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    • Several versions

    Effectiveness of Sleeve Gastrectomy for Metabolic Surgery in Korea

    Park, Young Suk, Ahn, Sang-Hoon, Park, Do Joong, Kim, Hyung-Ho
    Journal of obesity & metabolic syndrome, 30 September 2018, Vol.27(3), pp.131-133 [Peer Reviewed Journal]

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    Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells

    Yoon, Changhwan, Cho, Soo-Jeong, Aksoy, Bülent Arman, Park, Do Joong, Schultz, Nikolaus, Ryeom, Sandra W, Yoon, Sam S
    Clinical cancer research : an official journal of the American Association for Cancer Research, 15 February 2016, Vol.22(4), pp.971-83 [Peer Reviewed Journal]
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    Title: Chemotherapy Resistance in Diffuse-Type Gastric Adenocarcinoma Is Mediated by RhoA Activation in Cancer Stem-Like Cells
    Author: Yoon, Changhwan; Cho, Soo-Jeong; Aksoy, Bülent Arman; Park, Do Joong; Schultz, Nikolaus; Ryeom, Sandra W; Yoon, Sam S
    Subject: Adenocarcinoma -- Enzymology ; Antineoplastic Agents -- Pharmacology ; Cisplatin -- Pharmacology ; Neoplastic Stem Cells -- Enzymology ; Stomach Neoplasms -- Enzymology ; Rhoa Gtp-Binding Protein -- Metabolism
    Description: The Lauren diffuse type of gastric adenocarcinoma (DGA), as opposed to the intestinal type (IGA), often harbors mutations in RHOA, but little is known about the role of RhoA in DGA. We examined RhoA activity and RhoA pathway inhibition in DGA cell lines and in two mouse xenograft models. RhoA activity was also assessed in patient tumor samples. RhoA activity was higher in DGA compared with IGA cell lines and was further increased when grown as spheroids to enrich for cancer stem-like cells (CSCs) or when sorted using the gastric CSC marker CD44. RhoA shRNA or the RhoA inhibitor Rhosin decreased expression of the stem cell transcription factor, Sox2, and decreased spheroid formation by 78% to 81%. DGA spheroid cells had 3- to 5-fold greater migration and invasion than monolayer cells, and this activity was Rho-dependent. Diffuse GA spheroid cells were resistant in a cytotoxicity assay to 5-fluorouracil and cisplatin chemotherapy, and this resistance could be reversed with RhoA pathway inhibition. In two xenograft models, cisplatin inhibited tumor growth by 40% to 50%, RhoA inhibition by 32% to 60%, and the combination by 77% to 83%. In 288 patient tumors, increased RhoA activity correlated with worse overall survival in DGA patients (P = 0.017) but not in IGA patients (P = 0.612). RhoA signaling promotes CSC phenotypes in DGA cells. Increased RhoA activity is correlated with worse overall survival in DGA patients, and RhoA inhibition can reverse chemotherapy resistance in DGA CSC and in tumor xenografts. Thus, the RhoA pathway is a promising new target in DGA patients.
    Is part of: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 February 2016, Vol.22(4), pp.971-83
    Identifier: 1078-0432 (ISSN); 26482039 Version (PMID); 10.1158/1078-0432.CCR-15-1356 (DOI)

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    Is endoscopic surveillance necessary for patients who undergo total gastrectomy for gastric cancer?

    Park, Sung Jae, Park, Young Soo, Jung, In Sub, Yoon, Hyuk, Shin, Cheol Min, Ahn, Sang-Hoon, Park, Do Joong, Kim, Hyung Ho, Kim, Nayoung, Lee, Dong Ho
    PLoS ONE, 2018, Vol.13(6) [Peer Reviewed Journal]

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    Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition

    Cho, Soo-Jeong, Yoon, Changhwan, Lee, Jun Ho, Chang, Kevin K, Lin, Jian-Xian, Kim, Young-Ho, Kook, Myeong-Cherl, Aksoy, Bülent Arman, Park, Do Joong, Ashktorab, Hassan, Smoot, Duane T, Schultz, Nikolaus, Yoon, Sam S
    Clinical cancer research : an official journal of the American Association for Cancer Research, 15 December 2018, Vol.24(24), pp.6556-6569 [Peer Reviewed Journal]
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    Title: Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to-Mesenchymal Transition
    Author: Cho, Soo-Jeong; Yoon, Changhwan; Lee, Jun Ho; Chang, Kevin K; Lin, Jian-Xian; Kim, Young-Ho; Kook, Myeong-Cherl; Aksoy, Bülent Arman; Park, Do Joong; Ashktorab, Hassan; Smoot, Duane T; Schultz, Nikolaus; Yoon, Sam S
    Subject: Mutation ; Adenocarcinoma -- Genetics ; DNA-Binding Proteins -- Genetics ; Epithelial-Mesenchymal Transition -- Genetics ; Stomach Neoplasms -- Genetics
    Description: Lauren diffuse-type gastric adenocarcinomas (DGAs) are generally genomically stable. We identified lysine (K)-specific methyltransferase 2C () as a frequently mutated gene and examined its role in DGA progression. We performed whole exome sequencing on tumor samples of 27 patients with DGA who underwent gastrectomy. Lysine (K)-specific methyltransferase 2C () was analyzed in DGA cell lines and in patient tumors. was the most frequently mutated gene (11 of 27 tumors [41%]). KMT2C expression by immunohistochemistry in tumors from 135 patients with DGA undergoing gastrectomy inversely correlated with more advanced tumor stage ( = 0.023) and worse overall survival ( = 0.017). KMT2C shRNA knockdown in non-transformed HFE-145 gastric epithelial cells promoted epithelial-to-mesenchymal transition (EMT) as demonstrated by increased expression of EMT-related proteins N-cadherin and Slug. Migration and invasion in gastric epithelial cells following KMT2C knockdown increased by 47- to 88-fold. In the DGA cell lines MKN-45 and SNU-668, which have lost KMT2C expression, KMT2C re-expression decreased expression of EMT-related proteins, reduced cell migration by 52% to 60%, and reduced cell invasion by 50% to 74%. Flank xenografts derived from KMT2C-expressing DGA organoids, compared with wild-type organoids, grew more slowly and lost their infiltrative leading edge. EMT can lead to the acquisition of cancer... is frequently mutated in certain populations with DGA. KMT2C loss in DGA promotes EMT and is associated with worse overall survival.
    Is part of: Clinical cancer research : an official journal of the American Association for Cancer Research, 15 December 2018, Vol.24(24), pp.6556-6569
    Identifier: 1078-0432 (ISSN); 30108106 Version (PMID); 10.1158/1078-0432.CCR-17-1679 (DOI)

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    CD44 expression denotes a subpopulation of gastric cancer cells in which Hedgehog signaling promotes chemotherapy resistance

    Yoon, Changhwan, Park, Do Joong, Schmidt, Benjamin, Thomas, Nicholas J, Lee, Hae-June, Kim, Teresa S, Janjigian, Yelena Y, Cohen, Deirdre J, Yoon, Sam S
    Clinical cancer research : an official journal of the American Association for Cancer Research, 01 August 2014, Vol.20(15), pp.3974-88 [Peer Reviewed Journal]
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    Title: CD44 expression denotes a subpopulation of gastric cancer cells in which Hedgehog signaling promotes chemotherapy resistance
    Author: Yoon, Changhwan; Park, Do Joong; Schmidt, Benjamin; Thomas, Nicholas J; Lee, Hae-June; Kim, Teresa S; Janjigian, Yelena Y; Cohen, Deirdre J; Yoon, Sam S
    Subject: Drug Resistance, Neoplasm ; Adenocarcinoma -- Drug Therapy ; Antineoplastic Combined Chemotherapy Protocols -- Pharmacology ; Hedgehog Proteins -- Metabolism ; Hyaluronan Receptors -- Metabolism ; Neoplastic Stem Cells -- Pathology ; Stomach Neoplasms -- Drug Therapy
    Description: Gastric cancers may harbor a subset of cells with cancer stem cell (CSC) properties, including chemotherapy resistance, and CD44 is a gastric CSC marker. The Hedgehog (HH) pathway is a key developmental pathway that can be subverted by CSCs during tumorigenesis. Here, we examine the role of HH signaling in CD44(+) gastric cancer cells. Gastric cancer cell lines, tumor xenografts, and patient tumors were examined. Gastric cancer cell lines AGS, MKN-45, and NCI-N87 grown as spheroids or sorted for CD44(+) were found to have upregulation of HH pathway proteins. HH inhibition using Smoothened (Smo) shRNA or vismodegib (VIS) decreased spheroid formation and colony formation. CD44(+) cells, compared with unselected cells, were also resistant to 5-fluorouracil and cisplatin chemotherapy, and this resistance was reversed in vitro and in xenografts with Smo shRNA or VIS. CD44(+) cells also had significantly more migration, invasion, and anchorage-independent growth, and these properties could all be blocked with HH inhibition. Clinical tumor samples from a phase II trial of chemotherapy with or without VIS for advanced gastric cancer were analyzed for CD44 expression. In the chemotherapy alone group, high CD44 expression was associated with decreased survival, whereas in the chemotherapy plus VIS group, high CD44 expression was associated with improved survival. HH signaling maintains CSC phenotypes and malignant transformation phenotypes in CD44(+) gastric cancer cells, and HH inhibition can reverse chemotherapy resistance in CD44(+) cells. Gastric cancer is a heterogeneous disease, and the strategy of combining chemotherapy with HH inhibition may only be effective in tumors with high CD44 levels.
    Is part of: Clinical cancer research : an official journal of the American Association for Cancer Research, 01 August 2014, Vol.20(15), pp.3974-88
    Identifier: 1078-0432 (ISSN); 24947926 Version (PMID); 10.1158/1078-0432.CCR-14-0011 (DOI)

    • Several versions

    Laparoscopic Proximal Gastrectomy as a Surgical Treatment for Upper Third Early Gastric Cancer

    Park, Do Joong, Park, Young Suk, Ahn, Sang Hoon, Kim, Hyung Ho
    The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi, 25 September 2017, Vol.70(3), pp.134-140 [Peer Reviewed Journal]

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    Comparative study of clinical outcomes between laparoscopy-assisted proximal gastrectomy (LAPG) and laparoscopy-assisted total gastrectomy (LATG) for proximal gastric cancer

    Ahn, Sang-Hoon, Lee, Ju, Park, Do, Kim, Hyung-Ho
    Gastric Cancer, 2013, Vol.16(3), pp.282-289 [Peer Reviewed Journal]

    • Several versions

    Proximal Gastrectomy for Gastric Cancer

    Jung, Do Hyun, Ahn, Sang-Hoon, Park, Do Joong, Kim, Hyung-Ho
    Journal of gastric cancer, June 2015, Vol.15(2), pp.77-86 [Peer Reviewed Journal]

    • Several versions

    A case of anaphylactic shock attributed to latex allergy during gastric cancer surgery

    Lee, Woohyung, Lee, Jue Hee, Park, Do Joong, Kim, Hyung-Ho
    Journal of the Korean Surgical Society, December 2011, Vol.81 Suppl 1, pp.S30-3 [Peer Reviewed Journal]

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    Laparoscopy-assisted proximal gastrectomy for early gastric cancer is an ugly duckling with unsolved concerns: oncological safety, late complications, and functional benefit

    Ahn, Sang-Hoon, Lee, Ju Hee, Park, Do Joong, Kim, Hyung-Ho
    Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, July 2013, Vol.16(3), pp.448-50 [Peer Reviewed Journal]
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    Title: Laparoscopy-assisted proximal gastrectomy for early gastric cancer is an ugly duckling with unsolved concerns: oncological safety, late complications, and functional benefit
    Author: Ahn, Sang-Hoon; Lee, Ju Hee; Park, Do Joong; Kim, Hyung-Ho
    Subject: Gastrectomy -- Methods ; Laparoscopy -- Methods ; Stomach Neoplasms -- Surgery
    Is part of: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, July 2013, Vol.16(3), pp.448-50
    Identifier: 1436-3305 (E-ISSN); 23483303 Version (PMID); 10.1007/s10120-013-0245-y (DOI)