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[en] Pulse radiolysis of aqueous solutions containing adriamycin and redox indicators of known one-electron reduction potential (E1) shows that its E1 at pH 7 is -328 mV (vs NHE). The variation E1 with pH in the range 6-12 shows that the net charge on the semiquinone at pH 7 is zero. As well as the pKa values of 2.9 and greater than or equal to 14 established independently, the semiquinone has a pKa close to 9.2. The new data enable the structure and likely reactivity of the semiquinone to be specified
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Archives of Biochemistry and Biophysics; ISSN 0003-9861;
; v. 225(1); p. 116-121

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[en] In an effort to develop effictive combination treatments for use with radiation against solid tumors, the cytotoxic effects of the addition of mitomycin C or porfiromycin on treatment with Fluosol-DA/carbogen breathing and radiation in the FSaIIC tumor system were studied. In vitro mitomycin C and porfiromycin were both preferentially cytotoxic toward hypoxic FSaIIC cells. After in vivo exposure, however, the cytotoxicity of mitomycin C toward single cell tumor suspensions obtained from whole tumors was exponential over the dose range studied, but for porfiromycin a plateau in cell killing was observed. With Fluosol-DA/carbogen breathing and single dose radiaiton, addition of either mitomycin C or porfiromycin increased the tumor cell kill achieved at 5 Gy by approximately 1.2 and 1.0 logs, respectively. Less effect was seen with addition of the drugs at the 10 and 15 Gy radiation doses. In tumor growth delay experiments, the addition of either mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation resulted in primarily an additive increase in tumor growth delay. The survival of Hoechst 33342 dye-selected tumor cell subpopulations indicated that Fluosol-DA/carbogen breathing increased the cytotoxicity of radiation (10 Gy) more in the bright cell subpopulation (4-fold) than in the dim cell subpopulation (2-fold) resulting in an overall 4-fold sparing of the dim subpopulation. Mitomycin C and porfiromycin were both more toxic toward the dim cell subpopulations. Addition of mitomycin C or porfiromycin to Fluosol-DA/carbogen breathing and radiation (10 Gy) resulted in a primarily additive effect of the drugs and radiation killing in both tumor cell subpopulations. Thus, with mitomycin C/Fluosol-DA/carbogen and radiation there was a 2-fold sparing of dim cells and with profiromycin in the combined treatment a 1.6-fold sparing of the dim cell population. Our results indicate that treatment stragegies directed against both oxic and hypoxic tumor subpopulations can markedly increase the tumor cell kill achieved by radiation. (author). 56 refs.; 4 figs.; 1 tab
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[en] Hepatocellular carcinoma has a poor prognosis and is poorly responsive to systemic chemotherapy. Here a case is described with unresectable hepatocellular carcinoma who achieved a complete of adriamycin and etoposide (VP 16-213)
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[en] Doxorubicin was initially administered alone by continuous infusion for 5 days every 3 weeks in escalating doses to 13 patients with advanced metastatic and/or recurrent malignancies. The maximum tolerable dosage was 13 mg/m2 per day for 5 days. Kinetic data showed a steady level of 60 ng/ml for 4 days and a biphasic disappearance curve. Radiation therapy (150-200 cGy per session) was then administered in 5-day cycles, every 3 weeks, concomitantly with continuous infusion of doxorubicin (12 mg/m2 per day) to 21 patients with various advanced unresectable recurrent or metastatic malignancies. Four of 9 patients with soft tissue sarcomas achieved complete response after a radiation dose of 2,206 +/- 590 (SD) cGy and 3 had partial response; the median durations of the response were 142 +/- 65 (SD) weeks for complete response and 28 +/- 10 weeks for partial response. Of 4 patients with primary hepatoma, 2 achieved partial response after 1,290 +/- 210 cGy. No response was seen in any of the 7 patients with adenocarcinoma of the gastrointestinal tract or breast. Complications of this regimen included moderate leukopenia and thrombocytopenia, mucositis, skin erythema, and decrease of the ventricular ejection fraction at a cumulative doxorubicin dose of 840 mg/m2. We conclude that doxorubicin given by protracted infusion can be safely administered with concomitant radiation and appears to enhance the effects of radiation on most soft tissue sarcomas and on some hepatocellular carcinomas
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NCI Monographs; CODEN NCIME; (no.6); p. 285-290
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[en] In this work, we study magnetic nanotubes (MNTs) as drug carriers to control the loading and release of doxorubicin (Dox). The inner surfaces of MNTs where Dox molecules are stored are modified with C18-silane and pyridine–silane. By tuning the interaction between the drug molecules and inner surfaces of MNTs via pH, Dox can be effectively encapsulated at pH 7.2 and released at pH 4.5. The successful loading of Dox is confirmed with confocal microscopy studies. The release profiles of Dox from modified MNTs are detected by spectrofluorophotometry, with bare MNTs as control. With proper modifications, MNTs can be used for pH-dependent, controlled release of drug molecules
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22 refs, 5 figs
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Bulletin of the Korean Chemical Society; ISSN 0253-2964;
; v. 36(3); p. 772-776

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[en] p-Aminobenzoic acid (PABA), urocanic acid, and sodium urate were found to significantly enhance the photostability of doxorubicin hydrochloride [adriamycin, (ADR)]. d1-Methionine, thiourea, and glycine also increased the photostability of this drug, but to a lesser degree. Sodium thiosulfate on the other hand, was found to be detrimental to the photostability of ADR. The photostabilizing effect of PABA was found to increase with increase of its concentration and was influenced by the pH and the buffer species of the vehicle. The findings would have an impact on the enhancement of therapeutic efficacy of adriamycin when administered during radiation therapy
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[en] 155 adult patients with B-lymphoma in stage I and II who were treated in National Cancer Center Hospital between 1975 and 1986 were analyzed for treatment outcome. 5-year survival rates were about 66 % in these patients and almost equal in the patients treated with radiation alone, doxorubicin-containing combination chemotherapy alone, or combined chemoradiation therapy. However, when analysis was limited to patients in stage I, patients treated with chemotherapy alone seemed to have better survival rate than those treated with radiation alone. In the patients who were in stage III or more and had bulky mass more than 10 cm in diameter, small residual tumor was sometimes detected by restaging procedure after achieving apparent remission by multi-drug chemotherapy. In these patients, additional radiation therapy was quite usefull to eradicate residual tumor cell to cure. (author)
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[en] The mechanism that underlies doxorubicin-induced radiosensitization was investigated in a cell culture system (Hamster lung fibroblasts V79). Results show that doxorubicin inhibits the repair of radiation-induced dsb. Doxorubicin is known to change DNA conformation by the stabilization of DNA topoisomerase II complexes. It is possible that these changes alter the ability of repair enzymes to recognize and correct radiation-induced damage. (author)
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[en] The aminoglycosidic anthracycline adriamycin (ADM) plays an important role in the treatment of acute leukemia and solid tumors in man. For ten years now, it has been believed that ADM gives an intercalation complex with DNA molecules. However, it has been recently shown that immobilized ADM may exert its cytotoxic action only through interactions at the cell surface membrane. The nature of ADM-pharmacological target interactions has been investigated on ADM-DNA complexes by resonance Raman and FT-IR spectroscopy. Moreover, in vivo interactions between ADM and living cancer cells (K562) have been studied using resonance Raman and FT-IR spectroscopy on a small number of cells and by Raman microspectroscopy on a single cell. (author)
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10. symposium on molecularbiological mechanisms of antitumor antibiotics actions; Weimar (German Democratic Republic); 17-22 Sep 1984
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Studia Biophysica; ISSN 0081-6337;
; v. 104(1-3); p. 131-132

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[en] A facile synthesis of the title compounds is described. The key intermediate in the synthesis, 6-demethyl-7,7-(ethylenedioxy)-6-(phenylselenenyl)mitosane (4) was synthesized in five steps from mitomycin A. Treatment of 4 with [14C]methyl iodide in the presence of K2CO3 afforded the [14C]-labelled mitosane (5). The removal of the phenylselenenyl group of 5 and subsequent treatment of the resultant mitosane with ammonia led to the desired [14C]mitomycin C (MMC) with specific activity of 50 mCi/mmol. Similarly, [3H]-labelled MMC with highly specific activity of 78.4 Ci/mmol was obtained. (author)
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Journal of Labelled Compounds and Radiopharmaceuticals; ISSN 0362-4803;
; CODEN JLCRD; v. 29(8); p. 903-908

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