Prognostic significance of X-linked inhibitor of apoptosis protein in patients with gastrointestinal tract cancers: A meta-analysis.

BACKGROUND: The aim of this meta-analysis was to systematically evaluate the prognostic significance of X-linked inhibitor of apoptosis protein (XIAP) in patients with gastrointestinal tract (GIT) cancers. METHODS: PubMed, Web of Science, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for potentially eligible literature. The baseline characteristics and relevant data were extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to assess the prognostic role of XIAP in patients with GIT cancers. RESULTS: Twelve studies with 2,477 patients were included. The pooled HRs of higher expression of XIAP for overall survival (OS) and recurrence free survival (RFS) in patients with GIT cancers were 1.64 (95% CI, 1.27-2.13) and 1.06 (95% CI, 0.96-1.16), respectively. Subgroup analysis and sensitivity analysis were also performed. No significant publication bias was found. CONCLUSION: Our results suggested that XIAP could be a prognostic marker for OS but not RFS in patients with GIT cancers. Higher expression of XIAP was related to poorer OS. These findings may help evaluate the prognosis of patients and assist future research on novel therapeutic strategies of GIT cancers by targeting XIAP. However, more well-designed studies are warranted to verify the results.

RALBP1 regulates oral cancer cells via Akt and is a novel target of miR-148a-3p and miR-148b-3p.

BACKGROUND: Malignant tumors arising from the epithelium of the oral cavity are termed as squamous cell carcinomas (OSCC). The aim of the current work was to understand the role of an isoform of RAS-like protein (RAL), RALBP1, in mediating squamous cell tumorigenesis. The study also aims to understand epigenetic modifications of RALBP1 mediated through microRNA-148a/b-3p. METHODS: Biopsies of tumor and healthy tissues from 25 patients with OSCC were collected and subjected to RNA and protein extraction to confirm upregulation of RLBP1 in tumor tissues. Expression of RLBP1 was silenced in SCC-9, using shRNA, and HN6 was transfected with plasmid bearing genes for RLBP1 over expression. Tumorigenic traits such as increased glucose uptake, aerobic glycolysis, enhanced cellular survival, cell migration, and invasion were assessed. Probable, molecular machinery involved in the upregulation was also assessed using Western blots. Using Target Scan tool, the miRNAs targeting RLBP1 were identified. Rescue of phenotypes in presence of miRNAs were also evaluated. RESULTS: Over expression of RLBP1 was associated with increased glucose uptake and aerobic glycolysis mediated ATP synthesis. The cells divided at a faster rate with a higher rate of migration and invasion phenotype. miR-148a/b-3p were found to target RLBP1 and rescued RLBP1 mediated phenotype. CONCLUSION: RLBP1 may mediate squamous cell tumorigenesis in oral cavity, independently of the RAS protein and through Akt. miR-148a/b-3p functions as a tumor suppressor by targeting RLBP1.

Glycyrrhizin suppresses the expressions of HMGB1 and ameliorates inflammative effect after acute subarachnoid hemorrhage in rat model.

High-mobility group box 1 (HMGB1), a nuclear protein that has endogenous cytokine-like activity, is involved in early brain injury after subarachnoid hemorrhage (SAH) by mediating inflammatory response. This study was conducted to investigate the effect of glycyrrhizin as an inhibitor of HMGB1 in a rat SAH model. Experimental SAH was induced by using autologous blood injection to prechiasmatic cistern. 15 mg/kg glycyrrhizin was administered immediately after SAH induction, and then administered once at 6, 12 and 18 h. All the rats were sacrificed at 24 h after neurological assessment and frontal brain tissue was taken for assay. Blood-brain barrier (BBB) permeability was determined by Evans blue (EB) extravasation. The expression of HMGB1 were detected by immunofluorescence, western blot and quantitative real-time PCR. Inflammatory mediators (TNF-α, IL-1ß) were measured using specific ELISA. Fluoro-Jade C staining and TUNEL staining was performed for the quantitative assessment of neuronal injury. We found the use of glycyrrhizin significantly improved neurological scores, reduced HMGB1-positive cells, down-regulated mRNA and protein levels of HMGB1, inhibited BBB permeability, and attenuated neuronal cell death and apoptosis after SAH. The up-regulations of inflammation-related molecules (TNF-α, IL-1ß) in SAH rats were suppressed by glycyrrhizin treatment. These findings suggest that glycyrrhizin is a potential candidate for the treatment of inflammatory brain injury after SAH.

Accuracy of computed tomography angiography in detecting the underlying vascular abnormalities for spontaneous intracerebral hemorrhage: a comparative study and meta-analysis.

BACKGROUND: Computed tomography angiography (CTA) is a rapid, non-invasive procedure with a small risk for evaluating patients with various types of strokes. But the effectiveness of CTA in detecting the etiology of spontaneous intracerebral hemorrhage (SICH) has not been well established. AIM: To evaluate the diagnostic value of CTA for detecting underlying vascular abnormalities in patients with SICH. SETTINGS AND DESIGN: This is a comparative study to evaluate the diagnostic accuracy of CTA and digital subtraction angiography (DSA) in SICH. We also did a meta-analysis, combining our results with those of all previous studies to determine a more precise estimate of CTA in detecting the etiology of SICH.. MATERIALS AND METHODS: Between July 2009 and October 2011, CTA and DSA were routinely performed in consecutive young patients (age between 18 and 45 years) with acute non-hypertensive SICH. Imaging data were prospectively stored in the database for analysis. STATISTICAL ANALYSIS: The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and accuracy were used for evaluating the diagnostic value of CTA for vascular lesion. RESULTS: This study included 92 patients. The sensitivity, specificity, PPV, NPV, and accuracy of CTA for detecting DSA-positive pathologies were 94.6%, 100%, 100%, 96.5%, and 97.8%, respectively. A total of 544 cases were included for meta-analysis. The pooled sensitivity, specificity, PPV, NPV, and accuracy of CTA for detecting the etiology in SICH were 95.4%, 98.3%, 96.9%, 97.4%, and 97.2%, respectively. There was no substantial heterogeneity between the studies. CONCLUSIONS: CTA has high PPV and NPV for vascular pathologies. It should be performed as the initial vascular investigation for patients with acute SICH. Future technical advancement of CTA is still needed to eliminate the false-negative results.

Cerebellar tonsillectomy with suboccipital decompression and duraplasty by small incision for Chiari I malformation (with syringomyelia): long term follow-up of 76 surgically treated cases.

AIM: To explore the surgical effect of cerebellar tonsillectomy with suboccipital decompression and duraplasty by small surgical incision (3~4cm around the foramina magnum) on treating Chiari I Malformation (CM I) patients. MATERIAL AND METHODS: A retrospective study was undertaken on 76 CM I patients treated by this surgery. The surgical efficacy on clinical symptoms and syringomyelia were overall evaluated and analyzed. RESULTS: The study included 76 cases (36 men and 40 women; age range, 5-58 years; mean age at surgery, 38.8 years). Preoperative MRI confirmed 56 cases associated with syringomyelia. The follow-up period ranged from 25 to 58 months (median, 46 months). At the end of follow-up, 61 patients (80.26%) had improved, 12 patients (15.79%) were stabilized, and 3 patients (3.95%) had worsened. In MRI scan, syrinx of 55 patients (98.21%) had improved or stabilized compare with syrinx growth in only one patient (1.79%). Statistical analysis reveal the surgical effect tend to be much better in patients with short duration of preoperative symptoms (P=0.001). CONCLUSION: Cerebellar tonsillectomy with suboccipital decompression and duraplasty can provide long-time cure for most CM I cases. Early diagnosis and surgery is necessary to improve the surgical effect. A 3~4cm incision around foramen magnum is enough for these operations and may be conducive to reduce postoperative complications.