Adenoviral p53 gene therapy in head and neck squamous cell carcinoma cell lines

Higuchi, Yuzuru; Asaumi, Jun Ichi; Murakami, Jun; Wakasa, Toru; Inoue, Tetsuyoshi; Kuroda, Masahiro; Shibuya, Koichi; Shigehara, Hiroshi; Kawasaki, Shoji; Fukui, Kiichi; Kishi, Kanji; Hiraki, Yoshio

doi:10.3892/or.9.6.1233

Cited by 12 publications

(11 citation statements)

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“…Efforts have been made to combine p53-mediated gene therapy with chemotherapy 109 and radiotherapy. 52,57 DNAdamage induced by chemotherapy or radiotherapy may create a microenvironment favorable for exogenous p53 stabilization and activation. Development of more stable or active p53 variants are future directions for effective restoration of p53 functions.…”

Section: Restoring and Enhancing P53 Function For Cancer Therapymentioning

confidence: 99%

Restoring p53-Dependent Tumor Suppression

Wang¹,

Rastinejad²,

El‐Deiry³

2003

Cancer Biology & Therapy

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ABSTRACTp53 represents an ideal target for anti-cancer drug design, because p53 is mutated in more than half of human tumors. Most of the remaining tumors, although carrying wild-type p53, have defects in the p53-mediated apoptotic pathway. Activation of p53 activity by either chemotherapy or radiotherapy induces p53-dependent apoptosis in tumor cells with wild-type p53. Supplying exogenous wild-type p53 in cancer cells by gene delivery is effective in suppressing tumor growth of both mutant and wild-type p53-containing tumors. Blockage of p53 degradation pathways either by overexpression of ARF or interruption of MDM2:p53 interaction is effective in inducing p53 triggered tumor cell death. Since unlike most other tumor suppressor genes, mutant p53 is over expressed in tumor cells, a promising approach involves restoring tumor-suppressing function to mutant p53.

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Section: Restoring and Enhancing P53 Function For Cancer Therapymentioning

confidence: 99%

Restoring p53-Dependent Tumor Suppression

Wang¹,

Rastinejad²,

El‐Deiry³

2003

Cancer Biology & Therapy

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“…rAd-p53 shared a high sensitivity toward tumor cells, and by intratumor injection, wild-type p53 could be successfully transduced and perform multiple antitumor actions (14,27,28). Introduction of rAd-p53 into eight different types of carcinoma of head and neck could induce significant cell growth inhibition in 14.5% to 47% cells (29). It has been shown by many preclinical trials that rAd-p53 treatment could induce cell apoptosis of different degrees in various kinds of malignant tumor cells (30)(31)(32), and this effect was not associated with p53 gene condition of the tumor cells (32).…”

Section: Discussionmentioning

confidence: 99%

In vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Oral Leukoplakia

Zhang

et al. 2009

Clinical Cancer Research

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Purpose: Oral leukoplakia is a well-recognized precancerous lesion of squamous cell carcinoma. When accompanied with abnormal p53 expression, it suffered a higher risk of canceration. The present study was carried out to test whether the recombinant human adenovirus-p53 could introduce wild-type p53 gene to oral leukoplakia cells and induce cell cycle arrest and apoptosis. Experimental Design: We select p53(-) oral dysplastic keratinocyte POE-9n, to observe the growth inhibition, cell cycle change, apoptosis-induced effects, and elaborate the corresponding molecular mechanism of recombinant adenovirus-p53 on POE-9n cells. Meanwhile, we evaluate the feasibility, safety, and biological activity of multipoints intraepithelial injections of recombinant adenovirus-p53 in 22 patients with dysplastic oral leukoplakia. Results: Exogenous p53 could be successfully transduced into POE-9n cells by recombinant adenovirus-p53. The optimal infecting titer in this study was multiplicity of infection (MOI) = 100. Recombinant adenovirus-p53 could strongly inhibit cell proliferation, induce apoptosis, and arrest cell cycle in stage G 1 in POE-9n cells by inducing p21 CIP/WAF and downregulating bcl-2 expression. In the posttreatment patients, p53 protein and p21 CIP/WAF protein expression were significantly enhanced, yet bcl-2 protein presented low expression. Sixteen patients showed clinical response to the treatment, and 14 patients showed obvious histopathologic improvement. Conclusion: Intraepithelial injections of recombinant human adenovirus-p53 were safe, feasible, and biologically active for patients with dysplastic oral leukoplakia. (Clin Cancer Res 2009;15(21):6724-31)

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“…It is necessary to introduce a gene exclusively into cancer cells in order to ensure its beneficial effect. It is not sufficient to infect cancer cells, though the method of infecting cells with a gene by a virus vector is often adopted (5). The discovery of materials that bind specifically to cancer cells, and that can thus be used in cell-specific gene or drug delivery, is crucial for improved cancer diagnosis and therapy (16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…We have also tried to establish a conservative treatments that combine radiotherapy, chemotherapy, thermotherapy, immunotherapy, and gene therapy in oral cancer (1)(2)(3)(4)(5)(6)(7). Those studies reported on the usefulness of wild-type p53-bearing adenovirus vectors in a combination of radiotherapy, thermotherapy, and thermoradiotherapy (therapy combining hyperthermia with radiotherapy) to treat cell lines of human oral squamous cell carcinoma (SCC) and salivary gland adenocarcinoma (1,(3)(4)(5). However, to clinically apply the wild-type p53-bearing adenovirus vector to the treatment of human oral cancer, several problems must be solved.…”

Section: Introductionmentioning

confidence: 99%

Novel cell-surface peptides specific to human oral squamous cell carcinoma using an E. coli peptide display library

Kawai

Asaumi²,

Murakami³

et al. 2007

Oncol Rep

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Abstract. We attempted to find a specific antigen of oral squamous cell carcinoma (SCC) cells that could be safely applied to gene therapy in the conservative clinical treatment of oral cancer. We performed subtraction using normal human keratinocyte cells, followed by selection using four oral SCC cell lines. We isolated three clones from poorly differentiated SCC cells and four from well-differentiated SCC cells. These seven clones adsorbed to the oral SCC cells at rates 10-100 times those of normal human keratinocyte cells. The three clones from the poorly differentiated SCC cells showed the same peptide sequence (LAPRTHP). Of the four clones from the well-differentiated SCC cells, three showed the same peptide sequence (FGTLPGT) and the fourth showed a different one (VTPNSTP). Each peptide sequence may recognize the material that exists specifically on the oral SCC cell cortex. We can expect applications not only for tumortargeting treatment using a gene therapy virus vector but also for diagnosis using, as a tumor marker, the peculiar SCC surface material that these peptides recognize.

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Adenoviral p53 gene therapy in head and neck squamous cell carcinoma cell lines

Cited by 12 publications

References 0 publications

Restoring p53-Dependent Tumor Suppression

Restoring p53-Dependent Tumor Suppression

In vitro and Clinical Studies of Gene Therapy with Recombinant Human Adenovirus-p53 Injection for Oral Leukoplakia

Novel cell-surface peptides specific to human oral squamous cell carcinoma using an E. coli peptide display library

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