Tumor Tissue
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2021 ◽  
Vol 22 (20) ◽  
pp. 11091
Donghyuk Kim ◽  
Hyunjung Kim

Recently, photothermal therapy has attracted attention as an alternative treatment to conventional surgical techniques because it does not lead to bleeding and patients quickly recover after treatment compared to incisional surgery. Photothermal therapy induces tumor cell death through an increase in the temperature using the photothermal effect, which converts light energy into thermal energy. This study was conducted to perform numerical analysis based on heat transfer to induce apoptosis of tumor tissue under various heating conditions in photothermal therapy. The Monte Carlo method was applied to evaluate a multi-layered skin structure containing squamous cell carcinoma. Tissue-equivalent phantom experiments verified the numerical model. Based on the effective apoptosis retention ratio, the numerical analysis results showed the quantitative correlation for the laser intensity, volume fraction of gold nanorods injected into the tumor, and cooling time. This study reveals optimal conditions for maximizing apoptosis within tumor tissue while minimizing thermal damage to surrounding tissues under various heating conditions. This approach may be useful as a standard treatment when performing photothermal therapy.

2021 ◽  
Vol 102 (5) ◽  
pp. 716-725
K K Konyshev ◽  
S V Sazonov

The review looked at the issues of tumor heterogeneity in breast cancer. Tumor heterogeneity is classified according to the main feature demonstrating regional differences within a tumor (for example, heterogeneity of clinical manifestations, histological heterogeneity, heterogeneity of protein expression, etc.) and by tumor regions (differences between primary tumors and metastases, differences between cell clones within a single tumor node, etc.). Temporal heterogeneity is also distinguished, which manifests itself in the clonal evolution of tumor cells. The review covers the heterogeneity in the expression of four biomarkers from the gold standard for immunohistochemical staining of breast cancer: estrogen receptors, progesterone receptors, Her2/neu and Ki67 in primary tumor tissue and regional metastases. According to various studies, discordance in estrogen receptor status of primary tumor cells and metastases was observed with a frequency of 4 to 62%, progesterone receptors from 12 to 54%, Her2/neu from 0 to 24%, Ki67 from 4 to 39%. The results of studies of changes in the expression levels of individual markers in breast cancer metastases, as well as the heterogeneity of surrogate subtypes of tumor tissue in metastasis, are briefly described. Possible reasons for heterogeneity in the expression of key prognostic and predictive markers by primary tumor and metastatic cells, such as artificial factors at the preanalytic and analytic stages of the study, polyclonality of the primary tumor before metastasis, clonal evolution of tumor cells during metastasis, selection of tumor clones under the therapy are highlighted.

2021 ◽  
Sandhya Prabhakaran ◽  
Chandler Gatenbee ◽  
Mark Robertson-Tessi ◽  
Jeffrey West ◽  
Amer A Beg ◽  

Understanding the complex ecology of a tumor tissue and the spatio-temporal relationships between its cellular and microenvironment components is becoming a key component of translational research, especially in immune-oncology. The generation and analysis of multiplexed images from patient samples is of paramount importance to facilitate this understanding. In this work, we present Mistic, an open-source multiplexed image t-SNE viewer that enables the simultaneous viewing of multiple 2D images rendered using multiple layout options to provide an overall visual preview of the entire dataset. In particular, the positions of the images can be taken from t-SNE or UMAP coordinates. This grouped view of all the images further aids an exploratory understanding of the specific expression pattern of a given biomarker or collection of biomarkers across all images, helps to identify images expressing a particular phenotype or to select images for subsequent downstream analysis. Currently there is no freely available tool to generate such image t-SNEs. Mistic is open-source and can be downloaded at: https://github.com/MathOnco/Mistic.

Tao Zhang ◽  
Sixia Chen ◽  
Yi Peng ◽  
Changgang Wang ◽  
Xi Cheng ◽  

Background: Gene expression and alternative splicing (AS) can promote cancer development via complex mechanisms. We aimed to identify and verify the hub AS events and splicing factors associated with the progression of colorectal cancer (CRC).Methods: RNA-Seq data, clinical data, and AS events of 590 CRC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG, and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in five CRCs.Results: In this study, we first compared differentially expressed genes and gene AS events between normal and tumor tissues. Differentially expressed genes were different from genes with differentially expressed AS events. Prognostic analysis and co-expression network analysis of gene expression and gene AS events were conducted to screen five hub gene AS events involved in CRC progression: EPB41L2, CELF2, TMEM130, VCL, and SORBS2. Using qRT-PCR, we also verified that the gene AS events SORBS2 were downregulated in tumor tissue, and gene AS events EPB41L2, CELF2, TMEM130, and VCL were upregulated in tumor tissue. The genes whose mRNA levels were significantly related to the five hub gene AS events were significantly enriched in the GO term of cell division and Notch signaling pathway. Further coexpression of gene AS events and alternative splicing factor genes revealed NOVA1 as a crucial factor regulating the hub gene AS event expression in CRC. Through in vitro experiments, we found that NOVA1 inhibited gene AS event SORBS2, which induced the migration of CRC cells via the Notch pathway.Conclusion: Integrated analysis of gene expression and gene AS events and further experiments revealed that NOVA1-mediated SORBS2 promoted the migration of CRC, indicating its potential as a therapeutic target.

2021 ◽  
Lana Kovac Bilic ◽  
Jelena Knezevic ◽  
Maja Sutic ◽  
Srecko Branica ◽  
Krsto Dawidowsky ◽  

Abstract There are no biomarkers for diagnosis, prognosis and treatment of patients with laryngeal carcinoma. Methylation changes of ASC/TMS1 and MyD88 genes, in healthy and cancer tissue, might be related with development and progression of cancer. The study explored is there a difference in gene’s methylation in healthy and tumor tissue and does it correlate with protein expression. The total of 36 patients were enrolled in the study. Methylation of bisulphite converted DNA was quantified by pyrosequencing in fresh frozen cancer and adjacent non-malignant tissues. The overall methylation of MyD88 gene is significantly higher in healthy tissue and this finding correlates with protein expression and the overall methylation of ASC/TMS1 gene is unchanged but the protein expression of ASC/TMS1 is significantly higher in cancer. The methylation status of the ASC/TMS1 and MyD88 genes are promising prognostic biomarker candidates and may lead to earlier detection of laryngeal cancer.

2021 ◽  
Vol 11 (1) ◽  
Raquel Leon ◽  
Himar Fabelo ◽  
Samuel Ortega ◽  
Juan F. Piñeiro ◽  
Adam Szolna ◽  

AbstractCurrently, intraoperative guidance tools used for brain tumor resection assistance during surgery have several limitations. Hyperspectral (HS) imaging is arising as a novel imaging technique that could offer new capabilities to delineate brain tumor tissue in surgical-time. However, the HS acquisition systems have some limitations regarding spatial and spectral resolution depending on the spectral range to be captured. Image fusion techniques combine information from different sensors to obtain an HS cube with improved spatial and spectral resolution. This paper describes the contributions to HS image fusion using two push-broom HS cameras, covering the visual and near-infrared (VNIR) [400–1000 nm] and near-infrared (NIR) [900–1700 nm] spectral ranges, which are integrated into an intraoperative HS acquisition system developed to delineate brain tumor tissue during neurosurgical procedures. Both HS images were registered using intensity-based and feature-based techniques with different geometric transformations to perform the HS image fusion, obtaining an HS cube with wide spectral range [435–1638 nm]. Four HS datasets were captured to verify the image registration and the fusion process. Moreover, segmentation and classification methods were evaluated to compare the performance results between the use of the VNIR and NIR data, independently, with respect to the fused data. The results reveal that the proposed methodology for fusing VNIR–NIR data improves the classification results up to 21% of accuracy with respect to the use of each data modality independently, depending on the targeted classification problem.

2021 ◽  
Vol 18 (3) ◽  
pp. 508-517
S. V. Saakyan ◽  
I. P. Khoroshilova-Maslova ◽  
S. S. Tadevosyan ◽  
A. Yu. Tsygankov ◽  
G. P. Zakharova ◽  

Purpose. Determine the nature of tumor regression and possible complications associated with the retinotoxic effect of melphalan and carboplatin with local chemotherapy.Methods. A histological analysis of 19 enucleated eyes from 19 patients with retinoblastoma was performed after combined organ-preserving treatment, including systemic chemotherapy and local chemotherapy in various doses. The enucleated eyes were fixed in 10 % formalin and processed routinely for histological examination.Results. Significant changes in the tumor tissue such as tumor regression associated with the destruction of the tumor tissue and its replacement with fibrous tissue, glia proliferation, and the formation of petrificates were revealed. Complete regression of the tumor was detected in 3 out of 19 eyes, partial in 13 eyes. There were no signs of regression in 3 eyes. Tumor invasion into the choroid was found in 5 cases, into the anterior sector — in 3 cases, into the optic nerve — in 3 cases. The retrobulbar tumor was presented in 1 case. Retinotoxic complications revealed. Hemorrhagic changes associated with focal necrosis of the central retinal vessels (n = 4), destructive changes in retinal pigment epithelium (RPE; n = 10) associated with the accumulation of melphalan in RPE leading to atrophic processes in the retina. Complications in the form of secondary glaucoma, severe fibrosis and retinal detachment, despite the complete resorption of the tumor, led not only to loss of vision, but also hindered visualization of the fundus and substantiated the need for enucleation in 3 cases. In other cases, enucleation was performed due to continued tumor growth (n = 16) or progression during treatment (n = 3).Conclusions. Retinoblastoma can be controlled with local chemotherapy. However, clinical and morphological examinations of enucleated eyes revealed and confirmed, along with tumor resorption, intraocular complications as a result of the toxic effect of the drugs and the presence of active tumor tissue to varying degrees of therapeutic pathomorphism, which can be explained by the resistance of RB to these drugs. Thus, a further search is needed for drugs that destroy the tumor and minimize the retinotoxic effect.

2021 ◽  
Shaoling Li ◽  
Yan Huang ◽  
Liping Zhang ◽  
Zhengwei Dong ◽  
Wei Wu ◽  

Abstract Background: Visceral pleural invasion (VPI) is a critical component in the staging of peripheral non–small cell lung carcinoma (NSCLC). Single tumor tissue block for elastic stain is conducive to identifying pleural invasion in routine pathologic examination. We aim to investigate whether dual-block elastic stain increase VPI positivity compared with single-block elastic stain, further analyze the potential predictors of VPI status.Methods: Resected 8419 consecutive peripheral NSCLC cases including tumor size≤3cm 6008 patients were retrospectively reviewed. Total cases were divided into a cohort using one tumor tissue paraffin block (single-block group, n=5184) and a cohort using dual tumor tissue paraffin blocks (dual-block group, n=3235) for elastic stain. Each case was performed with Victoria-blue van Gieson staining to assess VPI status. The clinicopathologic features of patients were collected from the electronic medical record system.Results: The overall incidence of VPI was 12.4% (1047/8419) in peripheral NSCLC patients. The VPI positivity detected by dual-block elastic stain was significantly higher than that by single-block elastic stain (17.7% (573/3235) v.s. 9.1% (474/5184), P<0.001). The presence of VPI in T1 ≤3cm patients detected by single and dual block elastic stain was 6.3% (235/3730) and 12.0% (273/2278), respectively (P<0.001). Therefore, 5.7% T1 patients (stage IA) are additionally upstaged to T2a (stage IB) by dual block elastic stain. But the incidence of VPI in pT2a patients had no significant difference between single-block group and dual-block group (16.8% vs 17.1%, P=0.916). The lymphovascular invasion, lymph node metastasis, poor differentiated carcinomas and the presence of STAS status could be well significant predictors of VPI (P<0.001). Area under the ROC curve of adenocarcinoma morphology was 0.263 for lepidic pattern, 0.544 for acinar and papillary pattern, and 0.720 for micropapillary and solid pattern in predicting invasion of pleura.Conclusion: Our results indicated that using dual-block elastic stain identify more VPI positive T1 NSCLC patients who are upstaged to T2a and could benefit from optimal management after post-operation. The application of dual-block elastic stain is an efficient and practical method to detect VPI, especially for patients with high-risk prognostic factors.

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4812
Carolin Kastner ◽  
Anne Hendricks ◽  
Hanna Deinlein ◽  
Mohammed Hankir ◽  
Christoph-Thomas Germer ◽  

Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.

Rafael Roesler ◽  
Simone Dini ◽  
Gustavo Isolan

Brain tumors and brain metastases induce changes in brain tissue remodelling that lead to immunosuppression and trigger an inflammatory response within the tumor microenvironment. These immune and inflammatory changes can influence invasion and metastasis. Other neuroinflammatory and necrotic lesions may occur in patients with brain cancer or brain metastases as sequelae from treatment with radiotherapy. Glioblastoma (GBM) is the most aggressive primary malignant brain cancer in adults. Imaging methods such as positron-emission tomography (PET) and different magnetic resonance imaging (MRI) techniques are highly valuable for the diagnosis and therapeutic evaluation of GBM and other malignant brain tumors. However, differentiating between tumor tissue and inflamed brain tissue with imaging protocols remains a challenge. Here, we review recent advances in imaging methods that have helped to improve the specificity of primary tumor diagnosis versus evaluation of inflamed and necrotic brain lesions. We also comment on advances in differentiating metastasis from neuroinflammation processes. Recent advances include the radiosynthesis of 18F-FIMP, an L-type amino acid transporter 1 (LAT1)-specific PET probe that allows better differentiation between tumor tissue and inflammation compared to previous probes; and the combination different advanced imaging protocols with the inclusion of radiomics and machine learning algorithms.

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