Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

Sampaio, E. P.; Sarno, Euzenir Nunes; Galilly, Ruth; Cohn, Zanvil A.; Kaplan, Gilla

doi:10.1084/jem.173.3.699

Cited by 1,128 publications

(619 citation statements)

References 20 publications

Supporting

Mentioning

569

Contrasting

Unclassified

Order By: Relevance

“…We have show n similar effects to thalidomide firstly for three derivatives of phthalimide structurally related to thalidomide (Sasaki et al 1995) and secondly for pentoxifA-lline. w-hich differs from thalidomide in both structure and mechanism of TNT inhibition (Han et al 1990: Sampaio et al 1991. The augmentation of anti-tumour activitv bv these drugs (Figures 7-9) is difficult to assess statisticallv because DMXAA alone induces a percentage of cures.…”

Section: Determination Of Serum Tnfmentioning

confidence: 99%

Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity

Browne²,

Tchernegovski³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary DMXAA (5,6-dimethylxanthenone-4-acetic acid), a novel anti-tumour agent currently undergoing clinical evaluation. appears to mediate its anti-tumour effects through immune modulation and the production of the cytokine tumour necrosis factor-a (TNF). Our previous studies have shown that thalidomide, a potent inhibitor of TNF biosynthesis that has numerous biological effects, including inhibition of tumour angiogenesis. unexpectedly augments the anti-tumour response in mice to DMXAA. We show here that thalidomide (100 mg kg-) has no effect when administered with inactive doses of DMXAA, and that it must be given simultaneously with an active dose of DMXAA to have its maximum potentiating effect on the growth of the munne Colon 38 adenocarcinoma. To address the issue of whether inhibition of serum TNF production is important for potentiation of anti-tumour activity, we have tested three potent analogues of thalidomide. All three analogues. when co-administered with DMXAA to mice at doses lower than those used with thalidomide, inhibited TNF production and were effective in potentiating the anti-tumour activity of DMXAA against transplanted Colon 38 tumours. One of the analogues, N-phenethyltetrafluorophthalimide. was 1000-fold more potent than thalidomide and at a dose of 0.1 mg kg-' in combination with DMXAA (30 mg kg-') cured 1000 of mice. compared with 670o for the group treated with DMXAA alone. We also tested pentoxifylline and found it to suppress TNF production in response to DMXAA and to potentiate the anti-tumour effect of DMXAA. The results are compatible with the hypothesis that pharmacological reduction of serum TNF levels might benefit the anti-tumour effects of DMXAA and suggest new strategies for therapy using this agent.

show abstract

Section: Determination Of Serum Tnfmentioning

confidence: 99%

Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity

Browne²,

Tchernegovski³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…9 It inhibits the production of tumour necrosis factor-a by human macrophages by accelerating the degradation of tumour necrosis factor messenger RNA transcripts. 10 It has shown promising results in reversing weight loss in human immunodeficiency virus-induced cachexia.…”

Section: Introductionmentioning

confidence: 99%

Oesophageal cancer and cachexia: the effect of short‐term treatment with thalidomide on weight loss and lean body mass

Khan

Simpson²,

Cole

et al. 2003

Aliment Pharmacol Ther

View full text Add to dashboard Cite

SUMMARYBackground: Cachexia is common in patients with advanced cancer and has a direct impact on well-being and mortality. Aim: To test the hypothesis that thalidomide can promote weight gain and lean body mass in patients with advanced oesophageal cancer. Methods:In an open-label study, 11 patients with nonobstructing and inoperable oesophageal cancer were established on an isocaloric diet for 2 weeks, followed by 2 weeks on thalidomide, 200 mg daily. The primary end-points were weight change and lean body mass. Secondary end-points were quality of life and changes in resting energy expenditure.

show abstract

“…It has also proven beneficial in a host of other dermatologic conditions [4]. Its in vitro suppression of tumor necrosis factor-␣ production is well documented, and it has been used to alleviate the cachexia of the HIV-associated wasting syndrome [5,6]. In the hematology community, it has been used to treat graft-versushost disease and most recently, severe plasma cell disorders [1,2,7].…”

Section: Introductionmentioning

confidence: 99%

Thalidomide‐associated hepatitis: A case report

Fowler

Imrie

2001

American J Hematol

View full text Add to dashboard Cite

We report a case of hepatitis in a 58-year-old woman being treated with thalidomide for end-stage plasma cell leukemia. The patient had a medical history including chronic stable hepatitis C infection. At diagnosis there was a severe anemia, thrombocytopenia, hypercalcemia, IgG paraproteinemia, peripheral blood myeloma cells, and a marrow plasmacytosis with lytic bony lesion. The disease was refractory to standard chemotherapy, and she was treated with oral thalidomide. Within 1 week she became jaundiced and developed a marked transaminitis. This promptly resolved upon cessation of thalidomide alone. Thalidomide has recently enjoyed renewed interest as a treatment in many disorders, including plasma cell leukemia. To our knowledge, this is the first reported case of thalidomide-associated hepatotoxicity. Although the mechanism of its actions on the liver are uncertain, it is possible that thalidomide acts as a direct hepatotoxin or as an immuno-modulator, altering the activity of chronic viral hepatitis. We present this case to increase awareness of a new potential side effect of thalidomide as its clinical indications expand. Am. J. Hematol. 66:300-302, 2001.

show abstract

Thalidomide selectively inhibits tumor necrosis factor alpha production by stimulated human monocytes.

Cited by 1,128 publications

References 20 publications

Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity

Interaction of thalidomide, phthalimide analogues of thalidomide and pentoxifylline with the anti-tumour agent 5,6-dimethylxanthenone-4-acetic acid: concomitant reduction of serum tumour necrosis factor-alpha and enhancement of anti-tumour activity

Oesophageal cancer and cachexia: the effect of short‐term treatment with thalidomide on weight loss and lean body mass

Thalidomide‐associated hepatitis: A case report

Contact Info

Product

Resources

About