Introduction The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion Most of the TKR share intracellular signaling pathways; therefore, cancer cells tend to overcome the inhibition of one tyrosine kinase receptor by activating another. The future of TKI (Tyrosine Kinase Inhibitor) therapy will potentially come from multi-targeted TKIs that target different TKR simultaneously. It is crucial to understand the interaction of the FGF-FGFR axis with other known driver TKRs. Based on this, it is possible to develop therapeutic strategies targeting multiple connected TKRs at once. One correct step in this direction is the reassessment of multi target inhibitors considering the FGFR status of the tumor. Another opportunity arises from assessing the use of FGFR TKI on patients harboring FGFR alterations

M protein is a fibrous, predominantly a-helical, coiled-coil molecule extending from the cell surface of group A streptococci (1, 2). Through its ability to allow this organism to escape phagocytosis by the host's defenses, M protein acts as the primary virulence factor for these streptococci . Protection from streptococcal infection is due primarily to opsonization by type-specific antibodies directed against the M protein (3).Previously, serological crossreactions among purified M proteins of various serotypes proved limited (4, 5), with restricted crossprotection in phagocytic assays (5). These studies were confined, however, to fragments of the M protein that represent approximately the amino terminal half of the native molecule, distal to the streptococcal cell surface (6). Similar limited crossreactivity was seen (7-9) with peptides synthesized on the basis of amino acid sequence determinations within these amino terminal fragments. Opsonic antibodies in these studies, however, were type-specific. Recently, a study (10) using mAbs directed against the entire M6 protein suggested that the amino terminal region of the M protein molecule was variable with respect to antigenic epitopes shared among M serotypes. Conversely, more extensive crossreactions may be reserved for regions more proximal to the cell surface (i. e., the carboxy terminal half of the molecule). The mAb directed toward the amino terminal half of the M6 protein (10A11) crossreacted with 5 different M serotyping strains, whereas the mAb directed toward the carboxy terminal half (10136) did so with 20 of these serotyping strains. Through the use of DNA probes, the location of the conserved epitope was found (2) to be located more centrally in the native molecule, and just carboxy terminal to the pepsin cleavage site, which divides the molecule approximately in half. As a further definition of the antigenic structure of the M molecule, Manjula et al. (11) identified regions within the amino terminal half of the M5 and M6 proteins that crossreact, and they defined a hypervariable antigenic domain located in the amino terminal quarter of these proteins . In a more recent study using DNA probes of the M6 gene to identify constant and variable regions of M proteins in other serotypes, it was found that the carboxy terminal region of the M protein was conserved among strains of several different 1226 J. Exp. MED. C The Rockefeller University

Exosomes are membrane-enclosed entities of endocytic origin, which are generated during the fusion of multivesicular bodies (MVBs) and plasma membranes. Exosomes are released into the extracellular milieu or body fluids; this process was reported for mesenchymal, epithelial, endothelial, and different immune cells (B-cells and dendritic cells), and was reported to be correlated with normal physiological processes. The compositions and abundances of exosomes depend on their tissue origins and cell types. Exosomes range in size between 30 and 100 nm, and shuttle nucleic acids (DNA, messenger RNAs (mRNAs), microRNAs), proteins, and lipids between donor and target cells. Pathogenic microorganisms also secrete exosomes that modulate the host immune system and influence the fate of infections. Such immune-modulatory effect of exosomes can serve as a diagnostic biomarker of disease. On the other hand, the antigen-presenting and immune-stimulatory properties of exosomes enable them to trigger anti-tumor responses, and exosome release from cancerous cells suggests they contribute to the recruitment and reconstitution of components of tumor microenvironments. Furthermore, their modulation of physiological and pathological processes suggests they contribute to the developmental program, infections, and human diseases. Despite significant advances, our understanding of exosomes is far from complete, particularly regarding our understanding of the molecular mechanisms that subserve exosome formation, cargo packaging, and exosome release in different cellular backgrounds. The present study presents diverse biological aspects of exosomes, and highlights their diagnostic and therapeutic potentials.

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An efficient in vitro multiplication system via multiple shoot bud induction and regeneration has been developed in Chlorophytum arundinaceum using shoot crown explants. Optimum regeneration frequency (87%) and desirable organogenetic response in the form of de novo organized multiple shoot buds without an intervening callus phase was obtained on Murashige and Skoog's (MS) minimal organics medium containing 3% sucrose (w/v) supplemented with 4 x 10(-6) M Kn and 2 x 10(-6) MIBA. Axenic secondary explants with multiple shoot buds on subculturing elicited best response with 1 x 10(-5) M Kinetin (Kn) and 5 x 10(-6) M indole-3-butyric acid (IBA) giving rise to an average of 18.74 shoots per culture with mean shoot length of 7.6 cm +/- 1.73. Varying molar ratios of either Kn/IBA or Kn/NAA revealed statistically significant differences in the regeneration frequencies among the phytohormone treatments. It was observed that the shoot bud differentiation and regeneration was influenced by the molar ratios of cytokinins/auxin rather than their relative concentrations. Healthy regenerated shoots were rooted in half strength MS basal medium containing 3% sucrose (w/v) supplemented with 5 x 10(-6) M IBA. Following simple hardening procedures, rooted plantlets, were transferred to soil-sand (1:1; v/v) with more than 90% success. Genetic fidelity was assessed using random amplified polymorphic DNA (RAPD), karyotype analysis and meiotic behaviour of in vitro and in vivo plants. Five arbitrary decamers displayed same banding profile within all the micropropagated plants and in vivo explant donor. The cytological and molecular analysis complemented and compared well and showed no genomic alterations in the plants regenerated through shoot bud differentiation. High multiplication frequency, molecular, cytological and phenotypic stability ensures the efficacy of the protocol developed for the production and conservation of this important endangered medicinal herb.