Search

Sun Z-J, Cai Y, Chen G, Wang R, Jia J, Chen X-M, Zheng L-W & Zhao Y-F (2010) Histopathology 57, 622-632 LMO2 promotes angiogenesis probably by up-regulation of bFGF in endothelial cells: an implication of its pathophysiological role in infantile haemangioma Aims: Infantile haemangiomas (IHs) are common benign vascular tumours distinctive for their perinatal presentation, rapid growth during the first year of life and subsequent slow involution. Recent research has indicated that endothelial cells of haemangiomas express LIM-only protein 2 (LMO2). The aim of this study was to investigate the role of LMO2 in the pathogenesis of IHs was investigated. Methods and results: Immunoreactivity of LMO2 was assessed in specimens of 19 IH. Stable transfection of LMO2 into human endothelial cell lines (EAhy926) was performed to evaluate the role of LMO2 in terms of the change in cell proliferation, cell cycle and cell migration as well as the expression level of angiogenic factors. Immunoreactivity for LMO2 was detected in all IH specimens, specifically in the nucleus of the endothelial cells. The intensity of LMO2 immunostaining decreased significantly from proliferative to involuting stages. Furthermore, the overexpression of LMO2 enhanced the proliferation and migration of the endothelial cells and promoted G0/G1-S-phase transition in vitro, together with an up-regulation of bFGF expression. Conclusions: LMO2 probably promotes angiogenesis by up-regulation of bFGF expression and thereby consequently influences progression of IH. [ABSTRACT FROM AUTHOR]

The aim of this study is to analyze all the cases of benign fibro-osseous lesions treated at School and Hospital of Stomatology, Wuhan University, to compare the results obtained in this study with those previously documented by other authors. The 127 cases diagnosed as a fibro-osseous lesion were retrieved, and information about these lesions was documented. In all, 127 cases of benign fibro-osseous lesions were surgically treated. Of these, 55 were cemento-ossifying fibroma, 43 ossifying fibroma, and 29 fibrous dysplasia. Cemento-ossifying fibromas mostly occur in men of the second decades, mostly in the mandible. Ossifying fibromas had almost equal sex predilection and age distribution peaked in the second decades, mostly in the mandible. Fibrous dysplasia also had equal sex predilection, and age distribution peaked in the second and third decades, with equal occurrence in both jaws. The tumors needed to have a regular follow-up after the surgery. [ABSTRACT FROM AUTHOR]

Aziridines derived from bioactive molecules may have unique pharmacological activities, making them useful in pharmacology (e.g. mitomycin C). Furthermore, the substitution of the epoxide moiety in epothilone B with aziridine, an analog of epoxides, yielded a pronounced enhancement in its anticancer efficacy. Thus, there is interest in developing novel synthetic technologies to produce aziridines from bioactive molecules. However, known methods usually require metal catalysts, stoichiometric oxidants and/or pre-functionalized amination reagents, causing difficulty in application. A practical approach without a metal catalyst and extra-oxidant for the aziridination of bioactive molecules is in demand, yet challenging. Herein, we report an electro-oxidative flow protocol that accomplishes an oxidant-free aziridination of natural products. This process is achieved by an oxidative sulfonamide/alkene cross-coupling, in which sulfonamide and alkene undergo simultaneous oxidation or alkene is oxidized preferentially. Further anticancer treatments in cell lines have demonstrated the pharmacological activities of these aziridines, supporting the potential of this method for drug discovery. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted to analyse Obesity as a risk factor for Acute Mountain Sickness (AMS). It states that AMS is a syndrome associated with characteristics such as headache, dizziness and fatigue and mentions that the severity of AMS depends on several factors including patient's age, sex and ventilatory response to acute hypoxia. It discusses high-altitude cerebral edema (HACE) and high-altitude pulmonary edema (HAPE) to be the extreme cases of AMS.

The present study examined whether Panax notoginseng saponins (PNS) alleviated advanced glycation end product (AGE)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with 300 µg/ml AGEs alone or AGEs and PNS (0.05, 0.5 or 1 mg/ml) for 48 h. The results of the present study demonstrated that PNS effectively promoted cell viability, inhibited apoptosis and suppressed the activity of caspase-3 in AGE-induced HUVECs. The activities of monocyte chemoattractant protein-1 and malondialdehyde were reduced, and superoxide dismutase activity was increased following treatment with PNS. Furthermore, PNS significantly increased the expression of silent information regulator 1 (SIRT1) and transforming growth factor (TGF)-β1 proteins, and suppressed the expression of inducible nitric oxide synthase and cyclooxyggenase-2 proteins in AGE-induced HUVECs. Therefore, the present study demonstrated that PNS reduced AGE-induced apoptosis by upregulating SIRT1 and antioxidants in HUVECs. The present findings suggest that the PNS may as an important pharmacological agent for AGE-induced cardiovascular injury. [ABSTRACT FROM AUTHOR]

Background: NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambiguous. Methods: In our study, tissue microarrays, ELISA, sphere-forming assay, colony formation assay and Western blot analysis were performed to evaluate the effect of NLRP3 inflammasome on the development of CSCs in human SCCHN tissue specimen, cell lines, and transgenic mouse SCCHN model. Results: The components of NLRP3 inflammasome, namely, NLRP3, ASC, Caspase-1, and IL-18 were correlated with CSCs markers BMI1, ALDH1 and CD44 in human SCCHN specimens. Moreover, NLRP3, Caspase-1, IL-1β, and IL-18 were highly expressed in SCCHN cell lines. NLRP3 inflammasome activated by LPS and ATP promoted sphere-forming and colony formation capacities along with an upregulation of BMI1, ALDH1 and CD44. In addition, NLRP3 inflammasome blockade by NLRP3 inhibitor MCC950 reduced sphere and colony number, also decreased the expression of BMI1, ALDH1 and CD44 in SCCHN cell lines. Expression of NLRP3, ASC, Caspase-1, IL-1β, IL-18, BMI1, ALDH1 and CD44 was upregulated in Tgfbr1/Pten 2cKO mouse SCCHN model, and NLRP3 inflammasome expression was closely related to those CSCs makers in mice SCCHN. However, MCC950 treatment reduced the expression of NLRP3 inflammasome, CSCs markers BMI1, ALDH1 and CD44 in Tgfbr1/Pten 2cKO mice SCCHN. In addition, blockade of NLRP3 inflammasome can also delayed the tumor-burdened speed in SCCHN mice. Conclusions: Our study demonstrates that NLRP3 inflammasome was upregulated and associated with the carcinogenesis and CSCs self-renewal activation in SCCHN. NLRP3 inflammasome can be a potential target in the development of novel approaches for head and neck squamous cell carcinoma therapy. [ABSTRACT FROM AUTHOR]

Background: Cancer immunotherapy offers a promising approach in cancer treatment. The adenosine A2A receptor (A2AR) could protect cancerous tissues from immune clearance via inhibiting T cells response. To date, the role of A2AR in head and neck squamous cell carcinoma (HNSCC) has not been investigated. Here, we sought to explore the expression and immunotherapeutic value of A2AR blockade in HNSCC. Methods: The expression of A2AR was evaluated by immunostaining in 43 normal mucosae, 48 dysplasia and 165 primary HNSCC tissues. The immunotherapeutic value of A2AR blockade was assessed in vivo in genetically defined immunocompetent HNSCC mouse model. Results: Immunostaining of HNSCC tissue samples revealed that increased expression of A2AR on tumor infiltrating immune cells correlated with advanced pathological grade, larger tumor size and positive lymph node status. Elevated A2AR expression was also detected in recurrent HNSCC and HNSCC tissues with induction chemotherapy. The expression of A2AR was found to be significantly correlated with HIF-1α, CD73, CD8 and Foxp3. Furthermore, the increased population of CD4+Foxp3+ regulatory T cells (Tregs), which partially expressed A2AR, was observed in an immunocompetent mouse model that spontaneously develops HNSCC. Pharmacological blockade of A2AR by SCH58261 delayed the tumor growth in the HNSCC mouse model. Meanwhile, A2AR blockade significantly reduced the population of CD4+ Foxp3+ Tregs and enhanced the anti-tumor response of CD8+ T cells. Conclusions: These results offer a preclinical proof for the administration of A2AR inhibitor on prophylactic experimental therapy of HNSCC and suggest that A2AR blockade can be a potential novel strategy for HNSCC immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors. Methods: PAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events. Results: ACS patients with T2DM had higher PAPP-A (19.29±16.36 vs 13.29±13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs 13.6%, p = 0.002) than those without Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log10( PAPP-A), 95% CI 2.11-4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27-4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model. Conclusion: Patients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. [ABSTRACT FROM AUTHOR]

Adenoid cystic carcinoma (AdCC) of the salivary gland in the head and neck is characterized by indolent yet persistent growth, multiple local recurrences and early hematogenous metastasis. Considering the possible association between the epidermal growth factor receptor (EGFR) signaling pathway and angiogenesis in various types of cancer and the overexpression of EGFR in AdCC, it is reasonable to examine the correlation between angiogenesis and the EGFR signaling pathway in this carcinoma. In the present study, the expression of EGFR, CD31, CD146 and hypoxia-inducible factor-1a (HIF-1a) were evaluated by immunohistochemical staining with tissue microarray containing normal salivary gland (NSG), pleomorphic adenoma (PMA) and AdCC tissues. Pearson's correlation coefficient was conducted to demonstrate the correlation between EGFR, CD31, CD146 and HIF-1a. To determine their similarity and intimacy, hierarchical analysis was performed with Cluster 3.0 and then visualized using TreeView software. Immunohistochemical results of tissue microarrays were quantified, revealing that the expression of EGFR, CD146 and HIF-1a increased in AdCC compared with in PMA and NSG tissues. The association between the expression of EGFR and CD31 was significant and positive. The expression of CD146 and HIF-1a was positively correlated with EGFR and CD31, respectively. These findings suggest that the EGFR signaling pathway has a vital role in AdCC progression and may be associated with HIF-1a-mediated angiogenesis. These results may enhance our understanding of the mechanism underlying AdCC progression and provide potential clinical therapeutic strategies based on the inhibition of EGFR. [ABSTRACT FROM AUTHOR]

Increasing numbers of animal and clinical investigations have demonstrated the effectiveness of long-term electrical vagal nerve stimulation (VNS) on chronic heart failure (CHF). The present study investigated the effects of short-term VNS on the hemodynamics of cardiac remodeling and cardiac excitation-contraction coupling (ECP) in an animal model of CHF following a large myocardial infarction. At 3 weeks subsequent to ligation of the left coronary artery, the surviving rats were randomized into vagal and sham-stimulated groups. The right vagal nerve of the CHF rats was stimulated for 72 h. The vagal nerve was stimulated with rectangular pulses of 40 ms duration at 1 Hz, 5 V. The treated rats, compared with the untreated rats, had significantly higher left ventricular ejection fraction (54.86±9.73, vs. 45.60±5.51%; P=0.025) and left ventricular fractional shortening (25.31±6.30, vs. 15.42±8.49%; P=0.013), and lower levels of brain natriuretic peptide (10.07±2.63, vs. 19.95±5.22 ng/ml; P=0.001). The improvement in cardiac pumping function was accompanied by a decrease in left ventricular end diastolic volume (1.11±0.50, vs. 1.54±0.57 cm3; P=0.032) and left ventricular end systolic volume (0.50±0.28, vs. 0.87±0.36 cm3; P=0.007). Furthermore, the expression levels of ryanodine receptor type 2 (RyR2) and sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) were significantly higher in the treated rats compared with the untreated rats (P=0.011 and P=0.001 for RyR2 and SERCA2, respectively). Therefore, VNS was beneficial to the CHF rats through the prevention of cardiac remodeling and improvement of cardiac ECP. [ABSTRACT FROM AUTHOR]

Receptor for advanced glycation end products (RAGE) is critical in inflammatory diseases, including diabetes and atherosclerosis. The mechanism underlying the effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone (PIO) on RAGE expression in coronary artery smooth muscle cells (SMCs) stimulated by high glucose concentrations remains to be elucidated. In the present study, the effect and mechanism of action of PIO on RAGE expression in SMCs was investigated following treatment with high glucose concentrations. Rat coronary artery SMCs were pretreated with PIO alone, PIO and GW9662 (a PPARγ antagonist), diphenyleneiodonium (DPI; a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor) or the antioxidant pyrrolidine dithiocarbamate (PDTC; a nuclear factor-κB (NF-κB) inhibitor), followed by treatment with high glucose. RAGE mRNA and protein expression, reactive oxygen species (ROS) production and NF-κB nuclear translocation were investigated. Glucose induced RAGE expression in a dose-dependent manner, with maximal effect at a concentration of 25 mmol/l following treatment for 48 h. PIO, DPI and PDTC reduced high glucose-induced increases in RAGE protein and mRNA expression. PIO prominently downregulated RAGE expression and inhibited high glucose-induced increases in ROS production and NF-κB activation (P<0.05). Pretreatment with PIO and GW9662 did not exhibit this inhibitory effect. High glucose may stimulate RAGE expression in coronary artery SMCs through NADPH oxidase-mediated ROS generation and NF-κB activation. PIO downregulated RAGE expression and inhibited ROS production and NF-κB activation via PPARγ activation, which may prevent the inflammatory effect of AGE/RAGE system in diabetes. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAMmarkers in oral squamous cell carcinoma (OSCC) has not been elucidated. The present study was designed to investigate the correlation between the expression of TAMmarkers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC) markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P < 0.05). Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P < 0.05). TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC. [ABSTRACT FROM AUTHOR]

Aims The pathogenesis of infantile haemangiomas (IHs) is still far from clear despite the fact that they are common vascular tumours distinctive for their perinatal presentation, rapid growth during the first year of life and subsequent slow involution. Aims To determine the role of M2-polarised macrophages in IHs. Methods M2-polarised macrophages were initially identified in 20 specimens of IHs by both immunochemistry and immunofluorescence for CD68 and CD163. The immunopositive M2-polarised macrophages in different phases of IHs were quantified, and further analysed for their correlations with the expression levels of Ki67, vascular endothelial growth factor (VEGF) and macrophage colony-stimulating factor (M-CSF). Results The infiltrating macrophages in proliferative IHs were predominantly CD68/CD163, thus of the M2-polarised phenotype, whereas the density of these cells was significantly decreased in the involuting IHs. The high density of M2-polarised macrophages in proliferative IHs was closely correlated with overexpression of M-CSF, one of the cytokines considered to induce macrophages to polarise towards an M2 phenotype. The infiltrating M2-polarised macrophages probably contributed to the proliferation and angiogenesis of haemangioma endothelial cells, as evidenced by their close correlations with the immunoreactivities of Ki67 and VEGF. Conclusions Results indicate that the infiltrating M2-polarised macrophages may contribute to the progression of IHs by promoting the angiogenic process. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the expression of BCL-2 and BAD genes in tissues of breast carcinoma and investigate the relationship between the expression of BCL-2 and BAD in breast cancer cells with chemosensitivity. Methods: Immunohistochemical technique was used to detect the expression of BCL-2, BAD in 10 normal breast tissues, 10 breast fibroadenoma tissues, 40 youth human breast carcinoma tissues, 40 menopause human breast carcinoma tissues. And to detect the expression of ER, PR in 80 human breast carcinoma tissues. 20 Surgical samples of breast cancer, diagnosed by pathology, were obtained from The First Affiliated Hospital of Chongqing Medical University. The cancer sample cells were cultured separately in the incubator at 37°C, 5% CO2 in vitro. The rate of inhibition of cancer cells in 4 kinds of anticancer drugs- Epirubicin Adriamycin (EADM),5-Fluorouracil (5-Fu), Navelbine(NVB) and Diaminedichloroplatinum (DDP), were assayed by MTT method. Results: The expression of BCL-2, BAD genes in young human breast carcinoma tissues were lower than that in menopause human breast carcinoma tissues (P < 0.05). There was a negative correlation between the positive expression rate of BCL-2 and histologic grade or the lymph node metastasis (P < 0.05). There was a positive correlation between the expression rates of BCL-2 and of ER, PR (P < 0.05). The expression of BAD had no relationship with the expression of ER, PR, histologic grade and the lymph node metastasis(P = NS). Sensitivity rates of 20 breast cancer cells in 0.1 x PPC within 48 h in vitro were 30% EADM,20% 5-Fu,45% NVB and 25% DDP. Respectively, the rate of inhibition of EADM,5- Fu, NVB and DDP were significantly higher in the BCL-2 negative cancer cells than in the BCL-2 positive cancer cells. A negative correlation was found between expression of BCL-2 and chemosensitivity for all the 4 anticancer drugs. The inhibition rates of EADM and NVB were significantly lower in the BAD negative cancer cells than in the BAD positive cancer cells. A positive correlation was found between expression of BAD and chemosensitivity for Epirubicin. Conclusion: The expression of BCL-2 and BAD can be used as prognosis factors of breast cancer. Detection of the BCL-2 protein expression level, particularly, combined with the detection of the expression of BCL-2 and BAD as well as ER and PR were helpful in confirming the prognosis of breast carcinoma. The combined detection of BCL-2 and BAD may be markers for predicting the responses to anticancer drugs. [ABSTRACT FROM AUTHOR]