DrEdell needs to read: Effect of fish oil,etc. on remission ......

[Guest guest]

Effect of fish oil, arginine, and doxorubicin chemotherapy on remission and

survival time for dogs with lymphoma: a double-blind, randomized

placebo-controlled study.

 

BACKGROUND: Polyunsaturated n-3 fatty acids have been shown to inhibit the

growth and metastasis of tumors. This double-blind, randomized study was

designed to evaluate the hypothesis that polyunsaturated n-3 fatty acids can

improve

metabolic parameters, decrease chemical indices of inflammation, enhance

quality of life, and extend disease free interval and survival time for dogs

treated for lymphoblastic lymphoma with doxorubicin chemotherapy. METHODS:

Thirty-two dogs with lymphoma were randomized to receive one of two diets

supplemented

with menhaden fish oil and arginine (experimental diet) or an otherwise

identical diet supplemented with soybean oil (control diet). Diets were fed

before

and after remission was attained with up to five dosages of doxorubicin.

Parameters examined included blood concentrations of glucose, lactic acid, and

insulin in response to glucose and diet tolerance tests; alpha-1 acid

glycoprotein;

tumor necrosis factor; interleukin-6; body weight; amino acid profiles;

resting energy expenditure; disease free interval (DFI); survival time (ST); and

clinical performance scores. RESULTS: Dogs fed the experimental diet had

significantly (P < 0.05) higher mean serum levels of the n-3 fatty acids

docosahexaenoic acid (C22:6) and eicosapentaenoic acid (C20:5) compared with

controls.

Higher serum levels of C22:6 and C20:5 were associated with lesser (P < 0.05)

plasma lactic acid responses to intravenous glucose and diet tolerance testing.

Increasing C22:6 levels were significantly (P < 0.05) associated with longer

DFI and ST for dogs with Stage III lymphoma fed the experimental diet.

CONCLUSIONS: Fatty acids of the n-3 series normalize elevated blood lactic acid

in a

dose-dependent manner, resulting in an increase in DFI and ST for dogs with

lymphoma.

 

Cancer 2000 Apr 15;88(8):1916-28

 

Arginase activity in human breast cancer cell lines:

N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces

apoptosis in MDA-MB-

468 cells.

 

L-Arginine is the common substrate for two enzymes, arginase and nitric oxide

synthase (NOS). Arginase converts L-arginine to L-ornithine, which is the

precursor of polyamines, which are essential components of cell proliferation.

NOS converts L-arginine to produce NO, which inhibits proliferation of many cell

lines. Various human breast cancer cell lines were initially screened for the

presence of arginase and NOS. Two cell lines, BT-474 and MDA-MB-468, were

found to have relatively high arginase activity and very low NOS activity.

Another cell line, ZR-75-30, had the highest NOS activity and comparatively low

arginase activity. The basal proliferation rates of MDA-MB-468 and BT-474 were

found to be higher than the ZR-75-30 cell line. N-Hydroxy-L-arginine (NOHA), a

stable intermediate product formed during conversion of L-arginine to NO,

inhibited proliferation of the high arginase-expressing MDA-MB-468 cells and

induced

apoptosis after 48 h. NOHA arrested these cells in the S phase, increased the

expression of p21, and reduced spermine content. These effects of NOHA were

not observed in the ZR-75-30 cell line, which expresses high NOS and relatively

low arginase. The effects of NOHA were antagonized in the presence of

L-ornithine (500 microM), which suggests that in MDA-MB-468 cell line, the

arginase

pathway is very important for cell proliferation. Inhibition of the arginase

pathway led to depletion of intracellular spermine and apoptosis as observed by

terminal deoxynucleotidyl transferase (TdT)-mediated nick end labeling assay

and induction of caspase 3. In contrast, the ZR-75-30 cell line maintained its

viability and its L-ornithine and spermine levels in the presence of NOHA. We

conclude that NOHA has antiproliferative and apoptotic actions on

arginase-expressing human breast cancer cells that are independent of NO.

 

Cancer Res 2000 Jun 15;60(12):3305-12

 

Inhibition of the growth of human pancreatic cancer cells by the arginine

antimetabolite L-canavanine.

 

L-Canavanine (CAV), the L-2-amino-4-guanidinooxy structural analogue of

L-arginine (ARG), is a potent ARG antagonist which occurs in the jack bean,

Canavalia ensiformis. This ARG antimetabolite is active against L1210 murine

leukemia

and a solid colonic tumor in the rat. Our initial studies using a microtiter

assay show that CAV exhibits a 50% inhibitory concentration of approximately 2

mM against the human pancreatic adenocarcinoma cell line, MIA PaCa-2, when

these cells are grown in Dulbecco’s modified Eagle’s medium containing 0.4

mM

ARG. When the ARG concentration is reduced to 0.4 microM, the 50% inhibitory

concentration for CAV falls precipitously to 0.01 mM. The pronounced increase in

the ability of CAV to inhibit MIA PaCa-2 cell growth at the lower ARG

concentration may result from enhanced CAV competition with ARG for

incorporation

into newly synthesized cellular proteins. At 0.4 microM ARG, 30 mM CAV almost

completely inhibits cell growth by 6 h. In contrast, with 0.4 mM ARG, complete

inhibition does not occur until after 48 h. A dramatic reversal of growth

inhibition caused by a very high concentration of CAV was observed when cells

treated with CAV were replenished with a high concentration of ARG. Our results

suggest that CAV has real potential as a lead compound for the development of

analogues with enhanced activity against human pancreatic cancer.

 

Cancer Res 1994 Dec 1;54(23):6045-8

 

 

 

 

 

 

 

http://www.lef.org/magazine/mag2002/jul2002_abs_02.html

 

 

 

 

 

 

 

[Guest guest]

" a double-blind, randomized

placebo-controlled study. "

 

Why give a placebo to dogs? LOL!