Perioperative outcomes of laparoscopic low anterior resection using ArtiSential® versus robotic approach in patients with rectal cancer: a propensity score matching analysis.

BACKGROUND: Total mesorectal excision using conventional straight fixed devices may be technically difficult because of the narrow and concave pelvis. Several laparoscopic articulating tools have been introduced as an alternative to robotic systems. The aim of this study was to compare perioperative outcomes between laparoscopic low anterior resection using ArtiSential® and robot-assisted surgery for rectal cancer. METHODS: This retrospective study included 682 patients who underwent laparoscopic or robotic low anterior resection  for rectal cancer from September 2018 to December 2021. Among them, 82 underwent laparoscopic surgery using ArtiSential® (group A) and 201 underwent robotic surgery (group B). A total of 73 [group A; 66.37 ± 11.62; group B 65.79 ± 11.34] patients were selected for each group using a propensity score matching analysis. RESULTS: There was no significant difference in the baseline characteristics between group A and B. Mean operative time was longer in group B than A (163.5 ± 61.9 vs 250.1 ± 77.6 min, p < 0.001). Mean length of hospital stay was not significantly different between the two groups (6.2 ± 4.7 vs 6.7 ± 6.1 days, p = 0.617). Postoperative complications, reoperation, and readmission within 30 days after surgery were similar between the two groups. Pathological findings revealed that the circumferential resection margins were above 10 mm in both groups (11.00 ± 7.47 vs 10.17 ± 6.25 mm, p = 0.960). At least 12 lymph nodes were sufficiently harvested, with no significant difference in the number harvested between the groups (20.5 ± 9.9 vs 19.7 ± 7.3, p = 0.753). CONCLUSIONS: Laparoscopic low anterior resection using ArtiSential® can achieve acceptable clinical and oncologic outcomes. ArtiSential®, a multi-joint and articulating device, may serve a feasible alternative approach to robotic surgery in rectal cancer.

Imaging findings of granular cell tumours of the head and neck.

AIM: To review the imaging characteristics of granular cell tumours in the head and neck and assess their associations with pathological findings. MATERIALS AND METHODS: Eleven patients (10 [91%] women, mean age 43 years) with histopathologically confirmed granular cell tumours were included in this study. Preoperative imaging studies were performed, including computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. The location of the tumours, their imaging features, and histopathological findings were analysed. RESULTS: Among the 11 granular cell tumours, four (36%), three (27%), and two (18%) tumours were found in the submucosal layer, subcutaneous layer, and intramuscular area, respectively. On CT, all tumours exhibited homogeneous iso-attenuating enhancement compared with adjacent muscle, and nine out of the 11 tumours (81%) demonstrated well-defined margins. On T2-weighted imaging (T2WI), four out of five tumours (80%) demonstrated iso-signal intensity compared with adjacent muscles, and four tumours (80%) exhibited homogeneous signal intensity. The apparent diffusion coefficient (ADC) values ranged from 0.68-0.81 × 10-3 mm2/s. Histopathological examination revealed densely packed tumour cells with variable amounts of fibrous stroma. CONCLUSION: Granular cell tumours were characterised by well-defined and iso-signals on T2WI and low mean ADC values, and were predominantly located in the submucosal, subcutaneous, or intramuscular areas in middle-aged women. The characteristic locations, demographic characteristics, and imaging findings can help to differentiate granular cell tumours from other soft-tissue tumours in the head and neck.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Anti-diabetic efficacy of combination treatment with the nitric oxide metabolite nitrite and the endogenous antioxidant glutathione in diabetic mice: glutathione combination does not hamper the anti-diabetic effect of nitrite.

OBJECTIVE: The nitric oxide (NO) metabolite nitrite has been shown to attenuate hyperglycemia via its increase in insulin sensitivity and glucose uptake. However, the oral use of nitrite is limited due to its potential formation of the carcinogenic N-nitrosamines via reaction of acidic nitrite and the secondary amines. We investigated the anti-diabetic effect of sodium nitrite (SN) combined with glutathione (GSH) in streptozotocin (STZ)-induced diabetic mice for potential use of GSH as a protective agent in future nitrite therapy. MATERIALS AND METHODS: STZ-induced diabetic mice were orally treated for 5 weeks with vehicle, SN, GSH or SN + GSH. Oral glucose tolerance test and the measurement of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels were carried out to evaluate anti-diabetic effects of SN and SN + GSH. Plasma levels of total NO metabolites (NOx) were measured to confirm nitrite absorption. RESULTS: SN and SN + GSH significantly improved the glucose tolerance (p < 0.05), but GSH alone did not. The efficacy of combination treatment with SN and GSH in improving the glucose tolerance was higher than that of SN alone. Oral treatment with SN or SN + GSH significant reduced FBG and HbA1c levels (p < 0.05). Interestingly, daily oral administration of SN + GSH was more effective in reducing FBG and HbA1c levels than that of SN alone. Administration of SN or SN + GSH significantly increased plasma NOx levels (p < 0.05), and combination treatment with SN + GSH was more effective in increasing plasma NOx levels than that with SN alone. CONCLUSIONS: Combination treatment with SN and GSH is more effective in controlling hyperglycemia and increasing the plasma NOx levels in an experimental mouse model of diabetes. Since oral administration of GSH has been shown to be non-toxic in humans, the combination of SN and GSH may be important in potential future nitrite therapy.

Risk assessment of malignant transformation of oral leukoplakia in patients with previous oral squamous cell carcinoma.

The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan-Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate.

Familial risk for endometriosis and its interaction with smoking, age at menarche and body mass index: a population-based cohort study among siblings.

OBJECTIVE: To quantify familial risk of endometriosis among full siblings and examine interactions between family history and smoking, age at menarche or body mass index (BMI). DESIGN, SETTING AND POPULATION: Population-based nationwide cohort study. METHODS: Using data from the Korean National Health Insurance and Screening Programme databases on kinship, healthcare utilisation, lifestyle and anthropometrics, we identified 2 109 288 women with full siblings and their environmental risk factors from 2002 to 2018. Familial risks were estimated using Cox proportional-hazards models, represented as incidence risk ratios (IRR) with 95% CI. Interaction between family history and smoking, age at menarche or BMI were assessed on an additive scale. MAIN OUTCOME MEASURES: IRR of endometriosis among women with and without affected siblings. RESULTS: From 19 195 women with affected siblings, 1126 developed endometriosis with an incidence of 35.45/10 000 person-years. Familial risk of endometriosis with versus without affected siblings was increased to IRR 2.75 (95% CI 2.25-3.36), and the highest risk was with affected twins (IRR 6.98; 95% CI 4.19-11.62). Women with both a family history and either smoking, early menarche or low BMI had a significantly higher risk of endometriosis compared with the general population and can be regarded as a high-risk group, the IRRs were 4.28 (95% CI 2.43-7.55), 3.47 (95% CI 2.82-4.26) and 3.09 (95% CI 2.68-3.56), respectively. Substantial effect modification of the associations was noted by smoking and early menarche, as their combined risk with family history exceeded the sum of their individual risks, which was also statistically significant. CONCLUSION: Genetic factors are the primary contributor to the familial aggregation of endometriosis. Significant gene-environment interaction exists between family history and smoking or early menarche. TWEETABLE ABSTRACT: Significant gene-environment interaction exists between family history of endometriosis and smoking or early menarche.

Prediction of Human Papillomavirus Status and Overall Survival in Patients with Untreated Oropharyngeal Squamous Cell Carcinoma: Development and Validation of CT-Based Radiomics.

BACKGROUND AND PURPOSE: Human papillomavirus is a prognostic marker for oropharyngeal squamous cell carcinoma. We aimed to determine the value of CT-based radiomics for predicting the human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma. MATERIALS AND METHODS: Eighty-six patients with oropharyngeal squamous cell carcinoma were retrospectively collected and grouped into training (n = 61) and test (n = 25) sets. For human papillomavirus status and overall survival prediction, radiomics features were selected via a random forest-based algorithm and Cox regression analysis, respectively. Relevant features were used to build multivariate Cox regression models and calculate the radiomics score. Human papillomavirus status and overall survival prediction were assessed via the area under the curve and concordance index, respectively. The models were validated in the test and The Cancer Imaging Archive cohorts (n = 78). RESULTS: For prediction of human papillomavirus status, radiomics features yielded areas under the curve of 0.865, 0.747, and 0.834 in the training, test, and validation sets, respectively. In the univariate Cox regression, the human papillomavirus status (positive: hazard ratio, 0.257; 95% CI, 0.09-0.7; P = .008), T-stage (≥III: hazard ratio, 3.66; 95% CI, 1.34-9.99; P = .011), and radiomics score (high-risk: hazard ratio, 3.72; 95% CI, 1.21-11.46; P = .022) were associated with overall survival. The addition of the radiomics score to the clinical Cox model increased the concordance index from 0.702 to 0.733 (P = .01). Validation yielded concordance indices of 0.866 and 0.720. CONCLUSIONS: CT-based radiomics may be useful in predicting human papillomavirus status and overall survival in patients with oropharyngeal squamous cell carcinoma.

Caries Risk Prediction Models in a Medical Health Care Setting.

Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment (CRA) models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g., past caries experience) to predict future caries risk, with limited clinical/community applicability owing to relatively uncommon dental visits compared to frequent medical visits during the first year of life. The objective of this study was to construct and evaluate risk prediction models using information easily accessible to medical practitioners to forecast caries at 2 and 3 y of age. Data were obtained from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) mother-offspring cohort. Caries was diagnosed using modified International Caries Detection and Assessment System criteria. Risk prediction models were constructed using multivariable logistic regression coupled with receiver operating characteristic analyses. Imputation was performed using multiple imputation by chained equations to assess effect of missing data. Caries rates at ages 2 y (n = 535) and 3 y (n = 721) were 17.8% and 42.9%, respectively. Risk prediction models predicting overall caries risk at 2 and 3 y demonstrated area under the curve (AUC) (95% confidence interval) of 0.81 (0.75-0.87) and 0.79 (0.74-0.84), respectively, while those predicting moderate to extensive lesions showed 0.91 (0.85-0.97) and 0.79 (0.73-0.85), respectively. Postimputation results showed reduced AUC of 0.75 (0.74-0.81) and 0.71 (0.67-0.75) at years 2 and 3, respectively, for overall caries risk, while AUC was 0.84 (0.76-0.92) and 0.75 (0.70-0.80), respectively, for moderate to extensive caries. Addition of anterior caries significantly increased AUC in all year 3 models with or without imputation (all P < 0.05). Significant predictors/protectors were identified, including ethnicity, prenatal tobacco smoke exposure, history of allergies before 12 mo, history of chronic maternal illness, maternal brushing frequency, childbearing age, and so on. Integrating oral-general health care using medical CRA models may be promising in screening caries-susceptible infants/toddlers, especially when medical professionals are trained to "lift the lip" to identify anterior caries lesions.

A Scoring System for Prediction of Cervical Lymph Node Metastasis in Patients with Head and Neck Squamous Cell Carcinoma.

BACKGROUND AND PURPOSE: An accurate and comprehensive assessment of lymph node metastasis in patients with head and neck squamous cell cancer is crucial in daily practice. This study constructed a predictive model with a risk scoring system based on CT characteristics of lymph nodes and tumors for patients with head and neck squamous cell carcinoma to stratify the risk of lymph node metastasis. MATERIALS AND METHODS: Data included 476 cervical lymph nodes from 191 patients with head and neck squamous cell carcinoma from a historical cohort. We analyzed preoperative CT images of lymph nodes, including diameter, ratio of long-to-short axis diameter, necrosis, conglomeration, infiltration to adjacent soft tissue, laterality and T-stage of the primary tumor. The reference standard comprised pathologic results. Multivariable logistic regression analysis was performed to develop the risk scoring system. Internal validation was performed with 1000-iteration bootstrapping. RESULTS: Shortest axial diameter, ratio of long-to-short axis diameter, necrosis, and T-stage were used to develop a 9-point risk scoring system. The risk of malignancy ranged from 7.3% to 99.8%, which was positively associated with increased scores. Areas under the curve of the risk scoring systems were 0.886 (95% CI, 0.881-0.920) and 0.879 (95% CI, 0.845-0.914) in internal validation. The Hosmer-Lemeshow goodness-of-fit test indicated that the risk scoring system was well-calibrated (P = .160). CONCLUSIONS: We developed a comprehensive and simple risk scoring system using CT characteristics in patients with head and neck squamous cell carcinoma to stratify the risk of lymph node metastasis. It could facilitate decision-making in daily practice.

Left ventricular ejection fraction is associated with small vessel disease in ischaemic stroke patients.

BACKGROUND AND PURPOSE: The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients. METHODS: Consecutive first-ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid-attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose-response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated. RESULTS: A total of 841 patients were included [median WMH volume 2.98 (1.22-10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B = -0.052, P < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978, P = 0.012], CMBs (aOR = 0.96, P < 0.001) and moderate to severe EPVSs (aOR = 0.94, P < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P = 0.026), CMBs (P < 0.001) and EPVSs (P = 0.002). The total cSVD score also showed a negative association with LVEF in a dose-response manner (P < 0.001). CONCLUSIONS: The burden of cSVD is negatively correlated with the LVEF in a dose-response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.

PIN1 is a new therapeutic target of craniosynostosis.

Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies, including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase peptidyl-prolyl cis-trans isomerase interacting 1 (PIN1) plays a critical role in mediating FGFR signaling and that Pin1+/- mice exhibit delayed closure of cranial sutures. In this study, using both genetic and pharmacological approaches, we tested whether PIN1 modulation could be used as a therapeutic regimen against AS. In the genetic approach, we crossbred Fgfr2S252W/+, a mouse model of AS, and Pin1+/- mice. Downregulation of Pin1 gene dosage attenuated premature cranial suture closure and other phenotypes of AS in Fgfr2S252W/+ mutant mice. In the pharmacological approach, we intraperitoneally administered juglone, a PIN1 enzyme inhibitor, to pregnant Fgfr2S252W/+ mutant mice and found that this treatment successfully interrupted fetal development of AS phenotypes. Primary cultured osteoblasts from Fgfr2S252W/+ mutant mice expressed high levels of FGFR2 downstream target genes, but this phenotype was attenuated by PIN1 inhibition. Post-translational stabilization and activation of Runt-related transcription factor 2 (RUNX2) in Fgfr2S252W/+ osteoblasts were also attenuated by PIN1 inhibition. Based on these observations, we conclude that PIN1 enzyme activity is important for FGFR2-induced RUNX2 activation and craniofacial suture morphogenesis. Moreover, these findings highlight that juglone or other PIN1 inhibitors represent viable alternatives to surgical intervention for treatment of CS and other hyperostotic diseases.

Sequential chemotherapy/radiotherapy was comparable with concurrent chemoradiotherapy for stage I/II NK/T-cell lymphoma.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT + RT; RT + CT) and concurrent modalities (CCRT; CCRT + CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P = 0.027), prognostic index for NK/T-cell lymphoma (PINK) (P = 0.026) and types of initial treatment (P = 0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P = 0.021) and PINK-EBV DNA (PINK-E) (P = 0.002) significantly impacted on PFS; whereas ECOG performance score (P = 0.008) and stage (P < 0.001) significantly impacted on OS. For comparing CCRT ± CT and sequential CT + RT, CCRT ± CT patients (n = 190) were similar to sequential CT + RT patients (n = 54) in all evaluated clinicopathologic parameters except two significantly superior features (higher proportion of undetectable circulating EBV DNA on diagnosis and lower PINK-E scores). Despite more favorable pre-treatment characteristics, CCRT ± CT patients had CR rate, PFS and OS comparable with sequential CT + RT patients on multivariate and Cox regression analyses. Conclusions: In stage I/II NK/T-cell lymphomas, when effective chemotherapeutic regimens were used, CCRT and sequential CT + RT gave similar outcome.

Runx3 plays a critical role in restriction-point and defense against cellular transformation.

The restriction (R)-point decision is fundamental to normal differentiation and the G1-S transition, and the decision-making machinery is perturbed in nearly all cancer cells. The mechanisms underlying the cellular context-dependent R-point decision remain poorly understood. We found that the R-point was dysregulated in Runx3-/-mouse embryonic fibroblasts (MEFs), which formed tumors in nude mice. Ectopic expression of Runx3 restored the R-point and abolished the tumorigenicity of Runx3-/-MEFs and K-Ras-activated Runx3-/-MEFs (Runx3-/-;K-RasG12D/+). During the R-point, Runx3 transiently formed a complex with pRb and Brd2 and induced Cdkn1a (p21Waf1/Cip1/Sdi1; p21), a key regulator of the R-point transition. Cyclin D-CDK4/6 promoted dissociation of the pRb-Runx3-Brd2 complex, thus turning off p21 expression. However, cells harboring oncogenic K-Ras maintained the pRb-Runx3-Brd2 complex and p21 expression even after introduction of Cyclin D1. Thus, Runx3 plays a critical role in R-point regulation and defense against cellular transformation.

Epigenetic regulation of RNA polymerase III transcription in early breast tumorigenesis.

RNA polymerase III (Pol III) transcribes medium-sized non-coding RNAs (collectively termed Pol III genes). Emerging diverse roles of Pol III genes suggest that individual Pol III genes are exquisitely regulated by transcription and epigenetic factors. Here we report global Pol III expression/methylation profiles and molecular mechanisms of Pol III regulation that have not been as extensively studied, using nc886 as a representative Pol III gene. In a human mammary epithelial cell system that recapitulates early breast tumorigenesis, the fraction of actively transcribed Pol III genes increases reaching a plateau during immortalization. Hyper-methylation of Pol III genes inhibits Pol III binding to DNA via inducing repressed chromatin and is a determinant for the Pol III repertoire. When Pol III genes are hypo-methylated, MYC amplifies their transcription, regardless of its recognition DNA motif. Thus, Pol III expression during tumorigenesis is delineated by methylation and magnified by MYC.

Interobserver reproducibility of maximal axial diameter and tumour volume measurements from CT of patients with head and neck squamous cell carcinoma.

AIM: To evaluate the interobserver reproducibility of computed tomography (CT) measurements of maximum tumour diameter and tumour volume for head and neck squamous cell carcinoma. MATERIALS AND METHODS: Eighty consecutive patients who underwent neck CT for the initial evaluation of head and neck squamous cell carcinoma were included in this retrospective study. Two radiologists independently measured the maximal axial diameter and volume of tumours. The reproducibility between the two observers was assessed using 95% Bland-Altman limits of agreement, reproducibility coefficient, within-subject coefficient of variation, and intraclass correlation coefficient with subgroup analysis according to tumour location. Logistic regression analysis was performed to identify the risk factors for high variability in tumour volume. RESULTS: The 95% limits of agreement for maximal axial diameter and tumour volume were ±22.3% and ±42.8%, respectively. The within-subject coefficient of variation and reproducibility coefficient were 7.9% and 0.564 for maximal axial diameter and 22.9% and 5.069 for tumour volume. All intraclass correlation coefficients for maximal axial diameter and tumour volume demonstrated excellent agreement (all intraclass correlation coefficients >0.9). Peritumoural infiltration (odds ratio: 7.189; confidence interval: 1.815-28.469; p=0.005) was an independent risk factor for high interobserver variability. CONCLUSION: Changes in maximum axial diameter and tumour volume of <22.3% and 42.8%, respectively, were in the range of measurement error on CT. The presence of peritumoural infiltration on CT increases the error in tumour volume measurement.

Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells.

OBJECTIVES: Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. METHODS: To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. RESULTS: eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. CONCLUSION: Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression.Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186-193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2.

Bone mineral density among Korean females aged 20-50 years: influence of age at menarche (The Korea National Health and Nutrition Examination Survey 2008-2011).

To evaluate a possible correlation between bone mineral density (BMD) and age at menarche, the present study used the BMD dataset of the Korea National Health and Nutrition Examination Survey IV-V (KNHANES IV-V). Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. INTRODUCTION: To investigate any correlation between bone mineral density (BMD) and age at menarche in Korean females using data from the fourth and fifth Korea National Health and Nutrition Examination Survey (KNHANES IV-V; 2008-2011). METHODS: In total, 37,753 individuals participated in health examination surveys between 2008 and 2011. A total of 5032 premenopausal females aged 20-50 years were eligible. Age, height, weight, and age at menarche were assessed. RESULTS: Results from the univariate linear regression and analysis of covariance (ANCOVA) indicated that age (per 1 year), height (per 1 cm), weight (per 1 kg), exercise (per 1 day/week), familial osteoporosis history (yes), parity (n = 0 to ≥4), and menarche age distribution were associated with BMD of the total femur, femur neck, and lumbar spine. After stratifying the bone area and adjusting for age, parity, alcohol intake, smoking, exercise, and familial osteoporosis history, no effect was seen for the total femur or femur neck. Age at menarche 16~17 and ≥18 years groups were associated with BMD of the lumbar spine only. CONCLUSIONS: Age at menarche had a small but significant association with BMD of the lumbar spine in premenopausal Korean females, aged 20-50 years. Females with late menarche may achieve lower peak bone mass at some skeletal sites, which may put them at greater risk for osteoporosis in later life.