Neurovascular Structural Deviations in Patients Who Have Fused Hips: Implications for Total Hip Arthroplasty.

BACKGROUND: The purpose of this study was to compare the fused and normal sides of patients who have fused hips to determine the differences in neurovascular structures and factors that increase the risk of neurovascular injury. METHODS: We evaluated 38 patients who underwent total hip arthroplasty, with a fused hip between 2003 and 2021. Excluding patients who had bilateral lesions, differences in the location of neurovascular structures were measured by comparing the fused side with the normal side. The position of neurovascular structures was measured by the distance from the acetabular rim and the shortest distance to the particular bony structure. In addition, the patient's sex, weight, body mass index cause of fused hips, estimated age of fusion onset, and preoperative range of motion were investigated to examine the correlations with neurovascular deviation and these factors. RESULTS: The neurovascular distances for all the measured neurovascular structures were significantly reduced on the fused side compared with the normal side. Sex-based analysis revealed that women had significantly shorter distances to the femoral neurovascular bundle than men. Although height and body weight were associated with differences in neurovascular distances, body mass index was not associated with significant differences, except for the femoral nerve distance from the nearest bone. When classified by the estimated age of fusion onset, significant differences in neurovascular distances were found between the adolescent- and adult-onset groups. CONCLUSIONS: In patients who have fused hips, neurovascular structures are located closer to the bone than on the normal side. Moreover, patients in whom the fusion occurred before the completion of growth may exhibit a shorter neurovascular distance, thereby increasing the potential risk of direct injury during total hip arthroplasty .

25KDa branched polyethylenimine increases interferon-γ production in natural killer cells via improving translation efficiency.

BACKGROUND: Ex vivo cultivation is a promising strategy for increasing the number of NK cells and enhancing their antitumor activity prior to clinical application. Recent studies show that stimulation with 25KDa branched polyethylenimine (25KbPEI) generates NK cells with enhanced antitumor activity. To better understand how 25KbPEI primes NK cells, we explored the mechanism underlying increase in production of IFN-γ. METHODS: Chemical priming was performed on NK-92MI cells by incubating them with 5 µg/ml of 25KbPEI. The production of IFN-γ was evaluated by RT-qPCR, ELISA, and Flow cytometry. By evaluating the effect of pharmacological inhibition of ERK/mTOR-eIF4E signaling pathways on IFN-γ translation, the function of these signaling pathways in IFN-γ translation was examined. To comprehend the level of 25KbPEI activity on immune-related components in NK cells, RNA sequencing and proteomics analyses were conducted. RESULTS: 25KbPEI enhances the production of IFN-γ by NK cells without transcriptional activation. Activation of ERK and mTOR signaling pathways was found to be associated with 25KbPEI-mediated calcium influx in NK cells. The activation of ERK/mTOR signaling was linked to the phosphorylation of 4E-BP1, which resulted in the activation of translation initiation complex and subsequent IFN-γ translation. Analysis of RNA sequencing and proteomics data revealed that the activity of 25KbPEI to improve translation efficiency in NK cells could be extended to additional immune-related molecules. CONCLUSIONS: This study provides substantial insight into the process by which 25KbPEI primes NK cells. Our data demonstrated that the 25KbPEI mediated activation of ERK/mTOR signaling and subsequent stimulation of eIF4E is the primary mechanism by which the chemical stimulates translation of IFN-γ in NK cells. Video abstract.

Stricter correction of leg length discrepancy is required during total hip arthroplasty in patients with ankylosing spondylitis.

BACKGROUND: Patients with ankylosing spondylitis often have fusions in the spine and sacroiliac joints, such that it is difficult to compensate for leg length discrepancy (LLD). METHODS: We retrospectively measured the LLD after total hip arthroplasty (THA) in 89 patients with ankylosing spondylitis from June 2004 to February 2021 at our institute. Patients were divided into two groups based on an LLD of 5 mm. Clinical outcomes were investigated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Harris Hip Score (HHS). In addition, these points are investigated: patient satisfaction with the operation; whether there was a current difference in leg length; and whether there was a limping gait. RESULTS: The group with an LLD of 5-10 mm rather than < 5 mm had significantly worse WOMAC pain and stiffness. The survey revealed statistically significant differences in patient satisfaction with the operation, limping gait, and whether back pain had improved. CONCLUSION: For patients with ankylosing spondylitis, reducing the LLD to < 5 mm, which is more accurate than the current standard of < 10 mm, may produce greater improvement in clinical outcomes after hip arthroplasty.

ELK3 Controls Gastric Cancer Cell Migration and Invasion by Regulating ECM Remodeling-Related Genes.

Current therapeutic strategies for gastric cancer, including surgery and chemotherapy improve patient survival; however, the survival rate of patients with metastatic gastric cancer is very low. The molecular mechanisms underlying the dissemination of gastric cancer cells to distant organs are currently unknown. Here, we demonstrate that the E26 transformation-specific (ETS) transcription factor ELK3 (ELK3) gene is required for the migration and invasion of gastric cancer cells. The ELK3 gene modulates the expression of extracellular matrix (ECM) remodeling-related genes, such as bone morphogenetic protein (BMP1), lysyl oxidase like 2 (LOXL2), Snail family transcriptional repressor 1 (SNAI1), serpin family F member 1 (SERPINF1), decorin (DCN), and nidogen 1 (NID1) to facilitate cancer cell dissemination. Our in silico analyses indicated that ELK3 expression was positively associated with these ECM remodeling-related genes in gastric cancer cells and patient samples. The high expressions of ELK3 and other ECM remodeling-related genes were also closely associated with a worse prognosis of patients with gastric cancer. Collectively, these findings suggest that ELK3 acts as an important regulator of gastric cancer cell dissemination by regulating ECM remodeling.

Combined use of cisplatin plus natural killer cells overcomes immunoresistance of cisplatin resistant ovarian cancer.

Standard chemotherapy for ovarian cancers is often abrogated by drug resistance. Specifically, resistance to cisplatin is a major clinical obstacle to successful treatment of ovarian cancers. The aim of this study was to develop a therapeutic strategy using natural killer (NK) cells to treat cisplatin-resistant ovarian cancers. First, we compared the responses of ovarian cancer cell line A2780 and its cisplatin-resistant counterpart, A2780cis, to treatment with cisplatin plus NK92MI cells. Although combined treatment induces apoptosis of ovarian cancer cells via ROS-dependent and -independent mechanisms, A2780cis were resistant to NK92MI cell-mediated cytotoxicity. We found that A2780cis cells showed markedly higher expression of immune checkpoint protein, PD-L1, than the parental cells. Although pretreatment of A2780cis cells with cisplatin stimulated further expression of PD-L1, it also increased expression of ULBP ligands, which are activating receptors on NK92MI cells, both in vitro and in vivo. These findings suggest that combined use of cisplatin plus NK cell-mediated immunotherapy could overcome immunoresistance of chemoresistant ovarian cancers.

Cementless total hip arthroplasty for failed treatment of subtrochanteric fracture.

BACKGROUND: Failed treatment of subtrochanteric fractures commonly leads to pain, limping, and poor limb function. Cementless total hip arthroplasty (THA) could serve as an efficient salvage procedure in such cases. This study aimed to evaluate the outcomes and complications of salvage THA in failed subtrochanteric fracture fixation cases. METHODS: From January 2001 to December 2017, cementless THA for failed treatment of subtrochanteric fractures was performed in 18 hips of 11 men and 7 women (average age, 74 years; age range, 57.0-89.0 years). Patients were followed up for clinical and radiological assessments in terms of implant survival and complications after a minimum follow-up of 2 years. The Wagner femoral stems (Zimmer, Warsaw, USA) were used in all 18 patients (100%), with the long-length stem (Wagner SL stem) and standard-length stem (Wagner cone stem) used in 11 and 7 patients, respectively. RESULTS: The mean follow-up period was 5.2 years (range: 2.2-10.8 years). The mean Harris hip score (HHS) was 38.2 (range: 24-56) preoperatively and 85.4 (range: 79-92) at the last follow-up. The mean postoperative limb length discrepancy was 6.4 mm (range: 4-9 mm). Only one patient underwent revision due to bone in-growth failure of the femoral stem. One patient had an episode of postoperative dislocation and was treated with closed reduction without reoccurrence. Delayed union of the fracture site occurred in one patient. Patients who were previously treated with an intramedullary nail had a significantly shorter surgical duration, lesser intraoperative blood loss, and fewer blood transfusions than those who were previously treated with plate and screws. Kaplan-Meier survival rate with an endpoint of revision was 94.4% (95% confidence interval 72.7-99.9) at 5 years. CONCLUSION: Our results indicate that cementless THA is a beneficial and effective procedure for salvaging the failed treatment of subtrochanteric fractures. The Wagner conical prosthesis has shown satisfactory function outcomes, stable fixation, and survival rate for these complex situations. However, attention should be paid to increased operation time, blood loss, and complications when performing THA for subtrochanteric fractures with failed fixation devices especially, plates and screws.

Mid-term results of total hip arthroplasty with modified trochanteric osteotomy in Crowe type IV developmental dysplasia of the hip.

BACKGROUND: This study aimed to explore mid-term clinical results of cementless total hip arthroplasty (THA) with modified trochanteric osteotomy in Crowe type IV developmental dysplasia of the hip (DDH). METHODS: Thirteen patients (13 hips) with Crowe type IV DDH who underwent THA with modified trochanteric osteotomy between May 2013 and October 2015 were retrospectively analyzed. The mean follow-up duration was 5.2 years (range, 4.9-6.1 years). RESULTS: The mean Harris Hip Score (HHS) significantly (p < 0.05) improved from 30.7 (range, 22-38) to 87.5 (range, 83-93). The mean leg length discrepancy (LLD) was 53.4 mm (range, 42.1-68.5 mm) preoperatively. The final LLD was 5.6 mm (range, 2.4-9.1 mm; p < 0.05). The mean leg length after surgery was 47.4 mm (range, 33.6-67.2 mm) and the femur shortening distance was 43.8 mm (range, 31.2-53.4 mm). The average duration of bone union for the greater trochanter (GT) was 2.5 months (range, 1.5-3.6 months). There was no infection, GT non-union, or loosening (septic or aseptic) of the stem or cup in any case. CONCLUSIONS: THA with modified trochanteric osteotomy with a cementless cup is an effective treatment for Crowe type IV DDH. It can rebuild complex biomechanics and biology of hip dysplasia without increasing complications.

Survival Analysis of Total Hip Arthroplasty for High Hip Dislocation Secondary to Developmental Dysplasia or Septic Arthritis of the Hip.

BACKGROUND: This retrospective study was conducted to know clinical and radiographic outcomes, complication rate, and survival of THA in patients with high hip dislocation secondary to developmental dysplasia(DDH) or septic arthritis of the hip(SSH). METHODS: Between March 2005 and September 2014, there were consecutive series of 53 THAs in patients with a highly dislocated hip secondary to DDH or SSH. Of these, 48 hips (DDH 24 and SSH 24) were reviewed at a mean follow-up of 7.9 years(range, 5.0-14.3 years). The mean age at the time of THA was 39.1 years(range, 18.0-59.0 years). RESULTS: Intraoperative blood loss, total drainage and blood transfusion amounts, and mean time to greater trochanter union were significantly lower in the DDH group than in the SSH group (P = .001, P = .039 and P = .014, and P = .015, respectively). No significant difference in Kaplan-Meier survivorship was observed between groups (log-rank, P = .343). The survival rates with an endpoint of cup aseptic loosening in cases with a cemented cup at 7.9 and 10 years (68.1% and 60.5%, respectively) were significantly lower than those in cementless cup cases (100%) at the same checkpoints (P = .019).. CONCLUSION: We found similar clinical outcomes between the DDH and SSH groups. However, due to poor bone quality and a lack of containment, cementless acetabular cups could not be performed in more than 50% of patients. Our experience shows that revision cementless fixation cup was possible due to reconstitution of the acetabulum in cases with failed cemented fixation.

TGFam-Finder: a novel solution for target-gene family annotation in plants.

Whole-genome annotation error that omits essential protein-coding genes hinders further research. We developed Target Gene Family Finder (TGFam-Finder), an alternative tool for the structural annotation of protein-coding genes containing target domain(s) of interest in plant genomes. TGFam-Finder took considerably reduced annotation run-time and improved accuracy compared to conventional annotation tools. Large-scale re-annotation of 50 plant genomes identified an average of 150, 166 and 86 additional far-red-impaired response 1, nucleotide-binding and leucine-rich-repeat, and cytochrome P450 genes, respectively, that were missed in previous annotations. We detected significantly higher number of translated genes in the new annotations using mass spectrometry data from seven plant species compared to previous annotations. TGFam-Finder along with the new gene models can provide an optimized platform for comprehensive functional, comparative, and evolutionary studies in plants.

A novel PI3K/mTOR dual inhibitor, CMG002, overcomes the chemoresistance in ovarian cancer.

OBJECTIVE: Ovarian cancer is the leading cause of gynecologic-related mortality worldwide. Despite successful initial treatment, overall survival rates are very low because tumors develop resistance to chemotherapeutic drugs. The PI3K/mTOR pathway is a key signaling pathway involved in drug resistance of ovarian cancer cells. The aim of this study was to examine the effect of a newly developed PI3K/mTOR dual inhibitor, CMG002, on chemoresistant ovarian cancer cells. METHODS: We examined the effects of CMG002, and its synergistic effects when combined with paclitaxel or cisplatin, on cell viability, cell cycle arrest, and apoptosis of PTX-resistant SKpac17 or cisplatin-resistant A2780cis ovarian cancer cells in vitro. Western blot analysis was performed to assess expression of PI3K, p-mTOR, p-Akt, p-S6, Bim, and caspase-3. In vivo studies were carried out in a xenograft mouse model, followed by TUNEL and immunohistochemical staining of excised tumor tissue. RESULTS: CMG002 showed marked toxicity against chemoresistant ovarian cancer cells and re-sensitized these cells to chemotherapeutic agents by suppressing cell proliferation and inducing G1 cell cycle arrest and apoptosis. In vivo xenograft studies revealed that treatment with CMG002, either alone or in combination with paclitaxel or cisplatin, led to a marked reduction in tumor growth. CMG002 caused marked suppression of mTOR (Ser2448), Akt (Ser473), Akt (Thr308), and S6 (Ser235/236) phosphorylation, both in vitro and in vivo. CONCLUSION: Taken together, CMG002, a very potent PI3K/mTOR dual inhibitor, induced cytotoxicity in chemoresistant ovarian cancer cells, suggesting that this novel inhibitor might be a new therapeutic strategy for chemoresistant ovarian cancer.

Revision total hip arthroplasty with metal on metal bearing for ceramic bearing fractures.

BACKGROUND: Due to concern of potential metallosis caused by residual microscopic ceramic particles, metal-on-metal (MoM) bearing is deemed undesirable in revision total hip arthroplasty (THA) for ceramic bearing fracture. We determined whether MoM bearing is suitable to be used in revision THA for ceramic fractures and also evaluated whether this treatment increases serum iron levels compared with MoM bearing revision THA for polyethylene failure. METHODS: Between 2006 and 2012, 22 patients underwent revision surgery using MoM bearing (28 mm femoral head in 18 hips and 32 mm in 4 hips) for ceramic bearing fracture and followed average 52.1 months. We assessed radiological parameter and functional outcome using Harris hip score (HHS) and WOMAC score. Also, serum cobalt (Co) and chromium (Cr) blood tests were performed and compared with the result obtained from age, sex- and follow-up duration-matched patients with MoM revision THA for failed polyethylene bearing. RESULTS: The mean HHS improved from 60.6 preoperatively to 90.3 at final follow-up. There were no changes in cup position, progression of osteolytic lesions, and measurable wear of MoM bearing articulation at final follow-up radiographs. There was one case of recurrent dislocation after surgery, which was treated with greater trochanter distal advancement and one case of deep infection, which underwent two-stage revision. Mean serum Co level (1.7 vs. 1.4 µg/dl; p = 0.211) and Cr level (0.70 vs. 1.01 µg/dl; p = 0.327) showed no significant difference. CONCLUSIONS: MoM articulation with liner cementation into the acetabular cup along with total synovectomy can be chosen in revision surgery for ceramic fracture with good midterm follow-up. However, the use of MoM bearing is indicated when the stem and metal shell can be retained and ceramic on ceramic or ceramic on polyethylene bearing cannot be selected. Also long-term outcome needs to be further evaluated.

Importance of postoperative sesamoid reduction on the outcomes of proximal chevron osteotomy for moderate to severe hallux valgus deformity.

BACKGROUND: The purpose of this study was to compare the clinical and radiographic outcomes between feet with or without postoperative sesamoid reduction of proximal metatarsal chevron osteotomy for moderate to severe hallux valgus deformity. METHODS: All of 110 feet were allocated into two groups (reduction group; 66 feet, non-reduction group; 44 feet) according to the reduction status of sesamoid at 6 months after surgery. The clinical and radiographic results of the two groups were compared preoperatively, 6 months follow-up, and at last follow-up. RESULTS: The overall improvement in clinical outcomes was similar in both groups at average 4-year follow-up. However, the radiographic outcomes and recurrence rate were significantly worse in the sesamoid non-reduction group. CONCLUSIONS: Our results suggested that postoperative incomplete reduction of sesamoid may increase a risk for the recurrence of hallux valgus deformity.

ELK3-GATA3 axis modulates MDA-MB-231 metastasis by regulating cell-cell adhesion-related genes.

GATA3 is a master regulator that drives mammary epithelial cell differentiation, and the suppression of GATA3 expression is associated with the development of aggressive breast cancer. However, the mechanism through which GATA3 loss drives cancer development is poorly understood. Previously, we reported that ELK3 suppression in MDA-MB-231 (ELK3 KD) resulted in the reprogramming of these cells from a basal to luminal subtype, which was associated with the induction of GATA3 expression, and that the ELK3-GATA3 axis orchestrated the metastatic characteristics of MDA-MB-231. Here, we show that GATA3 suppression in ELK3 knockdown MDA-MB-231 cells (ELK3/GATA3 DKD) restores the metastatic ability comparably to that of control MDA-MB-231 cells, even though the epithelial cell morphology and TGF-ß signaling of ELK3 KD are not recovered in ELK3/GATA3 DKD. The expression of E-cadherin and tight junctional proteins, including occludin, claudin and ZO-1, which is activated in ELK3 KD, is suppressed in ELK3/GATA3 DKD. These results reveal the possibility that the ELK3-GATA3 axis determines the metastatic characteristics of MDA-MB-231 by regulating the expression of cell-cell adhesion factors.

Muscle pedicle bone grafting using the anterior one-third of the gluteus medius attached to the greater trochanter for treatment of Association Research Circulation Osseous stage II osteonecrosis of the femoral head.

PURPOSE: The aim of this study was to evaluate the effectiveness of our technique on further collapse of the femoral head in Association Research Circulation Osseous (ARCO) stage II, patient's functional improvements, and analyze the survival rate of the affected hip. METHODS: Between June 2007 and March 2015, 24 hips diagnosed with osteonecrosis of the femoral head (ONFH) were treated with our muscle pedicle bone grafting (MPBG) technique using anterior one-third of gluteus medius attached to the greater trochanter. The group was consisted of 15 men and eight women, mean age of 36 years at the time of surgery. Mean follow-up was 6.2 years. RESULTS: Four hips showed regeneration, 11 hips showed no progression, and nine hips showed slight extent of the lesion. But during the follow-up, three hips underwent total hip arthroplasty at the mean follow-up of 5.8 years after the surgery. The survival rate at the last follow-up was approximately 87.5%. Excluding the three failed cases, the mean total Harris hip score was improved from 57.2 to 82.3 points (p < 0.05). We had no case of complications such as limping, numbness, wound infection, heterotopic ossification, nor intra- and post-operative fracture. CONCLUSION: We showed 87.5% of survival rate by average of 6.2-year follow-up, maximum of 10.1 years. And compared to other reports, our technique showed relatively good results. In the short term, our modified MPBG technique seems to be effective in ARCO stage II ONFH. We, therefore, suggest this technique as one of the promising treatments of choices for patients with ARCO stage II ONFH.

The role of ELK3 to regulate peritumoral lymphangiogenesis and VEGF-C production in triple negative breast cancer cells.

Tumor-induced lymphangiogenesis, a major conduit for cancer cell dissemination from the primary tumor site to lymph nodes and beyond, eventually leads to metastasis in cancer patients. Given the recent evidence revealing that the suppression of ELK3 inhibits the metastasis of triple-negative breast cancer cells, we aimed to study the underlying mechanism of impaired metastasis in ELK3-suppressed MDA-MB-231 cells (ELK3 KD) with regard to lymphangiogenesis. We found that the secretome of ELK3 KD cells inhibited tube formation, whereas it promoted the migration and invasion of lymphatic endothelial cells (LECs) in vitro. In vivo analysis revealed that peritumoral lymphatic vessels were not developed around the xenografted tumors of ELK3 KD. We further revealed that the suppression of NF-κB signaling in ELK3 KD was the primary cause of the reduced VEGFC expression. Taken together, we suggest that ELK3 is an upstream regulator of the NF-κB signaling pathway, the inhibition of which leads to the suppression of peritumoral lymphatic vessel development, possibly due to a low VEGFC expression.

Revision Total Hip Arthroplasty Using an Acetabular Reinforcement Ring With a Hook: A Precise Follow-Up, at Average 11.4 Years, of a Previous Report.

BACKGROUND: This study aims at determining the average long-term result of revision total hip arthroplasty (THA) using the acetabular reinforcement ring with a hook (ARRH) and bone grafting in severe acetabular bony defect. Expected 15-year survival of ARRH in revision THA is included in the study. METHODS: Retrospective review of 48 patients (48 hips) with follow-up duration of average 11.4 years (range, 6.1-21.4 years) was conducted. At each follow-up, Harris hip score was used to assess functional outcome, and radiographic acetabular component osteolysis was measured by DeLee and Charnley classification. Bone defects were assessed preoperatively and intraoperatively using American academy of orthopedic surgeons and Paprosky classification. The common modes of ARRH failures were evaluated. Bone consolidation, presence of heterotopic ossification, and complications such as infection and dislocation were recorded. RESULTS: The bone defects were varied and included cavitary, segmental, and combined defects without any pelvic discontinuity. Mean Harris hip score improved from 52.6 points preoperatively to 82.0 points postoperatively. Nine acetabular revisions and 3 stem revisions (2 concurrent with acetabular revisions and 1 isolated stem revision) were performed. There were 5 infected cases and 1 patient with recurrent dislocation. The 11.4-year survival of revision THA with ARRH was 71% as the end point for acetabular revision surgery for any reason. The expected 15-year survival of revision THA with ARRH was 60%. The most common failure mode of ARRH was superomedial migration followed by lateral migration. CONCLUSION: ARRH combined with bone grafting produces relatively good average long-term clinical results.

Could -79 °C Spray-Type Cryotherapy Be an Effective Monotherapy for the Treatment of Keloid?

Cryotherapy has been regarded as an effective modality for the treatment of keloids, and the spray-type device is one of the novel cryotherapeutic units. However, the biological mechanisms and therapeutic effects of this technique are incompletely studied. We evaluated the clinical efficacy of our cryotherapy protocol with molecular and pathologic evidence for the treatment of keloids. We evenly split each of ten keloid lesions into a non-treated (C-) and treated (C+) area; the C+ area was subjected to two freeze-thaw cycles of spray-type cryotherapy using -79 °C spray-type CryoPen™. This treatment was repeated after an interval of two weeks. The proliferation and migration abilities of the fibroblasts isolated from the dermis under the cryotherapy-treated or untreated keloid tissues (at least 5 mm deep) were compared and pathologic findings of the full layer were evaluated. Molecular analysis revealed that the number of dermal fibroblasts was significantly higher in C+ group as compared with C- group. The dermal fibroblasts from C+ group showed more than two-fold increase in the migration ability as compared with the fibroblasts from C- group. The expression of matrix metallopeptidase 9 was increased by more than two-fold and a significant increase in transforming growth factor beta 1 expression and Smad2/3 phosphorylation level was observed in C+ group. C+ group showed more extensive lymphoplasmacytic infiltration with thicker fibrosis and occasional "proliferating core collagen" as compared with C- group. Thus, -79 °C spray-type cryotherapy is ineffective as a monotherapy and should be used in combination with intralesional corticosteroids or botulinum toxin A for favourable outcomes in the treatment of thick keloids.

PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy.

Drug resistance in breast cancer remains a major obstacle of clinical therapy. We found that suppression of ELK3 in the triple negative breast cancer cell line MDA-MB-231 impaired autophagy and led to a hypersensitive response to doxorubicin treatment. In ELK3-knockdown MDA-MB-231 cells (ELK3 KD), autophagy was not activated under starvation conditions, which is a major stimulus of autophagy activation. We revealed that activation of the PI3K/Akt pathway was the main cause of impaired autophagy in ELK3 KD. Our results suggest that targeting ELK3 may be a potential approach to overcome doxorubicin resistance in breast cancer therapeutics.

ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells.

ELK3 is a member of the Ets family of transcription factors. Its expression is associated with angiogenesis, vasculogenesis, and chondrogenesis. ELK3 inhibits endothelial migration and tube formation through the regulation of MT1-MMP transcription. This study assessed the function of ELK3 in breast cancer (BC) cells by comparing its expression between basal and luminal cells in silico and in vitro. In silico analysis showed that ELK3 expression was higher in the more aggressive basal BC cells than in luminal BC cells. Similarly, in vitro analysis showed that ELK3 mRNA and protein expression was higher in basal BC cells than in normal cells and luminal BC cells. To investigate whether ELK3 regulates basal cell migration or invasion, knockdown was achieved by siRNA in the basal BC cell line MDA-MB-231. Inhibition of ELK3 expression decreased cell migration and invasion and downregulated MT1-MMP, the expression of which is positively correlated with tumor cell invasion. In silico analysis revealed that ELK3 expression was associated with that of MT1-MMP in several BC cell lines (0.98 Pearson correlation coefficient). Though MT1-MMP expression was upregulated upon ELK3 nuclear translocation, ELK3 did not directly bind to the 1.3-kb promoter region of the MT1-MMP gene. These results suggest that ELK3 plays a positive role in the metastasis of BC cells by indirectly regulating MT1-MMP expression.

The Survival Analysis in Third-Generation Ceramic-On-Ceramic Total Hip Arthroplasty.

A total of 527 patients (577 hips) who underwent primary THA using third-generation ceramic-on-ceramic (CoC) articulation were retrospectively reviewed. They were followed up for an average of 5.9 years. Seven hips experienced liner fracture and 14 hips experienced head fracture. Squeaking occurred in eight hips. The revision rate in this study was 5.2%, but excluding the cases of ceramic head and liner fracture, there were nine cases (1.6%) of revision surgery. Considering revision for any reason as the end point, mean survivorship was 93% at 10 years. According to the femoral head size and neck length, 28 mm head with short neck has the worst survivorship of 89% at 10 years. Overall, our study showed a higher rate of ceramic fracture compared with other studies.