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Homo sapiens

ABSTRACT: Single-nuncleus RNA sequencing for circulating tumor cell-derived xenograft models of non-metastatic non-small cell lung cancer

PROVIDER: PRJNA755249 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15403611.fastq.gz	Fastqsanger.gz
	SRR15403612.fastq.gz	Fastqsanger.gz
	SRR15403613.fastq.gz	Fastqsanger.gz
	SRR15403614.fastq.gz	Fastqsanger.gz

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Homo sapiens

Project description:Whole genome sequencing of non-metastatic non-small cell lung cancer primary tumor, patient-derived xenografts and Circulating tumor cells derived xenograft

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Project description:Large numbers of cells are generally required for quantitative global proteome profiling due to the significant surface adsorption losses associated with sample processing. Such bulk measurement obscures important cell-to-cell variability (cell heterogeneity) and makes proteomic profiling impossible for rare cell populations (e.g., circulating tumor cells (CTCs)). Here we report a surfactant-assisted one-pot sample preparation coupled with mass spectrometry (MS) termed SOP-MS for label-free global single-cell proteomics. SOP-MS capitalizes on the combination of a MS-compatible nonionic surfactant, n-Dodecyl-β-D-maltoside, and hydrophobic surface-based low-bind tubes or multi-well plates for ‘all-in-one’ one-pot sample preparation. This ‘all-in-one’ method including elimination of all sample transfer steps maximally reduces surface adsorption losses for effective processing of single cells, thus significantly improving detection sensitivity for single-cell proteomics. This method allows convenient label-free quantification of hundreds of proteins from single human cells and ~1200 proteins from small tissue sections (close to ~20 cells). When applied to a patient CTC-derived xenograft (PCDX) model at the single-cell resolution, SOP-MS can reveal distinct protein signatures between primary tumor cells and early metastatic lung cells, which are related to the selection pressure of anti-tumor immunity during breast cancer metastasis. The approach paves the way for routine, precise, quantitative single-cell proteomics.

2021-03-11 | PXD022827 | panorama

Sensitive monitoring of xenograft cancer models using cell-free DNA

Project description:Tumor-derived xenograft mouse models are widely used tools in cancer studies. We reported that in xenograft models without recognizable tumors, however, circulating tumor-derived cell-free DNA (cfDNA) was persistently detectable in peripheral blood long after engraftment, suggesting that measurement of tumor-derived cfDNA could be more sensitive for tumor assessment in xenograft models as well as serve as valuable supplementary parameters in outcome interpretations, especially for those without visible tumors.

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Project description:Purpose: Our previous clinical trials have been demonstrated that Anlotinib can inhibit tumor growth upon refractory advanced non-small cell lung cancer (NSCLC) patients with the possibility mechanism of anti-angiogenesis. The present study sought to reveal the underlying molecular mechanism of Anlotinib-induced anti-angiogenesis in advanced NSCLC. Experimental Design: Computed tomography (CT) was used to evaluate the treatment effect of Anlotinib upon refractory advanced NSCLC patients. Transcriptome profiling was performed to identify the key gene expression alteration in NCI-H1975 cells before and after Anlotinib treatment. NCI-H1975 derived xenograft model was applied to investigate treatment effect and verify anti-angiogenesis mechanism of Anlotinib. Results: Anlotinib induces tumor cytotoxicity on refractory advanced NSCLC patients, NCI-H1975 derived xenograft models and lung adenocarcinoma cell lines. Transcriptome profiling revealed CCL2 blockade could be responsible for Anlotinib-induced anti-angiogenesis. NCI-H1975 derived xenograft model demonstrated Anlotinib-induced CCL2 blockade play an important role in anti-angiogenesis. Conclusions: This study not only offered the first evidence that Anlotinib inhibits angiogenesis via blocking CCL2 expression, but also provided a novel theoretical basis for the application of Anlotinib in advanced NSCLC patients.

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