ABSTRACT
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is a pro-inflammatory cytokine that stimulates myeloid stem cell maturation, proliferation, and migration into circulation. Despite being a known growth factor, the impact of G-CSF on solid tumours has not been well examined. G-CSF receptor (G-CSFR) is expressed by some tumours, and thus the aim of this study was to examine the expression and impact of G-CSF and G-CSFR on gastrointestinal tumours. METHODS: In this study, G-CSF expression was examined in human gastric and colon tumours and by tumour-derived stromal myofibroblasts and carcinoma cells. G-CSFR expression was examined on carcinoma cells isolated from human tissues. The effects of G-CSF on gastric and colon carcinoma cell proliferation, migration, and signalling were examined. RESULTS: G-CSFR was highly expressed in 90% of human gastric and colon carcinomas. G-CSF was also found to be highly produced by stromal myofibroblasts and carcinoma cells. Exposure of carcinoma cells to G-CSF led to increased proliferation and migration, and expansion of a sub-population of carcinoma cells expressing stem-like markers. These processes were dependent on ERK1/2 and RSK1 phosphorylation. CONCLUSIONS: These data suggest that the G-CSF/R axis promotes gastric and colorectal cancer development and suggest they are potential tumour targets.
Subject(s)
Carcinoma/genetics , Carcinoma/pathology , Cell Movement/genetics , Colonic Neoplasms/genetics , Granulocyte Colony-Stimulating Factor/genetics , Receptors, Granulocyte Colony-Stimulating Factor/genetics , Stomach Neoplasms/genetics , Caco-2 Cells , Cell Growth Processes/genetics , Cell Line, Tumor , Colonic Neoplasms/pathology , Humans , MAP Kinase Signaling System/genetics , Myofibroblasts/pathology , Ribosomal Protein S6 Kinases, 90-kDa/genetics , Stomach Neoplasms/pathologyABSTRACT
Methods for scoring the severity of radiological change in patients with ankylosing spondylitis using plain X-rays of the sacroiliac (SI) joints and lumbar spine and computerized tomographic (CT) scans of the SI joints were evaluated in a cohort of 70 patients. Analysis of reproducibility was by the kappa statistic. Significant change over 12 months in a subgroup of patients was demonstrated by these scores. Ankylosis correlates negatively with erosions and sclerosis and the change in SI joint ankylosis correlates negatively with change in SI joint erosions as seen on CT scan. The clinical and laboratory correlates of these findings were examined. Pain, stiffness and sleep disturbance correlated positively with increasing SI joint sclerosis on CT scanning (r = 0.45; P less than 0.05) but negatively with ankylosis (r = -0.43; P less than 0.05). Orosomucoid levels predicted an increase in the radiological lumbar spine score. No other clinical or laboratory variable predicted radiological change.
Subject(s)
Spondylitis, Ankylosing/diagnosis , Cohort Studies , Humans , Longitudinal Studies , Lumbar Vertebrae/diagnostic imaging , Observer Variation , Orosomucoid/metabolism , Pain Measurement , Reproducibility of Results , Sacroiliac Joint/diagnostic imaging , Severity of Illness Index , Spondylitis, Ankylosing/blood , Spondylitis, Ankylosing/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
In a 12-month double-blind placebo-controlled trial, the effect of sulphasalazine was studied in 40 patients with ankylosing spondylitis. The treatment group showed significant improvement in pain, stiffness, sleep disturbance (p less than 0.05), finger/floor distance, erythrocyte sedimentation rate, C-reactive protein, orosomucoid and IgA levels (p less than 0.01). There was improvement in sleep disturbance (p less than 0.05), finger/floor distance and erythrocyte sedimentation rate (p less than 0.01) in the placebo group. Sulphasalazine did not retard radiological progression as measured either by plain X-ray or computerised tomographic scans. Multiple analysis of variance did not show a significant difference in disease activity indicators between the 2 groups.
Subject(s)
Spondylitis, Ankylosing/drug therapy , Sulfasalazine/therapeutic use , Analysis of Variance , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Blood Sedimentation/drug effects , C-Reactive Protein/metabolism , Cohort Studies , Double-Blind Method , Haptoglobins/metabolism , Humans , Immunoglobulin A/metabolism , Orosomucoid/metabolism , Spondylitis, Ankylosing/diagnostic imaging , Spondylitis, Ankylosing/metabolism , Spondylitis, Ankylosing/pathology , Sulfasalazine/pharmacology , Tomography, X-Ray ComputedABSTRACT
Quantitative sacroiliac and lumbar spine radio-isotope (Tc-99m MDP) scans were performed in 42 patients with ankylosing spondylitis, and repeated 12 months later in 25. Clinical and laboratory assessments as well as computerised tomographic (CT) scans of the sacroiliac joints (SIJ) and lateral lumbar spine x-rays, were performed. Bone (using the L3/4 area of the lumbar spine, sacrum, SIJ's and knee) to soft tissue (ST) ratios all correlated strongly with each other. Patients with high SIJ:ST ratios had significantly greater low-back stiffness (p less than 0.05). Change in serum IgA levels correlated negatively with change in bone: ST ratios. There was no relationship between bone: ST ratios and any other clinical or laboratory variables. The change in SIJ:ST ratios correlated positively with change in CT erosion score (p less than 0.05) and negatively with change in CT ankylosis score (p less than 0.05).
