Restoration of the Immunocompetence by IL-2 Activation and TCR-CD3 Engagement of the In Vivo Anergized Tumor-Specific CTL from Lung Cancer Patients

Stau1 is a pluripotent RNA-binding protein that is responsible for the post-transcriptional regulation of a multitude of transcripts. Here, we observed that lung cancer patients with a high Stau1 expression have a longer recurrence free survival. Strikingly, Stau1 did not impair cell proliferation in vitro, but rather cell migration and cell adhesion. In vivo, Stau1 depletion favored tumor progression and metastases development. In addition, Stau1 depletion strongly impaired vessel maturation. Among a panel of candidate genes, we specifically identified the mRNA encoding the cell adhesion molecule Thrombospondin 1 (THBS1) as a new target for Staufen-mediated mRNA decay. Altogether, our results suggest that regulation of THBS1 expression by Stau1 may be a key process involved in lung cancer progression.

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Enumeration and Molecular Characterization of Circulating Tumor Cells in Lung Cancer Patients Using the Gilupi Cellcollector™, An Effective in Vivo Device for Capturing Ctcs

Annals of Oncology ◽

10.1093/annonc/mdv045.14 ◽

2015 ◽

Vol 26 ◽

pp. i10 ◽

Cited By ~ 1

Author(s):

N. Scheumann ◽

T. Gorges ◽

N. Penkalla ◽

B. Nowack ◽

T. Schalk ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Molecular Characterization ◽

Circulating Tumor Cells ◽

Lung Cancer Patients

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Hepatic sugar phosphate levels reflect gluconeogenesis in lung cancer: simultaneous turnover measurements and 31P magnetic resonance spectroscopy in vivo

Clinical Science ◽

10.1042/cs0980167 ◽

2000 ◽

Vol 98 (2) ◽

pp. 167-174 ◽

Cited By ~ 5

Author(s):

Susanne LEIJ-HALFWERK ◽

Pieter C. DAGNELIE ◽

J. Willem O. VAN DEN BERG ◽

J. H. Paul WILSON ◽

Paul E. SIJENS

Keyword(s):

Lung Cancer ◽

Weight Loss ◽

Magnetic Resonance ◽

Cancer Patients ◽

Healthy Subjects ◽

Whole Body ◽

Glucose Turnover ◽

Lung Cancer Patients ◽

Gluconeogenesis From Alanine

Stable-isotope tracers were used to assess whether levels of phosphomonoesters (PME) and phosphodiesters (PDE) in the livers of lung cancer patients, as observed by 31P magnetic resonance (MR) spectroscopy, reflect elevated whole-body glucose turnover and gluconeogenesis from alanine. Patients with advanced non-small-cell lung cancer without liver metastases (n = 24; weight loss 0–24%) and healthy control subjects (n = 13) were studied after an overnight fast. 31P MR spectra of the liver in vivo were obtained, and glucose turnover and gluconeogenesis from alanine were determined simultaneously using primed-constant infusions of [6,6-2H2]glucose and [3-13C]alanine. Liver PME concentrations were 6% higher in lung cancer patients compared with controls (not significant); PME levels in patients with ⩾ 5% weight loss were significantly higher than in patients with < 5% weight loss (P < 0.01). PDE levels did not differ between the groups. In lung cancer patients, whole-body glucose production was 19% higher (not significant) and gluconeogenesis from alanine was 42% higher (P < 0.05) compared with healthy subjects; turnover rates in lung cancer patients with ⩾ 5% weight loss were significantly elevated compared with both patients with < 5% weight loss and healthy subjects (P < 0.05). PME levels were significantly correlated with glucose turnover and gluconeogenesis from alanine in lung cancer patients (r = 0.48 and r = 0.48 respectively; P < 0.05). In conclusion, elevated PME levels in lung cancer patients appear to reflect increased glucose flux and gluconeogenesis from alanine. These results are consistent with the hypothesis that elevated PME levels are due to contributions from gluconeogenic intermediates.

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LPTO-04. GENERATION AND CHARACTERIZATION OF PATIENT-DERIVED PRECLINICAL MODELS FROM TUMOR CELLS ISOLATED FROM CEREBROSPINAL FLUID

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.027 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i7-i7

Author(s):

Michael Offin ◽

Morana Vojnic ◽

Zebing Liu ◽

Allan Lui ◽

Evan Siau ◽

...

Keyword(s):

Lung Cancer ◽

Cell Line ◽

Cancer Patients ◽

Tumor Cells ◽

Nsclc Patient ◽

Leptomeningeal Disease ◽

Preclinical Models ◽

Lung Cancer Patients ◽

Met Amplification

Abstract BACKGROUND: CNS metastases occur in 20–50% of lung cancer patients during their disease; leptomeningeal disease (LMD) representing 5–8%, classically carries a poor prognosis with a median overall survival ranging from 1–11 months. There is a paucity of patient-derived preclinical disease models using tumor cells isolated from the CSF. Models that faithfully recapitulate the biology of CNS tumors would offer new insights into the biology of the disease as well as provide the basis for developing more effective therapy. METHODS: To create more representative preclinical models to study LMD we isolated tumor cells from CSF of 5 patients with cytologically proven LMD and implanted the cells into the subcutaneous flank of immune-compromised mice. Where possible, cell lines were also generated from PDX tissues. Models were characterized by next generation sequencing (NGS), growth rates, expression of driver oncogenes and sensitivity to small molecule inhibitors. RESULTS: To date, one PDX (LUAD-0048A) and cell line model were successfully derived from CSF samples (NSCLC patient with MET amplification) and 4 are pending. MET amplification and mRNA over-expression were confirmed by quantitative PCR in the PDX tissue and the cell line. Western blot analysis indicated that over-expressed MET was phosphorylated in both PDX tissue and cell line. These results were confirmed by immunohistochemistry. Growth of LUAD-0048A cells were unaffected by 3 MET inhibitors (crizotinib, cabozantinib, glesatinib). Similarly, MET inhibitors did not induce apoptosis in the cells. CONCLUSION: LMD represents an aggressive metastatic event in lung cancer patients. Here we were able to successfully establish a PDX from the CSF of a patient with LMD and trial targeted therapies in vivo. Translational collaborations where patients with clinical suspicion of LMD undergo CSF sampling, NGS/ctDNA analysis, and PDX modeling are crucial in improving our understanding of this metastatic compartment and investigating novel treatment paradigms.

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PDS5B inhibits cell proliferation, migration, and invasion via upregulation of LATS1 in lung cancer cells

Cell Death Discovery ◽

10.1038/s41420-021-00537-6 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Hui Xu ◽

Wenjing Zhou ◽

Fan Zhang ◽

Linhui Wu ◽

Juan Li ◽

...

Keyword(s):

Lung Cancer ◽

Cell Viability ◽

Cancer Patients ◽

Immunohistochemical Study ◽

Migration And Invasion ◽

Tissue Samples ◽

Lung Cancer Patients ◽

Underlying Mechanisms ◽

Mtt Assays

AbstractPDS5B (precocious dissociation of sisters 5B) plays a pivotal role in carcinogenesis and progression. However, the biological functions of PDS5B in lung cancer and its underlying mechanisms are not fully elucidated. In the present study, we used MTT assays, wound-healing assays, and transwell migration and invasion approach to examine the cell viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells after PDS5B modulation. Moreover, we investigated the function of PDS5B overexpression in vivo. Furthermore, we detected the expression of PDS5B in tissue samples of lung cancer patients by immunohistochemical study. We found that upregulation of PDS5B repressed cell viability, migration, and invasion in NSCLC cells, whereas downregulation of PDS5B had the opposite effects. We also observed that PDS5B overexpression retarded tumor growth in nude mice. Notably, PDS5B positively regulated LATS1 expression in NSCLC cells. Strikingly, low expression of PDS5B was associated with lymph node metastasis in lung cancer patients. Our findings suggest that PDS5B might be a therapeutic target for lung cancer.

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Capilliposide C from Lysimachia capillipes Restores Radiosensitivity in Ionizing Radiation-Resistant Lung Cancer Cells Through Regulation of ERRFI1/EGFR/STAT3 Signaling Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.644117 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kan Wu ◽

Xueqin Chen ◽

Jianguo Feng ◽

Shirong Zhang ◽

Yasi Xu ◽

...

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Cancer Cells ◽

Cancer Patients ◽

Lung Cancer Cells ◽

Rna Seq ◽

Lung Cancer Cell ◽

Lung Cancer Patients ◽

Damage Repair

AimsRadiation therapy is used as the primary treatment for lung cancer. Unfortunately, radiation resistance remains to be the major clinic problem for lung cancer patients. Lysimachia capillipes capilliposide C (LC-C), an extract from LC Hemsl, has demonstrated multiple anti-cancer effects in several types of cancer. Here, we investigated the potential therapeutic impacts of LC-C on radiosensitivity in lung cancer cells and their underlying mechanisms.MethodsNon-small cell lung cancer cell lines were initially irradiated to generate ionizing radiation (IR)-resistant lung cancer cell lines. RNA-seq analysis was used to examine the whole-transcriptome alteration in IR-resistant lung cancer cells treated with or without LC-C, and the differentially expressed genes with most significance were verified by RT-qPCR. Colony formation assays were performed to determine the effect of LC-C and the target gene ErbB receptor feedback inhibitor 1 (ERRFI1) on radiosensitivity of IR-resistant lung cancer cells. In addition, effects of ERRFI1 on cell cycle distribution, DNA damage repair activity were assessed by flow cytometry and γ-H2AX immunofluorescence staining respectively. Western blotting was performed to identify the activation of related signaling pathways. Tumor xenograft experiments were conducted to observe the effect of LC-C and ERRFI1 on radiosensitivity of IR-resistant lung cancer cells in vivo.ResultsCompared with parental cells, IR-resistant lung cancer cells were more resistant to radiation. LC-C significantly enhanced the effect of radiation in IR-resistant lung cancer cells both in vitro and in vivo and validated ERRFI1 as a candidate downstream gene by RNA-seq. Forced expression of ERRFI1 alone could significantly increase the radiosensitivity of IR-resistant lung cancer cells, while silencing of ERRFI1 attenuated the radiosensitizing function of LC-C. Accordingly, LC-C and ERRFI1 effectively inhibited IR-induced DNA damage repair, and ERRFI1 significantly induced G2/M checkpoint arrest. Additional investigations revealed that down-regulation of EGFR/STAT3 pathway played an important role in radiosensitization between ERRFI1 and LC-C. Furthermore, the high expression level of ERRFI1 was associated with high overall survival rates in lung cancer patients.ConclusionsTreatment of LC-C may serve as a promising therapeutic strategy to overcome the radiation resistance and ERRFI1 may be a potential therapeutic target in NSCLC.

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