[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.

[Survival among patients with prostate cancer after distant radiotherapy and low-intensity near-infrared phototherapy].

The paper discusses the effect of photography with near-infrared photography on survival of patients with prostate cancer (PC) after distant radio- (DRT) and hormonal therapy (January 2000 - June 2007). The control group (n=251) were treated with standard radio- and hormonal therapy alone. Besides, patients of the study group (n=308) received phototherapeutic treatment to prevent radiation-induced injuries of the urinary bladder and rectum. The groups were compared relatively to PC cell differentiation, DRT and hormonal treatment. Survival was evaluated (Caplan-Meyer); log-rank test was used to compare the results. Overall survival in the study group of patients with localized (T1-2N0 M0) and generalized (T1-4N0-1 M1) tumors did not differ from that of controls (p > or = 0.05). In patients with locally advanced tumors (T3-4N0-1 M0, T1-4N1 M0), significant differences in survival between controls and study group were recorded beginning from year 3 of the investigation: 5-year survival rates were 67% and 89%, respectively (p < or = 0.05).

[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.

[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.

[Changes in the surface and activation of circulating leukocytes after autologous transfusion of UV-irradiated blood]. / Izmeneniia poverkhnosti i aktivatsii tsirkuliruiushchikh leikotsitov pri autotransfuziiakh UF-obluchennoi krovi.

Under study was the dynamics of functional properties of leukocytes of healthy people and patients after UV-irradiation of their blood, mixing the UV-irradiated and non-irradiated blood. It was shown that UV-irradiation and mixing the irradiated and non-irradiated blood facilitated the liberation of bactericidal cation proteins of leukocytes, higher expression of membrane receptors, growth factors, activation of reparation of DNA after its injury by gamma-rays. It proves the role of immediate activation of leukocytes of the circulating blood in trigger mechanisms of effects of autotransfusion of UV-irradiated blood.

[The relationship of the potassium transport function of human erythrocyte membranes to the structural state of the glycocalyx]. / O sviazi kaliitransportnoi funktsii membran éritrotsitov cheloveka so strukturnym sostoianiem glikokaliksa.

The two structural-functional state parameters of erythrocyte membrane in healthy donors and ischemic heart disease patients have been compared--the potassium exchange rate constant (x), and the quantity of Alcian blue sorption capacity of glycocalyx (y). The connection between the first parameter--x--and the other one--y--has been observed in cases, when the value of the latter experienced both the seasonal oscillations (the coefficient of lineal correlation was: r = -0.87, P less than 0.01) and the changes in the cause of ischemic heart disease (r = -0.72, P less than 0.01) and its treatment (the coefficients of correlation attitude of each of parameter changes were: eta xy = 0.83, P less than 0.01; eta yx = 0.52, P less than 0.05). The above connection may indicate the participation of membrane glycoproteins and glycolipids in a regulation of the cation transport function of the erythrocyte membrane.

[The effect of UV irradiation and of UV-irradiated autologous blood on the functional state of human peripheral blood lymphocytes]. / Vliianie UF-oblucheniia i UF-obluchennoi autologichnoi krovi na funktsional'noe sostoianie limfotsitov perifericheskoi krovi cheloveka.

The effect of UV irradiation (UVI, 254 nm) and of UV-irradiated autologous blood on the spontaneous and mitogen-induced DNA-synthetic activity of intact lymphocytes has been studied. Lymphocytes were isolated from nonirradiated and irradiated blood, and from the mixture of UV-irradiated blood with the intact one in the volume ratio close to that in the blood stream during UV-irradiated blood autotransfusion (1:10, 1:40, 1:160). It has been shown that UVI of the whole blood caused in some donors the increase in spontaneous DNA synthesis, while in others the decrease or no statistically significant changes were observed. The analysis of the results obtained shows an inverse relation of the UVI effect to the initial level of spontaneous DNA synthesis (r = -0.68). In contrast to direct UVI effect, an addition of UV-irradiated blood to the autologous intact one resulted in an increase in spontaneous DNA synthesis in lymphocytes of all the samples examined. A 7-day cocultivation of lymphocytes, isolated from irradiated and nonirradiated blood samples, revealed a 1.8 times increase compared to the calculated value. The mitogen-induced DNA synthesis has a low sensitivity to UV rays, since the mitogens and the irradiation of optical range have presumably the common targets. It is assumed that photomodification of HLA-D/DR antigens can be a trigger mechanism for activation of immunocompetent cells by UVI.

[Trigger mechanisms of the therapeutic effects of autologous transfusion of UV-irradiated blood (membranotropic effect on erythrocytes and thrombocytes)]. / Puskovye mekhanizmy lechebnykh éffektov autotransfuzii UF-obluchennoi krovi (membranotropnoe deistvie na éritrotsity i trombotsity).

The article sums up numerous investigations of the authors on studying different parameters of membrane-dependent properties of erythrocytes and thrombocytes after UV irradiation of blood samples, mixing of irradiated and nonirradiated blood, transfusions of UV-irradiated auto blood. It was shown that membranotropic action of UV-irradiated blood and transfusion of UV-irradiated blood are responsible for rheological and hemostatic properties of blood.

[Functional and structural changes in the surface of human erythrocytes following irradiation with ultraviolet rays of various wave lengths. V. Modification of the glycocalyx in autotransfusions of UV-irradiated blood]. / Funktsionalnye i strukturnye izmeneniia poverkhnosti éritrotsitov cheloveka posle oblucheniia UF luchami raznoi dliny volny. V. Mofifikatsiia glikokaliksa pri autotransfuziiakh UF-obluchennoi krovi.

A study was made of the structural and functional state of the erythrocyte surface components of patients with ischemic heart disease, and of patients with ulcer disease during the treatment with UV-irradiated blood autotransfusions. The cytochemical and isoserological methods employed showed some structural disturbances in the state of erythrocyte, glycocalyx and its modification in the course of treatment. The clinical results of treatment correlated with these changes.

[Functional and structural changes in the surface of human erythrocytes after UV irradiation with rays of various wavelengths. IV. Changes in the physicochemical properties of autotransfused UV-irradiated blood]. / Funktsional'nye i strukturnye izmeneniia poverkhnosti éritrotsitov cheloveka posle oblucheniia UF luchami raznoi dliny volny. IV. Izmeneniia fiziko-khimicheskikh svoistv pri autotransfuziiakh UF-obluchennoi krovi.

Properties of erythrocyte surface were investigated for patients with ischemic heart disease in the course of treatment with the UV-irradiated blood autotransfusion (UVIBA). Application of methods of light-scattering, photometry and cytochemistry revealed rapid and significant changes in deformability and aggregation properties of the erythrocytes immediately following each UVIBA procedure, which was accompanied by considerable blood viscosity decrease.

[Structural-functional characteristics of the surface of the blood mononucleocytes in children suffering from chronic dermatoses. I. The correction of the glycocalyx structure by UV irradiation of the blood and in the course of treatment with an autotransfusion of UV-irradiated blood]. / Strukturno-funktsional'nye osobennsoti poverkhnosti mononuklearov krovi detei, stradaiushchikh khronicheskimi dermatozami. I. Korrektsiia struktury glikokaliksa pri UF-obluchenii krovi i v kurse lecheniia autotransfuziei UF-obluchennoi krovi.

In children suffering from chronic dermatoses (psoriasis and neurodermatitis), the glycocalix of blood mononuclears displays an Alcian blue dye sorption by 23-25% less than that in healthy children. The UV irradiation of their blood (254 nm), in addition to a course of UV-irradiated blood autotransfusion, resulted in an elevated sorption capacity of the mononuclear glycocalix up to the normal. A possible involvement of these changes in immunocompetent cell glycocalix in the pathogenesis of chronic dermatoses is discussed, as well as the significance of glycocalix normalization in the medicinal effect of UV-irradiated blood autotransfusion.

[Effect of UV radiation and the autotransfusion of UV-irradiated blood on the content of cationic proteins in the neutrophilic granulocytes of calves]. / Vliianie UF izlucheniia i autotransfuzii UF-obluchennoi krovi na soderzhanie kationnykh belkov v neitrofil'nykh granulotsitakh teliat.

A study was made of the influence of UV-irradiation (254 nm) of blood in vitro, of the autotransfusion of UV-irradiated blood (AUVIB), and of the mixture of UV-irradiated and intact blood in vitro on the content of bactericidal cation proteins (CP) in blood neutrophil of calves suffered from dyspepsia and broncho-pneumonia. Age differences were noticed in CP contents and their decrease in neutrophils following AUVIB in vivo and administration of the mixture of blood in vitro. The decrease in cell CP contents is presumably due to neutrophil degranulation and CP release into the blood plasma. Since the initial mechanisms of neutrophil degranulation are located on the cell surface, the CP release is supposed to result from a membranotropic effect of UV-irradiated blood on the intact autologous blood. This effect may explain the increase in nonspecific resistance of organism after the AUVIB, being one of the main therapeutic phenomena of the AUVIB-therapy.

[Changes in the leukocyte phagocytic activity of donor blood after its UV irradiation. II. Simulation of the effect of the autotransfusion of UV-irradiated blood]. / Izmenenie fagotsitarnoi aktivnosti leikotsitov donorskoi krovi posle ee UF-oblucheniia. II. Modelirovanie éffekta autotransfuzii UF-obluchennoi krovi.

The UV-irradiated blood of healthy adults was supplemented with non-irradiated blood in the ratio 1:10. The phagocytic activity (PhA) of monocytes and granulocytes was seen to increase markedly in the whole mixture of blood. In this case the rise of PhA was pronounced 1.4-1.7 times as much as in the case of the non-supplemented, directly UV-irradiated blood. The enhancement of PhA depends on its initial level and may occur simultaneously with structural changes of the cell surface components. It seems reasonable to propose that PhA stimulation may be one of the earliest mechanisms in immunocorrection by UV-irradiated blood therapy.

[Changes in the leukocyte phagocytic activity of donor blood after its UV irradiation. I. Its relation to the irradiation dose and initial level of phagocytic activity]. / Izmenenie fagotsitarnoi aktivnosti leikotsitov donorskoi krovi posle ee UF-oblucheniia. I. Zavisimost' ot dozy oblucheniia i iskhodnogo urovnia fagotsitarnoi aktivnosti.

Phagocytic activity of human mono- and granulocytes increased markedly after UV blood irradiation in the apparatus "Izolda" used in hospitals of the USSR for medical treatment. With the rise of irradiation dose the ratio of cells ingesting latex particles increased, although the average number of particles ingested per cell decreased. The integrative phagocytic index poorly depended on the irradiation dose. In patients with a low initial level of phagocytic index, after UV blood irradiation it became more pronounced than in those with the initial elevated level. The enhancement of phagocytic activity is the result of a direct UV-stimulation of cells. This stimulation not mediated by irradiated blood plasma is known to inhibit the phagocytic activity of leucocytes. A possible mechanism of phagocytic activity stimulation is discussed.

[Growth-stimulating effect of UF-irradiated blood. I. The radiation dose dependence of the initial growth potencies of blood and of the functional state of the target cells]. / Rostostimuliruiushchii éffekt obluchennoi UF luchami krovi. I. Zavisimost' ot dozy oblucheniia iskhodnykh rostovykh potentsii krovi i funktsional'nogo sostoianiia kletok-mishenei.

UV irradiation (UVI) of donor blood in the apparatus used in hospitals of the USSR with the therapeutic aim of autotransfusion of UV-irradiated blood (AUVIB), results in an increase of connective tissue cell growth potency: being added into culture media the supernatants of irradiated blood stimulate DNA-synthetic and proliferative activity of cultured human embryonic cells. The high activity of cells persists for about 2 days. The effect is great with low initial levels of cell proliferative activity. In this case the effect is maximum (about 125% of the control). It is suggested that the above effect may be involved in the mechanism of stimulation of regeneration processes in the organism after AUVIB.

[Functional and structural changes in the surface of human erythrocytes after irradiation by different wave lengths of UV rays. III. The immediate effect of the autotransfusion of UV-irradiated blood]. / Funktsional'nye i strukturnye izmeneniia poverkhnosti éritrotsitov cheloveka posle oblucheniia UF luchami raznoi dliny volny. III. Nemedlennyi éffekt autotransfuzii UF-obluchennoi krovi.

The autotransfusion of UV-irradiated blood (70-200 ml) results in the structural modification of cell surface in all the circulating erythrocytes of cardiological patients. The effect is registered within 1 hour after transfusion and involves some decrease in the distribution coefficient of erythrocytes registered in two-phase polymer system dextran-poly(ethylene glycol), which depends on membrane surface properties other than charge. This effect is suggested to be responsible for the main peculiarities of the therapeutic effect of UV-irradiated blood autotransfusion--high rate of appearance, prolongation and wide spectrum of the therapeutic action.