Canine as a Comparative and Translational Model for Human Mammary Tumor.

Despite the advances in research and treatment of human breast cancer, its incidence rate continues to increase by 0.5% per year, and the discovery of novel therapeutic strategies for specific subtypes of human breast cancer remains challenging. Traditional laboratory mouse models have contributed tremendously to human breast cancer research. However, mice do not develop tumors spontaneously; consequently, genetically engineered mouse models or patient-derived xenograft models are often relied upon for more sophisticated human breast cancer studies. Since human breast cancer develops spontaneously, there is a need for alternative, yet complementary, models that can better recapitulate the features of human breast cancer to better understand the molecular and clinical complexities of the disease in developing new therapeutic strategies. Canine mammary tumors are one such alternative model that share features with human breast cancer, including prevalence rate, subtype classification, treatment, and mutational profiles, all of which are described in this review

Exploring the Potential Utility of Pet Dogs With Cancer for Studying Radiation-Induced Immunogenic Cell Death Strategies

Radiotherapy serves as a foundational pillar for the therapeutic management of diverse solid tumors through the generation of lethal DNA damage and induction of cell death. While the direct cytotoxic effects of radiation therapy remain a cornerstone for cancer management, in the era of immunooncology there is renewed and focused interest in exploiting the indirect bystander activities of radiation, termed abscopal effects. In radioimmunobiologic terms, abscopal effects describe the radiotherapy-induced regression of cancerous lesions distant from the primary site of radiation delivery and rely upon the induction of immunogenic cell death and consequent systemic anticancer immune activation. Despite the promise of radiation therapy for awaking potent anticancer immune responses, the purposeful harnessing of abscopal effects with radiotherapy remain clinically elusive. In part, failure to fully leverage and clinically implement the promise of radiation-induced abscopal effects stems from limitations associated with existing conventional tumor models which inadequately recapitulate the complexity of malignant transformation and the dynamic nature of tumor immune surveillance. To supplement this existing gap in modeling systems, pet dogs diagnosed with solid tumors including melanoma and osteosarcoma, which are both metastatic and immunogenic in nature, could potentially serve as unique resources for exploring the fundamental underpinnings required for maximizing radiation-induced abscopal effects. Given the spontaneous course of cancer development in the context of operative immune mechanisms, pet dogs treated with radiotherapy for metastatic solid tumors might be leveraged as valuable model systems for realizing the science and best clinical practices necessary to generate potent abscopal effects with anti-metastatic immune activities

Response of the South China Sea to tropical cyclone Ernie 1996

Journal of Geophysical Research, American Geophysical Union, 105, 13991-14009.A moving tropical cyclone is an intense localized source of surface wind stress and wind stress curl that produces a significant response in the ocean environment, especially in the ocean thermal structure, the upper ocean currents, and the sea surface elevation. Such a response has been well identified in the open-ocean region, but not in the coastal ocean region. In this study we use the Princeton Ocean Model with 20 km horizontal resolution and 23 sigma levels conforming to a realistic bottom topography to identify the response of the South China Sea to Tropical Cyclone Ernie 1996. Results show strong similarities in the responses between open ocean and coastal regions, including near-surface strong a symmetric response such as divergent currents with near-inertial oscillations, significant sea surface temperature cooling, biase to the right of the storm track, sea surface depressions in the wake of the storm, and subsurface intense upwelling and cooling at the base of the mixed layer to the right of the storm track. The unique features of the SCS response to Ernie are also discussed

Optically controlled spin-glasses in multi-qubit cavity systems

Recent advances in nanostructure fabrication and optical control, suggest that it will soon be possible to prepare collections of interacting two-level systems (i.e. qubits) within an optical cavity. Here we show theoretically that such systems could exhibit novel phase transition phenomena involving spin-glass phases. By contrast with traditional realizations using magnetic solids, these phase transition phenomena are associated with both matter and radiation subsystems. Moreover the various phase transitions should be tunable simply by varying the matter-radiation coupling strength.Comment: 4 pages, 3 figure

Continuum and Emission-Line Properties of Broad Absorption Line Quasars

We investigate the continuum and emission-line properties of 224 broad absorption line quasars (BALQSOs) with 0.9<z<4.4 drawn from the Sloan Digital Sky Survey (SDSS) Early Data Release (EDR), which contains 3814 bona fide quasars. We find that low-ionization BALQSOs (LoBALs) are significantly reddened as compared to normal quasars, in agreement with previous work. High-ionization BALQSOs (HiBALs) are also more reddened than the average nonBALQSO. Assuming SMC-like dust reddening at the quasar redshift, the amount of reddening needed to explain HiBALs is E(B-V)~0.023 and LoBALs is E(B-V)~0.077 (compared to the ensemble average of the entire quasar sample). We find that there are differences in the emission-line properties between the average HiBAL, LoBAL, and nonBAL quasar. These differences, along with differences in the absorption line troughs, may be related to intrinsic quasar properties such as the slope of the intrinsic (unreddened) continuum; more extreme absorption properties are correlated with bluer intrinsic continua. Despite the differences among BALQSO sub-types and nonBALQSOs, BALQSOs appear to be drawn from the same parent population as nonBALQSOs when both are selected by their UV/optical properties. We find that the overall fraction of traditionally defined BALQSOs, after correcting for color-dependent selection effects due to different SEDs of BALQSO and nonBALQSOs, is 13.4+/-1.2% and shows no significant redshift dependence for 1.7<z<3.45. After a rough completeness correction for the effects of dust extinction, we find that approximately one in every six quasars is a BALQSO.Comment: 35 pages, 11 figures (1 color), 1 table; accepted by A

Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A

We encapsulated cyclosporine A (CsA) in poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs) by nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100 nm in diameter with a narrow particle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio during formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum albumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1) showed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs suppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay, the IC50 values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35 ng/mL, respectively. This nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and potentially reduced toxicity

Noninvasive Liquid Diet Delivery of Stable Isotopes into Mouse Models for Deep Metabolic Network Tracing

Delivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive introduction of 13C6-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive 13C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of 13C6-glucose feeding. Applying this approach to patient-derived lung tumor xenografts (PDTX), we show that the liver supplies glucose-derived Gln via the blood to the PDTX to fuel Glu and glutathione synthesis while gluconeogenesis occurs in the PDTX. Comparison of PDTX with ex vivo tumor cultures and arsenic-transformed lung cells versus xenografts reveals differential glucose metabolism that could reflect distinct tumor microenvironment. We further found differences in glucose metabolism between the primary PDTX and distant lymph node metastases

STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects

<p>Abstract</p> <p>Background</p> <p>Asthma is characterised by increased numbers of Th2-like cells in the airways and IgE secretion. Generation of Th2 cells requires interleukin (IL)-4 and IL-13 acting through their specific receptors and activating the transcription factor, signal transducer and activator of transcription 6 (STAT6). STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses.</p> <p>Methods</p> <p>We have investigated the expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naïve stable asthmatic patients.</p> <p>Results</p> <p>STAT6 expression was variable and was detected in T-lymphocytes, macrophages and bronchial epithelial cells from all subjects with no difference between normal and stable asthmatic subjects.</p> <p>Conclusions</p> <p>STAT6 expression in different cells suggests that it may be important in regulating the expression of not only Th2-like cytokines in T cells of man, but may also regulate STAT-inducible genes in alveolar macrophages and airway epithelial cells.</p