論文 - 齋藤　豪

3細胞間タイト結合蛋白LSRはHippo pathwayを介して子宮内膜癌の悪性化に関与している

嶋田 浩志, 郷久 晴朗, 金野 匠, 高橋 駿太, 畠山 翔翼, 幸野 貴之, 田中 綾一, 寺本 瑞絵, 岩崎 雅宏, 小島 隆, 齋藤 豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 )  34 ( 3 ) 416 - 416  2016年06月

Matrix metalloproteinase-10 regulates stemness of ovarian cancer stem-like cells by activation of canonical Wnt signaling and can be a target of chemotherapy-resistant ovarian cancer

Tasuku Mariya, Yoshihiko Hirohashi, Toshihiko Torigoe, Yuta Tabuchi, Takuya Asano, Hiroshi Saijo, Takafumi Kuroda, Kazuyo Yasuda, Masahito Mizuuchi, Tsuyoshi Saito, Noriyuki Sato

ONCOTARGET ( IMPACT JOURNALS LLC )  7 ( 18 ) 26806 - 26822  2016年05月  [査読有り]

　概要を見る

Epithelial ovarian cancer (EOC) is one of the most lethal cancers in females. Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) have been reported to be origin of primary and recurrent cancers and to be resistant to several treatments. In this study, we identified matrix metalloproteinase-10 (MMP10) is expressed in CSCs/CICs of EOC. An immunohistochemical study revealed that a high expression level of MMP10 is a marker for poor prognosis and platinum resistance in multivariate analysis. MMP10 gene overexpression experiments and MMP10 gene knockdown experiments using siRNAs revealed that MMP10 has a role in the maintenance of CSCs/CICs in EOC and resistance to platinum reagent. Furthermore, MMP10 activate canonical Wnt signaling by inhibiting noncanonical Wnt signaling ligand Wnt5a. Therefore, MMP10 is a novel marker for CSCs/CICs in EOC and that targeting MMP10 is a novel promising approach for chemotherapy-resistant CSCs/CICs in EOC.

DOI

MAPK13 is preferentially expressed in gynecological cancer stem cells and has a role in the tumor-initiation.

Kazuyo Yasuda, Yoshihiko Hirohashi, Takafumi Kuroda, Akari Takaya, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Tadashi Hasegawa, Tsuyoshi Saito, Noriyuki Sato, Toshihiko Torigoe

Biochemical and biophysical research communications   472 ( 4 ) 643 - 7  2016年04月  [国際誌]

　概要を見る

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as small subpopulation of cancer cells that are endowed with higher tumor-initiating ability. CSCs/CICs are resistant to standard cancer therapies including chemotherapy and radiotherapy, and they are thus thought to be responsible for cancer recurrence and metastasis. Therefore, elucidation of molecular mechanisms of CSCs/CICs is essential to cure cancer. In this study, we analyzed the gene expression profiles of gynecological CSCs/CICs isolated as aldehyde dehydrogenase high (ALDH(high)) cells, and found that MAPK13, PTTG1IP, CAPN1 and UBQLN2 were preferentially expressed in CSCs/CICs. MAPK13 is expressed in uterine, ovary, stomach, colon, liver and kidney cancer tissues at higher levels compared with adjacent normal tissues. MAPK13 gene knockdown using siRNA reduced the ALDH(high) population and abrogated the tumor-initiating ability. These results indicate that MAPK13 is expressed in gynecological CSCs/CICs and has roles in the maintenance of CSCs/CICs and tumor-initiating ability, and MAPK13 might be a novel molecular target for treatment-resistant CSCs/CICs.

DOI PubMed

子宮体癌初代培養細胞株における癌幹細胞の分離同定とその解析

田渕 雄大, 廣橋 良彦, 真里谷 奨, 浅野 拓也, 黒田 敬史, 齋藤 豪, 鳥越 俊彦

日本病理学会会誌 ( (一社)日本病理学会 )  105 ( 1 ) 397 - 398  2016年04月

Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy

Takuya Asano, Yoshihiko Hirohashi, Toshihiko Torigoe, Tasuku Mariya, Ryota Horibe, Takafumi Kuroda, Yuta Tabuchi, Hiroshi Saijo, Kazuyo Yasuda, Masahito Mizuuchi, Akari Takahashi, Hiroko Asanuma, Tadashi Hasegawa, Tsuyoshi Saito, Noriyuki Sato

ONCOTARGET ( IMPACT JOURNALS LLC )  7 ( 10 ) 11223 - 11237  2016年03月  [査読有り]

　概要を見る

Cervical cancer is a major cause of cancer death in females worldwide. Cervical cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are resistant to conventional radiotherapy and chemotherapy, and CSCs/CICs are thought to be responsible for recurrence. Eradication of CSCs/CICs is thus essential to cure cervical cancer. In this study, we isolated cervical CSCs/CICs by sphere culture, and we identified a cancer testis (CT) antigen, CTCFL/BORIS, that is expressed in cervical CSCs/CICs. BORIS has 23 mRNA isoform variants classified by 6 subfamilies (sfs), and they encode 17 different BORIS peptides. BORIS sf1 and sf4 are expressed in both CSCs/CICs and non-CSCs/CICs, whereas BORIS sf6 is expressed only in CSCs/CICs. Overexpression of BORIS sf6 in cervical cancer cells increased sphere formation and tumor-initiating ability compared with those in control cells, whereas overexpression of BORIS sf1 and BORIS sf4 resulted in only slight increases. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. BORIS sf6 contains a specific c-terminal domain (C34), and we identified a human leukocyte antigen (HLA)-A2-restricted antigenic peptide, BORIS C34_24(9) encoded by BORIS sf6. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6-overexpressing cervical cancer cells. Furthermore, the CTL clone significantly suppressed sphere formation of CaSki cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy.

Obstetrical prognosis of patients with cervical intraepithelial neoplasia (CIN) after "coin-shaped" conization

Miseon Kim, Shinichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Tsuyoshi Saito

ARCHIVES OF GYNECOLOGY AND OBSTETRICS ( SPRINGER HEIDELBERG )  293 ( 3 ) 651 - 657  2016年03月  [査読有り]

　概要を見る

Purpose Uterine cervical conization is related to adverse pregnancy outcomes in subsequent pregnancies. To deal with this problem, we started conservative coin-shaped conization for reproductive-aged patients with cervical intraepithelial neoplasia (CIN). Here we report both the obstetrical and oncological impacts of this operation in comparison with the standard cone-shaped resection. Methods A total of 401 women 44 years old or younger were treated in our hospital by CO2 laser conization between 2003 and 2012, and subsequently 50 patients became pregnant. The patients were divided into two groups, a standard cone-shaped conization group (until 2008) and a shallow coin-shaped conization group (beginning in 2008). The pregnancy courses and oncological prognoses of these two groups were studied. Results Cone height reduction of about 3 mm was done. However, there were no significant differences between the two groups with regard to the occurrence of oncological complications. In the standard conization group, 18 of the 25 patients delivered at term. In the coin-shaped conization group, 20 of the 25 patients delivered at term. There were no significant differences between the two groups with regard to the occurrence of various obstetrical complications. However, the reduction rate of cervical length over the pregnancy was smaller in the coin-shaped group and the number of patients with a short cervix length of 2 cm or less was smaller in the coin-shaped group. Conclusions Although conservative coin-shaped conization did not markedly improve the obstetrical prognosis, this operative procedure improved the reduction rate of uterine cervical length over the pregnancy without any increase in oncological complications.

DOI

術後20年目に局所再発した子宮体癌の1例

鈴木 将裕, 松浦 基樹, 山下 芙貴子, 箕輪 智幸, 田渕 雄大, 高田 さくら, 玉手 雅人, 寺本 瑞絵, 郷久 晴朗, 田中 綾一, 岩崎 雅宏, 齋藤 豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 )  60 ( 1 ) 71 - 71  2016年03月

一期的手術を施行した血管内平滑筋腫の1例

箕輪 智幸, 松浦 基樹, 山下 芙貴子, 鈴木 将裕, 田渕 雄大, 高田 さくら, 玉手 雅人, 寺本 瑞絵, 郷久 晴朗, 田中 綾一, 岩崎 雅宏, 齋藤 豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 )  60 ( 1 ) 62 - 63  2016年03月

成熟嚢胞性奇形腫の悪性転化が疑われたが、術後に卵巣カルチノイドと診断された1例の後方視的検討

鹿内 智史, 玉手 雅人, 馬場 敦志, 高橋 円, 明石 祐史, 郷久 晴朗, 寺本 瑞絵, 田中 綾一, 岩崎 雅宏, 齋藤 豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 )  60 ( 1 ) 64 - 65  2016年03月

化学療法による血小板減少に対する加味帰脾湯の効果

山下 芙貴子, 松浦 基樹, 箕輪 智幸, 鈴木 将裕, 田渕 雄大, 高田 さくら, 玉手 雅人, 寺本 瑞絵, 郷久 晴朗, 田中 綾一, 岩崎 雅宏, 齋藤 豪

北海道産科婦人科学会会誌 ( 北海道産科婦人科学会 )  60 ( 1 ) 68 - 68  2016年03月

肥満による子宮内膜癌の悪性化におけるLSR(lipolysis-stimulated lipoprotein receptor)の役割

嶋田 浩志, 郷久 晴朗, 寺本 瑞絵, 田中 綾一, 岩崎 雅宏, 小島 隆, 齋藤 豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 )  68 ( 2 ) 631 - 631  2016年02月

子宮体癌3期症例に関する治療成績の検討

伊坂 五沙, 玉手 雅人, 竹浪 奈穂子, 郷久 晴朗, 鈴木 美和, 寺本 瑞絵, 田中 綾一, 岩崎 雅宏, 齋藤 豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 )  68 ( 2 ) 890 - 890  2016年02月

腹水セルブロックにおける免疫組織学的検討が組織型・治療方針決定に有用であった腹膜原発粘液性腺癌の1例

長尾 沙智子, 玉手 雅人, 染谷 真行, 竹田 倫子, 岡村 直樹, 齋藤 豪

日本産科婦人科学会雑誌 ( (公社)日本産科婦人科学会 )  68 ( 2 ) 887 - 887  2016年02月

BMI66.5kg/m2の高度肥満妊婦における帝王切開の経験

森下 美幸, 嶋田 浩志, 馬場 剛, 石岡 伸一, 遠藤 俊明, 齋藤 豪

産科と婦人科 ( (株)診断と治療社 )  83 ( 2 ) 226 - 231  2016年02月

　概要を見る

高度肥満妊婦における帝王切開の経験を報告する。症例は33歳初産の女性。胃腸炎症状にて救急外来を受診するまで妊娠に気がつかず、CTで妊娠20週と判明。妊娠中に体重増加し当院に紹介されてから帝王切開決定、帝王切開の様子、術後の経過について若干の文献的考察とともに紹介する。(著者抄録)

再発を来した悪性卵巣胚細胞腫瘍の検討

嶋田 浩志, 田中 綾一, 鈴木 美和, 高橋 円, 郷久 晴朗, 寺本 瑞絵, 岩崎 雅宏, 齋藤 豪

日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 )  34 ( 1 ) 26 - 36  2016年01月

　概要を見る

2006年1月から2014年8月までに当院で治療を行った悪性卵巣胚細胞腫瘍(Malignant ovarian germ cell tumors:MOGCTs)20症例のうち3例の再発症例について検討および報告する。年齢は20歳、15歳、24歳で、進行期はそれぞれIIIc期(T3bN1M0)、Ic期(T1cNXM0)、Ia期(T1aNXM0)であった。組織型は2例がImmature teratoma(G3)、1例が一部にImmature teratoma(G1)を含むYolk sac tumorであった。全例に初回治療で妊孕性温存手術が実施され、ブレオマイシン、エトポシド、シスプラチンの3剤併用療法(BEP療法)を実施した。全例に再発巣の摘出術(Secondary debulking surgery:SDS)が施行され、術後にパクリタキセル、イソフォスファミド、シスプラチン併用療法(TIP療法)が施行された。再発までの期間は全例4ヵ月、初回治療から2例は12、26ヵ月で死亡、1例は30ヵ月経過し無病生存している。前者はSDS後に早期に再発し死亡に至っており、SDSが予後を改善した可能性は低い。しかし、後者は無病生存しているため、SDSが予後を改善した可能性もあり、今後のさらなる検討が必要である。(著者抄録)

The roles of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in malignancy of human endometrial cancer cells.

Shimada H, Satohisa S, Kohno T, Takahashi S, Hatakeyama T, Konno K, Tsujiwaki M, Saito T, Kojima T

Oncotarget   7(19):27735-52.  2016年  [査読有り]

PubMed

不妊治療前の治療的腹腔鏡/子宮鏡にて、子宮内膜増殖症を伴う子宮ポリープ状異型腺筋腫(APAM)と診断した1例

玉手 雅人, 明石 祐史, 長尾 沙智子, 西澤 庸子, 杉尾 明香, 松浦 基樹, 齋藤 豪

日本内視鏡外科学会雑誌 ( (一社)日本内視鏡外科学会 )  20 ( 7 ) OS217 - 6  2015年12月

Preservation of fertility and subsequent childbirth after methotrexate treatment of placenta percreta: a case report.

Tamate M, Matsuura M, Habata S, Akashi Y, Tanaka R, Ishioka S, Endo T, Saito T

Journal of medical case reports   9   232  2015年10月  [査読有り]

DOI PubMed

BORIS variant subfamily 6は癌幹細胞性に関与し免疫療法の標的となりうる

浅野 拓也, 廣橋 良彦, 真里谷 奨, 黒田 敬史, 浅沼 広子, 鳥越 俊彦, 齋藤 豪

日本癌学会総会記事 ( (一社)日本癌学会 )  74回   P - 1233  2015年10月

腹腔鏡および子宮鏡にて子宮内膜増殖症を伴う子宮ポリープ状異型腺筋腫と診断した1例

玉手 雅人, 寺本 瑞絵, 竹田 倫子, 松浦 基樹, 郷久 晴朗, 田中 綾一, 岩崎 雅宏, 齋藤 豪

日本臨床細胞学会雑誌 ( (公社)日本臨床細胞学会 )  54 ( Suppl.2 ) 561 - 561  2015年10月