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  • American Association for Cancer Research (AACR)  (6)
  • Hyung, Woo Jin  (6)
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  • American Association for Cancer Research (AACR)  (6)
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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 661-661
    Abstract: Background: There is increasing interest in the influence of body composition on oncologic outcomes. Using computed tomography (CT) scan, we evaluated the role of skeletal muscle and fat among patients with gastric cancer (GC) who underwent gastrectomy with or without adjuvant chemotherapy, as well as those changes' associations with survival outcomes. Methods: The present study evaluated 136 patients with GC who were enrolled in the CLASSIC trial at Yonsei Cancer Center. Baseline body compositions including skeletal muscle area, Hounsfield units (HU), visceral fat area, and subcutaneous fat area were measured by preoperative CT scan. The L3 region contains the psoas, paraspinal muscles, and abdominal muscles, which were quantified using the pre-established HU thresholds for skeletal muscle tissue (HU: -30~150). Visceral fat and subcutaneous fat areas (HU:-150~-30) were measured using axial slices at the level of the lumbar vertebra (L3). CT before and after the gastrectomy was used to determine the 6-month relative changes in body composition parameters. Continuous variables were dichotomized according to the best cut-off values by Contal and O'Quigley method. Results: Seventy-three patients (53.7%) underwent surgery alone, and 63 patients (46.3%) underwent surgery followed by adjuvant chemotherapy. The median baseline values were 46.8 cm2/m2 for SMI, 47.5 HU, 33.9 cm2/m2 for VFI, and 34.6 cm2/m2 for SFI. The baseline body composition parameters were not associated with disease-free survival (DFS) or overall survival (OS). However, patients with marked loss of skeletal muscle mass ( & lt;-11%), visceral fat area ( & lt;-48%), or subcutaneous fat ( & lt;-47%) after gastrectomy (the value was determined by best cut-off point) had poorer DFS and OS compared to patients with lesser changes. Patients with a marked loss in at least one significant body composition parameter had significantly shorter DFS (hazard ratio: 2.9, 95% confidence interval: 1.7-4.8, P & lt;0.001) and OS (hazard ratio: 2.9, 95% confidence interval: 1.7-5.0, P & lt;0.001). Conclusion: Marked loss in body composition parameters significantly predicted shorter DFS and OS among patients with GC who underwent gastrectomy. Postoperative nutrition and active health care interventions could improve the prognosis of these GC patients. CT data are readily obtainable during routine clinical practice, which makes this approach useful for identifying prognostic biomarkers. Citation Format: Si Won Lee, Hyung Soon Park, Seung Hoon Beom, Sun Young Rha, Woo Jin Hyung, Song-Ee Baek, Minkyu Jung. CT scan reveals that marked loss of muscle, visceral fat or subcutaneous fat after gastrectomy was a poor prognostic marker in advanced gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 661.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4692-4692
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 4692-4692
    Abstract: Introduction: MSI-high (MSI-H) colorectal cancer is known to be associated with increased tumor-infiltrating lymphocytes (TILs) and good prognosis. In gastric cancer, however, MSI status has rarely been evaluated in accordance with TILs. The objectives of our study were to clarify the relationships between MSI status and antitumor host immune response and to identify the impact of these factors on the prognosis of gastric cancer. Methods: We evaluated 345 patients with gastric cancer who underwent gastrectomy with MSI typing. The numbers of TILs in tumor center was counted after immunohistochemical staining with anti-CD3, CD4, CD8, Foxp3, and granzyme B to quantify the subset of TILs. To evaluate systemic immune response, differential white blood cell count and prognostic nutritional index (PNI) were obtained. Results: Of the 345 patients, 57 were MSI-H and 288 were non-MSI-H groups. MSI-H tumors carried significantly higher numbers of CD8+ T-cells, Foxp3+ T-cells, GZB+ T cells and higher ratio of Foxp3/CD4 and GZB/CD8. The prognostic effect of TILs was different in MSI-H and non-MSI-H groups. All subsets of TILs were not significant prognostic factor for recurrent-free survival (RFS) and overall survival (OS) in MSI-H group. However, in non-MSI-H group, multivariate analysis showed that stage, PNI and CD4+ T cells was independent prognostic factor for RFS; on the other hand, stage, PNI and ratio of Foxp3/CD4 was independent prognostic factor for OS. Conclusions: The number of subset of TILs and the prognostic influence of systemic and local immune response were different between MSI-H and non-MSI-H tumors. The immunogenicity caused by microsatellite instability and subsequent host immune response is associated with cancer progression and patient prognosis of gastric cancer. Citation Format: Hyoung-Il Kim, Su-Jin Shin, Sang Yong Kim, Yoon Young Choi, Taeil Son, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh. High density of cytotoxic and regulatory T-lymphocytes in gastric cancers with microsatellite instability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4692.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 1037-1037
    Abstract: Background: Recent cancer research is focused on precision medicine with the advent of next generation sequencing (NGS) technology and patient tumor derived model systems. Here, we present molecular characteristics of gastric cancer patient derived xenograft (PDX) models and explore the potential of molecularly defined PDX model based drug development. Materials and Methods: We generated PDX models from patient tumors with advanced gastric cancer. The genomic alterations of tumors were profiled by whole exome sequencing (WES), RNA sequencing (RNAseq), targeted sequencing, in-situ hybridization (ISH) and immunohistochemistry (IHC). Further, we developed overcoming strategy of chemotherapy resistance mechanism by combination of signaling pathway inhibitor and standard chemotherapy regimen in “N-of-1” PDX trial. Results: Thirty-five PDX models were successfully established and categorized into four subgroups of The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) classifications: EBV (2.9%), MSI (20.6%), GS (23.5%) and CIN (52.9%) subtypes by TCGA while MSI type (11.4%), MSS/EMT type (17.1%), MSS/TP53+ (31.4%) and MSS/TP53- type (40.0%) by ACRG. In the protein levels by IHC, there were 21 cases (60.0%) of any RTK proteins overexpression; nine of HER2 (25.7%), 14 of EGFR (40.0%), and 16 of c-MET (45.7%). Five tumors (14.3%) were related to PTEN loss and 22 tumors (62.9%) showed p53 overexpression or null. Targeted sequencing identified that ERBB2 (25.7%), KRAS (11.4%), and CCND1 (11.4%) were found frequently amplified gene while PIK3CA (11.4%) and CTNNB1 (8.6%) were found most mutated genes. N-of-1 PDX trial demonstrated that the response to FOLFOX in PDX tumor was concordant with that of corresponding patient. In FOLFOX resistant tumors, multiple signaling pathways were up-regulated and inhibition of these signaling pathways was regressed tumor growth. Conclusions: The utilization of molecularly catalogued gastric cancer PDX models will guide precision medicine for cancer therapy and be a useful tool for drug development and repurposing. Citation Format: Jae Eun Lee, Yoon Young Choi, Ju Yeon Lim, Su-Jin Shin, Gunho Lee, Eun Young Kim, Taeil Son, Hyoung-Il Kim, Woo Jin Hyung, Sung Hoon Noh, Hyunki Kim, Minkyu Jung, Sangwoo Kim, Soonmyung Paik, Jae-Ho Cheong. Comprehensive molecular profiles of gastric cancer patient derived xenograft (PDX) models and its implication in precision cancer medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1037.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 4157-4157
    Abstract: Purpose: The incidence of multiple primary cancers has increased as survival of cancer patients has improved. The most common type of multiple primary cancers is the combination of stomach and colon cancer in Korea. Patients affected by two primary cancers at early age would be mainly related to their own genetic risk, however, germline variant of patients with double primary cancer have not been well evaluated. Methods: Patient who is with pathologically confirmed cancers in both stomach and colon in Severance hospital between January, 2000 and December, 2016 were enrolled in this study. The patients were classified into two groups: early-age group was defined as both cancers were diagnosed before 55-years, and others were considered as late-age group. The overall early-age group (n=19) and randomly selected a fourth of late-age group (n=36) were enrolled in this study. The DNA was extracted from an archived formalin fixed paraffin embedded normal mucosa that was retrospectively reviewed. Target sequencing analysis focused on 65 genes that are known to be related to hereditary cancer was conducted. The characteristics of both cancers and family history were also evaluated. Results: Overall 11 pathogenic/likely pathogenic germline variants (PGVs) were detected in nine patients (16.4%, 9/55, MLH1 [n=7], BLM [n=1] , BRCA1 [n=1], MSH6 [n=1] , and MSH2 [n=1]). The incidence of PGVs was 36.8% (7/19) and 5.6% (2/36) in early and late-age group, respectively (p & lt;0.001). The early-age (Odds ratio[OR]: 9.92, 95% confidence interval [CI] : 1.81-54.49, p=0.008), Amsterdam_II criteria (OR: 24.29, 95% CI: 2.45-241.36, p=0.006), multiple lesions either gastric and colon cancer (OR: 13.13, 95% CI: 2.48-69.55, p=0.002) and mucinous/poorly differentiated histology of colon cancer (OR: 10.75, 95% CI: 1.48-78.06, p=0.019) were significant risk factors of PGVs in patients with double primary cancer at stomach and colon. Conclusions: The Lynch syndrome related PGVs were identified in patients with double primary cancer at stomach and colon. Patients with double primary cancers at stomach and colon related to early age, multiple lesions, family history especially Amsterdam_II criteria, and poorly differentiated histology of colon cancer would be good candidate for genetic evaluation. Citation Format: Yoon Young Choi, Ji Soo Park, Seung-Tae Lee, Su-Jin Shin, Jae Eun Lee, Jeong-Hyeon Jo, Eun Ji Nam, Taeil Son, Hyoung-Il Kim, Woo Jin Hyung, Sung Hoon Noh, Jae-Ho Cheong. Idenitificaiton of pathogenic germline variants of patients with double primary cancer of stomach and colon [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4157.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2650-2650
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2650-2650
    Abstract: Purpose: The role of microsatellite instability is well established in advanced gastric cancer. However, its clinical implication has not been well addressed in early gastric cancer. The purpose of this study is to evaluate the clinical characteristics of microsatellite instability in early gastric cancer. Methods: Patients who underwent gastrectomy with curative intent in Severance hospital from January, 2005 to December, 2010 and diagnosed as early gastric cancer (pT1a/b) were enrolled in this study. Remnant gastric cancer and patients who received chemotherapy before operation were excluded. Microsatellite instability status was evaluated by two mononucleotide repeat markers (BAT25 and BAT26) and three dinucleotide repeat markers (D5S346, D2S123, and D17S250) and instability in two or more markers was defined as miscrosatellite instability high (MSI-H), otherwise classified as microsatellite stable (MSS). Results: Of 1156 tumors that included the final analysis, 85 (7.4%) were MSI-H. MSI-H cancer was related to frequent female gender (54.1% vs. 32.8%, p & lt;0.001), older age (63.4 ± 10.65 vs. 56.7 ± 11.50, p & lt;0.001), lower body (81.2% vs. 59.7%, p=0.002), intestinal histology (63.5% vs. 48.2%, p=0.005), lympho-vascular invasion (25.9% vs. 13.3%, p=0.001), submucosal invasion (63.5% vs. 48.3%, p=0.007), and trend of lymph node metastasis (17.6% vs. 10.8%, p=0.056) compared to MSS type. Lymph node metastasis and lymph-vascular invasion was not differed by MSI status in mucosal gastric cancer (3.2% vs. 2.3%, p=0.755 and 3.2% vs. 2.3%, p=0.755, respectively). In sumbucosal gastric cancer, however, lympho-vascular invasion was frequently observed in MSI-H tumor (38.9% vs. 25.0%, p=0.027) but there was no difference in lymph node metastasis (25.9% vs. 19.9%, p=0.298). When we compared the disease free survival by MSI status, the prognosis of MSI-H tumor was similar compared to that of MSS tumor (log-rank test p=0.797, adjusted Hazard ratio of MSI-H by age, sex, pTstage and number of metastatic LNs: 0.932 [95% confidence interval: 0.423-2.054, p=0.861]). Conclusions: MSI status could not be a useful biomarker in early gastric cancer to predict prognosis of it. However, frequent lympho-vascular invasion of MSI-H early gastric cancer would be a warning that careful patient's selection for endoscopic treatment or limited lymph node dissection for surgery is necessary. Citation Format: Yoon Young Choi, Dong Gyu Kim, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh. Clinical implication of microsatellite instability in early gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2650.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2017
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 26, No. 5_Supplement ( 2017-05-01), p. B28-B28
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 26, No. 5_Supplement ( 2017-05-01), p. B28-B28
    Abstract: Background: Because most cases of cancer recurrence occur within 5 years, routine surveillance is also recommended for first five years. However, few patients experience late recurrence of disease, and the mechanism of late recurrence is not clearly revealed. The purpose of this study is to evaluate the clinicopathological features predicting the risk of late recurrence in gastric cancer patients. Methods: From January 2006 to December 2013, we retrospectively reviewed 813 patients who were diagnosed and treated with gastric cancer in Yonsei cancer center. Result: Among 226 patients who experienced recurrence of gastric cancer, 212 patients were diagnosed with recurrence within first five years from the curative resection of primary cancer, and 14 patients were diagnosed with recurrence of disease beyond 5 years. In comparison with early recurrence (≤ 5 years), the patients with late recurrence ( & gt; 5 years) had primary disease of stage I/II (vs. stage III; HR, 4.5; 95% CI, 1.5-14.1; P=0.009), well or moderately differentiated histology (vs. poorly differentiated or signet ring cell; HR, 4.2; 95% CI, 1.4-13.1; P=0.013), and did not receive adjuvant chemotherapy (HR, 0.3; 95% CI, 0.1-0.9; P=0.028). All the 21 patients with HER2 positive gastric cancer experienced early recurrence. Conclusion: Late recurrence of gastric cancer is possibly not influenced by advanced stage of primary disease. More attempts to find high risk groups for late recurrence of gastric cancer are needed. Citation Format: Ji Soo Park, Chu Ree Won, Taeil Son, Hyoung-Il Kim, Woo Jin Hyung, Sung Hoon Noh, Tae Il Kim. Clinicopathological features associated with late recurrence of gastric cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr B28.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2017
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    detail.hit.zdb_id: 1153420-5
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