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In this study, we evaluate the analgesic effect of strontium-89 (Sr-89) for patients with breast cancer having multiple bone metastases and identify positive predictive factors. We retrospectively evaluated 15 patients who were administered Sr-89 for painful bone metastases from breast cancer at St. Marianna University Hospital between January 2010 and April 2014. For patients receiving multiple doses, only the first dose was evaluated. Pain relief was defined as a decrease in the score of the Numeric Rating Scale (NRS) or requirement of reduced doses of pain medication 1 - 2 months after being on Sr-89 administration. The associations between pain relief owing to Sr-89 and that owing to bone scan index, interval from bone metastasis onset to Sr-89 administration, zoledronate and denosumab treatment history, hormone therapy/aromatase inhibitor history, and chemotherapy history were assessed. A logistic model was used for statistical analysis. Pain relief was observed in 11 (73.3%) of 15 patients. No statistically significant value was observed between pain relief and bone scan index, interval from bone metastasis onset to Sr-89 administration, zoledronate and denosumab treatment history, hormone therapy/aromatase inhibitor history, and chemotherapy. Thus, Sr-89 was effective for 70% of patients with breast cancer bone metastases, although positive predictive factors for pain relief could not be determined.

Background Standard chemoradiotherapy (CRT) using 5-FU and CDDP is the optimal treatment for patients with stage II/III (non-T4) esophageal carcinoma. However, patient quality of life (QOL) cannot necessarily be maintained during this therapy, because 5-FU must be continuously infused for 24 h and CDDP administration requires a large transfusion volume. Therefore, hospitalization is unavoidable. We conducted a study of definitive CRT with S-1 and nedaplatin.

Although radical hysterectomy is the standard surgical treatment for patients with stage IB and II cervical cancer, it does not improve the prognosis of high-risk patients even if postoperative radiotherapy is added. There is therefore a need to establish some other therapeutic regimen. In the present retrospective study, the efficacy of concurrent nedaplatin after radical hysterectomy in high-risk stage IB to II cervical cancer was analyzed. From 1995 through 2005, patients with an International Federation of Gynecology and Obstetrics stage of IB2 and II cervical cancer who were given only radiotherapy (RT; n = 17) or postoperative concurrent chemoradiotherapy with biweekly nedaplatin at 70 mg/m(2) (p-CCRT; n = 13) were entered. All of the patients had at least one of the following risk factors: lymphovascular space infiltration, positive lymph nodes, or parametrial invasion. There was no significant difference between the RT and p-CCRT groups with regard to mean age and risk factors, except that more patients in the p-CCRT group had positive lymph nodes (P < 0.05). Five-year progression-free survival and overall survival after RT versus p-CCRT were 76.0% versus 83.3%, and 81.9% versus 83.3%, respectively. Although many patients in the p-CCRT group had positive lymph nodes, there was no significant difference in either PFS or OS. No grade 4 myelosuppression or other severe side effects were seen in the p-CCRT group. As CCRT with nedaplatin might have some benefit, a randomized control trial should be conducted in the future.

The breast and ovarian tumor suppressor BRCA1 constitutes a RING heterodimer E3 ligase with BARD1. BRCA1-associated protein 1 (BAP1) is a ubiquitin COOH-terminal hydrolase that was initially identified as a protein that bound to the RING finger domain of BRCA1. However, how BAP1 contributes to the E3 activity of BRCA1/BARD1 is unclear. Here, we report that BAP1 interacts with BARD1 to inhibit the E3 ligase activity of BRCA1/BARD1. Domains comprised by residues 182-365 of BAP1 interact with the RING finger domain of BARD1, and surface plasmon resonance spectroscopy (BIAcore) analyses showed that BAP1 interferes with the BRCA1/BARD1 association. The perturbation resulted in inhibition of BRCA1 autoubiquitination and NPM1/B23 ubiquitination by BRCA1/BARD1. Although BAP1 was capable of deubiquitinating the polyubiquitin chains mediated by BRCA1/BARD1 in vitro, a catalytically inactive mutant of BAP1, C91S, still inhibited the ubiquitination in vitro and in vivo, implicating a second mechanism of action. Importantly, inhibition of BAP1 expression by short hairpin RNA resulted in hypersensitivity of the cells to ionizing irradiation and in retardation of S-phase progression. Together, these results suggest that BAP1 and BRCA1/BARD1 coordinately regulate ubiquitination during the DNA damage response and the cell cycle. [Cancer Res 2009;69(1):111–9]