[The efficacy of polychromatic visible and infrared radiation used for the postoperative immunological rehabilitation of patients with breast cancer].

The immunological rehabilitation of the patients with oncological problems after the completion of standard anti-tumour therapy remains a topical problem in modern medicine. The up-to-date phototherapeutic methods find the increasingly wider application for the treatment of such patients including the use of monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers and photodiodes. The objective of the present study was to substantiate the expediency of postoperative immune rehabilitation of the patients with breast cancer (BC) by means of irradiation of the body surface with polychromatic visible (pVIS) in combination with polychromatic infrared (pIR) light similar to the natural solar radiation without its minor UV component. The study included 19 patients with stage I--II BC at the mean age of 54.0 +/- 4.28 years having the infiltrative-ductal form of the tumour who had undergone mastectomy. These patients were randomly allocated to two groups, one given the standard course of postoperative rehabilitation (control), the other (study group) additionally treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1 to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter of 15 cm). The modern standard immunological methods were employed. It was found that mastectomy induced changes of many characteristics of cellular and humoral immunity; many of them in different patients were oppositely directed. These changes were apparent within the first 7 days postoperatively. The course of phototherapy (PT) was shown to prevent the postoperative decrease in the counts of monocytes and natural killer (NK) cells, the total amount of CD3+ -T-lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells) and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted bacteria. Moreover PT promoted faster normalization of postoperative leukocytosis and activation of cytotoxic CD8+ -T-LPC, reduced the elevated concentration of immune complexes in blood. Among the six tested cytokines, viz. IL-1beta, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma, only the latter two underwent significant elevation of their blood concentrations (IL-6 within 1 day) and IFN-gamma (within 7 days after mastectomy). The course of PT resulted in the decrease of their levels to the initial values. The follow-up of the treated patients during 4 years revealed neither recurrence of the disease nor the appearance of metastases.

[Proliferation of normal and tumor cells at the presence of serum from patients with breast cancer after phototherapy with visible and near infrared light].

Simultaneous low-intensity visible (VIS) and near infrared (nIR) irradiation from laser and non-laser sources was used for treatment of complications developing in cancer patients after surgical tumor resection, chemo- and radiation therapy. However, the question remains about the impact of this physiotherapeutic method on proliferative activity of the patients' tumor cells and cells involved in wound healing, fibroblasts (FB) and keratinocytes (KC). In this paper, we studied the effect blood serum obtained from the patients with breast cancer after the course of irradiation with visible and NI light (480--3400 nm, 95 % polarization, 40 mW/cm2, 12 J/cm2) in postoperative period on the proliferative activity of primary cultures of human FB and KC, and of several human tumor cell lines (BT-474, HBL-100, Hs578T and A431). Seven-day course of phototherapy increase proliferation of FB (as compared to the initial level) and KC (as compared to postoperative level) by 22 and 28 %, respectively. The tumor cells BT-474, Hs578T and A431 showed statistically significant decrease in proliferative activity compared with the preoperative (initial) level by 31.5, 8.97 and 6.47%, respectively, whereas the cells BT-474, HBL-100, Hs578T and A431 also reduced their proliferative activity by 32,16, 8.65 and 6.26%, respectively, as compared with postperative level. The results obtained demonstrate the safety of the phototherapy with the visible and NI light for BC patients in the postoperative period.

[Application of low-power visible and near infrared radiation in clinical oncology].

Although low-power visible (VIS) and near infrared (nIR) radiation emitted from lasers, photodiodes, and other sources does not cause neoplastic transformation of the tissue, these phototherapeutic techniques are looked at with a great deal of caution for fear of their stimulatory effect on tumour growth. This apprehension arises in the first place from the reports on the possibility that the proliferative activity of tumour cells may increase after their in vitro exposure to light. Much less is known that these phototherapeutic modalities have been successfully used for the prevention and management of complications developing after surgery, chemo- and radiotherapy. The objective of the present review is to summarize the results of applications of low-power visible and near infrared radiation for the treatment of patients with oncological diseases during the last 20-25 years. It should be emphasized that 2-4 year-long follow-up observations have not revealed any increase in the frequency of tumour recurrence and metastasis.

[Changes in cytokine content in the peripheral blood of volunteers after their exposure to polychromatic visible and infrared light].

Anti-inflammatory, immunomodulating and wound-healing effects of visible and infrared (IR) radiation from laser and non-laser sources are widely used in current medicine. However, the role of pro- and anti-inflammatory cytokines in development of these effects has been poorly studied. A randomized, placebo-controlled, double blind study was made. Using ELISA, the content of 10 cytokines was studied in the peripheral blood of volunteers after a single and four daily irradiations of the sacral area (D = 15 cm) with polychromatic visible + IR polarized light (480-3400 nm, 12 J/cm2). The phototherapeutic sessions were accompanied by four blood exfusions for the study (to a total volume of 80 ml). In the control (placebo) group, irradiation was imitated, and blood samples of the same volume were drawn at the same time intervals as in volunteers of the main group. A fast decrease in the level of pro-inflammatory cytokines was revealed as soon as in 0.5 h after the irradiation. This level was retained until the end of the phototherapeutic course. At the parameters exceeding the norm, the contents of TNF-alpha, IL-6 and IFN-gamma fell, on average, by 34, 12 and 1.5 times, respectively. By the end of the course, the levels of IFN-gamma and of IL-12 decreased by 5 and 15 times, respectively. A fast decrease (by two-fold) was also characteristic of normal values of IL-6. Neither IL-1beta, nor IL-2 were detected in blood plasma of the examined people both before and after the irradiation. In parallel with a decrease in the proinflammatory factor levels the amount of anti-inflammatory cytokines was found to rise: that of IL-10--by 2.7-3.5 times in 0.5 h and at later terms at the initially normal parameters, and that of TGF-beta1--by 1.4-1.5 times at the initially decreased level. The IL-4 content did not change. A characteristic feature of the light effect was a fast rise of IFN-gamma amount--by 3.3-4.0 times in individuals with its initially normal level, with no changes in IFN-alpha content. The above-reported regularities of the light effects were also recorded at a direct (in vitro) irradiation of the examined volunteers' blood, as well as on addition of irradiated blood to a 10-fold volume of non-irradiated autologous blood, i.e. at a modeling of mixing, of a small amount of transcutaneously photomodified blood with its main circulating volume in the vascular bed of an irradiated person. Such a similarity of effects in blood following its irradiation in vivo and in vitro enables us to associate the fast changes of the cytokine content in the entire volume of peripheral blood with the transcutaneous photomodification of its small amounts, and with a "transfer" of the light effects by photomodified blood to the whole pool of circulating blood.

[Modulation of proliferation of peripheral blood lymphocytes after irradiation of volunteers with polychromatic visible and infrared light]. / Moduliatsiia proliferatsii limfotsitov perifericheskoi krovi posle oblucheniia dobrovol'tsev polikhromaticheskim vidimym i infrakrasnym svetom.

Effects on human immune system of visible and infrared (IR) radiation, the dominating types of solar light on Earth, still remain poorly studied. In the present work, a small area of the volunteers' body surface was irradiated with polychromatic visible + IR polarized (VIP) light, whose spectral range is close to the natural one (400-3400 nm, 12 J/cm2), and spontaneous and phytohemagglutinin (PHA)-induced DNA syntheses were studied by radiometric method in lymphocytes (Lym) of peripheral blood. This Irradiation stimulated both spontaneous and PHA-induced DNA synthesis in Lym but only in volunteers with initially decreased parameters of synthesis (on average, by 2.5 and 2.7 times, respectively), which was recorded 24 h after irradiation of volunteers, and after a 72 h cultivation of separated mononuclears. In the parallel experiments, blood of each volunteer was irradiated in vitro. Besides, by modeling situation in vivo, when a small amount of transcutaneously photomodified blood contacts its much larger circulating volume, the irradiated and non-irradiated samples of autologous blood were mixed at a 1:10 volume ratio. In Lym with the initially decreased synthesis level, the spontaneous synthesis elevated by 2 and 3 times, respectively, whereas stimulation of PHA-synthesis was observed only after addition of the irradiated blood to the intact one (by 2.2 and 1.6 times, respectively). A high degree of positive correlation in changing the studied parameters is revealed in irradiation of blood in vivo and in vitro. This makes it possible to associate the light-stimulating effect on Lym of the entire circulating blood with transcutaneous photomodification of its small amounts, and with action of such blood on the rest of blood. A similarity in the direction and additivity of mitogenic effects of VIP light and PHA was revealed. The obtained data enable us to suggest that therapy employing polychromatic visible and IR light would promote presumably an increase in the number of Lym in peripheral blood and an enhancement of their response to antigenic stimulus.

[Enhancement of fibroblast growth promoting activity of human blood after its irradiation in vivo (transcutaneously) and in vitro with visible and infrared polarized light]. / Povyshenie rostostimuliruiushchei aktivnosti krovi cheloveka dlia fibroblastov posle ee oblucheniia in vivo (transkutanno) i in vitro vidimym i infrakrasnym poliarizovannym svetom.

Visible and infrared (IR) irradiation of laser and non-laser sources has a pronounced wound-healing effect promoting tissue repair without hyperproduction of connective tissue elements. This effect develops as a consequence of local and systemic light effects, but many aspects of their mechanism have been yet unclear. In the present work, we have shown that in 0.5 h after irradiation of a small area of the volunteers' body surface with polychromatic visible + IR light (400-3400 nm, 95% polarization, 12 J/cm2) the amounts of PDGF and TGF-beta 1 in the blood serum increase, on average, by 20 and 43%, respectively. This effect is preserved for at least 24 h to be recorded only in volunteers with the initially normal and decreased levels of the growth factors; the initially elevated content of PDGF-AB decreases. Addition of such a plasma (2.5%) to the nutrient medium of primary cultures of human embryonal fibroblasts stimulates cell proliferation, on average, by 10 and 17%, but only in the case if the initial growth-promoting (GP) blood activity was low. Similar changes occur in parallel experiments following irradiation of blood samples of the same volunteers in vitro, as well as at mixing irradiated and non-irradiated autologous blood at the ratio 1:10 (v/v), i.e. at modeling a situation in the vascular bed, when the transcutaneously photomodified blood contacts with the rest of its volume. Similar changes in the blood GP activity under conditions in vitro were recorded as well after 4-9 daily phototherapy sessions. This allows us to suggest that changes in GP activity of circulating blood of the irradiated volunteers may be, to a large extent, the consequence of effect exerted on the blood by small amounts of transcutaneously photomodified blood. The obtained results are discussed in terms of light effect on wound healing and scar tissue formation, with regard to the authors' previous data on much higher GP of the irradiated blood in respect to keratinocytes, the fast decrease in proinflammatory cytokine levels, and the increase in IFN-gamma content.

[Changes in the expression of membrane markers and in the number of human blood monocytes after single and repeated courses of visible and infrared light at therapeutic doses]. / Izmeneniia ékspressii membrannykh markerov i kolichestva mononuklearov krovi cheloveka posle ee oblucheniia in vivo i in vitro vidimym i infrakrasnym svetom v terapevticheskikh dozakh.

An attempt has been made to prove that the immunomodulating effect of therapeutic doses of polychromatic visible + infrared polarized (VIP) light at its application to a small body surface area is connected with a transcutaneous photomodification of a small amount of blood in superficial skin microvessels. For this purpose, in parallel experiments, using monoclonal antibodies, the membrane phenotype of circulating blood mononuclears was studied after irradiation of volunteers, of samples of their blood in vitvo, and of a mixture of the irradiated and non-irradiated autologous blood in a 1:10 volume ratio, thereby modeling events in vivo, when a small amount of the transcutaneously photomodified blood in the vascular bed contacts its main circulating volume. In this variant of experiment, a great similarity has been established of changes in expression of mononuclear membrane markers (CD3, CD4, CD8, CD20, CD16, HLA-DR and to a lesser degree of CD25); the ability has been proven of the photomodified blood to "translate" the light-induced changes to a much higher volume of non-irradiated blood, which might represent a mechanism of the systemic immunomodulating effect of phototherapy. Under conditions in vivo and in vitro, the most "reactive" were HLA-DR+, CD20+, CD16+, CD4+, and 0-cells. An increase of the total number of lymphocytes and monocytes has been shown by the end of the 10-day-long phototherapeutic course. The regulatory character of the single and course sessions of the VIP light on the blood immunocompetent cells is substantiated: depending on the initial state of the immune system, the VIP light can produce both stimulating and inhibitory effect on lymphoid cell subpopulations, which opens large possibilities of using this method for correction of immunological disturbances in diseases of different etiopathogenesis.