Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene

Inoue, Akira; Narumi, Kunihiro; Matsubara, N.; Sugawara, Shun; Saijo, Yasuo; Satoh, Ken; Nukiwa, Toshihiro

doi:10.1016/s0304-3835(00)00480-8

Cited by 59 publications

(44 citation statements)

References 22 publications

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“…As a control vector, the expression vector for LacZ was used. Adenovirus carrying cDNA was propagated in HEK293 cells, purified by CsCl gradient centrifugation, and titered by serialdilution end point assay (23)(24)(25). The cells were incubated with 10 8 plaqueforming units/ml adenovirus in DMEM supplemented with 10% FCS for 1 h, the medium was removed, and the cells were incubated with the culture medium above.…”

Section: Methodsmentioning

confidence: 99%

Constitutive and Induced CD44 Shedding by ADAM-Like Proteases and Membrane-Type 1 Matrix Metalloproteinase

et al. 2004

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CD44 is a receptor for hyaluronan and mediates signaling that regulates complex cell behavior including cancer cell migration and invasion. Shedding of the extracellular portion of CD44 is the last step in the regulation of the molecule-releasing interaction between the ligand and cell. However, highly glycosylated forms of CD44 have hampered the identification of the exact cleavage sites for shedding and the responsible proteases. In this study, we found that expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) increased shedding of the 65-70 kDa CD44H (standard form) fragments and generated two additional smaller fragments. We purified the shed fragments and identified the cleaved sites by mass spectrometry. Specific antibodies that recognize the newly exposed COOH terminus by cleavage were prepared and used to analyze shedding at each site. Shedding of the 65-70 kDa fragments was inhibited by tissue inhibitor of metalloproteinase 3 (TIMP-3) but not by TIMP-1 and TIMP-2, suggesting involvement of a disintegrin and metalloproteinase (ADAM)-like proteases, although shedding is affected by MT1-MMP. Conversely, shedding of the two smaller fragments was inhibited by TIMP-2 and TIMP-3 but not TIMP-1, suggesting involvement of MT1-MMP itself. Shed fragments cleaved at these sites were also detected in human tumor tissues. Increased shedding at one of the MT1-MMP-sensitive sites was observed in the tumor compared with the surrounding normal tissue. However, no significant difference was observed with shedding by ADAM-like proteases. Thus, the cleavage sites for the shedding of CD44H were identified for the first time, and the results provide a basis for exploring the unknown biologic roles of shedding at different sites.

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Section: Methodsmentioning

confidence: 99%

Constitutive and Induced CD44 Shedding by ADAM-Like Proteases and Membrane-Type 1 Matrix Metalloproteinase

et al. 2004

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“…Gene therapy in which wild-type p53 gene is transferred into tumors that are deficient in functional p53 has shown a significant tumor suppressing efficacy both in lung cancer cell line and in animal systems (Inoue et al, 2000;Osaki et al, 2000;Kawabe et al, 2001). Roth et al(1996) firstly reported that in a clinical setting, the replacement of a tumor suppressor gene was shown to mediate tumor regression and, more importantly, vector-related toxicity was minimal.…”

Section: Discussionmentioning

confidence: 99%

“…Also, pregnant or nursing patients, patients with uncontrolled serious infections, and patients with acute or chronic respiratory distress were excluded for the enrollment. The p53 gene mutation was not required specially for enrolling because studies in vitro had proven that the p53 gene increased anti-tumor effect regardless of the cellular p53 status (Inoue et al, 2000;Kawabe et al, 2001). …”

Section: Enrollment Criteriamentioning

confidence: 99%

“…Over the past decade, many gene therapy approaches have been tested in vitro, in animal models or clinical trials (Osaki et al, 2000;Inoue et al, 2000;Kawabe et al, 2001). At the beginning of 2005, there were a total of 1020 clinical trials for gene therapy world wide (http://www.wiley.co.uk/genetherapy/ clinical), while over 60% of them were conducted in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

Guan

Liu

Zou

et al. 2009

J. Zhejiang Univ. Sci. B

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Abstract:Objective: In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene (rAd-p53) injection in patients with advanced non-small-cell lung cancer (NSCLC) in the combination with the therapy of bronchial arterial infusion (BAI). Methods: A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 (the combo group), while the remaining 39 were treated with only BAI (the control group). Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer Institute's Common Toxicity Criteria and response evaluation criteria in solid tumor (RECIST), respectively. Time to progression (TTP) and survival rates were also analyzed by Kaplan-Meier method. Results: In the combo group, 19 patients received a total of 49 injections of rAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia (P<0.05) but more arthralgia, fever, influenza-like symptom, and myalgia (P<0.05), compared with the control group. The overall response rates (complete response (CR)+partial response (PR)) were 47.3% and 38.4% for the combo group and the control group, respectively (P>0.05). Patients in the combo group had a longer TTP than those in the control group (a median 7.75 vs 5.5 months, P=0.018). However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, compared with 92.31%, 69.23%, and 38.83% in the control group (P=0.224). Conclusion: Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the quality of life and delayed the disease progression. A further study to better determine the efficacy of this combination therapy is warranted.

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“…About a half of human malignancies show loss of p53 functions, resulting in increased resistance to DNA-damaging agents (Shiraishi et al 2004). Transduction of tumors with Ad-p53 has demonstrated inhibition of the tumor growth and enhanced the susceptibility to anticancer agents (Blagosklonny et al 1998;Inoue et al 2000;Schuler et al 2001;Sah et al 2003;Schwartzenberg et al 2004;Wang et al 2006). Animal experiments also showed the therapeutic effects to various cancers by way of intratumoral injection and in combination with an anticancer agent or agents.…”

Section: Clinical Trials With Ad-p53mentioning

confidence: 99%

Gene medicine for cancer treatment: Commercially available medicine and accumulated clinical data in China

Tagawa¹

2008

DDDT

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Loss of p53 function compromises genetic homeostasis, which induces deregulated DNA replication, damages DNA, and subsequently results in increased resistance to anticancer agents. Pharmacological approaches using recombinant adenoviruses (Ad) have been developed to restore the p53 functions. Another approach for gene medicine is to modify Ad replication in a tumor-specifi c manner, which induces tumor cell death without damaging normal tissues in the vicinity. The Ad-derived gene medicines, Ad expressing the wild-type p53 gene and replication-competent Ad defective of the E1B-55kDa gene, have been tested for their clinical feasibility and became commercially available in China. These agents demonstrated their antitumor activities as a monotherapy and in combination with conventional chemotherapeutic agents. In this article, we summarize the outcomes of clinical trials in China, most of which have been published in domestic Chinese journals, and discuss potential directions of cancer gene therapy with these agents.

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Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene

Cited by 59 publications

References 22 publications

Constitutive and Induced CD44 Shedding by ADAM-Like Proteases and Membrane-Type 1 Matrix Metalloproteinase

Constitutive and Induced CD44 Shedding by ADAM-Like Proteases and Membrane-Type 1 Matrix Metalloproteinase

Adenovirus-mediated wild-type p53 gene transfer in combination with bronchial arterial infusion for treatment of advanced non-small-cell lung cancer, one year follow-up

Gene medicine for cancer treatment: Commercially available medicine and accumulated clinical data in China

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