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Dermatologic Therapy Jan 2021Local angiogenesis accompanies inflammation in psoriasis-affected skin. To determine the serum concentrations of selected pro- and anti-angiogenic factors and their...
Local angiogenesis accompanies inflammation in psoriasis-affected skin. To determine the serum concentrations of selected pro- and anti-angiogenic factors and their interrelationships in patients with plaque psoriasis. The study included 41 men diagnosed with psoriasis, aged 43.5 ± 11.7 years. The Psoriasis Area and Severity Index score was 23.4 ± 5.2 points. The control group consisted of 38 healthy, age-matched men. The levels of pro-angiogenic cytokines and angiogenesis inhibitors, including fibroblast growth factor 1 (FGF-1), vascular endothelial growth factor A (VEGF-A), endostatin, and angiostatin, were determined from the serum of patients and controls using enzyme-linked immunosorbent assays. Compared with controls, patients with psoriasis had a significantly lower concentration of FGF-1 (P = .01) but higher concentrations of endostatin (P = .04) and angiostatin (P = .02). The concentration of VEGF-A was also higher in patients with psoriasis but not significantly (P = .25). The concentration of C-reactive protein (CRP) was significantly higher among patients with psoriasis than controls (P < .0001). Among controls, CRP concentrations did not correlate significantly with the concentrations of FGF-1, VEGF-A, endostatin, or angiostatin. Among patients with psoriasis, CRP concentrations correlated moderately with the concentrations of VEGF-A (r = .35; P = .02) and angiostatin (r = .31; P = .04). The concentration of VEGF-A correlated positively with PASI (r = .05; P = .0009) and BSA values (r = .39; P = .01). Psoriasis is associated with an altered systemic balance between pro-angiogenic and anti-angiogenic factors. The increase in serum angiogenesis inhibitors may be associated with unfavorable changes in the development of coronary collateral circulation. However, the clinical significance of this has not yet been established.
Topics: Adult; Angiogenic Proteins; Angiostatins; Endostatins; Fibroblast Growth Factor 1; Humans; Male; Middle Aged; Psoriasis; Skin; Vascular Endothelial Growth Factor A
PubMed: 33381893
DOI: 10.1111/dth.14727 -
Journal of Oncology 2020During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth...
During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth and metastasis. Additionally, the participation of oxidative stress and chronic inflammation in BC pathogenesis is indicated. The aim of the study was to evaluate the urinary levels of parameters of angiogenesis, stimulating angiogenin (ANG) and inhibiting angiostatin (ANGST), 8-iso-prostaglandin F2 (8-iso-PGF2) as a marker of oxidative stress, -synuclein (SNCG) as a cancer progression parameter, and interleukin-13 (IL-13) as an anti-inflammatory immunomodulator. The levels of ANG, ANGST, 8-iso-PGF2, SNCG, and IL-13 in the urine of BC patients and healthy controls were measured by the enzyme-linked immunosorbent assay. These parameters were examined in the whole group of BC patients and in subgroups depending on the clinical stage: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC); histopathologic malignancy: low grade (LG) and high grade (HG) and in primary and recurrent BC. Significantly, higher urinary parameters were found n BC patients in comparison to controls. Levels of all parameters increased with the development of cancer, with the exception of 8-iso-prostaglandin F2, in which the level was higher in the early stages of the disease, but these differences were not statistically significant. Some correlations have been demonstrated between parameters in BC patients. Based on the receiver operating characteristic curves, ANG and ANGST had the best diagnostic value for BC. The obtained results indicate the important role of the examined parameters of angiogenesis, oxidative stress, and inflammation in the pathogenesis and development of BC. It is reasonable to continue research in order to thoroughly assess the impact of various associated processes on the course of BC. It is also important to carry out similar tests in patients with other urological diseases.
PubMed: 33343662
DOI: 10.1155/2020/4848752 -
Journal of Oncology 2020The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67),...
The aim of the study is to investigate the expression of angiogenesis (VEGF and PDGF), angiogenesis inhibitor markers (angiostatin and endostatin), proliferation (Ki67), and apoptosis markers (p53 and p16) of cervical cancer in Indian population and to correlate them with the clinicopathological profile. It is a descriptive study of consecutive cases of cervical cancer from Saveetha Medical College and Hospital between January 2017 and December 2018. The expression of angiogenesis, angiogenesis inhibitor markers, Ki67, p53, and p16 in 60 cases of cervical sections were detected by the immunohistochemical method and analyzed with clinicopathological data. VEGF expression was positive in 16 cases (26.67%) and negative in 20 cases (33.33%). As of PDGF, 3 cases (3.33%) have shown positivity to PDGF and 33 cases have shown negativity. Angiostatin and endostatin expression was reported to be positive in 10 (16.67%) and 21 (35%) cases, respectively. Most of the cases 57 (95%) have shown both p16 and Ki67 positivity. Although p53 expression was positive in 48 cases (80%), the remaining 12 cases (20%) were p53-negative. The PDGF expression was significantly correlated to the stage of tumors. No statistically significant association was observed between angiogenesis inhibitor markers and clinicopathological parameters. A significant positive correlation was noticed between the Ki67 expression and stage of tumors.
PubMed: 33273920
DOI: 10.1155/2020/8541415 -
Pharmaceutical Biology Dec 2020(Leyss. ex Fr.) Karst. (Polyporaceae) triterpenoids (GLTs), the main components and bioactive metabolites of , have antitumour activity. (Comparative Study)
Comparative Study
CONTEXT
(Leyss. ex Fr.) Karst. (Polyporaceae) triterpenoids (GLTs), the main components and bioactive metabolites of , have antitumour activity.
OBJECTIVE
We investigated the effects of GLTs in lung cancer tumour-bearing nude mice and their potential mechanism.
MATERIALS AND METHODS
Forty BALB/c nude mice were randomly divided into four groups: saline control, GLT (1 g/kg/day), gefitinib (GEF, 15 mg/kg/day), and GLT (1 g/kg/day) + GEF (15 mg/kg/day) for 14 days. Cell viability was conducted using the Cell Counting Kit-8 assay. The tumour volume, inhibition rate, histopathological, microvessel density (MVD), mRNAs, and proteins were determined.
RESULTS
GLTs inhibited the cell viability of A549 cells with an IC value of 14.38 ± 0.29 mg/L, while the IC value of GEF was 10.26 ± 0.47 μmol/L. The tumour inhibition rate in the GLT + GEF group (51.54%) was significantly decreased relative to the saline control… group ( < 0.05). The MVD in the GLT + GEF group (2.9 ± 0.7) was significantly decreased than that in the saline control group (12.8 ± 1.4, < 0.05). The angiostatin, endostatin, and Bax protein expression in the GLT, GEF, and GLT + GEF groups were significantly increased compared to those in the saline control group, while the VEGFR2 and Bcl-2 protein expression were decreased.
DISCUSSION AND CONCLUSIONS
Our study provided evidence that GLT and GEF combination therapy may be a promising candidate for the treatment of lung cancer and as an experimental basis for clinical treatment.
Topics: Animals; Cell Line, Tumor; Cell Survival; Female; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neovascularization, Pathologic; Reishi; Triterpenes
PubMed: 33161828
DOI: 10.1080/13880209.2020.1839111 -
PloS One 2020Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery....
Extracellular vesicles (EVs) are subcellular membrane blebs that include exosomes and microparticles, which represent a potential source for cancer biomarker discovery. We assess EVs characteristics as a tool to evaluate the endothelial and anti-tumor treatment injury during adjuvant chemotherapy in breast (BC) and colon cancer (CC) patients. Blood samples were taken from 29 BC and 25 CC patients before and after chemotherapy, as well as from healthy control donors (HC). Circulating blood EVs were isolated and characterized by size/concentration, membrane antigens for cell origin, thrombogenicity, and protein content. We observed higher EVs concentration and particle size in CC patients after chemotherapy compared with HC. Higher levels of endothelial EVs (CD144-positive) and vascular endothelial growth factor receptor 1 (VEGFR1), apparently as an indication of endothelial dysfunction, were found in all cancer patients, regardless of a given treatment, compared to HC. Levels of EVs labeled CD62E, CD34+41-, the lymphocyte markers CD11+ and CD-14+, Annexin-V, and the coagulation proteins TF and TFPI, however, sometimes demonstrate significant differences between patients, although HC did not show significant differences between patients pre- and post-chemotherapy. Most importantly, increasing levels of EVs encapsulated Angiostatin were found in patients with CC, while chemotherapy treatment leads to its notable rise in circulating blood EVs. Our results demonstrate the potential of EVs encapsulated Angiostatin as a tool to evaluate endothelial damage during adjuvant chemotherapy in BC and CC patients.
Topics: Aged; Aged, 80 and over; Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cadherins; Case-Control Studies; Chemotherapy, Adjuvant; Colonic Neoplasms; Endothelium; Extracellular Vesicles; Female; Humans; Male; Middle Aged; Particle Size; Vascular Endothelial Growth Factor Receptor-2
PubMed: 33108394
DOI: 10.1371/journal.pone.0240994 -
Fish & Shellfish Immunology Nov 2020Extracellular double-stranded RNA (dsRNA) is an important modulator in innate immunity in both vertebrates and invertebrates. In shrimp, extracellular dsRNA can trigger...
Extracellular double-stranded RNA (dsRNA) is an important modulator in innate immunity in both vertebrates and invertebrates. In shrimp, extracellular dsRNA can trigger RNAi pathway and serves as antiviral defense mechanism. However, the mechanism of dsRNA internalization into the cells has not yet known in shrimp cells. This study identified candidate cell surface proteins from shrimp hepatopancreatic cells that could interact with dsRNA by a ligand blot assay. Among the candidate proteins, a cell-surface beta subunit of ATP synthase was shown to be capable of internalizing dsRNA into shrimp hepatopancreatic cells that could rapidly occur in just 1 min upon dsRNA challenge. Colocalization between dsRNA and ATP synthase beta subunit implied correlation between dsRNA and ATP synthase beta subunit during dsRNA internalization. Furthermore, dsRNA showed colocalization with Ras-related endocytic proteins, Rab5 and Rab7 indicating that dsRNA was internalized via the receptor-mediated endocytosis. For the above evidences as well as the reduction of dsRNA internalization by angiostatin and antibodies against ATP synthase beta subunit, we propose that dsRNA interacts with ATP synthase via a nucleotide binding site in the beta subunit prior to internalize dsRNA into cells.
Topics: Animals; Cells, Cultured; Endocytosis; Hepatopancreas; Mitochondrial Proton-Translocating ATPases; Penaeidae; RNA, Double-Stranded
PubMed: 32920201
DOI: 10.1016/j.fsi.2020.09.010 -
Gastroenterology Report Aug 2020Neoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one...
BACKGROUND
Neoadjuvant chemoradiotherapy (nCRT) is associated with post-operative anastomotic complications in rectal-cancer patients. Anastomosis involving at least one non-irradiated margin reportedly significantly reduces the risk of post-operative anastomotic complications in radiation enteritis. However, the exact scope of radiotherapy on the remaining sigmoid colon remains unknown.
METHODS
We evaluated the radiation damage of proximally resected colorectal segments in 44 patients with rectal cancer, who received nCRT followed by conventional resection (nCRT-C, = 21) or proximally extended resection (nCRT-E, = 23). The segments from another 13 patients undergoing neoadjuvant chemotherapy (nCT) were used as control. We dissected these samples at a distance of 2 cm between the two adjacent sections. Radiation damage in proximally resected colorectal segments was evaluated using the radiation injury score (RIS) and the concentration and distribution patterns of angiostatin.
RESULTS
Compared to those in the nCT group, the nCRT group showed higher RIS, levels of angiostatin, and proportion of diffuse pattern of angiostatin. With increasing distance from the tumor site, these parameters all gradually decreased; and the differences came to be not significant at the site that is over 20 cm from the tumor. The nCRT-E group showed lower RIS (median: 2 vs 4, = 0.002) and a greater proportion of non-diffuse angiostatin (87% vs 55%, = 0.039) at the proximal margins compared with the nCRT-C group.
CONCLUSIONS
The severity of the radiation damage of the proximal colon is inversely proportional to the proximal-resection margin length. Little damage was left on the proximal margin that was over 20 cm from the tumor. Removal of an initial length of ≥20 cm from the tumor may be beneficial for rectal-cancer patients after nCRT.
PubMed: 32843974
DOI: 10.1093/gastro/goz047 -
Zhonghua Wei Chang Wai Ke Za Zhi =... Aug 2020Radiation intestinal injury is one of the most common complications after abdominal pelvic radiotherapy, which seriously affects the quality of life for patients....
Radiation intestinal injury is one of the most common complications after abdominal pelvic radiotherapy, which seriously affects the quality of life for patients. According to the site of occurrence, it is divided into radiation enteritis, colitis and proctitis. The pathological characteristics of radiation intestinal injury mainly include interstitial fibrosis, mucosal edema, ulcers, and inflammatory cell infiltration, and significant vascular lesions as well. It showed telangiectasia and hemorrhage under endoscopy. Under ultrasound examination, it showed diffusive thickening of the intestinal wall and increased blood flow signals. In addition, it also has other features such as increased thickness of the distal sigmoid colon and rectal wall, and increased width of the presacral space. The key factors in the incidence and development of radiation intestinal injury include angiostatin, PDGF, CXCL16, . The mechanisms to be clarified include abnormally heightened angiostatin through which signal pathways specifically affect vascular endothelial cells and inhibit angiogenesis and vascular homeostasis, how CXCL16 expressed by macrophages interacting with receptor promotes the transformation of fibroblasts and vascular smooth muscle cells into myofibroblasts, . Therapy targeted on basics of vascular damage will be a promising field of radiation intestinal injury research.
Topics: Endothelial Cells; Humans; Proctitis; Quality of Life; Radiation Injuries; Rectum
PubMed: 32810958
DOI: 10.3760/cma.j.cn.441530-20200511-00270 -
Journal of Oral Science Sep 2020Tissue engineering for fibrocartilage regeneration using mesenchymal stromal cells (MSC) and biomaterial scaffolds is emerging as a promising strategy, but inhibiting...
Tissue engineering for fibrocartilage regeneration using mesenchymal stromal cells (MSC) and biomaterial scaffolds is emerging as a promising strategy, but inhibiting vascularization to prevent endochondral ossification is important to develop stable implants. The objective of this study was to investigate the effect of angiostatin on inhibition of angiogenesis and promotion of chondrogenesis by collagen scaffolds with or without MSC implanted subcutaneously in rats. One scaffold from the following groups was implanted in each animal: Collagen scaffolds only, scaffolds functionalized with angiostatin, scaffolds loaded with MSC and scaffolds functionalized with angiostatin and loaded with MSC. The various scaffolds were harvested after 2 and 8 weeks for histological analysis, Real-time quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence quantification. Results demonstrated significantly decreased expression of inflammatory (interleukin 1 alpha and beta) and angiogenic genes (platelet and endothelial cell adhesion molecule 1) in scaffolds functionalized with angiostatin after 2 weeks in vivo. Histologically, after 8 weeks, the scaffolds with angiostatin had less inflammatory cells and more collagen matrix formation, but no fibrocartilage formation was detected. Thus, although angiostatin suppressed angiogenesis, it did not stimulate ectopic chondrogenesis in tissue engineered constructs in vivo.
Topics: Angiostatins; Animals; Chondrogenesis; Collagen; Mesenchymal Stem Cells; Rats; Tissue Scaffolds
PubMed: 32684573
DOI: 10.2334/josnusd.19-0327 -
Physiological Reports Jun 2020Ozone is a toxic and highly reactive gaseous oxidizing chemical with well-documented adverse health effects in humans. On the basis of animal and human data,...
Ozone is a toxic and highly reactive gaseous oxidizing chemical with well-documented adverse health effects in humans. On the basis of animal and human data, environmental guidelines and air quality standards recommend a threshold for exposure of no more than 0.063 ppm of ozone (daily concentrations). This research describes a standardized sensitive model of sterile murine lung inflammation induced by exposing mice to acute (0, 4 or 24 hr), yet low, levels of ozone (0.005, 0.05 or 0.5 ppm), one that are below the current recommendations for what is considered a safe or "ambient" ozone concentration for humans. Ozone led to concentration and time-dependent phlogistic cell death in the bronchoalveolar lavage, lung epithelial damage and hemorrhage. Interestingly, we observed distinct large bright CD11b positive cells in the bronchoalveolar lavage, upregulation of lung vascular and alveolar ATP synthase as well as plasminogen and bronchiolar angiostatin expression in ozone-exposed mice, platelet and neutrophil accumulation in the lung vasculature and an eotaxin-2, IL-16, CXCL5, CXCL12, and CXCL13 dominant inflammatory response leading to lung injury. Using a fluorescent intravital microscopy set up, we quantified ozone-induced extensive alveolar cellular damage. We observed ozone-induced actin filament disorganization, perturbed respiratory mechanics, acute suppression of the alveolar reactive oxygen species (ROS) production and mitochondrial potential in ventilated lungs. We present evidence of systemic, as well as pulmonary toxicity, at 40-fold lower ozone concentrations than previously reported in mice. The findings are important in establishing a sensitive means of quantifying structural and functional lung disorganization following exposure to an aerosolized pollutant, even at levels of ozone exposure previously thought to be safe in humans.
Topics: Acute Lung Injury; Animals; Inflammation Mediators; Male; Mice, Inbred C57BL; Ozone; Pneumonia
PubMed: 32524776
DOI: 10.14814/phy2.14463