VEGF Concentrations Research Articles

Differential analysis of aqueous humor cytokine levels in patients with macular edema secondary to diabetic retinopathy or retinal vein occlusion.

To evaluate the difference and the correlation between the concentrations of cytokines in the aqueous humor of eyes with macular edema secondary to diabetic retinopathy (DR) or retinal vein occlusion (RVO). This is a retrospective case control study. The aqueous humor samples were collected during intravitreal injection of anti-vascular endothelial growth factor (VEGF) for patients diagnosed with macular edema secondary to DR (DME) or RVO (RVO-ME) at Xijing Hospital from August 2021 to July 2022. Meanwhile, aqueous humor samples during vitrectomy from patients with idiopathic macular hole (IMH) were also collected and served as controls. The aqueous humor concentrations of VEGF, platelet-derived factor (PDGF), interleukin (IL)-6, IL-8, IL-18, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) were measured with Human Premixed Multi-Analyte Kit (Luminex). The difference of the aqueous cytokines and the correlation between the two diseases were analyzed. A total of 40 eyes of 38 patients were enrolled in the study, including 13 eyes of 11 DME patients (DME group), 16 eyes of 16 RVO-ME patients (RVO-ME group) and 11 eyes of 11 IMH patients (control group). The VEGF, PDGF, IL-6, IL-8, and MCP-1 levels of the aqueous humor were higher in both DME and RVO-ME groups compared with the control group (all P<0.05), the levels of TNF-α was higher in the DME group than in the control group (P<0.05). The VEGF, IL-6, MCP-1, and TNF-α levels in the aqueous humor were significantly higher in the DR group than those in the RVO group (all P<0.05). Correlation analyses revealed that there were complex positive correlations between IL-6, IL-8, IL-18, MCP-1, and TNF-α levels in the aqueous humor of eyes with two diseases. Although ischemic and inflammatory factors are similarly involved in the pathogenesis of DME and RVO-ME, the roles of these factors are more significant or more likely to be activated in DR patients, suggesting different treatment strategies should be considered for the two diseases.

Issues of cytokine regulation in vibration disease and associated conditions

The article presents the data on the state of cytokine regulation and indicators of endothelial damage when exposed to industrial vibration (general or local) and in combination with arterial hypertension. Changes in the levels of pro-inflammatory and anti-inflammatory cytokines are described, and biomarkers of endothelial dysfunction in the combined course of vibration disease and arterial hypertension are investigated. The study of the cytokine profile and biomarkers of damage to the vascular endothelium in this pathology will allow making early diagnosis of vascular disorders and optimizing preventive measures for workers in vibration hazard industries. Purpose of the study. Improving the quality of early diagnosis and prevention of vibration dis ease in an isolated course and its combination with arterial hypertension based on a study of the cytokine profile and biomarkers of endothelial dysfunction in this pathology. Material and research methods. A comprehensive study included 84 patients with vibration disease from the exposure to local and general vibration of the first and second degree, 61 patients with a combined course of vibration disease from the exposure to local and general second degree vibration and arterial hypertension, and 30 participants in the control group not exposed to industrial vibration and healthy according to medical examination. The levels of pro-inflammatory (IL-1β, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) and the biomark ers of endothelial damage (EDN1, TGF-β1, VEGF-A, PDGF-BB, fibronectin, and von Willebrand factor) were determined by enzyme immunoassay. Results. The response of the immune system to the effects of industrial vibration is characterized by a cytokine imbalance — an increase in the level of pro-inflammatory cytokines (IL-1β, IL-8, TNFα) and a decrease in the level of anti-inflammatory cytokine (IL-4). With a combined course of vibration disease and arterial hypertension, the cytokine imbalance is characterized by an even more significant increase in serum concentration of IL-1β, IL-8, TNFα and a decrease in serum IL-4 concentration. Endothelial dysfunction in vibration disease from the exposure to both local and general vibration in combination with arterial hypertension is characterized by a significant increase in the serum concentration of EDN1, TGF-β1, VEGF-A, PDGF-BB, fibronectin, and von Willebrand factor. Conclusion. The study of the cytokine profile and biomarkers of damage to the vascular endothelium in this pathology will allow making early diagnosis of vascular disorders and optimizing preventive measures for workers in vibration hazard industries.

Role of Angiopoietic Coronary Endothelial Dysfunction in the Pathogenesis of Ischemic Cardiomyopathy.

The angiopoietic endothelial dysfunction in ischemic cardiomyopathy (ICMP) remains unexplored. The identification of the imbalance of endothelial dysfunction mediators and the number of endothelial progenitor (EPC) and desquamated (EDC) cells in patients with coronary heart disease (CHD) with and without ICMP. A total of 87 patients (47 with ICMP and 40 without ICMP) were observed. The content of EPCs (CD14+CD34+VEGFR2+) in vein blood and EDCs (CD45-CD146+) in the blood from the coronary sinus and cubital vein was determined by flow cytometry. The contents of HIF-1α and HIF-2α in vein blood as well as that of ADMA and endothelin-1 in sinus plasma and angiopoietin-2, MMP-9 and galectin-3 in both samples were assessed using ELISA, and VEGF, PDGF, SDF-1 and MCP-1 contents using immunofluorescence. ADMA and endothelin-1 levels in the sinus blood were comparable between the patient groups; a deficiency of HIF-1α and excess of HIF-2α were detected in the vein blood of ICMP patients. The EDC content in the vein blood increased in CHD patients regardless of ICMP, and the concentrations of VEGF-A, VEGF-B, PDGF, MCP-1, angiopoietin-2, and MMP-9 were normal. In ICMP patients, vein blood was characterized by an excess of galectin-3 and sinus blood by an excess of EDCs, angiopoietin-2, MMP-9 and galectin-3. ICMP is accompanied by angiopoietic endothelial dysfunction.

VEGFR2 and CD34 expression associated with longer survival in patients with pleural mesothelioma in the IFCT-GFPC-0701 MAPS phase 3 trial

ObjectivesVEGF/VEGFR autocrine loop is a hallmark of pleural mesothelioma (PM). We thus assayed the prognostic and predictive values of VEGFR-2 [vascular endothelial growth factor receptor 2 or Flk-1] and CD34, a marker of endothelial cells, in samples from patients accrued in the Mesothelioma Avastin Cisplatin Pemetrexed Study ('MAPS', NCT00651456). Materials and MethodsVEGFR2 and CD34 expression were assayed using immunohistochemistry in 333 MAPS patients (74.3%), and their prognostic value was evaluated in terms of overall survival (OS) and progression-free survival (PFS) in univariate and multivariate analyses, before validation by bootstrap methodology. ResultsPositive VEGFR2 or CD34 staining was observed in 234/333 (70.2%) and 322/323 (99.6%) of tested specimens, respectively. VEGFR2 and CD34 staining correlated weakly, yet significantly, with each other (r = 0.36, p < 0.001). High VEGFR2 expression or high CD34 levels were associated with longer OS in PM patients in multivariate analysis (VEGFR2: adjusted [adj.] hazard ratio [HR]: 0.91, 95% confidence interval [CI] [0.88; 0.95], p < 0.001; CD34: adj. HR: 0.86, 95 %CI [0.76; 0.96], p = 0.010), with only high VEGFR2 expression resulting in significantly longer PFS (VEGFR2: adj. HR: 0.96, 95 %CI [0.92; 0.996], p = 0.032). Stability of these results was confirmed using bootstrap procedure. Nevertheless, VEGFR2 expression failed to specifically predict longer survival in bevacizumab-chemotherapy combination trial arm, regardless of whether the VEGFR2 score was combined or not with serum VEGF concentrations. ConclusionVEGFR2 overexpression independently correlated with longer OS or PFS in PM patients, such biomarker deserving prospective evaluation as stratification variable in future clinical trials.

Stromal vascular fraction gel promoted wound healing and peripheral nerve repair in diabetic rats via TLRs/MyD88/NF-κB signaling pathway.

Diabetes mellitus (DM) contributes to impaired wound healing. This study was aimed to evaluate the effect of stromal vascular fraction (SVF) gel extracted from rats on diabetic ulcers wound healing and peripheral nerve repair. 60 Sprague Dawley (SD) rats were divided into 6 groups, including control, model, SVF-gel low dose (SVF-gel-L), SVF-gel high dose (SVF-gel-H), ST2825, and SVF-gel-H + CL075 groups. Wound closure rate was recorded. The histopathological changes and deposition change of collagen fibre were identified. The content of TNF-α, IL-1β, VEGF, and bFGF were detected. Immunohistochemical, immunofluorescence and western blot were employed to determine the protein expression. We identified SVF-gel could promoted wound healing, restored normal cutaneous structures of the wound, promoted collagen deposition, while diminished fibrosis and inflammation. In addition, SVF-gel promoted angiogenesis and peripheral nerve recovery, diminished the expression of TLRs/MyD88/NF-κB signaling pathway. However, the protective effect of SVF-gel could be revised by CL075 co-treatment. Furthermore, ST2825 also promoted wound healing, but its effect was lower than that with SVF-gel-H treatment. SVF gel promotes the healing of diabetic skin ulcer tissue and regeneration of damaged peripheral nerve, diminished inflammatory factor infiltration. The mechanism maybe related to suppress the activation of TLRs/MyD88/NF-κB signaling pathway.

GSK-3 inhibitor elraglusib (9-ING-41) to enhance tumor-infiltrating immune cell activation in tumor biopsies and synergize with anti-PD-L1 in a murine model of colorectal cancer.

e15138 Background: Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase with key roles in myriad biological processes such as tumor progression, and inhibition of GSK-3 using a novel small-molecule elraglusib has shown promising preclinical antitumor activity in multiple tumor types. Methods: We characterize the effects of elraglusib in vitro on tumor and immune cells including cell killing and cytokine profiling , in vivo in combination with checkpoint inhibitors in a syngeneic murine colon carcinoma BALB/c model using MSS cell line CT-26, and in human tumor biopsies and plasma samples from patients with refractory solid tumors of multiple tissue origins enrolled in a Phase 1 clinical trial investigating elraglusib ( NCT03678883 ).We used human plasma samples from patients treated with elraglusib, paired pre- and post-treatment tumor biopsies and performed digital spatial proteomics. Results: Elraglusib promoted immune cell-mediated tumor cell killing, enhanced tumor cell pyroptosis, decreased tumor cell NF-κB-regulated survival protein expression, and increased immune cell effector molecule secretion. Synergy was observed between elraglusib and anti-PD-L1 in an immunocompetent murine model of colorectal cancer. Murine responders had more tumor-infiltrating T-cells, fewer tumor-infiltrating Tregs, lower tumorigenic circulating cytokine concentrations, and higher immunostimulatory circulating cytokine concentrations. Murine responders had lower serum concentrations of BAFF, CCL7, CCL12, VEGF, VEGFR2, and CCL21, and higher serum concentrations of CCL4, TWEAK, GM-CSF, CCL22, and IL-12p70 as compared to non-responders. We utilized human plasma samples from patients treated with elraglusib and correlated cytokine profiles with survival. Elevated baseline plasma levels of proteins such as IL-1 β and reduced levels of proteins such as VEGF correlated with improved PFS and OS. PFS was also found to be positively correlated with elevated plasma levels of immunostimulatory analytes such as Granzyme B, IFN-γ, and IL-2 at 24 hours post-treatment with elraglusib. Several of these secreted proteins correlated with results from the in vivo study where expression of proteins such as IL-1 β, CCL22, CCL4, and TWEAK was positively correlated with improved response to therapy while expression of proteins such as BAFF and VEGF negatively correlated with response to therapy. Using paired tumor biopsies, we found that CD45+ tumor-infiltrating immune cells had lower expression of inhibitory immune checkpoints and higher expression of T-cell activation markers in post-elraglusib patient biopsies. Conclusions: These results introduce several immunomodulatory mechanisms of GSK-3 inhibition using elraglusib, providing a rationale for the clinical evaluation of elraglusib in combination with immunotherapy.

Horse serum or equine platelet lysate increases total vascular endothelial growth factor A concentrations and correlates with vascular growth in an equine facial arterial ring assay.

To evaluate ex vivo angiogenesis of equine arterial rings in response to various growth media. Facial arteries were dissected from 11 horses post-euthanasia. Equine platelet lysate (ePL) was harvested from 6 horses. Arteries were exposed to endothelial growth media (EGM) + horse serum (HS) for first sprout (FS), vascular regression (VR), and (basement membrane matrix [Matrigel]) lysis (ML) evaluation. Additional rings supplemented with (1) EGM, (2) EGM + EDTA, (3) endothelial basal media (EBM), (4) EBM + HS, or (5) EBM + human VEGF were compared for vascular network area (VNA) and maximum network growth (MNG). Additional rings exposed to EGM + ePL at 10-(10xePL), 5-(5xePL), or 2-fold (2xePL) increases from baseline platelet concentration, EGM + HS, EGM + platelet-poor plasma (PPP), EBM + PPP and EBM were analyzed for branch number, density, VNA, and VEGF-A concentration from days 0-3. Arteries demonstrated sprouting in Matrigel supplemented with EBM alone. EGM + HS exposure resulted in no differences in FS (P = .3934), VR (P = .0607), or ML (P = .2364) between horses. VNA in EGM + HS was greater than EBM (P = .0015). MNG was greater in EGM + HS, EBM + HS, and EBM + hVEGF compared with EBM (P = .0001). ePL treatment did not have an overall significant angiogenic effect compared with supplementation with HS, PPP, or EBM alone; however, VEGF-A concentrations were higher for EGM + 10xePL, EGM + 5xePL, and EGM-HS compared with EBM and positively correlated with VNA (P = .0243). Equine arterial rings serve as an ex vivo model for angiogenesis but have a high degree of variability. HS, PPP, or ePL support vascular growth, and HS and ePL may stimulate the secretion and be sources of VEGF-A.

Comparison of the adjuvant effect of conbercept intravitreal injection at different times before vitrectomy for proliferative diabetic retinopathy.

To assess the optimal time of intravitreal conbercept (IVC) treatment prior to pars plana vitrectomy (PPV) in patients with severe proliferative diabetic retinopathy (PDR). This study was exploratory in nature. Forty-eight consecutive patients (48 eyes) with PDR were divided into four groups according to different IVC times (0.5 mg/0.05 mL) before PPV: group A (3 days), group B (7 days), group C (14 days), and group D (non-IVC). Intraoperative and postoperative effectiveness were assessed, and vitreous VEGF concentrations were detected. For intraoperative effectiveness, groups A and D had a higher incidence of intraoperative bleeding than groups B and C (P = 0.041). Furthermore, groups A-C required less surgical time than group D (P < 0.05). For postoperative effectiveness, group B had a significantly higher proportion of visual acuity that improved or remained unchanged than group D (P = 0.014), and groups A-C had lower proportions of postoperative bleeding than group D. The vitreous VEGF concentration of group B (67.04 ± 47.24 pg/mL) was significantly lower than that of group D (178.29 ± 110.50 pg/mL) (P = 0.005). IVC treatment that was administered 7 days preoperatively was associated with better effectiveness and a lower vitreous VEGF concentration than its administration at other time points.

Effect of VEGF Stimulation on CD11b Receptor on Peripheral Eosinophils in Asthmatics.

Asthma is a chronic, complex disease associated with heterogeneity in molecular pathways. Airway inflammation with different cell activation (e.g., eosinophils) and with hypersecretion of many cytokines (e.g., vascular endothelial growth factor-VEGF) might be relevant for asthma pathogenesis and responsible for airway hyperresponsiveness and remodeling. The aim of our study was to reveal the expression of activation marker CD11b on peripheral eosinophils unstimulated and after VEGF in vitro stimulation in asthmatics with different degrees of airway narrowing. The study population included a total of 118 adult subjects: 78 patients with asthma (among them 39 patients with irreversible bronchoconstriction and 39 patients with reversible bronchoconstriction according to the bronchodilation test) and 40 healthy participants as a control group. CD11b expression on peripheral blood eosinophils was detected in vitro using the flow cytometric method without exogenous stimulation (negative control), after N-formyl-methionine-leucyl-phenylalanine stimulation (fMLP; positive control) and after stimulation with VEGF in two concentrations (250 ng/mL and 500 ng/mL). CD11b marker was slightly presented on unstimulated eosinophils in asthmatics and the subgroup with irreversible airway narrowing (p = 0.06 and p = 0.07, respectively). Stimulation with VEGF enhanced the activity of peripheral eosinophils and induced CD11b expression in asthmatics in comparison with a healthy control (p < 0.05), but it was dependent neither on the concentration of VEGF nor on the degree of airways narrowing in patients with asthma. We present our findings to draw attention to the potential role of VEGF in the eosinophil priming and CD11b-mediated signaling in patients with asthma which is currently undervalued.

Comparison of Resuspension Techniques on the Cellular and Cytokine Characteristics of Platelet Rich Plasma: A Pilot Study

Background: Platelet Rich Plasma (PRP) is increasingly used for a variety of musculoskeletal ailments such as tendinopathy and arthritis. There are numerous protocols for preparing PRP, but to our knowledge there have been no studies to assess the impact that re-suspension techniques may have on the cellular characteristics and growth factor expression of the final PRP product. Hypothesis: The type of re-suspension technique used will alter the platelet characteristics and growth factor expression of PRP. Study Design: Descriptive laboratory study. Methods: Blood was collected from nine healthy volunteer donors between ages 26-60. Informed consent and ethics approval was obtained. A double spin technique was used resulting in a concentrated PRP product. Three commonly employed re-suspension techniques were utilized to re-suspend the final PRP product and the cellular characteristics and growth factor expression were analyzed using a reproducible protocol. This study was completed over a single day. Results: All three re-suspension techniques resulted in a 4.6-5.2-fold increase in platelet concentration with no difference between groups (p=0.31). This is consistent with the recommended PRP concentration in published literature. Each re-suspension technique also demonstrated in increase in concentration of PDGF and VEGF with no difference between groups (p=0.81 and p=0.97). Conclusion: This pilot study suggests that the re-suspension techniques may be equivalent and do not result in altered cellular or growth factor characteristics within the study limitations. Clinical Relevance: The mixing method can be labor and time intensive and prolong patient wait times. The vortex method can shorten the overall patient encounter time while still providing an optimal PRP product. Previously, there were only theoretical assumptions regarding how the re-suspension techniques may modify PRP characteristics.

Vascular endothelial growth factor levels in diabetic peripheral neuropathy: a systematic review and meta-analysis.

Vascular endothelial growth factors (VEGFs, including VEGF-A, VEGF-B, VEGF-C, VEGF-D and PLGF) have important roles in the development and function of the peripheral nervous system. Studies have confirmed that VEGFs, especially VEGF-A (so called VEGF) may be associated with the diabetic peripheral neuropathy (DPN) process. However, different studies have shown inconsistent levels of VEGFs in DPN patients. Therefore, we conducted this meta-analysis to evaluate the relationship between cycling levels of VEGFs and DPN. This study searched 7 databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, WanFang Database, and Chinese Biomedical Literature (CBM), to find the target researches. The random effects model was used to calculate the overall effect. 14 studies with 1983 participants were included, among which 13 studies were about VEGF and 1 was VEGF-B, so only the effects of VEGF were pooled. The result showed that there were obviously increased VEGF levels in DPN patients compared with diabetic patients without DPN (SMD:2.12[1.34, 2.90], p<0.00001) and healthy people (SMD:3.50[2.24, 4.75], p<0.00001). In addition, increased circulating VEGF levels were not associated with an increased risk of DPN (OR:1.02[0.99, 1.05], p<0.00001). Compared with healthy people and diabetic patients without DPN, VEGF content in the peripheral blood of DPN patients is increased, but current evidence does not support the correlation between VEGF levels and the risk of DPN. This suggests that VEGF may play a role in the pathogenesis and repairment of DPN.

Intra-individual variability in the neuroprotective and promyelinating properties of conditioned culture medium obtained from human adipose mesenchymal stromal cells

BackgroundGreater knowledge of mesenchymal stromal cell (MSC)-based therapies is driving the research into their secretome, identified as the main element responsible for their therapeutic effects. The aim of this study is to characterize the individual variability of the secretome of adipose tissue-derived MSCs (adMSCs) with regard to potential therapeutical applications in neurology.MethodsadMSCs were isolated from the intact adipose tissue of ten subjects undergoing abdominal plastic surgery or reduction mammoplasty. Two commercial lines were also included. We analyzed the expansion rate, production, and secretion of growth factors of interest for neurological applications (VEGF-A, BDNF, PDGF-AA and AA/BB, HGF, NGF, FGF-21, GDNF, IGF-I, IGF-II, EGF and FGF-2). To correlate these characteristics with the biological effects on the cellular targets, we used individual media conditioned with adMSCs from the various donors on primary cultures of neurons/astrocytes and oligodendrocyte precursor cells (OPCs) exposed to noxious stimuli (oxygen–glucose deprivation, OGD) to evaluate their protective and promyelinating properties, using MSC medium as a control group.ResultsThe MSC secretome showed significant individual variability within the considered population with regard to PDGF-AA, PDGF-AB/BB, VEGF-A and BDNF. None of the MSC-derived supernatants affected neuron viability in normoxia, while substantial protection by high BDNF-containing conditioned MSC medium was observed in neuronal cultures exposed to OGD conditions. In OPC cultures, the MSC-derived supernatants protected cells from OGD-induced cell death, also increasing the differentiation in mature oligodendrocytes. Neuroprotection showed a positive correlation with VEGF-A, BDNF and PDGF-AA concentrations in the culture supernatants, and an inverse correlation with HGF, while OPC differentiation following OGD was positively correlated to PDGF-AA concentration.ConclusionsDespite the limited number of adMSC donors, this study showed significant individual variability in the biological properties of interest for neurological applications for adMSC secretome, an under-researched aspect which may represent an important step in the translation of MSC-derived acellular products to clinical practice. We also showed the potential protection capability of MSC conditioned medium on neuronal and oligodendroglial lineages exposed to oxygen–glucose deprivation. These effects are directly correlated to the concentration of specific growth factors, and indicate that the remyelination should be included as a primary target in MSC-based therapies.

SproutAngio: an open-source bioimage informatics tool for quantitative analysis of sprouting angiogenesis and lumen space

Three-dimensional image analyses are required to improve the understanding of the regulation of blood vessel formation and heterogeneity. Currently, quantitation of 3D endothelial structures or vessel branches is often based on 2D projections of the images losing their volumetric information. Here, we developed SproutAngio, a Python-based open-source tool, for fully automated 3D segmentation and analysis of endothelial lumen space and sprout morphology. To test the SproutAngio, we produced a publicly available in vitro fibrin bead assay dataset with a gradually increasing VEGF-A concentration (https://doi.org/10.5281/zenodo.7240927). We demonstrate that our automated segmentation and sprout morphology analysis, including sprout number, length, and nuclei number, outperform the widely used ImageJ plugin. We also show that SproutAngio allows a more detailed and automated analysis of the mouse retinal vasculature in comparison to the commonly used radial expansion measurement. In addition, we provide two novel methods for automated analysis of endothelial lumen space: (1) width measurement from tip, stalk and root segments of the sprouts and (2) paired nuclei distance analysis. We show that these automated methods provided important additional information on the endothelial cell organization in the sprouts. The pipelines and source code of SproutAngio are publicly available (https://doi.org/10.5281/zenodo.7381732).

Proliferative and Osteogenic Supportive Effect of VEGF-Loaded Collagen-Chitosan Hydrogel System in Bone Marrow Derived Mesenchymal Stem Cells.

The use of hydrogel (HG) in regenerative medicine is an emerging field and thus several approaches have been proposed recently to find an appropriate hydrogel system. In this sense, this study developed a novel HG system using collagen, chitosan, and VEGF composites for culturing mesenchymal stem cells (MSCs), and investigated their ability for osteogenic differentiation and mineral deposition. Our results showed that the HG loaded with 100 ng/mL VEGF (HG-100) significantly supported the proliferation of undifferentiated MSCs, the fibrillary filament structure (HE stain), mineralization (alizarin red S and von Kossa stain), alkaline phosphatase, and the osteogenesis of differentiated MSCs compared to other hydrogels (loaded with 25 and 50 ng/mL VEGF) and control (without hydrogel). HG-100 showed a higher VEGF releasing rate from day 3 to day 7 than other HGs, which substantially supports the proliferative and osteogenic properties of HG-100. However, the HGs did not increase the cell growth in differentiated MSCs on days 14 and 21 due to the confluence state (reach stationary phase) and cell loading ability, regardless of the VEGF content. Similarly, the HGs alone did not stimulate the osteogenesis of MSCs; however, they increased the osteogenic ability of MSCs in presence of osteogenic supplements. Accordingly, a fabricated HG with VEGF could be used as an appropriate system to culture stem cells for bone and dental regeneration.

Synthesis, anticancer evaluation, and molecular docking study of some arylidenehydrazono analogues

A series of 2-(arylidenehydrazono)-5-(2-oxo-2-arylethyl)thiazolidin-4-one derivatives was synthesized, characterized by spectral analyses and evaluated for their in vitro antitumor activity. The IC50 determination of compounds was investigated on the human breast cancer cell line MCF-7. Among the series, compounds 3, 6, 10, 16, 17, and 24 showed remarkable anticancer activity with mean IC50 values 2.34, 0.73, 2.69, 3.40, 1.18, and 1.76 µg/mL, respectively, against MCF-7 cancer cells. Compound 16 enhanced the concentration of caspase-9, inhibited the concentration of Ki67 and showed a profound reduction in the amount of MMP9 secreted into the medium of MCF-7-treated cells. Furthermore, compound 16 revealed anti-angiogenic activity through downregulation of the concentration of VEGF in the medium of MCF-7-treated cells. Compound 16 exerted cytotoxic effects on MCF-7 tumor cells via antiproliferative, apoptotic, anti-angiogenic, and antimetastatic activities. Molecular docking methodology was performed for the most effective anticancer compounds to rationalize the possible interactions with active site of VEGFR-2 enzyme.

Abstract 5456: Application of a multiplex urinalysis test for predicting treatment response in patients with BCG unresponsive bladder cancer: a pilot study

Abstract Introduction and Objective: Recently, we reported that OncuriaTM, a multiplex urinalysis test, could be predictive of BCG treatment response. Furthermore, high-grade BCG unresponsive bladder cancer have limited treatment options. Such patients are offered either radical cystectomy or systemic therapy. One of the systemic therapies include immune-oncology agents, e.g., PD-1 or PD-L1 inhibitors. In this study, we tested the performance of OncuriaTM in a BCG unresponsive cohort to determine if it could predict response to a PDL1 inhibitor. Methods: OncuriaTM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 18 subjects who have BCG-unresponsive NMIBC with treatment of atezolizumab monotherapy or atezolizumab BCG combination (provided by Genentech, NCT02792192). The urine samples were collected prior to treatment in both arms. The OncuriaTM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. Predictive models were previously developed using supervised learning and cross-validation analyses. Model performance was validated using ROC curves. Results: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved sensitivity and specificity of &amp;gt;90%. Conclusion: Previous pilot study found that monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. In this study, we noted the performance of OncuriaTM for the prediction of systemic PDL1 inhibitor treatment response. A limitation of this study includes its small sample size. With further study, the multiplex OncuriaTM test may be applicable for the clinical evaluation of bladder cancer patients who have not previously responded to intravesical BCG treatment and is considering systemic immune-oncology options. Citation Format: Hideki Furuya, Kaoru Murakami, Ian Pagano, Runpu Chen, Yijun Sun, Nari Kim, Edward E. Kadel, Cheryl V. Wong, Nicole Davarpanah, Charles J. Rosser. Application of a multiplex urinalysis test for predicting treatment response in patients with BCG unresponsive bladder cancer: a pilot study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5456.

PD25-04 APPLICATION OF A MULTIPLEX URINALYSIS TEST FOR PREDICTING TREATMENT RESPONSE IN PATIENTS WITH BCG UNRESPONSIVE BLADDER CANCER: A PILOT STUDY

You have accessJournal of UrologyCME1 Apr 2023PD25-04 APPLICATION OF A MULTIPLEX URINALYSIS TEST FOR PREDICTING TREATMENT RESPONSE IN PATIENTS WITH BCG UNRESPONSIVE BLADDER CANCER: A PILOT STUDY Hideki Furuya, Kaoru Murakami, Ian Pagano, Runpu Chen, Yijun Sun, Nari Kim, Edward Kadel, Cheryl Wong, Nicole Davarpanah, and Charles Rosser Hideki FuruyaHideki Furuya More articles by this author , Kaoru MurakamiKaoru Murakami More articles by this author , Ian PaganoIan Pagano More articles by this author , Runpu ChenRunpu Chen More articles by this author , Yijun SunYijun Sun More articles by this author , Nari KimNari Kim More articles by this author , Edward KadelEdward Kadel More articles by this author , Cheryl WongCheryl Wong More articles by this author , Nicole DavarpanahNicole Davarpanah More articles by this author , and Charles RosserCharles Rosser More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003303.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recently, we reported that OncuriaTM, a multiplex urinalysis test, could be predictive of BCG treatment response. Furthermore, high-grade BCG unresponsive bladder cancer have limited treatment options. Such patients are offered either radical cystectomy or systemic therapy. One of the systemic therapies include immune-oncology agents, e.g., PD-1 or PD-L1 inhibitors. In this study, we tested the performance of OncuriaTM in a BCG unresponsive cohort to determine if it could predict response to a PDL1 inhibitor. METHODS: OncuriaTM data was evaluated in voided urine samples obtained from a prospectively collected cohort of 18 subjects who have BCG-unresponsive NMIBC with treatment of atezolizumab monotherapy or atezolizumab BCG combination (provided by Genentech, NCT02792192). The urine samples were collected prior to treatment in both arms. The OncuriaTM test, which measures 10 cancer-associated biomarkers was performed in an independent clinical laboratory. Predictive models were previously developed using supervised learning and cross-validation analyses. Model performance was validated using ROC curves. RESULTS: Pre-treatment urinary concentrations of MMP9, VEGFA, CA9, SDC1, PAI1, APOE, A1AT, ANG and MMP10 were increased in patients who developed disease recurrence. A combinatorial predictive model of treatment outcome achieved sensitivity and specificity of >90%. CONCLUSIONS: Previous pilot study found that monitoring the urinary levels of a cancer-associated biomarker panel enabled the discrimination of patients who did not respond to intravesical BCG therapy. In this study, we noted the performance of OncuriaTM for the prediction of systemic PDL1 inhibitor treatment response. A limitation of this study includes its small sample size. With further study, the multiplex OncuriaTM test may be applicable for the clinical evaluation of bladder cancer patients who have not previously responded to intravesical BCG treatment and is considering systemic immune-oncology options. Source of Funding: NIH/NCI R21CA263230, NIH/NCI R01CA198887 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e730 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hideki Furuya More articles by this author Kaoru Murakami More articles by this author Ian Pagano More articles by this author Runpu Chen More articles by this author Yijun Sun More articles by this author Nari Kim More articles by this author Edward Kadel More articles by this author Cheryl Wong More articles by this author Nicole Davarpanah More articles by this author Charles Rosser More articles by this author Expand All Advertisement PDF downloadLoading ...

ЭКСПЕРИМЕНТАЛЬНО КЛИНИЧЕСКОЕ СОПОСТАВЛЕНИЕ АЛКОГОЛЬ-ИНДУЦИРОВАННЫХ ИЗМЕНЕНИЙ ВАСКУЛЯРНО-ЭНДОТЕЛИАЛЬНОГО ФАКТОРА РОСТА

Aim: to comparatively estimate the nature and direction of alcohol-induced changes of vascular endothelial growth factor in the experiment and in the clinic. Materials and methods. The experimental part of the research was performed on 50 outbred mature rats (15 females and 15 males exposed to alcohol intoxication for 30 days, and 10 females and 10 males formed a control group). The average age of males was 38 (37.25–39) weeks, females - 40.5 (40-42.5) weeks. The body weight of females was 340 (329.5–345.5) g, males – 469 (464.5–474.25) g. After fixation, the control group animals were injected with intragastrically sterile 0.9% aqueous sodium chloride solution, the rest of the animals – 40% ethanol daily at the rate of 10 ml / kg, so that the animals reached a mild degree of intoxication. Clinical part of the research included 60 young patients: 30 males and 30 females, mean age was 35,97 (34,00-40,00) in females and 37,5 (34,00-41,00) in males, who were admitted to the narcological hospital for treatment of intoxication with diagnosed alcohol use disorder. The serum concentration of VEGF-A was evaluated in the blood serum of the studied patients and animals. Results. Alcohol intoxication caused an increase of serum concentration of VEGF-A in both animals and patients in comparison with control groups. The changes were unidirectional with no significant gender differences. Conclusion. The analysis of the experimental-clinical comparison of alcohol-induced changes in the serum content of VEGF-A indicates the unidirectional nature of the biological (angiogenic) effect in the form of VEGF-A expression under the action of ethanol. In the clinical interpretation of the physiological or pathological expression of angiogenesis, accompanied by an increase in the serum concentration of VEGF-A, it is necessary to take into account the specifics of the pathological process.

Effect of Intravitreal Conbercept Injection on Complications of Pars Plana Vitrectomy in Patients with Proliferative Diabetic Retinopathy.

The effect of intravitreal conbercept (IVC) before pars plana vitrectomy (PPV) on surgical complications in patients with proliferative diabetic retinopathy (PDR) was observed. A total of 152 patients with PDR operated on in Jiangsu Provincial People's Hospital from November 2019 to November 2020 were divided into two groups: 124 patients in the preoperative intravitreal conbercept injection + PPV group (IVC group) and 28 patients in the PPV only group (No-IVC group). Vitreous samples were collected in all eyes of patients who underwent vitrectomy, and the content of VEGF-A was measured by Luminex. The effect of conbercept on intraoperative and postoperative complications of PDR was assessed. The content of VEGF in the vitreous of the IVC group was significantly lower than that in the No-IVC group (64.50 ± 58.40 pg/mL vs. 805.17 ± 417.60 pg/mL, p < 0.001). During postoperative follow-up, early postoperative vitreous hemorrhage (VH) occurred in 13 of 142 eyes (9.15%). Compared with the No-IVC group, PDR patients with VH and fibrovascular membrane (FVM) or high complexity in the IVC group had lower intraoperative bleeding rates (p < 0.05). The early postoperative hemorrhage rate in the IVC group was lower than in the No-IVC group (6.03% vs. 23.08%, p < 0.05). The number of intraoperative electrocoagulation and iatrogenic retinal holes in the IVC group was significantly lower than in the No-IVC group (p < 0.05). There were no significant differences in intraocular hypertension and NVG numbers between the two groups. Visual acuity in both groups improved after PPV surgery, reaching the highest level in the 3rd month after the operation. IVC before PPV can reduce the level of VEGF-A in the vitreous body and reduce surgical complications.

A novel nomogram predicting the early recurrence of hepatocellular carcinoma patients after R0 resection.

Early tumor recurrence is one of the most significant poor prognostic factors for patients with HCC after R0 resection. The aim of this study is to identify risk factors of early recurrence, in addition, to develop a nomogram model predicting early recurrence of HCC patients. A total of 481 HCC patients after R0 resection were enrolled and divided into a training cohort (n = 337) and a validation cohort (n = 144). Risk factors for early recurrence were determined based on Cox regression analysis in the training cohort. A nomogram incorporating independent risk predictors was established and validated. Early recurrence occurred in 37.8% of the 481 patients who underwent curative liver resection of HCC. AFP ≥ 400 ng/mL (HR: 1.662; P = 0.008), VEGF-A among 127.8 to 240.3 pg/mL (HR: 1.781, P = 0.012), VEGF-A > 240.3 pg/mL (HR: 2.552, P < 0.001), M1 subgroup of MVI (HR: 2.221, P = 0.002), M2 subgroup of MVI (HR: 3.120, P < 0.001), intratumor necrosis (HR: 1.666, P = 0.011), surgical margin among 5.0 to 10.0mm (HR: 1.601, P = 0.043) and surgical margin < 5.0mm (HR: 1.790, P = 0.012) were found to be independent risk factors for recurrence-free survival in the training cohort and were used for constructing the nomogram. The nomogram indicated good predictive performance with an AUC of 0.781 (95% CI: 0.729-0.832) and 0.808 (95% CI: 0.731-0.886) in the training and validation cohorts, respectively. Elevated serum concentrations of AFP and VEGF-A, microvascular invasion, intratumor necrosis, surgical margin were independent risk factors of early intrahepatic recurrence. A reliable nomogram model which incorporated blood biomarkers and pathological variables was established and validated. The nomogram achieved desirable effectiveness in predicting early recurrence in HCC patients.