Transforming growth factor-β signaling in tumor initiation, progression and therapy in breast cancer: an update

Zu, Xuyu; Zhang, Qinghai; Cao, Renxian; Liu, Jianghua; Zhong, Jing; Wen, Ge; Cao, Deliang

doi:10.1007/s00441-011-1225-3

Cited by 48 publications

(43 citation statements)

References 129 publications

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“…Zu et al (2011) provide an update on the current understanding of TGF-β signaling in cancer development and its progression focusing on breast cancer. They also review the current approaches of TGF-β signaling-targeted therapeutics for human malignancies.…”

Section: A Brief Overview Of Articles In This Special Issuementioning

confidence: 99%

TGF-β in aging and disease

et al. 2011

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Section: A Brief Overview Of Articles In This Special Issuementioning

confidence: 99%

TGF-β in aging and disease

et al. 2011

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“…Previous literature indicates a dual function for the TGF-β signaling genes (TGF-β1, TGF-βRI, RUNX1, RUNX2, and RUNX3) in breast carcinogenesis as promoters or suppressors depending on transcriptional influence of surrounding genes [9][10].…”

Section: Specific Aimsmentioning

confidence: 99%

“…There is increasing evidence that the TGF-β signaling pathway plays a dual role in cancer, acting as a tumor suppressor and promoter through a SMAD-mediated process [10]. To simplify the nomenclature, SMAD is used to describe homologs of both the Drosophila protein, mothers against decapentaplegic (MAD) and the Caenorhabditis elegans protein SMA (from gene sma for small body size) [89].…”

Section: Tgf-β Signaling Pathway In Breast Cancermentioning

confidence: 99%

“…This pathway has been found to be the most commonly altered cellular signaling pathway in cancer, , and may suppress or promote tumors depending on the inactivity of core The most widely reported TGF-β1 SNPs are rs1982073 (T869C), located on exon 1, which results in a leucine to proline substitution at codon 10(Leu10Pro), and rs1800469 (C-509T) in the promoter region [10]. The variant allele of rs1982073 (C) has been found to be associated with increased serum and plasma concentrations of TGF-β1.…”

Section: Previous Literaturementioning

confidence: 99%

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TGF-B signaling pathway, ER-a and the heterogeneity of breast cancer risk among hispanic and non-hispanic white women.

Boone¹

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“…Extensive efforts have been made to investigate the role of TGFβ signalling in the development and progression of cancer and to develop drugs targeting the TGFβ signalling pathway for a number of cancer types, including breast cancer [154,[158][159][160]. The prognostic value of the components of TGFβ pathway have also been explored in breast cancer, though conflicting results have been noted [161][162][163][164].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of ascorbate to cancer cells: mathematical modelling, mechanisms and clinical implications

Chen¹

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Studies over the last few decades provided supportive evidence for further research on the use of intravenous administration of high-dose ascorbate (0.5 -1.5 grams per kilogram of body weight) in cancer treatment. Although intravenous ascorbate showed limited anticancer activity in the recent clinical trials, its potential beneficial effects were noted, such as improvement in quality of life, reduction of chemotherapy-associated toxicity, reduction of inflammation and stabilization of cancer progression. These observations were in agreement with the outcomes of three cancer patients who declined chemotherapy and received intravenous ascorbate as an alternative in a preliminary clinical case study (Chapter 4). It was commonly accepted that the cytotoxicity of ascorbate was mediated by hydrogen peroxide (H2O2). However, our analysis and interpretation of the published results were not consistent with this being the sole mechanism of cytotoxicity, and an additional dehydroascorbate-mediated mechanism was proposed in this thesis (Chapter 1).In order to have a holistic understanding of the differential effects of ascorbate treatment in in vitro, animal and human studies, the treatment-induced changes in the intracellular H2O2 concentrations of the targeted cells should be compared. However, precise measurement of intracellular H2O2concentrations in vivo is difficult. In Chapter 2, a mathematical model was established for estimating the extracellular and intracellular H2O2 concentrations in a biological system that was challenged with H2O2 and/or an agent that could induce H2O2 production (such as ascorbate). Simulation of the mathematical model was carried out with the values of variables estimated from the published scientific literature and the experimental data obtained from this study. Several predictions were made and validated with the experimental results. One simulation predicted a limited increase of intracellular H2O2 concentration in a typical intravenous ascorbate treatment, which should be insufficient to induce cell death in tumours. The mathematical model also provided methods for estimating intrinsic intracellular H2O2 production rate and intracellular H2O2 concentration based on extracellular H2O2 concentration and other cell-dependent parameters, which were easier to be obtained with the current experimental methods.In Chapter 3, it was demonstrated in vitro that the cytotoxicity of ascorbate was mediated by both H2O2 and dehydroascorbate (DHA). The associations between the responses of cells to ascorbate (0 -30 mM) and some extracellular, cellular and molecular variables, such as cell culture medium, serum, glucose, pyruvate, cell cycle, cell volume and the expression and activities of H2O2 ii decomposing enzymes catalase and glutathione peroxidase, were investigated. Pyruvate but not glucose showed protective effect on cells in DHA treatment. Increased oxygen reactive species (ROS) levels in the DHA-treated cells was observed. These results supported our hypothesis that DHA might be able t...

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Transforming growth factor-β signaling in tumor initiation, progression and therapy in breast cancer: an update

Cited by 48 publications

References 129 publications

TGF-β in aging and disease

TGF-β in aging and disease

TGF-B signaling pathway, ER-a and the heterogeneity of breast cancer risk among hispanic and non-hispanic white women.

Cytotoxicity of ascorbate to cancer cells: mathematical modelling, mechanisms and clinical implications

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