1.

論文(リポジトリ)

論文(リポジトリ)
Uehara, Karina ; Tanabe, Yasuka ; Hirota, Shintaro ; Higa, Saki ; Toyoda, Zensei ; Kurima, Kiyoto ; Kina, Shinichiro ; Nakasone, Toshiyuki ; Arasaki, Akira ; Kinjo, Takao
出版情報: BMC Cancer.  21  2021-06-10.  Springer Nature
URL: http://hdl.handle.net/20.500.12000/49986
概要: Background:Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types hav e been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1.\nMethods:We transduced HPV6, 11 and 16 E6/E7 genes and EBV LMP-1 gene into primary mouse embryonic fibroblasts. The cell lines were examined for indices of transformation activity such as proliferation, induction of DNA damage, resistance to apoptosis, anchorage-independent growth, and tumor formation in nude mice. To evaluate the signaling pathways involved in transformation, NF-κB and p53 activities were analyzed. We also assessed adhesion signaling molecules associated with anchorage-independent growth such as MMP-2, paxillin and Cat-1.\nResults:Co-expression of low-risk HPV6 E6 and EBV LMP-1 showed increased cell proliferation, elevated NF-κB activity and reduced p53 induction. Moreover, co-expression of low-risk HPV6 E6 and EBV LMP-1 induced DNA damage, escaped from apoptosis under genotoxic condition and suppression of DNA damage response (DDR). Co-expression of low-risk HPV11 E6/E7 and EBV LMP-1 demonstrated similar results. However, it led to no malignant characteristics such as anchorage-independent growth, invasiveness and tumor formation in nude mice. Compared with the cells co-expressing high-risk HPV16 E6 and EBV LMP-1 that induce transformation, co-expression of low-risk HPV6 E6 and EBV LMP-1 was associated with low MMP-2, paxillin and Cat-1 expression.\nConclusions:The co-expression of low-risk HPV E6/E7 and EBV LMP-1 does not induce malignant transformation, but it allows accumulation of somatic mutations secondary to increased DNA damage and suppression of DDR. Thus, double infection of low-risk HPV and EBV could lead to precancerous lesions.
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2.

学位論文(リポジトリ)

学位
Uehara, Karina ; 上原, 佳里奈
出版情報: scientific reports.  9  2020-04-23.  University of the Ryukyus
URL: http://hdl.handle.net/20.500.12000/46707
概要: Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are different, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the different clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer.
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3.

論文(リポジトリ)

論文(リポジトリ)
Tamanaha-Nakasone, Ayumi ; Uehara, Karina ; Tanabe, Yasuka ; Ishikawa, Haruna ; Yamakawa, Natsuko ; Toyoda, Zensei ; Kurima, Kiyoto ; Kina, Shinichiro ; Tsuneki, Masayuki ; Okubo, Yuko ; Yamaguchi, Sayaka ; Utsumi, Daisuke ; Takahashi, Kenzo ; Arakawa, Hirofumi ; Arasaki, Akira ; Kinjo, Takao
出版情報: Scientific Reports.  9  2019-04-23.  Nature Research
URL: http://hdl.handle.net/20.500.12000/0002019644
概要: Kaposi’s sarcoma-associated herpesvirus (KSHV) causes both AIDS-related Kaposi’s sarcoma (KS) and classic KS, but their clinical presentations are diferent, and respective mechanisms remain to be elucidated. The KSHV K1 gene is reportedly involved in tumorigenesis through the immunoreceptor tyrosine-based activation motif (ITAM). Since we found the sequence variations in the K1 gene of KSHV isolated from AIDS-related KS and classic KS, we hypothesized that the transformation activity of the K1 gene contributes to the diferent clinical presentations. To evaluate our hypothesis, we compared the transformation activities of the K1 gene between AIDS-related KS and classic KS. We also analyzed ITAM activities and the downstream AKT and NF-κB. We found that the transformation activity of AIDS-related K1 was greater than that of classic K1, and that AIDS-related K1 induced higher ITAM activity than classic K1, causing more potent Akt and NF-κB activities. K1 downregulation by siRNA in AIDS-related K1 expressing cells induced a loss of transformation properties and decreased both Akt and NF-κB activities, suggesting a correlation between the transformation activity of K1 and ITAM signaling. Our study indicates that the increased transformation activity of AIDS-related K1 is associated with its clinical aggressiveness, whereas the weak transformation activity of classic type K1 is associated with a mild clinical presentation and spontaneous regression. The mechanism of spontaneous regression of classic KS may provide new therapeutic strategy to cancer. 続きを見る
4.

論文(リポジトリ)

論文(リポジトリ)
Uehara, Karina ; Ikehara, Fukino ; Shibuya, Ryo ; Nakazato, Iwao ; Oshiro, Mariko ; Kiyuna, Masaya ; Tanabe, Yasuka ; Toyoda, Zensei ; Kurima, Kiyoto ; Kina, Shinichiro ; Hisaoka, Masanori ; Kinjo, Takao
出版情報: Pathology and Oncology Research (POR).  24  pp.861-869,  2018-10.  Frontiers Media
URL: http://hdl.handle.net/20.500.12000/0002019652
概要: Spindle cell/pleomorphic lipomas (SCLs), cellular angiofibromas (CAFs) and mammary-type myofibroblastomas (MFBs) are rar e benign mesenchymal tumors with monoallelic 13q14 deletion. They are predicted to have a common pathogenic mechanism due to shared similar histological and immunohistochemical features; however, pathological consequences of monoallelic 13q14 deletion remain unknown. We previously reported a CAF case with monoallelic 13q14 deletion in which the tumor expressed decreased levels of FOXO1 and RB1, both of which were encoded in 13q14, and increased reactive oxygen species (ROS) levels. We further demonstrated the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway induced by oxidative stress. We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs). We compared the expression levels of FOXO1, RB1, ROS markers and several signal transduction factors between SCLs and SFTs. SCLs expressed decreased levels of FOXO1 and RB1, whereas SFTs showed no change. Both tumor types exhibited increased markers of ROS; however, nuclear localization of phosphorylated p38 was significantly more frequent in SCLs than that in SFTs, suggesting p38 MAPK activation by oxidative stress. SFTs showed lower p38 MAPK activity and higher β-catenin expression, implying that oxidative stress was caused by increased cellular proliferation stress. Finally, CAFs and MFBs showed changes similar to those observed in SCLs. Overall, tumors with monoallelic 13q14 deletion showed shared molecular signatures that might be associated with pathogenesis. 続きを見る
5.

論文(リポジトリ)

論文(リポジトリ)
Uehara, Karina ; Iwashita, Hidehiko ; Tanabe, Yasuka ; Kurima, Kiyoto ; Oshiro, Mariko ; Kina, Shinichiro ; Ota, Atsuko ; Iwashita, Akinori ; Kinjo, Takao
出版情報: Open Medicine.  12  pp.335-339,  2017-10-17.  De Gruyter
URL: http://hdl.handle.net/20.500.12000/0002019639
概要: Esophageal xanthoma is a rare lesion which is an asymptomatic small yellowish polyp, and most of the reported cases were solitary lesion. Histologically, aggregations of foam cells are found under the papillary hypertrophic squamous epithelium and the foam cells express CD68. The etiology of esophageal xanthoma is unknown. The focal irritation of the esophageal mucosa and infiltrated inflammatory cells are presumed to contribute to its pathogenesis. Although the pathogenesis may be associated with inflammation, the type and nature of the macrophages remain unclear. Here we report a 46-year-old male with esophageal xanthoma, which was incidentally found by endoscopy. Histologically, acute inflammation was not noted, and immunohistochemistry revealed that the foam cells seen in this case of esophageal xanthoma expressed increased levels of M2 macrophage markers. These findings suggest that esophageal xanthoma is associated with late inflammatory and reparative processes long after the initial inflammation of esophageal squamous epithelium. 続きを見る
6.

論文(リポジトリ)

論文(リポジトリ)
Uehara, Karina ; Ikehara, Fukino ; Tanabe, Yasuka ; Nakazato, Iwao ; Oshiro, Mariko ; Inamine, Morihiko ; Kinjo, Takao
出版情報: Diagnostic Pathology.  11  2016-02-01.  BMC
URL: http://hdl.handle.net/20.500.12000/0002019636
概要: Backgound: Endometrial mixed carcinoma with the neuroendocrine carcinoma (NEC) component is rare and is believed to have a poor prognosis. CD10 expression is reported to be a favorable prognostic marker for some tumors such as B-lymphoblastic leukemia/lymphoma, but unfavorable for others. Here, we report the case of a 33-year-old woman diagnosed with endometrial mixed carcinoma with the NEC component expressing CD10 who showed a favorable outcome. Case presentation: The patient presented with lumbago and brownish discharge from the genitals. Imaging modalities revealed a large exophytic mass in the uterine corpus, and a small one in the uterine cervix. Radical hysterectomy with bilateral salpingo-oophorectomy was performed. Microscopic examination of the endometrial and cervical masses revealed that the NEC component accounted for the maximum area in both masses. However, small areas in both lesions showed well differentiated endometrioid adenocarcinoma (WDEA) components, and histological transition between the two components was also observed. In addition to CD56 and synaptophysin expression, the NEC component was positive for CD10 but negative for estrogen receptor (ER), progesterone receptor (PgR), and carcinoembryonic antigen (CEA). In contrast, the WDEA component expressed both ER and PgR, but neither CD10 nor neuroendocrine markers were demonstrated. The CD10 and neuroendocrine markers clearly distinguished between the NEC and WDEA components. Furthermore, retained expression of phosphatase and tensin homolog (PTEN) and weak phosphorylated Akt expression were found, which were assumed to suppress the aggressive behavior of the tumor. The patient received postoperative chemotherapy and has survived without recurrence for 6 years after the operation. Conclusion: This is the first case of endometrial mixed carcinoma with the NEC component expressing CD10 that showed a long survival. 続きを見る
7.

論文(リポジトリ)

論文(リポジトリ)
Arakaki, Kazunari ; Chinen, Katsuya ; Kamiya, Masuzo ; Tanabe, Yasuka ; Tawata, Natsumi ; Ikehara, Fukino ; Uehara, Karina ; Shimabukuro, Hiroichi ; Kinjo, Takao
出版情報: International Journal of Clinical and Experimental Pathology.  7  pp.8972-8979,  2014-12-01.  e-Century Publishing Corporation
URL: http://hdl.handle.net/20.500.12000/46329
概要: Cellular angiofibroma (CAF) is a rare soft tissue tumor characterized by random arrangement of spindle tumor cells in th e stroma with short collagen bundles and thick- and hyalinized small vessels. CAFs share histological characteristics with spindle cell lipomas and mammary type myofibroblastomas. Because these tumors harbor monoallelic 13q14, common genetic and molecular mechanism for tumorigenesis is presumed. In this study, we reported a case of CAF in a 69-year-old man with monoallelic 13q14. Immunohistochemical analysis revealed that FOXO1, which is located in chromosome 13q14, was not expressed in the tumor. We also detected oxidative stress markers and found p38 MAPK activation, which is often induced by cellular stressors such as reactive oxygen species (ROS). Because FOXO1 induces the expression of genes encoding enzymes that generate antioxidants, oxidative stress induced by loss of FOXO1 expression may be common among CAFs, spindle cell lipomas, and mammary type myofibroblastomas.
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