Targosomes: Anti-HER2 PLGA nanocarriers for bioimaging, chemotherapy and local photothermal treatment of tumors and remote metastases.

Developing combined cancer therapy strategies is of utmost importance as it can enhance treatment efficacy, overcome drug resistance, and ultimately improve patient outcomes by targeting multiple pathways and mechanisms involved in cancer growth and progression. Specifically, the potential of developing a combination chemo&photothermal therapy using targeted polymer nanoparticles as nanocarriers offers a promising approach for synergistic cancer treatment by combining the benefits of both therapies, such as targeted drug delivery and localized hyperthermia. Here, we report the first targeted anti-HER2 PLGA nanocarriers, called targosomes, that simultaneously possess photothermal, chemotherapeutic and diagnostic properties using only molecular payloads. Biocompatible poly(lactic-co-glycolic acid), PLGA, nanoparticles were loaded with photosensitizer phthalocyanine, diagnostic dye Nile Blue, and chemotherapeutic drug irinotecan, which was chosen as a result of screening a panel of theragnostic nanoparticles. The targeted delivery to cell surface oncomarker HER2 was ensured by nanoparticle modification with the anti-HER2 monoclonal antibody, trastuzumab, using the one-pot synthesis method without chemical conjugation. The irradiation tests revealed prominent photothermal properties of nanoparticles, namely heating by 35 °C in 10 min. Nanoparticles exhibited a 7-fold increase in binding and nearly an 18-fold increase in cytotoxicity for HER2-overexpressing cells compared to cells lacking HER2 expression. This enhancement of cytotoxicity was further amplified by >20-fold under NIR light irradiation. In vivo studies proved the efficacy of nanoparticles for bioimaging of primary tumor and metastasis sites and demonstrated 93% tumor growth inhibition, making these nanoparticles excellent candidates for translation into theragnostic applications.

[Endoscopical methods in the differential diagnosis of tuberculosis and cancer of the respiratory system].

For 25 years (1986-2011) in endoscopy unit of the branch of the 1 FBU "3 TSVKG Russian Ministry of Defense n. a. A.A. Vishnevskiy--" initially examined 18 169 patients admitted on the various forms of pulmonary tuberculosis. In the bronchial study tuberculosis of bronchus was diagnosed in 1544 patients, representing 8.5% of all TB patients. Complicated bronchial tuberculosis (infiltrative-ulcerative and broncho-fistulezny TB) were diagnosed in 382 (24.8%) patients. Neoplastic process in bronchi was detected in 145 (0.8%) patients, including the central cancer was found in 109, peripheral--at 36. An increase in tuberculosis and cancer of the respiratory system requires medical endoscopists to targeted search for endoscopic studies, not only the specific features of tuberculous bronchial lesions, but also the cancer process in them. In the case of detection of pathological changes in the pleura and lung parenchyma should be preferred thoracoscopy.

[Impaired gustatory sensitivity of the tongue to table salt as a risk factor of arterial hypertension].

The study included 630 patients with verified diagnosis of arterial hypertension (AH) in whom 24 hr AP monitoring was performed, threshold gustatory sensitivity of the tongue to table salt (TGS) measured, and habit to add salt to the cooked food evaluated. Measurement of Na in daily urine of 442 patients was followed by estimation of salt consumption. The results were compared with those obtained in 100 patients with newly diagnosed AH. The control group comprised 288 subjects. TGS in AH patients was significantly higher than in controls and directly related to clinical features of the disease, high AP values, age, smoking habits, hypercholesterolemia, abdominal-type obesity, and hereditary predisposition. TGS positively correlated with daily urinary excretion of NaCl (r = 0.4-0.7; p < 0.05-0.01). High TGS decreased under effect of hypotensive therapy.

[Bronchoscopy in differential diagnosis of bronchial lesions in the cases of tuberculosis and oncologic processes].

The bronchoscopic investigation was performed in 15 467 patients treated for respiratory tuberculosis in the Central Military Clinical Tuberculous Hospital N 4 for the last 20 years. The bronchial tuberculosis was revealed in 1315 (8,5%) patients. Among them the tumoral process was detected in 113 (8,6%), including the central cancer--in 84 patients,and the peripheral cancer--in 29. According to initial diagnosis these patients were distributed in the following way: the infiltrative pulmonary tuberculosis was in 70 (1,9%), the exudative pleurisy-- in 14 (12,4%), the tuberculosis of intrathoracic lymph nodes-- in 8 (7,1%), the tuberculoma--in 8 (7,1%), the condition after operation for tuberculosis--in 5 (4,5%), the cavernous tuberculosis--in 3 (2,6%), the cirrhotic tuberculosis--in 3 (2,5%) and the pneumonia--in 2 (1,8%). The biological material was obtained with the use of direct biopsy, brush biopsy, guided catheter-biopsy and bronchoalveolar lavage. All bronchological findings were confirmed by cytological and histological examinations.

Development of equipments for determination of BNCT source spectral parameters.

The knowledge of neutron and gamma ray energy spectra can strongly influence the BNCT information about delivered dose to target volume as well as to the surface healthy tissue region. This region is very often decisive to stay within the recommended healthy tissue limit. Modification of neutron Bonner spectrometer to one block i.e. Bonner spectrometer monoblock (BSM) and gamma ray Si semiconductor spectrometer are being developed and verified in real conditions of LVR-15 reactor beam. Test measurements were also carried out in conditions of known standard spectra. The accepted procedure and the first results documenting the sensitivity BSM to different spectra are presented.

[The efficacy of fiber bronchoscopy under outpatient polyclinic conditions]. / Effektivnost' nronkhofibroskopii v ambulatorno-poliklinicheskikh usloviiakh.

Basing on the experience of conducting 795 bronchofibroscopies under conditions of polyclinic authors discuss organized and methodological aspects ensuring maximal study safety permitting to avoid serious, danger for life complications. Pathologic changes of tracheobronchial tree were exposed in 64.6% cases, 46.5% of them--inflammations, 4.9% of cases--bronchus cancer. Morphologic cancer verification when conducting biopsy was 84.6%, when making cytologic examination of bronchial liquid-17.9%.

[The lipids of the erythrocyte stroma and myocardial ischemia in patients with iron-deficiency anemia]. / Lipidy stromy éritrotsitov i ishemiia miokarda u bol'nykh zhelezodefitsitnoi anemiei.

Red cell stromal lipid fractions (total lipids and phospholipids, triglycerides, free fatty acids, cholesterol and its esters, lisophospholipids, sphyngomyelins, phosphatidylserines, phosphatidylcholines, phosphatidylethanolamines, cardiolipins, phosphatide acids) were measured and ECG A leads at rest analyzed in 29 patients with iron-deficiency anemia to detect myocardial ischemia. Significant changes in red cell stroma lipid composition were revealed, particularly marked in women with myocardial ischemia. Measures aimed at normalization of red cell stromal lipid composition in patients with iron-deficiency anemia may be regarded as one of the factors inhibiting the development of myocardial ischemia.

[Interaction of formaldehyde with nucleic acids and their structural components in the presence of amines. V. Isotopic exchange of hydrogen 3H---1H at the C8 atom of dATP, adenosine, adenine, guanosine, and poly(A)]. / Vzaimodeistvie formal'degida s nukleinovovymi kislotami i ikh strukturnymi komponentami v prisutstvii aminov. V. Izotopnyi obmen vodoroda 3H---1H pri C8 atome dATP, adenozina, adenina, guanozina i poly(A).

It has been shown that the effect on [8-3H]dATP, [8-3H]A and [8-3H]poly(A) of the formaldehyde mixture with the primary aliphatic amine carrying an amino group at the chain terminus (glycine, its methyl and ethyl esters, tripeptide Gly-Gly-Gly, taurine, ethanolamine, methylamine, ethylamine), under conditions close to physiological ones (pH 5.5-9, 40-50 degrees), initiates a fast reaction of isotope H2 exchange: 3H-->1H at the C-8 atom of the adenine residue. Substitution of the primary amine for a secondary one decreases the rate of hydrogen exchange by more than two orders of magnitude. Under the effect of the formaldehyde mixture with Gly or Sar on guanosine or of the HCHO-Sar mixture on adenosine, the hydrogen exchange at the C-8 atom of the both nucleotides proceeds at the same rate. The mechanism of fast hydrogen exchange at the C-8 atom of 9-substituted adenines under conditions of the Mannich reaction via the N6,N7-cycloderivative (III) is discussed.

[Painless myocardial ischemia in patients with iron deficiency anemia]. / Bezbolevaia ishemiia miokarda u bol'nykh zhelezodefitsitnoi anemiei.

Resting and bicycle ergometric ECGs were examined in 159 patients with iron deficiency anemia, including 100 treated with iron-containing drugs. ST segment depression in the patients undergoing exercise was regarded as a sign of silent myocardial ischemia which is common in anemic patients, its detection rate increases as the disease progresses. In patients with iron deficiency anemia, silent myocardial ischemia results in a substantial decrease of threshold intensity, has a negative effect on cardiac output both at rest and during exercise, and significantly slows down the recovery of cardiac performance during therapy. This should be borne in mind while solving problems in medial labour examinations and making rehabilitative measures in patients with the above abnormality.

[Peripheral vein function of stenocardia patients]. / Sostoianie perifericheskikh ven u bol'nykh stenokardiei.

Occlusive venous plethysmography used for examination of 89 anginal male patients has shown a considerable rise of the tone of peripheral veins and the reduction of accessory venous capacity. An advance in angina pectoris results in a rise of the tone and reduction of accessory capacity of peripheral veins. Responses of the latter to nitroglycerin administration, smoking and treatment by cold were mostly of the same type and manifested themselves in the reduction of the tone and an increase in accessory venous capacity. Reactivity of peripheral veins partially accounted for individual clinical manifestations of angina pectoris.

[Amino acids as catalysts of the binding reaction of formaldehyde with adenine residue in polyadenylic acid]. / Aminokisloty kak katalizatory reaktsii sviazyvaniia formal'degida s adeninovym ostatkom v sostave poliadenilovoi kisloty.

Binding of formaldehyde and amino acids (Gly, Lys and Leu) with poly(A), poly(G), and poly(C) has been investigated in comparison with treatment with formaldehyde alone. It was found that in the case of poly(A) amino acids were found to catalyze the N-hydroxymethylation reaction on exocyclic amino groups of adenine. For example, at 20 degrees C and pH 6.0 the rate of this reaction increased about 10 fold in the presence of glycine.