Quantum-dots based simultaneous detection of multiple biomarkers of tumor stromal features to predict clinical outcomes in gastric cancer

Peng, Changhong; Tian, Qian; Yang, Guifang; Fang, Min; Zhang, Zhiling; Peng, Jun; Li, Yan; Pang, Dai‐Wen

doi:10.1016/j.biomaterials.2012.04.034

Cited by 45 publications

(28 citation statements)

References 49 publications

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“…Corresponding evaluation criteria have been established. 24 Cutoff point for LOX was explored by "the best cut-off approach by log-rank test". In all, 50% was defined as the cutoff point.…”

Section: Evaluation Of Qd Probe-based Molecular Imaging and Multispecmentioning

confidence: 99%

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Peng

Liu

Yang

et al. 2017

IJN

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Purpose Semiconductor quantum dots (QDs) are a promising alternative to organic fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have great advantages in holistically analyzing the complex interactions among cancer stromal components in situ. Patients and methods A QD probe-based multiplexed spectral molecular imaging method was established for simultaneous imaging. Three tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were constructed for the study. Multispectral analyses were performed for quantifying stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including infiltrating of immune cells (high density of macrophages), angiogenesis (high density of microvessel density [MVD], low neovessel maturation) and extracellular matrix (ECM) remodeling (low density of type IV collagen, intense expression of matrix metalloproteinase 9 [MMP-9]) was evaluated. Results This study compared the imaging features of the QD probe-based single molecular imaging method, immunohistochemistry, and organic dye-based immunofluorescent methods, and showed the advantages of the QD probe-based multiple molecular imaging method for simultaneously visualizing complex components of cancer stroma. The risk of macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9 expression and low type IV collagen was significantly increased for the expression of LOX. With the advantages of the established QD probe-based multiplexed molecular imaging method, the spatial relationship between LOX and stromal essential events could be simultaneously evaluated histologically. Stromal activation was defined and then evaluated. Survival analysis showed that the stromal activation was correlated with overall survival and disease-free survival ( P <0.001 for all). The expression of LOX was significantly increased in the intense activation subgroup ( P <0.001). Conclusion Quantifying assessment of the stroma indicates that the LOX may be a stromal marker for GC and stromal activation, which is not only responsible for the ECM remodeling morphologically, but also for the formation of invasive properties and recurrence. These results support the possibility to integrate morphological and molecular biomarker information for cancer research by the biomedical application of QDs.

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“…Corresponding evaluation criteria have been established. 24 Cutoff point for LOX was explored by "the best cut-off approach by log-rank test". In all, 50% was defined as the cutoff point.…”

Section: Evaluation Of Qd Probe-based Molecular Imaging and Multispecmentioning

confidence: 99%

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Peng

Liu

Yang

et al. 2017

IJN

Self Cite

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“…QDots possess excellent fluorescent properties such as a high photostability, very high brightness and very narrowand sizetunable emission spectra [4]. These properties enable a broad range of applications such as multiplexed imaging of fixed cells, tissues and even clinical tissue samples, enhancing the predictability of outcome of cancer progression at more early stages [5,6]. Owing to their high photostability and brightness, QDots are also extensively used for kinetic single molecule studies on cellular proteins such as kinesin or individual glycine receptors, providing detailed information on their intracellular mobility and processing that was not previously possible using organic fluorophores [7,8].…”

Section: Introductionmentioning

confidence: 99%

The performance of gradient alloy quantum dots in cell labeling

Soenen¹,

Manshian²,

Himmelreich³

et al. 2014

Biomaterials

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The interest in using quantum dots (QDots) as highly fluorescent and photostable nanoparticles in biomedicine is vastly increasing. One major hurdle that slows down the (pre)clinical translation of QDots is their potential toxicity. Several strategies have been employed to optimize common coreshell QDots, such as the use of gradient alloy (GA)-QDots. These particles no longer have a sizedependent emission wavelength, but the emission rather depends on the chemical composition of the gradient layer. Therefore, particles of identical sizes but with emission maxima spanning the entire visible spectrum can be generated. In the present study, two types of GA-QDots are studied with respect to their cytotoxicity and cellular uptake. A multiparametric cytotoxicity approach reveals concentration-dependent effects on cell viability, oxidative stress, cell morphology and cell functionality (stem cell differentiation and neurite outgrowth), where the particles are very robust against environmentally-induced breakdown. Non-toxic concentrations are defined and compared to common core-shell QDots analyzed under identical conditions. Additionally, this value is translated into a functional value by analyzing the potential of the particles for cell visualization. Interestingly, these particles result in clear endosomal localization, where different particles result in identical intracellular distributions. This is in contrast with CdTe QDots with the same surface coating, which resulted in clearly distinct intracellular distributions as a result of differences in nanoparticle diameter.The GA-QDots are therefore ideal platforms for cell labeling studies given their high brightness, low cytotoxicity and identical sizes, resulting in highly similar intracellular particle distributions which offer a lot of potential for optimizing drug delivery strategies.

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“…Traditional double-color fluorescent imaging techniques mark different cellular components separately and use image merging technology to compose a full image of the cell; however, this can not implement in situ , simultaneous or synchronous images of multiple cellular components, leading to errors in the integrity and completeness of cell image information (23,24). By contrast, the present study took advantage of the in situ , synchronous, double-color imaging technique which utilizes QD-based molecular probes.…”

Section: Discussionmentioning

confidence: 99%

Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay

Geng¹,

Fang²,

Liu³

et al. 2016

Molecular Medicine Reports

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This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF-7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot-based molecular targeted imaging techniques (which stained pan-cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF-7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot-based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

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Quantum-dots based simultaneous detection of multiple biomarkers of tumor stromal features to predict clinical outcomes in gastric cancer

Cited by 45 publications

References 49 publications

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

Lysyl oxidase activates cancer stromal cells and promotes gastric cancer progression: quantum dot-based identification of biomarkers in cancer stromal cells

The performance of gradient alloy quantum dots in cell labeling

Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay

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