Cytolytic tests with hyperimmune patient sera is a good prognostic tool in racotumomab immunotherapy in advanced non-small cell lung cancer

Aberrant accumulation of a specific sialic acid has been shown to exist in many human malignant cell membranes termed as N-glycolyl neuraminic acid (NeuGc). This particular ganglioside do not normally exist in normal human cells, due to the lack of an enzyme (cytidine monophospho-N-acetyl-neuraminic acid) which is responsible for the synthesis of N—glycolyl neurominic acid. The aberrant expression of NeuGcGM3 ganglioside in the cell surface of certain human tumors, made this molecule an attractive target for immunotherapy. By using 14 F7 monoclonal antibody directed to identify NeuGcGM3 in the tumor tissue, it is possible to select patients for anti-NeuGcGM3 immunotherapy. Racotumomab is an anti-idiotype vaccine, being a mirror image of NeuGcGm3 mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside.In this study, we monitored 12 patients with advanced non-small cell lung cancer (NSCLC) who are on racotumomab vaccine maintenance following chemotherapy. Cytotoxic tests with vaccinated patients’ sera were performed using L1210 cell lines at the 3rd, 6th, 9th, and 12th months of vaccination and the results were compared with clinical outcomes. Serum antibodies to NeuGcGm3 ganglioside were also checked before initiation and thereafter with the same intervals. The aim of the study was to investigate the value of antibodies and cytotoxic test as biomarkers for treatment outcome. Our observation confirmed that consistently higher cytotoxicity rates in the cell culture correlated with better progression free survivals of the patients who are on racotumomab maintenance.

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Aberrant expression of NEK2 and its clinical significance in non-small cell lung cancer

Oncology Letters ◽

10.3892/ol.2014.2396 ◽

2014 ◽

Vol 8 (4) ◽

pp. 1470-1476 ◽

Cited By ~ 13

Author(s):

XINWEN ZHONG ◽

XIAOJIAO GUAN ◽

WENKE LIU ◽

LIN ZHANG

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Significance ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Aberrant Expression

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Pro-opiomelanocortin gene expression and peptide secretion in human small-cell lung cancer cell lines

Journal of Molecular Endocrinology ◽

10.1677/jme.0.0030065 ◽

1989 ◽

Vol 3 (1) ◽

pp. 65-70 ◽

Cited By ~ 18

Author(s):

A. White ◽

M. F. Stewart ◽

W. E. Farrell ◽

S. R. Crosby ◽

P. M. Lavender ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cell Lung Cancer ◽

Blot Hybridization ◽

Small Cell ◽

Small Cell Lung ◽

Human Pituitary ◽

Aberrant Expression ◽

Pomc Gene

ABSTRACT Expression of the RNA coding for the ACTH—β-lipotrophin precursor, pro-opiomelanocortin (POMC), has been demonstrated in five human small-cell lung cancer (SCLC) cell lines. Using Northern and slot-blot hybridization analysis of RNA and a bovine POMC cDNA as probe, the processed POMC RNA from SCLC cells was found to be approximately 1350 nucleotides in length, which is larger than that found in the normal human pituitary. Expression of the POMC gene was confirmed by measurement of ACTH precursors secreted by the cells, using a novel two-site immunoradiometric assay based on monoclonal antibodies, which directly quantifies both POMC and pro-ACTH but does not recognize ACTH. Levels of POMC in medium accumulated throughout the growth of the cells, in contrast to POMC RNA which showed a relatively constant level of expression. We conclude that human SCLC cell lines are valuable models for studying the aberrant expression and regulation of the human POMC gene.

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Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer

Pathology & Oncology Research ◽

10.3389/pore.2021.529240 ◽

2021 ◽

Vol 27 ◽

Author(s):

Jin Ma ◽

Rao Du ◽

Yan Huang ◽

Wen Zhong ◽

Huan Gui ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Mrna Expression ◽

Cell Lung Cancer ◽

Expression Patterns ◽

Lung Squamous Cell Carcinoma ◽

Small Cell ◽

Small Cell Lung ◽

Aberrant Expression ◽

Expression Levels

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan–Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.

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Aberrant expression of miR‑4728 in patients with non‑small cell lung cancer and its regulatory effects on tumor progression in tumor cells

Experimental and Therapeutic Medicine ◽

10.3892/etm.2020.9141 ◽

2020 ◽

Vol 20 (5) ◽

pp. 1-1

Author(s):

Ying Hu ◽

Xinfang Zhang ◽

Cuixue Gong ◽

Jianzhao Li

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Tumor Progression ◽

Tumor Cells ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Aberrant Expression ◽

Regulatory Effects

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MicroRNA-520a Suppresses Pathogenesis and Progression of Non-Small-Cell Lung Cancer through Targeting the RRM2/Wnt Axis

Analytical Cellular Pathology ◽

10.1155/2021/9652420 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Yi Xie ◽

Congyu Xue ◽

Shuai Guo ◽

Lei Yang

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Wnt Signaling Pathway ◽

Small Cell ◽

Migration And Invasion ◽

Small Cell Lung ◽

Aberrant Expression ◽

Normal Tissues

MicroRNAs (miRNAs) regulate multiple cellular behaviors, and their aberrant expression is frequently associated with disease progression. This research focused on the effects of miR-520a on the development of non-small-cell lung cancer (NSCLC) and the molecules involved. Tumor and normal tissues from 24 patients with NSCLC were collected. Differentially expressed miRNAs between tumor tissues and normal tissues were screened using microarrays, and miR-520a was screened to be significantly poorly expressed in tumor samples. Artificial upregulation of miR-520a reduced proliferation, migration and invasion, and resistance to death of NSCLC A549 and H460 cells according to the MTT, EdU labeling, transwell, and flow cytometry assays, respectively. miR-520a upregulation suppressed growth and metastasis of xenograft tumors in vivo. The integrated bioinformatic analysis and dual luciferase assays suggested that miR-520a targeted ribonucleotide reductase subunit 2 (RRM2) mRNA and inactivated the Wnt/β-catenin signaling pathway in NSCLC cells. Upregulation of RRM2 enhanced the malignant behaviors of NSCLCs, but the oncogenic effects of RRM2 were blocked upon miR-520a overexpression. To conclude, this study evidenced that miR-520a inhibits NSCLC progression through suppressing RRM2 and the Wnt signaling pathway. This paper may offer novel insights into NSCLC treatment.

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Stimulation of the aberrant expression of a paraneoplastic antigen, recoverin, in small cell lung cancer cell lines

Lung Cancer ◽

10.1016/j.lungcan.2004.02.015 ◽

2004 ◽

Vol 45 (3) ◽

pp. 299-305 ◽

Cited By ~ 10

Author(s):

Alexandr V Bazhin ◽

Marina S Savchenko ◽

Eugene V Belousov ◽

Gabriele Jaques ◽

Pavel P Philippov

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cell Lung Cancer ◽

Small Cell ◽

Lung Cancer Cell ◽

Small Cell Lung ◽

Aberrant Expression ◽

Stimulation Of

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Long Non-Coding RNA XLOC_008466 Functions as an Oncogene in Human Non-Small Cell Lung Cancer by Targeting miR-874

Cellular Physiology and Biochemistry ◽

10.1159/000477121 ◽

2017 ◽

Vol 42 (1) ◽

pp. 126-136 ◽

Cited By ~ 25

Author(s):

Rui Yang ◽

Ping Li ◽

Guojun Zhang ◽

Chunya Lu ◽

Huaqi Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Matrix Metalloproteinase 2 ◽

Luciferase Reporter ◽

Small Cell Lung ◽

Aberrant Expression

Background: The therapy and prognosis of lung cancer are difficult because of multiple genetic and epigenetic alterations. Long non-coding RNAs (lncRNAs) have been verified as new mediators of cancer development and progression by virtue of their various functions. Here, we focused on the lncRNA XLOC_008466 based on previous microarray data. However, whether aberrant expression of XLOC_008466 in human non-small cell lung cancer (NSCLC) is correlated with malignancy, metastasis or prognosis has not been elucidated. Methods: We performed real-time PCR, CCK-8, flow cytometry, trans-well, western blotting, luciferase reporter assays, RNA immunoprecipitation (RIP) assay and surface plasmon resonance (SPR) assay to detect the function of XLOC_008466 in NSCLC. Results: Up-regulation of XLOC_008466 in NSCLC patients was related to lymph node metastasis and the TNM stage. In vitro, down-regulation of XLOC_008466 inhibited cell proliferation and invasion of A549 and H460 cells in vitro, but promoted cell apoptosis. Experiments on mechanisms revealed that XLOC_008466 functioned as a ceRNA, directly binding to miR-874, and could affect cell proliferation, apoptosis and invasion through regulation of miR-874 expression as well as by increasing matrix metalloproteinase 2 (MMP2) and X-linked inhibitor of apoptosis (XIAP) expression. Conclusions: XLOC_008466 functions as an oncogene in NSCLC by regulating the miR-874-MMP2/XIAP axis, which indicates that XLOC_008466 may be a useful marker and potential therapeutic target in NSCLC.

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