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  • 1
    Abstract: The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFalpha can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFalpha in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes. A reverse correlation between tumor weight and the number of tumor-reactive PD-1 tumor-infiltrating lymphocytes (TILs) was observed, suggesting that these T cells could target and kill tumor cells. It is interesting to note that, local expression of cytokines did not affect intratumoral levels of T-regulatory cells (Tregs), which had previously been associated with systemic IL2 therapy. Instead, Ad5-IL2 induced upregulation of IL2 receptor alpha-chain (CD25) on conventional CD4CD25Foxp3 cells, indicating that these CD4 T cells may contribute to CD8 T-cell activation and/or homing. Signs of therapy-induced resistance were also observed as the expression of PD-L1 on tumor-infiltrating granulocytic myeloid-derived suppressor cells was upregulated as a reaction to PD-1+ TILs. Finally, beneficial ratios between tumor-reactive PD-1 CD8 TILs and immunosuppressive cell subsets (Tregs and nitric oxide-producing myeloid-derived suppressor cells) were observed in primary and secondary tumor sites, indicating that local delivery of IL2 and TNFalpha coding adenoviruses can systemically modify the cellular composition of the tumor microenvironment in favor of adoptively transferred T cells.
    Type of Publication: Journal article published
    PubMed ID: 27741089
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  • 2
    Abstract: Pancreatic stellate cells are stromal cells that have multiple physiological functions such as the production of extracellular matrix, stimulation of amylase secretion, phagocytosis and immunity. In pancreatic cancer, stellate cells exhibit a different myofibroblastic-like morphology with the expression of alpha-smooth muscle actin, the activated form is engaged in several mechanisms that support tumorigenesis and cancer invasion and progression. In contrast to the aforementioned observations, eliminating the stromal cells that are positive for alpha-smooth muscle actin resulted in immune-evasion of the cancer cells and resulted in worse prognosis in animal models. Understanding the cancer-stromal signaling in pancreatic adenocarcinoma will provide novel strategies for therapy. Here we provide an updated review of studies that handle the topic "pancreatic stellate cells in cancer" and recent experimental approaches that can be the base for future directions in therapy.
    Type of Publication: Journal article published
    PubMed ID: 28601475
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Biology and fertility of soils 2 (1986), S. 83-86 
    ISSN: 1432-0789
    Keywords: Fixed ammonium ; Available residual ammonium ; Maize ; KOBr-extractable N
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary To estimate the availability of residual fixed NH 4 + -N to crops and its participation in the general nitrogen cycle, a field experiment without N fertilization was conducted with maize as the test crop planted at two densities. The experiments were carried out on the layout of a previous experiment, where the maize was cropped with identical densities but was fertilized with five different N treatments. Irrespective of planting density, the residual fixec NH 4 + -N and KOBr-extractable N content in soil decreased with increase in the period of crop growth. N uptake by the plant was significantly higher in plot with the high- than the low-density planting. Availability of residual fixed NH 4 − -N to the crop is discussed.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1181
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract  Void fraction and pressure drop correlations play an important role in predicting the performance of natural circulation loops. Hence an assessment of the commonly used and often cited correlations for pressure drop and void fraction has been carried out with data from natural circulation loops. This assessment considered 33 void fraction correlations and 14 pressure drop correlations. The void fraction correlations were initially tested against the various limiting conditions. Only 14 correlations were found to satisfy at least two limiting conditions (i.e., at x = 0; α = 0 and at x = 1; α = 1) and were assessed against the data. This assessment showed that the Chexal et al. (1996) correlation is better than all the others considered. The assessment of pressure drop correlations were carried out with the Chexal et al. (1996) correlation for void fraction and Saha-Zuber model for the onset of subcooled boiling. This assessment showed that most correlations give predictions close to each other.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1588-2780
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract An investigation is conducted on the status of trace and minor elements in some foodstuffs (cereals, vegetables, milk, egg and fish), commonly consumed in Bangladesh, using proton induced X-ray emission (PIXE) and radioisotope-induced X-ray fluorescence (XRF) techniques. In PIXE measurements, the samples were irradiated in air with 2.0 MeV (energy on the target) protons having the beam intensity of 30 nA for characteristic X-ray excitation, while in XRF analysis, the samples were excited for 5000 seconds with a 10 mCi Cd-109 annular X-ray source. The elemental concentration of K, Ca, Mn, Fe, Ni, Cu, Zn, Se, As, Br, Rb, Sr, Mo, and Pb were determined in the samples by comparison with X-ray yield curves constructed from IAEA and NBS standard reference materials. The validity of the analytical procedures (PIXE and XRF) followed in this study has been confirmed by comparative measurements of Cu, Zn and Mn in some varieties of rice with atomic absorption spectrophotometry. The results indicate that none of the food regimes investigated here is burdened with heavy metals beyond permissible limits except five species of vegetables with chromium having the range of 0.99–3.59 mg/kg compared to the literature value of 0.0–0.36 mg/kg (dry weight basis). An average value of 0.2 mg/kg of arsenic was observed both in IRRI (n=16) and local Aman (n=12) varieties of rice and only one hen egg contained 1.7 mg/kg of lead in yolk. The zinc content in some marine fish from Bay of Bengal was reported to be 5.4–19.5 mg/kg, whereas in the present study of sweet-water fish, the level is found to be 15.2–62.1 mg/kg (fresh weight basis) for five species. In human milk, both Cu (0.12–0.25 mg/l, n=8) and Zn (0.28–1.80 mg/l, n=8) levels appear to be almost half the literature values (n=25). On the other hand formula milk has higher values of Cu (0.32–1.63 mg/kg, n=16) and Zn (5.16–19.8 mg/kg, n=16).
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillian Magazines Ltd.
    Nature 416 (2002), S. 413-416 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only ...
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Czechoslovak journal of physics 41 (1991), S. 569-582 
    ISSN: 1572-9486
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Propagation of longitudinal surface waves on the surface of a rotating monoclinic piezoelectric half space has been considered taking into account generalized thermal coupling as in Green and Lindsay model. Variations of piezoelectric potential, particle displacement, temperature, etc. with depth into the medium and the piezoelectric Poynting vector together with power fiow components have been derived, assuming the existence of a shorting plane at a certain distance above the free surface of the half space.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Clinica Chimica Acta 55 (1974), S. 5-9 
    ISSN: 0009-8981
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 0003-2697
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 10
    Publication Date: 2018-07-17
    Description: Purpose: Glioblastoma (GBM), a fatal brain cancer, contains a subpopulation of GBM stem-like cells (GSCs) that contribute to resistance to current therapy. Angiogenesis also plays a key role in GBM progression. Therefore, we developed a strategy to target the complex GBM microenvironment, including GSCs and tumor vasculature. Experimental Design: We evaluated the cytotoxic effects of VEFGR tyrosine kinase inhibitor (TKI) axitinib in vitro and then tested antitumor efficacy of axitinib in combination with oncolytic herpes simplex virus (oHSV) expressing antiangiogenic cytokine murine IL12 (G47-mIL12) in two orthotopic GSC-derived GBM models: patient-derived recurrent MGG123 GSCs, forming vascular xenografts in immunodeficient mice; and mouse 005 GSCs, forming syngeneic tumors in immunocompetent mice. Results: GSCs form endothelial-like tubes and were sensitive to axitinib. G47-mIL12 significantly improved survival, as did axitinib, while dual combinations further extended survival significantly compared with single therapies alone in both models. In MGG123 tumors, axitinib was effective only at high doses (50 mg/kg), alone and in combination with G47-mIL12, and this was associated with greatly decreased vascularity, increased macrophage infiltration, extensive tumor necrosis, and PDGFR/ERK pathway inhibition. In the mouse 005 model, antiglioma activity, after single and combination therapy, was only observed in immunocompetent mice and not the T-cell–deficient athymic mice. Interestingly, immune checkpoint inhibition did not improve efficacy. Conclusions: Systemic TKI (axitinib) beneficially combines with G47-mIL12 to enhance antitumor efficacy in both immunodeficient and immunocompetent orthotopic GBM models. Our results support further investigation of TKIs in combination with oHSV for GBM treatment. Clin Cancer Res; 24(14); 3409–22. ©2018 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
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