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Progress in Clinical and Biological... 1989
Review
Topics: Administration, Intravesical; Carcinoma in Situ; Humans; Instillation, Drug; Mitomycin; Mitomycins; Urinary Bladder Neoplasms
PubMed: 2506555
DOI: No ID Found -
Urologia Oct 2016If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been...
If we think about the launch date of Mitomycin C, we could think that this supplement is very much focused on history of Medicine, and, yes, Mitomycin certainly has been a main contributor to the history of Urology. However, it is even more striking to think that even after fifty years of its use by Urologists worlwide, Mitomycin C remains an absolute "Must". The simplicity of use, the efficacy and the tolerability of Mitomycin explain its established role. In fact, "long standing" does not mean "old". The new technologies, introduced progressively in the last decades, have fully confirmed the present and future role of this drug, that is well illustrated in the articles contained in this supplement. I hope you will enjoy reading it and (re)discovering Mitomycin C.
Topics: Humans; Mitomycin
PubMed: 27768212
DOI: 10.5301/RU.2016.16271 -
Seminars in Oncology Jun 1988The pharmacokinetics of mitomycin C are reviewed from reports using specific and sensitive high-performance liquid chromatography (HPLC) assays. These studies... (Review)
Review
The pharmacokinetics of mitomycin C are reviewed from reports using specific and sensitive high-performance liquid chromatography (HPLC) assays. These studies demonstrate a rapid, biphasic elimination pattern for the drug: alpha half-life of 8 minutes and beta, or terminal, half-life of 48 minutes. Urinary elimination of intact drug is minimal (8% to 10% of a dose), whereas biliary drug levels may exceed those in the plasma. There was no evidence of dose dependent pharmacokinetics over a wide range of doses and patient populations, including pediatric solid tumor patients. Metabolic studies with mitomycin C have demonstrated an absolute requirement for reductive enzymatic activation of the drug to mono- and bifunctional alkylating species. The preferred DNA target for covalent attachment by mitomycin C was found to be the N2 position of guanine. Chemical metabolites of activated mitomycin C were also demonstrated to include 2, 7 diaminomitosene and its cis- and trans-1-hydroxy or 1-phosphate analogues. Also, there was no evidence for hypoxic cell selectivity for mitomycin C in several human tumor cell lines, although some animal tumors unequivocally display this phenomenon. Finally, there are new observations of the development of the multidrug-resistance phenotype in mitomycin C-treated L-1210 cells in vitro. These cells became collaterally resistant to anthracyclines and vinca alkaloids and expressed the P-glycoprotein in cell membranes. The implications of these findings for mitomycin C use in solid tumors in humans is discussed.
Topics: Biotransformation; Drug Resistance; Free Radicals; Humans; Mitomycin; Mitomycins
PubMed: 3134696
DOI: No ID Found -
Bioorganic Chemistry Nov 2019Mitomycin C (MC), an anti-cancer drug, and its analog, decarbamoylmitomycin C (DMC), are DNA-alkylating agents. MC is currently used in the clinics and its cytotoxicity...
Mitomycin C (MC), an anti-cancer drug, and its analog, decarbamoylmitomycin C (DMC), are DNA-alkylating agents. MC is currently used in the clinics and its cytotoxicity is mainly due to its ability to form Interstrand Crosslinks (ICLs) which impede DNA replication and, thereby, block cancer cells proliferation. However, both MC and DMC are also able to generate monoadducts with DNA. In particular, we recently discovered that DMC, like MC, can form deoxyadenosine (dA) monoadducts with DNA. The biological role played by these monoadducts is worthy of investigation. To probe the role of these adducts and to detect them in enzymatic digests of DNA extracted from culture cells treated by both drugs, we need access to reference compounds i.e. MC and DMC dA-mononucleoside adducts. Previous biomimetic methods used to generate MC and DMC mononucleoside adducts are cumbersome and very low yielding. Here, we describe the diastereospecific chemical synthesis of both C-1 epimers of MC and DMC deoxyadenosine adducts. The key step of the synthesis involves an aromatic substitution reaction between a 6-fluoropurine 2'-deoxyribonucleoside and appropriately protected stereoisomeric triaminomitosenes to form protected-MC-dA adducts with either an S or R stereochemical configuration at the adenine-mitosene linkage. Fluoride-based deprotection methods generated the final four reference compounds: the two stereoisomeric MC-dA adducts and the two stereoisomeric DMC-dA adducts. The MC and DMC-dA adducts synthesized here will serve as standards for the detection and identification of such adducts formed in the DNA of culture cells treated with both drugs.
Topics: Alkylation; DNA Adducts; Deoxyadenosines; Fungal Proteins; Mitomycin; Mitomycins; Molecular Conformation; Single-Strand Specific DNA and RNA Endonucleases; Stereoisomerism
PubMed: 31539740
DOI: 10.1016/j.bioorg.2019.103280 -
Seminars in Oncology Jun 1988Mitomycin C has a documented response rate of 20% to 30% when used as treatment in advanced breast cancer. Because of its delayed and cumulative hematologic toxicity,... (Review)
Review
Mitomycin C has a documented response rate of 20% to 30% when used as treatment in advanced breast cancer. Because of its delayed and cumulative hematologic toxicity, there has been a reluctance to use this agent. However, by lowering the drug dosage, the hematologic, pulmonary, and renal toxicities have been reduced. The reduced dosage does not appear to have compromised the treatment results.
Topics: Breast Neoplasms; Female; Humans; Mitomycin; Mitomycins
PubMed: 3134697
DOI: No ID Found -
Cancer Mar 1983Mitomycin C extravasation produces a chronic painful ulceration similar to that of adriamycin. Pain marks the extravasation of this chemotherapeutic agent when it...
Mitomycin C extravasation produces a chronic painful ulceration similar to that of adriamycin. Pain marks the extravasation of this chemotherapeutic agent when it occurs. A complaint of pain during mitomycin administration should prompt immediate cessation of infusion and regular frequent follow-up. Ulceration may not appear for one to two weeks after initial injury. Wide local excision with subsequent split thickness skin grafting is recommended.
Topics: Female; Humans; Infusions, Parenteral; Male; Middle Aged; Mitomycin; Mitomycins; Prognosis; Skin Transplantation; Skin Ulcer
PubMed: 6401597
DOI: 10.1002/1097-0142(19830315)51:6<1080::aid-cncr2820510618>3.0.co;2-y -
Science (New York, N.Y.) Nov 1963The presence of an aziridine ring in mitomycin C suggests that the mechanism of action of the antibiotic is like that of the antitumor alkylating agents. However the...
The presence of an aziridine ring in mitomycin C suggests that the mechanism of action of the antibiotic is like that of the antitumor alkylating agents. However the compound is unexpectedly stable during aerobic incubation with rat liver homogenates although rapidly metabolized anaerobically. Mitomycin is not reactive with gamma-(4-nitrobenzyl) pyridine and reacts only slowly at acid p(H) with thiosulfate. It is proposed that mitomycin is activated in vivo, possibly by a reduction which "unmasks" the potential activity of the fused aziridine ring.
Topics: Alkylation; Chemical Phenomena; Chemistry; Liver; Mitomycin; Mitomycins; Pharmacology; Rats; Research
PubMed: 14069241
DOI: 10.1126/science.142.3596.1181 -
Ophthalmology Nov 1992
Topics: Eye Diseases; Humans; Mitomycin; Postoperative Complications; Pterygium; Recurrence
PubMed: 1454337
DOI: 10.1016/s0161-6420(92)31750-6 -
Contact Dermatitis Jan 1991
Topics: Administration, Intravesical; Aged; Antineoplastic Agents; Dermatitis, Contact; Female; Humans; Mitomycin; Mitomycins
PubMed: 1904339
DOI: 10.1111/j.1600-0536.1991.tb01645.x -
The Biochemical Journal Feb 1995Poly[d(G-m5C)] was modified by reductively activated mitomycin C, an anti-tumour drug, under buffer conditions which are known to favour either the B or the Z...
Poly[d(G-m5C)] was modified by reductively activated mitomycin C, an anti-tumour drug, under buffer conditions which are known to favour either the B or the Z conformations of DNA. C.d. and 31P-n.m.r. were used to characterize the poly[d(G-m5C)]-mitomycin cross-linked complexes, as well as the effects on the equilibrium between the B and Z forms of the polynucleotide. Mitomycin C appears to inhibit the B-->Z transition, even in the presence of 3 mM MgCl2, while the Z-form of poly[d(G-m5C)] does not interact significantly with the drug under bifunctionally activating conditions; thus no reversion from the Z-form to the B-form of the polynucleotide can be observed under the salt conditions which are required for the Z-form to exist.
Topics: Circular Dichroism; Cross-Linking Reagents; DNA; Magnetic Resonance Spectroscopy; Mitomycin; Nucleic Acid Conformation; Polydeoxyribonucleotides; Sonication
PubMed: 7864808
DOI: 10.1042/bj3060185