Antitumor effect of nanophotothermolysis mediated by zinc phthalocyanine particles.

Nanophotothermolysis (NPhT) effect is considered to be an approach for the development of highly selective modalities for anticancer treatment. Herein, we evaluated an antitumor efficacy of NPhT with intravenously injected zinc phthalocyanine particles (ZnPcPs) in murine subcutaneous syngeneic tumor models. In S37 sarcoma-bearing mice a biodistribution of ZnPcPs was studied and the high antitumor efficacy of ZnPcPs-mediated NPhT was shown, including a response of metastatic lesions.

Predictive significance of HIF-1α, Snail, and PD-L1 expression in breast cancer.

Currently, the prediction of breast cancer (BC) effectiveness to drug treatment is based on determining the expression level of steroid hormone receptors and human epidermal growth factor receptor type 2 (HER2). However, significant differences in individual response to drug treatment require the search for new predictive markers. Here, by comprehensively examining HIF-1α, Snail, and PD-L1 expression in BC tumor tissue, we demonstrate that high levels of these markers correlate with unfavorable factors of BC prognosis: the presence of regional and distant metastases and lymphovascular and perineural invasion.

On normalizing of urinary KIM-1 level to urine creatinine in patients with renal cell cancer.

KIM-1 (kidney injury molecule 1), a marker of acute kidney injury, is produced by epithelial cells of renal proximal tubules. Elevated KIM-1 levels in urine and plasma are associated with renal cell carcinoma (RCC). The aim of this study was to compare the significance of non-normalized uKIM-1 values and those normalized to urine creatinine, as urinary biomarkers in RCC.

Genetically Modified DR5-Specific TRAIL Variant DR5-B Revealed Dual Antitumor and Protumoral Effect in Colon Cancer Xenografts and an Improved Pharmacokinetic Profile.

Despite the weak clinical efficacy of TRAIL death receptor agonists, a search is under way for new agents that more efficiently activate apoptotic signaling. We previously created a TRAIL DR5-selective variant DR5-B without affinity for the DR4, DcR1, DcR2, and OPG receptors and increased proapoptotic activity in tumor cells. Here we showed that DR5-B significantly inhibited tumor growth in HCT116 and Caco-2 but not in HT-29 xenografts.

Antitumor Activity of Auger Electron Emitter In Delivered by Modular Nanotransporter for Treatment of Bladder Cancer With EGFR Overexpression.

Gamma-ray emitting In, which is extensively used for imaging, is also a source of short-range Auger electrons (AE). While exhibiting negligible effect outside cells, these AE become highly toxic near DNA within the cell nucleus. Therefore, these radionuclides can be used as a therapeutic anticancer agent if delivered precisely into the nuclei of tumor target cells.

Synthesis and Investigation of Photophysical and Biological Properties of Novel S-Containing Bacteriopurpurinimides.

Novel hybrid molecule containing 2-mercaptoethylamine was synthesized starting from O-propyloxime-N-propoxy bacteriopurpurinimide (dipropoxy-BPI), which was readily oxidized in oxygen atmosphere yielding the corresponding disulfide analogue (disulfide-BPI). Spectral, photophysical, photodynamic, and biological properties of compound were properly evaluated. Compounds bearing disulfide moiety can directly interact with glutathione (GSH), thereby reducing its intracellular concentration.

[The test system to identify mucin MUC1 in human blood serum using the technique of immune-enzyme analysis based on monoclonal antibody ICO25].

On the basis of genuine mouse monoclonal antibody ICO25 the test system IEA ICO25 was developed and standardized to quantitative detect tumor-associated antigen, mucin1 in human blood serum in format of inhibitory immune-enzyme analysis. The analytic characteristics of test-system correspond to the standards applied to immune-enzyme diagnostic kits. The results of identification of MUC1 in blood serum of healthy donors and female patients with breast pathology using IEA ICO25 fully correlate with the data concerning the detection of antigen CA15-3 using certified commercial kits.

[Antibodies to synthetic peptides for the detection of survivin in tumor tissues].

Survivin, an endogenous protein, is a promising marker for the diagnosis of cancer. The aim of the present work was to obtain antibodies specific to survivin and capable of detecting this protein in tumor tissues. Four peptides corresponding to fragments (1-22), (54-74), (80-88)-(153-165), and (118-144) of the survivin-2B sequence were selected and synthesized.

13,15-N-cycloimide derivatives of chlorin p6 with isonicotinyl substituent are photosensitizers targeted to lysosomes.

Four monocationic cycloimide derivatives of chlorin p(6) (CICD) were studied as photosensitizers and compared to a structurally similar neutral derivative. Cationic CICD are highly photostable (quantum yield of photobleaching is about 1 x 10(-5), generate singlet oxygen under irradiation (quantum yields are 0.3-0.

[Effect of substituents on photochemical and biological properties of 13,15-N-cycloimide derivatives of chlorin p6].

The effect of electron-accepting substituents in position 3 of the chlorine p6 macrocycle in neutral and carboxyl-containing negatively charged cycloimide derivatives of chlorin p6 (CIC) on the photochemical and biological properties of these photosensitizers was studied. A relationship between the structure and properties of CICs was analyzed on the basis of information on their photoinduced cytotoxicity, efficiency of the generation of reactive oxygen species, photostability, intracellular localization, quantitative parameters of accumulation in cells, and cellular pharmacokinetics. It was shown that these compounds can be used for the development of photosensitizers with intense light absorption at 740 nm, controlled intracellular localization, and a high photodynamic activity toward tumor cells.

Tissue distribution and in vivo photosensitizing activity of 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester.

Photosensitizers 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 (HPC) and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester (MMC) absorb at 711 nm and possess high photoinduced cytotoxicity in vitro. Here we report, that photodynamic therapy with HPC and MMC provide considerable antitumor effect in mice bearing subcutaneous P338 lymphoma. The highest antitumor effect was achieved at a dose of 4 micromol/kg when 1.

[Photobiological properties of 13,15-N-(carboxymethyl)- and 13,15-N-(2-carboxyethyl)cycloimide derivatives of chlorin p6].

Lipophilic derivatives of chlorin p6, 13,15-N-(carboxymethyl)cycloimide methyl ester (CIC1) and 13,15-N-(2-carboxyethyl)cycloimide methyl ester (CIC2), were shown to absorb light in 710 nm region and to be efficient IR photosensitizers. They exhibit similar phototoxicities on the cells of A549 human lung adenocarcinoma, which are 40- and 100-fold higher than those of chlorin p6 and the clinically used Photogem, respectively, and are not toxic in the absence of light irradiation. The confocal spectral imaging technique allowed us to demonstrate that the high phototoxicity of CIC1 and CIC2 is due to their ability to readily penetrate to cells and to be bound to the cell membranes and lipid-containing structures in the monomeric photoactive form.

Distribution of metal-free sulfonated phthalocyanine in subcutaneously transplanted murine tumors.

Metal-free sulfonated phthalocyanine with the average number of sulfonate groups per molecule 2.4 (H(2)PcS(2.4)) was recently proved to be an efficient photosensitizer for the photodynamic therapy.

Comparative study of photodynamic properties of 13,15-N-cycloimide derivatives of chlorin p6.

Comparative study of 13,15-[N-(2-hydroxyethyl)]cycloimide chlorin p6 (2), 13,15-(N-acetoxy)cycloimide chlorin p6 (3), 13,15-(N-hydroxy)cycloimide chlorin p6 methyl ester (4) and 13,15-(N-methoxy)cycloimide chlorin p6 methyl ester (5) together with the previously investigated 13,15-[N-(3-hydroxypropyl)]cycloimide chlorin p6 (1) was performed. The dependence of the key photodynamic properties of 1-5 on the introduced substituents was analyzed. The photoinduced cell-killing activity of 4 is 100- and 280-fold higher than that of chlorin p6 and Photogem, respectively, as estimated on A549 human lung adenocarcinoma cells.

Near-infrared photosensitizer based on a cycloimide derivative of chlorin p6: 13,15-N-(3'-hydroxypropyl)cycloimide chlorin p6.

The 13,15-N-(3'-hydroxypropylcycloimide) chlorin p6 (CIC), which absorbs at 711 nm, possesses considerable photoinduced cell-killing activity. It is 43-, 61- and 110-fold more active than chlorin p6, 3-formyl-3-devinyl chlorin p6 and Photogem, respectively, and has no cytotoxicity without irradiation as estimated on A549 human adenocarcinoma cells. To attain the highest intracellular penetration and activity the monomeric form of CIC should be stabilized.

Chelation with metal is not essential for antitumor photodynamic activity of sulfonated phthalocyanines.

It is generally assumed that a central metal is essential for the efficiency of phthalocyanines in photodynamic therapy (PDT) of cancer. Contrary to the set opinion, the results of the present study indicate that the metal-free sulfonated phthalocyanines (H2PcSn, where n is the number of sulfonate groups per molecule) possess a considerable photoactivity. The relative phototoxicities of H2PcS1.

Immunoconjugates of soybean Bowman-Birk protease inhibitor as targeted antitumor polymeric agents.

To enhance the antitumor potential of soybean Bowman-Birk inhibitor (BBI), the conjugate of BBI with an antibody via a macromolecular carrier was prepared. Clinical dextran (D) was used as a biocompatible biodegradable carrier for co-immobilization of BBI and antibody. A model immunoglobulin isolated from sheep serum (sIgG), raised against human IgM was utilized to develop the procedure of immunoconjugate synthesis.

Potential of block copolymer- and immuno-conjugates for tumor-targeted delivery of Bowman-Birk soybean proteinase inhibitor.

The present work reports the effect of conjugation of the anticarcinogenic and antitumor soybean Bowman-Birk protease inhibitor (BBI) with amphiphilic block copolymer of ethylene oxide and propylene oxide (PEO-PPO) as well as with monoclonal antibody via clinical dextran (D) on tumor-targeted delivery of BBI.

Influence of the substitution of 3-vinyl by 3-formyl group on the photodynamic properties of chlorin P6: molecular, cellular and in vivo studies.

Molecular in vitro and in vivo properties of 3-devinyl-3-formylchlorin p6 (FCp6) were examined in order to characterize this derivative as a new prospective photosensitizer. The long-wavelength absorption maximum of FCp6 was 690-696 nm (depending on environment). FCp6 was found to bind readily to membranous structures and form complexes with some proteins.

[Study of localization and molecular interactions of biologically active compounds in living cells and tissue slices based on confocal microspectroscopy and reconstruction of the spectral images].

The confocal spectral imaging (CSI) technique is described, its basic principles are considered, and a brief review of its applications to the study of biologically active compounds (BAC) within living cells and in tissue slices is presented. This technique is based on measurements and analysis of fluorescence or resonance Raman spectra in each point of the specimen under microscope with a three-dimensional resolution of about cubic micrometer. This technique is applicable to the study of stained fluorescent and nonfluorescent compounds.

Confocal raman microspectroscopy and imaging study of theraphthal in living cancer cells.

Binary systems combining a transition metal complex and ascorbate have been proposed recently for catalytic therapy of malignant tumors. The killing effect on tumor cells is achieved by production of free radicals in the course of accelerated oxidation of ascorbate by dioxygen in the presence of transition metal complexes. Further progress in the development of binary catalytic systems (BCSs) requires a special method for their investigation in cells and tissues, because neither component of BCSs fluoresces.

[Metaplastic breast cancer].

Three groups of metaplastic mammary carcinoma are distinguished: squamous cell carcinoma, invasive ductal carcinoma with partial squamous metaplasia and carcinoma with formation of heterologous elements. Squamous cell carcinoma is subdivided into 5 variants: solid and spindle cell variants, carcinoma in preexisting cyst and fibroadenoma; carcinoma resulting from total squamous metaplasia of invasive ductal carcinoma. Squamous cell mammary carcinoma has a relatively favourable prognosis.

[Various forms of breast cancer].

844 observations of mammary carcinoma special forms were analyzed. In 48% of cases there was a combined structure, primary multiple carcinoma was in 23.6%, bilateral in 2.

[Pharmacokinetics of human milk lactoferrin in intact mice and tumor-carrying animals].

Pharmacokinetics of iodine containing and native lactoferrin from human milk was studied in intact mice and the animals with Ehrlich ascites carcinoma. Both these antigens, native and I-lactoferrin, were similarly distributed in intact mice body. The same pharmacokinetics was found in tumor-bearing animals.