MedWorm: Hepatoblastoma

Acquired Antithrombin Type IIb Deficiency After Liver Transplantation: A Case Report

American Journal of Transplantation — Thu, 02 Feb 2012 05:00:00 +0100

A 3‐year‐old girl with multifocal hepatoblastoma was referred to our clinic for living‐donor liver transplantation, the patient's father being the donor. Pretransplant evaluation revealed that the father presented partial asymptomatic antithrombin (AT) deficiency, with no inherited AT deficiency found in the girl. The genetic testing showed an AT type IIb deficiency responsible for a defect in the heparin‐binding region of AT which is less thrombogenic but more common than the other AT qualitative defects. Her mother was ABO incompatible. Despite the thrombophilia on the father's side, transplantation was successfully performed under replacement therapy with intravenous AT concentrate and low‐molecular‐weight heparin thromboprophylaxis given to both the recipient and the donor....

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Paediatric malignant liver tumours.

Bulletin du Cancer — Thu, 19 Jan 2012 05:00:00 +0100

Authors: Brugières L, Branchereau S, Laithier V Abstract Tumours and pseudotumours of the liver are a heterogeneous group of neoplasm including 60% of malignant tumours. Malignant liver tumours account for less than 2% of the lesions in children and vary considerably in incidence throughout the paediatric age range, with hepatoblastoma, rhabdoid tumour of the liver, hemangioendothelioma, biliary tract rhabdomysosarcoma and mesenchymal hamartoma in the first two years of life and hepatocellular carcinoma, focal nodular hyperplasia, and undifferentiated sarcoma in older children and adolescents. Treatment of malignant epithelial tumours is based on the surgical resection of the tumour associated with pre- and postoperative chemotherapy including cisplatinum. Modalities of the treatm...

Hepatoblastoma: recent developments in research and treatment

Seminars in Pediatric Surgery — Wed, 18 Jan 2012 06:36:29 +0100

Hepatoblastoma is the most common liver tumor of early childhood. According to recent studies its incidence seems to be increasing in North America and Europe. Since new histological variants have been described recently the formerly clear-cut distinction of hepatoblastoma and hepatocellular carcinoma may not be valid anymore and a new histological classification will be inaugurated by an international working group. Recent research identified prognostically relevant gene signatures as well as potential molecular targets for therapy of hepatoblastoma. The multicentric study groups in the USA, Europe and Japan recommend cisplatin based chemotherapy for neoadjuvant and adjuvant treatment. However, their risk stratification systems and general treatment strategies differ substantially. Theref...

Surgical treatment of lung metastases in patients with embryonal pediatric solid tumors: an update

Seminars in Pediatric Surgery — Wed, 18 Jan 2012 06:36:29 +0100

Distant metastases regularly occur in children with solid tumors. The most affected organ is the lung. Nearly in all extracranial pediatric solid tumors, the presence of lung metastases is associated with an adverse prognosis for the children. Therefore, the correct treatment of lung metastases is essential and influences the outcome. Despite different national and international trials for pediatric tumor entities, specific surgical aspects or guidelines for lung metastases are usually not addressed thoroughly in these protocols. The aim of this article is to present the diagnostic challenges and principles of surgical treatment by focusing on the influence of surgery on the outcome of children. Special points of interest are discussed that emphasize sarcomas, nephroblastomas, hepatoblasto...

Tumor necrosis predicts survival following neo‐adjuvant chemotherapy for hepatoblastoma

Pediatric Blood and Cancer — Tue, 20 Dec 2011 05:00:00 +0100

ConclusionsExtent of tumor necrosis following neo‐adjuvant chemotherapy is an independent prognostic factor in patients with newly diagnosed HB. Histological response may potentially be used in strategies to modify post‐surgical therapy to improve survival in HB. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Treatment effects of the multikinase inhibitor sorafenib on hepatoblastoma cell lines and xenografts in NMRI‐Foxn1nu mice

Liver International — Mon, 19 Dec 2011 09:07:46 +0100

ConclusionTreatment with sorafenib led to a potent inhibition of cell viability, tumour progression and angiogenesis. Sorafenib might therefore also be a promising treatment option for high risk or recurrent HB. (Source: Liver International)

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Mutations of PTCH1, MLL2, and MLL3 are not frequent events in hepatoblastoma

Pediatric Blood and Cancer — Mon, 19 Dec 2011 05:00:00 +0100

(Source: Pediatric Blood and Cancer)

Myc Target miRs and Liver Cancer: Small Molecules to Get Myc Sick

Gastroenterology — Mon, 19 Dec 2011 05:00:00 +0100

Primary liver cancer is a disease arising from malignant transformation of hepatocytes, which account for up to 80% of the liver tissue. In infants, the most common form of liver tumor is hepatoblastoma (HB), a rare childhood tumor that mostly affects kids (Source: Gastroenterology)

DLK1, a serum marker for hepatoblastoma in young infants

Pediatric Blood and Cancer — Fri, 16 Dec 2011 05:00:00 +0100

In this report, we show that Delta‐like 1 homolog (DLK1), a protein highly expressed during fetal development, but almost completely absent after birth, and an established liver‐stem cell marker, is a new candidate serum marker of hepatoblastoma, especially in young infants. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc. (Source: Pediatric Blood and Cancer)

Wnt signaling and telomerase activation of hepatoblastoma: correlation with chemosensitivity and surgical resectability

Journal of Pediatric Surgery — Thu, 01 Dec 2011 05:00:00 +0100

Conclusions: Wnt/β-catenin signaling in the HBLs without CTNNB1 mutations was activated by high expression of TERT. The clinical courses in HBLs without CTNNB1 mutations seemed to be unfavorable because of chemoresistance and low rates of resectability. (Source: Journal of Pediatric Surgery)

Hepatoblastoma in the nordic countries

International Journal of Cancer — Fri, 18 Nov 2011 05:00:00 +0100

This study indicates that intrauterine and/or neonatal factors are associated with increased risk of hepatoblastoma. These may include low birth weight and asphyxia leading to neonatal intensive care. Alternatively, the factors may be a consequence of hepatoblastoma developing in utero. (Source: International Journal of Cancer)

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Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export

Journal of Gastroenterology and Hepatology — Fri, 18 Nov 2011 05:00:00 +0100

Conclusions: Inflammation disrupted PPAR‐LXR‐CYP7A1/ABCA1‐mediated bile acid synthesis and cholesterol efflux resulting in exacerbated cholesterol accumulation in livers of C57BL/6J mice and HepG2 cells. (Source: Journal of Gastroenterology and Hepatology)

The effects of garlic‐derived sulfur compounds on cell proliferation, caspase 3 activity, thiol levels and anaerobic sulfur metabolism in human hepatoblastoma HepG2 cells

Cell Biochemistry and Function — Fri, 18 Nov 2011 05:00:00 +0100

The aim of the present studies was to determine whether the mechanism of biological action of garlic‐derived sulfur compounds in human hepatoma (HepG2) cells can be dependent on the presence of labile sulfane sulfur in their molecules. We investigated the effect of allyl sulfides from garlic: monosulfide, disulfide and trisulfide on cell proliferation and viability, caspase 3 activity and hydrogen peroxide (H2O2) production in HepG2 cells. In parallel, we also examined the influence of the previously mentioned compounds on the levels of thiols, glutathione, cysteine and cysteinyl‐glycine, and on the level of sulfane sulfur and the activity of its metabolic enzymes: rhodanese, 3‐mercaptopyruvate sulfurtransferase and cystathionase. Among the compounds under study, diallyl trisulfide (...

Outcome of Hepatoblastoma in the Indian Context.

Indian Pediatrics — Tue, 01 Nov 2011 04:00:00 +0100

Authors: Arora RS Abstract A comprehensive review and critical appraisal of published and grey literature was undertaken to identify current treatment practices and outcomes of children with hepatoblastoma in India. Eight single-centre studies with 157 patients (range five to 36 patients in each study) were included. Pre-operative chemotherapy (mainly cisplatin and doxorubicin) followed by surgical resection and additional chemotherapy was the usual practice. There was no stratification of treatment by risk group in any of the studies. The median event-free survival ranged from 33-100%. The two main reasons for treatment failure were treatment-related mortality (0-50%) and progression of disease (0-30%). PMID: 22080621 [PubMed - as supplied by publisher] (Source: Indian Pediatr...

Deregulation of Hippo kinase signalling in Human hepatic malignancies

Liver International — Thu, 20 Oct 2011 04:00:00 +0100

ConclusionsThese data show that Yap induction mediated by inactivation of Lats is observed in hepatic malignancies. These studies highlight Hippo kinase pathway as a novel therapeutic target for hepatic malignancies. (Source: Liver International)

Cardiopulmonary Arrest on Arrival in an Infant due to Ruptured Hepatoblastoma

The Journal of Pediatrics — Thu, 13 Oct 2011 04:00:00 +0100

Primary tumors of the liver account for approximately 1% of malignancies in children, with an annual incidence of 1.6 cases per million children in the United States. Between 50% and 60% of hepatic tumors in children are malignant, and >65% of these are hepatoblastomas. Hepatoblastoma occurs predominantly in children (Source: The Journal of Pediatrics)

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HGF/c-Met related activation of beta-catenin in Hepatoblastoma

Journal of Experimental and Clinical Cancer Research — Wed, 12 Oct 2011 04:00:00 +0100

In this study we have investigated alternative activation of beta-catenin by HGF/c-Met signaling in a large cohort of 84 HB patients enrolled in the SIOPEL-3 clinical trial. Methods: We performed immunohistochemistry, using antibodies to total beta-catenin and tyrosine654-phosphorylated beta-catenin, which is a good surrogate marker of HGF/c-Met activation. CTNNB1 mutation analysis was also carried out on all samples. We also investigated beta-catenin pathway activation in two liver cancer cell lines, HuH-6 and HuH-7. Results: Aberrant beta-catenin expression was seen in the cytoplasm and/or nucleus of 87% of tumour samples. Our results also revealed a large subset of HB, 83%, with cytoplasmic expression of tyrosine654-phosphorylated beta-catenin and 30% showing additional nuclear accumula...

Apoptosis sensitizers enhance cytotoxicity in hepatoblastoma cells

Pediatric Surgery International — Wed, 05 Oct 2011 05:49:22 +0100

Conclusion The data provide evidence that ABT-737 and obatoclax might improve treatment results in children with HB. Content Type Journal ArticleCategory Original ArticlePages 1-11DOI 10.1007/s00383-011-2988-zAuthors Justus Lieber, Department of Pediatric Surgery and Pediatric Urology, University Children’s Hospital, Hoppe-Seyler-Strasse 1, 72076 Tübingen, GermanyVerena Ellerkamp, Department of Pediatric Surgery and Pediatric Urology, University Children’s Hospital, Hoppe-Seyler-Strasse 1, 72076 Tübingen, GermanyJulia Wenz, Department of Pediatric Surgery and Pediatric Urology, University Children’s Hospital, Hoppe-Seyler-Strasse 1, 72076 Tübingen, GermanyBettina Kirchner, Department of Pediatric Surgery and Pediatric Urology, University Children’s Hospital, ...

Inhibition of autophagy may suppress the development of hepatoblastoma

FEBS Journal — Tue, 04 Oct 2011 04:00:00 +0100

AbstractHepatoblastoma(HB) is rare cancer but represents the most common liver malignancy in children before the age of 3 years. Nevertheless, a clear understanding of the pathogenesis is yet lacking. Although HB treatment has dramatically improved by combining chemotherapy regimens with surgery, its fatal outcome of fast development and recurrence makes new treatment strategies essential which depending on new understanding of the pathogenesis. Autophagy is believed to be important in the progression of cancers. However, the role of autophagy in HB remains to be elucidated. Here, we show that autophagy is activated in HB tissues and cells under the conditions of starvation or chemotherapy, coupled with the overexpression of autophagic related genes BECN1 and ATG5. Suppression of autophagy...

Effects of transient overexpression or knockdown of cytochrome P450 reductase on reactive oxygen species generation and hypoxia-reoxygenation injury in liver cells.

Clinical and Experimental Pharmacology and Physiology — Tue, 04 Oct 2011 04:00:00 +0100

Authors: Pillai VC, Snyder RO, Gumaste U, Thekkumkara TJ, Mehvar R Abstract 1 Literature data suggest that the electron-donating enzyme cytochrome P450 reductase (CPR) may act as a source of reactive oxygen species (ROS). However, the role of CPR in pathophysiologic conditions associated with oxidative stress is unknown. The aim of this study was to study the role of CPR in the generation of ROS and cellular injury under basal conditions and after simulated in vitro ischemia-reperfusion (IR). 2 Plasmid DNA or siRNA approaches were used to transiently overexpress or knockdown human CPR gene in rat liver epithelial (WB-F344) or human hepatoblastoma (HepG2) cells, respectively. The generation of ROS and/or cellular injury was then studied under the basal conditions and after sim...

Initial liver transplantation for unresectable hepatoblastoma after chemotherapy

Pediatric Blood and Cancer — Fri, 09 Sep 2011 04:00:00 +0100

ConclusionsApplication of SIOPEL protocols for treatment of HBL in a specialized multidisciplinary team with access to liver transplantation has resulted in excellent survival. Initial extrahepatic disease should not be considered a contraindication. Future refinements of the protocol need to be considered to reduce toxicity. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

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Nuclear receptor mRNA expression by HBV in human hepatoblastoma cell lines

Cancer Letters — Fri, 09 Sep 2011 04:00:00 +0100

Highlights: ► Nuclear receptor-signal pathways in HepG2.2.15 are different from those in HepG2. ► HBV affects nuclear receptors and their related signal transduction. ► We focused on androgen receptor and histone deacetylase among nuclear receptors. ► Nuclear receptors play important roles in viral replication and hepatocarcinogenesis.Abstract: Recent studies have implicated nuclear receptors (NRs) in the development of hepatocarcinogenesis. We assumed that hepatitis B virus (HBV) alters the expression of NRs and coregulators, and compared the gene expression profiling for 84 NRs and related genes between HpeG2.2.15, which secretes complete HBV virion, and HepG2 by real-time RT-PCR with SyBr green. Forty (47.6%) genes were upregulated 2-fold or greater, and only 5 (5.9%) were downr...

Role of Organ Transplantation in the Treatment of Malignancies - Hepatocellular Carcinoma as the Most Common Tumour Treated with Transplantation.

Pathology Oncology Research — Wed, 07 Sep 2011 04:00:00 +0100

Authors: Végső G, Görög D, Fehérvári I, Nemes B, Doros A, Langer RM, Kóbori L Abstract There are only few malignant tumours where organ transplantation is the treatment of choice. Transplantation can be considered individually in certain lung carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin tumour. It is acceptable in unresectable chemosensitive hepatoblastoma, epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and as the most common indication, the early hepatocellular carcinoma (HCC) in cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan criteria as a "gold standard" are excellent. Time of LT has a great influence on the results. While patients are on waiting list, locoregional therapie...

The BH3 mimetic ABT-737 increases treatment efficiency of paclitaxel against hepatoblastoma

BMC Cancer — Thu, 18 Aug 2011 23:00:00 +0100

Conclusions: Our results demonstrate enhancement of chemotherapy by using modulators of apoptosis. Further analyses should include improved pharmacological formulations of paclitaxel and BH3 mimetics in order to reduce toxicological effects. Sensitising HB to apoptosis may also render resistant HB susceptible to established chemotherapy regimens. (Source: BMC Cancer)

Smad2/3 and HNF4{alpha} Binding Regions in HepG2 Cells [Signal Transduction]

Journal of Biological Chemistry — Thu, 18 Aug 2011 23:00:00 +0100

In this study, we determined Smad2 and Smad3 (Smad2/3) binding regions in the promoters of known genes in HepG2 hepatoblastoma cells, and we compared them with those in HaCaT epidermal keratinocytes to elucidate the mechanisms of cell type- and context-dependent regulation of transcription induced by TGF-β. Our results show that 81% of the Smad2/3 binding regions in HepG2 cells were not shared with those found in HaCaT cells. Hepatocyte nuclear factor 4α (HNF4α) is expressed in HepG2 cells but not in HaCaT cells, and the HNF4α-binding motif was identified as an enriched motif in the HepG2-specific Smad2/3 binding regions. Chromatin immunoprecipitation sequencing analysis of HNF4α binding regions under TGF-β stimulation revealed that 32.5% of the Smad2/3 binding regions overlapped HNF...

Complete Surgical Resection Is Curative for Children With Hepatoblastoma With Pure Fetal Histology: A Report From the Children's Oncology Group [Pediatric Oncology]

Journal of Clinical Oncology — Wed, 17 Aug 2011 23:00:00 +0100

Conclusion Children with completely resected PFH hepatoblastoma can achieve long-term survival without additional chemotherapy. When feasible, surgical resection of hepatoblastoma at diagnosis, without chemotherapy, can identify children for whom no additional therapy is necessary. (Source: Journal of Clinical Oncology)

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Liver toxicity and carcinogenicity in f344/n rats and b6c3f1 mice exposed to Kava Kava.

Food and Chemical Toxicology — Wed, 17 Aug 2011 23:00:00 +0100

Authors: Behl M, Nyska A, Chhabra RS, Travlos GS, Fomby LM, Sparrow BR, Hejtmancik MR, Chan PC Abstract Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125 to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in...

Human liver fatty acid binding protein (hFABP1) gene is regulated by liver-enriched transcription factors HNF3β and C/EBPα

Biochimie — Mon, 15 Aug 2011 23:00:00 +0100

Authors: Wu YL, Peng XE, Wang D, Chen WN, Lin X Abstract The human liver fatty acid binding protein (hFABP1) participates in cellular long-chain fatty acid trafficking and regulation of lipid metabolism and changes in hFABP1 are associated with an increased risk for type 2 diabetes, cardiovascular disease (CVD), and metabolic syndromes. Gene regulation of hFABP1 is not fully understood. Therefore, in the present study, the full length hFABP1 promoter (nucleotides -2125 to +51) and a series of truncated promoter regions were cloned. A luciferase reporter assay revealed that nucleotides -255 to +50 in the promoter region contained full of maximum hFABP1 promoter activity compared with the full length promoter. Furthermore high activity was shown when the plasmid was transfected i...

Hepatitis B virus and hepatocellular carcinoma at the miRNA level.

World Journal of Gastroenterology : WJG — Wed, 27 Jul 2011 23:00:00 +0100

CONCLUSION: Our analysis provides insights into HBV infection and related HCC in relation to miRNAs, and reveals some candidate miRNAs for future studies. PMID: 21876625 [PubMed - in process] (Source: World Journal of Gastroenterology : WJG)

Anti‐tumor activity of the HSP90 inhibitor SNX‐2112 in pediatric cancer cell lines

Pediatric Blood and Cancer — Tue, 26 Jul 2011 23:00:00 +0100

ConclusionsSNX‐2112 showed marked single‐agent activity in pediatric cancer cell lines with downstream effects on HSP90 client proteins. The combination of SNX‐2112 and CP showed synergistic activity in two cell lines tested. Further studies of HSP90 inhibitors such as SNX‐2112 as a single agent or in combination with chemotherapy are warranted in pediatric cancer. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

What Are the Indications for PET and PET/CT?

PediatricEducation.org — Mon, 25 Jul 2011 18:12:31 +0100

Discussion Positron emission tomography test (PET) and PET/CT that combines PET with computed tomography (CT) was first begun in the 1950s. In 2000 it was the TIME magazine invention of the year. PET gives functional, metabolic data about the human body. When combined with CT’s anatomical, structural data, PET/CT can give both data types concurrently. PET uses radioactive tracers linked to metabolites. One of the most common tracers is 18F-fluorodeoxyglucose (FDG), a glucose metabolite. Since FDG contains glucose, there will be background tracer uptake particularly in the skeletal muscle, brain, thymus, brown fat, heart, and gastrointestinal track. The tracer is excreted by the kidneys but not reabsorbed, so increased background may be seen in the urinary system. Increasing filtratio...

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Complete resection cures stage 1 pediatric hepatoblastoma

Modern Medicine — Thu, 21 Jul 2011 23:00:00 +0100

NEW YORK (Reuters Health) - A subgroup of children with hepatoblastoma can be treated with surgery alone, according to results of a small study. (Source: Modern Medicine)

Hepatic response to aluminum toxicity: Dyslipidemia and liver diseases.

Experimental Cell Research — Tue, 19 Jul 2011 23:00:00 +0100

Authors: Mailloux RJ, Lemire J, Appanna VD Aluminum (Al) is a metal toxin that has been implicated in the etiology of a number of diseases including Alzheimer's, Parkinson's, dialysis encephalopathy, and osteomalacia. Al has been shown to exert its effects by disrupting lipid membrane fluidity, perturbing iron (Fe), magnesium, and calcium homeostasis, and causing oxidative stress. However, the exact molecular targets of aluminum's toxicity have remained elusive. In the present review, we describe how the use of a systems biology approach in cultured hepatoblastoma cells (HepG2) allowed the identification of the molecular targets of Al toxicity. Mitochondrial metabolism is the main site of the toxicological action of Al. Fe-dependent and redox sensitive enzymes in the tricarboxylic acid...

Totally Robotic Right Hepatectomy: Surgical Technique and Outcomes [Original Article]

Archives of Surgery — Sun, 17 Jul 2011 23:00:00 +0100

Conclusions The zero mortality and acceptable morbidity of our series indicate that in experienced hands, robotic right hepatectomy is feasible and safe. Robotic surgery offers a new technical option for minimally invasive major hepatic resections. Long-term results seem to confirm oncologic effectiveness of the procedure. (Source: Archives of Surgery)

{alpha}-Fetoprotein

Archives of Disease in Childhood - Education and Practice — Mon, 11 Jul 2011 23:00:00 +0100

α-Fetoprotein (AFP) measurements have clinical implications in fetal medicine and, in infants and older children, in detection, differential diagnosis and monitoring of malignant disease. Maternal serum AFP levels constitute part of a multiple-marker test used in early second-trimester screening to predict risk of fetal chromosomal abnormalities. Those individuals with increased risk are offered further definitive diagnostic investigation. Second-trimester screening is now increasingly being superseded by first-trimester screening with other serum markers and ultrasound. As AFP is only produced physiologically during fetal development, elevated serum levels after the first two post-natal years usually indicate the presence of a malignant disease process. Before this time, levels may ...

Cytoplasmic Staining of TTF-1 Antibody in the Diagnosis of Hepatocellular Carcinoma: Study on 299 Cases Using Tissue Microarray

Advances in Pharmacological Sciences — Wed, 06 Jul 2011 14:50:08 +0100

The diagnosis of hepatocellular carcinoma (HCC) remains obscure in some complicated cases. Thyroid transcription factor-1 (TTF-1) was presumed to be helpful in the diagnosis of HCC. This paper aims to study the utility of TTF-1 in the diagnosis and differential diagnosis of HCC and to assign clinicopathological correlations. Immunohistochemical detection of TTF-1 is performed with tissue microarray which contains a total of 781 cases including 299 hepatocellular carcinomas (HCCs), 31 intrahepaticcholangiocarcinomas (ICCs), 86 metastatic adenocarcinomas (MACs), 5 metastatic hepatocellular carcinomas (mHCCs), 9 hepatoblastomas (HBs), 40 renal clear cell carcinomas (RCCs), 215 adjacent nonneoplastic hepatic tissue, and 96 normal hepatic tissue. The result shows that TTF-1 is positive in 55.2%...

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The comparison of grey-scale ultrasonic and clinical features of hepatoblastoma and hepatocellular carcinoma in children: a retrospective study for ten years

BMC Gastroenterology — Fri, 24 Jun 2011 23:00:00 +0100

Conclusion: Ultrasonic features combined with clinical manifestations are valuable for differentiating HBL from HCC in children. (Source: BMC Gastroenterology)

The use of everolimus in pediatric liver transplant recipients: First experience in a single center

Pediatric Transplantation — Tue, 31 May 2011 23:00:00 +0100

Nielsen D, Briem‐Richter A, Sornsakrin M, Fischer L, Nashan B, Ganschow R. The use of everolimus in pediatric liver transplant recipients: First experience in a single center. Pediatr Transplantation 2011: 00: 000–000. © 2011 John Wiley & Sons A/S.Abstract: The role of mTOR inhibitors, such as EVL, has not been established for pediatric liver transplant recipients up to now, although data from adult solid organ graft transplantation are very promising. Major complications following pediatric liver transplantation in the long‐term course include chronic graft rejection and CNI‐derived nephrotoxicity. The purpose of our study was to report first results using EVL as a rescue therapy in pediatric liver transplant recipients for the following indications: chronic graft dysfun...

Hepatoblastoma and prune belly syndrome: a potential association

Pediatric Nephrology — Thu, 19 May 2011 16:30:45 +0100

We describe a set of 4 pediatric patients with PBS and HBL. All individuals were born after 2002. These subjects lacked genetic, natal, or environmental factors known to confer risk of HBL. The occurrence of PBS and HBL in these patients constitutes a novel potential association. Content Type Journal ArticlePages 1-5DOI 10.1007/s00467-011-1874-1Authors Brian Becknell, Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH 43205, USAPriya Pais, Division of Nephrology, Children’s Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI 53201, USAGrace Onimoe, Department of Pediatrics, Ohio State University College of Medicine, Columbus, OH 43205, USAHemalatha Rangarajan, Division of Hematology and Oncology, Children’s Hospital of Wisconsin, M...

Socioeconomic status and the incidence of non-central nervous system childhood embryonal tumours in Brazil

BMC Cancer — Wed, 04 May 2011 23:00:00 +0100

Conclusion: Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil. (Source: BMC Cancer)

Epithelioid Angiomyolipoma: A Morphologically Distinct Variant That Mimics a Variety of Intra-abdominal Neoplasms.

Archives of Pathology and Laboratory Medicine — Sat, 30 Apr 2011 23:00:00 +0100

Authors: Mete O, van der Kwast TH Abstract This review examines the histopathologic, immunohistochemical, ultrastructural, and molecular biologic features of epithelioid angiomyolipoma (EAML), with an emphasis on the differential diagnosis of intra-abdominal EAML. Epithelioid angiomyolipoma is an uncommon mesenchymal tumor with malignant potential, frequently associated with tuberous sclerosis complex. Histologically, EAML is characterized by sheets or nests of large polygonal epithelioid cells with abundant eosinophilic or occasionally clear cytoplasm, often with prominent nucleoli, and EAML may include multinucleated and markedly pleomorphic forms. As these tumors share a distinctive perivascular epithelioid cell phenotype, they belong to the PEComa tumor family. Nearly all EAMLs sho...

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Treatment outcomes for hepatoblastoma: experience of 35 cases at a single institution.

J Formos Med Assoc — Sat, 30 Apr 2011 23:00:00 +0100

Authors: Tsay PK, Lai JY, Yang CP, Hung IJ, Hsueh C, Tsai MH, Jaing TH Hepatoblastoma is the most common malignant liver tumor in children. Comparative studies have elucidated the optimal pre- or postoperative chemotherapeutic regimens. The aim of this study was to investigate the prognostic significance of baseline tumor characteristics for overall survival and disease-free survival in children with hepatoblastoma. PMID: 21621153 [PubMed - in process] (Source: J Formos Med Assoc)

Liver Neoplasia in Children

Clinics in Liver Disease — Sat, 30 Apr 2011 23:00:00 +0100

Management of pediatric liver tumors has significantly improved over the last 2 decades. The management options for hepatocelluar carcinoma (HCC) are not well defined. In the pediatric context, the main clinical aims are to reduce chemotherapy toxicity (predominantly ototoxicity and nephrotoxicity) in children treated for hepatoblastoma and to investigate additional modes of treatment for HCC. An increasing number of children develop HCC in the background of chronic liver disease, and screening methods need to be better observed. (Source: Clinics in Liver Disease)

Impact of Pelvic CT on Staging, Surveillance, and Survival of Pediatric Patients With Wilms Tumor and Hepatoblastoma

American Journal of Roentgenology — Wed, 20 Apr 2011 23:00:00 +0100

CONCLUSION. In our study population, abdominopelvic CT did not detect pelvic metastases to affect subsequent treatment. Given the low rate of pelvic involvement at relapse in children with Wilms tumor and hepatoblastoma, frequent abdominopelvic CT may not be necessary. Replacing these examinations with abdomen-only CT should be considered to decrease radiation burden to this population. (Source: American Journal of Roentgenology)

Inflammatory stress exacerbates hepatic cholesterol accumulation via increasing cholesterol uptake and de novo synthesis

Journal of Gastroenterology and Hepatology — Wed, 13 Apr 2011 17:03:42 +0100

Conclusion: Inflammatory stress disrupted hepatic SREBP2‐mediated low‐density lipoprotein receptor and HMGCoA‐r feedback regulation resulting in exacerbated cholesterol accumulation in livers of C57BL/6J mice and HepG2 cells. (Source: Journal of Gastroenterology and Hepatology)

The clinical course in pediatric solid tumor patients with focal nodular hyperplasia of the liver

International Journal of Clinical Oncology — Thu, 31 Mar 2011 17:36:43 +0100

Conclusion FNH appears to be a late complication of iatrogenic disease in NB stage 4 patients. The therapeutic agents for NB stage 4 and estrogen replacement therapy should be considered as risk factors for the development of FNH. Content Type Journal ArticlePages 1-6DOI 10.1007/s10147-011-0210-xAuthors Kiminobu Sugito, Department of Pediatric Surgery, Nihon University School of Medicine, 30-1, Ohyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610 JapanShota Uekusa, Department of Pediatric Surgery, Nihon University School of Medicine, 30-1, Ohyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610 JapanHiroyuki Kawashima, Department of Pediatric Surgery, Nihon University School of Medicine, 30-1, Ohyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610 JapanTakeshi Furuya, Department o...

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Neonatal hepatoblastoma in a newborn with severe phenotype of Beckwith–Wiedemann syndrome

European Journal of Pediatrics — Tue, 29 Mar 2011 17:33:19 +0100

Abstract Beckwith–Wiedemann syndrome is an overgrowth disorder characterized by neonatal macrosomia, abdominal wall defects, macroglossia, renal anomalies, organomegaly, hypoglycemia, and cancer predisposition. Hepatoblastoma is the second most frequent tumor and periodic serum alpha-fetoprotein (αFP) dosage is the cornerstone of the tumor surveillance for its early detection. In this report, we describe the outstanding case of a Beckwith–Wiedemann syndrome (BWS) newborn with severe phenotype and paternal chromosome 11 uniparental disomy (UPD11) associated with a high tumor risk. Based on the clinical picture and previous reports, a close monitoring of αFP was commenced. The marker was normal immediately after birth, but rapidly raised in 20 days, leading to the...

Continuing Medical Education: AFIP Archives: From the Archives of the AFIP: Pediatric Liver Masses: Radiologic-Pathologic Correlation Part 2. Malignant Tumors [Pediatric Imaging]

Radiographics recent issues — Thu, 17 Mar 2011 00:00:00 +0100

Malignant primary hepatic tumors in children include lesions unique to the pediatric age group and others that are more common in adults. Important considerations when evaluating a child with a liver tumor are the age of the patient, laboratory findings, and specific imaging features. The most common primary malignant hepatic tumor in the pediatric population, hepatoblastoma occurs almost exclusively in patients younger than 5 years with no history of liver disease. Hepatoblastoma is associated with elevated serum α-fetoprotein (AFP) level and appears predominantly solid. Hepatocellular carcinoma (HCC) is the most common malignant liver tumor in older children, often with a history of liver disease. HCC is associated with elevated serum AFP level and also appears as a solid mass. Fib...

From the Archives of the AFIP: Pediatric Liver Masses: Radiologic-Pathologic Correlation Part 2. Malignant Tumors [AFIP Archives]

Radiographics recent issues — Thu, 17 Mar 2011 00:00:00 +0100

Hemi-hepatectomy in pediatric patients using two-surgeon technique and a liver hanging maneuver.

World Journal of Gastroenterology — Mon, 14 Mar 2011 00:00:00 +0100

Authors: Mochizuki K, Eguchi S, Hirose R, Kosaka T, Takatsuki M, Kanematsu T To evaluate the efficacy of the two-surgeon technique with the liver hanging maneuver (LHM) for hepatectomies in pediatric patients with hepatoblastoma. PMID: 21455336 [PubMed - in process] (Source: World Journal of Gastroenterology)

Gene expression profiling of human hepatoblastoma using archived formalin-fixed and paraffin-embedded tissues

Virchows Archiv — Thu, 03 Mar 2011 08:46:37 +0100

Abstract We elucidated the genetic profile of hepatoblastomas (HBLs) to identify diagnostic and prognostic markers. RNA was extracted from 32 formalin-fixed, paraffin-embedded HBLs and corresponding nonneoplastic liver (NNL) tissues, and cDNA-mediated annealing, selection, extension, and ligation (DASL) chip assays were performed. Immunohistochemistry was performed to confirm the expression of Yin Yang 1 (YY1) protein in HBL. Twenty-four genes that were associated with signal transduction, cell–cell adhesion, cell cycle regulation, and apoptosis were differentially expressed in HBL and NNL tissues. Two apoptosis-associated genes, MYCN and BIRC5, were highly upregulated in HBL. Eight genes, including YY1 and IGF1, were upregulated in HBL cases that had a poor prognosis. Thi...

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Prognostic implications of serum alpha‐fetoprotein response during treatment of hepatoblastoma

Pediatric Blood and Cancer — Wed, 02 Mar 2011 00:00:00 +0100

ConclusionsSerial monitoring of changes in AFP levels during the treatment, especially perioperative changes, may help identify favorable and poor responders to chemotherapy. Alternative treatment, such as liver transplantation, should be considered for poor responders. Pediatr Blood Cancer © 2011 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Inhibitory effects of Zuo-Jin-Wan and its alkaloidal ingredients on activator protein 1, nuclear factor-κB, and cellular transformation in HepG2 cells.

Fitoterapia — Fri, 25 Feb 2011 00:00:00 +0100

In conclusion, ZJW and its constituents, berberine and evodiamine, suppressed tumor promotion primarily through AP-1 and/or NF-κB pathways in HepG2 cells. PMID: 21356280 [PubMed - as supplied by publisher] (Source: Fitoterapia)

Irinotecan as a maintenance therapy for hepatoblastoma: A comment

Journal of Cancer Research and Therapeutics — Thu, 24 Feb 2011 00:00:00 +0100

V WiwanitkitJournal of Cancer Research and Therapeutics 2010 6(4):588-588 (Source: Journal of Cancer Research and Therapeutics)

The almighty MYC: Orchestrating the micro-RNA universe to generate aggressive liver cancer

Journal of Hepatology — Wed, 23 Feb 2011 00:00:00 +0100

COMMENTARY ON:: Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer. Cairo S, Wang Y, de Reyniès A, Duroure K, Dahan J, Redon MJ, Fabre M, McClelland M, Wang XW, Croce CM, Buendia MA. PNAS, 2010, November 23, 107(47), 20471–20476. Copyright (2010) by the National Academy of Sciences. Abstract reprinted with permission from the National Academy of Sciences.http://www.ncbi.nlm.nih.gov/pubmed/21059911Abstract: Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371–3 cluster with concomitant ...

Fibrolamellar Carcinoma: A Review with Focus on Genetics and Comparison to Other Malignant Primary Liver Tumors

Seminars in Liver Disease — Tue, 22 Feb 2011 00:00:00 +0100

Semin Liver Dis 2011; 31: 061-070DOI: 10.1055/s-0031-1272835ABSTRACTFibrolamellar carcinoma is a rare primary malignant liver neoplasm that usually affects adolescents and young adults with no underlying liver disease. Morphologically, the tumor cells resemble oncocytic hepatocytes arranged in cords with a stroma of lamellated collagen fibers. Immunohistochemical studies have found that fibrolamellar carcinomas express markers associated with both biliary (CK7 and epithelial membrane antigen) and hepatocytic (heppar-1and glypican-3) differentiation, as well as markers associated with hepatic progenitor cells (CK19 and EpCAM) and stem cells (CD133 and CD44). Genetic studies show fewer alterations compared with classic hepatocellular carcinoma. Pooled data from comparative genomic hybridizat...

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Shades of Truth: Cultural and Psychological Factors Affecting Communication in Pediatric Palliative Care

Journal of Pain and Symptom Management — Tue, 01 Feb 2011 00:00:00 +0100

This article presents the case of a 12-year-old Japanese boy with advanced hepatoblastoma. The patient also was diagnosed with Asperger’s syndrome, which impairs interpersonal communication. The case is discussed from the perspective of clinical ethics, especially with regard to truth telling. The health care team faced an ethical dilemma because of the complications involved. Physicians treating children with cancer should be aware of these issues to be able to effectively communicate with their patients. (Source: Journal of Pain and Symptom Management)

Role of Chemoembolization as a Rescue Treatment for Recurrence of Resected Hepatoblastoma in Adult Patients.

Surgical Innovation — Wed, 19 Jan 2011 00:00:00 +0100

CONCLUSION: The TACE was well tolerated by the patient and controlled the recurrence. The patient survived 11 months after recurrence of disease and died 1 year after the liver resection. The use of TACE to treat the hepatic recurrence was never described. PMID: 21247961 [PubMed - as supplied by publisher] (Source: Surgical Innovation)

Differential expression of glutamine synthetase and cytochrome P450 isoforms in human hepatoblastoma.

Toxicology — Thu, 13 Jan 2011 00:00:00 +0100

This study was aimed to analyse the connection of β-Catenin signalling and GS/CYP expression in human paediatric tumours. Samples from 23 paediatric tumours were analysed for activating mutations in CTNNB1. Protein expression of the model β-Catenin target GS and of various CYP isoforms was analysed and correlated with CTNNB1 mutational status and histological findings. Activating CTNNB1 mutations were frequent in hepatoblastoma (80%) and nephroblastoma (31%), but absent from neuroblastoma, rhabdomyosarcoma, and other soft tissue sarcoma. In CTNNB1-mutated hepatoblastoma, expression of GS was only detected in tumour areas with epithelial, not with mesenchymal differentiation. Particularly high expression of glutamine synthetase was found in hepatoblastoma cells directly neighbouring a mes...

Idiopathic corporeal hemihypertrophy associated with hemihypertrichosis.

Annales d'Endocrinologie — Tue, 11 Jan 2011 00:00:00 +0100

We report the case of a 22-month-old infant, who was referred by his pediatrician at the age of 15 months for a corporeal hemihypertrophy associated with hemihypertrichosis. In his medical history, a second degree parental consanguinity and a hypospadias in the father and a paternal uncle were found. Clinical examination found a weight and a size greater than chronological age (3 standard deviations), a hemihypertrophy of entire left side with a difference of length and diameter between the left and right limbs of 2cm. The hemihypertrichosis was widespread in the left body and the genital examination found a hypospadias. Biological and radiological assessments did not show any abnormality, with the exception of an initially high plasma testosterone level, which gradually normalized. Thus, ...

Hepatoblastoma: Analysis of treatment outcome from a tertiary care center

Journal of Indian Association of Pediatric Surgeons — Mon, 03 Jan 2011 00:00:00 +0100

Conclusions: Treatment of HB with multidisciplinary approach was well tolerated. OS and EFS of patients were comparable with published studies. (Source: Journal of Indian Association of Pediatric Surgeons)

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Synthesis and in vitro anti-hepatitis B virus activity of six-membered azanucleoside analogues.

Bioorganic and Medicinal Chemistry — Sat, 01 Jan 2011 00:00:00 +0100

Authors: Wang D, Li YH, Wang YP, Gao RM, Zhang LH, Ye XS Fifteen novel six-membered azanucleoside derivatives were prepared and evaluated for their anti-hepatitis B virus (HBV) activity and cytotoxicity in human hepatoblastoma-derived liver Hep-G2 cells. The most potent compound 16b with an IC(50) value of 2.74μg/mL (lower than 3TC) and a SI value of 13.5 was disclosed. The key synthetic steps involved the rearrangement of lactones (which were readily obtained from monosaccharides) and the Lewis acid-catalyzed condensation of nucleobases with azasugar donors. Using the versatile acetylated azasugar donors, azanucleosides covering three types of azasugars and four types of natural nucleobases were successfully obtained. The experimental results showed that some six-membered azanucleosi...

Living Related Donor Liver Transplantation in Children

Transplantation Proceedings — Sat, 01 Jan 2011 00:00:00 +0100

Conclusions: Despite the heightened possibility of complications (mainly vascular), LRDLT represented a good alternative to transplantation from cadaveric donors in pediatric populations. It was associated with a high survival ratio. (Source: Transplantation Proceedings)

Reduction of hepatocellular carcinoma in childhood after introduction of selective vaccination against hepatitis B virus for infants born to HBV carrier mothers

Cancer Causes and Control — Wed, 29 Dec 2010 17:11:55 +0100

Conclusion The prevention program against maternal HBV infection of infants born to HBV carrier mothers may have decreased the occurrence of HBV-related HCC in childhood. Content Type Journal ArticleDOI 10.1007/s10552-010-9721-4Authors Hitoshi Tajiri, Department of Paediatrics, Osaka General Medical Center, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka 558-8558, JapanHideo Tanaka, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, JapanStephen Brooks, Department of Microbiology/Immunology, State University of New York at Buffalo, Buffalo, NY USATomoko Takano, Department of Paediatrics, Osaka General Medical Center, 3-1-56 Bandaihigashi, Sumiyoshi-ku, Osaka 558-8558, Japan Journal Cancer Causes and ControlOnline ISSN 1573-7225P...

Pediatric Liver Tumors

Springer Medicine titles — Wed, 22 Dec 2010 00:02:06 +0100

series:Pediatric OncologyThe field of liver tumors in children, and in particular hepatoblastoma in infants and young children, has seen tremendous therapeutic advances over recent years. This has been achieved through a much better understanding of the biology of disease, improved diagnostic procedures, refined methods of pretreatment tumor staging, the implementation of highly efficient chemotherapy and surgery, ... (Source: Springer Medicine titles)

miR‐492 is processed from the keratin 19 gene and upregulated in metastatic hepatoblastoma

Hepatology — Mon, 13 Dec 2010 00:00:00 +0100

Conclusion:A close functional relationship between KRT19 and miR‐492 was identified that may play an important role in the progression of malignant embryonal liver tumors. Additionally, miR‐492 and its associated targets might serve as new HB biomarkers of clinical utility and could assist to explore targeted therapies especially in metastatic HB with still poor prognosis. (HEPATOLOGY 2010.) (Source: Hepatology)

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MicroRNA‐492 is processed from the keratin 19 gene and up‐regulated in metastatic hepatoblastoma

Hepatology — Mon, 13 Dec 2010 00:00:00 +0100

Conclusion: A close functional relationship between KRT19 and miR‐492 was identified that may play an important role in the progression of malignant embryonal liver tumors. Additionally, miR‐492 and its associated targets might serve as new HB biomarkers of clinical utility and could assist to explore targeted therapies, especially in metastatic HB with a poor prognosis. (HEPATOLOGY 2011) (Source: Hepatology)

Hepatoblastoma in a 4 year old girl with Fanconi anemia

Acta Paediatrica — Wed, 08 Dec 2010 20:30:50 +0100

Conclusion: We describe the first case of hepatoblastoma in a patient with FA in order to raise awareness of this tumor type in the close clinical observation of early cancer‐prone forms of this condition, particularly in the presence of FANCD1/BRCA2 mutations. The present case also underscores the importance of FA testing in patients with VACTERL(‐H). (Source: Acta Paediatrica)

Hepatoblastoma in a 4‐year‐old girl with Fanconi anaemia

Acta Paediatrica — Wed, 08 Dec 2010 00:00:00 +0100

Conclusion: We describe the first case of hepatoblastoma in a patient with FA to raise awareness of this tumour type in the close clinical observation of early cancer‐prone forms of this condition, particularly in the presence of FANCD1/BRCA2 mutations. The present case also underscores the importance of FA testing in patients with VACTERL(‐H). (Source: Acta Paediatrica)

Critical review of controversial issues in the management of advanced pediatric liver tumors

Pediatric Blood and Cancer — Wed, 01 Dec 2010 00:00:00 +0100

AbstractHepatocellular carcinoma (HCC) and hepatoblastoma (HB) are the most common primary tumors of liver in children. The management of patients with locally advanced, unresectable disease or those with extra‐hepatic distant metastases provides substantial challenges to pediatric oncologists, hepatologists, and surgeons. Herein, we critically debate the two sides of three specific controversies: (1) the role of chemotherapy in the treatment of advanced pediatric HCC; (2) the indications for liver transplantation in children with HCC, specifically, the appropriateness of using adult Milan criteria; and (3) the role of liver trasplantation in children with unresectable HB that present with metastatic disease. Pediatr Blood Cancer © 2010 Wiley‐Liss, Inc. (Source: Pediatric Blood and Ca...

Chemoresistant hepatoblastoma in a patient with mosaic trisomy 18 treated with orthotopic liver transplantation

Pediatric Blood and Cancer — Sun, 28 Nov 2010 00:00:00 +0100

This report demonstrates the use of orthotopic liver transplantation in a child with mosaic trisomy 18 and hepatoblastoma. Pediatr Blood Cancer. © 2010 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

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Stem cell-like micro-RNA signature driven by Myc in aggressive liver cancer [Medical_Sciences]

Proceedings of the National Academy of Sciences — Tue, 23 Nov 2010 00:00:00 +0100

Myc activation has been implicated in the pathogenesis of hepatoblastoma (HB), a rare embryonal neoplasm derived from liver progenitor cells. Here, microRNA (miR) expression profiling of 65 HBs evidenced differential patterns related to developmental stage and Myc activity. Undifferentiated aggressive HBs overexpressed the miR-371–3 cluster with concomitant down-regulation of the miR-100/let-7a-2/miR-125b-1 cluster, evoking an ES cell expression profile. ChIP and Myc inhibition assays in hepatoma cells demonstrated that both miR clusters are regulated by Myc in an opposite manner. We show that the two miR clusters exert antagonistic effects on cell proliferation and tumorigenicity. Moreover, their combined deregulation cooperated in modulating the hepatic tumor phenotype, implicating...

Spectroscopic Characterization and Antiproliferative Activity on HepG2 Human Hepatoblastoma Cells of Flavonoid C-Glycosides from Petrorhagia velutina

Journal of Natural Products — Tue, 16 Nov 2010 14:36:15 +0100

Journal of Natural ProductsDOI: 10.1021/np100255u (Source: Journal of Natural Products)

Successful nontransplant resection of POST‐TEXT III and IV hepatoblastoma

Cancer — Mon, 15 Nov 2010 00:00:00 +0100

CONCLUSIONS:Excellent survival (93%) was obtained with aggressive resection in children with POST‐TEXT III and IV hepatoblastoma meeting criteria for transplant referral. The 1 death occurred in a patient with unfavorable small cell histology. These children should be managed at institutions experienced in both advanced pediatric hepatobiliary surgery and transplantation. Operative exploration was frequently required to ultimately determine which tumors can be resected and which require transplantation. Cancer 2010. © 2010 American Cancer Society. (Source: Cancer)

Survival by race among children with extracranial solid tumors in the United States between 1985 and 2005

Pediatric Blood and Cancer — Thu, 11 Nov 2010 00:00:00 +0100

ConclusionsMale children from minority groups have poorer survival from extracranial solid malignancies than White male children. Future efforts should be directed at understanding the causes of these differences and at developing practical clinical interventions to eliminate them. Pediatr Blood Cancer © 2010 Wiley‐Liss, Inc. (Source: Pediatric Blood and Cancer)

Loss of Heterozygosity on Chromosome 11p15.5 and Relapse in Hepatoblastomas

European Journal of Pediatric Surgery — Thu, 04 Nov 2010 00:00:00 +0100

Eur J Pediatr SurgDOI: 10.1055/s-0030-1267208AbstractBackground: IGF2 is a tumor suppressor gene at locus 11p15. Many hepatoblastomas have loss of heterozygosity (LOH) at this locus. Earlier studies have not demonstrated any association between LOH and prognosis. Aim of the study was to evaluate the prognostic significance of LOH at 11p15.5 in hepatoblastomas.[...]© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Abstract | Full text (Source: European Journal of Pediatric Surgery)

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Hepatoblastoma in association with bilateral polycystic kidneys

Journal of Pediatric Surgery — Fri, 29 Oct 2010 22:28:28 +0100

We describe the first known case of hepatoblastoma associated with bilateral autosomal recessive polycystic kidney disease in a preterm twin boy. The diagnostic and therapeutic considerations are addressed. The patient survived after primary hepatectomy operation and administration of modified adjuvant chemotherapy. (Source: Journal of Pediatric Surgery)

Use of laparoscopic surgical resection for pediatric malignant solid tumors: a case series

Surgical Endoscopy — Tue, 26 Oct 2010 06:49:34 +0100

Conclusions Laparoscopic surgical resection for selected pediatric malignant solid tumors was found to be feasible and safe. Long-term follow-up data are essential to confirm oncologic safety. Content Type Journal ArticleDOI 10.1007/s00464-010-1418-yAuthors Taehoon Kim, Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Asanbyungwon-Gil 86 Songpa-Gu, Seoul, 138-736 Republic of KoreaDae-Yeon Kim, Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Asanbyungwon-Gil 86 Songpa-Gu, Seoul, 138-736 Republic of KoreaMin Jeong Cho, Department of Pediatric Surgery, Asan Medical Center, University of Ulsan College of Medicine, Asanbyungwon-Gil 86 Songpa-Gu, Seoul, 138-736 Republic of KoreaSeo...

High-Risk Hepatoblastoma: Results in a Pediatric Liver Transplantation Center

European Journal of Pediatric Surgery — Sun, 10 Oct 2010 23:00:00 +0100

Eur J Pediatr SurgDOI: 10.1055/s-0030-1262798AbstractAim: Aim of the study was assess the results of the treatment of High-Risk Hepatoblastoma (HRH) in a tertiary center where all liver surgery facilities, including pediatric transplantation (LT), are available.[...]© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Abstract | Full text (Source: European Journal of Pediatric Surgery)

Isolation and identification of cancer stem cells from a side population of a human hepatoblastoma cell line, HuH-6 clone-5

Pediatric Surgery International — Sat, 09 Oct 2010 16:48:08 +0100

Conclusion Cancer stem-like cells were separated by the SP fraction method from hepatoblastoma cells. The in vivo experiment proved that SP fraction cells inoculated into mice were self-replicated, and the existence of cancer stem-like cells was identified. Content Type Journal ArticleDOI 10.1007/s00383-010-2719-xAuthors Shinichi Hayashi, Department of Pediatric Surgery, Saitama Medical University, 38 Morohongo Moroyama-machi, Iruma-gun, Saitama, 350-0495 JapanKeiko Fujita, Department of Anatomy, Saitama Medical University, 38 Morohongo Moroyama-machi, Iruma-gun, Saitama, 350-0495 JapanSachiko Matsumoto, Division of Morphological Science, Biomedical Research Center, Saitama Medical University, 38 Morohongo Moroyama-machi, Iruma-gun, Saitama, 350-0495 JapanMasumi Akit...

Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT

Pediatric Surgery International — Tue, 05 Oct 2010 05:45:29 +0100

Conclusions JPLT-2 protocol achieved satisfactory survival among children with non-metastatic hepatoblastoma. New approaches are needed for patients with metastatic diseases. Content Type Journal ArticleDOI 10.1007/s00383-010-2708-0Authors Tomoro Hishiki, Department of Pediatric Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677 JapanTadashi Matsunaga, Department of Pediatric Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677 JapanFumiaki Sasaki, Department of Pediatric Surgery, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 JapanMichihiro Yano, Department of Pediatrics, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543 JapanKohmei Ida, Departme...

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Fetal and neonatal liver tumours

Early Human Development — Thu, 30 Sep 2010 23:00:00 +0100

Abstract: Liver tumours are rare in children and account for about 5% of all tumours in the fetus and newborn. The most frequently occurring are benign vascular tumours and mesenchymal hamartomas although malignancy in the form of hepatoblastoma is a possibility. While the diagnosis can be suspected antenatally (by ultrasound and MR scan), a precise diagnosis is often difficult due to the complexity of the tumours. Inutero development of such tumours may be associated with polyhydramnios, fetal hydrops and extreme cases the maternal mirror syndrome. Postnatal symptoms may include abdominal distension, cardiac failure, consumptive coagulopathy and bleeding due to tumour rupture, but is dependent on the nature of the actual tumour. Treatment options may include watchful waiting, surgical res...

Biocatalytic Fabrication of Fast-Degradable, Water-Soluble Polycarbonate Functionalized with Tertiary Amine Groups in Backbone.

Biomacromolecules — Sun, 12 Sep 2010 23:00:00 +0100

We reported herein the synthesis and characterization of a water-soluble and fast-degradable polycarbonate, functionalized with tertiary amine groups in the backbone. A novel cyclic carbonate monomer, namely, 6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione (ADMC)(2), was synthesized and polymerized to provide the title polycarbonate [poly(ADMC)] via Novozym-435 lipase or tin(II) 2-ethylheaxanoate [Sn(Oct)(2)] catalyzed ring-opening polymerization (ROP). Novozym-435 lipase exhibited high activity toward the ROP in terms of molecular weight (M(n)) and monomer conversion, whereas the attempt with Sn(Oct)(2) failed. In the presence of molecular sieves-4 Ã, the highest M(n) value of 1.2 Ã 10(4) g/mol was obtained in toluene with an initial monomer concentration of 0....

HIV-Tat–Mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenicity of Hepatoma Cells

Gastroenterology — Mon, 06 Sep 2010 00:00:00 +0100

Conclusions: Transduction of hepatoma cells with a fusion protein that contains the C-terminal, functional fragment of LPTS and human immunodeficiency virus Tat (TAT–LPTS-LC) causes telomere shortening, limits proliferation, and inhibits growth of tumors from these cells in mice. TAT–LPTS-LC inhibits telomerase activity and might be developed as an anticancer agent. (Source: Gastroenterology)

Acute lymphocytic leukaemia in a child with Beckwith-Wiedemann syndrome harbouring a CDKN1C mutation.

European Journal of Medical Genetics — Thu, 02 Sep 2010 23:00:00 +0100

We report the case of a 10-year-old patient diagnosed with BWS, harbouring a CDKN1C (p57(KIP2)) mutation, who developed a T-type acute lymphoblastic leukaemia. To our knowledge it is the first report of an acute lymphoblastic leukaemia of T- type in a child with BWS. We discuss the possibility of a link between BWS and leukaemia via one of the few known negative regulator of hematopoiesis, the transforming growth factor beta pathway, depending upon the up-regulation of the CDKN1C. PMID: 20826236 [PubMed - as supplied by publisher] (Source: European Journal of Medical Genetics)

Apoptotic protein expression, glycogen content, DNA ploidy and cell proliferation in hepatoblastoma subtyping and their role in prognostication

Pediatric Surgery International — Fri, 27 Aug 2010 17:12:39 +0100

Conclusion Fetal and embryonal areas show different staining patterns for PCNA, Bax and Bcl-xL. DNA ploidy and glycogen content are significant prognostic variables. Content Type Journal ArticleDOI 10.1007/s00383-010-2699-xAuthors Anita Chopra, Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029 IndiaVenkateswaran K. Iyer, Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029 IndiaSandeep Agarwala, Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, IndiaSandeep R. Mathur, Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029 IndiaManju Aron, Department of Pathology, All India Institute of Medical Scien...

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In Vitro Assessment of Poly-iodinated Triglyceride Reconstituted Low-Density Lipoprotein: Initial Steps Toward CT Molecular Imaging

Academic Radiology — Wed, 18 Aug 2010 23:00:00 +0100

Conclusion: The in vitro results of this study suggest that (rITG)LDL can provide adequate image enhancement for CT molecular imaging. Potential applications include breast imaging and small animal imaging at low x-ray energies. In vivo experiments will be required to verify that tumor uptake of (rITG)LDL is sufficient for enhanced detection. Use at higher x-ray energies, as used in conventional CT, will require a further increase in iodine loading. (Source: Academic Radiology)

Frequent down-regulation and deletion of KLF6 in primary hepatocellular carcinoma

Journal of Huazhong University of Science and Technology -- Medical Sciences -- — Tue, 17 Aug 2010 05:53:59 +0100

Summary Kruppel-like factor 6 (KLF6) was reported as tumor suppressor in multiple cancers. However, loss of chromosomal locus spanning KLF6 is relatively infrequent in previous published studies. To explore the role of KLF6 in hepatocellular carcinoma (HCC), we examined the gene for expression change, loss of heterozygosity (LOH) and mutation in 26 HCC samples. The expression levels of KLF6 were significantly down-regulated in HCCs, as detected by qRT-PCR. LOH occurred in 11 (52%) of 21 tumors, and all the samples with LOH showed KLF6 down-regulation. The mutational frequency was 24%, and sequence changes located in activation domain of KLF6. Furthermore, MTT assay showed a significant antiproliferative effect of the wt KLF6 transfected in HepG2 hepatoblastoma cells. Fluor...

Inhibition of Bcl‐2 and Bcl‐X enhances chemotherapy sensitivity in hepatoblastoma cells

Pediatric Blood and Cancer — Mon, 09 Aug 2010 08:14:25 +0100

(Source: Pediatric Blood and Cancer)

Synthesis, and Characterization, and Evaluation of Cellular Effects of the FOL-PEG-g-PEI-GAL Nanoparticles as a Potential Non-Viral Vector for Gene Delivery

Journal of Nanomaterials — Tue, 03 Aug 2010 09:17:46 +0100

In this manuscript, we synthesized the potential non viral vector for gene delivery with proper transfection efficiency and low cytotoxicity. Polyethylenimine (PEI) is a well-known cationic polymer which has high positive surface charge for condensing plasmid DNA. However; it is highly cytotoxic in many cell lines because of the high surface charge, non-biodegradability and non-biocompatibility. To enhance PEI biodegradability, the graft copolymer “PEG-g-PEI” was synthesized. To target cancer liver cells, two targeting ligands folic acid and galactose (lactobionic acid) which are over expressed on human hepatocyte carcinoma were attached to graft copolymer and “FOL-PEG-g-PEI-GAL” copolymer was synthesized. Composition of this grafted copolymer was characterized usin...

Inhibition of Bcl-2 and Bcl-X enhances chemotherapy sensitivity in hepatoblastoma cells

Pediatric Blood and Cancer — Sun, 01 Aug 2010 23:00:00 +0100

An increased expression of anti-apoptotic proteins is regularly found in malignant cells, contributing to their clonal expansion by conferring an improved survival ability. In Hepatoblastoma (HB) apoptosis regulation contributes to resistance and therapy failure, therefore we modulated apoptosis sensitivity of HB cells for an improved cytotoxic activity of commonly used drugs.Apoptosis-related proteins were quantified in HB cells (HuH6 and HepT1) using protein assays. Interaction of ABT-737, a small-molecule inhibitor of Bcl-2, Bcl-xL, and Bcl-W with cytotoxic drugs was monitored in a proliferation assay. Apoptosis induction was measured by caspase-3 activity.We found high levels of the anti-apoptotic protein Bcl-2 and Bcl-X as well as low levels of pro-apoptotic protein Bax and Bad in bot...

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Solid tumours of childhood

Surgery (Medicine Publishing) — Sat, 31 Jul 2010 23:00:00 +0100

Abstract: The commonest solid tumours occurring in childhood are neuroblastoma, Wilms’ tumour, rhabdomyosarcoma, germ cell tumours, hepatoblastoma and lymphoma. Childhood tumours are unique in that they often originate from primitive embryonic cell types and therefore are usually chemosensitive and radiosensitive.The survival from solid tumours in childhood has improved steadily with a reduction in morbidity and mortality related to treatment. This is due to the enrolment of patients in large multicentre studies led by International oncology groups. The care of children with cancer is multidisciplinary, involving oncologists, radiotherapists, surgeons, radiologists, pathologists, pharmacists and specialist nurses.Surgery plays a major role in the management of most solid tumours of child...

A Child With an FGFR3 Mutation, a Laterality Disorder and an Hepatoblastoma: Novel Associations and Possible Gene-Environment Interactions.

Twin Research and Human Genetics — Sat, 31 Jul 2010 23:00:00 +0100

We report on a 3-year-old girl, from a 3-generation family with an FGFR3 Pro250Arg mutation, who in addition to craniosynostosis, had a laterality disorder and hepatoblastoma, following a pregnancy complicated by maternal insulin-dependent diabetes. The clinical features possibly result from the combined effects of the maternal diabetes and the familial FGFR3 mutation, thus representing a unique gene-environment interaction that may have implications for the understanding of the phenotypes described in this child. PMID: 20707699 [PubMed - in process] (Source: Twin Research and Human Genetics)

Tobacco smoking and cancer in Brazil: evidence and prospects

Revista Brasileira de Epidemiologia — Fri, 09 Jul 2010 07:13:47 +0100

Neste artigo analisa-se a tendência temporal da prevalência do tabagismo no Brasil, bem como as assimetrias da prevalência de acordo com as regiões do país, a idade, o gênero e o nível socioeconômico da população. Desde o estabelecimento da relação entre tabagismo e câncer de pulmão há 60 anos, o número de tumores malignos com evidências de associação causal com o tabagismo ascendeu a vinte. O declínio da prevalência do tabagismo na população brasileira tem sido constante desde o final da década de 80. Até 2003, foi mais intenso entre os homens. A partir daquele ano, a queda tornou-se mais pronunciada entre as mulheres. As mais altas prevalências de tabagismo encontram-se no Sudeste e Sul, as duas regiões com maiores incidências de neoplasias estritamente relaci...

A pictorial review of imaging of abdominal tumours in adolescence

Pediatric Radiology — Sun, 04 Jul 2010 22:41:01 +0100

Abstract Neoplastic abdominal tumours, particularly those originating from embryonal tissue (such as hepatoblastoma and nephroblastoma) and neural crest cells (such as neuroblastoma), are well-documented in young children. Neoplasms of adulthood, most commonly carcinoma of different visceral organs, are also well-documented. Abdominal tumours in adolescence constitute a distinct pathological group. The radiological features of some of these tumours have been described only in isolated reports. The purpose of this pictorial essay was to review the imaging findings of various kinds of abdominal tumours in adolescent patients (with an age range of 10–16 years) who presented to the Children Cancer Center of our institution in the past 15 years. Some tumours, though ...

Tyrosinemia Type 1: Metastatic Hepatoblastoma With a Favorable Outcome

PEDIATRICS — Thu, 01 Jul 2010 15:02:55 +0100

We report here the case of a patient with a diagnosis of tyrosinemia type 1 at 5 months of age who was treated with NTBC and dietary restriction and in whom a liver neoplasm with lung metastases, histologically determined to be HCC, was found at the age of 15 months. A conservative approach that consisted of chemotherapy and partial hepatectomy resulted in a 12-year disease-free period. The excellent postchemotherapy course, in sharp contrast to the expected course of HCC, led to histologic reevaluation with reclassification of the neoplasm as hepatoblastoma. A diagnosis of hepatoblastoma would no longer be a mandate for a liver transplant for patients with tyrosinemia type 1 undergoing NTBC treatment. We encourage clinicians to perform more accurate evaluation of liver histology, because ...

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Pathology of pediatric liver tumors, a single center experience from south of Iran.

Indian Journal of Pathology and Microbiology — Wed, 30 Jun 2010 23:00:00 +0100

Conclusions: The spectrum of hepatic tumors in children is different from that found in the older age group (adults) and also different in different populations. PMID: 20699496 [PubMed - in process] (Source: Indian Journal of Pathology and Microbiology)

Congenital absence of the portal vein - Case report and a review of literature

Clinical Anatomy — Mon, 07 Jun 2010 23:00:00 +0100

This article also illustrates the radiological findings of CAPV. Radiological evaluation by ultrasound, CT, and MRI is helpful to detect coexisting abnormalities. Clin. Anat., 2010. © 2010 Wiley-Liss, Inc. (Source: Clinical Anatomy)

In vitro antiviral activity of lutein against hepatitis B virus

Phytotherapy Research — Sun, 06 Jun 2010 23:00:00 +0100

Despite the availability of an effective vaccine, the hepatitis B virus (HBV) infection and its treatment remains one of the foremost public health problems in the world. The present study was performed in order to investigate the anti-HBV activity of lutein in vitro. The antiviral activity of lutein was examined by detecting the levels of HBsAg, HBeAg and extracellular HBV DNA in stable HBV-producing human hepatoblastoma HepG2 2.2.15 cells. It was found that lutein effectively suppressed the secretion of HBsAg from HepG2 2.2.15 cells in a dose-dependent manner, and it also suppressed the amount of extracellular HBV DNA. A luciferase reporter gene assay was used to determine the effects of lutein on the activities of HBV promoters. The results showed that lutein inhibited the activity of H...

A phase II trial and pharmacokinetic study of oxaliplatin in children with refractory solid tumors: A Children's Oncology Group study

Pediatric Blood and Cancer — Mon, 24 May 2010 23:00:00 +0100

Platinating agents are used in the treatment of a spectrum of childhood cancers. Oxaliplatin, a third generation platinum compound, may provide less toxicity and be more effective. A phase 2 study was performed to estimate the response rate to single agent oxaliplatin in patients with refractory pediatric solid tumors, and to further describe the toxicities and pharmacokinetics of the drug in this population.Subjects, [le]21 years of age at original diagnosis, received oxaliplatin (130 mg/m2) intravenously every 21 days. Prior platinum exposure was acceptable. Histologies included: Ewing sarcoma/peripheral PNET, osteosarcoma, rhabdomyosarcoma, neuroblastoma, high and low grade astrocytoma, brain stem glioma, ependymoma, hepatoblastoma and selected rare tumors. A two-stage design, enrolling...

Successful Treatment of Childhood High-Risk Hepatoblastoma With Dose-Intensive Multiagent Chemotherapy and Surgery: Final Results of the SIOPEL-3HR Study [Pediatric Oncology]

Journal of Clinical Oncology — Tue, 18 May 2010 22:01:51 +0100

Conclusion The applied treatment rendered a great proportion of tumors resectable, and, in comparison with previously published results, led to an improved survival in patients with high-risk hepatoblastoma. (Source: Journal of Clinical Oncology)

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Kabuki syndrome and cancer in two patients

American Journal of Medical Genetics Part A — Mon, 10 May 2010 23:00:00 +0100

Both hepatoblastoma and neuroblastoma are occasionally associated with congenital syndromes such as Beckwith-Wiedemann syndrome and trisomy 18. There have been no reports of hepatoblastoma in patients with Kabuki syndrome, whereas one patient with neuroblastoma and this syndrome has been reported. In this paper we present two patients with Kabuki syndrome and a neoplasm: a child of 6 years with hepatoblastoma and an infant, of 6 months affected by neuroblastoma. © 2010 Wiley-Liss, Inc. (Source: American Journal of Medical Genetics Part A)

Sterol regulatory element-binding protein 2 and nuclear factor Y controls human farnesyl diphosphate synthase expression and affects cell proliferation in hepatoblastoma cells

BJ Gene — Thu, 06 May 2010 23:00:00 +0100

In this study, we characterized the sterol-response element and nuclear factor Y-binding site in the human FDPS promoter. Using a luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we demonstrated that these elements are responsible for the transcription of the FDPS gene, and that its transcriptional activation is mediated by sterol regulatory element-binding protein 2 (SREBP-2) and nuclear factor Y (NF-Y). We also investigated whether sterol-mediated FDPS expression is involved in the cell proliferation induced by zoledronic acid, an FDPS inhibitor. We show that the SREBP-2 and NF-Y-mediated regulation of FDPS gene transcription modulates cell proliferation. These results suggest that SREBP-2 and NF-Y are required to trigger cell proliferation...

Sterol regulatory element-binding protein 2 and nuclear factor Y controls human farnesyl diphosphate synthase expression and affects cell proliferation in hepatoblastoma cells.

The Biochemical Journal — Thu, 06 May 2010 23:00:00 +0100

Cure of multifocal panhepatic hepatoblastoma: is liver transplantation always necessary?

Journal of Pediatric Surgery — Fri, 30 Apr 2010 23:00:00 +0100

Conclusions: Conservative surgery may be curative in some multinodular PRETEXT IV HB patients, with a good response to preoperative chemotherapy and complete excision of all macroscopic tumor remnants. However, because of the lack of reliable predictors of sterilization of the microscopic disease in the residual liver, with subsequent poor prognosis, total hepatectomy and liver transplantation remain currently recommended in patients with multinodular PRETEXT IV HB without extrahepatic disease, even though some of these children are probably overtreated. (Source: Journal of Pediatric Surgery)

Intensive Therapy Improves Survival in High-Risk Hepatoblastoma

Medscape Medical News Headlines — Thu, 22 Apr 2010 17:49:03 +0100

Treatment with dose-intensive multi-agent chemotherapy and surgery improves survival in patients with high-risk hepatoblastoma, according to results of the SIOPEL-3HR Study. Reuters Health Information (Source: Medscape Medical News Headlines)

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The overlap between Sotos and Beckwith-Wiedemann syndromes

The Journal of Pediatrics — Wed, 14 Apr 2010 23:00:00 +0100

To the Editor: We read with great interest the recent report by Kato et al describing the noteworthy occurrence of a hepatoblastoma in a child with Sotos syndrome and typical NSD1 microdeletion. This is a remarkable finding, given that only one previous case has been reported. Conversely, the occurrence of hepatoblastoma is characteristic of Beckwith-Wiedemann syndrome, another overgrowth condition with cancer predisposition caused by epigenetic deregulation of chromosomal region 11p15. In this case, despite a normal genotype, DNA methylation anomalies led to tissue growth factor overexpression and cyclin deregulation responsible for the phenotype and cancer development. The mechanisms causing these methylation anomalies have not yet been fully explained, however. (Source: The Journal of ...

Combined en bloc liver–double kidney transplantation in an infant with IVC thrombosis

Pediatric Transplantation — Mon, 12 Apr 2010 23:00:00 +0100

We report a case of a pediatric en bloc liver-double kidney transplant in a patient with IVC thrombosis below the renal veins. The patient is an 11-month-old girl diagnosed with congenital nephrotic syndrome at two months of age. Multifocal liver masses were identified on routine ultrasound at eight months of age. Alpha fetoprotein level was 55 319. Biopsy confirmed hepatoblastoma. CT scan confirmed multiple lesions in both lobes, which would require liver transplantation for resection. She was also found to have thrombosis of her infrarenal IVC secondary to multiple central lines. She was listed for combined liver[ndash]kidney transplant and began chemotherapy. After four cycles of chemotherapy, she underwent bilateral nephrectomies followed by a combined en bloc liver-double kidney trans...

Genome-wide analysis of allelic imbalances reveals 4q deletions as a poor prognostic factor and MDM4 amplification at 1q32.1 in hepatoblastoma

Genes, Chromosomes and Cancer — Mon, 12 Apr 2010 23:00:00 +0100

In a single-nucleotide polymorphism array-based analysis of 56 hepatoblastoma (HB) tumors, allelic imbalances were detected in 37 tumors (66%). Chromosome gains were found in 1q (28 tumors), 2q (24), 6p (8), 8q (8), 17q (6), and 20pq (10), and losses in 1p (6), 4q (9), and 16q (4). Fine mapping delineated the shortest overlapping region (SOR) of gains at 1q32.1 (1.3 Mb) and 2q24.2-q24.3 (4.8 Mb), and losses at 4q34.3-q35.2 (8.7 Mb) and 4q32.3 (1.6 Mb). Uniparental disomy of 11pter-11p15.4 (IGF2) and loss of 11pter-p14.1 were found in 11 and 2 tumors, respectively. Expression of HTATIP2 (11p15.1) was absent in 9 of 20 tumors. Amplification was identified in four tumors at 1q32.1, where the candidate oncogene MDM4 is located. In the 4q32.3-SRO, ANXA10S, a variant of the candidate tumor suppr...

Adult hepatoblastoma successfully treated with multimodal treatment

Langenbeck's Archives of Surgery — Sun, 11 Apr 2010 05:49:52 +0100

Conclusions To our knowledge, this is the first report demonstrating long-term survival of a patient with initially unresectable adult hepatoblastoma. Our new therapeutic strategy may provide new insights into the treatment of this fatal disease. Content Type Journal ArticleCategory Case Management & Clinical ConsequencesDOI 10.1007/s00423-010-0630-5Authors Shinji Nakamura, Nara Medical University Department of Surgery 840 Shijo-cho Kashihara Nara 634-8522 JapanMasayuki Sho, Nara Medical University Department of Surgery 840 Shijo-cho Kashihara Nara 634-8522 JapanHiromichi Kanehiro, Nara Medical University Department of Surgery 840 Shijo-cho Kashihara Nara 634-8522 JapanToshihiro Tanaka, Nara Medical University Department of Radiology Kashihara Nara JapanKimihiko Kich...

Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation.

International Journal of Oncology — Fri, 09 Apr 2010 12:02:25 +0100

Authors: Grotegut S, Kappler R, Tarimoradi S, Lehembre F, Christofori G, Von Schweinitz D Hepatocyte growth factor/scatter factor (HGF) is a ubiquitously expressed molecule that elicits pleiotropic functions on epithelial cells, including mitogenic, motogenic, differentiating, angiogenic and morphogenic effects. In hepatoblastoma (HB), post-operative residual tumor growth and tumor recurrences are often associated with markedly elevated serum levels of HGF, suggesting a link between this molecule and tumor malignancy. Here, we demonstrate that HGF has no impact on overall cell viability and proliferation of HB cells, although signal transduction occurs downstream of HGF, such as c-Met phosphorylation, activation of phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kina...

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Novel Tween(R) 20 derivatives enable the formation of efficient pH-sensitive drug delivery vehicles for human hepatoblastoma.

Bioorganic and Medicinal Chemistry Letters — Thu, 08 Apr 2010 23:00:00 +0100

We describe the synthesis, the physicochemical characterization and the biological evaluation of three novel pH-sensitive systems prepared derivatizing polysorbate 20 (Tween(R) 20) with glycine, N-methyl-glycine and N,N-dimethyl-glycine (TW20-GLY, TW20-MMG and TW20-DMG). These derivatives form pH-sensitive vesicles and translocate small molecules into cells. The reported systems are efficient drug delivery systems for human hepatoblastoma cells. PMID: 20427183 [PubMed - as supplied by publisher] (Source: Bioorganic and Medicinal Chemistry Letters)

A mutant of hepatitis B virus X protein (HBxDelta127) enhances hepatoma cell migration via osteopontin involving 5-lipoxygenase.

Acta Pharmacologica Sinica — Sun, 04 Apr 2010 23:00:00 +0100

Conclusion:HBxDelta127 strongly promotes hepatoma cell migration via activation of OPN involving 5-LOX. PMID: 20364155 [PubMed - as supplied by publisher] (Source: Acta Pharmacologica Sinica)

Auditory Late Effects of Childhood Cancer Therapy: A Report From the Children's Oncology Group

PEDIATRICS — Thu, 01 Apr 2010 15:02:44 +0100

Children treated for malignancies may be at risk for early- or delayed-onset hearing loss that can affect learning, communication, school performance, social interaction, and overall quality of life. Survivors at particular risk include those treated with platinum compounds (cisplatin and/or carboplatin) for neuroblastoma, hepatoblastoma, osteosarcoma, or germ-cell tumors and/or those treated with radiation that affects the ear at doses of >30 Gy for pediatric head and neck tumors. The aims of the Auditory/Hearing Late Effects Task Force of the Children's Oncology Group in this report were to (1) review ototoxicity resulting from childhood cancer therapy including platinum compounds (cisplatin and carboplatin) and radiation, (2) describe briefly cochlear pathophysiology and genetics of ...

6-Dehydrogingerdione Sensitizes Human Hepatoblastoma Hep G2 Cells to TRAIL-Induced Apoptosis via Reactive Oxygen Species-Mediated Increase of DR5

Journal of Agricultural and Food Chemistry — Wed, 31 Mar 2010 16:41:29 +0100

Journal of Agricultural and Food Chemistry, Volume 0, Issue 0, Articles ASAP (As Soon As Publishable). (Source: Journal of Agricultural and Food Chemistry)

Autotaxin expression and its connection with the TNF-alpha-NF-kappaB axis in human hepatocellular carcinoma

Molecular Cancer — Tue, 30 Mar 2010 23:00:00 +0100

Conclusions: This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC. Our observation that links the TNF-alpha/NF-kappaB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumorigenesis. (Source: Molecular Cancer)

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High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma

Pediatric Transplantation — Mon, 22 Mar 2010 00:00:00 +0100

Kosola S, Lauronen J, Sairanen H, Heikinheimo M, Jalanko H, Pakarinen M. High survival rates after liver transplantation for hepatoblastoma and hepatocellular carcinoma.Pediatr Transplantation 2010. © 2010 John Wiley & Sons A/S.Abstract: Unresectable malignant liver tumors may be treated by LTx. We evaluated the results of LTx for HB and HCC. All patients transplanted for HB or HCC between 1990 and 2007 were included. Effects of histologic tumor type, primary tumor resection, disease staging, and serum AFP levels at diagnosis and at transplantation on disease recurrence and survival were evaluated. Twelve patients with median age of five (range, 2[ndash]16) were transplanted and followed for a median of 11 (2[ndash]18) yr. Six patients had HB and six had HCC. At diagnosis, eight patients ...

Progress in the surgical treatment of malignant liver tumors in children

Cancer Treatment Reviews — Mon, 15 Mar 2010 00:00:00 +0100

Summary: During the last decade, important progress has been made in the surgical treatment of malignant liver tumors in children. For hepatoblastoma, there is a general consensus for combining surgical resection with neoadjuvant (and adjuvant) chemotherapy. Long-term disease-free survival of around 85–90% can be achieved for resectable HB involving no more than three sections of the liver (PRETEXT I–III). For unresectable HB without extrahepatic invasion (PRETEXT IV with involvement of all four sections and some cases of PRETEXT III with invasion of, or close contact with major venous structures), similar results can be obtained with total hepatectomy and liver transplantation.For hepatocellular carcinoma, most often without underlying liver disease in children of the western world, r...

Fine needle aspiration cytology of infantile haemangioendothelioma of the liver: a report of two cases

Cytopathology — Thu, 11 Mar 2010 00:00:00 +0100

Conclusion: Radiological diagnosis of IHL is possible in a majority of cases, but sometimes features may overlap with hepatoblastoma and fine needle aspiration may be performed inadvertently. Characteristic kinked nuclei and intermixed normal liver tissue might suggest IHL in the differential diagnosis of a spindle cell vasoformative tumour. (Source: Cytopathology)

Outcome of central hepatectomy for hepatoblastomas

Journal of Pediatric Surgery — Mon, 01 Mar 2010 00:00:00 +0100

Conclusions: Our study demonstrates the feasibility of CH for CHBL without operative mortality or local recurrence. Central hepatectomy is an alternative to extensive liver resections in selected patients. (Source: Journal of Pediatric Surgery)

Infantile hemangioendothelioma with elevated serum α fetoprotein: report of 2 cases with immunohistochemical analysis

Human Pathology — Mon, 15 Feb 2010 00:00:00 +0100

We report 2 cases of solitary hepatic infantile hemangioendothelioma and demonstrate immunohistochemically that hepatocytes near or entrapped within the tumor were the source of the increased serum levels of α fetoprotein explaining the unusual clinical presentation. (Source: Human Pathology)

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First report of combined ectopic ACTH-syndrome and PTHrP-induced hypercalcemia due to a hepatoblastoma.

European Journal of Endocrinology — Thu, 04 Feb 2010 00:00:00 +0100

Conclusions: This is the first report of an endocrine active hepatoblastoma causing both Cushing's syndrome and PTHrP-related "humoral hypercalcemia of malignancy". This information should be added to the well-known beta-hCG-related paraneoplastic effects of hepatoblastoma in children. PMID: 20133447 [PubMed - as supplied by publisher] (Source: European Journal of Endocrinology)

Increased expression of the hedgehog signaling pathway in pediatric solid malignancies

Journal of Pediatric Surgery — Mon, 01 Feb 2010 00:00:00 +0100

Conclusions: These findings suggest that the Shh-Ptch1-Gli1 signaling pathways are frequently activated in most pediatric malignant tumors. The Hh signaling pathway may therefore play an important role in the differentiation and malignant potential of pediatric malignancies. (Source: Journal of Pediatric Surgery)

Synthesis and anticancer activities of new 3-allylthio-6-(mono or disubstituted)aminopyridazines.

Archives of Pharmacal Research — Mon, 01 Feb 2010 00:00:00 +0100

Authors: Won YH, Park MS A new series of 3-allylthio-6-(mono or disubstituted) aminopyridazines was synthesized by reacting 3-allylthio-6-chloropyridazine with several amines to develop new anticancer agents. These new compounds showed antiproliferative activities against lung cancer (A549), hepatoblastoma (Hep3b), prostate cancer (PC3), colon cancer (SW480) and cervical cancer (HeLa) cells in MTT assays, and could be promising candidates for chemotherapy of carcinomas. Compound 5 (3-allylthio-6-homopiperidinylaminopyridazine) showed higher potencies than 5-FU for inhibiting the growth of these cell lines. This suggests the potential anticancer activity of compound 5. PMID: 20195817 [PubMed - in process] (Source: Archives of Pharmacal Research)

Histiocytosis X: A Rare Indication for Pediatric Liver Transplant

Journal of Surgical Research — Mon, 25 Jan 2010 16:42:33 +0100

Langerhans cell histiocytosis (LCH) is a rare disorder in children, characterized by clonal proliferation of dendritic cells resembling Langerhans cells of the skin. Two presentations have been described: local disease affecting skin, bone, and/or lymph nodes and extensive, multifocal disease involving the lung, liver, and/or bone marrow. In multifocal liver involvement progressing to end stage disease, orthotopic liver transplantation (OLT) has been heralded as definitive therapy. However; due to its infrequency, information regarding post-transplant outcomes is limited to case reports and small retrospective reviews. Aim: To determine clinical outcomes post-OLT in patients with LCH in comparison to similar liver pathologies. Methods: The UNOS database of liver transplantation as of Augus...

Image Analysis of Hepatoblastoma Decay during Induction Chemotherapy

Journal of Surgical Research — Mon, 25 Jan 2010 16:41:44 +0100

Conclusions: During induction chemotherapy, hepatoblastomas typically decay towards the IVC rather than centripetally. Image margins approximate the closest surgical margin for solitary tumors. Although direction of tumor regression may vary between Couinaud hepatic segments, the margin of the tumor with respect to the IVC does not change significantly during induction chemotherapy. Additional cycles of induction therapy to achieve greater separation of tumor margins from the IVC and hepatic vein confluence appear unnecessary and may only increase the risk for treatment toxicities. (Source: Journal of Surgical Research)

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Cisplatin pharmacokinetics in a child receiving peritoneal dialysis

Pediatric Nephrology — Mon, 18 Jan 2010 18:45:55 +0100

Abstract Cisplatin is a highly effective and frequently used drug in the chemotherapy of solid tumors in children, but there is currently no information to guide dosing in children requiring dialysis. Here, we present the case of a 2-year-old boy with end-stage renal disease managed with peritoneal dialysis and requiring cisplatin for a newly diagnosed hepatoblastoma. A pharmacokinetic study was performed to personalize the cisplatin dose with the goal of providing adequate cisplatin exposure and avoiding excessive exposure and toxicity. Accordingly, 25% of the standard cisplatin dose was infused intravenously over 4 h. Serial blood and peritoneal fluid samples were obtained, and free cisplatin levels were subjected to noncompartmental pharmacokinetic analysis. The disposi...

Successful treatment of unresectable advanced hepatoblastoma: Living liver transplantation after surgical removal of lung metastasis

Pediatric Transplantation — Mon, 11 Jan 2010 00:00:00 +0100

We report one successful case of advanced unresectable hepatoblastoma with multiple lung metastases. Intensive chemotherapy consisting of high-dose chemotherapy with autologous hematopoietic stem cell transplantation was not effective. We performed living liver transplantation after surgical resection of residual lung metastases, which were histologically viable. After liver transplantation, the level of tumor marker decreased gradually. The patient experienced no severe complications. This case suggested that living liver transplantation could be effective in cases of advanced refractory hepatoblastoma after control of distant metastases. (Source: Pediatric Transplantation)

Irinotecan as maintenance therapy in high-risk hepatoblastoma

Pediatric Blood and Cancer — Fri, 08 Jan 2010 00:00:00 +0100

We describe three patients who were treated with irinotecan (two in combination with vincristine). In two patients, this contributed to a clinical remission. All three patients received a 1- to 2-year course of irinotecan as maintenance therapy and all remain disease free. Treatment was well tolerated with minimal toxicity. Further evaluation of the use of irinotecan as maintenance therapy in high-risk and recurrent HB patients is warranted. Pediatr Blood Cancer. © 2009 Wiley-Liss, Inc. (Source: Pediatric Blood and Cancer)

Intraoperative examination (IOE) in pediatric extracranial tumors

Pediatric Blood and Cancer — Tue, 05 Jan 2010 00:00:00 +0100

Intraoperative evaluation of surgical specimens by frozen sections (IOE) is required to distinguish benign and malignant lesions, assess surgical margins, and determine sample adequacy of biopsies. In the last years, it has been used also for therapeutic decisions, particularly in children, who may need other ancillary procedures, in case of malignancies. Our purpose was the evaluation of diagnostic accuracy, limits, and different role of IOE in pediatric pathology.From 1990 to 2001, 416 IOEs were performed in 341 children, affected by lymph node pathology, soft tissue tumors, neuroblastic tumors, gonadal germ cell, and stromal tumors, hepatic lesions, renal tumors, and others; the technique was also used to assess surgical margins during major surgeries. IOEs were obtained from Tru-cut bi...

Defining hepatoblastoma responsiveness to induction therapy as measured by tumor volume and serum α-fetoprotein kinetics

Journal of Pediatric Surgery — Thu, 31 Dec 2009 15:18:28 +0100

Conclusions: Measuring TV and sAFP kinetics accurately reflects hepatoblastoma responsiveness to induction therapy. Treatment toxicities may be reduced by earlier resection and tailoring of chemotherapeutic regimens. (Source: Journal of Pediatric Surgery)

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[Newsdesk] Research brief

The Lancet Infectious Diseases — Mon, 21 Dec 2009 00:00:00 +0100

The current standard treatment for hepatitis C virus (HCV) infections—pegylated interferon-alfa and ribavirin—clears HCV in only 50% of patients and has serious side-effects. Now, two papers offer hope that a more effective treatment for HCV infections might be found in the near future. In the first paper, researchers report that treatment of chronically infected chimpanzees with a locked nucleic-acid-modified oligonucleotide (SPC3649) complementary to miR-122—a liver-expressed microRNA that HCV needs for replication in human liver cells—leads to long-lasting suppression of HCV viraemia and improvement of HCV-induced liver pathology with no evidence of viral resistance or side-effects. In the second paper, researchers describe an unbiased screening system for the identification of ...

Hepatitis C Virus Impairs p53 via Persistent Overexpression of 3{beta}-Hydroxysterol {Delta}24-Reductase [Mechanisms Of Signal Transduction]

Journal of Biological Chemistry — Fri, 18 Dec 2009 14:37:48 +0100

Persistent infection with hepatitis C virus (HCV) induces tumorigenicity in hepatocytes. To gain insight into the mechanisms underlying this process, we generated monoclonal antibodies on a genome-wide scale against an HCV-expressing human hepatoblastoma-derived cell line, RzM6-LC, showing augmented tumorigenicity. We identified 3β-hydroxysterol 24-reductase (DHCR24) from this screen and showed that its expression reflected tumorigenicity. HCV induced the DHCR24 overexpression in human hepatocytes. Ectopic or HCV-induced DHCR24 overexpression resulted in resistance to oxidative stress-induced apoptosis and suppressed p53 activity. DHCR24 overexpression in these cells paralleled the increased interaction between p53 and MDM2 (also known as HDM2), a p53-specific E3 ubiquitin ligase, in ...

Iron-Dependent Regulation of MDM2 Influences p53 Activity and Hepatic Carcinogenesis.

The American Journal of Pathology — Thu, 17 Dec 2009 00:00:00 +0100

In conclusion, iron status influences p53 activity and antioxidant response by modulating MDM2 expression. MDM2 inhibitors may enhance the antiproliferative activity of iron chelators. PMID: 20019189 [PubMed - as supplied by publisher] (Source: The American Journal of Pathology)

In Vivo Bioluminescence Imaging of Murine Xenograft Cancer Models with a Red-shifted Thermostable Luciferase

Molecular Imaging and Biology — Wed, 25 Nov 2009 17:02:01 +0100

Conclusion Two different bioluminescent mouse cancer models demonstrate the utility of a new red-shifted thermostable luciferase, Ppy RE-TS, that improved the in vivo imaging performance when compared with wild-type P. Pyralis luciferase. While wild-type luciferase is currently a popular reporter for in vivo imaging methods, this study demonstrates the potential of red-emitting firefly luciferase mutants to enhance the performance of bioluminescence imaging experiments. Content Type Journal ArticleCategory Research ArticleDOI 10.1007/s11307-009-0291-3Authors Laura Mezzanotte, University of Bologna Department of Pharmaceutical Sciences Via Belmeloro 6 40126 Bologna ItalyRaffaella Fazzina, University of Bologna Department of Pediatrics, S’Orsola Hospital Bologna Italy...

Induction of p53 Renders ATM-Deficient Mice Refractory to Hepatocarcinogenesis

Gastroenterology — Tue, 17 Nov 2009 00:00:00 +0100

Conclusions: Hepatocarcinogenesis is abrogated in ATM-deficient mice in association with induction of ATR, Chk1, p53, and p19ARF. Resultant cell cycle arrest and apoptosis of DNA-damaged cells are possible mechanisms that underlie this unique “refractoriness” to malignant transformation in DEN-initiated ATM−/− hepatocytes. The findings also show that prolonged up-regulation of p53 associated with some features of senescence does not inevitably cause organ failure. (Source: Gastroenterology)

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Hepatoblastoma in a Patient with Sotos Syndrome

The Journal of Pediatrics — Mon, 16 Nov 2009 15:11:15 +0100

We report a case of hepatoblastoma that developed in a child with Sotos syndrome, an overgrowth syndrome with an increased risk of neoplasms. Genome-wide analysis of copy number alterations showed a gain of chromosome 2, uniparental disomy of 18q, and microdeletion of 5q35. (Source: The Journal of Pediatrics)

Mixed hepatoblastoma and teratoma of the liver in a 3-year-old child: a unique combination and clinical challenge

Diagnostic Pathology — Thu, 12 Nov 2009 00:00:00 +0100

In this report, we describe the diagnosis and clinical management of a large liver tumor in a 3-year-old child that displayed the features of both, conventional hepatoblastoma and malignant teratoma. Pathological assessment on a pre-operative bioptical specimen showed an immature teratoid tumor with no area of hepatoblastic differentiation present. Histological and immunhistological examination of the resected tumor specimen additionally showed tumor areas of very different differentiation pattern intermixed with each other, namely areas of hepatoblastoma-typical and neuroblastoma-like morphology as well a areas of rhadomyosarcomatous differentiation.After chemotherapy the tumor size increased and an extended right hemihepatectomy was performed. Post-operatively, the general condition of t...

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation

Journal of Pediatric Surgery — Sun, 01 Nov 2009 00:00:00 +0100

Conclusion: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate. (Source: Journal of Pediatric Surgery)

Cisplatin alone safe and effective for patients with standard-risk hepatoblastoma

HemOncToday.com — Thu, 22 Oct 2009 14:16:00 +0100

(Source: HemOncToday.com)

Doxorubicin doesn't add benefit in treatment of standard-risk hepatoblastoma

NeLM - Oncology — Wed, 21 Oct 2009 23:00:00 +0100

Source: NEJM Area: News Cisplatin alone is as effective as cisplatin plus doxorubicin in children with standard-risk hepatoblastoma, according to a controlled trial. Hepatoblastoma is a rare (10-15 each year in the UK) liver tumour occurring in children and usually presenting before age 2. Standard treatment was cisplatin plus doxorubicin based on the results of a trial carried out in the early 1990's, however evidence then became available that the doxorubicin component may not be necessary. This multi-centre trial aimed to clarify whether cisplatin alone was equally effective. It involved patients aged under 16 with standard-risk hepatoblastoma who were randomised to treatment with cisplatin with or without doxorubicin. Primary outcome was the rate of complete resect...

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Cisplatin Alone Effective in Children With Hepatoblastoma

Modern Medicine — Tue, 20 Oct 2009 23:00:00 +0100

Cisplatin alone is just as effective as, but less toxic than, cisplatin plus doxorubicin in children with standard-risk hepatoblastoma, according to a study in the Oct. 22 issue of the New England Journal of Medicine. (Source: Modern Medicine)

Cisplatin versus Cisplatin plus Doxorubicin for Standard-Risk Hepatoblastoma

New England Journal of Medicine — Tue, 20 Oct 2009 23:00:00 +0100

In this randomized trial involving children with standard-risk hepatoblastoma, treatment with cisplatin alone caused fewer adverse events and achieved rates of complete resection and survival that were similar to rates achieved with treatment with cisplatin plus doxorubicin. These findings suggest that doxorubicin is not needed in treating children with hepatoblastoma who are not at high risk for a poor outcome. (Source: New England Journal of Medicine)

Pim-2 Activates API-5 to Inhibit the Apoptosis of Hepatocellular Carcinoma Cells Through NF-kappaB Pathway.

Pathology Oncology Research — Sun, 11 Oct 2009 23:00:00 +0100

Authors: Ren K, Zhang W, Shi Y, Gong J Pim-2 is proved to be relevant to the tumorigenesis of hepatocellular carcinoma (HCC), but the mechanism is unclear. We studied the relationship among Pim-2, NF-kappaB and API-5. In our experiment, expression level of the three factors and phosphorylation level of API-5, as well as NF-kappaB activity, were detected in HCC tissues and the nontumorous controls. Then Pim-2 gene was transfected into nontumorous liver cells L02, and Pim-2 SiRNA was transfected into hepatoblastoma cell line HepG2. Parthenolide was added as NF-kappaB inhibitor. The same detections as above were repeated in the cells, along with the apoptosis analysis. We found the levels of Pim-2, NF-kappaB and API-5, as well as NF-kappaB activity, were significantly higher in HCC tissue...

Hepatoblastoma, cisplatin, and ototoxicity

Cancer — Thu, 08 Oct 2009 23:00:00 +0100

Young infants with hepatoblastoma now have an excellent chance of cure, but many will be left with significant cisplatin-related hearing loss, which may impair their language and social development and may affect later learning with a lifetime of hearing loss. A report from the Children's Oncology Group of a randomized trial of amifostine for the prevention of platinum-related toxicity in infants with hepatoblastoma demonstrated that amifostine has no benefit in reducing cisplatin ototoxicity. Several new agents, such as sodium thiosulfate, currently are entering clinical trials as otoprotectants; however, as the goal for some childhood malignancies shifts from disease cure to enhancing the quality of long-term survival, there is a need to ensure that the design and conduct of cancer-contr...

Amifostine does not prevent platinum-induced hearing loss associated with the treatment of children with hepatoblastoma

Cancer — Tue, 06 Oct 2009 23:00:00 +0100

The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum-containing regimens in children with hepatoblastoma (HB).Patients were enrolled on P9645 beginning in March of 1999. Patients who had stage I/II disease received treatment with 4 cycles of combined cisplatin, 5-fluorouracil, and vincristine (C5V) with or without amifostine. Patients who had stage III/IV disease were randomized to receive treatment with 6 cycles of either C5V with or without amifostine or carboplatin alternating with cisplatin (CC) with or without amifostine. Patients who were randomized to receive amifostine were given a dose of 740 mg/m2 intravenously over 15 minutes before each administration of a platinum agent.Eighty-two...

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Using acetaminophen's toxicity mechanism to enhance cisplatin efficacy in hepatocarcinoma and hepatoblastoma cell lines.

Neoplasia — Wed, 30 Sep 2009 23:00:00 +0100

CONCLUSIONS: Our results suggest that a chemotherapeutic regimen containing both AAP and CDDP with delayed NAC rescue has the potential to enhance chemotherapeutic efficacy while decreasing adverse effects. This would be a promising approach particularly for hepatoblastomas regardless of cellular CYP2E1 protein level but could also be beneficial in other malignancies. PMID: 19794959 [PubMed - in process] (Source: Neoplasia)

RNAi-mediated silencing of insulin receptor substrate-4 enhances actinomycin D- and tumor necrosis factor-[alpha]-induced cell death in hepatocarcinoma cancer cell lines

Journal of Cellular Biochemistry — Tue, 29 Sep 2009 23:00:00 +0100

Insulin receptor substrate-4 (IRS-4) transmits signals from the insulin-like growth factor receptor (IGF-IR) and the insulin receptor (IR) to the PI3K/AKT and the ERK1/2 pathways. IRS-4 expression increases dramatically after partial hepatectomy and plays an important role in HepG2 hepatoblastoma cell line proliferation/differentiation. In human hepatocarcinoma, IRS-4 overexpression has been associated with tumor development. Herein, we describe the mechanism whereby IRS-4 depletion induced by RNA interference (siRNA) sensitizes HepG2 cells to treatment with actinomycin D (Act D) and combined treatment with Act D plus tumor necrosis factor-[alpha] (TNF-[alpha]). Similar results have been obtained in HuH 7 and Chang cell lines. Act D therapy drove the cells to a mitochondrial-dependent apop...

Hepatic progenitor cells in liver cancers from Asian children

Liver International — Mon, 28 Sep 2009 23:00:00 +0100

Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are the two most common primary malignant liver tumours in children. Hepatic progenitor cells have been described and can be stained with K19, EpCAM and CD117. We investigated the morphology and staining patterns of primary liver tumours in Asian children. Four pathologists studied slides from 39 paediatric patients from Vietnam and Korea aged 8 months to 16 years. We performed immunohistochemical stains for K19, EpCAM and CD117, and polymerase chain reaction for tissue hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA. There was agreement on the diagnosis of 24 cases of HCC and 10 cases of HB (one recurrent case). The diagnosis was split for six cases (HCC/HB). All 20 cases of HCC tested were HBV DNA+ and HCV RNA[minus]. All...

Cytogenetic and array comparative genomic hybridization analysis of a series of hepatoblastomas

Cancer Genetics and Cytogenetics — Thu, 24 Sep 2009 17:36:29 +0100

Abstract: Hepatoblastoma is the most common primary hepatic tumor in children, and only a limited number of detailed karyotypic analyses have been reported to date. In the present study, cytogenetic abnormalities were identified in nine cases of hepatoblastoma from a single institution. Among characteristic chromosomal changes detected were simple numerical aberrations, structural alterations of chromosomes 1, 2, and 8, and the recurrent unbalanced rearrangements der(4)t(1;4)(q25.2;q35.1) and der(6)t(1;6)(q21;q26). Array comparative genomic hybridization was applied in four of the cases. The combined cytogenetic, molecular cytogenetic, and histopathologic analyses are presented here, together with clinical data. The results substantially confirm previous findings of aberrations involving c...