The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant (P<0.01). VEGF staining of the rats in the 17-day old experimental group was significantly stronger, with an increasing positive rate, than that of the rats in the 17-day old control group (P<0.01). PEDF staining of the rats of 22 days old was weaker than that of the rats of 17 days old in the experimental groups (P<0.01). There was no significant difference in serum VEGF concentration among all groups (P>0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group (P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old (P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.
Animals ; Eye Proteins ; blood ; metabolism ; Nerve Growth Factors ; blood ; metabolism ; Oxygen ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Retina ; metabolism ; Retinal Diseases ; etiology ; metabolism ; Serpins ; blood ; metabolism ; Time and Motion Studies ; Vascular Endothelial Growth Factor A ; blood ; metabolism

OBJECTIVE: All patients with stage IB1 cervical cancer do not need to undergo parametrectomy. Some low-risk criteria for parametrial involvement (PI) have been proposed based on pathological findings. The aim of this study was to determine pretreatment risk factors for PI in stage IB1 cervical cancer. METHODS: We retrospectively reviewed 115 patients with stage IB1 cervical cancer who underwent radical hysterectomy or radical trachelectomy. Magnetic resonance imaging (MRI) was performed and serum concentrations of squamous cell carcinoma antigen (SCC-Ag) and cancer antigen 125 (CA-125) were determined in all patients before initial treatment. The following pretreatment factors were investigated: histological variant, maximum tumor diameter, tumor volume (volume index), pelvic lymph node enlargement, and serum tumor markers. Logistic regression analysis was used to select the independent risk factors for PI. RESULTS: Eighteen of the 115 patients (15.7%) were pathologically diagnosed with PI. Multivariate analysis confirmed the following independent risk factors for PI: MRI-based tumor diameter > or =25 mm (odds ratio [OR], 9.9; 95% confidence interval [CI], 2.1 to 48.1), MRI-based volume index > or =5,000 mm3 (OR, 13.3; 95% CI, 1.4 to 125.0), and positive serum tumor markers SCC-Ag > or =1.5 ng/mL or CA-125 > or =35 U/mL (OR, 5.7; 95% CI, 1.3 to 25.1). Of 53 patients with no risk factors for PI, none had PI. CONCLUSION: Less radical surgery may become one of the treatment options for stage IB1 cervical cancer patients with MRI-based tumor diameter <25 mm, MRI-based volume index <5,000 mm3, and negativity for SCC-Ag and CA-125.
Adult ; Aged ; Antigens, Neoplasm/metabolism ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Hysterectomy/methods ; Lymphatic Metastasis ; Magnetic Resonance Imaging/methods ; Middle Aged ; Neoplasm Staging ; Observer Variation ; Retrospective Studies ; Risk Factors ; Serpins/metabolism ; Uterine Cervical Neoplasms/metabolism/*pathology/surgery ; Young Adult

OBJECTIVE: To examine the expression of Maspin in the bladder carcinoma, and to explore the relationship among Maspin expression, clinical pathology and lymph node metastasis.
 METHODS: The expression of Maspin in 72 bladder cancer tissues and 12 normal bladder tissues were detected by immunohistochemistry. Preoperative pelvic CT images and postoperative pathological results of lymph node metastasis in 72 bladder cancer patients were analyzed retrospectively. The sensibility, specificity, positive predictive value and negative predictive value were calculated, and the advantage for diagnosis of lymph node metastasis was compared between Maspin examination and CT scan.
 RESULTS: 1) The expression of Maspin in 72 bladder cancer tissues was significantly lower than that in the normal bladder tissues (P<0.05); 2) The expression of Maspin was obviously decreased with the progress in clinical stage, pathlogical grade and lymph node metastasis, with significant difference (all P<0.05); 3) There were 27 patients diagnosed as pelvic lymph node metastasis by CT scan, and the positive rate was 37.5% (27/72); there were 22 patients diagnosed as pelvic lymph node metastasis by pathological results, and the positive rate was 30.5% (22/72). The pathological diagnose for pelvic lymph node metastasis was the gold standard. The sensitivity, specificity, positive predictive value and negative predictive value for CT was 45.5%, 73.3%, 37.0%, and 66.7%, respectively; the sensibility, specificity, positive predictive value and negative predictive value was 81.8%, 50%, 41.8% and 86.2% in the diagnosis of lymph node metastasis for the 72 bladder cancer cases by Maspin examination; the sensitivity, specificity, positive predictive value and negative predictive was 90.9%, 78.0%, 64.5% and 95.0% in the diagnose of lymph node metastasis by Maspin examination combined with CT scan.
 CONCLUSION The expression of Maspin in bladder cancer is significantly lower than that in normal bladder cancer, and a statistically significant correlation is also observed between Maspin expression and lymph node metastasis. Maspin maybe a valuable biomarker in diagnose of bladder cancer with lymph node metastasis. Maspin examination combined with CT scan has more advantage in the evaluation of bladder cancer with lymph node metastasis than Maspin or CT alone.
Biomarkers, Tumor ; metabolism ; Humans ; Immunohistochemistry ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; Neoplasm Staging ; Retrospective Studies ; Sensitivity and Specificity ; Serpins ; metabolism ; Tomography, X-Ray Computed ; Urinary Bladder Neoplasms ; metabolism ; pathology

OBJECTIVE: To analyze the expression of Maspin and Ki67 in EN-NK/TCL and the significance. METHOD: The expressions of Maspin and Ki67 were detected by immunohistochemistry in 34 cases of EN-NK/TCL and 11 cases of chronic sinusitis. RESULT: Maspin was low expressed in EN-NK/TCL, Ki67 was highly expressed in EN-NK/TCL. Negative correlation was found between the expression of Maspin and Ki67 in EN-NK/TCL. CONCLUSION The combined examination of Maspin and Ki67 has important significance in the diagnosis in EN-NK/ TCL.
Biomarkers, Tumor ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; Serpins ; metabolism

Pigment epithelium-derived factor (PEDF) is a multifunctional protein with anti-inflammatory, antioxidant and antithrombotic properties and plays a protective role against atherosclerosis (AS). The purpose of the present study is to explore the effects of oxidized low density lipoprotein (ox-LDL) on the expression of PEDF in cultured human umbilical vein endothelial cells (HUVECs). HUVECs were cultured and incubated with ox-LDL at different concentrations (6.25, 12.5, 25, 50, 100 and 150 mg/L) for 24 h. Apoptosis of endothelial cells were assayed by morphological staining and flow cytometry. The intracellular reactive oxygen species (ROS) levels were measured by flow cytometry. Cell viability was assayed by MTT assay. PEDF protein and mRNA expressions in HUVECs were analyzed by Western blot and quantitative real-time PCR, respectively. The results showed that ox-LDL significantly induced apoptosis, reduced cell viability, increased intracellular ROS levels and decreased the PEDF expression in HUVECs in a concentration-dependent manner. Ox-LDL at 50 mg/L obviously decreased the PEDF protein expression compared with control group (P < 0.05), whereas 25 mg/L ox-LDL already markedly reduced the PEDF mRNA expression (P < 0.05). In conclusion, the results suggest that ox-LDL down-regulates the PEDF expression through an increased ox-LDL-induced intracellular production of ROS.
Apoptosis ; Cells, Cultured ; Down-Regulation ; Eye Proteins ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; Humans ; Lipoproteins, LDL ; pharmacology ; Nerve Growth Factors ; metabolism ; Reactive Oxygen Species ; metabolism ; Serpins ; metabolism

Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

A variety of biomarkers have been identified in recent prospective and retrospective reports as being potentially predictive of venous thromboembolis (VTE), particularly idiopathic deep venous thrombosis (IDVT). This study identified a serum tumor biomarker for early screening of IDVT. A total of 128 IDVT patients (54 females and 74 males; average age: 50.9±17.4 years) were included. Carcinoembryonic antigen (CEA), ferritin, β2-microglobulin, cancer antigen (CA) 125, CA 15-3, CA 19-9, squamous cell carcinoma antigen (SCC), alpha-fetoprotein (AFP), prostate specific antigen (PSA), free PSA (f-PSA), and beta-human chorionic gonadotropin (β-HCG) in patients with IDVT were detected. Malignancies were histo- or cytopathologically confirmed. Of the 128 IDVT patients, 16 (12.5%) were found to have malignancies. Serum CEA, CA 125, CA 15-3, and CA 19-9 were found to be helpful for detecting malignancies in IDVT patients. Our study revealed a positive association between these markers and tumors in IDVT patients. On the other hand, SCC and AFP were not sensitive enough to be markers for detecting tumors in patients with IDVT. No significant differences were found in positive rates of ferritin and β2-microglobulin between tumor and non-tumor groups, and no significant difference exists in serum levels of ferritin and β2-microglobulin between the two groups. Carbohydrate antigens, CA 15-3 in particular, may be useful for differential diagnosis and prediction of malignancies in patients with IDVT.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, Neoplasm ; blood ; Antigens, Tumor-Associated, Carbohydrate ; blood ; Biomarkers, Tumor ; blood ; CA-125 Antigen ; blood ; CA-19-9 Antigen ; blood ; Carcinoembryonic Antigen ; blood ; Chorionic Gonadotropin, beta Subunit, Human ; Female ; Humans ; Male ; Middle Aged ; Mucin-1 ; blood ; Neoplasms ; blood ; complications ; diagnosis ; Prostate-Specific Antigen ; blood ; Retrospective Studies ; Sensitivity and Specificity ; Serpins ; blood ; Venous Thrombosis ; blood ; complications ; Young Adult ; alpha-Fetoproteins ; metabolism

OBJECTIVETo study the correlation between adipocytokines levels and metabolic syndrome (MS) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

METHODSSixty-eight patients with newly diagnosed T2DM, including 51 cases with MS and 17 without MS, were examined for blood pressure (BP), fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (IRI), waist to hip ratio (W/H), body mass index (BMI), and serum adipocytokine levels (IL-6, vaspin, and adiponectin).

RESULTSThe diabetic patients with MS had higher BMI, HbA1c, FBG, FINS, IRI, TG, TC, and SBP than those without MS. Serum IL-6 level was higher but adiponectin level was lower in patients with MS than in those without MS. There was no significant difference in vaspin level between the two groups. Adiponectin level was positively correlated with TG (r=-0.30, P=0.02) and inversely with BMI (r=-0.47, P=0.39) and HOMA-IR (r=-0.30, P=0.03); vaspin level was positively correlated with HOMA-IR (r=0.347, P=0.02) and inversely with HDL-L (r=-0.45, P=0.01); IL-6 level was positively correlated with LDL-L (r=0.18, P=0.25) and inversely with HDL-L (r=-0.45, P=0.01).

CONCLUSIONAdiponectin and IL-6 levels are closely related to MS, but the relationship between vaspin and MS needs further investigation.

Adipokines ; blood ; Adiponectin ; blood ; Adipose Tissue ; metabolism ; Adult ; Diabetes Mellitus, Type 2 ; blood ; complications ; Female ; Humans ; Interleukin-6 ; blood ; Male ; Metabolic Syndrome ; complications ; Middle Aged ; Serpins ; blood

BACKGROUNDThe common pathological characteristics of corneal injury include inflammatory factors activation, vascular endothelial cells or inflammatory cells infiltration into lesions, corneal edema, corneal neovascularization (CNV), and scar formation. PEDF-34 is the functional fragment of pigment epithelium-derived factor (PEDF) that has anti-angiogenic and anti-inflammatory properties and contains an N-terminal 34-amino acid peptide. This study was to investigate the anti-inflammatory effects of PEDF-34 on H2O2-induced corneal injury in vitro.

METHODSAfter cultured in H2O2 (0.1 mmol/L) for 2 hours, human corneal fibroblasts (HCFs) and human umbilical vein endothelial cells (HUVECs) were treated with PEDF-34-nanoparticles (NPs) at different concentrations (0.1, 0.5, 1.0, 2.0 µg/ml) or 2.0 µg/ml control-NPs for 24 hours. The viable cells were quantified using the MTT assay. Western blotting or ELISA analysis was performed for measuring the human vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) expression of both HCFs and HUVECs. VEGF and nuclear factor κB (NF-κB) mRNA levels of HCFs were semi-quantified by RT-PCR.

RESULTSThe survival rates of HCFs or HUVECs stimulated by H2O2 did not decrease significantly (P > 0.05) compared to those in the normal conditions. As compared to control-NP group, PEDF-34-NPs had dose-dependent inhibitive effect on HUVECs with the MTT assay, but not HCFs. Western blotting analysis showed that the VEGF and ICAM-1 levels in the HCFs and HUVECs stimulated by H2O2 were significantly higher than those in the normal conditions, which were decreased dramatically in those treated with PEDF-34-NPs. RT-PCR analysis revealed that the VEGF mRNA and NF-κB mRNA levels increased in H2O2-stimulated HCFs, while both of them decreased in PEDF-34-NP groups dose dependently.

CONCLUSIONSPEDF-34-NPs may play an important role in regulating the NF-κB pathway, inhibiting inflammatory activity. PEDF-34-NPs may be a potential new drug for treating corneal injury in the future.

Anti-Inflammatory Agents ; chemistry ; pharmacology ; Cells, Cultured ; Corneal Injuries ; chemically induced ; metabolism ; Eye Proteins ; chemistry ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Hydrogen Peroxide ; pharmacology ; Nerve Growth Factors ; chemistry ; Peptides ; chemistry ; pharmacology ; Serpins ; chemistry

Adenocarcinoma ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Adult ; Antigens, Neoplasm ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Squamous Cell ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy, Adjuvant ; Chemotherapy, Adjuvant ; Female ; Humans ; Hysterectomy ; Iridium Radioisotopes ; therapeutic use ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; Preoperative Period ; Radiotherapy, Adjuvant ; Retrospective Studies ; Serpins ; metabolism ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; immunology ; pathology ; radiotherapy ; surgery