研究者詳細 - 島田　聡子

Predictive Performance of Radiomic Features Extracted from Breast MR Imaging in Postoperative Upgrading of Ductal Carcinoma in Situ to Invasive Carcinoma

Satake, H; Kinoshita, F; Ishigaki, S; Kato, K; Jo, Y; Shimada, S; Masuda, N; Naganawa, S

MAGNETIC RESONANCE IN MEDICAL SCIENCES advpub 巻 ( 0 ) 2024年5月

Clinicopathological characteristics associated with the engraftment of patient lymphoma cells in NOG mice

Sahashi, S; Shimada, K; Takagi, Y; Aoki, T; Kunou, S; Sakamoto, A; Murase, A; Furukawa, K; Kagaya, Y; Yamaga, Y; Takai, M; Tokuyama, K; Shimada, S; Nakamura, S; Kiyoi, H

INTERNATIONAL JOURNAL OF HEMATOLOGY 118 巻 ( 2 ) 頁： 221 - 230 2023年8月

記述言語：英語出版者・発行元：International Journal of Hematology

Patient-derived xenograft (PDX) mouse models are useful for deepening our understanding of the biology of malignant lymphoma; however, factors associated with the success of the PDX lymphoma model are largely unknown. We retrospectively analyzed the characteristics of 66 xenotransplantations from 65 patients. In all, 43 (65%) specimens were obtained from patients aged > 60 years, and 42 (64%) specimens were obtained at diagnosis. Specimens were obtained from patients with the following diseases: diffuse large B-cell lymphoma (n = 30), intravascular large B-cell lymphoma (n = 12), follicular lymphoma (n = 8), peripheral T-cell lymphoma (n = 7), mantle cell lymphoma (n = 2), and other (n = 7). The specimens were sourced mainly from bone marrow (n = 31, 47%) and extranodal tumors (n = 13, 20%). Engraftment was successful in 33/66 (50%) xenotransplantations. The median age of patients who provided successful specimens was significantly higher than that for unsuccessful specimens (p = 0.013). Specimens with a high proportion of tumor cells in the graft and those obtained from patients with relapsed/refractory disease showed higher tendencies toward successful engraftment. Taken together, these data suggest that tumor cells with a highly malignant potential might have a high likelihood of engraftment.

DOI： 10.1007/s12185-023-03604-z

Exosomes secreted from cancer-associated fibroblasts elicit anti-pyrimidine drug resistance through modulation of its transporter in malignant lymphoma

Two cases of solitary fibrous tumor/hemangiopericytoma with different clinical features according to the World Health Organization classification: case report and review of the literature.

Nishii T, Nagashima Y, Nishimura Y, Ito H, Oyama T, Matsuo M, Sakakibara A, Shimada S, Saito R

Journal of spine surgery (Hong Kong) 7 巻 ( 4 ) 頁： 532 - 539 2021年12月

Kunou Shunsuke, Shimada Kazuyuki, Takai Mika, Sakamoto Akihiko, Aoki Tomohiro, Hikita Tomoya, Kagaya Yusuke, Iwamoto Eisuke, Sanada Masashi, Shimada Satoko, Hayakawa Fumihiko, Oneyama Chitose, Kiyoi Hitoshi

ONCOGENE 40 巻 ( 23 ) 頁： 3989 - 4003 2021年6月

記述言語：日本語出版者・発行元：Oncogene

The tumor microenvironment is deeply involved in the process of tumor growth and development. In this study, we focused on cancer-associated fibroblasts (CAFs) and their derived exosomes on the lymphoma microenvironment to uncover their clinical significance. CAFs were established from primary lymphoma samples, and exosomes secreted from CAFs were obtained by standard procedures. We then investigated the roles of CAFs and their derived exosomes in the survival and drug resistance of lymphoma cells. CAFs supported the survival of lymphoma cells through increased glycolysis, and the extent differed among CAFs. Exosomes were identified as a major component of the extracellular vesicles from CAFs, and they also supported the survival of lymphoma cells. The suppression of RAB27B, which is involved in the secretion of exosomes, using a specific siRNA resulted in reduced exosome secretion and decreased survival of lymphoma cells. Moreover, anti-pyrimidine drug resistance was induced in the presence of exosomes through the suppression of the pyrimidine transporter, equilibrative nucleoside transporter 2 (ENT2), and the suppression of ENT2 was significant in in vivo experiments and clinical samples. RNA sequencing analysis of miRNAs in exosomes identified miR-4717-5p as one of the most abundant miRNAs in the exosome, which suppressed the expression of ENT2 and induced anti-pyrimidine drug resistance in vitro. Our results suggest that exosomes including miR-4717-5p secreted from CAFs play a pivotal role in the lymphoma microenvironment, indicating that they are a promising therapeutic target.

DOI： 10.1038/s41388-021-01829-y

The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma

Morichika Kazuho, Karube Kennosuke, Sakihama Shugo, Watanabe Risa, Kawaki Mamoru, Nishi Yukiko, Nakachi Sawako, Okamoto Shiki, Takahara Taishi, Satou Akira, Shimada Satoko, Shimada Kazuyuki, Tsuzuki Toyonori, Fukushima Takuya, Morishima Satoko, Masuzaki Hiroaki

AMERICAN JOURNAL OF SURGICAL PATHOLOGY 45 巻 ( 6 ) 頁： 832 - 840 2021年6月

記述言語：日本語出版者・発行元：American Journal of Surgical Pathology

On the basis of immunohistochemistry, diffuse large B-cell lymphoma (DLBCL) is categorized as a germinal center B-cell (GCB) or non-GCB subtype. Recent integrated genomic analyses have highlighted the importance of the JAK-STAT3 pathway in the molecular pathogenesis of DLBCL. However, its relevance to clinical outcomes remains controversial. Therefore, we evaluated the extent of the nuclear expression of phosphorylated STAT3 (pSTAT3), a surrogate marker of signal transducer and activator of transcription 3 (STAT3) activation, by immunohistochemistry. We also analyzed the potential relationship between pSTAT3 positivity (defined as ≥ 40% positive neoplastic cells) and clinicopathologic characteristics in 294 patients with DLBCL. pSTAT3 was detected in 122 patients (42%), with a higher rate in the non-GCB subtype than in the GCB subtype (57% vs. 28%, P < 0.001). Factors potentially activating STAT3, MYD88L265P, and Epstein-Barr virus-encoded small RNA were identified in the pSTAT3-positive non-GCB subtype, whereas the pSTAT3-positive GCB subtype often showed STAT3 mutations and lacked EZH2 mutations and the rearrangements of BCL2 and MYC. Multivariate analyses revealed that the pSTAT3-positive GCB subtype showed a favorable prognosis (HR: 0.17; 95% confidence interval, 0.04-0.7; P = 0.014). These findings suggest that pSTAT3 positivity may have a unique impact on the clinicopathologic characteristics of DLBCL, making it a promising novel marker for the favorable prognosis of patients with the GCB subtype.

DOI： 10.1097/PAS.0000000000001691