scholarly journals Tumor cell phenotype and heterogeneity differences in IDH1 mutant vs wild-type gliomas

2019 ◽  
Author(s):  
Michael E. Berens ◽  
Anup Sood ◽  
Jill S. Barnholtz-Sloan ◽  
John F. Graf ◽  
Sanghee Cho ◽  
...  

AbstractGlioma is recognized to be a highly heterogeneous CNS malignancy, whose diverse cellular composition and cellular interactions have not been well characterized. To gain new clinical- and biological-insights into the genetically-bifurcated IDH1 mutant (mt) vs wildtype (wt) forms of glioma, we integrated multiplexed immunofluorescence single cell data for 43 protein markers across cancer hallmarks, in addition to cell spatial metrics, genomic sequencing and magnetic resonance imaging (MRI) quantitative features. Molecular and spatial heterogeneity scores for angiogenesis and cell invasion differ between IDHmt and wt gliomas irrespective of prior treatment and tumor grade; these differences also persisted in the MR imaging features of peritumoral edema and contrast enhancement volumes. Longer overall survival for IDH1mt glioma patients may reflect generalized altered cellular, molecular, spatial heterogeneity which manifest in discernable radiological manifestations.

2021 ◽  
pp. 197140092199896
Author(s):  
Ahmed Abdel Khalek Abdel Razek

Bone-related disorders of the jaw (BRDJ) include a spectrum of non-neoplastic and neoplastic lesions of the maxillofacial region that have been recently classified into fibro-osseous lesions, giant cell lesions and osseous tumours. The histopathological features of BRDJ can be similar and overlie each other. Imaging is important in order to reach a specific diagnosis. However, the appearance of BRDJ on imaging is non-specific in some cases. Computed tomography (CT) and magnetic resonance imaging (MRI) are used for accurate localisation, characterisation of the tumour matrix, delineation of the lesion extension and establishment of the relation of BRDJ to the surrounding structures. Imaging is usually done to detect the relationship with the adjacent surrounding vital structures and to diagnose aggressive forms, malignant transformation and associated syndromes. The correlation of the demographic findings, the location and the clinical presentations with the imaging features are important for the diagnosis of BRDJ. The proposed clinico-radiological diagnostic algorithm with CT and MRI helps a specific diagnosis to be reached in some cases.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi23-vi23
Author(s):  
Alexandra Calinescu ◽  
Zain Sultan ◽  
McKenzie Kauss ◽  
Wajd Al-Holou ◽  
Jason Heth

Abstract Glioblastoma (GBM) is the most common and deadly primary brain tumor in adults. Recurrence of the disease is attributed in part to the presence of Glioma Stem Cells (GSC), which are resistant to chemo- and radiotherapy and can initiate tumor formation. Molecularly, GSCs resemble the mesenchymal subtype that is associated with worse prognosis. GSCs share many characteristics with Neural Stem Cells (NSCs) including proliferative potential, migratory capacity, telomerase activity, diverse progeny and similar gene signature, however differ fundamentally from NSCs in their tumor forming ability. RNA-Seq analysis of GSCs and NSCs illustrates significant enrichment in GSCs of transcription factors (TFs) known to be dysregulated in cancer, chief among them being SIX1, a developmental TF with documented roles in progression of multiple cancers. Overexpression of SIX1 in A172 GBM cells enhances proliferation, promotes resistance to radiotherapy and alters expression of a core set of 4 developmental TFs (POU3F2, SALL2, OLIG2 and SOX2) capable to reprogram differentiated GBM cells into GSCs (Suva et al., 2014). Analysis of SIX1 in surgical samples from glioma patients illustrates that high expression of SIX1 correlates with tumor grade, finding corroborated in the TCGA and CGGA data sets. Surprisingly, primary NSCs, after extended time in culture, increase their proliferation rate, acquire a mesenchymal transcriptional signature akin to GSCs, including high expression of SIX1, and form deadly tumors when implanted into the brains of mice. Comparing the epigenetic landscape of transformed and normal NSCs we identify a significant enrichment of accessible chromatin at promoter and enhancer loci in transformed NSCs, including at regulatory regions of SIX1 and of genes that define mesenchymal GBM. These data suggest that SIX1 may represent an upstream regulator of the GSC phenotype and may drive malignant transformation of NSCs. Genetic and epigenetic loss of function analyses are ongoing to test this hypothesis.


2021 ◽  
pp. 20210030
Author(s):  
Junjie Zeng ◽  
Lan Liu ◽  
Jiayong Li ◽  
Qiling Huang ◽  
Leiming Pi ◽  
...  

Objective: To retrospectively analyze magnetic resonance imaging (MRI) features of various pathological subtypes of sinonasal rhabdomyosarcoma (RMS) and explore correlations between imaging features and pathological subtypes. Methods: In total, 11 cases with embryonal, alveolar or pleomorphic sinonasal RMSs, confirmed by surgical pathology, were selected. Their characteristics and distinctive imaging features were analysed, and the correlation between pathology and imaging features was explored. Results: Bone destruction was observed in all 11 cases with RMS. Expansive growth was predominant in three alveolar and three embryonal RMS cases, and creeping growth was predominant in two alveolar, two embryonal and one pleomorphic RMS cases. Signs of residual mucosa were observed in all 11 cases, and 10 cases showed involvement of multiple sinus cavities and orbital cavities. All cases exhibited mild-to-intermediate enhancement. Conclusion: Sinonasal RMSs have the following characteristic MRI features: ethmoid sinuses and middle nasal conchae are the prevalent sites; lesions are mainly of mild enhancement; tumours exhibit signs of residual mucosa, mild-to-intermediate enhancement and frequent orbital involvement; bone invasion and bone destruction are frequently observed; and haematogenous metastasis is not as common as lymphatic metastasis. RMSs of various pathological subtypes were not significantly distinct by imaging.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Minghao Shao ◽  
Jun Yin ◽  
Feizhou Lu ◽  
Chaojun Zheng ◽  
Hongli Wang ◽  
...  

Objective.To evaluate the forward shifting of cervical spinal cords in different segments of patients with Hirayama disease to determine whether the disease is self-limiting.Methods.This study was performed on 11 healthy subjects and 64 patients. According to the duration, the patients were divided into 5 groups (≤1 year, 1-2 years, 2-3 years, 3-4 years, and ≥4 years). Cervical magnetic resonance imaging (MRI) of flexion and conventional position was performed. The distances between the posterior edge of the spinal cord and the cervical spinal canal (X), the anterior and posterior wall of the cervical spinal canal (Y), and the anterior-posterior (A) and the transverse diameter (B) of spinal cord cross sections were measured at different cervical spinal segments (C4 to T1).Results.In cervical flexion position, a significant increase inX/Yof C4-5 segments was found in groups 2–5, the C5-6 and C6-7 segments in groups 1–5, and the C7-T1 segments in group 5 (P<0.05). The degree of the increasedX/Yand cervical flexionX/Yof C5-6 segments were different among the 5 groups (P<0.05), which was likely due to rapid increases inX/Yduring the course of Hirayama’s disease.Conclusion.TheX/Ychange progression indicates that Hirayama disease may not be self-limiting.


2017 ◽  
Vol 41 (S1) ◽  
pp. S629-S630 ◽  
Author(s):  
A. Zacharzewska-Gondek ◽  
T. Gondek ◽  
M. Sąsiadek ◽  
J. Bladowska

IntroductionNormal pressure hydrocephalus (NPH) occurs in 0.5% of persons over 65 years old. The etiology of NPH is still unknown. Clinically NPH is characterised by cognitive deterioration, gait impairment and urinary incontinence. NPH is a possible reversible cause of dementia. Neuroimaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) allow to assess typical brain changes in this disorder.The objectives are to present the typical findings of NPH on CT and MRI and to demonstrate differences between NPH and central brain atrophy in neuroimaging.ResultsThe imaging features of NPH include: supratentorial ventriculomegaly with callosal angle less than 90o, tight sulci at the vertex and considerable out of proportion enlargement of Sylvian fissures. In case of central brain atrophy there may be a predominance of ventriculomegaly and/or widened sulci without crowding of the gyri at the vertex and callosal angle greater than 90o. In both entities, the decrease of density in periventricular region may be seen: in NPH could be a sign of transependymal oedema or in brain atrophy as an accompanying leukoaraiosis. Additionally, it is possible to assess changes in flow of cerebrospinal fluid (CSF) on MRI: in NPH an increased pulsatile CSF circulation in aqueduct as flow void sign may be observed.ConclusionsCorrect diagnosis of NPH on CT or MRI in relation to clinical data is very important. Treatment with ventriculoperitoneal shunt or third ventriculostomy may partially improve the quality of life in some patients with cognitive impairment due to NPH.Disclosure of interestThe authors have not supplied their declaration of competing interest.


Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1361
Author(s):  
Agnieszka M. Jurga ◽  
Martyna Paleczna ◽  
Justyna Kadluczka ◽  
Katarzyna Z. Kuter

The idea of central nervous system as one-man band favoring neurons is long gone. Now we all are aware that neurons and neuroglia are team players and constant communication between those various cell types is essential to maintain functional efficiency and a quick response to danger. Here, we summarize and discuss known and new markers of astroglial multiple functions, their natural heterogeneity, cellular interactions, aging and disease-induced dysfunctions. This review is focused on newly reported facts regarding astrocytes, which are beyond the old stereotypes. We present an up-to-date list of marker proteins used to identify a broad spectrum of astroglial phenotypes related to the various physiological and pathological nervous system conditions. The aim of this review is to help choose markers that are well-tailored for specific needs of further experimental studies, precisely recognizing differential glial phenotypes, or for diagnostic purposes. We hope it will help to categorize the functional and structural diversity of the astroglial population and ease a clear readout of future experimental results.


2013 ◽  
Vol 2013 ◽  
pp. 1-2
Author(s):  
Kirsti S. V. Lee ◽  
Niranjan Sritharan ◽  
Allan Forrest

This case report highlights an unusual case of sudden sensorineural hearing loss related to superficial siderosis (SS). Our patient had a craniotomy for medulloblastoma 23 years earlier, and this may represent a delayed complication related to this procedure. Magnetic resonance imaging (MRI) remains the key diagnostic investigation to illustrate the imaging features of superficial siderosis and exclude other pathologies. Increased awareness of progressive and sudden hearing complications caused by SS is important in the otolaryngologic community to expedite management and better counsel patients during the consent process.


2017 ◽  
Vol 50 (2) ◽  
pp. 115-125 ◽  
Author(s):  
Miguel Ramalho ◽  
António P. Matos ◽  
Mamdoh AlObaidy ◽  
Fernanda Velloni ◽  
Ersan Altun ◽  
...  

Abstract In the second part of this review, we will describe the ancillary imaging features of hepatocellular carcinoma (HCC) that can be seen on standard magnetic resonance imaging (MRI) protocol, and on novel and emerging protocols such as diffusion weighted imaging and utilization of hepatocyte-specific/hepatobiliary contrast agent. We will also describe the morphologic sub-types of HCC, and give a simplified non-invasive diagnostic algorithm for HCC, followed by a brief description of the liver imaging reporting and data system (LI-RADS), and MRI assessment of tumor response following locoregional therapy.


2018 ◽  
Author(s):  
Walter P Maksymowych

Classification of spondyloarthritis (SpA) is aimed at including patients with radiographic evidence of sacroiliitis and those with early disease who do not yet meet radiographic criteria but have positive features on magnetic resonance imaging (MRI). Most studies report a prevalence of SpA of 0.1 to 0.6%. Human leukocyte antigen (HLA)-B27 contributes approximately 20% of the heritability of SpA, and non–major histocompatibility complex loci identified to date (n = 113) contribute another approximately 10%. To date, 160 subtypes of HLA-B*27 have been reported, although population-based disease association studies are limited to only a few subtypes. Subtypes HLA-B*27:05 and HLA-B*27:04 are examples of subtypes associated with disease, whereas HLA-B*27:06 and HLA-B*27:09 are nonassociated. Properties of the B27 molecule relevant to pathogenesis include antigen presentation, propensity to misfold, and formation of homodimers. Key pathways identified by genetic studies include the interleukin (IL)-23 and M1-aminopeptidase pathways. The latter pathway is involved in peptide trimming in the endoplasmic reticulum, changing both the length and amino acid composition of peptides available for HLA class I presentation. IL-23 is a key cytokine regulating expression of IL-17 in a specific T helper cell phenotype, Th17, and also a variety of cells of the innate immune system. The IL-23–IL-17 pathway has been directly implicated in inflammation at sites that are inflamed in SpA. Increasing evidence based on prospective clinical and imaging data supports a link between inflammation and ankylosis, especially if the resolution of inflammation is followed by the appearance of a particular type of reparative tissue, namely, fat metaplasia, on T1-weighted MRI. This review contains 8 figures, 5 tables and 33 references Key words: association, classification, genetics, heritability, innate immunity, prevalence, spondyloarthritis


2020 ◽  
Vol 185 (Supplement_1) ◽  
pp. 279-285
Author(s):  
Mulugu V Brahmajothi ◽  
Mohamed B Abou-Donia

Abstract Introduction Posttraumatic stress disorder (PTSD) can develop during the aftermath of traumatic events. Although many are impacted by several stressors, nearly 3.6% suffer from PTSD in the United States with higher incidence reported in military service personnel. Any injury to the blood-brain barrier can ignite an array of biological signaling molecules in the immune-privileged brain parenchyma, which can disrupt the synaptic neural network, resulting in altered behavior. Materials and Methods In this preliminary study, we compared 20 PTSD veterans with age-matched healthy veterans to identify plasma levels of brain-specific protein markers using enzyme-linked immunosorbent assay/immunofluorometric sandwich assay for neurotrophic factors and neuropoietic cytokines, and catalytic activity of matrix metalloproteinase (MMP) by zymography. Results We observed an increased level of glial fibrillary acidic protein, tumor necrosis factor-alpha, interleukin 6, and MMP2 and MMP9 but decreased level of brain-derived neurotrophic factor, nerve growth factor-beta, and negligible difference in astroglial marker S100 calcium-binding protein B compared to controls. Conclusion Identification of neural biomarkers is essential to understand the subclinical symptoms for the diagnosis PTSD, which may not be visible by magnetic resonance imaging (MRI/fMRI) and may take years to clinically manifest.


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