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Disease relevance of Vinca

  • PURPOSE: This report determines the incidence of pathologic complete response in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with mitomycin, vinca alkaloid, and high-dose cisplatin (MVP) chemotherapy, and estimates the effect of MVP on survival [1].
  • In these studies, we report on the nature and specificity of the human anti-murine antibody (HAMA) response in patients given single and multiple infusions of the two Vinca alkaloid conjugates of the MoAb KS1/4, which recognizes tumor-associated antigens in a variety of adenocarcinomas [2].
  • Increase of cyclic adenosine 3':5'-monophosphate concentration in transplantable lymphoma cells by vinca alkaloids [3].
  • The Vinca alkaloid vincristine and the epipodophyllotoxin derivative teniposide significantly elevate steady state levels of methotrexate in the Ehrlich ascites tumor cell in vitro [4].
  • Active [3H]vinblastine (VBL) transport (efflux) was documented for inside-out plasma membrane vesicles from murine erythroleukemia cells (MEL/VCR-6) resistant to vinca alkaloids and overexpressing MDR 3 P-glycoprotein (P-gp) 80-fold [5].

High impact information on Vinca

  • In continuous-exposure assays, however, the MRP4 transfectants did not display increased resistance for either methotrexate or natural product cytotoxic agents (anthracyclines, etoposide, vinca alkaloids, and paclitaxel [Taxol]) [6].
  • In multidrug resistance, cells become simultaneously resistant to anthracyclines, vinca alkaloids, epipodophyllotoxins, and certain other natural product cytotoxic drugs [7].
  • Unlike classical antimicrotubule agents like colchicine and the vinca alkaloids, which induce depolymerization of microtubules, taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules [8].
  • A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2 [9].
  • These sublines are cross-resistant to daunorubicin, VP16-213, Vinca alkaloids, colchicine, gramicidin D, and 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) [10].

Chemical compound and disease context of Vinca


Biological context of Vinca


Anatomical context of Vinca

  • We report here the characterization of a human leukemic cell line (CEM/VM-1) with "atypical" multiple drug resistance: despite resistance and cross-resistance to etoposide, anthracyclines, mitoxantrone, and 4'-[(9-acridinyl)amino]methanesulphon-m-anisidide (mAMSA), these cells retain sensitivity to the Vinca alkaloids [21].
  • It has been concluded that the process of paracrystal induction by Vinca alkaloids in Lymnaea neurons is very much the same as in mammalian neurons and may be largely responsible for the neurotoxic effects of the Vinca drugs, because it impairs axonal transport of neuronal secretory granules [22].
  • In addition to the loss of E(2)17betaG transport, HeLa cells stably transfected with W1246C-MRP1 cDNA were not resistant to the Vinca alkaloid vincristine and accumulated levels of [(3)H]vincristine comparable to those in vector control-transfected cells [23].
  • Inhibition of phytohemagglutinin-, periodate- and A23187-induced lymphocyte transformation by vinca alkaloids [24].
  • In addition, regimens combining cisplatin with vinca alkaloids have no substantial deleterious effects on the lung, marrow or esophagus to aggravate radiation-induced complications [25].

Associations of Vinca with chemical compounds

  • Information from this analysis may be useful when comparing the response data of completed studies in similar patients, in designing future trials, and in the selection of cisplatin plus vinca alkaloid therapy for individual patients with advanced NSCLC [26].
  • However, AdR1.2 was most resistant to Adriamycin among the nine agents tested, and SRA1.2 was most resistant to Vinca alkaloids [27].
  • In comparison with the leukemic line CCRF-CEM, using a growth inhibition assay, LALW-2 cells were resistant to Vinca alkaloids and actinomycin D (relative resistance, 200-fold or more), were slightly resistant to Adriamycin (relative resistance, 4-fold), and showed no resistance to daunorubicin or teniposide [28].
  • Both vinca alkaloids and cyclophosphamide are especially useful [29].
  • [3H]Vinblastine accumulation was increased by 24-72% in both MES-SA and Dx5 cells in the presence of verapamil, although cytotoxicity of the Vinca alkaloids was not affected [30].

Gene context of Vinca

  • Lines lacking functional P-gp were, on average, markedly more sensitive to paclitaxel (16-fold), anthracyclines (4-fold) and Vinca alkaloids (3-fold) [31].
  • Vinca alkaloids are important chemotherapeutic agents, and their pharmacokinetic properties display significant interindividual variations, possibly due to CYP3A4-mediated metabolism [32].
  • Among tumoral resistances, multidrug resistance (MDR) is characterized as cross-resistance to a variety of structurally and functionally unrelated drugs such as vinca alkaloids, colchicine, and anthracyclines [33].
  • Human multidrug resistance protein 1 (MRP1) confers resistance to the Vinca alkaloids, the anthracyclines, and the epipodophyllotoxins [34].
  • Lines lacking both P-gp and Mrp1 were (compared with wild-type lines) hypersensitive to an even broader array of drugs, including epipodophyllotoxins (4-7-fold), anthracyclines (6-7-fold), camptothecins (3-fold), arsenite (4-fold) and Vinca alkaloids, especially vincristine (28-fold) [31].

Analytical, diagnostic and therapeutic context of Vinca


  1. Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials. Pisters, K.M., Kris, M.G., Gralla, R.J., Zaman, M.B., Heelan, R.T., Martini, N. J. Clin. Oncol. (1993) [Pubmed]
  2. The human immune response to KS1/4-desacetylvinblastine (LY256787) and KS1/4-desacetylvinblastine hydrazide (LY203728) in single and multiple dose clinical studies. Petersen, B.H., DeHerdt, S.V., Schneck, D.W., Bumol, T.F. Cancer Res. (1991) [Pubmed]
  3. Increase of cyclic adenosine 3':5'-monophosphate concentration in transplantable lymphoma cells by vinca alkaloids. Kotani, M., Koizumi, Y., Yamada, T., Kawasaki, A., Akabane, T. Cancer Res. (1978) [Pubmed]
  4. Serum protein reduction of the enhancement of methotrexate accumulation by vincristine and 4'-demethylepipodophyllotoxin in the Ehrlich ascites tumor cell in vitro. Gewirtz, D.A. Cancer Res. (1985) [Pubmed]
  5. Functional studies of P-glycoprotein in inside-out plasma membrane vesicles derived from murine erythroleukemia cells overexpressing MDR 3. Properties and kinetics of the interaction of vinblastine with P-glycoprotein and evidence for its active mediated transport. Schlemmer, S.R., Sirotnak, F.M. J. Biol. Chem. (1994) [Pubmed]
  6. Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells. Lee, K., Klein-Szanto, A.J., Kruh, G.D. J. Natl. Cancer Inst. (2000) [Pubmed]
  7. Expression of a human complementary DNA for the multidrug resistance gene in murine hematopoietic precursor cells with the use of retroviral gene transfer. McLachlin, J.R., Eglitis, M.A., Ueda, K., Kantoff, P.W., Pastan, I.H., Anderson, W.F., Gottesman, M.M. J. Natl. Cancer Inst. (1990) [Pubmed]
  8. Taxol: a novel investigational antimicrotubule agent. Rowinsky, E.K., Cazenave, L.A., Donehower, R.C. J. Natl. Cancer Inst. (1990) [Pubmed]
  9. A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2. Menke, F.L., Champion, A., Kijne, J.W., Memelink, J. EMBO J. (1999) [Pubmed]
  10. Genetic transfer of non-P-glycoprotein-mediated multidrug resistance (MDR) in somatic cell fusion: dissection of a compound MDR phenotype. Eijdems, E.W., Borst, P., Jongsma, A.P., de Jong, S., de Vries, E.G., van Groenigen, M., Versantvoort, C.H., Nieuwint, A.W., Baas, F. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  11. Prostaglandin F2 alpha in the treatment of vinca alkaloid-induced ileus. Saito, H., Yamamoto, T., Kimura, M., Shimokata, K. Am. J. Med. (1993) [Pubmed]
  12. A reduction in energy-dependent amino acid transport by microtubular inhibitors in Ehrlich ascites tumor cells. Fyfe, M.J., Loftfield, S., Goldman, I.D. J. Cell. Physiol. (1975) [Pubmed]
  13. Potentiation of radiation therapy by vinorelbine (Navelbine) in non-small cell lung cancer. Edelstein, M.P., Wolfe, L.A., Duch, D.S. Semin. Oncol. (1996) [Pubmed]
  14. Vinorelbine and carboplatin in recurrent and/or metastatic squamous cell carcinoma of the head and neck. Kornek, V., Scheithauer, W., Glaser, C., Toth, J., Duman, M., Formanek, M., Hejna, M., Kornfehl, J. Oncology (1999) [Pubmed]
  15. Chemoimmunoconjugate development for ovarian carcinoma therapy: preclinical studies with vinca alkaloid-monoclonal antibody constructs. Apelgren, L.D., Bailey, D.L., Briggs, S.L., Barton, R.L., Guttman-Carlisle, D., Koppel, G.A., Nichols, C.L., Scott, W.L., Lindstrom, T.D., Baker, A.L. Bioconjug. Chem. (1993) [Pubmed]
  16. Additivity of dilantin and vinblastine inhibitory effects on microtubule assembly. Lobert, S., Ingram, J.W., Correia, J.J. Cancer Res. (1999) [Pubmed]
  17. Abnormally banded chromosomal regions in doxorubicin-resistant B16-BL6 murine melanoma cells. Slovak, M.L., Hoeltge, G.A., Ganapathi, R. Cancer Res. (1986) [Pubmed]
  18. Reversal of Vinca alkaloid resistance but not multiple drug resistance in human leukemic cells by verapamil. Beck, W.T., Cirtain, M.C., Look, A.T., Ashmun, R.A. Cancer Res. (1986) [Pubmed]
  19. Comparative effects of vindesine, vinblastine, and vincristine on mitotic arrest and hormonal response of L1210 leukemia cells. Howard, S.M., Theologides, A., Sheppard, J.R. Cancer Res. (1980) [Pubmed]
  20. Plasma pharmacokinetics of vinblastine and the investigational Vinca alkaloid N-(deacetyl-O-4-vinblastoyl-23)-L-ethyl isoleucinate in mice as determined by high-performance liquid chromatography. van Tellingen, O., Beijnen, J.H., Nooijen, W.J., Bult, A. Cancer Res. (1993) [Pubmed]
  21. Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26). Danks, M.K., Yalowich, J.C., Beck, W.T. Cancer Res. (1987) [Pubmed]
  22. Snail neurons as a possible model for testing neurotoxic side effects of antitumor agents: paracrystal formation by Vinca alkaloids. Müller, L.J., Moorer-van Delft, C.M., Roubos, E.W. Cancer Res. (1988) [Pubmed]
  23. Mutation of a single conserved tryptophan in multidrug resistance protein 1 (MRP1/ABCC1) results in loss of drug resistance and selective loss of organic anion transport. Ito, K., Olsen, S.L., Qiu, W., Deeley, R.G., Cole, S.P. J. Biol. Chem. (2001) [Pubmed]
  24. Inhibition of phytohemagglutinin-, periodate- and A23187-induced lymphocyte transformation by vinca alkaloids. Schultz, J.C., Martin, J.M., Shahidi, N.T. Exp. Cell Res. (1979) [Pubmed]
  25. Role of chemotherapy in the treatment of lung cancer: evolving strategies for non-small cell histologies. Muggia, F.M., Blum, R.H., Foreman, J.D. Int. J. Radiat. Oncol. Biol. Phys. (1984) [Pubmed]
  26. Frequency and prognostic importance of pretreatment clinical characteristics in patients with advanced non-small-cell lung cancer treated with combination chemotherapy. O'Connell, J.P., Kris, M.G., Gralla, R.J., Groshen, S., Trust, A., Fiore, J.J., Kelsen, D.P., Heelan, R.T., Golbey, R.B. J. Clin. Oncol. (1986) [Pubmed]
  27. Biological characterization of multidrug-resistant human colon carcinoma sublines induced/selected by two methods. Yang, L.Y., Trujillo, J.M. Cancer Res. (1990) [Pubmed]
  28. Atypical multidrug resistance in a therapy-induced drug-resistant human leukemia cell line (LALW-2): resistance to Vinca alkaloids independent of P-glycoprotein. Haber, M., Norris, M.D., Kavallaris, M., Bell, D.R., Davey, R.A., White, L., Stewart, B.W. Cancer Res. (1989) [Pubmed]
  29. Treatment of idiopathic thrombocytopenic purpura (ITP). Ahn, Y.S., Harrington, W.J. Annu. Rev. Med. (1977) [Pubmed]
  30. Verapamil-mediated sensitization of doxorubicin-selected pleiotropic resistance in human sarcoma cells: selectivity for drugs which produce DNA scission. Harker, W.G., Bauer, D., Etiz, B.B., Newman, R.A., Sikic, B.I. Cancer Res. (1986) [Pubmed]
  31. Extensive contribution of the multidrug transporters P-glycoprotein and Mrp1 to basal drug resistance. Allen, J.D., Brinkhuis, R.F., van Deemter, L., Wijnholds, J., Schinkel, A.H. Cancer Res. (2000) [Pubmed]
  32. Detoxication of vinca alkaloids by human P450 CYP3A4-mediated metabolism: implications for the development of drug resistance. Yao, D., Ding, S., Burchell, B., Wolf, C.R., Friedberg, T. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  33. Lipids: A key role in multidrug resistance? (Review). Pallarés-Trujillo, J., López-Soriano, F.J., Argilés, J.M. Int. J. Oncol. (2000) [Pubmed]
  34. Identification and characterization of the canine multidrug resistance-associated protein. Ma, L., Pratt, S.E., Cao, J., Dantzig, A.H., Moore, R.E., Slapak, C.A. Mol. Cancer Ther. (2002) [Pubmed]
  35. An update on the anticancer effects of a combination of chemotherapy and hyperthermia. Bull, J.M. Cancer Res. (1984) [Pubmed]
  36. Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D. Johnson, D.A., Laguzza, B.C. Cancer Res. (1987) [Pubmed]
  37. In vitro antagonism between cisplatin and vinca alkaloids. Lee, K., Tanaka, M., Kanamaru, H., Hashimura, T., Yamamoto, I., Konishi, J., Kuze, F. Br. J. Cancer (1989) [Pubmed]
  38. Molecular characterization of a cytokinin-inducible periwinkle protein showing sequence homology with pathogenesis-related proteins and the Bet v 1 allergen family. Carpin, S., Laffer, S., Schoentgen, F., Valenta, R., Chénieux, J.C., Rideau, M., Hamdi, S. Plant Mol. Biol. (1998) [Pubmed]
  39. Progesterone biotransformation by plant cell suspension cultures. Yagen, B., Gallili, G.E., Mateles, R.I. Appl. Environ. Microbiol. (1978) [Pubmed]
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