Higher Levels Of PDGF-BB Research Articles

Comparisons of Cytokines, Growth Factors and Clinical Efficacy between Platelet-Rich Plasma and Autologous Conditioned Serum for Knee Osteoarthritis Management

This study aimed to directly compare the contents and the clinical efficacy of the two autologous blood-derived products, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) for osteoarthritis (OA) treatment. The contents of standard-prepared PRP and ACS prepared at 37 °C for 1 h, 3 h, 6 h, and 24 h from healthy volunteers were compared. The clinical efficacy of pain relief in patients with Stage III knee OA was evaluated by a patient-reported visual analog scale (VAS) pain rating. PDGF-BB levels in ACS 1 h were significantly higher than those in PRP, and the levels in ACS preparations remained stable. IGF-1 level of ACS 24 h showed a significant increase compared to those of other ACS preparations and PRP. ACS 3 h showed a turning of IL-1Ra level and revealed a time-dependent increase up to 24 h. ACS 6 h showed a turning increase in TNF-α levels. ACS 3 h was chosen for clinical comparison with PRP. The reduction in pain VAS in the ACS group was significantly more compared to those of the PRP group (p = 0.028). However, PRP showed significant earlier improvement (p < 0.001). Conclusion: ACS contained higher levels of PDGF-BB and IL-1Ra and provided better improvement in pain relief compared to PRP.

The Effect of Platelet Rich Fibrin (PRF) and Bone Graft (Carbonate Apatite) Applications on Platelet Derived Growth Factor-BB Post Flap Surgery in Patients with Chronic Periodontitis

Chronic periodontitis characterized by a periodontal pocket over 5 mm, alveolar bone resorption accompanied by tooth mobility, requires periodontal surgical treatment. Conventional surgical treatment can not achieve the regeneration of periodontal tissue and thus requires regenerative procedures, such as with the addition of PRF. PDGF-BB is a growth factor that plays an important role in wound healing. Developments in additional bioactive ingredients in surgical procedures are used to regulate inflammation and increase the speed of the healing process. The purpose of this study was to determine the effect of PRF and bone graft (carbonate apatite) on PDGF-BB levels post-surgical flap in patients with chronic periodontitis. The experimental study with open label and consecutive sampling was conducted on 10 subjects of chronic periodontitis who received surgical flap treatment with bone graft and PRF; and 10 subjects without PRF. GCF samples were collected immediately before surgery and 7 days post flap surgery for examination of PDGF-BB levels by ELISA method. The data were calculated statistically by Mann-Whitney test (p &lt;0.05). The results showed that the mean difference of PDGF-BB level in PRF group was 9.44 pg/ml (-1.20 – 37.79 pg/ml) with p value (0.013) and Non-PRF group was 7.97 pg/ml (-6.62 - 44.42 pg/ml) with p value (0.059). The p value in the PRF group &gt; 0.05 means a significant increase in PDGF-BB levels on the 7th day post flap surgery. Examination of PDGF levels, especially PDGF-BB, should be done in each healing phase of the wound from the inflammatory phase to the maturation and remodeling phase, for example on the 3rd, 7th, 14th and 28th days when PDGF levels approach zero and the healing process it's almost over, referring to the results of Alzahrani's research (2018) and also Matsuoka and Grotendorst (1989) which showed higher levels of PDGF-BB and VEGF in GCF on days 1, 3, 7 and 14 after surgery with minimally invasive surgery (MIS) technique. The conclusions of this study showed that the application of Platelet Rich Fibrin (PRF) and bone graft had an effect on the level of Platelet Derived Growth Factor (PDGF-BB) post-surgical flap in patients with chronic periodontitis, and elevated levels of PDGF-BB post-surgical flap with PRF application higher than surgical flap without the PRF application. Increased levels of PGDF-BB in the group applied to the PRF were higher than those that were not applied PRF, although statistically significant differences were not found, there was a tendency for the healing process of the PRF group to be better than the Non PRF group.

Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots

Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B4 (LTB4) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB4, a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots.

The Role of PDGFs and PDGFRs in Colorectal Cancer

Introduction. Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Angiogenesis was reported as one important mechanism activated in colorectal carcinogenesis. Tumor microenvironment associated angiogenesis involves a large spectrum of signaling molecules and deciphering their role in colorectal carcinogenesis still represents a major challenge. The aim of our study is to point out the diagnosis and prediction role of PDGF family and their receptors in colorectal carcinogenesis. Material and Methods. A systematic search in Medline and PubMed for studies reporting the role of platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) in tumor biology related to CRC was made. Results. PDGFs are important growth factors for normal tissue growth and division, with an important role in blood vessel formation. PDGFs/PDGFRs signaling pathway has been demonstrated to be involved in angiogenesis mainly by targeting pericytes and vascular smooth muscle cells. High levels of PDGF-BB were reported in CRC patients compared to those with adenomas, while elevated levels of PDGFR α/β in the stroma of CRC patients were correlated with invasion and metastasis. Moreover, PDGF-AB and PDGF-C were correlated with early diagnosis, cancer grading, and metastatic disease. Conclusions. Both PDGFs and PDGFRs families play an important role in colorectal carcinogenesis and could be considered to be investigated as useful biomarkers both for diagnosis and treatment of CRC.

Gender biased immune-biomarkers in active tuberculosis and correlation of their profiles to efficacy of therapy

Active pulmonary TB is an inflammatory disease and is increasingly viewed as an imbalance of immune responses to Mycobacterium tuberculosis (M.tb.) infection. In addition, this immune imbalance may be gender biased (males have a higher prevalence of TB) but reasons for such bias are uncertain. We hypothesized that studies on profiles of immune-biomarkers will not only provide insight into molecular basis of gender bias but may also help identify biomarkers to monitor efficacy of TB therapy. We examined 10 plasma cytokine/chemokine/growth-factor and 8 antibody (against 8 M.tb. antigens) biomarkers (elevated in TB patients) by multiplex microbead immunoassays. In addition, we examined these biomarkers in patients under anti-tuberculosis therapy (ATT). The results showed that female patients contained significantly higher levels of CXCL9 (MIG) and CXCL10 (IP-10), while males contained higher levels of PDGF-BB. In contrast, more males than females contained antibodies against several antigens. Our results also show that there are progressive and substantial decreases in plasma levels of CXCL9, CXCL10, PDGF-BB, IFNγ, and IL-18, correlating with treatment success. Our results suggest that studies on gender bias in immunebiomarkers will enhance understanding of host responses in TB and would be valuable as biomarkers for monitoring efficacy of ATT.

P.19.4 PDGF-BB is expressed by muscle fibers in myopathies and regulates growth and migration of satellite cells and pericytes

PDGF-AA and BB belong to the family of Platelet Derived Growth factors (PDGFs). They activate two different receptors: PDGF-RcfN and PDGF-RcfOfnrespectivelyf∣fnPDGF-AA has been recently involved in the process of fibrosis in muscle dystrophies. In contrast, PDGF-BB could be important in myoblast activation and differentiation. Its role in pathological conditions has not been investigated. Our objective is to study the expression and function of PDGF-BB in human skeletal muscle both in normal and pathological conditions. We studied PDGF-BB and PDGF-Rcβ expression on muscle biopsies from controls and patients with different muscle dystrophies and also in vitro in myoblasts, pericytes and myotubes using immunohistochemistry, WB and ELISA. To study the effect of PDGF-BB on myoblasts and pericytes we performed growth curves, differentiation studies and transwells assays. PDGF-BB is normally expressed in vessels but not in muscle fibers. Muscle fiber expression of PDGF paralleled the degree of muscle degeneration/regeneration in myopathies. In vitro experiments demonstrated that myoblasts and pericytes expressed PDGF-RcfO in the membrane, but did not produce PDGF-BB. In contrast, myotubes did express low levels of PDGF-BB, that increased after injury with ionomycine, SDS or a mechanical damage using glass beads. Moreover, we also observed that myotubes from dystrophinopathy patients expressed higher levels of PDGF-BB than myotubes from controls, facioscapulohumeral muscular dystrophy or dysferlinopathy patients. Finally, PDGF-BB promoted an increase in the growth ratio of myoblasts and pericytes and increased cell migration in the transwell-assays. Our results indicate that PDGF-BB is expressed in muscle fibers during degeneration/regeneration. Further, PDGF-BB may have an important role in growth, activation and migration of muscle stem cells with myogenic potential.

Expression and prognostic value of circulating angiogenic cytokines in pancreatic cancer

BackgroundThe utility of circulating angiogenic cytokines (CAC) as biomarkers in pancreatic cancer has not been clarified yet. We investigated the expression and prognostic associations of seven CAC in patients with pancreatic cancer.MethodsSerum samples were collected preoperatively in patients undergoing surgery for localized pancreatic cancer (n = 74), metastatic pancreatic cancer (n = 24) or chronic pancreatitis (n = 20) and in healthy controls (n = 48). Quantitative enzyme-linked immunosorbent assays and multiplex protein arrays were used to determine circulating levels of VEGF, VEGFR-1, PlGF, PDGF-AA, PDGF-BB, Ang-1 and EGF. Multivariate analyses on cancer-specific survival were performed with a Cox proportional hazards model.ResultsVEGF (p < 0.0001), PDGF-AA (p < 0.0001), Ang-1 (p = 0.002) and EGF (p < 0.0001) were differentially expressed in patients with pancreatic cancer compared to healthy controls. The presence of lymph node metastases was associated with increased levels of all CAC except for PlGF, whereas there were only minor associations of CAC with other clinicopathologic variables. The multivariate model including the entire angiogenic panel revealed high levels of circulating PDGF-AA (hazard ratio 4.58; 95% confidence interval 1.43 - 14.69) as predictor of poor cancer-specific survival, whereas high levels of PDGF-BB (0.15; 0.15 - 0.88), Ang-1 (0.30; 0.10 - 0.93) and VEGF (0.24; 0.09 - 0.57) were associated with a favorable prognosis.ConclusionCirculating levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer, if a panel of several CAC is considered simultaneously. These data should be considered in future studies evaluating angiogenic factors as prognostic biomarkers and therapeutic targets in patients with pancreatic cancer.

Palliative treatment of unresectable pancreatico-biliary cancer by either gemcitabine or octreotide/imatinib: Impact on biomarkers of angiogenesis

15101 Background: Gemcitabine represents standard Tx for unresectable cancers of the pancreas / distal biliary tract. Recent interest has focused on antiangiogenic properties in a mouse model of pancreatic cancer (JCI 2003); either VEGF or PDGF inhibition alone were less effective than the combination of both in terms of angiogenesis. In humans, imatinib (targeting PDGF) alone has been shown to be equivalent to gemcitabine in terms of survival (Cancer Lett. 2006;233:328–37), while most trials for octreotide (targeting IGF-1, VEGF) were disappointing. In HCC pts. we recently evaluated the impact of biomarkers on disease progression and survival (Cancer Res Clin Oncol 2006; 132:699–708). Methods: To investigate in a phase I/II trial the feasability of a combination (group I, n=11) of octreotide (30 mg im every 4 weeks, targeting VEGF-A) plus imatinib (400 mg po daily, targeting PDGF-B) vs gemcitable (group II, n=11, 1000mg/m2 weekly for 7/8 wks, then for 3/4 wks). Pts had either unresectable pancreatic cancer (n=18) or ampullary cancer (n=4). Primary outcome measure were changes in biomarkers (VEGF-A, PDGF-BB, soluble E-selectin, Ca19–9, CEA). Secondary outcome measures were TTP and OS. Results: 19/22 pts. had biomarker data available within the first 12 wks, changes over time are shwon in table . Median TTP was 109 vs 166 days (p&lt;0.05) and median OS was 163 vs 325 days (p=NS) for group I vs II. Baseline Ca19–9 levels correlated with prognosis independent of Tx (p=0.05). In group I, high levels of PDGF-BB and VEGF-A levels at wk 12 but in group II, low levels of VEGF-A and s-E-selectin correlated with a better OS (p&lt;0.05 each). TTP showed no correlations with biomarkers. Conclusions: The combination of octreotide plus imatinib is clinically less effective compared to gemcitabine. Although the absolute changes of angiogenesis markers are comparable between groups, chemotherapy compared to targeted therapy has a different impact on these in terms of survival. [Table: see text] No significant financial relationships to disclose.