Blood serum proteins as biomarkers for prediction of survival, locoregional control and distant metastasis rate in radiotherapy and radio-chemotherapy for non-small cell lung cancer

Suwiński, Rafał; Giglok, Monika; Galwas-Kliber, K.; Idasiak, Adam; Jochymek, B.; Deja, R.; Masłyk, Barbara; Mrochem-Kwarciak, Jolanta; Butkiewicz, Dorota

doi:10.1186/s12885-019-5617-1

Cited by 26 publications

(20 citation statements)

References 34 publications

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“…Lung cancer, as one of the most common malignant tumors, is the leading cause of cancer-related death worldwide [1]. It has a dismal prognosis and a five year survival rate lower than 15% [2]. Non-small cell lung cancer (NSCLC), which includes squamous cell carinoma, adenocarcinoma and large-cell carcinoma, is a classic subtype of lung cancer and accounts for 85% of all lung cancer cases [3].…”

Section: Introductionmentioning

confidence: 99%

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Teng

Mei

Zhou

et al. 2020

Cancers

244

146

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Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1β and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen Cancers 2020, 12, 193 2 of 27 species (ROS) levels in A549 and H1299 cells, and N-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.

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Section: Introductionmentioning

confidence: 99%

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Teng

Mei

Zhou

et al. 2020

Cancers

244

146

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“…Non-covalent protein-protein interactions underlie many biological and physiological processes, including protein self-assembly, [1][2][3] protein aggregation, [4][5][6] antibody-antigen recognition, [7][8][9] muscle contraction, 10 and cellular communication. 11 One fundamental application of measuring protein-protein interactions is based on immuno-assays for the detection of biomarkers in body fluids, primarily human serum, related to various diseases including cancer, [12][13][14][15] protein misfolding diseases, [16][17][18][19][20][21] auto-immune diseases, 22 and graft rejection. 23 In the latter, detection of antibodies against donor Human Leukocyte Antigens (HLA), termed alloantibodies, in patient serum serve as strong indicator for potential rejection of transplants.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Antibody Affinity Profiling for In-Solution Characterisation of Alloantibody - HLA Interactions in Human Serum

Schneider

Scheidt

et al. 2020

Preprint

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The detection and characterisation of antibodies in human blood is a key for clinical diagnostics and risk assessmentn for autoimmunity, infectious diseases and transplantation. Antibody titre derived from immunoassays is a commonly used measure for antibody response, but this metric does not resolve readily the two fundamental properties of antibodies in solution, namely their affinity and concentration. This difficulty originates from the fact that the fundamental parameters describing the binding interaction, affinity and ligand concentration, are convoluted into the titre measurement; moreover, the difficulty of controlling the surface concentration and activity of the immobilised ligand can make it challenging to distinguish between avidity and affinity. To address these challenges, we developed microfluidic antibody affinity profiling, an assay which allows the simultaneous determination of both affinity and antibody concentration, directly in solution, without surface immobilisation or antibody purification. We demonstrate these measurements in the context of alloantibody characterisation in organ transplantation, using complex patient sera, and quantify the concentration and affinity of alloantibodies against donor Human Leukocyte Antigens (HLA), an extensively used clinical biomarker to access the risk of allograft rejection. These results outline a path towards detection and in depth profiling of antibody response in patient sera.

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“…2) Acetylated HMGB1, which has been released, activates macrophages to upregulate nuclear factor kappa B, thereby promoting the synthesis and secretion of vascular endothelial growth factor and indirectly promoting the formation of new blood vessels ( 38 , 39 ). 3) HMGB1 can upregulate the expression of fibroblast growth factor (FGF) ( 40 ), stimulate the secretion of platelet-derived growth factor (PDGF) ( 41 , 42 ), and greatly enhance the proliferation and migration ability of endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

HMGB1, the Next Predictor of Transcatheter Arterial Chemoembolization for Liver Metastasis of Colorectal Cancer?

et al. 2020

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HMGB1 is an important mediator of inflammation during ischemia–reperfusion injury on organs. The serum expression of HMGB1 was increased significantly on the 1st day after TACE and decreased significantly which was lower on the 30th day after TACE. Tumor markers of post-DEB-TACE decreased significantly. The correlational analysis showed that patients with low HMGB1 expression had lower risks of fever and liver injury compared those with the higher expression, while the ORR is relatively worse. Patients with lower expression of HMGB1 had longer PFS, better efficacy, and higher quality of life. With the high post-expression, the low expression had lower incidence of fever and liver injury too. There was no statistical difference in the one-year survival among the different groups. The quality of life of all patients was improved significantly. The over-expression of HMGB1 in LMCRC is an adverse prognostic feature and a positive predictor of response to TACE.

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Blood serum proteins as biomarkers for prediction of survival, locoregional control and distant metastasis rate in radiotherapy and radio-chemotherapy for non-small cell lung cancer

Cited by 26 publications

References 34 publications

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Microfluidic Antibody Affinity Profiling for In-Solution Characterisation of Alloantibody - HLA Interactions in Human Serum

HMGB1, the Next Predictor of Transcatheter Arterial Chemoembolization for Liver Metastasis of Colorectal Cancer?

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