scholarly journals Validated method for automated glioma diagnosis from GFAP immunohistological images: a complete pipeline

2022 ◽  
Author(s):  
Aurora Campo ◽  
Francisco Fernandez-Flores ◽  
Marti Pumarola

Background and objective: Glial fibrillar acid protein is a common marker for brain tumor because of its particular rearrangement during tumor development. It is commonly used in manually histological glioma detection and grading. An automatic pipeline for tumor diagnosis based on GFAP is proposed in the present manuscript for detecting and grading canine brain glioma in stages III and IV. Methods: The study was performed on canine brain tumor stages III and IV as well as healthy tissue immunohistochemically stained for gliofibrillar astroglial protein. Four stereological indexes were developed using the area of the image as reference unit: density of glioma protein, density of neuropil, density of astrocytes and the glioma nuclei number density. Images of the slides were subset for image analysis (n=1415) and indexed. The stereological indexes of each subset constituted an array of data describing the tumor phase of the subset. A 5% of these arrays were used as training set for decision tree classification with PCA. The other arrays were further classified in a supervised approach. ANOVA and PCA analysis were applied to the indexes. Results: The final pipeline is able to detect brain tumor and to grade it automatically. Added to it, the role the neuropil during tumor development has been quantified for the first time. While astroglial cells tend to disappear, glioma cells invade all the tumor area almost to a saturation in stage III before reducing the density in stage IV. The density of the neuropil is reduced during the tumour growth. Conclusions: The method validated ere allows the automated diagnosis and grading of glioma in dogs. This method opens the research of the role of the neuropil in tumor development.

2021 ◽  
Vol 22 (5) ◽  
pp. 2250
Author(s):  
Evita Athanasiou ◽  
Antonios N. Gargalionis ◽  
Fotini Boufidou ◽  
Athanassios Tsakris

The role of certain viruses in malignant brain tumor development remains controversial. Experimental data demonstrate that human herpesviruses (HHVs), particularly cytomegalovirus (CMV), Epstein–Barr virus (EBV) and human herpes virus 6 (HHV-6), are implicated in brain tumor pathology, although their direct role has not yet been proven. CMV is present in most gliomas and medulloblastomas and is known to facilitate oncomodulation and/or immunomodulation, thus promoting cancer cell proliferation, invasion, apoptosis, angiogenesis, and immunosuppression. EBV and HHV-6 have also been detected in brain tumors and high-grade gliomas, showing high rates of expression and an inflammatory potential. On the other hand, due to the neurotropic nature of HHVs, novel studies have highlighted the engagement of such viruses in the development of new immunotherapeutic approaches in the context of oncolytic viral treatment and vaccine-based strategies against brain tumors. This review provides a comprehensive evaluation of recent scientific data concerning the emerging dual role of HHVs in malignant brain pathology, either as potential causative agents or as immunotherapeutic tools in the fight against these devastating diseases.


2010 ◽  
Vol 128 (9) ◽  
pp. 2230-2239 ◽  
Author(s):  
Taichang Jang ◽  
Joy M. Calaoagan ◽  
Eunice Kwon ◽  
Steven Samuelsson ◽  
Lawrence Recht ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3222
Author(s):  
Pedro M. Rodrigues ◽  
Arndt Vogel ◽  
Marco Arrese ◽  
Domingo C. Balderramo ◽  
Juan W. Valle ◽  
...  

The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.


2020 ◽  
Vol 13 (3) ◽  
pp. 1311-1316
Author(s):  
Ryoko Semba ◽  
Yoshiya Horimoto ◽  
Atsushi Arakawa ◽  
Yoko Edahiro ◽  
Tomoiku Takaku ◽  
...  

A 46-year-old woman with erythema of the right breast presented to our hospital and was diagnosed with stage IV breast cancer (HER2-positive invasive ductal carcinoma). She received 4 courses of anthracycline-based regimens and 4 courses of trastuzumab + pertuzumab + docetaxel (Tmab + Pmab + DTX). Since she responded well to these therapies, only Tmab + Pmab was continued thereafter. Twenty-three months after starting treatment, she developed a headache. A tumor was identified in the right temporal lobe. Craniotomy was performed for definitive diagnosis. Intraoperative pathological assessment suggested the tumor to be brain metastasis of breast cancer. However, the final pathological diagnosis was diffuse large B-cell lymphoma of central nervous system (DLBCL-CNS) based on re-assessment with immunohistochemical examinations. Therefore, the Tmab + Pmab was discontinued, and 6 courses of high-dose methotrexate therapy were administered. This case highlights the importance of considering rare entities, such as DLBCL, when diagnosing a solitary brain tumor in a patient with a primary cancer, based on imaging and pathological findings.


1999 ◽  
Vol 48 (4) ◽  
pp. 363-373 ◽  
Author(s):  
Sergey E Ilyin ◽  
Dave Gayle ◽  
Ignacio González-Gómez ◽  
Mary E Miele ◽  
Carlos R Plata-Salamán

2005 ◽  
Vol 163 (4) ◽  
pp. 424-432 ◽  
Author(s):  
Siegal Sadetzki ◽  
Angela Chetrit ◽  
Laurence Freedman ◽  
Marilyn Stovall ◽  
Baruch Modan ◽  
...  

Author(s):  
Kelsey Yetsko ◽  
Jessica Farrell ◽  
Maximilian R. Stammnitz ◽  
Liam Whitmore ◽  
Jenny Whilde ◽  
...  

AbstractSea turtle populations are directly and indirectly under threat from a range of anthropogenic processes. Perhaps the most visibly apparent of these is the disfiguring tumor disease epizootic (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at a number of affected sites globally. Environmental exposures seem key to inducing tumor development, possibly through weakening host immune systems to the point of enabling pathogen-induced tumor formation. However, we do not yet understand the precise molecular and mutational events driving fibropapillomatosis tumor formation and progression. Similarly, many open questions remain about the role of the herpesvirus (chelonid herpesvirus 5, ChHV5) associated with the disease as a potential co-trigger, and whether its occurrence within tumors is causative or opportunistic. Without improved understanding of the basic biology of this disease epizootic, treatment, containment and mitigation options are severely hampered.To address fundamental questions relating to the oncogenic signaling, mutational spectrum, viral load, viral transcriptional status (lytic or latent) and spread, we employed transcriptomic profiling, whole genome sequencing, immunohistochemistry and environmental (e)DNA-based monitoring of viral shedding. In particular we focused on the mutational landscape of tumors and assessing the transcriptional similarity of external (skin) and internal (visceral organs) tumors, and the oncogenic signaling events driving early stage tumor growth and post-surgical tumor regrowth. These analyses revealed that internal fibropapillomatosis tumors are molecularly distinct from the more common external tumors. However, our molecular analyses also revealed that there are a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common between internal and external tumors, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. We also determined that the tumor genomes can harbor copy number gains, indicating potentially viral-independent oncogenic processes. Genes within such mutated genomic regions have known roles in human skin cancer, including MAPK-associated genes. Turtles attempt to mount an immune response, but in some animals this appears to be insufficient to prevent tumor development and growth. ChHV5 was transcriptionally latent in all tumor stages sequenced, including early stage and recurrent tumors. We also revealed that the tumors themselves are the primary source of viral shedding into the marine environment and, if they are surgically removed, the level of ChHV5 in the water column drops.Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, therapeutic treatment, and appropriate quarantine responses for this wildlife epizootic. Furthermore, they provide insights into human pathogen-induced cancers, particularly mechanisms which are difficult to study in the human and terrestrial context, such as time-course quantification-based monitoring of viral shedding.


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