Vascular Growth Factor Research Articles

WOUND HEALING CLTI WITHOUT AMPUTATION USING TIME ORIGINAL: A CASE STUDY

Chronic limb-threatening ischemia (CLTI) is clinical syndrome defined by presence PAD in the combination rest pain, gangrene, or lower limb ulceration more than 2 weeks. Arterial ulcers as complication ischemia ulcers risk limb loss, the lesion are generally refractory to healing unless tissue perfusion can be improved prone to progress infection or gangrene. With or without surgery arterial ulcer cause of chronic limb ischemia need wound care treatment. The method is using case study, there are present female 61 years old complain necrotic right & left leg after CABG surgery 1 month ago. Glucose uncontrolled, angiography hard occlusion artery popliteal sinistra and tibialis anterior. Wound management using moist concept with TIME original Framework; tissue management with sharp and safe debridement continue using autolytic debridement using hydrogel base, infection control with iodosorb powder & nano colloidal silver spray alternate every 2 weeks, moisture imbalance using calcium alginate and hydro foam, Migration cell epithelial need the support with collagen lotion to prevent break down periwound skin. This case in wound care management necrotic tissue causes of CLTI failed healing after surgery CABG, using TIME original framework have significant result and wound healing at four months without amputation. Case of wound in critical limb-threatening ischemia need appropriate wound care management to heal the wound. Occlusion artery as problem because cannot heal the wound, but the moist condition granulate tissue will grow with helping vascular endothelium growth factor as angiogenesis process. Using moist concept TIME original framework to create and promote healing without amputation and saving feet to saving lives.
 

Sidaxue, a traditional Guizhou Miao herbal medicine formula, reduces necroptosis and synovial vascular proliferation in rats with collagen-induced arthritis by inhibiting the RIPK1/RIPK3/MLKL pathway

To explore the inhibitory effect of Sidaxue (SX), a traditional Guizhou Miao herbal medicine formula, on necrotic apoptosis and synovial angiogenesis in rats with collagen-induced arthritis (CIA) and the role of the RIPK1/RIPK3/MLKL pathway in mediating this effect. Forty-two SD rats were randomized into 6 groups (n=7), including a normal control group, a CIA model group, 3 SX treatment groups at low (10 g/kg), moderate (20 g/kg) and high (40 g/kg) doses, and a GTW treatment group. CIA rat models were established by subcutaneous injections of bovine type II collagen, and the treatments were administered daily by gavage for 21 days. The rats were observed for swelling of the hind limb joints, which was rated using the arthritis index (AI) score on a weekly basis. Serum levels of TNF-α, IL-1β and IL-17 in the rats were detected using ELISA, and the pathological changes in the synovium were observed with HE staining. Real-time PCR was performed to detect the mRNA expression levels of VEGF, MMP-9, Ang-1, RIPK1, RIPK3, and caspase-8 in the synovial tissues, and the protein expressions of VEGF, MMP9, Ang-1, Stat-3, RIPK1, RIPK3, MLKLl, p-MLKL and caspase-8 were detected using Western blotting. Compared with those in CIA model group, the rats receiving treatment with GTW and SX showed milder swelling of the hind limb joints with significantly lower AI scores (P < 0.05). In CIA model group, a large number of inflammatory cells were observed in the synovium with obvious damages of the tissue structure. In the drug treatment groups, inflammatory cell infiltration, synovial angiogenesis and synovial hyperplasia were alleviated, and the therapeutic effects were obviously enhanced as SX dose increased. Compared with those in the model group, the rats treated with GTW and high-dose SX showed significantly decreased serum levels of IL-1β, IL-17 and TNF-α (P < 0.05), lower mRNA and protein expressions of RIPK1, RIPK3, VEGF, Ang-1, and MMP9 (P < 0.05), higher expressions of caspase-8 (P < 0.01), and obviously lowered expression of Stat-3 protein and phosphorylation level of MLKL (P < 0.05). SX can improve synovial angiogenesis in CIA rats possibly by inhibiting the activation of RIP1/RIP3/MLKL signaling pathway and down-regulating the expression of the vascular growth factors VEGF, Ang-1, MMP9, and Stat-3.

Long-term clinical effects of intravitreal injections of conbercept for the treatment of choroidal neovascularization in patients with pathological myopia.

To observe the long-term clinical efficacy of intravitreal injections of conbercept, a novel vascular growth factor inhibitor, for the treatment of pathological myopia choroidal neovascularization (PM-CNV). A total of 67 eyes (from 67 patients; mean age, 54.90±12.7y) with PM-CNV were retrospectively researched. Based on the different schemes used for the administration of the drug, the patients were divided into two groups: group A (n=35; average age, 53.31±13.6y; average diopter, 9.25±1.72 D), which received only one injection of pro re nata (PRN; 1+PRN regimen), and group B (n=32; average age, 56.49±11.8y; average diopter, 9.63±2.24 D), which received one injection per month for 3mo (3+PRN regimen). Best-corrected visual acuity (BCVA) analysis, intraocular pressure (IOP) examination, slit-lamp microscopy, fundus examination and optical coherence tomography were performed at each follow-up. The recurrence and treatment times of CNV were recorded. The patients were followed up for at least 12mo. The BCVA was increased in 29 eyes (82.9%) in group A and 30 eyes (93.75%) in group B; no increase or decrease was observed in 6 (17.1%) and 2 (6.25%) eyes in groups A and B, respectively. The BCVA (logMAR) values before treatment (0.67±0.48 and 0.71±0.56) were significantly higher than those 12mo after treatment (0.31±0.26 and 0.33±0.17) in groups A and B, respectively (P<0.05). The mean central macular thickness (CMT) values had significantly decreased from 346.49±65.99 and 360.10±82.31 µm at baseline to 257.29±40.47 and 251.97±48.26 µm in groups A and B, respectively, after 12mo of treatment. A total of 21 eyes in group A needed reinjection (60%; average number of injections, 2.51±0.98); the corresponding values in group B were 6 eyes (18.75%; average number of injections, 3.74±1.22). There were no adverse ocular and systemic complications during the treatment and follow-up. Intravitreal injection of conbercept with 1+PRN or 3+PRN improve the visual acuity, reduce macular edema and reduce the level of CMT in patients with PM-CNV. The 3+PRN regimen demonstrates a lower recurrence rate of CNV than the 1+PRN regimen, but requires more treatment. However, both treatment regimens demonstrate long-term safety and efficacy for the treatment of PM-CNV.

The role of retinal Müller cells in diabetic retinopathy and related therapeutic advances.

Diabetic retinopathy (DR) is a significant complication of diabetes. During the pathogenesis of retinal microangiopathy and neuronopathy, activated retinal Müller cells (RMCs) undergo morphological and structural changes such as increased expression of glial fibrillary acidic protein, disturbance of potassium and water transport regulation, and onset of production of a large number of inflammatory and vascular growth factors as well as chemokines. Evidently, activated RMCs are necessary for the pathogenesis of DR; therefore, exploring the role of RMCs in DR may provide a new target for the treatment thereof. This article reviews the mechanism of RMCs involvement in DR and the progress in related treatments.

Impact of repeated intravenous infusions of umbilical cord-derived versus bone marrow-derived mesenchymal stem cells on angiogenesis in a pregnant experimentally induced deep venous thrombosis rat model.

Deep venous thrombosis (DVT) therapy during pregnancy warrants special consideration for the woman and the fetus. This study aimed to evaluate the impact of umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) in terms of pro-angiogenic capacity and amelioration of pregnancy outcomes. The pregnant DVT rat model was successfully established by the "stenosis" method. Three consecutive injections of both UC-MSCs and BM-MSCs improved angiogenesis and ameliorated the embryo absorption rate in pregnant SD rats with DVT, in which UC-MSCs promoted angiogenesis more significantly. Furthermore, the levels of serum vascular endothelial growth factor-A (VEGF-A) and epidermal growth factor (EGF) were significantly higher in the UC-MSC group compared to those of the BM-MSC group. Thereafter, differentially expressed genes (DEGs) in thrombosed inferior vena cava tissues in the UC-MSC and BM-MSC groups were identified using transcriptome sequencing and further assessed by RT-qPCR and western blotting. The bioinformatics analysis indicated that the enriched DEG terms occurred in the cytokine activity, and the DEG pathways were significantly enriched in the cytokine-cytokine receptor interaction. In addition, both the mRNA and protein levels of angiogenic genes and their receptors, including VEGF-A, VEGF receptor-1, EGF, and EGF receptor, were significantly higher in the UC-MSC group. In conclusion, the BM-MSCs and UC-MSCs both significantly stimulate angiogenesis and ameliorate the embryo absorption rate in pregnant SD rats with DVT, but the difference in cytokine secretion causes UC-MSCs to have more potent angiogenic effects than BM-MSCs.

Evaluation of effectiveness of cosmetic procedures in postmenopausal women

The study is devoted to the study of the content of collagen types I and III, laminin in the epidermis and dermis, insulin-like and vascular growth factors in the skin of women with a preserved menstrual cycle and women in menopause. A study was also made of the content of the same indicators after cosmetic procedures aimed at improving the quality of the skin. The degree of effectiveness of cosmetic procedures for skin regeneration was determined depending on the presence or absence of menopause.

Brain AVMs-Related microRNAs: Machine Learning Algorithm for Expression Profiles of Target Genes.

microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.

Administration of botulinum toxin a and vascular endhotelial growth factor reduce norepinephrine levels and increase viability of modified mcfarlane flap in wistar rat

Local hyperadrenergic states after a random flap elevation mediated by humoral vasoconstrictors can lead to flap necrosis. This study aimed to evaluate the effect of Botulinum Toxin A (BoNT-A) on reducing levels of Norepinephrine (NE) as the main humoral vasoactive substance, as well as its additive effect with Vascular Endothelial Growth Factor (VEGF) in increasing the viability of random flap. 28 Wistar Rats with Caudally Based Modified McFarlane Flap were divided into four groups. Group I received BoNT-A 3 days before flap elevation, group II received VEGF immediately after flap elevation, group III received a combination of BoNT-A and VEGF, group IV was a control group. Result in this study NE levels lowest was found in the BoNT-A+VEGF combination group (94.63 ± 5 .25 ng/ml, p&lt;0.05 in group I, p&lt;0.01 in groups II and IV). The highest value of FVR was shown in the BoNT-A+VEGF combination group (93.37 ± 2.19 %, p &lt; 0.05 in group I, p &lt; 0.01 in groups II and IV). Meanwhile, the increase in flap viability in the VEGF group was not statistically significant. So Conclusion administration of BoNT-A in combination with VEGF can increase the viability of random flaps by decreasing NE levels.

Abstract 14789: Vascular Growth Factors and Their Association With Arterial Stiffness in the 1986 Jamaica Birth Cohort: A Longitudinal Analysis

Introduction: Vascular growth factors (VasGFs) and increased arterial stiffness provide an early indication of structural and functional blood vessel changes that lead to cardiovascular disease. We aimed to determine if there was an association between serum levels of vascular endothelial growth factor (VEGF), epidermal growth factor (EFG), angiopoietin 1 (Angp1) and angiopoietin 2 (Angp2) with arterial stiffness in 28-30-year-old adults from a birth cohort. Methods: Participants were a subset of members of a longitudinal study of children born in Jamaica between September and October 1986. Sociodemographic and anthropometric measurements were taken at the 18-20 and 28-30 follow-up visits, while serum was collected at the 18-20 year old visit. The pulse wave velocity (Arteriograph TM ) was used to measure arterial stiffness at the 28-30-year-old visit. Analyses were limited to participants who had pulse wave velocity measurements. Multiple imputation using chained equations was done to account for missing data on the explanatory variables. Linear regression models were used to explore bivariate associations. The final multivariable model included VEGF, EGF, Angp1, Angp2, age, sex, BMI, SBP, DBP, smoking and education. Results: Analyses included 387 participants (47% male). At 18-20yrs median serum concentrations of VEGF 75.4 pg/ml; EGF 951.4 pg/ml; Angp1 67863.7 pg/ml; and Angp2 691 pg/ml. At 28-30 there were sex differences in BMI (M:25.2 vs F:28.8kg/m 2 ), SBP (M:114 vs F:108 mmHg), current smokers (M:29% vs F: 5.4%) tertiary education (M:22% vs F:39%) and arterial stiffness (M:6.4 vs F:6.8m/s). In the final multivariable model both VEGF and EGF were associated with arterial stiffness. VEGF coef (95%CI) 0.095 (0.014, 0.176) p= 0.022 and EGF -0.087 (-0.169, -0.004) p =0.039. There was no association between angp1 or angp2 and pulse wave velocity. Conclusion: VEGF concentrations at 18-20 of was positively associated with arterial stiffness at 28-30 years old, while and EGF showed inverse association. VEGF and EGF may be useful biomarkers of vascular function in young adults.

Ultrasonic Nano emulsification of Apricot Kernel Oil and Its Therapeutics Effects on Suppression of Human Lung Cancer Cells (A549)

ABSTRACT This study was conducted with the aim of synthesising nanoemulsion of apricot kernel oil (AKO-NE) and evaluating its cytotoxic, pro-apoptotic, antioxidant and anti-angiogenic effects. The AKO-NE was synthesised by ultrasound (150 watt for 2 min) using a combination of Tween 20 and 80 as surfactant and ethylene glycol as co surfactant. Antioxidant capacity (ABTS, DPPH scavenging free radicals) and toxicity of AKO-NE (MTT assay) and its effects on the process of apoptosis (Flow cytometry and qPCR for BCL-2, Caspase 3, 7, 9) were evaluated by specialised methods. Then, the effect of AKO-NE on angiogenesis was measured by CAM and qPCR (VEGF and VEGFR) methods. The AKO-NE showed acceptable antioxidant power and selective toxicity effects against lung cancer cells (162.7 µl/mL). The pro-apoptotic effects of AKO-NE were confirmed by increasing the number of SubG1 phase cells in flow cytometry and increasing the expression of Cas-3, 7 and 9 genes and decreasing the expression of BCL-2 gene in qPCR method. Decreased vascular and foetal growth factors in the CAM model as well as decreased expression of VEGF and VEGF-R genes in AKO-NE-treated cells confirmed the inhibitory effects of AKO-NE on angiogenesis. Inhibitory effects of AKO-NE on the growth and proliferation of A549 cancer cells and induction of apoptosis, as well as its effects on reducing angiogenesis, can suggest this nanoemulsion as a useful combination in cancer therapy.

Peculiarities of serum levels of vascular growth factor and its receptors in dialysis patients

Recent research has shown that VEGF may influence the condition and survival of patients with chronic kidney disease (CKD), including those treated with dialysis procedures. Identifying the value of this factor is important to uncover the mechanisms of CKD progression and improve treatment strategies.&#x0D; The present study aimed to determine the mean serum levels of vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and their correlations with pro-inflammatory cytokines (TNF-α, MCP-1, IL -6, IL -8) in dialysis patients stratified by dialysis modality and Carnivit use.&#x0D; Methods. In this prospective cohort study, serum levels of VEGF, VEGF-R, and proinflammatory cytokines were determined in 41 hemodialysis (HD) patients (group 1) and 14 peritoneal dialysis (PD) patients (group 2), 28 of whom were treated with Carnivit. The assay was performed with the enzyme immunoassay "SunRise TouchScreen" using IBL International (Germany) test systems. The limits of normal values (reference range) were determined based on the results of a study with 20 conditionally healthy individuals.&#x0D; Results. All included patients had significantly higher serum levels of VEGF compared to healthy donors (p=0.006); a significant increase in this mediator was observed in both HD and PD treated subjects (p=0.002 and p=0.007, respectively). Carnivit treatment resulted in a significant decrease (p=0.023) in this mediator to normal levels in all patients. Subgroup analysis showed a significant decrease in VEGF (p=0.016) and VEGF-R (p=0.005) in HD patients after therapy. Mean concentrations of growth factor in HD patients (p=0.098) and PD patients (p=0.160) did not differ from those of healthy subjects.&#x0D; A positive correlation was observed between serum levels of VEGF and its receptors in the studied patients both before and after treatment (p &lt; 0.0001).&#x0D; A direct correlation between IL -8 and VEGF and VEGF-R was observed in HD patients and an inverse correlation between MCP-1 and VEGF-R was observed in PD patients. After Carnivit treatment, the correlation between serum levels of IL -8 and VEGF-R (0.782, p=0.01) and between VEGF and VEGF-R (0.770, p=0.01) remained in group 1 and between VEGF and VEGF-R (0.829, p=0.03) in group 2.&#x0D; Conclusion. Increased concentrations of VEGF and its receptors were detected in the blood of dialysis patients, with a positive correlation between them and the pro-inflammatory IL -8. Treatment with Carnivit resulted in a significant decrease in cytokines with the maintenance of the balance between vascular growth factor and its receptors, which we consider a positive effect for the inhibition of inflammation with the progression of endothelial dysfunction.

Lpar1-mediated Effects in Endothelial Progenitor Cells Are Crucial for Lung Repair in Acute Respiratory Distress Syndrome/Acute Lung Injury.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) involves acute respiratory failure characterized by vascular endothelial and lung alveolar epithelial injury. Endothelial progenitor cells (EPCs) can mediate vasculogenesis. However, the limitations of EPCs, such as low survival and differentiation, are believed to inhibit the effectiveness of autologous cell therapies. This study demonstrated that lysophosphatidic acid (LPA), a bioactive small molecule without immunogenicity, is involved in the survival and antiapoptotic effects in human umbilical cord mesenchymal stem cells. This study aimed to explore whether LPA improves the survival of EPCs, enhancing the cellular therapeutic efficacy in ARDS, and these results will expand the application of LPA in stem cells and regenerative medicine. LPA promoted the colony formation, proliferation, and migration of EPCs and upregulated the expression of vascular endothelial-derived growth factor (VEGF) in EPCs. LPA pretreatment of transplanted EPCs improved the therapeutic effect by increasing EPC numbers in the rat lungs. LPA enhanced EPC proliferation and migration through Lpar1 coupled to Gi/o and Gq/11, respectively. Activation of extracellular signal-related kinase 1/2, or ERK1/2, was related to LPA-induced EPC proliferation but not migration. LPA/Lpar1-mediated Gi/o protein was also shown to be involved in promoting VEGF expression and inhibiting IL-1α expression in EPCs. Low LPA concentrations are present after lung injury; thus, the restoration of LPA may promote endothelial cell homeostasis and lung repair in ARDS. Inhalation of LPA significantly promoted the homing of endogenous EPCs to the lung and reduced lung injury in both rats with LPS-induced ALI and Streptococcus pneumoniae-infected mice. Taken together, these data indicated that LPA/Lpar1-mediated effects in EPCs are involved in maintaining endothelial cell homeostasis and lung tissue repair under physiological conditions.

Molecular mechanism of VEGF and its role in pathological angiogenesis.

Over the last seven decades, a significant scientific contribution took place in the delineation of the implications of vascular endothelial-derived growth factor (VEGF) in the processes of angiogenesis. Under pathological conditions, mainly in response to hypoxia or ischemia, elevated VEGF levels promote vascular damage and the growth of abnormal blood vessels. Indeed, the development of VEGF biology has revolutionized our understanding of its role in pathological conditions. Hence, targeting VEGF or VEGF-mediated molecular pathways could be an excellent therapeutic strategy for managing cancers and intraocular neovascular disorders. Although anti-VEGF therapies, such as monoclonal antibodiesand small-molecule tyrosine kinase inhibitors, have limited clinical efficacy, they can still significantly improve the overall survival rate. This thus demands further investigation through the development of alternative strategies in the management of VEGF-mediated pathological angiogenesis. This review article focuses on the recent developments towardthe delineation of the functional biology of VEGF and the role of anti-VEGF strategies in the management of tumor and eye pathologies. Moreover, therapeutic angiogenesis, an exciting frontier for the treatment of ischemic disorders, is highlighted in this review, including wound healing.

Horticultural Therapy for Improving the Work Performance and Interpersonal Relationships of Persons with Intellectual Disabilities.

For the occupational adaptation and social integration of the intellectually disabled, it is helpful to improve their work performance and interpersonal skills. The purpose of the study was to evaluate the effectiveness of horticultural therapy (HT) programs to improve work performance and interpersonal relationships of persons with intellectual disabilities. Based on observations and analyses of how people with intellectual disabilities work, we have developed a 12-session HT program that includes upper limb movements and physical activities to improve hand function. We recruited, with the consent of their legal guardians, 14 (6 males, 8 females) participants who had intellectual disabilities and were working at a sheltered workshop in K-gu, Seoul, South Korea. The program consisted of twelve sixty-minute sessions that were conducted twice a week at a rooftop garden. For pre- and post-evaluation of the program, the survey of functional adaptive behavior (SFAB), interpersonal negotiation strategies, a horticultural job evaluation (self), hand function tests (pegboard, pinch gauge, fingertips), and blood sample tests for physiological indicators of exercise were conducted. Interpersonal negotiation strategies, functional adaptive behaviors, and physical abilities for job behaviors, including agility and grasping of the hand, improved significantly from before to after the program (p < 0.05). A positive result of VEGF (vascular endothermic growth factor) in blood sample tests implies the need for further research on cognitive changes caused by horticultural activities. This study has limitations due to the small number of participants, but the results suggest that low- to medium-intensity horticultural treatment programs using the upper body and hands could be effective for vocational rehabilitation of the intellectually disabled.

Luteinizing hormone receptor promotes angiogenesis in ovarian endothelial cells of Macaca fascicularis and Homo sapiens†.

Angiogenesis within the ovarian follicle is an important component of ovulation. New capillary growth is initiated by the ovulatory surge of luteinizing hormone (LH), and angiogenesis is well underway at the time of follicle rupture. LH-stimulated follicular production of vascular growth factors has been shown to promote new capillary formation in the ovulatory follicle. The possibility that LH acts directly on ovarian endothelial cells to promote ovulatory angiogenesis has not been addressed. For these studies, ovaries containing ovulatory follicles were obtained from cynomolgus macaques and used for histological examination of ovarian vascular endothelial cells, and monkey ovarian microvascular endothelial cells (mOMECs) were enriched from ovulatory follicles for in vitro studies. mOMECs expressed LHCGR mRNA and protein, and immunostaining confirmed LHCGR protein in endothelial cells of ovulatory follicles in vivo. Human chorionic gonadotropin (hCG), a ligand for LHCGR, increased mOMEC proliferation, migration and capillary-like sprout formation in vitro. Treatment of mOMECs with hCG increased cAMP, a common intracellular signal generated by LHCGR activation. The cAMP analog dibutyryl cAMP increased mOMEC proliferation in the absence of hCG. Both the protein kinase A (PKA) inhibitor H89 and the phospholipase C (PLC) inhibitor U73122 blocked hCG-stimulated mOMEC proliferation, suggesting that multiple G-proteins may mediate LHCGR action. Human ovarian microvascular endothelial cells (hOMECs) enriched from ovarian aspirates obtained from healthy oocyte donors also expressed LHCGR. hOMECs also migrated and proliferated in response to hCG. Overall, these findings indicate that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle.

Research progress on infiltrating zone and microvascular invasion of hepatic alveolar echinococcosis

Hepatic alveolar echinococcosis (AE) is a parasitic disease with biological characteristics similar to malignant tumor. It has no obvious clinical symptoms in the early stage. Most patients have complications such as jaundice, ascites and gastrointestinal bleeding when they see a doctor. At this time, the course of disease is at an advanced stage. In addition, the incomplete resection of the AE lesion(s) leads to a high postoperative recurrence rate, which has a serious impact on the physical and mental health of patients. Based on the summary of the latest research at home and abroad and the analysis of blood supply, microvascular invasion and vascular growth factor expression in the "infiltrating zone" adjacent to the lesions of hepatic AE, this article has a deep understanding of the occurrence and development process of hepatic AE, aiming to better guide clinical practice and improve the quality of life of patients.

Targeting angiopoietin-2 as a novel treatment option for kidney fibrosis

Kidney fibrosis is a hallmark of chronic kidney disease yet is poorly treated. Chang etal. determined that plasma and kidney levels of the vascular growth factor, angiopoietin-2, were elevated in patients with chronic kidney disease and mice with kidney disease. Angiopoietin-2 inhibited the renoprotective effects of angiopoietin-1 and promoted CC chemokine ligand 2-mediated kidney damage, endothelial cell apoptosis, vascular rarefaction, inflammation, fibrosis, and kidney dysfunction. Hence, therapeutically inhibiting angiopoietin-2 may represent a novel means of treating these chronic kidney disease-associated pathologies.

Management of Immune-Related Adverse Events from Immune-Checkpoint Inhibitors in Advanced or Metastatic Renal Cell Carcinoma.

Simple SummaryToday, most patients with metastatic renal cancer receive systemic treatment with so-called immune-checkpoint inhibitors that shall activate a patient’s immune system. For patients without prior therapy, these therapeutic agents are combined with a second immunotherapeutic drug or with a therapeutic agent intended to reduce the tumour’s blood supply, namely tyrosine kinase inhibitors directed against the vascular endothelial growth factor receptor (VEGFR-TKI). Both parts of the combination therapy cause side effects that need to be treated and handled differently depending on the therapeutic agent responsible for the complaints. Therefore, it is of crucial importance to recognize the side effects and relate them to the right therapeutic agent. Within this review we describe the most frequent immune-related side effects of immune-checkpoint inhibitors, especially focusing on their distinction from side effects caused by VEGFR-TKI. Additionally, we explain the management of these complaints as well as their impact on the therapy.Immune checkpoint inhibitors (ICI) are now, among other cancers, routinely used for the treatment of advanced or metastatic renal cell carcinoma (mRCC). In mRCC various combinations of ICIs and inhibitors of the vascular epidermal growth factor receptor tyrosine kinase (VEGFR-TKIs) as well as dual checkpoint inhibition (nivolumab + ipilimumab), the latter for patients with intermediate and poor risk according to IMDC only (international metastatic renal cell carcinoma database consortium), are now standard of care in the first line setting. Therefore, a profound understanding of immune-related adverse events (irAE) and the differential diagnosis of adverse reactions caused by other therapeutic agents in combination therapies is of paramount importance. Here we describe prevention, early diagnosis and clinical management of the most relevant irAE derived from ICI treatment focusing on the new VEGFR-TKI/ICI combinations.

Combination Treatment of TRPV4 Agonist with Cisplatin Promotes Vessel Normalization in an Animal Model of Oral Squamous Cell Carcinoma.

Background and Objectives: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4′s involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. Materials and Methods: Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT2 Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. Results: RT2 profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; p < 0.05) and Tie-2 (4.5-fold change; p < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (p < 0.01) and significantly increased the percentage of microvessels covered with pericytes (p < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (p < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. Conclusions: The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway.

EP16.03-045 The Effect of Vascular Endothelial Growth Factor Gene Polymorphisms in the Clinical Outcome of Patients with Lung Cancer

Lung cancer is the most common cancer in terms of incidence and mortality, worldwide. Indeed, multiple genetic and epigenetic alterations contribute to carcinogenesis and disease progression. Thus, understanding the molecular bases of carcinogenesis has contributed not only to the development of personalized therapy but also to angiogenesis inhibitors targeting vascular endothelium growth factor (VEGF), a key mediator of tumor angiogenesis. It has been proven that different polymorphisms in the VEGF gene result in a different expression of the VEGF protein in cancer cells, thus affecting the disease prognosis.