CT-guided pretreatment biopsy diagnosis in patients with thymic epithelial tumours: diagnostic accuracy and risk of seeding.

AIM: To investigate the diagnostic performance of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) for thymic epithelial tumours (TETs) and the complication rate after PTNB including seeding after PTNB. MATERIALS AND METHODS: This retrospective study identified PTNBs for anterior mediastinal lesions between May 2007 and September 2021. The diagnostic performance for TETs and complications were investigated. The concordance of the histological grades of TETs between PTNB and surgery was evaluated. The factors associated with pleural seeding after PTNB were determined using Cox regression analysis. RESULTS: Of 387 PTNBs, 235 PTNBs from 225 patients diagnosed as TETs (124 thymomas and 101 thymic carcinomas) and 150 PTNBs from 133 patients diagnosed as other than TETs were included. The sensitivity, specificity, and accuracy for TETs were 89.4% (210/235), 100% (210/210), and 93.5% (360/385), respectively, with an immediate complication rate of 4.4% (17/385). The concordance rate of the histological grades between PTNB and surgery was 73.3% (77/105) after excluding uncategorised types of thymomas. During follow-up after PTNB (median duration, 38.8 months; range, 0.3-164.6 months), no tract seeding was observed. Pleural seeding was observed in 26 patients. Thymic carcinoma (hazard ratio [HR], 5.94; 95% confidence interval [CI], 2.07-17.08; p=0.001) and incomplete resection (HR, 3.29; 95% CI, 1.20-9.02; p=0.02) were associated with pleural seeding, while the biopsy approach type (transpleural versus parasternal) was not associated (p=0.12). CONCLUSIONS: Pretreatment biopsy for TETs was accurate and safe and may be considered for diagnosing TETs, particularly when the diagnosis is challenging and histological diagnosis is mandatory.

High-mobility group box 1 protein induces epithelialmesenchymal transition in upper airway epithelial cells.

BACKGROUND: In the treatment of rhinosinusitis, nasal polyps are a major problem, and the epithelial-to-mesenchymal transition (EMT) process is considered pivotal in their development. Although various studies have addressed the role of high mobility group box 1 (HMGB1) nuclear protein in this setting, its impact on EMT has yet to be evaluated. Our aim was the pathogenic mechanism of HMGB1 in EMT and EMT-induced upper respiratory nasal polyps. METHODS: We investigated the EMT-related effects of HMGB1 in human nasal epithelial (HNE) cells using western blot analysis, transepithelial-electrical resistance (TEER) testing, wound healing assay, and immunofluorescence. HNE cells were incubated in a low-oxygen environment to evaluate the role of HMGB1 in hypoxia-induced EMT. Further support for our in vitro findings was obtained through murine models. Human nasal polyps and nasal lavage fluid samples were collected for western blotting, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). RESULTS: HMGB1 increased mesenchymal markers and decreased epithelial markers in HNE cells. Hypoxia-induced HMGB1 in turn induced EMT, apparently through RAGE signaling. We verified HMGB1-induced EMT in the upper respiratory epithelium of mice by instilling intranasal HMGB1. In testing of human nasal polyps, HMGB1 and mesenchymal markers were heightened, whereas epithelial markers were reduced, compared with tissue controls. CONCLUSION: HMGB1 secretion in nasal epithelium may be a major pathogenic factor in upper respiratory EMT, contributing to nasal polyps.

Association of low skeletal muscle mass with the presence of advanced colorectal neoplasm: integrative analysis using three skeletal muscle mass indices.

AIM: This study aimed to evaluate an association between colorectal neoplasm (CRN) and skeletal muscle mass using three widely accepted skeletal muscle mass indices (SMIs) in a large population at average risk. METHOD: We performed a cross-sectional study using a screening colonoscopy database of 33 958 asymptomatic subjects aged 40-75 years. Appendicular skeletal muscle mass (ASM) was measured using a bioelectrical impedance analyser. ASM adjusted for height squared (ASM/ht2 ), weight (ASM/wt) and body mass index (ASM/BMI) were used as indices for muscle mass. Logistic regression models were used to evaluate the association between SMIs and CRN. RESULTS: In a multivariable-adjusted model, the risk of an advanced CRN increased linearly with decreasing quartiles for all three SMIs. The adjusted odds ratios (ORs) for advanced CRN in quartiles 1, 2 and 3 of ASM/wt compared with that in quartile 4 were 1.279, 1.196 and 1.179, respectively (Ptrend  = 0.017); for ASM/BMI, ORs were 1.307, 1.144 and 1.091, respectively (Ptrend  = 0.002); and for ASM/ht2 , ORs were 1.342, 1.169 and 1.062, respectively (Ptrend  = 0.002). The risk of distally located advanced CRN was higher in quartile 1 than in quartile 4 for all three SMIs (ASM/wt, OR = 1.356; ASM/BMI, OR = 1.383; ASM/ht2 , OR = 1.430). CONCLUSION: Our study demonstrated that low skeletal muscle mass was consistently associated with the presence of advanced CRN in a population at average risk regardless of the operational definition of the SMI, and it was particularly associated with distal advanced CRN.

Surgeon volume and prognosis of patients with advanced papillary thyroid cancer and lateral nodal metastasis.

BACKGROUND: Surgery is the most important treatment modality for papillary thyroid cancer (PTC). However, the relationship between surgeon volume and long-term oncological outcomes has not been explored. METHODS: Patients diagnosed with N1b PTC after initial thyroid surgery between 1 July 1994 and 31 December 2011 were eligible for inclusion in the study. Surgeons were categorized into high (at least 100 operations per year) and low (fewer than 100 operations per year) volume groups. Kaplan-Meier survival analysis according to surgeon volume was performed, and Cox proportional hazard modelling was used to estimate hazard ratios (HRs) with 95 per cent confidence intervals according to patient, tumour and surgeon factors. RESULTS: A total of 1103 patients with a median follow-up of 81 (i.q.r. 62-108) months were included in the study. During follow-up, 200 patients (18·1 per cent) developed structural recurrence. A high surgeon volume was associated with low structural recurrence (P = 0·006). After adjustment for age, sex and conventional risk factors for recurrence (histology, tumour size, gross extrathyroidal extension, margin status, more than 5 positive lymph nodes, radioactive iodine therapy), the adjusted HR for structural recurrence for low-volume surgeons was 1·46 (95 per cent c.i. 1·08 to 1·96), compared with high-volume surgeons. Distant metastasis (P = 0·242) and disease-specific mortality (P = 0·288) were not affected by surgeon volume. CONCLUSION: Surgeon volume is associated with structural recurrence, but not distant metastasis or cancer-specific death in patients with N1b PTC. Surgeon volume is important in initial surgery for advanced PTC with extensive nodal metastasis in order to ensure curative outcome and reduce treatment-related morbidity.

Salivary gland ultrasonography findings are associated with clinical, histological, and serologic features of Sjögren's syndrome.

OBJECTIVE: Salivary gland ultrasonography (SGUS) has been applied in the diagnosis of Sjögren's syndrome (SS). The aim of this study is to investigate the association of SGUS findings with clinical, histological, and serologic features of SS. METHODS: A total of 104 patients with suspected SS underwent SGUS for evaluation of salivary gland involvement. Patients with primary SS were determined according to the classification criteria for SS. The parenchymal inhomogeneity of bilateral parotid and submandibular glands was graded from 0 (homogeneity) to 4 (gross inhomogeneity). Receiver operating characteristic curve analysis was performed to compare the diagnostic performance of different SGUS scoring methods. Clinical and serologic features were compared between groups classified by SGUS score. The association between SGUS and these features of SS was explored by multivariable linear regression analysis. RESULTS: Study participants were predominantly women (96.2%) and had a mean age of 54.1 years. Eighty-seven patients and 88 patients with primary SS were identified based on AECG criteria and ACR/EULAR classification criteria for SS, respectively. Among the different scoring methods, the sum of the grades of four salivary glands (range 0-16) had the best diagnostic performance, with sensitivity of 77.3% and specificity of 87.5% (cutoff value, 7) for distinguishing primary SS from sicca non-SS. SGUS score was associated with focus score in labial salivary gland biopsy (ß = 0.240, p = 0.033) and anti-Ro/SSA serology (ß = 0.283, p = 0.016) and inversely associated with unstimulated whole salivary flow (ß = -0.298, p = 0.011). CONCLUSION: Ultrasonography of major salivary glands is associated with histopathology of minor salivary glands, serology of SS, and salivary gland function.

Effect of alcohol consumption and smoking on disease damage in systemic lupus erythematosus: data from the Korean Lupus Network (KORNET) registry.

Background We assessed correlations of smoking habits and alcohol consumption with disease activity or damage in patients with systemic lupus erythematosus (SLE). Methods A total of 505 patients with SLE were enrolled in the Korean Lupus Network (KORNET) SLE registry from January 2014 to January 2016. Disease activity and organ damage were measured by the SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index, respectively. Multivariate logistic regression analysis was used to analyze associations with cutaneous lesions. Results There were no differences in SLEDAI-2K and SLICC/ACR damage indices according to either smoking status or alcohol consumption. More frequent cutaneous damage was observed in current alcohol drinkers compared with non-current alcohol drinkers ( p = 0.020). Cutaneous damage was significantly associated with alcohol consumption (odds ratio (OR) 4.048, 95% confidence interval (CI) 1.251-12.102, p = 0.020). Both low (1-5 glasses/week) and high (≥6 glasses/week) amounts of alcohol consumption had a significant impact on cutaneous damage compared with the absence of current alcohol consumption ( p = 0.033 and p = 0.027, respectively). Pairwise comparison of alcohol consumption and smoking status with cutaneous damage showed that only alcohol consumption was significantly associated with the presence of cutaneous damage, compared with non-current alcohol consumption and non-current smoking (OR 3.513, 95% CI 1.130-10.920, p =0.030). Conclusions Current alcohol consumption, but not smoking, might influence the development of cutaneous damage in patients with SLE.

Patterns, predictive factors and prognostic impact of multilevel metastasis in N1b papillary thyroid carcinoma.

BACKGROUND: The patterns, predictive factors and prognostic impact of multilevel metastasis in patients with N1b papillary thyroid carcinoma (PTC) were investigated. METHODS: A retrospective review of patients with N1b PTC from a tertiary referral centre in Korea who underwent unilateral modified radical neck dissection was undertaken. RESULTS: Of 658 patients, multilevel metastasis was found in 73·9 per cent; the most common type was metastasis in two levels. Tumour size per 0·1-cm increment (adjusted odds ratio (OR) 1·33, 95 per cent c.i. 1·08 to 1·64), microscopic extrathyroidal extension (adjusted OR 1·72, 1·10 to 2·71), gross extrathyroidal extension (adjusted OR 2·35, 1·24 to 4·46), unilateral central lymph node metastasis (adjusted OR 2·45, 1·53 to 3·92) and bilateral central lymph node metastasis (adjusted OR 4·06, 2·29 to 7·18) were independent predictors of multilevel metastasis. Only four-level metastasis significantly increased the risk of overall locoregional recurrence (LRR) (adjusted hazard ratio (HR) 7·41, 95 per cent c.i. 2·20 to 24·53) and lateral neck LRR (adjusted HR 7·22, 1·82 to 28·65), compared with one-level metastasis. Two subgroup analyses were conducted, showing that only three-level metastasis including metastasis in level V significantly increased the risk of overall LRR (adjusted HR 5·66, 1·20 to 26·75). In addition, having level V metastasis was an independent predictor of both overall (adjusted HR 3·26, 1·72 to 6·18; P < 0·001) and lateral neck (adjusted HR 3·28, 1·50 to 7·16; P = 0·003) LRR. CONCLUSION: Level V metastasis rather than multilevel metastasis itself is associated with an increased risk of LRR. Patients with N1b PTC and level V metastasis require risk restratification and meticulous follow-up.

Pain, xerostomia, and younger age are major determinants of fatigue in Korean patients with primary Sjögren's syndrome: a cohort study.

OBJECTIVES: Fatigue is a common clinical manifestation in patients with primary Sjögren's syndrome (pSS). The aims of this study were to investigate the association between fatigue severity and other clinical characteristics in pSS patients and to determine the factors contributing to fatigue. METHOD: We analysed 257 participants from the Korean Initiative of pSS (KISS), a prospective pSS cohort. Fatigue was assessed according to the fatigue domain of the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient-Reported Index (ESSPRI). Health-related quality of life (HRQoL) was evaluated using the EuroQol-5 dimensions (EQ-5D) questionnaire. Multiple linear regression analysis was used to estimate the effect of each variable on fatigue severity. RESULTS: The median total ESSPRI score was 5 [interquartile range (IQR) 4-6]. Thirty-four per cent of patients reported a fatigue score > 5. Younger and premenopausal patients presented with more fatigue (p = 0.013 and p < 0.001, respectively). Higher Xerostomia Inventory (XI) scale (p < 0.001) and Ocular Surface Dryness Index (OSDI) (p < 0.001) scores were observed in patients with a fatigue score > 5. Pain, xerostomia, and age were determined to be significantly associated with fatigue severity after adjusting for depression/anxiety, OSDI score, and the presence of fibromyalgia using a multivariate general linear model. The ESSPRI fatigue score was correlated with the EQ-5D by time trade-off (TTO) values and visual analogue scale (VAS) scores. CONCLUSIONS: In Korean patients with pSS, younger age, xerostomia, and pain were correlated significantly with fatigue, and fatigue was associated with HRQoL.

Failure to increase the thickness of thin endometria with intrauterine infusion of granulocyte colony stimulating factor (G-CSF).

PURPOSE: To corroborate or refute a previous study suggesting that intrauterine infusion of granulocyte colony stimulating factor (G-CSF) could significantly improve endometrial thickness into more fertile levels when the endometrial thickness was ≤ five mm. MATERIALS AND METHODS: Three women whose endometrial thickness never exceeded five mm on the in vitro fertilization-embryo transfer (IVF-ET) cycle or subsequent attempted frozen ETs using graduated estradiol had intrauterine infusion of G-CSF to the estradiol regimen. RESULTS: Not one of the three women improved the endometrial thickness beyond five mm and none conceived on the G-CSF cycle. One woman had a subsequent pregnancy following a frozen ET with only a four-mm thickness with no infusion of G-CSF. CONCLUSIONS: These data do not confirm the efficacy of intrauterine infusion of G-CSF for poor endometrial thickness. Perhaps only certain cases will respond. A larger series could take time to accumulate since other studies have shown that only 0.3% of women with ≤ five mm endometrial thickness in the late proliferative phase during an IVF-ET cycle will not improve the endometrial thickness > five mm using graduated estradiol protocols.

Survival Benefit of Early Cancer Detection Through Regular Endoscopic Screening for De Novo Gastric and Colorectal Cancers in Korean Liver Transplant Recipients.

BACKGROUND: De novo malignancy is not uncommon after liver transplantation (LT). Gastric cancer is one of the most common malignancies in both the Korean general population and LT recipients, and colorectal cancer prevalence is gradually increasing. METHODS: Among 3690 adult recipients who underwent LT from January 1999 and December 2013, the screening patterns and prognosis of 26 cases of gastric cancer and 22 cases of colorectal cancer were analyzed. RESULTS: For gastric cancer, the mean patient age was 54.6 ± 6.2 years at LT and 59.5 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 60.2 ± 29.8 months. Patients were divided into regular (n = 18) and non-regular (n = 8) screening groups, with early cancer found in 14 and 0 patients; their 2-year survival rates after cancer diagnosis were 93.1% and 33.3% (P = .006), respectively. Endoscopic resection was successfully performed in 8 patients, all in the regular screening group. For colorectal cancer, the mean patient age was 53.3 ± 6.1 years at LT and 58.1 ± 6.7 years at cancer diagnosis, with a post-transplant interval of 54.3 ± 38.0 months. Patients were divided into regular (n = 19) and non-regular (n = 3) screening groups, with early cancer found in 12 and 0 patients; their 2-year survival rates after cancer diagnosis of 92.3% and 33.3% (P = .003), respectively. Endoscopic resection was successfully performed in 6 patients, all in the regular screening group. CONCLUSIONS: LT recipients are strongly advised to undergo regular screening studies for various de novo malignancies, especially cancers common in the general population. Regular endoscopic screening contributes to the timely detection of gastric and colorectal cancers, improving post-treatment survival outcomes.

Reliability of classification of ring and little finger carpometacarpal joint fracture subluxations: a comparison between two-dimensional computed tomography and three-dimensional computed tomography classifications.

The aims of this study were to develop a classification for ring and little finger carpometacarpal joint fracture subluxations based on three-dimensional computed tomography images and evaluate the inter- and intraobserver reliability of the three-dimensional computed tomography classification. A retrospective review was performed of 30 cases of ring and little finger carpometacarpal joint fracture subluxations from 2005 to 2013. We classified ring and little finger carpometacarpal joint fracture subluxations into three types based on three-dimensional computed tomography images. An orthopaedic surgeon with 2 years of experience, a consultant hand surgeon with 8 years of experience, and a consultant radiologist with 9 years of experience, who were completely blind to the treatment algorithm, evaluated 30 cases twice at a 2-week interval using our new classification based on three-dimensional computed tomography images and the other classification based on two-dimensional computed tomography images. Our three-dimensional computed tomography classification showed almost perfect interobserver and intraobserver reliability and resulted in a better level of agreement than two-dimensional computed tomography classification.

Effect of taking a one time injection of one mg leuprolide acetate three days after embryo transfer on pregnancy outcome and level of first beta human chorionic gonadotropin (beta-hCG) level.

PURPOSE: To determine if the injection of a gonadotropin releasing hormone agonist (GnRHa) three days after embryo transfer will improve pregnancy and implantation rates. MATERIALS AND METHODS: One mg s.c. of leuprolide acetate was randomly given based on patient decision three days after embryo transfer to some patients undergoing in vitro fertilization-embryo transfer (IVF-ET). RESULTS: For women aged ≤ 43 the clinical pregnancy rate for those not taking the GnRHa was 39.5% (68/122) vs. 54.5% (42/77) for those taking leuprolide acetate (Chi-square, p = 0.0275). The respective implantation rates were 22.6% vs. 30.2% (p = 0.0495). There was no difference in first serum beta human chorionic gonadotropin (beta-hCG) levels according to whether leuprolide was used or not. CONCLUSIONS: Leuprolide acetate similar to other GnRH agonists can improve implantation rates following IVF-ET when injected once in mid-luteal phase. The beneficial effect may be on GnRH receptors in the endometrium rather than the embryo (which had been hypothesized to direct increased placental production of hCG).

Mid-luteal phase injection of subcutaneous leuprolide acetate improves live delivered pregnancy and implantation rates in younger women undergoing in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To see if the single injection of one mg of the gonadotropin releasing hormone agonist (GnRHa) leuprolide acetate given in the mid-luteal phase can increase live delivered pregnancy and implantation rates. Furthermore the purpose was to determine if improvement was found, did the mechanism involve increased secretion of human chorionic gonadotropin (hCG). MATERIALS AND METHODS: A prospective study was conducted in women aged 35 who were undergoing in vitro fertilization-embryo transfer (IVF-ET). They were advised of data from Tesarik et al. and a previous pilot study conducted in the present IVF center showing improved pregnancy rates with the injection of a GnRHa three days after embryo transfer. They were offered the option of returning for a one-mg injection s.c. of leuprolide acetate or not. Clinical and live delivered pregnancy rates were compared according to those taking or not the leuprolide acetate one-mg injection. Chi-square analysis was used for statistical comparisons. Serum beta-hCG levels were compared between those conceiving with or without the extra injection of leuprolide. RESULTS: There was a non-significant trend for higher live delivered pregnancy rates in those taking leuprolide (47.8%, 64/134) vs. those not taking it (38.6%, 76/197). For those pregnant there was no difference in hCG levels according to taking the GnRHa or not. CONCLUSIONS: The 25% increased live delivered pregnancy rate per transfer was insufficiently powered to detect a significant difference. The results do justify continuing the study. Perhaps the difference could be wider using a slightly older age group whose embryos are frequently less hearty.

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PURPOSE: To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. MATERIALS AND METHODS: Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. RESULTS: A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. CONCLUSIONS: A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

Improved Survival with Anti-VEGF Therapy in the Treatment of Unresectable Appendiceal Epithelial Neoplasms.

BACKGROUND: Currently, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are accepted treatments for surgically resectable appendiceal epithelial neoplasms. However, for nonsurgical candidates, systemic treatment may be considered. The purpose of this analysis was to determine the benefit of biologic therapy (anti-vascular endothelial growth factor and anti-epidermal growth factor receptor) in addition to systemic chemotherapy in this select patient population. METHODS: The MD Anderson Cancer Center tumor registry was retrospectively reviewed for systemic treatment-naive appendiceal epithelial neoplasm patients registered between January 2000 to July 2007 for prior cytoreductive surgery and hyperthermic intraperitoneal chemotherapy status, histologic grade, signet ring pathology, systemic chemotherapy, biologic therapy, tumor markers (carcinoembryonic antigen, carbohydrate antigen [CA] 125, and/or CA19-9), progression-free survival (PFS), overall survival (OS), and disease control rate. Kaplan-Meier method, log-rank, and Cox proportional hazard regression models were used for statistical analysis. RESULTS: A total of 353 patients were identified; 130 patients met the inclusion criteria. Fifty-nine patients received biologic therapy. The use of the anti-vascular endothelial growth factor (VEGF) agent bevacizumab improved both OS (42 months vs. 76 months, hazard ratio 0.49 [95 % confidence interval 0.25-0.94] P = 0.03) and PFS (4 months vs. 9 months, hazard ratio 0.69 [95 % confidence interval 0.47-0.995], P = 0.047) for all histologic subtypes. Moderately differentiated tumors had an improved PFS relative to well-differentiated tumors, 9 months versus 3 months (P = 0.05). CONCLUSIONS: Bevacizumab in combination with chemotherapy appears to play a role in surgically unresectable appendiceal epithelial neoplasm patients, with an improvement in PFS and OS. Anti-VEGF agents should be strongly considered in the management of patients with higher-grade appendiceal epithelial neoplasms who are suboptimal candidates for surgical resection.

Failure to improve a thin endometrium in the late proliferative phase with uterine infusion of granulocyte-colony stimulating factor.

PURPOSE: To determine if the treatment with uterine infusion of granulocyte colony-stimulating factor (G-CSF) can improve endometrial thickness in an infertile woman with a double uterus, who consistently showed a thin endometrium in the late proliferative phase either in controlled ovarian hyperstimulation (COH) IVF-ET cycles or with graduated estrogen/sildenafil protocols for frozen embryo transfer (ET). MATERIALS AND METHODS: A single uterine infusion of G-CSF was performed in the late proliferative phase in a woman who only attained a five-mm thickness despite a high dose vaginal and oral estradiol regimen plus sildenafil. RESULTS: No increase was found within a couple days. CONCLUSIONS: A previous four-case study in another center found 100% improvement in the endometrial thickness in women with consistently thin endometria. Perhaps the uterine anomaly in the present case prevented the response of the endometrium.

A multifunctional protein EWS regulates the expression of Drosha and microRNAs.

EWS (Ewing's Sarcoma) gene encodes an RNA/DNA-binding protein that is ubiquitously expressed and involved in various cellular processes. EWS deficiency leads to impaired development and early senescence through unknown mechanisms. We found that EWS regulates the expression of Drosha and microRNAs (miRNAs). EWS deficiency resulted in increased expression of Drosha, a well-known microprocessor, and increased levels of miR-29b and miR-18b. Importantly, miR-29b and miR-18b were directly involved in the post-transcriptional regulation of collagen IV alpha 1 (Col4a1) and connective tissue growth factor (CTGF) in EWS knock-out (KO) mouse embryonic fibroblast cells. The upregulation of Drosha, miR-29b and miR-18b and the sequential downregulation of Col4a1 and CTGF contributed to the deregulation of dermal development in EWS KO mice. Otherwise, knockdown of Drosha rescued miRNA-dependent downregulation of Col4a1 and CTGF proteins. Taken together, our data indicate that EWS is involved in post-transcriptional regulation of Col4a1 and CTGF via a Drosha-miRNA-dependent pathway. This finding suggests that EWS has a novel role in dermal morphogenesis through the modulation of miRNA biogenesis.

PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling.

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.

A study to determine the efficacy of controlled ovarian hyperstimulation regimen using a gonadotropin releasing hormone agonist versus antagonist in women of advanced reproductive age with varying degrees of oocyte reserve on outcome following in vitro fertilization-embryo transfer.

PURPOSE: To determine if the use of gonadotropin releasing hormone (GnRH) agonists (a) or antagonists (ant) allow better pregnancy rates when used in controlled ovarian hyperstimulation protocols in women of advanced reproductive age. Furthermore the study aimed to determine if the status of ovarian oocyte reserve has a confounding effect. MATERIALS AND METHODS: A 12-year retrospective review was performed on all in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-44. Pregnancy rates were determined according to whether a GnRH-a or GnRH-ant was used. The data were also stratified according to normal or low oocyte reserve. RESULTS: There was no significant difference in pregnancy rates according to whether a GnRH-a or GnRH-ant was used in women with normal oocyte reserve. Though a large majority of the women used a GnRH-ant, there was a 9% live pregnancy rate vs 0% in the women using a GnRH-a. CONCLUSION: Since it is unlikely that a larger study will ever be conducted, it is probably wise to use a GnRH-ant for the controlled ovarian hyperstimulation regimen in women aged 40-44 with diminished oocyte reserve.