Purpose: Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway. Methods: In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed. Results: Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim. Conclusion Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.

Purpose: Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway. Methods: In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed. Results: Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim. Conclusion Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.

Purpose: Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway. Methods: In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed. Results: Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim. Conclusion Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.

Background and Objectives: Tinnitus, although being a common chronic disease, can be an intractable disease that causes depression and insomnia. This study aimed to analyze the results of the Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI), and Pittsburgh Sleep Quality Index (PSQI) questionnaire surveys before and after clonazepam therapy. In addition, we analyzed the association of three pre-treatment questionnaires and evaluated whether pre-treatment factors could predict the post-treatment THI index.Subjects and Method Patients were selected from those who visited a tertiary hospital from 2019 to 2021 for the treatment of chronic tinnitus they had for more than 3 months and who were over 20 years old. Patients were excluded from the study if they were diagnosed with acute sudden hearing loss, Meniere’s disease, brain/internal auditory canal tumors, or muscular/vascular tinnitus. The questionnaire surveys of THI, BDI, PSQI were conducted before and after 3 months of clonazepam therapy (Rivotril [Roche Inc.] 0.25 or 0.5 mg). Questionnaire scores were compared using the paired t-test. Multiple regression analysis was used to determine the relationships among the three questionnaires. Results: A total of 76 patients (38 males and 38 females) with the mean age of 57.2±9.01 years was analyzed. The average hearing threshold was 30.4±20.67 dB HL on the right and 31.7±17.06 dB HL on the left. The pre-treatment THI, BDI, and PSQI scores were 44.3±23.4, 7.96±2.36, and 6.85±4.68, respectively. The relationships between the THI and BDI and the THI and PSQI were significant (p=0.0027 and p<0.0001, respectively). The pre-THI score showed no significant association with age, sex, or hearing threshold (p=0.91, 0.85, and 0.23, respectively). The post-treatment THI score was 33.6±17.1, which was significantly lower than the pre-THI scores (p<0.0001). Post-BDI and post-PSQI were 7.38±2.25 and 4.04±3.20, respectively. Post-PSQI also significantly decreased compared with pre-PSQI (p=0.0002), but post-BDI did not significantly decrease (p=0.1231). In the THI survey, Question 7 (sleep disturbance) showed decrease the most, followed by Question 25 (unstable mood). The post-treatment THI could be predicted by using the formula, 0.7673+0.6947×pre-THI+0.3572×pre-PSQI. Conclusion The appropriate/optional use of clonazepam at low doses (0.25-0.5 mg) can significantly improve chronic tinnitus and sleep quality. Tinnitus was significantly associated with the scores of THI, BDI, PSQI and the usage of Clonazepam significantly reduced the THI and PSQI scores. However, clonazepam did not affect the BDI score.

Purpose: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes;however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. Methods: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. Results: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. Conclusion As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2.A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Purpose: Li-Fraumeni syndrome (LFS) is a rare autosomal cancer syndrome caused by a germline mutation in the TP53 gene. Breast cancer in LFS patients is of various subtypes;however, limited data are available on the clinicopathological features of these subtypes and their appropriate treatments. This study aimed to review the clinical features and treatments for breast cancer in South Korean patients with germline TP53 mutations. Methods: Data on the clinicopathological features and treatment of all breast cancer patients with LFS were collected retrospectively from the available database of 4 tertiary hospitals in the Republic of Korea. Results: Twenty-one breast cancer cases in 12 unrelated women with confirmed germline TP53 mutations were included in the study. The median age at diagnosis was 33.5 years. The histopathological diagnosis included invasive ductal carcinoma (n = 16), ductal carcinoma in situ (n = 3), and malignant phyllodes tumor (n = 2). While 42% and 31% of the cases were positive for estrogen and progesterone receptors, respectively, 52.6% were human epidermal growth factor receptor 2 (HER2) positive, and 21% were triple-negative. The treatments included mastectomy (52%) and breast-conserving surgery (38%). Five patients underwent radiotherapy (RT). The median follow-up period was 87.5 (8–222) months. There were 3 ipsilateral and 4 contralateral breast recurrences during the follow-up, and 8 patients developed new primary cancers. In the post-RT subgroup, there were 2 ipsilateral and 2 contralateral breast recurrences in 1 patient, and 4 patients had a new primary cancer. Conclusion As reported in other countries, breast cancer in LFS patients in South Korea had an early onset and were predominantly but not exclusively positive for HER2.A multidisciplinary approach with adherence to the treatment guidelines, considering mastectomy, and avoiding RT is encouraged to prevent RT-associated sequelae in LFS patients.

Background and Objectives: Acute low-tone hearing loss (ALHL) is gaining attention as an independent disease identity with close association with endolymphatic hydrops and early stage Meniere’s disease (MD). This study aims to compare patients of ALHL with patients exhibiting low-tone hearing loss and ear fullness without vertigo in various audio-vestibular assessments and in progression to overt MD.Subjects and Method A total of 249 patients with low-tone hearing loss with ear fullness without vertigo was enrolled in this study. Of these patients, 58 patients met criteria for ALHL, which was defined as having an average hearing loss of ≥30 dB at 125, 250, and 500 Hz and ≤20 dB at 2, 4, and 8 kHz. Demographics, electrocochleography (ECoG) abnormality, rate of hearing improvement, vestibular functions, and progression to MD were analyzed. Results: An average low-tone hearing loss of ALHL patients was 42.8 dB, which recovered to 18.9 dB following a combined treatment of diuretics and oral steroid therapy. The hearing recovery rate of this group was 87.9% and the ECoG abnormality ratio was 42.5%. Also, 15.5% of ALHL patients eventually progressed to MD. Conclusion This study described demographics and characteristics of ALHL, demonstrating a successful response to the combined treatment of diuretics and oral steroid. Also, this report demonstrated a close relationship between the degree of low-tone hearing loss and ECoG abnormality and observed the progression to MD in ALHL patients. These data can be usefully applied in clinical setting to explain clinical outcomes of ALHL.

OBJECTIVES: Nicotine has various adverse effects including negative impacts associated with maternal exposure. In the current study, we examined nicotine-induced damage of hair cells and embryotoxicity during zebrafish development. METHODS: Zebrafish embryos were exposed to nicotine at several concentrations (5, 10, 20, and 40 μM) and embryotoxicity were evaluated at 72 hours, including hatching rate, mortality, teratogenicity rate, and heart rate. Hair cells within the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1) neuromasts were identified at 120 hours. Apoptosis and mitochondrial damage of hair cells were analyzed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling) and DASPEI (2-[4-(dimethylamino)styryl]-N-ethylpyridinium iodide) assays, respectively, and changes of ultrastructure were observed by scanning electron microscopy. RESULTS: The control group without nicotine appeared normal with overall mortality and teratogenicity rate < 5%. The hatching rate and mortality rate was not significantly different according to nicotine concentration (n=400 each). The abnormal morphology rate (n=400) increased and heart rate (n=150) decreased with increasing nicotine concentration (P < 0.05). Nicotine-induced hair cell damage significantly increased as nicotine concentration increased. A significantly greater number of TUNEL-positive cells (P < 0.01) and markedly smaller DASPEI area (P < 0.01) were shown as nicotine concentration increased. CONCLUSION: The current results suggest that nicotine induces dose-dependent hair cell toxicity in embryos by promoting apoptosis and mitochondrial and structural damage.
Apoptosis ; Embryonic Structures ; Female ; Hair* ; Heart Rate ; In Situ Nick-End Labeling ; Maternal Exposure ; Microscopy, Electron, Scanning ; Mortality ; Nicotine* ; Tobacco ; Zebrafish*

We report a rare case of a 47-year-old male with posttraumatic phlegmasia cerulea dolens caused by a ruptured right external iliac vein and treated with an endovascular venous stent graft. The patient was the victim of motor vehicle accident, and suffered direct injuries to the head and abdomen. The patient had a cyanotic and swollen right lower leg. Abdominal and lower extremity computed tomography angiography revealed a large retroperitoneal hematoma caused by a ruptured right external iliac vein, and grade I liver injury. The right external iliac vein rupture was successfully treated with a venous stent graft, followed by inferior vena cava filtering, because a venous thrombus was identified below the stent graft. He initially was hemodynamically unstable but recovered following treatment. The patient was comatose when presenting at the emergency department. He was discharged, fully recovered, on hospital day 18.
Abdomen ; Angiography ; Blood Vessel Prosthesis ; Coma ; Emergency Service, Hospital ; Head ; Hematoma ; Humans ; Iliac Vein* ; Leg ; Liver ; Lower Extremity ; Male ; Middle Aged ; Motor Vehicles ; Rupture* ; Thrombosis ; Vena Cava, Inferior