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1.
Cancers (Basel) ; 16(7)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38611100

ABSTRACT

Hepatocellular carcinoma (HCC) stands as the most prevalent form of primary liver cancer and is highly invasive and easily recurs. For HCC, chemotherapy shows limited effect. The gold standard for HCC treatment includes curative surgical resection or liver transplantation. However, the recurrence rate at 5 years after liver resection is estimated at approximately 70% and even at 5 years after liver transplantation, it is 20%. Therefore, improving survival outcomes after curative surgical resection of liver cancer is crucial. This review highlights the importance of identifying risk factors for HCC recurrence following radical surgical resection and adjuvant therapy options that may reduce the recurrence risk and improve overall survival, including local adjuvant therapy (e.g., transcatheter arterial chemoembolization and radiotherapy), adjuvant systemic therapy (e.g., small molecule targeted therapy and immunotherapy), and other adjuvant therapies (e.g., chemotherapy). However, further research is needed to refine the use of these therapies and optimize their effectiveness in preventing HCC recurrence.

2.
J Gastrointest Surg ; 28(5): 719-724, 2024 May.
Article in English | MEDLINE | ID: mdl-38503593

ABSTRACT

BACKGROUND: Common bile duct (CBD) stones commonly occur in cholecystectomy cases. The management options include laparoscopic CBD exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (ERCP) followed by laparoscopic cholecystectomy (LC). Although ERCP is fully developed, it has complications, and LCBDE is a proven alternative. This study aimed to evaluate the safety and efficacy of these treatments in elderly individuals aged ≥70 years. METHODS: A retrospective study between January 2015 and July 2022 included 160 elderly patients (aged ≥70 years) diagnosed with cholelithiasis and choledocholithiasis. The patients were divided into 1-stage (LCBDE [n = 80]) or 2-stage (ERCP followed by LC [n = 80]) treatment groups. Data collected encompassed comorbidities, symptoms, bile duct clearance, postoperative complications, and long-term outcomes for systematic analysis. RESULTS: This study analyzed 160 patients treated for CBD stones, comparing 1-stage and 2-stage groups. The 1-stage group had more female patients than the 2-stage group (57.5% vs 37.5%, respectively). The 1-stage group had a mean age of 80.55 ± 7.00 years, which was higher than the mean age in the 2-stage group. American Society of Anesthesiologists classification, Charlson Comorbidity Index, and laboratory findings were similar. Pancreatitis and cholangitis occurred after ERCP in the 2-stage group. Stone clearance rates (92.35% [1-stage group] vs 95.00% [2-stage group]) and biliary leakage incidence (7.5% [1-stage group] vs 3.0% [2-stage group]) were similar, as were postoperative complications and long-term recurrence rates (13.0% [1-stage group] vs 12.5% [2-stage group]). CONCLUSION: Our research indicates that both the combination of LCBDE and LC and the sequence of ERCP followed by LC are equally efficient and secure when treating CBD stones in elderly patients. Consequently, the 1-stage procedure may be considered the preferred treatment approach for this demographic.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Cholecystectomy, Laparoscopic , Choledocholithiasis , Gallstones , Humans , Cholangiopancreatography, Endoscopic Retrograde/methods , Female , Male , Aged , Retrospective Studies , Cholecystectomy, Laparoscopic/methods , Cholecystectomy, Laparoscopic/adverse effects , Choledocholithiasis/surgery , Aged, 80 and over , Gallstones/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome , Common Bile Duct/surgery , Laparoscopy/methods , Laparoscopy/adverse effects
3.
Medicina (Kaunas) ; 60(2)2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38399483

ABSTRACT

Background and Objectives: Optimal opioid analgesia is an excellent analgesia that does not present unexpected adverse effects. Nalbuphine, acting on the opioid receptor as a partial mu antagonist and kappa agonist, is considered a suitable option for patients undergoing laparoscopic surgery. Therefore, we aim to investigate the appropriate dosage of nalbuphine for post-operative pain management in patients with laparoscopic cholecystectomy. Materials and Methods: Patients were randomly categorized into low, medium, and high nalbuphine groups. In each group, a patient control device for post-operative pain control was programed with a low (0.05 mg/kg), medium (0.10 mg/kg), or high (0.20 mg/kg) nalbuphine dose as a loading dose and each bolus dose with a lockout interval of 7 min and without background infusion. Primary and secondary outcomes included the post-operative pain scale and nalbuphine consumption, and episodes of post-operative opioid-related adverse events and satisfactory scores. Results: The low-dosage group presented a higher initial self-reported pain score in comparison to the other two groups for the two hours post-op (p = 0.039) but presented lower nalbuphine consumption than the other two groups for four hours post-op (p = 0.047). There was no significant difference in the analysis of the satisfactory score and adverse events. Conclusions: An appropriate administration of nalbuphine could be 0.1 to 0.2 mg/kg at the initial four hours; this formula could be modified to a lower dosage (0.05 mg/kg) in the post-operative management of laparoscopic cholecystectomy.


Subject(s)
Analgesia , Cholecystectomy, Laparoscopic , Nalbuphine , Humans , Nalbuphine/adverse effects , Analgesics, Opioid/adverse effects , Cholecystectomy, Laparoscopic/adverse effects , Pain, Postoperative/drug therapy
4.
Adv Sci (Weinh) ; 10(23): e2300644, 2023 08.
Article in English | MEDLINE | ID: mdl-37316966

ABSTRACT

Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge on how the virus remodels the metabolic and immune response toward hepatic pathologic environment is limited. The transcriptomic and multiple evidences reveal that the HCV core protein-intestine-specific homeobox (ISX) axis promotes a spectrum of metabolic, fibrogenic, and immune modulators (e.g., kynurenine, PD-L1, and B7-2), regulating HCV-infection relevant pathogenic phenotype in vitro and in vivo. In a transgenic mice model, the HCV core protein-ISX axis enhance metabolic disturbance (particularly lipid and glucose metabolism) and immune suppression, and finally, chronic liver fibrosis in a high-fat diet (HFD)-induced disease model. Mechanistically, cells with HCV JFH-1 replicons upregulate ISX and, consequently, the expressions of metabolic, fibrosis progenitor, and immune modulators via core protein-induced nuclear factor-κB signaling. Conversely, cells with specific ISX shRNAi inhibit HCV core protein-induced metabolic disturbance and immune suppression. Clinically, the HCV core level is significantly correlated with ISX, IDOs, PD-L1, and B7-2 levels in HCC patients with HCV infection. Therefore, it highlights the significance of HCV core protein-ISX axis as an important mechanism in the development of HCV-induced chronic liver disease and can be a specific therapeutic target clinically.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis C, Chronic , Hepatitis C , Liver Neoplasms , Mice , Animals , Hepatitis C, Chronic/metabolism , Hepatitis C, Chronic/pathology , B7-H1 Antigen/metabolism , Hepatitis C/metabolism , Mice, Transgenic , Disease Progression
6.
Cell Biol Toxicol ; 39(4): 1471-1487, 2023 08.
Article in English | MEDLINE | ID: mdl-35687267

ABSTRACT

B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common childhood cancer, originates from lymphoid precursor cells in bone marrow committed to the B-cell lineage. Environmental factors and genetic abnormalities disturb the normal maturation of these precursor cells, promoting the formation of leukemia cells and suppressing normal hematopoiesis. The underlying mechanisms of progression are unclear, but BCP-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. This study hypothesized that air pollution and haze are risk factors for BCP-ALL progression. The current study revealed that indeno(1,2,3-cd)pyrene (IP), a major component of polycyclic aromatic hydrocarbons (PAHs) in air, promotes oncogenic activities (proliferation, transformation, and disease relapse) in vitro and in vivo. Mechanistically, IP treatment activated the aryl hydrocarbon receptor (AHR)-indoleamine-2,3-dioxygenase (IDOs) axis, thereby enhancing tryptophan metabolism and kynurenine (KYN) level and consequent promoting the KYN-AHR feedback loop. IP treatment decreased the time to disease relapse and increased the BCP-ALL cell count in an orthotopic xenograft mouse model. Additionally, in 50 clinical BCP-ALL samples, AHR and IDO were co-expressed in a disease-specific manner at mRNA and protein levels, while their mRNA levels showed a significant correlation with disease-free survival duration. These results indicated that PAH/IP exposure promotes BCP-ALL disease progression.


Subject(s)
Neoplasms , Polycyclic Aromatic Hydrocarbons , Humans , Mice , Animals , Kynurenine/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism
8.
Surg Endosc ; 36(11): 8672-8683, 2022 11.
Article in English | MEDLINE | ID: mdl-35697855

ABSTRACT

BACKGROUND: We developed laparoscopic transfistulous bile duct exploration (LTBDE) for Mirizzi syndrome (MS) McSherry type II in September 2011. Then, single-incision LTBDE (SILTBDE) was adopted as a preferred technique since August 2013. This retrospective study aims to analyze the outcome of LTBDE in 7.7 years and to compare SILTBDE with four-incision LTBDE (4ILTBDE). METHODS: Seventeen consecutive patients underwent LTBDE for MS McSherry type II from September 2011 to May 2019. Transfistulous removal of the impacted stone(s), choledochoscopic bile duct exploration, and primary closure of the gallbladder remnant were performed without biliary drainage. RESULTS: The sex ratio is 12:5 (male: female) with an average age of 39.4 ± 10.3 (24-56) years. Ten patients (58.8%) had their diagnoses of MS established by preoperative imaging. According to the Csendes classification, three type II (17.6%), nine type III (52.9%), and five type IV (29.4%) were identified. The operative time was 264.8 ± 60.3 min (156-358 min). The stone clearance rate was 100%. The postoperative hospital stay was 4.7 ± 1.9 (2-10) days. No procedure was converted to an open operation. Two postoperative transient hyperamylasemia (11.8%) and one superficial wound infection (5.9%) occurred and all recovered well under conservative treatment (Clavien-Dindo grade I). During an average 2.2-year follow-up period, no biliary stricture or stone recurrence occurred. No significant difference exists between the SILTBDE and 4ILTBDE groups. Nevertheless, an insignificant trend of shorter postoperative hospital stay was observed in the former. A diagnosis of MS Csendes type IV implicates prolonged total and postoperative hospital stays (p < 0.01). CONCLUSIONS: LTBDE is safe and efficacious for MS McSherry type II. It provides a simple solution for various types of MS and avoids undesirable complications following bilioenteric anastomosis. SILTBDE is comparable to 4ILTBDE for selected patients. Patients with MS Csendes type IV need more time to recover after surgery.


Subject(s)
Laparoscopy , Mirizzi Syndrome , Surgical Wound , Humans , Male , Female , Adult , Middle Aged , Mirizzi Syndrome/surgery , Retrospective Studies , Common Bile Duct/surgery , Bile Ducts , Laparoscopy/methods
9.
Cancer Lett ; 520: 160-171, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34265398

ABSTRACT

Nuclear translocation regulated by phosphorylation is a key step in providing activated mitogen-activated protein kinases (MAPKs) access to their nuclear targets; however, the mechanisms linking MAPK-induced nuclear translocation and target gene expression mediating oncologic activity remain obscure. Here, we show that the MAPK extracellular signal-regulated kinase (ERK) 1, but not ERK2, phosphorylated intestine-specific homeobox (ISX), leading to its nuclear translocation and downstream oncogenic signaling. Mechanistically, ERK1 phosphorylated serine 183 of ISX, facilitating its nuclear translocation and downstream target gene expression. In contrast, dominant-negative ERK1 expression in hepatoma cells inhibited the nuclear translocation of ISX and the expression of downstream genes involved in cell proliferation, malignant transformation, and epithelial-mesenchymal transition in vitro and in vivo. An activating mutation in ISX (S183D) exhibited a constitutive nuclear localization and resistance to sorafenib. Additionally, in 576 paired clinical hepatocellular carcinoma (HCC) samples and adjacent normal tissues, ERK1 and ISX were co-expressed in a tumor-specific manner at mRNA and protein levels, while their mRNA levels showed significant correlation with survival duration, tumor size, number, and stage. These results highlight the significance of ERK1/ISX signaling in HCC progression and its potential as a prognostic and therapeutic target in HCC.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Homeodomain Proteins/genetics , Liver Neoplasms/drug therapy , Mitogen-Activated Protein Kinase 3/genetics , Transcription Factors/genetics , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Intestines/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Mice , Phosphorylation , Signal Transduction/drug effects , Sorafenib/pharmacology
10.
Cancer Med ; 10(16): 5545-5556, 2021 08.
Article in English | MEDLINE | ID: mdl-34173348

ABSTRACT

Epigenetic regulation is important for cancer tumor metastasis and progression, including lung and liver cancer. However, the mechanism of epigenetic regulation in liver cancer leaves much to be discussed. According to a previous study, p300/CBP-associated factor (PCAF) mediated epithelial-mesenchymal transition (EMT) and promotes cancer metastasis by recruiting intestine-specific homeobox (ISX) and bromodomain-containing protein 4 (BRD4) in lung cancer. To figure out whether the three genes are also expressed in patients with hepatocellular carcinoma (HCC) or not, and their correlation with patients' outcome, BRD4, PCAF, and ISX messenger RNA (mRNA) expression levels in 377 patients with HCC were investigated using quantitative polymerase chain reaction and confocal fluorescence imaging. The correlation of the gene expression (PCAF, ISX, and BRD4) in liver cancer is also being investigated. Here, we show that the mRNA expression of PCAF, BRD4, and ISX in 377 paired specimens from patients with HCC, and the adjacent normal tissues exhibited a tumor-specific expression pattern, highly correlated with disease pathogenesis, patient survival time, progression stage, and poor prognosis. The results show that ISX and BRD4 can potentially be a target for improving the survival rate.


Subject(s)
Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/mortality , Cell Cycle Proteins/genetics , Homeodomain Proteins/genetics , Liver Neoplasms/mortality , Transcription Factors/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cell Line, Tumor , Child , Epigenesis, Genetic , Female , Follow-Up Studies , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Hepatectomy , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Young Adult , p300-CBP Transcription Factors/genetics
11.
Autophagy ; 17(12): 4202-4217, 2021 12.
Article in English | MEDLINE | ID: mdl-33853474

ABSTRACT

We propose that beyond its role in WNT secretion, WLS/GPR177 (wntless, WNT ligand secretion mediator) acts as an essential regulator controlling protein glycosylation, endoplasmic reticulum (ER) homeostasis, and dendritic cell (DC)-mediated immunity. WLS deficiency in bone marrow-derived DCs (BMDCs) resulted in poor growth and an inability to mount cytokine and T-cell responses in vitro, phenotypes that were irreversible by the addition of exogenous WNTs. In fact, WLS was discovered to integrate a protein complex in N-glycan-dependent and WLS domain-selective manners, comprising ER stress sensors and lectin chaperones. WLS deficiency in BMDCs led to increased ER stress response and macroautophagy/autophagy, decreased calcium efflux from the ER, and the loss of CALR (calreticulin)-CANX (calnexin) cycle, and hence protein hypo-glycosylation. Consequently, DC-specific wls-null mice were unable to develop both Th1-, Th2- and Th17-associated responses in the respective autoimmune and allergic disease models. These results suggest that WLS is a critical chaperone in maintaining ER homeostasis, glycoprotein quality control and calcium dynamics in DCs.Abbreviations: ATF6: activating transcription factor 6; ATG5: autophagy related 5; ATG12: autophagy related 12; ATG16L1: autophagy related 16 like 1; ATP2A1/SERCA1: ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1; BALF: bronchoalveolar lavage fluid; BFA: brefeldin A; BMDC: bone marrow-derived dendritic cell; CALR: calreticulin; CANX: calnexin; CCL2/MCP-1: C-C motif chemokine ligand 2; CNS: central nervous system; CT: C-terminal domain; DTT: dithiothreitol; DNAJB9/ERDJ4: DnaJ heat shock protein family (Hsp40) member B9; EAE: experimental autoimmune encephalomyelitis; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; GFP: green fluorescent protein; HSPA5/GRP78/BiP: heat shock protein A5; IFNA: interferon alpha; IFNAR1: interferon alpha and beta receptor subunit 1; IFNB: interferon beta; IFNG/INFγ: interferon gamma; IFNGR2: interferon gamma receptor 2; IL6: interleukin 6; IL10: interleukin 10; IL12A: interleukin 12A; IL23A: interleukin 23 subunit alpha; ITGAX/CD11c: integrin subunit alpha X; ITPR1/InsP3R1: inositol 1,4,5-trisphosphate receptor type 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; OVA: ovalbumin; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PLF: predicted lipocalin fold; PPP1R15A/GADD34: protein phosphatase 1 regulatory subunit 15A; RYR1/RyanR1: ryanodine receptor 1, skeletal muscle; SD: signal domain; TGFB/TGF-ß: transforming growth factor beta family; Th1: T helper cell type 1; Th17: T helper cell type 17; TM: tunicamycin; TNF/TNF-α: tumor necrosis factor; UPR: unfolded protein response; WLS/wntless: WNT ligand secretion mediator.


Subject(s)
Autophagy , Wnt Signaling Pathway , Animals , Autophagy/physiology , Dendritic Cells , Endoplasmic Reticulum Stress , Homeostasis , Mice
12.
J Inflamm Res ; 14: 299-311, 2021.
Article in English | MEDLINE | ID: mdl-33574691

ABSTRACT

BACKGROUND: Club cells play an important role in maintaining lung homeostasis and aryl hydrocarbon receptor (AhR) is known to be important in xenobiotic metabolism, but its role in regulating club cells is currently unknown. METHODS: To this end, mice with club cell-specific AhR deficiency were generated and evaluated in a model of antigen (ovalbumin, OVA)-induced airway inflammation for the number of infiltrating inflammatory cells, the levels of cytokines and CC10 and Notch signaling by standard methods. RESULTS: After OVA sensitization and challenge, Scgb1a1-Cre; Ahrflox/flox mice showed aggravated levels of pulmonary inflammation with increased levels of inflammatory cells and cytokines 1 day after challenge as compared to those seen in their littermate controls, but in contrast to the littermate controls, no significant change in the levels of CC10 and SP-D was noted in Scgb1a1-Cre; Ahrflox/flox mice. Surprisingly, 7 days after the challenge, while, as expected, wild-type mice recovered from acute inflammation, significantly increased lymphocytic infiltration was noted in Scgb1a1-Cre; Ahrflox/flox mice, suggesting their defective mechanism of recovery. Mechanistically, this was due, in part, to the decreased Notch1 signaling and expression of its downstream gene, HES5, while AhR was shown to positively regulate Notch1 expression via its transactivating activity targeting the xenobiotic response element in the promoter region of Notch1 gene. CONCLUSION: Under the condition of pulmonary inflammation, AhR is critical in controlling lung club cell homeostasis via targeting Notch1 signaling and the generation of anti-inflammatory mediators.

13.
Cancer Biomark ; 28(3): 341-350, 2020.
Article in English | MEDLINE | ID: mdl-32390596

ABSTRACT

BACKGROUND: Effective prognostic biomarkers and powerful target-therapeutic drugs are needed for improving the treatment of Hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to evaluate the expression of FOXM1 and Aurora-A and their prognostic value in HCC. METHODS: We determined the differentially expressed genes signature in HCC using the Gene Set Enrichment Analysis (GSEA), and then evaluated the expression of FOXM1 and Aurora-A in TCGA and KMUH cohort. Associations between co-expression of FOXM1 and Aurora-A and clinical variables were calculated. Overall survival (OS) and recurrence-free survival (RFS) were estimated with different FOXM1 and Aurora-A expression status. RESULTS: FOXM1-related gene sets were mostly associated with cell cycle regulation in HCC tissues. We found a positive correlation between the expression of FOXM1 and Aurora-A. Overexpression of FOXM1 and Aurora-A was associated with larger tumor size, advanced stage, higher grade, and double-positive for HBV and HCV. The coordinated overexpression of FOXM1 and Aurora-A was the most significant independent prognostic factor for OS and RFS. Furthermore, the concomitant high expression of FOXM1 and Aurora-A predicted the worst OS of sorafenib-treated patients with HCC. CONCLUSIONS: The co-expression of FOXM1 and Aurora-A could be a reliable biomarker to predict the sorafenib response and prognosis of HCC patients.


Subject(s)
Aurora Kinase A/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/drug therapy , Forkhead Box Protein M1/metabolism , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/epidemiology , Sorafenib/pharmacology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Datasets as Topic , Disease-Free Survival , Drug Resistance, Neoplasm , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Humans , Liver/pathology , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/genetics , Prognosis , Sorafenib/therapeutic use , Up-Regulation , Young Adult
14.
EMBO Rep ; 21(2): e48795, 2020 02 05.
Article in English | MEDLINE | ID: mdl-31908141

ABSTRACT

Epigenetic regulation is important for cancer progression; however, the underlying mechanisms, particularly those involving protein acetylation, remain to be fully understood. Here, we show that p300/CBP-associated factor (PCAF)-dependent acetylation of the transcription factor intestine-specific homeobox (ISX) regulates epithelial-mesenchymal transition (EMT) and promotes cancer metastasis. Mechanistically, PCAF acetylation of ISX at lysine 69 promotes the interaction with acetylated bromodomain-containing protein 4 (BRD4) at lysine 332 in tumor cells, and the translocation of the resulting complex into the nucleus. There, it binds to promoters of EMT genes, where acetylation of histone 3 at lysines 9, 14, and 18 initiates chromatin remodeling and subsequent transcriptional activation. Ectopic ISX expression enhances EMT marker expression, including TWIST1, Snail1, and VEGF, induces cancer metastasis, but suppresses E-cadherin expression. In lung cancer, ectopic expression of PCAF-ISX-BRD4 axis components correlates with clinical metastatic features and poor prognosis. These results suggest that the PCAF-ISX-BRD4 axis mediates EMT signaling and regulates tumor initiation and metastasis.


Subject(s)
Epithelial-Mesenchymal Transition , Neoplasms , Transcription Factors , Acetylation , Epigenesis, Genetic , Epithelial-Mesenchymal Transition/genetics , Genes, Homeobox , Humans , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , p300-CBP Transcription Factors/metabolism
15.
Hepatobiliary Surg Nutr ; 8(4): 345-360, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31489304

ABSTRACT

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

16.
Hepatobiliary Surg Nutr ; 8(4): 345-360, Aug. 2019.
Article in English | BIGG - GRADE guidelines | ID: biblio-1026256

ABSTRACT

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.


Subject(s)
Humans , Pancreatectomy/rehabilitation , Pancreatic Diseases/diagnosis , Pancreaticoduodenectomy/methods , Surgery, Computer-Assisted/methods , Delphi Technique
17.
Cancers (Basel) ; 11(5)2019 May 03.
Article in English | MEDLINE | ID: mdl-31058850

ABSTRACT

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Homeobox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Homeobox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.

18.
Oncogene ; 38(4): 518-532, 2019 01.
Article in English | MEDLINE | ID: mdl-30154425

ABSTRACT

Metastasis is the main cause of cancer mortality. However, the triggering mechanisms and regulation of epithelial-mesenchymal transition (EMT) factors in the commitment of metastasis have not been well characterized. Spermatogenic Zip 1 (SPZ1) acts as a proto-oncogene and an upstream regulator of EMT during tumorigenesis. Here we report that the HIV-1 Tat-interacting protein 60 kDa (Tip60) acetyltransferase mediates acetylation at lysine residues of SPZ1 at positions 369 and 374, and of TWIST1 at positions 73 and 76, which are required for SPZ1-TWIST1 complex formation and cancer cell migration in vitro and in vivo. Ectopic SPZ1 and TWIST1 expression, but not that of TWIST1 alone, enhanced vascular endothelial growth factor (VEGF) expression via the recruitment of bromodomain-containing protein 4 (BRD4), thus enhancing RNA-Pol II-dependent transcription and inducing metastasis. Neutralization of VEGF using humanized monoclonal antibodies such as Avastin, effectively abrogated the EMT and oncogenesis induced by the acetylated SPZ1-TWIST1 complex. Our findings highlight the importance of acetylation signaling in the SPZ1-TWIST1-BRD4 axis in the mediation of EMT and its regulation during tumor initiation and metastasis.


Subject(s)
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/physiology , Epithelial-Mesenchymal Transition/physiology , Liver Neoplasms/metabolism , Lysine Acetyltransferase 5/physiology , Neoplasm Proteins/physiology , Nuclear Proteins/physiology , Protein Processing, Post-Translational , Transcription Factors/physiology , Twist-Related Protein 1/physiology , Acetylation , Animals , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Carcinogenesis , Cell Cycle Proteins , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Liver Neoplasms, Experimental/blood supply , Liver Neoplasms, Experimental/drug therapy , Liver Neoplasms, Experimental/genetics , Mice , Mice, Nude , Mice, Transgenic , Neoplasm Invasiveness , Neoplasm Metastasis , Neovascularization, Pathologic/metabolism , Protein Interaction Mapping , Proto-Oncogene Mas , Signal Transduction , Sorafenib/pharmacology , Sorafenib/therapeutic use , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor A/genetics , Xenograft Model Antitumor Assays
19.
Surg Endosc ; 32(9): 3918-3924, 2018 09.
Article in English | MEDLINE | ID: mdl-29488090

ABSTRACT

BACKGROUND: Most liver resections are currently performed using an open approach. Robotic hepatectomy has been suggested as a safe and effective approach for hepatocellular carcinoma; however, studies regarding oncological and surgical outcomes are still limited. Accordingly, we performed this study to compare the surgical and oncological outcomes between robotic and open approaches. METHODS: Between June, 2013 and July, 2016, a total of 63 HCC patients undergoing robotic hepatectomy, and 177 patients undergoing open hepatectomy were included in this study to assess the surgical and oncological outcomes after hepatectomy. The data of demographic, clinical features, hepatitis profile, tumor characters, TNM stage, surgical type, pathological outcomes, and postoperative results were collected prospectively and analyzed retrospectively. RESULTS: The demographic and clinical features of patients with HCC in both groups were statistically comparable. The robotic group had longer operative times (296 ± 84 vs. 182 ± 51 min, p = 0.032). The postoperative complications rate was slightly lower in the robotic group (11.1 vs. 15.3%, p = 0.418). The rate of Ro resection was similar in both groups (93.7 vs. 96%, p = 0.56). The length of hospital stay was significantly shorter in the robotic group (6.21 ± 2.06 vs. 8.18 ± 6.99 days, p = 0.001). The overall recurrence rate of HCC was lower in the robotic group (27 vs. 37.3%, p = 0.140). The 1, 2, 3 year disease-free survival rates were 72.5, 64.3, and 61.6%, respectively, for the open group, while they were 77.8, 71.9, and 71.9%, respectively, for the robotic group, (p = 0.325). The 1, 2, 3 year overall survival rates were 95.4, 92.3, and 92.3%, respectively, for the open group, while they were 100, 97.7, and 97.7%, respectively, for the robotic group (p = 0.137). CONCLUSION: Robotic surgery is a safe and feasible procedure for liver resection in selected patients. The oncological and surgical outcomes of robotic hepatectomy were comparable to open surgery. The robotic hepatectomy carried significantly shorter length of hospital stay.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy/methods , Liver Neoplasms/surgery , Robotic Surgical Procedures , Aged , Carcinoma, Hepatocellular/mortality , Disease-Free Survival , Female , Humans , Length of Stay/statistics & numerical data , Liver Neoplasms/mortality , Male , Neoplasm Recurrence, Local , Operative Time , Postoperative Complications , Retrospective Studies
20.
World J Surg ; 42(10): 3312-3315, 2018 10.
Article in English | MEDLINE | ID: mdl-29589115

ABSTRACT

AIM: This paper aims to describe an intracorporeal tourniquet method for laparoscopic Pringle maneuver (PM). METHODS: One shortened Foley tube with side-hole on the tip was put into the abdomen. Then, the tail was pulled out through the side-hole to make a loop to encircle porta hepatis for inflow control. RESULT: It is easy to keep the tension by a metallic clip, and when released, the clip can be removed and the loop loosened. CONCLUSION: Therefore, PM could be performed inside the abdomen without special instrument nor extra trocar port. The intracorporeal Pringle maneuver with Huang's loop could be routinely used during laparoscopic liver resection even for a laparoscopic beginner because it is so easily learnt, safe, and effective.


Subject(s)
Hepatectomy/methods , Laparoscopy/methods , Liver/surgery , Abdominal Cavity/surgery , Hepatectomy/instrumentation , Humans
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