Polychromatic light (480-3400nm) similar to the terrestrial solar spectrum without its UV component in post-surgical immunorehabilitation of breast cancer patients.

To this day, two methods of phototherapy (PT) have been successfully used in post-surgical immunorehabilitation of patients with breast cancer (BC): intravenous laser irradiation of the patients' blood and reinfusion of lympholeukosuspension of BC patients after single irradiation with HeNe laser. The objective of this pilot experimental study was to verify the effectiveness of the percutaneous use of polychromatic visible light combined with polychromatic infrared (pVIS+pIR) radiation similar to the major components of natural solar spectrum in post-surgical management of BC patients. Patients with BC (adenocarcinoma) of I-II stages, n=19 who had undergone mastectomy, were divided into 2 groups. The control group of patients (n=8) underwent a conventional course of post-surgical rehabilitation and sham irradiation. Patients of the PT group (n=11) additionally received 7days of daily treatment with polychromatic light on the sacral area, D=15cm. The PT course began on the day after mastectomy (Bioptron-2 device; Switzerland, 480-3400nm, 95% polarization, 40mW/cm2, 24J/cm2). Mastectomy produced many changes in cellular and humoral immunity, which was recorded on the 1st and 8th post-surgical days. The PT course resulted in a faster normalization of post-surgical leukocytosis and activation of cytotoxic CD8+ T-lymphocytes (Lym), reduced the elevated concentration in blood of immune complexes and in parallel promoted cytotoxic activity of CD16+/CD56+ NK-cells. The PT up-regulated the number of NK-cells in patients with its decrease on the 1st post-surgical day and prevented the decrease in the amount of monocytes, CD19+ B-Lym, CD3+ T-Lym, CD4+ T-helpers, activated CD3+/HLADR+ T-Lym, and the decrease of the phagocytotic capability of neutrophils. PT blocked the down-regulation of the IgM, IgA concentration and abnormally sharp increase of the proinflammatory cytokine IFN-γ content. Therefore, a 7-day course with polychromatic light prevented the development of immunosupression in the BC patients at the early post-mastectomy period.

Exogenously delivered heat shock protein 70 displaces its endogenous analogue and sensitizes cancer cells to lymphocytes-mediated cytotoxicity.

Hsp70 chaperone is known to stimulate anti-tumour immunity in a variety of cancer models. Here we demonstrated that the addition of purified recombinant Hsp70 to the culture medium facilitated cancer cell cytolysis by lymphocytes. Importantly, exogenous Hsp70 triggered secretion of the intracellular Hsp70 to a cell surface and extracellular milieu, which played a role in cytolysis because down-regulation of the endogenous Hsp70 reduced both its presence at the cell surface and the lymphocyte-mediated cytolysis. Inhibitors that target both the ATPase and the peptide-binding domains of Hsp70 molecule potently decreased its anti-tumor effect. Using a variety of cell transport markers and inhibitors, we showed that the exchange of exogenous and intracellular Hsp70 is supported by classical and non-classical transport pathways, with a particular role of lipid rafts in the chaperone's intracellular transport. In conclusion, exogenous Hsp70 can eject endogenous Hsp70, thus exerting anticancer activity.

Interactions of C-Reactive Protein and Serum Amyloid P Component with Interleukin-8 and Their Role in Regulation of Neutrophil Functions.

C-reactive protein (CRP) and serum amyloid P component (SAP) are acute phase proteins, whose concentrations increase within 24 h of inflammation along with concentration of IL-8. Polymorphonuclear neutrophil leukocytes (PMNs) form the earliest barrier protecting an injured organ during acute phase response. The aim of present work was to study interactions between CRP, SAP and IL-8, and to estimate the role of these interactions in regulation of neutrophil transendothelial migration. The results have shown that IL-8 binds to immobilized but not to free CRP. Binding of IL-8 to immobilized SAP was less strong. SAP like IL-8 increased CD11/CD18 integrin expression. IL-8 did not abolish the effect of SAP, and the mixture of IL-8 and SAP has stimulated CD11/CD18 expression. CRP upregulated CD18 but not CD11b expression. Under simultaneous action of CRP and IL-8, the stimulatory effect on CD11b and CD18 was abolished. The expression of fibronectin receptor was reduced by either IL-8 or CRP but increased by SAP. Effect of each protein was downregulated after following preincubations: CRP+SAP, CRP+IL-8 or SAP+IL-8. The mixtures of CRP with SAP, CRP with IL-8 or SAP with IL-8 showed no chemotactic activity, although each of the proteins was chemoattractive. Thus, acute phase proteins and IL-8 can act as anti-inflammatory factors upon binding each other. In summary, CRP and SAP influence PMN adhesion, migration and expression of CD11b/CD18 and fibronectin receptors, and can modulate the action of IL-8 on PMN attachment to endothelium and fibronectin, and on PMN traffic through the extracellular matrix during transendothelial migration.