Production of Monoclonal Antibodies against a New Carcinoma-associated Marker in View of Developing a Serological Test

1990 ◽  
Vol 5 (3) ◽  
pp. 109-117 ◽  
Author(s):  
E. Tagliabue ◽  
F. Centis ◽  
A. Mastroianni ◽  
S. Martignone ◽  
S. Ménard ◽  
...  

By immunizing a mouse with human metastatic breast tumor cells from patient effusions and infiltrated lymph nodes, a monoclonal antibody (MLuC2), which identifies a new carcinoma-associated marker, was raised. The reactivity of this reagent was studied by immunohistochemistry on live and fixed cells from tumor cell lines and on frozen sections from surgical specimens. Besides reacting with 73% of breast carcinomas, MLuC2 also reacted with 93% of non-small cell lung carcinoma (NSCLC) and with a few normal tissues. The MLuC2-recognized molecule (CaMLuC2), whose MW was 90 KDa according to immunoblotting experiments, was found to be detectable in the serum and could therefore be of particular interest for serological diagnostic applications. Since the CaMLuC2 epitope was not polyexpressed on the bearing molecule, we produced a new generation of MAbs in order to define epitopes coexpressed with CaMLuC2 on the same 90 KDa molecule, and which are therefore suitable to develop a double-determinant immunoradiometric assay (DDIRMA) for the detection of this marker in the sera of lung carcinoma patients. Different analyses by immunohistochemistry, binding inhibition tests and DDIRMA, proved that the two new reagents developed, MLuC8 and MLuC9, recognize the same or closely related epitopes, which are however different from CaMLuC2, but which are all present on the same molecule. Preliminary immunoradiometric tests performed on sera from lung cancer and control patients showed a good specificity but a low sensitivity. In fact, only 42% of the 28 tested sera samples from NSCLC patients scored positive despite the fact that more than 90% of the NSCLC expressed the relevant antigen

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chuanqiang Wang ◽  
Xiangbo Tao ◽  
Jungong Wei

Abstract Background The study was done to investigate the effect of LncRNA MEG3 on the immunity and autophagy of non-small cell lung carcinoma through the IDO signaling pathway. Methods A total of 78 cases of early NSCLC patients (research group; RG) and 69 cases of health controls (control group; CG) during the same time were included. The contents of LncRNA MEG3 and miR-543 in peripheral blood and tissues and their diagnostic values for NSCLC were detected. The relationship between LncRNA MEG3 and miR-543 and their posttreatment contents and influence on the prognosis of NSCLC patients were tested. The expression of LncRNA MEG3, miR-543, and IDO (IDO1, IDO2, and TDO proteins) in the lung tissue of rats and the immune function in the CG and the RG were detected. The effects of LncRNA MEG3 and miR-543 on the biological behavior of NSCLC cells were determined. The role of LncRNA MEG3, miR-543, and IDO in NSCLC was verified. Results LncRNA MEG3 was low in peripheral blood and tissues, while miR-543 was high (P < 0.05); both had good diagnostic values for NSCLC (P < 0.05). LncRNA MEG3 had a negative correlation with miR-543 (P < 0.05) and influenced the prognosis of NSCLC patients (P < 0.05). LncRNA MEG3 in the lung tissue of rats using IDO inhibitor was elevated compared with that of lung carcinoma model rats (P < 0.05). The level of miR-543 was declined compared with that of lung carcinoma model rats (P < 0.05). The levels of IDO1, IDO2, and TDO proteins were evidently declined compared with those of lung carcinoma model rats (P < 0.05). Compared with lung carcinoma model rats, CD3+, CD4+, and CD4+/CD8+ of IDO inhibitor rats were elevated, while CD8+ was declined (P < 0.05). Cell proliferation and invasion ability and IDO1, IDO2, TDO, Beclin-1, and LC3-II proteins were declined in the sh-LncRNA MEG3 group (P < 0.05), while those in the mimics-miR-543 group were evidently elevated (P < 0.05). However, the double luciferase activity detection and RIP experiment confirmed that there was targeted regulation among them (P < 0.05). Conclusion MEG3 has low expression in NSCLC and affects the immunity and autophagy of NSCLC cells via regulating the miR-543/IDO signaling pathway, which is effective for the treatment of NSCLC.


Author(s):  
Arun Chairmadurai ◽  
Sandeep K. Jain ◽  
Aklank Jain ◽  
Hridayesh Prakash

: In conjunction with Radio-chemotherapy, pulmonary resection is recommended for early-stage Non-small-cell lung carcinoma but not for advanced-stage NSCLC patients with having high-grade metastatic lesions. In these cases, Rapid Arc-Stereotactic body radiotherapy (Ra-SBRT) technique offers a therapeutic advantage by delivering focal irradiation to metastatic lung lesions and reduces the bystander toxicity to normal tissues. We have previously demonstrated that Ra-SBRT ablates metastatic lesions and induces tumor immune rejection of metastatic tumors by promoting in situ programming of M2 TAM towards M1-TAM and infiltration of Siglec-8+ Eosinophils. Most interestingly, Ra SBRT has very low abscopal impact and spares normal tissues, which are the significant limitations with conventional radiotherapy. In view of this and Immune adjuvant potential of Ra SBRT, it promotes normalization of aberrant vasculature and inhibits the metastatic potential of NSCLC lesions. In view of this we here propose that Ra-SBRT indeed represents an immunogenic approach for the effective management of advanced-stage NSCLC.


2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e21239-e21239
Author(s):  
Andre Kunert ◽  
Edwin A. Basak ◽  
Daan Hurkmans ◽  
Yarne Klaver ◽  
Mandy van Brakel ◽  
...  

2019 ◽  
Author(s):  
Zhongcheng Li ◽  
Guoqing Zhang ◽  
Jin Li ◽  
Hongbo Ma ◽  
Zhenxin Wang ◽  
...  

Abstract Background: Thymidine kinase 1 (TK1) is a key enzyme involved in DNA synthesis. The aim is to assess the prognostic significance of serum TK1 protein concentration (STK1p) and its role in monitoring of individual customized therapy in non-small cell lung carcinoma (NSCLC) patients in routine clinical setting. Methods: A prospective study of 129 NSCLC patients was confirmed by imager, /pathology and treated by radical resection (RR) combined with individual-chemotherapy or individual-chemotherapy alone, in 2010 to 2017. The STK1p was measured using an ECL dot blot assay in sera of patients. Results: Comparisons between 2-cycle-post-individual-chemotherapy and pre-individual-chemotherapy showed that STK1p was significantly associated with treatment effect (p<0.001), and the STK1p low-group correlated significantly to the early/middle clinical stage, as well as the treatment with RR+ individual-chemotherapy (p < 0.05). A significantly poor overall survival (OS) was found in elevated-risk STK1p vs. low-risk STK1p values (p=0.016), in advantage clinical stage vs. early/middle clinical stage (p=0.004), in SCC patients compare vs. AC patients (p=0.003) and in chemotherapy alone vs. RR combined with individual-chemotherapy (p=0.001). The multivariate analysis showed that STK1p (hazard risk=2.295, p=0.010), and RR combined with individual-chemotherapy (hazard risk=3.04, p=0.0001), were independently survival factors. Conclusions: STK1p correlates significantly to survival and is an independent multivariate prognostic factor in NSCLC patients. STK1p as a low-cost assay, is a useful tool to combine with imager for a rational approach to increase the efficacy in early detection of tumor in lung cancer screening and assessment of individual adjusted therapy in NSCLC patients.


PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52885 ◽  
Author(s):  
Albert D. Donnenberg ◽  
Ludovic Zimmerlin ◽  
Rodney J. Landreneau ◽  
James D. Luketich ◽  
Vera S. Donnenberg

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Rancés Blanco ◽  
Elizabeth Domínguez ◽  
Orlando Morales ◽  
Damián Blanco ◽  
Darel Martínez ◽  
...  

The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p=0.006) and proliferation index (p=0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p=0.020) and multivariate (p=0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended.


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