In that study, high HIF2α expression was also correlated with VEGF expression, microvessel density, and decreased survival.97 Multiple studies have suggested that HIF1α is a prognostic factor for tumor recurrence in human and murine HCC.98, 99 Some studies have shown that high expression of HIF1α in nonmalignant liver tissue adjacent to resected HCC is a negative predictor of disease-free survival, and may correlate with up-regulation

of HIF1α-dependent genes involved in cell migration and invasion.100 Lastly, patients with HCC whose tumors had high levels of expression of p28(GANK) had a high risk of recurrence, metastasis, and high mortality; interestingly, high p28(GANK) Gamma-secretase inhibitor expression correlated with higher levels of HIF1α.101 These observations imply that HIF1α inhibition may play a role in anticancer therapeutics. RNA-mediated inhibition of HIF1α was able to slow tumor growth.102 The antitumor efficiency of doxorubicin was increased Ivacaftor ic50 when combined with an HIF1α antisense oligonucleotide.103 Rapamycin inhibits signaling by the mammalian target of rapamycin (mTOR) complex pathway, and has shown some efficacy against HCC. The prevention of HCC tumor growth by rapamycin in a rodent model was correlated with suppression of HIF1α by rapamycin.104 Another compound, silibinin, was demonstrated to have some antitumor efficacy through phosphorylation of mTOR, and was also associated

with suppression of HIF1α signaling.105 Hypoxia has been implicated in the pathogenesis of a broad range of hepatic disease. In most of these models, some data exist to implicate a role for hypoxia inducible factors. Consideration of the role of HIFs in liver diseases should include multiple cell types, as HIF1α

activity has been implicated in hepatocytes as well as myeloid (Kupffer cells) and lymphoid (T-cells) lineage immune cells. Taken collectively, these findings strongly suggest that anti-HIF therapies promise useful interventions in the management of hepatic diseases of various etiologies. “
“Fanconi anemia (FA) is an inherited bone marrow failure syndrome due to defective DNA inter-strand cross-link repair. Hematopoietic stem cell transplantation (HSCT) is curative for pancytopenia, but Decitabine nmr may not prevent the development of non-hematological malignancies. We describe a 26-year-old male patient with FA and Marfan syndrome who in 1994 underwent successful HSCT with bone marrow stem cells from his human leukocyte antigen (HLA)-identical sister. In 2006, three lesions in the liver were detected and resected. The three lesions all showed activation of the β-catenin pathway and were histologically characterized by a highly differentiated steatotic hepatocellular carcinoma (HCC) with remnants of the underlying adenoma from which it arose, a hepatocellular adenoma with foci of well-differentiated HCC, and a cholestatic adenoma.