Serum Vascular Endothelial Growth Factor Research Articles

Diagnostic Significance of Serum VEGF, bFGF, and Wound Tissue EGFR in Diabetic Chronic Refractory Wounds.

Patients with diabetes mellitus (DM) face a higher risk of developing chronic refractory wounds. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and epidermal growth factor receptor (EGFR) plays an important role in diabetes-related complications. This study aims to analyze the correlation between the 3 indicators and diabetic chronic refractory wounds, in order to establish the diagnostic value of these 3 indicators and provide reference for the treatment. We selected 168 patients, with 84 in healing group and 84 in refractory group. The levels of serum VEGF, bFGF, and wound tissue EGFR were compared before treatment, and the correlation between the 3 indicators and the refractory wounds was analyzed. After the specific treatment in refractory group, the clinical efficacy and wound closure index was recorded, and the correlation between them and the 3 indicators were analyzed. The 3 indicators were all protective factors for diabetic chronic refractory wounds (p < .05). The serum VEGF and bFGF had relatively low diagnostic value for diabetic chronic refractory wounds, while wound tissue EGFR demonstrated higher diagnostic value (p < .05). The 3 indicators had a positive correlation with both the clinical efficacy and the wound closure index (p < .05). Higher levels of serum VEGF, bFGF, and wound tissue EGFR are conducive to reducing the incidence of diabetic chronic refractory wounds. The combined measurement of these indicators holds high diagnostic value for the disease. Moreover, the higher the expression levels of these 3 indicators, the more favorable the clinical outcomes.

Activity of Selected Bone Formation and Angiogenesis Markers During the Treatment of Limb Length Discrepancy in Children Using Distraction Osteogenesis with the Circular Hexapod External Fixator

Background/Objectives: Limb lengthening and deformity correction techniques, particularly distraction osteogenesis, have significantly evolved in pediatric orthopedics. This study examines the temporal changes of key biochemical markers—vascular endothelial growth factor (VEGF), fibroblast growth factor 1 (FGF-1), and the propeptide of type I collagen (P1NP)—during the limb lengthening process. Methods: Twenty pediatric patients (aged 13–16) underwent distraction osteogenesis using the Circular Hexapod External Fixator. Peripheral blood samples were collected pre-treatment, three weeks after initiating distraction, and one month post-lengthening. Marker levels were measured using ELISA. Results: Serum VEGF concentrations significantly increased during treatment, peaking at T2 (T1 35.91 ± SD 5.54 vs. T2 293.47 ± SD 69.57, p &lt; 0.0001), then declined at T3 (293.47 ± SD 69.57 vs. 40.86 ± SD 6.26, p &lt; 0.0001). FGF-1 showed minor fluctuations initially but significantly increased by T3 (18.14 ± SD 4.57 vs. 41.56 ± SD 17.15, p &lt; 0.01), about 2.3 times higher than baseline. P1NP concentrations exhibited a linear increase, with a significant rise from T2 to T3 (234.06 ± SD 36.57 vs. 280.68 ± SD 35.63, p &lt; 0.05), while the T1 to T2 increase was not statistically significant, indicating ongoing osteoblastic activity and bone formation. Conclusions: This study highlights the dynamic changes in VEGF, FGF-1, and P1NP during distraction osteogenesis, emphasizing their roles as biomarkers of bone regeneration. These findings enhance the understanding of bone healing mechanisms and could inform future therapeutic strategies for pediatric limb lengthening. Further research is warranted to explore their clinical utility.

Prognostic Correlation of Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor with Radiological Tumor Size in Pediatric Nephroblastoma and Neuroblastoma: A Prospective Study

ABSTRACT Introduction: Angiogenesis plays an important role in the growth, progression, and metastasis of solid tumors. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF); both are potent angiogenic factors implicated with the growth and metastasis of solid tumors mostly in adult studies. Rapidly growing and large-size tumors have a positive correlation with these factors which are measured in serum and urine samples of patients. There is little literature available for pediatric patients that compare the computed tomography findings (size) of pediatric solid tumors with serum VEGF and serum/urinary bFGF. This prospective study aims to determine the correlation of serum VEGF and serum/urinary bFGF with the size of common pediatric solid tumors (nephroblastoma and neuroblastoma [NB]) to determine its diagnostic and prognostic significance. Materials and Methods: A prospective case–control study was done for 3 years (December 2020 to November 2023) at our institute. All children aged 1 day to 18 years admitted with the diagnosis of NB and nephroblastoma (Wilms’ tumor [WT]) were included after parental consent. The control group includes children of varying ages without any malignancy. Blood and urinary samples were collected at admission before or a week after the biopsy and the level of bFGF and VEGF was analyzed with the ELISA method. Triple-phase computed tomographies along with recommended evaluation were performed according to the tumor as per international standard protocols. Appropriate statistical analyses were done. Results: A total of 30 patients were included in the cohort, of which 13 patients were with the diagnosis of WT. Only 7 patients had metastatic disease. All the patients were treated with neoadjuvant chemotherapy, surgery, and radiotherapy according to their presentation and tumor stage. Both the growth factors, i.e., VEGF (median value - 314.38 pg/mL) and bFGF (median value - 18.96 pg/mL), are elevated in all the tumor patients in comparison with the controls (median VEGF - 100.51 pg/mL and bFGF - 15.6 pg/mL). When compared with the tumor size, no significant associations are found (with VEGF P - 0.40 and with bFGF P - 0.44). Conclusion: Although no satistically significant correlations were found between serum/urinary levels of bFGF and VEGF with tumor size, this study showed the raised median serum value of bFGF and VEGF in patients with NB and WT in comparison to controls and provided the rationale to explore this issue on a larger group of patients.

Bushen Zhuyun Decoction Enhances Endometrial Receptivity via the IL-6/STAT3 Signaling Pathway in Rats

Background: Reproductive endocrine disorder can impair endometrial receptivity, preventing embryo implantation and increasing miscarriage risk. Impaired endometrial receptivity contributes significantly to female infertility. Inflammatory signaling pathways including the IL-6/STAT3 pathway help embryos implant. Therefore, it is crucial to explore the relationship between the IL-6/STAT3 signaling pathway and endometrial receptivity. Objective: To investigate the mechanism by which Bushen Zhuyun decoction (BSZY) enhances endometrial receptivity in rats through the IL-6/STAT3 signaling pathway. Methods: Mifepristone-induced poor endometrial receptivity models of female SD rats were established, followed by histopathological observation. ELISA was used to measure serum sex hormones and VEGF. Western blotting or IHC was used to measure steroid receptors, IGFBP1, and IL-6/STAT3 pathway activation in the uterus during each estrus cycle and early gestation of normal rats. The Treg/Th17 balance was assessed using flow cytometry. Results: Significant differences were found in the protein expressions of steroid receptors, IL6, STAT3, and p-STAT3 during each estrus cycle and early gestation of normal rats. The protein expressions of STAT3 and PR were strongly correlated with each other. BSZY notably improved uterine morphology increased the expression of implantation markers and raised the serum concentrations of sex hormones and VEGF. BSZY enhanced the expressions of IL-6 and its receptors and restored the expressions of STAT3 and p-STAT3 in the uterus of pregnant rats. In addition, BSZY effectively restored the Treg/Th17 balance in the peripheral blood of pregnant rats. Conclusion: BSZY enhances endometrial receptivity and promotes decidualization in SD rats via the IL-6/STAT3 signaling pathway.

Unlocking the diagnostic potential of vascular endothelial growth factor and interleukin-17: Advancing early detection strategies for hepatocellular carcinoma.

Tian et al investigated the diagnostic value of serum vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) in primary hepatocellular carcinoma (PHC). Their retrospective study, published in the World Journal of Gastrointestinal Surgery, revealed that the serum levels of VEGF and IL-17 are significantly elevated in PHC patients compared with healthy controls. These biomarkers are closely associated with pathological features such as tumor metastasis and clinical tumor node metastasis stage. A receiver operating characteristic analysis further confirmed the diagnostic efficacy thereof, suggesting that VEGF and IL-17 could serve as valuable tools for early detection and treatment guidance. This study underscores the potential of integrating these biomarkers into clinical practice to increase diagnostic accuracy and improve patient management in PHC.

Association of proteinuria with improved prognosis in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab, and the predictive role of serum vascular endothelial growth factorD levels: A multicenter retrospective study.

Atezolizumab/bevacizumab is a first-line therapy for unresectable hepatocellular carcinoma (HCC). Among several adverse events, grade ≥2 proteinuria is considered a significant adverse event that may cause bevacizumab interruption. Studies have shown that proteinuria might predict improved prognosis, although data are scarce and the association remains controversial, and the mechanisms and predictive factors remain unclear. We aimed to clarify these. In this multicenter retrospective study, we screened patients with HCC treated with atezolizumab/bevacizumab. The prognostic impact of grade ≥2 proteinuria was examined in patients with proper clinical data and preserved serum for growth factor analysis. For biomarker analysis predicting proteinuria, baseline serum vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D levels were analyzed. This study included 75 patients, and 32 (42.7%) experienced grade ≥2 proteinuria. No significant differences were observed between those with or without proteinuria, except for aspartate transaminase and alanine transaminase levels. Time-dependent Cox proportional hazards analysis revealed that grade ≥2 proteinuria was significantly associated with better prognosis (hazard ratio 0.221; 95% confidence interval 0.082-0.592; p=0.003). In biomarker analysis, low baseline serum VEGF-C and VEGF-D levels were significantly associated with proteinuria, and multivariate analysis demonstrated that baseline serum VEGF-D level was significantly associated with grade ≥2 proteinuria (hazard ratio 0.101; 95% confidence interval 0.029-0.357; p<0.001). Grade ≥2 proteinuria in patients with unresectable HCC treated with atezolizumab/bevacizumab indicates a better prognosis, and baseline serum VEGF-D levels can help predict its occurrence. These findings can help in managing adverse events and prognosis in advanced HCC treated with atezolizumab/bevacizumab.

Analysis of musculoskeletal ultrasound findings and cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica

We sought to clarify the musculoskeletal ultrasound (MSUS) findings and serum concentrations of cytokines/growth factors in glucocorticoid-resistant polymyalgia rheumatica (GC-R PMR). Patients with PMR admitted to Nagasaki University Hospital (n = 41) were enrolled. MSUS of both shoulder joints was performed in 36 patients. Patients’ sera were analyzed for cytokines/growth factors using multiplex assay kits. We examined the cases of 17 males and 24 females (median age 70 years). There were 27 GC-R patients and 14 non-GC-R patients. PD signals were detected in significantly more GC-R patients (65.2%) than non-GC-R patients (23.1%) (p = 0.035). The median serum level of vascular endothelial growth factor (VEGF) was significantly higher in the GC-R group at 871.4 pg/mL than the non-GC-R group (422.8 pg/mL) (p = 0.03) and significantly higher in the PD-positive versus PD-negative patients (p = 0.04). A multivariate analysis revealed that a high serum VEGF level was an independent variable contributing to GC resistance (p = 0.017, odds ratio: 10.34). These results suggest that a high serum VEGF level is a biomarker of GC resistance in PMR, which might be explained by PD-positive neovascularization in inflamed joints of PMR.

NCMP-12. AN ATYPICAL CASE OF POEMS WITH MACROFOCAL MYELOMA

Abstract Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell dyscrasia. Symptoms of peripheral neuropathy dominate the clinical picture and is postulated to be related to serum vascular endothelial growth factor (VEGF) mediated altered permeability of the blood nerve barrier. The classic presentation includes a solitary osteosclerotic plasmacytoma and an elevation of VEGF. In this case, we present a patient with neither of these features who met diagnostic criteria for POEMS though had predominantly osteolytic lesions and was diagnosed with macrofocal myeloma, a unique subset of multiple myeloma. Our patient is a young male who presented with progressive leg numbness/weakness and was found to have marked ankle weakness, diffuse areflexia and unilateral gynecomastia on examination. EMG showed a motor predominant demyelinating polyneuropathy. Labs showed a serum IgG lambda M protein, low estradiol and low testosterone. He had a normal serum VEGF level though the lab was drawn after treatment initiation. Bone biopsy of a dominant osteolytic lesion was consistent with a plasma cell neoplasm (light chain restricted). Of note, he had mild cauda equina nerve root and ventral conus enhancement initially concerning for leptomeningeal involvement however, two lumbar punctures were negative for malignant cells. Spinal enhancement has been reported in POEMS. The patient underwent chemotherapy, radiation therapy and autologous stem cell transplantation. We present a patient diagnosed with MFMM, a rare subset of multiple myeloma, comprising only 3% of all cases, along with POEMS, a rare paraneoplastic syndrome. Interestingly, as osteolytic lesions can be seen in POEMS alone though not predominantly so, it is possible the patient could have atypical POEMS without underlying multiple myeloma. POEMS may remain under-recognized when presentations or setting are atypical.

Comprehensive serum biomarker analysis reveals IL-8 changes as the only predictor of the effectiveness of immune checkpoint inhibitors for patients with advanced non-small cell lung cancer

ObjectivesProgrammed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting. Materials and MethodsThis was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab. ResultsAmong the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45–2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low. ConclusionComprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.

Is Serum VEGF-A Level an Indicator of Early-Onset Poststroke Depression?

Background and Objectives: Poststroke depression (PSD) is a psychiatric complication occurring after a stroke, and is known to negatively impact quality of life. In the present study, the possible relationship between serum vascular endothelial growth factor (VEGF-A) levels and early-onset PSD, as well as the predictive value of serum VEGF-A levels for early-onset PSD, were investigated. Materials and Methods: The study included 88 individuals diagnosed with acute ischemic stroke (AIS). Demographic data, clinical characteristics, and serum VEGF-A levels were recorded, and radiological images were examined to determine the lesion locations. The National Institutes of Health Stroke Scale (NIHSS), Montreal Cognitive Assessment (MoCA), and Hamilton depression scale (HAMD-17) were administered to the patients. Furthermore, serum VEGF-A levels were measured in all participants. Results: Although the body mass index (BMI) and VEGF-A levels were similar between the groups, MoCA scores were lower [(19.2 ± 4.4) vs. (22.3 ± 3), p = 0.001] and NIHSS scores were higher [18 (8-28) vs. 14 (3-24), p = 0.006] in individuals with PSD than in those without it. When the patients with PSD were categorized into three groups, patients with severe PSD had higher NIHSS scores [26 (23-27) vs. 15 (8-23), p = 0.006] and lower MoCA scores [(14.3 ± 1) vs. (20.9 ± 3.8), p = 0.005] than those with mild PSD. Moreover, VEGF-A levels and lesion localization were similar between mild, moderate, and severe PSD groups (p = 0.130). The MoCA score was negatively (r = -0.498, p < 0.001) correlated and the NIHSS score was positively correlated (r = 0.497, p < 0.001) with the HAMD-17 score. Conclusions: Our findings suggest that longitudinal studies in large cohorts including healthy control groups are needed to examine the possibility of using serum VEGF-A level as a marker for predicting early-onset PSD.

COMPARATIVE ANALYSIS OF THE DIAGNOSTIC ACCURACY OF ENDOSTATIN AND VEGF SERUM LEVELS IN PATIENTS WITH BONE SARCOMAS

Introduction. Angiogenesis regulators are of particular interest as new serum markers in cancer patients, since they reflect the intensity of tumor growth and metastasis. Currently, many works are dedicated to the study of vascular endothelial growth factor (VEGF), which activates angiogenesis, and endostatin, which inhibits it. However, a comparative study of the diagnostic accuracy of serum levels of these two markers in patients with bone sarcomas has not been conducted yet. Аim. A comparative analysis of the diagnostic accuracy indicators and prognostic significance of VEGF and endostatin in the blood serum of patients with primary malignant bone tumors. Methods. During the study, the levels of endostatin and VEGF in blood serum samples from 123 patients with a newly diagnosed and morphologically verified bone sarcoma were measured. Patients were examined at the Federal State Budgetary Institution “National Medical Research Center of Oncology named after N.N. Blokhin” of the Russian Ministry of Health from July 2001 to December 2022. Sixty age- and gender-matched healthy donors were included in the control group. Results. Median serum concentrations of endostatin and VEGF in the patient group were statistically significantly increased compared to the control group by 1.3 and 1.4 times, respectively (p &lt; 0.01). Statistically significant differences in the serum concentrations of VEGF and endostatin depending on the T category and the tumor grade and stage were not identified. The cut-off value of VEGF was 279 pg/ml, and the cut-off value of endostatin was 121 ng/ml. With the same sensitivity of 75.6%, endostatin is characterized by higher specificity than VEGF (73.0 and 67.6%, respectively). The proportional hazards model characterizing the effect of serum VEGF and endostatin levels on overall and survival was not statistically significant. Conclusion. Endostatin in the blood serum of patients with bone tumors is more informative compared to VEGF; however, both markers are not predictors of overall and survival.

Efficacy of propranolol and pingyangmycin combination therapy in infantile hemangiomas: Correlation with VEGF Levels

BackgroundInfantile hemangiomas (IH) represent the most prevalent vascular tumors in infants, often necessitating prompt medical intervention due to their potential for rapid growth and complications. This retrospective study aims to evaluate the efficacy of propranolol combined with Pingyangmycin in the treatment of IH and to investigate its correlation with vascular endothelial growth factor (VEGF) levels. MethodsA prospective, observational study was conducted over 12 months, enrolling 120 IH patients. Patients received a combination therapy of propranolol and pingyangmycin for 3 to 6 months. Hemangioma Activity Score (HAS) and serum VEGF levels were assessed at baseline, 30th day, and 90th day post-treatment. ResultsA total of 120 patients diagnosed with IH, including 68 males and 52 females with a mean age of 1.2 years, were enrolled in this study. The HAS at baseline was 8.5 ± 1.7, which significantly decreased to 4.2 ± 1.0 by Day 30 and further reduced to 2.1 ± 0.8 by Day 90 (P < 0.001 for both comparisons). Serum VEGF levels also showed a significant reduction from a baseline of 235.6 ± 42.1 pg/mL to 180.3 ± 34.7 pg/mL at Day 30 and to 122.8 ± 28.9 pg/mL at Day 90 (P = 0.02 and P = 0.01, respectively). The correlation analysis revealed a positive correlation between VEGF levels and HAS scores at all time points, with Pearson correlation coefficients ranging from -0.82 to -0.89 (P < 0.001). Adverse events were mild and transient, occurring in 15% of patients, with the most common being mild hypoglycemia (8%), transient bronchospasm (5%), and gastrointestinal discomfort (2%). All adverse events resolved with symptomatic treatment, and no patient discontinued therapy due to adverse reactions. ConclusionPropranolol treatment for infants with proliferative hemangiomas is significantly effective with minor adverse effects. The mechanism of action may be associated with the downregulation of serum VEGF levels.

Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial

BackgroundPoor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.MethodsIn this randomized, triple-blind, placebo-controlled trial, 60 infertile POR patients from POSEIDON Group 4 (the poorest prognosis category, age > 35 and poor ovarian reserve (anti-müllerian hormone < 1.2 ng/ml or antral follicle count < 5) undergoing intracytoplasmic sperm injection were enrolled. Patients were assigned to receive either 12 mg/day AST or placebo for eight weeks. All patients underwent a gonadotropin-releasing hormone antagonist regimen for COS. ART outcomes were compared between groups. Blood serum and follicular fluid (FF) were analyzed for OS markers (superoxide dismutase [SOD], total antioxidant capacity [TAC], and malondialdehyde [MDA]), and pro-inflammatory cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and vascular endothelial growth factor [VEGF]) via enzyme-linked immunosorbent assay kits, and cell-free DNA [cfDNA] (apoptotic marker) via ALU quantitative polymerase chain reaction.ResultsAfter the intervention, the AST group exhibited a significant elevation in serum (P = 0.013) and TAC (P = 0.030), accompanied by a significant reduction in serum MDA (P = 0.005). No significant differences between AST and placebo groups were observed in OS markers in FF. AST group showed significant reductions in the serum IL-6 (P < 0.001), IL-8 (P = 0.001), and VEGF (P = 0.002) levels following AST therapy. In the AST group, FF levels of IL-6 (P = 0 < 001), IL-8 (P = 0.036), VEGF (P = 0.006), and cfDNA (P < 0.001) were significantly lower than in the placebo group. Between-group comparisons showed significant differences in the alterations of serum SOD (P = 0.027), IL-6 (P < 0.001), and IL-8 (P = 0.035) levels between AST and placebo groups. The AST group showed significant increases in the number of retrieved oocytes (P = 0.003), MII oocytes (P = 0.004), frozen embryos (P = 0.037), and high-quality embryos (P = 0.014) compared to the placebo group.ConclusionAST shows promise as a COS adjuvant therapy, potentially enhancing some ART outcomes in POR through alleviating OS, inflammation, and apoptosis.Trial registrationClinical trial registration number: IRCT20230223057510N1, URL: https://irct.behdasht.gov.ir/trial/68870, registration date: 2023 March 16.Graphical

Profiling of Toll-like Receptors and Related Signaling Mediators in the Pathogenesis of Morphea.

Morphea, also known as localized scleroderma, is a rare fibrosing inflammatory disease of unknown pathogenesis. Although the genetic basis for morphea is important, reports on the evaluation of Toll-like receptors (TLR) in this disease is quite limited. We aimed to evaluate TLR expression levels and serum IL-6, IL-17A, TGF-β1, FGF, and VEGF levels in patients with morphea and compare these results with healthy controls. The expression levels of TLRs in the lesional and non-lesional adjacent skin of patients with morphea and in normal skin of healthy controls were evaluated by RT-PCR, whereas serum levels of IL-6, IL-17A, TGF-β1, FGF, and VEGF were evaluated by ELISA. Based on our findings, TLR1 gene expression increased 34.3-fold in the lesional skin of patients with morphea. In addition, IL-6, IL-17A, TGF-β, FGF, and VEGF were found to be higher in the blood samples of the patient group than in the healthy group. TLRs are important parts of the pathogenesis of morphea, and a better understanding of them will lead to more directed, effective treatments. We believe that this study will be important for pioneering TLR-targeted therapeutic approaches in the treatment of morphea in the future.

Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients. We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded. The cohort had a median follow-up duration of 12.5 months (range 4-30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9-26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7-14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (P=0.028) and VEGF-A (P=0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (P=0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (P=0.326) in patients in whom HGF was reduced post-SBRT. We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.

ANGIOGENIC FACTORS AS PREDICTORS OF SURVIVAL IN PATIENTS WITH BONE SARCOMAS

Introduction. Primary bone sarcomas are relatively rare neoplasms. They occur predominantly in adolescents and young adults, are characterized by an aggressive clinical course and a high metastatic potential, have a poor prognosis. In this regard, the problem of stratifying the risk of metastasis and death in order to select the optimal treatment tactics always remains relevant. The study of such markers as endostatin, vascular endothelial growth factor (VEGF), insulin-like growth factors IGF-1, IGF-2 as potentially informative predictors of survival in patients with bone sarcomas is pathogenetically determined by their involvement in the processes of tumor growth and metastasis. Aim – to analyze the relationship between pre-treatment serum levels of endostatin, VEGF, IGF-1 and IGF-2 with overall survival rates in patients with bone sarcomas. Material and methods. An analysis of overall survival rates was carried out in 134 patients with malignant bone tumors aged from 1 to 73 years (Me=27.0 years; Q1–Q3: 18.0 – 43.0 years), among them 87 men (64.9%) and 47 women (35.1%). All patients comprised 4 groups: osteosarcoma (n=58), undifferentiated pleomorphic sarcoma (n=5), Ewing sarcoma (n=29), chondrosarcoma (n=42). In all of them, before the start of specific antitumor treatment, the levels of endostatin, VEGF, IGF-1, and IGF-2 in the blood serum were determined using enzyme immunoassay. The follow-up period ranged from 1 to 229 months (Me=23.0 months; Q1–Q3: 10.0–121.0 months). To analyze overall survival, life tables and Kaplan–Meier curves were constructed. The effect of the studied serum markers on survival rates was assessed using the logrank test and Cox proportional hazards regression model. Results. During observation, death occurred in 51 patients (38.1%). In the group of deceased patients, serum levels of endostatin and IGF-2 were statistically significantly increased compared to the group of surviving patients (p 0.001 and p=0.011, respectively). Kaplan-Meier survival analysis using the logrank test revealed statistically significant differences in overall survival between the four groups of patients with different serum levels of endostatin, IGF-1 and IGF-2. The Cox regression method established the prognostic significance of endostatin as a predictor of overall survival (HR=1.012; p=0.013). Conclusion. Endostatin, IGF-1, IGF-2 can serve as predictors of overall survival of patients with bone sarcomas.

Effect of N-acetylcysteine in treatment of COPD with pulmonary interstitial fibrosis, inflammatory factors and VEGF levels

Purpose: To investigate the efficacy of N-acetylcysteine as an adjuvant therapy in chronic obstructive pulmonary disease (COPD) with pulmonary interstitial fibrosis (PIF), and its effect on inflammatory factors and serum vascular endothelial growth factor (VEGF) levels. Methods: A total of 94 patients with COPD-PIF from May 2020 to May 2022 in Wuhan Fourth Hospital, China were equally randomized into study and control groups. Control group was administered conventional treatment while the study group was given N-acetylcysteine in addition to conventional treatment. Therapeutic efficacy, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, blood gas, pulmonary fibrosis, and oxidative stress were evaluated. Changes in inflammatory factors, serum vascular endothelial growth factor (VEGF), and incidence of adverse drug reactions were compared. Results: The study group showed significantly higher efficacy, FEV1, FVC, FEV1/FVC compared to control group (p &lt; 0.05). Also, study group showed significantly higher partial pressure of oxygen (PaO2), blood oxygen saturation, superoxide dismutase (SOD), and glutathione (GSH) levels after treatment compared to control group (p &lt; 0.05). Platelet-derived growth factor (PDGF), transforming growth factor (TGF-β), vascular cell adhesion molecule (VCAM), tumor necrosis factor (TNF), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) levels after treatment were significantly lower in the study group than in the control group (p &lt; 0.05). Conclusion: N-acetylcysteine as an adjuvant therapy for COPD-IF is highly effective, improves lung function and oxidative stress, reduces airway inflammation, and VEGF, and attenuates the degree of hypoxia and pulmonary fibrosis with no serious adverse effects. A larger sample size, multicenter, randomized trials to validate these findings and evaluate the downstream regulatory mechanism of Nacetylcysteine in COPD-PIF.

Retraction Note: optical imaging medical diagnosis and analysis of drug treatment for endometriosis and the impact of serum VEGF and MMP-9

Retraction Note: optical imaging medical diagnosis and analysis of drug treatment for endometriosis and the impact of serum VEGF and MMP-9

Vascular Endothelial Growth Factor as a Predictor Marker of Progression in Childhood Interstitial Lung Disease

Abstract Background Childhood interstitial lung disease (chILD) encompasses a group of heterogeneous diseases characterized by varying degrees of aberrant inflammation and fibrosis of the lung parenchyma. Vascular endothelial growth factor (VEGF) is a signal protein produced by cells that stimulates the formation of blood vessels and might be implicated in the abnormal signaling in the pathogenesis of chILD. Objectives To measure the level of VEGF in serum among patients with chILD and determine its relation to the clinical severity. Patients and Methods This cross sectional study has been conducted at Pediatric Pulmonology clinic; Ain Shams University Children’s Hospital located in Cairo during the period from January 2023 to June 2023. The study included 35 children compared to 35 sex- and age-matched healthy controls. All patients were assessed in terms of demographic, clinical data and laboratory investigations including serum VGEF using enzyme-linked immunosorbent assay (ELISA) technique along with radiological findings. Results The most common clinical finding was cough (93.3%) while the most common systemic symptom was anorexia and weight loss (46.7%). Serum VGEF level was significantly elevated among chILD patients 120 (80 - 200) pg/ml compared to controls 13 (9-16) pg/ml. Moreover, serum VEGF was significantly elevated among severe cases of chILD compared to non severe ones, p-value&amp;lt;0.001. Conclusion Serum VGEF was significantly higher among chILD patients especially severe cases.

High Serum Vascular Endothelial Growth Factor (VEGF) Level Is Associated with Vascular Lesions in Glomerular Diseases

High Serum Vascular Endothelial Growth Factor (VEGF) Level Is Associated with Vascular Lesions in Glomerular Diseases