Adriamycin association

Recently, electron microscopy revealed that adriamycin-associaled magnetic albumin mtcnnpheros traverse the vascular endothelium of the target tissue after... 

Cumulative organ toxicity also presents a significant obstacle for effective chemotherapy. In many cases, the severity of the toxicity impedes the broader use of an agent. Other specific toxicities are associated with specific agents, for example cardiotoxicity with adriamycin (32), renal toxicity with i7j -platinum (28), and neurotoxicity with vincristine (49). 

In MDR cells, a significant fraction of P-gp is found associated with caveolin-rich membranes, and there is a substantial increase in the number of caveolae and caveolin-1 protein level. For example, both multidrug resistant human colon adenocarcinoma HT-29 cells and adriamycin-resistant breast adenocarcinoma MCF-7 cells display about a 12-fold increase in caveolin expression, which correlates with an approximate fivefold increase in morphologically identifiable caveolae [55], In addition, these cells exhibit increased amounts of phospholipase D and lipids such as cholesterol, glucosylceramide, and sphingomyelin [56, 57], Similarly, taxol-resistant A549 cells display both increased caveolin expression and caveolae numbers [58], While these correlations track with MDR, they do not suggest a simple mechanism for the role of... 

Ross WE, Glaubiger DL, Kohn KW (1978) Protein-associated DNA breaks in cells treated with adriamycin or elhpticine. Biochim Biophys Acta 519(l) 23-30 Rothfuss A, Grompe M (2004) Repair kinetics of genomic interstrand DNA cross-hnks evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway. Mol Cell Biol 24(1) 123-134... 

Short term treatment with TPA sensitized human 2008 ovarian carcinoma cells to cis-platin. This sensitization disappeared completely by seven hours after treatment, indicating that not inhibition, but activation of PKC sensitizes 2008 cells to the antiproliferative activity of cis-platin (Isonishi et al., 1990). Pretreatment of HeLa cells with TPA or PdBu caused a 9-fold increase in cellular sensitivity to cis-platin and 2.5-fold to melphalan, but had now effect on the antiproliferative activity of bleomycin, adriamycin, vincristine, or mitomycin C. The sensitization of HeLa cells by TPA was associated with a 6-fold stimulation of PKC activation and a concentration- and time-dependent increase in cellular platinum content. (Basu et al. 1990). PKC activity was found to be decreased significantly in cis-platin-resistant human small cell lung H69/CP cancer cells compared to the drug-sensitive variant. A similar reduction in PKC activity was noted in ovarian carcinoma 2008 cells that were resistant to cis-platin. A modest decrease in PKC activity was also observed in etoposide-resistant H69 cells but not in taxol-resistant H69 cells or bleomycin-resistant human head and neck carcinoma A-253 cells (Basu et al., 1996), indicating that reduced PKC activity leads to decreased sensitivity in this system. 

Martin (1980) reported self-association of daunomycin (an adriamycin analogue). Therefore, the conjugated ADR is considered to work as a very good carrier of the physically entrapped ADR by providing speciLc interactions between the two ADR molecules as well as nonspeciLc hydrophobic interactions (Yokoyama et al., 1998). 

The three principal classes of cytotoxic agents used in the treatment of cancer all contain carcinogens, for example, Melphalen, a nitrogen mustard, adriamycin, an antitumor antibiotic, and methotrexate, an antimetabolite. Diethylstilbestrol (DES), a drug formerly widely used, has been associated with cancer of the cervix and vagina in the offspring of treated women. 

Yeh, G.C. et al. (1987) Adriamycin resistance in human tumor cells associated with marked alterations in the regulation of the hexose monophosphate shunt and its response to oxidant stress, Cancer Res. 47, 5994-5999. 

Daunomycin and its analog adriamycin are in clinical use as potent antitumor agents in combination chemotherapy against acute lymphocytic leukemia. It has been suggested that the antitumor properties are associated with intercalation of the anthracycline ring of the antibiotic into the DNA of rapidly proliferating neoplastic cells and subsequent blocking of RNA synthesis (72-75). [5]... 

Fig. 5.14 NMR spectroscopy of cellular lipids of sensitive (K562wt), adriamycin-resist-ant (K562adr), and (K562 ads) tumor cells (top to bottom). (Reprinted from Fig. 1 of ref. 101 with permission from the American Association for Cancer ppm Research)...

The formal potentials of adriamycin and quinizarin are almost identical. Therefore, binary monolayers, formed by simultaneous adsorption of both anthraquinones, exhibit only a single voltammetric peak. In these circumstances, traditional elec-troanalytical techniques cannot be used to determine the surface coverages of the individual species. However, as illustrated in Figure 5.29, the large difference in rate constant for the oxidation of the two anthraquinones can be exploited to temporally resolve the charge associated with oxidizing each adsorbate. The only requirement of this approach is that the interfacial kinetics of the individual components should be sufficiently different that two single exponential decays are observed. 

Onuma, M. Odawara, T. Watarai, S. Aida, Y. Ochiai, K. Syuto, B. Matsumoto, K. Yashuda, T. Eujimoto, Y. Izawa, H. Kawakami, Y. Antitumor effect of adriamycin entrapped in liposomes conjugated with monoclonal antibody against tumor-associated antigen of bovine leukemia cells. Jpn. J. Cancer Res. 1986, 77, 1161-1167. 

Curran CF, Luce JK. Ocular adverse reactions associated with adriamycin (doxorubicin). Am J Ophthalmol 1989 108(6) 709-11. 

Mergenthaler HG, BinsackT,WilmannsW. Carcinoma-associated hemolytic-uremic syndrome in a patient receiving 5-fluorour-acil-adriamycin-mitomycin C combination chemotherapy. Oncology 45 11-4,1988. 

AR is a 48-year-old woman who was treated for Hodgkin s disease 15 years ago with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). She now presents with breast cancer and her oncologist feels that chemotherapy with FAC (fluorouracil, doxorubicin [Adriamycin], and cyclophosphamide) is the most appropriate regimen. Her previous chemotherapy included a total of 300 mg/m doxorubicin exposure. Which of the following agents may be utilized to reduce risk of cardiotoxicity associated with the anthracycline therapy she is about to receive ... 

Drummond, J. T., Anthoney, A., Brown, R., and Modrich, P. (1996) Cisplatin and adriamycin resistance are associated with MutLalpha and mismatch repair deficiency in an ovarian tumor cell line. J. Biol. Chem. 16, 19,645-19,648. 

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