Endotoxin-Induced Tumor Necrosis Factor

Oettgen, Herbert F.; Carswell, Elizabeth A.; Kassel, Robert; Fiore, Nancy; Williamson, Barbara; Hoffmann, Michael K.; Haranaka, Katsuyuki; Old, Lloyd J.

doi:10.1007/978-3-642-81491-4_32

Cited by 37 publications

(28 citation statements)

References 7 publications

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“…(Algire et al, 1952). In contrast to LPS, TNF displays a direct cytotoxic activity for cultured tumour cells of both mouse and human origin Matthews & Watkins, 1978;Old, 1976). The hypothesis that LPS causes release of a tumouricidal factor, TNF, from activated macrophages has been confirmed (Matthews, 1978;Mannel et al, 1980;Satomi et al, 1981).…”

Section: Resultsmentioning

confidence: 98%

“…Activation of macrophages by agents such as BCG and P. acnes has been found to produce a high TNF activity. The spleen and liver weights are increased by such stimulation because of RES activation, based on histological and functional examinations (Old et al, 1960). At an early stage of P. acnes administration, polymorphonuclear cell infiltration is dominant and no TNF activity is produced.…”

Section: Resultsmentioning

confidence: 99%

“…Certain agents which activate the RES, such as BCG, Corynebacterium parvum (C. parvum) and zymosan, have been found to alter the development of a number of experimental tumours (Old et al, 1960;Piessens et al, 1957).…”

mentioning

confidence: 99%

“…TNF exhibits a direct cytotoxicity against murine or human cancer cells in vitro but has no cytotoxicity against normal or embryonal cells Matthews & Watkins, 1978;Old, 1976). The in vitro cytotoxic activity is of particular interest because the observed properties of tumour cell sensitivity and species independence are characteristic of the in vitro toxic activity of activated macrophages (Oettgen et al, 1980;Piessens et al, 1957).…”

mentioning

confidence: 99%

“…The in vitro cytotoxic activity is of particular interest because the observed properties of tumour cell sensitivity and species independence are characteristic of the in vitro toxic activity of activated macrophages (Oettgen et al, 1980;Piessens et al, 1957). Our previous studies demonstrated that TNF is produced from activated macrophages .…”

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confidence: 99%

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Differences in tumour necrosis factor productive ability among rodents

Haranaka¹,

Satomi²,

Sakurai³

1984

Br J Cancer

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Summary Large differences in tumour necrosis factor (TNF) productive ability were observed among various strains of mice. DDY, CD-1, ICR and DBA/2 mice could produce a high titre of TNF activity, whereas Balb/c, C3H/HeJms and A/J mice produced a low titre of TNF activity. Administration of 200pg/mouse of LPS to some strains of mice, i.e. DDD and C57B1/6J resulted in good production of TNF. ICRnu/nu mice produced the highest TNF activity among the nude mice. Balb/cnu/nu and DDDnu/nu mice exhibited very low titres of TNF activity. Nude mice required a rather higher dose of the priming agent, Propionibacterium acnes, than heterozygote littermates. Although it is commonly accepted that dual stimulation is necessary for TNF production, TNF activity was detected without the priming agent in SD rats and Golden hamsters by single injection of LPS. In these animals, much higher TNF production was observed after Propionibacterium acnes treatment than after a single injection of LPS. Large differences in TNF productive ability also existed among strains of rats. Although all animals receiving priming agents revealed hyperplasia of reticuloendothelial system, the sensitivity of the animals to LPS is considered to be the most important factor in their TNF productive ability.

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Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Differences in tumour necrosis factor productive ability among rodents

Haranaka¹,

Satomi²,

Sakurai³

1984

Br J Cancer

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A phase I clinical trial of recombinant human tumor necrosis factor

Creagan

Kovach

Moertel

et al. 1988

Cancer

121

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We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF-alpha) in 27 patients with advanced solid neoplasms. Therapy consisted of a 30-minute intravenous (IV) infusion on days 1 through 5, every 2 to 3 weeks. Daily doses ranged from 5 micrograms/m2 to 200 micrograms/m2. Dose-limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38 degrees C) were not clearly dose-related between 5 micrograms/m2/d and 150 micrograms/m2/d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3, 1.2 X 10(3)/microliters in two patients) at a dose of 5 micrograms/m2/d and 150 micrograms/m2/d, respectively; and thrombocytopenia (leukocyte count, 73 X 10(3)/microliters) at 10 micrograms/m2/d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/microliters compared with a subsequent median of 462 cells/microliters. We also detected hypertriglyceridemia in all patients. The median baseline increased from 93 mg/dl (range, 56 to 219 mg/dl) to 203 mg/dl (range, 94 to 454 mg/dl). From our experience, a clinically manageable outpatient regimen for Phase II trials consists of rTNF-alpha (150 micrograms/m2) followed by a 1-hour IV infusion of 500 ml of normal saline to abrogate hypotension daily for 5 days every 2 weeks for four cycles, then every 3 weeks thereafter to facilitate recovery from constitutional sequelae.

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A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma

Kemeny

Childs

Larchian

et al. 1990

Cancer

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Sixteen previously treated (with only one prior regimen) patients with histologically proven metastatic or locally recurrent colorectal carcinoma were treated with recombinant tumor necrosis factor (rTNF) administered by 30-minute i.v. infusions twice daily for 5 consecutive days every other week for 8 weeks. Patients received 100 micrograms/m2 twice daily on day 1 of cycle 1 with escalation to 150 micrograms/m2 twice daily thereafter. Patients were concomitantly treated with indomethacin 25 mg every 6 hours and acetaminophen 650 mg every 4 hours to obviate fever and chills. Toxicities included: nausea/vomiting (69%), headache (25%), chills (69%), pain at tumor sites (63%), hypotension (31%), and hypertension (38%). Hematologic toxicity included leukopenia less than 2000 cells/mm3 (38%) and thrombocytopenia less than 100,000 cells/mm3 (13%). Liver function abnormalities occurred independently of the site or extent of metastatic disease and inconsistently in each treatment cycle. Four patients developed bilirubinemia greater than 2.5 x baseline values (range, 2.5 to 10.3 U/L); five patients had greater than 2.5 x elevations in alkaline phosphatase (range, 624 to 1663 U/L). Two patients developed retinal vein thrombosis in the absence of hemostatic abnormalities. In both instances, this complication occurred several weeks after completion of therapy. No objective responses were noted in 14 evaluable patients (95% confidence interval: 0 to 0.23). Three patients had stable disease for a median duration of 4.5 months. In conclusion, i.v. rTNF at this dose and schedule has no demonstrable antitumor efficacy. Twice-daily i.v. administration of this agent is associated with more hepatotoxicity than previously reported in trials using subcutaneous or once daily i.v. administration. Retinal vein thrombosis may be a late complication of i.v. rTNF at this dose and schedule.

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Endotoxin-Induced Tumor Necrosis Factor

Cited by 37 publications

References 7 publications

Differences in tumour necrosis factor productive ability among rodents

Differences in tumour necrosis factor productive ability among rodents

A phase I clinical trial of recombinant human tumor necrosis factor

A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma

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