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Medical Forum / Diseases and Disorders / Cancer / November 2008Liver Cancer And Diabetes
High iron has been linked to diabetes developement. "NIH Clinical Trial / Iron Depletion in Type 2 Diabetes" Liver cancer is prevented BY iron depletion in Hepatitis. "None developed hepatocellular carcinoma (HCC)." One might think the increased liver cancer rates in diabetes may be related to increased iron .. ? Liver cancer patients have high diabetes prevalence Fri Nov 14, 2008 NEW YORK (Reuters Health) - Patients with hepatocellular carcinoma (HCC) have a significantly higher prevalence of type 2 diabetes mellitus (DM) compared to the general population, according to findings from a case-control study conducted in Italy. "The association of type (DM2) ... with hepatocellular carcinoma (HCC) has been long suspected," Dr. Valter Donadon, at Pordenone Hospital, and co-authors note in the October 7 issue of the World Journal of Gastroenterology. "However, the temporal relationship between onset of diabetes and development of HCC, and the clinical and metabolic characteristics of patients with DM2 and HCC have not been well examined." Their study included 465 consecutive Caucasian HCC patients and 490 age- and sex-matched controls. Overall, 145 hepatocellular carcinoma patients (31 percent) and 62 control cases (13 percent) had type 2 diabetes (odds ratio 3.1). Moreover, the authors note, diabetes had been diagnosed at least 6 months prior to the diagnosis of hepatocellular carcinoma in 84 percent of cases, suggesting that diabetes may be a cause rather than a consequence of liver cancer. Men with DM and HCC were more likely to be treated with insulin than male diabetics in the control group (38 percent vs 18 percent, p = 0.009), leading the researchers to recommend "close surveillance for HCC in patients with chronic liver disease and DM2, particularly (among) males and (those) treated with insulin." They also advise that metabolic control be attempted with insulin- sensitizers, such as metformin and glitazones, in preference to insulin or oral secretogogues. World J Gastroenterol 2008;14:5695-5700. ------------------- "None of these patients developed hepatocellular carcinoma (HCC)." http://cancerres.aacrjournals.org/cgi/content/abstract/61/24/8697 Clinical Investigations Normalization of Elevated Hepatic 8-Hydroxy-2'-Deoxyguanosine Levels in Chronic Hepatitis C Patients by Phlebotomy and Low Iron Diet1 Junji Kato, Masayoshi Kobune, Tokiko Nakamura, Ganji Kuroiwa, Kohichi Takada, Rishu Takimoto, Yasuhiro Sato, Koshi Fujikawa, Minoru Takahashi, Tetsuji Takayama, Tatsuru Ikeda and Yoshiro Niitsu2 Fourth Department of Internal Medicine [J. K., T. N., G. K., K. T., R. T., Y. S., K. F., M. T., T. T., Y. N.] and Department of Molecular Medicine [M. K.], Sapporo Medical University School of Medicine, and Department of Clinical Pathology, Sapporo Medical University Hospital [T. I.], Sapporo 060-8543, Japan Accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA, which may result from the continuous reactive oxygen species (ROS) generation associated with chronic inflammation, has been reported in various human preneoplastic lesions and in cancerous tissues. However, no direct causative relationship between the 8-OHdG formation and carcinogenesis has been thus far demonstrated in humans. Directly proving the causality requires showing that depletion of 8- OHdG levels in tissue by interfering with ROS generation results in a reduction in cancer. Chronic hepatitis C virus (HCV) infection is associated with a high risk of hepatocellular carcinoma (HCC). Several studies on patients with chronic HCV have shown that hepatic iron overload is attributable to liver injury and that iron depletion improved serum aminotransferase levels. Excess iron is known to generate ROS within cells, which causes mutagenic lesions, such as 8-OHdG. In this study, therefore, we have evaluated whether therapeutic iron reduction (phlebotomy and low iron diet) with a long-term follow-up (6 years) would decrease the hepatic 8-OHdG levels and the risk of HCC development in patients with chronic HCV. Patients (34) enrolled were those who had undergone standard IFN therapy but had no sustained response. Quantitative immunohistochemistry using the KS-400 image analyzing system and electrochemical detection was used for 8-OHdG detection. With this treatment, elevated hepatic 8-OHdG levels in patients with chronic hepatitis C (8.3 ± 4.6/105 dG) significantly decreased to almost normal levels (2.2 ± 0.9/105 dG; P < 0.001) with concomitant improvement of hepatitis severity, including fibrosis, whereas HCV titers were unaffected. None of these patients developed HCC. Thus, long-term iron reduction therapy in patients with chronic hepatitis C may potentially lower the risk of progression to HCC. ------------------ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Nov 15, 8:01 am, ironjustice <teamtan...@hotmail.com> wrote: One might think the increased liver cancer rates in diabetes may be related to increased iron << "Iron removal treatment suppresses the hepatocarcinogenesis" Inhibition of hepatocarcinogenesis by iron reduction therapy OKAMOTO TETSURO (Sapporo Medical Univ., School of Medicine, JPN) KATO JUNJI(Sapporo Medical Univ., School of Medicine, JPN) KATO YOJIRO(Sapporo Medical Univ., School of Medicine, JPN) Journal Title;Kan, Tan, Sui Journal Code:Z0248B ISSN:0389-4991 VOL.47;NO.4;PAGE.531-538(2003) Figure&Table&Reference;FIG.5, TBL.1, REF.19 Pub. Country;Japan Language;Japanese Abstract; The author has carried out the therapy which uses the bloodletting therapy jointly with the diet therapy which limits the iron for the chronic hepatitis C patient. Then, it was clarified that 8OHdG with the index to mutagenicity of the DNA which is related to the carcinogenesis decreased in those patients. In this paper, production accentuation and carcinogenic mechanism of ROS which the iron excess caused on the basis of this research result were outlined. The result of indicating that the control of ROS production through the iron removal treatment relieves hepatocyte failure of the chronic hepatitis C patient and that it suppresses the hepatocarcinogenesis was introduced. Accession number;03A0739429 ------------------ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Nov 16, 7:49 am, "ironjust...@aol.com" <ironjust...@aol.com> wrote:Liver cancer patients have high diabetes prevalence << "Indicates that the prevention of liver cancer by iron depletion is possible" Prevention Therapy for Hepatocellular Carcinoma. Iron depletion therapy. NIITSU YOSHIRO(Sapporoidai Naikagakudai4) KATO JUNJI(Sapporoidai Naikagakudai4) Journal Title;Kan, Tan, Sui Abstract; The relation between hepatocarcinoma and iron was described. The generation of active oxygen is promoted when the iron becomes superfluous for some reasons, and 8-OHdG which is the mutagenicity index becomes high value, that is to say, it seems to become the preparation condition of the hepatocarcinoma. Though the LEC rat which is copper and iron metabolism abnormality contracts the fulminant hepatitis and liver cancer, either crisis is not recognized when it is raised in the low iron. It indicates that the prevention of liver cancer by the iron depletion is possible. The treatment which combined the low iron eclipse with conducting phlebotomy was carried out for 34 chronic type C hepatitis patients in order to clarify the effect of the iron depletion therapy. As the result, AST, and ALT began to lower directly after the start of the treatment, and ALT value was lowered within 80 in all cases in about 12 weeks. And, the phlephlebitis disease and fibrous disease were improved when the progress of HAI score was followed. The 8-OHdG level lowered in the normal liver level, and the hepatocarcinogenesis has not been recognized for 6 years. The possibility of hepatocarcinoma prevention by the iron depletion was indicated strongly. Accession number;01A0992066 Journal Code:Z0248B ISSN:0389-4991 VOL.43;NO.3;PAGE.359-363(2001) ------------------ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Nov 18, 9:11 am, "ironjust...@aol.com" <ironjust...@aol.com> wrote: :Liver cancer patients have high diabetes prevalence . "Indicates that the prevention of liver cancer by iron depletion is possible" << Any heart problems out there .. ? "We're very excited" "We just received funding" "To see if chloroquine can treat heart disease" "Use of agents which decrease the iron content" Common cause of heart disease, diabetes may be treatable with malaria drug By Michael Purdy Nov. 7, 2006 -- Studies of a rare genetic condition that increases cancer risk have unveiled a potential treatment for metabolic syndrome, a common disorder that afflicts as many as one in every four American adults and puts them at sharply increased risk of type 2 diabetes and clogged arteries. http://www.sciencedaily.com/releases/2006/11/061108124721.htm -------------------------------------------------------------------------------- Effect of chronic chloroquine administration on iron loading in the liver and reticuloendothelial system and on oxidative responses by the alveolar macrophages Auteur(s) / Author(s) LEGSSYER R. (1) ; WARD R. J. (2) ; CRICHTON R. R. (1) ; BOELAERT J. R. (3) ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s) (1) Unité de Biochimie, Université Catholique de Louvain, Louvain-la-Neuve, BELGIQUE (2) Biologie du Comportement, Université Catholique de Louvain, Louvain-la-Neuve, BELGIQUE (3) Unit of Renal and Infectious Diseases, Algemeen Ziekenhuis St Jan, Brugge, BELGIQUE Résumé / Abstract The ability of chloroquine to alter iron loading in the liver, spleen, and alveolar macrophages was investigated in iron-loaded or -depleted rats. Chloroquine significantly reduced incorporation of iron into the liver, spleen, and alveolar macrophages of animals loaded in vivo with iron dextran. The ability of these macrophages to respond to oxidative stress was assayed by their capacity to release reactive nitrogen intermediates after lipopolysaccharide (LPS) stimulation. A significant reduction in nitrite release was observed in primary cultures of macrophages isolated from chloroquine/iron dextran-administered rats in comparison to macrophages lavaged from rats iron-loaded alone. Macrophages isolated from iron-deficient rats showed a significant increase in nitrite after LPS stimulation, whereas nitrite release in the macrophages lavaged from the rats which had also received chloroquine during the iron depletion regime was much lower. These results indicate that the use of agents which decrease the iron content and diminish the oxidative response of the cell to altered iron status may be of therapeutic value in patients with iron loading, particularly of the reticuloendothelial system. Revue / Journal Title Biochemical pharmacology (Biochem. pharmacol.) ISSN 0006-2952 CODEN BCPCA6 Source / Source 1999, vol. 57, no8, pp. 907-911 (36 ref.) Langue / Language Anglais Editeur / Publisher Elsevier Science, New York, NY, ETATS-UNIS (1958) (Revue) ------------------ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk On Nov 19, 12:10 pm, ironjustice <teamtan...@hotmail.com> wrote::Liver cancer patients have high diabetes prevalence . "Indicates that the prevention of liver cancer by iron depletion is possible" << "Association between diabetes mellitus and excessive iron storage in birds" "Iron-elimination therapy" Diabetes mellitus concurrent with hepatic haemosiderosis in two macaws (Ara severa, Ara militaris) Authors: Gancz, Ady Y.1; Wellehan, James F. X.2; Boutette, James3; Malka, Shachar4; Lee, Shannon E.5; Smith, Dale A.6; Taylor, Michael5 Source: Avian Pathology, Volume 36, Number 4, August 2007 , pp. 331-336 (6) Publisher: Taylor and Francis Ltd Abstract: Diabetes mellitus was diagnosed in a 5-year-old male chestnut-fronted macaw (Ara severa) and an 8-year-old female Military macaw (Ara militaris) based on persistent hyperglycaemia and glucosuria. Hepatic biopsies showed marked hepatic haemosiderosis, while pancreatic biopsies showed no inflammatory lesions. Repeatable and titratable responses to bovine or porcine protamine zinc insulin were recorded in both patients, who were followed up for more than 2 years. In addition, iron-elimination therapy was initiated by chelation or phlebotomy, and the birds' diet was changed to low-iron content pellets. Both birds responded favourably to this therapy, showing a decreased demand for extrinsic insulin. Follow-up biopsies demonstrated marked reduction in hepatic haemosiderin. Plasma fructosamine and β-hydroxybutyric acid levels were measured periodically in both birds and compared with euglycaemic psittacines. Both tests appeared useful for monitoring treatment success. The potential association between diabetes mellitus and excessive iron storage in birds should be further investigated. Document Type: Research article DOI: 10.1080/03079450701466093 Affiliations: 1: Koret School of Veterinary Medicine, The Hebrew University in Jerusalem, Rehovot, Israel 2: Zoological Medicine Service, University of Florida, Gainesville, FL, USA 3: Animal & Bird Health Care Center & Hospital, NJ, USA 4: Companion Avian and Exotic Pet Service, Veterinary Medical Teaching Hospital, University of California, Davis, CA, USA 5: Veterinary Teaching Hospital, The Ontario Veterinary College, University of Guelph, Guelph, ON, Canada, USA 6: Department of Pathobiology, The Ontario Veterinary College, University of Guelph, Guelph, ON, Canada ------------------ Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk hepatocarcinogenesis << Vegetable lecithin .. ? JOURNAL OF HEPATOLOGY Vol. 47 Issue 1 Jul 2007 Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: in vitro and in vivo experiments. Authors: Sakakima, Yoshikazu Hayakawa, Akemi Nagasaka, Tetsuro Nakao, Akimasa Affiliation: Department of Surgery II, Nagoya University School of Medicine, Nagoya, Aichi, Japan. sakakima@med.nagoya-u.ac.jp Abstract: BACKGROUND/AIMS: We examined whether phosphatidylcholine inhibited growth of hepatic cancer, as previously shown for menaquinone-4 (vitamin K2). METHODS: Growth inhibitions by phosphatidylcholine and/or menaquinone-4 and apoptosis induction by phosphatidylcholine were evaluated in vitro using human hepatic cancer cell lines (Hep-3B, Hep-G2, HuH-7, and Alexander). Effects of these agents were then investigated in male Sprague-Dawley rats against hepatocarcinogenesis induced by diethylnitrosamine plus phenobarbital. All rats were killed to examine livers to evaluate inhibitory potential macroscopically and immunohistochemically using an antibody against the marker of carcinogenesis, glutathione S-transferase and apoptotic induction by phosphatidylcholine using TUNEL staining. Blood samples were obtained by cardiac puncture. RESULTS: In vitro, phosphatidylcholine and menaquinone-4 each inhibited cancer cell growth and phosphatidylcholine induced apoptosis dose- dependently. Moreover, exposure to both synergistically inhibited growth in Hep-3B. In vivo, diets containing phosphatidylcholine with or without menaquinone-4 significantly reduced the number of macroscopic hepatic tumor nodules and the extent of abnormally immunoreactive foci conserving hepatic function on serum examinations compared with controls given only the carcinogens. Moreover, phosphatidylcholine supplementation induced apoptosis on TUNEL staining of liver sections. CONCLUSIONS: Given together, phosphatidylcholine and menaquinone-4 may exhibit synergy against hepatocarcinogenesis conserving hepatic function that could benefit patients at high risk for hepatocellular carcinoma.} PreMedline Identifier (PMID): 17399847 Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk hepatocarcinogenesis << Targeting iron in liver cancer leads to a 700% increased .. survival .. That's a good thing .. "Lactoferrin" "Survival rates were 12.5% vs. 91.7%" Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats. J Hepatol. 2008 Mar;48(3):486-93. Epub 2007 Dec 27. Tsubota A, Yoshikawa T, Nariai K, Mitsunaga M, Yumoto Y, Fukushima K, Hoshina S, Fujise K. Institute of Clinical Medicine and Research (ICMR), Jikei University School of Medicine, Kashiwa, Chiba, Japan. ats...@jikei.ac.jp BACKGROUND/AIMS: To assess the effect of lactoferrin on oxidative liver damage and its mechanism, we used Long-Evans Cinnamon (LEC) rats that spontaneously develop fulminant-like hepatitis and lethal hepatic failure. METHODS: Four-week-old female LEC rats were divided into the untreated and treated groups. The latter was fed bovine lactoferrin at 2% mixed with conventional diet. RESULTS: The cumulative survival rates were 75.0% vs. 100% at 14 weeks, 37.5% vs. 91.7% at 15 weeks, and 12.5% vs. 91.7% at 16 weeks, respectively, for untreated and treated rats (P=0.0008). The 8-OHdG levels in liver mitochondrial DNA and malondialdehyde in plasma and liver tissues were significantly lower in treated than untreated rats (P<0.001, =0.017 and 0.034, respectively). Mitochondrial DNA mutations were more common in untreated rats. OGG1 mRNA and protein expression levels were significantly lower in untreated than treated rats (P=0.003 and 0.007, respectively). Hypermethylation of the second CpG island located upstream of OGG1 gene was observed in untreated rats. CONCLUSIONS: survival rates were 12.5% vs. 91.7% Our findings indicated that lactoferrin inhibits oxidative liver damage in LEC rats. Lactoferrin could be potentially useful for the treatment of oxidative stress-induced liver diseases. Publication Types: Research Support, Non-U.S. Gov't PMID: 18191270 -------------------------------------------------------------------------------- Antibiotic Properties and Applications of Lactoferrin. Curr Pharm Des 2007; 13(8):801-802. Weinberg ED Lactoferrin (Lf), a mammalian iron scavenging defense protein, constitutively is present in exocrine secretions that consistently are exposed to microbial flora: milk, tears, tubotympanum and nasal exudate, saliva, bronchial mucus, gastrointestinal fluids, cervicovaginal mucus, and seminal fluid. Additionally, Lf is promptly delivered by circulating neutrophils to sites of microbial invasion. At these sites, the protein effectively scavenges iron at pH values as low as 3.5. Recombinant bovine and human lactoferrin is now available for development into nutraceutical/preservative/pharmaceutical products. Among conditions for which the products are being investigated are: angiogenesis; bone remodeling; food preservation; infection in animals, humans, plants; neoplasia in animals, humans; inflammation in intestine, joints; wound healing; as well as enhancement of antimicrobial and antineoplastic drugs, and prevention of iron induced oxidation of milk formula. Curr Pharm Des -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://tinyurl.com/634q5a Man Is A Herbivore! http://tinyurl.com/4rq595 DEAD PEOPLE WALKING http://tinyurl.com/zk9fk |
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