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上原 慶一郎医学部附属病院 病理診断科講師
研究活動情報
■ 論文- Late-onset hypogonadism (LOH) syndrome is characterized by age-related testosterone deficiency and negatively affects the quality of life of older men. A promising therapeutic approach for LOH syndrome is transplantation of testosterone-producing Leydig-like cells (LLCs) derived from human induced pluripotent stem cells (hiPSCs). However, previous studies have encountered obstacles, such as limited cell longevity, insufficient testosterone production, and inefficiency of differentiation. To address these issues, we developed a novel protocol that includes forced NR5A1 expression, a cytokine cocktail promoting mesoderm differentiation, and a transitional shift from 3D to 2D cultures. The resultant cells survived on culture dishes for over 16 weeks, produced 22-fold more testosterone than the conventional method, and constituted a homogeneous population of LLCs with a differentiation efficiency exceeding 99% without purification. Furthermore, these LLCs were successfully engrafted subcutaneously into mice, resulting in increased serum testosterone levels. Our study will facilitate innovative therapeutic strategies for LOH syndrome.2025年01月, Stem cell reports, 102392 - 102392, 英語, 国際誌研究論文(学術雑誌)
- INTRODUCTION: Renal cell carcinoma with an inferior vena cava tumor thrombus is a challenging disease that requires a multimodal treatment approach. Pembrolizumab plus lenvatinib has displayed promising efficacy in metastatic renal cell carcinoma. CASE PRESENTATION: A 61-year-old man was diagnosed with metastatic renal cell carcinoma and a tumor thrombus adhering to the inferior vena cava wall by cine magnetic resonance imaging. After 6 months of pembrolizumab and lenvatinib therapy, tumor shrinkage was detected, excluding the advanced portion of the inferior vena cava thrombus, and nephrectomy and thrombectomy were performed. Adhesion of the tumor thrombus to the inferior vena cava wall was observed during surgery. Resection produced a remarkable pathological complete response with no viable cells in the resected specimens, including the thrombus site. CONCLUSION: This case highlights the potential of pembrolizumab plus lenvatinib for treating advanced renal cell carcinoma with an inferior vena cava thrombus and the utility of cine magnetic resonance imaging for evaluating thrombus adhesion to the inferior vena cava.2024年01月, IJU case reports, 7(1) (1), 60 - 63, 英語, 国際誌
- Objectives Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC. Methods We examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro. Results Among the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression. Conclusion Increased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC.Public Library of Science (PLoS), 2022年05月, PLOS ONE, 17(5) (5), e0266620 - e0266620, 英語, 国際誌研究論文(学術雑誌)
- Intestinal metaplasia is related to gastric carcinogenesis. Previous studies have suggested the important role of CDX2 in intestinal metaplasia, and several reports have shown that the overexpression of CDX2 in mouse gastric mucosa caused intestinal metaplasia. However, no study has examined the induction of intestinal metaplasia using human gastric mucosa. In the present study, to produce an intestinal metaplasia model in human gastric mucosa in vitro, we differentiated human-induced pluripotent stem cells (hiPSC) to gastric organoids, followed by the overexpression of CDX2 using a tet-on system. The overexpression of CDX2 induced, although not completely, intestinal phenotypes and the enhanced expression of many, but not all, intestinal genes and previously reported intestinal metaplasia-related genes in the gastric organoids. This model can help clarify the mechanisms underlying intestinal metaplasia and carcinogenesis in human gastric mucosa and develop therapies to restitute precursor conditions of gastric cancer to normal mucosa.2022年05月, iScience, 25(5) (5), 104314 - 104314, 英語, 国際誌研究論文(学術雑誌)
- Human gastric development has not been well studied. The generation of human pluripotent stem cell-derived gastric organoids (hGOs) comprising gastric marker-expressing epithelium without an apparent smooth muscle (SM) structure has been reported. We modified previously reported protocols to generate hGOs with muscularis mucosa (MM) from hiPSCs. Time course analyses revealed that epithelium development occurred prior to MM formation. Sonic hedgehog (SHH) and TGF-β1 were secreted by the epithelium. HH and TGF-β signal inhibition prevented subepithelial MM formation. A mechanical property of the substrate promoted SM differentiation around hGOs in the presence of TGF-β. TGF-β signaling was shown to influence the HH signaling and mechanical properties. In addition, clinical specimen findings suggested the involvement of TGF-β signaling in MM formation in recovering gastric ulcers. HH and TGF-β signaling from the epithelium to the stroma and the mechanical properties of the subepithelial environment may influence the emergence of MM in human stomach tissue.2022年04月, Stem cell reports, 17(4) (4), 820 - 834, 英語, 国際誌研究論文(学術雑誌)
- Late-onset hypogonadism (LOH) syndrome, due to a partial lack of testosterone, decreases the quality of life of older men. Testosterone is mainly secreted by Leydig cells in the testes. Leydig cell transplantation is expected to be a promising alternative to conventional testosterone replacement therapy for LOH syndrome. We herein report a simple and robust protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into Leydig-like cells by doxycycline-inducible overexpression of NR5A1 and treatment with a combination of 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP) and forskolin. The differentiated cells expressed the steroidogenic enzyme genes STAR, CYP11A1, CYP17A1, and HSD3B2 and the specific markers of adult Leydig cells HSD17B3, INSL3, and LHCGR. Furthermore, we confirmed the secretion of functional testosterone from the cells into the culture supernatant by a testosterone-sensitive cell proliferation assay. These findings showed that the hiPSCs were able to be differentiated into Leydig-like cells, supporting the expectation that hiPSC-derived Leydig-like cells can be novel tools for treating LOH syndrome.2021年12月, Endocrinology, 162(12) (12), 英語, 国際誌研究論文(学術雑誌)
- (一社)日本病理学会, 2021年03月, 日本病理学会会誌, 110(1) (1), 360 - 360, 日本語脾EBウイルス関連炎症性偽腫瘍が考えられた一例
- In the original publication of the article, the following errors were noted and corrected in this correction.2020年10月, Journal of gastroenterology, 55(10) (10), 1010 - 1011, 英語, 国内誌
- BACKGROUND: The esophagus is known to be derived from the foregut. However, the mechanisms regulating this process remain unclear. In particular, the details of the human esophagus itself have been poorly researched. In this decade, studies using human induced pluripotent stem cells (hiPSCs) have proven powerful tools for clarifying the developmental biology of various human organs. Several studies using hiPSCs have demonstrated that retinoic acid (RA) signaling promotes the differentiation of foregut into tissues such as lung and pancreas. However, the effect of RA signaling on the differentiation of foregut into esophagus remains unclear. METHODS: We established a novel stepwise protocol with transwell culture and an air-liquid interface system for esophageal epithelial cell (EEC) differentiation from hiPSCs. We then evaluated the effect of all-trans retinoic acid (ATRA), which is a retinoic acid receptor (RAR)α, RARβ and RARγ agonist, on the differentiation from the hiPSC-derived foregut. Finally, to identify which RAR subtype was involved in the differentiation, we used synthetic agonists and antagonists of RARα and RARγ, which are known to be expressed in esophagus. RESULTS: We successfully generated stratified layers of cells expressing EEC marker genes that were positive for lugol staining. The enhancing effect of ATRA on EEC differentiation was clearly demonstrated with quantitative reverse transcription polymerase chain reaction, immunohistology, lugol-staining and RNA sequencing analyses. RARγ agonist and antagonist enhanced and suppressed EEC differentiation, respectively. RARα agonist had no effect on the differentiation. CONCLUSION: We revealed that RARγ activation promotes the differentiation of hiPSCs-derived foregut into EECs.2020年08月, Journal of gastroenterology, 55(8) (8), 763 - 774, 英語, 国内誌研究論文(学術雑誌)
- For augmentation or reconstruction of urinary bladder after cystectomy, bladder urothelium derived from human induced pluripotent stem cells (hiPSCs) has recently received focus. However, previous studies have only shown the emergence of cells expressing some urothelial markers among derivatives of hiPSCs, and no report has demonstrated the stratified structure, which is a particularly important attribute of the barrier function of mature bladder urothelium. In present study, we developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium. The caudal hindgut, from which the bladder urothelium develops, was predominantly induced via the high-dose administration of CHIR99021 during definitive endoderm induction, and this treatment subsequently increased the expressions of uroplakins. Terminal differentiation, characterized by the increased expression of uroplakins, CK13, and CK20, was induced with the combination of Troglitazone + PD153035. FGF10 enhanced the expression of uroplakins and the stratification of the epithelium, and the transwell culture system further enhanced such stratification. Furthermore, the barrier function of our urothelium was demonstrated by a permeability assay using FITC-dextran. According to an immunohistological analysis, the stratified uroplakin II-positive epithelium was observed in the transwells. This method might be useful in the field of regenerative medicine of the bladder.2019年07月, Scientific reports, 9(1) (1), 10506 - 10506, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2019年04月, Journal of Urology, 英語[査読有り]研究論文(学術雑誌)
- (一社)日本病理学会, 2019年04月, 日本病理学会会誌, 108(1) (1), 449 - 449, 日本語心筋炎を発症した心筋組織に浸潤するマクロファージの免疫組織化学的評価
- Springer Science and Business Media {LLC}, 2019年03月, European Urology Supplements, 18(1) (1), e1763, 英語[査読有り]研究論文(学術雑誌)
- A 45-year-old woman was diagnosed with hepatosplenic T-cell lymphoma (HSTCL), a rare subtype of peripheral T-cell lymphoma. She received different types of chemotherapy, but disease progression was observed. To reduce the tumor burden before an unrelated bone marrow transplantation, combination chemotherapy consisting of the gemcitabine, carboplatin, and dexamethasone (GCD) was administered as bridging therapy, resulting in a reduction in the number of lymphoma cells. We were then able to perform bone marrow transplantation. Although she experienced some adverse events, she successfully achieved long-term remission. We herein report a successful case of HSTCL treated with unrelated stem cell transplantation following the GCD regimen as bridging chemotherapy.2019年03月, Intern Med., 58(5) (5), 707 - 712, 英語, 国内誌[査読有り]研究論文(学術雑誌)
- ROS proto-oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer is rare and comprises only 1% of lung adenocarcinoma cases. It has recently been reported to have good response to crizotinib, a tyrosine kinase inhibitor of anaplastic lymphoma kinase. Driver oncogene mutations with approved therapies seldom coexist with a high expression of Programmed death-ligand 1 (PD-L1). The present case report describes a rare case of ROS1 rearrangement with high-PD-L1-expressing occult lung adenocarcinoma. A 32-year-old woman presented with chest pain and a prolonged cough. Chest computed tomography (CT) revealed a 57×36-mm tumor in the mediastinum, with no tumors detected in other regions. Positron emission tomography (PET)-CT showed a strong fluorodeoxyglucose accumulation in the tumor (SUVmax 13.2). Mediastinal tumor resection was completely resected using a video-assisted thoracic surgery approach. Pathological examination showed the tumor cells were positive for thyroid transcription factor 1, Napsin-A, ROS1, and PD-L1 (tumor proportion score >99%). ROS1 rearrangement was confirmed by fluorescence in situ hybridization. The mediastinal tumor was diagnosed as mediastinal lymph node metastasis of ROS1-rearranged PD-L1 high-expression undifferentiated lung adenocarcinoma (pathological stage 3, TxN2M0). Two months after the operation, the CT scan showed multiple mediastinum lymph nodes metastases with rapid tumor growth. The patient achieved a complete response after three cycles of S-1 plus cisplatin with concurrent radiotherapy 60 Gy/30 Fr.2019年01月, Oncol Lett, 17(1) (1), 488 - 491, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- The clinicopathological and immunohistochemical characteristics of clinically occult extrapulmonary lymphangioleiomyomatosis in lymph nodes (LN-LAM) being dissected during surgical staging of pelvic malignancy have not been well investigated. We assessed samples from nine female patients (median age, 61). None had past or familial history of tuberous sclerosis and had LAM lesions other than LN such as lung. The primary malignancies included four endometrial endometrioid carcinomas, one endometrial carcinosarcoma, three ovarian serous carcinomas and one urothelial carcinoma. Median follow-up was 43 months. The number of affected LNs ranged from 1 to 15 (median, 2) with sizes ranging from 1 to 13 mm (median, 3.0). Six cases had clinically occult LN-LAM only within the pelvic LNs, two only within para-aortic LNs, and one within both pelvic and para-aortic lymph nodes. Immunohistochemically, LAM cells exhibited a strong diffuse positivity for β-catenin and E-cadherin in all nine cases. Clinically occult LN-LAM mainly affects peri- or post-menopausal women. On rare occasions, occult LN-LAM may manifest as systemic LAM, including in the lung. β-catenin and E-cadherin carry potential utility as additional diagnostic markers.2019年01月, Pathology international, 69(1) (1), 29 - 36, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- 2018年11月, Haematologica, 103(11) (11), e553-e556 - e556, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- (地独)神戸市民病院機構, 2018年03月, 神戸市立病院紀要, (56) (56), 71 - 72, 日本語肺腫瘍血栓性微小血管症(PTTM)による呼吸不全のため急激に死の転機をたどった舌下腺腺様嚢胞癌症例[査読有り]
- INTRODUCTION: Nivolumab has demonstrated efficacy against metastatic NSCLC. Four programmed cell death ligand 1 (PD-L1) immunohistochemistry (IHC) assay systems are available for identification of responders among patients with NSCLC, and these assays show some differing characteristics. Accordingly, in this study, we evaluated the ability of these assays to identify responders to nivolumab therapy. METHODS: We retrospectively analyzed patients with previously treated advanced NSCLC, who received nivolumab between January 2016 and September 2016. Specimens were stained using four PD-L1 IHC assays (28-8, 22C3, SP142, and SP263). We classified patients as having test results that were strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS 1%-49%), or negative (TPS <1%). RESULTS: A total of 40 patients with NSCLC and their specimens were analyzed. Analytical comparisons demonstrated good concordance of PD-L1-stained tumor cells among the 28-8, 22C3, and SP263 assays (weighted κ coefficient 0.64-0.71), whereas the SP142 assay showed lower concordance with other assays (weighted κ coefficient 0.39-0.55). Progression-free survival in patients showing strongly positive PD-L1 staining classified by 28-8, 22C3, and SP263 assays was significantly longer than that in patients with a negative result for PD-L1 staining. Predictive performance of response to nivolumab, as assessed by receiver operating characteristic analysis, was also equivalent among the 28-8, 22C3, and SP263 assays (area under the curve 0.75-0.82), whereas the SP142 assay exhibited lower predictive performance (area under the curve 0.68). CONCLUSIONS: The 28-8, 22C3, and SP263 PD-L1 IHC assays showed equivalent predictive performance, whereas the SP142 assay showed lower predictive performance.2018年03月, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 13(3) (3), 377 - 386, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- A 61-year-old man with a left renal mass, which was detected by ultrasound during a routine health examination, was referred to our department. The patient had a surgical history of two pneumothorax operations, and the patient's brother also had a history of pneumothorax surgery. A case of Birt-Hogg-Dubé (BHD) syndrome was suspected based on patient history. The pathological di泌尿器科紀要刊行会, 2018年03月, 泌尿器科紀要 = Acta urologica Japonica, 64(3) (3), 107 - 110, 日本語, 国内誌[査読有り]研究論文(学術雑誌)
- Reduced Tumour Proportion Scores for Programmed Cell Death Ligand 1 in Stored Paraffin Tissue Sections.BACKGROUND/AIM: We evaluated the effects of storage of formalin-fixed, paraffin-embedded (FFPE) sections on the tumour proportion score (TPS) for programmed cell death ligand 1 (PD-L1), as indicator in non-small cell lung cancer (NSCLC) tissues of treatment efficacy. MATERIALS AND METHODS: NSCLC postoperative specimens with PD-L1 TPS ≥50% were obtained and cut into five serial sections. One section was stained immediately, and four were stored at 4°C for 2, 4, 6, or 8 weeks. Slides were subjected to PD-L1 immunohistochemistry using the anti-PD-L1 clone 28-8. PD-L1 TPS were blindly evaluated by two independent pathologists. RESULTS: Twelve specimens (60 slides) were evaluated. After slide storage for 2, 4, 6, and 8 weeks, a TPS of <50% was obtained in five (41%), four (33%), seven (58%), and eight (67%) patients, respectively. CONCLUSION: TPS values for PD-L1 were reduced by long-term slide storage of FFPE specimens. Sectioned slides should be stained for PD-L1 without delay.2018年, Anticancer Research, 38(3) (3), 1401 - 1405, 英語, 国際誌[査読有り]研究論文(学術雑誌)
- Elsevier Inc., 2018年, Clinical Lung Cancer, 英語[査読有り]研究論文(学術雑誌)
- 2017年12月, Journal of Thoracic Oncology, 12(12) (12), 1798 - 1805, 英語[査読有り]研究論文(学術雑誌)
- 2017年11月, RESPIROLOGY, 22(8) (8), 1615 - 1621, 英語[査読有り]研究論文(学術雑誌)
- 2017年09月, SCIENTIFIC REPORTS, 7, 英語[査読有り]研究論文(学術雑誌)
- 金原出版, 2017年08月, 皮膚科の臨床, 59(9) (9), 1407 - 1410, 日本語著明な石灰化を伴う基底細胞癌の1例 (特集 悪性上皮系腫瘍)[査読有り]研究論文(学術雑誌)
- 2017年07月, LUNG CANCER, 109, 58 - 61, 英語[査読有り]研究論文(学術雑誌)
- (NPO)日本肺癌学会, 2017年06月, 肺癌, 57(3) (3), 242 - 242, 日本語Osimertinibが奏効した肺腺癌脈絡膜転移の1例
- (NPO)日本頭頸部外科学会, 2017年06月, 頭頸部外科, 27(1) (1), 117 - 121, 日本語[査読有り]研究論文(学術雑誌)
- (一社)日本呼吸器学会, 2017年03月, 日本呼吸器学会誌, 6(増刊) (増刊), 122 - 122, 日本語
- 日本頭頸部癌学会, 2017年, 頭頸部癌, 43(4) (4), 403 - 408, 日本語[査読有り]研究論文(学術雑誌)
- (NPO)日本肺癌学会, 2016年12月, 肺癌, 56(7) (7), 1065 - 1065, 日本語視野障害を契機に診断に至りアファチニブが奏効した肺腺癌脈絡膜転移の1例
- 2016年11月, BMC CANCER, 16, 英語[査読有り]研究論文(学術雑誌)
- 2016年05月, 日本腎臓学会誌, 58(3号) (3号), 313, 日本語消化管粘膜における炭酸ランタン沈着の様式研究論文(その他学術会議資料等)
- 一般社団法人 日本消化器外科学会, 2016年, 日本消化器外科学会雑誌, 49(11) (11), 1108 - 1116, 日本語[査読有り]研究論文(学術雑誌)
- 2016年, Clinical Journal of Gastroenterology, 英語The prospect of endoscopic submucosal dissection for early anal canal squamous cell carcinoma.[査読有り]研究論文(学術雑誌)
- <p>肛門管癌は比較的まれな疾患で,進行癌の状態で発見されることが多い.近年,早期食道癌と同様にNBI併用拡大内視鏡が早期肛門管扁平上皮癌の診断に有用であるとの報告があり,粘膜内癌であると考えれば食道癌と同様にESD(内視鏡的粘膜下層剥離術)による一括切除した症例も報告されている.当院では,NBI併用拡大内視鏡を用いて早期肛門管扁平上皮癌と診断した症例に対してESDを施行した.病理診断は粘膜内癌で脈管侵襲は陰性であり,追加治療なしで現在のところ無再発生存である.肛門管扁平上皮癌の局在診断には,食道癌と同様にNBI併用拡大内視鏡が有用であると考えられ,粘膜内癌であると診断できればESDにより一括切除できる可能性がある.</p>一般社団法人 日本消化器内視鏡学会, 2016年, 日本消化器内視鏡学会雑誌, 58(9) (9), 1426 - 1431, 日本語[査読有り]研究論文(学術雑誌)
- 2015年11月, LUNG CANCER, 90(2) (2), 364 - 368, 英語[査読有り]研究論文(学術雑誌)
- 日本病院歯科口腔外科協議会, 2015年06月, Hospital Dentistry & Oral-Maxillofacial Surgery, 27(1) (1), 29 - 34, 日本語副耳下腺由来が疑われた頬部多形腺腫の1例
- 2015年03月, PATHOLOGY INTERNATIONAL, 65(3) (3), 144 - 147, 英語[査読有り]研究論文(学術雑誌)
- 症例は92歳女性.貧血による労作時呼吸苦で入院し,消化管出血の精査目的で施行した造影CTで上部空腸に動脈相で濃染する小病変を認め,カプセル内視鏡でも同部位に血性腸液の貯留を認めた.ダブルバルーン内視鏡を施行し,上部空腸にoozingを呈する径5mmの発赤調の隆起性病変を認め,血管腫が疑われた.内視鏡的粘膜切除術を施行したところ,切除断端から拍動性出血を認めたが,内視鏡的止血術が可能であった.その後,貧血は改善を認め,再出血を認めなかった.病理組織検査では動静脈奇形という術前と異なる診断であったが,内視鏡的治療が可能であった.ダブルバルーン内視鏡によって診断・治療した小腸動静脈奇形は稀であるため報告する.一般社団法人 日本消化器内視鏡学会, 2015年, 日本消化器内視鏡学会雑誌, 57(10) (10), 2448 - 2454, 日本語[査読有り]研究論文(学術雑誌)
- 一般社団法人 日本消化器外科学会, 2015年, 日本消化器外科学会雑誌, 48(6) (6), 473 - 480, 日本語[査読有り]研究論文(学術雑誌)
- (一社)日本消化器外科学会, 2014年10月, 日本消化器外科学会雑誌, 47(Suppl.2) (Suppl.2), 220 - 220, 日本語術前に肝原発と診断し得たガストリノーマの1切除例
- 2014年06月, BMC PEDIATRICS, 14, 英語[査読有り]研究論文(学術雑誌)
- 2014年03月, 日本病理学会会誌, 103(1号) (1号), 309, 日本語頭頸部領域に発生した成人型横紋筋腫の2例研究論文(その他学術会議資料等)
- 2014年03月, 日本病理学会会誌, 103(1号) (1号), 385, 日本語婦人科郭清リンパ節内に偶発的に発見された微小なリンパ脈管筋腫症4例の報告研究論文(研究会,シンポジウム資料等)
- 2014年03月, 日本病理学会会誌, 103(1号) (1号), 272, 日本語肺門部肺外腫瘍として認められた近位型類上皮肉腫の1例研究論文(その他学術会議資料等)
- 2013年11月, ANNALS OF HEPATOLOGY, 12(6) (6), 969 - 973, 英語[査読有り]研究論文(学術雑誌)
- 2013年10月, 日本臨床細胞学会雑誌, 52(Suppl.2) (Suppl.2), 654, 日本語気管支擦過細胞診にてアレルギー性気管支肺アスペルギルス症が疑われた1症例研究論文(その他学術会議資料等)
- (一社)日本病理学会, 2013年04月, 日本病理学会会誌, 102(1) (1), 428 - 428, 日本語PTTM(pulmonary tumor thrombotic microangiopathy)の2剖検例[査読有り]
- 2013年04月, 日本病理学会会誌, 102(1号) (1号), 426, 日本語右肺末梢に発生した肺動脈内膜肉腫の一例研究論文(その他学術会議資料等)
- 2013年04月, 日本病理学会会誌, 102(1号) (1号), 451, 日本語粘表皮癌を合併した甲状腺低分化癌の1例研究論文(その他学術会議資料等)
- 2013年04月, 日本病理学会会誌, 102(1号) (1号), 395, 日本語神経線維腫症1型の若年男性に発症した中脳水道rossette-forming glioneuronal tumorの1例研究論文(その他学術会議資料等)
- 2013年04月, 日本病理学会会誌, 102(1号) (1号), 393, 日本語初発及び再発時に血管肉腫と神経鞘腫、再々発時に血管肉腫と髄膜腫の混合像を呈した小脳橋角部腫瘍の1例研究論文(その他学術会議資料等)
- 2013年04月, 日本病理学会会誌, 102(1号) (1号), 393, 日本語横紋筋様変化を伴った小脳血管芽腫の一例研究論文(その他学術会議資料等)
- 2013年04月, 日本病理学会会誌, 102(1号) (1号), 406, 日本語Embryonal hyperplasia of Bowman's capsular epitheliumを合併した終末期摘出腎の1例研究論文(その他学術会議資料等)
- 2012年10月, JOURNAL OF CLINICAL NEUROSCIENCE, 19(10) (10), 1453 - 1455, 英語[査読有り]研究論文(学術雑誌)
- 2012年04月, 診断病理 : Japanese journal of diagnostic pathology, 29(2) (2), 101 - 104, 日本語神経内分泌性格を有する卵巣癌肉腫の1例[査読有り]研究論文(学術雑誌)
- 2012年04月, 診断病理 : Japanese journal of diagnostic pathology, 29(2) (2), 105 - 107, 日本語色素性類上皮黒色腫 (pigmented epithelioid melanocytoma) の1症例[査読有り]研究論文(学術雑誌)
- 2011年10月, DIAGNOSTIC PATHOLOGY, 6, 英語[査読有り]研究論文(学術雑誌)
- 日本脳腫瘍病理学会, 2019年05月, Brain Tumor Pathology, 36(Suppl.) (Suppl.), 075 - 075, 日本語小児松果体部low grade gliomanの1例
- 2019年04月, JOURNAL OF UROLOGY, 201(4) (4), E155 - E156, 英語ENHANCED DIFFERENTIATION AND STRATIFICATION OF BLADDER UROTHELIUM FROM HUMAN INDUCED PLURIPOTENT STEM CELL研究発表ペーパー・要旨(国際会議)
- 2017年10月, ANNALS OF ONCOLOGY, 28, 英語Comparison between four PD-L1 IHC assays and association with efficacy of Nivolumab in previously treated NSCLC patients regular研究発表ペーパー・要旨(国際会議)
- (一社)日本乳癌学会, 2016年06月, 日本乳癌学会総会プログラム抄録集, 24回, 296 - 296, 日本語術前ホルモン治療によるLuminal乳癌の生物学的特性の変化、特にLuminal HER2乳癌への誘導についての解析
- (一社)日本病理学会, 2016年04月, 日本病理学会会誌, 105(1) (1), 489 - 489, 日本語小腸血管性病変の4例の検討
- (一社)日本乳癌学会, 2015年07月, 日本乳癌学会総会プログラム抄録集, 23回, 574 - 574, 日本語Adjuvant Trastuzumab投与中の心機能低下のモニターとしてのbrain natriuretic peptide(BNP)測定の有用性
- (一社)日本胃癌学会, 2015年03月, 日本胃癌学会総会記事, 87回, 408 - 408, 日本語術前診断が困難であった5型胃癌の2例
- (一社)日本病理学会, 2015年03月, 日本病理学会会誌, 104(1) (1), 339 - 339, 日本語胸腺多嚢胞性病変15例の検討
- (一社)日本病理学会, 2015年03月, 日本病理学会会誌, 104(1) (1), 412 - 412, 日本語大腸癌を合併した18例を含む107例の大腸穿孔例の病理学的検討
- 2015年02月, LABORATORY INVESTIGATION, 95, 312A - 312A, 英語Minute Lymphangioleiomyomatosis in Pelvic and Paraaortic Lymph Nodes: A Study of 8 Cases研究発表ペーパー・要旨(国際会議)
- 2015年02月, MODERN PATHOLOGY, 28, 312A - 312A, 英語Minute Lymphangioleiomyomatosis in Pelvic and Paraaortic Lymph Nodes: A Study of 8 Cases研究発表ペーパー・要旨(国際会議)
- (一社)日本内視鏡外科学会, 2014年10月, 日本内視鏡外科学会雑誌, 19(7) (7), 645 - 645, 日本語高CA19-9血症を呈した脾類表皮嚢胞の1例
- (一社)日本内視鏡外科学会, 2014年10月, 日本内視鏡外科学会雑誌, 19(7) (7), 482 - 482, 日本語FDG-PETにて高集積を呈したSolid pseudopapillary tumorに対して腹腔鏡下尾側膵切除を施行した2例
- (一社)日本病理学会, 2014年03月, 日本病理学会会誌, 103(1) (1), 349 - 349, 日本語IgG4関連炎症性腹部大動脈瘤の1例
- 日本脳腫瘍病理学会, 2010年05月, Brain Tumor Pathology, 27(Suppl.) (Suppl.), 125 - 125, 日本語繰り返す痙攣にて発症した成人cortical ependymomaの1例
■ 講演・口頭発表等
- The 34th Annual EAU Congress, 2019年03月, 英語, バルセロナ, 国際会議Directed differentiation of feeder-free human induced pluripotent stem cells into stratified bladder urotheliumポスター発表
- 34th Annual EAU Congress, 2019年03月, 英語, Barcelona, 国際会議Directed differentiation of feeder-free human induced pluripotent stem cells into stratified bladder urotheliumポスター発表
- 日本神経学会第109回近畿地方会, 2017年12月, 日本語, 日本神経学会, 大阪, 国内会議多発性脳梗塞, 頭蓋内主幹動脈狭窄を認め, 原発性中枢神経血管炎と鑑別を要した血管内リンパ腫の一例口頭発表(一般)
- The 18th annual symposium of Japanese Society for the Advancement of Women's Imaging, 2017年09月, 日本語, Japanese Society for the Advancement of Women's Imaging, 兵庫, 国内会議子宮発生腺肉腫の 1例:術前 PETMRI画像と病理標本との対比ポスター発表
- 第52回日本臨床細胞学会秋期大会, 2013年10月, 日本語, 日本臨床細胞学会, 大阪, 国内会議気管支擦過細胞診にてアレルギー性気管支肺アスペルギルス症が疑われた1症例ポスター発表
- 第102回病理学会総会, 2013年06月, 日本語, 日本病理学会, 札幌, 国内会議粘表皮癌を合併した甲状腺低分化癌の1例ポスター発表
- 第102回日本病理学会総会, 2013年06月, 日本語, 日本病理学会, 札幌, 国内会議神経線維腫症1型の若年男性に発症した中脳水道rosette-forming glioneuronal tumorの1例ポスター発表
- 第102回日本病理学会総会, 2013年06月, 日本語, 日本病理学会, 札幌, 国内会議初発及び再発時に血管肉腫と神経鞘腫、再々発時に血管肉腫と髄膜腫の混合像を呈した小脳橋角部腫瘍の1例ポスター発表
- 第102回日本病理学会総会, 2013年06月, 日本語, 日本病理学会, 札幌, 国内会議横紋筋様変化を伴った小脳血管芽腫の一例ポスター発表
- 第102回日本病理学会総会, 2013年06月, 日本語, 日本病理学会, 札幌, 国内会議PTTM (pulmonary tumor thrombotic microangiopathy) の2剖検例ポスター発表
- 第102回日本病理学会総会, 2013年06月, 日本語, 日本病理学会, 札幌, 国内会議Embryonal hyperplasia of Bowman's capsular epitheliumを合併した終末期摘出腎の1例ポスター発表
- 第60回日本病理学会近畿支部学術集会, 2013年02月, 日本語, 日本病理学会, 兵庫, 国内会議頚部リンパ節腫大の1例口頭発表(一般)
- 第59回日本病理学会近畿支部学術集会, 2012年12月, 日本語, 日本病理学会, 京都, 国内会議脾臓原発悪性リンパ腫の1例口頭発表(一般)
- 第59回日本病理学会近畿支部学術集会, 2012年12月, 日本語, 日本病理学会, 京都, 国内会議甲状腺腫瘍の1例口頭発表(一般)
- 98th Scientific Assembly and Annual Meeting of The Radiological Society of North America, 2012年11月, 英語, The Radiological Society of North America, U.S.A , Chicago, 国際会議Combination Efficacy of MGMT Promoter Methylation Status and MIB-1 Labeling Index for Pattern of Recurrence in Glioblastoma Treated with Multimodal Treatmentポスター発表
- 第58回日本病理学会近畿支部学術集会, 2012年09月, 日本語, 日本病理学会, 兵庫, 国内会議特徴的な上皮細胞増生を伴った終末期摘出腎の1例口頭発表(一般)
- The 14th Asian Oceanian Congress of Radiology, 2012年08月, 英語, The 14th Asian Oceanian Congress of Radiology, Australia,Sydney, Purpose: The purpose of this study is to evaluate the outcomes of radiation therapy for brainstem gliomas both in children and adults.Methods: Between 1990 and 2010, 25 patients with brainstem gliomas were treated with radiotherapy. Thirteen were children with a median age of 8 years old (Range: 2 – 18 years old) and 12 were adults with a median age of 56 years old (Range: 29 –, 国際会議Radiation therapy for brainstem gliomas in children and adultsポスター発表
- The 6th S.Takahashi Memorial Symposium & The 6th Japan-US Cancer Therapy International Joint Symposium, 2012年07月, 英語, 高橋信次記念三次元原体照射国際学会, 広島県(広島国際会議場), Purpose:The purpose of this study is to evaluate the outcomes of radiation therapy for brainstem gliomas both in children and adults.Methods: Between 1990 and 2010, 25 patients with brainstem gliomas were treated with radiotherapy. Thirteen were children with a median age of 8 years old (Range: 2 – 18 years old) and 12 were adults with a median age of 56 years old (Range: 29 –, 国際会議Radiation therapy for brainstem gliomas in children and adultsポスター発表
- The 6th S.Takahashi Memorial Symposium & The 6th Japan-US Cancer Therapy International Joint Symposium, 2012年07月, 英語, 高橋信次記念三次元原体照射国際学会, 広島県(広島国際会議場), 国際会議Impact of MGDG Promoter Methylation Status and MIB-1 Labeling Index on Recurrence Pattern after Multimodal Treatment in Glioblastomaポスター発表
- 53rd ASTRO, 2011年10月, 英語, ASTRO, マイアミビーチ, アメリカ, 国際会議Radiation Therapy For Brain Stem Gliomas In Children And Adults口頭発表(一般)
- 53rd ASTRO, 2011年10月, 英語, ASTRO, マイアミビーチ, アメリカ, 国際会議Dosimetric Analysis of Patterns of Failure for High-grade Glioma with Multimodality Treatment: Relationship to MIB-1 Labeling Index口頭発表(一般)
- 53rd ASTRO, 2011年10月, 英語, ASTRO, マイアミビーチ, アメリカ, 国際会議Combined Modality Therapy Including Radiotherapy for Squamous Cell Carcinomas of Maxillary Sinus: A Retrospective Study口頭発表(一般)
- 16th ECCO, 2011年09月, 英語, ECCO, ストックホルム, ドイツ, 国際会議Combined Modality Therapy Including Radiotherapy for Squamous Cell Carcinomas of Maxillary Sinus - a Retrospective Study口頭発表(一般)
- 第49回日本病理学会近畿支部学術集会, 2010年05月, 日本語, 日本病理学会近畿支部事務局, 大阪, 国内会議頭蓋骨腫瘍の1例口頭発表(一般)
- 第99回日本病理学会総会, 2010年04月, 日本語, 日本病理学会, 東京, 国内会議Candida glabrataによる感染性心内膜炎の一例ポスター発表
- 第91回日本肺癌学会関西支部会, 2010年01月, 日本語, 日本肺癌学会, 大津, 国内会議胸腔鏡下に切除した後縦隔発生Castleman病の1例口頭発表(一般)
- 第45回日本肝癌研究会, 2009年07月, 日本語, 日本肝癌研究会, 福岡, 国内会議胆管細胞癌との鑑別が困難であった肝瘢痕性病変の1例ポスター発表
- 日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2024年04月01日 - 2028年03月31日テラヘルツ波を用いた甲状腺腫瘍に対する革新的診断技術の確立
- 日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2020年04月01日 - 2022年03月31日iPS細胞由来胃オルガノイドによる粘膜筋板形成及び破綻のメカニズム胃粘膜筋板の形成に関する研究はヒト以外の実験動物では研究がなされているが、ヒトに関しては報告がない。ヒトでの組織発生の研究する方法として、ヒトiPS細胞での分化誘導を利用し、研究することができる。今までの研究でヒトiPS細胞から胃への分化誘導に関して胃の表層を覆う上皮のみ分化誘導されていることが報告されているが、胃壁を形成する上皮以外の構造は認められなかった。本研究では、既報よりも長期培養することで上皮以下の粘膜筋板を伴った胃オルガノイドをヒトiPS細胞から誘導することができた。その胃オルガノイドは、免疫染色による組織構造解析や網羅的な遺伝子発現解析でも胃と遜色がなかった。また、胃オルガノイドの粘膜筋板は上皮が誘導された後に分化してくることが判明した。 まず、この粘膜筋板を伴った胃オルガノイドを用いて粘膜筋板形成に関わる上皮由来のシグナルを探索した。ヘッジホッグシグナルとTGFβシグナルを阻害すると粘膜筋板の形成が抑制された。また、胃オルガノイドが培養皿底部に接着することで周囲に平滑筋が増生しており、粘膜筋板形成が促進した。以上のことから胃粘膜筋板形成にヘッジホッグシグナル、TGFβシグナル、基質の硬度が関わっていることが判明した。 粘膜切除後の胃上皮では、免疫染色にてTGFβの発現が亢進しており、粘膜筋板の再生に関わっていることが示唆された。 粘膜筋板形成に関わるこれらの3つの因子が判明したことによって胃潰瘍だけでなく癌の浸潤と粘膜筋板の関連を調査することができる。今後の癌の予後予測や粘膜下層内への癌浸潤の阻止、転移を抑制することにつながる可能性があるものと考えられる。