Linked Life Data

1305681

Source:http://linkedlifedata.com/resource/pubmed/id/1305681

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1993-7-22
pubmed:abstractText
Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) widely used for treatment of inflammatory arthritis. Recent experimental and clinical studies suggest that piroxicam, as well as other NSAIDs, may be useful for chemoprevention of colon cancer. While there is less information regarding NSAIDs for chemoprevention of urinary bladder malignancy, there are compelling data which suggest that this should be evaluated. A major effect of NSAIDs is inhibition of cyclooxygenase, the rate-limiting enzyme for conversion of arachidonic acid to important signal molecules, including prostaglandins, which profoundly affect cellular functions in many tissues. The initial enzyme reaction leading to formation of prostaglandin H can be accompanied by cooxidation of xenobiotics resulting in extrahepatic and local tissue production of reactive products which are carcinogenic. The end product prostaglandins, especially prostaglandin E2 (PGE2), are biological modifiers which can significantly affect cell proliferation and tumor growth. High levels of PGE2 stimulate growth of certain tumor cell lines while inhibition of prostaglandin synthesis with indomethacin or piroxicam can cause suppression. The mechanisms for this effect are unclear. Studies in cultured cells exposed to indomethacin show inhibition of G1-to-S phase progression of the cell cycle and a reduction in overall DNA synthesis. It is unclear whether this effect on cell growth results from some direct action of the NSAID or a reduction in prostaglandins or indirectly from modulation of important control signals, such as calcium flux. In addition to cyclooxygenase, NSAIDs can inhibit activity of other enzymes, including phosphodiesterases and cyclic GMP-AMP protein kinases, which may be central to cancer initiation and promotion. NSAIDs can also interfere with transmembrane ion fluxes and with cell-to-cell binding. Prostaglandins can modulate a variety of immunological responses and thereby play an important role in host antitumor immunity. For example, high levels of tissue PGE2 are frequently associated with suppression of immune surveillance and killing of malignant cells. Conversely, immune responses are generally enhanced by drugs that inhibit prostaglandin synthesis. PGE2 can act as a feedback inhibitor for cellular immune processes, such as T-cell proliferation, lymphokine production, and cytotoxicity. This effect is also seen for macrophage activity and natural killer cell toxicity. In general, either increased production of PGE2 or increased sensitivity to normal amounts of PGE2 results in depressed cellular immunity. Cyclooxygenase inhibitors (NSAIDs) such as piroxicam which decrease PGE2 production can stimulate cellular immune function both in vitro and in vivo. A variety of tumor cell lines and human malignancies produce large quantities of prostaglandins.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0733-1959
pubmed:author
pubmed:issnType
Print
pubmed:volume
16I
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
156-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Piroxicam and other cyclooxygenase inhibitors: potential for cancer chemoprevention.
pubmed:affiliation
Department of Medicine, University of Arizona, Tucson 85724.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Review, Clinical Trial, Phase II