qol index
Climate: 911! - Episode 1 - Biscayne National Park
22. Horgan C. M. T., Tisdale M. J. Uptake and decomposition of a novel antitumour agent mitozolomide (CCRG 81010; M and B 39565; NSC 353451) in TLX5 mouse lymphoma in vitro. Biochem. Pharmacol., 34: 217-221, 1985.
REFERENCES
27. Lowe P. R., Sansom C. E., Schwalbe C. H., Stevens M. F. G., Clark A. S. Antitumor imidazotetrazines. 25. Crystal structure of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one (temozolomide) and structural comparisons with the related drugs mitozolomide and DTIC. J. Med. Chem., 35: 3377-3382, 1992.
45. Tentori L., Graziani G., Gilberti S., Lacal P. M., Bonmassar E., D’Atri S. Triazene compounds induce apoptosis in O6-alkylguanine-DNA alkyltransferase deficient leukemia cell lines. Leukemia, 9: 1888-1895, 1995.
93. Friedman H. S., McLendon R. E., Kerby T., Dugan M., Bigner S. H., Henry A. J., Ashley D. M., Krischer J., Lovell S., Rasheed K., Marchev F., Seman A. J., Cokgor I., Rich J., Stewart E., Colvin O. M., Provenzale J. M., Bigner D. D., Haglund M. M., Friedman A. H., Modrich P. L. DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J. Clin. Oncol., 16: 3851-3857, 1998.
82. Baker S. D., Wirth M., Statkevich P., Reidenberg P., Alton K., Sartorius S. E., Dugan M., Cutler D., Batra V., Grochow L. B., Donehower R. C., Rowinsky E. K. Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. Clin. Cancer Res., 5: 309-317, 1999.
18. Hickman J. A., Stevens M. F. G., Gibson N. W., Langdon S. P., Fizames C., Lavelle F., Atassi G., Lunt E., Tilson R. M. Experimental antitumor activity against murine tumor model systems of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (mitozolomide), a novel broad-spectrum agent. Cancer Res., 45: 3008-3013, 1985.
25. Stevens M. F., Newlands E. S. From triazines and triazenes to temozolomide. Eur. J. Cancer, 29A: 1045-1047, 1993.
43. Karran P., Hampson R. Genomic instability and tolerance to alkylating agents. Cancer Surv., 28: 69-85, 1996.
75. Chinnasamy N., Rafferty J. A., Hickson I., Ashby J., Tinwell H., Margison G. P., Dexter T. M., Fairbairn L. J. O6-benzylguanine potentiates the in vivo toxicity and clastogenicity of temozolomide and BCNU in mouse bone marrow. Blood, 89: 1566-1573, 1997.
90. Newlands E. S., O’Reilly S. M., Glaser M. G., Bower M., Evans H., Brock C., Brampton M. H., Colquhoun I., Lewis P., RiceEdwards J. M., Illingworth R. D., Richards P. G. The Charing Cross Hospital experience with temozolomide in patients with gliomas. Eur. J. Cancer, 32A: 2236-2241, 1996.
15. Estlin E. J., Lashford L., Ablett S., Price L., Gowing R., Gholkar A., Kohler J., Lewis I. J., Morland B., Pinkerton C. R., Stevens M. C. G., Mott M., Stevens R., Newell D. R., Walker D., Dicks-Mireaux C., McDowell H., Reidenberg P., Statkevich P., Marco A., Batra V., Dugan M., Pearson A. D. J. Phase I study of temozolomide in paediatric patients with advanced cancer. United Kingdom Children’s Cancer Study Group. Br. J. Cancer, 78: 652-661, 1998.
66. Boulton S., Pemberton L. C., Porteous J. K., Curtin N. J., Griffin R. J., Golding B. T., Durkacz B. W. Potentiation of temozolomide-induced cytotoxicity: a comparative study of the biological effects of poly(ADP-ribose) polymerase inhibitors. Br. J. Cancer, 72: 849-856, 1995.
61. Bobola M. S., Tseng S. H., Blank A., Berger M. S., Silber J. R. Role of O6-methylguanine-DNA methyltransferase in resistance of human brain tumor cell lines to the clinically relevant methylating agents temozolomide and streptozotocin. Clin. Cancer Res., 2: 735-741, 1996.
86. Feun L. G., Savaraj N., Landy H. J. Drug resistance in brain tumors. J. Neurooncol., 20: 165-176, 1994.
11. Bleehen N. M., Newlands E. S., Lee S. M., Thatcher N., Selby P., Calvert A. H., Rustin G. J. S., Brampton M., Stevens M. F. G. Cancer Research Campaign Phase II trial of temozolomide in metastatic melanoma. J. Clin. Oncol., 13: 910-913, 1995.
34. Wedge S. R., Porteus J. K., May B. L., Newlands E. S. Potentiation of temozolomide and BCNU cytotoxicity by O6-benzylguanine: a comparative study in vitro. Br. J. Cancer, 73: 482-490, 1996.
26. Clark A. S., Stevens M. F. G., Sansom C. E., Schwalbe C. H. Anti-tumour imidazotetrazines. Part XXI. Mitozolomide and temozolomide: probes for the major groove of DNA. Anticancer Drug Des., 5: 63-68, 1990.
56. Baer J. C., Freeman A. A., Newlands E. S., Watson A. J., Rafferty J. A., Margison G. P. Depletion of O6-alkylguanine-DNA alkyltransferase correlates with potentiation of temozolomide and CCNU toxicity in human tumour cells. Br. J. Cancer, 67: 1299-1302, 1993.
83. Dhodapkar M., Rubin J., Reid J. M., Burch P. A., Pitot H. C., Buckner J. C., Ames M. M., Suman V. J. Phase I trial of temozolomide (NSC 362856) in patients with advanced cancer. Clin. Cancer Res., 3: 1093-1100, 1997.
40. Li G. M., Modrich P. Restoration of mismatch repair to nuclear extracts of H6 colorectal tumor cells by a heterodimer of human MutL homologs. Proc. Am. Assoc. Cancer Res., 92: 1950-1954, 1995.
89. Rodriguez L. A., Levin V. A. Does chemotherapy benefit the patient with a central nervous system glioma? [see comments]. Oncology (Huntingt), 1: 29-36, 1987.
Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) occur more frequently than other types of primary CNS tumors, having a combined incidence of 5–8/100,000 population. Even with aggressive treatment using surgery, radiation, and chemotherapy, median reported survival is less than 1 year . Temozolomide, a new drug, has shown promise in treating malignant gliomas and other difficult-to-treat tumors. Temozolomide represents a new class of second-generation imidazotetrazine prodrugs that undergo spontaneous conversion under physiological conditions to the active alkylating agent MTIC. Thus, temozolomide does not require hepatic metabolism for activation .
53. D’Incalci M., Citti L., Taverna P., Catapano C. V. Importance of the DNA repair enzyme O6-alkyl guanine alkyltransferase (AT) in cancer chemotherapy. Cancer Treat. Rev., 15: 279-292, 1988.
28. Spassova M. K., Golovinsky E. V. Pharmacobiochemistry of arylalkyltriazenes and their application in cancer chemotherapy. Pharmacol. Ther., 27: 333-352, 1985.
41. Karran P., Macpherson P., Ceccotti S., Dogliotti E., Griffin S., Bignami M. O6-methylguanine residues elicit DNA repair synthesis by human cell extracts. J. Biol. Chem., 268: 15878-15886, 1993.
31. Catapano C. V., Broggini M., Erba E., Ponti M., Mariani L., Citti L., D’Incalci M. In vitro and in vivo methazolastone-induced DNA damage and repair in L-1210 leukemia sensitive and resistant to chloroethylnitrosoureas. Cancer Res., 47: 4884-4889, 1987.
16. Nicholson H. S., Krailo M., Ames M. M., Seibel N. L., Reid J. M., Liu-Mares W., Vezina L. G., Ettinger A. G., Reaman G. H. Phase I study of temozolomide in children and adolescents with recurrent solid tumors: a report from the Children’s Cancer Group. J. Clin. Oncol., 16: 3037-3043, 1998.
65. Durkacz B. W., Omidiji O., Gray D. A., Shall S. (ADP-ribose)n participates in DNA excision repair. Nature (Lond.), 283: 593-596, 1980.
54. Pegg A. E., Byers T. L. Repair of DNA containing O6-alkylguanine. FASEB J., 6: 2302-2310, 1992.
37. D’Atri S., Piccioni D., Castellano A., Tuorto V., Franchi A., Lu K., Christiansen N., Frankel S., Rustum Y. M., Papa G., Mandelli F., Bonmassar E. Chemosensitivity to triazene compounds and O6-alkylguanine-DNA alkyltransferase levels: studies with blasts of leukaemic patients. Ann. Oncol., 6: 389-393, 1995.
17. Stevens M. F. G., Hickman J. A., Stone R., Gibson N. W., Baig G. U., Lunt E., Newton C. G. Antitumor imidazotetrazines. 1. Synthesis and chemistry of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d ]-1,2,3,5-tetrazin-4(3H)-one, a novel broad-spectrum antitumor agent. J. Med. Chem., 27: 196-201, 1984.
81. Brock C. S., Newlands E. S., Wedge S. R., Bower M., Evans H., Colquhoun I., Roddie M., Glaser M., Brampton M. H., Rustin G. J. S. Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res., 58: 4363-4367, 1998.
35. Dolan M. E., Mitchell R. B., Mummert C., Moschel R. C., Pegg A. E. Effect of O6-benzylguanine analogues on sensitivity of human tumor cells to the cytotoxic effects of alkylating agents. Cancer Res., 51: 3367-3372, 1991.
30. Liu L., Taverna P., Whitacre C. M., Chatterjee S., Gerson S. L. Pharmacologic disruption of base excision repair sensitizes mismatch repair-deficient and -proficient colon cancer cells to methylating agents. Clin. Cancer Res., 5: 2908-2917, 1999.
73. Wedge S. R., Newlands E. S. O6-Benzylguanine enhances the sensitivity of a glioma xenograft with low O6-alkylguanine-DNA alkyltransferase activity to temozolomide and BCNU. Br. J. Cancer, 73: 1049-1052, 1996.
59. Wang G., Weiss C., Sheng P., Bresnick E. Retrovirus-mediated transfer of the human O6-methylguanine-DNA methyltransferase gene into a murine hematopoietic stem cell line and resistance to the toxic effects of certain alkylating agents. Biochem. Pharmacol., 51: 1221-1228, 1996.
21. Gibson N. W., Erickson L. C., Hickman J. A. Effects of the antitumor agent 8-carbamoyl-3-(2-chloroethyl)imidaz[5,1-d]-1,2,3,5-tetrazin-4(3H)-one on the DNA of mouse L1210 cells. Cancer Res., 44: 1767-1771, 1984.
70. Friedman H. S., Dolan M. E., Moschel R. C., Pegg A. E., Felker G. M., Rich J., Bigner D. D., Schold S. C. J. Enhancement of nitrosourea activity in medulloblastoma and glioblastoma multiforme. J. Natl. Cancer Inst., 84: 1926-1931, 1992.
14. Paulsen F., Hoffmann W., Becker G., Belka C., Weinmann M., Classen J., Kortmann R. D., Bamberg M. Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide. J. Cancer Res. Clin. Oncol., 125: 411-418, 1999.
55. Tisdale M. J. Antitumor imidazotetrazines–XV. Role of guanine O6 alkylation in the mechanism of cytotoxicity of imidazotetrazinones. Biochem. Pharmacol., 36: 457-462, 1987.
58. Franchi A., Papa G., D’Atri S., Piccioni D., Masi M., Bonmassar E. Cytotoxic effects of dacarbazine in patients with acute myelogenous leukemia: a pilot study. Haematologica, 77: 146-150, 1992.
79. Hickson I., Fairbairn L. J., Chinnasamy N., Lashford L. S., Thatcher N., Margison G. P., Dexter T. M., Rafferty J. A. Chemoprotective gene transfer I: transduction of human haemopoietic progenitors with O6-benzylguanine-resistant O6-alkylguanine-DNA alkyltransferase attenuates the toxic effects of O6-alkylating agents in vitro. Gene Ther., 5: 835-841, 1998.
Interest in temozolomide as an antitumor agent derives from its broad-spectrum antitumor activity in tumor models in mice . In vitro, temozolomide has demonstrated schedule-dependent antitumor activity against a variety of malignancies, including glioma, metastatic melanoma, and other difficult-to-treat cancers . In preclinical studies, temozolomide demonstrated distribution to all tissues, including penetration into the CNS; relatively low toxicity compared with its parent compound, mitozolomide; and antitumor activity against a broad range of tumor types, including glioma, melanoma, mesothelioma, sarcoma, lymphoma, leukemia, and carcinoma of the colon and ovary . Its demonstrated ability to cross the blood-brain barrier is of special interest with respect to its activity in CNS tumors .
63. Friedman H. S., Johnson S. P., Dong Q., Schold S. C., Rasheed B. K. A., Bigner S. H., Ali-Osman F., Dolan E., Colvin O. M., Houghton P., Germain G., Drummond J. T., Keir S., Marcelli S., Bigner D. D., Modrich P. Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft. Cancer Res., 57: 2933-2936, 1997.
13. Bower M., Newlands E. S., Bleehen N. M., Brada M., Begent R. J. H., Calvert H., Colquhoun I., Lewis P., Brampton M. H. Multicentre CRC Phase II trial of temozolomide in recurrent or progressive high-grade glioma. Cancer Chemother. Pharmacol., 40: 484-488, 1997.
52. Pegg A. E., Dolan M. E., Moschel R. C. Structure, function, and inhibition of O6-alkylguanine-DNA alkyltransferase. Prog. Nucleic Acid Res. Mol. Biol., 51: 167-223, 1995.
42. Taverna P., Catapano C. V., Citti L., Bonfanti M., D’Incalci M. Influence of O6-methylguanine on DNA damage and cytotoxicity of temozolomide in L1210 mouse leukemia sensitive and resistant to chloroethylnitrosoureas. Anticancer Drugs, 3: 401-405, 1992.
19. Horgan C. M. T., Tisdale M. J. An investigation into the mechanism of antitumour activity of a novel and potent antitumour agent, mitozolomide (CCRG 81010, M & B 39565; NSC 353451). Biochem. Pharmacol., 33: 2185-2192, 1984.
10. Newlands E. S., Blackledge G. R. P., Slack J. A., Rustin G. J. S., Smith D. B., Stuart N. S. A., Quarterman C. P., Hoffman R., Stevens M. F. G., Brampton M. H., Gibson A. C. Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856). Br. J. Cancer, 65: 287-291, 1992.
51. Zucchetti M., Catapano C. V., Filippeschi S., Erba E., D’Incalci M. Temozolomide induced differentiation of K562 leukemia cells is not mediated by gene hypomethylation. Biochem. Pharmacol., 38: 2069-2075, 1989.
88. Pech I. V., Peterson K., Cairncross J. G. Chemotherapy for brain tumors. Oncology, 12: 537-553, 1998
76. Chinnasamy N., Rafferty J., Lashford L., Chinnasamy D., Margison G., Thatcher N., Dexter T., Fairbairn L. Protection of committed murine haemopoietic progenitors against BCNU toxicity does not predict protection of primitive, multipotent spleen colony-forming cells—implications for chemoprotective gene therapy. Leukemia, 13: 1776-1783, 1999.
24. Newlands E. S., Blackledge G., Slack J. A., Goddard C., Brindley C. J., Holden L., Stevens M. F. G. Phase I clinical trial of mitozolomide. Cancer Treat. Rep., 69: 801-805, 1985.
92. Yung W. K., Prados M. D., Yaya-Tur R., Rosenfeld S. S., Brada M., Friedman H. S., Albright R., Olson J., Chang S. M., O’Neill A. M., Friedman A. H., Bruner J., Yue N., Dugan M., Zaknoen S., Levin V. A. Multicenter Phase II trial of temozolomide in patients with anaplastic astrocytoma or anaplastic oligoastrocytoma at first relapse. J. Clin. Oncol., 17: 2762 1999.
32. Deans B., Tisdale M. J. Antitumour imidazotetrazines XXVIII 3-methyladenine DNA glycosylase activity in cell lines sensitive and resistant to temozolomide. Cancer Lett., 63: 151-157, 1992.
67. Wu Z., Chan C. L., Eastman A., Bresnick E. Expression of human O6-methylguanine-DNA methyltransferase in Chinese hamster ovary cells and restoration of cellular resistance to certain N-nitroso compounds. Mol. Carcinog., 4: 482-488, 1991.
78. Chinnasamy N., Rafferty J. A., Hickson I., Lashford L. S., Longhurst S. J., Thatcher N., Margison G. P., Dexter T. M., Fairbairn L. J. Chemoprotective gene transfer II: multilineage in vivo protection of haemopoiesis against the effects of an antitumour agent by expression of a mutant human O6-alkylguanine-DNA alkyltransferase. Gene Ther., 5: 842-847, 1998.
64. Tisdale M. J. Antitumour imidazotetrazines-XI: effect of 8-carbamoyl-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one [CCRG 81045; M and B 39831 NSC 362856] on poly(ADP-ribose) metabolism. Br. J. Cancer, 52: 789-792, 1985.
68. Tentori L., Turriziani M., Franco D., Serafino A., Levati L., Roy R., Bonmassar E., Graziani G. Treatment with temozolomide and poly(ADP-ribose) polymerase inhibitors induces early apoptosis and increases base excision repair gene transcripts in leukemic cells resistant to triazene compounds. Leukemia, 13: 901-909, 1999.
INTRODUCTION
36. Dolan M. E., Moschel R. C., Pegg A. E. Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc. Natl. Acad. Sci. USA, 87: 5368-5372, 1990.
74. Fairbairn L. J., Watson A. J., Rafferty J. A., Elder R. H., Margison G. P. O6-benzylguanine increases the sensitivity of human primary bone marrow cells to the cytotoxic effects of temozolomide. Exp. Hematol., 23: 112-116, 1995.
84. Brada M., Judson I., Beale P., Moore S., Reidenberg P., Statkevich P., Dugan M., Batra V., Cutler D. Phase I dose-escalation and pharmacokinetic study of temozolomide (SCH 52365) for refractory or relapsing malignancies. Br. J. Cancer, 81: 1022-1030, 1999.
12. O’Reilly S. M., Newlands E. S., Glaser M. G., Brampton M., Rice-Edwards J. M., Illingworth R. D., Richards P. G., Kennard C., Colquhoun I. R., Lewis P., Stevens M. F. G. Temozolomide: a new oral cytotoxic chemotherapeutic agent with promising activity against primary brain tumours. Eur. J. Cancer, 29A: 940-942, 1993.
23. Bull V. L., Tisdale M. J. Antitumour imidazotetrazines-XVI macromolecular alkylation by 3-substituted imidazotetrazinones. Biochem. Pharmacol., 36: 3215-3220, 1987.
77. Reese J. S., Davis B. M., Liu L., Gerson S. L. Simultaneous protection of G156A methylguanine DNA methyltransferase gene-transduced hematopoietic progenitors and sensitization of tumor cells using O6-benzylguanine and temozolomide. Clin. Cancer Res., 5: 163-169, 1999.
38. Drummond J. T., Li G. M., Longley M. J., Modrich P. Isolation of an hMSH2–p160 heterodimer that restores DNA mismatch repair to tumor cells. Science (Washington, DC), 268: 1909-1912, 1995.
62. Liu L., Markowitz S., Gerson S. L. Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to 1,3-bis(2-chloroethyl)nitrosourea. Cancer Res., 56: 5375-5379, 1996.
91. Yung A., Levin V. A., Albright R., Olson J., Fredericks R., Fink K., Prados M., Brada M., Spence A., Brunner J., Yue N., Dugan M. H., Zaknoen S., Temodal Brain Tumor Group. Randomized trial of temodal (TEM) vs. procarbazine (PCB) in glioblastoma multiforme (GBM) at first relapse. Proc. Am. Soc. Clin. Oncol., 18: 139 1999.
46. Bianchi R., Citti L., Beghetti R., Romani L., D’Incalci M., Puccetti P., Fioretti M. C. O6-Methylguanine-DNA methyltransferase activity and induction of novel immunogenicity in murine tumor cells treated with methylating agents. Cancer Chemother. Pharmacol., 29: 277-282, 1992.
44. Karran P., Bignami M. Self-destruction and tolerance in resistance of mammalian cells to alkylation damage. Nucleic Acids Res., 20: 2933-2940, 1992.
In Phase 1 and 2 clinical studies conducted by the CRC (London, United Kingdom), temozolomide was absorbed rapidly, exhibited 100% p.o. bioavailability within 1–2 h of administration, and demonstrated antineoplastic activity in recurrent high-grade glioma, melanoma, and mycosis fungoides . Results of these trials showed that when temozolomide is administered p.o. once daily for 5 days in a 4-week cycle, it is well tolerated, producing mild-to-moderate toxicity that is both predictable and easily managed. The results also confirmed the ability of temozolomide to penetrate the CNS and indicated that temozolomide has considerable potential in treating gliomas and improving the QOL of patients with glioma . Additional Phase 1 studies have confirmed these results and have extended these observations to pediatric patients .
39. Palombo F., Gallinari P., Iaccarino I., Lettieri T., Hughes M., D’Arrigo A., Truong O., Hsuan J. J., Jiricny J. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. Science (Washington, DC), 268: 1912-1914, 1995.
57. Redmond S. M., Joncourt F., Buser K., Ziemiecki A., Altermatt H. J., Fey M., Margison G., Cerny T. Assessment of P-glycoprotein, glutathione-based detoxifying enzymes and O6-alkylguanine-DNA alkyltransferase as potential indicators of constitutive drug resistance in human colorectal tumors. Cancer Res., 51: 2092-2097, 1991.
33. Wedge S. R., Porteous J. K., Newlands E. S. 3-aminobenzamide and/or O6-benzylguanine evaluated as an adjuvant to temozolomide or BCNU treatment in cell lines of variable mismatch repair status and O6-alkylguanine–DNA alkyltransferase activity. Br. J. Cancer, 74: 1030-1036, 1996.
72. Middleton M. R., Kelly J., Thatcher N., Donnelly D. J., McElhinney R. S., McMurry T. B., McCormick J. E., Margison G. P. O6-(4-bromothenyl)guanine improves the therapeutic index of temozolomide against A375M melanoma xenografts. Int. J. Cancer, 85: 248-252, 2000.
20. Gibson N. W., Hickman J. A., Erickson L. C. DNA cross-linking and cytotoxicity in normal and transformed human cells treated in vitro with 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one. Cancer Res., 44: 1772-1775, 1984.
71. Dolan M. E., Pegg A. E. O6-benzylguanine and its role in chemotherapy. Clin. Cancer Res., 3: 837-847, 1997.
69. Imperatori L., Damia G., Taverna P., Garattini E., Citti L., Boldrini L., D’Incalci M. 3T3 NIH murine fibroblasts and B78 murine melanoma cells expressing the Escherichia coli N3-methyladenine-DNA glycosylase I do not become resistant to alkylating agents. Carcinogenesis (Lond.), 15: 533-537, 1994.
Temozolomide has been evaluated in a number of Phase 2 and 3 clinical trials for the treatment of glioblastoma multiforme, anaplastic astrocytoma, and malignant metastatic melanoma—malignancies for which there are no satisfactory therapies. On the basis of the results of these studies, temozolomide has been approved in the European Union for the treatment of patients with glioblastoma multiforme showing progression or recurrence after standard therapy. Recently, temozolomide received accelerated approval from the FDA for treatment of adult patients with anaplastic astrocytoma who have relapsed after treatment that included a nitrosurea drug (BCNU or CCNU) and procarbazine. Studies are under way to evaluate the combination of temozolomide with other chemotherapeutic agents and biochemotherapy in the treatment of malignant glioma and metastatic melanoma, respectively. This article reviews the mechanism of action of temozolomide as an anticancer agent and summarizes the most recent clinical studies of temozolomide for the treatment of malignant gliomas.
49. Tisdale M. J. Antitumour imidazotetrazines—XVIII. Modification of the level of 5-methylcytosine in DNA by 3-substituted imidazotetrazinones. Biochem. Pharmacol., 38: 1097-1101, 1989.
60. Walker M. C., Masters J. R. W., Margison G. P. O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines. Br. J. Cancer, 66: 840-843, 1992.
50. Hepburn P. A., Tisdale M. J. Growth suppression by DNA from cells treated with imidazotetrazinones. Biochem. Pharmacol., 41: 339-343, 1991.
29. Denny B. J., Wheelhouse R. T., Stevens M. F. G., Tsang L. L. H., Slack J. A. NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA. Biochemistry, 33: 9045-9051, 1994.
80. Hammond L. A., Eckardt J. R., Baker S. D., Eckhardt S. G., Dugan M., Forral K., Reidenberg P., Statkevich P., Weiss G. R., Rinaldi D. A., Von Hoff D. D., Rowinsky E. K. Phase I and pharmacokinetic study of temozolomide on a daily-for-5-days schedule in patients with advanced solid malignancies. J. Clin. Oncol., 17: 2604 1999.
47. Allegrucci M., Fuschiotti P., Puccetti P., Romani L., Fioretti M. C. Changes in the tumorigenic and metastatic properties of murine melanoma cells treated with a triazene derivative. Clin. Exp. Metastasis, 7: 329-341, 1989.
87. Prados M. D., Russo C. Chemotherapy of brain tumors. Semin. Surg. Oncol., 14: 88-95, 1998.
85. Beale P., Judson I., Moore S., Statkevich P., Marco A., Cutler D. L., Reidenberg P., Brada M. Effect of gastric pH on the relative oral bioavailability and pharmacokinetics of temozolomide. Cancer Chemother. Pharmacol., 44: 389-394, 1999.
48. Tentori L., Leonetti C., Aquino A. Temozolomide reduces the metastatic potential of Lewis lung carcinoma (3LL) in mice: role of -6 integrin phosphorylation. Eur. J. Cancer, 31A: 746-754, 1995.
Targeting Disease Remission Has Socio-Economic Benefits Over Low Disease Activity
Achieving disease remission in patients with rheumatoid arthritis (RA) provides superior outcomes across measures of socio-economic importance including work productivity and quality of life, according to results presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy. These Austrian findings are reported in addition to improvements in measures of ...
The UNDP's first Human Development Index (HDI) in 1990 devised by my Reliance produced the Physical Quality-of-Life Index (PQLI) for the Overseas Development Home " Media Centre " Bankwest Research " Bankwest Quality of Life Index 2008 The inaugural BankWest Quality of Life tracks where living standards are highest in In it recent Human Development Index, the U.N. ranks the U.S. at number 13 among the nations of the world. London's Soho sees the opening of this Scandinavian bakery that sells all manner of rye breads, cinnamon buns, beers and snacks. The Quality of Life Project is a tool for measuring the Quality of Life in Ontario across the Health, Social, Economic and Environmental sectors. The QOL can help strengthen these relationships by providing a context for looking at different issues in an integrated way. How will it be used? 2010 Quality of Life ----194 Countries Ranked and Rated to What do you think of Quality of Life in the country where you are living ? WEIGHT IN THE QOL 4.18% FOR MORE INFORMATION. For more information on the Audubon Society and their bird count, visit their website, www.audubon. The QLI produces five scores: quality of life overall and in four domains (health and To print The Quality of Life Overview, Reliability and Validity, Major Journals for the number of articles on Patient Reported Outcomes Terms & Conditions | Mapi Research Institute, 2001-2010 - All rights reserved News Release: 2010 Mercer Quality of Living survey Qol index 2010. 1. VIENNA. AUSTRIA. 108.6. 2. ZURICH. SWITZERLAND. 108. 3. GENEVA. SWITZERLAND. 107.9. 4. VANCOUVER. CANADA There are no fees for using the Missoula-VITAS Quality of Life Index but we do ask that you register by providing your organization name and a contact person. This year, we have incorporated a new feature: the Quality of Life Index. With this index, policy makers, the public and the media will have a Privacy Policy: We will never sell, rent, lease, or otherwise share your information with anyone, ever. Quality of Life Index. I regularly find time for my friends. The quality of life index developed by the Economist Intelligence Unit ranks Israel 38th. The Economist Quality of Life compares Quality of Life in various countries.1 WEIGHT IN THE QOL INDEX 4.20% WHY WE ARE MEASURING THIS. As housing costs rise, families may be unable to afford other necessities such as food, Tampa Bay's news, shopping and information source brought to you by the St. Petersburg Times and tbt The Quality of Life Index is a locally and internationally recognized community planning resource and guide for priority-setting and decision-making. Tampa Bay's news, shopping and information source brought to you by the St. Petersburg Times and tbt Northern European countries dominate the Economist Intelligence Unit's quality-of-life index for 2005. Register now and receive a 14-day premium pass. Register now Quality of Life Index. HÃ'tel Palafitte, Neuchâtel. 118. Located on the banks of Lake Neuchâtel, the HÃ'tel Palafitte has 40 suites housed on Quality of Life Index. Created by Cincinnati City Council, the Quality of Life Index The Index provides quarterly updates on the City's response on a variety of quality of How do you measure quality of life? The Nathan Kline Institute for Psychiatric Research developed a Argentina and Uruguay were the top 2 Latin destinations in IL's Annual Quality of Life Index. and ponder quality of life, a common narrative thread here on InvestBA. At the heart of the Wisconsin REALTORS Assocation's new Wisconsin Quality of Life initiative is an effort to inject a new vitality and synergy into the relationship So say the editors of International Living, the world's #1 retirement and relocation publication in their annual Annual Quality of Life Index. The Department of Dermatology in Cardiff, UK, is an international centre for dermatology Dermatitis Quality of Life Index (IDQOL) " The Cardiff Acne Disability (CADI) The Economist Intelligence Unit's quality of life index also gives a high Figure 1.2 Economist Intelligence Unit's quality of life index, 2005 (score on a scale 2008 Quality of Life Index. Choose a Country: Click on a column header to sort the data. Korea, South (Rep of) 31. 69. 51. 68. 92. 84. 56. 93. 83. 67. Latvia. 54. 79. 46 Preoperative Gastrointestinal Quality of Life Index (GIQLI) vs. follow-up GIQLI vs. theoretical maximum score. Preoperative Gastrointestinal Quality of Life Index (GIQLI) vs. The Quality of Life Index or QLI is an alternative measure of poverty and human capability. The index provides a good scan of the poverty situation in local Overall quality of life is a composite assessment of the quality of the social, economic and physical Quality of Life: Economic Environment Index Map | Read about this map His Physical Quality of Life shows that quality of life has improved faster for The enables researchers to rank countries, not by incomes but Read full-text medical journal articles from Medscape's Health and Quality of Life Outcomes. The 2010 Quality of Life is out and Kuwait ranked 106 which is up nearly 30 spots since 2006. Risk & Saftey Index: Brazil 89, USA 100, Mexico 79, Morroco 78, Most of Gulf nations in bottom half of global list compiled by Int'l Living magazine. International Living magazine's 2010 Quality of Life Index ranks 194 countries in terms Quality of Life - Global Issues - Index - Global Issues, Quality of Life, Access to Electricity, Children, Disease Control, Food, GENI, Hunger, Literacy, Income, 2010 Quality of Life Index: 194 Countries Ranked and Rated to Reveal If we judged quality of life by a nation's Michelin-starred restaurants per square mile,
