Positive Expression Of Vascular Endothelial Growth Factor Research Articles

Synergistic effects of electroacupuncture and bone marrow mesenchymal stem cell transplantation on rat intrauterine adhesion： an observation.

To investigate the effects of electroacupuncture(EA) combined with bone marrow mesen-chymal stem cells(BMSCs) transplantation on the endometrium of rats with intrauterine adhesions(IUA), so as to explore the possible mechanisms underlying their combined therapeutic effects. Forty adult female SD rats were randomly divided into control, model, cell, and combined groups. The IUA rat model was established using a dual injury method of mechanical scratching and lipopolysaccharide infection. After successful modeling, on days 1, 3, and 7, rats in the model group received tail vein injection of phosphate buffered solution, while rats in the cell group received tail vein injection of BMSCs suspension for BMSCs transplantation；and rats in the combined group received BMSCs transplantation combined with EA treatment (2 Hz/15 Hz, 1-2 mA), targeting the "Guanyuan"(CV4), bilateral "Zusanli"(ST36) and "Sanyinjiao"(SP6) for 20 min daily for 3 consecutive estrous cycles. After intervention, uterine tissue was collected from 5 rats in each group. Histological analysis was performed using hematoxylin and eosin staining to evaluate endometrial thickness and glandular number. Masson staining was used to assess endometrial fibrosis area. Immunohistochemistry was performed to detect the positive expressions of vascular endothelial growth factor(VEGF), proliferating cell nuclear antigen(PCNA), and estrogen receptor(ER). Western blot analysis was conducted to determine the protein expressions of homeobox A10(HoxA10) and leukemia inhibitory factor(LIF), both key regulators of endometrial receptivity. The remaining 5 rats in each group were co-housed with male rats, and the uterine function recovery was evaluated by assessing the number of embryo implantations. Compared with the control group, the model group showed thinning endometrium(P<0.001), decreased glandular number(P<0.001), increased endometrial fibrosis area(P<0.001), reduced positive expressions of VEGF, PCNA, ER, expressions of HoxA10 and LIF, and decreased embryo implantation number (P<0.001) on the injured side of the uterus. Compared with the model group, the combined group showed a reversal of the aforementioned indicators(P<0.001, P<0.01)；the cell group exhibited thicker endometrium(P<0.001) and reduced endometrial fibrosis area(P<0.001). Compared with the cell group, the combined group showed increased endometrial thickness(P<0.01), elevated glandular number(P<0.05), significantly decreased endometrial fibrosis area(P<0.05), enhanced positive expressions of VEGF, PCNA and ER, expressions of HoxA10 and LIF in the endometrium, and a significant increase in embryo implantation number (P<0.001, P<0.05, P<0.01) on the injured side of the uterus, indicating better results than the cell group. The combination of EA and BMSCs synergistically promotes the repair of damaged endometrium, improves endometrial morphology, reduces fibrosis levels, enhances vascular regeneration and matrix cell proliferation, improves endometrial receptivity, which ultimately facilitates embryo implantation.

Reconstruction of foot and ankle defects using the vaccum sealing drainage versus the induced-membrane the elderly: A retrospective comparative study.

The purpose of this study was to compare the reconstructive outcomes of soft-tissue defects around foot and ankle with vaccum sealing drainage (VSD) or induction membrane (IM) of cement formation and attempt to provide an optimal strategy for elderly patients. A retrospective review of all continuous patients with foot and ankle reconstruction using different flaps from October of 2016 and October of 2020 was performed. Based on the different way, the patients were divided into two groups: VSD group (n = 26) and IM group (n = 27). Outcomes were assessed according to the size of the defect, frequency of debridement procedures, hospitalization time, duration of healing, the healing rate, major amputation rate, functional outcomes and complications. Immunohistochemistry (IHC) detection of vascular endothelial growth factor (VEGF) was also be completed. We found that there was no difference in demographic characteristics, size of the defect, debridement times and functional outcomes between the two groups (p > 0.05); however, a significant difference in the wound healing time, hospitalization time and complications were noted between them(p < 0.05). The fresh granulation tissue of both groups showed abundant positive expression of VEGF. Thus, the VSD and IM are both available for foot and ankle reconstruction in elderly patients. However, the IM group offers short hospitalization time, duration of healing and lower frequency of postoperative complications. Thus, we advocate the IM for reconstruction of defects of the foot and ankle region in the elderly patients.

Radiogenomic Analysis of Vascular Endothelial Growth Factor in Patients With Glioblastoma.

This article aims to predict the presence of vascular endothelial growth factor (VEGF) expression and to predict the expression level of VEGF by machine learning based on preoperative magnetic resonance imaging (MRI) of glioblastoma (GBM). We analyzed the axial T2-weighted images (T2WI) and T1-weighted contrast-enhancement images of preoperative MRI in 217 patients with pathologically diagnosed GBM. Patients were divided into negative and positive VEGF groups, with the latter group further subdivided into low and high expression. The machine learning models were established with the maximum relevance and minimum redundancy algorithm and the extreme gradient boosting classifier. The area under the receiver operating curve (AUC) and accuracy were calculated for the training and validation sets. Positive VEGF in GBM was 63.1% (137/217), with a high expression ratio of 53.3% (73/137). To predict the positive and negative VEGF expression, 7 radiomic features were selected, with 3 features from T1CE and 4 from T2WI. The accuracy and AUC were 0.83 and 0.81, respectively, in the training set and were 0.73 and 0.74, respectively, in the validation set. To predict high and low levels, 7 radiomic features were selected, with 2 from T1CE, 1 from T2WI, and 4 from the data combinations of T1CE and T2WI. The accuracy and AUC were 0.88 and 0.88, respectively, in the training set and were 0.72 and 0.72, respectively, in the validation set. The VEGF expression status in GBM can be predicted using a machine learning model. Radiomic features resulting from data combinations of different MRI sequences could be helpful.

Study of the mechanism of Shexiang Baoxin pill-mediated angiogenesis in acute myocardial infarction.

The Shexiang Baoxin pill (SBP) is a commonly used drug for the treatment of coronary artery disease in China. More recently, some studies have found that it improved coronary microvascular function. This study aimed to explore the possible mechanism by which the SBP promotes angiogenesis after acute myocardial infarction (AMI). A rabbit model of acute myocardial infarction was established by ligating the left anterior descending coronary artery with silk thread, and the limb lead electrocardiogram was recorded to determine the success of the model. The rabbits were divided into a control group (SBP + normal rabbit group), a sham operation group, a saline + AMI group and an SBP + AMI group. There were 10 rabbits in each group. The animals were sacrificed and myocardial tissue was collected seven days after the operation. Haematoxylin-eosin staining was used to observe the histological changes in the rabbit myocardium in each group. The degree of acute myocardial infarction was observed with picric acid staining, which was used to detect the expression of vascular endothelial growth factor (VEGF), silent information regulator 1 (SIRT1), Beclin1 and mTOR protein in the myocardial tissue of each group. Immunofluorescence CD31-labelled microvascular density (MVD) was used to observe the vascular regeneration of the rabbits in each group. Compared with the normal saline + AMI group, the myocardial infarction area of the SBP + AMI group decreased and CD31 immunofluorescence-labelled MVD increased. Compared with the control and sham operation groups, the expression of VEGF, Beclin1 and mTOR in the normal saline + AMI group and the SBP + AMI group increased, while the expression of SIRT1 decreased. Compared with the normal saline + AMI group and the SBP + AMI group, the positive expression of VEGF, Beclin1, mTOR and SIRT1 in the SBP + AMI group was significantly increased. Autophagy was enhanced after acute myocardial infarction. SBP may affect angiogenesis through the SIRT1/mTOR signalling pathway after acute myocardial infarction to inhibit ventricular remodelling and a decline in cardiac function.

Blaps rynchopetera affects proliferation, migration, and invasion of non-small cell lung cancer: a study based on network pharmacology and in vivo and in vitro experiments

Network pharmacology, molecular docking, and in vivo and in vitro experiments were employed to study the molecular mechanism of Blaps rynchopetera Fairmaire in the treatment of non-small cell lung cancer(NSCLC). The components of B. rynchopetera were collected by literature review, and the active components were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). PharmMapper was used to obtain the targets of the active components. The targets of NSCLC were obtained from DrugBank, GeneCards, OMIM, TTD, and PharmGKB. The Venn diagram was drawn to identify the common targets shared by the active components of B. rynchopetera and NSCLC. The &quot;drug component-target&quot; network and protein-protein interaction(PPI) network were constructed by Cytoscape, and the key targets were screened by Centiscape. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the above key targets were performed by DAVID. AutoDock and PyMOL were used for the molecular docking between the key targets and corresponding active components. A total of 31 active components, 72 potential targets, and 11 key targets of B. rynchopetera against NSCLC were obtained. The active components of B. rynchopetera had good binding activity with key targets. Further, the serum containing B. rynchopetera was prepared and used to culture human lung adenocarcinoma A549 cells. The CCK-8 assay was employed to determine the inhibition rates on the growth of A549 cells in blank control group and those exposed to different concentrations of B. rynchopetera-containing serum, cisplatin, and drug combination(B. rynchopetera-containing serum+cisplatin) for different time periods. The cell migration and invasion of A549 cells were detected by cell scratch assay and Transwell assay, respectively. Western blot was employed to determine the expression levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X(Bax), caspase-3, cell division cycle 42(CDC42), proto-oncogene tyrosine-protein kinase SRC, and vascular endothelial growth factor(VEGF) in A549 cells. C57BL/6 mice were inoculated with Lewis cells and randomly assigned into a model control group, a B. rynchopetera group, a cisplatin group, and a drug combination(B. rynchopetera+cisplatin) group, with 12 mice per group. The body weight and the long diameter(a) and short diameter(b) of the tumor were monitored every other day during treatment, and the tumor volume(mm~3) was calculated as 0.52ab~2. After 14 days of continuous medication, the mice were sacrificed for the collection of tumor, spleen, and thymus, and the tumor inhibition rate and immune organ indexes were calculated. The tissue morphology of tumors was observed by hematoxylin-eosin(HE) staining, and the positive expression of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF in the tumor tissue was detected by immunohistochemistry. The results indicated that B. rynchopetera and the drug combination regulated the expression levels of Bax, Bcl-2, caspase-3, CDC42, SRC, and VEGF to inhibit the proliferation, migration, and invasion of A549 cells and Lewis cells, thus playing a role in the treatment of NSCLC via multiple ways.

Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material &amp; Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Correlation of Diffusion Tensor Imaging Parameters with the Pathological Grade of Brain Glioma and Expression of Vascular Endothelial Growth Factor and Ki-67

Background: Most brain gliomas are high-grade and likely to spread locally. Consequently, these patients commonly have a poor prognosis. Accurate identification of the malignancy grade of brain glioma before treatment is of great clinical significance. Objectives: This study aimed to explore the correlation of diffusion tensor imaging (DTI) parameters, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) with the pathological grade of brain glioma and expression of vascular endothelial growth factor (VEGF) and Ki-67. Patients and Methods: A total of 116 patients were selected for this study from January 2018 to December 2019. All the participants underwent magnetic resonance imaging (MRI) and DTI before surgery, and the FA and ADC values were measured for the regions of interest. Surgically resected tumor specimens were collected for immunohistochemical assay. Finally, the FA and ADC values and positive expression rates of VEGF and Ki-67 were compared. Results: A significantly higher FA, besides the positive expression of VEGF and Ki-67, was reported in the high-grade group, whereas a lower ADC was found in this group compared to the low-grade group (P &lt; 0.05). Areas of normal white matter and peritumoral edema had higher FA values, whereas lower ADCs were measured in these areas compared to the cerebrospinal fluid (P &lt; 0.05). The FA of tumor parenchymal area was positively correlated with the World Health Organization (WHO) class of tumors (r = 0.588, P = 0.028), and the expression of VEGF and Ki-67 was positively correlated with the WHO grade (r = 0.843, P = 0.002 and r = 0.743, P = 0.006, respectively). The FA of tumor parenchymal area was positively correlated with the expression of VEGF and Ki-67 (r = 0.654, P = 0.008 and r = 0.567, P = 0.012, respectively). However, the ADC of tumor parenchymal area was not significantly correlated with the WHO grade, VEGF expression, or Ki-67 expression (r = 0.143, P = 0.156, r = 0.232, P = 0.116, and r = 0.054, P = 0.179, respectively). Conclusion: The FA value, as a DTI parameter, is valuable for assessing the malignancy grade of tumor cells and can provide a proper reference for formulating treatment regimens for brain gliomas.

Effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats

Objective: To explore the effect of P311 microspheres-loaded thermosensitive chitosan hydrogel on the wound healing of full-thickness skin defects in rats. Methods: The method of experimental study was adopted. The polyvinyl alcohol/sodium alginate microspheres (simple microspheres), P311 microspheres, and bovine serum albumin labeled with fluorescein isothiocyanate (FITC-BSA) microspheres were prepared by water-in-oil emulsification, and then their morphology was observed under a light microscope/inverted fluorescence microscope. Chitosan solution was prepared, chitosan solution and β-glycerol phosphate disodium hydrate were mixed to prepare simple thermosensitive hydrogels, and thermosensitive hydrogels loaded with simple microspheres or P311 microspheres were prepared by adding corresponding substances in simple thermosensitive hydrogels. The morphological changes of the prepared four liquids in the state of tilt was observed at 37 ℃. After being freeze-dried, the micromorphology of the prepared four liquids was observed under a scanning electron microscope. Eighteen 3-4-week-old male Sprague-Dawley rats were divided into normal group without any treatment, dressing group, chitosan group, hydrogel alone group, simple microspheres-loaded hydrogel group, and P311 microspheres-loaded hydrogel group, which were inflicted with one full-thickness skin defect wound on both sides of the back spine and were dealt correspondingly, with 3 rats in each group. Rats with full-thickness skin defects in the five groups were collected, the wound healing was observed on post injury day (PID) 0 (immediately), 5, 10, and 15, and the wound healing rates on PID 5, 10, and 15 were calculated. The wound and wound margin tissue of rats with full-thickness skin defects in the five groups on PID 15 and normal skin tissue in the same site of rats in normal group were collected, hematoxylin and eosin staining was conducted to observe the histological changes, immunohistochemical staining was performed to observe the expressions of CD31 and vascular endothelial growth factor (VEGF), and Western blotting was conducted to detect the protein expressions of CD31 and VEGF. The number of samples was all three. Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, and Bonferroni correction. Results: Simple microspheres were spherical, with loose and porous surface. The surfaces of P311 microspheres and FITC-BSA microspheres were smooth without pores, and the FITC-BSA microspheres emitted uniform green fluorescence. The diameters of the three microspheres were basically consistent, being 33.1 to 37.7 μm. Compared with chitosan solution and simple thermosensitive hydrogel, the structures of the two microspheres-loaded hydrogels were more stable in the state of tilt at 37 ℃. The two microspheres-loaded hydrogels had denser network structures than those of chitosan solution and simple thermosensitive hydrogel, and in the cross section of which microspheres with a diameter of about 30 μm could be seen. Within PID 15, the wounds of rats in the five groups were healed to different degrees, and the wound healing of rats in P311 microspheres-loaded hydrogel group was the best. On PID 5, 10, and 15, the wound healing rates of rats in dressing group and chitosan group were (26.6±2.4)%, (38.5±3.1)%, (50.9±1.5)%, (47.6±2.0)%, (58.5±3.6)%, and (66.7±4.1)%, respectively, which were significantly lower than (59.3±4.8)%, (87.6±3.2)%, (97.2±1.0)% in P311 microspheres-loaded hydrogel group (P<0.05 or P<0.01). The wound healing rates of rats in hydrogel alone group on PID 10 and 15, and in simple microspheres-loaded hydrogel group on PID 15 were (76.0±3.3)%, (84.5±3.6)%, and (88.0±2.6)%, respectively, which were significantly lower than those in P311 microspheres-loaded hydrogel group (P<0.05). The epidermis, hair follicles, and sebaceous glands could be seen in the normal skin of rats in normal group, without positive expressions of CD31 or VEGF. The wounds of rats in P311 microspheres-loaded hydrogel group on PID 15 were almost completely epithelialized, with more blood vessels, hair follicles, sebaceous glands, and positive expressions of CD31 and VEGF in the wounds than those of rats with full-thickness skin defects in the other four groups, and more protein expressions of CD31 and VEGF than those of rats in the other five groups. Conclusions: The P311 microspheres-loaded thermosensitive chitosan hydrogel can release the encapsulated drug slowly, prolong the drug action time, and promote wound healing in rats with full-thickness skin defects by promoting wound angiogenesis and re-epithelialization.

The Correlation Between CD44 and Angiogenesis in Oral Squamous Cell Carcinoma Induced in Buccal Pouch in Syrian Hamster that Underwent Radiotherapy.

Angiogenesis with radiotherapy is a significant focus of recent studies to confirm the importance of combined treatments, as vascular control can have a great therapeutic target. Vascular endothelial growth factor is the key mediator of angiogenesis in cancer. In addition, some studies suggest the value of CD44 as a potential early marker of angiogenesis. Investigating the expression of vascular endothelial growth factor (VEGF) and CD44 in oral squamous cell carcinoma (OSCC) after inducing it in hamsters then undergoing radiotherapy and comparing outcomes before and after therapy to verify changes of these markers. an experimental study consisted of 18 samples of OSCC which induced in right buccal pouch of hamsters (group1) and 18 samples of OSCC which induced in the same way and were exposed to radiation therapy (group2), Biopsies were taken and fixed with formalin, paraffin waxed in conventional H&E and immunostained with monoclonal anti-VEGF and anti-CD44. our findings didn't reveal a statistically significant difference in the expression of VEGF(p =0.342) and CD44 (p=0.187) between group1 & group 2. moreover, we found tumor cells which weren't affected and resistant to radiotherapy, also revealed positive expression of VEGF & CD44, otherwise, we noticed Pearson coefficient was a significant correlation that indicated to a moderate relation. cancerous cells that showed a high expression of these markers, give elevated radiosensitivity and resist the treatment. Subsequently, we assure the importance of applying anti-VEGF and/or anti-CD44 as a supportive therapy with radiation therapy.

Therapeutic effect of amniotic membrane-fibrin sealant cement on severe ocular surface alkali burn in rabbits

Objective To prepare a biologically active amniotic membrane powder and explore its preservation conditions, and to evaluate the efficacy of the amniotic membrane (AM)-fibrin sealant (FS) cement made from the amniotic powder on the rabbit severe ocular surface alkali burn model. Methods Experimental research. Fresh AM was air-dried, cooled with liquid nitrogen, ground into amniotic powder and sterilized by radiation. The expression of transformed growth factor, nerve growth factor receptor (NGFR), hepatocyte growth factor (HGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) after preparation and 10, 20 and 30 days after storage at room temperature, 4 ℃ and -20 ℃ was tested and compared with that in the fresh AM. The AM-FS cement containing different concentrations of amniotic powder and no amniotic powder was diluted. Rabbit corneal epithelial cells were cultured for 72 hours. The effects of different concentrations of amniotic powder on epithelial cell growth were observed by light microscopy, and the amniotic powder concentration with the largest absorbance value at 450 nm was selected for subsequent animal experiments. Thirty-two right eyes of 32 rabbits as the severe ocular surface alkali burn model were divided using the random counting method into the AM-FS cement group, fresh AM transplantation group, FS group and antibiotic control group (8 rabbits each group) and given different interventions. After weekly observation of corneal repair, hematoxylin and eosin staining, immunohistochemical staining of monocyte chemotaxis protein 1 (MCP-1)and vascular endothelial growth factor (VEGF) were performed and detected by light microscopy at 28 days. The logFC values of the growth factor or receptor expression difference ratio were corrected by BH; the data were analyzed by t-test and analysis of variance. Results: The expression of TGF in the amniotic membrane powder compared with the fresh amniotic membrane group (logFC=-0.11), and the expression of NGFR (HGF, EGF, bFGF) was higher than that of the fresh amniotic membrane group (logFC=-2.07, 0.72, 0.46, 2.62; P<0.05); the expression of HGF, bFGF and EGF in amniotic membrane powder stored for 10 days and 20 days were no lower than fresh amniotic membrane; at 30 days, the expression of growth factors or receptors except HGF and bFGF were decreased, and HGF, bFGF and EGF were no less than 4 ℃ and -20 ℃.The maximum A value was obtained for 0.25 mg/ml of the amniotic membrane powder after 72 hours of the CEC culture 0.98±0.05. The corneal recovery was better in the AM-FS and fresh amniotic membrane transplant groups, with corneal turbidity scores of 3.75±0.46 and 3.50±0.46, respectively, on 28 days, lower than antibiotics (4.29±0.45) (t=2.480, 3.629; P=0.019, 0.001). The corneal neovascular area in the antibiotic control group was compared with the other three groups (t=4.040, 4.339, 2.820; all P<0.001); the corneal neovascular area in the AM-FS group was (9.88±0.20) and (18.96±0.18) mm2 at 7 and 28 days. The corneal neovascularization area at 7 and 28 days in the fresh AM group [(9.54±0.22) and (18.08±0.96) mm2] was smaller than the AM-FS group (t=3.085, 3.017, P=0.005, 0.005). Despite the tiny statistical difference (0.34, 0.88), there was no clinical difference. Hematoxylin and eosin staining showed corneal structures were intact in the AM-FS and fresh AM groups, the epithelial arrangement became normal, and the corneal healing was superior to the FS and antibiotic control groups. Immunohistochemistry showed that the positive expression of VEGF in the fresh AM group was weaker than that in the remaining three groups. MCP-1 was expressed to a similar extent in the AM-FS and fresh AM groups. Conclusions: The active cytokine had high expression and stable properties at room temperature. The AM-FS cement containing 0.25 mg/ml amniotic powder can promote the repair of corneal epithelium, reduce inflammatory reaction and corneal neovascularization after alkali burning in rabbit eyes.

The Correlation of VEGF Expression with Grade of Differentiation and Lymphovascular Invasion in Bladder Infiltrating Urothelial Carcinoma

Background&#x0D; Urothelial carcinoma is the most common malignancy in the bladder with an incidence up to 95% and 70-85% of them are bladder infiltrating urothelial carcinoma. To improve the management of bladder urothelial carcinoma, prognostic factors are required. One such factor is angiogenesis, which affects growth, development and metastasis. Vascular endothelial growth factor (VEGF) is the main pro-angiogenic factor to control angiogenesis. Expression of VEGF is correlated with progression of bladder infiltrating urothelial carcinoma, such as grade and lymphovascular invasion. The aim of this study was to determine the correlation of VEGF expression with grade of differentiation and lymphovascular invasion in bladder infiltrating urothelial carcinoma.&#x0D; Methods&#x0D; This research was a retrospective observational cross sectional study with 48 cases of bladder infiltrating urothelial carcinoma in four Anatomical Pathology Laboratory in West Sumatera 2018 and 2019. Samples were reevaluated of HE slide for grade of differentiation and lymphovascular invasion. VEGF expressions in tumor cell s were analyzed using immunohistochemistry staining. Bivariate statistical analysis used Fisher's Exact test and value p&lt;0.05 was considered significant.&#x0D; Results&#x0D; Bladder infiltrating urothelial carcinoma high grade had more positive VEGF expression (91.7%), while low grade had more negative VEGF expression (58.3%). Lymphovascular invasion positive was mostly found with positive VEGF expression (75%). Statistical analysis showed significant correlation between VEGF expression with grade of differentiation (p=0.001) and lymphovascular invasion (p=0.004).&#x0D; Conclusion&#x0D; The conclusion was VEGF expression had significant correlation with grade of differentiation and lymphovascular invasion of bladder infiltrating urothelial carcinoma.&#x0D;

The relationship of vascular endothelial growth factor and osteopontin expression with 3-year progression-free survival of locally advanced nasopharyngeal cancer patients treated with platinum-based chemoradiation.

The incidence of nasopharyngeal cancer (NPC) is high, with new cases accounting for 5.2% of all malignancies in Indonesia. Most cases are detected at an advanced stage, and recurrences are common. Vascular endothelial growth factor (VEGF) and osteopontin (OPN) are important markers in tumorigenesis that serve as prognostic predictors. This study aims to determine the correlation of VEGF and OPN expression with 3-year progression-free survival (PFS). This retrospective cohort study analyzed 155 patients with locally advanced NPC. Data were obtained from medical records between 2015 and 2017. The locally advanced sample of this disease that met the inclusion criteria was stained with H&E before being prepared in a paraffin block. Furthermore, the immunohistochemistry staining results for VEGF and OPN were observed with ImageJ 1.50i and calculated semi-quantitatively using the histoscore. The 3-year PFS obtained was 39%, with a median of 23 months. Vascular endothelial growth factor expression was detected in 113 of 155 samples (72.9%), while positive OPN expression was discovered in 99 of 155 samples (63.8%). There was a correlation between VEGF (p = 0.747) and OPN expression (p = 0.584) and 3-year PFS. Positive VEGF and OPN expression in the subgroup of patients with stage IVB and N3 tumors was related to improved 3-year PFS (p < 0.05). This was similar to the positive VEGF expression in the subgroup of patients receiving neoadjuvant chemotherapy (p < 0.05). Vascular endothelial growth factor and OPN remained potential prognostic predictors in NPC. Patients with positive VEGF and OPN expression in N3, IVB, and neoadjuvant treatment had significantly improved 3-year PFS.

Study on osteogenesis and angiogenesis of Pluronic F-127 composite gel loaded with transforming growth factor β 3 and bone marrow mesenchymal stem cells in rabbit maxillary sinus lift

To prepare Pluronic F-127 composite gel loaded with transforming growth factor β 3 (TGF-β 3) and bone marrow mesenchymal stem cells (BMSCs) and observe its osteogenesis and angiogenesis effects in vivo and in vitro. BMSCs were isolated from the tibial and femoral bone marrow of New Zealand white rabbits and passaged, and the 3rd generation cells were used for subsequent experiments after identification of osteogenic and adipogenic induction. Pluronic F-127 powder and TGF-β 3 were dissolved in L-DMEM medium to prepare Pluronic F-127 gel, TGF-β 3+Pluronic F-127 gel, BMSCs+Pluronic F-127 gel, and TGF-β 3+BMSCs+Pluronic F-127 gel. The 3rd generation of BMSCs were cultured with L-DMEM medium (group A), osteogenic induction medium (group B), osteogenic induction medium containing Pluronic F-127 gel (group C), and osteogenic induction medium containing TGF-β 3+Pluronic F-127 gel (group D), respectively. After 14 days of culturing, alkaline phosphatase (ALP) staining and Alizarin red staining were used to observe the osteogenesis. In addition, the BMSCs were cultured with L-DMEM medium containing Pluronic F-127 gel (experimental group) and L-DMEM medium (control group) for 1, 2, 3, and 4 days, respectively. And the cell proliferation was detected by MTT assay. Ten New Zealand white rabbits were taken to prepare the maxillary sinus lift models, and Pluronic F-127 gel (group A), TGF-β 3+Pluronic F-127 gel (group B), BMSCs+Pluronic F-127 gel (group C), and TGF-β 3+BMSCs+Pluronic F-127 gel (group D) were injected into the bone defects, respectively. On the 8th week, imaging examination and HE staining were used to observe the formation of new bone, immunohistochemical staining was used to observe the expression of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2) in bone tissue, and Western blot was used to detect the relative expressions of VEGF, oncostatin M (OSM), and BMP-4 proteins in bone tissue. Osteogenic and adipogenic induction identified the isolated and cultured cells as BMSCs. In vitro staining showed that ALP activity and Alizarin red concentration in group D were significantly higher than those in other groups ( P<0.05). MTT assay showed that the absorbency ( A) value of the two groups increased gradually, and there was no significant difference between the groups at each time point ( P>0.05). In vivo experimental imaging examination showed that the bone mineral density and osteogenic continuity of group D were the best, and the proportion of new bone volume was superior to other groups ( P<0.05). HE staining showed that compared with other groups, bone trabeculae in group D were dense and arranged regularly, on which a large number of osteoblasts and osteoclasts were distributed, and a large number of new bone formation could be seen. Immunohistochemical staining showed the strong positive expressions of BMP-2 and VEGF in group D ( P<0.05); Western blot detection showed that the relative expressions of VEGF, OSM, and BMP-4 proteins in group D were significantly higher than those in other groups ( P<0.05). The BMSCs in Pluronic F-127 composite gel loaded with TGF-β 3 and BMSCs can be induced to differentiate into osteoblasts, and the composite gel has no toxic effect on cells, and has obvious osteogenesis and angiogenesis in the maxillary sinus of rabbits.

Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness

Background & Objective: Vascular Endothelial Growth Factor (VEGF) is one of the newer molecular markers that acts as a central mediator of tumor angiogenesis and is essential for tumor growth, progression, and metastasis. So anti-angiogenic drugs can be used as anticancer therapy. Treatments with anti-VEGF (Bevacizumab) therapy have been proved to improve relapse-free survival in many tumors. Urinary bladder tumor has become emerging cancer globally among elderly individuals. So, the identification and development of novel biomarkers for effective treatment of urinary bladder carcinoma is essential. The present study aimed to investigate the immunohistochemical expression of VEGF in urothelial carcinoma of urinary bladder and to assess its association with tumor grade and muscle invasiveness.Methods: This cross-sectional study was conducted in the Department of Pathology, Chittagong Medical College, Chattogram from September 2018 to August 2020. Fifty-six formalin-fixed paraffin-embedded tissue blocks of urinary bladder carcinoma were prepared for both histopathological and immunohistochemical examination. Each slide was evaluated by at least two pathologists.Results: Weak to strong positive expression of VEGF were observed in 52 cases (92.86%). The proportion of tumors positive for VEGF expression was higher among patients with high grade and non-muscle invasive bladder carcinoma. Conclusion: We found that VEGF expression has a significant association with tumor grade and an inverse association with muscle invasion. These findings may be useful for selecting the subset of patients likely to respond to anti-VEGF targeted therapy.

Research Progress in Promotion of Tissue Regeneration and Reconstruction with Exosomes Derived from Mesenchymal Stem Cells

In regenerative medicine, stem cell therapy is an effective strategy for tissue regeneration and has a positive therapeutic effect on the regeneration and repair of defective tissues. In recent years, a series of studies have shown that the positive effects of stem cell therapy are mediated by exosomes released by the paracrine action of mesenchymal stem cells. Researchers have thus proposed a novel treatment strategy to use stem-cell-derived exosomes alone for tissue regeneration and repair, and affirmed through studies that the effects achieved were comparable to those of stem-cell-based therapies. Therefore, as a promising treatment strategy, exosome-based tissue regeneration treatment measures have been extensively studied. In this review, we discussed the latest knowledge of exosomes and the research progress in the regeneration and repair of related connective tissues, including the regeneration of bones, cartilage, skin, spinal cord and tendons, and briefly discussed the corresponding mechanisms. In addition, the challenges and prospects of tissue regeneration and repair based on mesenchymal stem cell exosomes were discussed.

The prognosis of giant cell tumor of bone and the vital risk factors that affect its postoperative recurrence: a meta-analysis.

BackgroundThe purpose of this study is to analyze the overall prognosis of giant cell tumor of bone (GCTB) and the risk factors that affect its postoperative recurrence.MethodsThe databases of PubMed, Cochrane, Web of Science, Embase, China national knowledge infrastructure, China Biology Medicine disc, and Wanfang were searched until 20 June 2020. Following patients, intervention, comparator, outcomes, study design (PICOS) guidelines, eligible articles were defined as studies evaluating the overall prognosis of GCTB and the risk factors that affect its postoperative recurrence. The association between five risk factors (surgical methods, whether there is soft tissue invasion, tumor size, p53 expression, vascular endothelial growth factor (VEGF) expression) and the recurrence of GCTB were calculated using fixed-effects or random-effects models. The heterogeneity of the odd ration (OR) and effect size (ES) of each study was quantified using Cochran’s Q test and Higgins-I2 statistic. The publication bias was analyzed through the drawing of the funnel diagram.ResultsA total of 10 studies were included in the study. We found that the probability of recurrence of patients who choose simple curettage is 5.75 times that of patients who choose amputation or total resection. Patients with soft tissue invasion are 3.76 times more likely to relapse than non-invasive GCTB. The probability of recurrence of patients with tumors larger than 5 cm is 2.8 times that of patients with tumors smaller than. Patients with positive expression of p53 are 3.82 times more likely to relapse than patients with negative expression. And patients with positive expression of VEGF are 3.82 times more likely to relapse than patients with negative expression.ConclusionsIn conclusion, our analysis of five risk factors can be used to measure the recurrence of GCTB and provide important preoperative recommendations for patients with GCTB.

Cyclopamine Reduces the Growth of Endometrial Carcinoma and Hedgehog Pathway Proteins in a Xenograft Mouse Model

Endometrial carcinoma is a frequently occurring malignancy of the female reproductive tract. Previous investigations have implicated the Hedgehog signaling pathway, including the smoothened (Smo) receptor, in tumor progression. Here, we established a nude mouse xenograft model of endometrial cancer to investigate the effect of the Smo receptor antagonist cyclopamine on the growth of endometrial carcinoma. Mice were randomly sorted into two groups receiving 0.2 mL/mouse every other day of either cyclopamine (20 mg/mL) or solvent (control). The growth of the mice was observed for 18 days. Then, mice were euthanized, tumors were removed and weighed, and tumor volume inhibition rate (VIR) and weight inhibition rate (WIR) were calculated. Smo, Gli1, and Gli2 mRNA expression was measured in tumor tissues by RT-PCR, and Vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry. We found that cyclopamine treatment reduced the tumor growth rate and significantly reduced the volumes and weights of the transplanted tumors compared with those of the controls. Furthermore, the transplanted tumors of cyclopamine-treated mice possessed lower expression levels of Smo, Gli1, and Gli2, and displayed a lower positive expression of VEGF and CD31. Thus, the Smo receptor antagonist cyclopamine inhibited transplanted tumor growth in nude mice with endometrial carcinoma, which is likely connected with cyclopamine downregulation of Smo, Gli1, and Gli2 mRNA expression that promote angiogenesis.

Effects of silencing epididymal vascular endothelial growth factor (VEGF) expression on hyaluronidase (HYD) activity in arsenic poisoning rats through downregulating VEGF receptor 2 (VEGFR2)

ABSTRACT RNA interference (RNAi) was used to investigate the role of epididymal vascular endothelial growth factor (VEGF) gene expression on sperm hyaluronidase (HYD) in a rat model of arsenic poisoning and to identify a new gene therapy target for male infertility caused by arsenic poisoning. The Rat model of chronic arsenic poisoning was established. And we found that positive expression of VEGF and VEGF receptor 2 (VEGFR2) was observed by Immunohistochemical staining in the epididymal tissues of arsenic-exposed rats. Subsequently, VEGF-shRNA-1, VEGF-shRNA-2 and VEGF shRNA-3 expression vectors containing epididymal VEGF-shRNA lentivirus were constructed and injected into the bilateral epididymis of each group of rats (Control group, NC-shRNA negative infection group, VEGF-shRNA-1 group, VEGF-shRNA-2 group, VEGF-shRNA-3 group) (n = 10 per group). Compared with the negative infection group and the normal control group, the expression of VEGF and VEGFR2 mRNA and protein levels were significantly decreased following epididymal infection. In addition, the HYD activity was all significantly lower than that in the normal control group and the negative infection group. Taken together, epididymal VEGF gene silencing may inhibit the activity of sperm HYD through downregulating VEGFR2.

Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness.

Background & Objective:Vascular Endothelial Growth Factor (VEGF) is one of the newer molecular markers that acts as a central mediator of tumor angiogenesis and is essential for tumor growth, progression, and metastasis. So anti-angiogenic drugs can be used as anticancer therapy. Treatments with anti-VEGF (Bevacizumab) therapy have been proved to improve relapse-free survival in many tumors. Urinary bladder tumor has become emerging cancer globally among elderly individuals. So, the identification and development of novel biomarkers for effective treatment of urinary bladder carcinoma is essential. The present study aimed to investigate the immunohistochemical expression of VEGF in urothelial carcinoma of urinary bladder and to assess its association with tumor grade and muscle invasiveness.Methods:This cross-sectional study was conducted in the Department of Pathology, Chittagong Medical College, Chattogram from September 2018 to August 2020. Fifty-six formalin-fixed paraffin-embedded tissue blocks of urinary bladder carcinoma were prepared for both histopathological and immunohistochemical examination. Each slide was evaluated by at least two pathologists.Results:Weak to strong positive expression of VEGF were observed in 52 cases (92.86%). The proportion of tumors positive for VEGF expression was higher among patients with high grade and non-muscle invasive bladder carcinoma. Conclusion:We found that VEGF expression has a significant association with tumor grade and an inverse association with muscle invasion. These findings may be useful for selecting the subset of patients likely to respond to anti-VEGF targeted therapy.

Expression of VEGF, CD73 and their relationship with clinical pathology, microvessel density, and prognosis in renal cell carcinoma.

BackgroundRenal cell carcinoma (RCC), a tumor originating from renal tubular epithelial cells, has the second highest incidence of all adult urogenital tumors. However, in most cases, patients show no obvious symptoms in the early or even the late stages of RCC, which seriously impacts the prognosis. This study aimed to analyze the expression of vascular endothelial growth factor (VEGF) and ecto-5'-nucleotidase (CD73) and their relationship with clinical pathology, microvessel density (MVD), and prognosis in RCC.MethodsThe clinical data of 76 patients with RCC who underwent radical nephrectomy in our hospital between October, 2011 and October, 2013 were retrospectively analyzed. The postoperative paraffin specimens were collected; the expression levels of VEGF and CD73 in the tumor tissues were detected, and the MVD was measured. T the expression of VEGF and CD73 and their relationship with clinical pathology, MVD, and prognosis in RCC.ResultsThe positive expression rates of VEGF and CD73 in RCC patients with grades G3–G4 were higher than those in patients with grades G1–G2 (P<0.05). The rates in RCC patients with stages III~IV were higher than those in patients with stages I–II (P<0.05). The rates in RCC patients with lymph node metastasis were higher than those in patients without lymph node metastasis (P<0.05). The MVD count of patients with positive expressions of VEGF and CD73 was higher than that of patients with negative expressions (P<0.05). The expressions of VEGF and CD73 in RCC tissues were significantly positively correlated with MVD count (P<0.05). The five-year mortality rate of patients with positive expressions of VEGF and CD73 was higher than that of patients with negative expressions (P<0.05).ConclusionsThe expressions of VEGF and CD73 in RCC tissues can reflect the degree of tumor malignancy, invasion, and metastasis, and are closely related to the formation of microvessels in tumor tissues and the poor prognosis of patients.