Chemotherapeutic agents mitomycin

Several of the naturally occurring indoles also have clinical importance. The dimeric vinca alkaloid vincristine and closely related compounds were among the first of the anti-mitotic class of chemotherapeutic agents for cancer[14]. The mitomycins[15] and derivatives of ellipticine[16] are other examples of compounds having anti-tumour activity. Reserpine, while not now a major drug, was one of the first compounds to show beneficial effects in treatment of mental disorders[17]... 

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). 

Combination studies with PKCa antisense and standard chemotherapeutic agents (cis-platin, mitomycin-C, vinblastine, estracyt and adriamycin) in nude mice that had been transplanted with a variety of human tumors (breast, prostate, large cell lung and small cell lung carcinomas, and melanomas) were found to be additive or superadditive (Geiger et al, 1998). 

Microbial sources have been a very rich source for cancer chemotherapeutic agents. Of particular note is the Strep-tomyces spp., which has been responsible for the production of many approved anticancer agents that are in clinical practice. These agents are represented by highly diverse structural classes exemplified by the anthracycline family (e.g., doxom-bicin, 73) (72-74), actinomycin family (e.g., dactinomycin, 74), glycopeptides family (e.g., bleomycins A2 and B2, 75 and 76) (75), and mitomycin family (e.g., mitomycin C, 77) (72, 76). All these compounds specifically interact with DNA for then-mode of action. 

AO and XO are cytosolic enzymes and are closely related. However, they differ in their substrate/inhibitor specificities. AO is involved in the metabolism of several clinically significant drugs such as famciclovir, zaleplon, zonisamide, and ziprasidone [69-72], XO has a narrower substrate specificity than AO and is mainly active toward purines and pyrimidines. XO plays a role in the oxidation of several chemotherapeutic agents and has been implicated in the bioactivation of mitomycin B [73]. 

There are experimental data which show a synergistic or a potentiating effect of chemotherapeutic agents on PDT [80]. The combination of ACNU and HPD-mediated PDT results in significantly increased cytotoxicity in the 9L gliosarcoma [81]. This effect could further be increased by adding hyperthermia as a third treatment modality. The RIF-1 tumor proved to be insensitive to PDT and to doxorubicin but sensitive to cisplatin with no increased cytotoxic effect when both modalities were combined. In the EMT-6 tumor model all three modalities showed a mild effect when used independently, doxorubicin enhanced significantly the effect of PDT, whereas cisplatin did not [82]. Mitomycin C potentiates the effect of PDT in adenocarcinoma [83]. There are no reported clinical data on the interaction of PDT and chemotherapy. 

Chemoembolization Chemoembolization with the combination of Ivalon and FUDR (800 mg), mitomycin C (10 mg), or cisplatin (150 mg) for colorectal hepatic metastases led to no significant improvement in response or survival. Yamashita et al. (1993), who treated 68 patients with various hepatic metastases using iodized oil and chemotherapeutic agents,noted a response rate of 22% and a median survival of 10 months. A similar result was observed by Inoue et al. (1989), i.e., a partial response rate of 16% and a median survival period of 11 months. We currently do not perform chemoembolization in patients with metastatic colorectal carcinoma because the survival rates have not improved compared to the less aggressive approach of intraarterial chemotherapy. However, Lang and Brown (1993) and Pentecost et al. (1992) are encouraged by their results for chemoembolization of hepatic metastases from colorectal cancer and they believe that the technique can be recommended as palliative treatment. More recently, Pajkos et al. (1998) treated 41 patients with metastatic colorectal carcinoma to the liver with chemoembolization consisting of Adriamycin (50 mg), mitomycin C (8 mg), cisplatin (50 mg), or carboplatin (150 mg), Lipiodol (10 ml), and starch microspheres every 6 weeks, as well as systemic 5FU (425 mg/m ) and leucovorin 20 mg/m for 5 days every 28 days. The response rate was 68% with a median survival time of 15 months. 

The ideal chemotherapeutic agent for transcatheter treatment of primary and metastatic liver cancer is yet to be developed. This agent should combine effectiveness against the tumor and reduced toxicity to the normal or cirrhotic liver. In the near future, some of the above novel drugs are expected to enter the clinical arena and be prospectively tested, whereas some of the currently used chemotherapeutic agents such as doxorubicin, cisplatin and mitomycin C are expected to be tested in a more systematic and prospective way. 

Tris-acryl gelatin microspheres have been proven to be stable in a standard chemoembolization solution and some centers have adopted their use [1]. Tris-acryl gelatin microspheres have been also tested for compatibility with several chemotherapeutic agents and can be mixed with carboplatin, mitomycin C, 5-fluorouracil, or pirarubicin for chemoembolization without any risk of harmfully altering their morphology, dimensions, or geometric characteristics [70]. 

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