A phase I study of Adp53 (INGN 201; ADVEXIN) for patients with platinum- and paclitaxel-resistant epithelial ovarian cancer

Wolf, Judith K.; Bodurka, Diane C.; Gano, Jacalyn B.; Deavers, Michael T.; Ramondetta, Lois M.; Ramírez, Pedro T.; Levenback, Charles; Gershenson, David M.

doi:10.1016/j.ygyno.2004.05.041

Cited by 59 publications

(30 citation statements)

References 21 publications

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“…26 More recently, a phase I study of adenoviral p53 for patients with platinum-and paclitaxel-resistant epithelial ovarian cancer has been completed. 27 In conclusion, using established cell lines or animal models in the present study, the recombinant replication-incompetent adenovirus vector in which the suicide gene CD::UPP was expressed under the control of the MDR1 promoter mediated an efficient therapeutic gene expression and specific killing effect in human Taxol-resistant ovarian cancer. The results indicated that this system might contribute to the development of safer adenoviral gene therapy in chemoresistant ovarian cancer for use alone or in combination with anticancer drugs in the near future.…”

Section: © 2 0 0 7 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 71%

Gene therapy for ovarian cancer using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene directed by MDR1 promoter

Lu¹,

Wang²,

Xiao³

et al. 2007

Cancer Biology & Therapy

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Section: © 2 0 0 7 L a N D E S B I O S C I E N C E D O N O T D I S mentioning

confidence: 71%

Gene therapy for ovarian cancer using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene directed by MDR1 promoter

Lu¹,

Wang²,

Xiao³

et al. 2007

Cancer Biology & Therapy

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“…p53 gene therapy has been examined in multiple clinical trials with different experimental approaches for the treatment of a variety of cancers [4,5,6,7,8]. The results of those trials, however, have mostly been disappointing because of the inability to achieve adequate effectiveness to eradicate those tumors.…”

Section: Discussionmentioning

confidence: 99%

“…The p53 protein has the function to induce cell-cycle arrest and programmed cell death, or apoptosis. More recently, researchers have conducted several studies in which adenoviral mediated wild-type p53 gene therapy was used to treat certain human cancers [4,5,6,7,8]. In addition, our department has conducted a phase I/II study of Ad5CMV-p53 (INGN 201) [9] delivered via intratumoral administration in patients with surgically incurable and chemoradiation-resistant ESCC [10].…”

Section: Introductionmentioning

confidence: 99%

Combined Effects of p53 Gene Therapy and Leptomycin B in Human Esophageal Squamous Cell Carcinoma

Hoshino

Matsubara²,

Komatsu³

et al. 2008

Oncology

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Background: p53 gene therapy has been examined in several clinical trials, however, the results of those trials have mostly been unsatisfactory due to the low efficacy of this therapy. Leptomycin B (LMB) is an antibiotic originally isolated from Streptomyces that has the ability to inhibit the export of proteins containing a nuclear export signal from the nucleus to the cytoplasm. Currently, it has been shown that p53 protein has a nuclear export signal. In this study, we assessed whether LMB augments the transduced p53 gene effect. Methods: Antiproliferative effect of LMB was assessed in human esophageal squamous cancer cell lines. Accumulation of p53 protein into the nucleus by LMB was observed by fluorescence microscopy. The combined effect of p53 and LMB was evaluated in in vitro experiments. Results: LMB induced cell death in a dose-dependent manner and p53 drastically accumulated in the nucleus after LMB treatment. The combinatory treatment of p53 gene and LMB significantly increases the efficiency compared to either agent alone. Conclusions: Our findings suggest that LMB has a potent ability to augment the effect of the tumor suppressor p53 in esophageal squamous cancer cell lines and that it is a promising component in p53 gene therapy.

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“…To achieve this goal, a recombinant adenovirus encoding p53 has been developed (Jekimovs et al, 2014). The results from clinical trials with two of the adenovirus-mediated p53 (Ad-p53) cancer gene therapies, advexin (Senzer and Nemunaitis, 2009;Wolf et al, 2004) and SCH-58500 (Atencio et al, 2006;Buller et al, 2002), demonstrated the safety and feasibility of their administration. However, the anti-tumor efficacy of these therapies has been limited in some cancer patients.…”

Section: Tp53 Dysregulationmentioning

confidence: 99%

Genomic landscape of gastric cancer: molecular classification and potential targets

Guo

et al. 2016

Sci. China Life Sci.

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Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, RhoA-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future. gastric cancer, chromatin remodeling, RhoA, p53, receptor tyrosine kinase, DNA methylation Citation:

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A phase I study of Adp53 (INGN 201; ADVEXIN) for patients with platinum- and paclitaxel-resistant epithelial ovarian cancer

Cited by 59 publications

References 21 publications

Gene therapy for ovarian cancer using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene directed by MDR1 promoter

Gene therapy for ovarian cancer using adenovirus-mediated transfer of cytosine deaminase gene and uracil phosphoribosyltransferase gene directed by MDR1 promoter

Combined Effects of p53 Gene Therapy and Leptomycin B in Human Esophageal Squamous Cell Carcinoma

Genomic landscape of gastric cancer: molecular classification and potential targets

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