caa a22 4500 469074426 CHVBK 20180323132931.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF01741553 doi (NATIONALLICENCE)springer-10.1007/BF01741553 Hierarchy of in vitro sensitivity and resistance of tumor cells to cytotoxic effector cells, cytokines, drugs and toxins [Elektronische Daten] [Jeffrey Safrit, Benjamin Bonavida] Summary: 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. Springer-Verlag, 1992 Cytotoxicity nationallicence Resistance nationallicence Sensitivity nationallicence Chemotherapy nationallicence Immune effector cells nationallicence Safrit Jeffrey Department of Microbiology and Immunology, UCLA School of Medicine and the Jonsson Comprehensive Cancer Center, University of California, 90 024, Los Angeles, CA, USA aut Bonavida Benjamin Department of Microbiology and Immunology, UCLA School of Medicine and the Jonsson Comprehensive Cancer Center, University of California, 90 024, Los Angeles, CA, USA aut Cancer Immunology, Immunotherapy Springer-Verlag 34/5(1992-09-01), 321-328 0340-7004 34:5<321 1992 34 262 https://doi.org/10.1007/BF01741553 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01741553 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Safrit Jeffrey Department of Microbiology and Immunology, UCLA School of Medicine and the Jonsson Comprehensive Cancer Center, University of California, 90 024, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Bonavida Benjamin Department of Microbiology and Immunology, UCLA School of Medicine and the Jonsson Comprehensive Cancer Center, University of California, 90 024, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 34/5(1992-09-01), 321-328 0340-7004 34:5<321 1992 34 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer