Effects of polyclonal activators on cell differentiation and cytokine production of cultured invasive breast carcinoma of no special type, their association with tumour histopathological parameters and lymph node metastasis
Autor: | A I Autenshlyus, V. A. Vavilin, Nikolay Varaksin, Vyacheslav V. Lyakhovich, Igor Marinkin, Elena Mikhailova, Sergey Arkhipov |
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Rok vydání: | 2020 |
Předmět: |
Adult
Lipopolysaccharides 0301 basic medicine polyclonal activators Lipopolysaccharide Cellular differentiation medicine.medical_treatment Immunology Breast Neoplasms tumour cells Metastasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Differentiation therapy invasive breast carcinoma of no special type Antineoplastic Combined Chemotherapy Protocols Biopsy Concanavalin A medicine Humans metastasis Immunology and Allergy Neoplasm Invasiveness Original Research Article Phytohemagglutinins Aged Phytohaemagglutinin Pharmacology biology medicine.diagnostic_test business.industry Carcinoma Cell Differentiation differentiation Middle Aged medicine.disease cytokines 030104 developmental biology Cytokine chemistry Polyclonal antibodies Lymphatic Metastasis 030220 oncology & carcinogenesis biology.protein Cancer research Female business Signal Transduction |
Zdroj: | International Journal of Immunopathology and Pharmacology |
ISSN: | 2058-7384 |
Popis: | Currently, a number of promising strategies and approaches to cancer treatment include differentiation therapy. However, theoretical and methodological foundations of this field are not yet well developed. The objective of this study was to determine the effects of a mixture of polyclonal activators (PAs; phytohaemagglutinin, concanavalin A and lipopolysaccharide) on cytokine production by biopsy samples of invasive breast carcinoma of no special type (IBC-NST) having various differentiation abilities and metastatic potentials as well as on differentiation status of the IBC-NST biopsy samples. We used ELISAs to investigate spontaneous and PA-stimulated cytokine production in the IBC-NST biopsy samples; from these data, we calculated a cytokine production stimulation index (SIPA). The effect of PAs on tumour cell differentiation was determined via a differentiation stimulation index (DSI). DSI was found to vary within the range 1.0–5.0. After treatment with PAs, in the IBC-NST biopsy samples of group I (DSI 1.25), the production of IL-6, IL-1β, IL-1Ra, TNF-α, G-CSF and GM-CSF significantly increased, while the production of VEGF-A decreased. Receiver operating characteristic (ROC) analysis of SIPA revealed that increased production of IL-18 in the IBC-NST biopsy samples after exposure to PAs may block the PA-driven, cytokine-mediated differentiation of moderately differentiated into highly differentiated tumour cells. The ROC analysis also uncovered an association between the responses of tumour cells to PAs and lymph node metastasis observed in the patients. The findings suggest that there is a need for research aimed at finding new drugs for differentiating cancer therapy and at searching for targeted inducers of cytokine production or specific suppressors of their induction. |
Databáze: | OpenAIRE |
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