http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Fink, Stephen P,Yang, Dong-Hoon,Barnholtz-Sloan, Jill S,Ryu, Yeon-Mi,Mikkola, Debra,Potter, John D,Lampe, Johanna W,Markowitz, Sanford D,Myung, Seung-Jae Plenum Pub. Corp.] 2013 Digestive diseases and sciences Vol.58 No.9
<P>15-Hydroxprostaglandin dehydrogenase (15-PGDH) mediates a colon neoplasia suppressor pathway, acting through metabolic antagonism of cyclooxygenase-mediated colon carcinogenesis. To determine whether the colon tumor prevention activity of 15-PGDH acts as a constant or variable effect among individuals, we determined whether 15-PGDH levels remain stable over subsite and time in the human colon, determined the extent of differences in 15-PGDH levels between different individuals, and determined whether 15-PGDH modulation mediates any part of the anti-colon tumor effect of aspirin.</P>
Yan, Min,Myung, Seung-Jae,Fink, Stephen P,Lawrence, Earl,Lutterbaugh, James,Yang, Peiying,Zhou, Xiaohua,Liu, Danielle,Rerko, Ronald M,Willis, Joseph,Dawson, Dawn,Tai, Hsin-Hsiung,Barnholtz-Sloan, Jill National Academy of Sciences 2009 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.106 No.23
<P>Pharmacologic inhibitors of the prostaglandin-synthesizing COX-2 oncogene prevent the development of premalignant human colon adenomas. However, resistance to treatment is common. In this study, we show that the adenoma prevention activity of the COX-2 inhibitor celecoxib requires the concomitant presence of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) tumor suppressor gene, and that loss of 15-PGDH expression imparts resistance to celecoxib's anti-tumor effects. We first demonstrate that the adenoma-preventive activity of celecoxib is abrogated in mice genetically lacking 15-PGDH. In FVB mice, celecoxib prevents 85% of azoxymethane-induced tumors >1 mm in size, but is essentially inactive in preventing tumor induction in 15-PGDH-null animals. Indeed, celecoxib treated 15-PGDH null animals develop more tumors than do celecoxib naive WT mice. In parallel with the loss of tumor prevention activity, celecoxib-mediated suppression of colonic PGE(2) levels is also markedly attenuated in 15-PGDH-null versus WT mice. Finally, as predicted by the murine models, humans with low colonic 15-PGDH levels also exhibit celecoxib resistance. Specifically, in a colon adenoma prevention trial, in all cases tested, individuals who developed new adenomas while receiving celecoxib treatment were also found as having low colonic 15-PGDH levels.</P>
Molecular Imaging of Colorectal Tumors by Targeting Colon Cancer Secreted Protein-2 (CCSP-2)
Kim, Jaeil,Do, Eun-ju,Moinova, Helen,Bae, Sang Mun,Kang, Ja Young,Hong, Seung-Mo,Fink, Stephen P.,Joo, Jinmyoung,Suh, Young-Ah,Jang, Se Jin,Hwang, Sung Wook,Park, Sang Hyoung,Yang, Dong-Hoon,Ye, Byong Neoplasia Press 2017 Neoplasia Vol.19 No.10
<P>A versatile biomarker for detecting colonic adenoma and colon cancer has yet to be developed. Colon cancer secreted protein-2 (CCSP-2) is a protein specifically expressed and secreted in colon adenomas and cancers. We developed a fluorescent imaging method based on CCSP-2 targeting for a more sensitive and specific detection of colorectal tumors. CCSP-2 expression was evaluated in human colon adenoma and colorectal specimens. Anti–CCSP-2 antibody was labeled with a near-infrared fluorescent dye, FPR-675, and molecular imaging of surgical human colorectal tumors was performed. Immunohistochemistry identified CCSP-2 expression in 87.0% of colorectal cancer specimens and 89.5% of colon adenoma specimens. Fluorescence imaging of surgical human colon specimens after spraying treatment with the probe permitted a clear distinction of cancer from paired normal colon tissue (target-to-background ratio, 4.09 ± 0.42; <I>P</I> < .001). CCSP-2 targeting imaging was also evaluated in patient-derived colon cancer xenograft mouse and liver metastasis murine models. CCSP-2–positive colon cancer xenografts and liver metastases were visualized by near-infrared fluorescence imaging after intravenous injection of the probe, which showed significantly higher fluorescence. Our results show that CCSP-2 is a promising marker for colorectal tumor detection in clinical settings and that a CCSP-2–targeting molecular imaging strategy might improve the diagnosis of colorectal tumors in metastatic or recurrent cancers and aid in early colonoscopic detection of premalignant lesions.</P>
Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration
Zhang, Yongyou,Desai, Amar,Yang, Sung Yeun,Bae, Ki Beom,Antczak, Monika I.,Fink, Stephen P.,Tiwari, Shruti,Willis, Joseph E.,Williams, Noelle S.,Dawson, Dawn M.,Wald, David,Chen, Wei-Dong,Wang, Zhengh American Association for the Advancement of Scienc 2015 Science Vol.348 No.6240
<P><B>A shot in the arm for damaged tissue</B></P><P>Tissue damage can be caused by injury, disease, and even certain medical treatments. There is great interest in identifying drugs that accelerate tissue regeneration and recovery, especially drugs that might benefit multiple organ systems. Zhang <I>et al.</I> describe a compound with this desired activity, at least in mice (see the Perspective by FitzGerald). SW033291 promotes recovery of the hematopoietic system after bone marrow transplantation, prevents the development of ulcerative colitis in the intestine, and accelerates liver regeneration after hepatic surgery. It acts by inhibiting an enzyme that degrades prostaglandins, lipid signaling molecules that have been implicated in tissue stem cell maintenance.</P><P><I>Science</I>, this issue 10.1126/science.aaa2340; see also p. 1208</P><P>Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.</P>
Ryu, Yeon-Mi,Myung, Seung-Jae,Park, Young Soo,Yang, Dong-Hoon,Song, Ho June,Jeong, Jin-Yong,Lee, Sun Mi,Song, Miyeoun,Kim, Do Hoon,Lee, Hyo-Jeong,Park, Soo-Kyung,Fink, Stephen P.,Markowitz, Sandy D.,J American Association for Cancer Research 2013 Cancer prevention research Vol.6 No.4
<P><I>Helicobacter pylori</I> (<I>H. pylori</I>) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with <I>H. pylori</I>. 15-PGDH expression in gastric biopsies from <I>H. pylori</I>–infected (<I>n</I> = 25) and noninfected (<I>n</I> = 15) subjects was analyzed by quantitative real-time PCR, Western blot analysis, and immunohistochemistry. 15-PGDH DNA methylation was evaluated by methylation-specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, extracellular signal–regulated kinase (ERK)1/2, TLR4, and MyD88 in response to <I>H. pylori</I> infection was assessed by immunoblot analysis. Compared with negative specimens, <I>H. pylori</I>–positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four <I>H. pylori–</I>infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by <I>H. pylori</I> eradication therapy. In parallel with suppressing 15-PGDH expression, <I>H. pylori</I> infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of EGF receptor (EGFR)-Snail. Inhibition of Snail and MyD88 reversed suppression of 15-PGDH expression, and siMyD88 reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 and EGFR inhibitor also restored 15-PGDH expression. <I>H. pylori</I> appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 or EGFR-Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in <I>H. pylori</I>–induced gastric carcinogenesis. <I>Cancer Prev Res; 6(4); 349–59. ©2013 AACR.</I></P>