Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling / 한국유방암학회지

PURPOSE: The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. METHODS: An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. RESULTS: Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. CONCLUSION: Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.

Safety and efficacy of transcutaneous bone conduction implant surgery for hearing improvement in microtia patients with bilateral hearing impairment

BACKGROUND@#In microtia patients with bilateral hearing impairment, hearing improvement is crucial for language development and performance. External auditory canal reconstruction (EACR) has been performed to improve hearing, but often results in complications. We performed transcutaneous bone conduction implant (TBCI) surgery in these patients. This study aimed to evaluate the safety and efficacy of TBCI surgery.@*METHODS@#A retrospective review was performed of five patients who underwent auricular reconstruction and TBCI surgery and 12 patients who underwent EACR between March 2007 and August 2018. Hearing improvement was measured based on the air-bone gap values using pure-tone audiometry over a 6-week postoperative period. We reviewed other studies on hearing improvement using EACR and compared the findings with our results. The surgical techniques for TBCI were reviewed through case analyses.@*RESULTS@#Postoperative hearing outcomes showed a significant improvement, with a mean gain of 34.1 dB in the TBCI cohort and 14.1 dB in the EACR cohort. Both gains were statistically significant; however, the TBCI cohort showed much larger gains. Only three of the 12 patients who underwent EACR achieved hearing gains of more than 20 dB, which is consistent with previous studies. All patients who underwent TBCI surgery demonstrated hearing gains of more than 20 dB and experienced no device-related complications.@*CONCLUSIONS@#TBCI is a safe and effective method of promoting hearing gains in microtia patients with bilateral hearing impairment. TBCI surgery provided better hearing outcomes than EACR and could be performed along with various auricular reconstruction techniques using virgin mastoid skin.

Impact of hormonal therapy and other adjuvant therapies on contralateral breast volume change after implant-based breast reconstruction

BACKGROUND: Adjuvant therapy after breast surgery, including tamoxifen or aromatase inhibitors, improves the postoperative outcomes and long-term survival of breast cancer patients. The aim of this study was to determine whether volume changes occurred in the contralateral breast during hormonal or other adjuvant therapies. METHODS: This study reviewed 90 patients who underwent unilateral breast reconstruction between September 2012 and April 2018 using tissue expanders and a permanent implant after the surgical removal of breast cancer. The volume of the contralateral breast was measured using a cast before the first (tissue expander insertion) and second (permanent implant change) stages of surgery. Changes in breast volume were evaluated to determine whether adjuvant therapy such as hormonal therapy, chemotherapy, and radiation therapy influenced the volume of the contralateral breast. RESULTS: The group receiving tamoxifen therapy demonstrated a significant decrease in volume compared with the group without tamoxifen (−7.8% vs. 1.0%; P=0.028). The aromatase inhibitor–treated group showed a significant increase in volume compared with those who did not receive therapy (−6.2% vs. 4.5%; P=0.023). There were no significant differences between groups treated with other hormonal therapy, chemotherapy, or radiation therapy. CONCLUSIONS: Patients who received tamoxifen therapy showed a significant decrease in volume in the contralateral breast, while no significant change in weight or body mass index was found. Our findings suggest that we should choose smaller implants for premenopausal patients, who have a high likelihood of receiving tamoxifen therapy.