Background:Hallmarks of the pathogenesis of rotator cuff disease (RCD) include an abnormal immune response, angiogenesis, and altered variables of vascularity. Degenerative changes enhance production of pro-inflammatory, anti-inflammatory, and vascular angiogenesis-related cytokines (ARC) that play a pivotal role in the immune response to arthroscopic surgery and participate in the pathogenesis of RCD. The purpose of this study was to evaluate the ARC profile, ie, interleukin (IL): IL-1β, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG), in human peripheral blood serum and correlate this with early degenerative changes in patients with RCD.Methods:Blood specimens were obtained from 200 patients with RCD and 200 patients seen in the orthopedic clinic for nonrotator cuff disorders. Angiogenesis imaging assays was performed using power Doppler ultrasound to evaluate variables of vascularity in the rotator cuff tendons. Expression of ARC was measured by commercial Bio-Plex Precision Pro Human Cytokine Assays.Results:Baseline concentrations of IL-1β, IL-8, and VEGF was significantly higher in RCD patients than in controls. Significantly higher serum VEGF levels were found in 85% of patients with RCD, and correlated with advanced stage of disease (r = 0.75; P < 0.0005), average microvascular density (r = 0.68, P < 0.005), and visual analog score (r = 0.75, P < 0.0002) in RCD patients. ANG and IL-10 levels were significantly lower in RCD patients versus controls. IL-1β and ANG levels were significantly correlated with degenerative tendon grade in RCD patients. No difference in IL-6 and bFGF levels was observed between RCD patients and controls. Patients with degenerative changes had markedly lower ANG levels compared with controls. Power Doppler ultrasound showed high blood vessel density in patients with tendon rupture.Conclusion:The pathogenesis of RCD is associated with an imbalance between pro-inflammatory, anti-inflammatory, and vascular ARC.
Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention.Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine) is an attractive concept for regulation of vascularization in pediatric osteosarcoma.
Background:Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis.Objectives:To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers.Methods:Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans.Results:Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals (P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors (P < 0.001).Conclusions:These results demonstrated that the combined biomarker ANG–IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG–IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.
Introduction: The presence of NA against EM regarding specificity and have gained increasing attention in proteome analysis for diagnosis, developing, monitoring and effective treatment of osteoarthritis of the knee (kOA). An understanding of the various regulatory systems controlling blood vessel growth, inflammation and pain in the join should lead to help explain kOA disease progression. To investigate the specific presence of NA (IgM, IgG, IgA) against EM (BK, AII, VEGF, bFGF) in the sera of kOA patients and control and to correlate this with process of joint destruction. Methods:In this study novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive ELISA method to directly detect immune complexes (NA-EM) in humans. Following this procedure, we examined variations in the levels of natural antibodies recognized a panel of self-antigens in the sera from healthy individuals and kOA patients. Blood samples were obtained from 250 patients with symptomatic kOA and 250 ages, sex-matched healthy individuals.Results: NA against EM was detected with novel ELISA assay in the sera of kOA patients as well as in the sera of control. At time of inclusion kOA patients (100%) had significantly higher BK-IgG levels relative to normal sera. The over expression BK-IgG were positively associated with destructive changes (KL>4; r=0.75; p<0.005). KOA patients in whom KL scores progress rapidly tend to have higher BK-IgG levels at all time point. Serum BK-IgG over expression in kOA patients were positively associated with destructive changes (KL>4; r=0.75; p<0.005). Elevated BK-IgG was significantly correlated with VAS (r=0.85; p<0.0001) and loss of functions (r=0.69; p<0.0003) in kOA patients. Affinity chromatography yielded EM-specific NA from the sera of healthy individuals and kOA patients. Conclusions:We showed that EM represents a group of novel self-antigens which are targeted by NA from kOA patients. Circulating BK-IgG in the sera has been proposed as a sensitive and specific marker of diagnosing kOA at early stages of the disease. Our results have potential applications for controlling unwanted angiogenesis, inflammation, pain and future response to therapy in kOA patients. Osteoarthritis of the knee (kOA) can be a progressive disabling disease, which results from the pathological imbalance of degradative and reparative processes, with concomitant inflammatory changes [2]. The clinical features of kOA include pain, stiffness, reduced motion, swelling, crepitus, and deformity [3][4][5]. Journal of Molecular Biomarkers & DiagnosisSeveral factors are considered for the pathogenesis of kOA [6][7][8][9][10][11][12][13][14]. Complicated path biological interactions between the KallikreinKinin System (KKS), the Rennin-Angiotensin (RAS), angiogenesis and natural immunity could contribute to joint destruction in the disease process of kOA [15][16][17][18][19]. It is also likely that biomarkers will be used in conjunction with imaging in order to establish stage of disease,...
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