HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level.

Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.

Design, synthesis of novel C-3'-N-sulfonyl modified taxane analogues from 1-deoxybaccatin VI and their impact on anti-HCC activity.

A new series of C-3'-N-sulfonyl paclitaxel analogs were designed and synthesized from 1-deoxybaccatin VI and their structures were confirmed by 1H NMR, 13C NMR and high resolution MS. The synthesized compounds were evaluated for their in vitro anti-Hepatocellular carcinoma (HCC) activity against human hepatoma (HepG2) cell line. Bioassay results showed that compounds 17c, 17d and 17f exhibited more potent inhibitory activity against HepG2 cell line in comparison with paclitaxel. It is suggested that paclitaxel analogs containing the C-3'-N-sulfonyl could be considered as a precursor structure for further synthesis of more potent analogues.

Synthesis and biological evaluation of novel A-seco-taxoids derived from 1-deoxybaccatin VI.

Three novel nor-seco-taxoids 13, 15, 23 in which the A rings are cleaved but the B, C, and D rings are retained were prepared from 1-deoxybaccatin VI via its nor-dioxo derivative and their structures were confirmed by 1H NMR, 13C NMR and high resolution MS. Oxidative introduction of C-1 hydroxyl to 1-deoxybaccatin VI with oxidising agent KBrO3 and catalyst RuCl3 led to the dioxo derivative 6 and its structure is determined by X-ray crystallographic analysis. A-seco taxoids 13, 15, 23 with a C-13 ester linkage were tested for cytotoxic activity and all compounds showed no measurable cytotoxic activity against HCT-116 cell line. However, 1-deoxy-9a-dihydrotaxane analogue 4 semi-synthesised from 1-deoxybaccatin VI is 10-fold less cytotoxic than paclitaxel, indicating the indispensible nature of the A ring double bond for the bioactivity of paclitaxel.

The efficacy of traditional Chinese Medical Exercise for Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Several studies assessed the efficacy of traditional Chinese medical exercise in the management of Parkinson's disease (PD), but its role remained controversial. Therefore, the purpose of this systematic review is to evaluate the evidence on the effect of traditional Chinese medical exercise for PD. METHODS: Seven English and Chinese electronic databases, up to October 2014, were searched to identify relevant studies. The PEDro scale was employed to assess the methodological quality of eligible studies. Meta-analysis was performed by RevMan 5.1 software. RESULTS: Fifteen trials were included in the review. Tai Chi and Qigong were used as assisting pharmacological treatments of PD in the previous studies. Tai Chi plus medication showed greater improvements in motor function (standardized mean difference, SMD, -0.57; 95% confidence intervals, CI, -1.11 to -0.04), Berg balance scale (BBS, SMD, -1.22; 95% CI -1.65 to -0.80), and time up and go test (SMD, -1.06; 95% CI -1.44 to -0.68). Compared with other therapy plus medication, Tai Chi plus medication also showed greater gains in motor function (SMD, -0.78; 95% CI -1.46 to -0.10), BBS (SMD, -0.99; 95% CI -1.44 to -0.54), and functional reach test (SMD, -0.77; 95% CI -1.51 to -0.03). However, Tai Chi plus medication did not showed better improvements in gait or quality of life. There was not sufficient evidence to support or refute the effect of Qigong plus medication for PD. CONCLUSIONS: In the previous studies, Tai Chi and Qigong were used as assisting pharmacological treatments of PD. The current systematic review showed positive evidence of Tai Chi plus medication for PD of mild-to-moderate severity. So Tai Chi plus medication should be recommended for PD management, especially in improving motor function and balance. Qigong plus medication also showed potential gains in the management of PD. However, more high quality studies with long follow-up are warrant to confirm the current findings.

Gastrointestinal stromal tumor: 15-years' experience in a single center.

BACKGROUND: Gastrointestinal stromal tumor (GIST) is known for its wide variability in biological behaviors and it is difficult to predict its malignant potential. The aim of this study is to explore the characteristics and prognostic factors of GIST. METHODS: Clinical and pathological data of 497 GIST patients in our center between 1997 and 2012 were reviewed. RESULTS: Patients were categorized into very low-, low-, intermediate- and high-risk groups according to modified National Institutes of Health (NIH) consensus classification system. Among the 401 patients untreated with imatinib mesylate (IM), 5-year overall survival (OS) in very low-, low-, intermediate- and high-risk groups was 100%, 100%, 89.6% and 65.9%; and 5-year relapse-free survival (RFS) was 100%, 98.1%, 90.9% and 44.5%, respectively. Univariate analysis revealed that sex, tumor size, mitotic rate, risk grade, CD34 expression, and adjacent involvement were predictors of OS or RFS. COX hazard proportional model (Forward LR) showed that large tumor size, high mitotic rate, and high risk grade were independent risk factors to OS, whereas high mitotic rate, high risk grade and adjacent organ involvement were independent risk factors to RFS. The intermediate-high risk patients who received IM adjuvant therapy (n = 87) had better 5-year OS and RFS than those who did not (n = 188) (94.9% vs. 72.1; 82.3% vs. 56.3%, respectively). Similarly, advanced GIST patients underwent IM therapy (n = 45) had better 3-year OS and 1-year progression-free survival (PFS) than those who didn't (n = 42) (75.6% vs. 6.8%; 87.6% vs. 12.4%, respectively). CONCLUSIONS: Very low- and low-risk GISTs can be treated with surgery alone. Large tumor size, high mitotic rate, high risk grade, and adjacent organ involvement contribute to the poor outcome. IM therapy significantly improves the survival of intermediate-high risk or advanced GIST patients.

Minimally invasive treatment of laparoscopic and endoscopic cooperative surgery for patients with gastric gastrointestinal stromal tumors.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery (LECS) for the treatment of gastric gastrointestinal stromal tumors (GISTs). METHODS: We retrospectively reviewed the data of 69 consecutive patients who underwent LECS, including laparoscopy-assisted endoscopic resection (LAER) and endoscopy-assisted laparoscopic wedge resection (EAWR), for pathologically confirmed gastric GISTs of less than 5 cm in diameter from January 2006 to October 2012. RESULTS: The tumor was located at the upper third of the stomach in 22 patients, the middle third in 38 and the lower third in nine, with a mean tumor size of 2.8 ± 1.6 cm. The operating time was 81.6 ± 31.8 min in the LAER group and 86.3 ± 28.5 min in the EAWR group (P = 0.776). Intraoperative blood loss was 29.8 ± 15.4 mL in the LAER group and 31.4 ± 11.6 mL in the EAWR group (P = 0.561). Most patients had a very low or low risk of tumor recurrence, while six had an intermediate risk of tumor recurrence. The mean length of postoperative hospital stay was 4.6 days. Only two patients had postoperative complications after LECS, both of whom were treated successfully without open surgery. During a median follow-up of 35 months, all patients were disease-free, with no tumor recurrence or metastases. CONCLUSION: LECS is a minimally invasive and safe alternative approach which can achieve fast recovery and satisfactory short-term outcomes for appropriately selected patients with gastric GISTs.

[Clinicopathological features and management of gastrointestinal stromal tumors complicated with synchronous other alimentary malignant tumor].

OBJECTIVE: To explore the clinicopathologic features, treatment and prognosis of gastrointestinal stromal tumor (GIST) complicated with synchronous other alimentary malignant tumors. METHODS: Clinical data of 525 patients with GIST undergoing surgical treatment from August 2004 to November 2012 in Shanghai Renji Hospital were reviewed retrospectively, among whom 46 patients presented synchronous other alimentary malignancy. RESULTS: GIST and other alimentary malignancy coexisting cases were less likely to be screened out preoperatively (2.2%, 1/46) and associated with elder age (P=0.001), more likely arise from stomach (P=0.000), smaller tumor maximum diameter (P=0.000), and lower mitotic count (P=0.000). According to NIH postoperative risk classification, there were 36 at very low risk, 9 at low risk, and 1 at high risk. Although the risk of GIST recurrence was lower for GIST and other alimentary malignancy coexisting cases, their 5-year survival rate was lower than that of patients with GIST alone (36.1%VS. 82.2%, P=0.000). CONCLUSIONS: GIST patients complicated with synchronous alimentary malignant tumor are usually low or very low risk and has minimal impact on the prognosis. Survival depends primarily on the synchronous alimentary malignant tumors. Therefore, it is reasonable to lay emphasis on the treatment of the alimentary malignant tumor, and perform synchronous resection of GIST if possible.

[Clinical analysis of laparoscopic and endoscopic cooperative surgery in the treatment of gastric gastrointestinal stromal tumor: report of 46 cases].

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic and endoscopic cooperative surgery for treating gastric gastrointestinal stromal tumors(GIST). METHODS: Retrospective analysis was performed on the clinical data of 46 patients with gastric GIST undergoing laparoscopic and endoscopic cooperative surgery between June 2009 and June 2011 at the Renji Hospital of Shanghai Jiaotong University School of Medicine. RESULTS: There were 27 males and 19 females with the mean age of 58.5 years. Thirty-three patients received endoscopy-assisted wedge resection, and 13 cases received laparoscopy-assisted endoscopic resection. All the operations were successful. The mean operative time was (85.5±29.3) min, the mean blood loss was (31.4±12.2) ml, the mean post-operative gastrointestinal functional recovery time was (31.6±14.9) h, and the mean post-operative hospital stay was (5.1±2.9) d. No post-operative complication occurred. NIH risk assessment showed that 34 cases were very low risk and 12 low risk. No recurrence or metastasis was found during the follow-up ranging from 2 to 26 months(median, 12.6 months). CONCLUSION: Laparoscopic and endoscopic cooperative surgery for gastric GIST is both feasible and safe with minimal invasiveness, fast recovery and satisfactory short-term outcomes.