Abstract. We previously reported satisfactory therapeutic results when using cisplatin-based cyclic balloon-occluded arterial infusion chemotherapy as neoadjuvant chemotherapy (NAC), which enabled hysterectomy to be performed for patients with locally advanced cervical cancer. Mitotic arrest deficiency 2 (MAD2) is a key component of the mitotic spindle checkpoint pathway. The expression of MAD2 is associated with tumor progression and resistance to chemotherapy. Therefore, the aim of the present study was to examine whether the expression of MAD2 is related to the efficacy of NAC for locally advanced uterine cervical cancer. We reviewed 53 cases of locally advanced uterine cervical cancer (stage IIIa-IIIb; based on the International Federation of Gynecology and Obstetrics criteria). These patients were initially treated at Osaka City University Medical School Hospital, Japan, from 1995 to 2008 and were under 70 years old. Tumor samples were obtained by biopsy prior to NAC. Cases were divided into two groups: one group in which NAC was effective, surgery was possible and radiotherapy was performed (NAC+OP+R group; n=33), and another group in which NAC was ineffective and radiation therapy was performed (NAC+R group; n=20). MAD2 expression was examined in paraffin-embedded sections using the avidin-biotin peroxidase complex method. The results showed that MAD2 expression was significantly higher in the NAC+R group compared to the NAC+OP+R group (P<0.001). There was no significant difference in overall survival between the two groups, although the prognosis for the NAC+OP+R group tended to be slightly better (P= 0.064). Taken together, these results suggest that the expression of MAD2 may predict the efficacy of NAC as a treatment for locally advanced uterine cervical cancer.

Mitotic-arrest deficiency 2 (MAD2) is a key component of spindle assembly checkpoint (SAC) function; SAC mediates spindle microtubule attachment to kinetochores on chromosomes and chromosomal segregation during mitosis. To determine whether MAD2 expression is associated with chemotherapy resistance in ovarian serous adenocarcinoma, we reviewed tumor samples from 41 cases of ovarian serous adenocarcinoma at Osaka City University Medical School Hospital (Osaka, Japan), 2000-2007. Of the 41 cases, 24 were recurrent and 17 were not recurrent. Expression of MAD2 was investigated in paraffin-embedded sections using a MAD2 antibody. Quantitative analysis of MAD2 expression gave mean weighted scores of 4.3 for the relapsed group and 7.2 for the relapse-free group; the expression was, thus, significantly greater in the relapse-free group compared to the relapsed group (P=0.023). When the 41 cases were classified into low- and high-expression, these classifications showed no significant difference in terms of progression-free survival (P=0.0685), however, overall survival for the low-expression group was significantly shorter than that of the high-expression group (P=0.0188). The present study implies that MAD2 expression levels can indicate sensitivity to anticancer agents, and risk for recurrence.

Abstract. The aim of the present study was to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with Müllerian carcinoma treated at our hospital. Nineteen patients with platinum-resistant Müllerian carcinoma were treated with intravenous PLD 50 mg/m 2 every 4 weeks. Tumor response was assessed by MRI following every 2-3 cycles of treatment. The severity of adverse events was assessed according to the Common Terminology Criteria for Adverse Events (v3.0). The best overall responses in the 19 patients were identified as 5 partial responses (PR), 6 stable diseases (SD) and 8 progressive diseases (PD). Response rate was 26.3%. The proportion of patients with CR, PR or SD was 57.9%. The median time to progression was 188.0 days. The median survival time was 381.0 days. Toxicity grades were identified as one grade III hand-foot syndrome, two grade III neutropenia, one grade IV hand-foot syndrome, one grade IV stomatitis and one grade IV neutropenia. The present study confirmed that PLD is an effective drug when administered as a salvage therapy for the treatment of Müllerian carcinoma and is associated with a reduced toxicity profile compared with current therapeutic options.

Abstract. Mitotic arrest deficiency 2 (MAD2) is a key component of the mitotic spindle checkpoint pathway. A compromised mitotic spindle checkpoint results in an abnormal number of chromosomes. This is referred to as chromosomal instability, and has been reported in most types of human cancer. The aim of this study was to examine the expression of MAD2 in mucinous ovarian tumors exhibiting varying degrees of malignancy. We reviewed 128 cases of mucinous ovarian tumors initially treated at Osaka City University Medical School Hospital, Japan. Tumor samples were obtained following surgery. The cases were divided into three groups: benign (group B; n=30), borderline malignant (group BM; n=55) and malignant (group M; n=43). MAD2 expression was examined in paraffin-embedded sections using the avidin-biotin peroxidase complex method. Results showed MAD2 expression to be significantly greater in group M compared to groups B and BM (P<0.05). In addition, there was a moderate correlation between MAD2 expression and the degree of malignancy (r=0.51, P<0.05). However, when the samples in group M were classified according to a low or high expression of MAD2, no difference was observed in terms of overall survival. These findings suggest that the overexpression of MAD2 may be correlated to carcinogenesis in mucinous ovarian tumors.