Caspase-8 levels correlate with the expression of signal transducer and activator of transcription 1 in high-grade but not lower grade neuroblastoma

Cancer ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 824-831 ◽  
Author(s):  
Andrea Muscat ◽  
Christine Hawkins ◽  
David M. Ashley
Keyword(s):  
Caspase 8 ◽  
Lower Grade ◽  
High Grade ◽  
Signal Transducer

scholarly journals PATH-11. PROSPECTIVE (EPI-)GENETIC CLASSIFICATION OF > 1,000 PEDIATRIC CNS TUMORS—THE MNP 2.0 STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii426-iii426
Author(s):  
Dominik Sturm ◽  
Felix Sahm ◽  
Felipe Andreiuolo ◽  
David Capper ◽  
Marco Gessi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Gene Panel ◽  
Cns Tumors ◽  
Lower Grade ◽  
High Grade ◽  
Sequencing Data ◽  
Cns Tumor ◽  
Gene Panel Sequencing ◽  
Tumor Entities ◽  
Panel Sequencing

Abstract The large variety of CNS tumor entities affecting children and adolescents, some of which are exceedingly rare, results in very diverging patient outcomes and renders accurate diagnosis challenging. To assess the diagnostic utility of routine DNA methylation-based CNS tumor classification and gene panel sequencing, the Molecular Neuropathology 2.0 study prospectively integrated these (epi-)genetic analyses with reference neuropathological diagnostics as an international trial for newly-diagnosed pediatric patients. In a four-year period, 1,215 patients with sufficient tissue were enrolled from 65 centers, receiving a reference neuropathological diagnosis according to the WHO classification in >97%. Using 10 FFPE sections as input, DNA methylation analysis was successfully performed in 95% of cases, of which 78% with sufficient tumor cell content were assigned to a distinct epigenetic tumor class. The remaining 22% did not match any of 82 represented classes, indicating novel rare tumor entities. Targeted gene panel sequencing of >130 genes performed for 96% of patients with matched blood samples detected diagnostically, prognostically, or therapeutically relevant somatic alterations in 48%. Germline DNA sequencing data indicated potential predisposition syndromes in ~10% of patients. Discrepant results by neuropathological and epigenetic classification (29%) were enriched in histological high-grade gliomas and implicated clinical relevance in 5% of all cases. Clinical follow-up suggests improved survival for some patients with high-grade glioma histology and lower-grade molecular profiles. Routine (epi-)genetic profiling at the time of primary diagnosis adds a valuable layer of information to neuropathological diagnostics and will improve clinical management of CNS tumors.

scholarly journals Gut Microbiome Alterations in Patients With Thyroid Nodules

2021 ◽  
Vol 11 ◽  
Author(s):  
Ang Li ◽  
Tiantian Li ◽  
Xinxin Gao ◽  
Hang Yan ◽  
Jingfeng Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Thyroid Nodules ◽  
Genome Wide Association Study ◽  
Adult Population ◽  
Lower Grade ◽  
High Grade ◽  
Microbial Composition ◽  
Thyroid Metabolism ◽  
Relative Abundances

Thyroid nodules are found in nearly half of the adult population. Accumulating evidence suggests that the gut microbiota plays an important role in thyroid metabolism, yet the association between gut microbiota capacity, thyroid nodules, and thyroid function has not been studied comprehensively. We performed a gut microbiome genome-wide association study in 196 patients with thyroid nodules and 283 controls by using whole-genome shotgun sequencing. We found that participants with high-grade thyroid nodules have decreased number of gut microbial species and gene families compared with those with lower grade nodules and controls. There are also significant alterations in the overall microbial composition in participants with high-grade thyroid nodules. The gut microbiome in participants with high-grade thyroid nodules is characterized by greater amino acid degradation and lower butyrate production. The relative abundances of multiple butyrate producing microbes are reduced in patients with high-grade thyroid nodules and the relative abundances of L-histidine metabolism pathways are associated with thyrotropin-releasing hormone. Our study describes the gut microbiome characteristics in thyroid nodules and a gut-thyroid link and highlight specific gut microbiota as a potential therapeutic target to regulate thyroid metabolism.

scholarly journals Multicellular ‘hotspots’ harbour high-grade potential in lower-grade gliomas

2021 ◽  
Author(s):  
Alastair J Kirby ◽  
José P Lavrador ◽  
Istvan Bodi ◽  
Francesco Vergani ◽  
Ranjeev Bhangoo ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Aminolevulinic Acid ◽  
Ex Vivo ◽  
Brain Slices ◽  
Glioma Cells ◽  
Malignant Progression ◽  
Lower Grade ◽  
High Grade ◽  
Human Brain Tissue

Abstract Background Lower-grade gliomas may be indolent for many years before developing malignant behaviour. The reasons mechanisms underlying malignant progression remain unclear. Methods We collected blocks of live human brain tissue donated by people undergoing glioma resection. The tissue blocks extended through the peritumoral cortex and into the glioma. The living human brain tissue was cut into ex vivo brain slices and bathed in 5-aminolevulinic acid (5-ALA). High-grade glioma cells avidly take up 5-aminolevulinic acid (5-ALA) and accumulate high levels of the fluorescent metabolite, Protoporphyrin IX (PpIX). We exploited the PpIX fluorescence emitted by higher-grade glioma cells to investigate the earliest stages of malignant progression in lower-grade gliomas. Results We found sparsely-distributed ‘hot-spots’ of PpIX-positive cells in living lower-grade glioma tissue. Glioma cells and endothelial cells formed part of the PpIX hotspots. Glioma cells in PpIX hotspots were IDH1 mutant and expressed nestin suggesting they had acquired stem-like properties. Spatial analysis with 5-ALA conjugated quantum dots indicated that these glioma cells replicated adjacent to blood vessels. PpIX hotspots formed in the absence of angiogenesis. Conclusion Our data show that PpIX hotspots represent microdomains of cells with high-grade potential within lower-grade gliomas and identify locations where malignant progression could start.

scholarly journals Predicting STAT1 as a prognostic marker in patients with solid cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592091755
Author(s):  
Jinguo Zhang ◽  
Fanchen Wang ◽  
Fangran Liu ◽  
Guoxiong Xu
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Value ◽  
Renal Carcinoma ◽  
The Cancer Genome Atlas ◽  
Solid Cancer ◽  
Lower Grade ◽  
High Grade ◽  
Large Tumor ◽  
Normal Tissues ◽  
Tumor Types

Background: Aberrant activities of signal transducer and activator of transcription 1 (STAT1) have been implicated in cancer development. However, the prognostic value of STAT1 remains unclear. This report identified the role of STAT1 in prognosis in patients with solid cancer through open literature and The Cancer Genome Atlas (TCGA) database. Methods: Published articles were obtained from PubMed, Web of Science, and Embase databases according to a search strategy up to October 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to assess the prognostic factors of patients. TCGA datasets were used to explore the prognostic value of STAT1 in various cancers. Results: A total of 15 studies incorporating 2839 patients with solid cancers were included. Pooled data showed that overexpressed STAT1 favored long overall survival (OS) (HR = 0.604, 95% CI = 0.431–0.846, p = 0.003) and disease-specific survival (DSS) (HR = 0.650, 95% CI = 0.512–0.825, p = 0.000). In subgroup analyses, highly expressed STAT1 was correlated with long OS of patients with high-grade serous ovarian cancer and oral squamous cell carcinoma. Data extracted from TCGA datasets unveiled that STAT1 expression was significantly higher in 12 cancers (e.g. bladder and breast) than their adjacent normal tissues. Again, highly expressed STAT1 favored long OS of patients with ovarian cancer as well as rectum adenocarcinoma, sarcoma, and skin cutaneous melanoma. However, in renal carcinoma, brain lower grade glioma, lung adenocarcinoma, and pancreatic cancer, highly expressed STAT1 was correlated with poor OS of patients. Particularly in renal carcinoma, increased STAT1 expression was associated with high grade, later stage, large tumor size, and lymph node and distant metastasis. Conclusion: STAT1 has been identified to have prognostic value in patients with solid cancer. Highly expressed STAT1 may predict prognosis in cancer patients based on their tumor types.

scholarly journals Expression of MMP-9 and VEGF in Meningiomas and Their Correlation with Peritumoral Brain Edema

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Joanna Reszec ◽  
Adam Hermanowicz ◽  
Robert Rutkowski ◽  
Grzegorz Turek ◽  
Zenon Mariak ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Brain Edema ◽  
Lower Grade ◽  
Vascular Endothelial ◽  
High Grade ◽  
Intracranial Tumors ◽  
Limited Data ◽  
Peritumoral Brain Edema ◽  
Endothelial Growth Factor

Meningiomas constitute up to 13% of all intracranial tumors. The predictive factors for meningioma have not been unambiguously defined; however some limited data suggest that the expression of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) may be associated with the presence of peritumoral brain edema (PTBE) and worse clinical outcome. The aim of this study was to analyze the expressions of MMP-9 and VEGF in a group of meningiomas of various grades and to study associations between these two markers and PTBE. The study included patients with supratentorial meningiomas. The patients were divided into low- (G1) and high-grade meningiomas (G2 and G3). PTBE was assessed on MRI. The expressions of VEGF and MMP-9 were determined immunohistochemically. The expression of MMP-9 was observed significantly more often in G3 meningiomas than in lower grade tumors. The presence of stage II or III PTBE was associated with a significant increase in MMP-9 expression. The expression of VEGF did not differ across the PTBE stages. Our findings point to a significant role of MMP-9 and VEGF in the pathogenesis of peritumoral brain edema in low- and high-grade meningiomas.

scholarly journals Transtensional origin of multi-order cross-folds in a high-grade gneiss complex, southwestern Grenville Province: formation during post-peak gravitational collapse

2016 ◽  
Vol 53 (12) ◽  
pp. 1511-1538 ◽  
Author(s):  
W.M. Schwerdtner ◽  
Toby Rivers ◽  
Jason Tsolas ◽  
Dennis H. Waddington ◽  
Sydney Page ◽  
...  
Keyword(s):  
Gravitational Collapse ◽  
Regional Scale ◽  
Dynamic Modelling ◽  
Amphibolite Facies ◽  
Lower Grade ◽  
High Grade ◽  
Thrust Sheet ◽  
Ottawa River ◽  
Gneiss Complex ◽  
The Cross

The well-mapped western part of the Ottawa River Gneiss Complex (ORGC; new name), a large metamorphic core complex, hosts a system of gently plunging cross-folds of outcrop to regional scale situated in the ductile detachment zone between the lower grade cover and high-grade core of the complex. The cross-folds are buckle structures that deform the attenuated gneissic layering, plunge parallel to the regional elongation lineation, range from upright to recumbent, and exhibit distinctive hinge-parallel elongation lineations, all features of extension-dominated ductile transtension. Our L–S fabric data are consistent both with kinematic modelling that predicts progressive constrictional strain in the hinge zones of transtensional folds, and with dynamic modelling that predicts rotation of flattened fold limbs into moderately dipping attitudes. On the basis of petrologic data, we show that cross-folding postdated the peak Ottawan metamorphism and took place during retrogression and exhumation of the thrust-sheet stack. The cross-folds form an inclined system that is principally developed in retrograde melt-weakened amphibolite-facies rocks, with the transtensional origin implying that exhumation and retrogression of the high-grade core of the complex took place in an oblique extensional setting. A transtensional origin for the cross-folds removes the need to appeal to orogen-parallel regional shortening, an implausible requirement of previous interpretations, and is compatible with data indicating that much of the visible fabric and structure of amphibolite-facies domains of the ORGC developed during post-peak exhumation, retrogression, and gravitational collapse of the thrust-sheet stack.

scholarly journals Loss of histone variant macroH2A2 expression associates with progression of anal neoplasm

2015 ◽  
Vol 69 (7) ◽  
pp. 627-631 ◽  
Author(s):  
Wan-Hsiang Hu ◽  
Katsumi Miyai ◽  
Judith C Sporn ◽  
Linda Luo ◽  
Jean Y J Wang ◽  
...  
Keyword(s):  
Intraepithelial Neoplasia ◽  
Disease Recurrence ◽  
Histone Variants ◽  
Histone Variant ◽  
Lower Grade ◽  
High Grade ◽  
Anal Squamous Cell Carcinoma ◽  
Papilloma Virus ◽  
Anal Neoplasm ◽  
Squamous Tissue

AimsThe macroH2A histone variants are epigenetic marks for inactivated chromatin. In this study, we examined the expression of macroH2A2 in anal neoplasm from anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (SCC).MethodsAIN and anal SCC samples were analysed for macroH2A2 expression, HIV and human papilloma virus (HPV). The association of macroH2A2 expression with clinical grade, disease recurrence, overall survival and viral involvement was determined.ResultsmacroH2A2 was expressed in normal squamous tissue and lower grade AIN (I and II). Expression was lost in 38% of high-grade AIN (III) and 71% of anal SCC (p=0.002). Patients with AIN with macroH2A2-negative lesions showed earlier recurrence than those with macroH2A2-positive neoplasm (p=0.017). With anal SCC, macroH2A2 loss was more prevalent in the HPV-negative tumours.ConclusionsLoss of histone variant macroH2A2 expression is associated with the progression of anal neoplasm and can be used as a prognostic biomarker for high-grade AIN and SCC.

scholarly journals A Single Centre Analysis of Clinical Characteristics and Treatment of Endocrine Pancreatic Tumours

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
M. T. Adil ◽  
R. Nagaraja ◽  
V. Varma ◽  
N. Mehta ◽  
V. Kumaran ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Cohort Analysis ◽  
Pancreatic Head ◽  
Uncinate Process ◽  
Lower Grade ◽  
High Grade ◽  
Single Centre ◽  
Term Survival ◽  
Surgical Interventions ◽  
Pancreatic Tumours

Background. Endocrine Pancreatic Tumours (PENs) are rare and can be nonfunctioning or functioning. They carry a good prognosis overall though high grade lesions show a relatively shorter survival. The aim of the current study is to describe a single centre analysis of the clinical characteristics and surgical treatment of PENs.Patients and Methods. This is a cohort analysis of 40 patients of PENs who underwent surgery at Sir Ganga Ram Hospital, New Delhi, India, from 1995 to 2013. Patient particulars, clinical features, surgical interventions, postoperative outcome, and followup were done and reviewed. The study group was divided based on grade (G1, G2, and G3) and functionality (nonfunctioning versus functioning) for comparison.Results. PENs comprised 6.3% of all pancreatic neoplasms (40 of 634). Twenty-eight patients (70%) had nonfunctioning tumours. Eighteen PENs (45%) were carcinomas (G3), all of which were nonfunctioning. 14 (78%) of these were located in the pancreatic head and uncinate process (P=0.09). The high grade (G3) lesions were significantly larger in size than the lower grade (G1 + G2) tumours (7.0 ± 3.5 cms versus 3.1 ± 1.6 cms,P=0.007). Pancreatoduodenectomy was performed in 18 (45%), distal pancreatectomy in 10 (25%), and local resection in 8 (20%) and nonresective procedures were performed in 4 patients (10%). Fourteen patients (35%) had postoperative complications. All G3 grade tumours which were resected had positive lymph nodes (100%) and 10 had angioinvasion (71%). Eight neoplasms (20%) were cystic, all being grade G3 carcinomas, while the rest were solid. The overall disease related mortality attributable to PEN was 14.3% (4 of 28) and for malignant PENs was 33.3% (4 of 12) after a mean follow-up period of 49.6 months (range: 2–137 months).Conclusion. Majority of PENs are nonfunctioning. They are more likely malignant if they are nonfunctioning and large in size, show cystic appearance, and are situated in the pancreatic head. Early surgery leads to good long term survival with acceptable postoperative morbidity.

scholarly journals Natural history of histologically confirmed high-grade cervical intraepithelial neoplasia during pregnancy: meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e048055
Author(s):  
Cheng Chen ◽  
Yu Xu ◽  
Wu Huang ◽  
Yi Du ◽  
Cui Hu
Keyword(s):  
Natural History ◽  
Cervical Intraepithelial Neoplasia ◽  
Meta Analysis ◽  
Intraepithelial Neoplasia ◽  
Progression Rate ◽  
Lower Grade ◽  
High Grade ◽  
Regression Rate ◽  
Persistence Rate ◽  
History Of

ObjectivesThis study aimed to conduct a meta-analysis of estimates of the natural history of high-grade cervical intraepithelial neoplasia (CIN) during pregnancy.SettingStudies examining the clinical courses of histologically confirmed high-grade CIN during pregnancy.ParticipantsWe searched PubMed, Web of Science and Embase for eligible studies. Studies were included if they reported the data regarding the natural history of histologically confirmed high-grade CIN during pregnancy. Final estimates were from the meta-analysis of 10 eligible studies.Primary outcome measuresThe regression rate, persistence rate and progression rate of histologically proven untreated high-grade CIN during pregnancy.ResultsA total of 10 original studies were included in this meta-analysis. During pregnancy, the regression rate, persistence rate and progression rate of high-grade CIN were 40% (95% CI 35% to 45%), 59% (95% CI 54% to 64%) and 1% (95% CI 0% to 2%), respectively. There was moderate heterogeneity among the studies. The results of the subgroup meta-analysis show that the pooled rates of regression and persistence during pregnancy were 59% (95% CI 54% to 65%) and 40% (95% CI 35% to 45%) for CIN2, and 29% (95% CI 25% to 33%) and 70% (95% CI 65% to 73%) for CIN3.ConclusionsDuring pregnancy, the majority of histologically confirmed high-grade CIN would be persistent or regressed to lower grade CIN or normal. However, it is still worth noting that a small percentage of high-grade CIN would progress to cervical cancer during pregnancy.

scholarly journals Intermediate- to high-grade histology of lymphomas carrying t(14;18) is associated with additional nonrandom chromosome changes

Blood ◽  
1987 ◽  
Vol 70 (2) ◽  
pp. 444-447 ◽  
Author(s):  
ME Richardson ◽  
QG Chen ◽  
DA Filippa ◽  
K Offit ◽  
A Hampton ◽  
...  
Keyword(s):  
Cytogenetic Study ◽  
Chromosome Abnormalities ◽  
Chromosome 7 ◽  
Hodgkin's Lymphoma ◽  
Memorial Hospital ◽  
Low Grade ◽  
Lower Grade ◽  
Chromosome 6 ◽  
High Grade ◽  
Histological Evidence

Abstract We describe additional nonrandom chromosome abnormalities in 18 cases of intermediate- to high-grade non-Hodgkin's lymphoma (NHL) bearing t(14;18) that were ascertained in a prospective cytogenetic study of all lymphomas seen at Memorial Hospital during the period January 1, 1984, to December 31, 1986. These included seven cases that had histological evidence of transformation from a lower grade and 11 that lacked such evidence. The most common of the additional changes seen in both groups affected chromosomes 6 and 7 and comprised the loss of chromosome 6 or del(6q) and the presence of more than two copies of chromosome 7 or duplication of 7q. Changes affecting these two chromosomes were less frequent in low-grade lymphomas with t(14;18) as well as in lymphomas lacking the translocation. These data suggest that common cytogenetic mechanisms underlie expression of high-grade histologies by lymphomas carrying t(14;18). In addition, they may serve as indicators of transformation when encountered in low-grade lymphomas with t(14;18).

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