Fatty pancreas: A possible risk factor for pancreatic cancer in animals and humans.
Fatty pancreas: A possible risk factor for pancreatic cancer in animals and humans.
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DOI：
10.1111/cas.13766
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发表时间：
2018-10
期刊：
影响因子：
5.7
通讯作者：
Nakagama H
中科院分区：
文献类型：
--
作者：
Takahashi M;Hori M;Ishigamori R;Mutoh M;Imai T;Nakagama H
肥胖、2型糖尿病（T2 DM）和衰老与胰腺癌风险相关，但这些因素导致胰腺癌发生的机制尚不清楚。叙利亚金仓鼠对N-亚硝基双（2-氧代丙基）胺（BOP）诱导的胰腺癌易感。衰老、BOP治疗和/或高脂饮食导致胰腺严重和分散的脂肪浸润（FI），伴脂肪因子产生异常，并促进胰腺导管腺癌（PDAC）的发展。KK-A y小鼠（一种T2 DM模型）也出现胰腺重度和分散性FI。BOP处理在KK‐A y小鼠的胰管中诱导了显著更高的细胞增殖，但在ICR和C57 BL/6 J小鼠的胰管中没有，这两种小鼠的特征都是不存在分散的FI。因此，我们假设严重分散的FI可能参与PDAC发展的易感性。事实上，在人类中观察到严重的胰腺FI或脂肪胰腺，并且与年龄、体重指数（BMI）和DM相关，这些是胰腺癌的风险因素。我们通过组织病理学分析了PDAC和接受胰腺癌切除术的非PDAC患者的非癌部分的FI程度，并证明PDAC病例的胰腺FI程度显著高于非PDAC对照。此外，与PDAC的关联是积极的，即使在调整BMI和DM的患病率之后。越来越多的证据表明，胰腺FI参与PDAC的发展在动物和人类，并进一步调查，以澄清遗传和环境因素，导致胰腺FI是必要的。
Obesity, type 2 diabetes mellitus (T2DM) and aging are associated with pancreatic cancer risk, but the mechanisms of pancreatic cancer development caused by these factors are not clearly understood. Syrian golden hamsters are susceptible to N‐nitrosobis(2‐oxopropyl)amine (BOP)‐induced pancreatic carcinogenesis. Aging, BOP treatment and/or a high‐fat diet cause severe and scattered fatty infiltration (FI) of the pancreas with abnormal adipokine production and promote pancreatic ductal adenocarcinoma (PDAC) development. The KK‐A y mouse, a T2DM model, also develops severe and scattered FI of the pancreas. Treatment with BOP induced significantly higher cell proliferation in the pancreatic ducts of KK‐A y mice, but not in those of ICR and C57BL/6J mice, both of which are characterized by an absence of scattered FI. Thus, we hypothesized that severely scattered FI may be involved in the susceptibility to PDAC development. Indeed, severe pancreatic FI, or fatty pancreas, is observed in humans and is associated with age, body mass index (BMI) and DM, which are risk factors for pancreatic cancer. We analyzed the degree of FI in the non‐cancerous parts of PDAC and non‐PDAC patients who had undergone pancreatoduodenectomy by histopathology and demonstrated that the degree of pancreatic FI in PDAC cases is significantly higher than that in non‐PDAC controls. Moreover, the association with PDAC is positive, even after adjusting for BMI and the prevalence of DM. Accumulating evidence suggests that pancreatic FI is involved in PDAC development in animals and humans, and further investigations to clarify the genetic and environmental factors that cause pancreatic FI are warranted.
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影响因子：
2.1
作者：
Hori, Mika;Onaya, Hiroaki;Nakagama, Hitoshi
通讯作者：
Nakagama, Hitoshi
影响因子：
7.7
作者：
Kodama, Keiichi;Toda, Kyoko;Butte, Atul J.
通讯作者：
Butte, Atul J.
影响因子：
4.8
作者：
Jones, BH;Standridge, MK;Moustaid, N
通讯作者：
Moustaid, N
影响因子：
4.8
作者：
Eibl G;Cruz-Monserrate Z;Korc M;Petrov MS;Goodarzi MO;Fisher WE;Habtezion A;Lugea A;Pandol SJ;Hart PA;Andersen DK;Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer
通讯作者：
Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer
影响因子：
5.7
作者：
Ito, Kumiko;Ishigamori, Rikako;Takahashi, Mami
通讯作者：
Takahashi, Mami