Solid tumors produce proteins that can induce the accumulation of bone marrow-derived cells in various tissues, and these enhance metastatic tumor growth by several mechanisms. 4T1 murine mammary are known to granulocyte colony-stimulating factor (G-CSF) increase numbers immunosuppressive CD11b+Gr1+ myeloid-derived suppressor (MDSCs) tissues such as spleen lungs tumor-bearing mice. While surgical resection primary decreases MDSC levels spleen, longevity impact MDSCs other immune after have...

The ultrasonographic image of an organ is a product scattering and reflection high-frequency ultrasound beams by discrete units tissue. number acoustic tissue interfaces vascularity affects the quantitative characteristics grey-scale images. This study was undertaken to examine influences scrotal/testicular integument blood flow on testicular echotexture parameters in ram. Serial images were obtained during surgical castration 7 Rideau Arcott rams aged 20-22 weeks. first 2 sets taken through...

Regulatory T cells (Tregs) facilitate primary and metastatic tumour growth through the suppression of anti-tumour immunity. Emerging evidence suggests a distinct role for Tregs in mediating tissue repair barrier integrity lungs by IL-33 mediated production factor amphiregulin (AREG). Dependent on type cancer local microenvironment, AREG may induce cell proliferation, invasion, migration or resistance to apoptosis signaling epidermal receptor (EGFR). We have found that is dramatically...

Despite advances in targeted therapy for lung cancer, survival patients remains poor and cancer the leading cause of cancer-related deaths worldwide. The type I insulin-like growth factor receptor (IGF-IR) has emerged as a potential target treatment, however, clinical trials to date have provided disappointing results. Further research is needed identify if certain would benefit from IGF-IR therapies ideal approach incorporate agents with current therapies. dual IGF-IR/insulin inhibitor,...

// S. Elizabeth Franks 1 , Ritesh Briah Robert A. Jones Roger Moorehead Department of Biomedical Science, Ontario Veterinary College, University Guelph, Ontario, Canada Correspondence to: Moorehead, e-mail: rmoorehe@uoguelph.ca Keywords: Akt, lung cancer, IGF-IR, transgenic mice, tumor development Received: July 27, 2015 Accepted: November 16, Published: December 07, ABSTRACT AKT is a serine-threonine kinase that becomes hyperactivated in number cancers including cancer. Based on AKT's...

Molecular profiling has allowed a more precise classification of human cancers. With respect to breast cancer, this approach been used identify five subtypes; luminal A, B, HER2-enriched, basal-like and claudin-low. In addition, can be determine the type tumor represented by particular cell lines or transgenic animal models. Therefore, was utilized classify mammary tumors that develop in MTB-IGFIR mice. It determined primary tumors, which due elevated expression I insulin-like growth factor...

ABSTRACT Bacillus anthracis , the causative agent of anthrax, relies on multiple virulence factors to subvert host immune defense. Using Caenorhabditis elegans as an infection model, we screened approximately 5,000 transposon mutants B. Sterne for decreased virulence. One attenuated resulted in loss expression yceG and yceH last two genes a six-gene cluster tellurite resistance genes. We generated analogous insertional mutant confirm phenotype characterize role yceGH defenses. Loss rendered...

Metastatic breast cancer is challenging to effectively treat, highlighting the need for an improved understanding of host factors that influence metastatic tumor cell colonization and growth in distant tissues. The lungs are a common site metastasis population tissue-resident eosinophils. Eosinophils granulocytic innate immune cells known their prominent roles allergy Th2 immunity. Though presence solid tumors metastases have been reported decades, eosinophils on unclear. We used transgenic...

Immune checkpoint blockade (ICB) therapy, while groundbreaking, must be improved to promote enhanced durable responses and prevent the development of treatment-refractory disease. Cancer therapies that engage, enable, expand antitumor immune response will likely require rationally designed combination strategies. Targeting multiple immunosuppressive pathways simultaneously may provide additional therapeutic benefit over singular targeting. We therefore hypothesized use two molecules which...

Cellular therapy has emerged as an attractive option for the treatment of cancer, and adoptive transfer chimeric antigen receptor (CAR) expressing T cells gained FDA approval in hematologic malignancy. However, limited efficacy been observed utilizing CAR-T solid tumors. Natural killer (NK) are crucial tumor surveillance exhibit potent killing capacity aberrant antigen-independent manner. Adoptive unmodified allogeneic or autologous NK shown clinical benefit due to factors including low cell...

The inositol lipid phosphatases PTEN and SHIP-1 play a crucial role in maintaining B cell anergy are reduced expression cells from systemic lupus erythematosus type 1 diabetes patients, consequent to aberrant regulation by miRNA-7 155. With an eye toward eventual use precision medicine therapeutic approaches autoimmunity, we explored the ability of p110δ inhibition compensate for PI3K pathway dysregulation mouse models autoimmunity. Low dosages inhibitor idelalisib, which spare mount immune...

Abstract There is strong evidence that chemotherapy can induce tumor necrosis which be exploited for the targeted delivery of immuno-oncology agents into microenvironment (TME). We hypothesized docetaxel, a chemotherapeutic agent induces necrosis, in combination with bifunctional molecule NHS-IL-12 (M9241), delivers recombinant IL-12 through specific targeting necrotic regions tumor, would provide significant antitumor benefit poorly inflamed murine model, EMT6 (breast), and moderately...

Mouse models of cancer play an important role in elucidating the molecular mechanisms that contribute to tumorigenesis. The extent which these resemble one another and their human counterparts at level is critical understanding In this study, we carried out a comparative gene expression analysis generate detailed portrait transgenic mouse model IGFIR-driven lung cancer. tumors displayed strong resemblance with established adenocarcinoma, particularly EGFR-driven highlighted by elevated...

Hypoxia develops in germinal centers (GCs) induced by model antigens; however, it is unknown whether tumor-reactive GCs are also hypoxic. We identified GC hypoxia lymph nodes (LNs) draining murine mammary tumors and lethally irradiated tumor cells, found that associated with the levels of antibody-secreting B cells. Hypoxic culture conditions impaired proliferation activated inhibited class-switching to IgG1 IgA immunoglobulin isotypes vitro. To assess role hypoxic response vivo, we deleted...

Abstract Tumor necrosis prior to therapy historically correlates with aggressive tumor phenotypes. However, in response chemotherapy leads increased progression-free and overall survival several cancer types. Chemotherapy docetaxel results inhibition of mitosis, leading necrosis. To exploit the therapeutic potential docetaxel, a bifunctional molecule consisting mAb specific for histone H1 two molecules IL-12 (NHS-IL-12), was engineered deliver rIL-12 microenvironment (TME) through targeting...

Abstract Lung cancer is the leading cause of related mortalities worldwide. Akt an important kinase in PI3K pathway growth factor signaling, and increased activation lung associated with poor prognosis. regulates cell growth, proliferation, survival, metabolism migration making it attractive target for molecular therapies. exists as three isoforms (Akt1-3) while was previously thought they were largely redundant activity, evidence differing roles emerging. Our lab has generated a...

Abstract Lung cancer is the leading cause of related mortalities worldwide. The type I insulin-like growth factor receptor (IGF-IR) frequently expressed at high levels in lung cancer. This involved cell proliferation, apoptosis, migration and differentiation emerging as a potential target for molecular therapies. Furthermore, IGF-IR downregulation has been reported to sensitize cells agents that promote apoptosis. To investigate importance tumorigenesis, our lab generated...

Abstract Variations in expression and/or function of a number genes confer increased risk development autoimmunity. Among these variations is the negative regulators PI3K pathway, whose activity critical maintaining B cell anergy. Anergy, which autoreactive cells are unresponsive to antigen, maintained via upregulation inositol phosphatases PTEN SHIP-1, hydrolyze PI(3,4,5)P3, product PI3K, yielding PI(4,5)P2 and PI(3,4)P2, respectively. Levels reduced SLE due aberrant regulation by miRNA-7...