scholarly journals Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4539
Author(s):  
Abraham Tsitlakidis ◽  
Anastasia S. Tsingotjidou ◽  
Aristeidis Kritis ◽  
Angeliki Cheva ◽  
Panagiotis Selviaridis ◽  
...  
Keyword(s):  
White Matter ◽  
Atomic Force Microscope ◽  
World Health ◽  
Diffuse Glioma ◽  
Diffuse Astrocytoma ◽  
Tissue Elasticity ◽  
Atomic Force ◽  
Idh Mutations ◽  
The Impact ◽  
Adjacent Brain

This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients (p = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients (p = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas (p = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas (p = 0.492) and glioblastomas (p = 0.593). During repetitive indentation, both tumor (p = 0.002) and white matter (p = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter (p = 0.942) and partially reversed in tumor (p = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.

scholarly journals P03.13 Evaluation of PIK3CA mutational status in glioma molecular subgroups

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii27-iii28
Author(s):  
C Brito ◽  
A Azevedo ◽  
S Esteves ◽  
C Martins ◽  
M Mafra ◽  
...  
Keyword(s):  
Who Classification ◽  
Response To Therapy ◽  
World Health ◽  
Diffuse Glioma ◽  
Molecular Subgroups ◽  
Egfr Amplification ◽  
Pik3ca Mutations ◽  
Mutational Status ◽  
Idh Mutations ◽  
Pten Deletion

Abstract BACKGROUND Gliomas are the most common and lethal malignant tumors of central nervous system. In 2016, World Health Organization (WHO) classification included IDH mutations and 1p/19q codeletion as diagnostic criteria to define glioma entities. However, new biomarkers for diagnosis, prognosis and response to therapy are needed. In this context, PIK3CA mutations have been described as constitutive mutations, which highlights their relevance in gliomas. Here we clarified the clinical relevance of PIK3CA mutations according to the 2016 WHO classification, the potential impact on diagnosis, prognosis, response to therapy, as well as their correlation with EGFR amplification and PTEN deletion. MATERIAL AND METHODS A cohort of 444 adult diffuse glioma samples from Instituto Português de Oncologia Lisboa Francisco Gentil (IPOLFG) was classified according to the 2016 WHO Classification. The mutational status of exon 9 and 20 of PIK3CA was evaluated in molecular subgroups of gliomas by Sanger sequencing. PTEN deletion and EGFR amplification were identified by Fluorescent in situ hybridization (FISH). RESULTS PIK3CA mutations showed a higher frequency in the subgroup of gliomas with IDH mutations and 1p/19q codeletion - oligodendrogliomas (10%). In Glioblastoma (GBM) IDH-mutant and IDH-wildtype these oncogenic mutations were observed in 9% and 3% of cases, respectively. Similar results were obtained using The Cancer Genome Atlas (TCGA) data, which was 8% and 2%, respectively. H1047R and E542K were the most frequent mutations identified in the glioma molecular subgroups. Importantly, we found 3 unreported pathogenic variants in exon 20 of PIK3CA (c.3112T>C, c.2988T>C, c.3040C>T) and one polymorphic variant (c.3210A>G). In addition, PIK3CA mutations, PTEN deletion and EGFR amplification were not mutually exclusive alterations in glioma molecular subgroups. For the first time in gliomas, it was identified the rs45455192 polymorphism at a frequency of 16% in astrocytomas IDH-mutant, 24% in oligodendrogliomas and 18% in both molecular subgroups of GBM, although this polymorphism did not have prognostic value. The analysis of PIK3CA mutations in glioma recurrences showed that these mutations are maintained during glioma progression. CONCLUSION In two independent cohorts (IPOLFG and TCGA), it was obtained similar frequencies of PIK3CA mutations in GBM molecular subgroups. In addition, these mutations are more relevant in less aggressive gliomas (IDH-mutated and 1p/19q codeleted). These alterations seem to be important in tumor maintenance and progression, which makes this gene a potential therapeutic target. In the future, we will investigate the effect of the in vitro pharmacological inhibition of PIK3CA in GBM mutant cell lines.

Traceable Dimension Metrology by AFM for Nanoscale Process Control

2008 ◽  
Vol 381-382 ◽  
pp. 549-552
Author(s):  
Tim Bao
Keyword(s):  
Process Control ◽  
Atomic Force Microscope ◽  
Significant Role ◽  
Manufacturing Industry ◽  
Shape Effect ◽  
Measurement Systems ◽  
Atomic Force ◽  
Dimension Measurement ◽  
The Impact ◽  
Reference Tool

Your 32nm is different from my 32nm! The paradoxical statement reflects one of the most essential debates in the field of nanoscale dimension metrology for process control in the modern nanoelectronic manufacturing industry. This baffling debate is all about accuracy and traceability of dimension measurement systems used on production floors. As the circuit geometry and density continues to scale to the 45nm node and below, the metrology bias and uncertainty play a more significant role, and the characterization becomes more difficult. This article assesses the capability of atomic force microscope (AFM) as an accurate inline calibration metrology tool and the correlation of AFM measurement to NIST traceable standards. It introduces the methodology of adopting AFM as a traceable reference tool for CD SEM and optical scatterometry used in inline process control. The focus is on height, linewidth, and pitch calibrations due to their critical but challenging roles for process control in today’s nanoelectronic manufacturing. Care must be taken to minimize the impact from factors that affect the traceability and accuracy in the AFM system, including tip width calibration, tip wear, tip shape effect, contamination, and linewidth roughness.

Development of a High-pressure Scanning Probe Microscope for the study of in situ corrosion mechanisms of metallic materials

2012 ◽  
Vol 1474 ◽  
Author(s):  
Christophe Harder ◽  
L. Berlu ◽  
B. Reneaume
Keyword(s):  
High Pressure ◽  
Atomic Force Microscope ◽  
Scanning Probe ◽  
Ex Situ ◽  
Scanning Tunneling ◽  
Gaseous Species ◽  
Atomic Force ◽  
Corrosion Mechanisms ◽  
The Impact

ABSTRACTCorrosion mechanisms take place at the extreme surface of materials before spreading in the bulk. In this way, in situ surface characterization techniques as scanning probe microscopy (Scanning Tunneling Microscopy (STM) and Atomic Force Microscopy (AFM)) allow the observations of the very initial reaction steps.To achieve that goal, an environmental cell has been designed ; it is able to integrate either an atomic force microscope (AFM) or a scanning tunneling microscope (STM). This cell can resist to internal pressures ranging from 10-5 to 20 atm. Heterogeneous “solid – gas” reactions that only occur with pressures above several atmospheres, can then be studied. This could be achieved by following the topographical evolution of samples reacting with gaseous species. Identification of the surface defects at the origin of corrosive attacks as well as proposition of reaction mechanisms will be describe in future works.The present work shows first in situ measurements that validate this new and unique experimental “HP-AFM” (High Pressure Atomic Force Microscope). The impact of the atmosphere’s composition as well as the pressure values on the topographical measurements recorded by the AFM system is especially studied.In this way, a calibration standard is used to detect a potential working drift of the AFM system (scanner head displacements, optical detection …) that could lead to eventual distortions of pictures recorded and misinterpretation of observations. This sample has been studied under several experimental conditions and the results have shown an identical behaviour of the AFM used ex situ and in situ under Ar or He up to 1.5 atm as well as a good stability during long recording acquisitions (up to 90 min) necessary for kinetic studies.

scholarly journals Prognostic irrelevance of ring sideroblast percentage in World Health Organization–defined myelodysplastic syndromes without excess blasts

Blood ◽  
2012 ◽  
Vol 119 (24) ◽  
pp. 5674-5677 ◽  
Author(s):  
Mrinal M. Patnaik ◽  
Curtis A. Hanson ◽  
Nanna H. Sulai ◽  
Janice M. Hodnefield ◽  
Ryan A. Knudson ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Multivariable Analysis ◽  
World Health ◽  
Refractory Anemia ◽  
Idh Mutations ◽  
Ring Sideroblasts ◽  
Transfusion Dependency ◽  
Health Organization ◽  
The Impact

Abstract The presence of ≥ 15% bone marrow (BM) ring sideroblasts (RS) and < 5% blasts is required for a diagnosis of refractory anemia with ring sideroblasts. We examined the phenotypic and prognostic relevance of this “15%” RS threshold in 200 patients with myelodysplastic syndromes (MDS) without excess blasts and with ≥ 1% RS. The impact of RS% was assessed both as a continuous and categorical variable: < 5% (n = 56), 5%-14% (n = 32), 15%-50% (n = 79), and > 50% (n = 33). RS% correlated (P < .05) directly with age, platelet count, transfusion dependency, BM cellularity, and mutant SF3B1 and inversely with hemoglobin level, multilineage dysplasia, and high-risk karyotype; but did not correlate with IDH mutations. At a median follow-up of 33 months, 156 (73%) deaths and 24 (12%) leukemic transformations were documented. Neither univariate nor multivariable analysis showed significant effect for RS% on overall or leukemia-free survival, suggesting the limited prognostic value of quantifying BM RS in MDS.

Heat transfer between a hot AFM tip and a cold sample: impact of the air pressure

2013 ◽  
Vol 1543 ◽  
pp. 159-164 ◽  
Author(s):  
Pierre-Olivier Chapuis ◽  
Emmanuel Rousseau ◽  
Ali Assy ◽  
Séverine Gomès ◽  
Stéphane Lefèvre ◽  
...  
Keyword(s):  
Heat Transfer ◽  
Heat Flux ◽  
Atomic Force Microscope ◽  
Air Pressure ◽  
Ballistic Regime ◽  
Sample Heat ◽  
Atomic Force ◽  
The Impact

ABSTRACTWe observe the heat flux exchanged by the hot tip of a scanning thermal microscope, which is an instrument based on the atomic force microscope. We first vary the pressure in order to analyze the impact on the hot tip temperature. Then the distance between the tip and a cold sample is varied down to few nanometers, in order to reach the ballistic regime. We observe the cooling of the tip due to the tip-sample heat flux and compare it to the current models in the literature.

scholarly journals Molecular Classification of Diffuse Gliomas

2020 ◽  
Vol 47 (4) ◽  
pp. 464-473
Author(s):  
Navya Kalidindi ◽  
Rosemarylin Or ◽  
Sam Babak ◽  
Warren Mason
Keyword(s):  
Dna Methylation ◽  
Molecular Markers ◽  
World Health ◽  
Low Grade ◽  
Diffuse Glioma ◽  
Isocitrate Dehydrogenase 1 ◽  
Anaplastic Gliomas ◽  
Diffuse Gliomas ◽  
The Impact

ABSTRACT:Technological advances in the field of molecular genetics have improved the ability to classify brain tumors into subgroups with distinct clinical features and important therapeutic implications. The World Health Organization’s newest update on classification of gliomas (2016) incorporated isocitrate dehydrogenase 1 and 2 mutations, ATRX loss, 1p/19q codeletion status, and TP53 mutations to allow for improved classification of glioblastomas, low-grade and anaplastic gliomas. This paper reviews current advances in the understanding of diffuse glioma classification and the impact of molecular markers and DNA methylation studies on survival of patients with these tumors. We also discuss whether the classification and grading of diffuse gliomas should be based on histological findings, molecular markers, or DNA methylation subgroups in future iterations of the classification system.

scholarly journals Clinical, Morphological, and Molecular Study of Diffuse WHO Grade II and III Astrocytomas: A Retrospective Analysis from a Single Tertiary Care Institute

2021 ◽  
Vol 42 (06) ◽  
pp. 569-576
Author(s):  
Ramya Lakshmi Veduruvada ◽  
Megha S. Uppin ◽  
Meher Lakshmi Konatam ◽  
Rajesh Alugolu ◽  
Vamsi Krishna Yeramneni ◽  
...  
Keyword(s):  
World Health ◽  
Survival Duration ◽  
Diffuse Astrocytoma ◽  
Wild Type ◽  
Immunohistochemical Expression ◽  
Who Grade ◽  
Genetic Characteristics ◽  
Integrated Diagnosis ◽  
Idh Mutations ◽  
Grade Ii

Abstract Introduction Astrocytomas are the most common gliomas, classified on the basis of grade and IDH mutation status according to the World Health Organization (WHO) 2016 update. IDH mutations are seen in 70 to 80% of diffuse grade II and III astrocytomas and are associated with better outcome. They serve as predictive biomarker in IDH-targeted therapies such as small-molecule inhibitors or vaccines. Objective The aim of this study was to analyze the clinical, morphological, immunohistochemical, and molecular genetic characteristics of diffuse astrocytoma (DA: grades II and III). The IDH mutant and wild-type tumors are compared and contrasted with survival analysis on follow-up. Materials and Methods This was a retrospective study conducted on surgically resected tumor specimens. The hematoxylin and eosin-stained slides were examined for histologic features. Immunohistochemistry (IHC) was performed using IDH1R132H, ATRX, p53, and Ki67. All cases of negative immunohistochemical expression of IDH1R132H were subjected to IDH1 mutation analysis by Sanger sequencing. Overall survival was estimated by the Kaplan-Meier method using the log-rank (Mantel–Cox) test. Results The study included 51 cases of DA in the age of 17 to 66 years, mean ± standard deviation was 35.5 ± 9.7 years, and male:female ratio was 2:1.The IDH1R132H cytoplasmic immunopositivity was seen in 36 cases (70.5%), of which 63.6% were of grade II and 72.5% were of grade III. ATRX showed loss of expression in 50 cases (98%), and p53 showed diffuse strong immunohistochemical expression in all the cases of IDH mutant tumors. The difference in the age at presentation for IDH mutant (32.5 years) and wild type tumors (38 years) was statistically significant. Median survival was 55.3 months and 22.2 months in of IDH mutant and wild type cases, respectively. Conclusion IHC and sequencing for IDH mutations is helpful in making an integrated diagnosis and classifying definite molecular subgroups of astrocytic tumors. Mutations in IDH core-elate with survival. IDH mutant tumors showed longer survival duration and are good prognostic indicators.

scholarly journals NI-20 IS GLIOMATOSIS CEREBRI DIAGNOSED AS GRADEII IN NEUROIMAGING A POTENTIALLY GRADEII GLIOMA?

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii29-ii29
Author(s):  
Etsuko Owashi ◽  
Hiroaki Takei ◽  
Yuka Ikegame ◽  
Yoshitaka Asano ◽  
Kazuhiro Miwa ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Who Classification ◽  
Gliomatosis Cerebri ◽  
World Health ◽  
Resonance Spectroscopy ◽  
Diffuse Glioma ◽  
Diffuse Astrocytoma ◽  
Positron Emission ◽  
The Mean ◽  
Met Pet

Abstract The 2007 World Health Organization (WHO) classification defined gliomatosis cerebri (GC) as a rare entity and an extensively infiltrating diffuse glioma involving three or more cerebral lobes. Although the revised 2016 WHO classification removed GC as a separate glioma entity due to the common histopathological findings shared with other gliomas, GC exhibits a distinct growth pattern and worse prognosis compared with other grade-matched gliomas. We retrospectively reviewed five patients with GC and five patients with insulo-opercular diffuse astrocytoma (IODA) who underwent both proton magnetic resonance spectroscopy (MRS) and [11C]-methionine positron emission tomography (MET-PET). The patients were diagnosed with GC or IODA by T2-weighted magnetic resonance imaging /fluid-attenuated inversion recovery from April 2014 to August 2019 at our institution. The locations of lesions where single-voxel MRS to measure the N-acetylaspartate (NAA)/choline (Cho) ratio and MET-PET to measure the tumor/normal (T/N) ratio were performed were the same in every patient. The mean age of all patients was 46.3±13.7 years. The mean ages of the GC (three males and two females) and IODA (two males and three females) groups were 54.0±14.0 and 38.6±8.7 years, respectively. The mean NAA/Cho ratios in the GC and IODA groups were 1.010±0.441 and 0.594±0.449, respectively. The mean T/N ratios in the GC and IODA groups were 1.201±0.050 and 1.169±0.009, respectively. The higher NAA/Cho ratio in the GC lesions may reflect the abundance of normal neural tissue in GC compared with IODA. Nonetheless, the T/N ratios of the two groups were comparable. The discrepancy suggests that GC cells have higher tumor metabolic activity than IODA cells. Therefore, when GC is simply classified as grade II glioma based on neuroimaging diagnosis, the possibility of underestimating its malignant potential at the single-cell level should be considered.

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