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Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

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Oncology Research 2024年第4期32卷 615-624页

作者： HYUNG SUN KIM YUN SUN LEE SEUNG MYUNG DONG HYO JUNG KIM DA EUN LEE HYEON WOONG KANG MYEONG JIN KIM JOON SEONG PARK Department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea Department of Surgery Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulKorea Gibiome Co. Ltd.Gyeonggi-doKorea

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been *** this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of *** found that N-WASP is markedly expressed in clinical patients with *** analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile *** of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and *** also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were *** N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic *** results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer *** findings may aid in the development of therapeutic strategies against pancreatic cancer.

关键词： Pancreatic cancer Neural Wiskott-Aldrich syndrome protein(N-WASP)signaling Metastasis Epithelial-mesenchymal transition(EMT) Lysyl oxidase-like 2(LOXL2)

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Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm

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Stroke & Vascular Neurology 2024年第3期9卷 295-305,I0251-I0263页

作者： Hae Rang Kim Min Jeoung Kim Sunyeup Kim Myung Soo Chang Dong Joon Kim Byung Moon Kim Keun Young Park Yong Bae Kim Christopher Seungkyu Lee Suk Ho Byeon Sung Soo Kim Seung Won Lee Yong Joon Kim Department of Ophthalmology CHA Bundang Medical CenterCHA University College of MedicineSeongnamKorea(the Republic of) Department of Neurosurgery Severance Stroke CenterSeverance HospitalYonsei University College of MedicineSeoulKorea(the Republic of) Department of Neurosurgery Uijeongbu St.Mary’s HospitalThe Catholic University of Korea College of MedicineUijeongbuKorea(the Republic of) Department of Medical AI Sungkyunkwan University School of MedicineSuwonKorea(the Republic of) Department of Ophthalmology Institute of Vision ResearchYonsei University College of MedicineSeoulKorea(the Republic of) Department of Radiology Severance Stroke CenterSeverance HospitalYonsei University College of MedicineSeoulKorea(the Republic of) Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonKorea(the Republic of)

Background To evaluate the association between retinal artery/arteriole occlusion(RAO)and unruptured intracranial aneurysm(UIA).Methods Incident UIA patients from a nationwide cohort(n=253240)were categorised into three groups based on subsequent treatment:observation(n=208993),microsurgical clipping(n=14168)and endovascular treatment(EVT)groups(n=30079).The incidence and the incident time of RAO were *** of RAO and associated risk factors were ***,a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of *** In the nationwide cohort analysis,the incidence of RAO was significantly higher in EVT group than in observation and clipping groups,especially within 60 days(early RAO(within 60 days):HR=4.00,95%CI:2.44 to 6.56);delayed RAO(after 60 days:HR=1.74,95%CI:1.13 to 2.68).Multivariable analysis showed that the presence of chronic kidney disease(p=0.009)and use of a balloon microcatheter during the procedure(p=0.013)were associated with a higher risk of *** hospital cohort analysis,11(0.8%)cases of RAO occurred after EVT,whereas none occurred after microsurgical clipping(p<0.001).Patients with RAO were younger and received balloon microcatheters more frequently than their *** cases of RAO(90.9%)occurred in paraclinoid aneurysms,where EVT was preferred over microsurgical *** Performing EVT for UIA may increase the risk of subsequent *** should be taken when treating paraclinoid aneurysms with balloon microcatheters.

关键词： treatment nationwide balloon

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Outcome after gastrectomy in gastric cancer patients with type 2 diabetes

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World Journal of Gastroenterology 2012年第1期18卷 49-54页

作者： Jong Won Kim Jae-Ho Cheong Woo Jin Hyung Seung-Ho Choi Sung Hoon Noh Department of Surgery Gangnam Severance Hospital Yonsei University College of Medicine Department of Surgery Severance Hospital Yonsei University College of Medicine

AIM: To evaluate the prognosis of type Ⅱ diabetes mellitus (T2DM) after gastrectomy and related factors in gastric cancer patients. METHODS: 403 gastric cancer patients with T2DM were studied, who underwent gastrectomy between May 2003 and September 2009. A review of medica records and telephone interviews was performed in this cross-sectional study. The factors included in the statistical analysis were as follows: gender, age, type of surgery, preoperative body mass index (BMI), current BMI, BMI reduction ratio, preoperative insulin or oral diabetic medicine requirement, follow-up duration, and current state of diabetes. Assessment of diabetes status after surgery was classified into four categories according to the change in hypoglycemic agents after surgery and present status of T2DM: resolution, improvement, same, and worse.(± 20.6 mo), preoperative BMI was 24.7 kg/m2 (± 3.0 kg/m2), and BMI reduction ratio was 9.8% (± 8.6%). After surgery, T2DM was cured in 58 patients (15.1%) and was improved in 117 patients (30.4%). According to the type of surgery, the BMI reduction ratio was signif icantly higher in the total gastrectomy and Roux-en-Y reconstruction group [14.2% ± 9.2% vs 9.2% ± 7.7% (Billroth Ⅱ group), P < 0.001] and signif icantly lower in the subtotal gastrectomy and Billroth Ⅰ reconstruction group [7.6% ± 8.0%, 9.2% ± 7.7% (Billroth Ⅱ group), P < 0.001]. The BMI reduction ratio, follow-up duration after surgery, type of surgery, extent of gastrectomy, and performance of duodenal bypass were signif icantly correlated to the course of T2DM (P < 0.05). The BMI reduction ratio was the most influential factor on T2DM status. In a subgroup analysis of patients with a BMI reduction ratio of 10% or less (n = 206), T2DM was cured in 15 (7.6%) patients and was improved in 57 (28.8%) patients after surgery, and only the duration of surgery was signif icantly correlated to T2DM status (P = 0.022).

关键词： Gastric cancer Diabetes mellitus Metabolic surgery Bariatric surgery

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A pilot clinical study to evaluate feasibility of using single patient classifier as a prognostic test in stage Ⅱ-Ⅲ gastric cancer patients

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Chinese Journal of Cancer Research 2024年第4期36卷 368-377页

作者： Ji Yeong An Sung Eun Oh Soomin Ahn Hyoung-II Kim Yoo Min Kim Minah Cho Keun Won Ryu Hong Man Yoon Young Kyu Park In Gyu Kwon Sung Hoon Noh Kyung Hee Lee In Cho Myoung Won Son Jong Won Kim Young-Woo Kim Department of Surgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351Republic of Korea Department of Pathology and Translational Genomics Samsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351Republic of Korea Department of Surgery Yonsei University College of MedicineSeoul 03722Republic of Korea Gastric Cancer Center Yonsei Cancer CenterYonsei University Health SystemSeoul 03722Republic of Korea Center for Gastric Cancer National Cancer CenterGoyang 10408Republic of Korea Department of Surgery Chonnam National University Hwasun HospitalChonnam National University College of MedicineGwangju 58128Republic of Korea Department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoul 06273Republic of Korea Department of Hematology-Oncology Yeungnam University Medical CenterDaegu 42415Republic of Korea Department of Surgery Soonchunhyang University College of MedicineBucheon 14584Republic of Korea Department of Surgery Soonchunhyang University Cheonan HospitalSoonchunhyang University College of MedicineCheonan 31151Republic of Korea Department of Surgery Chung-Ang University HospitalChung-Ang University College of MedicineSeoul 06973Republic of Korea

Objective:Precision medicine approaches emphasize the importance of reliable prognostic tools for guiding individualized therapy *** this study,we evaluated the clinical feasibility of the single patient classifier(SPC)test,a new clinical-grade prognostic assay,in stageⅡ-Ⅲgastric cancer ***:A prospective multicenter study was conducted,involving 237 patients who underwent gastrectomy between September 2019 and August 2020 across nine *** SPC test was employed to stratify patients into risk groups,and its feasibility and performance were *** primary endpoint was the proportion of the cases in which the test results were timely delivered before selecting postoperative ***,3-year disease-free survivals of risk groups were ***:The SPC test met the primary endpoint *** 99.5%of SPC tests were timely delivered to hospitals before the postoperative treatment *** a clinical setting,the median time from the specimen transfer to laboratory to the result delivery to hospital was 4 ***,3-year disease-free survivals were significantly different between risk groups classified with SPC ***:This study highlights the SPC test's feasibility in offering crucial information timely delivered for making informed decisions regarding postoperative treatment *** also provides evidence to support the implementation of a future prospective clinical trial aimed at evaluating the clinical utility of the SPC test in guiding personalized treatment decisions for gastric cancer patients.

关键词： Prognostic test advanced gastric cancer adjuvant chemotherapy feasibility gastrectomy

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Value of controlled attenuation parameter in fibrosis prediction in nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2019年第33期25卷 4959-4969页

作者： Jung Il Lee Hyun Woong Lee Kwan Sik Lee Department of Internal Medicine Gangnam Severance Hospital Yonsei University College of Medicine

BACKGROUND Liver stiffness measurement(LSM)tends to overestimate fibrosis stage in nonalcoholic fatty liver disease(NAFLD).Controlled attenuation parameter(CAP),provided by LSM device,has been introduced for noninvasive quantification of hepatic *** To determine the role of CAP values in predicting liver fibrosis stage by LSM in nonalcoholic steatohepatitis(NASH).METHODS One hundred eighty-four patients with biopsy proven NASH had LSM and CAP evaluated at *** them,130 patients had 1-year follow up LSM and analyzed for the changes of LSM after pioglitazone or ursodeoxycholic acid(UDCA)*** In Kleiner fibrosis stage F0-1,LSM values increased at higher CAP tertile(P=0.001),and in F2,at middle and higher tertiles(P=0.027).No difference across CAP tertiles was noticed in F3-4(P=0.752).Receiver operating characteristic curve for LSM cutoff in diagnosis of F≥2 identified 8.05 kPa for lower CAP tertile,9.35 kPa for middle,and 10.55 kPa for high *** changes in proportion of significant fibrosis(F≥2)were assessed among pioglitazone and UDCA treated patients considering CAP values,pioglitazone treated patients demonstrated decrease in proportion of high *** In patient with NAFLD,interpretation of LSM in association with CAP scores may provide helpful information sparing unnecessary liver biopsy.

关键词： Fibroscan Controlled attenuation parameter Liver stiffness Nonalcoholic steatohepatitis Liver fibrosis

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Nusinersen for spinal muscular atrophy types Ⅱ and Ⅲ:a retrospective single-center study in South Korea

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World Journal of Pediatrics 2023年第5期19卷 450-459页

作者： Hui Jin Shin Ji-Hoon Na Hyunjoo Lee Young-Mock Lee Department of Pediatrics Gangnam Severance HospitalYonsei University College of Medicine211 Eonju-RoGangnam-GuSeoul135-720Korea

Background This study investigated the efficacy and safety of nusinersen,an antisense oligonucleotide,in patients with spinal muscular atrophy(SMA)types II(OMIM:253,550)or III(OMIM:253,400),including those with severe scoliosis or requiring respiratory support via mechanical *** Data from 40 patients with genetically confirmed SMA who were treated with nusinersen at our institute from March 2019 to April 2022 were retrospectively *** these,30 patients with an age of onset<3 years and not on permanent ventilation were *** and genetic characteristics were investigated,and motor function was evaluated based on the Hammersmith Functional Motor Scale-Expanded(HFMSE)*** The mean age of symptom onset was 1.2 *** patients were diagnosed with SMA type II(27/30,90%).Nusinersen was administered via computed tomography-guided or direct intrathecal injection in 87%(26/30)and 13%(4/30)of the patients,*** the 6-,14-,22-,and 26-month follow-ups,72%,71%,88%,and 86%of patients showed motor improvement,respectively,with mean changes in HFMSE scores of 2.10,2.88,4.21,and 5.29,*** analysis showed that the use of noninvasive ventilation was associated with poorer outcomes of motor *** Patients with SMA type II or III who received nusinersen treatment showed significant improvement in motor function.A longer treatment duration led to a higher number of patients with improved motor *** significant side effects of nusinersen were *** with SMA,even those with severe scoliosis or on respiratory support,can be safely treated using nusinersen.

关键词： Hammersmith Functional Motor Scale Expanded Motor function Nusinersen South Korea Spinal muscular atrophy

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Risk factors of electrocoagulation syndrome after esophageal endoscopic submucosal dissection

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World Journal of Gastroenterology 2018年第10期24卷 1144-1151页

作者： Dae Won Ma Young Hoon Youn Da Hyun Jung Jae Jun Park Jie-Hyun Kim Hyojin Park Department of Internal Medicine Gangnam Severance Hospital Yonsei University College of Medicine

AIM To investigate post endoscopic submucosal dissection electrocoagulation syndrome(PEECS) of the *** We analyzed 55 consecutive cases with esophageal endoscopic submucosal dissection for superficial esophageal squamous neoplasms at a tertiary referral hospital in South Korea. Esophageal PEECS was defined as "mild" meeting one of the following criteria without any obvious perforation: fever(≥ 37.8 ℃), leukocytosis(> 10800 cells/μl), or regional chest pain more than 5/10 points as rated on a numeric pain intensity scale. The grade of PEECS was determined as "severe" when meet two or more of above *** We included 51 cases without obvious complications in the analysis. The incidence of mild and severe esophageal PEECS was 47.1% and 17.6%, respectively. Risk factor analysis revealed that resected area, procedure time, and muscle layer exposure were significantly associated with PEECS. In multivariate analysis, a resected area larger than 6.0 cm^2(OR = 4.995, 95%CI: 1.110-22.489, P = 0.036) and muscle layer exposure(OR = 5.661, 95%CI: 1.422-22.534, P = 0.014) were independent predictors of esophageal PEECS. All patients with PEECS had favorable outcomes with conservative management approaches, such as intravenous hydration or *** Clinicians should consider the possibility of esophageal PEECS when the resected area exceeds 6.0 cm^2 or when the muscle layer exposure is noted.

关键词： Electrocoagulation Endoscopic submucosal dissection Esophageal neoplasm Syndrome

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Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

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World Journal of Gastroenterology 2018年第7期24卷 862-869页

作者： Jun Won Kim Tae Hyung Kim Jie-Hyun Kim Ik Jae Lee Department of Radiation Oncology Gangnam Severance Hospital Yonsei University College of Medicine Department of Internal Medicine Gangnam Severance Hospital Yonsei University College of Medicine

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were *** Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate

关键词： Chemoradiotherapy Post-radiotherapy stenosis High-dose radiotherapy Cervical esophageal cancer

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Secondary endoscopic submucosal dissection for locally recurrent or incompletely resected gastric neoplasms

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World Journal of Gastroenterology 2018年第33期24卷 3776-3785页

作者： Da Hyun Jung Young Hoon Youn Jie-Hyun Kim Jae Jun Park Hyojin Park Department of Internal Medicine Gangnam Severance Hospital Yonsei University College of Medicine

AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric neoplasms at a single tertiary referral center. Among these, 28 patients underwent secondary ESD for a residual or locally recurrent tumor. Our analysis compared clinicopathologic factors between primary ESD and secondary ESD groups. RESULTS The en bloc resection and curative rate of resection of secondary ESD were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD was significantly longer than primary ESD(78.2 min vs 55.1 min, P = 0.004), and the adverse events rate was not significantly different but trended slightly higher in the secondary ESD group compared to the primary ESD group(10.7% vs 3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes without severe adverse events. During a mean follow-up period, no local recurrence occurred in patients who received secondary ESD. CONCLUSION Secondary ESD of residual or locally recurrent gastric tumors appears to be a feasible and curative treatment though it requires greater technical efficiency and longer procedure time.

关键词： Secondary endoscopic submucosal dissection Endoscopic submucosal dissection Gastric neoplasms Residual tumors Recurrent tumors

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Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence

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World Journal of Gastroenterology 2012年第39期18卷 5581-5588页

作者： Jae Yun Lim Sun Och Yoo Soon Won Hong Jong Won Kim Seung Ho Choi Jae Yong Cho Department of Medical Oncology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Pathology Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea Department of Surgery Gangnam Severance Cancer HospitalYonsei University College of MedicineSeoul 135-720South Korea

AIM:To evaluate the potential of thioredoxin (TXN) and thioredoxin-interacting protein (TXNIP) expression as biomarkers for predicting gastric cancer recurrence. METHODS:TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real- time reverse transcription polymerase chain reaction in 68 independent stage Ⅲ gastric cancer patients. The correlation between gene expression and cancer prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression patterns of each protein. RESULTS:TXN was a prognosis-related gene (P = 0.009), whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expression microarray data. In the 68 stage Ⅲ patients, the expression levels of both TXN and TXNIP had a statistically significant effect on recurrence-free survival (RFS, P = 0.008 and P = 0.036, respectively). The low TXN and high TXNIP expression group exhibited a better prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis (P < 0.001 for RFS and P = 0.001 for overall survival). More than half of the patients in the simulta-neously high TXN and low TXNIP expression group ex- perienced a recurrence within 1 year after curative surgery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors

关键词： Gastric cancer Thioredoxin Thioredoxin-interacting protein Biomarker Prognosis

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