CAM & Life Style > NSAIDS for NHL?

Last update: 09/24/2003

Please do not consider the abstracts within 
to be proof of benefit.  See Evaluating Medical Claims & Data for details.

Can the use of NSAIDs (non-steroidal anti-inflammatory drugs) help to reduce proliferation rates in some lymphomas and be utilized safely to help control the disease?  We do not have the answer.

DISCLAIMER: First, NSAIDs are prescription medications that requires a doctor's supervision. 
Second, it has not been proven that NSAIDs can inhibit or regress lymphomas. 
Finally, be aware that chronic doses of NSAIDs may cause bleeding as well as renal and hepatic problems.

Basis for the hypothesis:

• NSAIDs have been shown to decrease PGE2 and IL-6.

• NSAIDS may help to down-regulate NF-KB (NF-kappaB signal transduction pathway) , that promotes cancer and inflammation.

  NOTE: Fish oils may be an safer alternative to NSAIDs as the fatty acids in this oil also inhibit NF-KB.

• PGE2 and IL-6 seem to stimulate lymphoma progression.

• COX-2 was recently shown to be necessary for VEGF production by stromal cells. VEGF stimulates endothelial and tumor cell proliferation.

• NHL patients with progressing disease often have increasingly levels of VEGF.

Weaknesses of hypothesis:

• Malignant cells are adaptable.  

• The activity of NSAIDS may be too subtle to influence disease progression.  

Abstracts

NOTE:  These are complex issues and concepts.  The abstracts that follow are not proof, but a starting point of investigation.

• Lymphoma-specific: Celecoxib activates a novel mitochondrial apoptosis signaling pathway. 
  FASEB J. 2003 Aug;17(11):1547-9. Epub 2003 Jun 17. PMID: 12824303

NO-NSAIDS - Nitrogen Oxide releasing NSAIDS may prove safer and are potentially more potent.

• NO-releasing NSAIDs are caspase inhibitors. Trends Immunol. 2001 May;22(5):232-5. Review. PMID: 11323270

• IL-1 beta converting enzyme is a target for nitric oxide-releasing aspirin: new insights in the antiinflammatory mechanism of nitric oxide-releasing nonsteroidal antiinflammatory drugs. J Immunol. 2000 Nov 1;165(9):5245-54. PMID: 11046058

NF-KB

• Therapeutic potential of inhibition of the NF-B pathway in the treatment of inflammation and cancer 
  - J Clin Invest, January 2001 - jci.org

• Dysregulation of apoptosis in Waldenstrom's macroglobulinemia does not involve nuclear factor kappa B activation.
  Semin Oncol. 2003 Apr;30(2):161-4. PMID: 12720128

IL-6

• Hong SH, Ondrey FG, Avis IM, Chen Z, Loukinova E, Cavanaugh PF Jr, Van Waes C, Mulshine JL.
  Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation? FASEB J. 2000 Aug;14(11):1499-507. PMID: 10928984; UI: 20387210 Related Articles

• Podor TJ, Jirik FR, Loskutoff DJ, Carson DA, Lotz M. 
  Human endothelial cells produce IL-6. Lack of responses to exogenous IL-6.
  Ann N Y Acad Sci. 1989;557:374-85; discussion 386-7. PMID: 2660697; UI: 89285909 Related Articles

Other

• Padilla J, Kaur K, Harris SG, Phipps RP.
  PPAR-gamma-mediated regulation of normal and malignant B lineage cells.
  Ann N Y Acad Sci. 2000 Apr;905:97-109. PMID: 10818446; UI: 20278387 Related Articles

• Bertolini F, Paolucci M, Peccatori F, Cinieri S, Agazzi A, Ferrucci PF, Cocorocchio E, Goldhirsch A, Martinelli G.
  Angiogenic growth factors and endostatin in non-Hodgkin's lymphoma.
  Br J Haematol. 1999 Aug;106(2):504-9. PMID: 10460612; UI: 99390203 Related Articles

• Arai J, Yasukawa M, Yakushijin Y, Miyazaki T, Fujita S.
  Stromal cells in lymph nodes attract B-lymphoma cells via production of stromal cell-derived factor-1.
  Eur J Haematol. 2000 May;64(5):323-32. PMID: 10863978; UI: 20319974 Related Articles