Computational normalization of H&amp;E-stained histological images: Progress, challenges and future potential

Tosta, Tháına A. A.; Faria, Paulo Rogério de; Neves, Leandro Alves; Nascimento, Marcelo Zanchetta do

doi:10.1016/j.artmed.2018.10.004

Cited by 85 publications

(22 citation statements)

References 28 publications

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“…For histological evaluation (HE), mouse tumour-forming kidney and lung metastatic nodules were resected and fixed in 4% paraformaldehyde, followed by routine processing [19].…”

Section: Immunohistochemical Analysis and Evaluationmentioning

confidence: 99%

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Zhu

Zhong

et al. 2020

J Hematol Oncol

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Background: Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6-12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. Methods: AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. Results: AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions: AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

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“…For histological evaluation (HE), mouse tumour-forming kidney and lung metastatic nodules were resected and fixed in 4% paraformaldehyde, followed by routine processing [19].…”

Section: Immunohistochemical Analysis and Evaluationmentioning

confidence: 99%

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Zhu

Zhong

et al. 2020

J Hematol Oncol

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“…Concerning color variations, H&E staining can produce different shades of color intensity and hue, which can lead to variations in interpretation of results. To mitigate these effects, solutions such as the use of standard operating procedures for staining and stain normalization were proposed by researchers, as variations in the concentration of the solutions can impact the final coloration and affect results ( Azevedo Tosta TA et al, 2019 ; Chlipala E. A. et al, 2021 ). In our study, the staining procedure was implemented following the same pre-analytical procedure.…”

Section: Resultsmentioning

confidence: 99%

Beyond conventional microscopy: Observing kidney tissues by means of fourier ptychography

et al. 2023

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Kidney microscopy is a mainstay in studying the morphological structure, physiology and pathology of kidney tissues, as histology provides important results for a reliable diagnosis. A microscopy modality providing at same time high-resolution images and a wide field of view could be very useful for analyzing the whole architecture and the functioning of the renal tissue. Recently, Fourier Ptychography (FP) has been proofed to yield images of biology samples such as tissues and in vitro cells while providing high resolution and large field of view, thus making it a unique and attractive opportunity for histopathology. Moreover, FP offers tissue imaging with high contrast assuring visualization of small desirable features, although with a stain-free mode that avoids any chemical process in histopathology. Here we report an experimental measuring campaign for creating the first comprehensive and extensive collection of images of kidney tissues captured by this FP microscope. We show that FP microscopy unlocks a new opportunity for the physicians to observe and judge renal tissue slides through the novel FP quantitative phase-contrast microscopy. Phase-contrast images of kidney tissue are analyzed by comparing them with the corresponding renal images taken under a conventional bright-field microscope both for stained and unstained tissue samples of different thicknesses. In depth discussion on the advantages and limitations of this new stain-free microscopy modality is reported, showing its usefulness over the classical light microscopy and opening a potential route for using FP in clinical practice for histopathology of kidney.

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“…In the initiation stage, a microscopic analysis of the tissue components of an H&E-stained tumor sample slide allows pathologists to clearly differentiate the alkaliphilic nucleus and acidophilic cytoplasm of cells, providing an image of the spatial architecture. 147,148 However, without specific markers, we can only empirically divide cells into several large subgroups, such as parenchyma cells, fibroblasts, muscle cells, and inflammatory cells, which is not suitable for characterizing the spatial architecture of the TIME.…”

Section: Protein-based Single-cell Analysis-the Known Unknownmentioning

confidence: 99%

Technological advances in cancer immunity: from immunogenomics to single-cell analysis and artificial intelligence

et al. 2021

Sig Transduct Target Ther

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Immunotherapies play critical roles in cancer treatment. However, given that only a few patients respond to immune checkpoint blockades and other immunotherapeutic strategies, more novel technologies are needed to decipher the complicated interplay between tumor cells and the components of the tumor immune microenvironment (TIME). Tumor immunomics refers to the integrated study of the TIME using immunogenomics, immunoproteomics, immune-bioinformatics, and other multi-omics data reflecting the immune states of tumors, which has relied on the rapid development of next-generation sequencing. High-throughput genomic and transcriptomic data may be utilized for calculating the abundance of immune cells and predicting tumor antigens, referring to immunogenomics. However, as bulk sequencing represents the average characteristics of a heterogeneous cell population, it fails to distinguish distinct cell subtypes. Single-cell-based technologies enable better dissection of the TIME through precise immune cell subpopulation and spatial architecture investigations. In addition, radiomics and digital pathology-based deep learning models largely contribute to research on cancer immunity. These artificial intelligence technologies have performed well in predicting response to immunotherapy, with profound significance in cancer therapy. In this review, we briefly summarize conventional and state-of-the-art technologies in the field of immunogenomics, single-cell and artificial intelligence, and present prospects for future research.

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Computational normalization of H&E-stained histological images: Progress, challenges and future potential

Cited by 85 publications

References 28 publications

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Acylglycerol kinase promotes tumour growth and metastasis via activating the PI3K/AKT/GSK3β signalling pathway in renal cell carcinoma

Beyond conventional microscopy: Observing kidney tissues by means of fourier ptychography

Technological advances in cancer immunity: from immunogenomics to single-cell analysis and artificial intelligence

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