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Review

Modulation of carbonic anhydrase activity and its applications in therapy

, &
Pages 667-702 | Published online: 02 Mar 2005

Bibliography

  • SUPURAN CT, SCOZZAFAVA A, CASINI A: Carbonic anhydrase inhibitors. Med. Res. Rev (2003) 23:146–189.
  • ••Detailed review on CA inhibitors
  • SUPURAN CT, VULLO D, MANOLE G,CASINI A, SCOZZAFAVA A: Designing of novel carbonic anhydrase inhibitors and activators. Carr. Med. Chem. Cardiovasc. Hematel. Agents (2004) 2:49–68.
  • SUPURAN CT, SCOZZAFAVA A: Applications of carbonic anhydrase inhibitors and activators in therapy. Expert Opin. Ther. Patents (2002) 12:217–242.
  • SUPURAN CT, SCOZZAFAVA A: Carbonic anhydrase inhibitors. Curr. Med. Chem. Imm. Endoc. Metab. Agents (2001) 1:61–97.
  • SUPURAN CT, SCOZZAFAVA A: Carbonic anhydrase inhibitors and their therapeutic potential. Expert Opin. Ther. Patents (2000) 10:575–600.
  • COX EH, MCLENDON GL, MOREL FM et al.: The active site structure of Thalassiosira weissfloglicarbonic anhydrase 1. Biochemistry (2000) 39:12128–12130.
  • LANE TW, MOREL FM: A biological function for cadmium in marine diatoms. Proc Natl. Acad Sci. USA (2000) 97:4627–4631.
  • ••The first cadmium-containing enzyme everreported.
  • SO AK, ESPIE GS, WILLIAMS EB, SHIVELY JM, HEINHORST S, CANNON GC: A novel evolutionary lineage of carbonic anhydrase (epsilon class) is a component of the carboxysome shell. J. Bacteria (2004) 186:623–630.
  • ••This important paper reportes a new classof CAs, the e-CAs.
  • Carbonic anhydrase - its inhibitors and activate's. Supuran CT, Scozzafava A, Conway J (Eds), CRC Press, Boca Raton (FL), USA (2004):1–384 (and references cited therein).
  • ••Detailed monography on CA and itsinhibitors and activators, as well as their application in different fields of life science and therapeutics.
  • PASTOREKOVA S, PARKKILA S, PASTOREK J, SUPURAN CT: Carbonic anhydrases: current state of the art, therapeutic applications and future prospects. J. Enz. Inhib. Med. Chem. (in press).
  • ••Excellent review and update of CA research.
  • SUPURAN CT: Carbonic anhydrase inhibitors in the treatment and prophylaxis of obesity. Expert Opin. Ther: Patents (2003) 13:1545–1550.
  • MITSUHASHI S, MIZUSHIMA T, YAMASHITA E et al.: X-ray structure of I3-carbonic anhydrase from the red alga, Porphyridium purpureum, reveals a novel catalytic site for CO2 hydration. Biol . Chem. (2000) 275:5521–5526.
  • STROP P, SMITH KS, IVERSON TM, FERRY JG, REES DC: Crystal structure of the 'cab-type beta class carbonic anhydrase from the archaeon Methanobacterium thermeautotrophicum. J. Biol. Chem. (2001) 276:10299–10305.
  • KIMBER MS, PAT EF: The active site architecture of Pisum sativum beta-carbonic anhydrase is a mirror image of that of alpha-carbonic anhydrases. EMBO J. (2000) 19:1407–1418.
  • CRONK JD, ENDRIZZI JA, CRONK MR, O'NEILL JVV, ZHANG KY: Crystal structure of E. colil3-carbonic anhydrase, an enzyme with an unusual pH-dependent activity. Protein Sci. (2001) 10:911–922.
  • IVERSON TM, ALBER BE, KISKER C, FERRY JG, REES DC: A closer look at the active site of 7-class carbonic anhydrases: high-resolution crystallographic studies of the carbonic anhydrase from Methanosarcina thermophila. Biochemistry (2000) 39:9222–9231.
  • TRIPP BC, BELL CB III, CRUZ F, KREBS C, FERRY JG: A role for iron in an ancient carbonic anhydrase. Biol. Chem (2004) 279:6683–6687.
  • ••Interesting report regarding the presence ofiron(II) within the active site of y-CA.
  • MERLIN C, MASTERS M, MCATEER S, COULSON A: Why is carbonic anhydrase essential to Escherichia cull? Bacteriol. (2003) 185:6415–6424.
  • LEHTONEN J, SHEN B, VIHINEN M et al.: Characterization of CA XIII, a novel member of the carbonic anhydrase isozyme family. J. Biol Chem. (2004) 279:2719–2727.
  • ••Detailed characterisation of isozyme CA XIII.
  • WHITTINGTON DA, GRUBB JH, WAHEED A, SHAH GN, SLY WS, CHRISTIANSON DW: Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: Implications for selective inhibition of membrane-associated isozymes. J. Biol. Chem. (2004) 279:7223–7228.
  • SUPURAN CT, SCOZZAFAVA A: Activation of carbonic anhydrase isozymes. In: The Carbonic Anhydrases - New Horizons, Chegwidden WR, Carter N, Edwards Y (Eds), Birkhauser Verlag, Basel, Switzerland (2000):197–219.
  • ••An exhaustive review on CAAs and theirmechanism of action at the molecular level.
  • SUN MK, ALKON DL: Pharmacological enhancement of synaptic efficacy, spatial learning, and memory through carbonic anhydrase activation in rats.' PharmacoL Exp. Ther. (2001) 297:961–967.
  • ••The first study showing the clinical utilityof CAAs.
  • ABBATE F, CASINI A, OWA T, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg. Med. Chem. Lett. (2004) 14:217–223.
  • ••X-ray crystal study of indisularn complexedwith hCA II. Indisularn is the first antitumor sulfonamide with CA inhibitory properties to reach the clinical Phase II investigational stage.
  • CASINI A, ANTEL J, ABBATE F et al.: Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg. Med. Chem. Lett (2003) 13:841–845.
  • ••The report that TPM is a potent CAI, andits X-ray characterisation in complex with hCA II.
  • ABBATE F, COETZEE A, CASINI A, CIATTINI S, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride. Bioorg. Med. Chem. Lett. (2004) 14:337–341.
  • WEBER A, CASINI A, HEINE A et al: Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. Med. Chem (2004) 47:550–557.
  • ••The discovery that the COX-2-selectiveinhibitors of the sulfonamide type are also nanomolar CA inhibitors. X-ray crystal structure of the celecoxib-hCA II adduct.
  • FRANCHI M, VULLO D, GALLORI E et a/.: Carbonic anhydrase inhibitors: inhibition of human and murine mitochondrial isozymes V with anions. Bioorg. Med. Chem. Lett. (2003) 13:2857–2861.
  • VULLO D, FRANCHI M, GALL ORI Eet al.: Carbonic anhydrase inhibitors. inhibition of cytosolic isozymes I and II and transmembrane, cancer-associated isozyme IX with anions. I Enzyme Inhib. Med. Chem. (2003) 18:403–406.
  • SCOZZAFAVA A, SUPURAN CT: Hydroxyurea is a carbonic anhydrase inhibitor. Bioorg. Med. Chem. (2003) 11:2241–2246.
  • AGRAWAL VK, SRIVASTAVA S, KHADIKAR PV, SUPURAN CT: Quantitative structure-activity relationship study on sulfanilamide Schiff 's bases: carbonic anhydrase (CA) inhibitors. Bioorg. Med. Chem. (2003) 11:5353–5562.
  • THAKUR A, THAKUR M, KHADIKAR PV, SUPURAN CT, SUDELE P: QSAR study on benzenesulphonamide carbonic anhydrase inhibitors: topological approach using Balaban index. Bioorg. Med. Chem. (2004) 12:789–793.
  • CASINI A, MINCIONE F, VULLO D, MENABUONI L, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors with strong topical antiglaucoma properties incorporating a 442-aminopyrimidin-4-yl-amino)-benzenesulfonamide scaffold. Enzyme Inhib. Med. Chem. (2002) 17:9–18.
  • CASINI A, SCOZZAFAVA A, MINCION EF, MENABUONI L, SUPURAN CT: Carbonic anhydrase inhibitors: synthesis of water soluble sulfonamides incorporating a 4-sulfamoylphenylmethylthiourea scaffold, with potent intraocular pressure lowering properties. Enzyme Inhib. Mai Chem. (2002) 17:333–343.
  • CASINI A, SCOZZAFAVA A, MINCIONE F, MENABUONI L, STARNOTTI M, SUPURAN CT: Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating esters and amides of 3- and 4-carboxybenzolamide. Bioorg. Med. Chem. Lett. (2003) 13:2867–2873.
  • •The report of a class of very potent topically acting antiglaucoma sulfonamides.
  • WINUM JY, CASINI A, MINCIONE F et al.: Carbonic anhydrase inhibitors: N-(p-sulfamoylpheny1)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg. Med. Chem. Lett (2004) 14:225–229.
  • MAESTRELLI F, MURA P, CASINI A, MINCIONE F, SCOZZAFAVA A, SUPURAN CT: Cyclodextrin complexes of sulfonamide carbonic anhydrase inhibitors as long-lasting topically acting antiglaucoma agents. J. Pharm. Sci. (2002) 91:2211–2219.
  • SCOZZAFAVA A, OWA T, MASTROLORENZO A, SUPURAN CT: Anticancer and antiviral sulfonamides. Curr. Med. Chem. (2003) 10:925–953.
  • ••Detailed review on anticancersulfonamides, including the CAIs.
  • CASINI A, SCOZZAFAVA A, MASTROLORENZO A, SUPURAN CT: Sulfonamides and sulfonylated derivatives as anticancer agents. Curr. Cancer Drug Targets (2002) 2:55–75.
  • SUPURAN CT: Indisulam: an anticancer sulfonamide in clinical development. Expert Opin. Investig. Drugs (2003) 12: 283–287.
  • PASTOREKOVA S, PASTOREK J: Cancer-related carbonic anhydrase isozymes and their inhibition. In: Carbonic anhydrase - its inhibitors and activators. Supuran CT, Scozzafava A, Conway J (Eds), CRC Press, Boca Raton (FL), USA (2004):255–282.
  • ••Excellent review on the cancer-associatedCA isozymes.
  • VULLO D, FRANCHE M, GALLORI E et a/.: Carbonic anhydrase inhibitors: inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides. Bioorg. Med. Chem. Lett (2003) 13:1005–1009.
  • ••The first CA IX inhibition study with alarge number of sulfonamides.
  • ILIES MA, VULLO D, PASTOREK J et al.: Carbonic anhydrase inhibitors. Inhibition of tumor-associated isozyme IX by halogenosulfanilamide and halogenophenylaminobenzolamide derivatives. I Med. Chem. (2003) 46:2187H2196.
  • FRANCHI M, VULLO D, GALLORI E et al.: Carbonic anhydrase inhibitors. Inhibition of cytosolic isozymes I and II and transmembrane, cancer-associated isozyme IX with lipophilic sulfonamides. Enzyme Inhib. Med. Chem. (2003) 18:333H338.
  • PASTOREKOVA S, CASINI A, SCOZZAFAVA A, VULLO D, PASTOREK J, SUPURAN CT: Carbonic anhydrase inhibitors: The first selective, membrane-impermeant inhibitors targeting the tumor-associated isozyme IX. Bioorg. Med. Chem. Lett. (2004) 14:869–873.
  • ••The first membrane-impermeant and verypotent CA IX inhibitors reported.
  • WINUM JY, VULLO D, CASINI A, MONTERO JL, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors. Inhibition of cytosolic isozymes I and II and transmembrane, tumor-associated isozyme IX with sulfamates including EMATE also acting as steroid sulfatase inhibitors. Med. Chem. (2003) 46:2197–2204.
  • ••Detailed inhibition study of CA IX (andcytosolic isozymes) with aromatic/steroidal sulfamates.
  • WINUM JY, VULLO D, CASINI A, MONTERO JL, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors: inhibition of transmembrane, tumor-associated isozyme IX, and cytosolic isozymes I and II with aliphatic sulfamates. Med . Chem. (2003) 46:5471–5477.
  • ••The first study of a large series of aliphaticsulfamates as CA I, II and IX inhibitors.
  • PUROHIT A, WOO LW, CHANDER SK et al.: Steroid sulphatase inhibitors for breast cancer therapy. Steroid. Biochem. MM. Biol. (2003) 86:423–432.
  • VULLO D, FRANCHI M, GALLORI E, ANTEL J, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. Med. Chem. (2004) 47:1272–1279.
  • ••The first CA V-targeted inhibitorsreported.
  • ABBATE F, SUPURAN CT, SCOZZAFAVA A, ORIOLI P, STUBBS MT, KLEBE G: Non-aromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: role of hydrogen-bonding networks in ligand binding and drug design. Med . Chem. (2002) 45:3583–3587.
  • CASINI A, WINUM JY, MONTERO JL,SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors: inhibition of cytosolic isozymes I and II with sulfamide derivatives. Bioorg. Med. Chem. Lett. (2003) 13:837–840.
  • CASINI A, ABBATE F, SCOZZAFAVA A,SUPURAN CT: Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a bis-sulfonamide - two heads are better than one? Bioorg. Med. Chem. Lett. (2003) 13:2759–2763.
  • •Interesting crystallographic study of a bis-sulfonamide
  • ABBATE F, CASINI A, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the perfluorobenzoyl analogue of methazolamide. Implications for the drug design of fluorinated inhibitors. I Enzyme Inhib. Med. Chem. (2003) 18:303–308.
  • ••The detailed X-ray crystal structure of afluorinated sulfonamide in complex with hCA II.
  • ABBATE F, CASINI A, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors. X-ray crystallographic structure of the adduct of human isozyme II with a topically acting antiglaucoma sulfonamide. Bioolg. Med. Chem. Lett (2004) 14:2357–2361.
  • ABBATE F, WINUM JY, POTTER BV et al.: Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid sulfatase. Bioorg. Med. Chem. Lett. (2004) 14:231–234.
  • ••The X-ray crystal structure of the adduct ofhCA II with a steroidal sulfarnate acting as a dual inhibitor of CAs and steroid sulfatases, potentially useful as an anticancer agent for hormone-dependent tumours.
  • VICKER N, HO Y, ROBINSON J et al.:Docking studies of sulphamate inhibitors of estrone sulphatase in human carbonic anhydrase II. Bioorg. Med. Chem. Lett. (2003) 13:863–865.
  • VINCE JW, REITHMEIER RA: Identification of the carbonic anhydrase II binding site in the Cl/HCO3- anion exchanger AEl. Biochemistry (2000) 39:5527–5533.
  • ••The identification of the interactionsbetween CA II and AE1 in the first discovered metabolon involving CA.
  • MCMURTRIE HL, ALVAREZ BV, LOISELLE FB et al.: The bicarbonate transport metabolon. I Enzyme Inhib. Med. Chem. (in press).
  • ••Excellent review on the CA-basedmetabolons.
  • STERLING D, BROWN NJ, SUPURAN CT, CASEY JR: The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II. Am. I Physiol Cell Physiol. (2002) 283:C1522–C1529.
  • DAHL NK, JIANG L, CHERN OVA MN, STUART -TILLEY AK, SHMUKLER BE, ALPER SL: Deficient HCO3- transport in an AE1 mutant with normaltransportcan be rescued by carbonic anhydrase II presented on an adjacent AE1 protomer. Biol. Chem. (2003) 278:44949–44958.
  • SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase activators: human isozyme II is strongly activated by oligopeptides incorporating the carboxyterminal sequence of the bicarbonate anion exchanger AEl. Bioorg. Med. Chem. Lett. (2002) 12:1177–1180.
  • LI X, ALVAREZ B, CASEY JR, REITHMEIER RA, FLIE GEL L: Carbonic anhydrase II binds to and enhances activity of the Na+/I-1+ exchanger J. Biol. Chem. (2002) 277:36085–36091.
  • LOISELLE FB, MORGAN PE, ALVAREZ BV, CASEY JR: Regulation of the human NBC3 Na+/I-1CO3-Co-transporter by carbonic anhydrase II and protein kinase Am. I Physiol Cell Physiol (in press).
  • ALVAREZ BV, LOISELLE FB, SUPURAN CT, SCHWARTZ GJ, CASEY JR: Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Biochemistry (2003) 42:12321–12329.
  • CUTHBERT AW, SUPURAN CT, MACVINISH LJ: Bicarbonate-dependent chloride secretion in Calu-3 epithelia in response to 7,8-benzoquinoline. I Physiol (2003) 551:79–92.
  • BLANK ME, EHMKE H: Aquaporin-1 and HCO3-C1- transporter-mediated transport of CO2 across the human erythrocyte membrane J. Physiol. (2003) 550:419–429.
  • FANJUL M, ALVAREZ L, SALVADOR C et al.: Evidence for a membrane carbonic anhydrase IV anchored by its C-terminal peptide in normal human pancreatic ductal cells. Histochem.Cell Biol. (2004) 121:91–99.
  • VAUGHAN-JONES RD, SPITZER KW: Role of bicarbonate in the regulation of intracellular pH in the mammalian ventricular myocyte. Biochem. Cell. Biol. (2002) 80:579–596.
  • MINCIONE F, MENABUONI L, SUPURAN CT: Clinical applications of the carbonic anhydrase inhibitors in ophthalmology. In: Carbonic anhydrase, its inhibitors and activators Supuran CT, Scozzafava A, Conway J (Eds), CRC Press, Boca Raton (FL), USA (2000243–254.
  • LIAO SY, IVANOV S, IVANOVA A et al: Expression of cell surface transmembrane carbonic anhydrase genes CA9and CAI2in the human eye: overexpression of CA12 (CA XII) in glaucoma. I Med. Genet. (2003) 40:257–261.
  • ••The identification of the presence ofisozyme XII in the human eye, and its potential relationship to glaucoma.
  • AREND 0, HARRIS A, WOLTER P, REMKY A: Evaluation of retinal haemodynamics and retinal function after application of dorzolamide, timolol and latanoprost in newly diagnosed open-angle glaucoma patients. Acta. Ophthalmol Scand. (2003) 81:474–479.
  • JOSEFSSON A, SIGURDSSON SB, BANG K, EYSTEINSSON T: Doczolamide induces vasodilatation in isolated pre-contracted bovine retinal arteries. Exp. Eye Res. (2004) 78:215–221.
  • KIILGAARD JF, PEDERSEN DB, EYSTEINSSON T eta].: Optic nerve oxygen tension: the effects of timolol and dorzolamide. Br .Ophthalmol (2004) 88:276–279.
  • GIUSTI C, FORTE R, VINGOLO EM, GARGIULO P: Is acetazolamide effective in the treatment of diabetic macular edema? A pilot study. Int. Ophthahnol (2001) 24:79–88.
  • PIKKEL J, BEIRAN I, OPHIR A, MILLER B: Acetazolamide for central serous retinopathy. Ophthalmology (2002) 109:1723–1725.
  • VILLAIN MA, PAGEAUX GP, VEYRAC M, ARNAUD B, HARRIS A, GREENFIELD DS: Effect of acetazolamide on ocular hemodynamics in pseudotumor cerebri associated with inflammatory bowel disease. Am. J. Ophthalmol (2002) 134:778–780.
  • POTTER C, HARRIS AL: Hypoxia Inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle (2004) 3:164–167.
  • SVASTOVA E, ZILKA N, ZAT'OVICOVA M et al: Carbonic anhydrase IX reduces E-cadherin-mediated adhesion of MDCK cells via interaction with beta-catenin. Exp. Cell Res. (2003) 290:332–345.
  • ••Seminal study for the role of CA IXinteraction with E-cadherins and its role in turnorigenesis.
  • GUT MO, PARKKILA S, VERNEROVA Z et al.: Gastric hyperplasia in mice with targeted disruption of the carbonic anhydrase gene Car9. Gastroenterology (2002) 123: 1889-1903.
  • ••The description of CA IX knock-out mice.
  • ZAT'OVICOVA M, TARABKOVA K, SVASTOVA E et al.: Monoclonal antibodies generated in carbonic anhydrase IX-deficient mice recognize different domains of tumour-associated hypoxia-induced carbonic anhydrase IX. Immunol Methods (2003) 282:117–134.
  • ••Novel types of CA IX monoclonal antibodies.
  • KALUZ S, KALUZOVA M, CHRASTINA A et al: Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor la stabilization: a role for phosphatidylinositol 3'-kinase. Cancer Res. (2002) 62:4469–4477.
  • HOSKIN PJ, SIBTAIN A, DALEY FM, WILSON GD: GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. Br. Cancer (2003) 89:1290–1297.
  • HEDLEY D, PINTILIE M, WOO J et al: Carbonic anhydrase IX expression, hypoxia, and prognosis in patients with uterine cervical carcinomas. Clin. Cancer Res. (2003) 9:5666–5674.
  • BARTOSOVA M, PARKKILA S, POHLODEK K et al: Expression of carbonic anhydrase IX in breast is associated with malignant tissues and is related to overexpression of c-erbB2. Pathol (2002) 197:314–321.
  • TOMES L, EMBERLEY E, NIU Y et al:Necrosis and hypoxia in invasive breast carcinoma. Breast Cancer Res. Treat (2003) 81:61–69.
  • COLPAERT CG, VERMEULEN PB, FOX SB et al: The presence of a fibrotic focus in invasive breast carcinoma correlates with the expression of carbonic anhydrase IX and is a marker of hypoxia and poor prognosis. Breast Cancer Res. Treat. (2003) 81:137–147.
  • JUHASZ M, CHEN J, LENDECKEL U et al.: Expression of carbonic anhydrase IX in human pancreatic cancer. Ailment. Pharmacol Ther. (2003) 18:837–846.
  • MANDRIOTA SJ, TURNER KJ, DAVIES DR et al.: HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron. Cancer Cell (2002) 1:459–468.
  • HUI EP, CHAN AT, PEZZELLA F et al.:Coexpression of hypoxia-inducible factors 1-a and 2-a, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival. Clin. Cancer Res. (2002) 8:2595–2604.
  • VORDERMARK D, BROWN JM: Endogenous markers of tumor hypoxia predictors of clinical radiation resistance? Strahlenther Onkol. (2003) 179:801–811.
  • CHRASTINA A, PASTOREKOVA S, PASTOREK J: Immunotargeting of human cervical carcinoma xenograft expressing CA IX tumor-associated antigen by [1251]-labeled M75 monoclonal antibody. Neoplasma (2003) 50:13–21.
  • ••The first study contemplating the use of aradiolabelled CA IX antibody for the treatment of tumours.
  • CHRASTINA A, ZAVADA J, PARKKILA S et al.: Biodistribution and pharmacokinetics of [1251]-labeled monoclonal antibody M75 specific for carbonic anhydrase IX, an intrinsic marker of hypoxia, in nude mice xenografted with human colorectal carcinoma. Int. Cancer (2003) 105:873–881.
  • HERNANDEZ JM, BUT MH, HAN KR et al.: Novel kidney cancer immunotherapy based on the granulocyte-macrophage colony-stimulating factor and carbonic anhydrase IX fusion gene. Clin. Cancer Res. (2003) 9:1906–1916.
  • LEPPILAMPI M, SAARNIO J, KARTTUNEN TJ et al.: Carbonic anhydrase isozymes IX and XII in gastric tumors. World Casdoenterol (2003) 9:1398–1403.
  • ••Excellent study regarding the cancer-associated isozymes IX and XII in gastric tissues
  • ASHIDA S, NISHIMORI I, TANIMURA M, ONISHI S, SHUIN T: Effects of von Hippel-Lindau gene mutation and methylation status on expression of transmembrane carbonic anhydrases in renal cell carcinoma. Cancer Res. Clin. Oncol. (2002) 128:561–568.
  • KUO WH, CHIANG WL, YANG SF et al.: The differential expression of cytosolic carbonic anhydrase in human hepatocellular carcinoma. Life Sci (2003) 73:2211–2223.
  • LEPPILAMPI M, KOISTINEN P, SAVOLAINEN ER et al: The expression of carbonic anhydrase II in hematological malignancies. Gin. Cancer Res. (2002) 8:2240–2245.
  • MIYAJI E, NISHIMORI I, TANIUCHI K, TAKEUCHI T, OHTSUKI Y, ONISHI S: Overexpression of carbonic anhydrase-related protein VIII in human colorectal cancer. .1 Pathol (2003) 201:37–45.
  • ••The first study relating CARPs to tumours.
  • AKISAWA Y, NISHIMORI I, TANIUCHI K et al.: Expression of carbonic anhydrase-related protein CA-RP VIII in non-small cell lung cancer. VP-chows Arch (2003) 442:66–70.
  • HEDLEY D, PINTILIE M, WOO J et al:Upregulation of the redox mediators thioredwdn and apurinic/apyrimidinic excision (APE)/Ref-1 in hypoxic microregions of invasive cervical carcinomas, mapped using multispectral, wide-field fluorescence image analysis. Am. J. Athol (2004) 164:557–565.
  • MA B, XIANG Y, LIT, YU HM, LI XJ: Inhibitory effect of TPM on Lewis lung carcinoma metastasis and its relation with AQP 1 water channel. Acta Pharmacol Sin. (2004) 25:54–60.
  • LYNCH CJ, FOX H, HAZEN SA, STANLEY BA, DODGSON SJ, LANOUE KF: Role of hepatic carbonic anhydrase in de novo lipogenesis. Biochem. (1995) 310:197–202.
  • SHANK RP, GARDOCKI JF, VAUGHT JL et al.: TPM: preclinical evaluation of structurally novel anticonvulsant. Epikpsia (1994) 35:450–460.
  • EDMONDS HL, JIANG YD, ZHANG PY, SHANK RP: Anticonvulsant activity of TPM and phenytoin in a rat model of ischemia-induced epilepsy. Life Sci (1996) 59:127–131.
  • STRINGER JL: A comparison of TPM and acetazolamide on seizure duration and paired-pulse inhibition in the dentate gyrus of the rat. Epilepsy Res. (2000) 40:147–153.
  • SABERS A, GRAM L: Newer anticonvulsants : comparative review of drug interactions and adverse effects. Drugs (2000) 60:23–33.
  • BOURGEOIS BFD: Pharmacokinetics and pharmacodynamics of TPM. .1. Child. Naomi (2000) 15:S27–S30.
  • BIALER M, JOHANNESSEN SI, KUPFERBERG HJ, LEVY RH, LOISEAU P, PERUCCA E: Progress report on new antiepileptic drugs: summary of the Fifth Eilat Conference. Epiltpsy Res. (2001) 43:11–18.
  • GORDON A, PRICE LH: Mood stabilization and weight loss with TPM. Am. J. Psychiatry (1999) 156:968–969.
  • PICARD F, DESHAIES Y, LALONDE J, SAMSON P, RICHARD D: TPM reduces energy and fat gains in lean (Fal?) and obese (fa/fa) Zucker rats. Obesity Res. (2000) 8:656–663.
  • MASEREEL B, ROLIN S, ABBATE F, SCOZZAFAVA A, SUPURAN CT: Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. Med . Chem. (2002) 45:312–320.
  • PARKKILAS, PARKKILA A-K, KIVELAJ: Role of carbonic anhydrase and its inhibitors in biological science related to gastroenterology, neurology and nephrology. In: Carbonic anhydrase - its inhibitors and activators Supuran CT, Scozzafava A, Conway J (Eds), CRC Press, Boca Raton (FL), USA, (2004):283–302.
  • ••Excellent review of CAs in the gastric,neurological and renal systems.
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