Hepatocellular carcinoma (HCC) is a severe neoplastic disease associated with high morbidity and mortality rates. HCC is often detected at advanced stages leading to ineffective curative treatments. Recently, liquid biopsy has emerged as a non-invasive method to identify highly specific HCC biomarkers in bodily fluids such as blood, serum, urine, and saliva. Circulating cell-free nucleic acids (cfNAs), particularly cell-free DNA (cfDNA) and cell-free RNA (cfRNA), have become promising candidates for biomarkers in liquid biopsy applications. While cfDNA presented significant challenges, researchers have turned their attention to cfRNA, which can be efficiently identified through various methods and is considered a potential biomarker for cancer diagnosis and prognosis. This review primarily focuses on studies related to detecting various cfRNA in body fluids as biomarkers. The aim is to provide a summary of available information to assist researchers in their investigations and the development of new diagnostic and prognostic tools.
- Klíčová slova
- Biomarker, Cell-free RNA, Diagnostic, Hepatocellular carcinoma, Liquid biopsy, Prognostic,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hepatocellular carcinoma (HCC) is primary liver cancer, frequently diagnosed at advanced stages with limited therapeutic options. MicroRNAs (miRNAs) regulate target gene expression and through inhibitory competitive binding of miRNA influence cellular processes including carcinogenesis. Extensive evidence proved that certain miRNA's are specifically expressed in neoplastic tissues of HCC patients and are confirmed as important factors that can participate in the regulation of key signalling pathways in cancer cells. As such, miRNAs have a great potential in the clinical diagnosis and treatment of HCC and can improve the limitations of standard diagnosis and treatment. Long non-coding RNAs (lncRNAs) have a critical role in the development and progression of HCC. HCC-related lncRNAs have been demonstrated to exhibit abnormal expression and contribute to transformation process (such as proliferation, apoptosis, accelerated vascular formation, and gain of invasive potential) through their interaction with DNA, RNA, or proteins. LncRNAs can bind mRNAs to release their target mRNA and enable its translation. These lncRNA-miRNA networks regulate cancer cell expression and so its proliferation, apoptosis, invasion, metastasis, angiogenesis, epithelial-mesenchymal transition (EMT), drug resistance, and autophagy. In this narrative review, we focus on miRNA and lncRNA in HCC tumor tissue and their interaction as current tools, and biomarkers and therapeutic targets unravelled in recent years.
- Klíčová slova
- Biomarkers, Diagnostic, Hepatocellular carcinoma, Long noncoding Ribonucleic acid, Messenger Ribonucleic acid, Micro Ribonucleic acid, Prognostic,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: The management of pelvic venous disorders (PeVD) remains controversial. Open surgical and endovascular methods are currently used for treatment, but there are few data in the literature on the morphology and histology of the ectatic ovarian vein (OV). This study aimed to explore the histomorphological changes in a dilated OV in patients with PeVD and compare it with a normal OV obtained post-mortem and a normal great saphenous vein (GSV). METHODS: Histology of the OV was studied in 16 patients who underwent surgery for PeVD, 10 control cadavers from whom fragments of the OV without visible gross changes were taken at autopsy, and nine control patients in whom the GSV was resected to be used for coronary artery bypass. RESULTS: The OV wall in patients with PeVD consisted of three layers: intima, media, and adventitia. The OV looked very similar to the GSV wall because of a clearly developed layer of smooth muscle fibres. The thickness of the normal OV was significantly different to the OV wall in PeVD (475.3 μm, IQR 370.7, 607.6 vs. 776.3 μm, IQR 668.9, 879.6, p < .001) and did not differ significantly from the thickness of a normal GSV wall (784.3 μm, IQR 722.2, 898.2). The intima-media complex of the OV was significantly thinner than the GSV in PeVD (118.9 μm, IQR 75.6, 159.6 vs. 415 μm, IQR 399.5, 520.0, р < .001); however, the adventitia of the OV was significantly thicker than in normal OV and GSV (599.6 μm, IQR 444.3, 749.7 vs. 373.5 μm, IQR 323.8, 482.0 vs. 308.4 μm, IQR 275.9, 338.2, p < .001). CONCLUSION: Dilatation of the OV in patients with PeVD was accompanied by a significant increase in the overall thickness of the vein wall, which brings it closer in structure to the GSV. This implies that the OV may be used safely for transposition into the inferior vena cava or iliac vein.
- Klíčová slova
- Histology, Morphology, Nutcracker syndrome, Ovarian vein, Pelvic congestion syndrome, Pelvic venous disorders,
- MeSH
- koronární bypass MeSH
- lidé MeSH
- pánev MeSH
- varixy * chirurgie MeSH
- vena cava inferior MeSH
- vena saphena chirurgie MeSH
- žilní insuficience * chirurgie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The prognostic significance of mast cells and different phenotypes of macrophages in the microenvironment of hepatocellular carcinoma (HCC) following resection is unclear. We aimed in this study to assess the local distribution of infiltrating macrophages and mast cells of specific phenotypes in tissues of HCC and to evaluate their prognostic values for survival of post-surgical patients. METHODS: The clinicopathological and follow-up data of 70 patients with HCC, who underwent curative resection of tumor from 1997 to 2019, were collected. The infiltration of CD68+ and CD163+ macrophages and CD117+ mast cells was assessed immunohistochemically in representative resected specimens of HCC and adjacent tissues. The area fraction (AF) of positively stained cells was estimated automatically using QuPath image analysis software in several regions, such as tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells, individually and in associations, for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: High AF of CD68+ macrophages in TC and IM and high AF of mast cells in IM and PT area were associated with a longer DFS. High AF of CD163+ macrophages in PT area correlated with a shorter DFS. Patients from CD163TChigh & CD68TClow group had a shorter DFS compared to all the rest of the groups, and cases with CD163IMlow & CD68IMhigh demonstrated significantly longer DFS compared to low AF of both markers. Patients from CD68IMhigh & CD163PTlow group, CD117IMhigh & CD163PTlow group, and CD117PThigh & CD163PTlow group had a significantly longer DFS compared to all other combinations of respective cells. CONCLUSIONS: The individual prognostic impact of CD68+ and CD163+ macrophages and mast cells in the microenvironment of HCC after resection depends on their abundance and location, whereas the cumulative impact is built upon combination of different cell phenotypes within and between regions.
- Klíčová slova
- Disease-free survival, Hepatocellular carcinoma, Inner margin, Mast cells, Peritumor area, Tumor-infiltrating macrophages,
- MeSH
- hepatocelulární karcinom * patologie MeSH
- Kaplanův-Meierův odhad MeSH
- lidé MeSH
- makrofágy patologie MeSH
- mastocyty patologie MeSH
- nádorové mikroprostředí MeSH
- nádory jater * patologie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Colorectal cancer (CRC) is the third most common cancer worldwide, and metastatic CRC is a fatal disease. The CRC-affected tissues show several molecular markers that could be used as a fresh strategy to create newer methods of treating the condition. The liver and the peritoneum are where metastasis occurs most frequently. Once the tumor has metastasized to the liver, peritoneal carcinomatosis is frequently regarded as the disease's final stage. However, nearly 50% of CRC patients with peritoneal carcinomatosis do not have liver metastases. New diagnostic and therapeutic approaches must be developed due to the disease's poor response to present treatment choices in advanced stages and the necessity of an accurate diagnosis in the early stages. Many unique and amazing nanomaterials with promise for both diagnosis and treatment may be found in nanotechnology. Numerous nanomaterials and nanoformulations, including carbon nanotubes, dendrimers, liposomes, silica nanoparticles, gold nanoparticles, metal-organic frameworks, core-shell polymeric nano-formulations, and nano-emulsion systems, among others, can be used for targeted anticancer drug delivery and diagnostic purposes in CRC. Theranostic approaches combined with nanomedicine have been proposed as a revolutionary approach to improve CRC detection and treatment. This review highlights recent studies, potential, and challenges for the development of nanoplatforms for the detection and treatment of CRC.
- Klíčová slova
- cancer therapy, clinical status, colorectal cancer, nanomedicine, theranostics,
- MeSH
- individualizovaná medicína MeSH
- kolorektální nádory * diagnóza farmakoterapie MeSH
- kovové nanočástice * MeSH
- lidé MeSH
- nanočástice * terapeutické užití MeSH
- nanomedicína metody MeSH
- nanotrubičky uhlíkové * MeSH
- peritoneální nádory * MeSH
- systémy cílené aplikace léků metody MeSH
- teranostická nanomedicína MeSH
- zlato MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nanotrubičky uhlíkové * MeSH
- zlato MeSH
Hepatocellular carcinoma (HCC) is a global healthcare challenge, which affects more than 815,000 new cases every year. Activated hepatic stellate cells (aHSCs) remain the principal cells that drive HCC onset and growth. aHSCs suppress the anti-tumor immune response through interaction with different immune cells. They also increase the deposition of the extracellular matrix proteins, challenging the reversion of fibrosis and increasing HCC growth and metastasis. Therapy for HCC was reported to activate HSCs, which could explain the low efficacy of current treatments. Conversely, recent studies aimed at the deactivation of HSCs show that they have been able to inhibit HCC growth. In this review article, we discuss the role of aHSCs in HCC pathophysiology and therapy. Finally, we provide suggestions for the experimental implementation of HSCs in HCC therapies.
- Klíčová slova
- fibrosis regression, hepatic stellate cells, hepatocellular carcinoma, therapeutic studies,
- MeSH
- hepatocelulární karcinom * metabolismus MeSH
- jaterní hvězdicovité buňky metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory jater * metabolismus MeSH
- pohyb buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
As the current staging and grading systems are not sufficient to stratify patients for therapy and predict the outcome of the disease, there is an urgent need to understand cancer in its complexity. The mutual relationship between tumour and immune or stromal cells leads to rapid evolution and subsequent genetic and epigenetic changes. Immunoscore has been introduced as a diagnostic tool for colorectal cancer (CRC) only recently, emphasising the role of the specific tumor microenvironment in patient's prognosis and overall outcome. Despite the fact that non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), cannot be translated into proteins, they significantly affect cell's transcriptome and translatome. miRNA binding to mRNA efficiently blocks its translation and leads to mRNA destruction. On the other hand, miRNAs can be bound by lncRNAs or circular RNAs (circRNAs), which prevents them from interfering with translation. In this way, ncRNAs create a multi-step network that regulates the cell's translatome. ncRNAs are also shed by the cell as exogenous RNAs and they are also found in exosomes, suggesting their role in intercellular communication. Hence, these mechanisms affect the tumor microenvironment as much as protein signal molecules. In this review, we provide an insight into the current knowledge of the microenvironment, lncRNAs', and miRNAs' interplay. Understanding mechanisms that underlie the evolution of a tissue as complex as a tumour is crucial for the future success in therapy.
- Klíčová slova
- CAFs, CRC, colorectal cancer, lncRNA, lymphocytes, macrophages, miRNA, tumor microenvironment,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Hepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells. METHODS: Tissue samples were obtained from 67 HCC patients who had undergone resection. We analysed CD8+ T cells density, TERTp mutations, rs2853669 polymorphism, and CTNNB1 mutations. These variables were evaluated for time to recurrence (TTR) and disease free survival (DFS). RESULTS: TERTp mutations were found in 75.8% and CTNNB1 mutations in 35.6% of the patients. TERTp mutations were not associated with survival but polymorphism rs2853669 in TERTp was associated with improved TTR and DFS. CTNNB1 mutations were associated with improving TTR. High density of CD8+ T-lymphocytes in tumor center and invasive margin correlated with longer TTR and DFS. Combined genetic and immune factors further improved survival showing higher predictive values. E.g., combining CTNNB1 mutations and high density of CD8+ T-lymphocytes in tumor center yielded HRs of 0.12 (0.03-0.52), p = 0.005 for TTR and 0.25 (0.09-0.74), p = 0.01 for DFS. CONCLUSION: The results outline a novel integrative approach for prognostication through combining independent predictive factors from genetic and immune cell profiles. However, larger studies are needed to explore multiple cell types in the tumor microenvironment.
- Klíčová slova
- CD8+ cells, Hepatocellular carcinoma, TERT promoter, rs2853669, β-Catenin,
- MeSH
- beta-katenin genetika MeSH
- CD8-pozitivní T-lymfocyty patologie MeSH
- hepatocelulární karcinom * genetika patologie chirurgie MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- mutace MeSH
- nádorové mikroprostředí genetika MeSH
- nádory jater * genetika patologie chirurgie MeSH
- počet buněk MeSH
- telomerasa * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- beta-katenin MeSH
- CTNNB1 protein, human MeSH Prohlížeč
- telomerasa * MeSH
- TERT protein, human MeSH Prohlížeč
In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells' QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.
- Klíčová slova
- B-cells, T-cells, disease-free survival, hepatocellular carcinoma, heterogeneity, prognosis, stereology, time to recurrence, tumor invasive margin, tumor-infiltrating lymphocytes,
- Publikační typ
- časopisecké články MeSH
Only a fraction of specimens under study are usually selected for quantification in histology. Multilevel sampling or tissue probes, slides and fields of view (FOVs) in the regions of interest (ROIs) are required. In general, all parts of the organs under study should be given the same probability to be taken into account; that is, the sampling should be unbiased on all levels. The objective of our study was to provide an overview of the use of virtual microscopy in the context of developing sampling strategies of FOVs for stereological quantification. We elaborated this idea on 18 examples from multiple fields of histology, including quantification of extracellular matrix and muscle tissue, quantification of organ and tumour microvessels and tumour-infiltrating lymphocytes, assessing osseointegration of bone implants, healing of intestine anastomoses and osteochondral defects, counting brain neurons, counting nuclei in vitro cell cultures and others. We provided practical implications for the most common situations, such as exhaustive sampling of ROIs, sampling ROIs of different sizes, sampling the same ROIs for multiple histological methods, sampling more ROIs with variable intensities or using various objectives, multistage sampling and virtual sampling. Recommendations were provided for pilot studies on systematic uniform random sampling of FOVs as a part of optimizing the efficiency of histological quantification to prevent over- or undersampling. We critically discussed the pros and cons of using virtual sections for sampling FOVs from whole scanned sections. Our review demonstrated that whole slide scans of histological sections facilitate the design of sampling strategies for quantitative histology.
- Klíčová slova
- histological slides, quantitative microscopy, sampling, stereology, study design, veterinary histology,
- MeSH
- histologické techniky * veterinární MeSH
- kosti a kostní tkáň MeSH
- mikroskopie * veterinární MeSH
- mozek MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
