Study points to possible treatment target for aggressive liver cancer in kids

(Cincinnati Children's Hospital Medical Center) A protein in the cell nucleus already targeted therapeutically for several types of cancer has now been linked to an aggressive form of pediatric liver cancer called hepatoblastoma (HBL), according to a study published in the Nature journal Communications Biology. Scientists at Cincinnati Children's Hospital Medical Center report that laboratory testing indicates the protein, PARP1, may be an effective treatment target for the cancer, but emphasize additional research is needed to verify this.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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Despite recent advances, the prognosis for advanced stage hepatoblastoma remains poor, resulting in a desperate need for novel therapies. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM) kinases act as oncoproteins to promote cell survival in hepatoblastoma. In addition, PIM kinases promote the hepatoblastoma cancer stem cell phenotype, which may contribute to chemoresistance. We hypothesized that a novel PIM inhibitor, PIM447, would decrease oncogenicity and cancer cell stemness in a human hepatoblastoma, patient-derived xenograft (PDX) model.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Surgical oncology Source Type: research
Undifferentiated embryonal sarcoma of the liver (UESL) comprises approximately 10% of all pediatric liver malignancy after hepatoblastoma and hepatocellular carcinoma. We aimed to investigate the clinicopathologic characteristics and outcomes of pediatric UESL in the US during a contemporary era.
Source: Journal of the American College of Surgeons - Category: Surgery Authors: Tags: Pediatric surgery Source Type: research
s Sanford Simon Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly re...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionThis report shows that it is feasible to measure AUCs for both drugs and to individualize the dose of these drugs according to the PK results and clinical parameters. Our advice for future cases would be to calculate the starting dose of carboplatin using the (pediatric) Calvert formula, assuming a dialytic clearance of zero, and to adjust the dose if required, based on therapeutic drug monitoring.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
einitz Kappler Hepatoblastoma (HB) is the most common malignant liver tumor in childhood and it generally has a good prognosis. However, if associated with aggressive metastatic disease, outcome is still poor. The molecular mechanisms leading to metastatic spread in HB patients are still unknown. By combining RNA-sequencing and a genome-wide methylome analysis, we identified the transcription factor SP8 and the growth factor FGF8 among the most strongly upregulated genes in metastatic HB cases, with a concomitant robust demethylation of the respective promoter regions. Of note, high expression of both candidates was...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusions: CQ treatment inhibits cell survival in cell models of aggressive HB, presumably by perturbing NAD+ levels, impairing aspartate bioavailability, and inhibiting PARP expression. CQ thus holds potential as a new agent in the management of HB.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In conclusion, PRDX4 promotes embryonal hepatoblastoma cell migration but induces fetal cell differentiation. It can be adopted as an important marker for HB prognosis and a potential treatment target. PMID: 32655804 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
CONCLUSION: Overall, this meta-analysis has demonstrated for the first time that LINC00673 rs11655237 could increase susceptibility to cancer. PMID: 32650095 [PubMed - as supplied by publisher]
Source: Genomics - Category: Genetics & Stem Cells Authors: Tags: Genomics Source Type: research
Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were u...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
In conclusion, our results indicate that the rs6090311 A>G in the YTHDF1 gene is related to decreased hepatoblastoma risk.
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Research Paper Source Type: research
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