Search results for "Hepatocellular"
showing 10 items of 885 documents
TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies
2009
AIM: To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors, in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL), on overcoming TRAIL resistance in hepatocellular carcinoma (HCC) and to study the efficacy of agonistic TRAIL antibodies, as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS: Surface expression of TRAIL receptors (TRAIL-R1-4) and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting, respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNA…
Molecular mechanisms of sorafenib action in liver cancer cells.
2012
Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced hepatocellular carcinoma (HCC). However, as the clinical application of sorafenib evolves, there is increasing interest in defining the mechanisms underlying its anti-tumor activity. Considering that this specific inhibitor could target unexpected molecules depending on the biologic context, a precise understanding of its mechanism of action could be critical to maximize its treatment efficacy, while minimizing adverse effects. Two human HCC cell lines (HepG2 and Huh7), carrying different biological and genetic characteristics, were used in this study to examine the intracellular events leading …
HCC therapies--lessons learned.
2014
The antiangiogenic multikinase inhibitor sorafenib was the first systemic agent to demonstrate a significant improvement in the overall survival of patients with advanced hepatocellular carcinoma (HCC), thereby introducing molecularly-targeted therapy in a therapeutic field of unmet needs. However, survival benefits for patients on sorafenib treatment are modest in clinical practice and advancing the field is far more challenging than initially anticipated. Molecular and clinical heterogeneity diminishes signals of potential activity in unselected populations, and underlying liver cirrhosis seals the fate of many novel targeted agents by causing relevant toxicity and mortality. The failure …
Sorafenib in advanced hepatocellular carcinoma
2008
none 25 BACKGROUND: No effective systemic therapy exists for patients with advanced hepatocellular carcinoma. A preliminary study suggested that sorafenib, an oral multikinase inhibitor of the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and Raf may be effective in hepatocellular carcinoma. METHODS: In this multicenter, phase 3, double-blind, placebo-controlled trial, we randomly assigned 602 patients with advanced hepatocellular carcinoma who had not received previous systemic treatment to receive either sorafenib (at a dose of 400 mg twice daily) or placebo. Primary outcomes were overall survival and the time to symptomatic progression. Seconda…
Curative therapies are superior to standard of care (transarterial chemoembolization) for intermediate stage hepatocellular carcinoma.
2017
Background and aims the Barcelona Clinic Liver Cancer intermediate stage (BCLC-B) of hepatocellular carcinoma (HCC) includes extremely heterogeneous patients in terms of tumor burden and liver function. Transarterial-chemoembolization (TACE) is the first-line treatment for these patients although it may be risky/useless for someone, while others could undergo curative treatments. This study assesses the treatment type performed in a large cohort of BCLC-B patients and its outcome. Methods retrospective analysis of 485 consecutive BCLC-B patients from the ITA.LI.CA database diagnosed with naive HCC after 1999. Patients were stratified by treatment. Results 29 patients (6%) were lost to follo…
Sorafenib perpetuates cellular anti-cancer effector functions by modulating the cross talk between macrophages and natural killer cells.
2012
Alternatively polarized macrophages (Mϕ) shape the microenvironment of hepatocellular carcinoma (HCC) and temper anticancer immune responses. We investigated if sorafenib alters the HCC microenvironment by restoring classical macrophage polarization and triggering tumor-directed natural killer (NK) cell responses. In vivo experiments were conducted with sorafenib (25 mg/kg)-treated C57BL/6 wildtype as well as hepatitis B virus (HBV) and lymphotoxin transgenic mice with and without HCC. Monocyte-derived Mϕ or tumor-associated macrophages (TAM) isolated from HCC tissue were treated with sorafenib (0.07-5.0 μg/mL) and cocultured with autologous NK cells. Mϕ and NK cell activation was analyzed …
Field-practice study of sorafenib therapy for hepatocellular carcinoma: a prospective multicenter study in Italy
2011
A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or inter…
Multimodal approaches to the treatment of hepatocellular carcinoma.
2008
The prevalence of hepatocellular carcinoma in Europe and the US is increasing and is currently the leading cause of death in patients with cirrhosis. Surveillance programs for patients with cirrhosis aim to detect tumors at an early stage, when the greatest therapeutic benefits can be achieved. Curative treatments for early-stage tumors include liver transplantation, resection and percutaneous ablation. Transarterial chemoembolization (TACE) and sorafenib can improve survival for patients with intermediate and advanced tumors, respectively. In clinical practice, combination therapies are often used, despite limited evidence to support this approach from randomized controlled trials. Combina…
Future perspectives in hepatocellular carcinoma.
2010
Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies worldwide. Due to late diagnosis and advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefits have been available in up to 70% of patients. However, major progress has been achieved with regard to surveillance, early diagnosis, and multimodal treatment approaches during the last years leading to an improvement in prognosis. Particularly, the increasing knowledge of molecular hepatocarcinogenesis today provides the opportunity for targeted therapy. The multikinase inhibitor sorafenib has broadened the therapeutic horizon for patients with advanced disease and is current…
Sorafenib (SFB) treated elderly patients (E) with hepatocellular carcinoma (HCC): Chromogranine A (CGA) plus vascular endothelial growth factor (VEGF…
2012
e14676 Background: HCC accounts for approximately 90% of all primary liver cancers, and is the fifth most common cancer in the world and prognosis is so far very poor,particularly in E patients.Between all tentative of treatment till know SFB seems to be the most promising drug in patients with advanced or metastatic HCC.Aim of the study is to investigate if SFB is efficient and safe also in E HCC patients despite the comorbidities and other problems. Objectives: To investigate if CgA and VEGF work as predicting factors of Sorafenib treatment outcomes. Methods: 51 patients, mean age 68,9 (65-85) with HCC were enrolled . Serum CgA, VEGF and αFP were evaluated at baseline and after end of tr…