Supplementary Figures 1-10, Tables 1-3 from Targeted Methylation of Two Tumor Suppressor Genes Is Sufficient to Transform Mesenchymal Stem Cells into Cancer Stem/Initiating Cells
Curcumin (CUR) has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm 2 twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm 2 ) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF- κ B, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF- κ B, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.
Supplementary Figures 1-10, Tables 1-3 from Targeted Methylation of Two Tumor Suppressor Genes Is Sufficient to Transform Mesenchymal Stem Cells into Cancer Stem/Initiating Cells
Notch signaling is a candidate pathway that transmits environmental information into the cell and interferes with the epigenome of gastric cancer. This study aimed to explore if the Notch pathway was abnormally regulated during gastric tumorigenesis. To achieve the goal, Delta-like ligand 1 (DLL1) gene expression, Notch upstream signal, promoter methylation and its correlation with DLL1 expression were examined by methylation-specific polymerase chain reaction (PCR) and real-time PCR (RT-PCR) in cultured gastric cancer cell lines or gastric cancer patient samples. Immunostainings and tissue arrays (n = 40) were used to confirm the DLL1 expression was down-regulated in cancer cells. Transient or stable Notch1 active domain (NICD)-overexpression suppressed proliferation of the gastric cells but the in vivo tumor growth was enhanced. The results of abnormal DLL1 methylation and expression observed in early gastric lesions and in gastric cancers may be relevant to the pathogenesis of gastric cancer.
The expression level of extracellular proteins in an alkaliphilic bacterium, Bacillus sp. strain K-1, grown in a xylan-containing medium, is significantly increased when compared with that grown in the nonxylan culture medium. A proteomic approach has been efficiently applied to separate and characterize these differentially expressed secretory proteins. Eight prominent protein spots were identified and subjected to N-terminal amino acid sequencing. The results show that three spots share considerable similarity with the xylanolytic enzymes and that two spots share considerable similarity with the GltC regulatory protein and 3-dehydroquinate dehydratase, respectively. In addition, the three other proteins show little similarity with the known proteins in the database. In conclusion, our results demonstrate that the proteomic approach is a highly efficient method to rapidly study the differential expression of the secreted proteins by Bacillus sp. strain K-1 grown under xylan-induced condition.
This work demonstrated, for the first time, the combinatorial discovery and rational identification of small-molecule cycloammonium-based thermoresponsive ionic liquids that exhibit LCST phase transition and carry attractive Tc values in water.
During osteoclastogenesis, the maturation of osteoclast (OC) progenitors is stimulated by the receptor activator of nuclear factor-κB ligand (RANKL). Excess OC production plays a critical role in the pathogenesis of inflammatory bone disorders. Conversely, the inhibition of abnormal OC proliferation reduces inflammation-induced bone loss. Low concentrations of carbon monoxide (CO) are known to decrease inflammation and OC-mediated bone erosion but the molecular mechanism is unknown.
Abstract To explore if the Notch pathway were abnormally regulated during gastric tumorigenesis, abnormal DLL1 promoter methylation and inversely correlated mRNA expression were detected in cultured cell lines and patient samples. Elevated DLL1 expression was observed in gastric lesion like gastritis or erosion, but decreased DLL1 expression was detected in all four stages of gastric cancers (n = 44). To identify the effector genes and construct the possible Notch signaling network in gastric cancer, Myc-tagged Notch1 was overexpressed in gastric cancer cell line followed by the chromatin-immuno-precipitation sequencing (ChIP-seq) analysis. In ChIP-seq analysis, antibodies against Notch1, Rbpjκ, and Myc were used to identify the Notch1 targets while antibodies against trimethylated histone 3 at lysine 4 (H3K4me3) or lysine 27 (H3K27me3) were used to detect the associated epigenetic states. We found that the Notch1-overexpression suppressed the gastric tumoral growth, and the target loci-associated H3K4me3 (active chromatin) were reduced while the association with H3K27me3 (suppressive chromatin) were increased. Overall, the H3K4me3 and H3K27me3 combined bivalent marks were increased after Notch1-overexpression, and this was correlated with promoted stemness as indicated by the increased Oct4 and CD44 (reported gastric cancer stem cell like marker) expression. EZH2, a Polycomb protein, was found to be associated with Rbpjκ which further links the Notch signaling together with the maintenance of cell stemness. Therefore, Notch signaling might be critical for tumor formation in gastric cancer. (Supported by: NSC-102-2320-B-194-003-MY3 and NSC-102-2314-B-371-003-MY3, MOST Taiwan) Citation Format: Chia-Chen Chiu, Chien-Ju Lo, Chien-Heng Shen, Chung-Kuang Lu, Jian-Liang Chou, Pei-Yi Chu, Shu-Huei Hsiao, Min-Jen Tseng, Yu-Wei Leu, Chia-Chen Hsu. Increased Notch1 expression suppressed the growth but promoted the stemness of gastric cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-156. doi:10.1158/1538-7445.AM2015-LB-156
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