Shawn Pelletier | PubMed Health

PubMed2006

Hepatocellular carcinoma.

The number of patients who have hepatocellular carcinoma (HCC) is expected to more than double over the next 1 to 2 decades. Patients who have cirrhosis, regardless of cause, are at the highest risk for developing HCC. This article discusses surveillance of these patients for HCC by alpha-fetoprotein and ultrasound, evaluation using imaging, classification of HCC using the Barcelona staging classification, and treatment. Resection, transplantation, and percutaneous ablation are considered curative interventions and are applied to about 30% of all patients who have HCC. Currently, there is no standard therapy for advanced HCC.

Antineoplastic Agents↗

PubMed2004

Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia.

The Abl kinase inhibitor imatinib mesylate is the preferred treatment for Philadelphia chromosome-positive (Ph(+)) chronic myeloid leukemia (CML) in chronic phase but is much less effective in CML blast crisis or Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). Here, we show that Bcr-Abl activated the Src kinases Lyn, Hck and Fgr in B-lymphoid cells. BCR-ABL1 retrovirus-transduced marrow from mice lacking all three Src kinases efficiently induced CML but not B-ALL in recipients. The kinase inhibitor CGP76030 impaired the proliferation of B-lymphoid cells expressing Bcr-Abl in vitro and prolonged survival of mice with B-ALL but not CML. The combination of CGP76030 and imatinib was superior to imatinib alone in this regard. The biochemical target of CGP76030 in leukemia cells was Src kinases, not Bcr-Abl. These results implicate Src family kinases as therapeutic targets in Ph(+) B-ALL and suggest that simultaneous inhibition of Src and Bcr-Abl kinases may benefit individuals with Ph(+) acute leukemia.

Animals↗