scholarly journals Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma

2019 ◽  
Author(s):  
Kok-Siong Chen ◽  
Jens Bunt ◽  
Caitlin R. Bridges ◽  
Zorana Lynton ◽  
Jonathan W.C. Lim ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cellular Differentiation ◽  
Therapeutic Strategy ◽  
Cellular Level ◽  
Low Grade ◽  
High Grade ◽  
Differentiated Cells ◽  
High Grade Astrocytoma ◽  
Mature Astrocyte ◽  
Astrocytic Differentiation

AbstractAstrocytomas are composed of heterogeneous cell populations. Compared to grade IV glioblastoma, low-grade astrocytomas have more differentiated cells and are associated with a better prognosis. Therefore, inducing cellular differentiation may serve as a therapeutic strategy. The nuclear factor one (NFI) transcription factors are essential for normal astrocytic differentiation and therefore could be effectors of cellular differentiation in glioblastoma. We analysed expression of family membersNFIAandNFIBusing high-grade astrocytoma mRNA expression datasets, and with immunofluorescence co-staining. Their expression is reduced in glioblastomas and is associated with differentiated and mature astrocyte-like cells at a cellular level. Furthermore, induction of NFI expression is sufficient to promote cellular differentiation in patient-derived glioblastoma xenografts. Our findings indicate that NFI proteins may have an endogenous pro-differentiative function in astrocytomas, similar to their role in normal development. Overall, our study establishes a basis for further investigation of targeting NFI-mediated differentiation as a potential differentiation therapy.

scholarly journals Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma

2019 ◽  
Vol 146 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Kok-Siong Chen ◽  
Caitlin R. Bridges ◽  
Zorana Lynton ◽  
Jonathan W. C. Lim ◽  
Brett W. Stringer ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cellular Differentiation ◽  
High Grade ◽  
High Grade Astrocytoma

scholarly journals Immunohistochemical Study of c-erbB2/HER2 Tumor Marker in Primary Malignant Brain Tumors

2018 ◽  
Author(s):  
Mazaher Ramezani ◽  
Shadi Siami ◽  
Mansour Rezaei ◽  
Sedigheh Khazaei ◽  
Masoud Sadeghi
Keyword(s):  
Brain Tumors ◽  
Tumor Marker ◽  
Future Research ◽  
Low Grade ◽  
High Grade ◽  
Her2 Positive ◽  
Malignant Brain Tumors ◽  
High Grade Astrocytoma ◽  
Number Of Patients ◽  
The Brain

Background and objectives: Primary brain tumors include any tumors arising in the brain whose prognosis is poor due to their histologic characteristics. The aim of this research was to evaluate the frequency of HER2 tumor marker in primary malignant brain tumors. Materials and Methods: This descriptive study was conducted on the samples admitted to the pathology laboratory with diagnosis of primary brain tumor during 2008–2015. Results: From among 107 patients (61.7% males and the rest females) with mean age of 40.4 years, the highest frequency of tumor location was in supratentorial region of the brain (including lobes and ventricles) (63.85% cases). High-grade astrocytoma had the highest prevalence at diagnosis (43.9%), followed by low-grade astrocytoma (37.4%). As for HER2 score, 42.1% of patients were HER2-positive (scores 2 & 3). On the other hand, 5.6% of patients were HER2-negative (-), 40.2% were positive (+), and 54.2% were positive (++). The patients with high-grade astrocytoma had older age (P < 0.001), higher HER2 positivity (P = 0.024) and percentage (P < 0.001) compared to the patients with low-grade astrocytoma. Conclusions: HER2 expression is dependent on the type of brain tumors. High expression of HER2 in high-grade astrocytoma may be useful for therapeutic purposes. The future research is needed to confirm these results with a large number of patients in different areas.

Transforming growth factors in urine from patients with primary brain tumors

1988 ◽  
Vol 68 (5) ◽  
pp. 775-780 ◽  
Author(s):  
Hiroshi Kanno ◽  
Takeo Kuwabara ◽  
Hidetaro Yasumitsu ◽  
Makoto Umeda
Keyword(s):  
Molecular Weight ◽  
Growth Factors ◽  
Brain Tumors ◽  
High Molecular Weight ◽  
Soft Agar ◽  
Urine Samples ◽  
Low Grade ◽  
High Grade ◽  
Transforming Growth Factors ◽  
High Grade Astrocytoma

✓ Urine specimens obtained from 19 patients with primary brain tumors were examined for the activity of transforming growth factors (TGF's). Urine was assayed for TGF's by soft agar colony formation and iodine-125 (125I)-epidermal growth factor (EGF)-binding competition. Two nontransformed cell lines, clonal NRK49F and BALB/3T3 A31-1-1 cells, were used as indicator cells for the soft agar colony assay, while EGF receptorrich A431 cells were used for 125I-EGF-binding competition assay. Urine samples were dialyzed against acetic acid, then lyophilized, prepared with gel-permeation chromatography, and assayed. All 19 patients and a control group of healthy individuals showed high levels of α-type TGF's with low molecular weight (4 to 8 kD) in all urine samples. In addition, α-type TGF's of high molecular weight (20 to 50 kD) were detected at high levels in urine from all 10 patients with high-grade astrocytoma; at intermediate levels in urine from one of two patients with low-grade astrocytoma and from two of four patients with meningioma; and at low levels in urine from one of two patients with low-grade astrocytoma, from two of four patients with meningioma, from one patient with oligodendroglioma, from two patients with neurinoma, and from all healthy control individuals. The high level of α-type TGF's with high molecular weight detected in urine from patients with high-grade astrocytoma could be useful as a tumor marker.

Klinische Wertigkeit der Positronen-Emissions-Tomographie (PET) bei onkologischen Fragestellungen: Ergebnisse einer interdisziplinären Konsensuskonferenz

1996 ◽  
Vol 35 (02) ◽  
pp. 42-52 ◽  
Author(s):  
R. Bares ◽  
U. Bull ◽  
A. Guhlmann ◽  
E. Moser ◽  
M. F. Wannenmacher ◽  
...  
Keyword(s):  
Low Grade ◽  
High Grade ◽  
Klinische Anwendung ◽  
Wissenschaftliche Studien

Zusammenfassung Ziel: Es ist das Ziel der vorliegenden Arbeit, an Hand bisher publizierter Studienergebnisse eine Beurteilung des klinischen Stellenwertes von PET in der Onkologie zu erarbeiten. Methoden: Im Rahmen einer interdisziplinären Konferenz mit namhaften Experten wurde eine Wertung des gegenwärtigen Stands von PET in der Onkologie an Hand der in der Literatur dokumentierten Studienergebnisse erarbeitet. Angestrebt wurde eine differenzierte Bewertung von PET für die klinische Anwendung in fünf Klassen (1a, 1b, 2a, 2b, 3) von »angemessen« (1a), »akzeptabel« (1b), »hilfreich« (2a), »noch keine Bewertung möglich« (2b), »ohne Nutzen« (3). Ergebnisse: Für den klinischen Einsatz in der Onkologie ist 2-F18-Fluorodeoxyglukose (FDG) das Radiopharmakon der Wahl. PET ist klinisch in der Patientenversorgung zur Rezidivdiagnostik von high-grade Gliomen (FDG), low-grade Gliomen (C-11 Methionin oder F-18 Tyrosin), für die Dignitätsdiagnostik des peripheren Lungenrundherdes bei Risikopatienten sowie für die Diagnostik des Pankreaskarzioms indiziert (Indikation 1a). PET kann in der Patientenversorgung bei folgenden Indikationen (1b) eingesetzt werden: »low-grade« Gliome, Suche nach unbekanntem Primärtumor bei Kopf-Hals-Tumoren, Rezidivdiagnostik des nicht kleinzelligen Bronchialkarzinoms sowie des Rektumkarzinoms, Lymphknotenstaging beim nicht kleinzelligen Bronchial-Karzinom, Pan-kreas-Karzinom, muskelinvasiven Blasen-Karzinom und Hoden-Karzinom. Staging bei M. Hodgkin (Stad. I/II versus III), frühe Therapiekontrolle bei Resttumor und Rezidivdiagnostik bei M. Hodgkin und hochmalignen Non-Hodgkin-Lymphomen, Lymphknoten-Staging und Fern-metastasensuche beim malignen Melanom (Breslow >1,5 mm), Lymphknoten- und Fernmetastasen-Nachweis beim Schilddrüsen-Karzinommit erhöhtem hTg und nicht radiojodspeichernden Metastasen. Zahlreiche weitere Indikationen zeichnen sich bereits jetzt ab, sind jedoch noch weniger gut durch wissenschaftliche Studien belegt. Für die meisten Indikationen außerhalb wissenschaftlicher Studien ist eine individuelle Kosten-Nutzen-Betrachtung durch den verantwortlichen Arzt geboten. Schlußfolgerungen: Die metabolische Bildgebung von PET besitzt für eine Vielzahl onkologischer Fragestellungen prinzipielle Vorteile gegenüber der anatomisch-morphologisch orientierten Schnittbilddiagnostik. Für die klinische Indikationsstellung ist allerdings eine differenzierte Betrachtung der spezifischen Leistungsfähigkeit von PET geboten.

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

2014 ◽  
Vol 23 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Claudiu Margaritescu ◽  
Daniel Pirici ◽  
Irina Cherciu ◽  
Alexandru Barbalan ◽  
Tatiana Cârtâna ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Colon Carcinoma ◽  
Sodium Dodecyl ◽  
High Grade Dysplasia ◽  
Early Event ◽  
Low Grade ◽  
High Grade

Background & Aims: Colorectal cancer represents the third most common malignancy and the fourth most common cause of cancer death worldwide. The existence of drug-resistant colon cancer stem cells is thought to be one of the most important reasons behind treatment failure in colon cancer, their existence putatively leading to metastasis and recurrences. The aim of our study was to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, assessing their significance as prognostic markers.Methods. A total of 45 retrospective colon adenocarcinoma cases were investigated by enzymatic and multiple fluorescence immunohistochemistry for their CD133 and CD166 expression and colocalization.Results. Both CD133 and CD166 were expressed to different extents in all cancer specimens, with apredominant cytoplasmic pattern for CD133 and a more obvious membranous-like pattern for CD166.Overall, when comparing their reactivity for the tumoral tissue, CD166 expression areas seemed to be smaller than those of CD133. However, there was a direct correlation between CD133 and CD166 expression levels throughout the entire spectrum of lesions, with higher values for dysplastic lesions. Colocalization of CD133/ CD166 was obvious at the level of cells membranes, with higher coeficients in high grade dysplasia, followed by well and moderate differentiated tumours.Conclusions. CD133/CD166 colocalization is an early event occurring in colon tumorigenesis, with thehighest coeficients recorded for patients with high grade dysplasia, followed by well differentiated tumours. Thus, we consider that the coexpression of these two markers could be useful for further prognostic andtherapeutically stratification of patients with colon cancer.Abbreviations: AJCC - American Joint Committee on Cancer; CCD - charge-coupled device camera sensor; CD133 - prominin-1 (PROM1); CD166 - Activated Leukocyte Cell Adhesion Molecule (ALCAM); CRC - colorectal cancer; CSC - cancer stem cells; DAB - 3,3'-diaminobenzidine chromogen; DAPI - 4',6-diamidino- 2-phenylindole; HE - Hematoxylin and eosin staining; HGD - high grade dysplasia; HRP - horseradish peroxidase; LGD - low grade dysplasia; SDS - sodium dodecyl sulfate*Part of this work has been accepted as a poster presentation at the Digestive Disease Week (DDW) meeting, Chicago, IL, USA May 3-6, 2014

Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Characteristic Curve ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
High Grade ◽  
Extensive Resection ◽  
High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Survival Rates ◽  
Consensus Algorithm ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

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