200 research outputs found

    Photoionization Of Atomic Oxygen At The Multiplet Term Level From 20 To 212 Ev

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    The valence shell photoionization branching ratios of atomic oxygen are measured at the multiplet term level in a synchrotron-radiation-based electron spectrometry experiment and calculated using the multiconfiguration Hartree-Fock (MCHF) method for photon energies between 20 and 212 eV. The 2p (S-4,D-2,P-2) branching ratios, 2s P-2 to 2s P-4 intensity ratio, and 2s to 2p cross-section ratio for removal of a 2s of 2p electron are presented, and satisfactory agreement between the experiment and the MCHF calculation is found. In addition, the relative photoionization cross section is measured between 24 and 122 eV and is compared with calculations and a previous absolute cross-section measurement. Good agreement between the experimental and MCHF results is seen

    Immune-mediated mechanisms influencing the efficacy of anticancer therapies

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    Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease

    Principles of Modular Tumor Therapy

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    Nature is interwoven with communication and is represented and reproduced through communication acts. The central question is how may multimodal modularly acting and less toxic therapy approaches, defined as modular therapies, induce an objective response or even a continuous complete remission, although single stimulatory or inhibitingly acting drugs neither exert mono-activity in the respective metastatic tumor type nor are they directed to potentially ‘tumor-specific’ targets. Modularity in the present context is a formal pragmatic communicative systems concept, describing the degree to which systems objects (cells, pathways etc.) may be communicatively separated in a virtual continuum, and recombined and rededicated to alter validity and denotation of communication processes in the tumor. Intentional knowledge, discharging in reductionist therapies, disregards the risk-absorbing background knowledge of the tumor’s living world including the holistic communication processes, which we rely on in every therapy. At first, this knowledge constitutes the validity of informative intercellular processes, which is the prerequisite for therapeutic success. All communication-relevant steps, such as intentions, understandings, and the appreciation of messages, may be modulated simultaneously, even with a high grade of specificity. Thus, modular therapy approaches including risk-absorbing and validity-modifying background knowledge may overcome reductionist idealizations. Modular therapies show modular events assembled by the tumor’s living world as an additional evolution-constituting dimension. This way, modular knowledge may be acquired from the environment, either incidentally or constitutionally. The new communicatively defined modular coherency of environment, i.e. the tumor-associated microenvironment, and tumor cells open novel ways for the scientific community in ‘translational medicine’

    Neutrophils in cancer: neutral no more

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    Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

    Self-recognition and Ca2+-dependent carbohydrate–carbohydrate cell adhesion provide clues to the Cambrian explosion

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    Author Posting. © The Authors, 2009. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Molecular Biology and Evolution 26 (2009): 2551-2561, doi:10.1093/molbev/msp170.The Cambrian explosion of life was a relatively short period ca. 540 million years ago that marked a generalized acceleration in the evolution of most animal phyla, but the trigger of this key biological event remains elusive. Sponges are the oldest extant Precambrian metazoan phylum and thus a valid model to study factors that could have unleashed the rise of multicellular animals. One such factor is the advent of self/non-self recognition systems, which would be evolutionarily beneficial to organisms to prevent germ cell parasitism or the introduction of deleterious mutations resulting from fusion with genetically different individuals. However, the molecules responsible for allorecognition probably evolved gradually before the Cambrian period, and some other (external) factor remains to be identified as the missing triggering event. Sponge cells associate through calcium-dependent, multivalent carbohydrate-carbohydrate interactions of the g200 glycan found on extracellular proteoglycans. Single molecule force spectroscopy analysis of g200-g200 binding indicates that calcium affects the lifetime (+Ca/-Ca: 680 s/3 s) and bond reaction length (+Ca/-Ca: 3.47 Å/2.27 Å). Calculation of mean g200 dissociation times in low and high calcium within the theoretical framework of a cooperative binding model indicates the non-linear and divergent characteristics leading to either disaggregated cells or stable multicellular assemblies, respectively. This fundamental phenomenon can explain a switch from weak to strong adhesion between primitive metazoan cells caused by the well documented rise in ocean calcium levels at the end of Precambrian time. We propose that stronger cell adhesion allowed the integrity of genetically uniform animals composed only of “self” cells, facilitating genetic constitutions to remain within the metazoan individual and be passed down inheritance lines. The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self/non-self recognition, and of a surge in sea water calcium that increased the binding forces between their calcium-dependent cell adhesion molecules.D.A. and A.K. acknowledge financial support from the Collaborative Research Center SFB 613 from the Deutsche Forschungsgemeinschaft (DFG), and X.F.-B. acknowledges financial support from grants BIO2002-00128, BIO2005-01591, and CSD2006-00012 from the Ministerio de Ciencia y Tecnología, Spain, which included Fondo Europeo de Desarrollo Regional funds, and from grant 2005SGR-00037 from the Generalitat de Catalunya, Spain

    Transition of tumor-associated macrophages from MHC class IIhi to MHC class IIlow mediates tumor progression in mice

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    <p>Abstract</p> <p>Background</p> <p>Tumor-associated macrophages (TAMs) are the most abundant immune cells within the tumor stroma and play a crucial role in tumor development. Although clinical investigations indicate that high levels of macrophage (MΦ) infiltration into tumors are associated with a poor prognosis, the exact role played by TAMs during tumor development remains unclear. The present study aimed to investigate dynamic changes in TAM major histocompatibility complex (MHC) class II expression levels and to assess the effects of these changes on tumor progression.</p> <p>Results</p> <p>Significant inhibition of tumor growth in the murine hepatocellular carcinoma Hepa1-6 model was closely associated with partial TAM depletion. Strikingly, two distinct TAM subsets were found to coexist within the tumor microenvironment during Hepa1-6 tumor development. An MHC class II<sup>hi </sup>TAM population appeared during the early phase of tumor development and was associated with tumor suppression; however, an MHC class II<sup>low </sup>TAM population became increasingly predominant as the tumor progressed.</p> <p>Conclusions</p> <p>Tumor progression was positively correlated with increasing infiltration of the tumor tissues by MHC class II<sup>low </sup>TAMs. Thus, targeting the transition of MΦ may be a novel strategy for drug development and immunotherapy.</p

    Even-parity autoionizing states in the extreme-ultraviolet photoabsorption spectra of Mg, Al⁺, and Si²⁺

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    The dual-laser-produced plasma (DLP) photoabsorption technique has been used to study 2p→3s excitations in the isoelectronic species Mg, Al+, and Si2+ prepared in the excited configuration 2p63s3p. The autoionizing upper states belong to the 2p53s23p even-parity configuration. The versatility of the technique is demonstrated through a careful combination of space- and time-resolved photoabsorption scans. Plasma conditions optimized for the observation of the inaccessible parity regime were successfully reproduced along the isoelectronic sequence of interest. All the observed transitions were interpreted with the help of multiconfigurational atomic structure calculations. In the case of magnesium, the photoabsorption data are compared with the ejected-electron spectra excited by low-energy electron impact of Pejcev et al. [J. Phys. B 10, 2389 (1977)]
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