scholarly journals Radio-pathomic maps of cell density identify glioma invasion beyond traditional MR imaging defined margins

2021 ◽  
Author(s):  
Samuel A. Bobholz ◽  
Allison K. Lowman ◽  
Michael Brehler ◽  
Fitzgerald Kyereme ◽  
Savannah R. Duenweg ◽  
...  
Keyword(s):  
Cell Density ◽  
Brain Cancer ◽  
Diffusion Imaging ◽  
Single Image ◽  
Glioma Invasion ◽  
Gadolinium Contrast ◽  
Mixed Effect ◽  
Tissue Samples ◽  
Image Intensity ◽  
The Relationship

AbstractCurrent MRI signatures of brain cancer often fail to identify regions of hypercellularity beyond the contrast enhancing region. Therefore, this study used autopsy tissue samples aligned to clinical MRIs in order to quantify the relationship between intensity values and cellularity, as well as to develop a radio-pathomic model to predict cellularity using MRI data. This study used 93 samples collected at autopsy from 44 brain cancer patients. Tissue samples were processed, stained for hematoxylin and eosin (HE) and digitized for nuclei segmentation and cell density calculation. Pre- and post-gadolinium contrast T1-weighted images (T1, T1C), T2 fluid-attenuated inversion recovery (FLAIR) images, and apparent diffusion coefficient (ADC) images calculated from diffusion imaging were collected from each patients’ final acquisition prior to death. In-house software was used to align tissue samples to the FLAIR image via manually defined control points. Mixed effect models were used to assess the relationship between single image intensity and cellularity for each image. An ensemble learner was trained to predict cellularity using 5 by 5 voxel tiles from each image, employing a 2/3-1/3 train-test split for validation. Single image analyses found subtle associations between image intensity and cellularity, with a less pronounced relationship within GBM patients. The radio-pathomic model was able to accurately predict cellularity in the test set (RMSE = 1015 cells/mm2) and identified regions of hypercellularity beyond the contrast enhancing region. We concluded that a radio-pathomic model for cellularity is able to identify regions of hypercellular tumor beyond traditional imaging signatures.

Measurement of treatment dependent glioblastoma cell density in T1- weighted contrast enhancement at autopsy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14035-e14035
Author(s):  
Allison Lowman ◽  
Samuel Bobholz ◽  
Jennifer Marie Connelly ◽  
Elizabeth Cochran ◽  
Wade Mueller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Contrast Enhancement ◽  
Cell Density ◽  
Control Point ◽  
Tumor Burden ◽  
Mixed Effect ◽  
Post Contrast ◽  
Tissue Samples ◽  
Treatment Groups ◽  
Death Time

e14035 Background: With an average overall survival of 12-18 months, glioblastoma has a particularly grim diagnosis. Standard treatment of glioblastoma, following detection on MRI, is surgical resection followed by radiation therapy and chemotherapy and is monitored through MR imaging. Glioblastoma has a unique heterogenous nature that complicates visualization of subtly enhancing tumor. This study used autopsy tissue samples taken from glioblastoma patients with varying treatment, to examine the effects of treatment on cell density within regions of contrast enhancement, using T1-weighted subtraction maps (T1S) from the last MR images to death. Methods: Eight patients diagnosed with glioblastoma at autopsy were recruited for this study. Two patients had no treatment and six received a combination of chemo-radiation and other treatments, including but not limited to bevacizumab (Bev) and TTFields therapy. At autopsy, whole brain samples were sliced axially aligned to the patient’s final MRI to death. Time between last MRI and death ranged from 4-27 days (mean 16 days). Overall survival (OS) ranged from 4-538 days (mean 307 days). Large tissue samples were taken from regions of suspected tumor or treatment effect, for a total of 18 tissue samples. Tissue samples were processed, H&E stained, and digitized at 40X resolution (Huron Slide Scanner). Cell density (cells/mm2) was calculated using digital histology. T1S were created for each patient by subtracting intensity normalized T1 weighted images from T1 post contrast images (T1C). Digital histology was aligned and resampled into MRI space using manual control point registration. Mixed effect models were used to compare differences in cell density across contrast enhancement (T1SE vs. NE) as well as across treatment groups (treatment vs. no treatment). Results: Cellularity was compared across regions of T1S enhancement (T1SE) and non-enhancement (NE) within manually selected regions of interest. Cell density compared between regions of T1SE and NE was not different (p=0.219). Total cell density was increased in patients who had received treatment compared to no treatment in both regions of T1SE and NE (p=0.014). Conclusions: Overall, cell density was increased in patients who had received treatment after diagnosis of glioblastoma. Additional research is needed to examine the extent of treatment’s effect on cellularity of glioblastoma. This work begins to characterize the use of T1S in evaluating glioblastoma tumor burden in patients with varying treatment histories.[Table: see text]

Somatic mitochondrial DNA mutations in different grades of glioma

2021 ◽  
Author(s):  
Bee Hong Soon ◽  
Nadiah Abu ◽  
Nor Azian Abdul Murad ◽  
Sue-Mian Then ◽  
Azizi Abu Bakar ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Brain Cancer ◽  
Clinical Phenotype ◽  
Mitochondrial Respiratory Chain ◽  
Future Research ◽  
Glioma Tissue ◽  
Tissue Samples ◽  
Mtdna Mutations ◽  
Dna Mutations ◽  
The Relationship

Aim: Mitochondrial DNA (mtDNA) alterations play an important role in the multistep processes of cancer development. Gliomas are among the most diagnosed brain cancer. The relationship between mtDNA alterations and different grades of gliomas are still elusive. This study aimed to elucidate the profile of somatic mtDNA mutations in different grades of gliomas and correlate it with clinical phenotype. Materials & methods: Forty histopathologically confirmed glioma tissue samples and their matched blood were collected and subjected for mtDNA sequencing. Results & conclusion: About 75% of the gliomas harbored at least one somatic mutation in the mtDNA gene, and 45% of these mutations were pathogenic. Mutations were scattered across the mtDNA genome, and the commonest nonsynonymous mutations were located at complex I and IV of the mitochondrial respiratory chain. These findings may have implication for future research to determine the mitochondrial energetics and its downstream metabolomics on gliomas.

scholarly journals Association between Anxiety Levels and Weight Change in the Multiethnic Study of Atherosclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Katherine Rieke ◽  
Ramon Durazo-Arvizu ◽  
Kiang Liu ◽  
Erin D. Michos ◽  
Amy Luke ◽  
...  
Keyword(s):  
Weight Change ◽  
Inclusion Criteria ◽  
Mixed Effect ◽  
Effect Model ◽  
Lower Baseline ◽  
Multiethnic Cohort ◽  
Baseline Weight ◽  
Study Population ◽  
The Relationship

Objective. To examine the association between anxiety and weight change in a multiethnic cohort followed for approximately 10 years.Methods. The study population consisted of participants of the multiethnic study of atherosclerosis who met specified inclusion criteria (n= 5,799). Weight was measured at baseline and four subsequent follow-up exams. Anxiety was analyzed as sex-specific anxiety quartiles (QANX). The relationship between anxiety level and weight change was examined using a mixed-effect model with weight as the dependent variable, anxiety and time as the independent variables, and adjusted for covariates.Results. Average annual weight change (range) was −0.17 kg (−6.04 to 4.38 kg) for QANX 1 (lowest anxiety), −0.16 kg (−10.71 to 4.45 kg) for QANX 2, −0.15 kg (−8.69 to 6.39 kg) for QANX 3, and −0.20 kg (−7.12 to 3.95 kg) for QANX 4 (highest anxiety). No significant association was noted between QANX and weight change. However, the highest QANX was associated with a −2.48 kg (95% CI = −3.65, −1.31) lower baseline weight compared to the lowest QANX after adjustment for all covariates.Conclusions. Among adults, age 45–84, higher levels of anxiety, defined by the STPI trait anxiety scale, are associated with lower average baseline weight but not with weight change.

Abstract P777: Statistical Modeling of Proteomic Signaling During Stroke in Patients Undergoing Thrombectomy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sydney Claypoole ◽  
Jacqueline Frank ◽  
Madison Sands ◽  
Christopher J McLouth ◽  
Jill Roberts ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Statistical Modeling ◽  
Internal Control ◽  
Stepwise Regression ◽  
Infarct Volume ◽  
Tissue Samples ◽  
Bivariate Regression ◽  
Inflammatory Proteins ◽  
The Relationship ◽  
Proximity Extension Assay

Introduction: The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes mechanical thrombectomy to obtain tissue samples for banking. Peripheral blood proximal to the clot and intracranial blood distal from the clot were isolated. Proteomic and statistical analyses revealed normalized (intracranial-systemic) CCL19 expression was a predictor of infarct volume. Statistical modeling analyses were used determine the CCL19-associated proteomic signaling network occurring during ischemic stroke relating to infarct volume. Methods: Arterial intracranial and systemic blood samples underwent analysis for inflammatory proteins using Proximity Extension Assay (PEA) via Olink (Olink Proteomics, Boston, MA). Systemic expression was used as an internal control to normalize expression in the intracranial blood. Bivariate regression was used to examine the relationship between the intracranial normalized CCL19 expression and infarct volume. A backwards stepwise regression was then used to determine a model of predictability of infarct volume by CCL19 and associated inflammatory proteins. Results: 25 subjects (>18 yrs) with a mean infarct volume of 8,172 ± 82,284 mm 3 and mean infarct time of 513 ± 246 minutes were included in this study. Their median age was 64 (24-91) and 10 (40%) were male. 16 subjects (64%) had hypertension, 15 (60%) had BMI > 25, and 6 (24%) had a previous stroke. The stepwise regression model shows normalized expression of 16 proteins correlated with an increase in infarct volume (p<0.005): CCL20, CXCL1, OSM, CD6, OSMR, TGF-alpha, TRANCE, CXCL10, LIF-R, CCL19, CDCP1, Flt3L, CCL23, CD244, TRAIL, NOTCH1. Conclusions: In our model, the expression of these proteins were consistently changed, though the directionality differed. LIF-R, NOTCH1, TRAIL, CD6, CCL23, TGF-alpha, and CCL20 were positively correlated, while the expressions of Flt3L, OSM, OSMR, TRANCE, CD244, CDCP1, CXCL1, CXCL10, and CCL19 were negatively correlated with infarct volume. This model depicts the proteomic signaling occurring during stroke in relationship to infarct volume, which reveals potential biomarkers and therapeutic targets for the early phase of ischemic stroke.

scholarly journals 213Traditional Japanese Diet Score and healthy life expectancy - a longitudinal global study

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Tomoko Imai ◽  
Ayako Sezaki ◽  
Keiko Miyamoto ◽  
Chisato Abe ◽  
Fumiya Kawase ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Rate Of Change ◽  
Healthy Life Expectancy ◽  
Mixed Effect ◽  
Healthy Life ◽  
Global Database ◽  
Food Components ◽  
The Relationship ◽  
Diet Score ◽  
Japanese Diet

Abstract Background Traditional Japanese diets are considered to be health and longevity. We created a Traditional Japanese Diet Score (TJDS) and investigated the relationship between the TJDS and healthy life expectancy (HALE) longitudinally using global database. Methods Average food (g/day/capita) and energy supply (kcal/day/capita) by countries were identified by the Food and Agriculture Organization of the United Nations Statistics Division database. The sum of characterizing traditional Japanese foods supply (beneficial food components in Japanese diet; rice, fish, soybeans, vegetables, eggs, seaweeds, food components not use so much in Japanese diet; wheat, milk, and red meat) were divided as tertile (beneficial food components;-1, 0, 1, not use so much food components; 1, 0, -1). HALE values by country were derived from the Global Burden of Disease 2017 database. The longitudinal effects of TJDS on the rate of change in HALE from 1990 to 2013 were evaluated using a generalized mixed-effect model (GLMM), which takes into account the dependence of repeated observations within countries. The interaction between TJDS and survey year was applied to access the effects on HALE. This study covered 137 countries with populations of 1 million or greater. Results Longitudinal analysis controlled for covariates showed that smooth term of the interaction between TJDS and survey year was significant (p &lt; 0.001). The TJDS was negative associated with HALE in 1990, and in 1991, but positive associated after 2002. Conclusions The relationship between the TJDS as a healthy eating style and HALE is getting stronger since the 21st century. Key messages Well-balanced eating habits of traditional Japanese diets is supports healthy life expectancy.

Abstract 240: Serum Cholesterol and Angiotensin-Induced Abdominal Aortic Aneurysm in Hypercholesterolemic Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Petra A Prins ◽  
Michael Hill ◽  
David Airey ◽  
Sam Nwosu ◽  
Prudhvidhar R Perati ◽  
...  
Keyword(s):  
Aortic Aneurysms ◽  
Cholesterol Concentration ◽  
Linear Mixed Effect Model ◽  
Hemodynamic Parameters ◽  
Mixed Effect ◽  
Regression Methods ◽  
Effect Model ◽  
Abdominal Aortic ◽  
And Control ◽  
The Relationship

Background Although hyperlipidemia is known to augment the incidence of abdominal aortic aneurysms (AAA) in the AngII-induced model of apolipoprotein E -/- mice, its relationship to AAA size is unknown. Therefore, we evaluated the relationship between total cholesterol concentration (TC) and change (delta) in aortic diameter. Methods TC was measured in 36 male mice that underwent a 4-week infusion period with saline (n=9) or AngII (1500 ng/kg/min; n=27), along with serial measurements of pulse rate (PR), and pulse (PP), mean arterial (MAP), systolic (SBP) and diastolic (DBP) pressure. A linear mixed effect model was used to assess the relationship between all hemodynamic parameters and delta. Nonparametric and linear regression methods were used to evaluate TC in relation to delta. Results TC did not differ between AngII and control mice (Figure, bottom left) (p=0.18). The burden of atherosclerosis was greater among AngII-exposed mice versus control, but did not differ by presence or size of AAA (Figure, bottom right). None of the hemodynamic parameters were predictive of delta (SBP, p = 0.66; DBP, p = 0.66; MAP, p = 0.55; PP, p = 0.66; and PR, p = 0.39). Mean TC was higher among mice with large versus small AAA (552.6 vs. 393.5 mg/ ml, p<0.05; Figure, top right). The nonparametric smoothing line (Figure, top left) suggests a first order relationship between delta and TC (p for trend < 0.001). AngII (ß = 0.48, p < 0.001) and TC (ß = 0.0015, p = 0.003) were independent predictors in the linear model for delta. Conclusions Our findings suggest that TC is incrementally associated with AAA size. These findings may have potential clinical relevance for risk assessment in AAA patients. Figure

The level of cytoskeleton remodeling proteins in the blood serum and the expression of their mRNA in the tumor tissue in metastasis of the larynx and hypopharynx cancer

2021 ◽  
Author(s):  
Gelena Kakurina ◽  
Olga V Cheremisina ◽  
Elena E Sereda ◽  
Elena S Kolegova ◽  
Irina V Kondakova ◽  
...  
Keyword(s):  
Serum Level ◽  
Blood Serum ◽  
Mrna Expression ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Actin Binding ◽  
Tissue Samples ◽  
Signaling Systems ◽  
Cytoskeleton Remodeling ◽  
The Relationship

Abstract Purpose: Actin-binding proteins (ABPs) and various signaling systems are involved in the metastasis of squamous cell carcinoma of the larynx and hypopharynx (SCCLH). The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA level of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAIL and RND3 with metastasis in the SCCLH tissue. The serum level of the listed ABPs was estimated and the relationship of them with the expression of the corresponding mRNA was carried out. Materials and methods: The expression level of ABPs mRNA was measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T 1-4 N 0-1 M 0 ). Expression analysis was performed using the 2 - ΔΔ CT method. The level of ABPs in the blood serum was measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. Results: The mRNA expression of the studied genes in tumor tissue of patients with SCCLH T 1-3 N 0 M 0 and T 2-4 N 1-2 M 0 did not differ significantly. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T 2-4 N 1-2 M 0 patients the level of PFN1 was significantly lower by 21% and the level of CAP1 was higher by 75% compared with the group of patients with T 1-4 N 0 M 0 stage. Conclusion: According to our data RND3 is involved in the regulation of molecular cascades SCCLH metastasis. PFN1 and CAP1 serum level can be a good classifier of metastases in patients with SCCLH.

DRAXIN as a Novel Diagnostic Marker to Predict the Poor Prognosis of Glioma Patients

2021 ◽  
Author(s):  
Zhendong Liu ◽  
Runze Liu ◽  
Xingbo Cheng ◽  
Binfeng Liu ◽  
Yongjie Zhu ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Clinical Information ◽  
Drug Analysis ◽  
Bioinformatics Analyses ◽  
Carcinogenic Effect ◽  
Tissue Samples ◽  
Reverse Transcription Quantitative Pcr ◽  
Biological Target ◽  
The Relationship

Abstract An increasing number of evidences have shown that the carcinogenic effect of DRAXIN plays an important role in the malignant process of tumors, but the mechanism of its involvement in glioma has not yet been revealed. The main aim of this study is to explore the relationship between DRAXIN and the prognosis and pathogenesis of glioma through a large qualities of data analysis. Firstly, thousands of tissue samples with clinical information were collected based on various public databases. Then, a series of bioinformatics analyses were performed to mine data from information of glioma samples extracted from several reputable databases to reveal the key role of DRAXIN in glioma development and progression, with the confirmation of basic experiments. Our results showed high expression of the oncogene DRAXIN in tumor tissue and cells could be used as an independent risk factor for poor prognosis in glioma patients and was strongly associated with clinical risk features. The reverse transcription-quantitative PCR technique was then utilized to validate the DRAXIN expression results we obtained. In addition, co-expression analysis identified respectively top 10 genes that were closely associated with DRAXIN positively or negatively. Finally, four drugs that may have inhibitory effects on DRAXIN were gained by Cmap drug analysis. To sum up, this is the first report of DRAXIN being highly expressed in gliomas and leading to poor prognosis of glioma patients. DRAXIN may not only benefit to explore the pathogenesis of gliomas, but also serve as a novel biological target for the treatment of glioma.

DNA content in human colon cancer and non-neoplastic adjacent mucosa

1995 ◽  
Vol 10 (1) ◽  
pp. 11-16 ◽  
Author(s):  
G. Saccani Jotti ◽  
M. Fontanesi ◽  
N. Orsi ◽  
L. Sarli ◽  
N. Pietra ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Dna Content ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Fresh Tissue ◽  
Tissue Samples ◽  
Adjacent Mucosa ◽  
Aneuploid Tumor ◽  
The Relationship

DNA content was determined by flow cytometry in a series of 51 paired fresh tissue samples of primary colorectal carcinomas and the respective non-neoplastic adjacent mucosa in order to assess the relationship between DNA ploidy and the most commonly used prognostic factors. Aneuploidy was observed in 70.6% of the tumors and more than one aneuploid peak was present in 3.9%. Aneuploid tumor frequency was higher in left (93.3%) and right colon (64.7%) cancers than in rectal carcinomas (60.0%), and multiple aneuploid clones were detected more frequently in men than in women and in patients with advanced disease (Dukes stage D). Non-neoplastic mucosa adjacent to aneuploid tumors showed aneuploidy in 4 out of 51 samples (7.8%). The mucosa adjacent to diploid cancers had only diploid characteristics. Polidy did not correlate with histological abnormalities. These findings suggest that DNA content as determined by flow cytometry needs further study with adequate follow-up to evaluate possible correlations with relapse-free and overall survival. Furthermore the aneuploidy of non-neoplastic mucosa provides evidence for a field defect in mucosa adjacent to colorectal cancer and supports the concept that this alteration may be of influence on carcinogenesis.

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