OBJECTIVES: Fluorouracil chemotherapeutic drugs are the classic treatment drugs of gastric cancer. But the problem of drug resistance severely limits their clinical application. This study aims to investigate whether hypoxia microenvironment affects gastric cancer resistance to 5-fluorouracil (5-FU) and discuss the changes of gene and proteins directly related to drug resistance under hypoxia condition. METHODS: Gastric cancer cells were treated with 5-FU in hypoxia/normoxic environment, and were divided into a Normoxic+5-FU group and a Hypoxia+5-FU group. The apoptosis assay was conducted by flow cytometry Annexin V/PI double staining. The real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the expression level of hypoxia inducible factor-1α (HIF-1α), multidrug resistance (MDR1) gene, P-glycoprotein (P-gp), and vascular endothelial growth factor (VEGF) which were related to 5-FU drug-resistance. We analyzed the effect of hypoxia on the treatment of gastric cancer with 5-FU. RESULTS: Compared with the Normoxic+5-FU group, the apoptosis of gastric cancer cells treated with 5-FU in the Hypoxia+5-FU group was significantly reduced (P<0.05), and the expression of apoptosis promoter protein caspase 8 was also decreased. Compared with the the Normoxic+5-FU group, HIF-1α mRNA expression in the Hypoxia+5-FU group was significantly increased (P<0.05), and the mRNA and protein expression levels of MDR1, P-gp and VEGF were also significantly increased (all P<0.05). The increased expression of MDR1, P-gp and VEGF had the same trend with the expression of HIF-1α. CONCLUSIONS Hypoxia is a direct influencing factor in gastric cancer resistance to 5-FU chemotherapy. Improvement of the local hypoxia microenvironment of gastric cancer may be a new idea for overcoming the resistance to 5-FU in gastric cancer.
Humans ; Fluorouracil/therapeutic use* ; Vascular Endothelial Growth Factor A/metabolism* ; Stomach Neoplasms/drug therapy* ; Drug Resistance, Multiple ; Vascular Endothelial Growth Factors/metabolism* ; Hypoxia ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics* ; Cell Line, Tumor ; Cell Hypoxia ; RNA, Messenger/metabolism* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Tumor Microenvironment

OBJECTIVES: To investigate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in the treatment of retinopathy of prematurity (ROP) and the risk factors for recurrence. METHODS: A retrospective analysis was performed on the medical data of 159 infants with ROP who were born in the First Affiliated Hospital of Zhengzhou University and underwent anti-VEGF treatment from January 2016 to December 2021. According to the presence or absence of recurrence within the follow-up period after initial anti-VEGF treatment, they were divided into a recurrence group with 24 infants and a non-recurrence group with 135 infants. The medical data were compared between the two groups, and a multivariate logistic regression analysis was used to investigate the risk factors for the recurrence of ROP after anti-VEGF treatment. RESULTS: After one-time anti-VEGF treatment, all 159 infants showed regression of plus disease. Recurrence was observed in 24 infants (15.1%) after anti-VEGF treatment, with a mean interval of (8.4±2.6) weeks from treatment to recurrence. The multivariate logistic regression analysis showed that preoperative fundus hemorrhage and prolonged total oxygen supply time were risk factors for the recurrence of ROP (P<0.05), while gestational hypertension was a protective factor (P<0.05). CONCLUSIONS Intravitreal anti-VEGF injection is effective for ROP. Preoperative fundus hemorrhage and long duration of oxygen therapy may increase the risk of ROP recurrence, and further studies are needed to investigate the influence of gestational hypertension on the recurrence of ROP.
Female ; Humans ; Infant ; Infant, Newborn ; Pregnancy ; Angiogenesis Inhibitors/therapeutic use* ; Endothelial Growth Factors/therapeutic use* ; Hemorrhage ; Hypertension, Pregnancy-Induced ; Oxygen/therapeutic use* ; Retinopathy of Prematurity/drug therapy* ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.
Angiogenesis Inhibitors/therapeutic use* ; Diabetes Mellitus ; Diabetic Retinopathy/drug therapy* ; Humans ; Intravitreal Injections ; Macular Edema/drug therapy* ; Pharmaceutical Preparations ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors/therapeutic use*

This study was conducted to describe the incidence, risk factors, and current treatment status of retinopathy of prematurity (ROP) in very-low-birth-weight (VLBW) infants registered in the Korean Neonatal Network database. Medical records of 2,009 VLBW infants born between January 2013 and June 2014 who underwent examination by an ophthalmologist were reviewed. The total incidence of ROP was 34.1%. Of the patients, 11.6% showed ROP stage > or = 3 and 11.5% received treatment of VLBW. Among all infants who received treatment of ROP, 63.6% underwent operation only; 16.9%, anti-vascular endothelial growth factor (anti-VEGF) treatment only; and 19.5%, both operation and anti-VEGF treatment. The mean gestational age (GA) and birth weight (BW) were significantly lower and the prevalence rates of respiratory distress syndrome, patent ductus arteriosus (PDA), invasive ventilator duration, and sepsis were significantly higher in the VLBW infants with ROP than in those without ROP. In the multivariable logistic regression analysis, PDA (odd ratio [OR], 2.1; 95% confidence interval [CI], 1.11-3.79) and invasive ventilator duration (OR, 1.0; 95% CI, 1.00-1.02) were significant risk factors of ROP and ROP stage > or = 3. In conclusion, the high incidence of ROP is associated with low GA and BW, and attempt to reduce the aforementioned risk factors could reduce the incidence of ROP stage > or = 3 in VLBW infants.
Antibodies/therapeutic use ; Birth Weight ; Female ; Gestational Age ; Humans ; Incidence ; Infant ; Infant Mortality ; Infant, Newborn ; Infant, Premature ; *Infant, Very Low Birth Weight ; Logistic Models ; Male ; Odds Ratio ; Prevalence ; Republic of Korea/epidemiology ; Retinopathy of Prematurity/drug therapy/*epidemiology/mortality ; Retrospective Studies ; Risk Factors ; Vascular Endothelial Growth Factor A/immunology

Previous studies suggested that polymorphisms of proinflammatory cytokine genes are important host genetic factors in Helicobacter pylori infection. The present study evaluated whether IL-8-251 polymorphism affected H. pylori eradication rate and to investigate the effect of H. pylori eradication on angiogenesis and the inflammatory process according to the IL-8-251 polymorphism. A total of 250 H. pylori-positive patients treated by endoscopic resection of the gastric neoplasm were classified into 3 groups (134 H. pylori-eradicated group, 19 H. pylori-eradication failure group, and 97 H. pylori-infected group). H. pylori status, histology, and angiogenic factor levels were evaluated at baseline, 6 months, and 18 months. H. pylori eradication rate was 92.9% in AA genotype, 85.7% in AT genotype and 88.4% in TT genotype (P value = 0.731). Elevated IL-8 and matrix metalloproteinase-9 concentrations in H. pylori-infected gastric mucosa were reversible by successful eradication of H. pylori, independent of the IL-8-251 polymorphism. It is suggested that elevated IL-8 and MMP-9 concentrations in H. pylori-infected gastric mucosa are altered significantly after successful eradication and these conditions continue for 18 months. However, IL-8-251 polymorphism does not affect H. pylori eradication rate and the sequential changes of related angiogenic factors after H. pylori eradication in Koreans.
Aged ; Alleles ; Angiopoietin-1/analysis ; Anti-Bacterial Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Asian Continental Ancestry Group/*genetics ; Female ; Gastric Mucosa/metabolism/pathology ; Genotype ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori ; Humans ; Interleukin-8/analysis/*genetics ; Male ; Matrix Metalloproteinase 9/analysis ; Middle Aged ; *Polymorphism, Single Nucleotide ; Proton Pump Inhibitors/therapeutic use ; Republic of Korea ; Retrospective Studies ; Stomach Neoplasms/pathology/surgery ; Time Factors ; Vascular Endothelial Growth Factor A/analysis

OBJECTIVETo investigate the influence of aqueous extract of Aralia echinocaulis Hand.-Mazz on the expression of fracture healing-ralated factor receptors.

METHODSSingle factor model was set up in SD rat. Selecting 14 and 28 days in the experiment. Immunohistochemistry was employed to determine the expression of Fibroblast growth factor receptor 2 (FGFR2), Fms-like tyrosine kinase (Flt-1) and Fetal licer kinase (Flk-1) at 14 and 28 days after model establishing.

RESULTSThe expression of Flt-1 and Flk-1 at 14 days (the latter was more remarkable) were obviously promoted in High dose group of aqueous extract of Aralia echinocaulis Hand.-Mazz, and higher than that in normal group and model group. The expression of FGFR2 in the high dose group of Aralia echinocaulis Hand -Mazz was also promoted visibility, close to that in the compare group (traditional Chinese medicine), but higher than than in the model group. There was no significant difference among them. At 28 days, the expression of FGFR2, Flt-1 and Flk-1 in all groups decreased except normal group, and got higher expression in model groups than each control groups.

CONCLUSIONAqueous extract of Aralia echinocaulis Hand.-Mazz can promote angiogenesis in fracture healing, improve the activity and aggregation of fibroblasts, osteoblasts and chondrocytes. It also helps to quicken ossification in the cartilage and promote fracture healing.

Animals ; Aralia ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Female ; Fibroblast Growth Factors ; metabolism ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Wound Healing ; drug effects

Angiogenesis Inducing Agents ; metabolism ; Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Bevacizumab ; Drug Delivery Systems ; Endostatins ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; Neovascularization, Pathologic ; drug therapy ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; physiology ; Vascular Endothelial Growth Factors ; metabolism ; physiology

Angiogenesis Inhibitors ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; therapy ; Chemoembolization, Therapeutic ; methods ; Endostatins ; therapeutic use ; Humans ; Liver Neoplasms ; blood supply ; metabolism ; pathology ; therapy ; Microvessels ; pathology ; Neovascularization, Pathologic ; pathology ; Vascular Endothelial Growth Factors ; metabolism

Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV). However, the lack of ideal administration route is the biggest bottleneck preventing PEDF from wider clinical use. In this study, we developed a novel PEDF-carrying system which employed immuno-nano-liposomes (INLs) under ultrasound exposure. PEDF-loaded INLs were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and reversely encapsuling PEDF. RF/6A cells were incubated with PEDF-loaded INLs. CNV models of BN rats were injected with PEDF-loaded INLs. MTT assay was used to evaluate the cytotoxicity of the INLs on RF/6A cells. Flow cytometry was conducted to detect the apoptotic rate of cells. Laser scanning confocal microscopy was employed to observe the binding and transmitting process of PEDF-loaded INLs and to calculate the area of CNV in the rat model. The results showed that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal choroidal vessels. The CNV area was significantly decreased in PEDF treatment groups in comparison with control group (P<0.05). Moreover, PEDF-loaded INLs exposed under ultrasound were more efficient in reducing the CNV area (P<0.05). It was concluded that INLs in combination with ultrasonic exposure can transmit PEDF into cytoplasma with high specificity and efficiency, which strengthens the inhibitory effects of PEDF on CNV and reduces its side effects. PEDF-loaded INLs possibly represent a new treatment paradigm for patients with ocular neovascularization.
Animals ; Choroidal Neovascularization ; drug therapy ; Drug Delivery Systems ; Eye Proteins ; therapeutic use ; Female ; Liposomes ; administration & dosage ; Male ; Nanoparticles ; administration & dosage ; Nerve Growth Factors ; therapeutic use ; Peptides ; administration & dosage ; Rats ; Rats, Inbred BN ; Serpins ; therapeutic use ; Ultrasonics ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVESTo test the effect of rapamycin (RAPA) on hepatic tumor growth and metastasis in Sprague-Dawley (SD) rat model and explore the possible mechanism.

METHODSSD rat hepatocellular carcinoma (HCC) model with metastatic potential was induced by diethylnitrosamine (DEN) and N-nitrosomorpholine (NMOR). 120 SD rats were randomized into four groups 16 weeks after DEN and NMOR treatment, and received 4-week intraperitoneal injection of RAPA (1.5 or 4.5 mg x kg(-1) x d(-1)), CsA (25 mg x kg(-1) x d(-1)) or equal volume of 0.9% saline, respectively. Tumor growth and metastasis were checked after the 4-week treatment. Serum vascular endothelial growth factor (VEGF) was determined by enzyme-linked immunosorbent assay (ELISA). Antiangiogenetic effects were assessed by CD34 immunostaining. The levels of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and VEGF proteins and mRNAs were detected by immunohistochemistry, western blot and reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSThe mean liver weight (5.58% +/- 0.42% and 5.69% +/- 0.74%), the metastatic liver nodules (5.12 +/- 0.68 and 5.67 +/-1.12), the metastasis lung nodules (0.43 +/- 0.11 and 0.45 +/- 0.83), and the lung metastasis rate (17.2% and 14.8%) were lower in rats treated with RAPA 1.5 mg x kg(-1) x d(-1) or 4.5 mg x kg(-1) x d(-1) than those in rats treated with saline, which were 10.42% +/- 1.86%, 12.36 +/- 3.45, 1.81 +/- 0.3 and 50.0% respectively (P < 0.01 or P < 0.05). The intratumoral microvessel density (MVD), serum VEGF, and the levels of HIF-1 alpha and VEGF were lower in RAPA-treated rats than those in control rats. However, CsA-treated rats showed an opposite trend compared with the RAPA-treated rats.

CONCLUSIONRAPA can repress the expression of angiogenesis-promoting factors HIF-1 alpha and VEGF, and significantly inhibits the growth and metastasis of HCC.

Animals ; Carcinoma, Hepatocellular ; blood supply ; metabolism ; pathology ; Cyclosporine ; pharmacology ; therapeutic use ; Disease Models, Animal ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Immunohistochemistry ; Immunosuppressive Agents ; pharmacology ; therapeutic use ; Liver Neoplasms, Experimental ; blood supply ; metabolism ; pathology ; Male ; Microvessels ; pathology ; Neoplasm Metastasis ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Sirolimus ; pharmacology ; therapeutic use ; Vascular Endothelial Growth Factors ; genetics ; metabolism