Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer.
Recent progress on normal and malignant pancreatic stem/progenitor cell research: therapeutic implications for the treatment of type 1 or 2 diabetes mellitus and aggressive pancreatic cancer.
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胰腺正常及恶性干/祖细胞研究的最新进展：对1型或2型糖尿病以及侵袭性胰腺癌治疗的启示
DOI：
10.1136/gut.2008.150052
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发表时间：
2008-10
期刊：
影响因子：
24.5
通讯作者：
Batra SK
中科院分区：
文献类型：
--
作者：
Mimeault M;Batra SK
胰腺干/祖细胞研究的最新进展表明，推定的多能胰腺干/祖细胞和/或更定型的β细胞前体可能在成年人的胰腺中持续存在。具有干细胞样性质的未成熟胰腺细胞的存在提供了刺激其体内扩增和分化或将其离体扩增的后代用于基于β细胞扩增的疗法以治疗人类1型或2型糖尿病的可能性。此外，移植来源于胚胎、胎儿和其他组织驻留的成体干/祖细胞的产生胰岛素的β细胞或遗传修饰的成体干/祖细胞也可以构成用于治疗糖尿病患者的替代的有希望的疗法。然而，推定的胰腺成体干/祖细胞和/或其早期后代中的遗传和/或表观遗传改变可能导致其获得功能障碍行为以及其恶性转化为胰腺癌干/祖细胞。更具体地说，不同的致瘤信号级联的激活，包括刺猬，表皮生长因子-表皮生长因子受体，（EGF-EGFR）系统、无翼配体（Wnt）/β-连环蛋白和/或基质细胞衍生因子-1（SDF-1）-CXC趋化因子受体4（CXCR 4）途径可能在持续生长、存活、胰腺癌干/祖细胞及其进一步分化的后代的转移和/或耐药性。靶向胰腺癌干/祖细胞及其微环境中致癌元件的药物与常规化疗方案的组合可能代表有前途的治疗策略。这些新的靶向治疗应该导致更有效的治疗局部晚期和转移性胰腺癌的发展，这些癌症仍然无法治愈。
Recent progress on pancreatic stem/progenitor cell research has revealed that the putative multipotent pancreatic stem/progenitor cells and/or more committed beta cell precursors may persist in the pancreatic gland in adult life. The presence of immature pancreatic cells with stem cell-like properties offers the possibility of stimulating their in vivo expansion and differentiation or to use their ex vivo expanded progenies for beta cell replacement-based therapies for type 1 or 2 diabetes mellitus in humans. In addition, the transplantation of either insulin-producing beta cells derived from embryonic, fetal and other tissue-resident adult stem/progenitor cells or genetically modified adult stem/progenitor cells may also constitute alternative promising therapies for treating diabetic patients. The genetic and/or epigenetic alterations in putative pancreatic adult stem/progenitor cells and/or their early progenies may, however, contribute to their acquisition of a dysfunctional behaviour as well as their malignant transformation into pancreatic cancer stem/progenitor cells. More particularly, the activation of distinct tumorigenic signalling cascades, including the hedgehog, epidermal growth factor–epidermal growth factor receptor (EGF–EGFR) system, wingless ligand (Wnt)/β-catenin and/or stromal cell-derived factor-1 (SDF-1)–CXC chemokine receptor 4 (CXCR4) pathways may play a major role in the sustained growth, survival, metastasis and/or drug resistance of pancreatic cancer stem/progenitor cells and their further differentiated progenies. The combination of drugs that target the oncogenic elements in pancreatic cancer stem/progenitor cells and their microenvironment, with the conventional chemotherapeutic regimens, could represent promising therapeutic strategies. These novel targeted therapies should lead to the development of more effective treatments of locally advanced and metastatic pancreatic cancers, which remain incurable with current therapies.
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影响因子：
3.7
作者：
Pasca di Magliano M;Biankin AV;Heiser PW;Cano DA;Gutierrez PJ;Deramaudt T;Segara D;Dawson AC;Kench JG;Henshall SM;Sutherland RL;Dlugosz A;Rustgi AK;Hebrok M
通讯作者：
Hebrok M
DOI：
10.1073/pnas.0701117104
发表时间：
2007-03-13
影响因子：
11.1
作者：
Carriere, Catherine;Seeley, Elliott S.;Korc, Murray
通讯作者：
Korc, Murray
影响因子：
7.7
作者：
BONNERWEIR, S;BAXTER, LA;SMITH, FE
通讯作者：
SMITH, FE
DOI：
10.1016/j.bbrc.2007.03.157
发表时间：
2007-06-01
影响因子：
3.1
作者：
Chang, Chia-Ming;Kao, Chung-Lan;Ku, Hung-Hai
通讯作者：
Ku, Hung-Hai
影响因子：
5.2
作者：
Chaturvedi, Pallavi;Singh, Ajay P.;Batra, Surinder K.
通讯作者：
Batra, Surinder K.