Specificity of tumor necrosis factor toxicity for human mammary carcinomas relative to normal mammary epithelium and correlation with response to doxorubicin

Journal Article · Fri Jul 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.13.4740· OSTI ID:5641356

Dollbaum, C; Creasey, A A; Dairkee, S H; Hiller, A J; Rudolph, A R; Lin, L; Vitt, C; Smith, H S ^[1]

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1. Peralta Cancer Research Institute, Oakland, CA (USA)

By using a unique short-term culture system capable of growing both normal and malignant breast epithelial tissue, human recombinant tumor necrosis factor (TNF) showed preferential cytotoxicity to malignant cells as compared to the corresponding nonmalignant cells. Most of the malignant specimens were sensitive to TNF with 13 of 18 specimens showing 90% inhibition of clonal growth (ID{sub 90}). In contrast, all 13 nonmalignant specimens tested clustered at the resistant end of the TNF response spectrum. This differential sensitivity to TNF was seen in three cases in which malignant and nonmalignant breast epithelial tissues from the same patient were studied. To investigate the mechanism of resistance to TNF by normal cells, the presence of receptors for TNF was determined. Five of six cultures showed specific binding of {sup 125}I-labeled TNF and there was no relationship between the degree of resistance and the degree of specific binding. Simultaneous comparison of tumor responsiveness to doxorubicin and TNF revealed a positive correlation in ID{sub 90} values; these results may have important implications for the clinical use of TNF in cancer patients heavily pretreated with doxorubicin.

• OSTI ID: 5641356
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:13; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
DOXORUBICIN
BIOLOGICAL EFFECTS
PROTEINS
CROSS-LINKING
RECEPTORS
CARCINOMAS
CELL CULTURES
CHEMOTHERAPY
EPITHELIUM
IODINE 125
MAMMARY GLANDS
NECROSIS
PATIENTS
TOXICITY
TUMOR CELLS
WOMEN
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
BETA DECAY RADIOISOTOPES
BODY
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DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
FEMALES
GLANDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MAMMALS
MAN
MEMBRANE PROTEINS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
POLYMERIZATION
PRIMATES
RADIOISOTOPES
THERAPY
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550301* - Cytology- Tracer Techniques