Natural killer cell (NK) receptors for major histocompatibility complex (MHC) class I influence engraftment and graft-versus-tumor effects after allogeneic bone marrow transplantation. We find that SH2-containing inositol phosphatase (SHIP) influences the repertoire of NK receptors. In adult SHIP −/− mice, compartment is dominated by cells express two inhibitory capable binding either self or MHC ligands. This promiscuous has significant functional consequences, because mice fail to reject...

Abstract Previously we demonstrated that SHIP−/− mice accept allogeneic bone marrow transplants (BMT) without significant acute graft-vs-host disease (GvHD). In this study show splenocytes and lymph node cells are poor stimulators of T cell responses cause GvHD. Intriguingly, prime naive to peptide epitopes, but, conversely, partially impaired for priming whole Ag. However, dendritic (DC) purified from targets, Ag as effectively SHIP+/+ DC. These findings point an extrinsic effect on DC...

Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector cells. The transcription factor Ikaros is critical for lymphocyte development, especially We have previously shown downregulation occurs as a result its protein degradation ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed deregulation balance between Casein Kinase II (CK2) and phosphatase 1 (PP1), which...

Abstract Graft-vs-host disease (GVHD) is the leading cause of treatment-related death in allogeneic bone marrow (BM) transplantation. Immunosuppressive strategies to control GVHD are only partially effective and often lead life-threatening infections. We previously showed that engraftment MHC-mismatched BM enhanced abrogated recipients homozygous for a germline SHIP mutation. In this study, we report development genetic model which deficiency can be induced adult mice. Using model, show...

Background Pancreatic cancer is one of the most aggressive cancers, with tumor-induced myeloid-derived suppressor cells (MDSC) contributing to its pathogenesis and ineffective therapies. In response cytokine/chemokine receptor activation, src homology 2 domain-containing inositol 5′-phosphatase-1 (SHIP-1) influences phosphatidylinositol-3-kinase (PI3K) signaling events, which regulate immunohomeostasis. We hypothesize that factors from murine pancreatic cause down-regulation SHIP-1...

Pancreatic cancer (PC) has an extremely poor prognosis due to the expansion of immunosuppressive myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in inflammatory tumor microenvironment (TME), which halts recruitment effector immune renders immunotherapy ineffective. Thus, identification new molecular targets that can modulate TME is warranted for PC intervention. Src Homology-2 (SH2) domain-containing Inositol 5′-Phosphatase-1 (SHIP-1) a lipid signaling protein...

Pancreatic cancer (PC) is a deadly disease with grim prognosis. tumor derived factors (TDF) contribute to the induction of an immunosuppressive microenvironment (TME) that impedes effectiveness immunotherapy. PC-induced microRNA-155 (miRNA-155) represses expression Src homology 2 (SH2) domain-containing Inositol 5′-phosphatase-1 (SHIP-1), regulator myeloid cell development and function, thus impacting anti-tumor immunity. We recently reported bioflavonoid apigenin (API) increased SHIP-1...

Objective: Adipose tissue is a robust source of adipose-derived stem cells (ADSCs) that may be able to provide secreted factors promote the ability wounded heal. However, adipocytes also have potential dedifferentiate in culture with cell-like properties improve their behavior and functionality for certain applications. Approach: ADSCs are adult mesenchymal cultured from stromal vascular fraction adipose tissue. capable dedifferentiating into cell properties. In this case study, we compare...

Protein kinase CK2, formally known as casein II, is ubiquitously expressed and highly conserved serine/threonine or tyrosine enzyme that regulates diverse signaling pathways responsible for cellular processes (i.e., cell proliferation apoptosis) via interactions with over 500 substrates. The enzyme's physiological functions have been widely studied, most notably in the blood solid malignancies. CK2 has intrinsic role carcinogenesis overexpression of subunits (α, α`, β) deregulation its...

Protein kinase C (PKC) δ plays an important role in cellular proliferation and apoptosis where it is involved the caspase-3 mediated apoptotic pathway. Cleavage of PKCδI by releases a catalytically active C-terminal fragment that sufficient to induce apoptosis. In this paper, we identified novel human PKCδ isozyme, PKCδVIII (Genbank accession number DQ516383) teratocarcinoma (NT2) cells differentiate into hNT neurons upon retinoic acid (RA) treatment. Expression was confirmed real-time...

Myeloid derived suppressor cells (MDSC) suppress anti-tumor immune responses. Our recent publication provides evidence that SHIP-1 plays a prominent role in pancreatic tumor development by regulating MDSC. Therefore, may be potential therapeutic target for the treatment of MDSC-related hematological malignancies and solid tumors.

Genetic factors that influence inflammation and energy production/expenditure in cells may affect patient outcomes following treatment with external beam radiation therapy (EBRT). Sestrins, stress-inducible genes antioxidant properties, have recently been implicated several behaviors including fatigue. This proof-of-concept study explored whether the sestrin family of ( SESN1, SESN2, SESN3) were differentially expressed from baseline to midpoint EBRT a sample 26 Puerto Rican men...

MDSC are a heterogeneous population of immature macrophages, dendritic cells and granulocytes that accumulate in lymphoid organs pathological conditions including parasitic infection, inflammation, traumatic stress, graft-versus-host disease, diabetes cancer1-7. In mice, express Mac-1 (CD11b) Gr-1 (Ly6G Ly6C) surface antigens7. It is important to note well studied various tumor-bearing hosts where they significantly expanded suppress anti-tumor immune responses compared naïve...

Background Maintenance of T cell immune homeostasis is critical for adequate anti-tumor immunity. The transcription factor Ikaros essential lymphocyte development including cells. Alterations in expression occur blood malignancies humans and mice. In this study, we investigated the role regulating balance pancreatic cancer mouse models. Methodology Principal Findings Using our Panc02 tumor-bearing (TB) model, western blot analysis revealed a reduction proteins while qRT-PCR showed no...

Abstract Pancreatic Cancer (PC) is one of the most aggressive and deadliest types cancer, it projected to be second leading cause cancer-related deaths in U.S. by year 2030. PC evades immune surveillance disrupting homeostasis effector T cells (Teff). critical for proper anti-tumor responses. Preliminary flow cytometry data revealed that murine pancreatic (Panc02) cancer produce inflammatory soluble factors addition, express Major Histocompatibility Complex class I (MHC-I) Programmed Death...

Abstract Pancreatic cancer (PC) remains as a very aggressive malignancy with an extremely poor prognosis and overall 5-year survival rate of only 8%. Immunotherapies are promising against solid tumors exception PC. This is partly due to PC’s inflammatory tumor microenvironment, resulting in increased expression both Programmed Death-Ligand (PD-L1) cell death protein 1 (PD-1) on effector CD8+ T cells. Upon PD-L1/PD-1 interaction, cells exhibit anergy, allowing PC evasion progression. We...

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Abstract The alternatively spliced transcription factor Ikaros is crucial for normal lymphocyte development. plays a role as tumor suppressor in murine T cells. In pancreatic cancer hosts, the balance between effector and regulatory cells lost, leading to immunosuppression reduced anti-tumor immunity. this study, we aim identify of regulating cell homeostasis function microenvironment. Using our heterotopic model cancer, isolated splenocytes from tumor-bearing (TB) control mice performed...