Mitomycin Doxorubicin

Dextran cross-linked functionalized by carboxymethylation 10-30 Intratumor direct delivery Doxorubicin mitomycin... 

Carcinoma of lung Cisplatin plus taxane Methotrexate, vincristine, vinblastine, doxorubicin, mitomycin C... 

Solomon B, Soulen MC, Baum RA, et al. (1999) Chemo-embolization of hepatocellular carcinoma with cisplatin, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol prospective evaluation of response and survival in a U.S. population. J Vase Interv Radiol 10 793-798... 

Forgfics and Cserh iti [513] studied 21 anticancer drugs with the intention of determining the relative hydrophobicities of these drugs. Retention of these compounds (e.g., vinblastine, paraplatin, doxorubicin, mitomycin C, methotrexate. 

In an attempt to achieve higher tumour selectivity, antibody-directed enzyme prodrug therapy (ADEPT) has been applied to phosphate prodrugs of the anticancer drugs etoposide, doxorubicin, mitomycin and phenol mustard [127, 128]. The prodrugs release the parent drug at the tumour by hydrolysis catalyzed by alkaline phosphatase linked to a tumour-selective antibody. 

Table 2.5.2. Results of chemoembolization in hepatocellular cancer (literature review). (A, Adria Adriamycin, ADMOS doxorubicin+mitomycin+lipiodol, CDDP cisplatin, Collaghovine collagen, CTLS CDDP+pirarubicin, DSM degradable starch microspheres, Epi epirubicin, F 5-FU 5-fluorouracil, FUDR 5-fluorodeoxyuridine, Gel gelfoam, Lipi /ipiodol, M, Mito mitomycin, Mo months, N/A not available. Neuroend TM neuroendocrine tumors, PVA polyvinyl alcohol, STZ streptozotocin)...

The importance of superoxide-mediated damage to cancer cells was also demonstrated in the experiments with overexpressed mitochondrial MnSOD. Hirose et al. [186] showed that the overexpression of mitochondrial MnSOD enhanced the survival of human melanoma cells exposed to cytokines IL-1 and TNF-a, anticancer antibiotics doxorubicin and mitomycin C, and y-irradiation. Similarly, Motoori et al. [187] found that overexpression of MnSOD reduced the levels of reactive oxygen species in mitochondria, the intracellular production of 4-hydroxy-2-nonenal, and prevented radiation-induced cell death in human hepatocellular... 

I 12. The answer is b. (Hardman, pp 1264-1265J Dactinomycin s major toxicities include stomatitis, alopecia, and bone marrow depression. Bleomycin s toxicities include edema of the hands, alopecia, and stomatitis. Mitomycin causes marked bone marrow depression, renal toxicity, and interstitial pneumonitis. Plicamycin causes thrombocytopenia, leukopenia, liver toxicity, and hypocalcemia. The latter may be of use in the treatment of hypercalcemia. Doxorubicin causes cardiotoxicity, as well as alopecia and bone marrow depression. The cardiotoxicity has been linked to a lipid peroxidation within cardiac cells. 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

G. M. Dubowchik, K. Mosure, J. O. Knype, R. A. Firestone, Cathepsin B-Sensitive Dipeptide Prodrugs. 2. Models of Anticancer Drugs Pachtaxel, Mitomycin C and Doxorubicin , Bioorg. Med. Chem. Lett. 1998, 8, 3347-3352. 

The so-called self-immolative prodrugs are other relevant and intriguing examples as candidates for ADEPT (Fig. 8.17). Here, the primary bioactivation product is not the active agent, but an intermediate that breaks down spontaneously to liberate this active agent. Various cytotoxic drugs that bear an amino group were investigated, i. e., 4-[bis(2-chloroethyl)amino]aniline, actinomycin D, doxorubicin, and mitomycin C [206]. These were trans-... 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Difference in diameter of inhibition zone between Bacillus sublilis M45 (rec -) and HI 7 (rec +), diameter of inhibition zone on M45 minus that on H17 —diameters are same, =less than 2 mm, +=between 2 and 5 mm, ++=more than 5 mm. A positive control is mitomycin C (0.75 (ig/disk) the difference of inhibition zone is 6 mm. Inhibition zones of a negative control (kanamicin) were same for the both strains cCCfo of doxorubicin was 2 ng/mL. 

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer (see Chapter 62). In fact, most major anticancer drugs are derived from plants or microorganisms. Important examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, paclitaxel... 

Gastric adenocarcinoma Fluorouracil, doxorubicin (Adriamycin), and mitomycin (FAM), or fluorouracil and semustine. 

P-Carotene has been shown to enhance the cytotoxicity of melphalan and BCNU on human squamous carcinoma cells and of cisplatin and dacarbazine on melanoma cells. In mice with transplanted mammary carcinoma, P-carotene enhanced the antitumor effect of cyclophosphamide, and in mice transplanted with Fsall fibrosarcoma or SCC VII carcinoma, p-carotene enhanced the antitumor effect of melphalan, BCNU, doxorubicin, and etoposide. p-Carotene (5 to 50 mg/kg) has been shown to reduce the genotoxicity of cyclophosphamide in mice and of mitomycin C, methyl methanesulfonate, and bleomycin in cultured cells. P-Carotene also reduced the rate of tumor induction in animals receiving chronic low doses of cyclophosphamide. 

Carcinoma of cervix Radiation plus cisplatin (localized), cisplatin, carboplatin (metastatic) Lomustine, cyclophosphamide, doxorubicin, methotrexate, mitomycin, bleomycin, vincristine, interferon, 13-cA-retinoic acid... 

Insulinoma Streptozocin, interferon Doxorubicin, fluorouracil, mitomycin, streptozocin... 

Using PEGylated liposomal doxorubicin (Caelyx), Keller et al. [427] compared the efficacy of the liposomal formulation with that of a common regimen in patients with taxane-refractory advanced breast cancer. The regimen scheme was Caelyx (50 mg/m2 every 28 weeks) or vinorelbine (30 mg/m2) or mitomycin C (10 mg/m2 every 28 days) plus vinblastine (5mg/m2 at days 1,14, 28, 42). Finally, progression free survival and overall survival were similar for Caelyx and the comparative regimen. 

Keller, A. M., Mennel, R. G., Georgoulias, V. A., Nabholtz, J. M., Erazo, A., Lluch, A., Vogel, C. L., Kaufmann, M., Minckwitz, G., Henderson, G., Mellars, L., Alland, L., and Tendler, G. (2004), Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxane-refractory advanced breast cancer./. Clin. Oncol., 22, 3893-3901. 

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