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A collection of abstracts

Short versions:

Effects of Tochopherols and Selenite on Spontaneous Mutagenesis in LacZ Mouse Colon, Prostate and Lung.

Gutenplan, J.B. et al

American Health Foundation, Valhalla, NY

Ann's paraphrase: 5 groups of LacZ mice (an animal model for tumor initiation) were given 5 separate diets, two of which were selenium alone and two were selenium with alpha and gamma tocopherol.

Conclusion: "Thus, the combination of tocopherols + selenite were effective at reducing spontaneous mutagenesis in colon and possibly prostate." _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Role of Mitochondondrial Complexes I and II, Reactive Oxygen Species, and Arachidonic Acid Metabolism in Bile Salt-Induced Apoptosis

Washo-Tultz, D.E. et al

University of Arizona, Tucson, AZ

Ann's paraphrase: Apoptosis means programmed cell death and is desirable when dealing with cancer cells. These researchers wanted to find out how some substances might work with bile salts to cause apoptosis.

"The role of antioxidants in NaDOC-induced apoptosis was evaluated using melatonin, a fat and water soluble antioxidant; N--acetyl-cysteine, a GSH enhancer; U-74389G, a lzeroid that inhibits superoxide anion and free radical lipid peroxidation; and arachidonic acid metabloism..."

This was done with a human colon cancer epithelial cell line, HT-29.

Conclusions: "It is possible that the use of antioxidants and non-steroidal anti-inflammatory drugs (NSAIDS), both of which inhibit a survival pathway, in conjunction with apoptosis-inducing agents, may be effective chemopreventive strategies to rid the colon of malignant cells. In addition, non-genotoxic agents that are directed at specifically damaging mitochondria may also be useful in chemoprevention by activating a pro-apoptotic pathway." _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Suppression of iNOS by Curcumin and Its Hydrogenated Metabolites through Down Regulation of lkB Kinase and NFkB activation in Macrophages

Lin, J-K, et al.

Institute of Biochem, College of Medicine, National Taiwan University, Tapei, Taiwan

"We have observed that curcumin was biotransformed to dihydrocurcumin (DHC) , tetrahydrocurcumin (THC) and hexahydrocurcumin (HHC) and that these compounds subsequently were converted to monglucoronide conjugates in plasma of the mice. Nitric Oxide (NO) plays an important role in inflammation and multiple stages of carcinogenesis. In this study we investigated the inhibitory effects of curcumin and its metabolites, THC, HHC, and octahydrocurcumin (OHC) on the induction of iNOS..."

"Inhibition of NO production was observed when the cells were treated with curcumin..."

Conclusion: "These results suggest that curcumin may exert its antiinflammatory and anticarcinogenic properties by suppressing the activation of NFkb (a transcription factor necessary for iNOS induction) through inhibiting IKK activity." _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Genistein and Tamoxifen Mechanisms of Action: Regulation of mRNA leves in the Rat Uterus

Benetto, Chantelle Janine, University of Alabama, Birmingham, AL

"Genestein is a phytoestrogen component of soy that is being investigated for breast cancer chemoprevention. Tamoxifen, an ant-iestrogen in the mammary gland, is being usef for breast cancer therapy and is presently being evaluated for breast cancer prevention. Moreover Tamoxifen has been reported to have estogen action in the uterus.

The goal of this study was to investigate the combination of genestein and tamoxifen on the uterus."

Conclusions: Significant decreases (of uterine ER alpha and ER beta) were seen after tamoxifen , genistein and combination treatments. No synergistic effects were seen with combination treatments. Down regulation of ER-alpha and beta is consistent with these two compounds acting as estrogens in the uterus. However, down regulation of ERK-1 and jun-b suggest that these two chemicals also act independent of estrogen receptor activation."

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Growth Inhibition of Stomach Cancer Cells by Vitamin K3 is Associated with Erk1/2 Phoshorylation

Osada, S,, Saji, S., Second Dept. of Surgery, Gifu University School. of Medicine, Gifu, Japan

Ann's NOTE: This was a discussion of mechanisms of action but it was a given that this Vitamin was effective in inhibiting the growth of stomach cancer cells.

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Effects of 1-alpha Hydroxyvitamin D5 Are Selective to Malignant Breast Epithelial Cells

Metha, R.R. et al, University of Illinois, Chicago, IL

"Recently we showed that a relatively non-toxic analog of Vitamin D has potent cell differentiating and growth inhibitory actions in various human breast carcinoma cell lines. In this study we compared the effects of 1-alpha(OH)D5 on malignant and non malignant human breast tumors and nonmalignant breast tissues."

Results: "Following incubation with 1-alpha (OH)D5, increased apoptosis and cell death was observed."

Conclusions: "These results suggest that human breast tissues maintain original tissue architechture for up to 48 hours in vitro and 1-alpha (OH)D5 has no effect on normal breast tissue but induces apoptosis in malignant breast tumors.

Supported by DOD17-99-1-9223 and NCI RO1-82316

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ 1-alpha Hydroxy Vitamin D5 Induces Apoptosis and Cell Cycle Arrest in BT-474 Breast Cancer Cells

Hussain, E.A., University of Illinois, Chicago, IL

"Several epidemiological studies have shown an increased risk of breast cancer5 mortality with lower serum vitamin D levels. It is well established that the active metabolite of vitamin D, 1-alpha25(OH2)D3 (VD3) induces cell differentiation and inhibits cellular proliferation in vitro concentrations that would be hypercalcemic in vivo. Therefore various non-calcemic analogs of VD3 have been synthesized and characterized." _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

Licorice Root Extract

So far only a few of the very sickest patients have been helped, and most of them only lived a few months longer than they would have without the treatment. But experts say the drugs offer a targeted approach to cancer and may allow for more tailored treatments.

Dr. Daniel von Hoff, president of the American Association of Cancer Research (AACR), said the patients tested were dying despite getting the best treatment available.

“You have some agent that hits a specific target in patients who have already progressed on all other therapies,” he said in an interview on Tuesday. “To see anybody respond in that situation is a triumph.”

The AACR, along with the National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC) highlighted the experimental drugs at a meeting on basic cancer research.

One study shows that a compound found in licorice root, licochalcone-A, can work against acute leukemia, breast and prostate cancer tumors, at least in laboratory dishes.

Researchers said it lowers levels of bcl-2, a drug-resistant protein, in the tumors. “By decreasing the level of bcl-2, licochalcone-A may increase tumor sensitivity to anti-cancer agents,” Dr. Robert DiPaola of the Robert Wood Johnson Medical School in New Brunswick, New Jersey, said in a statement.

The extract seems to act as a phytoestrogen — a plant version of the hormone estrogen, known to be involved in many cancers, DiPaola told the meeting.

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