Vascular endothelial growth factor (VEGF) plays an essential role in the angiogenesis of growing cartilage. Although VEGF expression in cartilage vanishes in normal adults, VEGF is known to be ...expressed in chondrocytes of osteoarthritic (OA) cartilage. As little information is available on the VEGF expression in the cartilage of OA-like lesions of the temporomandibular joint (TMJ), VEGF expression in the condylar cartilage of TMJs of rats affected with OA was examined. To evoke OA, mechanical stress was applied by forced jaw opening for 10 or 20 days. After 20 days, marked OA-like lesions were observed in the condyle. VEGF was expressed in the chondrocytes of the mature and hypertrophic cell layers of the intermediate and posterior region of the condyle. The percentage of VEGF immunopositive chondrocytes significantly increased with the period of applied mechanical stress. Furthermore, tartrate-resistant acid phosphatase (TRAP) staining of the condylar cartilage showed significant increment of osteoclasts in the mineralized layer subjacent to the hypertrophic layer where high VEGF expression could be detected. The results suggest that VEGF plays an important role in the progression of OA.
To evaluate the role of prophylactic propranolol in the prevention of retinopathy of prematurity (ROP) in infants ≤32 weeks of gestational age and their visual outcome at 1 year of corrected ...gestational age.
Randomised double blind placebo controlled trial, parallel group nrolment with allocation ratio of 1:1.
Two level III neonatal intensive care units.
109 preterm neonates of ≤32 weeks of gestation with postnatal age ≤8 days old.
Infants with gestational age between 26 and 32 weeks were started on propranolol prophylaxis (0.5 mg/kg/dose every 12 hours) on seventh completed day of life, till a corrected gestational age of 37 weeks or complete vascularisation of retina whichever was later.
infants received a placebo.
: ROP of all grades;
: evaluation of complications due to propranolol, ROP needing treatment with laser and/or antivascular endothelial growth factor (anti-VEGF) and visual outcome at 12 months corrected age.
Prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in the incidence of ROP (56.8% vs 68.6%; p=0.39), need for laser therapy (21.56% vs 31.37%; p=0.37), treatment with anti-VEGF (3.92% vs 15.68%; p=0.09) or visual outcomes at 1 year in the study and control groups, respectively, though these reductions were not statistically significant. Decreasing trends favouring propranolol in all other ROP-related outcomes were also noted in the study group.
Prophylactic propranolol in the prescribed dose of 1 mg/kg/day showed a decreasing trend in all outcomes of ROP though statistically not significant.
CTRI/2013/11/004131.
Catheter-based intracoronary vascular endothelial growth factor (VEGF) gene transfer is a potential treatment for coronary heart disease. However, only limited data are available about local VEGF ...gene transfer given during angioplasty (PTCA) and stenting.
Patients with coronary heart disease (n=103; Canadian Cardiovascular Society class II to III; mean age, 58+/-6 years) were recruited in this randomized, placebo-controlled, double-blind phase II study. PTCA was performed with standard methods, followed by gene transfer with a perfusion-infusion catheter. Ninety percent of the patients were given stents; 37 patients received VEGF adenovirus (VEGF-Adv, 2x10(10) pfu), 28 patients received VEGF plasmid liposome (VEGF-P/L; 2000 microg of DNA with 2000 microL of DOTMA:DOPE 1:1 wt/wt), and 38 control patients received Ringer's lactate. Follow-up time was 6 months. Gene transfer to coronary arteries was feasible and well tolerated. The overall clinical restenosis rate was 6%. In quantitative coronary angiography analysis, the minimal lumen diameter and percent of diameter stenosis did not significantly differ between the study groups. However, myocardial perfusion showed a significant improvement in the VEGF-Adv-treated patients after the 6-month follow-up. Some inflammatory responses were transiently present in the VEGF-Adv group, but no increases were detected in the incidences of serious adverse events in any of the study groups.
Gene transfer with VEGF-Adv or VEGF-P/L during PTCA and stenting shows that (1) intracoronary gene transfer can be performed safely (no major gene transfer-related adverse effects were detected), (2) no differences in clinical restenosis rate or minimal lumen diameter were present after the 6-month follow-up, and (3) a significant increase was detected in myocardial perfusion in the VEGF-Adv-treated patients.
Purpose
Glioblastoma (GBM) is the commonest brain tumour in adults. A sub-population of cells within these tumours, known as cancer stem cells (CSCs), is thought to mediate their chemo-/radiotherapy ...resistance. CD133 is a cell surface marker that is used to identify and isolate GBM CSCs. However, its functional significance, as well as the relevant microenvironment in which to study CD133, have so far remained unknown. Here, we examined the effect of hypoxia on the expression of CD133 and on that of the hypoxia-related factors HIF-1α and HIF-2α, and the potential functional significance of CD133 expression on the acquisition of chemo-resistance by GBM cells.
Methods
CD133, HIF-1α, HIF-2α, VEFG and (control) HPRT mRNA expression analyses were carried out on GBM cells (U251, U87 and SNB19; 2D or 3D cultures) under both normoxic and hypoxic conditions, using qRT-PCR. siRNA was used to downregulate CD133, HIF-1α and HIF-2α expression in the GBM cells, which was confirmed by flow cytometry and qRT-PCR, respectively. Drug sensitivity-related IC50 values were established using an Alamar Blue cell viability assay in conjunction with the Graphpad prism software tool.
Results
We found that the expression of CD133 was upregulated under hypoxic conditions in both the 2D and 3D GBM cell culture models. In addition, an increased resistance to cisplatin, temozolomide and etoposide was observed in the GBM cells cultured under hypoxic conditions compared to normoxic conditions. siRNA-mediated knockdown of either HIF-1α or HIF-2α resulted in a reduced CD133 expression, with HIF-2α having a more long-term effect. We also found that HIF-2α downregulation sensitized the GBM cells to cisplatin to a greater extent than HIF-1α, whereas CD133 knockdown had a more marked effect on cisplatin sensitisation than knockdown of either one of the HIFs, suggesting the existence of a HIF-independent cisplatin resistance mechanism mediated by CD133. This same mechanism does not seem to be involved in temozolomide resistance, since we found that HIF-1α downregulation, but not HIF-2α or CD133 downregulation, sensitized GBM cells to temozolomide.
Conclusions
From our data we conclude that the mechanisms underlying hypoxia-induced CD133-mediated cisplatin resistance may be instrumental for the design of new GBM treatment strategies.
regular intravitreal anti-vascular endothelial growth factor (VEGF) treatment is crucial for patients with neovascular age-related macular degeneration (nAMD), and delayed treatment can exacerbate ...disease progression.
we compared the outcomes of on-time versus delayed intravitreal anti-VEGF treatment for patients with nAMD. This study was conducted during the coronavirus disease 2019 (COVID-19) pandemic with a 2-year follow-up period. The best-corrected visual acuity (BCVA) and anatomical findings were evaluated before the pandemic, during the pandemic, and at 6-, 12-, 18-, and 24-months post-pandemic.
The delayed and on-time groups comprised 54 and 72 patients, respectively. After the pandemic, the injection interval increased by 0.65 ± 1.51 months (
= 0.003), with 22.2% of the patients in the delayed group switching to the treat-and-extended regimen (
< 0.001). The delayed group showed greater mean BCVA deterioration (
= 0.027) and central subfield thickness (
= 0.037) at 6 months and worse maximum subretinal fluid height (
= 0.022) at 18 months than the on-time group. No difference was observed between the groups in the second year.
the negative effects of delaying anti-VEGF treatment because of the COVID-19 pandemic can be ameliorated by changing the treatment regimen and shortening treatment intervals.
OBJECTIVETo investigate the impact of supragingival scaling on the clinical outcomes of subgingival instrumentation completed after 1 week. METHOD AND MATERIALSIn 27 patients with Stage II and Stage ...III periodontitis, pairs of contralateral quadrants were randomly assigned into test group 1 (single sitting scaling and root planing) and test group 2 (supragingival scaling followed by subgingival instrumentation after 1 week). Periodontal parameters were recorded at baseline, 2, 4, and 6 months; Gingival crevicular fluid vascular endothelial growth factor (VEGF) estimation was done at baseline in both groups and 7 days after supragingival scaling in test group 2. RESULTSAt 6 months, significantly better improvement in test group 1 at sites with periodontal probing depth (PPD) > 5 mm; (∆PPD = 2.32 mm vs 1.41 mm, P = .001; ∆clinical attachmen level CAL = 2.34 mm vs 1.39 mm, P = .001) was observed. Supragingival scaling resulted in significant reduction in gingival crevicular fluid VEGF (42.46 to 27.88 pg/site) after 1 week. Regression analysis explained 14% variance in VEGF to baseline PPD at sites with PPD > 4 mm; and 21% variance in CAL improvement to VEGF at sites with PPD > 5 mm. The percentage of sites with PPD = 5 to 8 mm reaching the clinical endpoint was 52% and 40% for test group 1 and test group 2, respectively. Better results were noticed in bleeding on pocket probing-positive sites in both groups. CONCLUSIONThe sites with PPD > 5 mm where supragingival scaling was followed by subgingival instrumentation after 1 week resulted in less favourable treatment outcomes. (Clinical trial registry NCT05449964).
There were conflicting results about whether promoter polymorphisms (−2578C/A, −1154G/A) of vascular endothelial growth factor (VEGF) gene is a risk factor of Alzheimer's disease (AD). To determine ...the relationship between them, a meta-analysis is needed urgently. We searched all the reports about VEGF promoter polymorphisms (−2578C/A, −1154G/A) and AD risk from PubMed, Web of Science, Cochrane Collaboration and Google Scholar database for the period up to 1 August, 2012. A total of 7 studies were included in this meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated applying fixed or random effects models. There was no significant association between VEGF −2578C/A polymorphisms and AD risk in all gene models (OR=1.08, 95% CI=0.94–1.23 for A vs. C; OR=1.19, 95% CI=0.89–1.59 for AA vs. CC; OR=1.15, 95% CI=0.91–1.45 for AA vs. CC+CA; OR=1.11, 95% CI=0.98–1.25 for AA+CA vs. CC). Similar results were provided in subgroup analysis by ethnicity. For the VEGF −1154G/A polymorphisms, lack of an association was also found (A vs. G: OR=0.89, 95% CI=0.79–1.01; AA vs. GG: OR=0.82, 95% CI=0.62–1.08; AA vs. GA+GG: OR=0.89, 95% CI=0.68–1.16; AA+AG vs. GG: OR=0.85, 95% CI=0.72–1.00). Conclusively, the result of this meta-analysis suggested that VEGF promoter polymorphisms (−2578C/A, −1154G/A) might not contribute to the susceptibility of AD.
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► We examined VEGF polymorphisms and AD risk by meta-analysis. ► VEGF polymorphisms have no association with AD risk. ► Meta-analysis can increase the statistical power by pooling different studies. ► This meta-analysis will be helpful in clarifying current controversies.
We investigated whether adhesion formation is prevented by the inhibition of angiogenesis in a rat uterine horn adhesion model. A single-dose of bevacizumab was effective in preventing postoperative ...intraperitoneal adhesion formation among 30 Wistar albino rats that underwent serosal injury by use of a standard technique after laparotomy with intraperitoneal bevacizumab.
The tumor microenvironment plays a critical role in determining the fate of tumor cells. We have previously reported that adhesion of human myeloma and leukemia cell lines to the extracellular matrix ...protein, fibronectin, confers a multidrug-resistant phenotype. Mechanisms associated with this cell adhesion-mediated drug resistance are drug-type specific. In the present study, we examined the influence of bone marrow stromal cells (BMSCs) on myeloma cell response to the topoisomerase II inhibitor, mitoxantrone. Apoptosis was inhibited by more than 50% when cells were adhered to BMSCs as compared to myeloma cells maintained in suspension. To investigate the mechanisms contributing to the resistance of myeloma cells in contact with BMSCs, we examined the protective effects of BMSCs under four separate conditions: (1) direct cell contact; (2) BMSCs conditioned medium; (3) medium conditioned by coculturing myeloma cells in direct contact with BMSCs; and (4) medium conditioned by coculturing myeloma cells and BMSCs without direct physical contact. Conditioned medium from BMSCs alone was not sufficient to protect myeloma cells from drug-induced apoptosis; however, soluble factors produced during the myeloma-BMSCs interaction decreased the sensitivity of myeloma cells to mitoxantrone, suggesting a dynamic interaction between myeloma cells and BMSCs. We also found that myeloma cells in direct contact with BMSCs underwent growth arrest, whereas soluble factors produced by myeloma cells-BMSCs coincubation stimulated the proliferation of myeloma cells. These data show that both cell-cell adhesion of BMSCs with myeloma cells and soluble factors induced by this cell-cell interaction are involved in the protection of myeloma cells from mitoxantrone-induced apoptosis; however, the mechanisms contributing to the drug resistance are different.
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