-Herbal Medicine, Healing, and Cancer :Herbal Medicine Healing & Cancer..Herbal Medicine, Healing and Cancer is for humans but the information within it is so awesome and it contains preventative tips also. Donald Yance has reviewed the literature and has treated human cancer victims for over twenty years..amazon sells it for less than $16 dollars! For instance, I almost bought Melatonin for Yuki who just had radical surgery in case of mammary cancer(thank goodness it was a cyst) because of that book. I wish I had known about two years ago when I started the search to keep Morgan alive. He also explains why possibly flaxseed and cottage cheese may work-He explains what butryic acid is.

Here is his excerpt on flaxseed oil and sulphur rich protein

Herbal Medicine, Healing & Cancer" by Donald Yance
"Flaxseed oil is rich in essential fatty acids, particularly ALA, which, when taken in combination with sulfur-rich proteins, actually works to create a new food. This was first discovered and made famous by Johanna Budwig, a West German physician who had done a great deal of research on the oil-protein combination. She discovered that EFAs need to bind to sulfur-rich proteins (she used low-fat cottage cheese) before the body can properly assimilate them. Budwig found that by feeding people with terminal cancer this oil-protein combination, the yellowish-green substance in their blood was replaced by the healthy red pigment, hemaglobin. The phosphatides returned and the lipoproteins reappeared.
Of all the deficiencies that may exist in people with cancer, perhaps those that are most important and totally ignored are EFAs, which, when taken with protein, enhance our albumin levels. Albumin is a blood protein of immense importance to good health. When flaxseed oil and sulfur-rich protein are combined, the ALA and the EFAs in the flaxseed oil become water-soluble and electron-rich; this causes the cell membrane to become more stable by making it more flexible and fluidlike. The electron-rich fatty acids now allow for efficient transport of materials and energy between the inner and outer cell membrane. This is important to the health of all cells and to the entire immune system.
A simple recipe for achieving these cellular benefits is to add 1 to 2 teaspoons of flaxseed oil or ground flaxseeds to 1 cup of organic yogurt (preferabley goat or soy yogurt).
Omega-3 fatty acids are extremely important because they modulate prostaglandins, which are very active biological substances important to nearly every bodily function. They suppress tumor-promoting prostaglandin E2 by increasing prostiglandin E3 and suppressing AA. They also inhibit cancer wasting. EPA and ALA, as well as other related omega-3 fatty acids, plus GLA from evening primrose oil, have been found to kill a number of tumor-cell lines and cause a significant reduction in tumor growth in animal studies." (pp.219-220)


Mutat Res. 2004 Jul 13;551(1-2):213-22. : The influence of dietary flaxseed and other grains, fruits and vegetables on the frequency of spontaneous chromosomal damage in mice.
Trentin GA, Moody J, Torous DK, Thompson LU, Heddle JA.
Department of Biology, York University, 4700 Keele Street, Toronto, Ont., Canada M3J 1P3.

Spontaneous genetic damage, whether mutations or chromosomal aberrations, undoubtedly arise from a variety of sources including replication errors, oxidative damage, background radiation, and chemical exposure. Given the numerous correlations between diet and cancer, it seemed possible that diet could influence the spontaneous rate of DNA damage and its genetic consequences. Since diets high in vegetables, fruits, and grains are associated with lower rates of cancer, we supplemented the diets of mice and measured the frequency of micronuclei in the peripheral blood. Micronuclei arise from broken chromosomes or chromosome loss in the erythroblast. They are first seen in the short reticulocyte stage of the red blood cell but persist for the entire 30-day lifespan of the cell in mice. C57Bl mice were placed on a defined diet (AIN-93G) supplemented to 20% final dry weight with grains or freeze-dried fruits or vegetables. The micronucleus frequency was measured in a pre-exposure blood sample and every 2 weeks thereafter for 6 weeks. This was possible in spite of the low spontaneous frequency of 1/1000-2/1000 cells by the use of a novel flow cytometric method, which permitted the analysis of both the mature red blood cells and reticulocytes. Of the foods tested, flaxseed proved to be the most protective by reducing the incidence of micronuclei in both the reticulocyte and normochromatic erythrocyte cell populations by 30 and 11%, respectively. The results show that at least one class of spontaneous genetic damage can be modified by diet and suggests that short-term experiments with small numbers of animals can be used to identify dietary anticarcinogens that may influence human cancer rates.
Urology. 2004 May;63(5):900-4. : Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.
Demark-Wahnefried W, Robertson CN, Walther PJ, Polascik TJ, Paulson DF, Vollmer RT.
Division of Urologic Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth. Am J Clin Nutr. 2004 Feb;79(2):318-25. : Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy.
Brooks JD, Ward WE, Lewis JE, Hilditch J, Nickell L, Wong E, Thompson LU.
Department of Nutritional Sciences, University of Toronto, Toronto, Canada.

BACKGROUND: Phytoestrogens, which are abundant in flaxseed and soy, have chemical structures resembling those of endogenous estrogens and have been shown to exert hormonal effects, thereby affecting chronic diseases. OBJECTIVE: We compared the effects of consuming equal amounts of flaxseed or soy on estrogen metabolism and biochemical markers of bone metabolism in postmenopausal women. DESIGN: In a parallel design, the diet of postmenopausal women (n = 46) was supplemented with either a placebo, soy (25 g soy flour), or flaxseed (25 g ground flaxseed) muffin for 16 wk. Blood and 24-h urine samples were collected at baseline and at the endpoint. Urine samples were analyzed for phytoestrogens, estrogen metabolites (2-hydroxyestrone, 16alpha-hydroxyestrone), and serum hormones (estradiol, estrone, estrone sulfate). Serum and urine samples were also analyzed for biochemical markers of bone metabolism. RESULTS: Urinary concentrations of 2-hydroxyestrone, but not of 16alpha-hydroxyestrone, increased significantly in the flaxseed group (P = 0.05). In the flaxseed group, the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone was positively correlated with urinary lignan excretion (r = 0.579, P = 0.02). In the soy and placebo groups, no significant correlation was observed. No significant change in serum hormones or biochemical markers of bone metabolism was observed within or between the treatment groups. CONCLUSIONS: Supplementation with flaxseed modifies urinary estrogen metabolite excretion to a greater extent than does supplementation with an equal amount of soy. This modification by flaxseed is associated with an increase in urinary lignan excretion. Despite the shift in estrogen metabolism to favor the less biologically active estrogens, a negative effect on bone cell metabolism was not observed.
Kidney Int. 2003 Dec;64(6):2100-2107. : Dietary flaxseed meal reduces proteinuria and ameliorates nephropathy in an animal model of type II diabetes mellitus.
Velasquez MT, Bhathena SJ, Ranich T, Schwartz AM, Kardon DE, Ali AA, Haudenschild CC, Hansen CT.
Department of Medicine and Department of Pathology, George Washington University Medical Center, Washington D.C.; Phytonutrients Laboratory, Beltsville Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture, Beltsville, Maryland; Jerome Holland Laboratories, American Red Cross, Rockville, Maryland; and National Institutes of Health, Animal Genetic Resource, Bethesda, Maryland.

Background. Evidence is emerging that varying the type or source of dietary protein intake can have beneficial effects on chronic renal disease. Consumption of soybean and soy-based food products, as the source of plant protein, can retard the development and progression of chronic renal disease. We studied the obese spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat, a model of obesity and type II diabetes mellitus that consistently develops nephropathy resembling diabetic nephropathy. We specifically sought to determine whether changing the source of protein intake from animal protein, casein, to plant protein in the form of either soy protein concentrate or flaxseed protein in the diet has a different impact on renal function and nephropathy in this model. Methods. Male obese SHR/N-cp rats were randomly assigned to one of three diets containing either 20% casein, 20% soy protein concentrate, or 20% flaxseed meal. Except for the protein source, all three diets were identical and contained similar amounts of protein, fat, carbohydrates, minerals, and vitamins. All animals were maintained on these diets for 6 months. At the end of the study, blood sampling and 24-hour urine collections were performed for renal functional measurements, and the kidneys were harvested and examined for histologic evaluation. Results. All three groups had similar amounts of food intake and body weight gain and exhibited fasting hyperglycemia and hyperinsulinemia. Plasma glucose levels did not differ among the three groups, but plasma insulin concentration was significantly lower in rats fed flaxseed meal than those fed either casein or soy protein concentrate. Mean plasma creatinine, creatinine clearance, and urinary urea excretion also did not differ significantly between the three groups. By contrast, urinary protein excretion was significantly lower (P < 0.01) in rats fed flaxseed than in rats fed either casein or soy protein concentrate. Morphologic analysis of renal structural lesions showed that the percentage of abnormal glomeruli with mesangial expansion and the tubulointerstitial score (an index of severity of tubulointerstitial damage) were significantly reduced in rats fed flaxmeal compared to those fed casein or soy protein concentrate. Conclusion. We conclude that dietary protein substitution with flaxseed meal reduces proteinuria and glomerular and tubulointerstitial lesions in obese SHR/N-cp rats and that flaxseed meal is more effective than soy protein in reducing proteinuria and renal histologic abnormalities in this model. The reduction in proteinuria and renal injury was independent of the amount of protein intake and glycemic control. Which dietary component(s) present in flaxseed meal is (are) responsible for the renal protective effect remains to be determined.
: Am Fam Physician. 2004 Jul 1;70(1):133-40. : Comment in: Am Fam Physician. 2004 Jul 1;70(1):34-5.
Omega-3 fatty acids.
Covington MB.
University of Maryland School of Medicine, Center for Integrative Medicine, Baltimore, Maryland 21207, USA.
mcovington@compmed.umm.edu

Omega-3 fatty acids have been shown to significantly reduce the risk for sudden death caused by cardiac arrhythmias and all-cause mortality in patients with known coronary heart disease. Fatty fish, such as salmon and tuna, and fish oil are rich sources of the omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid. Flaxseed, canola oil, and walnuts also are good dietary sources of omega-3 fatty acids. In addition to being antiarrhythmic, the omega-3 fatty acids are antithrombotic and anti-inflammatory. In contrast, omega-6 fatty acids, which are present in most seeds, vegetable oils, and meat, are prothrombotic and proinflammatory. Omega-3 fatty acids also are used to treat hyperlipidemia, hypertension, and rheumatoid arthritis. There are no significant drug interactions with omega-3 fatty acids. The American Heart Association recommends consumption of two servings of fish per week for persons with no history of coronary heart disease and at least one serving of fish daily for those with known coronary heart disease. Approximately 1 g per day of eicosapentaenoic acid plus docosahexaenoic acid is recommended for cardioprotection. Higher dosages of omega-3 fatty acids are required to reduce elevated triglyceride levels (2 to 4 g per day) and to reduce morning stiffness and the number of tender joints in patients with rheumatoid arthritis (at least 3 g per day). Modest decreases in blood pressure occur with significantly higher dosages of omega-3 fatty acids.

Gut. 2003 Oct;52(10):1479-86. : Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial.
Fearon KC, Von Meyenfeldt MF, Moses AG, Van Geenen R, Roy A, Gouma DJ, Giacosa A, Van Gossum A, Bauer J, Barber MD, Aaronson NK, Voss AC, Tisdale MJ.
Royal Infirmary of Edinburgh, Edinburgh, UK.

AIM: N-3 fatty acids, especially eicosapentaenoic acid (EPA)[ie oil from cold water fish], may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. METHODS: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. RESULTS: At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. CONCLUSION: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.
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Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts
Angiogenesis is important in tumor growth, progression and metastatic dissemination. Vascular endothelial growth factor (VEGF) is one key factor in promotion of breast cancer angiogenesis. VEGFs are bioactive in the extracellular space where they become available to the endothelial cells. Phytoestrogens such as lignans have been shown to alter breast cancer incidence and be cancer-protective in rats. We show that supplementation of 10% flaxseed, the richest source of mammalian lignans, to nude mice with established human breast tumors reduced tumor growth and metastasis. Moreover, flaxseed decreased extracellular levels of VEGF, which may be one mechanistic explanation to the decreased tumor growth and metastasis
J Nutr 2002 Nov;132(11 Suppl):3508S-3512S : Omega-3 fatty acids to augment cancer therapy.
Hardman WE.
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.
hardmawe@pbrc.edu

The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include 1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor; 2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion; 3) inducing differentiation of cancer cells; 4) suppressing nuclear factor-kappaB activation and bcl-2 expression, thus allowing apoptosis of cancer cells; and 5) reducing cancer-induced cachexia. It seems reasonable to assume that after appropriate cancer therapy, consumption of omega-3 fatty acids might slow or stop the growth of metastatic cancer cells, increase longevity of cancer patients and improve their quality of life.
Am J Med 2002 Dec 30;113 Suppl 9B:71-88 : Bioactive compounds in foods: their role in the prevention of cardiovascular disease and cancer.
Kris-Etherton PM, Hecker KD, Bonanome A, Coval SM, Binkoski AE, Hilpert KF, Griel AE, Etherton TD.
Graduate Program in Nutrition, Pennsylvania State University, (PMK, KDH, SMC, AEB, KFH, AEG, TDE), University Park, Pennsylvania, USA

"Bioactive compounds" are extranutritional constituents that typically occur in small quantities in foods. They are being intensively studied to evaluate their effects on health. The impetus sparking this scientific inquiry was the result of many epidemiologic studies that have shown protective effects of plant-based diets on cardiovascular disease (CVD) and cancer. Many bioactive compounds have been discovered. These compounds vary widely in chemical structure and function and are grouped accordingly. Phenolic compounds, including their subcategory, flavonoids, are present in all plants and have been studied extensively in cereals, legumes, nuts, olive oil, vegetables, fruits, tea, and red wine. Many phenolic compounds have antioxidant properties, and some studies have demonstrated favorable effects on thrombosis and tumorogenesis and promotion. Although some epidemiologic studies have reported protective associations between flavonoids or other phenolics and CVD and cancer, other studies have not found these associations. Various phytoestrogens are present in soy, but also in flaxseed oil, whole grains, fruits, and vegetables. They have antioxidant properties, and some studies demonstrated favorable effects on other CVD risk factors, and in animal and cell culture models of cancer. However, because phytoestrogens act both as partial estrogen agonists and antagonists, their effects on cancer are likely complex. Hydroxytyrosol, one of many phenolics in olives and olive oil, is a potent antioxidant. Resveratrol, found in nuts and red wine, has antioxidant, antithrombotic, and anti-inflammatory properties, and inhibits carcinogenesis. Lycopene, a potent antioxidant carotenoid in tomatoes and other fruits, is thought to protect against prostate and other cancers, and inhibits tumor cell growth in animals. Organosulfur compounds in garlic and onions, isothiocyanates in cruciferous vegetables, and monoterpenes in citrus fruits, cherries, and herbs have anticarcinogenic actions in experimental models, as well as cardioprotective effects. In summary, numerous bioactive compounds appear to have beneficial health effects. Much scientific research needs to be conducted before we can begin to make science-based dietary recommendations. Despite this, there is sufficient evidence to recommend consuming food sources rich in bioactive compounds. From a practical perspective, this translates to recommending a diet rich in a variety of fruits, vegetables, whole grains, legumes, oils, and nuts.

US Animal Nutritionals

Polyunsaturated fatty acids are potent neuroprotectors.
Lauritzen I, Blondeau N, Heurteaux C, Widmann C, Romey G, Lazdunski M.
Institut de Pharmacologie Moleculaire et Cellulaire, CNRS UPR 411, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France
. Results reported in this work suggest a potential therapeutic value of polyunsaturated fatty acids for cerebral pathologies as previously proposed by others for cardiac diseases. We show that the polyunsaturated fatty acid linolenic acid prevents neuronal death in an animal model of transient global ischemia even when administered after the insult. Linolenic acid also protects animals treated with kainate against seizures and hippocampal lesions. The same effects have been observed in an in vitro model of seizure-like activity using glutamatergic neurons and they have been shown to be associated with blockade of glutamatergic transmission by low concentrations of distinct polyunsaturated fatty acids. Our data suggest that the opening of background K(+) channels, like TREK-1 and TRAAK, which are activated by arachidonic acid and other polyunsaturated fatty acids such as docosahexaenoic acid and linolenic acid, is a significant factor in this neuroprotective effect. These channels are abundant in the brain where they are located both pre- and post-synaptically, and are insensitive to saturated fatty acids, which offer no neuroprotection.
Biosynthetic pathway to the cancer chemopreventive secoisolariciresinol diglucoside-hydroxymethyl glutaryl ester-linked lignan oligomers in flax (Linum usitatissimum) seed.
Application of stable and radioisotope precursor/tracer experiments resulted in the identification of various phenylpropanoid, monolignol, and lignan metabolites involved in the biosynthesis of the cancer chemopreventive secoisolariciresinol diglucoside (SDG; 1)-containing ester-linked "polymer(s)" in flax (Linum usitatissimum) seed.
Results from this study will facilitate future isolation and characterization of the proteins and enzymes involved in biosynthesis of the SDG-HMG ester-linked oligomers in flax seed.
"1: Carcinogenesis 1996 Jun;17(6):1373-6
Flaxseed and its lignan and oil components reduce mammary tumor growth at a late stage of carcinogenesis.
Thompson LU, Rickard SE, Orcheson LJ, Seidl MM.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
Flaxseed, a rich source of mammalian lignan precursor secoisolariciresinol-diglycoside (S.D.) and alpha-linolenic acid (ALA), has been shown to be protective at the early promotion stage of carcinogenesis. The objective of this study was to determine whether supplementation with flaxseed, its lignan or oil fractions, beginning 13 weeks after carcinogen administration, would reduce the size of established mammary tumors (present at the start of treatment) and appearance of new tumors in rats. Dietary groups consisted of the basal diet (BD, 20% corn oil) alone or supplemented with a gavage of 2200 nmol/day S.D. [S.D., equal to level in 5% flaxseed (F)], 1.82% flaxseed oil (OIL, equal to level in 5% F) or 2.5% or 5% flaxseed (2.5% F and 5% F, respectively). After 7 weeks of treatment, established tumor volume was over 50% smaller in all treatment groups (OIL, 2.5% F, 5% F, P < 0.04; S.D., P < 0.08) while there was no change in the BD group. New tumor number and volume were lowest in the S.D. (P < 0.02) and 2.5% F (P < 0.07) groups. The combined established and new tumor volumes were smaller for the S.D., 2.5% F and 5% F groups (P < 0.02) compared to the OIL and BD groups. The high negative correlation (r = -0.997, P < 0.001) between established tumor volume and urinary mammalian lignan excretion in the BD, S.D., 2.5% F and 5% F groups indicates that the reduction in tumor size is due in part to the lignans derived from the S.D. in flaxseed. However, there was no relationship between new or total tumor development and urinary lignan levels. The effect of flaxseed oil may be related to its high ALA content. In conclusion, the S.D. in flaxseed appears to be beneficial throughout the promotional phase of carcinogenesis whereas the oil component is more effective at the stage when tumors have already been established.
Clin Cancer Res. 2003 Oct 15;9(13):4653-65. : Targeted anti-interleukin-6 monoclonal antibody therapy for cancer: a review of the rationale and clinical evidence. Trikha M, Corringham R, Klein B, Rossi JF.
Centocor, Malvern, Pennsylvania 19355 [M. T., R. C.], and Unit of Cellular Therapy and INSERM U475 [B. K.] and Service d'Hematologie et d'Oncologie Medicale and INSERM U475 [J-F. R.], Montpellier, France 34295.

Interleukin (IL)-6, a pleiotropic cytokine with varied systemic functions, plays a major role in inflammatory processes. It modulates the transcription of several liver-specific genes during acute inflammatory states, particularly C-reactive protein, and controls the survival of normal plasmablastic cells. In addition, IL-6 has been implicated in hematopoiesis as a cofactor in stem cell amplification and differentiation. This article is the first review of clinical studies in the 1990s with anti-IL-6 monoclonal antibodies (mAbs) in the treatment of patients with cancer and related lymphoproliferative disorders. In six clinical studies of mAbs to IL-6 with BE-8 or CNTO 328 in patients with multiple myeloma, renal cell carcinoma, and B-lymphoproliferative disorders, anti-IL-6 mAb treatment decreased C-reactive protein levels in all patients. In most patients, levels decreased below detectable limits. The antibodies were well tolerated, and no serious adverse effects were observed in the vast majority of studies. The fact that anti-IL-6 mAb therapy decreased the incidence of cancer-related anorexia and cachexia may also be useful in the treatment of cancer patients
Am J Clin Nutr. 2000 Jan;71(1 Suppl):343S-8S. : Dietary polyunsaturated fatty acids and inflammatory mediator production
. James MJ, Gibson RA, Cleland LG.
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, Australia, and the Department of Pediatrics and Child Health, Flinders Medical Center, Bedford Park, Australia.

Many antiinflammatory pharmaceutical products inhibit the production of certain eicosanoids and cytokines and it is here that possibilities exist for therapies that incorporate n-3 and n-9 dietary fatty acids. The proinflammatory eicosanoids prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)) are derived from the n-6 fatty acid arachidonic acid (AA), which is maintained at high cellular concentrations by the high n-6 and low n-3 polyunsaturated fatty acid content of the modern Western diet. Flaxseed oil contains the 18-carbon n-3 fatty acid alpha-linolenic acid, which can be converted after ingestion to the 20-carbon n-3 fatty acid eicosapentaenoic acid (EPA). Fish oils contain both 20- and 22-carbon n-3 fatty acids, EPA and docosahexaenoic acid. EPA can act as a competitive inhibitor of AA conversion to PGE(2) and LTB(4), and decreased synthesis of one or both of these eicosanoids has been observed after inclusion of flaxseed oil or fish oil in the diet. Analogous to the effect of n-3 fatty acids, inclusion of the 20-carbon n-9 fatty acid eicosatrienoic acid in the diet also results in decreased synthesis of LTB(4). Regarding the proinflammatory ctyokines, tumor necrosis factor alpha and interleukin 1beta, studies of healthy volunteers and rheumatoid arthritis patients have shown < or = 90% inhibition of cytokine production after dietary supplementation with fish oil. Use of flaxseed oil in domestic food preparation also reduced production of these cytokines. Novel antiinflammatory therapies can be developed that take advantage of positive interactions between the dietary fats and existing or newly developed pharmaceutical products.
: Curr Opin Clin Nutr Metab Care 2003 Mar;6(2):195-201 : Metabolic and nutritional support in acute cardiac failure.
Berger MM, Mustafa I.
Intensive Care Unit and Burns Centre, University Hospital, Lausanne, Switzerland; and Intensive Care Unit, National Cardiac Center, Jakarta, Indonesia.

PURPOSE OF REVIEW Cardiovascular disease is one of the most important causes of morbidity and mortality in western countries, generating an increasing number of admissions to intensive care units. Cardiac failure has long been associated with nutritional disorders, malnutrition and cachexia being frequent during the late phases of congestive heart failure: undernutrition is also a determinant of outcome, even after cardiac transplantation.RECENT FINDINGS It has been shown that early metabolic support can improve the recovery of the ischaemic heart. This paper reviews recent findings on substrates that can support the failing myocardium, which are mainly glucose-insulin, glutamine, taurine, selenium, thiamine, folic acid, and omega-3 fatty acids. Ischaemia-reperfusion generates tissue lesions that can be partly prevented through substrate manipulation.SUMMARY Shifting the substrate metabolism from lipids to carbohydrates and reinforcing the antioxidant status reduces the deleterious biological and clinical consequences of acute ischaemic events. The use of the glucose-insulin-potassium infusion has become widespread with the re-discovery of its value in modulating cellular metabolism and accelerating recovery of the ischaemic myocardium. Antioxidants have gained acceptance in the perioperative phase, as well as in chronic heart failure. This constitutes another piece of evidence in favour of early metabolic and nutritional intervention. There also appears to be room for the prevention of acute deterioration of cardiac function after surgery with the preoperative administration of oral supplements containing omega-3 fatty acids.

PMID: 8681458 [PubMed - indexed for MEDLINE]"medline

Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents.
Experimental evidence directly implicates complex carbohydrates in recognition processes, including adhesion between cells, adhesion of cells to the extracellular matrix, and specific recognition of cells by one another. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Lectins are nonenzymatic proteins present in plants and animals, which preferentially bind to specific carbohydrate structures and play an important role in cell recognition. Modified carbohydrates and oligosaccharides have the ability to interfere with carbohydrate-protein interactions and therefore, inhibit the cell-cell recognition and adhesion processes, which play an important role in cancer growth and progression. Carbohydrate ligands therefore, are candidates to play important roles in cancer therapeutics.
" 1: Cancer Lett 1999 Jul 19;142(1):91-6
Dietary supplementation with secoisolariciresinol diglycoside (SDG) reduces experimental metastasis of melanoma cells in mice.
Li D, Yee JA, Thompson LU, Yan L.
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68124-0405, USA.
We investigated the effect of dietary supplementation with secoisolariciresinol diglycoside (SDG), a lignan precursor isolated from flaxseed, on experimental metastasis of B16BL6 murine melanoma cells in C57BL/6 mice. Four diets were compared: a basal diet (control group) and the basal diet supplemented with SDG at 73, 147 or 293 micromol/kg (equivalent to SDG provided in the 2.5, 5 or 10% flaxseed diet). Mice were fed the diet for 2 weeks before and after an intravenous injection of 0.6 x 10(5) tumor cells. At necropsy, the number and size of tumors that formed in the lungs were determined. The median number of tumors in the control group was 62, and those in the SDG-supplemented groups were 38, 36 and 29, respectively. The last was significantly different from the control (P < 0.01). Dietary supplementation with SDG at 73, 147 and 293 micromol/kg also decreased tumor size (tumor cross-sectional area and volume) in a dose-dependent manner compared with the control values. These results show that SDG reduced pulmonary metastasis of melanoma cells and inhibited the growth of metastatic tumors that formed in the lungs. It is concluded that dietary supplementation with SDG reduces experimental metastasis of melanoma cells in mice.
PMID: 10424786 [PubMed - indexed forflaxseed melanoma-medline MEDLINE] "
Protective effects of dietary phytoestrogens in chronic renal disease.1: J Ren Nutr 2001 Oct;11(4):183-93
Protective effects of dietary phytoestrogens in chronic renal disease.
Ranich T, Bhathena SJ, Velasquez MT.
Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington, DC 20037, USA.
Phytoestrogens are naturally occuring plant compounds that are present primarily in soybeans as isoflavones and in flaxseed as lignans. Because of their structural similarity to endogenous estrogens, phytoestrogens bind to both estrogen receptors (ER)-alpha and beta (but more strongly to ER-beta) and exert estrogen-like effects. There is increasing evidence that dietary phytoestrogens have a beneficial role in chronic renal disease. Nutritional intervention studies have shown that consumption of soy-based protein and flaxseed reduces proteinuria and attenuates renal functional or structural damage in animals and humans with various forms of chronic renal disease. It is not clear which component(s) of the soybean or flaxseed is (are) responsible for the protective effects observed in experimental animals and in limited studies in humans. Vegetable protein has been shown to have a beneficial effect on renal disease in animals and humans. Thus, the role of soy and flaxseed cannot be ruled out. Isoflavones and lignans are readily absorbed from the gut and converted to active metabolites, which may be partly responsible for the beneficial renal effects of soy protein and flaxseed. In addition, an interaction between type of protein and phytoestrogens is also possible. The biological actions of isoflavones and lignans have been well defined in different cell types in vitro and also in vivo, but how these compounds might reduce renal injury remains to be elucidated. Possible mechanisms include inhibition of cell growth and proliferation via ER-mediated mechanisms or non-ER-mediated pathways through inhibition of tyrosine protein kinases, modulation of growth factors involved in extracellular matrix synthesis and fibrogenesis, inhibition of cytokine-induced activation of transcription factors, inhibition of angiogenesis, antioxidative action, suppression of platelet activating factor and platelet aggregation, and immunomodulatory activity. To date, clinical trials in humans are few, of relatively short duration, and involve a small number of patients. Prospective randomized trials are needed to evaluate the long-term safety and effectiveness of dietary phytoestrogens on renal disease progression in patients with chronic renal failure. Copyright 2001 by the National Kidney Foundation, Inc.
Friday April 13 06:39 PM EDT Study: Common Seed Fights Cancer A recent Canadian study shows that a common seed may be a promising new cancer fighter, researchers say. Dr. Paul Gross of Princess Margaret Hospital and a team of researchers from the University of Toronto asked a group of newly diagnosed breast cancer patients to eat two tablespoons of ground flaxseed in a muffin each day. Then, Gross' research team analyzed samples of their tumors. The study found that flax actually slowed the growth of breast cancer. "The scientific community is very interested in this study," Gross said. "We've been bombarded by other investigators from around the world." Researchers found that in less than a month, the women taking flaxseed slowed their rate of tumor growth by up to 33 percent. There also was nearly a 60-percent drop in the spread of the most aggressive cancer cells. "Flaxseed is the first nutritional product that has been studied, and that has produced hard scientific evidence," Gross said. According to the study, researchers believe that a fiber in the seed helps to sweep the hormone estrogen out of the body, which blocks its ability to make tumors grow. Flax would be the first cancer treatment that isn't a chemical, researchers said. However, since flax is a food, it doesn't have the backing of a drug company. Researchers said that they don't know how much longer they would be able to continue their work. Some cancer support groups believe that the data shouldn't be ignored. "There is a community out there who are hungry for this kind of information, and it won't bother them that it's not a pharmaceutical," Sue Wright of the Willow Breast Cancer Support Center. "In fact, it might even encourage them."
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Studies on Fish Oil which make one wonder about possible drawbacks-

J Nutr. 2003 Apr;133(4):999-1003. : IRP1 activity and expression are increased in the liver and the spleen of rats fed fish oil-rich diets and are related to oxidative stress.
Miret S, McKie AT, Saiz MP, Bomford A, Mitjavila MT.
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Spain.

Many clinical studies have indicated that diets rich in fish oil (FO) reduce the risk of cardiovascular disease and have anti-inflammatory and antithrombotic properties. Although the therapeutic effects of FO have been well described, their impact on iron metabolism remains unclear. The aim of this work was to study the activity and expression of IRP1 in the liver and the spleen of rats fed FO-rich diets with 0 (FO-0) or 100 (FO-1) mg/kg of all-rac-alpha-tocopherol acetate. We also measured nonheme iron, alpha-tocopherol and retinol concentrations, and superoxide (SOD) and catalase activity in these organs. Rats fed FO were compared to rats fed a corn oil (CO)-rich diet with 100 mg/kg all-rac-alpha-tocopherol acetate. The activity and expression of IRP1 in both the liver and the spleen of rats fed FO diets were greater than in those fed the CO diet. FO-fed rats also had lower nonheme iron concentrations in these organs. Hepatic alpha-tocopherol and retinol concentrations and SOD activity were lower in FO-0-fed rats compared to those fed the CO diet. In the spleen, alpha-tocopherol and retinal concentrations were not altered but SOD activity was lower in FO-0- fed rats, whereas catalase activity was greater than in rats fed CO. The results indicate that there is an increase in oxidative stress in the liver and in the spleen of rats fed FO diets. These changes, together with the reduction of nonheme iron concentrations in both FO-0- and FO-1-fed rats, may explain the increase in activity and expression of IRP1. Therefore, the ingestion of FO-rich diets should be monitored under close supervision.


Br J Nutr. 2003 Jan;89(1):11-8. : Effects of fish oil- and olive oil-rich diets on iron metabolism and oxidative stress in the rat.
Miret S, Saiz MP, Mitjavila MT.
Departament de Fisiologia, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal, 645, Spain.

The objective of the present study was to examine the effects of fish oil (FO)- and olive oil (OO)-rich diets on Fe metabolism and oxidative stress. Rats were fed for 16 weeks with diets containing 50 g lipids/kg; either OO, maize oil (MO) or FO. OO or MO diets contained a standard amount (100 mg/kg) of all-rac-alpha-tocopheryl acetate. FO diets were supplemented with 0, 100 or 200 mg all-rac-alpha-tocopheryl acetate/kg (FO-0, FO-1 or FO-2 diets, respectively). At the end of the feeding period, we measured non-haem Fe stores in liver and spleen, and erythrocyte and reticulocyte count. We also determined antioxidants and products derived from lipid peroxidation in plasma and erythrocytes. Our results showed reduced non-haem Fe stores in rats fed any of the FO diets. Reticulocyte percentage was higher in the rats fed FO-0 and FO-1. Plasma alpha-tocopherol was very low in rats fed the FO-0 diet. Rats fed the FO-1 and FO-2 diets showed higher alpha-tocopherol in plasma than the FO-0 group but lower than the MO or OO groups. We did not observe such differences in the alpha-tocopherol content in erythrocyte membranes. Superoxide dismutase and glutathione peroxidase activities were lower in the erythrocytes of rats fed the FO-0 diet. The products derived from lipid peroxidation were also higher in the FO groups. The administration of FO-rich diets increased lipid peroxidation and affected Fe metabolism. On the other hand, the OO-rich diet did not increase oxidative stress and did not alter Fe metabolism. Based on these results, we conclude that FO supplementation should be advised carefully.
Oxidative Stress

Br J Dermatol. 2003 May;148(5):913-22. : Oxidative stress in malignant melanoma and non-melanoma skin cancer.
Sander CS, Hamm F, Elsner P, Thiele JJ.
Department of Dermatology, Friedrich Schiller University Jena, Erfurter Strasse 35, D-07740 Jena, Germany.

Background Solar ultraviolet (UV) radiation is considered to be a major aetiological factor in melanoma and non-melanoma skin cancer. A growing body of evidence indicates that oxidative stress is involved in photocarcinogenesis. However, in vivo data for human skin are still lacking. Reactive oxygen species participate in a number of pathophysiological processes including DNA damage and lipid peroxidation (LPO) and are considered to be a key factor in tumour progression. Objectives We hypothesized that in human skin cancer the natural redox balance is disturbed and that this imbalance may result in an accumulation of LPO products. Methods To test this, skin biopsies of superficial spreading melanoma were compared with age-matched benign melanocytic naevi and young healthy controls. Additionally, non-melanoma skin cancers (basal cell carcinoma, squamous cell carcinoma) and actinic keratosis were investigated (n = 18 each). Expression of the antioxidant enzymes, copper-zinc superoxide dismutase, manganese superoxide dismutase and catalase was analysed by immunohistochemical techniques. To detect LPO products, protein-bound malondialdehyde (MDA) was visualized. Results In human melanoma biopsies, a significant overexpression of the antioxidant enzymes was found when compared with surrounding non-tumour tissue, benign melanocytic naevi, and young controls. Intriguingly, the LPO marker MDA was significantly increased in melanoma tissue. MDA was located not only in typical melanoma cells, but also occurred in surrounding keratinocytes. In contrast, a severely disturbed antioxidant balance with diminished antioxidant enzymes was found in non-melanoma tumours, whereas MDA was elevated only in squamous cell carcinomas. Conclusions These findings indicate that oxidative stress may play different roles in the pathogenesis of human skin cancers. In non-melanoma skin cancer, a diminished antioxidant defence caused by chronic UV exposure might contribute to multistep carcinogenesis, whereas melanoma cells exhibit increased oxidative stress which could damage surrounding tissue and thus support the progression of metastasis.
: Eur J Med Chem. 2003 May;38(5):451-7.: The association of vitamins C and K(3) kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy.
Verrax J, Cadrobbi J, Delvaux M, Jamison JM, Gilloteaux J, Summers JL, Taper HS, Buc Calderon P.
Unite de Pharmacocinetique, Metabolisme, Nutrition et Toxicologie, Departement des sciences pharmaceutiques, Universite Catholique de Louvain, Bruxelles, Belgium

Deficiency of alkaline and acid DNase is a hallmark in all non-necrotic cancer cells in animals and humans. These enzymes are reactivated at early stages of cancer cell death by vitamin C (acid DNase) and vitamin K(3) (alkaline DNase). Moreover, the coadministration of these vitamins (in a ratio of 100:1, for C and K(3), respectively) produced selective cancer cell death. Detailed morphological studies indicated that cell death is produced mainly by autoschizis, a new type of cancer cell death. Several mechanisms are involved in such a cell death induced by CK(3), they included: formation of H(2)O(2) during vitamins redox cycling, oxidative stress, DNA fragmentation, no caspase-3 activation, and cell membrane injury with progressive loss of organelle-free cytoplasm. Changes in the phosphorylation level of some critical proteins leading to inactivation of NF-kappaB appear as main intracellular signal transduction pathways. The increase knowledge in the mechanisms underlying cancer cells death by CK(3) may ameliorate the techniques of their in vivo administration. The aim is to prepare the introduction of the association of vitamins C and K(3) into human clinics as a new, non-toxic adjuvant cancer therapy.
FASEB J. 2003 May 20 [Epub ahead of print]. : Tetracycline-dependent regulation of formamidopyrimidine DNA glycosylase in transgenic mice conditionally reduces oxidative DNA damage in vivo.
Laposa RR, Henderson JT, Wells PG.

8-Oxo-deoxyguanosine (8-oxo-dG) is a pervasive oxidative DNA lesion formed by endogenous oxidative stress and enhanced by drugs and environmental chemicals. This lesion results in transcriptional errors and mutations and is linked to neurodegeneration, teratogenesis, cancer, and other pathologies. We demonstrate that the neonatal central nervous system of transgenic mice carrying the tetracycline-regulable DNA repair gene formamidopyrimidine DNA glycosylase (fpg) has a 50% reduction in 8-oxo-dG levels. This enhanced DNA repair is suppressed by treatment with doxycycline. For the first time, this murine model permits the level of a specific DNA oxidation product to be regulated in a temporally and spatially specific manner, allowing its role as a primary or secondary factor in neurodegenerative disease to be determined in vivo.
Free Radic Biol Med. 2003 Jun 1;34(11):1369-82. : Oxidative stress and calcium signaling in the adverse effects of environmental particles (PM(10)).
Donaldson K, Stone V, Borm PJ, Jimenez LA, Gilmour PS, Schins RP, Knaapen AM, Rahman I, Faux SP, Brown DM, MacNee W.
Colt/ELEGI Laboratories, Centre for Inflammation Research, The University of Edinburgh Medical School, Edinburgh, UK

This review focuses on the potential role that oxidative stress plays in the adverse effects of PM(10). The central hypothesis is that the ability of PM(10) to cause oxidative stress underlies the association between increased exposure to PM(10) and both exacerbations of lung disease and lung cancer. Pulmonary inflammation may also underlie the cardiovascular effects seen following increased PM(10), although the mechanisms of the cardiovascular effects of PM(10) are not well understood. PM(10) is a complex mix of various particle types and several of the components of PM(10) are likely to be involved in the induction of oxidative stress. The most likely of these are transition metals, ultrafine particle surfaces, and organic compounds. In support of this hypothesis, oxidative stress arising from PM(10) has been shown to activate a number of redox-responsive signaling pathways in lung target cells. These pathways are involved in expression of genes that play a role in responses relevant to inflammation and pathological change, including MAPKs, NF-kappaB, AP-1, and histone acetylation. Oxidative stress from particles is also likely to play an important role in the carcinogenic effects associated with PM(10) and hydroxyl radicals from PM(10) cause DNA damage in vitro.
J Toxicol Environ Health A. 2003 Mar 14;66(5):411-5. : Glutathione and glutathione-related enzymes in colorectal cancer patients.
Saygili EI, Akcay T, Konukoglu D, Papilla C.
Department of Biochemistry, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey.
ilksaygili@mynet.com

In recent years much attention has been focused on the role of glutathione (GSH) and GSH-related enzymes such as glutathione peroxidase (GSH Px), glutathione reductase (GSH Red), and glutathione S-transferase (GST) in the inhibition of free radical-induced carcinogenesis. In this study, erythrocyte GSH levels and activities of GSH Px, GSH Red, and GST were determined in patients with colorectal tumors (n = 20, mean age 54.5 +/- 8.3 yr). Erythrocyte GSH Red and GST activities were significantly higher in patients with colorectal tumors. Erythrocyte GSH levels and GSH Px activities were found to be significantly decreased in the patients. When the patients were classified based on their clinical grading (Dukes classifications), there was no significant difference in studied parameters between Dukes B and Dukes C. Our results suggest that oxidative stress may play an important role in colorectal tumorigenesis and that these events have no effect on the clinical grading of the colorectal tumor.
Biochim Biophys Acta. 2003 Apr 11;1647(1-2):127-30. : Antitumor effect of vitamin B6 and its mechanisms.
Komatsu S, Yanaka N, Matsubara K, Kato N.
Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.

Epidemiological studies have reported an inverse association between vitamin B(6) intake and colon cancer risk. Our recent study has been conducted to examine the effect of dietary vitamin B(6) on colon tumorigenesis in mice. Mice were fed diets containing 1, 7, 14 or 36 mg/kg pyridoxine for 22 weeks, and given a weekly injection of azoxymethane (AOM) for the initial 10 weeks. Compared with the 1 mg/kg pyridoxine diet, 7, 14 and 35 mg/kg pyridoxine diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. Supplemental vitamin B(6) lowered the levels of colonic 8-hydroxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE, oxidative stress markers) and inducible nitric oxide (NO) synthase protein. In an ex vivo serum-free matrix culture model using rat aortic ring, supplemental pyridoxine and pyridoxal 5'-phosphate (PLP) had antiangiogenic effect. The results suggest that dietary vitamin B(6) suppresses colon tumorigenesis by reducing cell proliferation, oxidative stress, NO production and angiogenesis.
Curr Med Chem. 2003 Jun;10(12):1021-34. : The role of iron chelation in cancer therapy.
Buss JL, Torti FM, Torti SV.
Drug Discovery Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil / BL, Switzerland.
christoph.boss@actelion.com and
christoph.binkert@actelion.com

This review focuses on advances and strategies in the use of iron chelators as anti-tumor therapies. Although the development of iron chelators for human disease has focused primarily on their use in the treatment of secondary iron overload, chelators may also be useful anti-tumor agents. They can deplete iron or cause oxidative stress in the tumor due to redox perturbations in its environment. Iron chelators have been tested for their anti-tumor activity in cell culture experiments, animal models and human clinical trials. Largely for pragmatic reasons, clinical studies of the anti-tumor activity of iron chelators have generally focused on desferrioxamine (DFO), a drug approved for the treatment of iron overload. These studies have shown that DFO can retard tumor growth in many different experimental contexts. However, the activity of DFO is modest, and advances in the use of chelators as anti-cancer agents will require the development of new chelators based on new paradigms. Examples of iron chelators that have shown promising anti-tumor activity (in various stages of development) include heterocyclic carboxaldehyde thiosemicarbazones, analogs of pyridoxal isonicotinoyl hydrazone, tachpyridine, O-trensox, desferrithiocin, and other natural and synthetic chelators. Apart from their use as single agents, chelators may also synergize with other anti-cancer therapies. The development of chelators as anticancer agents is largely an unexplored field, but one with extraordinary potential to impact human cancer.