| Item type |
文献 / Documents(1) |
| 公開日 |
2023-06-14 |
| アクセス権 |
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アクセス権 |
open access |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
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資源タイプ |
doctoral thesis |
| 出版社版DOI |
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関連識別子 |
https://doi.org/10.1016/j.prp.2021.153559 |
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関連名称 |
10.1016/j.prp.2021.153559 |
| 出版タイプ |
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出版タイプ |
NA |
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出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
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タイトル |
Neonatal streptozotocin treatment rapidly causes different subtype of hepatocellular carcinoma without persistent hyperglycemia in 4CS mice fed on a normal diet |
| タイトル別表記 |
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その他のタイトル |
新生仔期におけるストレプトゾトシン投与は、標準食摂取下の4CSマウスにおいて、持続的な高血糖を伴わずに異なるサブタイプの肝細胞癌を急速に引き起こす |
| 著者 |
小林, 智子
(市村)清水, 真祐子
尾矢, 剛志
小川, 博久
松本, 穣
モリモト, ユウキ
スミダ, サトシ
柿本, 拓海
山下, 理子
ストウ, ミツコ
トヨハラ, シュンジ
ホカオ, リョウジ
Cheng, Chunmei
常山, 幸一
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| 抄録 |
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内容記述 |
Although diabetes mellitus (DM) is a well-known risk factor for hepatocellular carcinoma (HCC), the underlying mechanisms have not yet to be defined. We previously reported that DIAR mice fed with standard murine diet developed type 1 diabetes and HCC at age of 16 weeks old with a neonatal streptozotocin treatment (n-STZ). Because DIAR mice did not manifest obesity nor develop steatohepatitis, hyperglycemia with streptozotocin trigger or streptozotocin alone might turn on the hepato-carcinogenesis. An insulin-recruitment to DIAR-nSTZ mice showed an increased frequency of HCC during the first 12 weeks of age, although the diabetic indications notably improved. To elucidate the role of hyperglycemia in hepato-carcinogenesis, we performed a head-to-head comparative study by using 4CS mice and DIAR mice with n-STZ treatment. Newborn 4CS mice and DIAR mice were divided into STZ treated group and control group. The blood glucose levels of DIAR-nSTZ mice increased at age of eight weeks, while that of 4CS-nSTZ mice were maintained in the normal range. At eight weeks old, three out of five DIAR-nSTZ mice (60%) and one out of ten 4CS-nSTZ mice (10%) developed multiple liver tumors. At age of 12 weeks old, all eight of DIAR-nSTZ mice (100%) and two of 10 4CS-nSTZ mice (20%) developed multiple liver tumors. At 16 weeks old, all animals of DIAR-nSTZ and 4CS-nSTZ mice occurred liver tumors. DIAR-nSTZ showed hyperglycemia and HCC, and 4CS-nSTZ developed HCC without hyperglycemia. These results were interpreted that the onset of HCC maybe not related to the presence or absence of hyperglycemia but nSTZ treatment. On the other hand, since the carcinogenesis of 4CS-nSTZ is delayed compared to DIAR-nSTZ, hyperglycemia may play a role in the progression of carcinogenesis. Histologically, the liver tumor appeared irregularly trabecular arrangements of hepatocytes with various degrees of nuclear atypia. By immunohistochemical analyses, all liver tumors showed positive staining of glutamine synthetase (GS), an established human HCC marker. The expression pattern of GS was divided into a strong diffuse pattern and weak patchy pattern, respectively. The liver tumor showing the weak GS-patchy pattern expressed biliary/stem markers, EpCAM, and SALL4, partially. Because 4CS-nSTZ mice did not show any metabolic complications such as gaining body weight or high blood glucose level, it is a unique animal model with a simple condition to investigate hepatic carcinogenesis by excluding other factors. |
| キーワード |
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主題 |
Animal model |
| キーワード |
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主題 |
Hyperglycemia |
| キーワード |
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主題 |
Hepatocellular carcinoma |
| キーワード |
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主題 |
HCC subclasses |
| キーワード |
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主題 |
Streptozotocin |
| 書誌情報 |
en : Pathology - Research and Practice
巻 225,
p. 153559,
発行日 2021-07-21
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| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
03440338 |
| 収録物ID |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
16180631 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA00769966 |
| 収録物ID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA1208415X |
| 出版者 |
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出版者 |
Elsevier |
| 備考 |
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値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Tomoko Kobayashiの学位論文として提出され，学位審査・授与の対象となっている。
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| EID |
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識別子 |
380929 |
| 言語 |
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言語 |
eng |
| 報告番号 |
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学位授与番号 |
甲第3695号 |
| 学位記番号 |
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|
値 |
甲医第1564号 |
| 学位授与年月日 |
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学位授与年月日 |
2023-03-23 |
| 学位名 |
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学位名 |
博士（医学） |
| 学位授与機関 |
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学位授与機関名 |
徳島大学 |
k3695_abstract.pdf (135 KB)
