[Clinical application of Fastpass Scorpion suture passer for arthroscopic Bankart repair].

Objective: To explore the effectiveness and advantages of using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair compared with traditional arthroscopic suture shuttle. Methods: The clinical data of 41 patients with Bankart lesion, who met the selection criteria and were admitted between August 2019 and October 2021, was retrospectively analyzed. Under arthroscopy, the inferior capsulolabral complex was stitched with Fastpass Scorpion suture passer in 27 patients (FS group) and with arthroscopic suture shuttle in 14 patients (ASS group). There was no significant difference between the two groups ( P>0.05) in gender, age, injured side, frequency of shoulder dislocation, time from first dislocation to operation, and preoperative Rowe score of shoulder. Taking successful suture and pull-tightening as the criteria for completion of repair, the number of patients that were repaired at 5∶00 to 6∶00 (<6:00) and 6∶00 to 7∶00 positions of the glenoid in the two groups was compared. The operation time, and the difference of Rowe shoulder score betwee pre- and post-operation, the occurrence of shoulder joint dislocation, the results of apprehension test, and the constituent ratio of recovery to the pre-injury movement level between the two groups at 1 year after operation. Results: Both groups completed the repair at 5∶00 to 6∶00 (<6∶00), and the constituent ratio of patients completed at 6∶00 to 7∶00 was significantly greater in the FS group than in the ASS group ( P<0.05). The operation time was significantly shorter in the FS group than in the ASS group ( P<0.05). All incisions in the two groups healed by first intention. All patients were followed up 12-36 months (mean, 19.1 months). No anchor displacement or neurovascular injury occurred during follow-up. Rowe score of shoulder in the two groups significantly improved at 1 year after operation than preoperative scores ( P<0.05), and there was no significant difference in the difference of Rowe shoulder score between pre- and post-operation between the two groups ( P>0.05). At 1 year after operation, no re-dislocation occurred, and there was no significant difference in the apprehension test and the constituent ratio of recovery to the pre-injury movement level between the two groups ( P>0.05). Conclusion: Compared with the arthroscopic suture shuttle, using Fastpass Scorpion suture passer to stitch the inferior capsulolabral complex in arthroscopic Bankart repair is more convenient, saves operation time, and has good effectiveness.

Berberine targets KIF20A and CCNE2 to inhibit the progression of nonsmall cell lung cancer via the PI3K/AKT pathway.

BACKGROUND: Nonsmall cell lung cancer (NSCLC) is the main type of lung cancer, accounting for approximately 85%. Berberine (BBR), a commonly used traditional Chinese medicine, has been reported to exhibit a potential antitumor effect in various cancers. In this research, we explored the function of BBR and its underlying mechanisms in the development of NSCLC. METHODS: Cell Counting Kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation assays, flow cytometry, and transwell invasion assay were employed to determine cell growth, the apoptotic rate, cell invasion of NSCLC cells, respectively. Western blot was applied for detecting the protein expression of c-Myc, matrix metalloprotease 9 (MMP9), kinesin family member 20A (KIF20A), cyclin E2 (CCNE2), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway-related proteins. Glycolysis was evaluated by detecting glucose consumption, lactate production, and adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio with the matched kits. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to analyze the level of KIF20A and CCNE2. Tumor model was established to evaluate the function of BBR on tumor growth in NSCLC in vivo. In addition, immunohistochemistry assay was employed to detect the level of KIF20A, CCNE2, c-Myc, and MMP9 in mice tissues. RESULTS: BBR exhibited suppressive effects on the progression of NSCLC, as evidenced by inhibiting cell growth, invasion, glycolysis, and facilitating cell apoptosis in H1299 and A549 cells. KIF20A and CCNE2 were upregulated in NSCLC tissues and cells. Moreover, BBR treatment significantly decreased the expression of KIF20A and CCNE2. KIF20A or CCNE2 downregulation could repress cell proliferation, invasion, glycolysis, and induce cell apoptosis in both H1299 and A549 cells. The inhibition effects of BBR treatment on cell proliferation, invasion, glycolysis, and promotion effect on cell apoptosis were rescued by KIF20A or CCNE2 overexpression in NSCLC cells. The inactivation of PI3K/AKT pathway caused by BBR treatment in H1299 and A549 cells was restored by KIF20A or CCNE2 upregulation. In vivo experiments also demonstrated that BBR treatment could repress tumor growth by regulating KIF20A and CCNE2 and inactivating the PI3K/AKT pathway. CONCLUSION: BBR treatment showed the suppressive impact on the progression of NSCLC by targeting KIF20A and CCNE2, thereby inhibiting the activation of the PI3K/AKT pathway.

Impacts of neoadjuvant therapy on the number of dissected lymph nodes in esophagogastric junction cancer patients.

BACKGROUND: Neoadjuvant therapy favors the prognosis of various cancers, including esophagogastric junction cancer (EGC). However, the impacts of neoadjuvant therapy on the number of dissected lymph nodes (LNs) have not yet been evaluated in EGC. METHODS: We selected EGC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2006-2017). The optimal number of resected LNs was determined using X-tile software. Overall survival (OS) curves were plotted with the Kaplan-Meier method. Prognostic factors were evaluated using univariate and multivariate COX regression analyses. RESULTS: Neoadjuvant radiotherapy significantly decreased the mean number of LN examination compared to the mean number of patients without neoadjuvant therapy (12.2 vs. 17.5, P = 0.003). The mean LN number of patients with neoadjuvant chemoradiotherapy was 16.3, which was also statistically lower than 17.5 (P = 0.001). In contrast, neoadjuvant chemotherapy caused a significant increase in the number of dissected LNs (21.0, P < 0.001). For patients with neoadjuvant chemotherapy, the optimal cutoff value was 19. Patients with > 19 LNs had a better prognosis than those with 1-19 LNs (P < 0.05). For patients with neoadjuvant chemoradiotherapy, the optimal cutoff value was 9. Patients with > 9 LNs had a better prognosis than those with 1-9 LNs (P < 0.05). CONCLUSIONS: Neoadjuvant radiotherapy and chemoradiotherapy decreased the number of dissected LNs, while neoadjuvant chemotherapy increased it in EGC patients. Hence, at least 10 LNs should be dissected for neoadjuvant chemoradiotherapy and 20 for neoadjuvant chemotherapy, which could be applied in clinical practice.

In vitro anti-cancer effect of marmesin by suppression of PI3K/Akt pathway in esophagus cancer cells.

BACKGROUND: Marmesin, an important coumarin isolated from Broussonetia kazinoki, has been proposed to possess many pharmacological activities including anti-tumor activity. However, the anti-cancer effect of marmesin on esophageal cancer (EC) has not been characterized. The study aimed to explore the anti-cancer role of marmesin using EC cell lines in vitro. METHODS AND RESULTS: Cell proliferation was evaluated by CCK-8 and Edu cell proliferation assays and apoptosis was detected by TUNEL assay. Western blot analysis was used to determine the expression of Ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, phosphatidylinositol 3-kinase (PI3K), phosphoryrated-PI3K (p-PI3K), protein kinase B (Akt), and phosphoryrated-Akt (p-Akt). The mechanism of action of marmesin was analyzed using network pharmacology approach. Marmesin exhibited anti-proliferative effect against EC cells, which was further confirmed by the reduced expression of Ki67 and PCNA. Marmesin exerted pro-apoptotic activity on EC cells by downregulating Bcl-2 and upregulating Bax. According to the results from network pharmacology approach, we speculated that PI3K/Akt pathway may participate in the effect of marmesin on EC cells. Additionally, the PI3K/Akt pathway was suppressed by marmesin in EC cells. Moreover, forced expression of Akt reversed the inhibition of cell proliferation and induction of apoptosis induced by marmesin in EC cells. CONCLUSIONS: Marmesin exerted anti-cancer activity in EC cells by inhibiting the PI3K/Akt pathway.

Oesophagectomy following noncurative endoscopic resection for oesophageal carcinoma: does interval matter?

OBJECTIVES: Oesophagectomy was always recommended after noncurative endoscopic resection (ER). And the optimal time interval from ER to oesophagectomy remains unclear. This study was to explore the effect of interval on pathologic stage and prognosis. METHODS: We included 155 patients who underwent ER for cT1N0M0 oesophageal cancer and then received subsequent oesophagectomy from 2009 to 2019. Overall survival and disease-free survival (DFS) were analysed to find an optimal cut-off of interval from ER to oesophagectomy. In addition, pathologic stage after ER was compared to that of oesophagectomy. Logistic regression model was built to identify risk factors for pathological upstage. RESULTS: The greatest difference of DFS was found in the groups who underwent oesophagectomy before and after 30 days (P = 0.016). Among total 155 patients, 106 (68.39%) received oesophagectomy within 30 days, while 49 (31.61%) had interval over 30 days. Comparing the pathologic stage between ER and oesophagectomy, 26 patients had upstage and thus had worse DFS (hazard ratio = 3.780, P = 0.042). T1b invasion, lymphovascular invasion and interval >30-day group had a higher upstage rate (P = 0.014, P < 0.001 and P < 0.001, respectively). And they were independent risk factors for pathologic upstage (odds ratio = 3.782, 4.522 and 2.844, respectively). CONCLUSIONS: It was the first study exploring the relationship between time interval and prognosis in oesophageal cancer. The longer interval between noncurative ER and additional oesophagectomy was associated with a worse DFS, so oesophagectomy was recommended performed within 1 month after ER. Older age, T1b stage, lymphovascular invasion and interval >30 days were significantly associated with pathologic upstage, which is related to the worse outcome too.

Tears of the Popliteomeniscal Fascicles of the Lateral Meniscus: An Arthroscopic Classification.

OBJECTIVE: To bring forward an arthroscopic classification of the popliteomeniscal fascicles of the lateral meniscus (PFLM) tears. DESIGN: Six fresh frozen knee joint samples of adult males were chosen, and the lateral meniscus at the popliteal hiatus region were measured to analyze their anatomic relationship. Patients who had received magnetic resonance imaging scan at knee joint before the surgery and diagnosed as PFLM tears by arthroscopy from April 2014 to October 2017 were selected. Data regarding the integrity of PFLM were prospectively recorded in a data registry. Tear morphology and treatment received were subsequently extracted by 2 independent reviewers from operative notes and arthroscopic surgical photos. RESULTS: The average length and thickness of the popliteal hiatus of the lateral meniscus were 2.09 ± 0.21 cm and 0.43 ± 0.08 cm, respectively. The average length of anterosuperior popliteomeniscal fascicle (APF) was 0.87 ± 0.18 cm, and the posterosuperior popliteomeniscal fascicle (PPF) was 0.72 ± 0.15 cm. A total of 36 PFLM tears in 36 patients were divided as type I (APF tear; n = 5, 13.9%), type II (PPF tear; n = 20, 55.6%), and type III (both APF and PPF tears; n = 11, 30.6%). All patients were treated with arthroscopic all-inside repair using a suture hook for the PFLM tears and follow-up for 21.1 months. All patients have done well with significantly improved Lysholm and International Knee Documentation Committee scores at the last follow-up relative to preoperative scores (P < 0.01). CONCLUSION: This study suggests to possibly classify the PFLM tears for clinical practice.

The Chinese Knot Stitch Technique Using a Footprint Ultrasuture Anchor for Rotator Cuff Repair.

Management of the rotator cuff presents specific challenges to orthopaedic surgeons. Several locking suture methods have been reported but often fail for a number of reasons. We describe a different technique that is easy to perform and inspired by the Chinese knot, an arthroscopic double-locking suture using a footprint ultrasuture anchor. This technique is similar to the suture-bridge structure on the bursal side of the tendon in that it increases tissue grip and stabilizes initial tendon-to-bone fixation. This technique is especially suitable for the patients who have bursal-side partial-thickness or degenerative small- and medium-sized rotator cuff tears.

Conformational analysis of the disaccharide methyl α-D-mannopyranosyl-(1→3)-2-O-acetyl-ß-D-mannopyranoside monohydrate.

The crystal structure of methyl α-D-mannopyranosyl-(1→3)-2-O-acetyl-ß-D-mannopyranoside monohydrate, C15H26O12·H2O, (II), has been determined and the structural parameters for its constituent α-D-mannopyranosyl residue compared with those for methyl α-D-mannopyranoside. Mono-O-acetylation appears to promote the crystallization of (II), inferred from the difficulty in crystallizing methyl α-D-mannopyranosyl-(1→3)-ß-D-mannopyranoside despite repeated attempts. The conformational properties of the O-acetyl side chain in (II) are similar to those observed in recent studies of peracetylated mannose-containing oligosaccharides, having a preferred geometry in which the C2-H2 bond eclipses the C=O bond of the acetyl group. The C2-O2 bond in (II) elongates by ∼0.02 Šupon O-acetylation. The phi (φ) and psi (ψ) torsion angles that dictate the conformation of the internal O-glycosidic linkage in (II) are similar to those determined recently in aqueous solution by NMR spectroscopy for unacetylated (II) using the statistical program MA'AT, with a greater disparity found for ψ (Δ = ∼16°) than for φ (Δ = ∼6°).

Pigment Epithelium-Derived Factor Promotes the Growth and Migration of Human Esophageal Squamous Cell Carcinoma.

Pigment epithelium-derived factor (PEDF) is an oncogene found in various types of cancers. However, how PEDF affects the development of human esophageal squamous cell carcinoma (ESCC) is unknown. This study investigates the role of PEDF in ESCC cell proliferation, migration, and cell cycle both in vitro and in vivo. The PEDF expression was examined in patient tumor samples and ESCC cell lines. Short hairpin RNA technology was used to inhibit the PEDF expression in ESCC EC9706 and KYSE150 cells. In vitro cell proliferation and migration assays were performed. The effects of PEDF on tumor growth and progression were examined in vivo in murine subcutaneous xenograft tumor models. It was found that PEDF was overexpressed in esophageal cancer cells and patient tumor tissues compared to normal control samples. PEDF enhanced cell cycle progression and inhibited cell apoptosis. Knock down of PEDF inhibited esophageal cell proliferation and migration in vitro. Moreover, Inhibition of PEDF significantly reduced tumor growth and tumor size in vivo. These results indicate that PEDF induce tumorigenesis in ESCC and can be a potential therapeutic target for cancer treatment.

The inhibitory effects of ginsenoside Rd on the human glioma U251 cells and its underlying mechanisms.

OBJECTIVE: The current study was designed to investigate the inhibitory effects of ginsenoside Rd (Gs-Rd) on human glioma U251 cells in vitro and its possible underlying mechanisms. METHODS: The groups included blank control group, low concentration Gs-Rd treatment group (20 µM), mid concentration Gs-Rd treatment group (40 µM), and high concentration Gs-Rd treatment group (80 µM). The proliferative activity of human glioma U251 cells was detected by the MTT assay. Flow cytometry was performed to measure cell apoptosis of human glioma U251 cells. In addition, the ELISA assay was used to measure the telomerase activities in different groups on 24 hours, 48 hours, and 72 hours. Furthermore, real-time quantitative polymerase chain reaction (RT-PCR) and Western blot analysis were performed to measure the expression of Bcl-2, human telomerase catalytic subunit (hTERT), and caspase-3 in different groups on 48 hours at both messenger RNA (mRNA) and protein levels. RESULTS: The proliferation of U251 cells was inhibited by Gs-Rd with different concentrations in the dose- and time-dependent manners. In addition, Gs-Rd promoted U251 cell apoptosis rate in a dose-dependent manner. Gs-Rd with different concentrations (20 µM, 40 µM, and 80 µM) significantly enhanced the expression of teleomerase on 24 hours and 48 hours. In addition, Gs-Rd with different concentrations significantly increased caspase-3 and decreased Bcl-2 and hTERT expressions at both mRNA and protein levels. CONCLUSION: The Gs-Rd can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to inhibiting telomerase activity, downregulating expression of Bcl-2 and hTERT, and upregulating expression of caspase-3 of human glioma U251 cells.

microRNA-383 regulates cell viability and apoptosis by mediating Wnt/ß-catenin signaling pathway in non-small cell lung cancer.

The aim of this study was to investigate the roles of microRNA-383 (miRNA-383) in progression of non-small cell lung cancer (NSCLC) and the potential mechanism. The expressions of miR-383 and Wnt1 protein were detected in lung cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. After the transfection of miR-383 mimics, si-Wnt1 or miR-383+Wnt1, the viability and apoptosis of NSCLC cells were detected by cell counting kit-8 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, respectively. The interaction between miR-383 and Wnt1 was investigated by luciferase activity and Western blot analysis. Cells stably transfected with miR-383 mimics were inoculated into the right axillary of nude mice by subcutaneous injection. The tumor volume and weight were measured, and the expressions of miR-383, Wnt1, ß-catenin, and cyclin D1 were detected by qRT-PCR and Western blot analysis. The expression of miR-383 was significantly decreased, and the level of Wnt1 was significantly increased (P < 0.05) in lung cancer tissues and cells. Upregulation of miR-383 or inhibition of Wnt1 expression inhibited the cell viability and induce apoptosis in NSCLC cells. Moreover, Wnt1 was the target gene of miR-383, and its overexpression weakened the regulatory effect of miR-383 on cell viability and apoptosis in NSCLC cells. Besides, the addition of miR-383 decreased the tumor volume and size and inhibited the expressions of Wnt1, ß-catenin, and cyclin D1 at the protein level in nude mice. Collectively, miR-383 induced apoptosis and inhibited cell viability as well as tumorigenic capacity in nude mice via regulating the Wnt/ß-catenin signaling pathway.

Effect of GDF11 on proliferation and apoptosis of esophageal cancer cells.

This study was aimed at investigating the effect of growth differentiation factor 11 (GDF11) on the proliferation and apoptosis of esophageal cancer cells. Serum levels of GDF11 in esophageal cancer patients were determined with ELISA kits, and the correlation between serum GDF11 and pathological features of esophageal cancer were determined. The effect of recombinant GDF11 on the growth of esophageal cancer cells was measured by CCK6 method. In order to investigate the effect of recombinant GDF11 on the proliferation and apoptosis of esophageal cancer cells, the expression of apoptosis-promoting protein Bax and proliferative-associated protein Bcl-2 in esophageal cancer cells were determined using western blot. Moreover, GDF11 was used to treat esophageal cancer cells, and its effect on proliferation and apoptosis was determined with MTT assay and flow cytometry, respectively. The serum content of GDF11 was much less in esophageal cancer patients than in the control group. Esophageal GDF II in cancer patients was correlated with cancer differentiation: the higher the degree of differentiation, the higher the content of GDF11. GDF11 inhibits proliferation and apoptosis of esophageal cancer cells.

Downregulation of KLK13 promotes the invasiveness and metastasis of oesophageal squamous cell carcinoma.

KLK13 downregulation occurs in tumour tissues in comparison with adjacent normal tissues from patients with oesophageal squamous cell carcinoma (OSCC). KLK13 mRNA levels were tested in OSCC tumour tissues and adjacent noncancerous tissues from 138 patients. In addition, the correlation between KLK13 mRNA levels and OSCC clinicopathologic features was analysed. KLK13 mRNA levels decreased notably in tumour tissues compared with those in adjacent noncancerous tissues. And decreased KLK13 mRNA levels indicated significant correlations with higher tumour grade, elevated TNM (UICC, 2009) stage classification, deeper infiltration and more lymph node metastases. And thus KLK13 may be a promising diagnostic marker. Decreased KLK13 mRNA levels also correlate with poor survival, which indicates that KLK13 mRNA expression may be a potential prognostic marker, although it could not be an independent prognostic factor by multivariate analysis. In vitro experiments of the OSCC cell lines KYSE150 and KYSE450 demonstrated that overexpression of KLK13 inhibits cell invasion and migration. Thus, KLK13 is a unique novel molecule useful for monitoring OSCC progression. Full elucidation of the role of KLK13 in OSCC may reveal avenues for investigating the molecule's functional potential as a novel therapeutic drug for targeting OSCC.

Adverse events risk associated with anti-VEGFR agents in the treatment of advanced nonsmall-cell lung cancer: A meta-analysis.

To perform this meta-analysis, we investigated the risk of the most clinically relevant adverse events related to antivascular endothelial growth factor receptor (VEGFR) agents in advanced nonsmall-cell lung cancer (NSCLC).A comprehensive literature search for studies published up to October 2015 was performed. Prospective randomized controlled phase II/III clinical trials that comparing therapy with or without anti-VEGFR agents for advanced NSCLC were included for analysis. Summary relative risk (RR) and 95% confidence intervals (CIs) were calculated using random effects or fixed effects according to the heterogeneity among included trials.A total of 11,701 patients from 18 clinical trials were included for analysis. Pooled RR showed that the use of anti-VEGFR agents significantly increased the risk of developing hypertension (RR 4.71, 95% CI 3.29-6.73, P < 0.001) and fatal adverse events (RR 1.33, 95% CI 1.12-1.58, P = 0.001). No statistically significant differences were found for gastrointestinal (GI) perforation (P = 0.41), arterial or venous thromboembolic events (P = 0.49 and P = 0.16, respectively), or hemorrhagic events (P = 0.81). Sensitive analysis indicated that the significance estimate of pooled RR of fatal adverse event (FAEs) was not significantly influenced by omitting any single study.The use of anti-VEGFR agents in advanced NSCLC does significantly increase the risk of hypertension and fatal adverse events, but not for arterial or venous thromboembolic events, GI perforation, or hemorrhagic events.

High expression of long non-coding RNA AFAP1-AS1 predicts chemoradioresistance and poor prognosis in patients with esophageal squamous cell carcinoma treated with definitive chemoradiotherapy.

To evaluate the clinical significance of lncRNAs in the resistance to cisplatin-based chemoradiotherapy in esophageal squamous cell carcinoma (ESCC). We focused on lncRNAs which were frequently reported in ESCC or were involved in chemoradiotherapy resistance. LncRNA expressions were examined in paired cisplatin-resistant and parental ESCC cell lines. Dysregulated lncRNAs were further measured in 162 pretreatment biopsy specimens of ESCC who received definitive chemoradiotherapy (dCRT). Then the correlations between lncRNA expression and response to dCRT and prognosis were analyzed. Three lncRNAs (AFAP1-AS1, UCA1, HOTAIR) were found to be deregulated in cisplatin-resistant cells compared with their parent cells. AFAP1-AS1 was significantly up-regulated in tumor tissues compared with adjacent normal tissues (P = 0.006). Furthermore, overexpression of AFAP1-AS1 was closely associated with lymph node metastasis (P < 0.001), distant metastasis (P = 0.016), advanced clinical stage (P = 0.002), and response to dCRT (P < 0.001). Kaplan-Meier survival analysis revealed that high expression of AFAP1-AS1 was significantly associated with shorter progression free survival (PFS) (median, 15 months vs. 27 months, P < 0.001) and overall survival (OS) (median, 29 months vs. 42 months, P < 0.001). In the multivariate analysis, high expression of AFAP1-AS1 was found to be an independent risk factor to predict poor PFS (HR, 1.626; P = 0.027) and OS (HR, 1.888; P = 0.004). Thus, high expression of AFAP1-AS1 could serve as a potential biomarker to predict tumor response and survival. Determination of this lncRNA expression might be useful for selection ESCC patients for dCRT. © 2016 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

Implication of lncRNAs in pathogenesis of esophageal cancer.

Long non-coding RNAs (lncRNAs), transcripts as longer than 200 nt in length with a great number of varieties in human genomics, play important roles in the regulation of genetics and epigenetics including gene transcription and post-transcription. Increasing evidence have demonstrated the upregulation of lncRNAs in tumorigenesis and metastasis of esophageal cancer (EC), a type of malignant tumors particularly in Asia. In this review, we briefly discuss the profiles and functions of lncRNAs involved in the progression of EC, which may provide a new approach to improve EC diagnosis and treatment.

Effect of fasudil on hypoxic pulmonary hypertension and right ventricular hypertrophy in rats.

OBJECTIVE: To investigate whether right ventricular hypertrophy in hypoxic pulmonary hypertension (HPH) rats could be prevented by treatment with Rho kinase inhibitor fasudil. METHODS: The rat model of pulmonary hypertension was established by exposing rats to normobaric intermitent hypoxia [(10 ± 0.5)% O2]. Twenty-four Spraque-Dawley male rats were randomly divided into control group, hypoxic model group and hypoxia with fasudil groups (n=8 each). The mean pulmonary arterial pressure (mPAP), and right ventricle hypertrophy index (RVHI) were measured. Ultrastructure of the right ventricular myocardial cells was observed under transmission electron microscope (TEM). - RESULTS: The level of mPAP (31.38 ± 1.98) mmHg and RVHI (0.47 ± 0.03) were significantly higher in the hypoxic model group than (15.25 ± 0.91) mmHg and (0.25 ± 0.02) in control group respectively (P<0.01). Transmission electron microscope (TEM) revealed the model group right ventricular mitochondria increased significantly, swelling, cristae blurred, lost, heart muscle Siming dark band was not clear. The level of mPAP (16.63 ± 1.53) mmHg and RVHI (0.27 ± 0.02) were significantly lower in fasudil treatment group than in model group respectively (P<0.01). After the intervention of fasudil right ventricular myocardial injury was significantly reduced. CONCLUSIONS: Fasudil may partly prevent and reverse the development of pulmonary hypertension and right ventricular hypertrophy and myocardial cell injury.

Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.

Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC.

Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC. METHODS: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC. RESULTS: ESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%). CONCLUSIONS: Plasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the combination of POU3F3 and SCCA was more efficient for ESCC detection, in particular for early tumor screening.

Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP.

BACKGROUND/AIMS: Esophageal carcinoma is one of the most aggressive human cancers, and novel treatment modality is required. Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of esophageal cancer cells exhibit resistance to the cytotoxic effect of this ligand. Licochalcone-A (LA), a flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties such as anticancer, antioxidant, and anti-inflammatory activities. METHODOLOGY: Eca109 and TE1 cells were cultured and transfected, then their viability was detected using MTT assay. Immunoprecipitation and immunoblotting analysis and RT-PCR analysis were also performed. RESULTS: In this study, we found that LA synergistically caused the TRAIL-induced apoptosis in Eca109 and TE1 cells. Such potentiation was achieved through inhibiting Akt activation and promoting proteasomal degradation of X-linked Inhibitor of Apoptosis Protein (XIAP) which mediated the survival signals and allow the cells to escape from apoptosis in various human cancers. CONCLUSIONS: The combination of TRAIL and LA might be a novel therapeutic strategy for esophageal carcinoma patients who fail to respond to standard chemotherapy.