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Kim, Jie-Hyun,Choi, Yeun Jung,Lee, Sang Hun,Shin, Hyun Soo,Lee, In Ohk,Kim, Yu Jin,Kim, Hyunki,Yang, Woo Ick,Kim, Hoguen,Lee, Yong Chan Spandidos Publications 2010 ONCOLOGY REPORTS Vol.23 No.6
<P>This study aimed to investigate the effect of Helicobacter pylori (H. pylori) infection on the sonic Hedgehog (Shh) signaling in gastric cancer. Shh, Patched (Ptch), and transcription factor Gli1 were overexpressed in H. pylori-infected gastric cancer cells. The oncoprotein, CagA positive H. pylori resulted in significantly higher Shh expression. Pretreatment with MG-132 or PDTC significantly lowered Shh expression. Significant overexpression of Shh and Gli1 were noted in H. pylori-infected compared to non-infected gastric cancer tissues. Conclusively, H. pylori activated the Shh signaling pathway in CagA-dependent manner partly through the NF-kappaB pathway in gastric cancer cells.</P>
Kim, Bun,Kim, Eun Hye,Park, Soo Jung,Cheon, Jae Hee,Kim, Tae Il,Kim, Won Ho,Kim, Hoguen,Hong, Sung Pil Wolters Kluwer Health 2016 Medicine Vol.95 No.37
<P><B>Abstract</B></P><P>Though endoscopic treatment is an option for T1 colorectal cancer (CRC), the optimal indications and long-term outcomes of this strategy need to be validated. Therefore, the aim of this study is to investigate long-term outcomes of endoscopy versus surgery and optimal indications for endoscopic treatment of T1 CRC.</P><P>This retrospective study included 428 T1 CRC patients treated with initial endoscopy (n = 224) or surgery (n = 204) at Severance Hospital between 2005 and 2012. Patients were subdivided into 4 groups according to conventional indications (CIs) for endoscopic treatment: negative lateral/vertical margins; submucosal invasion depth within 1000 μm; no lymphovascular invasion (LVI); well or moderately differentiated. For prognosis evaluation, short-term outcomes (resection margin and complications) and long-term outcomes (recurrence and cancer-specific mortality) were evaluated.</P><P>Endoscopic treatment achieved en bloc resection in 86.6% of 224 patients. Recurrence and mortality did not differ between the endoscopy and surgery groups with or without CIs. For patients with CIs, although 80 patients were treated endoscopically with 1 (1.3%) recurrence and 0 mortality, 75 patients were treated surgically with 2 (2.7%) recurrence and 1 (1.3%) mortality. Multivariate analysis revealed that LVI positivity and poorly differentiated histology were independently associated with lymph node metastasis (LNM; <I>P</I> < 0.001 and <I>P</I> = 0.001, respectively).</P><P>To determine whether the depth of submucosal invasion among criteria of CIs could be extended for endoscopic treatment, LNM was analyzed by extending the depth of submucosal invasion. There was no LNM in 155 patients within conventional indication. When the depth of submucosal invasion was extended up to 1500 μm, LNM was occurred (1/197 patient [0.5%]). In addition, when the depth of submucosal invasion was extended up to 2000 μm, LNM was increased (4/271 patient [1.5%]).</P><P>Endoscopic treatment is safe, effective, and is associated with favorable long-term outcomes compared to surgery for initial treatment of T1 CRC patients with CIs. However, the risk of LNM makes it unsafe to extend the CIs for endoscopic therapy in these patients.</P>
김진석,김원호,김중선,조용석,김남규,김호근,박인서 대한소화기내시경학회 2000 Clinical Endoscopy Vol.20 No.3
Background/Aims: The aim of this study was to evaluate the characteristics of colorectal polyps, especially distal colorectal polyps and their frequency in patients with colon cancer located proximal to the splenic flexure. Methods: Among 1,250 patients with colorectal cancer, 269 patients (21.5%) had colon cancer located proximal to the splenic flexure. Of these, 183 patients were involved in this study because complete colonoscopic evaluations to the cecum or to the level of proximal colon cancer were possible. Results: 54 patients (29.5%) had one or more distal colorectal polyps, 33 patients (18.1%) had one or more adenomatous distal polyps, and 3 patients (1.6%) had synchronous distal carcinoma. The percentage of patients without distal polyps was 70.5% of 183 patients with proximal colon cancer, and 80.3% of patients without distal neoplastic lesions. The percentage of patients with advanced lesions (villous component, high-grade dysplasia, or ≥1 cm in diameter) was 40.7% of 54 patients with distal coloectal polyps. Conclusions: Flexible sigmoidoscopy is insensitive and ineffective for the detection of proximal colon cancer. Ongoing evaluation of colonoscopy as a general screening test is appropriate.
Coxsackie and Adenovirus Receptor Binding Ablation Reduces Adenovirus Liver Tropism and Toxicity
Yun, Chae-Ok,Yoon, A-Rum,Yoo, Ji Young,Kim, Hoguen,Kim, Minjung,Ha, Taeyong,Kim, Gwi Eon,Kim, Hyunhee,Kim, Joo-Hang Mary Ann Liebert 2005 Human gene therapy Vol.16 No.2
<P>Human adenovirus-based vectors have emerged as a new promising vehicle for in vivo gene transfer-mediated therapy. However, the full potential of this methodology has not been fully realized because of the nonspecific tissue distribution of adenoviral vectors. Adenovirus infection is initiated by forming a complex between the fiber protein and a ubiquitously expressed host cell membrane protein, coxsackie B virus and adenovirus receptor (CAR). Therefore, ablating the adenovirus vector's ability to bind to the CAR is the first step in redirecting adenoviral tropism. To ablate CAR binding, we mutated the Bbeta sheet of the fiber knob, generating CAR-binding ablated replication-incompetent (dl-K420A-Z) and replication-competent (YKLK420A) adenoviral vectors. The in vitro transduction efficiency of dl-K420A-Z was significantly reduced in comparison to dl-LacZ carrying the wild-type fiber in CAR-positive cells but not in CAR-negative cells, suggesting that the mutation introduced in the Bbeta sheet of the fiber knob could disable the CAR-dependent transduction pathway. The in vivo transduction was also dramatically reduced in the liver and other organs for mice treated with dl-K420A-Z, compared with a cognate control vector, dl-LacZ. Concomitant with this attenuated gene transfer efficiency in vivo was a substantial reduction in the amount of general toxicity observed in the YKL-K420A-treated mice. Diminished toxicity was surmised from quantitative measurement of serum level of enzymes for liver and kidney function, hematologic chemistries, histopathology, and differences in lethality. Significant decrease in serum transaminases (alanine transferase [ALT] and aspartate transferase [AST]) was observed in mice treated with YKL-K420A. In addition, the lethality was lower in the YKLK420A- treated groups compared to the YKL-1-treated groups at all doses examined. Furthermore, the hepatopathologic analysis revealed that YKL-1 induced focal zonal necrosis and hepatocyte degeneration, while YKL-K420A induced mild spotty necrosis. In summary, this decreased vector tropism of CAR-binding ablated adenoviruses in normal tissues may increase the amount of virus available for infecting tumor cells and thus increase the antitumor efficacy with fewer unwanted side effects.</P>
Kim, Won Kyu,Yun, SeongJu,Park, Cheol Keun,Bauer, Sebastian,Kim, Jiyoon,Lee, Min Goo,Kim, Hoguen American Association for Cancer Research 2017 Clinical Cancer Research Vol.23 No.3
<P><B>Purpose:</B> Tumorigenesis of gastrointestinal stromal tumors (GIST) is driven by gain-of-function mutations in the <I>KIT</I> gene, which result in overexpression of activated mutant KIT proteins (MT-KIT). However, the mechanism of MT-KIT overexpression is poorly understood.</P><P><B>Experimental Design:</B> By protein expression analysis and immunofluorescent microscopic analysis, we determine the stability and localization of MT-KIT in four GIST cell lines with different mutations and HeLa cells transfected with mutant KIT model vectors. We also used 154 human GIST tissues to analyze the relationship between the expression of PKC-θ and MT-KITs, and correlations between PKC-θ overexpression and clinicopathological parameters.</P><P><B>Results:</B> We report that four different MT-KIT proteins are intrinsically less stable than wild-type KIT due to proteasome-mediated degradation and abnormally localized to the endoplasmic reticulum (ER) or the Golgi complex. By screening a MT-KIT-stabilizing factor, we find that PKC-θ is strongly and exclusively expressed in GISTs and interacts with intracellular MT-KIT to promote its stabilization by increased retention in the Golgi complex. In addition, Western blotting analysis using 50 GIST samples shows strong correlation between PKC-θ and MT-KIT expression (correlation coefficient = 0.682, <I>P</I> < 0.000001). Immunohistochemical analysis using 154 GISTs further demonstrates that PKC-θ overexpression significantly correlates with several clinicopathological parameters such as high tumor grade, frequent recurrence/metastasis, and poor patient survival.</P><P><B>Conclusions:</B> Our findings suggest that sustained MT-KIT overexpression through PKC-θ-mediated stabilization in the Golgi contributes to GIST progression and provides a rationale for anti-PKC-θ therapy in GISTs. <I>Clin Cancer Res; 23(3); 845–56. ©2016 AACR</I>.</P>
Kim, Young-Wan,Kim, Nam-Kyu,Min, Byung-Soh,Lee, Kang-Young,Sohn, Seung-Kook,Cho, Chang-Hwan,Kim, Hoguen,Keum, Ki-Chang,Ahn, Jung-Bai Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of surgical oncology Vol.100 No.1
<B>Background</B><P>We aimed to assess factors associated with the number of nodes retrieved and the impact of the number of lymph nodes in rectal cancer patients who underwent neoadjuvant chemoradiation with radical surgery.</P><B>Methods</B><P>A total of 258 patients were enrolled. Lymph nodes were retrieved from specimens using a manual dissection technique.</P><B>Results</B><P>Of the 258 patients, nine patients had an absence of lymph nodes (ypNx), 150 patients had a node-negative status (ypN(−)) and 99 patients had node-positive disease (ypN(+)). An advanced ypT classification (ypT3,4) and larger tumor (>4 cm) were associated with an increased number of nodes retrieved. The pretreatment CEA level (>5 ng/ml) and ypN(+) classification were significant risk factors for cancer specific and recurrence free survival. There was no significant difference of oncological outcomes among ypNx patients and a subset of ypN(−) patients based on the number of nodes retrieved using three cutoff values (1–11, 12–25, and 25–65 nodes).</P><B>Conclusions</B><P>In a neoadjuvant setting, ypN(+) disease was an independent risk factor for oncological outcomes. An absence of nodes does not represent an inferior oncological outcome. The number of nodes does not seen to impact survival and recurrence in ypN(−) patients. J. Surg. Oncol. 2009;100:1–7. © 2009 Wiley-Liss, Inc.</P>