Letter to the Editor Unexpected increase in the bone marrow toxicity of

MMC, a product of Streptomyces caespitosus, is known to be one of the most active agents for various neoplasms and has been widely used throughout the world for over 40 years (Wakaki et al, 1958; Hortobagyi, 1985). Recently, however, we have noticed an unexpected increase in MMC’s toxicity. Although the reasons for this are under investigation, we feel it necessary to draw this matter to the attention of clinicians who prescribe the drug. From 1990 to 1996, we performed a prospective randomized clinical trial comparing the effects of CMF versus MMC plus CMF (MCMF) in the treatment of node-positive, premenopausal breast cancer patients (age ≤ 50) in an adjuvant setting after obtained informed consent. In the MCMF group, the dose and time schedule of MMC was 14 mg/m2 on day 1 immediately after surgery, and 8 mg/m2 on day 2, and 6 cycles of CMF chemotherapy were started after recovery from the toxicity o

RESEARCH ARTICLE XRCC2 Is Required for the Formation of Rad51 Foci Induced by Ionizing Radiation and DNA Cross-Linking Agent

XRCC2 protein shares weak amino acid sequence similarity with Rad51, which is a central player in homologous recombinational repair (HRR). Rad51 proteins assemble at the sites of HRR and form visible nuclear foci in response to DNA damage. Xrcc2 hamster mutant irs1 cells are incapable of forming Rad51 foci after ionizing irradiation or DNA cross-linking agent mitomycin C treatment, though the Rad51 protein level is normal in the mutant. The defect can be corrected in an XRCC2 transformant. Time course study showed that the irs1 cells primarily lacked the early response (2 hours after irradiation) to form small Rad51 foci (type 1) and later response (8 hours after irradiation) to form large foci (type 2). These results suggested that XRCC2 is essential for the assembly of the DNA damage-induced Rad51 foci and that XRCC2 may play an important role in the early stage of HRR

Chemical Modification of DNA with Muta- Carcinogens. III. Reductive Alkylation of

Mitomycin C (MMC) binds to DNA after its reductive activation by catalytic hydrogenation with Pd on charcoal. Three modified nucleotides, named MG-1, MG-2, and MA, were isolated from the modified DNA after enzymatic hydrolysis to 5'-nucleotides. The structures of these modified nucleotides were deduced from their 1H-NMR and UV spectra, and from studies of the chemically transformed derivatives (hydrolysis, methylation, diazotization, and thioketonization). These three modified nucleotides were concluded to be 1,2-trans-2,7-diamino-1-(N2-deoxyguanylyl)mitosene (MG-1), 2,7-diamino-1-(06-deoxyguanylyl)mitosene (MG-2) and 2,7-diamino-l-(N-deoxyadenylyl)mitosene (MA). The same modified nucleotides were identified in DNA extracted from the livers of rats treated with MMC

ORIGINAL ARTICLE – GASTROINTESTINAL ONCOLOGY Incidence, Risk Factors, and Impact of Severe Neutropenia After

Background. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are considered the standard of care for patients with peritoneal dissemination of appendiceal cancer and are increasingly being evaluated for use in patients with carcinomatosis from colon cancer. Mitomycin C (MMC) is one of the most frequently used HIPEC agents in the management of peritoneal-based gastrointestinal malignancies. This study analyzes the incidence and risk factors for developing neutropenia following MMC-HIPEC combined with CRS. Methods. All patients undergoing CRS and MMC-HIPEC for appendiceal cancer between January 1993 and October 2006 were retrospectively reviewed. Logistic regression was used to identify risk factors for the development o

Original Article Comparison of the Outcome of Repeat Trabeculectomy with

Purpose: To compare the efficacy and safety of repeat and initial trabeculectomy with mitomycine C (MMC). Methods: Eighty seven patients, who had underwent repeat (repeat group) or initial (initial group) trabeculectomy with MMC, were enrolled in this prospective trial. Postoperative outcome measures included the amount of decrease in intraocular pressure (IOP), the number of anti-glaucoma medications, and the complications. The success of trabeculectomy was defined on the basis of three definitions which were: IOP ≤18 mmHg (definition 1), IOP ≤21 mmHg (definition 2), and the amount of decrease in IOP from baseline ≥30 % (definition 3). Success was further defined as “complete ” when these criteria were obtained without any anti-glaucoma medications and “qualified ” with or without medical therapy and no further surgical procedures. Results: Fifty nine eyes underwent initial and 28 eyes underwent repeat trabeculectomy. The mean follow-up period was 19.1 ± 5.9 months. Complete success rates were significantly greater in the initial trabeculectomy group (p = 0.02 for definition 1, p = 0.038 for definition 2, p = 0.003 for definition 3). A higher proportion of eyes in the initial group achieved qualified success relative to the group A eyes, but the differences were not statistically significant (p = 0.33 for definition 1, p = 0.99 for definition 2, p = 0.24 for definition 3). The mean number of antiglaucomatous medications at the last examination was 1.2 ± 1.2 in repeat group and 0.7 ± 1.1 in initial group (p = 0.01). The number of complications during the follow up period did not differ significantly between the two groups (p = 0.65)

Treatment of Low-Grade Bulbar Transitional Cell Carcinoma with Urethral Instillation of

A 63-year old man was referred to us after three rapid recurrences of low-grade urethral papillary transitional cell carcinoma of the bulbar urethra, after repeated primary excision. Cystoscopy confirmed 3-4 low-grade urethral transitional cell carcinomas, which were subsequently fulgurated. After urethral healing, a solution of Mitomycin C (40 mg/80 cc) was instilled into the urethra for fifteen minutes and held in place with a penile clamp. Urethral instillations were repeated weekly for six weeks. The patient is currently disease-free more than one year and three months posttreatment. This case highlights the successful treatment of urethral carcinoma with topical chemotherapy, which is usually reserved for the bladder, using a slight modification of standard technique. Copyright © 2008 E. J. Melonakos and R. A. Santucci. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

Priority Report In vivo Role of NAD(P)H:Quinone Oxidoreductase 1 in Metabolic

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TABLE 1 Response of Bronchogenic Carcinoma to Single Agent Chemotherapy by Cell Type

Hodgkin's disease, and breast cancer [19-22]. The rationale for combination chemotherapy is based upon the concept that the effectiveness of antitumor agents may be enhanced by concurrent and sequential inhibition of metabolic pathways for DNA biosynthesis [23], which could yield additive or synergistic effects. Additionally, it is possible that the use of multiple agents, by analogy to antibiotic usage in the management of infectious disease, could reduce the development of drug resistance [24]. In actual clinical practice, however, combinations of drugs are generally selected on the basis of known effectiveness of each component drug in the disease and divergent toxicity of the component drugs. Despite the widespread use of combination chemotherapy, relatively little attention has been given to possible detrimental results. Drug interactions could prove to be antagonistic, so that agents, known to be effective when used singly, would become ineffective in combination. There is also the potential for ineffectiveness of a known active compound, when used in combination, due to the dose-response requirements of the individual agent. Combinations generally include doses lower than those used when compounds are administered singly. Certain agents, to be effective, may require higher doses to elicit a response than those doses employed in combinations. In the design of clinical trials with drugs in combinations, consideration of these possible adverse effects is merited. NON-SMALL CELL CARCINOMA In evaluating antitumor response in patients with non-small cell carcinoma, the effectiveness of treatment may be assessed in relation to cell type and stage of disease (Table 1) [1 1]. Factors such as performance status, complicating illness, and age are important determinants in the outcome [25,26]. Early studies with single agent chemotherapy in cases with advanced disease suggested generally low response rates in patients with epidermoid carcinoma and

Cystic Bleb Formation and Related Complications in Limbus- versus Fornix- Based Conjunctival Flaps in Pediatric and Young Adult Trabeculectomy with

Objective: Comparison of fornix- and limbus-based conjunctival flaps with respect to cystic bleb-related complications of trabeculectomy with high-dose mitomycin C (MMC) in pediatric and young adult glaucoma. Design: Retrospective nonrandomized comparative interventional case series. Participants: Thirty-seven patients. Methods: Identification of patients aged �30 years from operating theater records from 1995 and 1996 of the Moorfields Pediatric Glaucoma Service who had trabeculectomy with an MMC concentration of �0.4 mg/ml. Over a 2-year period, 37 consecutive operations matching these criteria were performed by a single surgeon: 20 with a limbus-based flap and 17 with a fornix-based flap. Except for the conjunctival incision and associated alteration in antimetabolite application and wound closure, the surgical technique was not significantly different between the groups. Main Outcome Measures: Bleb evolution and complications. Results: The age at time of surgery, MMC concentration, history of one or more previous surgeries, and follow-up were similar in the 2 groups. The risk of cystic bleb formation was greater in the limbus-based flap group (90 % in the limbus-based group vs. 29 % in the fornix-based group; P�0.001). Late hypotony and bleb-related ocular infection were more common in the limbus-based flap group (P�0.05) and occurred earlier