1.Study on the Mechanism of Piperlongumine Inducing Ferroptosis in K562/ADR Cells through the miR-214-3p/GPX4 Pathway.
Ting ZHANG ; Cui-Cui WANG ; Cong ZHU ; Xin-Yu ZHOU ; Xiu-Hong JIA
Journal of Experimental Hematology 2025;33(4):1007-1015
OBJECTIVE:
To investigate the effect of piperlongumine(PL) on the proliferation and ferroptosis of human adriamycin-resistant chronic myeloid leukemia K562/ADR cells, and to explore its possible molecular mechanism.
METHODS:
CCK-8 assay was used to detect the effect of PL on the survival rate of K562/ADR cells and to screen the appropriate drug concentration. After K562/ADR cells were treated with low, medium and high concentrations of PL(2, 4, and 6 μmol/L), EdU proliferation assay and plate colony formation assay were used to detect cell proliferation and colony formation ability. CCK-8 assay was used to detect the effects of different inhibitors (Fer-1, Z-VAD, Nec-1) combined with PL on cell proliferation. The intracellular Fe2+, ROS, malondialdehyde(MDA) and glutathine(GSH) contents were respectively detected by iron ion colorimetry, DCFH-DA fluorescent probe, MDA and GSH kits. RT-qPCR and Western blot were respectively used to detect the expression level of GPX4 mRNA and protein in cells. Bioinformatics websites predicted miRNA that could target and regulate GPX4 . RT-qPCR was used to detect the effects of different concentrations of PL on the expression levels of the predicted miRNA. Dual luciferase gene reporter assay was used to verify the targeting relationship between miR-214-3p and GPX4 . After treating cells with PL or PL+miR-214-3p inhibitor, the Fe2+, ROS, MDA, GSH centents and GPX4 protein expression levels in cells were detected.
RESULTS:
PL inhibited K562/ADR cell proliferation in a concentration-dependent manner(r =0.979). Compared with the blank control group, the survival rate, EdU positive cells rate in low, medium and high concentration PL groups were significantly decreased (P < 0.01). Compared with the PL group alone, the survival rate of cells in the Z-VAD+PL group was increased slightly (P < 0.05). The cell survival rate was significantly increased in medium or high concentration PL+Fer-1 group (P < 0.01). Compared with blank control group, ROS expression level in low concentration PL group was slightly increased (P < 0.05), and GSH content was slightly decreased (P < 0.05). In medium and high concentration PL groups, the contents of Fe2+, ROS and MDA were significantly increased (P < 0.01), while the contents of GSH, expression of GPX4 mRNA and protein were significantly decreased(P < 0.01). Bioinformatics prediction and double luciferase reporter gene experiment confirmed the targeting relationship between GPX4 and miR-214-3p. Compared with the blank control group, the expression level of miR-214-3p in cells of medium and high concentration PL groups was significantly increased (P < 0.01). Compared with PL group alone, the intracellular Fe2+, ROS and MDA contents in PL+miR-214-3p inhibitor group were all decreased (P < 0.01), while GSH content and GPX4 protein expression levels were significantly increased (P < 0.01).
CONCLUSION
Medium and high concentrations of PL can inhibit the proliferation of K562/ADR cells by inducing ferroptosis, which is related to the regulation of miR-214-3p pathway.
Humans
;
Ferroptosis/drug effects*
;
MicroRNAs/metabolism*
;
Dioxolanes/pharmacology*
;
Cell Proliferation/drug effects*
;
K562 Cells
;
Phospholipid Hydroperoxide Glutathione Peroxidase
;
Reactive Oxygen Species
;
Doxorubicin/pharmacology*
;
Signal Transduction
;
Piperidones
2.Advances in Endoscopic Ultrasound-Guided Biliary Drainage: A Comprehensive Review.
Savreet SARKARIA ; Ho Su LEE ; Monica GAIDHANE ; Michel KAHALEH
Gut and Liver 2013;7(2):129-136
Endoscopic retrograde cholangiopancreatography (ERCP) has become the first-line therapy for bile duct drainage. In the hands of experienced endoscopists, conventional ERCP results in a failed cannulation rate of 3% to 5%. This failure can occur more commonly in the setting of altered anatomy or technically difficult cases due to either duodenal or biliary obstruction. In cases of ERCP failure, patients have traditionally been referred for either percutaneous transhepatic biliary drainage (PTBD) or surgery. However, both PTBD and surgery have higher than desirable complication rates. Within the last decade, endoscopic ultrasound-guided biliary drainage (EUS-BD) has become an attractive alternative to PTBD after failed ERCP. Many groups have reported on the feasibility, efficacy and safety of this technique. This article reviews the indications for ERCP and the currently practiced EUS-BD techniques, including EUS-guided rendezvous, EUS-guided choledochoduodenostomy and EUS-guided hepaticogastrostomy.
Bile Ducts
;
Catheterization
;
Cholangiopancreatography, Endoscopic Retrograde
;
Choledochostomy
;
Dioxolanes
;
Drainage
;
Fluorocarbons
;
Hand
;
Humans
3.Percutaneous Transhepatic Biliary Drainage Using a Ligated Catheter for Recurrent Catheter Obstruction: Antireflux Technique.
Tsuyoshi HAMADA ; Takeshi TSUJINO ; Hiroyuki ISAYAMA ; Ryunosuke HAKUTA ; Yukiko ITO ; Ryo NAKATA ; Kazuhiko KOIKE
Gut and Liver 2013;7(2):255-257
Percutaneous transhepatic biliary drainage (PTBD) is an established procedure for biliary obstruction. However, duodenobiliary or jejunobiliary reflux of the intestinal contents through a PTBD catheter sometimes causes recurrent catheter obstruction or cholangitis. A 64-year-old female patient with a history of choledochojejunostomy was referred to our department with acute cholangitis due to choledochojejunal anastomotic obstruction. Emergent PTBD was performed, but frequent obstructions of the catheter due to the reflux of intestinal contents complicated the post-PTBD course. We therefore introduced a catheter with an antireflux mechanism to prevent jejunobiliary reflux. A commercially available catheter was modified; side holes were made at 1 cm and 5 to 10 cm (1 cm apart) from the tip of the catheter, and the catheter was ligated with a nylon thread just proximal to the first side hole. Using this novel "antireflux PTBD technique," jejunobiliary reflux was prevented successfully, resulting in a longer patency of the catheter.
Catheter Obstruction
;
Catheters
;
Cholangitis
;
Choledochostomy
;
Dioxolanes
;
Drainage
;
Female
;
Fluorocarbons
;
Gastrointestinal Contents
;
Humans
;
Nylons
4.New Strategy in Cases of Failed Endoscopic Intervention of Biliary Strictures after Living Donor Liver Transplantation: Percutaneous Transhepatic Biliary Stent Insertion and Subsequent Endoscopic Treatment.
Sang Myung WOO ; Hyun Beom KIM ; Kwang Woong LEE ; Woo Jin LEE ; Young Kyu KIM ; Sung Sik HAN ; Sang Jae PARK
The Journal of the Korean Society for Transplantation 2012;26(3):188-195
BACKGROUND: In cases of endoscopic intervention treatment for biliary stricture which fail, a percutaneous approach can be subsequently attempted. However, the quality of life is lower for those patients with percutaneous transhepatic biliary drainage (PTBD) tubes than those with endoscopic retrograde biliary drainage tubes. In this study, we report the outcome of the application of percutaneous transhepatic biliary stenting (PTBS) for use in subsequent endoscopic treatment of biliary stricture after living donor liver transplantation (LDLT). METHODS: Of 165 patients who underwent LDLT, 40 (24.2%) were diagnosed with anastomotic biliary strictures. Of these patients, seven agreed to treatment using PTBS using a plastic stent with endoscopic follow-up instead of treatment by insertion of a PTBD tube, and were enrolled in this study. RESULTS: In all seven patients, the use of this technique enabled effective advancement of a guide wire and successful placement of one or two plastic stents (7 or 10 Fr) into the PTBD tract. There were no PTBS-related complications associated with the procedure. The median duration for stent use was 40.3 weeks (range; 27.6~65.0). Upon final removal of all stents, the stricture had been resolved in four (57%) of the seven patients. CONCLUSIONS: Our study data suggested that, after failed use of ERCP in the treatment of biliary stricture after LDLT, the use of PTBS and ERCP may be an effective and safe treatment.
Bile Ducts
;
Cholangiopancreatography, Endoscopic Retrograde
;
Constriction, Pathologic
;
Dioxolanes
;
Drainage
;
Fluorocarbons
;
Follow-Up Studies
;
Humans
;
Liver
;
Liver Transplantation
;
Living Donors
;
Plastics
;
Quality of Life
;
Stents
5.Successful percutaneous management of bronchobiliary fistula after radiofrequency ablation of metastatic cholangiocarcinoma in a patient who has a postoperative stricture of hepaticojejunostomy site.
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2012;16(3):110-114
Bronchobiliary fistula (BBF) is a rare condition that is defined as an abnormal communication between the biliary system and bronchial tree. Furthermore, a BBF is an extremely rare complication of radiofrequency ablation (RFA). A 54 year-old man with a history of extrahepatic biliary cancer had been suffering with a benign stricture of hepaticojejunostomy site and was treated with RFA for metastatic cholangicarcinoma. In this report, we describe a patient with BBF complicated by an abscess which occurred after RFA. He was treated by placement of external drainage catheter into the liver abscess and percutaneous transhepatic biliary drainage (PTBD) into the right intrahepatic duct. After 6 weeks, a complete obliteration of the BBF was confirmed by a repeated follow-up of computed tomography scan and cholangiography through PTBD.
Abscess
;
Biliary Fistula
;
Biliary Tract
;
Bronchial Fistula
;
Catheter Ablation
;
Catheters
;
Cholangiocarcinoma
;
Cholangiography
;
Constriction, Pathologic
;
Dioxolanes
;
Drainage
;
Fistula
;
Fluorocarbons
;
Follow-Up Studies
;
Humans
;
Liver Abscess
;
Stress, Psychological
6.Solitary percutaneous transhepatic biliary drainage tract metastasis after curative resection of perihilar cholangiocarcinoma: report of a case.
Shin HWANG ; Sung Won JUNG ; Jung Man NAMGOONG ; Sam Youl YOON ; Gil Chun PARK ; Dong Hwan JUNG ; Gi Won SONG ; Tae Yong HA ; Gi Young KO ; Dong Wan SUH ; Sung Gyu LEE
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2011;15(3):179-183
Percutaneous transhepatic biliary drainage (PTBD) has been widely used, but it has a potential risk of tumor spread along the catheter tract. We herein present a case of solitary PTBD tract metastasis after curative resection of perihilar cholangiocarcinoma. Initially, endoscopic nasobiliary drainage was done on a 65 year-old female patient, but the cholangitis did not resolve. Thus a PTBD catheter was inserted into the right posterior duct. Right portal vein embolization was also performed. Curative surgery including right hepatectomy and bile duct resection was performed 16 days after PTBD. After 12 months, serum CA19-9 had increased gradually without any symptoms. Finally, a small right pleural metastasis was found through strict tumor surveillance for 6 months. Chemoradiation therapy was performed, but there was no response to treatment. As the tumor progressed, she complained of severe dyspnea and finally died from tumor dissemination to the chest and bones 18 months after the first detection of PTBD tract recurrence and 36 months after surgery. No intra-abdominal recurrence was found until the terminal stage. This PTBD tract recurrence was attributed to the PTBD even though it was in place for only 16 days. Although such recurrence is rare, its risk should be taken into account during follow-up of patients who have received PTBD before.
Bile Ducts
;
Catheters
;
Cholangiocarcinoma
;
Cholangitis
;
Dioxolanes
;
Drainage
;
Dyspnea
;
Female
;
Fluorocarbons
;
Follow-Up Studies
;
Hepatectomy
;
Humans
;
Hypogonadism
;
Mitochondrial Diseases
;
Neoplasm Metastasis
;
Ophthalmoplegia
;
Portal Vein
;
Recurrence
;
Thorax
7.Comparison of Bile Drainage Methods after Laparoscopic CBD Exploration.
Seong Uk KWON ; In Seok CHOI ; Ju Ik MOON ; Yu Mi RA ; Sang Eok LEE ; Won Jun CHOI ; Dae Sung YOON ; Hyun Sik MIN
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2011;15(2):117-122
PURPOSE: T-tube is a major procedure that prevents complication by biliary decompression, but which is accompanied by complications. Therefore, several procedures such as ENBD, PTBD, and antegrade biliary stent have been attempted, but with controversies as to which procedure is superior. Also, there are no standard procedures after laparoscopic CBD exploration. We performed this study to ascertain the most appropriate biliary drainage procedure after laparoscopic CBD exploration. METHODS: From March 2001 to December 2009, 121 patients who underwent Laparoscopic CBD exploration in Gunyang University were included for retrospective analysis. The patients were divided to 4 groups according to type of procedure, and we compared clinical parameters including age and gender, operation time, hospital stay, start of post-operative diet, and complications. RESULTS: There was no difference in age, gender, mean operation time, postoperative diet between the 4 groups. Hospital stay in the Stent group was shorter than T-tube group. There were 10 (7%) complications that occurred. Two 2 occurred in the T-tube, 3 in PTBD, and 5 in the Antegrade stent group. There were more complications in Stent group but no significant statistical difference. In 5 cases with remnant CBD stone, a total of 4 (3 PTBD, 1 Stent) was performed by endoscopic CBD stone removal. One T-tube case was removed easily by choledochoscopy through the T-tube. Three migrated and the impacted stents were removed by additional endoscopy. Perioperative biliary leakage (1) and peritonitis (1) post t-tube removal were resolved by conservative treatment. CONCLUSION: T-tube appears to be an appropriate method to patients who are suspected to have remnant CBD stones. Multiple procedures may be performed on a case by case basis such as performing PTBD first in a suspected cholangitis patient.
Bile
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Cholangitis
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Decompression
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Diet
;
Dioxolanes
;
Drainage
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Endoscopy
;
Fluorocarbons
;
Humans
;
Length of Stay
;
Peritonitis
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Retrospective Studies
;
Stents
8.Comparison of Long-term Complication of Malignant Biliary Obstruction after Percutaneous Transhepatic Biliary Drainage Versus Metallic Biliary Drainage.
Kosin Medical Journal 2011;26(1):30-35
OBJECTIVES: Several advances in the diagnosis, therapy and palliation of patients affected by malignant biliary obstruction have occurred during the last decades. Unresectable malignant biliary obstruction has usually been treated by percutaneous transhepatic biliary drainage (PTBD) versus metallic biliary drainage (MBD). The optimal management of complications after biliary drainage is still an unresolved problem. To compare the complications of malignant biliary obstruction after PTBD and MBD. METHODS: We enrolled 51 patients of malignant biliary obstruction after biliary drainage. The clinical characteristics and complications of each groups were assessed and compared. RESULTS: The complications after biliary drainage of MBD are lower than those of PTBD (59.1% vs 82.8%, P = 0.06, respectively). Patients with PTBD tended to have a shorter event of complication time compared to MBD patients (2.9 months vs 7.1 months, P < 0.01). Patients with older age in PTBD tended to have a longer event of complication time compared to younger patients (4.6 months vs 2.3 months, P < 0.01). CONCLUSIONS: The method of biliary drainage in malignant biliary obstruction have statistically significant impact on the complication time. The clinical efficacy of metallic stent in patients with malignant biliary obstruction is better than that of PTBD.
Dioxolanes
;
Drainage
;
Fluorocarbons
;
Humans
;
Radiography, Interventional
;
Stents
9.EUS-Guided Biliary Drainage.
Kenji YAMAO ; Kazuo HARA ; Nobumasa MIZUNO ; Akira SAWAKI ; Susumu HIJIOKA ; Yasumasa NIWA ; Masahiro TAJIKA ; Hiroki KAWAI ; Shinya KONDO ; Yasuhiro SHIMIZU ; Vikram BHATIA
Gut and Liver 2010;4(Suppl 1):S67-S75
Endoscopic ultrasonography (EUS) combines endoscopy and intraluminal ultrasonography, and allows imaging with a high-frequency transducer over a short distance to generate high-resolution ultrasonographic images. EUS is now a widely accepted modality for diagnosing pancreatobiliary diseases. EUS-guided fine-needle aspiration (EUS-FNA) using a curved linear-array echoendoscope was initially described more than 20 years ago, and since then many researchers have expanded its indications to sample diverse lesions and have also used it for various therapeutic purposes. EUS-guided biliary drainage (EUS-BD) is one of the therapeutic procedures that has been developed using a curved linear-array echoendoscope. Technically, EUS-BD includes rendezvous techniques via transesophageal, transgastric, and transduodenal routes, EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS). Published data have demonstrated a high success rate, albeit with a comparatively high rate of nonfatal complications for EUS-CDS and EUS-HGS, and a comparatively low success rate with a low complication rate for the rendezvous technique. At present, these procedures represent an alternative to surgery or percutaneous transhepatic biliary drainage (PTBD) for patients with obstructive jaundice when endoscopic biliary drainage (EBD) has failed. However, these procedures should be performed in centers with extensive experience in linear EUS and therapeutic biliary ERCP. Large prospective studies are needed in the near future to establish standardized EUS-BD procedures as well as to perform controlled comparative trials between EUS-BD and PTBD, between rendezvous techniques and direct-access techniques (EUS-CDS and EUS-HGS), and between EBD and EUS-BD.
Biopsy, Fine-Needle
;
Cholangiopancreatography, Endoscopic Retrograde
;
Choledochostomy
;
Dioxolanes
;
Drainage
;
Endoscopy
;
Endosonography
;
Fluorocarbons
;
Humans
;
Jaundice, Obstructive
;
Transducers
10.Usefulness of the Rendezvous Technique for Biliary Stricture after Adult Right-Lobe Living-Donor Liver Transplantation with Duct-To-Duct Anastomosis.
Jae Hyuck CHANG ; In Seok LEE ; Ho Jong CHUN ; Jong Young CHOI ; Seung Kyoo YOON ; Dong Goo KIM ; Young Kyoung YOU ; Myung Gyu CHOI ; Kyu Yong CHOI ; In Sik CHUNG
Gut and Liver 2010;4(1):68-75
BACKGROUND/AIMS: Replacement of a percutaneous transhepatic biliary drainage (PTBD) catheter with inside stents using endoscopic retrograde cholangiography is difficult in patients with angulated or twisted biliary anastomotic stricture after living donor liver transplantation (LDLT). We evaluated the usefulness and safety of the rendezvous technique for the management of biliary stricture after LDLT. METHODS: Twenty patients with PTBD because of biliary stricture after LDLT with duct-to-duct anastomosis underwent the placement of inside stents using the rendezvous technique. RESULTS: Inside stents were successfully placed in the 20 patients using the rendezvous technique. The median procedure time was 29.6 (range, 7.5-71.8) minutes. The number of inside stents placed was one in 12 patients and two in eight patients. One mild acute pancreatitis and one acute cholangitis occurred, which improved within a few days. Inside stent related sludge or stone was identified in 12 patients during follow-up. Thirteen patients achieved stent-free status for a median of 281 (range, 70-1,351) days after removal of the inside stents. CONCLUSIONS: The rendezvous technique is a useful and safe method for the replacement of PTBD catheter with inside stent in patients with biliary stricture after LDLT with duct-to-duct anastomosis. The rendezvous technique could be recommended to patients with angulated or twisted strictures.
Adult
;
Catheters
;
Cholangiography
;
Cholangitis
;
Constriction, Pathologic
;
Dioxolanes
;
Drainage
;
Fluorocarbons
;
Follow-Up Studies
;
Humans
;
Liver
;
Liver Transplantation
;
Living Donors
;
Pancreatitis
;
Sewage
;
Stents

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