The Roles of Tumor-Derived Exosomes in Cancer Pathogenesis

Exosomes are endosome-derived, 30–100 nm small membrane vesicles released by most cell types including tumor cells. They are enriched in a selective repertoire of proteins and nucleic acids from parental cells and are thought to be actively involved in conferring intercellular signals. Tumor-derived exosomes have been viewed as a source of tumor antigens that can be used to induce antitumor immune responses. However, tumor-derived exosomes also have been found to possess immunosuppressive properties and are able to facilitate tumor growth, metastasis, and the development of drug resistance. These different effects of tumor-derived exosomes contribute to the pathogenesis of cancer. This review will discuss the roles of tumor-derived exosomes in cancer pathogenesis, therapy, and diagnostics

Immunosuppressive Exosomes: A New Approach for Treating Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease and one of the leading causes of disability in the USA. Although certain biological therapies, including protein and antibodies targeting inflammatory factors such as the tumor necrosis factor, are effective in reducing symptoms of RA, these treatments do not reverse disease. Also, although novel gene therapy approaches have shown promise in preclinical and clinical studies to treat RA, it is still unclear whether gene therapy can be readily and safely applied to treat the large number of RA patients. Recently, nanosized, endocytic-derived membrane vesicles “exosomes” were demonstrated to function in cell-to-cell communication and to possess potent immunoregulatory properties. In particular, immunosuppressive DC-derived exosomes and blood plasma- or serum-derived exosomes have shown potent therapeutic effects in animal models of inflammatory and autoimmune disease including RA. This paper discusses the current knowledge on the production, efficacy, mechanism of action, and potential therapeutic use of immunosuppressive exosomes for arthritis therapy

Infinite products involving binary digit sums

Let $(u_n)_{n\ge 0}$ denote the Thue-Morse sequence with values $\pm 1$. The Woods-Robbins identity below and several of its generalisations are well-known in the literature \begin{equation*}\label{WR}\prod_{n=0}^\infty\left(\frac{2n+1}{2n+2}\right)^{u_n}=\frac{1}{\sqrt 2}.\end{equation*} No other such product involving a rational function in $n$ and the sequence $u_n$ seems to be known in closed form. To understand these products in detail we study the function \begin{equation*}f(b,c)=\prod_{n=1}^\infty\left(\frac{n+b}{n+c}\right)^{u_n}.\end{equation*} We prove some analytical properties of $f$. We also obtain some new identities similar to the Woods-Robbins product.Comment: Accepted in Proc. AMMCS 2017, updated according to the referees' comment

Dedifferentiation rescues senescence of progeria cells but only while pluripotent

Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disease in which children develop pathologies associated with old age. HGPS is caused by a mutation in the LMNA gene, resulting in the formation of a dominant negative form of the intermediate filament, nuclear structural protein lamin A, termed progerin. Expression of progerin alters the nuclear architecture and heterochromatin, affecting cell cycle progression and genomic stability. Two groups recently reported the successful generation and characterization of induced pluripotent stem cells (iPSCs) from HGPS fibroblasts. Remarkably, progerin expression and senescence phenotypes are lost in iPSCs but not in differentiated progeny. These new HGPS iPSCs are valuable for characterizing the role of progerin in driving HGPS and aging and for screening therapeutic strategies to prevent or delay cell senescence

Arthritis gene therapy's first death

In July 2007 a subject died while enrolled in an arthritis gene therapy trial. The study was placed on clinical hold while the circumstances surrounding this tragedy were investigated. Early in December 2007 the Food and Drug Administration removed the clinical hold, allowing the study to resume with minor changes to the protocol. In the present article we collate the information we were able to obtain about this clinical trial and discuss it in the wider context of arthritis gene therapy

SIRT1 Negatively Regulates the Mammalian Target of Rapamycin

The IGF/mTOR pathway, which is modulated by nutrients, growth factors, energy status and cellular stress regulates aging in various organisms. SIRT1 is a NAD+ dependent deacetylase that is known to regulate caloric restriction mediated longevity in model organisms, and has also been linked to the insulin/IGF signaling pathway. Here we investigated the potential regulation of mTOR signaling by SIRT1 in response to nutrients and cellular stress. We demonstrate that SIRT1 deficiency results in elevated mTOR signaling, which is not abolished by stress conditions. The SIRT1 activator resveratrol reduces, whereas SIRT1 inhibitor nicotinamide enhances mTOR activity in a SIRT1 dependent manner. Furthermore, we demonstrate that SIRT1 interacts with TSC2, a component of the mTOR inhibitory-complex upstream to mTORC1, and regulates mTOR signaling in a TSC2 dependent manner. These results demonstrate that SIRT1 negatively regulates mTOR signaling potentially through the TSC1/2 complex

Algorithmic Randomness and Capacity of Closed Sets

We investigate the connection between measure, capacity and algorithmic randomness for the space of closed sets. For any computable measure m, a computable capacity T may be defined by letting T(Q) be the measure of the family of closed sets K which have nonempty intersection with Q. We prove an effective version of Choquet's capacity theorem by showing that every computable capacity may be obtained from a computable measure in this way. We establish conditions on the measure m that characterize when the capacity of an m-random closed set equals zero. This includes new results in classical probability theory as well as results for algorithmic randomness. For certain computable measures, we construct effectively closed sets with positive capacity and with Lebesgue measure zero. We show that for computable measures, a real q is upper semi-computable if and only if there is an effectively closed set with capacity q