Selection of surrogate marker genes in primary central nervous system lymphomas for radio-chemotherapy by DNA array analysis of gene expression profiles

Author(s):  
Ryuya Yamanaka ◽  
Shigeru Akutagawa ◽  
Fumiko Taguchi ◽  
Naoki Yajima ◽  
Naoto Tsuchiya ◽  
...  
2021 ◽  
Vol 288 (1945) ◽  
pp. 20202793
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  

Neuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer's disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system. Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor and T cell receptor repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system of aged male mice. Furthermore, many of these B cells were of the IgM and IgD isotypes, and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.


2020 ◽  
Author(s):  
Alexander Yermanos ◽  
Daniel Neumeier ◽  
Ioana Sandu ◽  
Mariana Borsa ◽  
Ann Cathrin Waindok ◽  
...  

AbstractNeuroinflammation plays a crucial role during ageing and various neurological conditions, including Alzheimer’s disease, multiple sclerosis and infection. Technical limitations, however, have prevented an integrative analysis of how lymphocyte immune receptor repertoires and their accompanying transcriptional states change with age in the central nervous system (CNS). Here, we leveraged single-cell sequencing to simultaneously profile B cell receptor (BCR) and T cell receptor (TCR) repertoires and accompanying gene expression profiles in young and old mouse brains. We observed the presence of clonally expanded B and T cells in the central nervous system (CNS) of aged mice. Furthermore, many of these B cells were of the IgM and IgD isotype and had low levels of somatic hypermutation. Integrating gene expression information additionally revealed distinct transcriptional profiles of these clonally expanded lymphocytes. Our findings implicate that clonally related T and B cells in the CNS of elderly mice may contribute to neuroinflammation accompanying homeostatic ageing.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1814 ◽  
Author(s):  
Keren Maor-Landaw ◽  
Oren Levy

It is well-established that there is a hierarchy of susceptibilities amongst coral genera during heat-stress. However, molecular mechanisms governing these differences are still poorly understood. Here we explored if specific corals possessing different morphologies and different susceptibilities to heat stress may manifest varied gene expression patterns. We examined expression patterns of seven genes in the branching coralsStylophora pistillataandAcropora eurystomaand additionally in the massive robust coral,Poritessp. The tested genes are representatives of key cellular processes occurring during heat-stress in Cnidaria: oxidative stress, ER stress, energy metabolism, DNA repair and apoptosis. Varied response to the heat-stress, in terms of visual coral paling, algal maximum quantum yield and host gene expression was evident in the different growth forms. The two branching corals exhibited similar overall responses that differed from that of the massive coral.A. eurystomathat is considered as a susceptible species did not bleach in our experiment, but tissue sloughing was evident at 34 °C. Interestingly, in this species redox regulation genes were up-regulated at the very onset of the thermal challenge. InS. pistillata, bleaching was evident at 34 °C and most of the stress markers were already up-regulated at 32 °C, either remaining highly expressed or decreasing when temperatures reached 34 °C. The massivePoritesspecies displayed severe bleaching at 32 °C but stress marker genes were only significantly elevated at 34 °C. We postulate that by expelling the algal symbionts fromPoritestissues, oxidation damages are reduced and stress genes are activated only at a progressed stage. The differential gene expression responses exhibited here can be correlated with the literature well-documented hierarchy of susceptibilities amongst coral morphologies and genera in Eilat’s coral reef.


2004 ◽  
Vol 363 (3) ◽  
pp. 233-238 ◽  
Author(s):  
Baochuan Lin ◽  
Glenn D. Ritchie ◽  
John Rossi ◽  
Joseph J. Pancrazio

2014 ◽  
Vol 16 (7) ◽  
pp. 581-586 ◽  
Author(s):  
Masanao Murakami ◽  
Yumiko Hashida ◽  
Masayuki Imajoh ◽  
Akihiko Maeda ◽  
Mikio Kamioka ◽  
...  

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23142-e23142 ◽  
Author(s):  
Anton Buzdin ◽  
Maxim Sorokin ◽  
Alexander Glusker ◽  
Andrew Garazha ◽  
Elena Poddubskaya ◽  
...  

e23142 Background: Anticancer target drugs (ATDs) specifically bind and inhibit molecular targets that play important roles in tumorigenesis. More than 150 different ATDs have been approved for clinical use worldwide, and the clinicians are faced with the problem of choosing the best therapeutic solution for each patient. The problem of efficient ATD selection remains largely unsolved and personalized approaches are needed to select the best ATD candidates for individual patients. Methods: We propose a new approach termed OncoFinder. It is based on digesting gene expression profiles for the analysis of activation of intracellular signalling pathways as a marker for the selection of target therapies. The original bioinformatic algorithms were integrated with the databases featuring molecular drug targets, compositions of signalling pathways, including the functional role of each gene product, for more than 1700 pathways (Buzdin, Front.Genet 2014; Ozerov, Nature Communications 2016). Results: We showed that pathway activation strengths are more stable and reliable biomarkers of cancer than the expressions of individual genes. OncoFinder allows to detect changes at the level of pathway activation and to predict the effectiveness of drugs based on the knowledge of their molecular targets. We applied it to find new biomarkers of clinical response to the ATD cetuximab; for modelling the combined chemotherapy of acute myeloid leukemia and combined anti-VEGF/BRAF therapy of melanoma. For two unrelated datasets obtained for colon cancer patients before treatment with the ATD bevacizumab, we were able to distinguish between those who responded to treatment and not (p < 0.01). We next assayed biopsies for kidney cancer patients with known responses to the ATD sorafenib. The responders and non-responders showed a significant difference (p = 0.02). Finally, the OncoFinder platform was prospectively used for decision making support to patients with advanced metastatic solid tumors (n = 23). The efficiency of the ATD treatment was 61% (complete + partial response, RECIST). Conclusions: OncoFinder method may be effective for predicting response to ATD based on high throughput gene expression profiles.


2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Yvonne E. Pittelkow ◽  
Susan R. Wilson

Scientific advances are raising expectations that patient-tailored treatment will soon be available. The development of resulting clinical approaches needs to be based on well-designed experimental and observational procedures that provide data to which proper biostatistical analyses are applied. Gene expression microarray and related technology are rapidly evolving. It is providing extremely large gene expression profiles containing many thousands of measurements. Choosing a subset from these gene expression measurements to include in a gene expression signature is one of the many challenges needing to be met. Choice of this signature depends on many factors, including the selection of patients in the training set. So the reliability and reproducibility of the resultant prognostic gene signature needs to be evaluated, in such a way as to be relevant to the clinical setting. A relatively straightforward approach is based on cross validation, with separate selection of genes at each iteration to avoid selection bias. Within this approach we developed two different methods, one based on forward selection, the other on genes that were statistically significant in all training blocks of data. We demonstrate our approach to gene signature evaluation with a well-known breast cancer data set.


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