scholarly journals Immuno-PET imaging for non-invasive assessment of cetuximab accumulation in non-small cell lung cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aiko Yamaguchi ◽  
Arifudin Achmad ◽  
Hirofumi Hanaoka ◽  
Yusri Dwi Heryanto ◽  
Anu Bhattarai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pet Imaging ◽  
Small Cell ◽  
Expression Level ◽  
Tumor Uptake ◽  
Small Cell Lung ◽  
Non Invasive ◽  
Egfr Expression

Abstract Backgrounds Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels. Methods The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either 111In- or 64Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting. Results We found that tumors with high EGFR expression had significantly higher [111In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [111In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [64Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [64Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors. Conclusion Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.

scholarly journals Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

2020 ◽  
Vol 245 (16) ◽  
pp. 1428-1436
Author(s):  
Zhi-Jun Zhang ◽  
Xing-Guo Song ◽  
Li Xie ◽  
Kang-Yu Wang ◽  
You-Yong Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Diagnostic Biomarkers ◽  
Non Invasive ◽  
Early Stage Nsclc ◽  
Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

scholarly journals miRNA-486 and miRNA-499 in human plasma evaluate the clinical stages of lung cancer and play a role as a tumor suppressor in lung tumorigeneisis not pathogenesis

2016 ◽  
Vol 11 (1) ◽  
pp. 264 ◽  
Author(s):  
Youchao Jia ◽  
Aimin Zang ◽  
Yanguang Feng ◽  
Xiao-Fang Li ◽  
Ke Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Statistical Significance ◽  
Small Cell ◽  
Expression Level ◽  
Control Group ◽  
Small Cell Lung ◽  
Lung Cancer Patients

<p class="Abstract">It was aimed to explore the expression level of miRNA-486 and miRNA-499 in the plasma of lung cancer patients and analysis their differences in expre-ssion. The expression level of both miRNA-486 and miRNA-499 in the plasma of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) were lower than that of the control group (p&lt;0.05) and the decrease was more obvious in NSCLC. Compare with the miRNA-499，expression quantity in NSCLC patients plasma. There was statistical significance difference (p&lt;0.05) between III～Ⅳstage and I～II stage. The expression quantity of miRNA in plasma of patients with extensive-stage SCLC was lower than that of patients with limited-stage SCLC (p&lt;0.05). The sensitivity and specificity of plasms miRNA-486 respectively were 88.5% and 83.3%. The expression of miRNA-499 and miRNA-486 in lung cancer patients were up-regulated, and might be closely related to the occurrence and prognosis of lung cancer, and might be used as potential screening and prognosis index for lung cancer.</p><p> </p>

scholarly journals Comprehensive Analysis of Inhibitor of Apoptosis Protein Expression and Prognostic Significance in Non–Small Cell Lung Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Liu ◽  
Yi Lu ◽  
Wenan Huang ◽  
Zhibo He
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Prognostic Significance ◽  
Small Cell ◽  
Expression Level ◽  
Mrna Levels ◽  
Small Cell Lung ◽  
Normal Tissues ◽  
Apoptosis Protein

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.

scholarly journals PET imaging of patients with non-small cell lung cancer employing an EGF receptor targeting drug as tracer

2011 ◽  
Vol 105 (12) ◽  
pp. 1850-1855 ◽  
Author(s):  
A A Memon ◽  
B Weber ◽  
M Winterdahl ◽  
S Jakobsen ◽  
P Meldgaard ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pet Imaging ◽  
Egf Receptor ◽  
Small Cell ◽  
Small Cell Lung ◽  
Receptor Targeting
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