scholarly journals Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-zheng Zou ◽  
Jun-feng Hao ◽  
Xiu-hua Zhou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Small Molecule ◽  
Aerobic Glycolysis ◽  
Small Molecule Inhibitor ◽  
Advanced Hepatocellular Carcinoma ◽  
Antitumor Effects ◽  
Advanced Hcc ◽  
Molecule Inhibitor ◽  
Hcc Cells

Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expression in RFA of advanced HCC was elucidated. In patients with advanced HCC receiving RFA, a high level of endogenous SREBP-1 expression correlated to poor survival. Inhibition of SREBP-1 activation using a novel small-molecule inhibitor, SI-1, not only inhibited the aerobic glycolysis of HCC cells, it also enhanced the antitumor effects of RFA on xenograft tumors. Overall, our results: (i) revealed the correlation between SREBP-1 and HCC severity; (ii) indicated that inhibition of SREBP-1 activation could be a promising approach for treatment of advanced HCC.

scholarly journals Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma

2018 ◽  
Vol 144 (10) ◽  
pp. 2613-2624 ◽  
Author(s):  
Giuseppa Augello ◽  
Maria Rita Emma ◽  
Antonella Cusimano ◽  
Antonina Azzolina ◽  
Sarah Mongiovì ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Molecule ◽  
Treatment Strategy ◽  
Small Molecule Inhibitor ◽  
Molecule Inhibitor

scholarly journals Hypoxic hepatocellular carcinoma cells acquire arsenic trioxide resistance through upregulating HIF-1α expression

2020 ◽  
Author(s):  
Yaoting Chen ◽  
Huiqing Li ◽  
Dong Chen ◽  
Xiongying Jiang ◽  
Weidong Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Expression ◽  
Arsenic Trioxide ◽  
Therapeutic Effects ◽  
Advanced Hepatocellular Carcinoma ◽  
Antitumor Effects ◽  
P Glycoprotein ◽  
Hcc Cells

Abstract Background : Although arsenic trioxide (ATO) is used in the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials, it is not satisfactory in terms of improving HCC patients’ overall survival. Intratumoral hypoxia and overexpression of hypoxia-inducible-1α (HIF-1α) may result in ATO-resistance and tumor progression. We investigated the mechanisms involving HIF-1α expression and acquired ATO chemoresistance in HCC cells and mice. Methods: The therapeutic effects of ATO in normoxic and hypoxic HCC cells were assessed using cell viability and apoptosis assays in vitro and a xenograft model in vivo . mRNA and protein expression of HIF-1α, P-glycoprotein, and VEGF were measured by qRT-PCR and western blotting. HIF-1α inhibition was performed to investigate the mechanism of ATO-resistance. VEGF secretion was tested using ELISA and tube-formation assays. Results : Compared to normoxic cells, hypoxic HCC cells were more resistant to ATO, with higher IC 50 values and less apoptosis, and upregulated HIF-1α protein expression, accompanied with the enhancement of P-glycoprotein and VEGF synthesis after ATO treatment. VEGF secretion was elevated in the supernatant of ATO-treated HCC cells, and this change can potentiate angiogenesis in vitro . HIF-1α inhibition attenuated ATO-resistance and angiogenesis, and promoted the anticancer effects of ATO both in vitro and in vivo by downregulating therapy-induced P-glycoprotein and VEGF overexpression. Conclusions : Hypoxic HCC cells acquire ATO resistance by upregulating HIF-1α levels; thus, combining ATO with a HIF-1α-targeting agent may lead to enhanced antitumor effects in HCC.

Tailored combined treatment with radiofrequency ablation plus octreotide in advanced hepatocellular carcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15173-15173 ◽  
Author(s):  
S. del Prete ◽  
R. Addeo ◽  
M. Caraglia ◽  
V. Faiola ◽  
R. Guarrasi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Somatostatin Receptor ◽  
Combined Treatment ◽  
Tolerability Profile ◽  
Receptor Subtypes ◽  
Treatment Schedule ◽  
Advanced Hepatocellular Carcinoma ◽  
Small Hepatocellular Carcinoma ◽  
Advanced Hcc

15173 Background: Local therapies represent a valuable choice in small hepatocellular carcinoma (HCC), however, radiofrequency ablation (RFA) is increasingly used in advanced tumors. Medical treatments generally gave frustrating results in advanced hepatocellular carcinoma. Several biological non chemotherapeutic drugs are currently tested in HCC. Based on the expression of somatostatin receptor subtypes by HCC and the tolerability profile, octreotide was evaluated in single cases and small series of HCC patients and conflicting results are reported. Methods: 35 advanced HCC (26 males, 9 females; age range 55–85 years, median 73 years) were treated with RFA and octreotide with the aim to evaluate safety and determine the effect on disease control and survival. Testing regular and increasing doses of long-acting octreotide (from 20 to 30 mg monthly) were planned in the treatment schedule. Child A and Child B patients were 60% and about 34% of the cases, respectively. Only two patients with Child C compensated cirrhosis were included. All patients have multiple liver HCC nodules and one had bone metastases. Treatment with octreotide was maintained until disease progression or unacceptable toxicity. RFA was performed before or during treatment with octreotide according to medical evaluation. Results: In the majority of patients (65,7%) stable disease was obtained. In 3 patients (8,5%) progression of disease was documented. Clinical progression of underlying cirrhosis was identified in four patients and appear to condition the outcome, independently from HCC. Both medical and local treatments were well tolerated. Statistical evaluation was presented at ASCO 2007. Conclusions: The combined treatment with RFA and octreotide can be feasible in advanced HCC patients. No significant financial relationships to disclose.

Role and strategies of radiofrequency ablation in treating advanced hepatocellular carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14701-e14701
Author(s):  
Min Hua Chen ◽  
Wei Yang ◽  
Jie Wu ◽  
Wei Wu ◽  
Kun Yan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Radiofrequency Ablation ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Percutaneous Ablation ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Tnm System ◽  
Liver Protection

e14701 Background: To investigate the application value and strategies of ultrasound-guided percutaneous radiofrequency ablation (RFA) in treating advanced hepatocellular carcinoma (HCC) which is common in china. Methods: A total of 655 patients with unresectablely advanced HCC underwent percuatenous RFA therapy and 92 patients with 136 tumors among them were enrolled into the study. According to the 6th UICC/AJCC-TNM system, 82 and 10 patients were in stage III and IV, respectively. The tumor size ranged from 1.5 to 8.0 cm (mean±SD, 4.5±1.6 cm). 59 patients had solitary tumor and the remaining 33 patients had multiple tumors. The Child-Pugh classification of A, B and C were 58,32 and 2 patients, respectively. Established strategies included: (1) select RFA indications based on the contrast-enhanced ultrasound (CEUS) results; (2) design radical protocols based on invasive range showed by CEUS; (3) multiple overlapping ablations based on mathematical protocol; (4) two or three bipolar RFA electrodes with three dimensional localization; (5) color US guided percutaneous ablation of tumor feeding artery (including TACE) + RFA for HCC with rich supply. The patients underwent follow-up using enhanced CT at one month, and then every three months after RFA. The ablation was considered a success if no abnormal enhancement or wash-out was detected in the treated area on the CT scan at one month. All patients after RFA received liver protection treatments. Overall survival was estimated by Kaplan-Meier analysis. Results: Early complete tumor necrosis rate after initial RFA was 90.4% (123/136 tumors). Serious complications were developed in two patients (2.2%) and no treatment-related death occurred. 3~129 months were followed up. Local recurrence rate was 15.4 %(21/136 tumors). The 1-, 3-, 5-year overall survival rates were 83.3 %, 48.3 %, 21.9%, respectively, and the median survival time was 35 months. Conclusions: RFA treatment of advanced HCC proved to be feasible. Paying attention to apply treatment strategies and liver protection therapies in RFA can effectively improve the survival.

Amplitude-modulated radiofrequency electromagnetic fields target hepatocellular carcinoma stem cells through activation of Cav 3.2 T-type calcium channels.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 332-332
Author(s):  
Hugo Jimenez ◽  
Minghui Wang ◽  
Jacquelyn W. Zimmerman ◽  
Michael J. Pennison ◽  
Sambad Sharma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Calcium Channels ◽  
Electromagnetic Fields ◽  
Human Exposure ◽  
Whole Body ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Radiofrequency Electromagnetic Fields ◽  
Hcc Cells

332 Background: Amplitude-modulated 27.12 MHz radiofrequency electromagnetic fields (AM RF EMF) delivered via a spoon-shaped antenna placed on the patient’s tongue result in shrinkage of the primary and metastatic tumors in patients with advanced hepatocellular carcinoma (HCC). (Costa FP, et al. Br J Cancer. 2011;105:640-648.) The mechanism by which AM RF EMF have direct antiproliferative effect and disruption of the mitotic spindle on cancer cells is largely unknown. (Zimmerman JW, et al. Br J Cancer. 2012;106:307-313.) Methods: We assessed the Specific Absorption Rate (SAR) level and distribution inside the human body. In vitro experiments with HCC cells were performed as previously described (Zimmerman). Immunodeficient mice were subcutaneously implanted with Huh-7 HCC cells or patient-derived xenografts (PDX). Mice were exposed to HCC-specific AM RF EMF using systems replicating human exposure levels and treatment duration. Tumor samples were examined for EMT and cell cycle markers. Results: Intrabuccal delivery results in whole-body absorption of AM RF EMF. Proliferation of hepatitis B positive and negative cell lines as well as HCC cancer stem cells (CSCs) are blocked by AM RF EMF through Cav 3.2 T-type voltage gated calcium channels (VGCC). Proliferation of HCC is inhibited in vivo and tumor shrinkage occurs by dedifferentiation of HCC cells into quiescent myofibroblasts while the growth of intestinal and blood marrow cells is unaltered. Conclusions: Whole-body SAR ranges from 0.2 to 1 mW/kg and is significantly below the international safety limits for human exposure. Intrabucally-administered AM RF EMF is a novel targeted therapy for systemic treatment of advanced HCC with minimal off target effects. Inhibition of HCC CSCs may explain the extremely long term survival (>5 years) of several patients with advanced HCC.

scholarly journals Dramatic Antitumor Effects of the Dual MET/RON Small-Molecule Inhibitor LY2801653 in Non–Small Cell Lung Cancer

2013 ◽  
Vol 74 (3) ◽  
pp. 884-895 ◽  
Author(s):  
Ichiro Kawada ◽  
Rifat Hasina ◽  
Qudsia Arif ◽  
Jeffrey Mueller ◽  
Erin Smithberger ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Small Molecule ◽  
Cell Lung Cancer ◽  
Small Molecule Inhibitor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antitumor Effects ◽  
Molecule Inhibitor

scholarly journals Locoregional Combined With Systemic Therapies for Advanced Hepatocellular Carcinoma: An Inevitable Trend of Rapid Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Li ◽  
Yaxi Wang ◽  
Xin Ye ◽  
Ping Liang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Rapid Development ◽  
Locoregional Therapy ◽  
Current Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Antitumor Effects ◽  
Primary Tumors ◽  
Advanced Hcc ◽  
Number Of Patients ◽  
Locoregional Therapies

Despite the application of antiviral drugs and improved surveillance tools, the number of patients diagnosed with hepatocellular carcinoma (HCC) at an advanced stage and with a dismal prognosis is still on the rise. Systemic treatment with multiple multitargeted tyrosine kinase inhibitors (TKIs), such as sorafenib, has been a widely utilized approach for a decade. In addition, the use of a combination of TKIs with other types of compounds, including immune checkpoint inhibitors (ICIs) and antiangiogenic inhibitors, has shown efficacy in treating advanced HCC. However, the presence of intolerable adverse events, low disease response and control rates, and relative short overall survival of such combinatory therapies makes novel or optimized therapies for advance HCC urgently needed. Locoregional therapy (transarterial chemoembolization, and thermal ablation) can destroy primary tumors and decrease tumor burden and is widely used for HCC management. This type of treatment modality can result in local hypoxia and increased vascular permeability, inducing immunogenic effects by releasing tumor antigens from dying cancer cells and producing damage-associated molecular patterns that facilitate antiangiogenic therapy and antitumor immunity. The combination of systemic and locoregional therapies may further produce synergistic effects without overlapping toxicity that can improve prognoses for advanced HCC. In preliminary studies, several combinations of therapeutic modes exhibited promising levels of safety, feasibility, and antitumor effects in a clinical setting and have, thus, garnered much attention. This review aims to provide a comprehensive, up-to-date overview of the underlying mechanisms of combined systemic and locoregional therapies in the treatment of advanced HCC, commenting on both their current status and future direction.

scholarly journals Advanced hepatocellular carcinoma treated by radiofrequency ablation combined with oncolytic virus and anti-PD-1 antibody therapy: a case report and literature review

2021 ◽  
Vol 49 (9) ◽  
pp. 030006052110445
Author(s):  
Anqing Xie ◽  
Feng Xia ◽  
Jun Pei ◽  
Ximing Sun ◽  
Zongtao Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Literature Review ◽  
Oncolytic Virus ◽  
Antibody Therapy ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc

The development of an effective therapy for advanced hepatocellular carcinoma (HCC) represents an important global concern. In recent years, the combination of multiple treatment methods with immunotherapy has achieved great progress in patients with advanced HCC. Patient survival has been significantly prolonged, but cases of complete response (CR) remain rare. Here, we report two cases in which CR was achieved by radiofrequency ablation combined with an oncolytic virus (recombinant human adenovirus type 5) and anti-programmed cell death protein 1 antibody. Additionally, a literature review is presented to describe similar advancements in this field and explore viable methods for the treatment of advanced HCC.

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