Hsp90α Mediates BMI1 Expression in Breast Cancer Stem/Progenitor Cells through Facilitating Nuclear Translocation of c-Myc and EZH2.

Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer. Through immunoprecipitation analysis, we found that BMI1 did not interact with Hsp90α and that the downregulation of BMI1 by 17-DMAG was mediated by the inhibition of c-Myc and enhancement of zeste homolog 2 (EZH2) expression. The transcriptional and BMI1 promoter-binding activities of c-Myc in BCSCs were inhibited by 17-DMAG treatment. The overexpression of EZH2 attenuated the inhibitory effect of 17-DMAG on BMI1 and c-Myc expression. Furthermore, Hsp90α could be co-immunoprecipitated with c-Myc and EZH2 and bind to the BMI1 promoter. Treatment with 17-DMAG decreased the nuclear expression of EZH2 and c-Myc but not that of Hsp90α. In conclusion, our data suggested that Hsp90α could positively regulate the self-renewal of BCSCs by facilitating the nuclear translocation of c-Myc and EZH2 to maintain BMI1 expression.

Impact of background music listening on anxiety in cancer patients undergoing initial radiation therapy: a randomized clinical trial.

BACKGROUND: Patients undergoing radiation therapy (RT) often experience anxiety, which may jeopardize the treatment success. The efficacy of music interventions in reducing anxiety remains contentious. This randomized trial aimed to evaluate the impact of music listening on anxiety symptoms in patients undergoing initial RT. METHODS: First-time RT patients were randomly allocated to experimental and control groups. The Brief Symptom Rating Scale (BSRS-5), Distress Thermometer (DT), and Beck Anxiety Inventory (BAI-C) were administered pre- and post-RT. Changes in physiological anxiety symptoms were monitored over 10 consecutive days starting from the first day of RT. The experimental group received music during RT; the control group did not. The generalized linear mixed model was used to estimate the pre-post difference in the BSRS-5, DT, and BAI-C scores between the music intervention and control group. RESULTS: This study included 50 patients each in the experimental and control groups. BSRS-5 and DT scores were significantly reduced in the experimental group post-RT (p = 0.0114 and p = 0.0023, respectively). When music listening was discontinued, these scores rebounded. While the posttest BAI-C score was significantly lower in the experimental group (p < 0.0001), the pre-post difference between the two groups was not significant (p = 0.0619). On cessation of music listening, the BAI-C score also rebounded. CONCLUSIONS: For cancer patients undergoing initial RT, music listening intervention significantly reduced anxiety symptoms measured using the BSRS-5, DT, and BAI-C scores after two weeks. Our results demonstrate the effectiveness of music listening intervention in reducing anxiety symptoms, thereby potentially improving the quality of life of cancer patients undergoing RT.

Effectiveness of multimedia courses in improving self-care among patients with breast cancer undergoing radiotherapy.

BACKGROUND: Ninety percent of patients receiving radiation therapy experience side effects. Busy schedules and intensive health education programs may lead to incomplete education content delivery and inaccurate patient self-care implementation. This study investigated whether multimedia health education improves the accuracy of patient self-care implementation compared with paper-based education. METHODS: From March 11, 2020 to February 28, 2021, 110 patients were randomly divided into experimental and control groups, each comprising 55 participants. Paper-based materials were used along with multimedia materials. Radiology self-care awareness questionnaires were administered to both groups before the first treatment and on day 10. The differences in radiology self-care awareness between the two groups was analyzed with inferential statistics, independent t tests, categorical data, and Pearson's chi-squared test. Differences between the two groups were considered significant at a p value of < 0.05. RESULTS: The treatment accuracy rate improved from 10.9 to 79.1% in the control group and from 24.8 to 98.5% in the experimental group, indicating an improvement in both groups. The difference was significant. These results indicate that the intervention could improve the effectiveness of self-care. CONCLUSIONS: Participants who used pretreatment multimedia health education exhibited a higher rate of having a correct understanding of treatment self-care than did the control group. These findings can inform the development of a patient-centered cancer treatment knowledge base for improved quality of care.

Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation.

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44⁺ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G¹ phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.