Eribulin Treatment Induces High Expression of miR-195 and Inactivates the Wnt/β - catenin Signaling Pathway in Triple-negative Breast Cancer

Triple-negative breast cancer （TNBC） accounts for 10-15％ of all breast cancer cases and shows a poor prognosis with 30％ distant metastasis. With few specific target molecules and ineffective hormonal and anti-HER2 treatment, an alternative therapeutic method for TNBC is urgently required. Recently, a non-taxane inhibitor of microtubule dynamics called eribulin was developed for breast cancer therapy. Eribulin induces irreversible mitotic mass formation in cancer cells during the G2-M phase, initiating apoptosis; however, the mechanism underlying this eribulin activity remains unclear. We reported previously that exposing non-basal-like （NBL） TNBC cells to eribulin increases miR-195 expression, which in turn decreases the expression of targeted Wnt3a. The present study sought to further clarify the mechanism of this antitumor effect by exploring how eribulin affects Wnt/β - catenin signaling based on miRNA expression changes in TNBC. In an NBL type of human breast cancer cell line （MDA-MB-231 cells）, we compared the expression levels of Wnt/β catenin signaling pathway proteins in cells exposed to an miR-195 mimic （cells transfected with miR-195 and in which Wnt3a expression was suppressed） and in cells exposed to eribulin. Expression levels of Wnt3a, β -catenin, and GSK-3β were measured by ELISA and observed by fluorescence immunostaining. Wnt3a and β -catenin expression was significantly lower and GSK-3β expression was significantly higher in the cells exposed to eribulin and transfected with miR-195 mimic than in the untreated controls, suggesting that eribulin inactivates the Wnt/β -catenin signaling pathway. Therefore, a novel antitumor mechanism of eribulin was determined, whereby eribulin induces high expression of miR-195 to inactivate the Wnt/β -catenin signaling pathway in NBL-type TNBC

Co-existence of acute myeloid leukemia with multilineage dysplasia and Epstein-Barr virus-associated T-cell lymphoproliferative disorder in a patient with rheumatoid arthritis: a case report

Rheumatoid arthritis (RA) is an autoimmune disease mediated by inflammatory processes mainly at the joints. Recently, awareness of Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (T-LPD) has been heightened for its association with methotraxate usage in RA patients. In the contrary, acute myeloid leukemia with multilineage dysplasia (AML-MLD) has never been documented to be present concomitantly with the above two conditions. In this report we present a case of an autopsy-proven co-existence of AML-MLD and EBV-associated T-LPD in a patient with RA

Influence of dosing times on cisplatin-induced peripheral neuropathy in rats

Background: Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. Methods: CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. Results: In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. Conclusions: It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy

Pattern of item score change in Stroke Impairment Assessment Set in comprehensive inpatient rehabilitation wards

OBJECTIVES: Although numerous studies have examined activities of daily living (ADL) in stroke rehabilitation, there has been little focus on impairment, despite its close relationship to ADL. Therefore, we evaluated the change in impairment from admission to discharge of patients with stroke in comprehensive inpatient rehabilitation wards using the Stroke Impairment Assessment Set (SIAS). METHODS: Data from 3279 patients with first stroke who were admitted to comprehensive inpatient rehabilitation wards between 2004 and 2016 were analyzed. A scattergram of the items showing the percentage of the highest score on admission and the percentage of patients whose score improved during hospitalization was plotted. The items of the SIAS were grouped by their location on the scattergram. RESULTS: Three clusters could be discriminated on the scattergram. The upper right group, showed an improved score during hospitalization in combination with a high percentage of patients with the highest score on admission. This group consisted of the verticality, unaffected-side quadriceps, visuospatial, and pain items of the SIAS. The upper left group improved during hospitalization, but only contained a small percentage of patients with a high score on admission, and consisted of motor function items. The lower group was characterized by poor improvement during hospitalization and consisted of sensory, tone, range of motion, speech, and grip power items. CONCLUSIONS: Understanding the change in impairment during hospitalization using the three groups described above will facilitate design of a plan for stroke rehabilitation on admission

Effects of a rifampicin pre-treatment on linezolid pharmacokinetics.

Linezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes