<i>p</i>53 gene therapy‐based transarterial chemoembolization for unresectable hepatocellular carcinoma: A prospective cohort study

Shen, Ai; Liu, Shihong; Yu, Weiqian; Deng, Hejun; Li, Qingdong

doi:10.1111/jgh.13009

Cited by 15 publications

(17 citation statements)

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“…It was proved that H101 was able to efficiently infect and replicate in tumor cell lines in vitro [19] and in vivo [20], leading to observed tumor cell killing and growth inhibition. Some studies have evaluated the efficacy and safety of a transarterial infusion of H101 combined with TACE in patients with intermediate-advanced HCC [21, 22]. Some studies have examined the utility of available staging systems, such as the tumor-node-metastasis (TNM), the Cancer of the Liver Italian Program (CLIP) and the Barcelona Clinic Liver Cancer (BCLC) staging scores, for predicting the survival of patients undergoing TACE.…”

Section: Introductionmentioning

confidence: 99%

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101

Lin

2017

PLoS ONE

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BackgroundThe systemic inflammatory response plays an important role in cancer development and progression. An original inflammation-based staging system for predicting survival in patients undergoing transarterial chemoembolization (TACE) combined with recombinant human type-5 adenovirus H101 is not available. This study aimed to validate the prognostic value of inflammation scores for patients with hepatocellular carcinoma (HCC) who were treated with TACE combined with H101.MethodsThe data from 216 patients with HCC who underwent TACE combined with H101 from January 2007 to July 2015 were retrospectively collected, and the association of the inflammation scores with overall survival (OS) was analyzed. Univariate and multivariate analyses were performed to identify variables associated with OS. The prognostic value of the inflammation scores, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil/ platelet-to-lymphocyte ratio (NLR-PLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), prognostic index (PI), tumor-node-metastasis (TNM), Barcelona Clinic Liver Cancer (BCLC) and Cancer of the Liver Italian Program (CLIP) staging systems were analyzed and compared using the areas under the receiver operating characteristic curves (AUROCs).ResultsThe estimated 1-, 2-, and 3-year OS rates were 61.3%, 44.2%, and 40.5% for the entire study cohort, respectively; the median OS was 17 months. According to the multivariate Cox proportional hazards model, the pretreatment NLR, tumor diameter and pretreatment alpha-fetoprotein (AFP) levels were independent predictors of OS. The CLIP score had superior discriminative abilities compared with other staging systems, and the NLR-PLR score consistently displayed a higher AUROC value than the other inflammation-based prognostic scores. The combination of the NLR-PLR and CLIP scores exhibited a superior prognostic ability for OS compared to the NLR-PLR or CLIP scores alone.ConclusionsThe NLR-PLR score is a more powerful predictive system than the other inflammation-based scores for patients with HCC who were treated with TACE and H101. The predictive ability may be improved by utilizing a combination of the NLR-PLR and CLIP scores.

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Section: Introductionmentioning

confidence: 99%

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101

Lin

2017

PLoS ONE

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“…However, most HCC patients, who often have liver cirrhosis and chronic hepatitis B infection, have a low tolerance for treatment, poor rates of surgical resection, a tendency for postoperative HCC recurrence and metastasis, and unsatisfactory chemotherapy results. Therefore, new treatments such as gene therapy may be effective supplements to conventional treatments 5 .…”

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confidence: 99%

Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

Xue

Feng

Wang

et al. 2016

Sci Rep

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We developed a nanovector with double targeting properties for efficiently delivering the tumor suppressor gene RASSF1A specifically into hepatocellular carcinoma (HCC) cells by preparing galactosylated-carboxymethyl chitosan-magnetic iron oxide nanoparticles (Gal-CMCS-Fe3O4-NPs). After conjugating galactose and CMCS to the surface of Fe3O4-NPs, we observed that Gal-CMCS-Fe3O4-NPs were round with a relatively stable zeta potential of +6.5 mV and an mean hydrodynamic size of 40.1 ± 5.3 nm. Gal-CMCS-Fe3O4-NPs had strong DNA condensing power in pH 7 solution and were largely nontoxic. In vitro experiments demonstrated that Gal-CMCS-Fe3O4-NPs were highly selective for HCC cells and liver cells. In vivo experiments showed the specific accumulation of Gal-CMCS-Fe3O4-NPs in HCC tissue, especially with the aid of an external magnetic field. Nude mice with orthotopically transplanted HCC received an intravenous injection of the Gal-CMCS-Fe3O4-NPs/pcDNA3.1(+)RASSF1A compound and intraperitoneal injection of mitomycin and had an external magnetic field applied to the tumor area. These mice had the smallest tumors, largest percentage of TUNEL-positive cells, and highest caspase-3 expression levels in tumor tissue compared to other groups of treated mice. These results suggest the potential application of Gal-CMCS-Fe3O4-NPs for RASSF1A gene delivery for the treatment of HCC.

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“…46 , 47 H101 may be more effective for tumors in which p53 gene mutations or deletions are more frequent. 48 What is more, blood flow is abundant in HCC with a heavy tumor burden. 49 Higher H101 concentrations in vascular-rich areas where tumor cells grow faster may inhibit tumor cell growth in a timely and effective manner.…”

Section: Discussionmentioning

confidence: 99%

Increased Overall Survival and Decreased Cancer-Specific Mortality in Patients with Hepatocellular Carcinoma Treated by Transarterial Chemoembolization and Human Adenovirus Type-5 Combination Therapy: a Competing Risk Analysis

Zhang

Lin

2018

Journal of Gastrointestinal Surgery

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BackgroundIn analyzing cancer patient survival data, the problem of competing risks is often ignored. This study used a competing risk approach to evaluate the efficacy of recombinant human type-5 adenovirus (H101) in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE).MethodsIn this retrospective study, 476 patients were included. The cumulative probabilities of cancer-specific mortalities were analyzed by the Kaplan-Meier (KM) method and a competing risk model. Competing risk regression was used to assess the predictive factors for cumulative cancer-specific mortalities.ResultsTwo hundred thirty-eight HCC patients received combination TACE and H101 therapy, and another 238 HCC patients received TACE therapy alone. For patients in the TACE with H101 group, estimated 1-, 2-, and 3-year overall survival (OS) rates were 61.0, 40.0, and 31.5%, respectively, while for patients in the TACE group, the estimated 1-, 2-, and 3-year OS rates were 55.0, 33.4, and 22.3%, respectively. The 1-, 2-, and 3-year cancer-specific mortality rates for patients in the TACE with H101 group vs. the TACE group were 37.3 vs. 42.0%, 55.7 vs. 63.5%, and 61.9 vs. 74.7%, respectively. Multivariate competing risk analysis established that a combination of TACE and H101 therapy was an independent factor in decreasing cancer-specific mortality.ConclusionsCompared with TACE therapy, patients who were diagnosed with unresectable HCC treated with combined TACE and H101 therapy had increased OS and decreased cancer-specific mortality. The survival benefit was more obvious in patients with elevated AFP, absence of metastasis, single tumor, enlarged tumor, and HBsAg-positivity.

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p53 gene therapy‐based transarterial chemoembolization for unresectable hepatocellular carcinoma: A prospective cohort study

Abstract: rAd-p53-based TACE treatment strategy is effective and safe for treating unresectable HCC. Large-scale randomized clinical trials are needed to verify these results.

Cited by 15 publications

References 34 publications

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101

Inflammation scores predict the survival of patients with hepatocellular carcinoma who were treated with transarterial chemoembolization and recombinant human type-5 adenovirus H101

Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

Increased Overall Survival and Decreased Cancer-Specific Mortality in Patients with Hepatocellular Carcinoma Treated by Transarterial Chemoembolization and Human Adenovirus Type-5 Combination Therapy: a Competing Risk Analysis

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