Background: Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC. Methods: Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN. Results: FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups. Conclusions We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.

Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC. Methods: First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients.Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients. Results: The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features:T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status. Conclusion FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.

Background: Microtia with constricted features is characterized by a short helical length of variable severity, upper antihelical or scaphal deficiency, and a downfolded upper ear. No consensus has been reached regarding the most appropriate surgical method for this condition. In this study, we aimed to introduce a simple and safe surgical method for the correction or reconstruction of upper helix ear deformities. Methods: Between February 2011 and June 2014, eight patients with microtia with constricted upper helix ear deformity underwent reconstruction of the ear deformity. The upper ear helical framework was constructed by carving and curving the eighth rib cartilage harvested from the ipsilateral chest wall, covering this cartilage with a superficial temporal fascial flap, and adjusting the skin graft to align with the ear contour. To evaluate their satisfaction, patients were asked to complete a questionnaire regarding ear shape, symmetry, position, color, and overall outcome scored on a 5-point scale at 12 months postoperatively. Results: None of the patients experienced severe complications in the reconstructed ear. The preoperative and postoperative vertical ear length ratios were 0.88 and 1.02, respectively. And the mean patient satisfaction scores for shape, symmetry, position, color, and overall outcome were 4.2, 4.5, 4.7, 4.4, and 4.6 out of 5 points, respectively. All patients expressed a high level of satisfaction at 12 months postoperatively. Conclusions Our technique provides a good alternative method for the reconstruction of moderate constricted upper helix ear deformities in patients who meet the surgical indications with satisfactory outcomes and few complications.

Purpose: Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs). Methods: Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs. Results: At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased.The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower. Conclusion This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.

Purpose: In patients with locally advanced breast cancer, neoadjuvant chemotherapy is widely used. It has a distinct advantage in the downstaging of the primary tumor and provides important information about treatment response. With its increasing usage, concerns over the appropriate management of the axilla have emerged. In this study, we compared oncological outcomes of conventional axillary lymph node dissection (ALND) over axillary sampling (AS) with radiotherapy (RT) in patients who received neoadjuvant chemotherapy. Methods: In this retrospective study, we included female patients with triple negative breast cancer (TNBC) and HER2 type breast cancer who underwent breast and axillary surgery after neoadjuvant chemotherapy between May 2011 to December 2016. A total of 89 patients’ medical records were eligible for analysis. We defined AS as removal of at least four axillary lymph nodes located near the sentinel lymph nodes without full exposure of the axillary vein, long thoracic nerve, and thoracodorsal nerve. Results: The median follow-up period was 47.00 months. The disease-free survival was 69.66 months in the AS with RT group and 69.02 months in the ALND group (p=0.280). The invasive disease-free survival was 75.16 months in the AS with RT group and 78.44 months in the ALND group (p=0.218). Conclusion AS with radiotherapy might be a feasible surgical option in patients with TNBC and HER2 type breast cancer after neoadjuvant chemotherapy.

Objectives: Coronary heart disease (CHD) risk increases in women after menopause, but menopausal hormone therapy (MHT) helps prevent CHD if started early after menopause. To explore the mechanism underlying the direct vascular actions of estrogen, the effects of 17β-estradiol (E2) on apoptosis of vascular smooth muscle cells (VSMCs) induced with lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, were investigated in the present study. Methods: VSMCs were isolated from rat aortas. Apoptosis and protein expression of caspases were assessed using propidium iodide staining and Western blot analysis, respectively. Intracellular formation of reactive oxygen species (ROS) was examined using dichlorofluorescein diacetate, a cell-permeable oxidation-sensitive probe, and quantitated with flow cytometry. Nuclear factor-κB (NF-κB) activation was determined after transfection with a reporter plasmid containing the luciferase reporter gene. Results: After pre-treatment for 24 hours, 17β-E2 suppressed lysoPC-induced (15 mM) apoptotic cell death in a dose-dependent manner with statistical significance at near physiological concentration. 17β-E2 (10−6 M) also increased protein levels of caspase-9 and -8 precursors and decreased the active form of caspase-3. Western blot analysis using subcellular fractions showed that 17β-E2 decreased mitochondrial Bax levels and concomitantly increased cytosolic Bax expression. Furthermore, intracellular production of ROS and NF- κB-mediated transcriptional activity were reduced with 17β-E2. In addition, estrogen effects on apoptosis were partially blocked by ICI 182,780, a specific estrogen receptor antagonist. Conclusions In cultured VSMCs treated with lysoPC, 17β-E2 reduced apoptotic cell death by down-regulating both extrinsic and intrinsic apoptosis pathways, contributing to the preventive action of MHT against CHD.

Objectives: When administered soon after menopause, hormone therapy can prevent coronary heart diseases in women. To explore the mechanism underlying the cardioprotective actions of estrogen, we investigated the effects of 17β-estradiol (17β-E2) on the plasminogen activator system using cultured vascular smooth muscle cells (VSMCs). Methods: VSMCs were isolated from rat aortas. Protein expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) were evaluated using Western blotting and enzyme-linked immunosorbent assay, respectively. The enzyme activity of PAI-1 in a conditioned medium was assessed via reverse fibrin overlay zymography and that of t-PA was assessed via fibrin overlay zymography. Gene expression was quantified using real-time reverse transcription-polymerase chain reaction. Results: Following pre-treatment for 24 hours, 17β-E2 suppressed both protein expression and enzyme activity of PAI-1 stimulated by lysophosphatidylcholine (lysoPC) in a significant and dose-dependent manner at a near physiological concentration. Moreover, 17β-E2 (10−7 M) inhibited PAI-1 gene expression, and ICI 182,780—a specific estrogen receptor antagonist—blocked the effects of 17β-E2 on the PAI-1 protein. 17β-E2 did not affect t-PA secretion but significantly enhanced free t-PA activity through reduced binding to PAI-1. Furthermore, 17β-E2 suppressed intracellular reactive oxygen species production and nuclear factor-κB-mediated transcription. Conclusions In VSMCs stimulated with lysoPC, 17β-E2 reduced PAI-1 expression through a non-receptor-mediated mechanism via antioxidant activity as well as a receptor-mediated mechanism; however, it did not alter t-PA secretion. Of note, 17β-E2 suppressed PAI- 1 activity and concurrently enhanced t-PA activity, suggesting a beneficial influence on fibrinolysis.

In recent years, there has been a notable increase in the rate of refractory donor site seroma, defined as seroma that persists for at least 3 months postoperatively, as the number of breast reconstructions using a latissimus dorsi (LD) musculocutaneous flap has increased. Various factors have been proposed to be related, including smoking, obesity, flap mass, and body weight, and several studies have been conducted to explore treatment methods. Typically, surgical treatment, such as capsulectomy, has been considered for refractory seroma, but in this case report, we describe positive outcomes achieved by using Abnobaviscum to treat three female patients who developed a donor site seroma at least 3 months after breast reconstruction using an LD flap.
Body Weight ; Breast ; Female ; Humans ; Mammaplasty ; Myocutaneous Flap ; Obesity ; Seroma ; Smoke ; Smoking ; Superficial Back Muscles ; Tissue Donors

BACKGROUND: Numerous condylar repositioning methods have been reported. However, most of them are 2-dimensional or are complex procedures that require a longer operation time and a highly trained surgeon. This study aims to introduce a new technique using a condylar repositioning plate and a centric relation splint to achieve a centric relationship. METHODS: We evaluated 387 patients who had undergone surgery for skeletal jaw deformities. During the operation, a centric relation splint, intermediate splint, final centric occlusion splint, and condylar repositioning plate along with an L-type mini-plate for LeFort I osteotomy or a bicortical screw for bilateral sagittal split ramus osteotomy were utilized for rigid fixation. The evaluation included: a physical examination to detect preoperative and postoperative temporomandibular joint dysfunction, 3-dimensional computed tomography and oblique transcranial temporomandibular joint radiography to measure 3-dimensional condylar head movement, and posteroanterior and lateral cephalometric radiography to measure the preoperative and postoperative movement of the bony segment and relapse rate. RESULTS: A 0.3% relapse rate was observed in the coronal plane, and a 2.8% relapse rate in the sagittal plane, which is indistinguishable from the dental relapse rate in orthodontic treatment. The condylar repositioning plate could not fully prevent movement of the condylar head, but the relapse rate was minimal, implying that the movement of the condylar head was within tolerable limits. CONCLUSIONS: Our condylar repositioning method using a centric relation splint and mini-plate in orthognathic surgery was found to be simple and effective for patients suffering from skeletal jaw deformities.
Centric Relation ; Congenital Abnormalities ; Head ; Head Movements ; Humans ; Jaw ; Methods ; Orthognathic Surgery ; Osteotomy ; Osteotomy, Le Fort ; Osteotomy, Sagittal Split Ramus ; Physical Examination ; Radiography ; Recurrence* ; Splints ; Temporomandibular Joint

BACKGROUND: In contrast to fillers made from artificial substances, platelet-rich fibrin matrix (PRFM) filler does not cause hypersensitivity reactions or foreign body reactions. PRFM is also highly accessible in terms of cost. Hence, in this study, the efficacy of PRFM for soft tissue augmentation and volume maintenance was evaluated in an animal experiment. METHODS: Twenty nude mice were injected with hyaluronic acid filler, fibrin glue, PRFM filler, and normal saline (control). The remaining volume was measured 4 times over the course of 8 weeks using the volumetric taping bowl method and magnetic resonance imaging. RESULTS: All nude mice survived and showed no signs of infection, such as erythema or edematous changes, during the study period. Migration of the injected substance was not detected at 2, 4, or 8 weeks after the procedure. The remaining volumes of normal saline at 2, 4, and 8 weeks were 10.50%, 2.00%, and 0.00%; fibrin glue, 20.50%, 9.00%, and 2.50%; hyaluronic acid filler, 82.00%, 35.00%, and 17.33%; and PRFM filler, 70.31%, 26.75%, and 14.37%, respectively. CONCLUSIONS: PRFM filler had a high soft-tissue filling capacity compared with the control. It also showed a similar effect to hyaluronic acid filler. Thus, PRFM filler could be a good alternative for correcting soft-tissue deficits.
Animal Experimentation ; Animals ; Cosmetic Techniques ; Erythema ; Fibrin Tissue Adhesive ; Fibrin* ; Foreign Bodies ; Hyaluronic Acid ; Hypersensitivity ; Magnetic Resonance Imaging ; Methods ; Mice ; Mice, Nude* ; Platelet-Rich Plasma