Portal hypertension, as one of the major complications of liver cirrhosis, is a common clinical syndrome characterized by an increased portal pressure and the formation of portal-systemic collaterals. Currently no ideal therapeutic agent has been available for portal hypertension. Sorafenib is an oral tyrosine kinase inhibitor that has been shown to significantly improve blood flow dynamics, inhibit angiogenesis, reduce liver fibrosis and decrease portal pressure in the treatment of portal hypertension. The authors review the progress in the research of sorafenib in the treatment of portal hypertension and the mechanisms of its actions.
Animals ; Humans ; Hypertension, Portal ; drug therapy ; Niacinamide ; analogs & derivatives ; pharmacology ; therapeutic use ; Phenylurea Compounds ; pharmacology ; therapeutic use

Antineoplastic Agents ; therapeutic use ; Benzenesulfonates ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; therapeutic use

Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVE: To compare the effects of medical ozone oil and urea ointment for prevention and treatment of hand-foot skin reaction (HFSR) caused by sorafenib in patients with hepatocellular carcinoma (HCC). METHODS: A total of 99 patients diagnosed with advanced HCC according to National Comprehensive Cancer Network (NCCN) who were scheduled to receive sorafenib treatment for the first time were enrolled in this study between April, 2018 and January, 2020. The patients were randomized into medical ozone oil group ( RESULTS: Eight patients were excluded for poor compliance or protocol violations, leaving a total of 91 patients for analysis, including 44 in medical ozone oil group and 47 in urea ointment group. Sixteen (36.4%) of patients in ozone oil group developed HFSR, a rate significantly lower than that in urea ointment group (57.4%; CONCLUSIONS Medical ozone oil can significantly reduce the incidence and severity of HFSR to improve the quality of life of HCC patients receiving sorafenib treatment.
Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Hand-Foot Syndrome/prevention & control* ; Humans ; Liver Neoplasms/drug therapy* ; Niacinamide/therapeutic use* ; Ozone/therapeutic use* ; Phenylurea Compounds/adverse effects* ; Quality of Life ; Sorafenib/therapeutic use*

OBJECTIVETo evaluate the efficacy and safety of the combination of sorafenib and transarterial chemoembolization (TACE)in the treatment of primary hepatocellular carcinoma (HCC).

METHODSThe clinical data of 10 patients with unresectable HCC treated by sorafenib combined with TACE in the Department of Radiology, the First Hospital of China Medical University were retrospectively analyzed. The efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors assessment. Survival was analyzed by Kaplan-Meier method. Safety was evaluated according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 3.0.

RESULTSAmong the 10 patients, 2 achieved complete response, 3 achieved partial response, 3 achieved stable disease, and 2 experienced progressive disease. The median overall survival of the cohort was 29.5 months. Different degree of adverse drug reactions (ADRs) occurred in 9 patients but all were at grade 3 or lower. The most common ADRs were hand-foot skin reaction (7/10) and diarrhea (6/10).

CONCLUSIONThe combination of sorafenib and TACE is an effective and safe treatment for HCC.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Chemoembolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; Retrospective Studies ; Treatment Outcome

BACKGROUNDThe prognosis of unresectable large hepatocellular carcinomas is poor. This study evaluated the efficacy and safety of sorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation in the treatment of hepatocellular carcinomas larger than 5 cm.

METHODSThe treatment of 22 patients with large, unresectable hepatocellular carcinomas (5.0-16.5 cm) treated with sorafenib after transcatheter arterial chemoembolization combined with radiofrequency ablation between 2007 and 2011 was reviewed. The local effects, survival rates, toxicity, and prognostic factors were analyzed.

RESULTSDuring a follow-up of 9-49 months, 19 patients died and three survived. The median overall survival was 32 months. The overall cumulative 12, 24, and 36-month survival rates were 85.9%, 66.8%, and 23.5% respectively. Technical effectiveness was achieved in 12 out of 28 lesions (42.85%) at the first CT check. The median time to tumor progression was 21 months. The progression-free survival rates at 6, 12, and 24 months were 90.9%, 72.0%, and 38.4%, respectively. Combined therapy was generally well tolerated. There was only one major procedure-related complication, biloma (4.5%). Sorafenib-related adverse events exceeding grade 3 were hand-foot skin reaction (2/22, 9.1%), gastrointestinal hemorrhage (1/22, 4.5%), and diarrhea (2/22, 9.1%). The absence of vascular invasion before treatment was found to be the best prognostic factor in the univariate analysis.

CONCLUSIONSSorafenib combined with transcatheter arterial chemoembolization and radiofrequency ablation is a promising approach to the treatment of large, unresectable hepatocellular carcinomas. However, large-scale randomized clinical trials are needed to determine the future role of this treatment.

Adult ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; therapy ; Catheter Ablation ; Chemoembolization, Therapeutic ; methods ; Female ; Humans ; Liver Neoplasms ; drug therapy ; therapy ; Male ; Middle Aged ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; Retrospective Studies ; Treatment Outcome

Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; mortality ; therapy ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Disease-Free Survival ; Humans ; Liver Neoplasms ; mortality ; therapy ; Middle Aged ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use

OBJECTIVE: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+). METHODS: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. RESULTS: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05). CONCLUSION Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.
Apoptosis ; Benzothiazoles ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Paclitaxel/therapeutic use* ; Phenylurea Compounds ; RNA, Messenger ; STAT5 Transcription Factor/pharmacology* ; Signal Transduction ; fms-Like Tyrosine Kinase 3

Hepatocellular carcinomas are highly vascular tumors, showing progressive hypervascularity by the process of neoangiogenesis. Tumor angiogenesis is critical for tumor growth as well as metastatic spread therefore, imaging and quantification of tumor neo-angiogenesis is essential for monitoring response to targeted therapies and predicting disease progression. Sorafenib is a molecular targeting agent used for treating hypervascular tumors. This drug is now the standard of care in treatment of patients with advanced hepatocellular carcinoma. Due to its anti-angiogenic and anti-proliferative actions, imaging findings following treatment with Sorafenib are quite distinct when compared to conventional chemotherapeutic agents. Liver MRI is a widely adopted imaging modality for assessing treatment response in hepatocellular carcinoma and imaging features may reflect pathophysiological changes within the tumor. In this mini-review, we will discuss MRI findings after Sorafenib treatment in hepatocellular carcinoma and review the feasibility of MRI as an early biomarker in differentiating responders from non-responders after treatment with molecular targeting agents.
Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/physiopathology/*radiography ; Female ; Humans ; Liver Neoplasms/drug therapy/physiopathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Tomography, X-Ray Computed

With an increasing number of patients with hepatocellular carcinoma (HCC) undergoing liver transplantation (LT), tumor recurrence remains the main limiting factor for long-term survival. Although sorafenib is available for advanced HCC, there is still a lack of data on the use of sorafenib for treatment of recurrent HCC after LT. Here, we report on four cases of the use of sorafenib for treatment of recurrent HCC after LT. The median time of recurrence from LT was 4 months (range, 1-16 months). Two of the four evaluated patients showed stable disease, which was the best response and the duration of stabilization was 11 months and 5 months, respectively. One patient also experienced stable disease and remained in stable disease without sorafenib therapy for 29 months and the total duration of stabilization was 38 months. The remaining patient showed partial response but stopped treatment due to radiological tumor progression during treatment. Although all cases were high risk group for recurrence such as above Milan criteria, vascular invasion and tumor biology, clinical outcomes showed some good results. Therefore, sorafenib may be an acceptable treatment option for recurrent HCC after LT.
Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/diagnosis/*drug therapy ; Female ; Humans ; Liver Neoplasms/diagnosis/*drug therapy ; *Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Positron-Emission Tomography ; Tomography, X-Ray Computed