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1.  Splenic infarction associated with sorafenib use in a hepatocellular carcinoma patient 
Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC). As the clinical use of sorafenib increases, many adverse effects have been reported, such as hand-foot skin reaction, diarrhea, anorexia, asthenia, alopecia, weight loss, hypertension and arterial thromboembolism. However, there are no prior reports of splenic infarction as an adverse effect of sorafenib. Here, a case of splenic infarction in a patient with HCC who was treated with sorafenib is reported. The patient had no other predisposing factors to explain the splenic infarction except for the administration of sorafenib. The splenic infarction improved after sorafenib was discontinued; however, the HCC progressed.
PMCID: PMC3020384  PMID: 21246003
Hepatocellular carcinoma; Sorafenib; Tyrosine kinase inhibitor; Adverse effects; Splenic infarction
2.  Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma 
AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.
METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d.
RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC.
CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.
PMCID: PMC3396196  PMID: 22807613
Hepatic arterial infusion chemotherapy; Floxuridine; Advanced hepatocellular carcinoma; Child-Pugh classification; Portal vein tumor thrombus
3.  Rapidly aggravated skeletal muscle metastases from an intrahepatic cholangiocarcinoma 
We present a rare case of intrahepatic cholangiocarcinoma (ICC) with multiple skeletal muscle metastases. The patient was a 55-year-old Asian woman presenting with abdominal pain; abdominal and pelvic computed tomography and magnetic resonance cholangiopancreatography revealed an unresectable ICC with hepatic metastasis and metastastatic lymphadenopathy in the porto-caval area. After 3 mo of treatment with palliative radiotherapy and chemotherapy, magnetic resonance imaging of the thoracolumbar spine detected right psoas muscle and paraspinous muscle metastases. We performed an ultrasound-guided percutaneous fine-needle biopsy that confirmed a similar pattern of poorly differentiated adenocarcinoma. The patient treated with palliative chemotherapy and achieved 10 mo of survival. Here we report the first case quickly spread to multiple sites of muscle even though the three-month treatment, compare to the other cases reported muscle metastases at diagnosis.
PMCID: PMC4323479
Intrahepatic cholangiocarcinoma; Skeletal muscle metastasis; Adenocarcinoma
4.  Retreatment with peginterferon and ribavirin in chronic hepatitis C 
The development of boceprevir and telaprevir was a major step forward in the treatment of chronic hepatitis C. In addition, the treatment of these infections has been recently revolutionized by the approval of sofosbuvir and simeprevir. However, there are several challenges associated with the application of novel drugs, such as new and more frequent adverse events, new drug interactions, and excessively high treatment costs. An additional concern is viral resistance. These considerations highlight the fact that direct-acting antiviral agents are not a panacea and may not be the best option for all patients who are in need of therapy. This retrospective study revealed that the sustained virologic response was not significantly reduced following peginterferon and ribavirin retreatment compared with the new therapy. We suggest that patients who experience relapse shortly after completing treatment with peginterferon and ribavirin have a reasonable chance of achieving a sustained virologic response when retreated with these drugs alone.
PMCID: PMC4323480
Chronic hepatitis C; Direct-acting antiviral agents; Peginterferon; Ribavirin; Retreatment
5.  A case of focal nodular hyperplasia with growth progression during pregnancy 
Clinical and Molecular Hepatology  2014;20(4):392-397.
Focal nodular hyperplasia (FNH) is the second most common benign solid tumor of the liver and is usually found in young females. In FNH, spontaneous bleeding or rupture rarely occurs and malignant transformation is unlikely. The etiology of FNH is unclear, but because of female predominance and young age at onset, it seems that female hormone has an important role for the development of FNH. Although the development and the complications of hepatocellular adenomas have been related to the use of oral contraceptives and pregnancy, the influence of oral contraceptives and pregnancy on the growth and complications of FNH is controversial. Most FNH are stable in size and rarely complicated during pregnancy. We describe here a case of FNH with growth progression during pregnancy in a 27-year-old female. Her course of pregnancy and delivery was uneventful. Two months after delivery, the size of FNH was decreased.
PMCID: PMC4278071  PMID: 25548746
Focal nodular hyperplasia; Pregnancy; Hepatic adenoma
6.  Simultaneous intrahepatic and subgaleal hemorrhage in antiphospholipid syndrome following anticoagulation therapy 
Warfarin is a widely used anticoagulant. Interindividual differences in drug response, a narrow therapeutic range and the risk of bleeding render warfarin difficult to use clinically. An 18-year-old woman with antiphospholipid syndrome received long-term warfarin therapy for a recurrent deep vein thrombosis. Six years later, she developed right flank pain. We diagnosed intrahepatic and subgaleal hemorrhages secondary to anticoagulation therapy. After stopping oral anticoagulation, a follow-up computed tomography showed improvement in the hemorrhage. After restarting warfarin because of a recurrent thrombosis, the intrahepatic hemorrhage recurred. We decided to start clopidogrel and hydroxychloroquine instead of warfarin. The patient has not developed further recurrent thrombotic or bleeding episodes. Intrahepatic hemorrhage is a very rare complication of warfarin, and our patient experienced intrahepatic and subgaleal hemorrhage although she did not have any risk factors for bleeding or instability of the international normalized ratio control.
PMCID: PMC3798414  PMID: 24151371
Warfarin; Liver; Subgaleal; Hemorrhage; Antiphospholipid syndrome
7.  Gastric ischemia after epinephrine injection in a patient with liver cirrhosis 
Endoscopic epinephrine injection is relatively easy, quick and inexpensive. Furthermore, it has a low rate of complications, and it is widely used for the management of nonvariceal upper gastrointestinal bleeding. There have been several case reports of gastric ischemia after endoscopic injection therapy. Inadvertent intra-arterial injection may result in either spasm or thrombosis, leading to subsequent tissue ischemia or necrosis, although the stomach has a rich vascular supply and the vascular reserve of the intramural anastomosis. In addition to endoscopic injection therapy, smoking, hypertension and atherosclerosis are risk factors of gastric ischemia. We report a case of gastric ischemia after submucosal epinephrine injection in a 51-year-old woman with hypertension and liver cirrhosis.
PMCID: PMC3554828  PMID: 23372366
Hematemesis; Epinephrine; Gastric ischemia; Liver cirrhosis; Hypertension
8.  A Case of Hepatic Angiomyolipoma Which Was Misdiagnosed as Hepatocellular Carcinoma in a Hepatitis B Carrier 
Case Reports in Hepatology  2012;2012:606108.
We report a rare case of resected hepatic AML, which was misdiagnosed as hepatocellular carcinoma in a chronic hepatitis B carrier. A 45-year-old woman who was a carrier of hepatitis B virus infection presented with a hepatic tumor. Her serum alpha-fetoprotein level was normal. Ultrasonography revealed a round and well-circumscribed echogenic hepatic tumor measuring 2.5 cm in the segment VI. On contrast-enhanced computed tomography, a hypervascular tumor was observed in the arterial phase and washing-out of the contrast medium in the portal phase and delayed phase. On MR T1-weighted in-phase images, the mass showed low signal intensity, and on out-of-phase images, the mass showed signal drop and dark signal intensity. On MR T2-weighted images, the mass showed high signal intensity. The mass demonstrated high signal intensity on arterial phase after contrast injection, suggestive of hepatocellular carcinoma. The patient underwent hepatic wedge resection and histopathological diagnosis was a hepatic angiomyolipoma.
PMCID: PMC4208446  PMID: 25374707
9.  Discrete Hypoechoic Ring in Hepatic Cavernous Hemangioma Resembling a Malignant Tumor: Correlation with Histologic Features 
Gut and Liver  2009;3(3):226-230.
Differential diagnoses of hepatic nodules include hepatocellular carcinoma, focal nodular hyperplasia, hepatic adenoma, regenerative nodule, focal fatty changes, and hemangioma. However, differentiation of these nodules can often be difficult. Hemangiomas are frequently encountered during ultrasonogram incidentally and can be diagnosed easily because they have an almost distinctive sonographic appearance: a homogeneous hyperechogenicity and discrete posterior acoustic enhancement. They also sometimes have atypical findings, for example an internal echogenicity including hypoechogenicity, heterogeneous echogenicity, hyperechoic rim, central hypoechogenicity due to various changes (e.g., internal hemorrhage, necrosis, thrombosis, myxomatous change, and fibrosis), and (rarely) calcification. We report herein the case of an atypical hemangioma presenting with a hypoechoic peripheral ring, mimicking a hepatic malignancy. To our knowledge, there have been no other reports demonstrating a cavernous hemangioma with a discrete hypoechoic ring and without a pseudocapsule.
PMCID: PMC2852708  PMID: 20431752
Hemangioma; Hypoechoic ring; Hepatic malignancy; Ultrasonography
10.  Thymosin Alpha-1 in Combination with Pegylated Interferon and Ribavirin in Chronic Hepatitis C Patients Who have Failed to Prior Pegylated Interferon and Ribavirin Treatment 
Gut and Liver  2007;1(1):87-89.
Combination therapy with inteferon-alpha and ribavirin is an approved therapy for patients with chronic hepatitis C. However, even with the use of pegylated interferon, response rates are still poor in many difficult-to-treat groups, especially with genotype 1 and high viral loads. Retreatment of these patients remains challenging. Newer combinations are being investigated to optimize chances of attaining a sustained response in these groups. Thymosin alpha 1 is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. Herein, we describe two cases of retreatment patients with chronic hepatitis C who have failed prior pegylated interferon and ribavirin therapy. They received triple combination therapies of thymosin alpha 1, pegylated interferon and ribavirin and achieved sustained virological responses. These cases support that thymosin-alpha 1 may increase the efficacy of pegylated interferon plus ribavirin in the treatment of non-responders to previous combination therapy.
PMCID: PMC2871658  PMID: 20485665
Chronic hepatitis C; Nonrespondents; Peginterferon alpha-2a; Ribavirin; Thymosin alpha 1 Introduction
11.  Sigmoidorectal intussusception of adenoma of sigmoid colon treated by laparoscopic anterior resection after sponge-on-the-stick-assisted manual reduction 
We present herein a case report of sigmoidorectal intussusception as an unusual case of sigmoid adenomatous polyp. The patient was a 56-year-old man who suffered from rectal bleeding for one day. He initially visited his general practitioner and was diagnosed as having an intraluminal mass of 15 cm from the anal verge. Several hours after admission to our coloproctology clinic, he suddenly presented with lower abdominal cramping pain with rectal bleeding during his bowel preparation using polyethylene glycol electrolyte solution. An emergency colonoscopy revealed that the invaginated colon with polypoid mass was protruded to the lower rectum. Gastrograffin enema showed that the invaginated bowel segment was 3 cm from the anal verge. CT scan showed the typical finding of intussusception. We performed laparoscopic anterior resection and anastomosis after the sponge-on-the-stick-assisted manual reduction. The permanent pathologic finding showed villotubular adenoma of the sigmoid colon.
PMCID: PMC4077479  PMID: 16440436
Sigmoidorectal intussusception; Adenomatous polyp; Laparoscopic resection
12.  Serological and Molecular Characteristics of the First Korean Case of Echinococcus multilocularis 
In December 2011, we reported an autochthonous case of Echinococcus multilocularis infection in a 42-year-old woman in Korea. The diagnosis was based on histopathological findings of the surgically resected liver cyst. In the present study, we evaluated the serological and molecular characteristics of this Korean E. multilocularis case. The patient's serum strongly reacted with affinity-purified native Em18 and recombinant Em18 antigens (specific for E. multilocularis) but negative for recombinant antigen B8/1 (reactive for Echinococcus granulosus). In immunoaffinity chromatography, the serum also strongly reacted with E. multilocularis and only weakly positive for E. granulosus. We determined the whole nucleotide sequence of cox1 (1,608 bp) using the paraffin-embedded cystic tissue which was compared with E. multilocularis isolates from China, Japan, Kazakhstan, Austria, France, and Slovakia. The Korean case showed 99.8-99.9% similarity with isolates from Asia (the highest similarity with an isolate from Sichuan, China), whereas the similarity with European isolates ranged from 99.5 to 99.6%.
PMCID: PMC3857511  PMID: 24327789
Echinococcus multilocularis; alveolar echinococcosis; immunodiagnosis; cox1; South Korea
13.  Efficacy and safety of entecavir plus carnitine complex (GODEX®) compared to entecavir monotherapy in patient with ALT elevated chronic hepatitis B: randomized, multicenter open-label trials. The GOAL study 
Clinical and molecular hepatology  2013;19(2):165-172.
Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients.
130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months.
Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment.
ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.
PMCID: PMC3701849  PMID: 23837141
Hepatitis B; Carnitine; Entecavir
14.  Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data 
While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.
The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.
The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).
The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.
PMCID: PMC3622854  PMID: 23593608
Gastric variceal bleeding; Rebleeding; Mortality; Cirrhosis
15.  Prognostic factors for gallbladder cancer in the laparoscopy era 
Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors.
A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109).
An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects.
This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.
PMCID: PMC3467389  PMID: 23091795
Gallbladder cancer; Laparoscopy; Prognosis
16.  Recurrent Hepatic Alveolar Echinococcosis: Report of The First Case in Korea with Unproven Infection Route 
Human alveolar echinococcosis (AE), a hepatic disorder that resembles liver cancer, is a highly aggressive and lethal zoonotic infection caused by the larval stage of the fox tapeworm, Echinococcus multilocularis. E. multilocularis is widely distributed in the northern hemisphere; the disease-endemic area stretches from north America through Europe to central and east Asia, including northern parts of Japan, but it has not been reported in Korea. Herein, we represent a first case of AE in Korea. A 41-year-old woman was found to have a large liver mass on routine medical examination. The excised mass showed multinodular, necrotic, and spongiform appearance with small irregular pseudocystic spaces. Microscopically, the mass was composed of chronic granulomatous inflammation with extensive coagulation necrosis and parasite-like structure, which was revealed as parasitic vesicles and laminated layer delineated by periodic acid-Schiff (PAS) stain. Clinical and histologic features were consistent with AE. After 8 years, a new liver mass and multiple metastatic pulmonary nodules were found and the recurred mass showed similar histologic features to the initial mass. She had never visited endemic areas of AE, and thus the exact infection route is unclear.
PMCID: PMC3279681  PMID: 22355210
Echinococcus multilocularis; alveolar echinococcosis; hepatic; human
17.  Lessons learned from 100 initial cases of laparoscopic liver surgery 
Laparoscopic liver resection (LLR) is now widely accepted and is being increasingly performed. The present study describes our experience with LLR at a single center over an eight-year period.
This retrospective study enrolled 100 patients between October 2002 and February 2010. Forty-six benign lesions and 54 malignant lesions were included. The LLR performed included 58 pure laparoscopy procedures, 18 hand-assisted laparoscopy procedures and 24 hybrid technique procedures.
The mean age of the patients was 57 years; among these patients, 31 were over 65 years of age. The mean operation time was 220 minutes. The overall morbidity was 11% and the mortality was zero. Among the 20 patients with simple hepatic cysts, 50% unexpectedly recurred. Among the 41 patients with hepatocellular carcinoma, 21 patients (51%) underwent preoperative radiofrequency ablation therapy or transarterial chemoembolization. During parenchymal-transection, 11 received blood transfusion. The width of the resection margins was under 0.5 cm in 11 cases (27%); 0.5 to 1 cm in 22 cases (54%) and over 1 cm in eight cases (12%). There was no port site seeding, but argon beam coagulation-induced tumor dissemination was observed in two cases. The overall two-year survival rate was 75%.
This study suggests that the applications for LLR can be gradually expanded when assuring that the safety and curability of LLR are equivalent to that of open liver resection.
PMCID: PMC3204701  PMID: 22066057
Laparoscopic liver resection; Hepatic cyst; Hapatocellular carcinoma; Resection margin
18.  Delayed Viral Clearance of Chronic Hepatitis C in Patients after Treatment Failure 
Gut and Liver  2011;5(1):110-114.
Hepatitis C virus (HCV) infection usually progresses to chronic hepatitis, with rare cases of spontaneous viral eradication. We present herein four cases involving patients that were initially declared to have failed to respond to treatments, based on the presence of HCV RNA that was still detectable after completion of the standard treatment for chronic hepatitis C with genotype 2. However, the HCV RNA became undetectable, with a delayed response, after discontinuation of therapy. Two of the four patients were diagnosed as treatment failures after extended treatment, and the other two received no further treatment after the standard treatment. All four patients maintained a sustained virological response during the periodic follow-up after delayed viral clearance.
PMCID: PMC3065086  PMID: 21461084
Delayed viral clearance; Chronic hepatitis C; Sustained virological response
19.  Gene transfer using liposome-complexed adenovirus seems to overcome limitations due to coxsackievirus and adenovirus receptor-deficiency of cancer cells, both in vitro and in vivo 
Experimental & Molecular Medicine  2008;40(4):427-434.
Use of adenoviruses as vehicle for gene therapy requires that target cells express appropriate receptors such as coxsakievirus and adenovirus receptor (CAR). We show here that CAR-deficiency in cancer cells, that limits adenoviral gene delivery, can be overcome by using adenovirus complexed with the liposome, Ad-PEGPE [1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly-ethylene glycol)-2000]. We first confirmed that CT-26 mouse colon cancer cells are deficient in CAR by RT-PCR, and then showed that CT-26 cells infected with Ad-GFP/PEGPE exhibited highly enhanced expression of green fluorescent protein (GFP), compared with those infected with Ad-GFP. GFP expression depends on the dose of liposome and adenovirus. Luciferase expression in livers treated with Ad-luc/PEGPE was about 1,000-fold less than those infected with Ad-luc. In a liver metastasis mouse tumor model developed by intrasplenic injection of CT-26 cells, luciferase expression following i.v. injection of Ad-luc/PEGPE was significantly higher in tumors than in adjacent non-neoplastic liver. Following systemic administration of Ad-GFP/PEGPE, GFP expression increased in tumors more than in adjacent liver while the reverse was true following administration of Ad-GFP. In the latter case, GFP expression was higher in liver than in tumors. This study demonstrates that systemic delivery of PEGPE-adenovirus complex is an effective tool of adenoviral delivery as it overcomes limitation due to CAR deficiency of target cells while reducing hepatic uptake and enhancing adenoviral gene expression in tumors.
PMCID: PMC2679272  PMID: 18779655
adenovirus; CXADR protein, human; gene therapy; gene transfer techniques; liposomes; models, animal

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