Quantitative prediction of tumor response to neoadjuvant chemotherapy in breast cancer: novel marker genes and prediction model using the expression levels

Sano, Hiroshi; Wada, Shin‐Ichiro; Eguchi, Hidetaka; Osaki, Akihiko; Sendo, Toshiaki; Nishiyama, Masahiko

doi:10.1007/s12282-011-0263-8

Cited by 13 publications

(12 citation statements)

References 37 publications

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“…It has been shown that docetaxel may have anti-angiogenic activity by reducing the synthesis of pro-angiogenic molecules (such as bFGF and VEGF) in cancer cells28. In addition, it was recently discovered that conventional cytotoxic chemotherapy can mobilize endothelial precursor cells, and hence, play an important role in inhibiting neovascularization and tumor growth29.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

Jia

Xu²,

Jiang³

et al. 2013

Int. J. Med. Sci.

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Background: Anti-angiogenesis is a promising therapeutic strategy for locally advanced breast cancer. We performed this phase II trial to evaluate the anti-angiogenesis and anti-tumor effect of rh-endostatin combined with docetaxel and epirubicin in patients with locally advanced breast cancer by dynamic contrast-enhanced magnetic resonance imaging in 70 previously untreated locally advanced breast cancer patients.Methods: The study population was randomly assigned to neoadjuvant chemotherapy with docetaxel and epirubicin (neoadjuvant chemotherapy group) or neoadjuvant chemotherapy combining rh-endostatin with docetaxel and epirubicin (neoadjuvant chemotherapy+rh-endostatin group). The anti-angiogenic and anti-tumor effects of both regimens were evaluated by serial dynamic contrast-enhanced magnetic resonance imaging and microvessel density measurements after final surgery.Results: The results suggested a higher clinical objective response (90.9% vs. 67.7%, P = 0.021) and greater reductions in tumor size (67.2% vs. 55.9%, P = 0.000), Ki-67 proliferation index (32.79% vs. 12.47%, P = 0.000), tumor signal enhanced ratio (64% vs. 48%, P = 0.018), and Ktrans (67% vs. 39%, P = 0.026) in neoadjuvant chemotherapy+rh-endostatin group than those in neoadjuvant chemotherapy group. In addition, the microvessel density value in the neoadjuvant chemotherapy+rh-endostatin group was significantly lower than in the neoadjuvant chemotherapy group (18.67 ± 6.53 vs. 36.05 ± 9.64, P = 0.000). Moreover, the microvessel density value was significantly correlated with Ktrans after neoadjuvant chemotherapy+rh-endostatin treatment (r=0.88, P = 0.00).Conclusions: The neoadjuvant chemotherapy+rh-endostatin treatment significantly repressed angiogenesis in locally advanced breast cancer and synergistically enhanced the anti-tumor effect of neoadjuvant chemotherapy. Serial dynamic contrast-enhanced magnetic resonance imaging data including reductions in tumor size and Ktrans, could provide non-invasive evaluation for chemotherapeutic efficacy and, consequently, optimization of individual chemotherapy for locally advanced breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

Jia

Xu²,

Jiang³

et al. 2013

Int. J. Med. Sci.

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“…22 The scanned image data were analyzed with Agilent Feature Extraction software (version 9.5, Agilent Technologies), and gene expression signals were normalized using GeneSpring GX (Agilent Technologies) and further analyzed using Spotfire software (Tibco Software).…”

Section: Dna Microarray Analysismentioning

confidence: 99%

Cadherin 13 overexpression as an important factor related to the absence of tumor fluorescence in 5-aminolevulinic acid–guided resection of glioma

Suzuki¹,

Wada

Eguchi

et al. 2013

JNS

Self Cite

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Object Gliomas contain aggressive malignant cancer, and resection rate remains an important factor in treatment. Currently, fluorescence-guided resection using orally administered 5-aminolevulinic acid (5-ALA) has proved to be beneficial in improving the prognosis of patients with gliomas. 5-ALA is metabolized to protoporphyrin IX (PpIX) that accumulates selectively in the tumor and exhibits strong fluorescence upon excitation, but glioma cells do not always respond to 5-ALA, which can result in incomplete or excessive resection. Several possible mechanisms for this phenomenon have been suggested, but they remain poorly understood. To clarify the probable mechanisms underlying the variable induction of fluorescence and to improve fluorescence-guided surgery, the authors searched for key negative regulators of fluorescent signal induced by 5-ALA. Methods A comprehensive gene expression analysis was performed using microarrays in 11 pairs of tumor specimens, fluorescence-positive and fluorescence-negative tumors, and screened genes overexpressed specifically in fluorescence-negative tumors as the possible candidates for key negative regulators of 5-ALA–induced fluorescence. The most possible candidate was selected through annotation analysis in combination with a comparison of expression levels, and the relevance of expression of the selected gene to 5-ALA–induced fluorescence in tumor tissues was confirmed in the quantified expression levels. The biological significance of an identified gene in PpIX accumulation and 5-ALA–induced fluorescence was evaluated by in vitro PpIX fluorescence intensity analysis and in vitro PpIX fluorescence molecular imaging in 4 human glioblastoma cell lines (A1207, NMCG1, U251, and U373). Knockdown analyses using a specific small interfering RNA in U251 cells was also performed to determine the mechanisms of action and genes working as partners in the 5-ALA metabolic pathway. Results The authors chose 251 probes that showed remarkably high expression only in fluorescent-negative tumors (median intensity of expression signal > 1.0), and eventually the cadherin 13 gene (CDH13) was selected as the most possible determinant of 5-ALA–induced fluorescent signal in gliomas. The mean expression level of CDH13 in the fluorescence-negative gliomas was statistically higher than that in positive ones (p = 0.027), and knockdown of CDH13 expression enhanced the fluorescence image and increased the amount of PpIX 13-fold over controls (p < 0.001) in U251 glioma cells treated with 5-ALA. Comprehensive gene expression analysis of the CDH13-knockdown U251 cells demonstrated another two genes possibly involved in the PpIX biosynthesis: ATP-binding cassette transporter (ABCG2) significantly decreased in the CDH13 knockdown, while oligopeptide transporter 1 (PEPT1) increased. Conclusions The cadherin 13 gene might play a role in the PpIX accumulation pathway and act as a negative regulator of 5-ALA–induced fluorescence in glioma cells. Although further studies to clarify the mechanisms of action in the 5-ALA metabolic pathway would be indispensable, the results of this study might lead to a novel fluorescent marker able to overcome the obstacles of existing fluorescence-guided resection and improve the limited resection rate.

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“…Recently, a series of investigation in DUSPs defined essential roles in cell proliferation and cancer [17][18][19][20][21][22][23] and their immune response. 4,24 Although there are at least 11 MKPs (many of them were thought to have a similar role to regulate MAPK cascades), it is obvious that each of them has different substrate specificities and physiological roles.…”

Section: Introductionmentioning

confidence: 99%

Dual-specificity phosphatases 2: surprising positive effect at the molecular level and a potential biomarker of diseases

et al. 2012

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Dual-specificity phosphatases (DUSPs) is an emerging subclass of the protein tyrosine phosphatase gene superfamily, a heterogeneous group of protein phosphatases that can dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues within the one substrate. Recently, a series of investigations of DUSPs defined their essential roles in cell proliferation, cancer and the immune response. This review will focus on DUSP2, its involvement in different diseases and its potential as a therapeutic target.

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Quantitative prediction of tumor response to neoadjuvant chemotherapy in breast cancer: novel marker genes and prediction model using the expression levels

Abstract: A study to validate the predictive values of the selected 4 genes is now planned, along with research to determine their functional roles.

Cited by 13 publications

References 37 publications

Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

Dynamic Contrast-Enhanced MR Imaging in a Phase Ⅱ Study on Neoadjuvant Chemotherapy Combining Rh-Endostatin with Docetaxel and Epirubicin for Locally Advanced Breast Cancer

Cadherin 13 overexpression as an important factor related to the absence of tumor fluorescence in 5-aminolevulinic acid–guided resection of glioma

Dual-specificity phosphatases 2: surprising positive effect at the molecular level and a potential biomarker of diseases

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