Antibody-Mediated p53 Protein Therapy Prevents Liver Metastasis<i>In vivo</i>

Hansen, James E.; Fischer, Laurice K.; Chan, Grace; Chang, Sophia S.; Baldwin, Scott; Aragon, Robert; Carter, Jacqueline J.; Lilly, Michael B.; Nishimura, Robert N.; Weisbart, Richard H.; Reeves, Mark E.

doi:10.1158/0008-5472.can-06-3783

Cited by 45 publications

(33 citation statements)

References 15 publications

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“…Mutation in the p53 tumor suppressor gene could be seen in about 50% of the human cancers and is one of the most frequently seen alterations in the malignant cells and the majority of the mutations are in the exons 5-8 (Horie et al, 2001;Park et al, 2002;Morita et al, 2008;Hansen et al, 2008;Parameswaran et al, 2010;Balta et al, 2012). In the thyroid gland, p53 mutations have been shown in 40-62% of undifferentiated carcinomas and 0-25% in well-differentiated carcinomas (Morita et al, 2008;Parameswaran et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathologic and Diagnostic Significance of p53 Protein Expression in Papillary Thyroid Carcinoma

Shin¹,

Kim²

2014

Asian Pacific Journal of Cancer Prevention

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Background: p53 protein expression has been detected immunohistochemically in papillary thyroid carcinoma(PTC). We investigated the relations between its expression and clinicopathologic features and its significance as a diagnostic marker. Materials and Methods: We compared and evaluated 93 patients in whom thyroidectomy with lymph node dissection had been performed to treat PTC for clinicopathologic significance and 102 patients with 23 papillary thyroid overt carcinomas (POC), 57 papillary thyroid microcarcinomas(PMC), 5 follicular adenomas (FA), 5 Hashimoto's thyroiditis (HT) and 12 nodular hyperplasias (NH) for significance as a diagnostic marker. Expression of p53 protein was evaluated immunohistochemically in sections of paraffinembedded tissue. Results: Statistical analysis showed significantly different expression of p53 in PTC versus other benign thyroid lesions (BTL).The diagnostic sensitivity and specificity were 85.0% and 72.7%, respectively. Overexpression of p53 protein was observed in 44 of the 93 PTC cases (47.3%), but no significant correlation between p53 protein overexpression and clinicopathologic features (age, size, multiplicity, lymph node metastasis, extrathyroidal extension and vascular invasion) was noted. Conclusions: p53 is valuable to distinguish PTC from other BTL, but there is no correlation between p53 protein overexpression and clinicopathologic features.

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Section: Discussionmentioning

confidence: 99%

“…Mutations in the p53 tumor suppressor gene are present in approximately 50% of all human cancers, and they represent the most common genetic changes in malignant cells (Horie et al, 2001;Moon et al, 2006;Zafon et al, 2007;Hansen et al, 2008;Morita et al, 2008;Kim et al, 2009;Parameswaran et al, 2010;Balta et al, 2012).…”

Section: Kyung Shin* Jeong Won Kimmentioning

confidence: 99%

Clinicopathologic and Diagnostic Significance of p53 Protein Expression in Papillary Thyroid Carcinoma

Shin¹,

Kim²

2014

Asian Pacific Journal of Cancer Prevention

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“…The mechanism of RDP-p53 induced cell death p53 gene is regarded as the ''guardian of the genome'', and encoding product p53 protein can inhibit or kill the tumor cells by various ways (Hansen et al, 2007;Yu et al, 2009;Yamada, 2013;Yan et al, 2012) including up-regulation of the expression of pro-apoptotic gene, down-regulation of the expression of anti-apoptotic gene for induction apoptosis, and prevention of cell cycle entry into M phase from G2 phase (Choi & Kim, 2009). In this study, to determine the anticancer mechanism of RDP-p53, the proteins were added into the media of SH-SY5Y cells for a certain time.…”

Section: Rdp-p53 Obviously Inhibited Sh-sy5y Cell Proliferationmentioning

confidence: 99%

A novel cell-permeable RDP-p53 fusion protein for specific inhibition on the growth of cancerous neural cells

Zhang

2015

Drug Delivery

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Objective: There is 25-35% mutation rate of p53 in cancerous neural cells and this rate reaches 70-76% in glioma cell line. Complement of wild-type p53 has become a potential strategy for protein therapy of cancerous neural cells. Here we investigated the feasibility of a novel RDP-p53 fusion protein for anti-proliferation of cancerous neural cell and the possible mechanism, which would provide an effective approach for targeted delivery of p53 protein to treat cancerous neural cells. Methods: The RDP-p53 fusion proteins are expressed in Escherichia coli, and they are labeled with FITC and rhodamine B by chemical modification. The fluorescence-labeled proteins are added to human hepatocellular carcinoma cells (HepG-2) and human neuroblastoma cells (SH-SY5Y) in order to investigate the possibility of RDP enhancing the cell uptake efficiency into neural cells as a cell-permeable carrier. The inhibitory effect of RDP-p53 on SH-SY5Y and human glioma cells (U251) was evaluated by MTT assay. Moreover, the anti-proliferation mechanism of RDP-p53 was determined by Apoptosis and Necrosis Assay Kit and flow cytometric analysis. Results:The results showed that RDP-p53 could enter SH-SY5Y cells with high efficiency and selectively inhibit the growth of cancerous neural cells, including SH-SY5Y and U251. Also, cell apoptosis pathway and cell-cycle arrest at the G2/M phase were associated with the inhibition mechanism of RDP-p53 according to the data of flow cytometric analysis. Conclusions: RDP-p53 could be a novel antitumor candidate for targeting treatment of cancerous neural cells.

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“…We previously identified a rare monoclonal anti-DNA antibody, 3E10, which penetrates living cells and localizes in the nucleus through an equilibrative nucleoside transporter without causing any apparent harm to the cell (2,3). 3E10 and its single-chain variable fragment (3E10 scFv) have been developed as an intracellular delivery system for macromolecules (4)(5)(6)(7)(8)(9). Notably, after localizing in the cell nucleus, 3E10 scFv is largely degraded within 4 hours, thus further minimizing any potential toxicity (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets

Weisbart

Gera

Chan

et al. 2012

Molecular Cancer Therapeutics

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The therapeutic use of antibodies is restricted by the limited access of antibodies to intracellular compartments. To overcome this limitation, we developed a cell-penetrating monoclonal antibody, mAb 3E10, as an intracellular delivery vehicle for the intracellular and intranuclear delivery of antibodies constructed as bispecific single-chain Fv fragments. Because MDM2 is an important target in cancer therapy, we selected monoclonal antibody (mAb) 3G5 for intracellular transport. mAb 3G5 binds MDM2 and blocks binding of MDM2 to p53. Here, we show that the resulting 3E10-3G5 bispecific antibody retains cell-penetrating and MDM2-binding activity, increases tumor p53 levels, and inhibits growth of MDM2-addicted tumors. The use of cell-penetrating bispecific antibodies in targeted molecular therapy will significantly broaden the spectrum of accessible intracellular targets and may have a profound impact in cancer therapy.

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Antibody-Mediated p53 Protein Therapy Prevents Liver MetastasisIn vivo

Cited by 45 publications

References 15 publications

Clinicopathologic and Diagnostic Significance of p53 Protein Expression in Papillary Thyroid Carcinoma

Clinicopathologic and Diagnostic Significance of p53 Protein Expression in Papillary Thyroid Carcinoma

A novel cell-permeable RDP-p53 fusion protein for specific inhibition on the growth of cancerous neural cells

A Cell-Penetrating Bispecific Antibody for Therapeutic Regulation of Intracellular Targets

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