Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma

Yang, Zhihui; Wang, Dong; Wang, Ge; Zhang, Qinhong; Liu, Jingmao; Peng, P.; Lu, Xiaohui

doi:10.1007/s00432-009-0701-6

Cited by 71 publications

(52 citation statements)

References 14 publications

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“…For example, Chen et al (26) demonstrated that p53-induced microRNA-107 inhibited brain tumor cell growth, which indicates that it serves as a tumor suppressor and thus, may be used as a target for glioma therapy. Additionally, Yang et al (27) suggested a combination of recombinant adenovirus-p53 (rAd-p53) with fractionated stereotactic radiotherapy (fSRT) is an effective and relatively safe method for the treatment of primary hepatocellular carcinoma (HCC) compared with fSRT monotherapy, indicating that rAd-p53 combined with fSRT may be preferred as a local method to treat primary HCC if the patients are unable to undergo surgery or refuse operation.…”

Section: Discussionmentioning

confidence: 99%

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

Liu

Yang

et al. 2017

Oncol Lett

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Abstract. Gliomas are the most common type of primary brain tumor in adults, where more than half of the cases are malignant, and the prognosis is poor. The early viral 1A (E1A) protein has been widely recognized to be essential for adenoviral replication and production of progeny virions in human cells, a process that is regulated by human telomerase reverse transcriptase. The p53 gene, as a tumor suppressor, regulates diverse cellular processes, including cell cycle arrest, cell autophagy, senescence and apoptosis. Dysfunction of the p53 pathways is common in malignant gliomas. Exogenous expression of p53 during adenovirus replication in human cancer cells may accelerate cell death and improve the release of early virus progeny. In the present study, a conditionally replicative adenovirus (CRAd) Ad-Tp-E1A-Gp-p53, which expressed functional p53 protein when replicating in cancer cells, was constructed. Next, the level of p53 expression in U251 cells was determined by western blot analysis, and the inhibitory effect of Ad-Tp-E1A-Gp-p53 on U251 cells was detected via an MTT assay. The results indicated that p53 expression was upregulated with an increase in the multiplicity of infection (MOI) of Ad-Tp-E1A-Gp-p53. Additionally, the inhibitory effects of Ad-Tp-E1A-Gp-p53 in different groups were significantly different (P<0.05), with the inhibition ratio of the experimental groups being higher, compared with the control group (P<0.05). Furthermore, the inhibition ratio increased with increases in the MOI of Ad-Tp-E1A-Gp-p53. Therefore, the expression of functional p53 and that of E1A may increase the potency of CRAd, and overexpression of p53 through CRAd is a promising approach to more effective treatments in a number of human cancer types.

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Section: Discussionmentioning

confidence: 99%

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

Liu

Yang

et al. 2017

Oncol Lett

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“…Therefore, a recombinant human adenovirus that expresses functional wild-type p53 has been approved by the Chinese government for the treatment of head and neck carcinoma (48)(49)(50). Treatments showed that antitumor efficacy was associated with the expression and activity of functional p53, and adverse effects were also significant (51)(52)(53)(54). Recently, pharmacologically activated wild-type p53 by small-molecule compound RITA is …”

Section: Current Strategies To Target the P53 Pathway In Tumor Metabomentioning

confidence: 99%

The Fundamental Role of the p53 Pathway in Tumor Metabolism and Its Implication in Tumor Therapy

Shen

Sun

et al. 2012

Clinical Cancer Research

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It is well established that the altered metabolism exhibited by cancer cells, including high rates of glycolysis, lactate production, and biosynthesis of lipids, nucleotides, and other macromolecules, and which may occur either as a consequence or as a cause of tumorigenesis, plays an essential role in cancer progression. Recently, the tumor suppressor p53 was found to play a central role in this process. Here, we review the role of p53 in modulating tumor metabolism. Specifically, we focus on the functions of p53 in regulating aerobic glycolysis, oxidative phosphorylation, the pentose phosphate pathway, fatty acid synthesis and oxidation, and glutamine metabolism, and we discuss the therapeutic strategy whereby p53 helps to prevent malignant progression.

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“…Despite the lack of randomized controlled trials, radiotherapy is becoming recognized as a potentially curative treatment option (13). Conformal radiotherapy (CRT) for HCC was reported to exert a significant effect (14)(15)(16), as was SBRT (17)(18)(19)(20). However, the number of studies on the application of CRT and SBRT for the treatment of huge HCCs is limited.…”

Section: Introductionmentioning

confidence: 99%

Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (≥10 cm) hepatocellular carcinomas: A clinical study

Zhong

Chen

2014

Molecular and Clinical Oncology

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Abstract. This study was conducted to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) for huge (≥10 cm) hepatocellular carcinomas (HCCs). Between May, 2006 and December, 2012, 72 patients with huge HCCs were treated by SBRT following incomplete TACE. The median total dose of 35.6 Gy was delivered over 12-14 days with a fractional dose of 2.6-3.0 Gy and 6 fractions per week. The patients were classified into those with tumor encapsulation (group A, n=33) and those without tumor encapsulation (group B, n=39). The clinical outcomes of tumor response, overall cumulative survival and toxicities/complications were retrospectively analyzed. Among the 72 patients, CR, PR, SD and PD were achieved in 6 (8.3%), 51 (70.8%), 9 (12.5%) and 6 patients (8.3%), respectively, within a median follow-up of 18 months. The objective response rate was 79.1%. The overall cumulative 1-, 3-and 5-year survival rates and the median survival time were 38, 12 and 3% and 12.2 months, respectively. In group A, the overall cumulative 1-, 3-and 5-year survival rates were 56, 21 and 6%, respectively, with a median survival of 19 months; in group B, the overall cumulative 1-, 3-and 5-year survival rates were 23, 4 and 0%, respectively, with a median survival of 10.8 months (P=0.023). The treatment was well tolerated, with no severe radiation-induced liver disease and no reported > grade 3 toxicity. Tumor encapsulation was found to be a significant prognostic factor for survival. In conclusion, the combination of SBRT and TACE was shown to be a safe and effective treatment option for patients with unresectable huge HCC.

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Clinical study of recombinant adenovirus-p53 combined with fractionated stereotactic radiotherapy for hepatocellular carcinoma

Cited by 71 publications

References 14 publications

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

A novel approach to glioma therapy using an oncolytic adenovirus with two specific promoters

The Fundamental Role of the p53 Pathway in Tumor Metabolism and Its Implication in Tumor Therapy

Stereotactic body radiotherapy combined with transarterial chemoembolization for huge (≥10 cm) hepatocellular carcinomas: A clinical study

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