Page 330 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

308 PART III Therapeutic Modalities for the Cancer Patient

Cell signaling event

VetBooks.ir activation or leukotriene PLA 2 activation activation or prostaglandin
Autocrine/paracrine
Autocrine/paracrine
receptors
and oxo-ETE receptors
Arachidonic acid release

Leukotriene Prostaglandin
synthase activity synthase activity
LTB 4 , PGE 2 ,
5-oxo-ETE, 5-LOX COX other
other eicosanoids eicosanoids
Nucleus

• Fig. 16.5 Arachidonic acid (AA) is released from the cell membrane as a result of cell signaling events that
lead to nuclear translocation of AA. Cyclooxygenase and lipoxygenase activity, coupled with leukotriene
synthase or prostaglandin synthase, allows the formation of bioactive eicosanoids; when released, these
can have autocrine or paracrine cell proliferation signaling activities, depending on receptor presence.

skeletal muscle in cats may respond to a higher protein intake by lean body mass and possibly reduce the tumor growth rate. 337–344
increasing lean mass slightly. With these ideas in mind, we often These fatty acids may transform into inert eicosanoids (PGE ,
3
recommend feeding cats higher protein (>35% dry matter) and fat LTB , 12-HEPE, and 5-HEPE) rather than proinflammatory
5
(>20% dry matter); dogs can be fed similarly, even though many eicosanoids (PGE , LTB , 12-HETE and 5-HETE). The pathways
2
4
commercial dog foods have lower protein levels (typically >30% and eicosanoids liberated are highly dependent on the enzymatic
dry matter is recommended) than cat food. machinery present in the cells. Although the addition of fatty acids
into the cell membrane may affect intracellular signaling events,
Amino Acids the intracellular enzymatic machinery that modifies the primary
fatty acid into promitogenic, or inert, eicosanoids may be more
The benefits of additional protein to the diet of cancer patients important. 343–346 Cell signaling events that lead to the release of
may result from increased circulating amino acids as inhibitory arachidonic acid from the cell membrane can be converted to eico-
molecules in neoplastic cell proliferation. 328 Arginine has received sanoids which, when released from the cell, can have local or para-
considerable attention, because low millimolar concentrations of crine effects on cell growth through interactions with eicosanoid
arginine can inhibit various neoplastic cell lines by altering cell receptors (Fig. 16.5). The two enzymes that have received the most
cycle progression. 331–334 A diet higher in arginine and omega-3 attention are cyclooxygenase and 5-lipoxygenase because of the
fatty acids improved remission and STs in dogs with lym- promitogenic mechanisms of action observed by their respective
phoma 257 ; however, the practicality of using an amino acid sup- eicosanoids, PGE (COX) and 5-oxoETE/LTB (5-LOX). 343–346
2
4
plement such as arginine leaves much to be desired, because the Although this may be relevant to many types of human cancers,
required dose is in excess of 100 mg/kg body weight. Additionally, little data is available on companion animals; the most intriguing
the bitter taste of arginine and the potential for creating amino studies focused on the use of COX inhibition in TCC. 347,348
acid imbalance prevent its use in long-term feeding regimens. The A study in dogs with cancer that were fed a fish-based. omega-3
benefits of glutamine also have been touted because of its abilities fatty acid–enhanced diet showed a small improvement in STs;
to preserve lean body mass and enhance mucosal barrier func- however, there were multiple changes in the dietary trial, including
tion 335,336 ; however, enterocytes’ ability to utilize glutamine and arginine and energy substrate differences, which may have played
first-pass hepatic metabolism do not allow glutamine to have any a role. 257 The increased EPA may inhibit promitogenic eicosanoid
pronounced effects on lean mass. The use of high-protein mixed formation 346 ; but it is unclear to what tumor types this may apply.
meals to support enterocyte health and mucosal barrier function Some neoplastic tissues use the proinflammatory cytokine milieu
often is recommended anyway. to promote proliferation or upregulate pathways that may pro-
mote metastasis. 349 The benefits of fish oils may go beyond mild
Polyunsaturated Fats suppression of tumor cell proliferation, because the antiinflam-
matory effects of fish oil may also quench the inflammatory reac-
Using fat in diets is helpful for increasing palatability and energy tions associated with certain cancers. 350–352 Hence, there is little
density, but in many instances the fatty acid constituents can downside to increasing dietary omega-3 fatty acid consumption in
influence neoplastic cell growth. Human and rodent model stud- cancer patients. The lack of clinical studies in this area precludes
ies suggest that consumption of high concentrations of omega-3 an optimal dosing regimen, and the findings of a recent meta-
fatty acids, namely eicosapentaenoic acid (EPA) and docosahexae- analysis of human trials using fish oils for quality of life issues were
noic acid (DHA), in the form of marine oils may perturb loss of inconclusive. 353 Additionally, cats seem to be more sensitive to fish