Shin-ichiro Yanagiya, Takeshi Honda, Hiroki Takanari, Kimiko Sogabe, Shingen Nakamura, Yoshimi Bando, Masahiro Abe and Hirokazu Miki : Raman Microspectroscopy for Label-Free Diagnosis of Amyloid Light-chain Amyloidosis in Various Organs, Journal of Raman Spectroscopy, 2024.
Tamaki Ohtani, Hitoshi Ikushima, Yoshimi Bando, Michiko Yamashita, Kenmei Kuwahara, Hideki Otsuka, Kazuya Kondo and Hirokazu Miyoshi : Early Prediction of Radiotherapeutic Effecacy in a Mouse Model of Non-Small Cell Lung Carcinoma Using 18F-FLT and 18F-FDG PET/CT, The Journal of Medical Investigation : JMI, Vol.70, No.3,4, 361-368, 2023.
(要約)
This study investigated the usefulness of [18F]-3'-deoxy-3'-fluorothymidine (18F-FLT) and [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging for predicting the therapeutic efficacy of non-small cell lung cancer (NSCLC) irradiation at an early stage after radiation treatment. Mice were xenografted with the human lung adenocarcinoma line A549 or large cell lung cancer line FT821. Tumour uptake of 18F-FLT and 18F-FDG was imaged using PET/CT before and 1 week after irradiation. In A549 tumours, 18F-FLT uptake was significantly decreased, and 18F-FDG uptake was unchanged post-irradiation compared with pre-irradiation. In FT821 tumours, uptake of both 18F-FLT and 18F-FDG uptake was substantially decreased post-irradiation compared with pre-irradiation. In both xenografts, tumour volumes in the irradiated groups were significantly decreased compared with those in the control group. 18F-FLT is expected to contribute to individual NSCLC therapy because it accurately evaluates the decrease in tumour activity that cannot be captured by 18F-FDG. 18F-FDG may be useful for evaluating surviving cells without being affected by the inflammatory reaction at an extremely early stage, approximately 1 week after irradiation. Combined use of 18F-FLT and 18F-FDG PET/CT imaging may increase the accurate prediction of radiotherapy efficacy, which may lead to improved patient outcomes and minimally invasive personalised therapy. J. Med. Invest. 70 : 361-368, August, 2023.
Masayuki Takahashi, Kei Daizumoto, Tomoya Fukawa, Yayoi Fukuhara, Yoshimi Bando, Minoru Kowada, Tsogt-Ochir Dondoo, Yutaro Sasaki, Ryotaro Tomida, Yoshiteru Ueno, Megumi Tsuda, Yoshito Kusuhara, Kunihisa Yamaguchi, Yasuyo Yamamoto, Hisanori Uehara and Hiroomi Kanayama : Insulin receptor expression to predict resistance to axitinib and elucidation of the underlying molecular mechanism in metastatic renal cell carcinoma., British Journal of Cancer, 2023.
(要約)
Decreased INSR in RCC could be a biomarker to predict axitinib resistance. Regarding the resistant mechanism, vascular endothelial cells with decreased INSR in RCC may secrete interferon-β and induce PD-L1.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : Dynamic contrast-enhanced MR imaging of uterine endometrial carcinoma with/without squamous differentiation, Abdominal Radiology, Vol.48, No.8, 2494-2502, 2023.
(要約)
Purpose: Endometrial carcinoma with strong enhancement on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is suggestive of high-grade type II endometrial carcinoma. However, low-grade type I endometrial carcinoma may also sometimes show strong enhancement. We hypothesized that squamous differentiation would contribute to the strong enhancement at the early phase on DCE-MRI-like uterine cervical squamous cell carcinoma and compared the DCE-MRI findings of endometrial carcinoma with and without squamous differentiation. Methods: DCE-MRI of endometrial carcinoma including 41 low-grade type I endometrial carcinomas without squamous differentiation (LG), 39 low-grade type I endometrial carcinomas with squamous differentiation (LGSD), and 20 high-grade type II endometrial carcinomas (HG) was retrospectively evaluated. Results: Significant difference in the time-intensity curves was found between LG and HG and LG and LGSD, whereas no significant difference was seen between HG and LGSD. Curve type 3 (initial signal rise which is steeper than that of the myometrium) was more frequent in HG (60%) and LGSD (77%) than in LG (34%). Conclusion: It should be recognized as a pitfall that high-grade type II endometrial carcinoma and low-grade type I endometrial carcinoma with squamous differentiation may show similar early strong enhancement on DCE-MRI.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : MR Imaging Findings of Uterine Adenomatoid Tumors., Magnetic Resonance in Medical Sciences, Vol.Online ahead of print, 2023.
(要約)
Adenomatoid tumor is a rare benign genital tract neoplasm of mesothelial origin. Uterine adenomatoid tumors occur in the outer myometrium and may mimic leiomyomas. Because hormonal treatment is not applicable to adenomatoid tumors and laparoscopic enucleation is not easy as myomectomy, it is important to differentiate adenomatoid tumors from leiomyomas for the adequate treatment. The purpose of this study is to evaluate the MRI findings of adenomatoid tumor for the differentiation from leiomyoma. MRI findings of surgically proven 10 uterine adenomatoid tumors in 9 women were retrospectively evaluated with correlation to histopathological findings. All 10 tumors appeared as solid myometrial masses and showed heterogeneous signal intensity with admixture of partially ill-defined slight high-intensity areas containing abundant tubular tumor cells and well-defined myoma-like low-intensity areas reflecting smooth muscle hypertrophy on T2WI including 4 lesions with peripheral ring-like high intensity. High-intensity areas on T2WI tended to show high intensity on diffusion-weighted imaging (DWI) with relatively high apparent diffusion coefficient (ADC), suggesting T2 shine-through effect due to abundant tubules. Intra-tumoral hemorrhage revealed on MRI was rare. Early intense contrast-enhanced areas on dynamic contrast-enhanced study were observed dominantly within the high-intensity areas but rarely within the low-intensity areas on T2WI. The outer myometrial mass with the admixture of well-defined low- and ill-defined high-intensity areas on T2WI may be suggestive of adenomatoid tumor. Peripheral ring-like high intensity on T2WI and DWI may also be suggestive. Dynamic contrast-enhanced MR study may be helpful for the differentiation from leiomyoma.
Satoshi Sumida, Mayuko Shimizu, Yuko Miyakami, Takumi Kakimoto, Tomoko Kobayashi, Yasuyo Saijo, Minoru Matsumoto, Hirohisa Ogawa, Takeshi Oya, Yoshimi Bando, Hisanori Uehara, Shu Taira, Mitsuo Shimada and Koichi Tsuneyama : Histological and immunohistochemical analysis of epithelial cells in epidermoid cysts in intrapancreatic accessory spleen., The Journal of Medical Investigation : JMI, Vol.70, No.1.2, 251-259, 2023.
(要約)
Novel histological features of epithelial cells of ECIPAS were indicated. Although more cases need to be evaluated, we propose that the cause of ECIPAS may be different from that of pancreatic ductal origin. J. Med. Invest. 70 : 251-259, February, 2023.
Takayoshi Shinya, Tomoki MATSUSHITA, Yuka HIROSHIMA, Youichi Otomi, Yasuhisa Kanematsu, Yoshimi Bando, Hisanori Uehara, Yoshiaki Kitamura and Masafumi Harada : Imaging features of a myoepithelial carcinoma of the nasal cavity: A case report and literature review, Radiology Case Reports, Vol.18, No.1, 386-391, 2022.
(要約)
Myoepithelial carcinoma of the nasal cavity is extremely rare. We report the case of a 66-year-old man with myoepithelial carcinoma of the nasal cavity. Computed tomography (CT) and magnetic resonance imaging revealed a lobulated soft tissue mass with central necrosis and hemorrhage, as well as an invasion of the skull base and left orbit. The patient presented with continuous nasal congestion and heavy head and had no elevated level of squamous cell carcinoma-related antigen. CT, magnetic resonance imaging, or F-fluorodeoxyglucose (FDG) positron emission tomography/CT revealed no evidence of a metastatic lesion. F-FDG accumulation in the tumor was inhomogeneous and moderate. Histopathological examination of the resected specimen confirmed a well-circumscribed solid tumor with septa, a small area of hemorrhage, and necrosis. The subsequent diagnosis was a myoepithelial carcinoma of the left nasal cavity. This case shows that nasal myoepithelial carcinoma might appear as a well-defined lobulated mass with hemorrhagic necrosis and intense contrast enhancement in the solid component. We conjecture that hemorrhagic necrosis and intense enhancement values may be potential markers of nasal myoepithelial carcinoma.
Shun-ichi Toki, Toshihiko Nishisho, Ryo Miyagi, Yoshimi Bando, Mika Sakaki, Yusuke Demizu, Tomoaki Okimoto and Koichi Sairyo : Combination chemotherapy of doxorubicin and ifosfamide with proton beam therapy for myoepithelial carcinoma originating in the paraspinal region: A case report and literature review., Molecular and Clinical Oncology, Vol.17, No.6, 2022.
(要約)
Soft tissue myoepithelial carcinoma (MEC) is an extremely rare mesenchymal tumor that has a poor prognosis unless complete surgical resection is achieved. The present study reported a case of a 38-year-old woman with a tumor in the left paraspinal region at L2 to L3 with vertebral destruction. MEC was diagnosed based on molecular pathological examination of a biopsy specimen. Because curative surgery was expected to be difficult, a combination of chemotherapy with doxorubicin and ifosfamide and proton beam therapy as local therapy was performed, resulting in long-term survival for at least 7.8 years. To the best of our knowledge, this is the first case of soft tissue MEC for which classical cytotoxic chemotherapy and proton beam therapy were effective. Although surgical resection with negative margins is the mainstay of treatment for MEC, adequate doxorubicin-based systemic therapy and high-dose radiation therapy may be a feasible alternative in patients with unresectable or advanced MEC. Future studies on the relationship between molecular pathological features, including biomarkers, and the selection of therapeutic agents are warranted.
Intratumoral HER2 heterogeneity is a well-described gastric cancer feature and may explain many false-negative results related to this oncogene. An 81-year-old man was diagnosed at our hospital with stage IV gastric cancer with multiple lymph node metastases. Immunohistochemistry (IHC) analysis indicated that the primary tumor was HER2-negative. After a chemotherapy course, we submitted a pretreatment biopsy specimen for comprehensive cancer genome profiling (CGP) to determine the last-line therapy. This revealed HER2 amplification. The specimen was reevaluated using fluorescence in situ hybridization and IHC with deeper-cut specimens, which confirmed that the tumor was indeed HER2-positive. Therefore, the patient was treated with chemotherapy plus trastuzumab, which elicited tumor shrinkage and conferred long-term survival. Our current data underscore the CGP importance, which can provide more accurate tumor profilings and inform subsequent treatment decisions.
Yasuhiko Nishioka, Yuko Toyoda, Ryoko Egashira, Takeshi Johkoh, Yasuhiro Terasaki, Akira Hebisawa, Kinya Abe, Tomohisa Baba, Yuji Fujikura, Etsuo Fujita, Naoki Hamada, Tomohiro Handa, Yoshinori Hasegawa, Koko Hidaka, Takeshi Hisada, Shu Hisata, Chisato Honjo, Kazuya Ichikado, Yoshikazu Inoue, Shinyu Izumi, Motoyasu Kato, Takumi Kishimoto, Masaki Okamoto, Keisuke Miki, Masamichi Mineshita, Yutaro Nakamura, Susumu Sakamoto, Masaaki Sano, Yoshikazu Tsukada, Mari Yamasue, Yoshimi Bando, Sakae Homma, Koichi Hagiwara, Takafumi Suda and Naohiko Inase : Nationwide retrospective observational study of idiopathic dendriform pulmonary ossification: clinical features with a progressive phenotype., BMJ Open Respiratory Research, Vol.9, No.1, e001337, 2022.
(要約)
Twenty-two cases of IDPO were identified. Most subjects (82%) were male, aged 22-56 years (mean (SD), 37.9 (9.1)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.)) at diagnosis. Nearly 80% of the subjects were asymptomatic, and the condition was discovered during a medical check-up. However, 36% of the subjects showed a decline in forced vital capacity (%FVC) predicted <80% at diagnosis. The typical radiological features of high-resolution CT (HRCT) are calcified branching structures that are predominantly distributed in the lower lung fields without any other conspicuous finding. Histopathological analysis also showed dendriform ossified lesions from the intraluminal areas to interstitial areas. Notably, during the follow-up period of 20 years, disease progression was found in 88% on HRCT and more than 50% on pulmonary function tests (FVC and/or forced expiratory volume in 1 s). Two cases with rapid decline of 10% /year in %FVC predicted were observed.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : Magnetic resonance imaging characteristics of polypoid endometriosis and review of the literature., The Journal of Obstetrics and Gynaecology Research, Vol.48, No.10, 2583-2593, 2022.
(要約)
Polypoid endometriosis is a rare variant of endometriosis and may mimic malignancy. The purpose of this study is to evaluate magnetic resonance (MR) imaging characteristics of polypoid endometriosis for the differential diagnosis with malignancy. MR imaging findings of four histologically proven polypoid endometriosis were retrospectively evaluated with the review of the literature. All polypoid endometriosis exhibited high signal intensity on T2-weighted images reflecting abundant dilated endometrial glands. Peritoneal lesions were surrounded by low signal intensity rim represented the "black rim sign" reflecting endometriotic fibrous adhesion. Two cases arising from endometriotic cysts showed transmural extension (peritoneal extension and myometrial infiltration). Endometriotic hemorrhagic foci were demonstrated in four lesions as high signal intensity on T1-weighted images and/or susceptibility-induced signal voids on susceptibility-weighted MR sequence. Diffusion-weighted images showed high signal intensity with relatively high apparent diffusion coefficient (ADC) due to T2 shine-through effect but no diffusion restriction, and dynamic contrast-enhanced (DCE) MR imaging showed gradually increasing contrast-enhancement pattern like benign pathologies. Polypoid endometriosis may mimic malignancy; however, black rim sign may be a characteristic MR imaging finding for the peritoneal lesions, and no diffusion restriction and gradually increasing contrast-enhancement pattern may reflect its benign nature.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : Dynamic contrast-enhanced magnetic resonance imaging of endometrial cancer with/without squamous differentiation, Proc. Intl. Soc. Mag. Reson. Med., 4233, 2022.
15.
Satoshi Teramae, Naoki Muguruma, Koichi Okamoto, Kumiko Oseto, Ryutaro Nishikawa, Takayuki Tanoue, Keiji Hirata, Shunichi Yanai, Takayuki Matsumoto, Seiji Shimizu, Jun Miwa, Yu Sakaki, Kazuo Yashima, Hiroyuki Ohnuma, Yasushi Sato, Yoshitaka Kitayama, Yoshio Ohda, Atsushi Yamauchi, Yoji Sanomura, Kumiko Tanaka, Yoshiaki Kubo, Hideki Ishikawa, Yoshimi Bando, TOmoko Sonoda and Tetsuji Takayama : Cancer risk and genotype-phenotype correlation in Japanese patients with Cowden syndrome., International Journal of Clinical Oncology, Vol.27, No.4, 639-647, 2022.
(要約)
Cowden syndrome (CS) is an autosomal-dominant hereditary disorder caused by a germline PTEN variant and characterized by multiple hamartomas and a high risk of cancers. However, no detailed data on CS in Asian patients nor genotype-phenotype correlation have been reported. We performed the first Japanese nationwide questionnaire survey on CS and obtained questionnaire response data on 49 CS patients. Patients included 26 females (median age 48 years). The incidence of breast, thyroid, endometrium, and colorectal cancer was 32.7%, 12.2%, 19.2% (among females), and 6.1%, respectively. The incidence of any cancers was relatively high among all patients (46.9%, 23/49), and particularly female patients (73.1%, 19/26), compared with previous reports from Western countries. Gastrointestinal (GI) polyps were more frequently found throughout the GI tract compared with previous studies. PTEN variants were detected in 95.6% (22/23) of patients; 12 in the N-terminal region (11 in phosphatase domain) and 10 in the C-terminal (C2 domain) region. The incidence of cancer in the C2 domain group was significantly higher than in the N-terminal region (phosphatase) group. All female patients with C2 domain variant had breast cancer. Our data suggest that Japanese patients with CS, particularly female patients and patients with C2 domain variant may have a high risk of cancers.
(キーワード)
Breast Neoplasms / Female / Genetic Association Studies / Hamartoma Syndrome, Multiple / Humans / Intestinal Polyps / Japan / Male / Middle Aged / PTEN Phosphohydrolase / Risk
Yutaka Morita, Atsuro Saijo, Hiroshi Nokihara, Atsushi Mitsuhashi, Hiroto Yoneda, Kenji Otsuka, Hirokazu Ogino, Yoshimi Bando and Yasuhiko Nishioka : Radiation therapy induces an abscopal effect and upregulates programmed death-ligand 1 expression in a patient with non-small cell lung cancer., Thoracic Cancer, Vol.13, No.7, 1079-1082, 2022.
(要約)
T cells, occasionally resulting in a systemic immune response to the tumor outside of the treatment field. The phenomenon of tumor regression at the site distant from irradiated fields is known as the abscopal effect. Several case reports have indicated a potential role of RT in overcoming primary and acquired resistance against immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and melanoma patients. We herein report an NSCLC patient who developed acquired resistance to an RT-induced abscopal effect and subsequently experienced reactivation of the systemic antitumor immune response by pembrolizumab, an antiprogrammed death 1 antibody. In this case, RT not only induced an abscopal effect but also upregulated the programmed death-ligand 1 expression outside of the irradiated field when the patient developed resistance to the abscopal effect. This case can facilitate our understanding of the mechanism underlying the RT-induced systemic immune response against cancer cells and adaptive resistance mechanism of cancer cells from immune surveillance. These findings highlight the promising results of current clinical trials combining RT and immune checkpoint inhibitors. Ongoing clinical trials will further establish evidence supporting combination therapy with RT and immune checkpoint inhibitors.
Takahiro Yoshida, Takeshi Nishino, Masakazu Goto, Seiya Inoue, Satoshi Fujiwara, Hiromitsu Takizawa, Akira Tangoku, Hisanori Uehara and Yoshimi Bando : ypN0 in Patients with Definitive cN-positive Status After Preoperative Treatment Is a Prognostic Factor in Esophageal Cancer, Anticancer Research, Vol.42, No.1, 195-203, 2022.
(要約)
Histopathological tumor regression grade is applied not to lymph nodes but primary tumors modified by preoperative treatments. This study focused on patients whose pathological examination at the time of surgery showed no residual tumor after chemo(radio)therapy in the primary lesion (ypT0) or lymph nodes (ypN0). A total of 87 patients with clinical stage II/III thoracic esophageal cancer underwent esophagectomy following preoperative treatments to evaluate significances between pathological response and clinical outcomes; 51 patients with clinically definitive lymph node metastasis (cN+) were analyzed as a subgroup. ypT0 rates were 20.7% and 23.5%, and ypN0 rates were 47.1% and 27.5% in the whole cohort and in the cN+ subgroup, respectively. Disease-free survival, from surgery to relapse or death, was significantly influenced by ypN status (p=0.035) but not by ypT status in the 51 patients with definitive cN+ disease. Preoperative chemoradiation was an independent favorable factor for achievement of ypN0 in the 51 patients (odds ratio=0.09; p=0.007). ypN status was a predictive factor for DFS in patients treated with docetaxel plus low-dose 5-fluorouracil and cisplatin combined chemotherapy, superior to ypT status, especially in patients with definitive cN+ disease.
Hirokazu Ogino, Makoto Tobiume, Kozo Kagawa, Hiroshi Kawano, Satoshi Sakaguchi, Atsuro Saijo, Daisuke Matsumoto, Hiromitsu Takizawa, Yuriko Morikawa, Yoshimi Bando, Hisatsugu Goto, Hiroshi Nokihara and Yasuhiko Nishioka : A Case of Radiation-associated Angiosarcoma Presenting as Massive Pleural Effusion., Internal Medicine, Vol.61, No.9, 1393-1397, 2021.
(要約)
A 67-year-old man was admitted to our hospital for massive pleural effusion. He had a history of mandibular gingival carcinoma treated with radiation therapy (RT). Based on the cytology findings of pleural effusion and a thoracoscopic pleural biopsy, we finally diagnosed him with radiation-associated angiosarcoma. Retrospective cell-block immunocytochemistry with pleural effusion also showed potential utility for the diagnosis. This case highlights the importance of considering the possibility of radiation-associated secondary cancer in patients with pleural effusion who have a history of RT.
Masanori Takehara, Hiroshi Miyamoto, Yasuteru Fujino, Tetsu Tomonari, Tatsuya Taniguchi, Shinji Kitamura, Koichi Okamoto, Masahiro Sogabe, Yasushi Sato, Naoki Muguruma, Yoshimi Bando and Tetsuji Takayama : Long-Term Survival due to Chemotherapy including Paclitaxel in a Patient with Metastatic Primary Splenic Angiosarcoma., Case Reports in Gastroenterology, Vol.15, No.3, 910-918, 2021.
(要約)
A primary splenic angiosarcoma is a rare type of soft tissue sarcoma and is associated with an extremely poor prognosis. In this study, we describe the case of a patient who was diagnosed with metastatic primary splenic angiosarcoma and survived for about 2 years. A 62-year-old female was referred to us for the treatment of splenic angiosarcoma with disseminated intravascular coagulation (DIC) and multiple liver and bone metastases. Paclitaxel therapy resulted in recovery from DIC and enabled her to continue sequential treatment through to sixth-line chemotherapy. We reviewed all splenic angiosarcoma case reports which were described as stage IV to date and compared with our case. From these data, we found that the median overall survival was 105 days, and the prognosis of splenic angiosarcoma of stage IV was worse than conventional case series. Splenectomy was performed in more patients than chemotherapy as a treatment. Moreover, various chemotherapeutic regimens were used. These data suggest that administering chemotherapy including paclitaxel to patients with splenic angiosarcoma might improve their prognosis.
Takayoshi Shinya, Otomi Yoichi, Toshihiko Nishisho, B Beuthien-Baumann, Saho Irahara, Michiko Kubo, Hideki Otsuka, Yoshimi Bando, Koichi Sairyo and Masafumi Harada : Clinical application of dynamic 18F-fluorodeoxyglucose positron-emission tomography / computed tomography in the differential diagnoses of musculoskeletal lesions, The Journal of Medical Investigation : JMI, Vol.68, No.1. 2, 96-104, 2021.
(要約)
<p>We aimed to assess the differential diagnostic efficacy of dynamic F-18 fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET / CT) and to evaluate the appropriate scan timings for diagnosis of musculoskeletal lesions (MSLs). Dynamic scans (5-15 [phase 1], 15-25 [phase 2], and 25-35 [phase 3] min after F-18 FDG injection) and dual-time-point scans (1 and 2 h after injection) were acquired for 23 MSLs [4 benign MSLs (BMSLs). 10 primary malignant musculoskeletal tumors (PMMSTs), and 9 metastatic musculoskeletal tumors (MMSTs)]. We compared the maximum standardized uptake values (SUVmax) and corresponding retention indices for dynamic (RI-SUVdyn) and dual-time-point (RI-SUVdual) scans and evaluated diagnostic efficacy using receiver operating characteristic (ROC) curve analyses. The SUVmax gradually decreased or was almost identical with minimal fluctuation in 3 BMSLs and 1 PMMST. SUVmax increased over time after phase 2 in 18 malignant MSLs (MMSLs). There were significant differences in SUVmax (for all time phases) and RI-SUV dual between BMSLs and MMSLs and between PMMSTs and MMSTs. In the ROC analyses, the areas under the curve for SUV in phases 2 and 3 were highest for differentiating BMSLs from MMSLs and PMMSTs from MMSTs, respectively. Dynamic F-18 FDG PET / CT is valuable for diagnosis of musculoskeletal lesions. J. Med. Invest. 68 : 96-104, February, 2021</p>
(キーワード)
bone and soft tissue tumors / dynamic scan / musculoskeletal lesion / positron emission tomography computed tomography / sarcoma
Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P. We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis. The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5'-flanking promoter region. These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence.
Naoki Miyamoto, Seiya Inoue, Takeshi Nishino, Masakazu Goto, Takahiro Yoshida, Tomoko Kobayashi, Yoshimi Bando, Hiromitsu Takizawa and Akira Tangoku : A CASE OF VAGUS NERVE SCHWANNOMA DIFFICULT TO DISTINGUISH FROM LYMPH NODAL METASTASIS OF ESOPHAGEAL CANCER., The Journal of Medical Investigation : JMI, Vol.68, No.1.2, 205-208, 2021.
(要約)
In this report, we describe a rare case of vagus nerve schwannoma associated with esophageal cancer. A 70-year-old man visited our hospital complaining of worsening dysphagia. His upper gastrointenstinal endoscopy revealed a mass in the esophagus. A contrast-enhanced chest computed tomography also detected a 15 mm nodule attached to the tracheal membrane. This nodule was diagnosed as a metastatic lymph node. Although the primary tumor reduced after neoadjuvant chemotherapy, the nodule remained intact ; it showed fluorodeoxyglucose accumulation on positron emission tomography. We had a clinical diagnosis of stage III after neoadjuvant chemotherapy and underwent surgery. Intraoperatively, the nodule could not be detached from the right vagus nerve ; therefore, we excised the nodule along with the adjacent vagus nerve. The nodule was pathologically diagnosed as a vagus schwannoma. The nodule was not a regional lymph node metastasis of esophageal cancer. His postoperative course was uneventful, and he is currently undergoing outpatient follow-up without recurrence. J. Med. Invest. 68 : 205-208, February, 2021.
Nobuhito Naito, Hiroshi Kawano, Yuya Yamashita, Mayo Kondou, Shotaro Haji, Ryosuke Miyamoto, Yuko Toyoda, Yasuhisa Kanematsu, Yuishin Izumi, Yoshimi Bando and Yasuhiko Nishioka : Neuropsychiatric systemic lupus erythematosus with cerebellar vasculitis and obstructive hydrocephalus requiring decompressive craniectomy., Modern Rheumatology Case Reports, Vol.5, No.1, 52-57, 2020.
(要約)
A 36-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE) was admitted to our hospital due to increasing disease SLE activity. Despite the intensification of immunosuppressive treatment, headache newly developed and worsened. Magnetic resonance imaging (MRI) revealed spreading of a high-intensity area along the sulci of the bilateral cerebellar hemispheres. She was diagnosed with neuropsychiatric SLE and methylprednisolone (mPSL) pulse therapy was started. However, consciousness disorder due to cerebellar oedema with obstructive hydrocephalus appeared and required decompressive craniectomy. The histological findings of the biopsy specimens from cerebellar vermis were compatible with features of vasculitis. She was successfully treated adding intravenous cyclophosphamide therapy.
Tetsu Tomonari, Yasushi Sato, Hironori Tanaka, Takahiro Tanaka, Tatsuya Taniguchi, Masahiro Sogabe, Koichi Okamoto, Hiroshi Miyamoto, Naoki Muguruma, Yu Saitou, Satoru Imura, Yoshimi Bando, Mitsuo Shimada and Tetsuji Takayama : Conversion therapy for unresectable hepatocellular carcinoma after lenvatinib Three case reports., Medicine, Vol.99, No.42, e22782, 2020.
(要約)
Lenvatinib (LEN) is a novel potent multi-tyrosine kinase inhibitor, approved as first-line treatment for unresectable hepatocellular carcinoma (HCC). Considering its high objective response rate, LEN therapy could be expected to achieve downstaging of tumors and lead to conversion therapy with hepatectomy or ablation. However, the feasibility of conversion therapy after LEN treatment in unresectable HCC remains largely unknown. Here, we reported 3 cases of unresectable HCC: case 1, a 69-year-old man diagnosed with ruptured HCC; case 2, a 72-year-old woman with nonalcoholic steatohepatitis-based HCC; and case 3, a 73-year-old man with a history of alcoholic cirrhosis-based HCC. In all cases, cirrhosis was classified as Child-Pugh 5 and modified albumin-bilirubin grade 1 or 2a. HCC was diagnosed as Barcelona Clinic Liver Cancer (BCLC) stage B. In all cases, LEN was initiated after conventional-transcatheter arterial embolization enforcement, while maintaining liver function. In all cases, the main tumor size decreased after 6 months of LEN treatment and no satellite nodes were detected, indicating downstaging of HCC to BCLC stage A. Subsequently, conversion hepatectomy or ablation was performed. After successful conversion therapy, the general condition of the patients was good, without tumor recurrence during the observation period (median 10 months). This study demonstrated that LEN enables downstaging of HCC and thus represents a bridge to successful surgery or ablation therapy. In particular, LEN treatment may facilitate the possibility for conversion therapy of initially unresectable HCC, while maintaining the hepatic functional reserve.
Takayoshi Shinya, Youichi Otomi, Toshihiko Nishisho, Bettina Beuthien-Baumann, Michiko Kubo, Hideki Otsuka, Yoshimi Bando, Hiroaki Yanagawa, Koichi Sairyo and Masafumi Harada : Preliminary clinical assessment of dynamic carbon-11 methionine positron-emission tomography/computed tomography for the diagnosis of the pathologies in patients with musculoskeletal lesions: a prospective study., European Journal of Hybrid Imaging, Vol.26, No.4, 15, 2020.
(要約)
Dynamic C-11 MET PET scans have the potential to be good predictors of discriminating MSLs in patients with primary unknown MSLs in clinical practice.
A case is20years old woman. She had previously noticed a mass in the left axilla. The mass grew, so she went to the hospital. Ultrasonography revealed a 71 × 51 mm well-defined tumor in the left axilla. We suspected a benign tumor but could not rule out axillary lymph node metastasis or accessory breast cancer. The findings of fine needle aspiration cytology suggested fibroadenoma or phyllodes tumor. Although we diagnosed fibroadenoma by needle biopsy, a definitive diagnosis was made by tumor resection because it is located in the axilla and large in size, and other diseases such as phyllodes tumors can be distinguished. The histopathological diagnosis of the excised specimen was juvenile fibroadenoma. We report a case of juvenile fibroadenoma arising from the axillary accessory mammary gland.
Although pancreatic cancer often invades into peripancreatic adipose tissue, little is known about the cancer-adipocyte interaction. We first investigated the ability of adipocytes to de-differentiate to cancer-associated adipocytes (CAAs) by co-culturing with pancreatic cancer cells. We then examined the effects of CAA-conditioned media (CAA-CM) on the malignant characteristics of cancer cells, the mechanism underlying those effects, and their clinical relevance in pancreatic cancer. When 3T3-L1 adipocytes were co-cultured with pancreatic cancer cells (PANC-1) using Transwell system, adipocytes lost their lipid droplets and morphologically changed to fibroblast-like cells (CAA). Adipocyte-specific marker mRNA levels significantly decreased but those of fibroblast-specific markers appeared, characteristic findings of CAA, as revealed by real-time PCR. When PANC-1 cells were cultured with CAA-CM, significantly higher migration/invasion capability, chemoresistance, and epithelial-mesenchymal transition (EMT) properties were observed compared with control cells. To investigate the mechanism underlying these effects, we performed microarray analysis of PANC-1 cells cultured with CAA-CM, and found 78.5-fold higher expression of SAA1 compared with control cells. When SAA1 gene in PANC-1 cells was knocked down with SAA1 siRNA, migration/invasion capability, chemoresistance, and EMT properties were significantly attenuated compared with control cells. Immunohistochemical analysis on human pancreatic cancer tissues revealed positive SAA1 expression in 46/61 (75.4%). Overall survival in the SAA1-positive group was significantly shorter than in the SAA1-negative group (p=0.013). In conclusion, we demonstrated that pancreatic cancer cells induced de-differentiation in adipocytes toward CAA, and CAA promoted malignant characteristics of pancreatic cancer via SAA1 expression, suggesting that SAA1 is a novel therapeutic target in pancreatic cancer.
Naoki Miyamoto, Mitsuteru Yoshida, Mitsuhiro Tsuboi, Kenji Otsuka, Yoshimi Bando, Takumi Kakimoto, Naoya Kawakita, Hiromitsu Takizawa, Kazuya Kondo and Akira Tangoku : A case of long-term unchanged calcifying fibrous tumor, General Thoracic and Cardiovascular Surgery, Vol.68, No.12, 1587-1590, 2020.
(要約)
A calcifying fibrous tumor (CFT) is a rare benign tumor that may occur in any part of the body. We report the case of an asymptomatic 21-year-old woman with thoracic tumors. Chest computed tomography showed multiple masses in the left costophrenic angle. As we were unable to diagnose the tumor with a CT-guided needle biopsy, we performed a thoracoscopic biopsy. We found smooth multilobulated masses on the pleura and multiple small nodules around the main tumors. Partial resection of the tumor was performed by VATS. Histological examination revealed that the tumor had hypocellular fibrosclerotic tissue and distributed psammomatous calcifications with inflammatory infiltrates. Immunohistochemistry demonstrated that the spindle cells were partially positive for CD34 and CD99, but negative for anaplastic lymphoma kinase-1, smooth muscle actin, BCL-2, STAT6, and S-100 protein. The tumor was diagnosed as CFT. The patient's postoperative recovery was uneventful, and no progression of the lesions was observed during follow-up.
Tadahiko Nakagawa, Yasushi Sato, Toshihito Tanahashi, Yasuhiro Mitsui, Yoshifumi Kida, Yasuteru Fujino, Misato Hirata, Shinji Kitamura, Hiroshi Miyamoto, Koichi Okamoto, Naoki Muguruma, Yoshimi Bando and Tetsuji Takayama : JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8., Gastric Cancer, Vol.23, No.3, 426-436, 2020.
(要約)
Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC. We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation. Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1. Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.
Naoya Kawakita, Hiroaki Toba, Yukikiyo Kawakami, Hiromitsu Takizawa, Yoshimi Bando, Hideki Otsuka, Daisuke Matsumoto, Mika Takashima, Mitsuhiro Tsuboi, Mitsuteru Yoshida, Kazuya Kondo and Akira Tangoku : Use of a prognostic risk score that aggregates the FDG-PET/CT SUVmax, tumor size, and histologic group for predicting the prognosis of pStage I lung adenocarcinoma, International Journal of Clinical Oncology, Vol.25, No.6, 1079-1089, 2020.
(要約)
pStage I includes clinicopathologically diverse groups. This study aimed to identify the prognostic factors for pStage I lung adenocarcinoma. We retrospectively reviewed 208 patients with pStage I adenocarcinomas who underwent curative resection in our institute between 2006 and 2013. The maximum standardized uptake value (SUVmax) on [F18]-fluoro-deoxy-D-glucose positron emission tomography-computed tomography (PET/CT) was evaluated. Adenocarcinomas were categorized into the following histologic groups: group 0 (minimally invasive adenocarcinoma and lepidic predominant adenocarcinoma), group 1 (papillary predominant adenocarcinoma), and group 2 (acinar predominant adenocarcinoma and all the remaining subtypes). We assessed the relationship between disease-free survival (DFS) and clinicopathological factors. Multivariate analysis of DFS demonstrated that SUVmax > 3.0 (p < 0.001), total tumor size > 20 mm (p = 0.016), and histologic groups (p < 0.05) were independent prognostic factors. The prognostic risk score (PRS) was calculated using the following equation: PRS = SUVmax (≤ 3.0: 0 point, > 3.0: 2 points) + total tumor size (≤ 20 mm: 0 point, > 20 mm: 1 point) + histologic group (group 0: 0 point, group 1: 1 point, group 2: 2 points). Patients were divided into the following three risk groups: low-risk (PRS 0-2 points, n = 136), intermediate-risk (PRS 3-4 points, n = 49), and high-risk groups (PRS 5 points, n = 13). The 5-year DFS rates were 93.2%, 50.6%, and 30.8% for the low-, intermediate-, and high-risk groups, respectively (p < 0.001). The PRS aggregating the FDG-PET/CT SUVmax, total tumor size, and histologic group predicts the prognosis of pStage I lung adenocarcinoma.
Taichi Murakami, Masanori Tamaki, Seiji Kishi, Kojiro Nagai, Hideharu Abe, Yoshimi Bando, Yuko Toyoda, Hirokazu Ogino, Yasuhiko Nishioka, Sayo Ueda, Toshio Doi and Motokazu Matsuura : Systemic Sarcoidosis Presenting with Renal Involvement Caused by Various Sarcoidosis-associated Pathophysiological Conditions, Internal Medicine, Vol.58, No.5, 679-684, 2019.
(要約)
A 61-year-old man was diagnosed with sarcoidosis involving the lungs, eyes, parotid gland and extrathoracic lymph nodes complicated by chronic kidney injury and hypercalcemia. Kidney biopsy showed non-specific interstitial nephritis and nephrosclerosis. However, immunohistochemical staining of cell surface markers revealed a multinucleated giant macrophage surrounded by T-cells, suggesting granulomatous interstitial nephritis. Corticosteroid improved the kidney function, and reduced the serum levels of calcium and angiotensin-converting enzyme. Sarcoid nephropathy may be caused by the combination of several sarcoidosis-associated pathophysiological conditions and a comprehensive kidney examination should be performed to assess the type of injury when determining a treatment strategy.
Hiroshi Miyamoto, Kumiko Tanaka, Fumika Nakamura, Takahiro Ikeda, Shinji Kitamura, Tetsuo Kimura, Koichi Okamoto, Masahiro Sogabe, Naoki Muguruma, Yoshimi Bando and Tetsuji Takayama : Massive hemobilia following plastic stent removal in common bile duct cancer associated with primary sclerosing cholangitis (with video)., Clinical Journal of Gastroenterology, Vol.12, No.1, 2019.
(要約)
Hemobilia is defined as bleeding into the biliary tract. Herein, we report a very rare case of massive hemobilia following plastic stent (PS) removal in common bile duct (CBD) cancer. A 72-year-old man with primary sclerosing cholangitis had undergone repeated insertion of a PS into the CBD. Biliary tract biopsy was performed based on suspicion of combined CBD cancer. Biopsy revealed poorly differentiated adenocarcinoma of the CBD. One month after the biliary tract biopsy, he was admitted for acute cholangitis, and endoscopic retrograde cholangiography was performed for the exchange of the PS. When one of the two biliary PSs was removed, spurting bleeding from the major papilla began abruptly. The massive bleeding caused the patient to be in a pre-shock state. A retrieval balloon catheter was compressed against the papilla for hemostasis. Although he was treated conservatively, the patient developed a bloody discharge. Upper gastrointestinal endoscopy revealed that the pulsatile bleeding beside the PSs started immediately after the removal of the coagula. Emergent contrast-enhanced computed tomography showed right hepatic artery aneurysm across the CBD. Therefore, transarterial embolization was performed. The patient's post-therapeutic course was uneventful. He received chemotherapy, but died about a half year after hemobilia occurred.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : Evaluation of Red Degeneration of Uterine Leiomyoma with Susceptibility-weighted MR Imaging, Magnetic Resonance in Medical Sciences, Vol.18, No.2, 158-162, 2018.
Mayo Kondo, Hirokazu Ogino, Hirohisa Ogawa, Tania Afroj, Yuko Toyoda, Satoshi Sakaguchi, Miki Tsuboi, Yoshimi Bando, Hisatsugu Goto, Koichi Tsuneyama and Yasuhiko Nishioka : A case of pulmonary pleomorphic carcinoma with malignant phenotypes induced by ZEB1-associated epithelial-mesenchymal transition., Respiratory Medicine Case Reports, Vol.25, 119-121, 2018.
(要約)
A 60-year-old man was admitted to our hospital with non-small cell lung cancer (NSCLC). Imaging and pathological studies revealed NSCLC, not otherwise specified (NOS), at clinical stage T3N1M0 stage IIIA. We started radiotherapy alone because of obstructive pneumonia and end-stage renal disease, but the tumors progressed rapidly and resulted in death due to air obstruction by pharyngeal metastasis. The cancer was diagnosed as pleomorphic carcinoma in an autopsy. Viable lung tumor cells, which were resistant to radiotherapy, and the pharyngeal metastasis had mesenchymal phenotypes and expressed ZEB1 but not SNAI1. These observations indicated that ZEB1-associated epithelial-mesenchymal transition has malignant features including resistance to radiotherapy and aggressive metastatic potential. ZEB1-associated EMT may be an important mechanism to understand the pathophysiology of pleomorphic carcinoma.
Yasuhiro Mitsui, Reiko Yokoyama, Shota Fujimoto, Kaizoh Kagemoto, Shinji Kitamura, Koichi Okamoto, Naoki Muguruma, Yoshimi Bando, Hidetaka Eguchi, Yasushi Okazaki, Hideyuki Ishida and Tetsuji Takayama : First report of an Asian family with gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) revealed with the germline mutation of the APC exon 1B promoter region., Gastric Cancer, Vol.21, No.6, 1058-1063, 2018.
(要約)
A 48-year-old Japanese female with left hypochondralgia presented at our hospital. Esophagogastroduodenoscopy (EGD) revealed gastric cancers and carpeting fundic gland polyposis (FGPs) without Helicobacter pylori infection. Computed tomography showed multiple liver metastases. Total colonoscopy revealed a colonic tubular adenoma but not polyposis. She was diagnosed as having advanced gastric cancer with liver metastasis and received chemotherapy. Her mother had died from gastric cancer, and her elderly brother and niece had FGPs as revealed by EGD. Thus, the pedigree was diagnosed as gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Germline mutation analysis exhibited a point mutation in exon1B of the APC gene (c.-191T > C). Adenocarcinoma showed a gastric mucinous phenotype and was positive for a somatic mutation of p53, suggesting that p53 mutation may play a role in FGPs carcinogenesis. This is the first family with GAPPS in Asia in whom germline mutation of APC exon 1B has been detected.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando, Masato Nishimura, Aki Hayashi and Masafumi Harada : A Case of Uterine Tumor Resembling Ovarian Sex-cord Tumor (UTROSCT) Exhibiting Similar Imaging Characteristics to Those of Ovarian Sex-cord Tumor., Magnetic Resonance in Medical Sciences, Vol.18, No.2, 113-114, 2018.
Kouzou Yoshikawa, Mitsuo Shimada, Jun Higashijima, Toshihiro Nakao, Masaaki Nishi, Chie Takasu, Hideya Kashihara, Syohei Eto and Yoshimi Bando : Ki-67 and Survivin as Predictive Factors for Rectal Cancer Treated with Preoperative Chemoradiotherapy., Anticancer Research, Vol.38, No.3, 1735-1739, 2018.
(要約)
To evaluate the usefulness of Ki-67 index and survivin as predictive prognostic factors for rectal cancer treated with preoperative chemoradiotherapy. The Ki-67 index and survivin expression were examined in patients with stage II/III rectal cancer (n=46) by immunohistochemistry. Patients were divided into a high-group and a low-group for the Ki-67 index, and positive and negative groups for survivin expression. Overall and disease-free survival were compared between the groups, and the correlation between Ki-67 index and survivin expression was assessed. The 5-year disease-free survival rate of the group with high Ki-67 index was significantly lower than that of the group with low Ki-67 index (53% and 88%, p=0.03), as was the 5-year overall survival rate (68% and 100%, p=0.03). Findings for survivin were not significant. Ki-67 index and survivin may be useful biomarkers for rectal cancer with preoperative CRT.
Toshiaki Yoshimoto, Satoru Imura, Yuji Morine, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Chie Takasu, Daichi Ishikawa, Hiroki Teraoku, Yoshimi Bando and Mitsuo Shimada : The Outcome of Sorafenib Therapy on Unresectable Hepatocellular Carcinoma: Experience of Conversion and Salvage Hepatectomy., Anticancer Research, Vol.38, No.1, 501-507, 2018.
(要約)
We report the outcomes of sorafenib therapy for advanced hepatocellular carcinoma (HCC) in our Department. Thirty-eight patients with unresectable HCC who were administrated sorafenib from 2009 to 2015 were investigated retrospectively. The 1-year overall survival rate was 59.3%. The macroscopic vascular invasion and response rate were independent prognostic factors of survival. Surgical resection after sorafenib achieved long-term survival in two cases. Case 1: A patient with locally unresectable HCC showed significant response induced by sorafenib, which allowed complete surgical resection. This tumor tested positive for FGF4. Case 2: A patient with a history of hepatectomy for HCC had multiple distant metastases. Most lesions were reduced in size after sorafenib therapy and new lesions in the remnant liver and residual lung metastases were resected. The sorafenib-resistant lesions were negative for FGF4. Sorafenib combined with surgical resection is a feasible option in advanced HCC patients, if sorafenib has been effective.
Although new image-enhanced endoscopy (IEE) technologies such as blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) have been developed, their utility for the detection of sessile serrated adenoma/polyps (SSA/Ps) is still unclear. This study aimed to evaluate the utility of BLI, BLI-bright, and LCI for SSA/P detection in still image examinations and in a prospective randomized controlled trial (RCT). A group of 6 expert and non-expert endoscopists read 200 endoscopic still images containing SSA/P lesions using white light image (WLI), BLI, BLI-bright, and LCI. Color differences were calculated using the color space method. A prospective RCT of tandem colonoscopy with WLI and LCI was performed. Patients with SSA/P and those with a history of SSA/P that had been endoscopically removed were enrolled and randomly allocated to WLI-LCI or LCI-WLI groups. Additional endoscopic detection rates for SSA/P were compared between the 2 groups. LCI showed the highest SSA/P detection rate among the 4 modes for both expert and non-expert endoscopists. The detection rate with LCI for the 6 expert endoscopists (mean 98.3 ± standard deviation 2.0 %) was significantly higher than that with WLI (86.7 ± 6.0 %, < 0.01). Likewise, the detection rate with LCI for the 6 non-expert endoscopists (92.3 ± 2.9 %) was significantly higher than that with WLI (72.7 ± 11.5 %, < 0.01). The color difference of SSA/P with LCI was the highest among the 4 modes, and was significantly higher than with WLI (median 15.9, (interquartile range 13.7 - 20.6) vs. 10.2, (7.6 - 14.2); < 0.0001). In the RCT, a total of 44 patients (WLI-LCI 22 vs. LCI-WLI 22) underwent colonoscopy. The additional detection rate for SSA/P in the second inspection in the WLI-LCI group (21.6 %, 8/37) was significantly higher than in the LCI-WLI group (3.2 %, 1/31; = 0.02). The small, flat, non-mucus and isochromatic SSA/Ps in the transverse colon were detected more frequently in the second inspection with LCI. LCI was the most sensitive mode for SSA/P detection among WLI, BLI, BLI-bright, and LCI in the still image examinations. Our RCT strongly suggests that LCI is superior to conventional WLI for SSA/P detection during colonoscopy. UMIN000017599.
Gastric xanthomas are frequently observed in the stomach as small yellowish plaques or nodules. A close relationship among Helicobacter pylori infection, atrophic gastritis, and xanthomas has been reported. We assessed the clinicopathological features of gastric cancer with or without xanthomas. A total of 91 patients who were diagnosed as having early gastric cancer were enrolled. We evaluated the gastritis status using scores for gastritis and atrophy, positivity of H. pylori infection, the prevalence rate of xanthomas, and the clinicopathological features of gastric cancer. Gastric xanthomas were observed in 72.5% of early gastric cancer cases. Scores for gastritis and atrophy were significantly higher in the xanthoma-positive group than those in the xanthoma-negative group. A higher prevalence of differentiated-type adenocarcinoma was found in the xanthoma-positive group. Among the cases with multiple gastric xanthomas, the prevalence of males was significantly higher than that of females. A high prevalence rate of gastric xanthomas in gastric cancer cases was shown. Xanthomas were highly associated with age, the severities of gastritis and atrophy, and differentiated-type adenocarcinoma. Regardless of the eradication of H. pylori, xanthomas may be useful predictive markers for the development of differentiated-type adenocarcinoma.
The rectal tonsil is a rare polypoid lesion exclusively found in the rectum and is considered a reactive proliferation of the lymphoid tissue. Although this lesion is benign, we recommend that it should be differentiated from carcinoid or polypoid type of mucosaassociated lymphoid tissue (MALT) lymphomas, based on gross findings. In this case report, we describe a case of rectal lesions with a unique appearance in a 41-year-old man. Colonoscopy revealed two 5-mm-sized nodules located opposite from each other on the left and right sides of the lower rectum. Endoscopic mucosal resection was conducted. Histopathologically, both lesions were mainly located in the submucosa and consisted of prominent lymphoid follicles with germinal centers of various sizes. No immunoreactivity of Bcl-2 was seen in the germinal centers. Immunohistochemical staining for kappa and lambda light chains revealed a polyclonal pattern. Therefore, these lesions were diagnosed as rectal tonsils.
Jun Okazaki, Naoki Muguruma, Shinji Kitamura, Tetsuo Kimura, Koichi Okamoto, Hiroshi Miyamoto, Kazuhiro Kishi, Yoshimi Bando, Takeshi Kondo, Itsuro Endo, Masahiro Abe and Tetsuji Takayama : Paraneoplastic hypocalcemia developed in gastric cancer accompanied by osteoblastic metastasis, Internal Medicine, Vol.56, No.11, 1345-1349, 2017.
(要約)
Paraneoplastic syndromes are generally defined as clinical disorders associated with malignant diseases, and hypocalcemia associated with cancer is a rare condition. A woman in her 60s was referred to our hospital for the further examination of massive ascites due to carcinoma of unknown primary origin. She complained of numbness around her lips, and marked hypocalcemia of 5.0 mg/dL was noted. After two courses of chemotherapy, computed tomography showed a decrease in the ascites, and her serum calcium level increased. Although hypocalcemia is a very rare condition in patients with gastric cancer, serum calcium values should be evaluated when neurological symptoms are observed.
Tetsuro Yoshimaru, Masaya Ono, Yoshimi Bando, Yi-An Chen, Kenji Mizuguchi, Hiroshi Shima, Masato Komatsu, Issei Imoto, Keisuke Izumi, Junko Honda, Yasuo Miyoshi, Mitsunori Sasa and Toyomasa Katagiri : A-kinase anchoring protein BIG3 coordinates oestrogen signalling in breast cancer cells., Nature Communications, Vol.8, No.15427, 2017.
(要約)
Approximately 70% of breast cancer cells express oestrogen receptor alpha (ER). Previous studies have shown that the Brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex has a crucial role in these cells. However, it remains unclear how BIG3 regulates the suppressive activity of PHB2. Here we demonstrate that BIG3 functions as an A-kinase anchoring protein that binds protein kinase A (PKA) and the isoform of the catalytic subunit of protein phosphatase 1 (PP1C), thereby dephosphorylating and inactivating PHB2. E2-induced PKA-mediated phosphorylation of BIG3-S305 and -S1208 serves to enhance PP1C activity, resulting in E2/ER signalling activation via PHB2 inactivation due to PHB2-S39 dephosphorylation. Furthermore, an analysis of independent cohorts of ER-positive breast cancers patients reveal that both BIG3 overexpression and PHB2-S39 dephosphorylation are strongly associated with poor prognosis. This is the first demonstration of the mechanism of E2/ER signalling activation via the BIG3-PKA-PP1C tri-complex in breast cancer cells.
Yuri Matsumoto, Hiroshi Miyamoto, Akira Fukuya, Fumika Nakamura, Takahiro Goji, Shinji Kitamura, Tetsuo Kimura, Koichi Okamoto, Masahiro Sogabe, Naoki Muguruma, Mitsuo Shimada, Yoshimi Bando and Tetsuji Takayama : Hemosuccus pancreaticus caused by a mucinous cystic neoplasm of the pancreas., Clinical Journal of Gastroenterology, Vol.10, No.2, 185-190, 2017.
(要約)
Hemosuccus pancreaticus is a gastrointestinal hemorrhage through the main pancreatic duct. Here, we report a rare case of hemosuccus pancreaticus due to a mucinous cystic neoplasm of the pancreas. A 62-year-old woman who had been followed for a branch duct intraductal papillary mucinous neoplasm visited our emergency room due to severe abdominal pain and bloody discharge. Computed tomography revealed that the pancreatic cyst increased the tension of the wall and a high-density area indicative of bleeding into the cyst was observed. Endoscopy showed opening of and hemorrhaging from the papilla of Vater. The patient was diagnosed with hemosuccus pancreaticus caused by hemorrhaging into the cyst from the branch duct intraductal papillary mucinous neoplasm. Based on this diagnosis, elective distal pancreatectomy was performed. The histopathological diagnosis was a mucinous cystic neoplasm with intermediate-grade dysplasia based upon the pathological findings that fibrous ovarian-type stroma existed abundantly and the stroma cells were positive for progesterone receptor and inhibin. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm is extremely rare and there has been only one case reported to date. In conclusion, it should be recognized that pancreatic cystic neoplasms including mucinous cystic neoplasms may cause hemosuccus pancreaticus.
Masakazu Goto, Takahiro Yoshida, Yota Yamamoto, Yoshihito Furukita, Seiya Inoue, Satoshi Fujiwara, Naoya Kawakita, Takeshi Nishino, Takuya Minato, Yasuhiro Yuasa, Hiromichi Yamai, Hirokazu Takechi, Jun-ichi Seike, Yoshimi Bando and Akira Tangoku : CXCR4 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma, Annals of Surgical Oncology, Vol.24, No.3, 832-840, 2017.
(要約)
Chemokines and their receptors are known to play important roles in the tumorigenesis of many malignancies. The chemokine CXCL12 and its receptors CXCR4 and CXCR7 were suggested to be involved in cancer invasion and metastasis. The aim of this retrospective study was to evaluate the prognostic impact of the expressions of CXCL12, CXCR4 and CXCR7 in patients with esophageal squamous cell carcinoma (ESCC). We used immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate the expressions of CXCL12, CXCR4, and CXCR7 in ESCC patients' tumor biopsy specimens obtained during preoperative endoscopy or surgery. These results were compared with the patients' clinicopathological parameters and survival. IHC was conducted for 172 patients. High expression of CXCR4 in the cytoplasm and nuclei and that of CXCR7 were associated with poor cause-specific survival (CSS) (P= .002 and .010, respectively). The specimens from 52 of the 172 patients were examined by RT-PCR and quantitative real-time PCR. The expression levels of messenger RNA (mRNA) of CXCR4 and CXCR7 were significantly increased in the tumors compared with normal esophageal mucosae (P < .0001). The expression level of mRNA of CXCR4 was associated with poor recurrence-free survival and CSS (P = .012 and .038, respectively). CXCR4 expression is associated with poor prognosis in patients with ESCC.
Motokazu Matsuura, Hideharu Abe, Tatsuya Tominaga, Akiko Sakurai, Taichi Murakami, Seiji Kishi, Yoshimi Bando, Jun Minakuchi, Kojiro Nagai and Toshio Doi : A Novel Method of DAPI Staining for Differential Diagnosis of Renal Amyloidosis., The Journal of Medical Investigation : JMI, Vol.64, No.3.4, 217-221, 2017.
(要約)
Amyloidosis is often overlooked because its clinical manifestations can mimic those of more-common diseases. It is important to get a precise diagnosis as early as possible for the prevention of further organ damages. Amyloidosis is a disorder caused by deposition of insoluble abnormal amyloid. The kidney is a frequent site of amyloid deposition. The amyloid fibrils have a characteristic appearance and generate birefringence under polarized light when stained with the Congo red dye. Classification of amyloidosis is based on the precursor protein that forms the amyloid fibrils and the distribution of amyloid deposits as either systemic or localized. Involvement of amyloid fibrils in kidneys mainly occurs as amyloid light-chain (AL) or amyloid A (AA) amyloidosis. The potassium permanganate method with Congo red staining was once used widely to discriminate AL and AA amyloidoses, but this method has a problem of false positive results. We found that extracellular and cytoplasmic glomerular 4', 6-diamidino-2-phenylindole (DAPI)-positive areas were clearly consistent with amyloid deposition in AL amyloidosis. In contrast, the overlapping staining was not seen in AA amyloidosis. Therefore, we propose that DAPI staining readily distinguishes AL renal amyloidosis from AA renal amyloidosis as a simple and reproducible histochemical method. J. Med. Invest. 64: 217-221, August, 2017.
(キーワード)
Amyloidosis / Kidney Diseases / Serum Amyloid A Protein / Staining and Labeling
Yuko Toyoda, Ryohiko Ozaki, Jun Kishi, Masaki Hanibuchi, Katsuhiro Kinoshita, Toshifumi Tezuka, Hisatsugu Goto, Hiroyuki Ono, Kojiro Nagai, Yoshimi Bando, Toshio Doi and Yasuhiko Nishioka : An Autopsy Case of Aortic Intimal Sarcoma Initially Diagnosed as Polyarteritis Nodosa., Internal Medicine, Vol.55, No.21, 3191-3195, 2016.
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A 61-year-old man had hypertension with stenosis in the left renal artery. When his fever, abdominal pain, and renal dysfunction progressed, he was admitted to our hospital. He was diagnosed with polyarthritis nodosa. His renal function rapidly deteriorated despite immunosuppressive therapy. His digestive tract perforated twice, and he subsequently died. An autopsy revealed that aortic intimal sarcoma caused stenosis in multiple arteries. Both polyarteritis nodosa and aortic intimal sarcoma are very rare diseases and the diagnoses are very difficult. It is very important to consider these entities when making a differential diagnosis of vasculitis.
Teruyoshi Kageji, Takeshi Miyamoto, Yumiko Kotani, Tuyoshi Kaji, Yoshimi Bando, Yoshifumi Mizobuchi, Kohhei Nakajima and Shinji Nagahiro : Congenital craniopharyngioma treated by radical surgery: case report and review of the literature, Child's Nervous System, Vol.33, No.2, 357-362, 2016.
(要約)
Craniopharyngiomas are 5-10 % of all pediatric tumors, but are seldomly encountered in the perinatal period. Only seven instances of a truly antenatal diagnosis of a congenital craniopharyngioma that subsequently underwent radical surgery have been reported. We present the case of a patient who received the diagnosis of a suprasellar tumor during the prenatal period and received radical surgery. We report a case of a neonatal craniopharyngioma treated surgically. The pregnancy progressed uneventfully until a routine ultrasound at 37 weeks of gestation showed a 15 × 15 mm high echoic mass in the center of the fetal head. Neonatal Gd-enhanced T1-weighted MRI at 5 days of life showed a homogenously enhanced mass (16×22×15 mm) in the sellar and suprasellar lesion. As the tumor showed rapid growth at the 3rd month of life, the patient underwent a surgical treatment and the mass was totally removed. Three years later, the physical and mental development of the patient was normal, and Gd-MRI studies showed no tumor recurrence. The present case is the eighth case of a truly antenatal diagnosis of a craniopharyngioma that underwent successful radical surgery. Craniopharyngioma is a benign tumor and thought to be a slow growing tumor in childhood. The results of radical surgery were very poor, and the mortality and morbidity rates were high in the previous reports due to the huge size of tumor at operation. The present case demonstrated the rapid growth in short interval of Gd-MRI. This is the first report of tumor kinetics of congenital craniopharyngioma with previous reports. The calculated tumor doubling time in our case was 37 days.
Tetsuo Kimura, Hiroshi Miyamoto, Akira Fukuya, Shinji Kitamura, Koichi Okamoto, Masako Kimura, Naoki Muguruma, Tetsuya Ikemoto, Mitsuo Shimada, Akiko Yoneda, Yoshimi Bando, Makoto Takishita and Tetsuji Takayama : Neuroendocrine carcinoma of the pancreas with similar genetic alterations to invasive ductal adenocarcinoma., Clinical Journal of Gastroenterology, Vol.9, No.4, 261-265, 2016.
(要約)
Neuroendocrine carcinoma (NEC) of the pancreas is very rare, and its origin is not fully elucidated. Here, we present a case of a small-size NEC of the pancreas that is genetically similar to invasive ductal adenocarcinoma (IDA). A 65-year-old man was referred to our hospital due to obstructive jaundice and found to have a 12-mm solid tumor in the pancreas head. The tumor exhibited low vascularity on enhanced computed tomography, and endoscopic retrograde pancreatographic imaging revealed an irregular obstruction in a branch duct of the pancreas. The patient was thereby diagnosed with a pancreatic ductal cancer, and stomach-preserving pancreaticoduodenectomy with regional lymph node resection was performed. Histochemical analysis of the resected tumor showed that the neoplastic cells with scanty cytoplasm and hyperchromatic nuclei strongly expressed chromogranin A and synaptophysin. The Ki-67 index was 40 % in the most proliferative tumor regions, and the tumor was diagnosed as a NEC of the pancreas. However, in the analysis of genetic alterations of the tumor tissue, the neoplastic cells showed altered KRAS, TP53, and SMAD4/DPC4, suggesting that the NEC in our case is genetically related to IDA. Our data suggest that poorly differentiated IDAs may transform into NECs.
Yoshihiko Miyamoto, Naoki Muguruma, Tetsuo Kimura, Koichi Okamoto, Masahiro Sogabe, Hiroshi Miyamoto, Seiya Kohno, Masahiko Nakasono, Hiroshige Hayashi, Yoshimi Bando and Tetsuji Takayama : Protein-losing enteropathy in a patient with familial adenomatous polyposis and advanced colon cancer., Clinical Journal of Gastroenterology, Vol.9, No.3, 134-139, 2016.
(要約)
A 29-year-old female visited a hospital because of increasingly severe lower leg edema. She was diagnosed as having multiple polyps in the stomach and colon by gastroscopy and sigmoidoscopy as well as multiple liver tumors by abdominal CT. She was referred to our hospital for further examination. Total colonoscopy revealed a type 2 tumor in the transverse colon and more than 200 polyps distributed throughout the colorectum. Biopsies of the tumor and polyps showed histological characteristics of adenocarcinoma and tubulovillous adenoma, respectively. Thus, she was diagnosed as having metastatic colon cancer derived from familial adenomatous polyposis (FAP). Laboratory tests showed a marked hypoalbuminemia of 1.1 g/dl. The fecal alpha-1 anti-trypsin test showed abnormal clearance (62.1 ml/day), and scintigraphy using 99mTc-human serum albumin revealed protein loss in the whole colon. Multiple ligation probe amplification analysis of the APC gene identified a germline duplication of exons 11-13. Direct sequencing of the reverse transcription PCR products of APC mRNA revealed a deletion of 25 base pairs and a tandem duplication of exons 11-13. This case was considered to be protein-losing enteropathy resulting from numerous colonic tubulovillous adenomas and advanced colon cancer in a FAP patient with unusual mutational events in APC.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando, Masato Nishimura, Akiko Yoneda and Masafumi Harada : A case of polypoid endometriosis with malignant transformation., Abdominal Radiology, Vol.41, No.9, 1699-1702, 2016.
(要約)
Polypoid endometriosis is a benign, rare variant of endometriosis which forms multiple polypoid nodules in the female pelvis mimicking malignant tumors; however, it may rarely cause malignant transformation. We report magnetic resonance imaging findings of a case of polypoid endometriosis with malignant transformation. Multiple high-signal intensity polypoid nodules in the cul-de-sac surrounded by low-signal intensity rim-like fibrous adhesion protruding to the posterior wall of the uterine body were demonstrated on T2-weighted images. The polypoid nodules showed weak contrast enhancement compared with that of uterine myometrium on post-contrast T1-weighted images, and slight high signal intensity on diffusion-weighted images with relatively high mean apparent diffusion coefficient. Reported cases of polypoid endometriosis showed intense contrast enhancement similar to that of uterine myometrium, and weak contrast enhancement similar to that of endometrial carcinoma may be suggestive for malignant transformation of polypoid endometriosis.
A 54-year-old man was referred to our hospital due to a mass shadow noted on a chest X-ray. Thoracoscopic lobectomy yielded a diagnosis of primary pulmonary synovial sarcoma according to the histology and SYT-SSX1 gene analyses. Five months after the thoracic surgery, he developed brain metastasis; therefore, we performed resection of the brain metastatic focus followed by radiotherapy. As a local recurrence in the thoracic cavity concurrently emerged, systemic chemotherapy was also administered. These observations indicated that a multidisciplinary approach may be useful against primary pulmonary synovial sarcoma, although there is presently no established therapeutic strategy due to its rarity and highly aggressive nature.
Miyuki Kanematsu, Masami Morimoto, Masako Takahashi, Junko Honda, Yoshimi Bando, Takuya Moriya, Yukiko Tadokoro, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Hiroaki Toba, Mitsuteru Yoshida, Aiichiro Kajikawa, Akira Tangoku, Issei Imoto and Mitsunori Sasa : Thirty percent of ductal carcinoma in situ of the breast in Japan is extremely low-grade ER(+)/HER2(-) type without comedo necrosis, The Journal of Medical Investigation : JMI, Vol.63, No.3-4, 192-198, 2016.
(要約)
Background Overdiagnosis in mammography (MMG) is a problem. Combination of MMG and ultrasonography for breast cancer screening may increase overdiagnosis. Most cases of overdiagnosis are low-grade ductal carcinoma in situ (LGD), but no reports have focused on them. Materials and methods We immunostained 169 ductal carcinoma in situ (DCIS) cases for ER, PgR, HER2 and Ki67 and classified them into 4 subtypes: ER(+)/HER2(-), ER(+)/HER2(+), ER(-)/HER2(-) and ER(-)/HER2(+). The Ki67 index was used to evaluate the grade of malignancy and examined for correlations with each ER/HER2 subtype and the nuclear grade (NG), with/without comedo necrosis. Results The Ki67 index correlated significantly with NG, both with/without comedo necrosis, and reliably evaluated the grade of malignancy. The index for ER(+)/HER2(-) (n=117, 69.2%) was 7.45±7.10, which was significantly lower than for each of the other types. The index was 5.71±6.94 for ER(+)/HER2(-) without comedo necrosis (n=52, 30.8%), which was significantly lower than with comedo necrosis. This was considered LGD, characterized by absence of microcalcification in MMG and either presence of a solid mass or cystic lesion or absence of hypoechoic areas in ultrasound. Conclusion In Japan, ER(+)/HER2(-) without comedo necrosis accounts for about 30% of DCIS and is LGD. This may be being overdiagnosed. J. Med. Invest. 63: 192-198, August, 2016.
Kojiro Nagai, Jun Kishi, Shun Morizumi, Jun Minakuchi, Yoshimi Bando, Yasuhiko Nishioka and Toshio Doi : Henoch-Schönlein purpura nephritis occurring postpartum in a patient with anti-PL-7 anti-synthetase syndrome., Modern Rheumatology, Vol.28, 1-4, 2015.
(要約)
A 37-year-old pregnant woman developed purpura which was subsequently diagnosed as Henoch-Schönlein purpura (HSP). After childbirth, the patient developed proteinuria and hematuria. Further examination revealed that the HSP nephritis (HSPN) was associated with anti-threonyl-tRNA synthetase anti-synthetase syndrome. The onset of HSPN during pregnancy or after childbirth is rare. Moreover, to our knowledge, this is the first case to describe renal involvement in anti-synthetase syndrome.
Masami Morimoto, Yoshimi Bando, Misako Nakagawa, Hirokazu Takechi, Takahiro Yoshida, Junko Honda, Yukiko Tadokoro, Takuya Moriya, Mitsunori Sasa and Akira Tangoku : Immunocytochemical results for HER2 and Ki67 in breast cancer touch-smear cell specimens are reliable., Breast Cancer, Vol.23, No.4, 577-582, 2015.
(要約)
HER2 and Ki67 were analyzed in TSC from 36 and 28 patients, respectively. The HER2 expression scores in the TSC and HS groups showed good agreement (kappa value =0.640) and significant correlation (correlation coefficient =0.860, p < 0.001). The Ki67 indexes in the TSC and HS groups also showed significant correlation (correlation coefficient =0.861, p < 0.001).
Satoshi Teramae, Hiroshi Miyamoto, Naoki Muguruma, Yasuyuki Okada, Takahiro Goji, Shinji Kitamura, Tetsuo Kimura, Masako Kimura, Yoshimi Bando and Tetsuji Takayama : Insulin-like growth factor II-producing metastatic colon cancer with recurrent hypoglycemia., Clinical Journal of Gastroenterology, Vol.8, No.1, 35-40, 2015.
(要約)
A 45-year-old man was referred to our hospital and found to have a tubular adenocarcinoma of the descending colon with multiple liver metastases. During hospitalization, the patient suffered recurrent hypoglycemic attacks that required intravenous 50% glucose infusion. He was diagnosed with non-islet cell tumor hypoglycemia (NICTH) because the colon cancer tissue obtained by biopsy was strongly stained for insulin-like growth factor-II (IGF-II) by immunohistochemistry. He received chemotherapy with oxaliplatin, 5-FU and leucovorin (FOLFOX) plus bevacizumab (Bmab), and showed a partial response. As the metastatic lesions decreased in size, the hypoglycemic attacks gradually disappeared. Subsequently, he received outpatient chemotherapy and maintained a high quality of life for about 10 months. Western blot analysis of IGF-II in serum at the time of admission showed a high-molecular-weight form of IGF-II, which was considered to have caused hypoglycemia. This patient presents a very rare case of colorectal cancer associated with NICTH syndrome due to production of high-molecular-weight IGF-II by cancer cells. It is important to investigate IGF-II expression in cancer tissues for establishing the diagnosis of NICTH in cases with intractable hypoglycemia complicated by advanced cancer.
(キーワード)
Adenocarcinoma / Blotting, Western / Colonic Neoplasms / Humans / Hypoglycemia / Immunohistochemistry / Insulin-Like Growth Factor II / Liver Neoplasms / Male / Middle Aged / Recurrence
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando, Mika Sakaki, Hiroyuki Furumoto and Masafumi Harada : Magnetic Resonance Manifestations of Villoglandular Papillary Adenocarcinoma of the Uterine Cervix with a Fern-leaf-like Appearance., Magnetic Resonance in Medical Sciences, Vol.13, No.4, 267-270, 2014.
(要約)
Villoglandular papillary adenocarcinoma (VGPA) is a rare subtype of cervical adenocarcinoma that generally affects young women and has a favorable prognosis. Its preoperative diagnosis is important to avoid excessive surgery. We report the magnetic resonance (MR) findings of a case in which the cervical tumor showed a fern-leaf-like appearance on high resolution T2-weighted images obtained at 3 tesla. MR imaging clearly showed this pathological feature that may suggest this disease.
(キーワード)
cervical cancer / MRI / uterus / villoglandular papillary adenocarcinoma
In recent years, an increase in the ratio of female physicians in Tokushima Prefecture, with a particularly notable rise among younger generations that has exceeded the national average, has been observed. However, these physicians continue to face severe working environments, and support measures are required for female physicians during childbirth and in the early stages of parenthood. To this end, the Tokushima City Medical Association has been involved in initiatives to support female physicians since 2008. First, we developed ``Net Joy,'' a website that provides the information necessary for female physicians to continue their clinical work through a bulletin board system that offers information on topics such as employment and childcare. Furthermore, we have administered questionnaire surveys related to working environments and support systems in clinical training hospitals and compiled a booklet entitled Support Notebook for Female Physicians that is available on the Net Joy website. Since 2011, as post-residency training in ultrasound techniques, we have held six separate practical training seminars at the Tokushima University Hospital Ultrasound Examination Center and the Tokushima City Medical Association Hall. Since 2014, we have been involved in efforts to enhance its training content and develop it into a long-term program.
(キーワード)
female physicians / website / practical training seminar
Youichi Otomi, Hideki Otsuka, Kaori Terazawa, Hayato Nose, Michiko Kubo, Kenji Matsuzaki, Hitoshi Ikushima, Yoshimi Bando and Masafumi Harada : Comparing the performance of visual estimation and standard uptake value of F-18 fluorodeoxyglucose positron emission tomography/computed tomography for detecting malignancy in pancreatic tumors other than invasive ductal carcinoma., The Journal of Medical Investigation : JMI, Vol.61, No.1-2, 171-179, 2014.
(要約)
The utility of FDG PET/CT for the detection and evaluation of invasive ductal carcinoma has been widely reported, but a few studies have assessed the utility of FDG PET/CT to detect malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma. To compare the diagnostic performance of visual estimation with the semi-quantitative scores of FDG PET/CT for detecting malignancy in a variety of pancreatic lesions other than invasive ductal carcinoma. Images of pathologically proven pancreatic lesions from 32 patients were retrospectively evaluated: 14 benign lesions, 7 borderline (low malignant) lesions, and 11 malignant lesions. The average scores from visual estimation by the two observers were compared to two semi-quantitative analyses of FDG uptake in the lesions, namely the maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean). Visual analysis value, SUVmax and SUVmean were 0.33 ± 0.21, 1.8 ± 0.7 and 1.5 ± 0.7 for the benign lesions, 0.70 ± 0.28, 5.0 ± 2.6 and 3.1±1.7 for the borderline lesions, and 0.73 ± 0.18, 4.7 ± 2.5 and 3.2 ± 1.6 for the malignant lesions, respectively. Receiver operating characteristic analysis revealed the areas under the curves for detecting non-benign (malignant or borderline) lesions through visual analysis, SUVmax, and SUVmean were 0.914, 0.954, and 0.875, respectively. For a variety of pancreatic lesions other than invasive ductal carcinoma, visual analysis and semi-quantitative analyses all showed strong diagnostic performance. However, semi-quantitative analysis with SUVmax proved to be the most effective method for detecting non-benign pancreatic lesions.
Shinji Kitamura, Mitsugi Yasuda, Naoki Muguruma, Koichi Okamoto, Hisashi Takeuchi, Yoshimi Bando, Hiroshi Miyamoto, Toshiya Okahisa, Mitsuyasu Yano, Ryusuke Torisu and Tetsuji Takayama : Prevalence and characteristics of nodular gastritis in Japanese elderly., Journal of Gastroenterology and Hepatology, Vol.28, No.7, 1154-1160, 2013.
(要約)
NG was found in 62 cases (0.94%) out of 6623 patients who underwent endoscopy, with a mean age of 47.3 ± 13.3 years. Female patients were present at a significantly higher rate in the elderly group (P < 0.001). The grade of neutrophil infiltration in the greater curvature of the upper gastric body was recognized at a significantly higher rate in the elderly group (P < 0.05). PG II was present at a higher rate and PG I/II at a lower rate in the elderly group (P < 0.05). The odds ratio for the risk of gastric cancer in patients with NG was 2.1 (95% confidence interval 0.3-15.3) in the elderly group.
(キーワード)
Age Factors / Aged / Aged, 80 and over / Asian Continental Ancestry Group / Gastritis / Gastroscopy / Humans / Japan / Prevalence / Risk Factors / Stomach Neoplasms
Hiroaki Toba, Kazuya Kondo, Yohei Sadohara, Hideki Otsuka, Masami Morimoto, Koichiro Kajiura, Yasushi Nakagawa, Mitsuteru Yoshida, Yukikiyo Kawakami, Hiromitsu Takizawa, Koichiro Kenzaki, Shoji Sakiyama, Yoshimi Bando and Akira Tangoku : 18F-fluorodeoxyglucose positron emission tomography/computed tomography and the relationship between fluorodeoxyglucose uptake and the expression of hypoxia-inducible factor-1, glucose transporter-1 and vascular endothelial growth factor in thymic epithelial tumours., European Journal of Cardio-Thoracic Surgery, Vol.44, No.2, e105-e112, 2013.
(要約)
OBJECTIVES: The objective of this study was to evaluate the usefulness of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the relationships among the expressions of hypoxia-inducible factor-1 (HIF-1), glucose transporter-1 (Glut-1) and vascular endothelial growth factor (VEGF), histological type, other clinical factors and FDG uptake in thymic epithelial tumours. METHODS: Thirty-three patients who underwent FDG-PET/CT before treatment were reviewed. All types of tumours were reclassified into three subgroups: low-risk thymomas (types A, AB and B1), high-risk thymomas (types B2 and B3) and thymic carcinomas. Tumour contour, pattern of FDG uptake, tumour size and maximum standardized uptake value (SUVmax) were obtained. Expressions of HIF-1, Glut-1 and VEGF were analysed immunohistochemically, and these expressions were evaluated using grading scales. RESULTS: FDG uptake was visually recognized in all (100%) tumours. A homogeneous pattern of FDG uptake was increasingly observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas (P = 0.016). SUVmax for thymic carcinomas was significantly higher than that for thymomas (P = 0.008). With the optimal cut-off value of SUVmax of 5.6, the sensitivity, specificity and accuracy for diagnosing thymic carcinoma were 0.75, 0.80 and 0.79, respectively. Regarding the mean scoring of HIF-1, Glut-1 and VEGF, increasing trends were observed in the order of low-risk thymomas to high-risk thymomas to thymic carcinomas. Tumour size revealed a significant correlation with SUVmax (r = 0.60, P < 0.001), and the expression of HIF-1 showed a moderate association, but the expression of Glut-1 showed no correlation with SUVmax. Regarding correlations between the expression of the three markers, there were moderate associations between HIF-1 and Glut-1, and HIF-1 and VEGF, and a significant correlation between Glut-1 and VEGF (r = 0.60, P < 0.001). In type B1 thymoma, HIF-1 and Glut-1 were partly expressed in non-neoplastic immature lymphocytes. CONCLUSIONS: FDG-PET/CT should be performed in patients with tumours in the anterior mediastinum because the pattern of FDG uptake and SUVmax are useful in the differential diagnosis of thymic epithelial tumours. Furthermore, the expressions of HIF-1, Glut-1 and VEGF might be associated with malignancy of thymic epithelial tumours. In contrast, FDG uptake might be dependent on tumour size rather than Glut-1 overexpression.
Yoshimi Bando, Tetsuyuki Takahashi, Hisanori Uehara, Teruyoshi Kageji, Shinji Nagahiro and Keisuke Izumi : Autopsy case of amebic granulomatous meningoencephalitis caused by Balamuthia mandrillaris in Japan, Pathology International, Vol.62, No.6, 418-423, 2012.
(要約)
Balamuthia mandrillaris is a free-living ameba that causes amebic encephalitis. Herein, we report an autopsy case of Balamuthia encephalitis proven with polymerase chain reaction (PCR) and immunohistochemistry from paraffin-embedded brain biopsy specimens. A 68-year-old Japanese male presented at a hospital with progressive right hemiparesis approximately 3 months before his death. An open-brain biopsy specimen showed diffuse meningitis with massive coagulative necrosis. The perivascular spaces contained numerous lymphocytes, histiocytes and giant cells, although the etiology was not determined. The patient deteriorated into coma and died from cerebral herniation. Autopsy revealed abundant trophozoites and cysts in the subarachnoid and Virchow-Robin's spaces. Electron-micrographs of the amebic cysts showed a characteristic triple-walled envelope. The amebas were identified as Balamuthia mandrillaris based on immunohistochemical analysis from the autopsy and biopsy specimens. Primer sets designed to amplify approximately 200 bp bands of mitochondrial 16S rRNA gene of Balamuthia by PCR produced positive results from the biopsy specimens but negative results from the autopsy specimens. In summary, PCR to amplify shorter segments of DNA may be of diagnostic value in detecting suspected cases of balamuthiasis in formalin-fixed, paraffin-embedded specimens. Increased awareness and timely diagnosis of Balamuthia encephalitis might lead to earlier initiation of therapy and improved outcome.
(キーワード)
Amebiasis / Balamuthia mandrillaris / Brain / Central Nervous System Protozoal Infections / Fatal Outcome / Humans / Japan / Magnetic Resonance Imaging / Male / Treatment Failure
Yota Yamamoto, Yamai Hiromichi, Jun-ichi Seike, Takahiro Yoshida, Hirokazu Takechi, Yoshihito Furukita, Koichiro Kajiura, Minato Takuya, Yoshimi Bando and Akira Tangoku : Prognosis of Esophageal Squamous Cell Carcinoma in Patients Positive for Human Epidermal Growth Factor Receptor Family Can Be Improved by Initial Chemotherapy with Docetaxel, Fluorouracil and Cisplatin, Annals of Surgical Oncology, Vol.19, No.3, 757-765, 2012.
(要約)
The human epidermal growth factor receptor (HER) family, Ki-67 and p53 are important biomarkers for several malignancies. However, few studies have examined the role of these in prognosis and therapeutic sensitivity of esophageal squamous cell carcinoma (ESCC). The efficacy of triple-drug combination therapy with docetaxel, fluorouracil and cisplatin has recently been expected for ESCC. Subjects comprised 142 patients with ESCC who underwent operation (OP group, n = 54), neoadjuvant chemotherapy with docetaxel, fluorouracil, and cisplatin (DFP therapy) followed by operation (NAC group, n = 37) or initial systemic DFP therapy (CT group, n = 51) between January 2004 and December 2010. Immunohistochemical expressions of epidermal growth factor receptor (EGFR), HER2, HER3, Ki-67, and p53 were evaluated and compared with prognosis and sensitivity to DFP therapy. Positive correlations existed between EGFR, HER2, and HER3 expressions. In the OP group, EGFR was independently associated with postoperative recurrence in multivariate analysis (P = .036). In the NAC group, EGFR correlated with pathological response to DFP therapy (P = .004). In the CT group, EGFR, HER2, and HER3 correlated with clinical response to DFP therapy and EGFR was independently associated with favorable prognosis in multivariate analysis (P = .022). EGFR represents a predictor of postoperative recurrence and sensitivity to triple-drug combination therapy including a taxane. EGFR-positive patients may show improved prognosis with taxane combination chemotherapy and molecular targeted therapy for HER family members.
Hiroaki Toba, Shoji Sakiyama, Koichiro Kenzaki, Yukikiyo Kawakami, Koh Uyama, Yoshimi Bando and Akira Tangoku : Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis, Journal of Thoracic and Cardiovascular Surgery, Vol.143, No.6, 1429-1435, 2012.
(要約)
Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung. Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated. Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis. Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung.
Takuya Minato, Yota Yamamoto, Jun-ichi Seike, Takahiro Yoshida, Hiromichi Yamai, Hirokazu Takechi, Yasuhiro Yuasa, Yoshihito Furukita, Masakazu Goto, Yoshimi Bando and Akira Tangoku : Aldehyde Dehydrogenase 1 Expression is Associated with Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma., Annals of Surgical Oncology, Vol.20, No.1, 209-217, 2012.
(要約)
BACKGROUND: Aldehyde dehydrogenase 1 (ALDH1) and CD44 act as important biomarkers in several solid tumors. However, few studies have examined the relationships between ALDH1 expression and the prognosis and clinical characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: This study was a retrospective case-control study and included 152 patients with ESCC. A total of 56 patients underwent surgery (OP group), 40 patients received neoadjuvant chemotherapy involving weekly docetaxel plus 5-fluorouracil and low-dose cisplatin (DFP therapy) prior to undergoing surgery (NAC group), and 56 patients received initial systemic DFP therapy (CT group). The ALDH1 and CD44 immunohistochemical expression levels of each tumor were evaluated and compared with the prognosis and clinical characteristics of the ESCC patients. RESULTS: In the OP and NAC groups, multivariate analysis found that ALDH1 was independently associated with postoperative recurrence and prognosis (OP group, P = 0.004 and 0.016, respectively; NAC group, P = 0.026 and 0.014, respectively). In addition, CD44 was found to be associated with postoperative recurrence in the OP group and prognosis in the NAC group (P = 0.024 and 0.047, respectively). Among the ALDH1-negative clinical stage II/III patients, the OP and NAC groups displayed better prognoses than the CT group (P < 0.001). However, among the ALDH1-positive clinical stage II/III patients, the OP and NAC groups displayed poorer prognoses than the CT group (P = 0.049). CONCLUSIONS: ALDH1 was found to be a predictor of postoperative recurrence and prognosis in ESCC, and CD44 might be a predictor of recurrence and prognosis. ALDH1 expression might affect the treatment strategy for ESCC.
Qi Li, Wei Wang, Tadaaki Yamada, Kunio Matsumoto, Katsuya Sakai, Yoshimi Bando, Hisanori Uehara, Yasuhiko Nishioka, Saburo Sone, Shotaro Iwakiri, Kazumi Itoi, Teruhiro Utsugi, Kazuo Yasumoto and Seiji Yano : Pleural mesothelioma instigates tumor-associated fibroblasts to promote progression via a malignant cytokine network., The American Journal of Pathology, Vol.179, No.3, 1483-1493, 2011.
(要約)
The tumor microenvironment is crucial to the progression of various malignancies. Malignant pleural mesothelioma (MPM), which originates from the pleura, grows aggressively in the thoracic cavity. Here we describe an orthotopic implantation SCID mouse model of MPM and demonstrate that α-SMA-positive fibroblast-like cells accumulate in the tumors produced by the human MPM cell lines MSTO-211H and Y-Meso-14. We assessed the interaction between MPM cells and their microenvironments, focusing on tumor-associated fibroblasts. MSTO-211H and Y-Meso-14 cells produced fibroblast growth factor-2 (FGF-2) and/or platelet-derived growth factor-AA (PDGF-AA); they also enhanced growth, migration, and production of hepatocyte growth factor (HGF) by human lung fibroblast MRC-5 cells. MRC-5 cells stimulated HGF-mediated growth and migration of MSTO-211H and Y-Meso-14 cells in an in vitro coculture system. In the orthotopic model, tumor formation by MSTO-211H and Y-Meso-14 cells was significantly inhibited by TSU-68, an inhibitor of FGF, VEGF, and PDGF receptors; imatinib, an inhibitor of PDGF receptors; and NK4, an antagonist of HGF. Histological analyses of clinical specimens from 51 MPM patients revealed considerable tumor-associated fibroblasts infiltration and expression of HGF, together with FGF-2 or PDGF-AA, in tumors. These findings indicate that MPM instigates tumor-associated fibroblasts, promoting tumor progression via a malignant cytokine network. Regulation of this cytokine network may be therapeutically useful for controlling MPM.
Hongchao Shan, Tetsuyuki Takahashi, Yoshimi Bando, Keisuke Izumi and Hisanori Uehara : Inhibitory effect of soluble PDGFRbeta on intraosseous growth of breast cancer cells in nude mice, Cancer Science, Vol.102, No.10, 1904-1910, 2011.
(要約)
Bone metastasis is a frequent complication of advanced breast cancer. On the basis of functional and molecular evidence, signaling mediated by the binding of platelet-derived growth factor (PDGF)-BB and -DD to PDGF receptor β (PDGFRβ) is critical for the survival and growth of metastatic breast cancer cells within the bone microenvironment. In this study, we propose a new approach to blocking PDGFRβ signaling using soluble PDGFRβ (sPDGFRβ) as a decoy receptor for PDGF-BB and -DD secreted from tumor cells and bone marrow stromal cells. A bone-seeking TNBCT/Bo cell line was established by in vivo selection from TNBCT human breast cancer cells, which are negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 protein expression. The TNBCT/Bo cells were transfected with a mammalian expression vector encoding the extracellular domain of PDGFRβ. A stable transfectant (TNBCT/Bo-sPDGFRβ) grew at a similar rate to that of control cells under normal culture conditions, although growth stimulation of human fibroblasts with PDGF-BB was neutralized by the culture medium from TNBCT/Bo-sPDGFRβ cells. Intratibial injection of TNBCT/Bo-sPDGFRβ cells into athymic nude mice resulted in a significant decrease in tumor incidence compared with control mice (P < 0.01). This attenuated growth correlated with decreased cancer cell proliferation, angiogenesis, and recruitment of stromal cells, and with an increase in the number of apoptotic cells. These findings suggest that sPDGFRβ is useful for the treatment of breast cancer bone metastasis.
Misako Nakagawa, Yoshimi Bando, Taeko Nagao, Masami Morimoto, Chikako Takai, Takamasa Ohnishi, Junko Honda, Takuya Moriya, Keisuke Izumi, Masako Takahashi, Mitsunori Sasa and Akira Tangoku : Expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A in triple-negative breast cancer., Anticancer Research, Vol.31, No.6, 2389-2393, 2011.
(要約)
Elucidation of the biological features of triple negative breast cancer (TNBC) is important for deciding treatment strategies. The expression of a number of biomarkers in TNBC was analyzed to elucidate those features. The subjects were 134 TNBC patients. Immunohistochemical staining was employed to analyze for eight biomarkers: cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR), p53, Ki-67 antigen (Ki-67), E-cadherin, N-cadherin, topoisomerase 2 alpha (TOP2A) and B-cell lymphoma 2 (BCL-2), which were then correlated with the nuclear grade (NG), tumor diameter, and the presence/absence of lymph node metastasis, distant recurrence and lymphatic infiltration. Significantly more high than low NG TNBC exhibited positive p53, Ki-67, E-cadherin and TOP2A. High N-cadherin and TOP2A expression was shown significantly in TNBC with lymphatic infiltration, and N-cadherin was also significantly positively expressed in node metastasis-positive cases. EGFR and CK5/6 were positively expressed in high NG TNBC, but not significantly. Analysis for expression of p53, Ki-67, E-cadherin, N-cadherin and TOP2A is meaningful for deciding treatment strategies for TNBC.
(キーワード)
Antigens, CD / Antigens, Neoplasm / Breast Neoplasms / Cadherins / DNA Topoisomerases, Type II / DNA-Binding Proteins / Female / Humans / Immunohistochemistry / Ki-67 Antigen / Middle Aged / Receptor, erbB-2 / Receptors, Estrogen / Receptors, Progesterone / Tumor Suppressor Protein p53
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21737670
Misako Nakagawa, Yoshimi Bando, Taeko Nagao, Chikako Takai, Takamasa Ohnishi, Junko Honda, Takuya Moriya, Keisuke Izumi, Masako Takahashi, Akira Tangoku and Mitsunori Sasa : Among triple-negative breast cancers, HER2(0) breast cancer shows a strong tendency to be basal-like compared with HER2(1+) breast cancer: preliminary results., Breast Cancer, Vol.19, No.1, 54-59, 2011.
(要約)
Diagnosis of triple-negative breast cancer (ER-negative, PgR-negative, HER2-negative; TNBC) is performed by means of immunohistological staining. HER2-negative includes HER2(0) and HER2(1+), based on differences in the staining intensity, but there have been no reports on comparison of these two types in TNBC. Accordingly, this study was designed to investigate the possible differences in the biological characteristics of HER2(0) breast cancer and HER2(1+) breast cancer in TNBC. Tissue specimens from 89 TNBC patients were immunohistochemically stained for CK5/6, EGFR, p53, Ki67, E-cadherin, TOP2A and Bcl-2. The expressions of these markers and the clinicopathological findings were compared between the HER2(0) patient group and the HER2(1+) patient group. When either CK5/6 or EGFR was positive, the specimen was judged to be the basal-like phenotype of breast cancer. The percentages of CK5/6- and/or EGFR-positive specimens in the HER2(0) and HER2(1+) groups were 44.9 and 16.8%, respectively, showing that there was a significantly greater number of basal-like phenotype patients in the HER2(0) group (p < 0.01). The percentage of E-cadherin-positive specimens in the HER2(0) group was 66.6%, which was significantly greater than the 40.0% recorded in the HER2(1+) group (p < 0.05). The respective percentages of TOP2A-positive specimens in the HER2(0) and HER2(1+) groups were 55.0 and 30.0%, and the difference was statistically significant (p < 0.05). In TNBC, HER2(0) breast cancer showed a strong tendency to include more of the basal-like phenotype compared with HER2(1+) breast cancer. The staining results indicated the possibility that HER2(0) breast cancer and HER2(1+) breast cancer have different characteristics.
(キーワード)
Antigens, Neoplasm / Breast Neoplasms / Cadherins / DNA Topoisomerases, Type II / DNA-Binding Proteins / Female / Humans / Ki-67 Antigen / Middle Aged / Receptor, Epidermal Growth Factor / Receptor, erbB-2 / Receptors, Estrogen / Receptors, Progesterone / Tumor Markers, Biological / Tumor Suppressor Protein p53
Yoichiro Hirata, Hirotsugu Kurobe, Masashi Akaike, Fumio Chikugo, Takaki Hori, Yoshimi Bando, Chika Nishio, Mayuko Higashida, Yutaka Nakaya, Tetsuya Kitagawa and Masataka Sata : Enhanced inflammation in epicardial fat in patients with coronary artery disease., International Heart Journal, Vol.52, No.3, 139-142, 2011.
(要約)
It has been hypothesized that epicardial fat, a local visceral fat depot with close proximity to coronary arteries, may serve as a source of inflammatory cytokines and cells in coronary atherosclerotic lesions. Here, we characterized infiltration of inflammatory cells and expression of adipocytokines in epicardial adipose tissue in patients with and without coronary artery disease (CAD). Pare samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 8; non-CAD, n = 9). Inflammatory cell infiltration was investigated by immunohistochemical staining using antibodies against CD3, CD4, CD8 and CD68. Expression of adipocytokines was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Infiltration of macrophages and CD8-positive T cells in the epicardial adipose tissue in the CAD group was greater than that in the non-CAD group. In contrast, there was no significant difference between the two groups in the number of inflammatory cells in subcutaneous adipose tissue. No statistical difference could be found between the CAD group and the non-CAD group in the expression levels of adiponectin and inflammatory cytokines in epicardial adipose tissue. Our findings suggest that inflammatory cell infiltration is enhanced in epicardial adipose tissue, but not in subcutaneous fat, in patients with coronary artery disease. Chronic inflammation in epicardial fat may influence the pathogenesis of coronary atherosclerosis.
Aki Fuminori, Yoshimi Bando, Tetsuyuki Takahashi, Hisanori Uehara, Numoto Satoshi, Ito Sueyoshi, Sasa Mitsunori and Keisuke Izumi : A retrospective study on TS mRNA expression and prediction of the effects of adjuvant oral 5-fluorouracil in breast cancer, Oncology Letters, Vol.1, No.6, 981-988, 2010.
(要約)
Nucleic acid-metabolizing enzymes, such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT), have attracted attention as candidates for response determinants of 5-fluorouracil (5-FU). Whether the expression levels of these enzymes can be adopted as valuable parameters for 5-FU sensitivity in breast cancer has yet to be elucidated. In the present study, intratumoral mRNA expression of TS, DPD, TP and OPRT were determined in formalin-fixed paraffin-embedded surgical specimens collected from 217 breast cancer patients, using the Danenberg Tumor Profile method, which combines microdissection and real-time-polymerase chain reaction. The significance of these enzymes as prognostic and 5-FU efficacy-predicting factors was evaluated. Our data showed that a low DPD expression is related to a high nuclear grade and other factors including hormone receptor-negativity. Low expression levels of TP were found in hormone receptor-negative tumors. TS and OPRT expression were not related to various clinicopathological factors, but patients with a high TS mRNA expression showed a significantly poorer prognosis in cases where 5-FU was not administered. The efficacy of 5-FU was more significant when administered for more than 6 months in the group with a high TS mRNA expression. These data suggest that TS mRNA expression in breast cancer tissue is an ideal predictor of outcomes for patients with no administration of 5-FU, and of the efficacy of 5-FU.
Lu Elaine Wang, Zhi-Rong Qian, Masahiko Nakasono, Toshihito Tanahashi, Katsuhiko Yoshimoto, Yoshimi Bando, Eiji Kudo, Mitsuo Shimada and Toshiaki Sano : High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer., British Journal of Cancer, Vol.102, No.5, 908-915, 2010.
(要約)
BACKGROUND: The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC). METHODS: The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed. RESULTS: Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS. CONCLUSION: Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.
Koji Ono, Yuji Shishido, Hwan Ki Park, Tomoya Kawazoe, Sanae Iwana, Seongpil Chung, Rabab Mohamed Abou El-Magd, Kazuko YORITA, Mai Okano, Takeshi Watanabe, Nobuya Sano, Yoshimi Bando, Kunimasa Arima, Takashi Sakai and Kiyoshi Fukui : Potential pathophysiological role of D-amino acid oxidase in schizophrenia: immunohistochemical and in situ hybridization study of the expression in human and rat brain, Journal of Neural Transmission, Vol.116, No.10, 1335-1347, 2009.
(要約)
D-Amino acid oxidase (DAO) is a peroxisomal flavoenzyme that catalyzes oxidative deamination of a wide range of D-amino acids. Among the possible substrates of DAO in vivo, D-serine is proposed to be a neuromodulator of the N-methyl-D-aspartate (NMDA) type glutamate receptor. The gene for DAO was reported to be associated with schizophrenia. Since DAO is expected to be one of the key enzymes in the regulation of NMDA neurotransmission, the modulation of the enzyme activity is expected to be therapeutical for neuronal disorders. In search of the pathophysiological role of DAO, we analyzed the distribution of DAO mRNA and protein in the rat and human brain. In rat, the distribution of DAO mRNA was newly detected in choroid plexus (CP) epithelial cells in addition to glial cells of pons, medulla oblongata, and especially Bergmann glia of cerebellum. Moreover, to investigate how DAO expression level is altered in schizophrenia, we performed immunohistochemistry in the human brain. In agreement with the results in the rat brain, the immunoreactivity for DAO was detected in glial cells of rhombencephalon and in CP. Furthermore, higher level of DAO expression was observed in schizophrenic CP epithelial cells than that in non-schizophrenic cases. These results suggest that an increase in DAO expression in parts of the brain is involved in aberrant D-amino acid metabolism. In particular, gene expression of DAO in CP suggests that DAO may regulate D-amino acid concentration by modulating the cerebrospinal fluid and may be regarded as a potential therapeutic target for schizophrenia.
Tsuchigauchi Takeshi, Tetsuyuki Takahashi, Ohnishi Takamasa, Hirohisa Ogawa, Yoshimi Bando, Hisanori Uehara, Takizawa Tamatsu, Kaneda Shinya, Nakai Tokiko, Hiroshi Shiota and Keisuke Izumi : Low susceptibility to N-ethyl-N-nitrosourea-induced transplacental carcinogenesis in Long-Evans Cinnamon (LEC) rats, The Journal of Medical Investigation : JMI, Vol.56, No.3-4, 93-98, 2009.
(要約)
The Long-Evans Cinnamon (LEC) rat, an animal model of Wilson's disease, is resistant to a variety of chemical carcinogenesis except liver and colon. In the present study, N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was examined in male and female LEC, Long-Evans Agouti (LEA), a sibling line of the LEC rat, and F344 rats (n=21). ENU was administered to pregnant rats as a single s.c. injection at a dose of 60 mg/kg body weight on the 17th day after conception. Cerebral/spinal gliomas and trigeminal/spinal nerve schwannomas developed in both LEA and F344 rats at 30 weeks of age, but no nervous system tumors developed in LEC rats, the difference being statistically significant. Lung adenomas also developed in LEA and F344 rats, but not in LEC rats. Semiquantitative RT-PCR demonstrated that metallothionein (MT)1a, MT2 and O(6)-methylguanine-DNA methyltransferase (MGMT) mRNA levels in the liver of LEC rats were higher than those in F344 and LEA rats. In addition, Western blot analysis showed that MT (MT1 plus MT2) in the liver of LEC rats was also higher than that in other strains. Present results suggest that high levels of MT and/or MGMT contribute to the resistance to nitrosamine-induced carcinogenesis in LEC rats.
Hiromichi Yamai, Naruhiko Sawada, Takahiro Yoshida, Junnichi Seike, Hiromitsu Takizawa, Koichiro Kenzaki, Takanori Miyoshi, Kazuya Kondo, Yoshimi Bando, Yoshinari Ohnishi and Akira Tangoku : Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo., International Journal of Cancer, Vol.125, No.4, 952-960, 2009.
(要約)
The antineoplastic effects of combinations of anticancer drugs (5-fluorouracil, irinotecan and cisplatin) and triterpenes (ursolic acid, betulinic acid, oleanolic acid and a Japanese apricot extract (JAE) containing triterpenes) on esophageal squamous carcinoma cells were examined by the WST-8 (2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) assay in vitro and by an animal model in vivo. Triterpenes and JAE showed additive and synergistic cytotoxic effects, respectively, on esophageal squamous carcinoma cells (YES-2cells) by combinational use of 5-fluorouracil. JAE and 5-fluorouracil induced cell cycle arrest at G2/M phase and at S phase, respectively, and caused apoptosis in YES-2 cells. A new animal model of esophageal cancer causing tumor colonization of the peritoneal cavity and producing bloody ascites was made by injecting YES-2 cells into the peritoneal cavity of a severe combined immunodeficiency mouse. In this model, 5-fluorouracil inhibited colonization of tumor cells in the peritoneum. The addition of JAE to 5-fluorouracil augmented the suppression of experimental metastasis of the peritoneum. The numbers of peritoneal nodules of more than 2 mm in diameter in mice treated with 5-fluorouracil and JAE were less than those in mice treated with 5-fluorouracil alone or JAE alone. These results suggest that triterpenes, especially JAE, are effective supplements for enhancing the chemotherapeutic effect of 5-fluorouracil on esophageal cancer. (c) 2009 UICC.
We experienced 3 resected cases of pleomorphic carcinoma of the lung. Each cases were 74-year-old man (case 1), 74-year-old woman (case 2) and 69-year-old man (case 3). Two patients (case 1 and 2) were histologically diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with giant cell carcinoma. One patient (case 3) was similarly diagnosed as pleomorphic carcinoma composed of spindle cell carcinoma with adenocarcinoma and squamous cell carcinoma. Although lymph nodes metastasis were not recognized in all patients, invasion to vessels were recognized in 2 patients (case 1 and 3). In one patient (case 1), recurrence was recognized at contralateral side 1 month after surgery and he died of other disease 2 months after surgery. The other 2 patients were alive without recurrence 24 and 5 months after surgery. Recently it is reported that recurrence is recognized at early phase after surgery and prognosis is poor in a case with vessel invasions in spite of pathological NO state. Since one patient (case 3) had nonmetastatic lymph nodes with vessel invasions, careful observation is considered to be necessary.
(キーワード)
Aged / Aged, 80 and over / Carcinoma / Diagnostic Imaging / Fatal Outcome / Female / Humans / Lung Neoplasms / Male / Neoplasm Staging / Treatment Outcome
(文献検索サイトへのリンク)
● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19280950
Mayumi Takeuchi, Kenji Matsuzaki, Hiromu Nishitani, Eiji Kudo and Yoshimi Bando : Adenosarcoma of the uterus: magnetic resonance imaging characteristics., Clinical Imaging, Vol.33, No.3, 244-247, 2009.
(要約)
Adenosarcoma of the uterus is a rare tumor containing benign glandular epithelial and malignant mesenchymal elements. Typical adenosarcoma is a low-grade tumor, presents as a large polypoid mass occupying the endometrial cavity, and may protrude into the vaginal cavity. The presence of small hyperintense cysts scattered within the mass on T(2)-weighted imaging, reflecting glandular epithelial components, and relatively low signal intensity on high b-value diffusion-weighted imaging, reflecting its low-grade nature, may be characteristic findings.
Toshiyuki Hirose, Junko Honda, Yoshimi Bando, Mitsunori Sasa, Yukiko Hirose, Taeko Nagao and Akira Tangoku : A case of matrix-producing carcinoma of the breast., World Journal of Surgical Oncology, Vol.6, 60, 2008.
(要約)
BACKGROUND: Matrix-producing carcinoma (MPC) of the breast is one variant type of metaplastic carcinoma. The cellular origin of MPC remains unclear. It has been suggested the tumor cells in MPC have the combined characteristics of both epithelial cells and mesenchymal cells. Several reports suggested that the tumor cells in MPC might originate from the myoepithelial cells, but others suggested the origin was basal-like cells. CASE PRESENTATION: The patient was a 42-year-old Japanese female. A tumor of about 2 cm in diameter was noted in the right breast. CT revealed the circumference of the tumor to have a ring-like structure, and fine needle aspiration cytology indicated suspicion for malignancy. Breast-conserving surgery was performed. Histopathological studies showed carcinoma cells, having cuboidal to oval-shaped nucleus, were proliferating in cord-like and sheet-like structures in the periphery. In the central areas of the tumor, myxoedematous area was observed with cartilaginous matrix and necrosis. The diagnosis was a matrix-producing carcinoma. Immunohistochemical findings showed the tumor cells had the characteristics of both epithelial cells and mesenchymal cells, while being negative for estrogen receptor, progesterone receptor, Her2, myoepithelial cell markers and basal cell markers. CONCLUSION: The findings for our present patient and many of the other MPC patients reported in the published literature indicate that this breast cancer has the properties of both epithelial cells and mesenchymal cells. In addition, there is a possibility that matrix-producing tumor cells of our present patient may have a feature of undifferentiated cells.
Tetsuyuki Takahashi, Hisanori Uehara, Yoshimi Bando and Keisuke Izumi : Soluble EP2 neutralizes prostaglandin E2-induced cell signaling and inhibits osteolytic tumor growth, Molecular Cancer Therapeutics, Vol.7, No.9, 2807-2816, 2008.
(要約)
Prostaglandin E2 (PGE2) plays a key role in osteolytic bone metastasis as well as roles in inflammation, cell growth, and tumor development. PGE2 exerts its effects by binding and activating E-prostanoid receptor (EP). In this study, we propose a new approach for blocking EP-mediated cell signaling using a soluble chimeric EP2 fragment. Mammalian expression vectors encoding several human EP2 cDNAs were introduced into 293 cells and the culture medium was tested for their function as a decoy receptor for PGE2. PGE2 binding assays revealed that culture medium containing the second extracellular region of EP2 (FuEP2/Ex2) had binding activity. FuEP2/Ex2 neutralized PGE2-induced cyclic AMP production, cyclic AMP-responsive element binding protein phosphorylation, and subsequent induction of cyclooxygenase-2, interleukin (IL)-1beta, and IL-6 mRNAs. In human osteoblasts, this culture medium neutralized the induction of receptor activator of nuclear factor-kappaB ligand mRNA. A stable transfectant expressing FuEP2/Ex2 was established from human prostate cancer PC-3 cells (PC3-FuEP2/Ex2). PC3-FuEP2/Ex2 cells grew at similar rates to vector control cells under normal culture conditions, although PGE2-induced growth stimulation was suppressed. Intraosseous injection of PC3-FuEP2/Ex2 cells into the tibia of athymic nude mice revealed that the degrees of tumor growth and osteolysis were decreased compared with control cell-injected mice, with decreased osteoclasts and increased apoptotic cells. Furthermore, the cyclooxygenase-2, IL-1beta, and IL-6 mRNA levels were reduced in the tumor lesions. These data suggest that FuEP2/Ex2 is useful for treating osteolytic bone metastasis and cancers that depend on EP signaling for their growth and development.
Keiko Kataoka, Sachiko Ogasa, Tomomi Kuwahara, Yoshimi Bando, Mari Hagiwara, Hideki Arimochi, Shuusuke Nakanishi, Teruaki Iwasaki and Yoshinari Ohnishi : Inhibitory effects of fermented brown rice on induction of acute colitis by dextran sulfate sodium in rats., Digestive Diseases and Sciences, Vol.53, No.6, 1601-1608, 2008.
(要約)
Although the pathogenic mechanisms of inflammatory bowel diseases are not fully understood, colonic microbiota may affect the induction of colonic inflammation, and some probiotics and prebiotics have been reported to suppress colitis. The inhibitory effects of brown rice fermented by Aspergillus oryzae (FBRA), a fiber-rich food, on the induction of acute colitis by dextran sulfate sodium (DSS) were examined. Feeding a 5% and 10% FBRA-containing diet significantly decreased the ulcer and erosion area in the rat colon stained with Alcian blue. In another experiment, 10% FBRA feeding decreased the ulcer index (percentage of the total length of ulcers in the full length of the colon) and colitis score, which were determined by macroscopic observation. It also decreased myeloperoxidase activity in the colonic mucosa. Viable cell numbers of Lactobacillus in the feces decreased after DSS administration and was reversely correlated with severity of colitis, while the cell number of Enterobacteriaceae increased after DSS treatment and was positively correlated with colitis severity. These results indicate that FBRA has a suppressive effect on the induction of colitis by DSS and suggest FBRA-mediated modification of colonic microbiota.
Junko Honda, Mitsunori Sasa, Takuya Moriya, Yoshimi Bando, Toshiyuki Hirose, Masako Takahashi, Taeko Nagao and Akira Tangoku : Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive factors of therapeutic efficacy of capecitabine monotherapy for breast cancer-preliminary results., The Journal of Medical Investigation : JMI, Vol.55, No.1-2, 54-60, 2008.
(要約)
Capecitabine monotherapy was administered for 25 patients with advanced or recurrent breast cancer, and the clinical therapeutic efficacy and its relationship to expression of 5-fluorouracil-related enzymes (i. e., thymidine phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD)) were investigated. The expressions of TP, TS and DPD were determined by immunohistochemical staining techniques and rated using a scoring system of 1~4. The expression score for TP/DPD showed a statistically significant correlation with the clinical response, whereas the expression score for TP/TS also showed a correlation but it was not statistically significant. The number of patients was small, but the results revealed the potential of application of the TP/DPD expression score as a factor for predicting the efficacy of the drug in individual patients.
Hiroyuki Kose, Yoshimi Bando, Keisuke Izumi, Takahisa Yamada and Kozo Matsumoto : Epistasis between hyperglycemic QTLs revealed in a double congenic of the OLETF rat, Mammalian Genome, Vol.18, No.8, 609-615, 2007.
(要約)
Glucose homeostasis is believed to be regulated by multiple genetic components, in addition to numerous external factors. It is therefore crucial to dissect and understand what roles each causative gene plays in maintaining proper glucose metabolism. In OLETF (Otsuka Long-Evans Tokushima Fatty) rat, a model of polygenic type 2 diabetes, at least 14 quantitative trait loci (QTLs) influencing plasma glucose levels were identified. In congenic strains some of the OLETF allelic variants were shown to increase glucose levels. In this study the focus was on two of the hyperglycemic loci, Nidd1/of and Nidd2/of. Congenic rats possessing OLETF genome fragment at either locus showed similar levels of mild hyperglycemia. A newly established double congenic rat showed a further aggravation of hyperglycemia. The Nidd1/of locus was also shown to function in the reduction of plasma leptin levels and fat weights, while the Nidd2/of locus led to increased plasma insulin and fat weights. Interestingly, both plasma leptin and fat weights reverted to the control levels in the double congenic rat. These results indicate that there is an epistatic interaction between the two loci. However, it is unlikely that the abnormal level of enhanced glucose homeostasis is mediated, at least not directly, by leptin or fat mass.
Taeko Nagao, Yoshimi Bando, Mitsunori Sasa, Tadaoki Morimoto, Nobuya Sano, Toshiyuki Hirose and Akira Tangoku : False-positive in fine-needle aspiration cytology of breast disease can be reduced with p63 immunostaining- A preliminary report, Anticancer Research, Vol.26, No.6B, 4373-4378, 2006.
(要約)
Myoepithelial cells of the mammary gland are considered to be a key to distinguishing benign from malignant disease in fine-needle aspiration (FNA) cytology. However, identification of these cells with Papanicolaou staining is not easy. The identification of myoepithelial cells was investigated using p63 antibodies to carry out immunostaining of FNA specimens that had been used at the time of Papanicolaou staining for 37 patients who yielded false-positives in FNA. Positively-stained cells were observed in overlying cell clusters or the background in 67.6% of the patients. There is a possibility that over-diagnosis could have been avoided by performing p63 staining for these patients. The controls consisted of stamp samples of fresh specimens obtained from 23 patients at the time of surgery for invasive carcinoma and the results of p63 immunostaining did not reveal any positive staining of tumor cells. Accordingly, these results indicate that there is a strong likelihood that there is no invasive carcinoma when many p63-positive cells are observed in the tumor cell population or the background and that p63 immunostaining has the potential to aid in reducing false-positives at the time of FNA diagnosis of breast disease.
Koichiro Kenzaki, Shoji Sakiyama, Kazuya Kondo, Mitsuteru Yoshida, Yukikiyo Kawakami, Masatsugu Takehisa, Hiromitsu Takizawa, Takanori Miyoshi, Yoshimi Bando, Akira Tangoku and Mingyao Liu : Lung regeneration: implantation of fetal rat lung fragments into adult rat lung parenchyma., Journal of Thoracic and Cardiovascular Surgery, Vol.131, No.5, 1148-1153, 2006.
(要約)
OBJECTIVE: The capability of regeneration of lung tissues in adults is limited after chronic destruction. Bone marrow-derived stem cells, retinoic acid, growth factors, and other approaches have been attempted to promote or facilitate this process. We hypothesized that fetal lung tissues, with great potential for growth and differentiation, could be used for lung regeneration. METHODS: Day 17 fetal lung tissue fragments at the pseudoglandular stage of lung development from Lewis rats were implanted into adult Lewis rat lungs. For group 1, fetal lung fragments were injected into the adult left lung parenchyma; for group 2, fetal fragments were injected with the left lung partially resected; for group 3, adult fragments were injected; and for groups 4 and 5, fetal fragments were implanted into the omentum and subcutaneous tissue, respectively. RESULTS: The grafts implanted into pulmonary parenchyma were differentiated with opening of the alveolar space after 4 weeks and were advanced further with morphologic features similar to those of neonatal lungs after 8 and 12 weeks. The implants were connected with pulmonary circulation determined by means of perfusion with India ink. These changes appeared to be further enhanced in animals with partial lung resection that might have facilitated the maturation of implanted fetal lung tissues through mechanical factors, soluble factors, or both. Fetal lung tissues did not mature when implanted into the omentum or subcutaneous tissue. Adult lung fragments did not expand after being reimplanted back into the same animal. CONCLUSIONS: Fetal lung tissue might be an option for further investigation into lung regeneration.
Shino Niki, Kiyotaka Oshikawa, Yasuhiro Mouri, Fumiko Hirota, Akemi Matsushima, Masashi Yano, Hongwei Han, Yoshimi Bando, Keisuke Izumi, Masaki Matsumoto, Keiichi I. Nakayama, Noriyuki Kuroda and Mitsuru Matsumoto : Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice, The Journal of Clinical Investigation, Vol.116, No.5, 1292-1301, 2006.
(要約)
Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type 1 diabetes caused by autoimmune attack against beta cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than beta cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of autoantibody against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathological change, the animals were resistant to the development of diabetes. The results suggest that Aire not only is critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus.
Dan Kinoshita, Fumiko Hirota, Tsuneyasu Kaisho, Michiyuki Kasai, Keisuke Izumi, Yoshimi Bando, Yasuhiro Mouri, Akemi Matsushima, Shino Niki, Hongwei Han, Kiyotaka Oshikawa, Noriyuki Kuroda, Masahiko Maegawa, Minoru Irahara, Kiyoshi Takeda, Shizuo Akira and Mitsuru Matsumoto : Essential role of IkappaB kinase alpha in thymic organogenesis required for the establishment of self-tolerance., The Journal of Immunology, Vol.176, No.7, 3995-4002, 2006.
(要約)
IkappaB kinase (IKK) alpha exhibits diverse biological activities through protein kinase-dependent and -independent functions, the former mediated predominantly through a noncanonical NF-kappaB activation pathway. The in vivo function of IKKalpha, however, still remains elusive. Because a natural strain of mice with mutant NF-kappaB-inducing kinase (NIK) manifests autoimmunity as a result of disorganized thymic structure with abnormal expression of Rel proteins in the thymic stroma, we speculated that the NIK-IKKalpha axis might constitute an essential step in the thymic organogenesis that is required for the establishment of self-tolerance. An autoimmune disease phenotype was induced in athymic nude mice by grafting embryonic thymus from IKKalpha-deficient mice. The thymic microenvironment that caused autoimmunity in an IKKalpha-dependent manner was associated with defective processing of NF-kappaB2, resulting in the impaired development of thymic epithelial cells. Thus, our results demonstrate a novel function for IKKalpha in thymic organogenesis for the establishment of central tolerance that depends on its protein kinase activity in cooperation with NIK.
Noriyuki Kuroda, Tasuku Mitani, Naoki Takeda, Naozumi Ishimaru, Rieko Arakaki, Yoshio Hayashi, Yoshimi Bando, Keisuke Izumi, Takeshi Takahashi, Takashi Nomura, Shimon Sakaguchi, Tomoo Ueno, Yousuke Takahama, Daisuke Uchida, Shijie Sun, Fumiko Kajiura, Yasuhiro Mouri, Hongwei Han, Akemi Matsushima, Gen Yamada and Mitsuru Matsumoto : Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice, The Journal of Immunology, Vol.174, No.4, 1862-1870, 2005.
(要約)
Autoimmune regulator (AIRE) gene mutation is responsible for the development of organ-specific autoimmune disease with monogenic autosomal recessive inheritance. Although Aire has been considered to regulate the elimination of autoreactive T cells through transcriptional control of tissue-specific Ags in thymic epithelial cells, other mechanisms of AIRE-dependent tolerance remain to be investigated. We have established Aire-deficient mice and examined the mechanisms underlying the breakdown of self-tolerance. The production and/or function of immunoregulatory T cells were retained in the Aire-deficient mice. The mice developed Sjogren's syndrome-like pathologic changes in the exocrine organs, and this was associated with autoimmunity against a ubiquitous protein, alpha-fodrin. Remarkably, transcriptional expression of alpha-fodrin was retained in the Aire-deficient thymus. These results suggest that Aire regulates the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus, at least against this ubiquitous protein. Rather, Aire may regulate the processing and/or presentation of self-proteins so that the maturing T cells can recognize the self-Ags in a form capable of efficiently triggering autoreactive T cells. With the use of inbred Aire-deficient mouse strains, we also demonstrate the presence of some additional factor(s) that determine the target-organ specificity of the autoimmune disease caused by Aire deficiency.
Piyawan Bunpo, Keiko Kataoka, Hideki Arimochi, Haruyuki Nakayama, Tomomi Kuwahara, Yoshimi Bando, Keisuke Izumi, Usanee Vinitketkumnuen and Yoshinari Ohnishi : Inhibitory effects of Centella asiatica on azoxymethane-induced aberrant crypt focus formation and carcinogenesis in the intestines of F344 rats, Food and Chemical Toxicology, Vol.42, No.12, 1987-1997, 2004.
(要約)
Effects of the water extract of Centella asiatica Linn. on formation of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and intestinal tumorigenesis in male F344 rats were investigated. Treatment with the extract significantly decreased the number of larger ACF (with four or more crypts per focus) in the large intestine in the early stage, while the number of methylated DNA adducts was not decreased compared with that in the AOM-treated group. In the post-initiation stage, the extract significantly decreased the total number of ACF and the number of larger ACF, accompanied by a decrease in the 5-bromo-2'-deoxyuridine-labeling index and an increase in the induction of apoptotic cells in the colonic mucosa. The incidences of neoplasms, the numbers of adenocarcinomas in the small intestines and entire intestines, and sizes of neoplasms in the entire intestines in rats fed C. asiatica extract at a dose of 10 mg/kg were smaller than those in rats given AOM alone (p < 0.05). The extract at a dose of 100 mg/kg significantly reduced the multiplicity of neoplasms in the small intestine (p < 0.05). These results suggest that inhibition of the formation of AOM-induced ACF by C. asiatica extract is associated with modification of cell proliferation and induction of apoptosis in colonic crypts and that the extract has a chemopreventive effect on colon tumorigenesis.
Tomoyuki Yuasa, Rei Kakuhata, Kazuhiro Kishi, Toshiyuki Obata, Yasuo Shinohara, Yoshimi Bando, Keisuke Izumi, Fumiko Kajiura, Mitsuru Matsumoto and Yousuke Ebina : Platelet-derived growth factor stimulates glucose transport in skeletal muscles of transgenic mice specifically expressing PDGF receptor in the muscle, but does not affect blood glucose levels, Diabetes, Vol.53, No.11, 2776-2786, 2004.
(要約)
Insulin stimulates the disposal of blood glucose into skeletal muscle and adipose tissues by the translocation of GLUT4 from intracellular pools to the plasma membrane, and consequently the concentration of blood glucose levels decreases rapidly in vivo. Phosphatidylinositol (PI) 3-kinase and Akt play a pivotal role in the stimulation of glucose transport by insulin, but detailed mechanisms are unknown. We and others reported that not only insulin but also platelet-derived growth factor (PDGF) and epidermal growth factor facilitate glucose uptake through GLUT4 translocation by activation of PI 3-kinase and Akt in cultured cells. However, opposite results were also reported. We generated transgenic mice that specifically express the PDGF receptor in skeletal muscle. In these mice, PDGF stimulated glucose transport into skeletal muscle in vitro and in vivo. Thus, PDGF apparently shares with insulin some of the signaling molecules needed for the stimulation of glucose transport. The degree of glucose uptake in vivo reached approximately 60% of that by insulin injection in skeletal muscle, but blood glucose levels were not decreased by PDGF in these mice. Therefore, PDGF-induced disposal of blood glucose into skeletal muscle is insufficient for rapid decrease of blood glucose levels.
Yoshiko Kanezaki, Toshiyuki Obata, Rie Matsushima, Asako Minami, Tomoyuki Yuasa, Kazuhiro Kishi, Yoshimi Bando, Hisanori Uehara, Keisuke Izumi, Tasuku Mitani, Mitsuru Matsumoto, Yukari Takeshita, Yutaka Nakaya, Toshio Matsumoto and Yousuke Ebina : KATP Channel Knockout Mice Crossbred with Transgenic Mice Expressing a Dominant-Negative Form of Human Insulin Receptor have Glucose Intolerance but not Diabetes, Endocrine Journal, Vol.51, No.2, 133-144, 2004.
(要約)
Impaired insulin secretion and insulin resistance are thought to be two major causes of type 2 diabetes mellitus. There are two kinds of diabetic model mice: one is a K(ATP) channel knockout (Kir6.2KO) mouse which is defective in glucose-induced insulin secretion, and the other is a transgenic mouse expressing the tyrosine kinase-deficient (dominant-negative form of) human insulin receptor (hIR(KM)TG), and which has insulin resistance in muscle and fat. However, all of these mice have no evidence of overt diabetes. To determine if the double mutant Kir6.2KO/hIR(KM)TG mice would have diabetes, we generated mutant mice by crossbreeding, which would show both impaired glucose-induced insulin secretion and insulin resistance in muscle and fat. We report here that: 1) blood glucose levels of randomly fed and 6 h fasted double mutant (Kir6.2KO/hIR(KM)TG) mice were comparable with those of wild type mice; 2) in intraperitoneal glucose tolerance test (ipGTT), Kir6.2KO/hIR(KM)TG mice had an impaired glucose tolerance; and 3) during ipGTT, insulin secretion was not induced in either Kir6.2KO/hIR(KM)TG or Kir6.2KO mice, while the hIR(KM)TG mice showed a more prolonged insulin secretion than did wild type mice; 4) hyperinsulinemic euglycemic clamp test revealed that Kir6.2KO, Kir6.2KO/hIR(KM)TG and hIR(KM)TG mice, showed decreased whole-body glucose disposal compared with wild type mice; 5) Kir6.2KO, but not Kir6.2KO/hIR(KM)TG mice had some obesity and hyperleptinemia compared with wild type mice. Thus, the defects in glucose-induced insulin secretion (Kir6.2KO) and an insulin resistance in muscle and fat (hIR(KM)TG) were not sufficient to lead to overt diabetes.
Fumiko Kajiura, Shijie Sun, Takashi Nomura, Keisuke Izumi, Tomoo Ueno, Yoshimi Bando, Noriyuki Kuroda, Hongwei Han, Yi Li, Akemi Matsushima, Yousuke Takahama, Shimon Sakaguchi, Tasuku Mitani and Mitsuru Matsumoto : NF-κB-inducing kinase establishes self-tolerance in a thymic stroma-dependent manner, The Journal of Immunology, Vol.172, No.4, 2067-2075, 2004.
(要約)
Physical contact between thymocytes and the thymic stroma is essential for T cell maturation and shapes the T cell repertoire in the periphery. Stromal elements that control these processes still remain elusive. We used a mouse strain with mutant NF-kappaB-inducing kinase (NIK) to examine the mechanisms underlying the breakdown of self-tolerance. This NIK-mutant strain manifests autoimmunity and disorganized thymic structure with abnormal expression of Rel proteins in the stroma. Production of immunoregulatory T cells that control autoreactive T cells was impaired in NIK-mutant mice. The autoimmune disease seen in NIK-mutant mice was reproduced in athymic nude mice by grafting embryonic thymus from NIK-mutant mice, and this was rescued by supply of exogenous immunoregulatory T cells. Impaired production of immunoregulatory T cells by thymic stroma without normal NIK was associated with altered expression of peripheral tissue-restricted Ags, suggesting an essential role of NIK in the thymic microenvironment in the establishment of central tolerance.
Yukiko Hiasa, Makoto Kunishige, Takao Mitsui, Shunsuke Kondo, Rika Kuriwaka, Shizuka Shigekiyo, Takanori Kanematsu, Nobuo Satake, Yoshimi Bando, Akira Kondo, Itsuro Endo, Yasushi Oshima and Toshio Matsumoto : Complicated paraneoplastic neurological syndromes: a report of two patients with small cell or non-small cell lung cancer, Clinical Neurology and Neurosurgery, Vol.106, No.12, 47-49, 2003.
(要約)
Paraneoplastic neurological syndromes are frequently associated in patients with small cell lung cancer (SCLC) and antineuronal antibodies are involved in the autoimmune mechanism. Multiple syndromes are sometimes complicated in a single patient with SCLC. However, little is known about non-SCLC-associated neurological manifestations. We report two patients with complicated paraneoplastic neurological syndromes. Patient 1 showed paraneoplastic limbic encephalitis (PLE), paraneoplastic sensory neuropathy (PSN) and Lambert-Eaton myasthenic syndrome (LEMS) associated with SCLC. Patient 2 developed opsoclonus-ataxia and probable PLE associated with non-SCLC. Analysis of various antineuronal antibodies revealed that anti-Hu and P/Q-type voltage-gated calcium channel (VGCC) antibodies were positive in Patient 1 but any antibodies were not in Patient 2. Brain MRI demonstrated high intensity signals in temporal lobes particularly on fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted images. These findings suggest that complicated paraneoplastic neurological syndromes occur in non-SCLC as well as SCLC and that unidentified antineuronal autoantibodies may underlie the pathophysiology.
(キーワード)
paraneoplastic neurological syndromes / lung cancer
A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS(-/-) mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS(-/-) mice was increased over that of APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.
Takanori Kanematsu, Seiji Yano, Hisanori Uehara, Yoshimi Bando and Saburo Sone : Phosphorylation, but not overexpression, of epidermal growth factor receptor is associated with poor prognosis of non-small cell lung cancer patients, Oncology Research, Vol.13, No.5, 289-298, 2003.
(要約)
Epidermal growth factor receptor (EGFR) is commonly overexpressed in non-small cell lung cancer (NSCLC) and its tyrosine kinase phosphorylation is thought to be an ideal target in the treatment of patients with NSCLC. In the present study, we examined surgically obtained specimens from a series of 36 NSCLC patients for expression of EGFR, phosphorylated EGFR (p-EGFR), and HER2 by immunohistochemistry, and also examined the correlation with clinical characteristics. The positive rate of EGFR, p-EGFR, and HER2 was 97.2%, 44.4%, and 88.6%, respectively, and the overexpression rate was 80.6%, 0.0%, and 27.8%, respectively. EGFR overexpression and phosphorylation were seen at almost the same rate in each histological type of squamous and nonsquamous cell carcinoma (squamous vs. nonsquamous; 78.6% vs. 81.8% for EGFR, 35.7% vs. 50.0% for p-EGFR), while HER2 overexpression was seen less frequently in squamous cell carcinoma than in nonsquamous cell carcinoma (0.0% vs. 45.5%, P = 0.003). Univariate analysis revealed that EGFR overexpression was related to good performance status (P = 0.038) but not related to EGFR phosphorylation. EGFR phosphorylation was correlated to short time to progression (TTP) (P = 0.002) and poor prognosis (P = 0.002), although EGFR overexpression, HER2 overexpression, or EGFR-HER2 coexpression were not correlated to TTP or survival. Bivariate analysis showed EGFR phosphorylation was related to short TTP and poor prognosis both in early and advanced stages. Multivariate analyses confirmed that clinical stage, performance status, and p-EGFR expression were independently associated with increasing risk of short TTP and poor prognosis. These results suggest that phosphorylation, but not overexpression, of EGFR may be an important predictor for clinical outcome of NSCLCs.
Yoshimi Bando, Tetsuya Kitagawa, Hisanori Uehara, Nobuya Sano, Nobuo Satake, Y Onose, Takashi Kitaichi, Osamu Miki, Itsuo Katoh and Keisuke Izumi : So-called mesothelial/monocytic incidental cardiac excrescences obtained during valve replacement surgery: report of three cases and literature review., Virchows Archiv, Vol.437, No.3, 331-335, 2000.
(要約)
We present three cases of so-called mesothelial/monocytic incidental cardiac excrescences (MICE) of the heart and a brief review of related literature. Case 1 was a 51-year-old woman who underwent mitral- and aortic-valve replacement. A tissue sample was submitted as a thrombus attached to the left atrial endocardium. Case 2 was a 69-year-old woman who underwent mitral-valve replacement. The sample was incidentally obtained as whitish clot-like fragments, but its exact origin was not known. Case 3 was a 68-year-old woman who underwent mitral-valve replacement for suspected infective endocarditis. The sample adherent to the pericardium was removed after valvular surgery. Histologically, these lesions were composed of a mixture of plump histiocytoid cells, a papillary arrangement of cuboidal cells, various sized vacuoles, and fibrin. The nests of cuboidal cells resembled cancer cells but showed features of mesothelial cells and no proliferative activity, immunohistochemically or ultrastructurally. In all cases, a suction tube placed in the left atrium was occasionally used to remove overflowing intrapericardial fluid during the surgery. The tip of the suction tube was covered with spiral wire, which is likely to transfer the stripped pericardial mesothelial cells to the left atrium. The significance of MICE is their possibility of being misdiagnosed as metastatic carcinoma by pathologists and a risk of arterial embolization by mesothelial debris clinically.
(キーワード)
Mesothelium / mesothelial/monocytic / incidental cardiac excrescences / cardiac surgery
Yoshimi Bando and Aki Kenji : Mechanisms of generation of oxygen radicals and reductive mobilization of ferritin iron by lipoamide dehydrogenase., The Journal of Biochemistry, Vol.109, 450-454, 1991.
111.
Yoshimi Bando and Kenji Aki : Superoxide-mediated release of iron from ferritin by some flavoenzymes., Biochemical and Biophysical Research Communications, Vol.168, No.2, 389-395, 1990.
Shogo Oota, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Yusuke Arakawa, Shuichi Iwahashi, Yu Saitou, Shin-ichiro Yamada, Yuuma Wada, Shoko Iwahashi, Yoshimi Bando and Mitsuo Shimada : Carbohydrate Antigen 19-9 Is a Prognostic Factor Which Correlates With HDAC1 and HIF-1 for Intrahepatic Cholangiocarcinoma., Anticancer Research, Vol.39, No.11, 6025-6033, 2019.
(要約)
Carbohydrate antigen 19-9 (CA19-9) is a poor prognostic marker in intrahepatic cholangiocarcinoma (IHCC). Previous studies have shown a link between hypoxia and CA19-9 in cancer, and we have previously demonstrated a correlation between HDAC1 and HIF-1 in IHCC. Here, we evaluated the expression and correlation of CA19-9 with HIF-1 and HDAC in IHCC. This study included 62 patients with IHCC who underwent primary hepatectomy at our department. Clinicopathological characteristics were examined. Immunohistochemical expression of HIF-1 and HDAC1 in specimens was quantitatively evaluated. Patients with high preoperative serum CA19-9 levels showed clinicopathological characteristics associated with tumour progression. High CA19-9 levels were associated with worse overall and recurrence-free survival. Univariate and multivariate analysis detected high CA19-9 levels as an independent poor prognostic factor for IHCC. Serum CA19-9 was significantly correlated with both HIF-1 and HDAC1 expression. High serum CA19-9 level is a poor prognostic factor for overall survival in IHCC and correlates with HIF-1 and HDAC1 expression.
Shoko Iwahashi, Masaaki Nishi, Toshiaki Yoshimoto, Hideya Kashihara, Chie Takasu, Takuya Tokunaga, Tomohiko Miyatani, Jun Higashijima, Kouzou Yoshikawa, Yuuma Wada, Yoshimi Bando and Mitsuo Shimada : A case of gastric heterotopic pancreas with gastroduodenal invagination., Surgical Case Reports, Vol.5, No.1, 110, 2019.
(要約)
Heterotopic pancreas (HP) is a rare disease commonly found incidentally on imaging studies, at endoscopy or at autopsy and can be associated with abdominal pain, vomiting, heart burn, gastric outlet obstruction, and even dysphagia in very rare cases. Heinrich's classified HP into three groups, types1-3, with Heinrich's type 3 HP the rarest and difficult to diagnose properly because it has only pancreatic ducts but has no islet and acini. The aim of this study is to report a case of gastric outlet obstruction caused by type 3 HP with gastroduodenal invagination with reference to the literature and diagnosed finally by immuno-histochemical analysis. The case presented is a 40-year-old male presenting with vomiting and abdominal pain. Computed tomography (CT) revealed a cystic mass in the upper abdomen and he was referred to the Tokushima University. Gastric fiber showed that the pedunculated mass originated from the stomach. An open distal gastrectomy was performed. Pathologically, there was small glands proliferation in the sub-mucosal (SM) layer which was membrane and cytoplasm (MUC)1 positive and muscle proliferation. This finding revealed the tumor as HP. Postoperative course was uneventful and the patient was discharged 12 days after surgery. The patient has remained well 12 months after surgery. HP should be considered in the differential diagnosis of SM tumors with gastroduodenal invagination even if this is a rare symptom.
Gizachew Yismaw Wubetu, Tohru Utsunomiya, Daichi Ishikawa, Shinichiro Yamada, Tetsuya Ikemoto, Yuji Morine, Shuichi Iwahashi, Yu Saitou, Yusuke Arakawa, Satoru Imura, Mami Kanamoto, Chengzhan Zhu, Yoshimi Bando and Mitsuo Shimada : High STAT4 expression is a better prognostic indicator in patients with hepatocellular carcinoma after hepatectomy., Annals of Surgical Oncology, Vol.21 Suppl 4, S721-8, 2014.
(要約)
Signal transducer and activator of transcription 4 (STAT4) mediates the intracellular effects of interleukin-12, leading to the production of interferon gamma (IFN-γ) and natural killer cells cytotoxicity. However, the clinical significance of STAT4 expression in patients with hepatocellular carcinoma (HCC) remains virtually unknown. A total of 66 HCC patients who underwent hepatectomy were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to determine STAT4 and IFNG mRNA expression levels. Tissue microarray-based immunohistochemistry was performed to examine CD8(+) T cells, STAT4, and INF-γ proteins. STAT4 was differentially expressed in tumor and nontumor tissues (P = 0.001) and positively correlated with IFNG expression (R (2) = 0.506, P < 0.05) and CD8(+) T cell infiltration (R (2) = 0.53, P < 0.001). Significant correlations were observed between STAT4 expression and tumor TNM stage (P = 0.043), hepatic venous invasion (P = 0.003), des-gamma-carboxy prothrombin (P = 0.011), tumor size (P = 0.036), and tumor differentiation (P = 0.034). Patients with high STAT4 expression had significantly better recurrence-free survival (P = 0.009). Low STAT4 expression (P = 0.030) and presence of portal venous invasion or hepatic venous invasion (P = 0.006) were independent risk factors for HCC recurrence. Downregulation of STAT4 in HCC indicated aggressive tumor behavior and predicted a worse clinical outcome. STAT4 might be a useful biomarker to identify patients at high risk of recurrence after hepatectomy.
Hirofumi Izaki, Masayuki Takahashi, Avirmed Shiirevnyamba, Ryuichi Taue, Hiroyuki Furumoto, Yoshimi Bando, Yoshihide Murakami, Tomoya Fukawa, Takahiro Koizumi, Yasuyo Yamamoto, Kunihisa Yamaguchi, Hiroyoshi Nakatsuji, Tomoteru Kishimoto, Tomoharu Fukumori and Hiro-omi Kanayama : Long-term recurrence-free survivor after laparoscopic removal of solitary adrenal metastasis from endometrial adenocarcinoma., The Journal of Medical Investigation : JMI, Vol.57, No.1-2, 174-177, 2010.
(要約)
Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection.
Yoshimi Bando, Tomoko Kobayashi, Yuko Miyakami, Satoshi Sumida, Takumi Kakimoto, Yasuyo Saijo and Hisanori Uehara : Triple-negative breast cancer and basal-like subtype : Pathology and targeted therapy., The Journal of Medical Investigation : JMI, Vol.68, No.3.4, 213-219, 2021.
(要約)
Triple-negative breast cancer (TNBC) is a heterogenous disease. For personalized medicine, it is essential to identify and classify tumor subtypes to develop effective therapeutic strategies. Although gene expression profiling has identified several TNBC subtypes, classification of these tumors remains complex. Most TNBCs exhibit an aggressive phenotype, but some rare types have a favorable clinical course. In this review, we summarize the classification and characteristics related to the various TNBC subtypes, including the rare types. Therapeutic methods that are suitable for each subtype are also discussed. Of the intrinsic breast cancer subtypes identified by gene expression analysis, the basal-like subtype specifically displayed decreased expression of an estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) cluster. We also present results that characterize the TNBC and basal-like phenotypes. TNBC may be categorized into four major classes : basal-like, immune-enriched, mesenchymal, and luminal androgen receptor. Therapeutic strategies for each subtype have been proposed along with newly approved targeted therapies for TNBC, such as immune checkpoint inhibitors. Understanding the classification of TNBC based on gene expression profiling in association with clinicopathological factors will facilitate accurate pathological diagnosis and effective treatment selection. J. Med. Invest. 68 : 213-219, August, 2021.
Immunohistochemical and fluorescence in situ hybridization(FISH)methods have been implemented to characterize triple negative breast cancer(TNBC)due to the lack of expression of estrogen receptor(ER)and progesterone receptor(PgR)as well as human epidermal growth factor receptor 2(HER2). TNBC exhibits adverse prognostic features, as both hormone and anti-HER2 therapies are ineffective, and thus chemotherapy is required. Among the intrinsic subtypes identified through gene expression analysis, the expression of ER and HER2cluster was found to be low specifically in the basal-like subtype. The basal-like subtype exhibits mammary myoepithelial cell(or basal cell)-like gene expression pattern. Most of the cells were triple negative in immunohistochemical method, and exhibited a characteristic expression of myoepithelial or basal cell markers, such as cytokeratin(CK)5/6, CK14, CK17, p63, and epidermal growth factor receptor(EGFR). Basal-like carcinoma is similar to TNBC in terms of histology and clinical features. Here, we have presented some of our study results indicating the characteristics of TNBC and basal-like phenotype. TNBC is a heterogeneous disease, and ongoing research is aimed at developing individualized treatment based on its biological characteristics. However, the effective treatment methods and therapeutic efficacy predictors are yet to be discovered. Recently, targeted therapies for TNBC, including the poly(ADP-ribose)polymerase(PARP)inhibitors for germline BRCA mutation-associated breast cancer and immune checkpoint inhibitors, have been approved. Moreover, the level of programmed death ligand1(PD-L1)in tumor-infiltrating immune cells is determined using the histopathological analysis of specimens to assess the effect of immune checkpoint inhibitors. In this review, the classification of TNBC subtypes and characteristics of basal-like carcinoma has been discussed.
(キーワード)
triple-negative breast cancer / basal-like / intrinsic subtype
A 40-year-old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin-based chemotherapy as postoperative adjuvant chemotherapy. The contrast-enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid-enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space-occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors.
Shuichi Iwahashi, Toru Utsunomiya, Mitsuo Shimada, Yu Saitou, Yuji Morine, Satoru Imura, Tetsuya Ikemoto, Hiroki Mori, Jun Hanaoka and Yoshimi Bando : High expressions of cancer stem cell markers in cholangiolocellular carcinoma., Surgery Today, Vol.43, No.6, 654-660, Jun. 2013.
(要約)
Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. CLC may have stronger features derived from HpSCs than an intermediate type of CHC.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : Dynamic contrast-enhanced magnetic resonance imaging of endometrial cancer with/without squamous differentiation, ISMRM2022, London, May 2022.
2.
Tamaki Otani, Hitoshi Ikushima, Yoshimi Bando, Kenmei Kuwahara, Hideki Otsuka, Kazuya Kondo and Hirokazu Miyoshi : Efficacy of 18F-fluorothymidine and 18F-fluorodeoxyglucose Positron Emission Tomography in Determining a Radiotherapy Effect., Annual Congress of the European Association of Nuclear Medicine, Oct. 2021.
3.
Mayumi Takeuchi, Kenji Matsuzaki, Yoshimi Bando and Masafumi Harada : Diagnostic and Therapeutic Strategy for Endometrial Carcinomas of the Uterus by Advanced MR Techniques, RSNA2012, Chicago, Nov. 2012.
4.
中川 美砂子, Morimoto Masami, Ikeda Mayumi, Misaki Mariko, 坂東 良美, Sasa Mitsunori, 丹黒 章 : PROGNOSTIC BIOMARKERS IN TRIPLE NEGATIVE BREAST CANCER, The Sixth International Symposium on Hormonal Oncogenesis, 2010年9月.
5.
Kenji Matsuzaki, Mayumi Takeuchi, Hiromu Nishitani and Yoshimi Bando : Vessel-penetrating sign in the liver, ECR 2010, Wien, Mar. 2010.
6.
Kazuma Kiyotani, Taisei Mushiroda, Mitsunori Sasa, Takashi Yamakawa, Koichi Hirata, Minoru Okazaki, Shozo Ohsumi, Yuichi Takatsuka, Yoshimi Bando, Ikuko Sumitomo, Tatsuhiko Tsunoda, Naoya Hosono, Michiaki Kubo, Yusuke Nakamura and Hitoshi Zembutsu : Association of polymorphisms of CYP2D6 and other PK-related genes on recurrence-free survival in Japanese breast cancer patients receiving adjuvant tamoxifen therapy., 59th Annual Meeting, the American society of Human Genetics, Honolulu, Oct. 2009.
7.
Kazuma Kiyotani, Hitoshi Zembutsu, Taisei Mushiroda, Mitsunori Sasa, Takashi Yamakawa, Koichi Hirata, Minoru Okazaki, Shozo Ohsumi, Yuichi Takatsuka, Yoshimi Bando, Ikuko Sumitomo, Tatsuhiko Tsunoda, Naoya Hosono, Michiaki Kubo and Yusuke Nakamura : Effects of polymorphisms in CYP2D6 and PK-related genes on clinical efficacy of adjuvant tamoxifen treatment in Japanese breast cancer patients., Cold Spring Harbor Laboratory Pharmacogenomics meeting, London, Sep. 2009.
8.
Kazuma Kiyotani, Hitoshi Zembutsu, Taisei Mushiroda, Mitsunori Sasa, Koichi Hirata, Minoru Okazaki, Yuichi Takatsuka, Yoshimi Bando, Ikuko Sumitomo, Naoya Hosono, Michiaki Kubo and Yusuke Nakamura : Effects of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy., The American Society of Human Genetics 58th Annual Meeting (ASHG2008), Philadelphia, Nov. 2008.