Preemptive lamivudine in lymphoma patients undergoing intensive chemotherapy can effectively prevent chemotherapy-related HBV reactivation. Nevertheless, the safety profile after withdrawal of lamivudine and the impact of rituximab-containing chemotherapy on HBV reactivation has not been defined. To illustrate the necessity of prolonged surveillance after cessation of preemptive lamivudine in lymphoma patients treated with rituximab and chemotherapy, four patients with B-cell NHL carrying HBV received rituximab plus CHOP. Preemptive lamivudine therapy was administered 1 week before chemotherapy until 4 weeks after completion of chemotherapy. Serial serum alanine aminotransferase (ALT), total bilirubin, and HBV-DNA levels were prospectively monitored in three patients. The fourth patient was closely monitored for ALT. The HBV DNA was checked after development of clinical overt hepatitis. The peripheral blood CD20+ B-lymphocyte counts were analyzed periodically in two patients. All of the three patients studied prospectively had virological relapses with surgence of HBV DNA 6-8 months after completion of rituximab-plus-CHOP (R+CHOP) therapy. Two of the three patients had biochemical relapses and one of them developed severe hepatitis. Sequencing for HBV polymerase gene in these patients failed to show evident emergence of lamivudine-resistant mutations. The fourth patient developed a hepatitis flare-up 6 months after completion of chemotherapy. The CD2+ lymphocytes were totally depleted when HBV DNA started to increase. Delayed HBV reactivation can occur in lymphoma patients receiving R+CHOP after withdrawal of preemptive lamivudine. More protracted lamivudine therapy may be an alternative to close monitoring following chemotherapy, and further studies are needed to define optimal duration of lamivudine therapy.
BackgroundThis study aimed to explore the effects of HMGA2 on cell proliferation and metastases in lung cancer and its underlying mechanism.Methods
HMGA2 expression in lung cancer tissues and its association with overall survival were analyzed based on data from a public database. The roles of HMGA2 were validated via loss‐of‐function and gain‐of‐function experiments in vitro. HMGA2 regulation by microRNA‐195 (miR‐195) was validated by real time‐PCR, Western blotting, and luciferase reporter assays.Results
HMGA2 was upregulated and associated with reduced overall survival in patients with lung adenocarcinoma. HMGA2 knockdown suppressed the proliferation and motility of H1299 cells, while HMGA2 ectopic expression in A549 cells increased cell proliferation and migration. HMGA2 affected cell apoptosis through caspase 3/9 and Bcl‐2, and regulated epithelial‐to‐mesenchymal transition by targeting Twist 1. Moreover, miR‐195 was found to directly target the 3′ untranslated region of HMGA2 messenger RNA and suppress its expression in lung cancer.ConclusionThis study demonstrated that HMGA2, regulated by miR‐195, played important roles in proliferation, metastases, and epithelial‐to‐mesenchymal transition in lung cancer. HMGA2 might serve as a biomarker and potential therapeutic target for lung cancer treatment.
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