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Berlin Brandenburg

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  • 1
    In: Neuro-Oncology, 2015, Vol. 17(suppl5), pp.v29-v29
    Description: Glioblastoma multiforme (GBM), characterized by an aggressive clinical course, therapeutic resistance and striking molecular heterogeneity, remains incurable. A large number GBMs have EGFR alterations and, despite poor clinical translation to date, EGFR inhibition remains of therapeutic relevance. Recent evidence, from our group and others, indicates that JAK2/STAT3 pathway is an important mediator of tumor cell survival, growth, and invasion in GBM. Interestingly, EGFR inhibition leads to activation of survival-signalling pathways such as STAT3, diminishing effectiveness of EGFR inhibition. We investigated the efficacy of a novel JAK2 inhibitor, pacritinib, in brain tumour initiating cell (BTIC) lines to evaluate potential use in the treatment of GBM patients. In a Phase III study of patients with myelofibrosis, pacritinib demonstrated manageable toxicity and clinically and statistically improved patient spleen volume and patient reported outcomes. Pacritinib results in on-target JAK2/STAT3 inhibition at 1-2 µM and dramatically reduces BTIC proliferation, regardless of endogenous MGMT promoter methylation or EGFR, PTEN, and TP53 mutational status. Pacritinib in combination with temozolomide prolongs survival, over either drug alone, in orthopically xenografted NOD-SCID. We are testing the hypothesis that concurrent inhibition of JAK/STAT and EGFR signalling may be an effective, clinically relevant therapeutic, strategy for GBM. We examined the in vitro actions of pacritinib on BTICs, in combination with three clinically approved EGFR inhibitors, erlotinib, afatinib and lapatinib and are investigating other clinically relevant EGFR inhibitors for GBM. Combinatorial treatment with pacritinib and EGFR inhibitors shows striking responses, with lowered IC50s and BTIC viability. The combinatorial actions of EGFR and STAT3 inhibition were particularly effective in BTIC lines with EGFR activating vIII and missense point mutations. On target activity was demonstrated with reduced phospho-EGFR, phospho-STAT3 and effectors of both pathways. Current studies are aimed at investigating the combined actions of Pacritinib and EGFR inhibitors, over single agents, in orthotopic xenograft animal survival.
    Keywords: Medicine;
    ISSN: 1522-8517
    E-ISSN: 1523-5866
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  • 2
    Language: English
    In: Euphytica, 2014, Vol.196(3), pp.375-384
    Description: Deployment of resistant soybean cultivars is the most effective and economical method of controlling Phytophthora root rot (PRR) incited by Phytophthora sojae , and characterization of Phytophthora resistance of the soybean cultivars greatly facilitates the effective utilization. The objective of this study was to characterize the resistance phenotype in 30 soybean cultivars/lines bred in Henan province and 4 ancestral cultivars which were inoculated with 26 P . sojae pathotypes. The 34 soybean cultivars/lines showed 34 different reaction types of resistance to 26 P . sojae pathotypes. The reaction types produced on the cultivars/lines were compared with those produced on the differential lines to postulate which Rps gene was present. The gene Rp s 5 and Rps3 a or gene combination Rps3 a+ 5 were postulated to be present in Zhoudou17 and Zheng77249, respectively. The other 32 cultivars/lines exhibited novel reaction types that were different from known single or two Rps gene combinations. The cluster analysis of the reaction types revealed 10 groups among the 34 soybean cultivars/lines, 17 differentials and the cultivar Williams at the similarity coefficient 0.6540. This study indicated that Phytophthora resistance was extremely diverse in this region. The cultivars/lines with broad spectrum resistance could provide effective sources of resistance for the control of PRR in the future.
    Keywords: Cluster analysis ; Gene postulation ; Phytophthora resistance ; Soybean ; Reaction type
    ISSN: 0014-2336
    E-ISSN: 1573-5060
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  • 3
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(7), p.e69799
    Description: Resistance to Phytophthora sojae isolate PsMC1 was evaluated in 102 F2∶3 families derived from a cross between the resistant soybean cultivar Wandou 15 and the susceptible cultivar Williams and genotyped using simple sequence repeat (SSR) markers. The segregation ratio of resistant, segregating,...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 4
    Language: English
    In: Cancer Research, 04/15/2012, Vol.72(8 Supplement), pp.1558-1558
    ISSN: 0008-5472
    E-ISSN: 1538-7445
    Source: CrossRef
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  • 5
    Language: English
    In: PLoS ONE, 01 January 2013, Vol.8(6), p.e66825
    Description: Myxoma virus (MYXV) is a well-established oncolytic agent against different types of tumors. MYXV is also known for its immunomodulatory properties in down-regulating major histocompatibility complex (MHC) I surface expression (via the M153R...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: Theoretical and Applied Genetics, 2013, Vol.126(6), pp.1555-1561
    Description: Phytophthora root rot (PRR), caused by Phytophthora sojae Kaufmann & Gerdemann, is one of the most destructive diseases of soybean [ Glycine max (L.) Merr.]. Deployment of resistance genes is the most economical and effective way of controlling the disease. The soybean cultivar ‘Yudou 29’ is resistant to many P. sojae isolates in China. The genetic basis of the resistance in ‘Yudou 29’ was elucidated through an inheritance study and molecular mapping. In response to 25 P . sojae isolates, ‘Yudou 29’ displayed a new resistance reaction pattern distinct from those of differentials carrying known Rps genes. A population of 214 F 2:3 families from a cross between ‘Jikedou 2’ (PRR susceptible) and ‘Yudou 29’ was used for Rps gene mapping. The segregation fit a ratio of 1:2:1 for resistance:segregation:susceptibility within this population, indicating that resistance in ‘Yudou 29’ is controlled by a single dominant gene. This gene was temporarily named RpsYD29 and mapped on soybean chromosome 03 (molecular linkage group N; MLG N) flanked by SSR markers SattWM82-50 and Satt1k4b at a genetic distance of 0.5 and 0.2 cM, respectively. Two nucleotide binding site-leucine rich repeat (NBS-LRR) type genes were detected in the 204.8 kb region between SattWM82-50 and Satt1k4b. These two genes showed high similarity to Rps1 k in amino acid sequence and could be candidate genes for PRR resistance. Based on the phenotype reactions and the physical position on soybean chromosome 03, RpsYD29 might be a novel allele at, or a novel gene tightly linked to, the Rps1 locus.
    ISSN: 0040-5752
    E-ISSN: 1432-2242
    Source: Springer Science & Business Media B.V.
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  • 7
    Language: English
    In: IEEE Sensors Journal, September 2010, Vol.10(9), pp.1447-1460
    Description: This paper presents an approach to people identification based on gait using floor pressure data. By using a large-area, high-resolution pressure sensing floor, we are able to obtain both the 1D pressure profile and 2D position trajectories of the centers of pressure (COP) of both feet to form a 3D COP trajectories over a footstep. From the 3D COP trajectories of a pair of footsteps, a set of features are extracted and used together with other features such as the mean pressure and stride length for people identification. The Fisher linear discriminant is used as the classifier. The speed-invariant properties of different features are examined and we have shown that the pressure features have good speed-invariance properties, much better than the stride length feature. The proposed algorithm has been extensively tested using a floor pressure dataset collected from 11 subjects in different walking styles, including varying speed walking and free style walking. Decent people identification results have been obtained using the proposed method with an average recognition rate of 92.3% and false alarm rate of 6.79% using the best performing feature set.
    Keywords: Foot ; Feature Extraction ; Legged Locomotion ; Pressure Measurement ; Testing ; Biometrics ; Application Software ; Terrorism ; Access Control ; Human Computer Interaction ; Biometrics ; Gait Recognition ; Pressure Analysis ; Engineering ; Geography
    ISSN: 1530-437X
    E-ISSN: 1558-1748
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  • 8
    In: Journal of Petroleum & Environmental Biotechnology, 2013, Vol.04(05)
    Description: The middle and lower parts of the Fourth Member of the Shahejie Formation in the Dongying Depression are representatives of evaporites and mud rocks in Eastern China. To investigate hydrocarbon potential, some deep wells, such as the Hk1 well and Fs2 well, were intensively cored...
    Keywords: Marine ; Mudstone ; Crude Oil ; Rocks ; Hydrocarbons ; Geochemistry ; Strontium ; Thermal Evolution ; China ; Environmental Engineering (General) (CE) ; Mineral Element ; Carbon Isotope ; Evaporite ; Hydrocarbon Generation ; Hydrocarbon Expulsion ; Dongying Depression;
    ISSN: Journal of Petroleum & Environmental Biotechnology
    E-ISSN: 21577463
    Source: CrossRef
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  • 9
    Language: English
    Description: In the present study, we characterized the ability of a novel oncolytic rhabdovirus - Maraba MG1 to boost Natural Killer (NK) cell activity. In tandem, we addressed the ability of this enhanced NK cell functionality to reduce the incidence of post-cancer surgery micrometastases. Due to the potential safety barriers associated with the use of a live virus immediately prior to surgery in cancer patients, we generated a single cycle replication virus (MG1-Gless) and UV-inactivated MG1 to stimulate NK cell function and reduce post-operative metastases. Our in vivo data demonstrate that significant NK cell activation and a similar level of reduction in postoperative tumor metastases was achieved with live MG1, MG1-Gless and UV-inactivated MG1, concluding that viral replication is important, but not necessary for NK cell activation. Mechanistically, we observed that dendritic cells (DCs) are necessary intermediates for MG1-induced NK cell activation. Finally, we characterized and compared a panel of UV-inactivated MG1 (2mins to 2hrs) to better understand the requirements for NK cell activation. Our results suggest that intact viral particle and cellular recognition and association are essential for NK cell mediated anti-tumor responses. These findings provide the preclinical rationale to develop safe and viable virotherapy-based interventional protocols that might reduce the risk of metastatic disease after cancer surgery.
    Keywords: Mg1 ; Natural Killer Cell ; Surgery ; Cancer Metastasis
    Source: Networked Digital Library of Theses and Dissertations
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  • 10
    In: Chinese Medical Journal, 2014, Vol.127(6), pp.1105-1109
    Description: BACKGROUND: Organ preservation keeps the quality of the organs under prolonged ischemia. Continuous machine perfusions are gaining an important position in clinical research and practice. The aim of this study was to evaluate the protective effect of continuous hypothermic machine perfusion transport system (AirdriveTM) on cold ischemic injury of canine kidney. METHODS: Ten kidneys of five healthy preserving canines were taken out after general anesthesia. Five kidneys were stored using common cold preservation (CCP group) by immersing it in the organ preservation solution, mixed with water and ice, and kept in a cold room at 4°C. The other five kidneys were stored using continuous machine perfusion preservation (CMP group) and were placed into the AirdriveTM continuous machine perfusion device at room temperature. The renal tissues were examined by histopathology, electron microscopy, and mitochondrial activity check at different time points. RESULTS: Histologic sections showed that the structures of the ten renal tissues were similar during the first 24 hours. After 48 hours, the CCP group showed more pronounced changes, as the renal tubular epithelial cells were more obvious than those in the glomeruli. Oxygen consumption rate of state III and IV respiration in the CCP group decreased after 12–48 hours and increased at 48 hours, respectively, when compared to the CMP group (P 〈0.05). Cortex respiratory control ratio and phosphorus oxygen ratio were significantly higher in the CMP group at 48 hours. CONCLUSION: With prolonged storage time, the effect of continuous hypothermic machine perfusion transport system is better than that of common cold preservation on canine kidney.
    Keywords: Kidney ; Organ Preservation -- Methods;
    ISSN: 0366-6999
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