Tumors secreting human TNF/cachectin induce cachexia in mice

Oliff, Allen; Defeo-Jones, Deborah; Boyer, Mark; Martinez, Douglas; Kiefer, David M.; Vuocolo, G A; Wolfe, Abigail; Socher, Susan H.

doi:10.1016/0092-8674(87)90028-6

Cited by 594 publications

(273 citation statements)

References 47 publications

Supporting

Mentioning

255

Contrasting

Unclassified

Order By: Relevance

“…We have transfected IL-6 cDNA to LLC cells in the expectation to see an anti-tumour effects as reported (Mule et al, 1990;Kitahara et al, 1990 Body weight loss is commonly observed in patients with cancer and is associated with other symptoms such as anorexia, nausea, asthenia, muscle weakness and anaemia ('cancer associated cachexia') (Oliff et al, 1987;Lonnroth et al, 1990;Gelin et al, 1991). Secretion of TNF and IL-1 from tumour cells has been reported to induce cachexia to tumour bearing mice (Oliff et al, 1987;Lonnroth et al, 1990;Gelin et al, 1991). In a more recent report, secretion of IL-6 from Chinese hamster ovarian cells cause cachexia, hypercalcaemia, leukocytosis and thrombocytosis in tumour-bearing nude mice (Black et al, 1991).…”

Section: Resultsmentioning

confidence: 99%

Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

et al. 1993

View full text Add to dashboard Cite

Summary HuIL-6 cDNA, cloned into a neomycin resistant conferring expression vector, BMGNeo, was transfected into Lewis Lung Carcinoma (LLC) cells. LLC cells (5 x 106 ml-X) transfected with IL-6 cDNA (LLC-IL6) secreted IL-6 into the culture supernatant at a concentration of 9.9 ngml-' within 48 h. When 1,000,000 of untransfected LLC, BMGNeo vector transfected LLC (LLC-Neo) or LLC-1L6 cells were transplanted into C57BL/6 mice subcutaneously, the mean ± s.d. of survival times of these mice were 33.3 ± 9.7, 34.3 ± 7.1 and 17.0 ± 3.1 days, respectively. The survival time of LLC-1L6 cells transplanted mice was significantly shorter than that of LLC (P<0.01) or LLC-Neo (P<0.01) cells transplanted mice without a measurable difference of tumour size. Plasma concentration of IL-6 steadily increased in LLC-IL6 transplanted mice. Body weight and serum albumin were significantly lower in LLC-1L6 transplanted mice than in LLC transplanted mice. Mouse IL-la and mouse TNF-a were not detected in the plasma of LLC-1L6 transplanted mice. These data suggested that secretion of IL-6 from LLC cells was unable to alter net tumour growth rate but rather caused a state similar to cachexia without detectable increase of IL-Ia and TNF-a in the plasma. This state may be responsible for the shortened survival of LLC-1L6 tumour-bearing mice.

show abstract

Section: Resultsmentioning

confidence: 99%

Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

et al. 1993

View full text Add to dashboard Cite

show abstract

“…Several cytokines, including tumor necrosis factor ␣ (TNF␣) and interleukin 1 (IL-1), IL-6, and IL-8, have been proposed as agents that cause or contribute to the condition. 3,[5][6][7][8] Oliff et al 9 demonstrated that TNF␣ induced a cachexia-like syndrome in mice, and other studies have supported these observations. 10,11 Increased TNF␣ levels were also associated with weight loss in patients with pancreatic carcinoma 12 and gastrointestinal carcinoma.…”

mentioning

confidence: 86%

Elevation of cytokine levels in cachectic patients with prostate carcinoma

Pfitzenmaier

Vessella

Higano

et al. 2003

Cancer

143

100

View full text Add to dashboard Cite

BACKGROUNDApproximately 60–70% of patients with advanced prostate carcinoma (CaP) suffer from cachexia, one of the most devastating conditions associated with advanced malignant disease. The pathophysiology of cachexia is multifactorial, and several cytokines, such as tumor necrosis factor α (TNFα) and interleukin 1 (IL‐1), IL‐6, and IL‐8, may be involved. The objective of the current study was to determine whether cachexia associated with advanced CaP is accompanied by increased serum levels of TNFα, IL‐1β, IL‐6, and IL‐8.METHODSThe levels of TNFα, IL‐1β, IL‐6, IL‐8, and prostate specific antigen (PSA) were examined in serum samples from normal donors (n = 10 donors), from patients with organ‐confined CaP (n = 19 patients), from patients with advanced CaP without cachexia (n = 17 patients), and from patients with cachectic CaP (n = 26 patients). DPC Immulite and Abbott IMx Total‐PSA assays were used to determine cytokine and PSA levels, respectively.RESULTSLevels of TNFα, IL‐6, and IL‐8 were elevated significantly in the group of patients with advanced, cachectic CaP compared with patients who were without cachexia. In the cachectic patients, levels of TNFα were correlated positively with IL‐8, and there was no correlation between PSA levels and any of the cytokine levels. IL‐1β levels were below the limit of detection in all samples.CONCLUSIONSThe current results show that levels of TNFα, IL‐6, and IL‐8 were increased in CaP patients with cachexia. Increased levels of these cytokines were not correlated with PSA levels, suggesting that they are regulated by a mechanism that is independent of PSA synthesis. Additional fundamental research is needed to determine the mechanisms involved and to identify potential therapeutic targets in patients with cachexia. Cancer 2003;97:1211–6. © 2003 American Cancer Society.DOI 10.1002/cncr.11178

show abstract

“…Several studies have demonstrated the ability of TNF to induce weight loss in experimental animals (Oliff et al, 1987). Weight loss produced by TNF is typified by a marked anorexia, and the decrease in food and water intake is directly proportional to the decrease in body weight .…”

Section: Mechanism Of Cachexiamentioning

confidence: 99%

Cancer cachexia

Tisdale¹

1991

Br J Cancer

View full text Add to dashboard Cite

Tumors secreting human TNF/cachectin induce cachexia in mice

Cited by 594 publications

References 47 publications

Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumour growth rate but cause weight loss and shortened survival in syngeneic mice

Elevation of cytokine levels in cachectic patients with prostate carcinoma

Cancer cachexia

Contact Info

Product

Resources

About