Document Detail


Hierarchy of in vitro sensitivity and resistance of tumor cells to cytotoxic effector cells, cytokines, drugs and toxins.
MedLine Citation:
PMID:  1540978     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Drug resistance of tumor cells has led to the development of other therapeutic modalities including biological response modifiers, lymphokine-activated killer cells (LAK), and cytokines alone and in combination. The premise of these alternative modalities is that drug resistance can be overcome by other cytotoxic agents or cytotoxic effector cells. However, the relationship between tumor cell sensitivity to these different agents and the cytotoxicity caused by drugs is not known or well understood. Thus, understanding the relationship between these different systems of tumor cell cytotoxicity is essential for optimal therapeutic intervention. To this end, we compared the tumor cell cytotoxicity mediated by recombinant tumor necrosis factor (rTNF), cytotoxic effector cells (natural killer cells, monocytes, LAK cells), chemotherapeutic drugs, and microbial toxins. Human tumor cell lines sensitive and resistant to rTNF or drugs were used to evaluate the effectiveness of the other cytotoxic modalities. Sensitivity was considered as tumor cell cytotoxicity above 15% while resistance refers to that below 10%. Cell lines tested consisted of several histological types such as brain, lung, colon and ovarian tumors. In our experiments, cell lines made resistant to rTNF by coculture were also relatively resistant to unactivated monocytes and their supernatants. These lines were sensitive to all other methods tested including activated monocytes, natural killer and LAK cells, drugs, and toxins. The tumor lines naturally resistant to rTNF were found to have various degrees of sensitivity and resistance to these other systems. Upon the analysis of our data, a pattern emerged that suggested a hierarchy of sensitivity and resistance of the tumor cells to the cytotoxic mechanisms explored. From a majority of cell lines resistant to rTNF to a minority of lines resistant to LAK, we found an interesting gradation of sensitivity and/or resistance to the other cytotoxic modalities employed. The hypothesis of an underlying common mechanism of action within these systems is discussed.
Authors:
J T Safrit; B Bonavida
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cancer immunology, immunotherapy : CII     Volume:  34     ISSN:  0340-7004     ISO Abbreviation:  Cancer Immunol. Immunother.     Publication Date:  1992  
Date Detail:
Created Date:  1992-04-07     Completed Date:  1992-04-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8605732     Medline TA:  Cancer Immunol Immunother     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  321-8     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, UCLA School of Medicine, University of California.
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MeSH Terms
Descriptor/Qualifier:
Bacterial Toxins / pharmacology
Cytokines / pharmacology
Cytotoxicity, Immunologic
Drug Resistance / immunology*
Humans
Interferon-gamma / pharmacology
Killer Cells, Lymphokine-Activated / immunology
Killer Cells, Natural / immunology
Macrophages / drug effects,  immunology
Monocytes / drug effects,  immunology
Recombinant Proteins / pharmacology
Tumor Cells, Cultured / drug effects,  immunology*,  pathology
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
ID/Acronym/Agency:
A107126//PHS HHS; CA43121/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Bacterial Toxins; 0/Cytokines; 0/Recombinant Proteins; 0/Tumor Necrosis Factor-alpha; 82115-62-6/Interferon-gamma

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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