Abstract PO056: The kinetics of the anti-glioblastoma immune response in immunocompetent mouse models is influenced by neglected factors

Author(s):  
Breanna R. Noffsinger ◽  
Alexandra Witter ◽  
Natasha Shebani ◽  
Aizhen Xiao ◽  
Qing Zhong ◽  
...  
Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 19
Author(s):  
Roxanne Wouters ◽  
Sien Bevers ◽  
Matteo Riva ◽  
Frederik De Smet ◽  
An Coosemans

Glioblastoma (GBM) is the most aggressive intrinsic brain tumor in adults. Despite maximal therapy consisting of surgery and radio/chemotherapy, GBM remains largely incurable with a median survival of less than 15 months. GBM has a strong immunosuppressive nature with a multitude of tumor and microenvironment (TME) derived factors that prohibit an effective immune response. To date, all clinical trials failed to provide lasting clinical efficacy, despite the relatively high success rates of preclinical studies to show effectivity of immunotherapy. Various factors may explain this discrepancy, including the inability of a single mouse model to fully recapitulate the complexity and heterogeneity of GBM. It is therefore critical to understand the features and limitations of each model, which should probably be combined to grab the full spectrum of the disease. In this review, we summarize the available knowledge concerning immune composition, stem cell characteristics and response to standard-of-care and immunotherapeutics for the most commonly available immunocompetent mouse models of GBM.


10.29007/ltkw ◽  
2019 ◽  
Author(s):  
Zifeng Liang

The aim of this paper is to identify the difference of type I interferon expression in 2- day neonatal and six-to-eight-weeks adult mice infected by Sendai virus (SeV), a single- stranded RNA virus of the family Paramyxoviridae. Sendai virus mimics the influence of respiratory syncytial virus (RSV) on humans, but does not infect humans. Although RSV has a fatal impact on people across age groups, little is understood about this common virus and the disparity between neonatal and adult immune response to it. It has been suggested by past findings that Type I interferon mRNA is present in higher levels in adults than in neonates, however there is a greater amount of interferon proteins in neonates rather than adults. To test the hypothesis that neonates are more capable of interferon production and preventing the translation of viral protein, I observed mouse models of respiratory viral infection and determined the expression of IFN-α1, IFN-α2, IFN-α5, IFN-α6, IFN-α7, IFN-β in archived mouse lung tissue samples harvested on different days post-infection with quantitative real time PCR. Expression of Glyceraldehyde 3-phosphate dehydrogenase(GAPDH), a housekeeping gene expressed constitutively in all mouse models, was used as a positive control of the experiment. To determine the ideal concentration of primer used in qPCR, primer reconstitution, primer optimization, and gel electrophoresis were conducted in advance. In addition, technical replicates and biological replicates were used to reduce error and confirm results in qPCR. In accordance with previous discovery, I found an upward trend in adults’ interferon expression from post-infection day 1 to day 5, and levels off in day 7. In contrast, neonatal levels were much higher on day 1 and remained high over the course of infection. This explains how type I interferon expression is altered in neonates to help them clear the virus at the same efficiency as adults without causing inflammation. Future research on immune response differences in human infection should focus on the evaluation of interferon protein amounts, as well as the analysis of activation of molecules downstream of the type I interferon receptors, such as signal transducer and activator of transcription (STAT) protein family. It is also crucial to compare immune cells like macrophages and natural killer cell activity in adult and neonatal mice during viral infection.


2020 ◽  
Vol 14 (6) ◽  
pp. 1928-1940
Author(s):  
Dieudonné Pascal Chuisseu Djamen ◽  
Roland Nankam Chimi ◽  
Arouna Njayou Ngapagna ◽  
Leonard Tedong ◽  
François-Marie Kanmangne ◽  
...  

The present work was to study the effects of Desmoduin adscendens, Khaya grandifoliola, Xylopia phloiodora extracts on growth parameters and selected blood parameters of broilers chickens. A total of 252 broiler chicks were randomly distributed into 4 groups. Chickens of control batch received commercial hepatoprotective (Hepaturyl 1 g/l) and the experimental groups received a formulation based on 3 extracts hepatoprotective plants at a concentration of 200, 100 and 50 mg/kg body weight. The mortality rate of control and experimental groups was 6.3% and 4.7% respectively. Average weight of batches at day 48 was, 2.6 for the control, 2.7 for the batch 2, 2.6 batch 3 and 2.5 kg batch 4 with an average consumption index ranging from 1.6 for the control and 1.7 for the experimental groups. Liver function in broilers was not altered (The values of alanine aminotransferase and aspartate aminotransferase were 5-25 IU/l and 50-350 IU/l respectively). Cholesterolemia, proteinemia and the triglyceridemia increased with the age of the animals (0.6- 4.1 mmol / l; 21-83 g / l; 0.3- 3.8 g / l respectively). The kinetics of the humoral immune response against infectious bursal disease was not influenced. This work has shown that the use of the formulation as hepatoprotective in chick drinking water shows results similar to those of commercial hepatoprotectors.Keywords: Broilers, hepatoprotective plants, hepatic functioning, growth performances, immune response


Oncotarget ◽  
2017 ◽  
Vol 8 (33) ◽  
pp. 54775-54787 ◽  
Author(s):  
Xianda Zhao ◽  
Lihua Li ◽  
Timothy K. Starr ◽  
Subbaya Subramanian

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.


1999 ◽  
Vol 188 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Enrica Tamburrini ◽  
Elena Ortona ◽  
Elena Visconti ◽  
Paola Mencarini ◽  
Paola Margutti ◽  
...  

2001 ◽  
Vol 23 (12) ◽  
pp. 641-653 ◽  
Author(s):  
K. Kanobana ◽  
L. Vervelde ◽  
M. Van Der Veer ◽  
M. Eysker ◽  
H.W. Ploeger

2020 ◽  
Vol 21 (6) ◽  
pp. 1946
Author(s):  
Antonio M. G. de Diego ◽  
Diana Ortega-Cruz ◽  
Antonio G. García

Synaptic disruption and altered neurotransmitter release occurs in the brains of patients and in murine models of neurodegenerative diseases (NDDs). During the last few years, evidence has accumulated suggesting that the sympathoadrenal axis is also affected as disease progresses. Here, we review a few studies done in adrenal medullary chromaffin cells (CCs), that are considered as the amplifying arm of the sympathetic nervous system; the sudden fast exocytotic release of their catecholamines—stored in noradrenergic and adrenergic cells—plays a fundamental role in the stress fight-or-flight response. Bulk exocytosis and the fine kinetics of single-vesicle exocytotic events have been studied in mouse models carrying a mutation linked to NDDs. For instance, in R6/1 mouse models of Huntington’s disease (HD), mutated huntingtin is overexpressed in CCs; this causes decreased quantal secretion, smaller quantal size and faster kinetics of the exocytotic fusion pore, pore expansion, and closure. This was accompanied by decreased sodium current, decreased acetylcholine-evoked action potentials, and attenuated [Ca2+]c transients with faster Ca2+ clearance. In the SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), CCs exhibited secretory single-vesicle spikes with a slower release rate but higher exocytosis. Finally, in the APP/PS1 mouse model of Alzheimer’s disease (AD), the stabilization, expansion, and closure of the fusion pore was faster, but the secretion was attenuated. Additionally, α-synuclein that is associated with Parkinson’s disease (PD) decreases exocytosis and promotes fusion pore dilation in adrenal CCs. Furthermore, Huntington-associated protein 1 (HAP1) interacts with the huntingtin that, when mutated, causes Huntington’s disease (HD); HAP1 reduces full fusion exocytosis by affecting vesicle docking and controlling fusion pore stabilization. The alterations described here are consistent with the hypothesis that central alterations undergone in various NDDs are also manifested at the peripheral sympathoadrenal axis to impair the stress fight-or-flight response in patients suffering from those diseases. Such alterations may occur: (i) primarily by the expression of mutated disease proteins in CCs; (ii) secondarily to stress adaptation imposed by disease progression and the limitations of patient autonomy.


2005 ◽  
Vol 55 (7) ◽  
pp. 785-796 ◽  
Author(s):  
Bernd Schlereth ◽  
Petra Kleindienst ◽  
Iduna Fichtner ◽  
Grit Lorenczewski ◽  
Klaus Brischwein ◽  
...  

1962 ◽  
Vol 115 (1) ◽  
pp. 209-230 ◽  
Author(s):  
G. J. V. Nossal ◽  
O. Mäkelä

The origin and growth kinetics of plasma cells have been investigated using autoradiographic labeling techniques. Rats immunized once with Salmonella flagella were given a single pulse of H3-thymidine 4 or 40 weeks later. 2 hours after the tracer injection, they received a secondary antigenic stimulus. When animals were sacrificed immediately only certain cells from the resting primarily immunized lymph nodes, notably large and medium lymphocytes, were labeled. Subsequent to secondary stimulation, animals were killed at intervals; nearly all the plasma cells formed within the next 5 to 6 days were labeled. They must thus have been the progeny of cells already capable of synthesizing DNA in resting nodes, most probably of large lymphocytes. Plasmacytopoiesis began with little or no lag following secondary immunization, and the number of labeled plasma cells rose exponentially between the 2nd and 4th day, with a doubling time of about 12 hours. Studies of mean grain counts of primitive cells also suggested that the generation time of plasmablasts was 12 hours or less. The hypothesis was proposed that immunological memory depended on the persistence, following primary stimulation, of a continuously dividing stem line of primitive lymphocytes, reactive at all times to further antigenic stimulation.


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