![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
University Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW, United Kingdom,
*
Isotope Biochemistry Laboratory, Scottish Universities Research and Reactor Centre, East Kilbride G75 0QF, United Kingdom and
Department of Clinical Chemistry, University of Liverpool L69 3BX, United Kingdom
3To whom correspondence should be addressed.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
-1-acid
glycoprotein, -1-antitrypsin, ceruloplasmin and C-reactive
protein (CRP) were significantly elevated in the cancer patients
compared with healthy controls, reflecting their roles as negative and
positive acute phase proteins, respectively. In the supplemented cancer
group, the only significant change in APP concentrations over the 4-wk
study period was an increase in transferrin. In the control cancer
group there were further significant reductions in albumin, transferrin
and pre-albumin, and a significant increase in CRP concentration.
These results suggest that many positive and negative APP are altered
in advanced pancreatic cancer. The APPR tends to progress in untreated
patients but may be stabilized by the administration of a fish
oil–enriched nutritional supplement. This may have implications for
reducing wasting in such patients.
KEY WORDS: • cancer cachexia • acute-phase protein response • fish oil • eicosapentaenoic acid • humans
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
) and is widely used as
a marker for the acute-phase response (APR) in clinical practice.
At diagnosis ~40% of patients with pancreatic cancer exhibit an
elevated serum level of CRP. This proportion increases to ~80% as
patients approach the time of death (Falconer et al. 1994
). We have found the presence of an elevated CRP level to
be an independent and robust predictor of poor survival in pancreatic
cancer (Falconer et al. 1995
).
In the human hepatocyte the production of APP is regulated by
interleukin (IL)-6 (Castell et al. 1990
). Thus the level
of the APR in vivo may be taken as indirect evidence of proinflammatory
cytokine production. From studies in animal models a variety of
proinflammatory cytokines have been strongly implicated in both the
anorexia and altered metabolism thought to contribute to cancer
cachexia (Tracey et al. 1988
, Yasumoto et al. 1995
). However, it is not known whether the loss of lean tissue
in cachexia is due to a direct effect of cytokines at the level of
skeletal muscle or whether net loss of muscle protein is due to
indirect effects of altered metabolism elsewhere, or a combination of
these two.
It has been suggested that with the induction of APR during inadequate
dietary intake, the imbalance in amino acid composition between
skeletal muscle and APP may contribute to increased loss of muscle
(Reeds et al. 1994
). Clearly, for this mechanism to be
important, there would have to be a uniform upregulation of the
positive APP whose serum concentrations are measured in gram quantities
and have a high turnover rate. However, there is little information on
the range of APP that are upregulated in cachectic cancer patients.
Cancer cachexia has proven resistant to intervention with supplemental
enteral or parenteral nutrition (Nixon et al. 1981
,
Ovesen et al. 1993
). This may be due to metabolic
changes, including the APPR, which at least in part, are stimulated by
increased tumor or host production of proinflammatory cytokines
(Castell et al. 1990
, Falconer et al. 1994
, Strassmann et al. 1993
, Yasumoto et al. 1995
). We have previously shown that fish oil or
eicosapentaenoic acid (EPA), a polyunsaturated fatty acid derived from
fish oil, administered to patients with advanced pancreatic cancer may
attenuate weight loss while down-regulating production of IL-6 and
serum levels of CRP (Wigmore et al. 1996
, Wigmore et al. 1997a
). Although in vitro work has suggested that EPA
may have differential effects on a spectrum of acute phase proteins
produced in response to IL-6 (Wigmore et al. 1997b
), it
is not known what effect EPA has on the concentration of a range of APP
when it is administered in vivo.
This study was designed to determine the effects of the administration of a nutritional supplement containing EPA-rich fish oil on the levels of individual APP in patients with advanced pancreatic cancer compared with patients receiving full supportive care alone.
|
METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
After informed consent and local ethical committee approval, 36 weight-losing patients with advanced pancreatic cancer were studied and compared with 6 healthy individuals. Diagnosis of advanced pancreatic cancer was based on histologic or unequivocal radiology or operative findings. Weight was measured with subject in light clothing without shoes using a beam scale (Avery, Birmingham, U.K.). No subjects had clinically evident edema or ascites.
All subjects underwent venous blood sampling at least 3 wk after surgery or bile duct stenting. The initial 18 patients received full supportive care alone and underwent a further venous blood sample after a median of 28 d. The subsequent 18 patients received 2 cans/d of a nutritional supplement enriched with fish oil providing a total of 2.6 MJ, 32.2 g protein, 99.4 g carbohydrate, 13 g fat, 2.18 g EPA and 0.92 g docosahexaenoic acid (DHA) in a volume of 480 mL (Ross Products Division, Columbus, OH). After a median of 24 d a second venous blood sample was taken.
Assay procedure.
Serum and plasma were stored at -70°C until analysis by
immunoturbidometry using Tina-Quant assay kits (Boehringer
Mannheim, Germany) on a Hitachi 911 analyser (Ealing, UK). The positive
APP C-reactive protein, -1-antitrypsin, -1-acid glycoprotein,
haptoglobin and ceruloplasmin, and the negative APP, albumin,
prealbumin and transferrin, were measured at both timepoints. The
positive APP fibrinogen was measured at baseline only by assessing
clotting time in the presence of a high-thrombin concentration on a
KC4A Coagulometer (Baxter Healthcare, Thetford, UK). CV of all assays
was 
3%.
Statistics.
Data are presented as median and interquartile range. Differences between groups were compared using the Mann-Whitney U test. Changes within groups over time were compared using the Wilcoxon signed rank test. Categorical variables were compared using the Chi-squared test (Statview, Abacus Concepts, Berkeley, CA). A P value of <0.05 is significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
Characteristics of the patient groups and controls are shown in
Table 1. Patients were well matched for age and disease stage. Cancer
patients were slightly older than healthy controls.
|
Serum concentrations of the negative APP, albumin, prealbumin and
transferrin were significantly lower in cancer patients than healthy
controls (Fig. 1
A). Concentrations of the positive APP, CRP, fibrinogen,
-1-antitrypsin, -1-acid glycoprotein, haptoglobin and
ceruloplasmin were significantly higher in cancer patients than healthy
controls (Fig. 1B)
.
|
Patient groups were well matched for baseline serum levels of APP
although ceruloplasmin concentration was significantly higher in
patients receiving supportive care alone (Table 2
). In patients receiving the nutritional supplement enriched with
fish oil, there were no significant changes from baseline in serum APP
levels over the assessment period apart from a rise in the
concentration of the negative APP transferrin (P = 0.031) (Fig. 2
). In patients receiving full supportive care, there was an increase in
the concentration of the positive APP CRP (P = 0.0013)
and a reduction in the concentration of the negative APP albumin,
prealbumin and transferrin (P = 0.012, 0.0048 and 0.038
respectively). There were significant differences in the changes
observed in the serum concentrations of CRP, albumin, prealbumin and
transferrin between supplemented and unsupplemented cancer patients
over the study period. There was a significant difference in the
pattern of weight loss between the two groups with those receiving the
supplement gaining a median of 1 kg while those receiving supportive
care lost a median of 2.8 kg (Table 3
).
|
|
|
Total measured positive APP did not change significantly in each group
although there was a trend towards an increase in the control group
(P = 0.07). However, there was a marked difference in
the pattern of total production of negative APP between the two patient
groups with a significant increase in those receiving the nutritional
supplement enriched with fish oil (P = 0.048) and a
significant decrease in those receiving supportive treatment
(P = 0.016). Thus, the difference between the groups
was highly significant (P = 0.0012, Table 4
).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
-1-antitrypsin, -1-acid glycoprotein, haptoglobin and
ceruloplasmin were significantly higher in cancer patients than in
healthy controls while albumin, prealbumin and transferrin were
significantly lower. This finding reflects the role of these proteins
as positive and negative APP respectively (Baumann and Gauldie 1994
) and confirms the tendency for patients with advanced
cancer to exhibit an APPR as observed previously in pancreatic and
other malignancies (Falconer et al. 1994
,
Staal-van den Brekel et al. 1995
, Wayman et al. 1997
). It is possible that the so-called negative APR (albumin, prealbumin and transferrin) might also have been reduced as a result of the relative protein-calorie malnutrition observed in the cancer patients. Indeed, following administration of the fish oil enriched-supplement the weight of patients increased as did transferrin concentration and this may reflect the role of the latter as a fast-turnover hepatic protein sensitive to short-term improvements in nutritional status.
Although hepatocyte albumin secretion may be reduced in vitro by
proinflammatory cytokines, (Castell et al. 1990
) we have
demonstrated recently that in cachectic cancer patients with
hypoalbuminaemia and an ongoing APPR, albumin synthesis rates are
unaltered. (Fearon et al. 1998
) Thus the low-serum
albumin concentration observed in the present study is likely to
reflect either an increased transcapillary escape rate, an increased
degradation rate or a combination of the two. Transcapillary escape has
been shown to occur at an elevated rate in weight-losing cancer
patients and has been suggested to contribute to the hypoalbuminemia of
the APR (Fleck et al. 1985
). However, lymphatic return
must be similarly increased as there is no relationship between
transcapillary escape and albumin concentration (Ballmer et al. 1994
) and no change in the intravascular albumin pool with
elevated transcapillary escape (Ballmer-Weber et al. 1995
). Further study of APP breakdown in cancer is required.
The demand for specific amino acids to manufacture positive APP in
patients with an inadequate nutritional intake has been suggested to
contribute to ongoing muscle protein breakdown (Reeds et al. 1994
) and in a prolonged APPR this may lead to accelerated
weight loss and a shortened survival. Although the present study was
not a formal randomized trial, cancer patients who received the fish
oil–enriched nutritional supplement had no change in the concentration
of total positive APP but total negative APP increased compared with
patients receiving supportive care alone. This suggests either an
attenuation of the APPR, an improvement in nutritional status or, more
likely, a combination of the two. The patients receiving supportive
care alone had no significant change in total positive APP but
sustained a further fall in negative APP. This suggests either
progression of the APPR, a further reduction in nutritional status or,
again, a combination of the two. It has been suggested, however, that
the negative APP are not good indicators of nutritional status in the
presence of an APR (Fleck 1989
).
The supplement used in this study contained appreciable amounts of the
DHA in addition to EPA. DHA is a closely related polyunsaturated fatty
acid, also of the (n-3) class, which is metabolised to EPA in vivo (von Schacky & Weber 1985
). The relative contribution of these two agents in
the present study is not clear. In addition, it is likely that the
patients receiving the supplement consumed more calories and protein
than those receiving supportive care so it is not possible to
discriminate an effect of EPA on the APPR and hence nutritional status
from a direct effect of the calories and protein supplied. However,
previous studies of conventional oral supplements in cancer patients
have demonstrated no effect on either serum albumin concentration or
body weight (Evans et al. 1987
, Ovesen et al. 1993
) suggesting that the effects observed in the present study
are at least in part due to the fish oil component of the supplement.
The link between the concentration of various plasma proteins and
changes in whole body nitrogen kinetics is complex. Under normal
circumstances hepatic protein synthesis is thought to contribute about
15–20% of whole body protein turnover. During an APPR the
contribution of hepatic protein synthesis is thought to rise, with the
synthesis of individual acute phase reactants increasing markedly
(Preston et al. 1998
). The measured concentration of a
plasma protein is the end result of a variety of processes including
synthesis, degradation and distribution between the extravascular and
intravascular pools. Thus although synthesis might increase, if
degradation also increases the net effect may be no change in the
plasma concentration but a significant alteration in overall protein
turnover. If the latter process is not 100% efficient, this would
result in net protein loss from the body and accelerated wasting. We
have previously demonstated that in fasting cancer patients with an
ongoing APPR fibrinogen synthesis is increased by ~200% while the
plasma concentration is increased by ~50% (Preston et al. 1998
). However, while the rate of albumin synthesis is
unchanged plasma concentrations may be decreased by ~25%
(Fearon et al. 1998
). Thus interpretation of the changes
in APP concentrations in the present study requires kinetic studies in
order to determine their true relation to nutritional status in general
and nitrogen economy in particular. Unfortunately, examination of the
synthesis and more so, degradation of many APP, is difficult due to
their relatively low-circulating concentrations.
Several explanations exist for the mechanism of the apparent
stabilization of the APPR in patients receiving the fish oil–enriched
supplement observed in the present study. In vitro, the APPR is largely
regulated by IL-6 (Castell et al. 1990
). We have
previously shown that patients with advanced pancreatic cancer
exhibiting an APPR have elevated production of IL-6 by isolated
peripheral blood mononuclear cells (Falconer et al. 1994
) and that the administration of a pure preparation of EPA
will reduce this production of IL-6 to control levels (Wigmore et al. 1997a
). In addition, the production of proinflammatory
cytokines and APP is controlled to some extent by the transcription
factor NF-
B (Beauparlant and Hiscott 1996
).
Polyunsaturated fatty acids have been shown to activate NF-B but
initial work suggests that EPA has little effect on this pathway in
vitro (Camandola et al. 1996
). The administration of
polyunsaturated fatty acids to hepatocytes in culture has suggested
that EPA may have direct effects on the modulation of APP production
(Wigmore et al. 1997b
). Additional elucidation of the
mechanism of action of the fish oil–enriched supplement used in the
present study and the relative contributions of its components requires
further study.
In summary the present study suggests that fish oil, rich in (n-3) fatty acids, in combination with a nutritional supplement, is able to prevent progression of the APPR and cachexia in weight losing patients with advanced cancer. Possible benefits of these findings in terms of patient quality of life and survival deserve further study in a formal randomized controlled trial.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
2 Financial support was received from Scotia
Pharmaceuticals, Stirling, UK and Ross Products Division, Abbott
Laboratories, Colombus, OH.
4 Abbreviations used: APP, acute phase protein;
APPR, acute phase protein response; APR, acute-phase response; CRP,
C-reactive protein; DHA, docosahexaenoic acid; EPA,
eicosapentaenoic acid; IL, interleukin.
Manuscript received November 9, 1998. Initial review completed January 11, 1999. Revision accepted March 1, 1999.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
|---|
1. Ballmer P. E., Oschsenbein A. F., Schütz-Hofmann S. Transcapillary escape rate of albumin positively correlates with plasma albumin in acute but not in chronic inflammatory disease. Metabolism 1994;43:697-705[Medline]
2. Ballmer-Weber B. K., Dummer R., Küng E., Burg G., Ballmer P. E. Interleukin 2-induced increase of vascular permeability without decrease of the intravascular albumin pool. Br. J. Cancer 1995;71:78-82[Medline]
3. Baumann H., Gauldie J. The acute phase response. Immunol. Today 1994;15:74-80[Medline]
4.
Beauparlant P., Hiscott J. Biological and biochemical inhibitors of the NF-B/Rel proteins and cytokine synthesis. Cytokine Growth Factor Rev 1996;7:175-190[Medline]
5. Camandola S., Leonarduzzi G., Musso T., Varesio L., Carini R., Scavazza A., Chiarpotto E., Baeuerle P. A., Poli G. Nuclear factor kB is activated by arachidonic acid but not by eicosapentaenoic acid. Biochem. Biophys. Res. Commun. 1996;229:643-647[Medline]
6. Castell J. V., Gómez-Lechón M. J., David M., Fabra R., Trullenque R., Heinrich P. C. Acute-phase response of human hepatocytes: Regulation of acute-phase protein synthesis by interleukin-6. Hepatology 1990;12:1179-1186[Medline]
7. Evans W. K., Nixon D. W., Daly J. M., Ellenberg S. S., Gardner L., Wolfe E., Shepherd F. A., Feld R., Gralla R., Fine S., Kemeny N., Jeejeebhoy K. N., Heymsfield S., Hoffman F. A. A randomised trial of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer. J. Clin. Oncol. 1987;5:113-124[Abstract]
8. Falconer J. S., Fearon K.C.H., Plester C. E., Ross J. A., Carter D. C. Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Ann. Surg. 1994;219:325-331[Medline]
9. Falconer J. S., Fearon K.C.H., Ross J. A., Elton R., Wigmore S. J., Garden O. J., Carter D. C. Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer 1995;75:2077-2082[Medline]
10. Fearon K.C.H., Falconer J. S., Slater C., McMillan D. C., Ross J. A., Preston T. Albumin synthesis rates are not decreased in hypoalbuminemic cachectc cancer patients with an ongoing acute-phase protein response. Ann. Surg. 1998;227:249-254[Medline]
11. Fleck A., Raines G., Hawker F., Trotter J., Wallace P. I., Ledingham I., McA. & Calman K. C. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet 1985;i:781-784
12. Fleck A. Clinical and nutritional aspects of changes in acute-phase proteins during inflammation. Proc. Nutr. Soc. 1989;48:347-354[Medline]
13. Hermreck A. S., Thomas C. Y., Friesen S. R. Importance of pathologic staging in the surgical management of adenocarcinoma of the exocrine pancreas. Am. J. Surg. 1974;12:653-657
14.
Nixon D. W., Lawson D. H., Kutner M., Ansley J., Schwarz M., Heymsfield S., Chawla R., Cartwright T. H., Rudman D. Hyperalimentation of the cancer patient with protein-calorie undernutrition. Cancer Res 1981;41:2038-2045
15. Ovesen L., Allingstrup L., Hannibal J., Mortensen E. L., Hansen O. P. Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: A prospective, randomised study. J. Clin. Onc. 1993;11:2043-2049
16.
Preston T., Slater C., McMillan D. C., Falconer J. S., Shenkin A., Fearon K.C.H. Fibrinogen synthesis is elevated in fasting cancer patients with an acute phase response. J. Nutr. 1998;128:1355-1360
17. Reeds P. J., Fjeld C. R., Jahoor F. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states?. J. Nutr. 1994;124:906-910
18. von Schacky C., Weber P. C. Metabolism and effects on platelet function of the purified eicosapentaenoic and docosahexaenoic acids in humans. J. Clin. Invest. 1985;76:2446-2450
19. Staal-van den Brekel A. J., Dentener M. A., Schols A.M.W.J., Buurman W. A., Wouters E.F.M. Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J. Clin. Oncol. 1995;13:2600-2605[Abstract]
20. Strassmann G., Fong M., Kenney J. S., Jacob C. O. Evidence for the involvement of interleukin 6 in experimental cancer cachexia. J. Clin. Invest. 1993;89:1681-1684
21.
Tracey K. J., Wei H., Manogue K. R., Fong Y., Hesse D. G., Nguyen H. T., Kuo G. C., Beutler B., Cotran R. S., Cerami A., Lowry S. F. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J. Exper. Med. 1988;167:1211-1227
22. Wayman J., O'Hanlon D., Hayes N., Shaw I., Griffin S. M. Fibrinogen levels correlate with stage of disease in patients with oesophageal cancer. Brit. J. Surg. 1997;84:185-188[Medline]
23. Wigmore S. J., Ross J. A., Falconer J. S., Plester C. E., Tisdale M. J., Carter D. C., Fearon K.C.H. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition 1996;12 Suppl:S27-S30[Medline]
24. Wigmore S. J., Fearon K.C.H, Maingay J. P., Ross J. A. Down-regulation of the acute-phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin-6. Clin. Sci. 1997;92:215-221[Medline]
25. Wigmore S. J., Fearon K.C., H & Ross J. A. Modulation of human hepatocyte acute phase protein production in vitro by n-3 and n-6 polyunsaturated fatty acids. Ann. Surg. 1997;225:103-111[Medline]
26.
Yasumoto K., Mukaida N., Harada A., Kuno K., Akiyama M., Nakashima E., Fujioka N., Mai M., Kasahara T., Fujimoto-Ouchi K., Mori K., Tanaka Y., Matsushima K. Molecular analysis of the cytokine network involved in cachexia in colon 26 adenocarcinoma-bearing mice. Cancer Res 1995;55:921-927
This article has been cited by other articles:
|
|
 |
|
  D. A. August, M. B. Huhmann, and the American Society for Parenteral and Enteral Nu A.S.P.E.N. Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation JPEN J Parenter Enteral Nutr, September 1, 2009; 33(5): 472 - 500. [Full Text] [PDF]
|
|
|
|
 |
|
 T. B. Farran, C. D. Reinhardt, D. A. Blasi, J. E. Minton, T. H. Elsasser, J. J. Higgins, and J. S. Drouillard Source of dietary lipid may modify the immune response in stressed feeder cattle J Anim Sci, June 1, 2008; 86(6): 1382 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Orchekowski, D. Hamelinck, L. Li, E. Gliwa, M. VanBrocklin, J. A. Marrero, G. F. Vande Woude, Z. Feng, R. Brand, and B. B. Haab Antibody Microarray Profiling Reveals Individual and Combined Serum Proteins Associated with Pancreatic Cancer Cancer Res., December 1, 2005; 65(23): 11193 - 11202. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hamelinck, H. Zhou, L. Li, C. Verweij, D. Dillon, Z. Feng, J. Costa, and B. B. Haab Optimized Normalization for Antibody Microarrays and Application to Serum-Protein Profiling Mol. Cell. Proteomics, June 1, 2005; 4(6): 773 - 784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Babcock, T. Dekoj, and N. J. Espat Experimental Studies Defining {omega}-3 Fatty Acid Antiinflammatory Mechanisms and Abrogation of Tumor-Related Syndromes Nutr Clin Pract, February 1, 2005; 20(1): 62 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Mantovani, C. Madeddu, A. Maccio, G. Gramignano, M. R. Lusso, E. Massa, G. Astara, and R. Serpe Cancer-Related Anorexia/Cachexia Syndrome and Oxidative Stress: An Innovative Approach beyond Current Treatment Cancer Epidemiol. Biomarkers Prev., October 1, 2004; 13(10): 1651 - 1659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Jho, S. M. Cole, E. M. Lee, and N. J. Espat Role of Omega-3 Fatty Acid Supplementation in Inflammation and Malignancy Integr Cancer Ther, June 1, 2004; 3(2): 98 - 111. [Abstract] [PDF]
|
|
|
|
 |
|
 R F Grimble Nutritional therapy for cancer cachexia Gut, October 1, 2003; 52(10): 1391 - 1392. [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. H. van Eijk and N. E. P. Deutz Plasma Protein Synthesis Measurements Using a Proteomics Strategy J. Nutr., June 1, 2003; 133(6): 2084S - 2089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Wanten, A. Rops, S. E. van Emst-de Vries, T. Naber, and P. H. G. M. Willems Prompt inhibition of fMLP-induced Ca2+ mobilization by parenteral lipid emulsions in human neutrophils J. Lipid Res., April 1, 2002; 43(4): 550 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Wallace Nutritional and Botanical Modulation of the Inflammatory Cascade--Eicosanoids, Cyclooxygenases, and Lipoxygenases-- As an Adjunct in Cancer Therapy Integr Cancer Ther, March 1, 2002; 1(1): 7 - 37. [Abstract] [PDF]
|
|
|
|
 |
|
 H. J. Agteresch, T. Rietveld, L. G.M. Kerkhofs, J. W. O. van den Berg, J. H. P. Wilson, and P. C. Dagnelie Beneficial Effects of Adenosine Triphosphate on Nutritional Status in Advanced Lung Cancer Patients: A Randomized Clinical Trial J. Clin. Oncol., January 15, 2002; 20(2): 371 - 378. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
