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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 established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical 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 studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We 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 modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These 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 metastasis.These 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)

Regional anesthesia in a patient with primary ciliary dyskinesia:A case report

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World Journal of Clinical Cases 2024年第17期12卷 3183-3187页

作者： hyung joon Park Ye Hwan Kim Young joon Yoon Sang Yun Cho Department of Anesthesiology and Pain Medicine Hanyang University Guri HospitalGuri-si 471-701Gyeonggi-doSouth Korea

BACKGROUND Primary ciliary dyskinesia(PCD)is an inherited autosomal-recessive disorder of impaired mucociliary clearance characterized by chronic respiratory diseases,otolaryngological diseases,central nervous system abnormalities,reproductive system abnormalities,and cardiac function abnormalities.General anesthesia in these patients is associated with a higher incidence of respiratory complications than in patients without the disease.CASE SUMMARY A 16-year-old male patient was referred to the emergency room complaining of right ankle pain due to distal tibiofibular fracture.Three years prior,he had been diagnosed with PCD.At that time,he had experienced several episodes of pneumonia,sinusitis,and chronic middle ear infections,for which he underwent surgical interventions.At the current admission,he presented with cough and sputum but no other respiratory symptoms.A chest computed tomography scan revealed centrilobular ground-glass opacities in both lower lobes and a calcified nodule in the left lower lobe.For the surgical procedure and postoperative pain management,combined spinal-epidural anesthesia was employed.The patient’s postoperative pain score was measured by the numerical rating scale(NRS).On the day of surgery,his NRS was 5 points.By the second postoperative day,the NRS score had decreased to 2–3 points.The epidural catheter was removed on the fourth day following the operation.The patient was subsequently discharged no respiratory complications.CONCLUSION We performed combined spinal-epidural anesthesia in a patient with PCD.The patient experienced no additional respiratory complications and was discharged with a low NRS score for pain.

关键词： Primary ciliary dyskinesia Combined spinal-epidural anesthesia Patient controlled epidural analgesia Lower limb operation Case report

Current management of hepatocellular carcinoma:An Eastern perspective

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World Journal of Gastroenterology 2015年第13期21卷 3826-3842页

作者： hyung joon yim Sang Jun Suh Soon Ho Um Division of Gastroenterology and Hepatology Department of Internal MedicineKorea University Ansan HospitalAnsan-si 425-707Gyeonggi-doSouth Korea Division of Gastroenterology and Hepatology Department of Internal MedicineKorea University Anam HospitalKorea University College of MedicineSeoul 136-705South Korea

Hepatocellular carcinoma(HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization( TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.

关键词： Hepatocellular carcinoma Eastern Treatment Guideli

Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein improves diagnostic accuracy for hepatocellular carcinoma

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World Journal of Gastroenterology 2021年第28期27卷 4687-4696页

作者： Han Ah Lee Yoo Ra Lee Young-Sun Lee Young Kul Jung Ji Hoon Kim hyunggin An hyung joon yim Yoon Tae Jeen Jong Eun Yeon Kwan Soo Byun Yeon Seok Seo Department of Internal Medicine Korea University College of MedicineSeoul 02841South Korea Department of Biostatistics Korea University Anam HospitalSeoul 02841South Korea

BACKGROUND Diagnostic accuracy of various tumor markers and their combinations for hepatocellular carcinoma(HCC)was not fully investigated.AIM To evaluate the diagnostic accuracy of alpha-fetoprotein(AFP),the Lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and protein induced by vitamin K absence or antagonist-II(PIVKA-II)and their combination for HCC diagnosis.METHODS Patients with newly detected liver mass or elevated serum AFP levels were considered eligible.Serum AFP level,AFP-L3 fraction,and PIVKA-II level were measured at the first visit.RESULTS In total,622 patients were included;355 patients(57.1%)had chronic liver disease,and 208(33.4%)had liver cirrhosis.HCC was diagnosed in 160 patients(25.7%).The area under the receiver operating characteristics curves(AUROCs)of the serum AFP,AFP-L3 fraction,AFP-L3,and PIVKA-II levels for the diagnosis of HCC were 0.775,0.792,0.814,and 0.834,respectively.A novel diagnostic model was developed by classifying patients in a 1:1 ratio into training and validation sets.Using the binary regression analysis of the training cohort,the AFP,AFP-L3 fraction,and PIVKA-II(ALPs)score was calculated as follows:ALPs score=3.8×[serum AFP level(ng/mL)×AFP-L3 fraction(%)×0.01]+0.2×PIVKA-II level(mAU/mL).The AUROC of the ALPs score for diagnosis of HCC was 0.878,significantly higher than that of serum AFP level(P<0.001),AFP-L3 fraction(P<0.001),PIVKA-II level(P=0.036),and AFP-L3 level(P=0.006).The optimal ALPs score cut-off was 5.3(sensitivity,85.0%,specificity 80.1%).The validation cohort showed similar results.CONCLUSION The ALPs score calculated using serum AFP level,AFP-L3 fraction,and PIVKA-II level showed improved accuracy in HCC diagnosis.

关键词： Alpha-fetoprotein Lens culinaris agglutinin-reactive fraction of alphafetoprotein Protein induced by vitamin K absence or antagonist-II Hepatocellular carcinoma

Diagnostic delay in inflammatory bowel disease increases the risk of intestinal surgery

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World Journal of Gastroenterology 2017年第35期23卷 6474-6481页

作者： Dong-won Lee Ja Seol Koo Jung Wan Choe Sang Jun Suh Seung Young Kim Jong Jin Hyun Sung Woo Jung Young Kul Jung hyung joon yim Sang Woo Lee Division of Gastroenterology and Hepatology Department of Internal MedicineKorea University Ansan Hospital

AIM To investigate the factors affecting diagnostic delay and outcomes of diagnostic delay in inflammatory bowel disease(IBD) METHODS We retrospectively studied 165 patients with Crohn's disease(CD) and 130 patients with ulcerative colitis(UC) who were diagnosed and had follow up durations > 6 mo at Korea University Ansan Hospital from January 2000 to December 2015. A diagnostic delay was defined as the time interval between the first symptom onset and IBD diagnosis in which the 76^(th) to 100^(th) percentiles of patients were diagnosed.RESULTS The median diagnostic time interval was 6.2 and 2.4 mo in the patients with CD and UC, respectively. Among the initial symptoms, perianal discomfort before diagnosis(OR = 10.2, 95%CI: 1.93-54.3, P = 0.006) was associated with diagnostic delays in patients with CD; however, no clinical factor was associated with diagnostic delays in patients with UC. Diagnostic delays, stricturing type, and penetrating type were associated with increased intestinal surgery risks in CD(OR = 2.54, 95%CI: 1.06-6.09; OR = 4.44, 95%CI: 1.67-11.8; OR = 3.79, 95%CI: 1.14-12.6, respectively). In UC, a diagnostic delay was the only factor associated increased intestinal surgery risks(OR = 6.81, 95%CI: 1.12-41.4).CONCLUSION A diagnostic delay was associated with poor outcomes, such as increased intestinal surgery risks in patients with CD and UC.

关键词： Diagnostic delay Intestinal surgery Inflammatory bowel disease Crohn’s disease Ulcerative colitis

Treatment strategies using adefovir dipivoxil for individuals with lamivudine-resistant chronic hepatitis B

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World Journal of Gastroenterology 2012年第47期18卷 6987-6995页

作者： Tae Jung Yun Jin Yong Jung Chang Ha Kim Soon Ho Um Hyonggin An Yeon Seok Seo Jin Dong Kim hyung joon yim Bora Keum Yong Sik Kim Yoon Tae Jeen Hong Sik Lee Hoon Jai Chun Chang Duck Kim Ho Sang Ryu Department of Internal Medicine Korea University College of MedicineSeoul 136-705South Korea Department of Biostatistics Korea University College of MedicineSeoul 136-705South Korea

AIM:To investigate retrospectively the long-term efficacy of various treatment strategies using adefovir dipivoxil(adefovir) in patients with lamivudine-resistant chronic hepatitis B.METHODS:We included 154 consecutive patients in two treatment groups:the "add-on" group(n = 79),in which adefovir was added to ongoing lamivudine treatment due to lamivudine resistance,and the "switch/combination" group(n = 75),in which lamivudine was first switched to adefovir and then re-added later as needed.The "switch/combination" group was then divided into two subgroups depending on whether participants followed(group A,n = 30) or violated(group B,n = 45) a proposed treatment strategy that determined whether to add lamivudine based on the serum hepatitis B virus(HBV) DNA levels(< 60 IU/mL or not) after 6 mo of treatment(roadmap concept).RESULTS:The cumulative probability of virologic response(HBV DNA < 60 IU/mL) was higher in group A than in the "add-on" group and in group B(P < 0.001).In contrast,the cumulative probability of virologic breakthrough was lower in the "add-on" group than in group B(P = 0.002).Furthermore,the risk of virologic breakthrough in the multivariate analysis was significantly lower in the "add-on" group than in group A(hazard ratio = 0.096;95%CI,0.015-0.629;P = 0.015).CONCLUSION:The selective combination of adefovir with lamivudine based upon early treatment responses increased the odds of virologic breakthrough relative to the use of uniform combination therapy from the beginning of treatment.

关键词：阿德福韦酯慢性乙型肝炎联合治疗拉米夫定耐药 DNA水平多变量分析病毒学

Early gastric cancer presenting as a typical submucosal tumor cured by endoscopic submucosal dissection:A case report

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World Journal of Gastroenterology 2022年第25期28卷 2994-3000页

作者： joon Hyun Cho Si hyung Lee Division of Gastroenterology and Hepatology Department of Internal MedicineYeungnam University College of MedicineDaegu 42415South Korea

BACKGROUND Submucosal tumor(SMT)-like gastric cancer is rare,and almost all cases undergo curative surgical treatment because the submucosal layer is usually deeply invaded by tumor cells or because histopathologic types of SMT-like gastric cancer are undifferentiated or poorly differentiated.No report has been issued on an SMT-like gastric cancer cured by endoscopic resection alone or on changes in the endoscopic features of this type of tumor over several years.CASE SUMMARY We describe an exceptional case of a 53-year-old male with a 1.5 cm-sized SMTlike lesion covered by normal-appearing mucosa discovered by esophagogastroduodenoscopy(EGD)at the gastric antrum.Endoscopic ultrasound(EUS)visualized a homogeneous,well-circumscribed hypoechogenic lesion arising from the second sonographic layer with associated subtle obliteration of the third sonographic layer.Initial endoscopic biopsy was negative for neoplasm.The patient refused to undergo an invasive procedure and was subsequently lost to follow-up.Three years after initial detection,EGD revealed the lesion had become markedly erythematous,and at 4 years after initial EGD it had increased in size to 1.8 cm and developed a central ulcer and a heterogeneous EUS echo.Finally,endoscopic submucosal dissection(ESD)was performed,and histopathologic examination revealed a moderately differentiated adenocarcinoma had minutely invaded the submucosal layer(invasion depth 169μm)but without lymphovascular invasion and with negative resection margins.Fortunately,no additional surgical treatment was required.He has been followed for 4 years after ESD without any evidence of local or distant recurrence.CONCLUSION This report describes an extremely rare case of early gastric cancer presenting as SMT that was cured by ESD after a treatment delay of 4 years and the endoscopic changes that occurred during this period.The report highlights the importance of considering the possibility of gastric cancer when SMT is encountered in clinical practice.

关键词： Subepithelial lesion Submucosal tumor Early gastric cancer Adenocarcinoma Endoscopic mucosal dissection Case report

Kohn–Sham time-dependent density functional theory with Tamm–Dancoff approximation on massively parallel GPUs

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npj Computational Materials 2023年第1期9卷 1556-1567页

作者： Inkoo Kim Daun Jeong Won-joon Son hyung-Jin Kim Young Min Rhee Yongsik Jung Hyeonho Choi Jinkyu yim Inkook Jang Dae Sin Kim Innovation Center Samsung ElectronicsHwaseong 18448Republic of Korea Department of Chemistry Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea Samsung Advanced Institute of Technology Samsung ElectronicsSuwon 16678Republic of Korea

We report a high-performance multi graphics processing unit(GPU)implementation of the Kohn–Sham time-dependent density functional theory(TDDFT)within the Tamm–Dancoff approximation.Our algorithm on massively parallel computing systems using multiple parallel models in tandem scales optimally with material size,considerably reducing the computational wall time.A benchmark TDDFT study was performed on a green fluorescent protein complex composed of 4353 atoms with 40,518 atomic orbitals represented by Gaussian-type functions,demonstrating the effect of distant protein residues on the excitation.As the largest molecule attempted to date to the best of our knowledge,the proposed strategy demonstrated reasonably high efficiencies up to 256 GPUs on a custom-built state-of-the-art GPU computing system with Nvidia A100 GPUs.We believe that our GPU-oriented algorithms,which empower first-principles simulation for very large-scale applications,may render deeper understanding of the molecular basis of material behaviors,eventually revealing new possibilities for breakthrough designs on new material systems.

关键词： GPUs graphics massive

Primary gastric dedifferentiated liposarcoma resected endoscopically:A case report

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World Journal of Gastroenterology 2022年第23期28卷 2625-2632页

作者： joon Hyun Cho Jun Hyeon Byeon Si hyung Lee Division of Gastroenterology and Hepatology Department of Internal MedicineYeungnam University College of MedicineDaegu 42415South Korea

BACKGROUND Liposarcoma is one of the most common adult mesenchymal tumors but is uncommon in the gastrointestinal tract and extremely rare in the stomach.Furthermore,the histological subtypes of liposarcoma usually reported in the stomach are well-differentiated or myxoid,and few reports have been issued on small-sized gastric liposarcomas resected endoscopically and followed up.Herein,we report a case of primary gastric dedifferentiated liposarcoma(DL)that was resected endoscopically.CASE SUMMARY A 67-year-old female Korean patient was referred to our institution for further evaluation of a gastric submucosal tumor(SMT)located in the lesser curvature of the gastric body by esophagogastroduodenoscopy.Endoscopic ultrasound revealed a well-circumscribed,slightly heterogeneous,isoechoic,17 mm×10 mm sized mass originating from the third sonographic layer.Computed tomography showed no evidence of significant lymph node enlargement or distant metastasis.Endoscopic resection was undertaken using the snare resection technique after mucosal precutting to provide a definitive histopathologic diagnosis,which proved to be consistent with DL,based on its morphology and the immunoexpressions of MDM2 and CDK4.The patient was planned for surgery because the deep resection margin was positive for malignancy.After declining any invasive procedure or adjuvant treatment,the patient was placed under close follow-up,and at one year after endoscopic resection,remained disease free.CONCLUSION This is the first reported case of a small primary gastric DL resected endoscopically and followed up.This report demonstrates that when diagnosis of a SMT is uncertain,the use of invasive techniques,including endoscopic resection,should be considered.

关键词： Gastric liposarcoma Dedifferentiated liposarcoma Submucosal tumor Endoscopic resection Case report