The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

DTICDome     (5E)-5- (dimethylaminohydrazinylidene) imida...

Synonyms: Deticene, Decarbazine, dacarbazine, Biocarbazine, DTIC, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DTIC-Dome


High impact information on DTIC-Dome


Chemical compound and disease context of DTIC-Dome

  • PURPOSE: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone [6].
  • (BALB/c X DBA/2) F1 (hereafter called CD2F1) mice bearing leukemia L1210 Ha were treated as follows: (a) DTIC for increasing the immunogenicity of the leukemic cells; (b) CY or BCNU; and (c) adoptive transfer of CD2F1 lymphocytes [7].
  • RESULTS: Numerous articles have reported an overall response rate of 47% (95% confidence limit, 39.25 to 54.75) when patients with metastatic melanoma are treated with the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP), and TAM (DBDT) [4].
  • CONCLUSION: While TAM as a single agent is minimally active in treating patients with metastatic melanoma, when it is combined with DTIC, BCNU, and DDP, a marked improvement in the overall response rate is observed [4].
  • CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma [8].

Biological context of DTIC-Dome

  • In the present report, we describe the results of studies aimed at restoring immunocompetence of DTIC-treated mice by means of adoptive transfer of syngeneic lymphoid cells [7].
  • The DTIC-treated leukemia (L1210D line) or the control line treated with MLP alone (L1210N line) showed comparable growth kinetics in vitro [9].
  • ATase levels in PBMCs were used as a surrogate for tumour ATase depletion to determine whether this correlated with either the pharmacokinetics of DTIC and its major metabolite AIC or other clinical sequelae [10].
  • We assessed whether split dosing with the methylating agent DTIC is an effective strategy for inactivating the DNA repair protein O6-alkylguanine DNA-ATase in order to decrease tumour resistance to BCNU [10].
  • In line with these results, we observed a nearly 3-fold increase of apoptosis for the combination of thalidomide and DTIC compared with the rate of apoptotic cells in DTIC-only-treated melanoma xenotransplants [11].

Anatomical context of DTIC-Dome

  • Strong and heritable increase of immunogenicity of L1210 Ha leukemia has been obtained in vitro following multiple treatments with 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC), metabolically activated by mouse liver preparations (MLP) containing liver microsomes [9].
  • PURPOSE: In an effort to reduce the frequency of central nervous system (CNS) progression in patients with metastatic melanoma with ongoing systemic response to biochemotherapy, we modified our standard concurrent biochemotherapy regimen by replacing dacarbazine (DTIC) with oral temozolomide [12].
  • A triazene-xenogenized tumor sub-line was derived from the mouse mastocytoma cell line P815 following several transplant generations in vivo on DTIC [13].
  • In addition to previous evidence for a role of L3T4+ T cells in the protective anti-parental tumor immunity induced by xenogenized variant cells of a murine lymphoma (L5178Y/DTIC), we have investigated the possible participation in this effect of L5178Y tumor-specific lymphocytes of the Lyt-2+ T cell subset [14].
  • Administration of anti-IFN-gamma MAb in vivo significantly impaired the resistance of L5178Y/DTIC-immune mice to challenge with parental cells, as manifested by survival criteria and increased tumor-cell proliferation in the spleens of antibody-treated mice [14].

Associations of DTIC-Dome with other chemical compounds

  • Three weeks from the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide, doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days [15].
  • The treatment consisted of cisplatin 20 mg/m2 daily for 4 days; vinblastine 1.6 mg/m2 daily for 4 days; and DTIC 800 mg/m2 intravenously (i.v.) day 1 with IL-2 9 x 10(6) IU/m2 i.v. by continuous infusion daily for 4 days and IFN-alpha 5 x 10(6) U/m2 subcutaneously daily for 5 days, repeated at 21-day intervals [16].
  • PATIENTS AND METHODS: Seventy-nine eligible patients were treated with BCNU 150 mg/m2/d, every 6 weeks, DTIC 220 mg/m2/d on days 1 to 3 every 3 weeks, DDP 25 mg/m2/d on days 1 to 3 every 3 weeks, and Tam 20 mg orally daily throughout treatment [17].
  • The four-drug chemotherapy regimen was as follows: dacarbazine (DTIC) 200 mg/m2 days 1 to 5, vincristine 1 mg/m2 days 1 and 4, bleomycin 15 mg days 2 and 5 intravenously (IV), and lomustine (CCNU) 80 mg day 1 orally [18].
  • Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC [8].

Gene context of DTIC-Dome

  • Antihuman CYP1A2 antiserum also inhibited DTIC N-demethylation [19].
  • The Km (Vmax) values for metabolism of DTIC by recombinant human CYP1A1 and CYP1A2 were 595 microM (0.684 nmol/min/mg protein) and 659 microM (1.74 nmol/min/mg protein), respectively [19].
  • We now report that the DTIC N-demethylation involved in MTIC formation by human liver microsomes is catalyzed by CYP1A1, CYP1A2, and CYP2E1 [19].
  • We have treated 18 patients with metastatic malignant melanoma (MM) with high-dose IL-2 administered by continuous iv infusion in combination with dacarbazine (DTIC), and correlated the clinical response with various hematologic and immunologic parameters [20].
  • However, there was no significant correlation of MMR expression alone or combined with MGMT levels with clinical response to DTIC-based chemotherapy in metastatic melanoma [21].

Analytical, diagnostic and therapeutic context of DTIC-Dome


  1. Efficacy of chemotherapeutic treatment of guinea pig hepatoma reflected in host's serum lipid composition. Schlager, S.I. J. Natl. Cancer Inst. (1983) [Pubmed]
  2. Carcinogenicity of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, and its metabolites in rats. Beal, D.D., Skibba, J.L., Croft, W.A., Cohen, S.M., Bryan, G.T. J. Natl. Cancer Inst. (1975) [Pubmed]
  3. Eosinophilia with DTIC chemotherapy. Movsesian, M.A., Merrill, J.M. Ann. Intern. Med. (1980) [Pubmed]
  4. Tamoxifen: is it useful in the treatment of patients with metastatic melanoma? McClay, E.F., McClay, M.E. J. Clin. Oncol. (1994) [Pubmed]
  5. Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group. Kaufmann, R., Spieth, K., Leiter, U., Mauch, C., von den Driesch, P., Vogt, T., Linse, R., Tilgen, W., Schadendorf, D., Becker, J.C., Sebastian, G., Krengel, S., Kretschmer, L., Garbe, C., Dummer, R. J. Clin. Oncol. (2005) [Pubmed]
  6. Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma. Bajetta, E., Di Leo, A., Zampino, M.G., Sertoli, M.R., Comella, G., Barduagni, M., Giannotti, B., Queirolo, P., Tribbia, G., Bernengo, M.G. J. Clin. Oncol. (1994) [Pubmed]
  7. Drug-mediated increase of tumor immunogenicity in vivo for a new approach to experimental cancer immunotherapy. Giampietri, A., Bonmassar, A., Puccetti, P., Circolo, A., Goldin, A., Bonmassar, E. Cancer Res. (1981) [Pubmed]
  8. Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. Middleton, M.R., Grob, J.J., Aaronson, N., Fierlbeck, G., Tilgen, W., Seiter, S., Gore, M., Aamdal, S., Cebon, J., Coates, A., Dreno, B., Henz, M., Schadendorf, D., Kapp, A., Weiss, J., Fraass, U., Statkevich, P., Muller, M., Thatcher, N. J. Clin. Oncol. (2000) [Pubmed]
  9. In vitro generation of a highly immunogenic subline of L1210 leukemia following exposure to 5-(3,3'-dimethyl-1-triazeno)imidazole-4-carboxamide. Contessa, A.R., Bonmassar, A., Giampietri, A., Circolo, A., Goldin, A., Fioretti, M.C. Cancer Res. (1981) [Pubmed]
  10. Pharmacokinetic, biochemical and clinical effects of dimethyltriazenoimidazole-4-carboxamide-bischloroethylnitrosourea combination therapy in patients with advanced breast cancer. Clemons, M., Ranson, M., Margison, J.M., El Teraifi, H., Griffiths, A., Kelly, J., Morris, C.Q., Howell, A., Margison, G.P. Int. J. Cancer (2003) [Pubmed]
  11. Thalidomide enhances the anti-tumor activity of standard chemotherapy in a human melanoma xenotransplatation model. Heere-Ress, E., Boehm, J., Thallinger, C., Hoeller, C., Wacheck, V., Birner, P., Wolff, K., Pehamberger, H., Jansen, B. J. Invest. Dermatol. (2005) [Pubmed]
  12. A phase II pilot trial of concurrent biochemotherapy with cisplatin, vinblastine, temozolomide, interleukin 2, and IFN-alpha 2B in patients with metastatic melanoma. Atkins, M.B., Gollob, J.A., Sosman, J.A., McDermott, D.F., Tutin, L., Sorokin, P., Parker, R.A., Mier, J.W. Clin. Cancer Res. (2002) [Pubmed]
  13. Immunogenic properties of retroviral protein P15E from drug-treated murine mastocytoma P815. Grohmann, U., Fioretti, M.C., Binaglia, L., Belladonna, M.L., Bianchi, R., Puccetti, P. Int. J. Cancer (1993) [Pubmed]
  14. T-cell subsets, IFN-gamma production and efferent specificity in anti-parental tumor immunity induced by mouse sensitization with xenogenized variant cells. Bianchi, R., Fioretti, M.C., Romani, L., Grohmann, U., Cenci, E., Puccetti, P. Int. J. Cancer (1990) [Pubmed]
  15. Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein, on chemotherapy-induced multilineage myelosuppression in patients with sarcoma. Vadhan-Raj, S., Papadopoulos, N.E., Burgess, M.A., Linke, K.A., Patel, S.R., Hays, C., Arcenas, A., Plager, C., Kudelka, A.P., Hittelman, W.N. J. Clin. Oncol. (1994) [Pubmed]
  16. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. Legha, S.S., Ring, S., Eton, O., Bedikian, A., Buzaid, A.C., Plager, C., Papadopoulos, N. J. Clin. Oncol. (1998) [Pubmed]
  17. Phase II study of carmustine, dacarbazine, cisplatin, and tamoxifen in advanced melanoma: a Southwest Oncology Group study. Margolin, K.A., Liu, P.Y., Flaherty, L.E., Sosman, J.A., Walker, M.J., Smith, J.W., Fletcher, W.S., Weiss, G.R., Unger, J.M., Sondak, V.K. J. Clin. Oncol. (1998) [Pubmed]
  18. A promising interferon plus four-drug chemotherapy regimen for metastatic melanoma. Pyrhönen, S., Hahka-Kemppinen, M., Muhonen, T. J. Clin. Oncol. (1992) [Pubmed]
  19. Metabolic activation of dacarbazine by human cytochromes P450: the role of CYP1A1, CYP1A2, and CYP2E1. Reid, J.M., Kuffel, M.J., Miller, J.K., Rios, R., Ames, M.M. Clin. Cancer Res. (1999) [Pubmed]
  20. Chemo-immunotherapy in patients with metastatic melanoma using sequential treatment with dacarbazine and recombinant human interleukin-2: evaluation of hematologic and immunologic parameters and correlation with clinical response. Isacson, R., Kedar, E., Barak, V., Gazit, Z., Yurim, O., Kalichman, I., Ben-Bassat, H., Biran, S., Schlesinger, M., Franks, C.R. Immunol. Lett. (1992) [Pubmed]
  21. Immunohistochemical analysis of DNA mismatch repair protein and O6-methylguanine-DNA methyltransferase in melanoma metastases in relation to clinical response to DTIC-based chemotherapy. Ma, S., Egyházi, S., Ringborg, U., Hansson, J. Oncol. Rep. (2002) [Pubmed]
  22. Current treatment options for malignant melanoma. Cohen, G.L., Falkson, C.I. Drugs (1998) [Pubmed]
  23. Response to chemotherapy of human, malignant melanoma xenografts in athymic, nude mice. Fodstad, O., Aass, N., Pihl, A. Int. J. Cancer (1980) [Pubmed]
  24. The immunodepressive and hematotoxic activity of imidazole-4-carboxamide,5-(3,3-dimethyl-1-triazeno) in mice. Vecchi, A., Fioretti, M.C., Mantovani, A., Barzi, A., Spreafico, F. Transplantation (1976) [Pubmed]
  25. Angiographic appearance of recurrent malignant melanoma before and after intra-arterial chemotherapy. Charnsangavej, C., Chuang, V.P., Wallace, S., Soo, C.S., Bowers, T. Radiology. (1982) [Pubmed]
WikiGenes - Universities