Research Topics
Genomes and Genes | George J BrewerSummaryAffiliation: University of Michigan Country: USA Publications
| Collaborators
|
Detail Information
Publications
The risks of free copper in the body and the development of useful anticopper drugsGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 5720, USA
Curr Opin Clin Nutr Metab Care 11:727-32. 2008..We will also review the anticopper drugs and how lowering free copper levels with an anticopper drug inhibits fibrosis, inflammation, and autoimmunity...
Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper--a reviewGeorge J Brewer
Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, 4009 Buhl Building, Ann Arbor, MI 48109 0618, USA
Integr Cancer Ther 1:327-37. 2002..The authors speculate that the copper level is a primitive angiogenesis and growth-signaling regulator that has been retained throughout evolution...- Comparison of lowering copper levels with tetrathiomolybdate and zinc on mouse tumor and doxorubicin modelsGuoqing Hou
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich 48109-0543, USA
Transl Res 148:309-14. 2006..It is also hypothesized that the differences between TM and zinc may be caused by TM's mechanism of action in which it binds copper already in the body, whereas zinc does not... - Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientineGeorge J Brewer
Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
Transl Res 154:70-7. 2009..Tetrathiomolybdate controlled copper less well in the dose regimen study (study 3) than in the previous 2 studies of tetrathiomolybdate treatment, probably because of a change in the way "away from food" tetrathiomolybdate was given... - Antitumor and antiinflammatory effects of tetrathiotungstate in comparison with tetrathiomolybdateGuoqing Hou
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48019 0534, USA
Transl Res 149:260-4. 2007..It was found that the 2 drugs were comparable in their effects when doses were used that lowered copper availability to the same extent... - Inhibition of key cytokines by tetrathiomolybdate in the bleomycin model of pulmonary fibrosisGeorge J Brewer
Department of Human Genetics, University of Michigan, 5022 Kresge Building II, Ann Arbor, MI 48109 0534, USA
J Inorg Biochem 98:2160-7. 2004..The inhibition of tumor necrosis factor alpha suggests that diseases of tumor necrosis factor alpha overexpression are also potential targets of tetrathiomolybdate therapy... - Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson diseaseGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, 5024 Kresge Bldg II, Ann Arbor, MI 48109 0534, USA
Arch Neurol 63:521-7. 2006..To compare tetrathiomolybdate and trientine in treating patients with the neurologic presentation of Wilson disease for the frequency of neurologic worsening, adverse effects, and degree of neurologic recovery... - Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesisQuintin Pan
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Cancer Res 62:4854-9. 2002..Our study suggests that a major mechanism of the antiangiogenic effect of copper deficiency induced by TM is suppression of NFkappaB, contributing to a global inhibition of NFkappaB-mediated transcription of proangiogenic factors... - Tetrathiomolybdate is effective in a mouse model of arthritisMark D McCubbin
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109-0534, USA
J Rheumatol 33:2501-6. 2006..CONCLUSION: Based on the positive results reported here, and the good safety profile of tetrathiomolybdate in human studies so far, a trial of tetrathiomolybdate in arthritis syndromes seems warranted... - Antiangiogenic tetrathiomolybdate enhances the efficacy of doxorubicin against breast carcinomaQuintin Pan
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Mol Cancer Ther 2:617-22. 2003..4 +/- 14.3% greater than that in doxorubicin-treated mice. These results suggest that TM may enhance the rate of pathological complete response when used in combination with an anthracycline in neoadjuvant therapy of breast carcinoma... - Treatment of primary biliary cirrhosis with tetrathiomolybdate: results of a double-blind trialFred Askari
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109 5720, USA
Transl Res 155:123-30. 2010.... 
Suppression of tumor recurrence and metastasis by a combination of the PHSCN sequence and the antiangiogenic compound tetrathiomolybdate in prostate carcinomaKenneth L van Golen
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109 0948, USA
Neoplasia 4:373-9. 2002..Improved survival, fewer metastatic lesions, and excellent tolerability were observed with the combination therapy...- Prognostic significance of neurologic examination findings in Wilson diseaseJames F Burke
Department of Neurology, University of Michigan, 1150 W Medical Center Dr, Ann Arbor, MI 48109 5604, USA
Parkinsonism Relat Disord 17:551-6. 2011..Our goal was to determine whether presenting clinical features of neurologic Wilson disease (WD) predict longer term neurologic outcomes in patients receiving anticopper treatment... - Efficacy of tetrathiomolybdate in a mouse model of multiple sclerosisGuoqing Hou
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich 48109 0534, USA
Transl Res 152:239-44. 2008..Finally, we find marked increases of inflammatory and immune-related cytokines in this model, and we find that TM strongly and significantly suppresses these increases... - Tetrathiomolybdate protects against cardiac damage by doxorubicin in miceGuoqing Hou
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, 48109, USA
J Lab Clin Med 146:299-303. 2005..Our working hypothesis, based on the inhibition of interleukin-2 by tetrathiomolybdate as shown here, is that tetrathiomolybdate interrupts the inflammatory cascade at the activated-T-lymphocyte stage... - Neurologically presenting Wilson's disease: epidemiology, pathophysiology and treatmentGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan 48109 0534, USA
CNS Drugs 19:185-92. 2005..In the absence of availability of tetrathiomolybdate, zinc or trientine are the next best choices... - Subclinical zinc deficiency in Alzheimer's disease and Parkinson's diseaseGeorge J Brewer
Deptartment of Human Genetics, University of Michigan, Ann Arbor, USA
Am J Alzheimers Dis Other Demen 25:572-5. 2010..Urine zinc excretion, normalized to urine creatinine excretion, was not significantly different in either patient group compared to controls. These patients are probably zinc deficient because of nutritional inadequacy... - Tetrathiomolybdate therapy protects against concanavalin a and carbon tetrachloride hepatic damage in miceFred K Askari
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
Exp Biol Med (Maywood) 229:857-63. 2004..In conclusion, tetrathiomolybdate protects against the hepatitis and fibrosis produced by these hepatotoxins, probably by inhibiting the excessive increase in inflammatory and fibrotic cytokines... - XIAP Is a copper binding protein deregulated in Wilson's disease and other copper toxicosis disordersArjmand R Mufti
Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109, USA
Mol Cell 21:775-85. 2006..These data provide an unsuspected link between copper homeostasis and the regulation of cell death through XIAP and may contribute to the pathophysiology of copper toxicosis disorders... - Improvement in dissolution of liver fibrosis in an animal model by tetrathiomolybdateGuoqing Hou
Department of Human Genetics, University of Michigan Medical School, G061X MBNI, Ann Arbor, MI 48109, USA
Exp Biol Med (Maywood) 234:662-5. 2009..It now becomes important to evaluate whether this approach will work in the human epidemic of cirrhotic disease resulting from diseases such as alcoholism, nonalcoholic steatohepatitis, and hepatitis C... - The use of tetrathiomolybdate in treating fibrotic, inflammatory, and autoimmune diseases, including the non-obese diabetic mouse modelGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, 5022 Kresge Building II, Ann Arbor MI 48109 0534, USA
J Inorg Biochem 100:927-30. 2006..Possible mechanisms of tetrathiomolybdate's protective effect are briefly considered... - Anticopper therapy against cancer and diseases of inflammation and fibrosisGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109 0534, USA
Drug Discov Today 10:1103-9. 2005..If clinical studies support the animal work, anticopper therapy holds promise for therapy of cancer, fibrotic disease and inflammatory and autoimmune diseases... - Control of copper status for cancer therapyVicki L Goodman
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA
Curr Cancer Drug Targets 5:543-9. 2005..Promising results from in vitro experiments, in pre-clinical animal models, and in a phase I clinical trial have led to several phase II trials of TM in patients with advanced cancers... - Novel therapeutic approaches to the treatment of Wilson's diseaseGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109 0534, USA
Expert Opin Pharmacother 7:317-24. 2006.... - Effects of tetrathiomolybdate in a mouse model of retinal neovascularizationSusan G Elner
Department of Ophthalmology, University of Michigan, Ann Arbor, MI 48105, USA
Invest Ophthalmol Vis Sci 46:299-303. 2005..The P10-treated mice also demonstrated a 24% reduction of VEGF compared with control animals (P=0.01). CONCLUSIONS: TM significantly inhibits retinal neovascularization and VEGF production in a mouse model of retinal neovascularization... - Tetrathiomolybdate is partially protective against hyperglycemia in rodent models of diabetesChunhua Zeng
University of Michigan Medical School, 5024 Kresge Bldg II, Ann Arbor, MI 48109 0534, USA
Exp Biol Med (Maywood) 233:1021-5. 2008..A metabolic effect of TM on blood glucose is possible but seems less likely. TM is also likely inhibiting inflammatory and/or fibrogenic effects in the kidneys of db/db mice... - Copper and ceruloplasmin abnormalities in Alzheimer's diseaseGeorge J Brewer
Department of Human Genetics, University of Michigan, Ann Arbor, 48103, USA
Am J Alzheimers Dis Other Demen 25:490-7. 2010..Increased exposure to environmental copper (eg, the spread of copper plumbing and the use of copper in supplements) and/or defective ceruloplasmin function may play a role in the current epidemic of Alzheimer's disease... - Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in miceGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor 48109 0618, USA
J Lab Clin Med 141:210-6. 2003..The protection afforded by TM was also reflected in significantly reduced bleomycin-induced body-weight loss. In the next phase of this work, we will seek to determine the mechanisms by which TM brings about this therapeutic benefit... - Zinc and tetrathiomolybdate for the treatment of Wilson's disease and the potential efficacy of anticopper therapy in a wide variety of diseasesGeorge J Brewer
Department of Human Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109 5720, USA
Metallomics 1:199-206. 2009..However, it should be understood that it is not completely free, always being bound to albumin and other molecules. It is this pool of free copper that is greatly expanded in untreated Wilson's patients undergoing copper toxicity... - Inhibition of the growth of squamous cell carcinoma by tetrathiomolybdate-induced copper suppression in a murine modelClaudell Cox
Department of Otolaryngology-Head and Neck Surgery, University of Michigan Health System, Ann Arbor, 48109, USA
Arch Otolaryngol Head Neck Surg 129:781-5. 2003.... - Evaluation of tetrathiomolybdate in the R6/2 model of Huntington diseaseSara J Tallaksen-Greene
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
Neurosci Lett 452:60-2. 2009..Given its known tolerability in humans with neurodegeneration, ammonium tetrathiomolybdate could be considered as a candidate for clinical trials in Huntington disease... - Wilson's disease: clinical management and therapyGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109-0534, USA
J Hepatol 42:S13-21. 2005 - Myelopolyneuropathy and pancytopenia due to copper deficiency and high zinc levels of unknown origin: further support for existence of a new zinc overload syndromePeter Hedera
Department of Neurology, University of Michigan, Ann Arbor, USA
Arch Neurol 60:1303-6. 2003..To describe a patient with idiopathic zinc overload without an identifiable source and secondary copper deficiency causing myelopolyneuropathy and pancytopenia... - Copper lowering therapy with tetrathiomolybdate as an antiangiogenic strategy in cancerGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, 5024 Kresge Bldg II, Ann Arbor, MI 48109 0534, USA
Curr Cancer Drug Targets 5:195-202. 2005..The inhibition of multiple angiogenic cytokines gives TM the potential to be a more global inhibitor of angiogenesis... - Treatment of Wilson's disease with zinc. XVIII. Initial treatment of the hepatic decompensation presentation with trientine and zincFred K Askari
Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
J Lab Clin Med 142:385-90. 2003..Moreover, TM warrants study to determine whether therapy for hepatic Wilson's disease can be further improved... - Fundamental problems lie ahead in the drug discovery and commercialization process: restructuring of the pharmaceutical industry and an improved partnership with academia are requiredGeorge J Brewer
Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
J Investig Med 54:291-302. 2006 - Drug development for orphan diseases in the context of personalized medicineGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich 48109 0534, USA
Transl Res 154:314-22. 2009.... - Phase II trial of tetrathiomolybdate in patients with advanced kidney cancerBruce G Redman
Division of Hematology and Oncology, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109 0948, USA
Clin Cancer Res 9:1666-72. 2003..Tetrathiomolybdate (TM), a copper-lowering agent, has been shown in preclinical murine tumor models to be antiangiogenic. We evaluated the antitumor activity of TM in patients with advanced kidney cancer in a Phase II trial... - Copper toxicity in Alzheimer's disease: cognitive loss from ingestion of inorganic copperGeorge J Brewer
The Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
J Trace Elem Med Biol 26:89-92. 2012..It is clear that some factor toxic to the brain is present in the environment in developed countries, but not undeveloped countries, and is a major risk factor for AD. I believe that that toxic factor is ingestion of inorganic copper... - Copper excess, zinc deficiency, and cognition loss in Alzheimer's diseaseGeorge J Brewer
Department of Human Genetics, Medical School University of Michigan, Ann Arbor, MI 48103, USA
Biofactors 38:107-13. 2012..These two factors may be linked in that zinc therapy significantly reduced free copper levels. Thus, zinc may act by lowering copper toxicity or by direct benefit on neuronal health, or both... - Risks of copper and iron toxicity during aging in humansGeorge J Brewer
Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Chem Res Toxicol 23:319-26. 2010..In the last part of this review, I will provide advice on how to lower risks from copper and iron toxicity... - Copper in medicineGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, 5024 Kresge Building II, Ann Arbor, MI 48109 0534, USA
Curr Opin Chem Biol 7:207-12. 2003..There have also been recent developments in the genetic and non-genetic abnormalities of copper, including the finding of new copper-related genes that potentially could cause disease if mutated... - Tetrathiomolybdate as an antiangiogenesis therapy for subfoveal choroidal neovascularization secondary to age-related macular degenerationAndrew K Vine
Department of Ophthalmology and Visual Sciences, University of Michigan Medical Center, Ann Arbor, USA
Trans Am Ophthalmol Soc 100:73-6; discussion 76-7. 2002..CONCLUSION: At the dosages used in this study, tetrathiomolybdate was ineffective in preventing the progression of CNV secondary to age-related macular degeneration... - The use of copper-lowering therapy with tetrathiomolybdate in medicineGeorge J Brewer
University of Michigan Medical School, Departments of Human Genetics and Internal Medicine, G061XMBNI, Ann Arbor, MI 48109 5720, USA
Expert Opin Investig Drugs 18:89-97. 2009..Clinical testing has been done relatively extensively in Wilson's disease and advanced cancers, but remains in its infancy in other diseases... - Radiotherapy and antiangiogenic TM in lung cancerMohamed K Khan
Department of Radiation Oncology, The University of Michigan Medical Center, Ann Arbor, MI 48109 0936, USA
Neoplasia 4:164-70. 2002..We also show that their therapeutic effects are additive, with no additional toxicity. We show that TM has no significant cytotoxicity in vitro against LLHM tumor cells, further supporting the antiangiogenic mechanism for its action... - A novel role for XIAP in copper homeostasis through regulation of MURR1Ezra Burstein
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
EMBO J 23:244-54. 2004..These findings represent the first described phenotypic alteration in Xiap-deficient mice and demonstrate that XIAP can function through MURR1 to regulate copper homeostasis... - The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's diseaseGeorge J Brewer
Departments of Human Genetics and Internal Medicine, University of Michigan Medical School, 3820 Gensley Road, Ann Arbor, MI 48103, USA
J Am Coll Nutr 28:238-42. 2009..I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population... - Atypical childhood Wilson's diseaseMartha D Carlson
Division of Pediatric Neurology, Department of Pediatrics, University of Michigan, Ann Arbor, Michigan 48109-0202, USA
Pediatr Neurol 30:57-60. 2004..Neurologic Wilson's disease may have diverse presentations, and should be considered in children who present with cortical features and signal change on magnetic resonance imaging... - Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapyGeorge J Brewer
Department of Human Genetics, University of Michigan Medical School, 4909 Buhl, Ann Arbor, MI 48109 0618, USA
Arch Neurol 60:379-85. 2003..It is unclear what anticopper drug to use for patients with Wilson disease who present with neurologic manifestations because penicillamine often makes them neurologically worse and zinc is slow acting... - Behavioral abnormalities in Wilson's diseaseGeorge J Brewer
Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
Adv Neurol 96:262-74. 2005 - Iron and copper toxicity in diseases of aging, particularly atherosclerosis and Alzheimer's diseaseGeorge J Brewer
Department of Human Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan USA
Exp Biol Med (Maywood) 232:323-35. 2007..Here, we examine the evidence that "normal" levels of iron and copper contribute to various diseases of aging... - White matter changes in Wilson diseasePeter Hedera
Department of Neurology, University of Michigan Medical Center, Ann Arbor, Mich 48109-0940, USA
Arch Neurol 59:866-7. 2002 - A phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final resultsHarvey I Pass
Department of Cardiothoracic Surgery, New York University School of Medicine, New York, New York 10016, USA
Ann Thorac Surg 86:383-9; discussion 390. 2008..We hypothesized that cytoreduction of malignant pleural mesothelioma followed by TM will delay time to progression... - Kayser-Fleischer ring as the presenting sign of Wilson diseaseMimi Liu
Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Am J Ophthalmol 133:832-4. 2002..To describe a case in which the recognition by the ophthalmologist of Kayser-Fleischer rings played a crucial role in the diagnosis of Wilson disease (hepatolenticular degeneration)... - Tetrathiomolybdate protects against bile duct ligation-induced cholestatic liver injury and fibrosisMing Song
Division of Gastroenterology Hepatology, Department of Internal Medicine, University of Louisville School of Medicine, 550 S Jackson St, Louisville, KY 40202, USA
J Pharmacol Exp Ther 325:409-16. 2008..The protective mechanism seems to be independent of oxidative stress. Our data provide further evidence that TM might be a potential therapy for hepatic fibrosis... - Comment on: "High concentration of zinc in sub-retinal pigment epithelial deposits" (Lengyel et al.) (Exp. Eye Res. 772-780, 84/4, 2007)David Newsome
Exp Eye Res 86:860-1; author reply 862-3. 2008 - Causes and diagnosis of copper deficiencyGeorge J Brewer
Am J Hematol 83:87-8. 2008 - Autonomic dysfunction in Wilson's diseaseGeorge J Brewer
Clin Auton Res 12:139-40. 2002 - Rediscovery of the susceptibility of G6PD deficient persons to methemoglobinemia from oxidant drugs, and to hemolysis from methylene blueGeorge J Brewer
Am J Hematol 82:87-8. 2007