Comparison of DNA damage in human lymphocytes from healthy individuals and asthma, COPD and lung cancer patients treated in vitro / ex vivo with the bulk nano forms of aspirin and ibuprofen

e15558 Background: Exosome concentration is known to be higher in cancer patients than in healthy individuals. In this study, we observed that the levels of exosomes differ in tumor-draining pulmonary blood and in peripheral blood in animal models and human subjects at different pathological stages of lung cancer. Methods: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from a peripheral vein in all groups, and pulmonary blood was collected intraoperatively from all groups, except the healthy human controls. Quantitative analysis of exosomes was performed by nanoparticle tracking assay, CD63 enzyme-linked immunosorbent assay, and western blotting. Results: The peripheral blood of lung cancer-bearing animals and patients with lung cancer carried higher amounts of exosome than that from healthy controls ( p < 0.01 and p < 0.001, respectively). Moreover, pulmonary blood from lung cancer-bearing animals and patients had significantly higher exosome levels, compared to preoperative peripheral blood ( p < 0.01 and p < 0.0001, respectively). In patients, pulmonary exosome levels showed higher correlation with pathological stages of lung cancer than the peripheral exosome levels. Conclusions: Exosome levels increased with increasing grade of lung cancer, and this trend was more prominent in the pulmonary than in the peripheral blood.

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PPM2 The Potential Healthcare and Economic Impact of the Implementation of the in Vitro Diagnostic Regulation on Non-Small-Cell Lung Cancer Patients in the European Union

Value in Health ◽

10.1016/j.jval.2021.04.974 ◽

2021 ◽

Vol 24 ◽

pp. S195

Author(s):

R. Henderson ◽

D. Smart ◽

D. French ◽

M. Lawler

Keyword(s):

Lung Cancer ◽

European Union ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Small Cell ◽

The European Union ◽

Small Cell Lung ◽

Lung Cancer Patients ◽

In Vitro Diagnostic

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High Level of Staufen1 Expression Confers Longer Recurrence Free Survival to Non-Small Cell Lung Cancer Patients by Promoting THBS1 mRNA Degradation

International Journal of Molecular Sciences ◽

10.3390/ijms23010215 ◽

2021 ◽

Vol 23 (1) ◽

pp. 215

Author(s):

Florence Bonnet-Magnaval ◽

Leïla Halidou Diallo ◽

Valérie Brunchault ◽

Nathalie Laugero ◽

Florent Morfoisse ◽

...

Keyword(s):

Lung Cancer ◽

Cell Adhesion ◽

Cancer Patients ◽

Cancer Progression ◽

Rna Binding ◽

Recurrence Free Survival ◽

Free Survival ◽

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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Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Blood to Distinguish Lung Cancer Patients from Healthy Subjects

Disease Markers ◽

10.1155/2020/8844698 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Xuming Zhu ◽

Huizhu Song ◽

Yan Chen ◽

Feifei Han ◽

Qiong Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Patients ◽

Healthy Subjects ◽

Control Group ◽

Healthy Individuals ◽

Platelet To Lymphocyte Ratio ◽

Lung Cancer Patients ◽

Lymphocyte Ratio ◽

Cancer Group ◽

Level Group

Objective. Inflammation-driven markers play a crucial role in tumorigenesis and tumor progression. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in blood are systemic inflammatory response markers. Some reports have showed that NLR and PLR are related to a poor prognosis in patients with lung cancer. However, little studies have reported whether NLR and PLR can be diagnostic markers for lung cancer. The aim of the current study is to investigate the roles of NLR and PLR in diagnosing lung cancer. Methods. This study analyzed data from lung cancer patients and healthy individuals in Wuxi People’s Hospital Affiliated with Nanjing Medical University. The Mann–Whitney U test was performed to compare differences between the lung cancer group and the control group. Based on white blood cell (WBC) counts, both lung cancer patients and healthy individuals were divided into the low-level group, moderate-level group, and high-level group. The Kruskal-Wallis test was applied to compare differences of NLR and PLR among those groups with different WBC counts. Spearman correlation analysis was used to assess correlations. Receiver operating characteristic (ROC) curves were performed to determine diagnostic accuracy. Results. 210 patients diagnosed with lung cancer and 261 healthy subjects were enrolled in this study. Levels of NLR and PLR increased in the lung cancer group compared with the control group ( P < 0.001 ). For the lung cancer group, NLR levels could rise with the increasing of WBC levels ( P < 0.001 ) while PLR levels had no significant variation with the increasing of WBC levels ( P = 0.206 ). For the control group, NLR levels could rise with the increasing of WBC levels ( P < 0.001 ) while PLR levels would decline with the increasing of WBC levels ( P < 0.001 ). In the lung cancer group, both NLR and PLR had no significant correlations with aspartate transaminase, urea, and glucose. The area under the curve (AUC) with 95% confidence interval (95% CI) of NLR and PLR to distinguish lung cancer patients from healthy subjects was, respectively, 0.684 (0.634-0.735) and 0.623 (0.571-0.674). When NLR and PLR were combined, AUC (95% CI) increased to 0.691 (0.642-0.740). Conclusions. NLR and PLR alone have moderate ability to distinguish lung cancer patients from healthy subjects. Furthermore, combination forms of NLR and PLR can improve diagnostic ability.

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MDM2 309 and TP53 Arg72Pro single nucleotide polymorphisms (SNPs) and clinical outcome in advanced lung cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.7636 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 7636-7636

Author(s):

S. Novello ◽

G. Mandrile ◽

D. F. Giachino ◽

P. Ghio ◽

G. Selvaggi ◽

...

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Clinical Outcome ◽

Cancer Patients ◽

Dna Damage Response ◽

Objective Response ◽

Disease Stage ◽

Lung Cancer Patients ◽

Tp53 Arg72pro ◽

Damage Response

7636 Background: The TP53 Arg72Pro (rs1042522:C>G) and MDM2 SNP309 (rs2279744:T>G) SNPs of the DNA damage response pathway have been shown to affect lung cancer risk. We aimed to investigate their relationship with the clinical outcome of chemotherapy (CT). Methods: We prospectively recruited 426 consecutive patients with advanced disease (352 NSCLC and 74 SCLC, 57% metastatic) referred for chemotherapy at our institution from July 2002 to January 2006: 82% male, median age at diagnosis 63 years, 56% current and 11% never smokers, 81% receiving combined platinum CT. Median follow up time was 10.5 months. Controls were 254 medical students. We designed specific TP53 and MDM2 primers for typing both SNPs using the Pyrosequencing assay. Results: Patients genotype frequencies were: TP53 Arg/Arg 51%, Arg/Pro 40%, Pro/Pro 8%, (61%, 35%, 4% among controls, p=0.02), MDM2 T/T 37%, T/G 46%, G/G 17%, (31%, 55%, 14% among controls, p=0.07). Both groups were in Hardy-Weinberg equilibrium. At multivariable analysis adjusted for gender, smoking status, type of chemotherapy, disease stage, and side effects, survival was significantly associated with performance status (PS) [HR 1.54 (1.2–2.0)], histology [SCLC vs. NSCLC - HR 1.51(1.1–2.1)] and objective response [yes vs. no HR 0.56 (0.4–0.7)] but with neither SNP; in contrast, grade 3–4 toxicity and objective response were concomitantly associated with the SNPs of TP53 [Pro carriers vs. Arg/Arg HR 1.40 (1.1–1.8) and 1.44 (1.0–2.0)] and MDM2 [GG vs. TT 0.57 (0.4–0.9) and 0.61 (0.4–0.97)]. These findings are in agreement with the notion that MDM2 GG homozygous cells express higher levels of mdm2, thus attenuating the p53 pathway, but don’t easily fit with the alleged greater apoptotic potential of p53 Arg72. We also observed significant associations of toxicity with platinum therapy, of objective response with histology and of both outcomes with PS (not shown). Conclusion: The study provides preliminary evidence that germ-line TP53 and MDM2 SNPs affect toxicity and objective response to CT in lung cancer patients, probably depending on a variable DNA damage response but not survival time that may mainly result from the tumor aggressiveness and somatic mutational status. [Table: see text]

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