Essential Role of Polo-like Kinase 1 (Plk1) Oncogene in Tumor Growth and Metastasis of Tamoxifen-Resistant Breast Cancer.

The most common therapy for estrogen receptor-positive breast cancer is antihormone therapy, such as tamoxifen. However, acquisition of resistance to tamoxifen in one third of patients presents a serious clinical problem. Polo-like kinase 1 (Plk1) is a key oncogenic regulator of completion of G2-M phase of the cell cycle. We assessed Plk1 expression in five chemoresistant cancer cell types and found that Plk1 and its downstream phosphatase Cdc25c were selectively overexpressed in tamoxifen-resistant MCF-7 (TAMR-MCF-7) breast cancer cells. Real-time monitoring of cell proliferation also showed that TAMR-MCF-7 cells were more sensitive to inhibition of cell proliferation by the ATP-competitive Plk1 inhibitor BI2536 than were the parent MCF-7 cells. Moreover, BI2536 suppressed expression of epithelial-mesenchymal transition marker proteins and 3D spheroid formation in TAMR-MCF-7 cells. Using TAMR-MCF-7 cell-implanted xenograft and spleen-liver metastasis models, we showed that BI2536 inhibited tumor growth and metastasis in vivo Our results suggest that Plk1 could be a novel target for the treatment of tamoxifen-resistant breast cancer. Mol Cancer Ther; 17(4); 825-37. ©2018 AACR.

Homicide and bipolar I disorder: a 22-year study.

BACKGROUND: Non-serious offenses in manic phase have been mainly studied in patients with bipolar disorder. However, some authors reported that depressive phase is related with the violent and homicidal manifestations of bipolar disorder. AIMS: We investigated the characteristics of homicide by the polarity of mood episode in patients with bipolar I disorder. METHODS: Among the offenders who were sentenced to undergo treatment at the National Institute of Forensic Psychiatry from October 1987 to January 2008, a total 219 offenders whose final diagnoses were bipolar I disorder based on DSM-III-R and DSM-IV were selected. Retrospective medical chart review was performed for characteristics of mood episodes. Descriptions of offenders were supplemented by review of the written records of the police or prosecutors. RESULTS: The general rate of total offense was higher in the manic phase than in the depressive phase (86.8% vs. 13.2%). However, the rate of homicide was higher in the depressive phase than in the manic phase. The victims of homicide were more likely to be family members of the patients in depressive phase than in manic phases (96.2% vs. 63.9%, p=0.001). However, parricide was committed only in manic phases. Altruistic motivation of homicide was significantly higher in depressive phase (34.6% vs. 0%, p<0.001) whereas impulsivity was the most common one in manic phases. CONCLUSIONS: The risk of offenses, particularly homicide for family members, should not be overlooked in the depressive phases of bipolar I disorder.

High-frequency microwave ablation method for enhanced cancer treatment with minimized collateral damage.

To overcome the limits of conventional microwave ablation, a new frequency spectrum above 6 GHz has been explored for low-power and low collateral damage ablation procedure. A planar coaxial probe-based applicator, suitable for easy insertion into the human body, was developed for our study to cover a wideband frequency up to 30 GHz. Thermal ablations with small input power (1-3 W) at various microwave frequencies were performed on nude mice xenografted with human breast cancer. Comparative study of ablation efficiencies revealed that 18-GHz microwave results in the largest difference in the temperature rise between cancer and normal tissues as well as the highest ablation efficiency, reaching 20 times that of 2 GHz. Thermal profile study on the composite region of cancer and fat also showed significantly reduced collateral damage using 18 GHz. Application of low-power (1 W) 18-GHz microwave on the nude mice xenografted with human breast cancer cells resulted in recurrence-free treatment. The proposed microwave ablation method can be a very effective process to treat small-sized tumor with minimized invasiveness and collateral damages.

In-vivo measurements of the dielectric properties of breast carcinoma xenografted on nude mice.

A developing method of cancer detection is to use electromagnetic waves to compare the dielectric properties of normal and cancerous tissue. Because most of the previous studies consisted of dielectric measurements taken ex-vivo, this study investigated the advantages of in-vivo measurements, obtained using the newly developed insertion-type planar probe, through the measurements of cancer (MDA MB 231), which was cultivated and implanted into the mammary fat pad of nude mice. Reflection coefficients were obtained in the broadband frequency range from 0.5 to 30 GHz, from which broadband complex permittivity data was extracted. Complex permittivity, in addition to other parameters such as conductivity and characteristic frequency, were used to make comparisons between cancerous tissue, normal muscle tissue and fat tissue, as well as comparisons between in-vivo and ex-vivo measurements. This study investigated the suitability of in-vivo cancer detection using microwaves with the newly developed insertion-type planar probe. Results showed that both sensitivity and specificity of the current method was 97%. In addition, predictive values were 99% for the positive and 94% for the negative, thus greatly enhancing the practicality of this method. In conclusion, it was demonstrated that in-vivo measurements are highly beneficial in studying the potential of microwaves as a diagnostic tool of breast cancer, especially in combination with the newly developed insertion-type planar probe.