No abstract

As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc. Importantly, RRM2 functions like a tumor driver in most types of cancer but little is known about the regulatory mechanism of RRM2 in cancer development. In this study, we found that the cAMP responsive element binding protein 1 (CREB1) acted as a transcription factor of RRM2 gene in human colorectal cancer (CRC). CREB1 directly bound to the promoter of RRM2 gene and induced its transcriptional activation. Knockdown of CREB1 decreased the expression of RRM2 at both mRNA and protein levels. Moreover, knockdown of RRM2 attenuated CREB1-induced aggressive phenotypes of CRC cells in vitro and in vivo. Analysis of the data from TCGA database and clinical CRC specimens with immunohistochemical staining also demonstrated a strong correlation between the co-expression of CREB1 and RRM2. Decreased disease survivals were observed in CRC patients with high expression levels of CREB1 or RRM2. Our results indicate CREB1 as a critical transcription factor of RRM2 which promotes tumor aggressiveness, and imply a significant correlation between CREB1 and RRM2 in CRC specimens. These may provide the possibility that CREB1 and RRM2 could be used as biomarkers or targets for CRC diagnosis and treatment.

Radiation enteropathy is a common complication in cancer patients following radiation therapy. Thus, there is a need for agents that can protect the intestinal epithelium against radiation. 12-O-tetradecanoylphorbol-13-acetate (TPA) has been shown to induce differentiation and/or apoptosis in multiple cell lines and primary cells. In the current report, we studied the function of TPA in radiation induced enteropathy in cultured rat intestinal epithelial cell line IEC-6 after ionizing radiation (IR) and in mice after high dose total-body gamma-IR (TBI). In IEC-6 cells, there were reduced apoptosis and cell cycle arrest in TPA treated cells after IR. We detected a four-fold increase in crypt cell survival and a two-fold increase in animal survival post TBI in TPA treated mice. The beneficial effects of TPA were accompanied by upregulation of stem cells markers and higher level of proteins that are involved in PKC signaling pathway. In addition, TPA also decreased the TBI-augmented levels of the DNA damage indicators. The effects were only observed when TPA was given before irradiation. These results suggest that TPA has the ability to modulate intestinal crypt stem cells survival and this may represent a promising countermeasure against radiation induced enteropathy.

Sarcomatoid carcinoma (SC) is a malignant tumor type of unclear pathogenesis, which rarely occurs in the liver. The present study reports the case of a 60-year-old woman who presented with multiple masses in her liver, with no fever, abdominal pain or jaundice. Serological markers for hepatitis B and C virus were negative, as was the test for α fetoprotein. Abdominal enhanced magnetic resonance imaging examination confirmed multiple lesions in the liver, and liquefactive necrosis was observed. The patient underwent a right hepatectomy, in addition to a cholecystectomy. Cytokeratin 8 (CK8), cluster of differentiation 117, pancytokeratin and vimentin were positively detected using immunohistochemistry, and thus the diagnosis of primary hepatic SC (PHSC) was established. During the follow-up period, characteristic imaging manifestations of tumor recurrence were detected, including peripheral enhancement, central necrosis, variable enhancement, venous invasion and intrahepatic metastasis. The immunohistochemical detection of CK, epithelial membrane antigen and vimentin, with CK8 as a critical indicator, may be useful for the diagnosis of PHSC. The preferred treatment for PHSC is surgical resection and the prognosis is poor.