IntroductionBone marrow (BM)-derived mesenchymal stem cells (MSCs) are rare residents of the BM microenvironment. 1 Isolated from their BM companions by their characteristic adherence to plastic, MSCs can be expanded from a single BM aspiration to produce millions of cells. 2 In addition to their powerful replicative capacity, MSCs are multipotential and capable of differentiating into osteocytes, chondrocytes, adipocytes, myocytes, endotheliocytes, and neurocytes. 3,4 Immunologically, MSCs have unique immunologic characteristics, such as low immunogenicity and immunoregulatory property. 5 They express negligible levels of major histocompatibility complex (MHC) class I and no MHC class II or Fas ligand, nor do they express CD80, CD86, CD40, or CD40L. 1,2 MSCs have also been reported to inhibit T-cell proliferation induced in a mixed lymphocyte reaction (MLR) or by nonspecific mitogens. 6 Dendritic cells (DCs), the most potent antigen-presenting cells (APCs), are pivotal and ubiquitously distributed in immune response. They are derived from CD34 ϩ BM stem cells and can be generated from monocytes in vitro by incubation with granulocytemacrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). 7 DCs plays a major role in the uptake, transport, and presentation of antigens with the unique capacity to stimulate naive T cell. 8 The ability of DCs to initiate an immune response depends on its transition from antigen processing to antigen-presenting cell, during which it up-regulates MHC class II and costimulatory molecules (CD80 and CD86) on the cell surface, a process referred to as DC maturation. 9 This transition is indispensable for mounting an immune response because immature DCs (imDCs) not only fail to prime T cells effectively 10 but also serve to promote tolerance induction. 11 In addition to their polarizing capacity on naive T cells, they can interact with B cells 12 and natural killer (NK) cells. 13 Notch is an evolutionarily conserved transmembrane protein that was first described as the product of a neurogenic gene in Drosophila. Vertebrate notch homologs have now been identified in various tissues, which play a critical role not only in embryogenesis, but also in the regulation of cell growth and differentiation of adult tissues. 14 There are 4 identified notch receptors (Notch1-4) and 5 ligands of the Jagged families (Jagged1, 2) and Delta-like families 3,4), but the precise functions of each ligand for receptor are not well understood. 15,16 Many studies have implicated functions of notch signaling in hematopoiesis and thymic development, 17,18 that determine all the choices between 19 between TCR␣␤ and TCR␥␦ decision 20 and between CD4 ϩ and CD8 ϩ T-cell production. 21 Moreover, they also play an essential role in the peripheral immune regulation. Hoyne et al observed that murine DCs overexpressed Serrate-1 (the homolog of the human Jagged-1) could generate antigen-specific regulatory T cell that transferred tolerance to naive recipient mice. 22 Ohishi et al also demonstrated that the...

Multiple zeta values (MZVs) in the usual sense are the special values of multiple variable zeta functions at positive integers. Their extensive studies are important in both mathematics and physics with broad connections and applications. In contrast, very little is known about the special values of multiple zeta functions at non-positive integers since the values are usually undefined. We define and study multiple zeta functions at integer values by adapting methods of renormalization from quantum field theory, and following the Hopf algebra approach of Connes and Kreimer. This definition of renormalized MZVs agrees with the convergent MZVs and extends the work of Ihara-Kaneko-Zagier on renormalization of MZVs with positive arguments. We further show that the important quasi-shuffle (stuffle) relation for usual MZVs remains true for the renormalized MZVs.

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As a promising therapeutic strategy, oncolytic virotherapy has shown potent anticancer efficacy in numerous pre-clinical and clinical trials. Oncolytic viruses have the capacity for conditional-replication within carcinoma cells leading to cell death via multiple mechanisms, including direct lysis of neoplasms, induction of immunogenic cell death, and elicitation of innate and adaptive immunity. In addition, these viruses can be engineered to express cytokines or chemokines to alter tumor microenvironments. Combination of oncolytic virotherapy with other antitumor therapeutic modalities, such as chemotherapy and radiation therapy as well as cancer immunotherapy can be used to target a wider range of tumors and promote therapeutic efficacy. In this review, we outline the basic biological characteristics of oncolytic viruses and the underlying mechanisms that support their use as promising antitumor drugs. We also describe the enhanced efficacy attributed to virotherapy combined with other drugs for the treatment of cancer.