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Thyroid gland is a rare site for distant metastases. The aim of this study is to present a rare case of an isolated metastatic clear cell renal cell cancer (ccRCC) in the thyroid gland seven years after left-sided nephrectomy. A neck cancer discovered by clinical examination, diagnosed by ultrasound -guided USG fine-needle biopsy was removed by surgery. Palliative thyroidectomy with consecutive neck radiotherapy was finished without any complications, except a temporary, asymptomatic hypocalcaemia. After six month remission, the patient's general condition deteriorated, multiorgan RCC dissection appeared leading to the patient's death. [ABSTRACT FROM AUTHOR]

Anti-cancer immunotherapies entirely changed the therapeutic approach to oncological patients. However, despite the undeniable success of anti-PD-1, PD-L1, and CTLA-4 antibody treatments, their effectiveness is limited either by certain types of malignancies or by the arising problem of cancer resistance. B7H4 (aliases B7x, B7H4, B7S1, VTCN1) is a member of a B7 immune checkpoint family with a distinct expression pattern from classical immune checkpoint pathways. The growing amount of research results seem to support the thesis that B7H4 might be a very potent therapeutic target. B7H4 was demonstrated to promote tumour progression in immune "cold" tumours by promoting migration, proliferation of tumour cells, and cancer stem cell persistence. B7H4 suppresses T cell effector functions, including inflammatory cytokine production, cytolytic activity, proliferation of T cells, and promoting the polarisation of naïve CD4 T cells into induced Tregs. This review aimed to summarise the available information about B7H4, focusing in particular on clinical implications, immunological mechanisms, potential strategies for malignancy treatment, and ongoing clinical trials.

Cancer immunotherapy is a rapidly developing field of medicine that aims to use the host's immune mechanisms to inhibit and eliminate cancer cells. Antibodies targeting CTLA-4, PD-1, and its ligand PD-L1 are used in various cancer therapies. However, the most thoroughly researched pathway targeting PD-1/PD-L1 has many limitations, and multiple malignancies resist its effects. Human endogenous retrovirus-H Long repeat-associating 2 (HHLA2, known as B7H5/B7H7/B7y) is the youngest known molecule from the B7 family. HHLA2/TMIGD2/KIRD3DL3 is one of the critical pathways in modulating the immune response. Recent studies have demonstrated that HHLA2 has a double effect in modulating the immune system. The connection of HHLA2 with TMIGD2 induces T cell growth and cytokine production via an AKT-dependent signaling cascade. On the other hand, the binding of HHLA2 and KIR3DL3 leads to the inhibition of T cells and mediates tumor resistance against NK cells. This review aimed to summarize novel information about HHLA2, focusing on immunological mechanisms and clinical features of the HHLA2/KIR3DL3/TMIGD2 pathway in the context of potential strategies for malignancy treatment.

V-set domain-containing T-cell activation inhibitor 1 (aliases VTCN1, B7H4) participates in tumour immune escape by delivering inhibitory signals to T cells. The purpose of this article was to assess the B7H4 prognostic value in solid cancers. Three databases were searched for relevant articles. The main endpoints were overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS). Appropriate hazard ratios (HRs) were pooled. The R studio software (version 4.0.3) was used for data analysis. Thirty-one studies met the inclusion criteria. High expression of B7H4 was associated with worse OS (HR = 1.52, 95% CI: 1.37-1.68) but not with DSS (HR = 1.14, 95% CI: 0.49-2.63), RFS (HR = 1.77, 95% CI: 0.75-4.18), DFS (HR = 1.29, 95% CI: 0.8-2.09), or PFS (HR = 1.71, 95% CI: 0.91-3.2) in patients with solid cancers. High expression of B7H4 is associated with a poorer prognosis in patients with solid cancers. B7H4 is a promising prognostic biomarker and immunotherapeutic target for various solid cancers because of its activity in cancer immunity and tumourigenesis.

HHLA2 is a checkpoint from the B7 family that can play a co-stimulatory or co-inhibitory role in cancer, depending on the binding receptor. The aim of this meta-analysis was to assess the relationship between HHLA2 levels and its impact on the prognosis of patients with solid cancers. The study used data from PubMed, Embase, Web of Science (WOS), Cochrane and SCOPUS databases. The R studio software was used for the data analysis. The study assessed overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-free survival (DFS) by pooling appropriate hazard ratios (HR). Eighteen studies (2880 patients' data) were included. High expression of HHLA2 was associated with worse OS (HR = 1.58, 95% CI: 1.23-2.03), shorter RFS (HR = 1.95, 95% CI: 1.38-2.77) and worse DFS (HR = 1.45, 95% CI: 1.01-2.09) in patients with solid cancers. The current study suggests that high expression of HHLA2 is associated with poorer prognosis in patients with solid cancers.

Background: Dysregulation of the autophagy process via ubiquitin is associated with the occurrence of a number of diseases, including cancer. The present study analyzed the changes in the transcriptional activity of autophagy-related genes and the ubiquitination process (UPS) in colorectal cancer tissue. (2) Methods: The process of measuring the transcriptional activity of autophagy-related genes was analyzed by comparing colorectal cancer samples from four clinical stages I-IV (CS I-IV) of adenocarcinoma to the control (C). The transcriptional activity of genes associated with the UPS pathway was determined via the microarray technique (HG-U133A, Affymetrix). (3) Results: Of the selected genes, only PTEN-induced kinase 1 (PINK1) indicated statistical significance for all groups of colon cancer tissue transcriptome compared to the control. The transcriptional activity of the protein tyrosine phosphatase non-receptor type 22 (PTPN22 ) gene increased in all stages of the cancer, but the p -value was only less than 0.05 in CSIV vs. C. Forkhead box O1 (FOXO 1 ) and ubiquitin B (UBB) are statistically overexpressed in CSI. (4) Conclusions: The pathological expression changes in the studied proteins observed especially in the early stages of colorectal cancer suggest that the dysregulation of ubiquitination and autophagy processes occur during early neoplastic transformation. Stopping or slowing down the processes of removal of damaged proteins and their accumulation may contribute to tumor progression and poor prognosis.

The study aimed to assess the expression of B7H3 concerning clinicopathological and histological parameters, including MSI/MSS status, CD-8 cells, tumour-infiltrating lymphocytes (TILs), budding, TNM scale and grading. Moreover, we analyzed the B7H3-related pathways using available online datasets and the immunological context of B7H3 expression, through the 48-cytokine screening panel of cancer tissues homogenates, immunogenic features and immune composition. The study included 158 patients diagnosed with CRC. To assess B7H3 levels, we performed an immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). To elucidate the immune composition of colorectal cancer, we performed the Bio-Plex Pro Human 48-cytokine panel. To study biological characteristics of B7H3, we used online databases. Expression of B7H3 was upregulated in CRC tumour tissues in comparison to adjacent noncancerous margin tissues. The concentrations of B7H3 in tumours were positively associated with T parameter of patients and negatively with tumour-infiltrating lymphocytes score. Additionally, Principal Component Analysis showed that B7H3 expression in tumours correlated positively with cytokines associated with M2-macrophages and protumour growth factors. The expression of B7H3 in tumours was independent of MSI/MSS status. These findings will improve our understanding of B7H3 role in colorectal cancer immunity. Our study suggests that B7-H3 is a promising potential target for cancer therapy. Further studies must clarify the mechanisms of B7H3 overexpression and its therapeutic importance in colorectal cancer.

The influence of chitinase-3-like protein 1 (YKL-40 or CHI3L1) expression on the immunological properties of the tumor microenvironment, which may affect the effectiveness of immunotherapy, is currently not sufficiently understood in colorectal cancer (CRC). The aim of this study was to investigate the relationship between YKL-40 expression and the immunological properties of the tumor microenvironment in CRC. We performed in silico analysis, including analysis of immune cell infiltration scores and the immune landscape depending on YKL-40 expression, gene set enrichment analysis (GSEA), and analysis of three Gene Expression Omnibus (GEO) datasets. In 48 CRC tissue homogenates and the surgical margin, we analyzed the expression of YKL-40, MMP8, IL17A, and PD-L1. Moreover, we analyzed the expression of YKL-40 in tissue homogenates retrieved from patients with coexisting diabetes, obesity, and smoking. The expression of YKL-40 was significantly higher in CRC tumor tissue compared to healthy tissue and correlated with MMP-8, IL17A, and PD-L1 expression. In silico analysis revealed an association of YKL-40 with disease recurrence, and GSEA revealed a potential link between elevated YKL-40 expression and immunosuppressive properties of the tumor microenvironment in CRC.

The study aimed to investigate correlations between HHLA2 levels and parameters, including microsatellite instability (MSI) status, CD8+ cells, and histopathological features: budding, tumor-infiltrating lymphocytes (TILs), TNM scale, grading, cytokines, chemokines, and cell signaling moleculesin colorectal cancer (CRC). Furthermore, the immune infiltration landscape and HHLA2-related pathways in colorectal cancer using available online datasets were analyzed. The study included 167 patients diagnosed with CRC. Expression of HHLA2 was detected by immunohistochemistry method (IHC) and enzyme-linked immunosorbent assay (ELISA). The IHC was used to evaluate the MSI and CD8+ status. The budding and TILs were measured using a light microscope. The concentrations of cytokines, chemokines, and cell signaling molecules were measured to analyze the data by the Bio-Plex Pro Human cytokine screening panel, 48 cytokine assay, and principal component analysis (PCA). Geneset enrichment analysis (GSEA) was conducted to identify HHLA2-related pathways. The biological function of HHLA2 was predicted by Gene Ontology (GO). Analysis of the immune infiltration landscape of HHLA2 in colorectal cancer was made by the web-based tool Camoip. High HHLA2 expression was detected in CRC tumor tissues compared to the adjacent noncancerous tissues. The percentage of HHLA2-positive tumors was 97%. GSEA and GO showed that HHLA2 upregulation correlated with cancer-related pathways and several biological functions. Tumor-infiltrating lymphocytes score correlated positively with IHC HHLA2 expression level percentage. There was a negative correlation between HHLA2, anti-tumor cytokines and pro-tumor growth factors. This study provides a valuable insight into the role of HHLA2 in CRC. We reveal the role of HHLA2 expression as well as a stimulatory and inhibitory immune checkpoint in colorectal cancer. Further research may verify the therapeutic values of the HHLA2-KIR3DL3/TMIGD2 pathway in colorectal cancer.

The immunotherapies based on ICIs in CRC are nowadays limited to microsatellite unstable tumours which are approximately 15% of all CRC cases. There are a few new immune checkpoints belonging to the B7 family, including B7H4. B7H4 expression is associated with so-called "cold tumours", and its function is linked to the downregulation of various immune cell populations. Our study aimed to investigate whether B7H4 expression is dependent on microsatellite status in CRC and on elucidating the immunological context in which the expression of B7H4 occurs. We enrolled 167 patients in the study. We prepared the homogenates from tumour tissues and healthy adjacent tissue to assess the B7H4 levels and the Bio-Plex Pro Human 48-cytokine panel. We assessed the microsatellite status of the tumour, B7H4 expression, CD8+ T cell population, and the TILs and budding in H + E stained slides by the IHC method. We used an online available database for further exploring the biological characteristics of B7H4. The expression of B7H4 was more frequent in microsatellite stable tumours, and was negatively associated with TILs. B7H4 is positively correlated with antitumour immunosuppressive iTME, thus contributing to the immunosuppressive environment in CRC.

(1) Background: Autophagy plays a dual role in oncogenesis-it contributes to the growth of the tumor and can inhibit its development. The aim of this study was to assess changes in the transcriptional activity of LAMP-2, BECN1, PINK1 , and FOXO1 genes involved in the autophagy process in histopathologically confirmed adenocarcinoma sections of colorectal cancer: (2) Methods: A gene expression profile analysis was performed using HG-U133A and the RT-qPCR reaction. The transcriptional activity of genes was compared in sections of colorectal cancer in the four clinical stages (CSI-CSIV) concerning the control group; (3) Results: In CSI, the transcriptional activity of the PINK1 gene is highest; in CS II, the LAMP-2 gene is highest, while FOXO1 increases gradually from CSI reaching a maximum in CSIII. There is no BECN1 gene expression in colorectal cancer cells; (4) Conclusions: The observed differences in the mRNA concentration profile of autophagy-related genes in colon cancer specimens may indicate the role of autophagy in the pathogenesis of this cancer. Genes involved in autophagy may be diagnostic tools for colorectal cancer screening and personalized therapy in the future.

Reconstructive surgery often confronts large tissue defects. This creates a need to look for materials that are immunogenic but offer the possibility of tissue filling. ADM-acellular dermal matrix-is a biological collagen matrix without immunogenicity, which is more commonly used in surgical treatment. Reconstructive surgery is still searching for various biocompatible materials that can be widely used in surgery. The available materials have their advantages and disadvantages. This paper is a literature review on the use of human acellular dermal matrix (ADM) in reconstructive surgery (surgical oncology, plastic and reconstructive surgery, and gynecologic reconstructive surgery). ADM appears to be a material of increasing use in various fields of surgery, and thus, further research in this area is required.

ADAM10 and ADAM17 have a role in inflammation and diseases associated with inflammation, such as diabetes, cardiovascular diseases (CVD) or cancer, e.g., colorectal cancer (CRC). The aim of this study was to evaluate whether ADAM10 and ADAM17 could be biomarkers of CRC. To achieve this goal, CRC tumors and a surgical margin from 72 patients with CRC were collected. The concentration of ADAM proteins was measured by the ELISA method. Results were analyzed statistically and compared with selected clinical parameters. We found that ADAM17 protein concentration in the tumor samples was higher in patients with diabetes mellitus type 2 (DMT2) (0.28 vs. 0.2 ng/µg protein; p = 0.01) and in the surgical margin was higher both in patients with coexisting DMT2 (0.22 vs. 0.16 ng/µg protein; p < 0.05) and CVD (0.21 vs. 0.13 ng/µg protein; p < 0.01). The concentration of ADAM10 was higher in the surgical margin than in the tumor (249.34 vs. 228.82 pg/µg protein), and the concentration of ADAM17 was higher in the tumor than in the margin (0.23 vs. 0.18 ng/µg protein), but results were not statistically significant. In conclusion, the results of our study indicate that ADAM10 and ADAM17 may be potential biomarkers in cancer linked with DMT2 and CVD as diseases associated with inflammation.

Colorectal cancer is one of the most prevalent cancers worldwide. There is a great interest and need to find simple, inexpensive, and minimally invasive diagnostic tests. The aim of the study was to analyze the salivary concentrations of chemerin, α-defensin 1, and TNF-α in colorectal cancer (CRC) patients and in a healthy control group. The concentration of these proteins was simultaneously determined in the serum of subjects. We also aimed to assess the correlation of these results and selected clinicopathological features. This prospective study was comprised of 39 CRC patients and 40 control group patients. Salivary and serum concentrations were determined by enzyme immunoassays. The salivary and serum concentrations of chemerin, α-defensin 1, and TNF-α were significantly higher in cancer patients compared to the control group. No correlation was found between concentrations of the proteins and the clinical stage of cancer and tumor location. The ROC curve analysis showed that although salivary concentrations of all proteins showed 100% sensitivity and 100% specificity, serum concentrations of the analyzed proteins were characterized by 100% sensitivity and over 90% specificity. The assessment of chemerin, α-defensin 1, and TNF-α concentrations in saliva seem to have great potential as quick and useful biomarkers in the early diagnosis of CRC.

Background and Objectives : Assessment of RANTES level and concentrations of inflammatory cytokines: programmed death ligand 1 (PD-L1), interferon gamma IFN-γ, tumor necrosis factor alpha (TNF-α), transforming growht factor β (TGF-β) (and angiogenesis factors: vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor C (VEGF C) in tumor and margin tissues of colorectal cancer (CRC,) and evaluation of RANTES influence on histopathological parameters (microvessel density (MVD), budding, tumor-infiltrating lymphocytes (TILs)), in relation to patients' clinical features. Materials and Methods : The study used 49 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of RANTES, PD-L1, IFN-γ, TNF-α, TGF-β, VEGF-A, and VEGF-C, we used the commercially available enzyme-linked immunosorbent assay kit. Additionally, RANTES and PD-L1 expression was assessed with the use of IHC staining in both tumor cells and TILS in randomly selected cases. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope. Results : We found significantly higher levels of RANTES, PD-L1, IFN-γ, TNF-α, TGF-β, VEGF-A, and VEGF-C in the tumor in comparison with the margin. The RANTES tumor levels correlated significantly with those of PD-L1, TNF-α, TGF-β, VEGF-A, and VEGF-C. The RANTES margin levels were significantly associated with the margin levels of all proteins investigated-PD-L1, IFN-γ, TNF-α, TGF-β, VEGF-A, and VEGF-C. Additionally, we observed RANTES- and PD-L1-positive immunostaining in TILs. In a group of 24 specimens, 6 different CRC tumors were positive for RANTES and PD-L1 immunostaining. The IFN-gamma concentration in both tumor and margin and TGF-β in tumor correlated with TILs. TILs were negatively associated with the patients' disease stage and N parameter. Conclusions : RANTES activity might be associated with angiogenesis, lymphogenesis, and immune escape in CRC. RANTES is an important chemokine that is a part of the chemokine-cytokine network involved in the modulation of TME composition in CRC. Further research may verify which processes are responsible for the associations observed in the study.

Background and Objectives : To assess the periostin level and the concentrations of pro-inflammatory cytokines: TNFα, IFN-γ, IL-1β and IL-17 in tumor and marginal tissues of CRC and to investigate the influence of periostin on angiogenesis by MVD (microvessel density) and concentration of VEGF-A in relation to clinicopathological parameters of patients. Materials and Methods : The study used 47 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of periostin, VEGF-A, TNFα, IFNγ, IL-1β and IL-17, we used the commercially available enzyme- linked immunosorbent assay kit. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope Results : We found significantly higher concentrations of periostin, VEGF-A, IFN-γ, IL-1 β, IL-17 and TNFα in the tumor samples compared with surgical tissue margins. The tumor concentrations of periostin were correlated with tumor levels of VEGF-A, IFN-γ, IL-1β and TNFα. We observed significant correlation between margin periostin and VEGF-A, IFN-γ, IL-17 and TNFα in tumor and margin specimens. Additionally, we found a significantly negative correlation between periostin tumor concentration and microvessel density at the invasive front. Tumor periostin levels were also correlated positively with tumor budding. Conclusions: Periostin activity may be associated with pro-inflammatory cytokine levels: TNFα, IFN-γ, IL-1β and IL-17. Our results also suggest the role of periostin in angiogenesis in CRC and its upregulation in poorly vascularized tumors. Further research on the regulations between periostin and cytokines are necessary to understand the interactions between tumor and immune tumor microenvironment, which could be helpful in the development of new targeted therapy.

Background and Objectives : Colorectal cancer (CRC) is the second-most common cause of cancer-related deaths worldwide. Angiogenesis is crucial for cancer growth, infiltration of surrounding tissues, and metastasis and plays a key role in the pathogenesis of CRC. Chemerin/chemokine-like receptor 1 (CMKLR1) is one of the biochemical pathways involved in the regulation of angiogenesis in solid tumors. The aim of the study was to assess the CMKLR1 level in tumor and margin tissues of CRC in relation to histopathological parameters: microvessel density (MVD), budding, tumor-infiltrating lymphocytes (TILs), TNM scale, and grading. Materials and Methods : The study involved 43 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of CMKLR1 a commercially available enzyme-linked immunosorbent assay kit was used. For 35 cases, we performed CD34 immunostaining. The MVD, budding, and TILs were assessed using a light microscope. Results : The levels of CMKLR1 in both tumor and margin were negatively correlated with MVD and budding. CMKLR1 concentration in margin was higher in tissues with lymphocytic infiltration. Conclusions : Low vascularity and low budding are associated with higher CMKLR1 expression. CMKLR1 might play a multifunctional role in CRC pathogenesis by influencing tumor budding and peritumoral lymphocytic infiltration.

Abstract: The inhibitor of apoptosis family proteins (IAPs) plays a crucial role in the process of carcinogenesis by regulating apoptosis and maintaining the tissue balance.In this study, a transcriptomic analysis of IAP-encoding genes in colon cancer was performed using oligonucleotide microarrays.Adenocarcinoma and healthy colon tissue samples were collected from 32 patients (16 females and 16 males) who underwent surgery due to colon cancer. The mRNA was extracted from tissue samples and tested using oligonucleotide microarrays (Affymetrix). The results were validated using the qRT-PCR technique. Hierarchical grouping was used to allocate 37 samples of normalized mRNA concentrations into 4 groups, with statistically significant differences in gene expression between these groups. The group of genes associated with colon cancer, including IAP-encoding gene - BIRC5 (Survivin), was selected for further testing.Our study confirmed an increased expression of BIRC5 in colon cancer tissue when compared to the control group. Increased levels of Neuronal Apoptosis Inhibitory Proteins were detected only in low-stage colon cancer, while the expression of Human X Chromosome-Encoded inhibitor of apoptosis family proteins decreased in colon cancer.The transcriptional activity of IAP-encoding genes varied, depending on the severity of colon cancer. The concentration of mRNA, encoding BIRC5 was elevated in samples obtained from more advanced colon cancer. Hence BIRC5 could be used as a complementary parameter for the diagnosis and prognosis of colon cancer., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide, responsible for over 880 000 deaths each year. Growth/differentiation factor 15 (GDF-15) is reported to be a promising diagnostic and prognostic factor in CRC. It induces pleiotropic effects in tumor cells: proliferation, stemness, invasion and metastasis. Some studies indicate that GDF-15 may stimulate angiogenesis in malignant neoplasms. However, it has not been investigated in CRC yet. The aim of our study was to determine the level of GDF-15 and the concentrations of hypoxia-inducible factor-1α (HIF-1α), VEGF-A and chemokine-like receptor 1 (CMKLR1) in tumor and margin specimens of CRC in relation to histological grade and TNM staging. The study comprised 33 samples of tumor and margin tissues obtained from CRC patients. To assess the concentration of GDF-15, HIF-1α, VEGF-A and CMKLR1, commercially available enzyme-linked immunosorbent assay (ELISA) kits were used. We found significantly increased levels of GDF-15 and CMKLR1 in tumor tissue compared to margin tissue and higher concentrations of HIF-1α and VEGF-A in margin tissue than in tumor tissue. The levels of GDF-15 and HIF-1α were significantly correlated with VEGF-A and CMKLR1 in margin tissue. In CRC, the increased level of GDF-15 might stimulate angiogenesis through upregulation of HIF-1α, VEGF A and CMKLR1 expression. Our study is the first one to reveal the correlation between the levels of GDF-15 and CMKLR1 in CRC. The elevated levels of HIF-1α and VEGF-A in tumor-free margin tissues suggest that noncancer cells in the tumor microenvironment are an important source of proangiogenic factors., (© 2021. Huazhong University of Science and Technology.)

Colorectal cancer is the second and third most common cancer in females and males, respectively. The PD-L1/PD-1 immune checkpoint is an important source of immunosuppression in the tumor microenvironment and is associated with IFNγ. Recent studies have revealed that a significant number of tumor suppressive miRNAs can regulate the expression of PD-L1.                The objective quantification of selected microRNAs using the miREIA method in CRC tissue was performed. We investigated the roles of miR-93-5p and miR-142-5p expression and the levels of IFNγ in regulating the expression of PD-L1 in tumor and margin tissues of CRC in relation to the histological grade, TNM classification, and tumor localization. 37 samples of tumor and margin tissues from CRC patients were evaluated. MiR-93-5p and miR-142-5p levels were measured by a method for quantitative measurement of human microRNA (miREIA). The concentrations of PD-L1 and IFNγ were determined by the ELISA kit. We found higher concentrations of miR-93-5p, PD-L1 and IFNγ in tumor samples compared to tumor margin samples. A significant correlation was found between PD-L1 and IFNγ in tumor and margin specimens; between miR-142-5p and miR-93-5p levels  in tumor and margin specimens. A higher level of miR-93-5p was found in tumor margin tissues on the left side of the colon. Patients with distant metastases were characterized by higher miR-93-5p concentration compared to patients without metastases. CRC is an important source of PD-L1, IFNγ and miR-93-5p expression. Understanding the mechanisms underlying intratumoral PD-L1 expression may open new opportunities for targeted immunotherapy for colorectal cancer.

Background: Autophagy plays a dual role of tumor suppression and tumor promotion in colorectal cancer. The study aimed to find those microRNAs (miRNAs) important in BECN1 , LAMP2 , and PINK1 regulation and to determine the possible role of the epigenetic changes in examined colorectal cancer using an in silico approach., Methods: A total of 44 pairs of surgically removed tumors at clinical stages I‒IV and healthy samples (marginal tissues) from patients' guts were analyzed. Analysis of the obtained results was conducted using the PL-Grid Infrastructure and Statistica 12.0 program. The miRNAs and CpG islands were estimated using the microrna.org database and MethPrimer program., Results: The autophagy-related genes were shown to be able to be regulated by miRNAs ( BECN1 -49 mRNA, LAMP2 -62 mRNA, PINK1 -6 mRNA). It was observed that promotion regions containing at least one CpG region were present in the sequence of each gene., Conclusions: The in silico analysis performed allowed us to determine the possible role of epigenetic mechanisms of regulation gene expression, which may be an interesting therapeutic target in the treatment of colorectal cancer.

Introduction: Colorectal cancer (CRC) is the second most common malignant neoplasm in men and third in women. It is also the third leading cause of cancer-related death, killing annually >700,000 patients in the world. The global burden of CRC is expected to increase by 60% to >2.2 million new cases and 1.1 million deaths by 2030. The pathogenesis of cancer mainly depends on angiogenesis. This process plays a key role in the growth and infiltration of tumors which is essential for distant metastases. A large number of biochemical pathways is involved in the regulation of angiogenesis. As a subject of our study, we chose chemerin/chemokine-like receptor 1 (CMKLR1) pathway which is responsible for the angiogenic processes in malignant neoplasms., Aim of the Study: To assess the CMKLR1 level and the concentrations of the two markers of angiogenesis, matrix metalloproteinase (MMP)-9 and vascular cell adhesion molecule (VCAM)-1, in tumor and margin tissues of CRC in relation to histological grade and TNM classification., Materials and Methods: The study used 47 samples of tumor and margin tissues derived from CRC patients. To determine the concentration of CMKLR1, MMP-9, and VCAM-1, we used the commercially available enzyme-linked immunosorbent assay kit., Results: We found a significantly higher concentration of CMKLR1 and MMP-9 in tumor tissue compared to margin. There was no difference in VCAM-1 concentration between tumor and margin. The margin concentration of CMKLR1 was significantly correlated with that of both MMP-9 and VCAM-1. The margin concentration of VCAM-1 was correlated with that of MMP-9. Additionally, we observed that the tumor levels of CMKLR1 and MMP-9 were positively correlated with the tumor size (T parameter)., Conclusion: CMKLR1 activity may be associated with the angiogenic process in CRC via MMP-9 activity. Further research, involving a larger sample, may verify whether chemerin/CMKLR1 axis could be considered as a suitable target in novel molecular therapies., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Colorectal cancer is one of the most common cancers in the world. Due to its still undetermined pathogenesis, we are searching for signaling pathways that are important in the development of colorectal cancer. In this article, we present results of study on the role of ADAM proteins in colorectal cancer. The study included 85 adult colorectal cancer patients (48 men, 37 women) and 25 patients in the control group (after diagnostic colonoscopy-without cancer). During hospitalization, a serum sample (3 cm 3 ) was collected from the study and control group, anthropometric measurements were conducted and others clinical data were analyzed. In the serum ADAM10, 12, 17, and 28, protein concentrations were determined and, in the next step, examined the relationship between ADAMs concentrations and selected clinical parameters in both groups. The analysis showed that serum levels of ADAM10 and ADAM28 are significantly higher in patients with colorectal cancer and correlate with histopathological grading and with presence of distant metastases. Moreover, noticed the trend to correlate concentrations of adamalysines with higher BMI score. One of the functions of adamalysines is the activation of growth factors involved in cancer, including IGF and TNF α . The increased activity of adamalysines in patients may play a role in the pathogenesis of colorectal cancer. Our study highlights the prevalence of metabolic disorders in the group of patients with diagnosed CRC, and this cancer seems to be a further complication of obesity., Competing Interests: The authors report no declarations of interest., (Copyright © 2019 Katarzyna Walkiewicz et al.)

Background: In pursuit of improvement in cardiopulmonary resuscitation (CPR), new technologies for the measurement and assessment of CPR quality are implemented. In our study, we assessed the kinematics of the rescuer during continuous chest compression (CCC-CPR). The proper performance of the procedure is a survival predictor for patients with cardiac arrest (CA). The purpose of the study was a prospective assessment of the kinematics of the rescuer's body with consideration given to the depth and rate of chest compression (CC) as the indicator of properly performed CC maneuver by professional and non-professional rescuers during a simulation of a 10-min CCC using a manikin., Methods: Forty participants were enrolled in the study. CCC-CPR was performed in accordance with the 2015 AHA guidelines on a manikin positioned on the floor. Kinematic data on the movement were obtained from the measuring system (X-sens MVN Biomech) transmitting information from 17 inertial sensors. Measurement data were imported to the author's program RKO-Kinemat written in the Matlab and C # environments. Two groups of results were distinguished: Group I-results of CC with the depth of ≥ 40 mm and Group 2-CC results with the depth of < 40 mm., Results: The multiple regression model demonstrated that the path length, left knee flexion angle, and left elbow flexion angle were the essential elements of the rescuer's kinematics that facilitated achieving and maintaining the normal depth of CC., Conclusions: We believe that raising the rescuer's hips by moving the center of the rescuer's body over the point of sternal compression increases the value of the CC force vector, thereby increasing the depth of CC. In addition, we observed that, during an effective CC, the rescuer was unable to maintain arms straight and, in consequence, a slight elbow flexion was observed. It, however, did not influence the quality of the maneuver.

In certain patients with advanced colorectal cancer, loss of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) activity is observed. PTEN is a major gatekeeper gene of the AKT serine/threonine kinase (AKT) signaling pathway responsible for the proliferative activity of cells. The assessment of AKT activity may be a prognostic factor or a predictor of response to the targeted therapies against particular signaling proteins. To precisely identify the cause and the place of the pathway deregulation, it is necessary to identify phosphorylation states and concentrations of several proteins located at different levels of the regulatory cascade. In the present study, we propose the simultaneous use of specific antibodies conjugated with different quantum dots to highlight the nature of AKT/PKB cascade deregulation in patients with colorectal cancer and the loss of PTEN expression in tumor tissue. Fifty patients with colorectal cancer of no specific location were enrolled in the study. The expression of the PTEN protein, and concentrations of phosphorylated/activated forms of 3-Phosphoinositide-dependent kinase 1 (PDK1) and AKT were assessed using quantum dot-conjugated antibodies. In patients with a diminished or complete loss of the PTEN expression in the tumor tissue increased levels of activated/phosphorylated forms of PDK1 (Phospho-PDK1-Ser241) and AKT (Phospho-AKT-Thr308) proteins were found, which are responsible for the permanent activation of the phosphoinositide 3-kinase/AKT/PTEN signaling pathway in certain cases of colorectal cancer.

There is evidence that autophagy can play a dual role in tumor cells – as a tumor suppressor, and a process involved in tumor cell survival. The aim of this work was to assess the expression of the genes engaged in the autophagy process in biopsies taken from the colon, confirmed as adenocarcinoma, and normal tissue and to relate them to the clinical stage of the tumor. A total of 20 pairs of surgically removed tumors and healthy (marginal) tissue samples from colorectal cancer patients at clinical stages (CS) I-IV were analyzed. Gene expression profile analysis was performed using HG-U133A microarrays. Differentially expressed genes were identified, using the PL-Grid Infrastructure. Only for CSI, there were two specific genes: FOXO1 and BNIP1; further in CSII – LAMP2, MET and BCL2L, in CSIII – HIF1A and 2 ID mRNAs for HGF and 18 genes were specific for CSIV in comparison to controls. PINK1 is the only gene that differentiates all transcriptome groups from controls. Furthermore, examination of the expression of genes associated with the autophagy process may allow for better knowledge and understanding of the processes occurring during the development of colon cancer. The presented genes may be used as prognostic markers of clinical stages of colorectal cancer, contributing to the development of new lines of therapy focused on reducing metastasis of the primary tumor.

The aim of the study is the assessment of the intensity of the infiltration of tumor-associated macrophages (TAMs) CD68 + /iNOS - and Tregs CD8 + /FoxP3 + in colorectal cancer (CRC) patients as prognostic factors with respect to disease-free survival (DFS) and overall survival (OS). In this retrospective study, tissue samples were obtained from 89 patients undergoing resection for CRC (stage IIA, pT3N0M0 and stages IIIB and IIIC, pT3N1-2M0). Recurrence was observed in 45 patients at the time of the follow-up (10 local recurrences, 35 distant metastases). In patients with recurrence the following were present: a tendency to an older average age at the time of diagnosis (p = 0.07), higher nodal involvement (p = 0.002) and more advanced clinical disease (p = 0.01). The analysis of the clinical data and immunohistochemical studies were performed with the methodology of identification of TAM and Treg subsets in histological sections, with the aim to use it in routine clinical management. Both DSF and OS were the clinical parameters assessed in the study. The presence of intense infiltration of TAMs in the tumor stroma was related to shorter DFS (p = 0.005) and OS (p = 0.006). The opposite tendency was observed in the tumor front (p = 0.061). The relative risks of recurrence and cancer-related death were more than twice higher in the group of patients with intense infiltration of TAMs in the tumor stroma (RR 2.05, 95% CI 1.33-3.14; p = 0.001 and RR 2.08, 95% CI 1.28-3.39; p = 0.003, respectively). Intense infiltration of Tregs in the tumor stroma was related to shorter DFS and OS (p < 0.0001). The relative risks of recurrence and death in a group of patients with intense infiltration of Tregs in the tumor stroma were more than 12 times higher than in patients with less intense infiltration (RR 12.3, 95% CI 5.44-27.9; p < 0.0001 and RR 12.5, 95% CI 4.9-32.4; p < 0.0001, respectively). Infiltration of TAMs CD68 + /iNOS - and Tregs CD8 + /FoxP3 + in the tumor stroma are negative prognostic factors with a positive correlation between them. Tregs may constitute an independent prognostic factor in patients with CRC.

The role of different types of human papillomavirus (HPV) in the development of oral and oropharyngeal papillomas remains unclear. High-risk HPV (HR-HPV) was shown to be involved in the pathogenesis of significant proportion of squamous cell carcinomas of the oropharynx. In this study, we hypothesized that in some oropharyngeal papillomas, low-risk HPV (LR-HPV) and HR-HPV infection could co-exist, similar to what is observed in genital warts, and thus contribute to the elevated risk of malignancy. To test this hypothesis, we used real-time PCR to assess the presence of HPV DNA of 16 types (2 LR-HPV and 14 HR-HPV), in 75 formalin-fixed and paraffin-embedded histopathological samples of oral and oropharyngeal papillomas and in 57 squamous cell carcinomas from the same regions. We investigated the biological activity of HPV by demonstrating accumulation of P16(INK4A) protein in the viral-infected tissue samples. The presence of the LR-HPV genome from the HPV6 or HPV11 types was confirmed in 42 (56%) papillomas and in no carcinomas. HPV6/HPV11 co-infection was detected in 17 (22.7%) of the papillomas. HR-HPV DNA presence and HR-HPV activity hallmarks were not observed in any of the investigated papillomas. Thus, a causative role for HR-HPV or its contribution to LR/HR-HPV co-infection in the pathogenesis of oral or oropharyngeal papillomas is unlikely. Additionally, HR-HPV and LR-HPV infections seem to be mutually exclusive in papillomas and squamous cell carcinomas of the oral cavity and oropharynx.

BACKGROUND Studies on the pathomechanism of colorectal cancer (CRC) expansion indicate a significant role of metalloproteinases and their inhibitors in the extracellular matrix. The results of the analysis of a profile of transcriptional activity of genes encoding metalloproteinases were the basis of the hypothesis indicating changes in the expression of genes encoding MMP9, MMP28, and TIMP1 as an additional diagnostic and prognostic marker of CRC. MATERIAL AND METHODS The material consisted of samples obtained from resected tumors and healthy tissue samples from 15 CRC patients (aged 46-72 years) at clinical stages (CSs) I and II-IV. Gene expression analysis was done using microarrays. Microarray data analysis was done using the GeneSpring 11.5 platform. The results were validated using the qRT-PCR technique. RESULTS We found high levels of expression of MMP9 at each CS, as well as in the tissues at the early stage of CRC. Additionally, we observed high levels of expression of TIMP1 and low levels of MMP28 genes in CS II-IV. No statistically significant differences based on the stage of CRC were observed. CONCLUSIONS MMP9 gene profile may be a complementary diagnostic marker in CRC. The results suggest a crucial role of MMP9 at the early stage of carcinogenesis in the large intestine. The increase in MMP9 and TIMP1 mRNA concentration and the decrease in MMP28 in the large intestinal tissue may be a confirmation of cancer, but it may not indicate the advance of CRC.

Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%-20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies., Competing Interests: The authors declare no conflict of interest.

Phosphatase and Tensin Homolog deleted on chromosome 10 (PTEN) gene is one of the most important tumor suppressor genes which is involved in the regulation of many signaling cascades (AKT/PKB and MAPK). Subtle changes in its activity lead to cancer susceptibility or aggressive tumor behaviour. Despite the diversity of mechanisms leading to PTEN inactivation, it is frequently associated with a decreased or complete loss of protein expression. About 20% decrease in PTEN expression could lead to the development of cancer. There have been no objective, quantitative methods of PTEN expression assessment that allow to measure the subtle variations of the protein concentration in a tissue-contextual manner. A new quantitative algorithm of immunostaining evaluation based on combination of color deconvolution and relative chromogen signal intensity was used in the study. The proposed algorithm was implemented in the popular ImageJ image analysis software and positively verified in cancer cell lines and tissue models as well as in the tissue samples of colorectal cancer (CRC) patients. The proposed quantitative method of PTEN expression assessment creates an alternative to currently available subjective methods and forms the basis for inter-case and inter-tissue comparisons. Using the algorithm it would be possible to identify three groups of patients with advanced colorectal cancer which could significantly differ in the overall survival. The research should be continued.

Background: Colorectal Cancer (CRC) is one of the most frequently diagnosed neoplasms and also one of the main death causes. Cell adhesion molecules are taking part in specific junctions, contributing to tissue integrality. Lower expression of the cadherins may be correlated with poorer differentiation of the CRC, and its more aggressive phenotype. The aim of the study is to designate the cadherin genes potentially useful for the diagnostics, prognostics, and the treatment of CRC., Material and Methods: Specimens were collected from 28 persons (14 female and 14 male), who were operated for CRC. The molecular analysis was performed using oligonucleotide microarrays, mRNA used was collected from adenocarcinoma, and macroscopically healthy tissue. The results were validated using qRT-PCR technique., Results: Agglomerative hierarchical clustering of normalized mRNA levels has shown 4 groups with statistically different gene expression. The control group was divided into 2 groups, the one was appropriate control (C1), the second (C2) had the genetic properties of the CRC, without pathological changes histologically and macroscopically. The other 2 groups were: LSC (Low stage cancer) and HSC (High stage cancer). Consolidated results of the fluorescency of all of the differential genes, designated two coding E-cadherin (CDH1) with the lower expression, and P-cadherin (CDH3) with higher expression in CRC tissue., Conclusions: The levels of genes expression are different for several groups of cadherins, and are related with the stage of CRC, therefore could be potentially the useful marker of the stage of the disease, also applicable in treatment and diagnostics of CRC.

Unlabelled: Wound healing is a complex pathophysiological process, in which platelets play a crucial role. Platelet alpha-granules release growth factors to the wound bed; the factors are necessary in the healing process. In chronic wounds, such as poorly healing lower-leg ulcers of venous origin, there is decreased activity of multiple growth factors, so the concept of exogenous delivery of such factors seems a logical strategy. Platelet-rich plasma therapy in patients with lower-leg ulcers of venous origin combined with conventional treatment methods (previously ineffective in these patients) seems, based on our observation, an important adjunct leading to recovery. The aim of the study was to present an original method of autologous platelet-rich plasma application through the creation of a sort of "biological chamber" containing a concentrate of growth factors., Material and Methods: The described therapy was implemented in 10 patients, who had been ineffectively treated for more than one year in the outpatient setting. Patients with exacerbation of inflammatory process, signs of wound infection and ankle brachial pressure index < 0.8 were excluded from the study. After the application of platelet-rich plasma, further treatment was continued with the use of moist therapy and compression therapy according to a uniform regimen., Results: Complete healing was achieved within 4-10 weeks from the beginning of the product administration in all patients., Conclusion: The presented method seems technically simple, effective and relatively inexpensive.

Background: Perianal fistulas are malformations of the anorectal area. Accurate preoperative assessment of perianal fistula tract is a main assumption in diagnosis of the disease, affecting the operation efficiency. The aim of the study was to present our experience in application of a new diagnostic protocol based on the magnetic resonance imaging (MRI) examination using a mixture of hydrogen peroxide (HP) and gadolinium as a direct contrast medium in evaluation of recurrent fistulas tract. The method is referred to as HPMRI., Material and Methods: The study group consisted of 12 subjects operated on from 2011. Direct HPMRI fistulography was performed in all subjects before the operation. All types of fistulas were precisely evaluated by HPMRI examination., Results: Intraoperative state confirmed complete course of fistulas in 11 cases. In 1 case, an internal opening was not found., Conclusions: We suggest that this new method of direct HPMRI fistulography may improve visualization of the tracts of recurrent fistulas and improve efficacy of surgical procedures.

Duodenal carcinoma is a rare tumor of the gastrointestinal tract of an insidious and secretive course, often diagnosed during the advanced stage of the disease. The study presented a case of a female patient diagnosed with duodenal carcinoma, subjected to two-staged surgery. The initial surgical intervention consisted in the implementation of a gastrointestinal anastomosis, followed by radical surgery by means of Whipple's method performed after three years.

Calcifying fibrous tumor is a rare disease entity, usually concerning the soft tissues of the limbs, neck, trunk, or scrotum. Cases of the above-mentioned pathology have also been reported considering the pleural and peritoneal cavity, and small bowel mesentery. The essence of the disease, whose etiology and pathogenesis remains unclear, is the fibrous tissue infiltration and diffuse inflammation with focal calcifications. The study presented a case of a 27-year old male patient subjected to surgical intervention, due to an abdominal cavity tumor. The tumor was radically removed, and its character and definitive diagnosis were established postoperatively. After a seven-year follow-up period, recurrence was not observed.

Advances in genomics, molecular pathology and metabolism have generated many candidate biomarkers of colorectal cancer with potential clinical value. Epidemiological and biological studies suggest a role for adiposity, dyslipidaemia, hyperinsulinemia, altered glucose homeostasis, and elevated expression of insulin-like growth factor (IGF) axis members in the risk and prognosis of cancer. This review discusses some recent past and current approaches being taken by researches in obesity and metabolic disorders. The authors describe three main systems as the most studied metabolic candidates of carcinogenesis: dyslipidemias, adipokines and insulin/IGF axis. However, each of these components is unsuccessful in defining the diseases risk and progression, while their co-occurrence increases cancer incidence and mortality in both men and women.

Aim: To demonstrate the presence and biological activity of human papilloma virus (HPV) in gastric cancer (GAC) tissues., Methods: The study involved 84 surgically treated patients with gastric adenocarcinoma, regardless of the clinical stage of the disease. The presence of HPV DNA of high oncogenic risk types in formalin-fixed, paraffin-embedded tumor samples was determined using quantitative polymerase chain reaction analysis. A stringent protocol of prevention of cross- and environmental contamination was applied during DNA isolation, and amplification, as well as confirmation of the biological activity of the virus in tumor cells, was implemented. The study utilized the Real-time High Risk HPV test, which detects the DNA of 14 HPV subtypes that are considered to have high oncogenic potential. The overexpression of the p16(INK4a) protein assessed immunohistochemically was considered confirmation of the HPV infection., Results: Among the 89 patients initially included in the study group, diagnostic results were obtained for 84 individuals. In five cases, either the histopathological material was too scant to isolate the necessary amount of DNA, or the isolated DNA was significantly degraded, resulting in the failure of internal control amplification within the predefined number of 35 cycles. Those patients were excluded from further analysis. The amplification of HPV DNA was demonstrated in none of the 84 tissue samples; thus, all cases were considered to have a negative DNA status of highly oncogenic HPV subtypes. Immunohistochemical staining provided diagnostic results for all of the examined tissue samples, and excluded the accumulation of the p16(INK4a) protein in tumor cells, thus confirming the lack of active HPV infection in all of the individuals., Conclusion: The study does not confirm the presence or biological activity of HPV in tumor tissues. Thus, the relationship between GAC and HPV infection, in the Central European population seems doubtful.

The aim of the study was to determine expression of the PTEN suppressor gene in colorectal adenocarcinoma and its precancerous lesions (adenomatous polyps) in correlation with common clinical and histopathological features. Forty-four patients with adenomatous polyps and 32 with primary adenocarcinoma of the colon or rectum were enrolled in the study. They underwent endoscopic removal of polyps or major surgery and postoperative adjuvant chemo- and radiotherapy depending on staging of the disease. No patient had received chemotherapy and/or radiotherapy before the surgery. PTEN expression was evaluated using immunohistochemical staining on paraffin-embedded specimens and compared to clinicopathological features of tumors. In colorectal cancers, PTEN expression was found to be significantly lower than in normal intestinal mucosa and adenomatous polyps. That was associated with complete loss of PTEN expression observed more frequently in colorectal cancer, contrary to reduction of PTEN expression occurring mostly in polyps. A correlation between polyp diameter and loss of PTEN was demonstrated as well as between tumor size and TNM advanced stage and PTEN expression. The obtained results suggest that the PTEN/PI3K/Akt pathway may play an important role in early stages of sporadic colorectal carcinogenesis and reduced PTEN expression in late oncogenesis is associated with some adverse clinical and pathological features.