The Use of Human Serum Samples to Study Malignant Transformation: A Pilot Study

Obesity and excess adiposity account for approximately 20% of all cancer cases; however, biomarkers of risk remain to be elucidated. While fibroblast growth factor-2 (FGF2) is emerging as an attractive candidate biomarker for visceral adipose tissue mass, the role of circulating FGF2 in malignant transformation remains unknown. Moreover, functional assays for biomarker discovery are limited. We sought to determine if human serum could stimulate the 3D growth of a non-tumorigenic cell line. This type of anchorage-independent 3D growth in soft agar is a surrogate marker for acquired tumorigenicity of cell lines. We found that human serum from cancer-free men and women has the potential to stimulate growth in soft agar of non-tumorigenic epithelial JB6 P+ cells. We examined circulating levels of FGF2 in humans in malignant transformation in vitro in a pilot study of n = 33 men and women. Serum FGF2 levels were not associated with colony formation in epithelial cells (r = 0.05, p = 0.80); however, a fibroblast growth factor receptor-1 (FGFR1) selective inhibitor significantly blocked serum-stimulated transformation, suggesting that FGF2 activation of FGFR1 may be necessary, but not sufficient for the transforming effects of human serum. This pilot study indicates that the FGF2/FGFR1 axis plays a role in JB6 P+ malignant transformation and describes an assay to determine critical serum factors that have the potential to promote tumorigenesis

Misdiagnosis and prevalence of rheumatological diseases in early inflammatory arthritis clinic: Results from a UK single-centre retrospective cohort study

ObjectivesNovel diagnostic tools have been developed to aid diagnosis and reduce misdiagnosis. However, the accuracy of these tools depends on estimates of disease prevalence. This study aimed to determine the prevalence of rheumatological diseases in a real-world cohort of patients and assess the rate of misdiagnosis at first presentation and follow-up.MethodsPatients with symptoms of inflammatory arthritis were referred by primary care. Rheumatologists made initial diagnoses, initiated treatment, and revised diagnoses during follow-up. Clinical data including diagnoses were extracted from electronic patient records. ResultsOver two years, 260 patients were seen. Most patients presented with peripheral joint symptoms (95%), and 23% had axial involvement. Psoriasis was present in 15%, inflammatory bowel disease in 4%, and uveitis in 4%. Autoantibodies were positive for CCP in 11% and rheumatoid factor in 12%.Seventeen percent (n=45) of patients were misdiagnosed, with 8% (n=20) initially diagnosed one of the five most common rheumatological conditions but later found to have a non-inflammatory disorder. Conversely, 7% (n=17) initially received a diagnosis of an “Other rheumatological disease” but later had their diagnoses revised to one of the five most common rheumatological conditions.ConclusionDisease prevalence is context-specific, and prevalence estimates in the intended setting should be determined prior to implementation of novel diagnostic tools. In real-world cohorts, non-inflammatory diseases like chronic pain syndromes were more prevalent than in observational studies and registries. Misdiagnosis occurs in about one-fifth of patients, highlighting the benefits of novel diagnostic tools for earlier, more accurate diagnosis.<br/

Misdiagnosis and prevalence of rheumatological diseases in early inflammatory arthritis clinic: Results from a UK single-centre retrospective cohort study

ObjectivesNovel diagnostic tools have been developed to aid diagnosis and reduce misdiagnosis. However, the accuracy of these tools depends on estimates of disease prevalence. This study aimed to determine the prevalence of rheumatological diseases in a real-world cohort of patients and assess the rate of misdiagnosis at first presentation and follow-up.MethodsPatients with symptoms of inflammatory arthritis were referred by primary care. Rheumatologists made initial diagnoses, initiated treatment, and revised diagnoses during follow-up. Clinical data including diagnoses were extracted from electronic patient records. ResultsOver two years, 260 patients were seen. Most patients presented with peripheral joint symptoms (95%), and 23% had axial involvement. Psoriasis was present in 15%, inflammatory bowel disease in 4%, and uveitis in 4%. Autoantibodies were positive for CCP in 11% and rheumatoid factor in 12%.Seventeen percent (n=45) of patients were misdiagnosed, with 8% (n=20) initially diagnosed one of the five most common rheumatological conditions but later found to have a non-inflammatory disorder. Conversely, 7% (n=17) initially received a diagnosis of an “Other rheumatological disease” but later had their diagnoses revised to one of the five most common rheumatological conditions.ConclusionDisease prevalence is context-specific, and prevalence estimates in the intended setting should be determined prior to implementation of novel diagnostic tools. In real-world cohorts, non-inflammatory diseases like chronic pain syndromes were more prevalent than in observational studies and registries. Misdiagnosis occurs in about one-fifth of patients, highlighting the benefits of novel diagnostic tools for earlier, more accurate diagnosis.<br/

The Use of Human Serum Samples to Study Malignant Transformation: A Pilot Study

Obesity and excess adiposity account for approximately 20% of all cancer cases; however, biomarkers of risk remain to be elucidated. While fibroblast growth factor-2 (FGF2) is emerging as an attractive candidate biomarker for visceral adipose tissue mass, the role of circulating FGF2 in malignant transformation remains unknown. Moreover, functional assays for biomarker discovery are limited. We sought to determine if human serum could stimulate the 3D growth of a non-tumorigenic cell line. This type of anchorage-independent 3D growth in soft agar is a surrogate marker for acquired tumorigenicity of cell lines. We found that human serum from cancer-free men and women has the potential to stimulate growth in soft agar of non-tumorigenic epithelial JB6 P+ cells. We examined circulating levels of FGF2 in humans in malignant transformation in vitro in a pilot study of n = 33 men and women. Serum FGF2 levels were not associated with colony formation in epithelial cells (r = 0.05, p = 0.80); however, a fibroblast growth factor receptor-1 (FGFR1) selective inhibitor significantly blocked serum-stimulated transformation, suggesting that FGF2 activation of FGFR1 may be necessary, but not sufficient for the transforming effects of human serum. This pilot study indicates that the FGF2/FGFR1 axis plays a role in JB6 P+ malignant transformation and describes an assay to determine critical serum factors that have the potential to promote tumorigenesis