Concurrent Longitudinal EPR Monitoring of Tissue Oxygenation, Acidosis, and Reducing Capacity in Mouse Xenograft Tumor Models

Tissue oxygenation, extracellular acidity and tissue reducing capacity are among crucial parameters of tumor microenvironment (TME) of significant importance for tumor pathophysiology. In this paper we demonstrate the complementary application of particulate lithium octa-n-butoxy-naphthalocyanine (LiNc-BuO) and soluble nitroxide (NR) paramagnetic probes for monitoring of these TME parameters using electron paramagnetic resonance (EPR) technique. Two different types of therapeutic interventions were studied: hypothermia and systemic administration of metabolically active drug. In summary, the results demonstrate utility of EPR technique for noninvasive concurrent longitudinal monitoring of physiologically relevant chemical parameters of TME in a mouse xenograft tumor models including that under therapeutic intervention

Nitro-Triarylmethyl Radical as Dual Oxygen and Superoxide Probe

Superoxide radical is involved in numerous physiological and pathophysiological processes. Tetrathiatriarylmethyl (TAM) radicals are knows to react with superoxide allowing measurement of superoxide production in biological media. We report the synthesis of a Nitro conjugated TAM radical showing a rate constant of 7 × 105 M−1s−1 which is two order of magnitude higher than other TAMs allowing high sensitivity measurement of superoxid

Nitro-Triarylmethyl Radical as Dual Oxygen and Superoxide Probe

Superoxide radical is involved in numerous physiological and pathophysiological processes. Tetrathiatriarylmethyl (TAM) radicals are knows to react with superoxide allowing measurement of superoxide production in biological media. We report the synthesis of a Nitro conjugated TAM radical showing a rate constant of 7 × 105 M−1s−1 which is two order of magnitude higher than other TAMs allowing high sensitivity measurement of superoxid

PATTERNS OF SILVER NANOPARTICLES CONCENTRATION SYNTHESIS

The article provides a view on a synthesis of the substance based on silver nanoparticles; there was also optimization of the synthesis process, with data obtained that describe the impact of various factors on silver nanoparticles synthesi

NCX-4040, a nitric oxide-releasing aspirin, sensitizes drug-resistant human ovarian xenograft tumors to cisplatin by depletion of cellular thiols

Background: Ovarian carcinoma is the leading cause of mortality among gynecological cancers in the world. The high mortality rate is associated with lack of early diagnosis and development of drug resistance. The antitumor efficacy and mechanism of NCX-4040, a nitric oxide-releasing aspirin derivative, against ovarian cancer is studied. Methods: NCX-4040, alone or in combination with cisplatin (cis-diamminedichloroplatinum, cDDP), was studied in cisplatin-sensitive (A2780 WT) and cisplatin-resistant (A2780 cDDP) cell lines as well as xenograft tumors grown in nude mice. Electron paramagnetic resonance (EPR) was used for measurements of nitric oxide and redox state. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice was used for mechanistic studies. Results: Cells treated with NCX-4040 (25 μM) showed a significant reduction of cell viability (A2780 WT, 34.9 ± 8.7%; A2780 cDDP, 41.7 ± 7.6%; p < 0.05). Further, NCX-4040 significantly enhanced the sensitivity of A2780 cDDP cells (cisplatin alone, 80.6 ± 11.8% versus NCX-4040+cisplatin, 26.4 ± 7.6%; p < 0.01) and xenograft tumors (cisplatin alone, 74.0 ± 4.4% versus NCX-4040+cisplatin, 56.4 ± 7.8%; p < 0.05), to cisplatin treatment. EPR imaging of tissue redox and thiol measurements showed a 5.5-fold reduction (p < 0.01) of glutathione in NCX-4040- treated A2780 cDDP tumors when compared to untreated controls. Immunoblotting analysis of A2780 cDDP tumor xenografts from mice treated with NCX-4040 and cisplatin revealed significant downregulation of pEGFR (Tyr845 and Tyr992) and pSTAT3 (Tyr705 and Ser727) expression. Conclusion: The results suggested that NCX-4040 could resensitize drug-resistant ovarian cancer cells to cisplatin possibly by depletion of cellular thiols. Thus NCX-4040 appears to be a potential therapeutic agent for the treatment of human ovarian carcinoma and cisplatin-resistant malignancies

Department of Pathology, Thomas Jefferson University, Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors. CONCLUSION: Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors

RECYCLING OF SECONDARY RAW MILK WHEY DEMINERALIZATION AFTER THE TREATMENT BY REVERSE OSMOSIS

The possibility and the results of laboratory studies with the use of electrodialysis removing minerals from whey have been presented. The technical parameters of the electrodialysis installation (EDR-Z) have been calculated and displayed

Development of Multifunctional Overhauser-enhanced Magnetic Rresonance Imaging for Concurrent in Vivo Mapping of Tumor Interstitial Oxygenation, Acidosis and Inorganic Phosphate Concentration

Tumor oxygenation (pO2), acidosis (pH) and interstitial inorganic phosphate concentration (Pi) are important parameters of the malignant behavior of cancer. A noninvasive procedure that enables visualization of these parameters may provide unique information about mechanisms of tumor pathophysiology and provide clues to new treatment targets. In this research, we present a multiparametric imaging method allowing for concurrent mapping of pH, spin probe concentration, pO2, and Pi using a single contrast agent and Overhauser-enhanced magnetic resonance imaging technique. The developed approach was applied to concurrent multifunctional imaging in phantom samples and in vivo in a mouse model of breast cancer. Tumor tissues showed higher heterogeneity of the distributions of the parameters compared with normal mammary gland and demonstrated the areas of significant acidosis, hypoxia, and elevated Pi content

REALIZATION OF STRATEGIC PARTNERSHIP OF «JSC DAIRY PLANT "STAVROPOLSKY"» AND NCFU ON COMPLEX FEDERAL PROJECT OF «LACTOSE» IN THE FRAMEWORK OF THE NATIONAL INITIATIVE TECHNOLOGY

In the framework of the emerging National Technology Initiative, contained information officially formalized materials implemented a comprehensive Federal project for creation of «Dairy plant "Stavropol"» unique for the Russian Federation high-tech production only in the biocenosis Earth carbohydrate of animal origin - lactose (milk sugar) food and Pharmacopoeia standards on the basis of long-term scientific studies of the creative team of scientific school «Living Systems» North-Caucasus Federal University. The purpose of information - to attract the reader's attention and thinking colleagues, with the possible participation of everyone to implement the Strategic Partnership between the State and Business