61 research outputs found

    DĆ¼ngewirkung organischer Nebenprodukte aus der Insektenzucht der Schwarzen Soldatenfliege (Hermetia illucens)

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    Untersucht wurde die DĆ¼ngewirkung von organischen Nebenprodukten aus der Insektenzucht mit unterschiedlichen Eigenschaften zu Staudenbasilikum. Eine hoher Frischmasseertrag wurde nach DĆ¼ngung von InsektenfraƟ aufgrund eines gĆ¼nstigen VerhƤltnis von N-P-K im DĆ¼ngemittel festgestellt

    Sensitizing Protective Tumor Microenvironments to Antibody-Mediated Therapy

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    Therapy-resistant microenvironments represent a major barrier toward effective elimination of disseminated malignancies. Here, we show that select microenvironments can underlie resistance to antibody-based therapy. Using a humanized model of treatment refractory B cell leukemia, we find that infiltration of leukemia cells into the bone marrow rewires the tumor microenvironment to inhibit engulfment of antibody-targeted tumor cells. Resistance to macrophage-mediated killing can be overcome by combination regimens involving therapeutic antibodies and chemotherapy. Specifically, the nitrogen mustard cyclophosphamide induces an acute secretory activating phenotype (ASAP), releasing CCL4, IL8, VEGF, and TNFĪ± from treated tumor cells. These factors induce macrophage infiltration and phagocytic activity in the bone marrow. Thus, the acute induction of stress-related cytokines can effectively target cancer cells for removal by the innate immune system. This synergistic chemoimmunotherapeutic regimen represents a potent strategy for using conventional anticancer agents to alter the tumor microenvironment and promote the efficacy of targeted therapeutics.Massachusetts Institute of Technology. Ludwig Center for Molecular OncologyKathy and Curt Marble Cancer Research FundSingapore-MIT Alliance for Research and TechnologyGerman Research Foundation (KFO286)German Research Foundation (Fellowship)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051

    Bioinformatics tools for cancer metabolomics

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    It is well known that significant metabolic change take place as cells are transformed from normal to malignant. This review focuses on the use of different bioinformatics tools in cancer metabolomics studies. The article begins by describing different metabolomics technologies and data generation techniques. Overview of the data pre-processing techniques is provided and multivariate data analysis techniques are discussed and illustrated with case studies, including principal component analysis, clustering techniques, self-organizing maps, partial least squares, and discriminant function analysis. Also included is a discussion of available software packages

    PI3K/BCL2: illusion or promise for RS?

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    In this issue of Blood, Iannello et al report that phosphatidylinositol 3-kinase (PI3K) inhibitors can sensitize samples from patients with Richter syndrome (RS) to BCL2 inhibitors by regulating the expression of antiapoptotic molecules via glycogen synthase kinase 3 beta (GSK3 beta). The authors have thus provided a rationale for a novel drug combination to treat patients with chronic lymphocytic leukemia (CLL) and RS.(1

    Does the applied polytrauma definition notably influence outcome and patient population? ā€“ a retrospective analysis

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    Abstract Background Although the term ā€œpolytraumaā€ has been in use for decades, no generally accepted definition exists. The aim of this study was to demonstrate that different polytrauma definitions applied to a specific patient population result in diverse subgroups of individuals, who in turn present a varying outcome. Methods All patients (ā‰„18Ā years) treated at our level I trauma center within a time period of threeĀ years were classified according to 11 selected polytrauma definitions and included in our study, if they were rated ā€œpolytraumatizedā€ by at least one of these definitions. All patients, who met the criteria of a certain definition, were combined to the relevant definition-positive group, thus resulting in 11 patient subgroups. Their demographic data (number of patients, mean patient age, mean Injury Severity Score value, median number of ventilator days, median length of stay at the intensive care unit and at the hospital, mortality rate and odds ratio) were statistically compared. Results Three hundred seventy-five patients (73% male) with a mean age of 47Ā years met the inclusion criteria and were allocated to the relevant subgroups; their patient number varied from 55 to 346 and their mean Injury Severity Score value ranged from 4 to 75. Not surprisingly, all examined parameters were subject to variations. Whereas most definition-positive groups showed a mortality rate of about 21% to 30%, 18% of the individuals, who met the criteria according to Blacker, and 40% of the polytrauma victims according to Schalamon died. The Pape 1-, Schalamon-, and Berlin-positive groups presented a significant odds ratio with regard to mortality that considerably exceeded 1. Discussion A polytrauma definition can only be a reliable tool in classifying trauma victims if it provides a significant odds ratio with regard to mortality that considerably exceeds 1 and if it succeeds in capturing patients with multiple severe injuries and a higher mortality rate without reducing the number of polytraumatized patients to a not representatively small number. Conclusions Solely the Berlin definition resulted in a patient number reflecting clinical reality, thus enabling a transparent evaluation of treatment results provided by different institutions and allowing objective comparison of published studies

    Concepts of Chronic Lymphocytic Leukemia Pathogenesis: DNA Damage Response and Tumor Microenvironment

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    Pathogenesis of chronic lymphocytic leukemia (CLL) is characterized by specific genetic aberrations and alterations of cellular signaling pathways. In particular, a disturbed DNA damage response (DDR) and an activated B-cell receptor signaling pathway play a major role in promoting CLL cell survival. External stimuli are similarly essential for CLL cell survival and lead to activation of the PI3K/AKT and MAPK pathways. Activation of nuclear factor-kappa B (NFkB) influences the disturbed antiapoptotic balance of CLL cells. Losses or disabling mutations in TP53 and ATM are frequent events in chemotherapy- naive patients and are further enriched in chemotherapy- resistant patients. As these lesions define key regulatory elements of the DDR pathway, they also determine treatment response to genotoxic therapy. Novel therapeutic strategies therefore try to circumvent defective DDR signaling and to suppress the pro-survival stimuli received from the tumor microenvironment. With increasing knowledge on specific genetic alterations of CLL, we may be able to target CLL cells more efficiently even in the situation of mutated DDR pathways or protection by microenvironmental stimuli. (C) 2016 S. Karger GmbH, Freibur
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