoma ,Plasma Cells ,CD34 ,Vimentin ,In situ hybridization ,medicine.disease_cause ,Granuloma, Plasma Cell ,Pathology and Forensic Medicine ,Myoblasts ,medicine ,Humans ,Molecular Biology ,Aged ,biology ,Histiocytoma, Benign Fibrous ,CD68 ,Splenic Neoplasms ,Cell Biology ,General Medicine ,Dendritic cell ,Fibroblasts ,Middle Aged ,Epstein–Barr virus ,Immunohistochemistry ,Immunoglobulin G ,biology.protein ,RNA, Viral ,Female ,Spleen - Abstract
Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare inflammatory tumor-like lesion composed of vascular nodules and non-neoplastic stroma including spindle cells and inflammatory cells. The focus of our study was on the stromal proliferating process in SANT. Nine cases of SANT were examined. All cases showed alpha-smooth muscle actin (alpha-SMA) and vimentin on the spindle cells but not CD21, CD31, CD34, CD68, desmin, S100, human herpes virus-8, or anaplastic lymphoma kinase-1. In one case, 20-30% of the myofibroblasts in Epstein-Barr-virus (EBV)-positive spindle cells were detected using double-labeling immunohistochemistry for alpha-SMA and EBV-encoded small RNA in situ hybridization. A quantitative analysis of IgG and IgG4-positive plasma cells (pPCs) in SANT was performed. The median densities of IgG-pPCs and IgG4-pPCs in SANT were approximately four-fold and 13-fold higher than those in the normal spleens, respectively. In addition, there was a statistically significant increase of IgG4/IgG-pPCs ratio in SANT in comparison to the control specimens. In conclusion, the fibrogenesis in a subset of SANT may be associated with EBV-infected myofibroblasts in an overlapping immune reaction indicated by the presence of infiltrating IgG4-pPCs. Further investigation is needed to elucidate the association between SANT and IgG4-related sclerosing disease.
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- 2007
64. Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia
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Bunsei Nobukawa, Keiko Mitani, Atsushi Arakawa, Shigetaka Yamasaki, Koichi Suda, Hiroshi Sonoue, and Keiko Abe
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Oncology ,Male ,Pathology ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Pancreatic Intraepithelial Neoplasia ,Cell-Cycle Regulatory Proteins ,Endocrinology ,Internal medicine ,Internal Medicine ,medicine ,Carcinoma ,Humans ,Neoplasm Invasiveness ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,Aged, 80 and over ,Hepatology ,business.industry ,Middle Aged ,medicine.disease ,Adenocarcinoma, Mucinous ,Immunohistochemistry ,Carcinoma, Papillary ,Pancreatic Neoplasms ,Ki-67 Antigen ,P53 protein ,Adenocarcinoma ,Female ,Tumor Suppressor Protein p53 ,business ,Carcinoma in Situ ,Carcinoma, Pancreatic Ductal - Abstract
To examine aberrations and differences of cell cycle regulatory proteins between intraductal papillary-mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasias (PanINs).In total, 47 IPMN lesions and 42 PanIN lesions were obtained from 26 patients with IPMN and 16 patients who underwent pancreatic surgery for invasive pancreatic ductal cancer or other diseases. They were subjected to conventional hematoxylin-eosin staining and immunostaining for p16INK4A and p53. The percentages of immunohistochemical positivity or negativity were compared between IPMN and PanIN, in accordance with the same histological grade of atypia. The Ki-67 labeling index was also counted in each lesion.Either the loss of p16INK4A expression or the overexpression of p53 was much more frequently observed among PanIN-3 than among carcinoma in situ in IPMN (P = 0.046 and 0.008, respectively). The Ki-67 labeling index was correlated with the histological grades of both PanINs and IPMNs (P = 0.0001 and P = 0.0001, respectively).There are different immunohistochemical expression patterns of p16INK4A and p53 between IPMNs and PanINs. These may substantiate their different genetic progressions to invasive carcinoma.
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- 2007
65. Vascular endothelial growth factor-D is increased in serum of patients with lymphangioleiomyomatosis
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Teruhiko Sato, Sanae Souma, Sigeru Tominaga, Kuniaki Seyama, Yoshinosuke Fukuchi, Keiko Mitani, Toshio Kumasaka, and Masatoshi Kurihara
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Adult ,Vascular Endothelial Growth Factor A ,Pathology ,medicine.medical_specialty ,Myocytes, Smooth Muscle ,Vascular Endothelial Growth Factor C ,Vital Capacity ,Vascular Endothelial Growth Factor D ,Metastasis ,immune system diseases ,hemic and lymphatic diseases ,Forced Expiratory Volume ,Myocyte ,Medicine ,Humans ,Lymphangioleiomyomatosis ,Lung ,Leiomyoma ,Surrogate endpoint ,business.industry ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Hormones ,Lymphangiogenesis ,Respiratory Function Tests ,Lymphatic system ,medicine.anatomical_structure ,Uterine Neoplasms ,lipids (amino acids, peptides, and proteins) ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Lymphangioleiomyomatosis (LAM) is a rare destructive lung disease characterized by an abnormal proliferation of smooth muscle-like cells (LAM cells) in the lung and along the axial lymphatics. LAM demonstrates a heterogeneous clinical course, but there is no serum surrogate marker available for assessing the disease severity or predicting the disease progression. Since the authors have recently demonstrated the extensive LAM-associated lymphangiogenesis and its potential role in progression and metastasis of LAM cells, they hypothesized that serum levels of lymphangiogenic growth factors might be increased in LAM and become a surrogate marker for disease severity.VEGF-A, VEGF-C, and VEGF-D in serum of 44 patients with LAM were measured by enzyme-linked immunosorbant assay. Only VEGF-D was significantly increased in LAM patients as compared with age- and gender-matched healthy volunteers (n=24) (LAM vs. control, geometric mean 95% CI; 1069.3 pg/mL (809.4 approximately 1412.6) vs. 295.9 pg/mL (262.6 approximately 333.5), p0.0001). Serum VEGF-D levels negatively correlated with variables of pulmonary function tests, FEV1/FVC (forced expiratory volume in one second/forced vital capacity) (r=-0.365, p0.05) and %DLco/VA (the percentage of diffusing capacity for carbon monoxide/alveolar volume to the predicted value) (r=-0.560, p0.001). As expected, the group who received hormone therapy showed more deteriorated pulmonary function with higher serum VEGF-D levels than the group who was just observed without hormone therapy. Immunohistochemical examination of lung specimens demonstrated the positive immunoreactivity of LAM cells for VEGF-D.Serum VEGF-D levels may be a valuable surrogate marker for evaluating the disease severity in LAM.
- Published
- 2006
66. Expression of transforming growth factor beta1, beta2, and beta3 in chronic, cancer-associated, obstructive pancreatitis
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Keiko Mitani, Yuki Fukumura, Koichi Suda, Toshio Kumasaka, and Kanae Karita
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Constriction, Pathologic ,Biology ,Pathology and Forensic Medicine ,Fibrosis ,Transforming Growth Factor beta ,medicine ,Humans ,Protein Isoforms ,Aged ,CD68 ,Pancreatic Ducts ,Cancer ,General Medicine ,Fibroblasts ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Pancreatic Neoplasms ,Medical Laboratory Technology ,Pancreatitis ,Chronic Disease ,Female ,Animal studies ,Myofibroblast ,Transforming growth factor - Abstract
Context.—Myofibroblasts are considered to play central roles in pancreatic fibrosis. The potent fibrogenic capacities of transforming growth factor βs (TGF-βs) have been emphasized in vitro and in animal studies. However, the roles of TGF-βs in human chronic pancreatitis have not been fully clarified. Objective.—To investigate whether expressions of TGF-βs are related to myofibroblast distribution in chronic, cancer-associated, obstructive pancreatitis (COP). Design.—Histopathologic studies using hematoxylin-eosin and Elastica-Masson trichrome and immunohistochemical studies using antibodies against α-smooth muscle actin (SMA); CD68; TGF-β1, -β2, and -β3; and TGF-β soluble receptor type II were performed in 19 COP cases and 6 controls. By classifying COP tissues into 3 fibrosis phases by the amount of collagen deposits, immunoreactivities for TGF-βs, histopathologic changes, and myofibroblast distribution were examined for each fibrosis phase. Results.—Six cases were categorized in the early stage of fibrosis, 8 in the intermediate stage, and 5 in the advanced stage. Immunoreactivities for all 3 isoforms of TGF-β were observed in occasional myofibroblasts. In the early and intermediate stages, TGF-β1–expressing macrophages and neutrophils were distributed in the midst of myofibroblasts. TGF-β2 and TGF-β3 expressions were observed in ductal structures, sometimes even in sites where no or few myofibroblasts were seen. TGF-β soluble receptor type II was immunoreactive for myofibroblasts, endothelium, and ductal structures. Conclusions.—All 3 isoforms of TGF-βs may contribute to fibrosis in COP. Macrophages and neutrophils may be sources of fibrogenic TGF-β1. Infiltration of these cells appears to play an important role in the progression of COP fibrosis.
- Published
- 2006
67. Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis
- Author
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Satoko Kashiwagi, Sanae Souma, Kiyoshi Gomi, Keiko Mitani, Teruhiko Sato, Akira Hebisawa, Toshio Kumasaka, Koichi Suda, Kazutoshi Shibuya, Kuniaki Seyama, Yoshinosuke Fukuchi, and Hajime Kubo
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Lymph Trunk ,Thoracic duct ,Pathology and Forensic Medicine ,Thoracic Duct ,Tuberous sclerosis ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Humans ,Lymphangioleiomyomatosis ,Lymphangiogenesis ,Neoplasm Metastasis ,Lymph node ,Chylous Ascites ,business.industry ,Endothelial Cells ,bacterial infections and mycoses ,medicine.disease ,Neoplastic Cells, Circulating ,Immunohistochemistry ,medicine.anatomical_structure ,Lymphatic system ,lipids (amino acids, peptides, and proteins) ,Surgery ,Female ,Lymph ,Anatomy ,business - Abstract
Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphol- ogically benign appearance. In the previous study, we reported LAM- associated lymphangiogenesis and implicated its role in the progres- sion of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lym- phatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retro- peritoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical (1 of 5) and axillary (0 of 5)). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.
- Published
- 2005
68. Benign clear cell "sugar" tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report.
- Author
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Yoko Gunji-Niitsu, Toshio Kumasaka, Shigehiro Kitamura, Yoshito Hoshika, Takuo Hayashi, Hitoshi Tokuda, Riichiro Morita, Etsuko Kobayashi, Keiko Mitani, Mika Kikkawa, Kazuhisa Takahashi, and Kuniaki Seyama
- Subjects
BIRT-Hogg-Dube syndrome ,CANCER cells ,DISEASES in women ,PUBLIC health ,GENETICS ,THERAPEUTICS - Abstract
Background: Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell "sugar" tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. Case presentation: In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2-associated genetic region was demonstrated. Conclusion: To our knowledge, this is the first report of CCST of the lung in a patient with BHDS, indicating that CCST should be added to the spectrum of pulmonary manifestations of BHDS. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
69. Lymphangiogenesis in lymphangioleiomyomatosis: its implication in the progression of lymphangioleiomyomatosis
- Author
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Kuniaki Seyama, Toshimasa Uekusa, Keiko Mitani, Masato Minami, Toshio Kumasaka, Seiji Hayashi, Yoshinosuke Fukuchi, Teruhiko Sato, Koichi Suda, Sanae Souma, and Takashi Kondo
- Subjects
CD31 ,Adult ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Angiogenesis ,government.form_of_government ,Vascular Endothelial Growth Factor C ,Pathology and Forensic Medicine ,chemistry.chemical_compound ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Tumor Cells, Cultured ,Humans ,Lymphangioleiomyomatosis ,Lymphangiogenesis ,Aged ,Lymphatic Vessels ,Aged, 80 and over ,Neovascularization, Pathologic ,business.industry ,bacterial infections and mycoses ,medicine.disease ,Prognosis ,Vascular Endothelial Growth Factor Receptor-3 ,Immunohistochemistry ,Vascular endothelial growth factor ,Lymphatic Endothelium ,Lymphatic system ,chemistry ,Vascular endothelial growth factor C ,government ,lipids (amino acids, peptides, and proteins) ,Surgery ,Female ,Anatomy ,business ,Biomarkers - Abstract
Lymphangioleiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells (LAM cells) in the lungs, lymph nodes, and/or other organs. We examined lymphangiogenesis using immunohistochemistry for Flt-4 (VEGFR-3), a new specific marker for lymphatic endothelial cells, as well as the expression of vascular endothelial growth factor (VEGF)-C in LAM. Specimens were obtained from 6 autopsy cases, a single lung transplant case, and 8 surgical cases for analyses. We demonstrated that lymphatics were extremely abundant in both pulmonary and extrapulmonary LAM and that lymphatic endothelial cells not only proliferated encompassing LAM foci but also infiltrated the intra-LAM foci, and that in advanced LAM, lymphangiogenesis involved vascular walls and interstitium surrounding the area where LAM cells proliferate. In contrast, angiogenesis, confirmed with CD31 immunostaining, was observed less in the LAM foci. LAM cells demonstrated positive reactivity against anti-VEGF-C antibody at varying intensities. Significant correlation (P < 0.001) was noted between the degree of lymphangiogenesis in LAM or VEGF-C expression on LAM cells and lymphagioleiomyomatosis histologic score (LHS), which represents the histologic severity of pulmonary LAM and has been reported to have prognostic significance. Our study is likely to provide a novel point of view on the pathophysiologic significance of lymphangiogenesis in LAM.
- Published
- 2004
70. Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung.
- Author
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Kazuya Takamochi, Hiroko Ohmiya, Masayoshi Itoh, Kaoru Mogushi, Tsuyoshi Saito, Kieko Hara, Keiko Mitani, Yasushi Kogo, Yasunari Yamanaka, Jun Kawai, Yoshihide Hayashizaki, Shiaki Oh, Kenji Suzuki, and Hideya Kawaji
- Subjects
LUNG cancer diagnosis ,LUNG cancer treatment ,BIOMARKERS ,SQUAMOUS cell carcinoma ,ADENOCARCINOMA ,INDIVIDUALIZED medicine ,NUCLEOTIDE sequencing - Abstract
Background: Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. Methods: Cap Analysis of Gene Expression (CAGE) is a method used to quantify promoter activities across the whole genome by determining the 5' ends of capped RNA molecules with next-generation sequencing. We performed CAGE on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD), and confirmed the findings by immunohistochemical analysis (IHC) in an independent group (29 SCC and 45 AD). Results: Using the genome-wide promoter activity profiles, we confirmed that the expression of known molecular markers used in IHC for SCC (CK5, CK6, p40 and desmoglein-3) and AD (TTF-1 and napsin A) were different between SCC and AD. We identified two novel marker candidates, SPATS2 for SCC and ST6GALNAC1 for AD, as showing comparable performance and complementary utility to the known markers in discriminating PDSCC and non-lepidic AD. We subsequently confirmed their utility at the protein level by IHC in an independent group. Conclusions: We identified two genes, SPATS2 and ST6GALNAC1, as novel complemental biomarkers discriminating SCC and AD. These findings will contribute to a more accurate diagnosis of NSCLC, which is crucial for precision medicine for lung cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
71. Isolation of individual cellular components from lung tissues of patients with lymphangioleiomyomatosis.
- Author
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Katsutoshi Ando, Yoshito Hoshika, Hiroki Ebana, Etsuko Kobayashi, Kazuhisa Takahashi, Kuniaki Seyama, Naoya Fujino, Chiharu Ota, Hiroshi Kubo, Keiko Mitani, Yoshinori Okada, Takashi Kondo, Teruaki Mizobuchi, Masatoshi Kurihara, and Kenji Suzuki
- Subjects
LYMPHANGIOMYOMATOSIS ,TISSUE analysis ,ENDOTHELIAL cells ,HETEROZYGOSITY ,TUBEROUS sclerosis ,GENETICS ,PATIENTS - Abstract
Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease entailing cystic destruction of the lungs and progressive respiratory failure. LAM lungs are histologically characterized by the proliferation of smooth muscle-like cells (LAM cells) and an abundance of lymphatic vessels. To elucidate the pathophysiological processes of LAM, cell-type-specific analyses are required. However, no method exists for isolating the individual types of cells in LAM lesions. Therefore, we established a fluorescenceactivated cell sorting (FACS)-based method for the direct isolation of LAM cells and other various cellular components from LAM-affected lung tissue. We obtained LAM-affected lung tissue from resections or transplant recipients and prepared single-cell suspensions. FACS, immunohistochemical, and molecular analysis were used cooperatively to isolate HMB45-positive LAM cells with tuberous sclerosis complex (TSC) 2 loss of heterozygosity (LOH). Using a combination of antibodies against an epithelial cell adhesion molecule (EpCAM) and podoplanin, we fractionated CD45-negative lung cells into three groups: lymphatic endothelial cells (LEC) (EpCAM
- /podoplaninhi subset), alveolar type II cells (EpCAMhi /podoplanin- subset), and mesenchymal cells (EpCAM- /podoplanin-/low subset). During subsequent analysis of HMB45 expression, as a LAM-specific marker, we clearly identified LAM cells in the mesenchymal cell population. We then discovered that CD90+ /CD34- cells in the mesenchymal cell population are not only positive for HBM45 but also had TSC2 LOH. These isolated cells were viable and subsequently amenable to cell culture. This method enables us to isolate LAM cells and other cellular components, including LAM-associated LEC, from LAMaffected lung tissues, providing new research opportunities in this field. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
72. Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential.
- Author
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Keisuke Akaike, Aiko Kurisaki-Arakawa, Kieko Hara, Yoshiyuki Suehara, Tatsuya Takagi, Keiko Mitani, Kazuo Kaneko, Takashi Yao, and Tsuyoshi Saito
- Published
- 2015
- Full Text
- View/download PDF
73. Deeply located low-grade fibromyxoid sarcoma with FUS-CREB3L2 gene fusion in a 5-year-old boy with review of literature.
- Author
-
Aiko Kurisaki-Arakawa, Yoshiyuki Suehara, Atsushi Arakawa, Tatsuya Takagi, Michiko Takahashi, Keiko Mitani, Kazuo Kaneko, Takashi Yao, and Tsuyoshi Saito
- Subjects
SARCOMA ,GENE fusion ,TUMORS ,CURVILINEAR motion ,FIBROSIS - Abstract
Background Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor typically affecting young to middle-aged adults. Despite its otherwise benign histologic appearance and indolent nature, it can have fully malignant behavior, and recurrence and metastasis may occur even decades later.Case history We report a case of LGFMS in the left lower leg of a 5-year-old Japanese boy. A magnetic resonance imaging (MRI) uncovered a well-demarcated intra-gastrocnemial tumor measuring 27 × 20 mm with a slightly high intensity on T1WI and heterogeneously high intensity on T2WI. Histologically, the tumor was composed of bland spindle-shaped cells with a whorled growth pattern. The tumor stroma was variably hyalinized and fibromyxoid with arcades of curvilinear capillaries and arterioles with associated perivascular fibrosis. Although LGFMS is known to affect children under 18 years of age, it is extremely rare in infants and children under 5 years of age. Despite the young age, this patient was accurately diagnosed by the typical histology and the detection of a FUS-CREB3L2 gene fusion. Conclusion Although LGFMS in children tends to be located superficially, this case presented with an intramuscular tumor in the region of the gastrocnemius. To the best of our knowledge, this is the first case of deep LGFMS arising in a child younger than 5 years of age. The patient is still alive with no evidence of the disease 4 months after diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
74. Histological subtypes and characteristic structures of HPV-associated oropharyngeal carcinoma; study with Japanese cases.
- Author
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Mitsuhisa Fujimaki, Yuki Fukumura, Keiko Mitani, Aiko Kurisaki, Junkichi Yokoyama, Katsuhisa Ikeda, and Takashi Yao
- Subjects
PAPILLOMAVIRUSES ,SQUAMOUS cell carcinoma ,KERATINIZATION ,IMMUNOHISTOCHEMISTRY ,NECROSIS - Abstract
Background Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC. Methods 66 OPC cases were categorized into conventional squamous cell carcinoma (SCC) and the variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status of all cases was determined using p16- immunohistochemistry and HPV-DNA ISH. Results Two histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC tended to be nHPV-OPC with statistical significance. Two histological structures, abrupt keratinization, defined in the text, and comedo-necrosis among non-maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended to exist for HPV-OPC with statistical significance. Conclusions This study showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two histological structures, abrupt keratinization and comedo-necrosis among non-maturing island, were considered characteristic histological features of HPV-OPC. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
75. Detection of Epstein–Barr virus-encoded small RNA-expressed myofibroblasts and IgG4-producing plasma cells in sclerosing angiomatoid nodular transformation of the spleen.
- Author
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Satoko Kashiwagi, Toshio Kumasaka, Nobukawa Bunsei, Yuki Fukumura, Shigetaka Yamasaki, Keiko Abe, Keiko Mitani, Hiroshi Abe, Toshiharu Matsumoto, and Koichi Suda
- Abstract
Abstract Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare inflammatory tumor-like lesion composed of vascular nodules and non-neoplastic stroma including spindle cells and inflammatory cells. The focus of our study was on the stromal proliferating process in SANT. Nine cases of SANT were examined. All cases showed α-smooth muscle actin (α-SMA) and vimentin on the spindle cells but not CD21, CD31, CD34, CD68, desmin, S100, human herpes virus-8, or anaplastic lymphoma kinase-1. In one case, 20–30% of the myofibroblasts in Epstein–Barr-virus (EBV)-positive spindle cells were detected using double-labeling immunohistochemistry for α-SMA and EBV-encoded small RNA in situ hybridization. A quantitative analysis of IgG and IgG4-positive plasma cells (pPCs) in SANT was performed. The median densities of IgG-pPCs and IgG4-pPCs in SANT were approximately four-fold and 13-fold higher than those in the normal spleens, respectively. In addition, there was a statistically significant increase of IgG4/IgG-pPCs ratio in SANT in comparison to the control specimens. In conclusion, the fibrogenesis in a subset of SANT may be associated with EBV-infected myofibroblasts in an overlapping immune reaction indicated by the presence of infiltrating IgG4-pPCs. Further investigation is needed to elucidate the association between SANT and IgG4-related sclerosing disease. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
76. Vascular Endothelial Growth Factor-D Is Increased in Serum of Patients with Lymphangioleiomyomatosis.
- Author
-
Kuniaki Seyama, Toshio Kumasaka, Sanae Souma, Teruhiko Sato, Masatoshi Kurihara, Keiko Mitani, Sigeru Tominaga, and Yoshinosuke Fukuchi
- Published
- 2006
77. Novel biomarkers that assist in accurate discrimination of squamous cell carcinoma from adenocarcinoma of the lung
- Author
-
Shiaki Oh, Kaoru Mogushi, Yasunari Yamanaka, Kazuya Takamochi, Masayoshi Itoh, Jun Kawai, Kenji Suzuki, Hideya Kawaji, Keiko Mitani, Hiroko Ohmiya, Yasushi Kogo, Tsuyoshi Saito, Yoshihide Hayashizaki, and Kieko Hara
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Cancer Research ,business.industry ,Cancer ,medicine.disease ,Precision medicine ,Cap analysis gene expression ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Surgical oncology ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Adenocarcinoma of the lung ,Genetics ,Adenocarcinoma ,Immunohistochemistry ,Lung cancer ,business ,Research Article - Abstract
Background Targeted therapies based on the molecular and histological features of cancer types are becoming standard practice. The most effective regimen in lung cancers is different between squamous cell carcinoma (SCC) and adenocarcinoma (AD). Therefore a precise diagnosis is crucial, but this has been difficult, particularly for poorly differentiated SCC (PDSCC) and AD without a lepidic growth component (non-lepidic AD). Biomarkers enabling a precise diagnosis are therefore urgently needed. Methods Cap Analysis of Gene Expression (CAGE) is a method used to quantify promoter activities across the whole genome by determining the 5’ ends of capped RNA molecules with next-generation sequencing. We performed CAGE on 97 frozen tissues from surgically resected lung cancers (22 SCC and 75 AD), and confirmed the findings by immunohistochemical analysis (IHC) in an independent group (29 SCC and 45 AD). Results Using the genome-wide promoter activity profiles, we confirmed that the expression of known molecular markers used in IHC for SCC (CK5, CK6, p40 and desmoglein-3) and AD (TTF-1 and napsin A) were different between SCC and AD. We identified two novel marker candidates, SPATS2 for SCC and ST6GALNAC1 for AD, as showing comparable performance and complementary utility to the known markers in discriminating PDSCC and non-lepidic AD. We subsequently confirmed their utility at the protein level by IHC in an independent group. Conclusions We identified two genes, SPATS2 and ST6GALNAC1, as novel complemental biomarkers discriminating SCC and AD. These findings will contribute to a more accurate diagnosis of NSCLC, which is crucial for precision medicine for lung cancer. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2792-1) contains supplementary material, which is available to authorized users.
- Full Text
- View/download PDF
78. Benign clear cell 'sugar' tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report
- Author
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Takuo Hayashi, Yoko Gunji-Niitsu, Yoshito Hoshika, Kazuhisa Takahashi, Mika Kikkawa, Kuniaki Seyama, Riichiro Morita, Hitoshi Tokuda, Shigehiro Kitamura, Toshio Kumasaka, Keiko Mitani, and Etsuko Kobayashi
- Subjects
Adult ,0301 basic medicine ,Lung Neoplasms ,Tumor suppressor gene ,Perivascular Epithelioid Cell Neoplasms ,Case Report ,Biology ,Birt–Hogg–Dubé syndrome ,Benign tumor ,Birt-Hogg-Dube Syndrome ,Tumor suppressor gene syndrome ,03 medical and health sciences ,Tuberous sclerosis ,0302 clinical medicine ,Proto-Oncogene Proteins ,Germline mutation ,medicine ,Genetics ,Humans ,Genetics(clinical) ,Folliculin ,Germ-Line Mutation ,Genetics (clinical) ,Tumor Suppressor Proteins ,Loss of heterozygosity ,Genodermatosis ,DNA ,Exons ,medicine.disease ,Pedigree ,Mutagenesis, Insertional ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,Female ,TSC1 ,TSC2 ,Tomography, X-Ray Computed - Abstract
Background Birt-Hogg-Dubé (BHD) syndrome is a rare inherited autosomal genodermatosis and caused by germline mutation of the folliculin (FLCN) gene, a tumor suppressor gene of which protein product is involved in mechanistic target of rapamycin (mTOR) signaling pathway regulating cell growth and metabolism. Clinical manifestations in BHD syndrome is characterized by fibrofolliculomas of the skin, pulmonary cysts with or without spontaneous pneumothorax, and renal neoplasms. There has been no pulmonary neoplasm reported in BHD syndrome, although the condition is due to deleterious sequence variants in a tumor suppressor gene. Here we report, for the first time to our knowledge, a patient with BHD syndrome who was complicated with a clear cell “sugar” tumor (CCST) of the lung, a benign tumor belonging to perivascular epithelioid cell tumors (PEComas) with frequent causative relation to tuberous sclerosis complex 1 (TSC1) or 2 (TSC2) gene. Case presentation In a 38-year-old Asian woman, two well-circumscribed nodules in the left lung and multiple thin-walled, irregularly shaped cysts on the basal and medial area of the lungs were disclosed by chest roentgenogram and computer-assisted tomography (CT) during a preoperative survey for a bilateral faucial tonsillectomy. Analysis of the resected tumor showed large polygonal cells with clear cytoplasm proliferating in a solid pattern. Immunohistochemistry revealed that these tumor cells were positive for microphthalmia-transcription factor, S100, and CD1a but negative for HMB45, indicating that the tumor was a CCST. Genetic testing indicated that the patient had a germline mutation on exon 12 of the FLCN gene, i.e., insertion of 7 nucleotides (CCACCCT) (c.1347_1353dupCCACCCT). Direct sequencing of the FLCN exon 12 using genomic DNA obtained from her microdissected CCST cells clearly revealed loss of the wild-type FLCN sequence, which confirmed complete functional loss of the FLCN gene. On the other hand, no loss of heterozygosity around TCS1- or TSC2-associated genetic region was demonstrated. Conclusion To our knowledge, this is the first report of CCST of the lung in a patient with BHDS, indicating that CCST should be added to the spectrum of pulmonary manifestations of BHDS.
- Full Text
- View/download PDF
79. Deeply located low-grade fibromyxoid sarcoma with FUS-CREB3L2 gene fusion in a 5-year-old boy with review of literature
- Author
-
Tatsuya Takagi, Atsushi Arakawa, Aiko Kurisaki-Arakawa, Kazuo Kaneko, Takashi Yao, Michiko Takahashi, Keiko Mitani, Yoshiyuki Suehara, and Tsuyoshi Saito
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Soft Tissue Neoplasm ,Histology ,Oncogene Proteins, Fusion ,Fibrosarcoma ,Case Report ,Young patients ,Soft Tissue Neoplasms ,Fusion gene ,Metastasis ,Low-grade fibromyxoid sarcoma ,Pathology and Forensic Medicine ,medicine ,Humans ,medicine.diagnostic_test ,business.industry ,Soft tissue ,Magnetic resonance imaging ,Sequence Analysis, DNA ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Basic-Leucine Zipper Transcription Factors ,Child, Preschool ,RNA-Binding Protein FUS ,Sarcoma ,FUS-CREB3L2 ,business - Abstract
Background Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor typically affecting young to middle-aged adults. Despite its otherwise benign histologic appearance and indolent nature, it can have fully malignant behavior, and recurrence and metastasis may occur even decades later. Case history We report a case of LGFMS in the left lower leg of a 5-year-old Japanese boy. A magnetic resonance imaging (MRI) uncovered a well-demarcated intra-gastrocnemial tumor measuring 27 × 20 mm with a slightly high intensity on T1WI and heterogeneously high intensity on T2WI. Histologically, the tumor was composed of bland spindle-shaped cells with a whorled growth pattern. The tumor stroma was variably hyalinized and fibromyxoid with arcades of curvilinear capillaries and arterioles with associated perivascular fibrosis. Although LGFMS is known to affect children under 18 years of age, it is extremely rare in infants and children under 5 years of age. Despite the young age, this patient was accurately diagnosed by the typical histology and the detection of a FUS-CREB3L2 gene fusion. Conclusion Although LGFMS in children tends to be located superficially, this case presented with an intramuscular tumor in the region of the gastrocnemius. To the best of our knowledge, this is the first case of deep LGFMS arising in a child younger than 5 years of age. The patient is still alive with no evidence of the disease 4 months after diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_163
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- View/download PDF
80. A resent trend in the sucrose contents in the commercial soft drinks
- Author
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Keiko Mitani, Makoto Shinomiya, Nobuko Kitamura, Yukitaro Sakakibara, and Haruo Nakagaki
- Subjects
chemistry.chemical_compound ,Sucrose ,chemistry ,Food science - Published
- 1987
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