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Background: The 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile.Methods: Invasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 μm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array.Results: DNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5' region of E-cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion.Conclusions: DNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma pneumoniae infection is usually self-limited, but some fulminant cases are fatal, even when occurring in previously healthy individuals. It can also be the cause of overwhelming postsplenectomy infection (OPSI). Case presentation: We report a case of OPSI in a 41-year-old woman with hypersplenism associated with hepatitis B cirrhosis. We detected a significant Mycoplasma pneumoniae agglutination titer, but no evidence of infection with Chlamydia pneumoniae, Legionnella spp., or any other bacterial or fungal pathogens. She eventually died despite aggressive therapy. Conclusions: M. pneumoniae could be an underestimated cause of OPSI, and should be suspected in fulminant infectious cases in asplenic patients. [ABSTRACT FROM AUTHOR]

Background: The 2010 Revisions to the McDonald Criteria have established that dissemination in time (DIT) of multiple sclerosis (MS) can be demonstrated by simultaneous presence of asymptomatic gadolinium-enhancing and nonenhancing lesions on a single magnetic resonance imaging (MRI). However, gadolinium-based contrast agents (GBCAs) have contraindications. Diffusion-weighted imaging (DWI) can detect diffusion alterations in active inflammatory lesions. The purpose of this study was to investigate if DWI can be an alternative to contrast-enhanced T1-weighted imaging (CE T1WI) for demonstrating DIT in MS.Methods: We selected patients with clinically definite MS and evaluated their baseline brain MRI. Asymptomatic lesions were identified as either hyperintense or nonhyperintense on DWI and enhancing or nonenhancing on CE T1WI. Fisher's exact test was performed to determine whether the hyperintensity on DWI was related to the enhancement on CE T1WI (P < 0.05). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the DWI to predict lesion enhancement were calculated.Results: Twenty-two patients with 384 demyelinating lesions that were hyperintense on T2-weighted imaging and more than 3 mm in size were recruited. The diffusion hyperintensity and lesion enhancement were significantly correlated (P <0.001). The sensitivity, specificity, PPV, NPV and accuracy were 100%, 67.9%, 32.3%, 100% and 72.1%, respectively.Conclusions: A hyperintense DWI finding does not necessarily overlap with contrast enhancement. There are many false positives, possibly representing other stages of lesion development. Although DWI may not replace CE T1WI imaging to demonstrate DIT due to the low PPV, it may serve as a screening MRI sequence where the use of GBCAs is a concern. [ABSTRACT FROM AUTHOR]

Background: Several cell-based therapies for adjunctive treatment of acute myocardial infarction have been investigated in multiple clinical trials, but the timing of transplantation remains controversial. We conducted a meta-analysis of randomized controlled trials to investigate the effects of timing on bone marrow-derived cell (BMC) therapy in acute myocardial infarction (AMI)., Methods: A systematic literature search of PubMed, MEDLINE, and Cochrane Evidence-Based Medicine databases from January 2000 to June 2017 was performed on randomized controlled trials with at least a 3-month follow-up for patients with AMI undergoing emergency percutaneous coronary intervention (PCI) and receiving intracoronary BMC transfer thereafter. The defined end points were left ventricular (LV) ejection fraction, LV end-diastolic and end-systolic index. The data were analyzed to evaluate the effects of timing on BMC therapy., Results: Thirty-four RCTs comprising a total of 2,307 patients were included; the results show that, compared to the control group, AMI patients who received BMC transplantation showed significantly improved cardiac function. BMC transplantation 3-7 days after PCI (+3.32%; 95% CI, 1.91 to 4.74; P < 0.00001) resulted in a significant increase of left ventricular ejection fraction (LVEF). As for the inhibitory effect on ventricular remodeling, BMC transplantation 3-7 days after PCI reduced LV end-diastolic indexes (-4.48; 95% CI, -7.98 to -0.98; P = 0.01) and LV end-systolic indexes (-6.73; 95% CI, -11.27 to -2.19; P = 0.004). However, in the groups who received BMC transplantation either within 24 hours or later than 7 days there was no significant effect on treatment outcome. In subgroup analysis, the group with LVEF ≤ 50% underwent a significant decrease in LV end-diastolic index after BMC transplantation (WMD = -3.29, 95% CI, -4.49 to -2.09; P < 0.00001); the decrease was even more remarkable in the LV end-systolic index after BMC transplantation in the group with LVEF ≤ 50% (WMD = -5.25, 95% CI, -9.30 to -1.20; P = 0.01), as well as in patients who received a dose of 10^7-10^8 cells (WMD = -12.99, 95% CI, -19.07 to -6.91; P < 0.0001). In the group with a follow-up of more than 12 months, this beneficial effect was significant and increased to a more pronounced effect of +3.58% (95% CI, 1.55 to 5.61; P = 0.0006) when compared with control., Conclusions: In this meta-analysis, BMC transfer at 3 to 7 days post-AMI was superior to transfer within 24 hours or more than 7 days after AMI in improving LVEF and decreasing LV end-systolic dimensions or LV end-diastolic dimensions. It is more effective in patients with lower baseline LVEF (≤50%) and the effect can last more than 12 months.

Background: The 5-year overall survival rates for head and neck cancer (HNC) relies on distant metastasis. Importantly, the epithelial-mesenchymal transition (EMT) is believed to be an initial step of metastasis. However, the relationship of epigenetic with EMT formation is still unexplored in HNC. This study focuses on invasive subclones of HNC cell lines through the simulation of invasion in vitro; and underlying mechanisms were analyzed including DNA methylation and gene expression profile., Methods: Invasive subclones of NHC cell lines were successfully obtained using transwell coated with Matrixgel. Cells invaded through 8 μm pore several times were subcultured and examined with EMT features including morphology, EMT marker genes expression, and invasive ability. Moreover, compared the profile of genes expression in parental and invasive cells was analyzed using mRNA expression array., Results: DNA methyltransferase 3B (DNMT 3B) was upregulated in invasive subclones and might control the 5' region of E-cadherin (E-cad) methylation and further inhibited E-cad protein expression. Interference of DNMT 3B by siRNA or miRNA 29b could reduce EMT and cell invasion. Expression array analysis revealed the most possible involved pathways in cell invasion including arginine and proline metabolism, TGF-beta, and focal adhesion., Conclusions: DNMT 3B might control EMT by DNA methylation manner in invasive HNC cell lines. Moreover, miR-29b mimic downregulated DNMT 3B and inhibited EMT and cell invasion indicated the role of therapeutic agent for invasive HNC. Genes identified from array data and new molecules are involved in metastasis of HNC need further validation.

Background: Aberrant insulin-like growth factor-binding protein 7 (IGFBP-7) expression has been found in various cancers such as prostate, breast, and colon. IGFBP-7 induced the apoptosis of tumor and potentially predicted the clinical outcome in some cancers is further demonstrated. This study investigates the causes and underlying mechanisms of aberrant IGFBP-7 expression in unravelling head and neck squamous cell carcinoma (HNSCC)., Methods: A total of 47 oral tongue cancer patient samples were primarily analyzed for the methylation status in 5' region of IGFBP-7 by methylation-specific PCR (MS-PCR). Subsequently the invasion, overexpression, and knockdown of IGFBP-7 in the HNSCC A253 invasive subpopulation were employed to examine the effect of IGFBP-7. The epithelial-mesenchymal transition (EMT) marker genes and AKT/GSK3β/β-catenin signaling were further evaluated by Western blot for the understanding the role of aberrant IGFBP-7 expression and thereof putative mechanism., Results: EMT expressed in the invasive subpopulation of HNSCC cell lines (A253 and RPMI 2650) was contemporary with the down-regulation of IGFBP-7. After treatment with 5-AZA-2' deoxycytidine, the de-methylated CpG sites in the 5' region of IGFBP-7 were observed and IGFBP-7 mRNA expression was also restored. Accordingly, re-expression IGFBP-7 in invasive subpopulation of A253 could induce the mesenchymal-epithelial transition (MET) and concurrently inhibited the cell invasion. Moreover, IGFBP-7 methylation status of 47 oral tongue tumors showed a positive correlation to invasive depth of the tumor, loco-regional recurrence, and cancer sequence., Conclusions: IGFBP-7 can alter EMT relative marker genes and suppress cell invasion in A253 cell through AKT/GSK3β/β-catenin signaling. The epigenetic control of IGFBP-7 in the invasion and metastasis of HNSCC was reported, suggesting that IGFBP-7 could be a prognostic factor for the probability of invasion and a therapeutic remedy.

Background: Maintenance therapy with imatinib during the post-transplant period has been used for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL); however, its efficacy has not been demonstrated. A study was designed to investigate the safety of imatinib and its efficacy in preventing hematological relapse and improving disease-free survival (DFS) when administered after allogeneic hematopoietic stem cell transplantation (allo-HCT)., Methods: Patients with Ph + ALL that received allo-HCT were enrolled in the study. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect BCR-ABL transcript levels. Imatinib therapy was initiated if patient neutrophil counts were > 1.0 × 10(9)/L and platelet counts were > 50.0 × 10(9)/L, or if they displayed either elevated BCR-ABL transcript levels in two consecutive tests, or a BCR-ABL transcript level ≥ 10(-2) after initial engraftment. Patients receiving imatinib after relapse were assigned to the non-imatinib group. The imatinib treatment was scheduled for 3-12 months, until BCR-ABL transcript levels were negative at least for three consecutive tests or complete molecular remission was sustained for at least 3 months., Results: A total of 82 patients were enrolled. Sixty-two patients initiated imatinib therapy post-HCT. Imatinib therapy was initiated at a median time of 70 days post-HCT. Grade 3-4 adverse events (AEs) occurred in 17.7% of patients. Ten patients (16.1%) terminated imatinib therapy owing to AEs. Among the patients in imatinib and non-imatinib groups, the estimated 5-year relapse rate was 10.2% and 33.1% (p = 0.016), and the 5-year probability of DFS was 81.5% and 33.5% (p = 0.000) with the median follow-up of 31 months (range, 2.5-76 months) and 24.5 months (range, 4-72 months), respectively. Multivariate analysis identified imatinib maintenance therapy post-HCT as an independent prognostic factor for DFS (p = 0.000, hazard ratio [HR] =4.8) and OS (p = 0.000, HR = 6.2)., Conclusions: These results indicate that relapse rate can be reduced and DFS may be improved in Ph + ALL patients with imatinib maintenance therapy after HCT. BCR-ABLmonitoring by qRT-PCR can guide maintenance therapy with imatinib including initiation time and treatment duration after allo-HCT.