VEGF in the culture of PMN and the serum in oral cavity cancer patients.

Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that plays a pivotal role in angiogenesis in vivo. In the present study we examined the ability of polymorphonuclear neutrophils (PMN) to secrete VEGF confronted with the serum levels in oral cavity cancer patients. To investigate whether VEGF may have a prognostic importance, its value in the serum and the culture supernatants was related to the clinical course of patients. The levels of VEGF in the culture supernatant of PMN from patients were significantly higher than those from control. Increased VEGF production by PMN according to clinical progression disease, observed in the present study, seems to suggest a stimulating role of tumour cells in VEGF production by PMN. Additionally, a decrease in the ability of PMN to VEGF release after surgery may be caused by a removal of the tumour mass and then the lack the effects of tumour cells on PMN function. Results obtained appear to suggest that PMN can contribute significantly to the initiation and amplification of tumour angiogenesis and metastasis in oral cavity cancer patients. Increased values of VEGF with progression of disease and decreased values after surgery treatment clearly suggest that VEGF can play a role as a tumour marker in oral cavity cancer patients.

TNF-alpha, IL-6 and their soluble receptor serum levels and secretion by neutrophils in cancer patients.

Simultaneous evaluation of cytokines and their soluble receptor production and the serum levels can be helpful in understanding the local and systemic immune response of a tumor-bearing host. In the present study we examined serum levels of TNF-alpha, IL-6 and their soluble receptors: sTNFRp55, sTNFRp75 and sIL-6R confronted with their production by the polymorphonuclear neutrophils (PMN) from cancer patients. Examinations were carried out in patients with adenocarcinoma breast cancer and squamous cell carcinoma of the oral cavity and related to the clinical course and to different phases of therapy. Secretion of IL-6, sTNFRp55 and sTNFRp75 by PMN appeared to be dependent on tumor type, clinical progression of disease as well as on therapy, suggesting a significant role of these cells at different phases of the immune response to cancer associated with these mediators. Changes in values of TNF-alpha, IL-6 and their soluble receptors in sera of both cancer groups, dependent on tumor type, clinical progression and cancer therapy, could have a diagnostic and prognostic role in cancer disease.

Effect of IL-15 on the secretion of IL-1beta, IL-1Ra and sIL-1RII by PMN from cancer patients.

In the present study, we demonstrate an effect of rhIL-15 on the simultaneous secretion of IL-1beta and its natural inhibitors IL-1Ra and sIL-1RII by human neutrophils isolated from normal and tumour-bearing hosts (oral cavity cancer and melanoma patients) compared with serum IL-15 levels. We found an rhIL-15 influence on IL-beta and IL-1Ra secreted by PMN from healthy controls. In contrast, the PMNs from cancer patients were not sensitive to rhIL-15 stimulation. However, we found a priming effect of rhIL-15 on IL-1beta production by LPS-stimulated cells in oral cavity cancer. We also found no effect on sIL-1RII release by PMN from cancer patients.

IL-1beta, IL-1Ra and sIL-1RII in the culture supernatants of PMN and PBMC and the serum levels in patients with inflammation and patients with cancer disease of the same location.

An inflammation or an other malignant process may create a microenvironment that modulates the production and activity of cytokines and their regulators. In the present study we compared the secretion of IL-1beta and its regulatory proteins: IL-IRa and sIL-1RII by PMN and PBMC derived from patients with inflammation and patients with cancer disease of the same location. We also examined the serum levels of these mediators in groups of patients. The results obtained revealed changes in the secretion of IL-1beta and IL-1Ra which are more characteristic of PMN and PBMC from cancer patients than of the cells from patients with inflammation. In contrast, the secretion of sIL-1RII is more characteristic of PMN and PBMC derived from patients with inflammation. Furthermore, PMN appear to play more significant role in the secretion of IL-1Ra into the circulation of cancer patients than PBMC. In contrast, PBMC affect to a large extent the secretion of IL-1beta and sIL-1RII into the circulation of patients with inflammation than PMN. Concluding, the secretion of IL-1beta and its regulatory proteins may depend on the type of immune cells and the type of the disease.

[GM-CSF in the culture supernatants of neutrophils and serum levels in patients with inflammation and squamous cell carcinoma of oral cavity]. / GM-CSF w hodowlach neutrofilów i w surowicy chorych ze stanem zapalnym i rakiem plaskonablonkowym jamy ustnej.

The aim of this study was to comparison GM-CSF concentrations in the culture supernatants of neutrophils (unstimulated and LPS-stimulated) and the serum of patients with inflammation and squamous cell carcinoma of oral cavity. PMN from both patient groups exhibited decreased the ability to release of GM-CSF. PMN from patients with inflammation secreted a lower concentrations of GM-CSF than those from cancer patients. PMN from patients with inflammation were more reactivity after LPS-stimulation in comparison with cells from cancer group. GM-CSF serum levels in patients with inflammation and cancer were nonsignificantly higher in comparison with control. There was no correlation between GM-CSF in the culture supernatants of PMN and the serum levels in patient groups. The decreased GM-CSF production may lead to unfavourable effects for immune response of patients with inflammation as well as patients with cancer disease.

Tumor necrosis factor-alpha and soluble tumor necrosis factor receptors in the culture supernatants of polymorphonuclear cells and peripheral blood mononuclear cells from cancer patients.

Recent clinical and experimental studies have focused on the measurement of cytokines and their regulators, produced by immunocompetent cells. Their estimation may be used as parameters for the immune potential of cancer patients. In the present study we studied the ability of unstimulated and lipopolysaccharide (LPS)-stimulated polymorphonuclear cells (PMN) and peripheral blood mononuclear cells (PBMC) from oral cavity cancer and breast cancer patients to release tumor necrosis factor alpha (TNF-alpha) and soluble tumor necrosis factor receptors (sTNFR). There were significant differences concerning the parameters examined for PMN and PBMC from cancer patients as compared with normal subjects. We found significantly higher concentrations of sTNF-R p75 than sTNF-R p55 in the cell-culture supernatants. The culture supernatants of cells from oral cavity cancer patients contained higher concentrations of TNF-alpha and lower concentrations of sTNF-R p55 and sTNF-R p75 in comparison with breast cancer cell supernatants. In contrast, cells from breast cancer patients secreted lower concentrations of TNF-alpha and higher concentrations of sTNF-R p55 and sTNF-R p75. Although PBMC secreted higher concentrations of mediators than PMN, the quantitative dominance of PMN in the peripheral blood suggests an essential role of these cells in the defense reactions controlled by TNF-alpha.

Soluble IL-6 receptor release by PMNs and PBMC in patients with oral cavity cancer.

It is known that the main source of cytokine and soluble cytokine receptors are mononuclear cells in the peripheral blood. Data including the release of soluble mediators by polymorphonuclear cells (PMNs) are controversial. In these examinations using an in vitro model, we studied the ability of spontaneous and LPS-stimulated PMNs to the release of soluble IL-6 receptor (IL-6sR) in oral cavity cancer patients. Obtained results were compared to the release of IL-6sR by a peripheral blood mononuclear cells (PBMC) and the serum levels. The concentrations of IL-6sR in the culture supernatants of cells and in the serum were tested by ELISA. The culture supernatants of spontaneous and LPS-stimulated PMNs derived from oral cavity cancer patients contained an insignificant lower concentrations of IL-6sR than those from healthy subjects. The concentrations of IL-6sR released by PBMC were higher than those released by PMNs in both control and patient groups. There was correlation between the amounts of IL-6sR in the culture supernatants of spontaneous PMNs and PBMC. The altered ability of PMNs and PBMC to the release of IL-6sR may influence the immune response of host to tumor mediated by IL-6.