1.Role of Ca2+ influx in the tert-butyl hydroperoxide-induced apoptosis of HepG2 human hepatoblastoma cellse.
Jung Ae KIM ; Young Shin KANG ; Young Ok KIM ; Sun Hee LEE ; Yong Soo LEE
Experimental & Molecular Medicine 1998;30(3):137-144
Oxidative stress appears to be implicated in the pathogenesis of various diseases including alcoholic liver injury. In this study we investigated the mechanism of apoptosis induced by tert-butyl hydroperoxide (TBHP) in HepG2 human hepatoblastoma cells. Treatment with TBHP significantly reduced glutathione content and glutathione reductase activity, and increased glutathione peroxidase activity, indicating that TBHP induced oxidative stress in the HepG2 cells. TBHP also induced reduction of cell viability and DNA fragmentation, a hallmark of apoptosis, in a dose-dependent manner. In addition, TBHP induced a sustained increase in intracellular Ca2+ concentration, which was completely prevented by the extracellular Ca2+ chelation with EGTA. TBHP also induced Mn2+ influx. These results indicate that the intracellular Ca2+ increase by TBHP is exclusively due to Ca2+ influx from the extracellular site. Treatment with either an extracellular (EGTA) or an intracellular Ca2+ chelator (BAPTA/AM) significantly suppressed the TBHP-induced apoptosis. Taken together, these results suggest that TBHP induced the apoptotic cell death in the HepG2 cells and that Ca2+ influx may play an important role in the apoptosis induced by TBHP.
Apoptosis/drug effects*
;
Calcium Signaling/drug effects*
;
Chelating Agents/pharmacology
;
Egtazic Acid/pharmacology
;
Egtazic Acid/analogs & derivatives
;
Hepatoblastoma/pathology*
;
Hepatoblastoma/metabolism
;
Hepatoblastoma/drug therapy
;
Human
;
Manganese/metabolism
;
Oxidative Stress/drug effects
;
Tumor Cells, Cultured
;
tert-Butylhydroperoxide/pharmacology*
2.Teratoid Hepatoblastoma: Multidirectional Differentiation of Stem Cell of the Liver.
Lucia KIM ; Young Nyun PARK ; Sung Eun KIM ; Tae Woong NOH ; Chanil PARK
Yonsei Medical Journal 2001;42(4):431-435
Hepatoblastoma is the most common malignant hepatic neoplasm of childhood, showing a wide spectrum of epithelial and mesenchymal components. Teratoid hepatoblastoma, which reveals multiple lines of tissue differentiation such as mucinous epithelium, melanin pigment, endocrine differentiation, glial and mesenchymal components, has rarely been observed. We report a case of teratoid hepatoblastoma in a 22-month-old girl. She had been diagnosed with hepatoblastoma through percutaneous needle biopsy of the liver and treated with 10 chemotherapy cycles of epirubicin, VP-16 and cisplatin and with hepatic artery embolization. After 10 months, an extended left lobectomy was performed. Grossly, a multinodular, partly well-demarcated, solid mass (7 x 5 cm) with dense fibrosis and focal cystic change occupied almost the entire specimen. There was extensive necrosis due to preoperative treatment. Microscopically, the tumor showed multiple lines of differentiation, which was composed of embryonal, fetal hepatocytes and mesenchymal elements with numerous foci of osteoid. There were also other components showing endodermal, neural, melanocytic and endocrine differentiation. These teratoid components were considered relatively resistant to preoperative chemotherapy, in contrast to extensive necrosis of both embryonal and fetal hepatocytes. These teratoid features of hepatoblastoma are considered to be a multidirectional differentiation of the small epithelial cells or stem cells of the tumor.
Case Report
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Cell Differentiation
;
Female
;
Hepatoblastoma/*pathology
;
Human
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Infant
;
Liver/*pathology
;
Liver Neoplasms/*pathology
;
Stem Cells/*pathology
3.Neonatal hepatoblastoma--a case report.
Zhao-hong CHEN ; Guang-jin LU ; Yu-kun HAN ; Wei-dong LI ; Zhi-jun WU
Chinese Journal of Pediatrics 2005;43(8):631-632
4.Surgical management of intrahepatic vessels in children with stage III/IV hepatoblastoma.
Yan-li PANG ; Wei ZHAO ; He-ying YANG ; Qiu-liang LIU ; Da ZHANG ; Pan QIN ; Ming YUE ; Lei WANG ; Jun-jie ZHANG ; Jia-xiang WANG
Chinese Medical Journal 2013;126(11):2134-2138
BACKGROUNDHepatoblastoma (HB) is a rare childhood tumor. We investigated the effect of intraoperative management of the intrahepatic major vessels in children with HB.
METHODSBetween April 2005 and August 2012, surgical resection was performed on 50 children with hepatoblastoma. These children were divided into a vessel-ligation group (n = 20) and a vessel-repair group (n = 30). In the vessel-ligation group, the intrahepatic major vessels were ligated and removed together with the tumor and the affected liver lobe/liver parenchyma. In the vessel-repair group, the affected intrahepatic major vessels were dissected and preserved as much as possible and the normal liver lobe/liver parenchyma and blood supply from these vessels were also preserved. The outcomes were analyzed by postoperative follow-up.
RESULTSIn the vessel-ligation group, two patients gave up surgery, six patients underwent palliative resection, and 12 patients underwent en bloc resection; four patients died of liver failure and eight patients fully recovered and were discharged. In the vessel-repair group, all 30 patients underwent en bloc resection and were discharged after satisfactory healing. After a follow-up time of 5 - 36 months (median: 20 months), two patient in the vessel-ligation group survived and 22 patients in the vessel-repair group survived.
CONCLUSIONSPatients with HB can be successfully treated by tumor resection with vascular repair. This method prevents postoperative liver failure, ensures patient safety during the perioperative period, and allows for early chemotherapy.
Child ; Child, Preschool ; Female ; Follow-Up Studies ; Hepatoblastoma ; blood supply ; pathology ; surgery ; Humans ; Infant ; Liver Neoplasms ; blood supply ; pathology ; surgery ; Male ; Neoplasm Staging
5.Expression of GRP78 and GRP94 in the liver tissues and their clinicopathological significance in children with hepatoblastoma.
Gan-Nong CHEN ; Yong MA ; Zhu-Lin YANG
Chinese Journal of Contemporary Pediatrics 2010;12(8):634-636
OBJECTIVETo study the expression of glucose-regulated protin 78 (GRP78) and glucose-regulated protin 94 (GRP94) in the liver tissues from children with hepatoblastoma (HB) and to investigate the possible clinicopathological values of GRP78 and GRP94 in HB.
METHODSLiver tissue specimens from 15 children with HB and 10 specimens of normal liver tissues were obtained. EnVison immunohistochemistry was used to detect the expression of GRP78 and GRP94 in the conventional paraffin-embedded liver sections.
RESULTSThe positive rates of GRP78 expression (53% vs 10%; P<0.05) and GRP94 expression (60% vs 10%; P<0.05) in HB liver tissues were significantly higher than those in the normal liver tissues. The positive rates of GRP78 expression in the cases without lymphnode metastasis or in clinical stage I-II were significantly lower than those in the cases with lymphnode metastasis or in clinical stage III-IV (P<0.05). GRP94 showed a decreased tendency of positive expression in the cases without lymphnode metastasis or in clinical stage I-II when compared with the cases with lymphnode metastasis or in clinical stage III-IV, although there were no statistical differences between them.
CONCLUSIONSGRP78 and GRP94 expression might play important roles in the pathogenesis and progression of pediatric HB.
Child ; Child, Preschool ; Female ; Heat-Shock Proteins ; analysis ; Hepatoblastoma ; chemistry ; pathology ; Humans ; Immunohistochemistry ; Infant ; Liver ; chemistry ; Liver Neoplasms ; chemistry ; pathology ; Male ; Membrane Glycoproteins ; analysis ; Neoplasm Staging
6.Glypican 3 expression in hepatoblastoma and its diagnostic implication.
Feng-hua WANG ; Jian-ming WEN ; E-mail: WENJM@MAIL.SYSU.EDU. ; Heong-ting VONG ; Yuk-ching YIP
Chinese Journal of Pathology 2013;42(12):806-809
OBJECTIVETo explore the expression and diagnostic significance of glypican-3 (GPC3) in hepatoblastoma.
METHODSFive tissue microarray paraffin blocks were constructed to include 54 cases of hepatoblastoma. The tumor tissue samples were obtained from 3 surgical biopsies, 33 needle biopsies, 5 stage I resection tumors, and 13 stage II resection tumors after transcatheter arterial chemoembolization. Ten samples of non-neoplastic hepatic tissue adjacent to tumor were used as control. Immunohistochemical staining of GPC3 (clone 1G12) was performed. Among the 54 cases of hepatoblastoma, 22 cases were fetal subtype, 24 cases were mixed fetal and embryonal subtype and 8 cases were mixed epithelial and mesenchymal type.
RESULTSGPC3 was positive in fetal epithelial cells (54/54, 100%), but negative or weakly positive in embryonic epithelial cells in all cases of hepatoblastoma. Undifferentiated small cells and all mesenchymal components were negative for the expression. Non-neoplastic hepatocytes adjacent to tumor were negative for GPC3 expression (0/10) .
CONCLUSIONSFetal epithelial components of hepatoblastoma express GPC3 protein detectable by immunohistochemistry. Normal hepatocytes after birth, small cell undifferentiated and embryonic epithelial components of hepatoblastoma do not or weakly express GPC3 protein. Therefore, GPC3 immunohistochemistry offers a valuable aid to the diagnosis of hepatoblastoma in infants and children.
Child ; Child, Preschool ; Diagnosis, Differential ; Epithelial Cells ; metabolism ; Female ; Glypicans ; metabolism ; Hepatoblastoma ; diagnosis ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Infant ; Infant, Newborn ; Liver Neoplasms ; diagnosis ; metabolism ; pathology ; Male
7.Ruptured Undifferentiated (Embryonal) Sarcoma of the Liver in an Adult.
Sang Hyun SHIN ; Je Hoon PARK ; Seong Woo HONG ; Yun Kyung KANG ; Hyucksang LEE
Korean Journal of Hepato-Biliary-Pancreatic Surgery 2005;9(3):185-188
The undifferentiated (embryonal) sarcoma of the liver (USL) has previously been called malignant mesenchymoma, undifferentiated sarcoma and fibromyxosarcoma. USL was named as an entity by Stocker and Ishak in 1978 on the basis of an Armed Forces Institute of Pathology (AFIP) series of 31 cases. The USL is a rare primary neoplasm of a mesenchymal origin and it predominantly occurs in children. Stocker reported that it was fourth in frequency among the liver tumors of childhood, following hepatoblastoma, hemangioendothelioma and hepatocellular carcinoma. Although there has been controversy as to the most appropriate treatment, the studies have reported that long term survival is possible after complete surgical resection with or without perioperative chemotherapy. This tumor's frequency in the adult population is extremely low. We report here on a case of USL in an adult woman with the review of the relevant literature.
Adult*
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Arm
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Carcinoma, Hepatocellular
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Child
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Drug Therapy
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Female
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Hemangioendothelioma
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Hepatoblastoma
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Humans
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Liver Neoplasms
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Liver*
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Mesenchymoma
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Neoplasms, Germ Cell and Embryonal
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Pathology
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Sarcoma*
8.A Clinical Study on Hepatoblasoma in Children.
Song Hee PARK ; Hyun Sang CHO ; Chuhl Joo LYU ; Chang Hyun YANG ; Kir Young KIM ; Byung Soo KIM
Korean Journal of Pediatric Hematology-Oncology 1999;6(1):88-94
PURPOSE: Hepatoblastoma comprises over two-thirds of the malignant tumors of the liver in childhood. Although complete resection is the cornerstone of successful management, combination chemotherapy has had a major impact in improving survival. The purpose of this report is to review the clinical finding, therapeutic response, and long- term result of combined modality in 10 children who diagnosed hepatoblastoma. METHODS: From September 1993 to May 1998, the initial diagnosis of hepatoblastoma was made in 10 children at Severance hospital. We analysed medical record retrospectively for clinical finding, therapeutic modality, and survival. RESULTS: 1) The 10 children ranged in age from 3 months to 51 months of age at diagnosis (median age: 21 months of age). 2) There were 9 boys and 1 girl 3) The children presented with either abdominal distension or a mass. Of 10 patients, 6 patients had thrombocytosis more than 500,000/muL and 7 patients had elevated alpha-fetoprotein (AFP) more than 30,000 IU/mL. 4) Pathology results were predominantly of epithelial histology except one case that had elements of mixed. 5) 7 children had right lobe involvement and one child had tumor in both lobe. 6) Surgery was undertaken at diagnosis in 6 patients and preoperative chemotherapy was taken in 4 patients. Preoperative chemotherapy significantly reduced the extent of resection to be necessary for complete resection in 3 patients. 7) 8 of 10 children (80%) are alive (4 to 51 months posttreatment) with no evidence of disease with median follow-up of 39 months. 2 children are lost to follow-up. Conclusions: Excellent cure rates has been achived with complete resection followed by multiagent chemotherapy for hepatoblastoma. Future studies are directed toward the identification of poor risk patients with protocols designed to improve survival for children with advanced disease.
alpha-Fetoproteins
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Child*
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Diagnosis
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Drug Therapy
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Drug Therapy, Combination
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Female
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Follow-Up Studies
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Hepatoblastoma
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Humans
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Liver
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Lost to Follow-Up
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Medical Records
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Pathology
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Retrospective Studies
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Thrombocytosis
9.Effects of antisense human telomerase reverse-transcript protein subunit (hTERT) gene on biological characteristics of hepatoblastoma cell line in vitro.
Lei LIU ; Chen-rong LI ; Lai-bao SUN ; Guo-bing WANG ; Bing WANG
Chinese Journal of Pediatrics 2004;42(7):481-485
OBJECTIVETelomerase, a complex of ribose and nucleoprotein, is a specific marker of tumor, which expresses in 98% infinite cell lines and 90% malignant tumor organizations and whose function is to maintain the length of telomere. Human telomerase reverse-transcript protein subunit (hTERT) is the key element and rate-limiting factor of telomerase activity. Our study was to investigate the effects of antisense hTERT gene on biological characteristics of hepatoblastoma cell line in vitro.
METHODSThe sense and antisense hTERT eukaryotic expression vectors that we had constructed before were transfected into hepatoblastoma cell line HepG2 by using the SuperFect transfection reagent (Qiagen) according to the manufacturer's instructions, then the HepG2-s and HepG2-as of G418-resistant colonies were obtained with G418 and identified for the presence of hTERT insert by PCR with T7 and pcDNA3.1/BGH reverse primers. After that, we have detected the endogenous hTERT mRNA expression and telomerase activity by quantitative real-time RT-PCR and TRAP-silver staining assay in cells from each group. Meanwhile, MTT cellular proliferation assay, soft agar colony formation assay and flow cytometry were employed to analyze if the proliferation capacity of liver cancer cells was affected in vitro and the tumor cells could be induced to apoptosis by antisense hTERT.
RESULTSAntisense hTERT significantly down-regulated the endogenous hTERT mRNA expression (15.35 +/- 1.72/HepG2-as, 43.8 +/- 2.89/HepG2-s, 45.2 +/- 3.46/HepG2) (n = 10, t = 7.61, P < 0.01) and telomerase activity in HepG2, compared to blank control and sense hTERT. After 20 passages of three group cells, a 7-day cell growth curve and the numbers (size) of soft agar colony formation showed the proliferation and the anchorage-independent growth in HepG2-as were significantly suppressed (50.6 +/- 4.8/HepG2-as, 113.52 +/- 8.15/HepG2-s, 119.12 +/- 10.82/HepG2) (n = 10, t = 4.54, P < 0.01 and n = 10, t = 3.96, P < 0.01), compared to HepG2 and HepG2-s. However there was a significant increase in apoptosis percentage of HepG2-as by flow cytometry (n = 10, t = 9.24, P < 0.01 and n = 10, t = 8.37, P < 0.01), compared to control group.
CONCLUSIONSAntisense hTERT could significantly suppress the hepatoblastoma cell growth and reverse its malignant phenotypes in vitro and cause the increase in apoptosis percentage of HepG2, thus it might be applied in malignant tumor gene therapy through the telomerase-targeted molecular mechanism.
Cell Division ; genetics ; Cell Line, Tumor ; DNA-Binding Proteins ; Hepatoblastoma ; genetics ; pathology ; Humans ; RNA, Antisense ; genetics ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Telomerase ; genetics
10.Chronic Gastric Volvulus as a Late Complication of Hepatectomy for Hepatoblastoma in a Child: A Case Report
Han Shin LEE ; Eun Jung JUNG ; Ji Sook PARK ; Taejin PARK
Pediatric Gastroenterology, Hepatology & Nutrition 2019;22(6):608-612
Gastric volvulus (GV) is an uncommon pathology, with 10-20% of cases occurring in children, typically before one year of age. It often occurs in people with congenital diaphragmatic hernias, intestinal malrotation, eventration of the diaphragm, paraesophageal hernias, wandering spleens, asplenism, or intra-abdominal adhesions. We report a rare case of chronic GV after left hemihepatectomy for hepatoblastoma in a child. The patient was a 9-year-old boy who complained of upper abdominal pain and postprandial upper abdominal distension for one year. At the age of 4 months, he was diagnosed with hepatoblastoma and had undergone left hemihepatectomy. The upper gastrointestinal contrast study revealed chronic organoaxial gastric volvulus. After a surgical procedure involving adhesiolysis and an anterior wall gastropexy, the patient improved and the symptoms resolved. Although GV is a rare disease, it should be suspected in a patient with a previous abdominal surgical history who is complaining of abdominal distension and pain.
Abdominal Pain
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Child
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Diaphragm
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Gastropexy
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Hepatectomy
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Hepatoblastoma
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Hernia, Hiatal
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Hernias, Diaphragmatic, Congenital
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Humans
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Male
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Pathology
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Rare Diseases
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Stomach Volvulus
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Wandering Spleen