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Matti Narkia

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - British J... - 1 views

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    Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.
    Michelakis ED, Webster L, Mackey JR.
    Br J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review.
    PMID: 18766181
    doi:10.1038/sj.bjc.6604554

    The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials

    More than 40 nonrandomised trials of DCA in small cohorts of patients have been reported, but the first two randomised control trials of chronic oral therapy with DCA in congenital mitochondrial diseases were reported in 2006. In the first, a blinded placebo-controlled study was performed with oral DCA administered at 25 mg kg-1 day-1 in 30 patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (Kaufmann et al, 2006). Most patients enrolled in the DCA arm developed symptomatic peripheral neuropathy, compared with 4 out of 15 in the placebo arm, leading to the termination of the study. Seventeen out of 19 patients had at least partial resolution of peripheral neurological symptoms by 9 months after discontinuation of DCA. This neurotoxicity res
Matti Narkia

Mechanisms of Berberine (Natural Yellow 18)-Induced Mitochondrial Dysfunction: Interact... - 0 views

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    Mechanisms of berberine (natural yellow 18)-induced mitochondrial dysfunction: interaction with the adenine nucleotide translocator.
    Pereira CV, Machado NG, Oliveira PJ.
    Toxicol Sci. 2008 Oct;105(2):408-17. Epub 2008 Jul 3.
    PMID: 18599498
    doi: 10.1124/jpet.107.128017

    The data from the present work appear to show that berberine also presents some degree of toxicity to "nontumor" systems, which should be carefully understood. ANT inhibition in nontumor cells by berberine would be responsible for a decrease in energy production and could also result in MPT induction. To the best of our knowledge, no full toxicity assessment exists for berberine in humans, although its use in several commercially available supplements suggests that the compound may present a relatively wide safety interval. In fact, a study with patients with congestive heart failure treated with 1.2 g/day of oral berberine revealed low toxicity and resulted into an average plasma concentration of 0.11 mg/l which would translate into 0.3µM (Zeng and Zeng, 1999Go). Repeated cumulative treatments, alternative forms of formulation (e.g., topical application vs. injection) or more importantly, active mitochondrial accumulation due to its positive charge would be expected to increase its concentration in cells into the range of concentrations used in this study.

    Empirical data from nontraditional medicines plus the use of extensive clinical assays would allow the use of berberine as a promising antimelanoma agent while maintaining its safety for humans. In radial/vertical forms of melanoma, a possible topical application of berberine would also be possible, thus minimizing side effects on other organs.

    In conclusion, the present work identifies the ANT as an important target for berberine, with clear relevance for its proposed antitumor effects.
Matti Narkia

Calcium, Dairy Foods, Vitamin D, and Colorectal Cancer Risk: The Fukuoka Colorectal Can... - 0 views

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    Calcium, dairy foods, vitamin D, and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.
    Mizoue T, Kimura Y, Toyomura K, Nagano J, Kono S, Mibu R, Tanaka M, Kakeji Y, Maehara Y, Okamura T, Ikejiri K, Futami K, Yasunami Y, Maekawa T, Takenaka K, Ichimiya H, Imaizumi N.
    Cancer Epidemiol Biomarkers Prev. 2008 Oct;17(10):2800-7.
    PMID: 18843026
Matti Narkia

Vitamin D From Dietary Intake and Sunlight Exposure and the Risk of Hormone-Receptor-De... - 0 views

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    Vitamin D from dietary intake and sunlight exposure and the risk of hormone-receptor-defined breast cancer.
    Blackmore KM, Lesosky M, Barnett H, Raboud JM, Vieth R, Knight JA.
    Am J Epidemiol. 2008 Oct 15;168(8):915-24. Epub 2008 Aug 27.
    PMID: 18756015
    doi:10.1093/aje/kwn198

    This study suggests that vitamin D is associated with a reduced risk of breast cancer regardless of ER/PR status of the tumor. Future studies with a larger number of receptor-negative and mixed tumors are required.
Matti Narkia

Scripps research team solves structure of 'beneficial' virus | Eureka! Science News - 0 views

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    D structure of the virus, known as Seneca Valley Virus-001, reveals that it is unlike any other known member of the Picornaviridae viral family, and confirms its recent designation as a separate genus "Senecavirus." The new study reveals that the virus's outer protein shell looks like a craggy golf ball¬-one with uneven divets and raised spikes-and the RNA strand beneath it is arranged in a round mesh rather like a whiffleball. "It is not at all like other known picornaviruses that we are familiar with, including poliovirus and rhinoviruses, which cause the common cold," says the study's senior author, Associate Professor Vijay S. Reddy, Ph.D., of The Scripps Research Institute. "This crystal structure will now help us understand how Senecavirus works, and how we can take advantage of it."

    The Senecavirus is a "new" virus, discovered several years ago by Neotropix Inc., a biotech company in Malvern, Pennsylvania. It was at first thought to be a laboratory contaminant, but researchers found it was a pathogen, now believed to originate from cows or pigs. Further investigation found that the virus was harmless to normal human cells, but could infect certain solid tumors, such as small cell lung cancer, the most common form of lung cancer.
Matti Narkia

Multi-targeted therapy of cancer by omega-3 fatty acids - Cancer Lett. 2008 Oct 8 - 0 views

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    Multi-targeted therapy of cancer by omega-3 fatty acids.
    Berquin IM, Edwards IJ, Chen YQ.
    Cancer Lett. 2008 Oct 8;269(2):363-77. Epub 2008 May 13. Review.
    PMID: 18479809
    doi:10.1016/j.canlet.2008.03.044
Matti Narkia

Bioavailability and Kinetics of Sulforaphane in Humans after Consumption of Cooked vers... - 0 views

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    Bioavailability and Kinetics of Sulforaphane in Humans after Consumption of Cooked versus Raw Broccoli
    Martijn Vermeulen*, Ineke W. A. A. Klpping-Ketelaars†, Robin van den Berg‡ and Wouter H. J. Vaes
    J. Agric. Food Chem., 2008, 56 (22), pp 10505-10509
    Publication Date (Web): October 24, 2008 (Article)
    DOI: 10.1021/jf801989e
Matti Narkia

Structure-function relationships of anthocyanins from various anthocyanin-rich extracts... - 0 views

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    Structure-function relationships of anthocyanins from various anthocyanin-rich extracts on the inhibition of colon cancer cell growth.
    Jing P, Bomser JA, Schwartz SJ, He J, Magnuson BA, Giusti MM.
    J Agric Food Chem. 2008 Oct 22;56(20):9391-8. Epub 2008 Sep 19.
    PMID: 18800807
    DOI: 10.1021/jf8005917
Matti Narkia

Vitamin C Antagonizes the Cytotoxic Effects of Antineoplastic Drugs - 0 views

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    Vitamin C antagonizes the cytotoxic effects of antineoplastic drugs.\nHeaney ML, Gardner JR, Karasavvas N, Golde DW, Scheinberg DA, Smith EA, O'Connor OA.\nCancer Res. 2008 Oct 1;68(19):8031-8.\nPMID: 18829561
Matti Narkia

Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer - British J... - 0 views

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    Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.\nMichelakis ED, Webster L, Mackey JR.\nBr J Cancer. 2008 Oct 7;99(7):989-94. Epub 2008 Sep 2. Review.\nPMID: 18766181 \ndoi:10.1038/sj.bjc.6604554 \n
Matti Narkia

Ginkgo biloba extract EGb(R)761 exerts anti-angiogenic effects via activation of tyrosi... - 0 views

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    Ginkgo biloba extract EGb(R)761 exerts anti-angiogenic effects via activation of tyrosine phosphatases.
    Koltermann A, Liebl J, Fürst R, Ammer H, Vollmar AM, Zahler S.
    J Cell Mol Med. 2008 Oct 23. [Epub ahead of print]
    PMID: 19175691
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