Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?

Metastasis is the principal cause of cancer mortality, with the lymphatic system being the first route of tumor dissemination. The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF) family, whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation, lymphatic system disorders and malignant tumor metastasis. They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell, resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis). Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Experimental and clinicopathological studies have linked the VEGF-C, VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors. The majority of these data are derived from surgical specimens and malignant cell series, rendering their clinical application questionable, due to subjectivity factors and post-treatment quantification. In an effort to overcome these drawbacks, an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric, esophageal and colorectal cancer. Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.

Subclinical atherosclerosis and impaired bone health in patients with primary Sjogren's syndrome: prevalence, clinical and laboratory associations.

INTRODUCTION: To determine the prevalence and clinical/laboratory associations of subclinical atherosclerosis and impaired bone health in primary Sjogren's syndrome (SS). METHODS: 64 consecutive patients with primary SS, 77 with rheumatoid arthritis (RA) and 60 healthy controls (HC) οf similar age and sex distribution were enrolled. Demographics, clinical/laboratory features, classical risk factors for atherosclerosis and osteoporosis (OP) were recorded. Intima-medial thickness scores (IMT) and carotid/femoral (C/F) plaque formation, as well as bone mineral density (BMD) and fractures were evaluated. Determinants of IMT/BMD levels and the presence of plaque were assessed by univariate and multivariate models. Serum levels of the Wnt signaling mediators Dickkopf-related protein 1(DKK1) and sclerostin were determined in primary SS patients and HC. RESULTS: Increased arterial wall thickening (IMT > 0.90 mm) and impaired bone health (defined as OP or osteopenia), were detected in approximately two-thirds of primary SS and RA patients, with a mean IMT value being significantly increased compared to HC. The presence of primary SS emerged as an independent risk factor for arterial wall thickening when traditional risk factors for cardiovascular disease (CVD) including age, sex, hypertension, smoking (pack/years), LDL and HDL levels were taken into account in a multivariate model [adjusted OR 95% (CI): 2.8 (1.04-7.54)]. In primary SS, age was revealed as independent predictor of increased IMT scores; age and lymphopenia as well as increased urine pH as independent determinants of C/F plaque formation and OP/osteopenia, respectively. An independent association of OP/osteopenia with plaque formation was observed when independent predictors for both variables were considered, with low DKK1 levels being associated with both plaque formation and lower BMD levels. CONCLUSIONS: Comorbidities such as subclinical atherosclerosis and impaired bone health occur frequently in primary SS, in association with disease related features and traditional risk factors. Wnt signaling mediators are potentially involved in the pathogenesis of both entities.

Role of the hematopoietic cytokines SCF, IL-3, GM-CSF and M-CSF in the diagnosis of pancreatic and ampullary cancer.

BACKGROUND: Previous studies have demonstrated altered levels of hematopoietic cytokines in the serum of patients with different types of cancer. METHODS: We measured the serum levels of the hematopoietic cytokines stem cell factor (SCF), interleukin 3 (IL-3), macrophage-colony stimulating factor (M-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) in 40 pancreatic and ampullary cancer patients and 40 healthy volunteers, using ELISA. We also assessed the most widely used pancreatic tumor markers, carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA), in both groups. We then correlated the concentrations of the cytokines' and the tumor markers in the patients' serum and we estimated their diagnostic ability by calculating diagnostic sensitivity and specificity, positive and negative predictive values and the receiver operating characteristic (ROC) curve. RESULTS: The SCF and IL-3 levels were significantly lower and the M-CSF levels significantly higher in pancreatic cancer patients than in controls. There were significant positive correlations between the serum levels of CEA and M-CSF, GM-CSF and SCF, and between GM-CSF and IL-3. The area under the ROC curve and diagnostic sensitivity of M-CSF were greater than those of SCF and IL-3. The diagnostic sensitivity of the combined use of SCF and M-CSF reached 97.5%. CONCLUSION: The diagnostic ability of M-CSF and SCF in pancreatic and ampullary cancer should stimulate further studies evaluating their clinical usefulness as tumor markers.