科学家提出，慢性炎症可能是造成目的是清除肝癌的手术后该病经常复发的机制之一。手术是治疗肝癌的优选方法，因为这一器官可以在广泛受损或切除后再生。 Rinat Abramovitch及其同事发现，慢些肝炎可以让细胞对手术损伤做出反应从而分裂，即便这些细胞已经受损而且可能最终成为癌细胞。这组科学家研究了具有一个突变基因的小鼠，这个突变基因能促进导致肝癌的慢性炎症。这组科学家发现，这种炎症导致了DNA的双链破损的增加，而这会让细胞更容易变成癌细胞。随着手术后这些分裂的细胞重新生长，它们逃避了通常会清除受损细胞的正常抗体应答。这组作者说，抑制炎症的疗法以及手术后帮助修复DNA的药物治疗方案有可能帮助预防肝癌的复发。
论文 #09-08867: "The accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double strand DNA breaks," 作者 Hila Barash, Eitan Gross, Yifat Edrei, Ezra Ella, Ariel Israel, Irit Cohen, Nathalie Corchia, Tehila Ben-Moshe, Orit Pappo, Eli Pikarsky等人
媒体联系人：Rinat Abramovitch，以色列Hadassah希伯来大学医学中心，Goldyne Savad基因疗法研究所
The Goldyne Savad Institute of Gene Therapy, Hadassah Hebrew University Medical Center, Jerusalem, ISRAEL
电话：+972-2-6777770 (白天), +972-50-4048017 (晚间)
电子邮件：rinat@hadassah.org.il
Published online before print January 25, 2010, doi: 10.1073/pnas.0908867107
Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks
Hila Barasha,b, Eitan R. Grossc, Yifat Edreia,b, Ezra Ellaa, Ariel Israela, Irit Cohena, Nathalie Corchiaa,b, Tehila Ben-Moshea, Orit Pappod, Eli Pikarskyd, Daniel Goldenberga, Yosef Shilohe, Eithan Galuna, and Rinat Abramovitcha,b,1
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide and is considered to be the outcome of chronic liver inflammation. Currently, the main treatment for HCC is surgical resection. However, survival rates are suboptimal partially because of tumor recurrence in the remaining liver. Our aim was to understand the molecular mechanisms linking liver regeneration under chronic inflammation to hepatic tumorigenesis. Mdr2-KO mice, a model of inflammation-associated cancer, underwent partial hepatectomy (PHx), which led to enhanced hepatocarcinogenesis. Moreover, liver regeneration in these mice was severely attenuated. We demonstrate the activation of the DNA damage-response machinery and increased genomic instability during early liver inflammatory stages resulting in hepatocyte apoptosis, cell-cycle arrest, and senescence and suggest their involvement in tumor growth acceleration subsequent to PHx. We propose that under the regenerative proliferative stress induced by liver resection, the genomic unstable hepatocytes generated during chronic inflammation escape senescence and apoptosis and reenter the cell cycle, triggering the enhanced tumorigenesis. Thus, we clarify the immediate and long-term contributions of the DNA damage response to HCC development and recurrence.
