Diagnostic transcranial magnetic stimulation as a method of objective evaluation of motor pathways in patients with neoplastic and infectious brain damage.

The aim of our study was to evaluate validity of transcranial magnetic stimulation as evaluation tool of motor pathways condition dynamics in patients with gliomas and meningitis. There were included 91 patients: 40 children with aseptic meningitis, 26 matching age controls, 10 adults with gliomas and 16 matching controls. All patients underwent transcranial magnetic stimulation (TMS) before and after the treatment. TMS showed good tolerability in all groups. Significant improvement of central motor pathways conductivity (MEPs amplitudes) was seen in both groups. In meningitis group significant rising of functional state of motoneurons was seen as well. We propose that TMS proved to be effective evaluation tool of motor pathways condition dynamic in patients with gliomas and meningitis.

[Oncolytic potential of recombinant influenza A virus vectors on a model of malignant glioma in vivo].

Malignant glioma is the most frequently occurring primary brain tumor. Despite significant progress in the diagnostics and treatment of neoplastic diseases the prognosis for patients with III-IV grade gliomas, remains extremely unfavorable. Rapidly developing area in oncology is the employment of therapeutic viruses with natural or genetically engineered oncolytic activity. In the present study we demonstrated the oncolytic potential of a recombinant influenza A virus vector with impaired interferon antagonism function of NS1 protein in treatment of malignant glioma. Recombinant influenza A virus (HA-DS-GFP) expressing green fluorescent protein from the NS1 open reading frame was used as a model vector. HA-DS-GFP virus has shown infectivity towards glioma cells both in vitro, and in vivo (experimental glioma model in rats). Intratumoral inoculation of HA-DS-GFP resulted in a substantial inhibition or complete regression of tumor growth. Our data demonstrate that recombinant influenza vectors have promising potential in therapy of malignant gliomas.

CHARACTERISTICS OF A172 AND T98G CELL LINES.

During continuous cultivation cell lines can lose a number of innate characteristics or acquire new ones. In this work we compared growth and phenotypic characteristics of human glioblastoma À172 and Ò98G lines from cell culture collection of Research Institute of Influenza of Ministry of Health of Russian Federation (St. Petersburg). The activity of genes encoding intracellular proteins that determine cell lines belonging to mesenchymal type, as well as several growth factor genes and extracellular matrix genes were estimated. Cell lines A172 and T98G varied in morphology and surface markers expression. A172 cells were characterized by higher expression of mesenchymal markers CD90, CD105, fibroblast activation protein, and tenascin C. Both cell lines showed high level of a2 smooth muscle actin expression. The obtained data indicating high activity of genes encoding major inductors of angiogenesis (VEGF, FGF2 (b), TGFb1) and thrombospondin-1 in foregoing cell lines are in agreement with published data. Reduction of fetal serum in culture medium from 10 to 5 % in both cell lines resulted in the increase of proportion of cells with surface antigens CD73 and CD105. Both A172 and T98G cell lines sustain the main features of glioblastomas and therefore can serve as research objects in investigation of this kind of neoplasms.

Characteristics of mesenchymal stromal cells isolated from patients with breast cancer.

Mesenchymal stromal cells were isolated from the adipose tissue obtained during surgery for breast cancer and cultured under conditions of normal or low oxygen concentrations. In patients that had received a course of radiation and polychemotherapy prior to surgery, the proliferative potential of mesenchymal stromal cells was irreversibly disturbed. In patients receiving no therapy prior to surgery, the morphological, growth, phenotypic, and differentiation characteristics of mesenchymal stromal cells did not differ from the corresponding parameters of mesenchymal stromal cells from healthy donors. Culturing under hypoxic conditions increased adipogenic differentiation potencies of mesenchymal stromal cells from donors and patients.

[Preliminary experience with assessing the motor pathways and central inhibition in patients with malignant cerebral gliomas in preparation for conformal radiotherapy].

We investigated central motor pathways and central inhibition in patients with brain gliomas by transcranial magnetic stimulation (TMS). 10 glioma patients and 16 matching controls were enrolled. Central motor conduction time, MEP latencies and amplitudes and silent period were evaluated. In 90% glioma patients TMS parameters were abnormal, mostly MEP shapes and thresholds were affected. In 40% of the cases central inhibition in glioma affected hemisphere was abnormally high. We propose that TMS is safe and informative tool in glioma patients; central inhibition seems to be affected in some cases by the glioma presence in the hemisphere. One of the possible causes of that may be GABA system activation.

[Potential of PET in the diagnosis and the assessment of treatment effectiveness in progressive malignant glioma].

Examination including MRI (CT), PET with sodium 11C-butyrate (11C-SB) and 18fluorodeoxyglucose (18F-FDG) was carried out in 59 patients with continuing growth of malignant glioma. It was established that 11C-SB-PET is characterized by high sensitivity (94.1%) in detecting continuing growth as well as to differentiating it from necrosis. Our data were instrumental in prognosis and assaying metabolic levels in tumor (T/NT ratios) which are regarded as indices of accumulation (IA) of 18F-FDG-PET (FDG-IA) prior to conservative treatment. There were a direct correlation between metabolic activity of neoplasms and an inverse one with FDG-IA (r=-0.24).

[Role of single-photon emission computer tomography in dynamic evaluation of combined treatment of malignant cerebral glioma].

Thirty-nine patients with malignant glioma of the brain were examined at the Center's Clinic. Tumor volume ranged 0.8-175.1 cu cm. Radionuclide diagnosis was obtained with the aid of single-photon emission tomography (E.Cam, Siemens). 99mTc-DTPA, 3-6 MBc/body, was injected intravenously. Smaller size of tumor and lower ratio of differentiated marker accumulation focus/contralateral area were registered in 34%. Simultaneously, a high index of the marker accumulation in the brain was reported, thus suggesting hyperimpermeability of the blood brain barrier. Another 26% revealed larger size of tumor and higher ratio of differentiated 99mTc-DTPA accumulation, likely due to lower impermeability of the blood brain barrier. Hence, use of single-photon emission tomography in diagnosis of malignant cerebral glioma provides a means of evaluating the level of the marker in a tumor node.

[Postoperative chemoradiotherapy for cerebral glioblastoma].

We developed a new method of accelerated chemoimmunoradiotherapy for cerebral glioblastoma and evaluated the immediate effects. A single focal dose of 3Gy was administered once a day 5 times a week until the total focal dose of 51 Gy was reached. Chemoradiotherapy was followed by a course of biotherapy with recombinant interleukine-2 (roncoleukine). On administering a total dose of 10 million units, a course of chemoimmunotherapeutic support was given after a 2-week break. Vincristine 1 mg was injected on day 1 and nitrosourea preparations (lomustine 160 mg or carmustine 100 mg) on day 2. Later on, the same regimen of roncoleukine was used. Our method was followed by longer survival as compared with standard treatment (control) and use of incomplete course chemoimmunotherapy.

[Main milestones of development and application of ductal cytometry at the Russian Federal Research Center for Radiology and Surgical Technology, St. Petersburg].

Ductal cytometry provides data on cellular DNA and RNA levels and overall profile of specific proteins identifiable by monoclonal antibodies. Results of its long-term use in clinical and oncological research are presented. Application of dosage ranging 0.28-1.1 mGy/sec was followed by stable 1.8-2-fold increase in the myelokariocyte profile cbering DNA synthesis. Bone marrow proliferation did not increase until relatively low dosage was used. A study of combined effects of prolonged gamma irradiation and lead and cadmium ions on rat's hemopoiesis pointed to radiation as the sole causative factor when cadmium chloride was used. Hemopoietic characteristics came back to normal when a combination of lead acetate and ionizing radiation was used, as a result of the oppositely directed action of the two factors. Standard monoclonal antibodies should not be employed for evaluating immunological vigor of patients with malignant gliomas due to the presence of a specific pathological link in their immune system.

[Proton magnetic resonance spectroscopy in postoperative radiochemotherapy of patients with cerebral glioblastoma].

The paper discusses the data from dynamic follow-up of immunohistologically confirmed glioblastomas of the brain using proton magnetic resonance imaging (+H MRI) (25). Study was undertaken before and after therapy and resumed for 6-8 months after. Cholin concentration peaks and N-acetyl-aspartate decrease in gliomas appeared to be higher than those in anaplastic astrocytomas. Moreover, N-acetyl-aspartate peaks were obliterated by large necrotic areas in glioblastoma. Instead, lipid and lactate concentrations peaked thus suggesting pathological changes. A necrotic area developed in the course of radiochemotherapy involving peaks for wide profile of lipid and lactate concentrations coupled with lowered levels of other metabolites.

[Accelerated postoperative chemoradiotherapy for malignant cerebral glioma].

Procedure of accelerated immunotherapy for cerebral glioma is presented. Large fractions of radiation ranged from 3 Gy, 5 times a week, to a total focal dose of 51 Gy. After accumulation of total doses of 18, 33 and 48 Gy, vincristine was injected intravenously. Urea derivatives were given on reaching 21, 36 and 51 Gy. Treatment with the immunomodulator roncoleukine was carried out on completion of radiotherapy. An evaluation of the immediate end results of accelerated immunotherapy showed improved survival as compared with standard treatment.

[The combained effects of the long-term gamma-irradiation and heavy metall ions on the haematopoietic system of rats].

The combiened effects of different dose rates (0.625 microGy/s - 1.1 mGy/s) of gamma-irradiation and of cuprum and of cadmium ions on the haematopoietic system of rats were studied. It was found that only low dose rates (0.625-10 microGy/s, summary doses 0.5-2.0 Gy) of gamma-irradiation yields in the increasing proliferative activity of bone marrow. The number of myelocariocytos in S-phase was increased at 1.5-1.8 times. In case of the treatment with both cadmium chloride and radiation the changes in proliferative activity of bone marrow are completely due to the radiation factor. Combination of cuprum acetate and ionizing radiation induce opposite effects providing formal normalization of the haematopoietic characteristic of bone marrow up to 3, 6 and 12 months after the end of the radiation and the chemical exposure of the animal.