The paper presents the latest potentialities of the endoscopic fluorescent diagnostics as well as endoscopic electric-, laser surgery and photodynamic therapy (PDT) of the early cancer in the respiratory and digestive tracts. We present in detail indication and factors determining the application of the endoscopic resection of the tumor. The advantages of the combination application of PDT, electro-, Nd:YAG laser surgery and brachitherapy are stressed. The near and remote results of endoscopic treatment of the early cancer in larynx (37), lung (109), esophagus (39) and stomach (58) are shown.

Experimental study of various modes of the semiconductor laser irradiation upon Ehrlich carcinoma in mice was carried out. Optimal patterns for distance laser scanning irradiation resulting in practically complete healing of experimental animals, were found. Selective damage of tumor tissue subjected to laser irradiation at 800 nm was evidenced in the absence of a photosensitizing agent. The results of a clinical trial completely corresponded to the experimental data. The treatment proved to be efficient in all 28 patients.

Background and objective Unsatisfactory results of traditional treatment of malignant tumors force oncologists to search new therapeutic modalities. Photodynamic therapy (PDT) is one ofthe promising and intensively developing techniques in cancer treatment. Materials and methods The results of application of photodynamic therapy for treatment of malignant tumors of various localizations were assessed. In 1992 - 1998 more than 1270 malignant tumors in 308 patients have been treated with PDT. Most of the patients have been taken into PDT for tumor recurrences or mtradermal metastases after surgery, gamma-therapy or combined treatment. Russian photosensitizers Photoheme and Photosense were used. Results Up to date we obtain the follow-up data in term from 2 months to 6 years. Therapeutic effect took place in 94.7% of cases. including complete tumor resorption in 55 .5% and partial resorption in 39.2% of cases. Conclusion The results of PDT application for treating malignant tumors allow one to estimate PDT as adequate technique. In some tumor localizations PDT may become optional technique.

The aim of the study was to determine the efficacy of photodynamic therapy (PDT) of tumors of different localization and histology with new photosensitizer aluminum sulfonated phthalocyanine (Photosense, Russia). PDT have been provided in 106 patients with different tumors. The initial dose (2.0 - 2.5 mg/kg) of PHS was significantly reduced till 0.5 - 0.8 mg/kg during clinical trials because of phototoxicity. The results of PDT, side effects and ways of their correction and prevention, as well as possibility to work out less toxic regimes of PDT with photosense, choice of laser and type of irradiation are discussed. Efficacy of PDT depended on tumor size and it's histological type. Using low doses of PHS we've reduced the phototoxicity of sensitizer with the same direct effectiveness of treatment. Undesirable changes in plasma content of antioxidants by means of high pressure liquid chromatography have been found in patients after PHS injection. Influence of short-term and long-term supplementation with beta- carotene and vitamin E on this parameters are discussed.

The frequency of tumor recurrences, according to the modern literature, remains high even in early stages of cancer (15% to 35%), the efficacy of conventional therapy for recurrent tumors is insufficient. In the State Research Center for Laser Medicine in 1992-97 photodynamic therapy with russian photosensitizers Photoheme ((lambda) equals 630 nm) and Photosense ((lambda) equals 670 nm) has been applied to 42 patients with recurrent and/or residual tumors (size corresponding to T₁ - T₄ symbols) of oropharyngeal area. We used laser irradiation for 3 - 30 minutes, power density used was from 0.05 to 1.0 W/cm², energy density - 300 J/cm². Therapeutic effect in term from 3 to 45 months was achieved in 39 (92.9%) patients. Complete resorption of tumors took place in 23 (54.8%) cases, partial resorption - in 16 (38.1%); in 3 cases (7.1%) the results of PDT were assessed as no response (tumor size decrease by less than 50%). Absolute resistance to PDT has not been noticed. The data obtained shows that PDT is a promising treatment modality for managing recurrent and residual tumors of oropharyngeal area.

The present work is based on a 12 month clinical observation period of 155 patients aged from 6 months to 15 years with multiple complications after chemoradiant treatment of hemoblastos and solid tumors. The application of Magnetic Infrared Laser therapy for different complications caused by chemoradiation treatment of children's malignant tumors is an entirely new method and for the first time has been tried in children's oncology.

A new method of radiosensitization is offered using low- intensity laser radiation (LILR). Theoretic and methodological aspects involved as well as specially developed apparatus are discussed. Radiotherapy combined with LILR was approved in 78 patients with cutaneous and oropharyngeal tumors II-IV. Combined treatment with LILR as a radiosensitizing procedure and subsequent radiotherapy doesn't increase the degree of local reactions in response to radiation, and provide the reliable improvement of the therapy outcome: the total index of significant plus pronounced tumor regression, owing to the radiosensitization, trustworthy rises from 65.7 +/- 5.8% to 84.3 +/- 4.3% (t equals 2.58; p < 0.05), the three-year survival index--from 44.6 +/- 5.5% up to 60.3 +/- 5.5% (t equals 2.02; p < 0.05).

The issue of stochastic effects of radiation exposure (mostly leukemia and cancer), and early detection of malignant tumors, as a key aspect of the problem, is of crucial importance to the population chronically exposed due to the activities of the Mayak Production Association in the Urals region (Russia). Given the large number of exposed population, screening is considered to be the most expedient method to organize medical observation of exposed persons. As was shown by the results of medical examinations conducted for 1 391 residents of the Techa riverside villages, laser correlation spectrometry (LCS) of blood plasma has proved to be a highly effective screening method for early (pre-clinical) detection of malignant neoplasms and pre-cancerous conditions. It was established that LC- spectra of blood plasma in persons with cancer and pre- cancer can easily be differentiated from non-cancer conditions. Of particular diagnostic significance is the high-frequency range of the spectrum. The development of a diagnostic algorithm has allowed to carry out a computer- based classification of blood plasma LC spectra as a component of exposed population health monitoring system.

Determination of a histological type of adrenal lesion at the preoperative or intraoperative stage allows to choose the optimal volume of surgery and in the short time effectively correct the postoperative hormonal therapy. 12 patients with different adrenal tumours (3 - lightcellular adenoma, 3 - mixedcellular adenoma, 1 - darkcellular adenoma, 1 - trabecular adenoma, 1 - malignant lymphoma, 3 - aldosteroma, 1 - pheochromocytoma, including the chance of combination of mixedcellular adenoma and aldosteroma of left adrenal) were operated on. The patients' aged varied from 33 to 62 years. For the first time we made intraoperative laser autofluorescent spectroscopy (IOLAS). The laser ve1ength was 632.8 nm. We defined a autofluorescent intensity. Portable equipment was used. The duration of the procedure did not exceed 2mm. The autofluorescent peak of adrenal tissue was 1.33±0.05 relativistic unit (RU) at 685 nm. The autofiurescent peaks of adrenal adenomas were 1 .07 RU, 0.9-1 .15 RU, 1.7-1 .9 RU, 3.4 RU accordingly for trabecular adenoma, lightcellular adenoma, mixedcellular adenoma, darkcellular adenoma Besides greater contribution of longwave component to auflurescence is characteristic for mixecellular adenoma and especially for darkcellular adenoma. The autofiurescent peaks of aldosteroma and pheochromocytoma were accordingly 1.2-1.4 RU and 2.2 RU. Spectral distribution of intensity was like mixedcellular adenoma's one. In the case of malignant lymphoma the autofiurescence peak was 2,3 RU and we also noted displacement of maximum of autoflurescence (-15 nm, from 685 nm to 670 nm).The results of IOLAS application as a adjuvant diagnosticmethod point to promise for intraoperative rapid diagnostics of adrenal tumours.

Today, it is real the use of the laser fluorescence diagnostic systems and procedures for optical noninvasive clinical diagnostic testing of oncologic, burn, suppurative and other destructive-inflammatory processes in tissues and organs. A lot of pathology cases are accompanied by the laser induced backfluorescing flux from soft tissues. And the intensity of that can provide a medical information of disorder's state. But it can be shown, that without mathematical calculations the correct biomedical informations can't be obtained because a number of phenomena answer for increasing of intensity of backfluorescence light. So, the mathematical inverse optical task solution has to be applied in medical fluorescence diagnostic systems.

A computerized fiber-optic spectrofluorometer based on a multifrequency Nd:YAG laser ((lambda) equals 355, 440, 532 and 660 nm, f equals 25 Hz, E equals 1 - 10 mJ, (tau) equals 12 ns) for tissue fluorescence registration in vivo and ex vivo has been developed. The less intensive fluorescence from a tumor of Sarcoma-45 bearing animal model in comparison with the surrounding normal tissue was observed at the spectral region around 450 nm. The influence of reabsorption, energy transfer and other physical factors on tumor fluorescence, sensitized by Photohem (hematoporphyrin derivative), disodium salt of fluorescein (FL) and chlorin e₆ (Chl) was investigated. The pharmacokinetic behavior of Chl in different organs and tumors of the animal models has been estimated. The most intensive Chl fluorescence of tumor tissue was observed at 18 hours after photosensitizer injection. The maximum of the tumor-to-healthy tissue ratio of fluorescence was reached 10 at 27 hours after pigment injection. The fluorescence spectra from different types of human tumors after i/v injection with FL or topical application of ALA were studied. A simple model of Nd:YAG laser system for tumor fluorescence diagnosis has been elaborated. Advantages of the laser fluorescence diagnosis of malignant tumors by solid state multifrequency Nd:YAG laser and the increase in accuracy and specificity of this method is discussed.

In this paper the results of an experimental-clinical study substantiating the use of low level laser radiation (LLLR) at certain wavelengths for treatment of cancer patients are given. In the first part of this study, with animal experiments, laser action parameters providing reliable renewal and regeneration stimulation are selected. It is shown that, under the effect of LLLR, the speed and quality of regeneration in wounds after tumor removal are changed as well as the intensity of dissemination and tumor growth. A change also occurs in the functional properties of lymphocytes, which have immunological control in the organism. On the basis of the experimental data obtained, the contingent of cancer patients for whom LLLR can be recommended was determined.

The second part of this paper presents the results of many years of research on the primary stages of the biological mechanism of LLLR action. The scanning electron microscopy method revealed some activation of the cell membrane in the irradiated human lymphocytes. This is shown in ultrastructure surface change. In the study on magnetic characteristics paramagnetic properties were fond at 633 nm irradiation of cell suspension, connected wit the formation of free-radical products as a result of primary photochemical processes. In order to identify the primary photoacceptor that sets off a chain of biochemical, structural and metabolic changes in the cell, biological action spectra were studied. With the laser cytodiffractometer coincidence between the action spectra and the absorption band of molecular oxygen was established.

The goal of this work is to study the laser-induced photosensitized oxidation of lipids of the artificial (lyposomes) and cell's (erythrocytes, leukocytes) membranes and human blood lipoproteins. As a exogenous photosensitizers we are used hematoporphyrin derivatives (HPD) and sulfonated phthalocyanine aluminum (Pc). Irradiation was performed by helium-neon laser (632.8 nm). It was found out the increasing of the products of lipid oxidation in the suspensions of a lyposomes, human blood apo-(beta) -lipoproteins, erythrocytes and leucocytes. Accumulation of the lipid oxidation products depend on as irradiation dose as HPD or Pc concentrations. Interaction of photosensitizers with the lyposomes, lipoproteins and erythrocytes was investigated.

We investigated the influence of He-Ne ((lambda) equals 632.8 nm) laser irradiation (LI) on a functional activity of human blood leucocytes. The method of luminol-dependent chemiluminescence with the zymosan-activated phagocytes was used. The leucocytes were irradiated without and in the presence of autologic human blood plasma, containing of the endogenous (porphyrins) and/or exogenous (phthalocyanine) photosensitizers. The LI initiated a priming of the leucocytes. Priming revealed itself after the activation of the phagocytes by zymosan. The changes of the calcium concentration in leucocytes cytoplasm were studied too. Fluorimetric method with Fura-2AM was used for this. The laser irradiation initiated the changes of the calcium concentration in the leucocytes cytoplasm. All the investigating parameters depended on the irradiation dose and on the concentration of photosensitizers. The results of this work allowed to formulate the main theses of the free radical mechanism of the low intensive laser irradiation action on human blood leucocytes.

Exposure of radiation ulcers in rats to low-power infrared laser radiation (LPLR) (wavelength--890 nm, pulse power--6 W, frequency--150 and 300 Hz, irradiation time--10 min) noticeably accelerates their healing, reduces exudative processes, increases number of specialized cells in wound. Application of LPLR prior to radiation damage decreases ulcer dimensions.

A novel stable water-soluble form of well known photosensitizer chlorin e₆ named `Photodithazine' has been obtained from Spirulina Platensis cyanobacteria as a noncovalent complex with N-methyl-D-glucosamine, and its biological characteristics evaluate, which proved to be as follows: in vitro photocytotoxicity was 1 (mu) M (EC<sub>50</sub>) as determined by the extent of DNA synthesis inhibition in CaOv cells after irradiation with 650 - 900 nm light, and 5 (mu) M (EC<sub>65</sub>) as determined using MTT test on PC12 cells after irradiation with 670 nm laser light at the doses of 15 and 20 J/cm<sup>2</sup>, respectively, with Al-sulfophthalocyanine `Photosense' (Russia) and oligomerized hematoporphyrin-IX mixture `Photogen' (Russia) being used as permitted reference drugs.

The objectives of the present work were to compare the kinetics of porphyrin exchange between different plasma lipoproteins and biological membranes. Isolated proteins were loaded by porphyrins (chlorin e6 derivatives and Zn- phthalocyanine) and the kinetics of pigment transfer from protein carrier to pigment-free proteins or biological membranes were analyzed by spectroscopic techniques. It was obtained that the rate of exchange depended strongly on the pigment polarity. A main trend was that the time required for equilibrium redistribution increased with decreasing dyes polarity. Its values changed from seconds for polar sensitizers to tens of minutes in the case of apolar dyes. Extremely slow redistribution (several hours) was observed when the recovery of apolar pigments (chlorin e6 trimethylester and Zn-phthalocyanine) from LDL was studied. The results clear indicate that the rate of pigment exchange between proteins and cells may contribute to the control of sensitizer distribution in blood and solid tissues.

Deuteroporphyrin IX derivatives are prospective PDT porphyrin photosensitizers (PS). The photodynamic effects of 6 new amphiphilic deuteroporphyrin derivatives with different hydrophobicity, as well as effects of known photosensitizers Photoheme and Photosens (used for comparison) on the firing of isolated crayfish mechanoreceptor neuron have been studied. After 30 min photosensitization, neurons were irradiated with He-Ne laser (632.8 nm, 0.3 W/cm²), and changes in neuron firing frequency were recorded. It has been shown that neuron firing is very sensitive to photodynamic impact and can serve as a sensitive indicator of cell photodamage.

The photodynamic effects of sulphonated zinc (ZnPcS₂, ZnPcS₃ and ZnPcS₄) and aluminum (AlPcS₃) phthalocyanines as well as phosphonated aluminum phthalocyanine on the firing of isolated crayfish mechanoreceptor neurons were studied. After 30 min photosensitization neurons were irradiated with He-Ne laser (632.8 nm, 0.3 W/cm²) and changes in neuron firing frequency were recorded. Neuron firing was found to be very sensitive to photodynamic impact and served as a sensitive indicator of cell photodamage. The dynamics of the neuron responses to photodynamic effects included stages of firing activation and/or inhibition prior to irreversible firing abolition and depended on the photosensitizer type and concentration. The comparison of the dependencies of neuron lifetime on photosensitizer concentrations showed that the most effective photosensitizer was ZnPcS₂. High photodynamic efficiencies of phthalocyanines was related with the weak dependence of photodynamic effect on sensitizer concentration indicating to the initiation about 3 secondary chain processes such as free radical membrane damage caused by photon absorption by one photosensitizer molecule.

The purpose of this study was to determine the changes in concentrations of the two Russian photosensitizers in blood plasma of patients under Photodynamic therapy. In this work were used two sensitizers of domestic production: Photohem (hematoporphyrin derivative) and Photosense (sulfonated aluminium phtalocyanine). It was found that one month after injection the concentrations of the photosensitizers in blood plasma remained high enough. Was shown alteration of level of apo-(beta) -lipoproteins oxidation and antioxidant activity of blood plasma under the influence of Photodynamic therapy.

The priority concept of the laser histochemical surgery as a potentially novel line in medicine is presented. The histochemical stains, selectively coloring some targets (address substrates), that are cells or their biochemical ingredients, sensitize them to the laser irradiation. Such sensitization to laser irradiation by staining turns the colored targets into targets for the laser beam. The action of the irradiation onto its specific targets beats out of the cell its ingredients which participate in a pathology process. In particular, the beating of a stained ferment out of the general stage of biochemical processes characteristic for the pathology interrupts their currence. The laser beam, when beating out its stained targets without any damage of the unstained tissues, acts like a scalpel that cuts off affected tissues not brushing healthy ones. A scheme for testing stains as sensitizers of the `address substrates' to the laser irradiation is presented. As the criterion of the stain sensitization the fact was chosen of absence or weakness of pathomorphologic and biochemical signs of the disease in an experimental model of the pathology irradiated with laser after a stain use, while the pathology signs are present in a control sample. The basis is done for study of the histochemical stains as potential means for the laser histochemical surgery of disseminated sclerosis, mucopolysaccharidosis, hypercholesterolemia, myocardial infarction, cardiosclerosis, caries and parodontosis.

The directions of laboratory and clinical studies oriented to experimental confirmation of the priority concept of `laser histochemical surgery' are presented. The goal of the studies is reproduction on experimental model of a number of pathologies (in vivo and in vitro) of the `sensitization to laser radiation by staining' effect. Testing of the histochemical stains as sensitizers to laser irradiation of their `address substrates', i.e. vitally stained intracellular structures which participate in the pathologic processes evolution is under planning. The processes include: (a) metabolic disorders in the brain cells, i.e. disseminated sclerosis; (b) generalized metabolic disorders- -mucopolysaccharidosis and collagenosises (periarteritis nodosa, rheumatism, rheumatoid arthritis, sclerodermia); (3) metabolic disorders in individual organs--vessel atherosclerosis, hypercholesterolemia, myocardial infarction, cardiosclerosis, caries and parodontosis. The conditions of the studies are detailed in the recommendations along the positions: (1) disease name; (2) disease characteristics: (a) pathomorphologic, (b) biochemical; (3) stains revealing the disease signs and recommended for testing; (4) `address substrates' of the stains that are targets for laser radiation; (5) lasers recommended for the testing after the cells staining in vivo in the corresponding pathology; (6) experimental models of the pathologies suggested for the testing; (7) criteria of the stain efficiency as target sensitizer to the laser light (criteria of the `laser sensitization by staining' efficiency). Possible perspectives for the experimental clinical medicine are indicated of common histochemical stains and lasers use and of practice introduction of the `laser histochemical surgery' in the case the described concept is confirmed in experiments and clinically.

This review reflect the latest achievements of Russian science in the field of creating laser and phototherapeutic combined technologies for oncology. This article tackles the problem of further developing laser-ultrasonic medical technologies and its applications in oncology. The comparison and the features of alternative sources for photodynamic therapy including the lasers, the lamps with spectral filters and LED array are considered. The application photomatrix system for treatment posmastectomy oedema are presented. The possibilities of laser transcutaneous photosensitizer delivery methods are discussed.

A possibility to construct an optical system with laser brightness amplifier for transformation with size reduction of tissues images recorded on liquid crystal matrix element or using TV laser acousto-optical system has been demonstrated. The active elements of copper, gold and strontium vapor lasers and titanium-sapphire or dye lasers were used as amplifying or generating elements for color images. The optical scheme has been created for the laser processing of tissue with the beam formed corresponding to the tissue shape or any other desired configuration.

For using in the complex for diagnostics and therapy tumors with the aid photodynamic therapy the special fiberscope was developed. Ergonomic principles are incorporated in the design of these compact and lightweight control heads. The efficiency of phototreatment could be improved by reducing the traumatism of normal tissues during the phototherapeutic procedures with achieving the homogeneous distribution of laser emission intensity on the tumor surface and with decreasing the labor intensiveness of phototreatment. The method forming and delivering the image of phototreatment to tumor with the aid special fiberscope was described.

Phase images of human colon carcinoma cells CX1, HCT15, HCT116 and human urinary bladder carcinoma cells EJ28 were obtained with laser phase microscope and have been analyzed. The phase shift images are compared with conventional light microscopy and confocal laser scanning microscopy data in order to detect the correspondence between morphological peculiarities and phase characteristics of measured cell. Influence of interactions between human carcinoma cells and specific antibodies (CC18 monoclonal antibody to cytokeratin and MRK 16 monoclonal antibody) on the cells phase images was studied.

The new design of high power laser diodes, based on partly phase-locked laser arrays was developed in this work. The high temporal and spatial stability of such design laser diodes make them more preferable for high stable diode- pumped solid-state lasers than broad-area stripe contact laser diodes. Furthermore, the long lifetime of laser diodes with partly phase-locked array permits to use them in the field of material processing and medical applications.