No abstract

No abstract

Terlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide, with few effective therapeutic options for advanced disease. At least 40% of HCCs are clonal, potentially arising from STAT3 þ , NANOG þ and OCT3/4 þ liver progenitor/stem cell transformation, along with inactivation of transforming growth factor-beta (TGF-b) signaling. Here we report significantly greater signal transducer and activator of transcription 3 (STAT3) and tyrosine phosphorylated STAT3 in human HCC tissues (Po0.0030 and Po0.0455, respectively) than in human normal liver. Further, in HCC cells with loss of response to TGF-b, NSC 74859, a STAT3-specific inhibitor, markedly suppresses growth. In contrast, CD133 þ status did not affect the response to STAT3 inhibition: both CD133 þ Huh-7 cells and CD133 -Huh-7 cells are equally sensitive to NSC 74859 treatment and STAT3 inhibition, with an IC 50 of 100 lM. Thus, the TGF-b/beta2 spectrin (b2SP) pathway may reflect a more functional 'stem/progenitor' state than CD133. Furthermore, NSC 74859 treatment of Huh-7 xenografts in nude mice significantly retarded tumor growth, with an effective dose of only 5 mg/kg. Moreover, NSC 74859 inhibited tyrosine phosphorylation of STAT3 in HCC cells in vivo. We conclude that inhibiting interleukin 6 (IL6)/STAT3 in HCCs with inactivation of the TGF-b/b2SP pathway is an effective approach in management of HCCs. Thus, IL6/STAT3, a major signaling pathway in HCC stem cell renewal and proliferation, can provide a novel approach to the treatment of specific HCCs.