Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma—A report from the German Cooperative Pediatric Liver Tumor Study HB-89

Wilkinson

American Journal of Transplantation

et al. 2002

The purpose of our study was to evaluate the outcome of children who underwent liver transplantation as treatment for unresectable hepatoblastoma. We prospectively collected data on 311 consecutive liver transplants performed at Children's Medical Center of Dallas between October 1984 and November 2000. There were nine recipients (five boys, four girls) with a diagnosis of unresectable hepatoblastoma. Postoperative survival of those currently alive ranged from 6 months to 16 years (mean 6.4 years, median 7.7 years). All recipients received preoperative chemotherapy; 67% received postoperative chemotherapy. Mean AFP level prior to transplantation was 1 448 000 ng/mL. Mean age at diagnosis was 0.81 years. Mean age at transplantation was 1.87 years. Only two patients experienced acute cellular rejection in the postoperative period. There was a total of three deaths and one recurrence. The only instance in which AFP levels did not decrease to low or undetectable levels post-transplantation was in the patient with recurrent tumor. Liver transplantation has an established role in the treatment of hepatoblastoma. It accounted for 3% of pediatric liver transplants, and provided the only opportunity for survival in otherwise incurable patients. Early diagnosis and treatment were found to be associated with better results. Response to chemotherapy may be an important factor influencing survival. Rising AFP levels after transplantation are associated with recurrence.

Section: Discussionmentioning

confidence: 99%

Treatment of Unresectable Hepatoblastoma with Liver Transplantation in the Pediatric Population

Wilkinson

American Journal of Transplantation

et al. 2002

“…Multidrug resistance has been identified as an important factor for diminished chemosensitivity (10,11). A well known mechanism of chemoresistance is the ATP-dependent excretion of drugs from the tumour cell via ABC transporters (12).…”

Section: Introductionmentioning

confidence: 99%

Development of a drug resistance model for hepatoblastoma

Eicher

Dewerth²,

Kirchner³

et al. 2011

Int J Oncol

Abstract. Multidrug resistance (MDR) is a major reason for poor treatment results in hepatoblastoma (HB). The objective of this study was to establish a drug resistance model for HB to analyse alternative treatment options in vitro. Both HB cell lines HUH6 and HepT1 were xenotransplanted in NMRI mice (nu/nu) and 2 cycles of cisplatin (CDDP) treatment were administered. Thereafter, xenotransplants were excised and viable tumour cells were re-cultured. 3D cultures of HUH6 and HepT1 cells were generated on a low binding culture surface. Cell viability in response to CDDP/DOXO (doxorubicin) and apoptosis was assessed by MTT-assay and caspase 3 activity, respectively. Efflux of doxorubicin was measured by flow cytometry. Cellular levels of ABC-transporters (MDR1, MRP1, cMOAT and BRCP) were determined by real time RT-PCR. Only HepT1 cells isolated from HB xenografts showed resistance to CDDP, but did not survive repeated passages. Culturing HUH6 and HepT1 cells as spheroids was successful and 3D cultures showed an IC 50 -drift to higher drug concentrations for CDDP and DOXO compared to 2D cultures. Treatment with CDDP and DOXO led to homogeneous apoptosis in spheroids. Increased doxorubicin efflux in HUH6 spheroids was not influenced by the P-glycoprotein inhibitor tariquidar. Expression levels of MDR1, MRP1, cMOAT and BRCP in 3D cultures were similar to those in 2D cultures and were higher in HepT1 than in HUH6 cells. In conclusion, a 3D cell culture model for multidrug resistance was established for hepatoblastoma. The underlying mechanism involves altered accessibility of the cells for drugs rather than up-regulation of ABC-transporters.

“…There is a correlation between AFP and extent of disease for all stages [2], and the rate of decline in AFP with treatment is prognostic [19,20]. Low AFP levels are associated with anaplastic histology and poor outcome.…”

Section: Epidemiologymentioning

confidence: 99%

Childhood Cancers: Hepatoblastoma

2000

Hepatoblastoma is the most common primary liver tumor in children, accounting for just over 1% of pediatric cancers. The etiology is unknown, but it has been associated with Beckwith-Weidemann syndrome, familial adenomatosis polypi, and low birth weight. The primary treatment is surgical resection, however, chemotherapy plays an important role by increasing the number of tumors that are resectable. The prognosis for patients with resectable tumors is fairly good, however, the outcome for those with nonresectable or recurrent disease is poor. Texas-Houston Medical School, 1515 Holcombe Blvd., Houston, Texas 77030, USA. Telephone: 713-745-0157; Fax 713-792-0608; e-mail: cherzog@ mdanderson.org Received June 21, 2000; accepted for publication September 6, 2000. ©AlphaMed Press 1083-7159/2000 INTRODUCTIONHepatoblastoma is the most common malignant tumor of the liver in children. Surgery remains the primary means of curative therapy, but the role of chemotherapy in both the adjuvant and neoadjuvant setting has become increasingly important over the past three decades. New insight has also been gained into the molecular biology of hepatoblastoma.