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Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. Li Y, Liu L, Tollefsbol TO. FASEB J. 2009 Dec 17. [Epub ahead of print] PMID: 20019239 doi: 10.1096/fj.09-149328 Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16(INK4a). Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. The altered gene expression was partly due to glucose restriction-induced DNA methylation changes and chromatin remodeling of the hTERT and p16 promoters in normal and immortalized WI-38 cells. Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches.

Age, stress, and poor nutrition can sap our immune system of its effectiveness. Influenza provides one example. During young adulthood, when the body can mount a robust immune response to this common virus, influenza is rarely fatal. Among the elderly, however, the virus is associated with significant rates of death and hospitalization (Nichol KL 2005). The impact of aging on the immune system is profound. As people age, a number of critical immune system components are reduced or slowed, including cellular response, response to vaccines, and antibody production. At the same time, susceptibilities to infection and cancer are increased. Some of this increased susceptibility to disease is linked to chronic inflammation, which is associated with many disorders of aging (Ershler WB et al 2000; Hamerman D 1999; Taaffe DR et al 2000).

A heat-stable extract of white button mushrooms (Agaricus bisporus) with potential chemopreventive and immunomodulating activities. Phytochemicals, such as polysaccharides and especially beta-D-glucans found in the white button mushroom extract, bind to and inhibit the activity of aromatase, an enzyme responsible for the conversion of androgens to estrogens and which is often upregulated in breast cancer cells. The consequent decrease in estrogen production may result in the suppression of estrogen-dependent cellular proliferation. In addition, this extract may promote dendritic cell (DC) maturation, increase interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) production, and may enhance natural killer (NK) cell activity, thus amplifying both innate and T cell-mediated immune responses against cancer cells. Check for active clinical trials or closed clinical trials using this agent.

One way tumors fly under the radar of the immune system is by using IDO, an enzyme used by fetuses to help avoid rejection, to recruit powerful regulatory T cells that turn down the immune response, researchers say.

MedWire News: Intralesional injection of interleukin (IL)-7 and IL-15 enhances the effects of radiofrequency thermal ablation (RFA) in inhibiting tumor development and metastases, animal study results show. RFA, used for the treatment of solid tumors and known for its localized tumor effects, may activate immune responses and thereby reduce the risk for local tumor recurrence or distant metastases through T cell stimulation. However, studies have suggested that additional adjuvant immunotherapy may improve the efficacy of RFA. This preclinical study, reported in Breast Cancer Research and Treatment, was conducted to evaluate the effect of addition of the cytokines IL-7 and IL-15 to RFA in models of breast cancer.

Beta glucan is a scientifically proven biological defense modifier (BDM) that nutritionally potentiates and modulates the immune response. As a supplement, after swallowing orally, Beta glucan is ingested primarily through macrophage and dendritic immune cells, to nutritionally and safely yield, through immune response potentiation and modulation, in many instances various therapeutic healing effects generated by the immune cells.  For many years Glucans have been investigated (History) for these immune enhancing properties, particularly their ability to activate macrophage immune cells and NK-Cells, plus in turn, the T-Cells, and B-Cells including selected cytokines and complement. 

2: Selenium and the immune response: 2. Enhancement of murine cytotoxic T-lymphocyte and natural killer cell cytotoxicity in vivo. Petrie HT, Klassen LW, Klassen PS, O'Dell JR, Kay HD. J Leukoc Biol. 1989 Mar;45(3):215-20. PMID: 2564412

A recently published study in Nutrition and Cancer (60(5), 643-651) by researchers at Kansai Medical University in Osaka, Japan has shown that AHCC (Active Hexose Correlated Compound) enhances immune function by increasing the number of dendritic cells (DCs). DCs are a key part of the immune system responsible for presenting foreign substances to other immune system cells. The study was conducted in a double-blind randomized fashion where twenty-one healthy subjects received a placebo or AHCC at 3.0 g/day for 4 weeks. Blood samples were obtained and measured at baseline and at 4 weeks. The number of circulating types of DCs was measured which included CD 11c+ DCs (myeloid DC population; DC1) and CD11c- DCs (lymphoid DC population; DC2). Other parameters measured included mixed-leukocyte reaction (MLR), natural killer (NK) cell activity, the proliferative response of T lymphocytes toward mitogen (phytohemagglutinin [PHA]) and cytokine production of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon gamma-gamma, and (alpha)-tumor necrosis factor.

A new study showing a reduction in the toxic side effects of ROS-generating chemotherapies with concurrent antioxidant supplementation will be presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO) that takes place June 1-5 at McCormick Place in Chicago. According to the study's authors, mitigating chemotherapy toxicity by supplementing with antioxidants may improve survival rates and tumor response by helping patients complete their prescribed treatment cycles.

Multiple roles for CD4+ T cells in anti-tumor immune responses. Kennedy R, Celis E. Immunol Rev. 2008 Apr;222:129-44. Review. PMID: 18363998 DOI: 10.1111/j.1600-065X.2008.00616.x

Ursolic acid is a pentacyclic triterpene acid, used in cosmetics,[2] that is also capable of inhibiting various types of cancer cells by inhibiting the STAT3 activation pathway[3][4] and human fibrosarcoma cells by reducing the expression of matrix metalloproteinase-9 by acting through the glucocorticoid receptor. Ursolic acid is present in many plants, including apples, basil, bilberries, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, prunes. Apple peels contain high quantity of ursolic acid and related compounds which are responsible for the anti-cancer activity of apple. Ursolic acid can also serve as a starting material for synthesis of more potent bioactive derivatives, such as anti-tumor agents

If you want to reduce your risk for getting cancer, heart disease, diabetes and a host of other diseases, the message is clear - eat a nutrient-rich, low-fat, high fiber diet, with plenty of fruit and vegetables. So why is this wisdom forgotten when a person is diagnosed with cancer, and the standard advice becomes: "Eat whatever you want, whatever you can tolerate," even when this may include a diet high in fat and refined sugars. \n\nAccording to two of the country's leading authorities on cancer and nutrition, David Katz, MD and Keith Block, MD, the typical American high-fat, empty calorie diet can set the stage for an inflammatory response that actually fuels a cancer patient's disease, undermines treatment, and promotes malnutrition.

Cancer immunology is the study of interactions between the immune system and cancer cells (also called tumors or malignancies). It is also a growing field of research that aims to discover innovative cancer immunotherapies to treat and retard progression of this disease. The immune response, including the recognition of cancer-specific antigens is of particular interest in this field as knowledge gained drives the development of new vaccines and antibody therapies. For instance in 2007, Ohtani published a paper finding tumour infiltrating lymphocytes to be quite significant in human colorectal cancer.[1] The host was given a better chance at survival if the cancer tissue showed infiltration of inflammatory cells, in particular lymphocytic reactions. The results yielded suggest some extent of anti-tumour immunity is present in colorectal cancers in humans.

Simultaneously Blocking Glycolysis and Fat Metabolism Can the use of DCA and a fatty acid metabolism blocker together force more cancer cells into using aerobic metabolism? Tim McGough used green tea extract, which contains EGCG, in his fantastic response. DCA works by reactivating mitochondria and shifts metabolism from glycolysis to glucose oxidation. Hopefully the cancer cell will then undergo apoptosis. However, cancer cells have an alternate energy source: fat metabolism. This page explores to possibility of blocking fat metabolism to help force the cell into apoptosis. Oral squamous cell carcinoma is a cancer that does not respond well to DCA. This study, Head and Neck Cancer Cell Lines Are Resistant to Mitochondrial-Depolarization-Induced Apoptosis states: "Results: ΔΨm in head and neck cell lines started to show slight loss of ΔΨm, while HL-60 showed significant loss of ΔΨm after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. Conclusions: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane-depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.(head and neck squamous cell carcinoma)" Note that although the cell lines were depolarized, apoptosis did not occur. So I checked to see if fatty acid metabolism is used by squamous cell carcinoma.

Derived from the cap and stem of the mushroom, Reishi mushroom is used as an immune stimulant by patients with HIV or cancer. The active constituents are thought to include both beta-glucan polysaccharides and triterpenes (1). Extracts of Reishi can stimulate macrophages and alter the levels of TNF and interleukins (2) (3) (4) (5). Reishi also inhibited platelet aggregation (11) (12) and improved lower urinary tract symptoms (LUTS) in men (9) (10). Studies done in rats have shown that Reishi extract may alleviate chemotherapy-induced nausea (13). In clinical studies, Reishi increased plasma antioxidant capacity (6) (7)and enhanced immune responses in advance-stage cancer patients (8).

Shiitake mushroom, native to East Asia, is cultivated worldwide for its purported health benefits. The fresh and dried forms of the mushroom are commonly used in East Asian cooking. It is also valued as an anticancer agent. Lentinan (1,3 Beta-D-glucan), a polysaccharide isolated from Shiitake, has been well studied and is thought responsible for its beneficial effects. It was shown to have anticancer effects in colon cancer cells (1), which may be due to its ability to suppress cytochrome P450 1A enzymes that are known to metabolize pro-carcinogens to active forms

Safety Study of Seneca Valley Virus in Patients With Solid Tumors With Neuroendocrine Features This study is currently recruiting participants. Verified by Neotropix, September 2008 This is the first study in man of Seneca Valley Virus, a virus which seeks and kills certain tumors in non-human model systems. Subjects in this trial will be patients with advanced cancer displaying certain specified neuroendocrine features, pathologically; they will have exhausted standard methods of treatment for their tumor. The primary purpose of the trial is to determine if the virus may be administered safely. Additional purposes are to learn about the distribution of the virus in the body, the elimination of the virus from the body, the immune response to the virus and whether the virus might have some beneficial effects upon the tumors which the patients have. The first patients will be treated with low amounts of virus and subsequent patients may receive higher amounts. At the end of the trial, it is intended to select a dose for further study.

The April issue of the journal Cancer Prevention Research published the results of a trial conducted by scientists at Tokyo University of Science, the University of Tsukuba in Japan, and Johns Hopkins University which determined that the isothiocyanate sulforaphane, a compound that occurs in high amounts in broccoli and its sprouts, helps suppress infection by Helicobacter pylori (H. pylori), the bacteria responsible for stomach ulcers and many cases of stomach cancer. The trial is the first to demonstrate an effect for broccoli against H. pylori in humans.

White button mushrooms appear to boost immune function It appears that a little fungus may be good for what ails you. That's the conclusion of a new study that found that eating white button mushrooms may boost the immune system and protect against infection. If the research, done on animals, translates to people, it could raise the health-benefit profile of the fungus, which also contains high concentrations of the super-antioxidant ergothioneine, which protects cells from damaging free radicals. "This is the first published study showing the effect of white button mushrooms on immune function," Dayong Wu, a scientist in the Immunology Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts and lead author of the study, published in the June issue of the Journal of Nutrition, told NutraIngredients.com. The research also suggests that the mushroom may boost both innate and acquired immune system health. The innate immune system, the one you're born with, is the body's first line of defense. The acquired immune system revs up if a pathogen makes its way past the innate system and customizes the immune response to target the invader.

Induction of ovarian cancer cell apoptosis by 1,25-dihydroxyvitamin D3 through the down-regulation of telomerase. Jiang F, Bao J, Li P, Nicosia SV, Bai W. J Biol Chem. 2004 Dec 17;279(51):53213-21. Epub 2004 Oct 12. PMID: 15485861 doi: 10.1074/jbc.M410395200 Overall, the study suggests that the down-regulation of telomerase activity by 1,25(OH)2VD3 and the resulting cell death are important components of the response of OCa cells to 1,25(OH)2VD3-induced growth suppression. Progressive shortening of telomere associated with cell divisions limits the life span of normal cells and eventually leads to senescence. To become immortal, human cancers including OCa are invariably associated with activation of mechanism that maintains telomere length. Approximately 85-90% of cancers show reactivation of telomerase. The present study shows that telomerase in OCa cells is down-regulated by 1,25(OH)2VD3. Down-regulation of telomerase is due to decreased stability of hTERT mRNA rather than VDRE-mediated transcriptional repression through the putative VDRE present in the regulatory region of the hTERT gene. It is known that the inhibition of telomerase may lead to a phenotypic lag during which cells would continue to divide until the point at which the telomeres became critically short. This phenomenon may explain why the apoptotic induction by 1,25(OH)2VD3 needs the treatment for more than 6 days. As mentioned in the results, no detectable shortening of telomeric repeats was observed in parental OVCAR3 cells after 9 days of treatment with 1,25(OH)2VD3 (Fig. 4D). This is likely due to the fact that the short telomere (about 3 kb) in OVCAR3 cells is very close to the minimal length required for survival and that cells with detectably shorter telomere may have been selected against apoptosis. It has been shown that transformed human cells enter crisis once the terminal restriction fragment of the telomere reaches a length of about 4 kb. This is insufficient to protect chro