Method For Treatment Of Hepatocellular Carcinoma Research Articles

Nonadherence to oral cancer chemotherapy in hepatocellular carcinoma: prevalence and predictive factors in Vietnam

PurposeStandard oral cancer chemotherapy (OCT) or targeted therapy (OTT) has expanded the treatment methods for hepatocellular carcinoma (HCC). However, its principal nonadherence causes a reduction in efficacy. We aimed to evaluate the status of nonadherence and influencing factors among outpatient patients with HCC.Patients and methodsIn 2021, a prospective observational study was conducted on 384 patients with either old or newly diagnosed HCC treated with OTT. Nonadherence to OCT was determined using the eight-item Morisky Medication Adherence Scale, with a score < 6 points. The patients were finished with a six-month follow-up investigation by questionnaires.Results54,8% of HCC outpatients were nonadherent to OCT, with a mean Morisky score of 5.19. They dropped out of the treatment mainly because of drug side effects, such as fatigue (72.4%), hand-foot syndrome (42.7%), diarrhea (38.3%), nausea (25%), insomnia (24.7%), abdominal pain (12%), and anxiety about these adverse events (65.9%). Additionally, financial difficulties and low relative copayments were significantly correlated with the noncompliant treatment of patients (OR = 2.29, 95% CI = 1.32–3.98, P = 0.003; OR = 4.36, 95% CI = 0.95–19.93, P = 0.039, respectively). Moreover, inadequate individual information about the clinical course, the art of treatment, and medication usage instructions were suggestive barriers to adherence to treatment (OR = 1.96, 95% CI = 1.08–3.55, P = 0.024; OR = 1.86, 95% CI = 1.1–3.14, P = 0.02; OR = 2.34, 95% CI = 1.29–4.26, P = 0.004, respectively). Finally, a low level of trust in doctors was an essential factor in nonadherence (Mean of the Anderson Trust in Physician Scale scores counted 38.12 vs. 43.97, respectively for non-adherence vs. adherence, P = 0.00001).ConclusionsThis study suggests a high rate of primary nonadherence to standard oral targeted therapy among HCC outpatient patients because of drug side effects, patient awareness of treatment, and lack of confidence in healthcare providers. Close supervision, proper medication instructions, appropriate dosage reductions, and comprehensive patient counseling might be necessary to control nonadherence.

Radioiodine-131-Labeled Theranostic Nanoparticles for Transarterial Radioembolization and Chemoembolization Combination Therapy of VX2 Liver Tumor.

In interventional treatment, materials are administered into the blood supply artery and directly delivered to tumors, offering proper scenarios for nanomedicine potential clinical applications. Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) are effective treatment methods for hepatocellular carcinoma (HCC), but postoperative residual tumor may result in intrahepatic recurrence and distant metastasis. The combination therapy of TACE and TARE based on multifunctional nanoparticles (NPs) is expected to overcome the drug resistance in hypoxic tumors and improve the therapeutic effect. Herein, BaGdF5 NPs are synthesized and then coated with polydopamine (PDA), conjugated with the chemotherapeuticdrug cis-diamminedichloride platinum (CDDP), radio-labeled with therapeutic radionuclide 131 I, yielding 131 I-BaGdF5 @PDA-CDDP NPs. The in vitro anti-cancer effects of 131 I-BaGdF5 @PDA-CDDP NPs are confirmed using CCK-8 and γ-H2AX assays in Huh7 cells. Mixed with Lipiodol, 131 I-BaGdF5 @PDA-CDDP NPs are injected into the hepatic artery via a microcatheter to realize the TACE and TARE combination therapy in a rabbit VX2 liver tumor model. The results indicate that glucose metabolism is clearly decreasedbased on 18 F-FDG PET imaging and the apoptosis of tumor cells is increased. Furthermore, 131 I and BaGdF5 NPs can be used for SPECT imaging and CT/MR imaging respectively, facilitating real-time monitoring of the in vivo biodistribution of 131 I-BaGdF5 @PDA-CDDP NPs.

The function of MSP-activated γδT cells in hepatocellular carcinoma

Immunotherapeutic strategies targeting γδT cells are now recognized as a promising treatment method for hepatocellular carcinoma (HCC). To date, no specific antigen or antigenic epitope recognized by γδT cells has been identified, limiting their application in the field of HCC treatment. Previously, we used an established screening strategy to identify a novel HCC protein antigen recognized by γδT cells called MSP. In this study, we explored the function of MSP activated-γδT cells in HCC. Results demonstrated that the proportions of γδT cells in the peripheral blood of HCC patients and the level of IFN-γ in the serum were higher than in healthy controls. We also determined that γδT cells can bind MSP protein. MSP-activated γδT cells were shown to contain a specific CDR3δ2 sequence that supports the recognition of MSP by γδT cells. We determined that MSP is highly expressed in HCC, MSP-activated γδT cells in the peripheral blood of HCC patients express co-stimulatory molecules, and MSP-activated γδT cells directly killed HCC cells. In conclusion, we demonstrated that the novel protein ligand MSP activated γδT cells, leading to the killing of HCC cells through direct and indirect mechanisms. These findings could provide a potential new target for the clinical diagnosis and treatment of HCC and a foundation for clinical treatment strategies in HCC.

Treatment strategy for hepatocellular carcinoma recurrence in the transplant era: Focusing on the Japan criteria.

To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria. The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging. Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging. Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.

Effects of Glycolysis-Related Genes on Prognosis and the Tumor Microenvironment of Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. Current treatment methods for hepatocellular carcinoma have many disadvantages; thus, it is urgent to improve the efficacy of these therapies. Glycolysis is critical in the occurrence and development of tumors. However, survival and prognosis biomarkers related to glycolysis in HCC patients remain to be fully identified. Methods: Glycolysis-related genes (GRGs) were downloaded from “The Molecular Signatures Database” (MSigDB), and the mRNA expression profiles and clinical information of HCC patients were obtained from TCGA. Consensus clustering was performed to classify the HCC patients into two subgroups. We used the least absolute shrinkage and selection operator (LASSO) regression analysis to construct the risk signature model. Kaplan–Meier (K-M) survival analysis was performed to evaluate the prognostic significance of the risk model, and the receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy. The independent prediction ability of the risk model was validated by univariate and multivariate Cox regression analyses. The differences of immune infiltrates and relevant oncogenic signaling between different risk groups were compared. Finally, biological experiments were performed to explore the functions of screened genes. Results: HCC patients were classified into two subgroups, according to the expression of prognostic-related GRGs. Almost all GRGs categorized in cluster 2 showed upregulated expressions, whereas GRGs in cluster 1 conferred survival advantages. GSEA identified a positive correlation between cluster 2 and the glycolysis process. Ten genes were selected for risk signature construction. Patients were assigned to high-risk and low-risk groups based on the median risk score, and K-M survival analysis indicated that the high-risk group had a shorter survival time. Additionally, the risk gene signature can partially affect immune infiltrates within the HCC microenvironment, and many oncogenic pathways were enriched in the high-risk group, including glycolysis, hypoxia, and DNA repair. Finally, in vitro knockdown of ME1 suppressed proliferation, migration, and invasion of hepatocellular carcinoma cells. Conclusion: In our study, we successfully constructed and verified a novel glycolysis-related risk signature for HCC prognosis prediction, which is meaningful for classifying HCC patients and offers potential targets for the treatment of hepatocellular carcinoma.

Metabolomics and integrated network pharmacology analysis reveal SNKAF decoction suppresses cell proliferation and induced cell apoptisis in hepatocellular carcinoma via PI3K/Akt/P53/FoxO signaling axis

BackgroundThere is no comprehensive treatment method for hepatocellular carcinoma (HCC); hence, research and development are still focused on systemic therapies, including drugs. Sinikangai fang (SNKAF) decoction, a classic Chinese herbal prescription, has been widely used to treat liver cancer. However, there is no research on its core active component and target.MethodsMouse models were established to measure the anticancer effect of SNKAF decoction on HCC. Further, we investigated the effect of SNKAF decoction on inhibition of hepatoma cells proliferation using cell viability, cloning and invasion assays in vitro. The components of SNKAF were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and TCM@Taiwan database. Metabolomic analysis was used to identify the potential genes and pathways in HCC treated with SNKAF decoction. Then, the expression of phosphoinositide 3-kinase (PI3K), Akt, P53, FoxO proteins of the potential signal pathways were detected using Western blot.ResultsThe animal experiments showed that SNKAF decoction inhibited tumor growth (P < 0.05) and induced no weight loss in the mice. In vitro data showed that HCCLM3 and MHCC97H cell proliferation was inhibited by SNKAF serum in a time- and concentration dependent manner. Further combined analysis network pharmacology with metabonomics showed that 217 target genes overlapped. The core target genes included BCL2, MCL1, Myc, PTEN, gsk3b, CASP9, CREB1, MDM2, pt53 and CCND1. Cancer-associated pathways were largely involved in SNKAF mechanisms, including P53, FoxO, and PI3K/Akt signaling pathways, which are closely related to induced-tumor cell apoptosis. In addition, Western bolt verified that 10% SNKAF serum significantly affected the main proteins of PI3K/Akt/P53/FoxO signaling pathway in both cell lines.ConclusionSNKAF decoction-containing serum inhibited HCCLM3 and MHCC97H cell proliferation, migration, invasion, and induced-tumor cell apoptosis in-vivo. We confirmed that SNKAF decoction is a promising alternative treatments for HCC patients.

Activation of p53 After Irradiation Impairs the Regenerative Capacity of the Mouse Liver.

Radiation therapy is one of the treatment methods for hepatocellular carcinoma. However, radiation tolerance of the liver is low, and the detailed effect of radiation on liver regeneration has not been clarified. C57BL/6J mice or hepatocyte‐specific p53 knockout (KO) mice (albumin [Alb]‐Cre Trp53flox/flox ) were irradiated with a single fraction of 10 Gy localized to the upper abdomen. We performed 70% partial hepatectomy (PHx) 24 hours after irradiation. Liver regeneration was assessed by proliferation cell nuclear antigen (PCNA)‐ and Ki‐67‐positive hepatocyte ratios and liver‐to‐body weight ratio after PHx. To establish a fibrosis model, CCl4 was orally administered for 8 weeks. The murine hepatocyte cell line BNL CL.2 (CL2) was irradiated with 10 Gy. Irradiation activated p53, induced downstream p21 in the liver, and delayed liver regeneration after PHx. While PHx increased hepatocyte growth factor (HGF) levels and activated Met with or without irradiation in the regenerative liver, it activated Akt and extracellular kinase 1 and 2 (Erk 1/2) less in irradiated mice than in nonirradiated mice. In CL2 cells cultured with HGF, irradiation suppressed cell growth by decreasing phosphorylated Akt and Erk 1/2 levels, which was abolished by small interfering RNA‐mediated p53 knockdown but not by p21 knockdown. Hepatocyte‐specific knockout of p53 in mice abolished the irradiation‐induced suppression of both liver regeneration and Akt and Erk 1/2 activation after PHx. In the fibrotic mouse model, the survival rate after PHx of irradiated p53 KO mice was higher than that of wild‐type mice. Conclusion: p53 but not p21 is involved in the impaired regenerative ability of the irradiated liver.

Recent update on comprehensive therapy for advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The treatment methods for HCC are diverse, mainly including surgical resection, ablation, and liver transplantation. The curative effect can be achieved only for early stage HCC, and it is easy to recur and metastasize after surgery, with a 5-year recurrence rate as high as 70%. Most patients with HCC are in the middle and advanced stage at the time of diagnosis and lose the chance of surgical resection. In recent years, with the in-depth study of the pathogenesis of HCC and the progress of medical science and technology, the systemic treatment of advanced HCC has made a breakthrough. At present, multidisciplinary comprehensive treatment including targeted therapy and immunotherapy has become an effective strategy and inevitable trend for the treatment of advanced HCC. Combined therapy has greatly improved the prognosis of HCC patients and opened up a new milestone in the treatment of this malignancy. In this article, we focus on the treatment progress of advanced HCC to further guide clinical practice.

CaCO3 -Encapuslated Microspheres for Enhanced Transhepatic Arterial Embolization Treatment of Hepatocellular Carcinoma.

Transcatheter arterial embolization (TAE) is an extensively applied treatment method for hepatocellular carcinoma (HCC). However, the worsened tumor microenvironment (TME, e.g., reduced pH post-TAE) may result in unsatisfactory therapeutic outcome. Herein, a new kind of embolic agent, calcium carbonate encapsulated alginate microspheres (CaCO3 -ALG MSs) are synthesized. Such CaCO3 -ALG MSs are able to neutralize the tumor pH owing to the reaction of CaCO3 with protons, which would not affect the overall morphology of microspheres after decomposition of CaCO3 . TAE treatment with CaCO3 -ALG MSs is then conducted in an orthotopic rat liver cancer model. 18 F-Fluorodeoxyglucose micropositron emission tomography/computed tomography imaging is conducted post-TAE and discovered that intra-arterial injection of CaCO3 -ALG MSs shows obvious enhanced therapeutic outcome compared to the same treatment with bare ALG MSs or the clinically used lipiodol. Further studies including analysis of immune cells in tumors, cytokine assays, and bioinformatics analysis all verify the reverse of immunosuppressive TME toward a more immunosupportive one after TAE with CaCO3 -ALG MSs. The research not only presents a new CaCO3 -containing embolic agent for enhanced TAE treatment of HCC but also highlights a clinically meaningful approach to improve cancer treatment via tumor pH neutralization.

Effect and Molecular Mechanisms of Jiedu Recipe on Hypoxia-Induced Angiogenesis after Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma.

Transcatheter arterial chemoembolization (TACE) is one of the effective treatment methods for hepatocellular carcinoma (HCC) in middle and late phases. However, TACE-induced hypoxia may promote the angiogenesis and section of some cytokines, such as IL-8, and, thereby, lead to tumor metastasis. Therefore, we investigated the effect of Jiedu Recipe (JR), which has been demonstrated as an effective Traditional Chinese Medicine (TCM) recipe on HCC, on TACE-induced cytokines upregulation and hypoxia-induced angiogenesis. A total of 88 hepatocellular carcinoma (HCC) patients treated with TACE were enrolled and divided into a JR group or control group. TACE induced significant increases of neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), IL-1β, IL-2R, IL-6, and IL-8. JR treatment significantly inhibited the elevation of IL-8 compared with control. In vitro, JR significantly inhibited the hypoxia-induced overexpression of IL-8, HIF-1α, and VEGF mRNA in Huh 7 cells. ELISA assay demonstrated the effect of JR on IL-8 expression. Both hypoxia and IL-8 may promote angiogenesis which was suppressed by JR. Western blot showed that IL-8 upregulated the expression of phosphorylation of AKT, ERK, NF-κB, and VEGFR, which were inhibited by JR. On the other hand, effects of IL-8 on the increase of p-AKT and p-ERK were also blocked by LY294002 and U0126, respectively. In conclusion, our results indicated that JR may inhibit hypoxia-induced angiogenesis through suppressing IL-8/HIF-1α/PI3K and MAPK/ERK pathways after TACE in HCC patients.

Safety and efficacy of percutaneous radiofrequency ablation for hepatocellular carcinoma patients with haemophilia.

This study aimed to evaluate the safety and efficacy of RFA for HCC in haemophilia patients. From July 2008 to June 2019, 217 patients with HCC underwent 300 RFA sessions. Of these, 18 sessions were performed in ten haemophilia patients (H group) and 282 in 207 non-haemophilia patients (NH group). The patients' characteristics, incidence of haemorrhagic complications and rates of local tumour recurrence were compared between the groups. A majority of the haemophilia patients received clotting factor concentrate replacement therapy before and after RFA treatment, with the aim of reaching a plasma clotting factor level of higher than 60%-80%. Twelve haemorrhagic complications were observed in the NH group (4.2%; 12/282). Major bleeding requiring control procedures was observed in two patients and minor bleeding with careful observation was noted in ten patients. No bleeding complications were observed in the H group (0/18). There were no significant differences in the 5-year local tumour recurrence rates after RFA treatment between the groups (35.0% in the H group and 32.1% in the NH group). RFA could be an effective and a safe method for HCC treatment in patients with haemophilia.

What Should Be the Rules for Downstaging for Hepatocellular Carcinoma?

Liver transplantation remains the main curative treatment method for hepatocellular carcinoma. There are several criteria for hepatocellular carcinoma to be eligible for liver transplantation, and it depends on main transplantation centers worldwide. Locoregional treatments and downstaging protocols are used for either to achieve these criteria or to prevent drop outs on the transplant waiting lists. But who can benefit from these bridging therapies effectively for the main purpose of curative treatment? Main contraindications are known for locoregional treatments like cirrhosis or low hepatic function, total main portal vein occlusion, and extrahepatic metastasis. HCCs, which are confined to liver but have high tumor burden, remains the main controversial issue. On this aspect, we reviewed the literature for downstaging protocols for hepatocellular carcinoma with their effect on survival and recurrence rates after liver transplantation. Although candidates for downstaging is still controversial, with the absence of main contraindications, LRT can be applied to selected HCCs, which have a certain degree of tumor burden.

Optimal Localization of a Novel Shifted 1T-Ring Based Microwave Ablation Probe in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most dangerous, and fatal cancers. Thermal ablation proved its power as the best treatment method for HCC. In microwave thermal ablation, microwave probes are used to generate electromagnetic waves (EMW) at microwave (MW) frequency 2.45GHz. In this paper, the design/model of a novel microwave ablation probe, namely a single slot with a shifted 1T-ring probe is presented for HCC therapy. A Finite Element Method (FEM) is employed to model the probe and the hepatic tumor liver tissues. The relation between the tip of probe position and the center of the hepatic tumor was studied to determine the best probe location at which a minimum MW power is required to ablate the entire tumor tissues with the smallest damage in the nearby healthy tissues to the tumor. The results indicated that the ablated part of the tissues varies depending on the MW probe type, the amount of used power, the location of the probe, and the exposure time. Hepatic tumors' diameters from 2-5cm were studied. It was shown that the proposed SSS 1T-ring (single slot with shifted 1T-ring) probe provided the best ablation performance when the probe's tip placed below the tumor's center by 11 mm, which achieved 100% damage in the tumor tissues using 6 W power for 10 minutes. When the probe's tip is located at the center of the tumor, the ablation rate was 73.45% in the tumor tissues under the same conditions.

The long noncoding RNA AK002107 negatively modulates miR-140-5p and targets TGFBR1 to induce epithelial-mesenchymal transition in hepatocellular carcinoma.

The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tissues was identified using microarrays, and the correlation between the expression of lncRNA AK002107 and the clinical prognosis of HCC was analyzed. We investigated the role of lncRNA AK002107 in HCC tumor biology in vitro using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT), colony formation, and Matrigel invasion assays and in vivo by assessing the growth of xenografted HCC tumors. The potential microRNAs that interact with lncRNA AK002107 were identified using online tools and were verified using PCR and luciferase reporter assay. The levels of TGFBR1, E‐cadherin, and vimentin were determined using western blot assays. We then further investigated the correlation between expression of lncRNA AK002107 with miR‐140‐5p and TGFBR1 expression in HCC tissues. The expression of lncRNA AK002107 is frequently upregulated in HCC samples and cell lines. Patients with HCC who have elevated lncRNA AK002107 expression exhibit poorer overall survival and disease‐free survival. Silencing lncRNA AK002107 expression significantly inhibited HCC cell proliferation, colony formation, and invasion both in vitro and in vivo. Furthermore, lncRNA AK002107 directly binds to miR‐140‐5p and significantly inhibits miR‐140‐5p expression. The functions of lncRNA AK002107 in cell growth and tumor invasion are mediated via miR‐140‐5p. lncRNA AK002107 upregulated TGFBR1 expression and then induced epithelial–mesenchymal transition (EMT) by inhibiting miR‐140‐5p expression. The expression of lncRNA AK002107 inversely correlated with miR‐140‐5p expression and positively correlated with TGFBR1 expression in HCC tissues. In summary, lncRNA AK002107 functions as an oncogene in tumors by inhibiting miR‐140‐5p, targeting TGFBR1, and then inducing EMT. The lncRNA AK002107/miR‐140‐5p/TGFBR1/EMT regulatory network may be a valuable target for the development of novel diagnostic and treatment methods for HCC.

Innovative treatment for hepatocellular carcinoma (HCC).

Indocyanine green (ICG) is not new in the field of liver surgery. Early studies performed in the 1980s and 1990s revealed the value of the ICG clearance test in predicting post-hepatectomy morbidity and mortality. ICG clearance and retention tests are crucial for determining precise liver function before liver surgery and offer several benefits for safe surgery. Whereas ICG is well-known and has long history in medicine, recent progress in infrared light technology over the last decade has highlighted another feature of ICG. For example, ICG fluorescence-guided surgery may change the next generation of liver surgery. In the near future, ICG with near-infrared (NIR) light photodynamic therapy (PDT) is expected to become a new treatment method for hepatocellular carcinoma (HCC). Furthermore, several aspects of the mechanisms of ICG accumulation in HCC cells have been revealed by important basic research studies. New imaging technologies and mechanistic findings keep ICG in the spotlight. In this article, we review three recently described topics of ICG which may contribute to the development of innovative and new treatments method for HCC, fluorescence-guided surgery, mechanism of ICG accumulation in HCC cells, PDT for HCC.

陽子線による放射線性十二指腸炎からの出血に対してアルゴンプラズマ凝固法が有用であった1例

Proton beam radiation is an effective treatment method for hepatocellular carcinoma. Radiation-induced duodenitis with severe hemorrhage is rare side effect by proton beam therapy. We report a case of hemorrhagic duodenitis caused by proton beam therapy for hepatocellular carcinoma, which was treated successfully with APC. A 65-year-old man, who had liver cirrhosis due to hepatitis C virus, was diagnosed hepatocellular carcinoma of right anterior segment. He received proton beam radiation. Three months later, he suffered anemia and hematochezia. Hemorrhagic duodenitis caused by proton beam radiation was found. We performed APC two times for hemorrhage from duodenitis. After the treatments, the patient had no relapse of hemorrhagic duodenitis for ten months until his death of hepatocellular carcinoma.

Knockdown of Myosin VI Inhibits Proliferation of Hepatocellular Carcinoma Cells In Vitro

Hepatocellular carcinoma is the primary malignancy of the liver and is the third leading cause of cancer-related death worldwide. Despite its severity, the treatment methods for hepatocellular carcinoma are limited due to poor prognosis. This study identified the short hairpin RNA-mediated silencing of myosin VI as a potential approach for the treatment of hepatocellular carcinoma. Firstly, the expression of myosin VI was analyzed in 57 hepatocellular carcinoma samples and 10 non-neoplastic samples by immunohistochemistry. The results demonstrated that myosin VI expression was much stronger in hepatocellular carcinoma tissues than in adjacent normal tissues. Myosin VI short hairpin RNA was then transduced into HepG2 and SMMC-7721 hepatocellular carcinoma cell lines, respectively, using a lentivirus delivery system. Knockdown of myosin VI led to a significant reduction in cell proliferation and colony-forming capacity, as well as a blockade of cell cycle progression. Moreover, an obvious decrease in PRAS40 phosphorylation and a concomitant increase in p38 phosphorylation were observed in myosin VI knockdown cells, which suggest that myosin VI silencing inhibits hepatocellular carcinoma cell growth invitro probably via inactivation of PRAS40 and activation of p38 mitogen-activated protein kinase-dependent signaling pathway. This study highlights the potential of myosin VI to be developed as a target for hepatocellular carcinoma therapy.

Targeting gene-virus-mediated manganese superoxide dismutase effectively suppresses tumor growth in hepatocellular carcinoma in vitro and in vivo.

Although the treatment methods for hepatocellular carcinoma (HCC) have made a great progress on patient survival rate and life quality, the HCC recurrence still is very high. To explore the novel effective anticancer strategies for HCC, the Cancer Targeting Gene-Viro-Therapy (CTGVT) strategy was applied through oncolytic virus-delivery antitumor gene. In this article, the dual-regulated oncolytic adenovirus Ad-AFP-E1A-E1B(Δ55kDa)-Mn-SOD (briefly named AD55-Mn-SOD) was constructed using a liver cancer-specific α-fetoprotein (AFP) promoter to control replication-essential E1A gene and deliver the novel tumor suppression gene Manganese superoxide dismutase (Mn-SOD). The results indicated that the constructed AD55-Mn-SOD exerted tumor-specific features, and induced dramatic cytotoxicity in HCC cells in vitro and suppress the HCC xenografted growth in nude mice. Moreover, the anticancer mechanism of AD55-Mn-SOD is due to the activation of caspase apoptotic pathway. These data suggested that AD55-Mn-SOD could become a potential anticancer agent for liver cancer.

340. Surgical treatment of cancer of the gallbladder

340. Surgical treatment of cancer of the gallbladder

A randomized single blind controlled trial of beads versus doxorubicin-eluting beads for arterial embolization of hepatocellular carcinoma (HCC).

143 Background: HAE using particles is a method of treatment for HCC. The added role of doxorubicin has never been fully understood biologically. To date, no study has demonstrated any difference in outcome using HAE versus trans-arterial chemoembolization (TACE). Methods: Patients (pts) with unresectable Okuda stage I or II HCC with adequate liver function were randomized to BB or LC loaded with 150 mg of doxorubicin. Pts were evaluated by multiphasic CT 2-3 weeks post-treatment. Progression by RECIST and/or evidence of ≤5% necrosis was considered treatment failure. Otherwise pts were followed with CT every 3 months until progression or death. Pts with either recurrent tumor or new tumor outside the treated area could be re-treated. The primary objective was response rate (RR) by RECIST. With 50 pts in each arm response rates can be estimated to within +/- 14%. Secondary objectives included assessing safety and tolerability, time to progression (TTP), progression free survival (PFS), and overall survival (OS). Quantification of tumor necrosis (TN) using CT volumetric data was correlated with outcome. Analyses were intention-to-treat. Results: Between December of 2007 and March of 2012, 101 pts were randomized, 51 to BB and 50 to LC. Demographics in the two groups were comparable: median age was 67, 77% were male and 81% were Okuda I. Median number of embolizations was 2 in both arms. There was no difference in adverse events, the most common being post-embolization syndrome of pain, fever, nausea, or vomiting (84% in both groups). There was no difference in RR: BB 11% vs LC 9% (p=0.58). Median TTP was not reached. 12 month TTP was 49 versus 56% (p=0.84), median PFS was 7 versus 9 (p=0.6), and OS 14 versus 16 months (p=0.7) for BB and LC respectively. Change in TN/tumor volume post treatment did not predict OS in either group (p=0.28). Conclusions: No difference in response was noted between pts treated with BB versus LC. Given the comparable safety profile, TTP, PFS and OS, HAE should be considered a reasonable and cost-effective therapeutic option and may be preferable to LC. Clinical trial information: NCT00539643.