forrás: http://www.ncbi.nlm.nih.gov/pubmed/20739263
2014-04-09 15:00:46
The concentration of deuterium is about 150 ppm (over 16 mmol/L) in surface water and more than 10 mmol/L in living organisms. Experiments with deuterium depleted water (30+/-5 ppm) revealed that due to D-depletion various tumorous cell lines (PC-3, human prostate, MDA, human breast, HT-29, human colon, M14, human melanoma) required longer time to multiply in vitro. DDW caused tumor regression in xenotransplanted mice (MDA and MCF-7, human breast, PC-3) and induced apoptosis in vitro and in vivo. Deuterium depleted water (25+/-5 ppm) induced complete or partial tumor regression in dogs and cats with spontaneous malignancies, it was registered as anticancer for veterinary use in 1999 (Vetera-DDW-25 A.U.V., 13/99 FVM). The hypodermic preparation of the registered veterinary drug was successfully tested in clinical investigations. Under the permission of the Hungarian Institute of Pharmacology (No. 5621/40/95) a randomized, double blind controlled, human Phase II clinical trial with prostate cancer was performed, in compliance with GCP principles, which exhibited a significant difference between the control and treated groups with respect to the examined parameters, median survival time and the extension of life-span. We suggest that cells are able to regulate the D/H ratio and the changes in the D/H ratio can trigger certain molecular mechanisms having a key role in cell cycle regulation. We suppose that not the shift in the intracellular pH, but the concomitant increase in the D/H ratio is the real trigger for the cells to enter into S phase. The decrease of D concentration can intervene in the signal transduction pathways thus leading to tumor regression. Deuterium depletion may open new perspectives in cancer treatment and prevention helping to increase the effectiveness of current oncotherapies.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/11251172
2014-03-11 13:52:27
Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrugresistant Plasmodium falciparum and P. vivax malaria.
ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines (mean GI50 values: 1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively).
Nonsmall cell lung cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM) indicating the lowest sensitivity towards ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with those of other standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel. None of these drug-resistant cell lines showed cross resistance to ART. To gain insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644. None of the other DNA repair or DNA check-point deficient isogenic strains were different from the wild-type. These results and the known low toxicity of ART are clues that ART may be a promising novel candidate for cancer chemotherapy.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/22842629
2014-02-18 10:10:50
Epidemiologic and case control population based studies over the past few decades have identified diet as an important determinant of cancerrisk. This evidence has kindled interest into research on bioactive food components and has till date resulted in the identification of many compounds with cancer preventive and therapeutic potential. Among such compounds has been fisetin (3,7,3',4'-tetrahydroxyflavone), a flavonol and a member of the flavonoid polyphenols that also include quercetin, myricetin and kaempferol. Fisetin is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers. We evaluated the effects of fisetin against melanoma and cancers of the prostate, pancreas and the lungs. Using prostate and lung adenocarcinoma cells, we demonstrated that fisetin acts as a dual inhibitor of the PI3K/Akt and the mTOR pathways. This is a significant finding considering the fact that mTOR is phosphorylated and its activation is more frequent in tumors with overexpression of PI3K/Akt. Dual inhibitors of PI3K/Akt and mTOR signaling have been suggested as valuable agents for treating such cancers. Here, we summarize our findings on the dietary flavonoid fisetin and its effects on cancer with particular focus on prostate cancer. Our observations and findings from other laboratories suggest that fisetin could be a useful chemotherapeutic agent that could be used either alone or as an adjuvant with conventional chemotherapeutic drugs for the management of prostate and other cancers.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/20739263
2014-04-09 15:00:46
A deutérium koncentrációja körülbelül 150 ppm (több, mint 16 mmol/L) a felszíni vizekben és több, mint 10 mmol/L az élő szervezetekben. A csökkentett deutérium tartalmú vízzel (30+/-5ppm) végzett kísérletek feltárták, hogy a csökkentett deutérium tartalomnak köszönhetően a különböző rákos sejtvonalaknak (PC-3, humán prosztata, MDA, humán mellkas, HT-29, humán vastagbél, M14, humán melanoma) hosszabb időre volt szükségük a szaporodáshoz in vitro. A deutériumban szegény víz (DDW) a tumor visszafejlődését idézte elő a xenotranszplantált egereknél (MDA és MCF-7 humán mell, PC-3) és programozott sejthalált idézett elő in vitro és in vivo. A deutérium szegény víz (25 +/- 5 ppm) teljes vagy részleges daganat csökkenést idézett elő a spontán rosszindulatú daganattal diagnosztizált kutyáknál és macskáknál és rákellenes szerként jegyezték be állatorvosi használatra 1999-ben (Vetera-DDW-25 A.U.V., 13/99 FVM). A bejegyzett állatgyógyászati szer bőr alá fecskendezhető készítményét sikeresen teszteltek klinikai kísérletek során. A Magyar Gyógyszerészeti Intézet engedélye (No. 5621/40/95) alapján véletlenszerű, kettős vakon ellenőrzött humán II. fázisú klinikai kipróbálást végeztek prosztata rákon, összhangban a GCP [bevett klinikai gyakorlat] elvekkel, ami jelentős eltérést mutatott a kontroll és a kezelésbe bevont csoportok között a vizsgált paraméterek, az átlagos túlélési idő és az élettartam meghosszabbodás tekintetében. Azt véljük, hogy a sejtek képesek a D/H arányt szabályozni és a D/H arányban bekövetkezett változások beindíthatnak bizonyos molekuláris mechanizmusokat, amelyeknek döntő szerepük van a sejtciklusok szabályozásában. Azt feltételezzük, hogy nem a sejten belüli pH érték eltolódása, hanem az ezt kísérő D/H arány megnövekedése a tényleges beindítója annak, hogy a sejtek belépnek az S fázisba. A D koncentráció csökkenése beavatkozhat a jelátalakító utakba, ilyen módon járulva hozzá a daganat visszafejlődéshez. A deutérium csökkentése új perspektívákat nyithat meg a rák kezelésében és megelőzésében, növelve a jelenlegi onkoterápiák hatékonyságát.
forrás: http://www.ncbi.nlm.nih.gov/pubmed/20739263
2014-04-09 15:00:46
Concentraţia în deuterium este de aproximativ 150 ppm (peste 16 mmol/L) în apa de suprafaţă şi mai mult de 10 mmol/L în organismele vii. Experimente cu apă sărăcită în deuteriu (30 +/- 5 ppm) au arătat că datorită sărăcirii în deuteriu, diferite linii celulare tumorale (PC-3, de prostată umană, MDA, de sân uman, HT-29, de colon uman, M14, de melanom uman) necesită mai mult timp pentru a se multiplica in vitro. Apa sărăcită în deuteriu a produs regresia tumorii la şoarecii xenotransplantaţi (MDA și MCF-7, sân uman, PC-3) şi a indus apoptoza in vitro şi in vivo. Apa sărăcită în deuteriu (25 +/- 5 ppm) a indus regresie completă sau parţială la câini şi pisici cu malignităţi spontane, fiind înregistrată ca anticancer pentru uz veterinar în 1999 (Vetera-DDW-25 A.U.V., 13/99 FVM). Preparatul subcutanat al medicamentului veterinar înregistrat, a fost testat cu succes în investigaţii clinice. Cu permisiunea Institutului Maghiar de Farmacologie (Nr. 5621/40/95 ) a fost desfăşurat un studiu clinic, randomizat cu control dublu orb, asupra cancerului uman de prostată în faza II, în acord cu principiile GCP, iar studiul a arătat o diferenţă semnificativă, între grupurile de control şi cele tratate, privitor la parametrii examinaţi, media timpului de supravieţuire şi extinderea speranţei de viaţă. Sugerăm că celulele sunt capabile să regleze raportul D/H şi că schimbările in raportul D/H pot declanşa anumite mecanisme moleculare cu rol cheie în reglarea ciclului celular. Presupunem că nu schimbarea ph-ului intracelular, ci creşterea concomitentă a raportului D/H este declanşatorul real pentru celule de a intra în faza S. Descreşterea concentraţiei în D poate interveni în mecanismele de transducţie a semnalului, conducând astfel la regresia tumorii. Sărăcirea în deuteriu poate deschide noi perspective în tratamentul şi prevenţia cancerului, ajutând la creşterea eficienţei terapiilor oncologice curente.
