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1.
Cancers (Basel) ; 16(7)2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38610951

ABSTRACT

This study investigates the roles of RUVBL1 and HIF1A in ccRCC development and explores their clinical significance as prognostic biomarkers. mRNA and protein expressions were analyzed using TCGA data and an institutional tissue cohort, respectively. Correlations with clinicopathological parameters and patient outcomes were assessed. TCGA data revealed significantly elevated RUVBL1 mRNA expression in ccRCC tissues, associated with advanced histological grade, T stage, lymph node metastasis, and clinical stage. High RUVBL1 mRNA expression correlated with inferior overall survival and served as an adverse prognostic factor. Similarly, HIF1A mRNA expression was significantly higher in ccRCC tissues, correlating with worse overall survival and acting as an adverse prognostic factor for treatment outcomes. Simultaneous evaluation of RUVBL1 and HIF1A mRNA expression demonstrated enhanced prognostic capacity, surpassing the predictive power of individual markers. Immunohistochemical staining confirmed substantial upregulation of both RUVBL1 and HIF-1α proteins in ccRCC tissues. Furthermore, high expression of both RUVBL1 and HIF-1α proteins was significantly associated with shorter patient survival time. Our findings underscore the significance of RUVBL1 and HIF-1α as potential prognostic markers in ccRCC, paving the way for further research to translate these insights into clinically relevant applications.

2.
Sci Rep ; 14(1): 9280, 2024 04 23.
Article in English | MEDLINE | ID: mdl-38654021

ABSTRACT

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC.


Subject(s)
Biomarkers, Tumor , Carcinoma, Renal Cell , Cyclins , Gene Expression Regulation, Neoplastic , Kidney Neoplasms , Female , Humans , Male , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/metabolism , Cyclins/metabolism , Cyclins/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Prognosis
3.
J Pathol Clin Res ; 10(2): e12365, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38436543

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial-mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT-related genes and transcription factors are associated with poor prognosis in ccRCC. EMT-related factors suppress E-cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), ß-catenin, and E-cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan-Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm-c levels compared to those with low MIFn and MIFm-c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced-stage ccRCC.


Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Macrophage Migration-Inhibitory Factors , Humans , Cadherins , Carcinoma, Renal Cell/genetics , Epigenesis, Genetic , Intramolecular Oxidoreductases/genetics , Kidney Neoplasms/genetics , Macrophage Migration-Inhibitory Factors/genetics , Prognosis
4.
Cancers (Basel) ; 16(5)2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38473264

ABSTRACT

Prostate cancer (PC) is a major global public health concern, imposing a significant burden on men and ranking as the second most prevalent malignancy. This study delves into the intricate world of ubiquitination processes and expression regulation, with a specific focus on understanding the roles of ubiquitin B (UBB), ubiquitin C (UBC), and ß-Catenin in PC development. We thoroughly analyze the expression profiles of UBB, UBC, and ß-Catenin, investigating their interactions and associations with clinical and histopathological data. These findings offer valuable insights into their potential as robust prognostic markers and their significance for patient survival. Our research uncovers the upregulation of UBB and UBC expression in PC tissues, and an even more pronounced expression in lymph node metastases, highlighting their pivotal roles in PC progression. Moreover, we identify a compelling correlation between high UBB and UBC levels and diminished overall survival in PC patients, emphasizing their clinical relevance. Additionally, we observe a significant reduction in membranous ß-Catenin expression in PC tissues. Importantly, abnormal ß-Catenin expression is strongly associated with shorter survival in PC patients and serves as a significant, independent prognostic factor for patient outcomes. Kaplan-Meier survival analysis indicates that patients with tumors characterized by simultaneous UBB and aberrant ß-Catenin expression exhibit the poorest overall survival. These collective insights underline the clinical importance of evaluating UBB, UBC, and ß-Catenin as combined prognostic markers in PC.

6.
Gels ; 9(6)2023 May 26.
Article in English | MEDLINE | ID: mdl-37367111

ABSTRACT

The aim of this study was to test the effect of hyaluronic acid cross-linked with polyethylene glycol containing micronized portions of calcium hydroxyapatite (Neauvia Stimulate) on both local tissue and systemic consequences, which are crucial from the perspective of long-term safety, in patients suffering from Hashimoto's disease. This most common autoimmune disease is a frequently mentioned contraindication to the use of fillers based on hyaluronic acid as well as biostimulants based on calcium hydroxyapatite. Broad-spectrum aspects of histopathology were analyzed to identify key features of inflammatory infiltration before the procedure and 5, 21, and 150 days after the procedure. A statistically significant effect on the reduction of the intensity of the inflammatory infiltration in the tissue in relation to the state before the procedure was demonstrated, combined with a reduction in the occurrence of both antigen-recognizing (CD4) and cytotoxic (CD8) T lymphocytes. With complete statistical certainty, it was demonstrated that the treatment with Neauvia Stimulate had no effect on the levels of these antibodies. All this corresponds with the risk analysis that showed no alarming symptoms during the time of observation. The choice of hyaluronic acid fillers cross-linked with polyethylene glycol should be considered justified and safe in the case of patients suffering from Hashimoto's disease.

7.
Arch Med Sci ; 19(2): 499-506, 2023.
Article in English | MEDLINE | ID: mdl-37034507

ABSTRACT

Introduction: The purpose of this research was to explore the correlation between Gleason score and pattern and the expression of the MLH1, MSH2, MDC1, TP53BP1 proteins in prostate cancer (PC). Prostate cancer development is related to errors in DNA, among others double-strand breaks (DSB) and changes in the base sequence of the DNA. These errors should be repaired through mismatch (MMR) or DSB repair proteins such as MSH2, MLH1, MDC1 and TP53BP1. Material and methods: A total of 500 prostate cancer specimens were recruited in this study. From among all gathered specimens the 52 most suitable cases were selected. The expression of examined proteins was detected by immunohistochemistry, and its correlation with the Gleason score and pattern were further analyzed through standard statistical algorithms. Results: The results show a significant correlation between Gleason pattern and the nuclear expression of the MSH2 protein and the cytoplasmic expression of the MLH1 protein. Gleason score significantly correlates with the nuclear and the cytoplasmic expression of the MSH2 protein and the cytoplasmic expression of the MDC1 protein. There is no correlation between the nuclear or cytoplasmic expression of the TP53BP1 protein and Gleason pattern or score. Conclusions: Our study suggests that the aberration in the MMR repair mechanism may be significantly more important regarding the grading among PC cells in comparison to the impact of alterations in the DSB repair mechanism. The lack of correlation between expression of the TP53BP1 protein and Gleason pattern and Gleason score suggests that the radiation resistance of PC is independent of alterations connected with TP53BP1.

8.
Anticancer Res ; 43(4): 1503-1511, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36974831

ABSTRACT

BACKGROUND/AIM: Renal cell carcinoma (RCC) continues to pose a challenge due to our limited understanding of its underlying pathophysiology. Aconitase 2 (ACO2) is a mitochondrial Fe-S cluster enzyme that catalyzes the stereospecific isomerization of citrate to isocitrate in the second step of the Krebs cycle. We investigated the relationship between ACO2 protein expression and the clinical course of RCC. MATERIALS AND METHODS: Tumor samples were evaluated in a commercial tissue microarray for ACO2 expression using the H-score. The tissue microarrays contained a total of 96 cores from primary tumors, matched metastases, and matched adjacent tissues derived from 32 patients with RCC. The mean follow-up was 82.74 months. Correlation analysis of clinicopathological data and survival was performed. Expression levels of ACO2 mRNA were compared using publicly available data. RESULTS: All the tissue samples showed cytoplasmic ACO2 expression, with median H-scores of 139.7, 130.3 and 166.7 in primary tumor, metastatic tissue, and matched control tissue, respectively. A significantly higher ACO2 expression was found in normal tissues compared to primary and metastatic RCC. The analysis demonstrated a significantly positive correlation between ACO2 expression in primary tumors and their metastases. The results also showed a significant correlation between the expression of ACO2 and worse overall survival among patients with RCC. CONCLUSION: ACO2 may be used as a prognostic factor in RCC. Significant alterations in ACO2 expression are thought to occur in the early stages of RCC carcinogenesis. Considering the physiological role of ACO2, its dysregulation may constitute an adaptive trait of RCC for escaping the equilibrium phase of immunoediting.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Prognosis , Biomarkers, Tumor/metabolism , RNA, Messenger , Aconitate Hydratase
9.
Biomedicines ; 11(2)2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36830863

ABSTRACT

Matrin 3 (MATR3) is one of the most abundant inner nuclear matrix proteins involved in multiple nuclear processes. However, to date, the biological role and prognostic relevance of MATR3 in human cancers still need to be explored. Therefore, the present study aimed to examine the expression levels and prognostic significance of MATR3 in clear cell renal cell carcinoma (ccRCC) patients. We assessed MATR3 immunohistochemical staining and RNA-seq data from publicly available data sets, and the results were analyzed with reference to clinicopathological characteristics and the overall survival of patients. Furthermore, the protein-protein interaction (PPI) network for MATR3 and its neighbors was constructed, functionally annotated, and screened for survival-related genes. MATR3 protein and mRNA levels were lower in tumor tissues compared to control tissues. Lower MATR3 protein (HR 2.36, 95%CI 1.41-3.97; p = 0.001) and mRNA (HR 2.01, 95%CI 1.46-2.75; p < 0.0001) expression levels were found to be a significant independent adverse prognostic factor for the patient's overall survival (OS). Moreover, of the candidate genes, the MRPL23 gene was identified as being the most predictive of OS, and combined MRPL23/MATR3 expression status predicted patient survival better than looking at each marker individually (HR 3.15, 95%CI 2.05-4.83; p < 0.0001). In conclusion, the results from the present investigation warrant further research into the biological and prognostic value of MATR3 and MRPL23 in ccRCC patients.

10.
Ultrasound Med Biol ; 49(3): 889-900, 2023 03.
Article in English | MEDLINE | ID: mdl-36572589

ABSTRACT

The aim of the study was to compare strain elastography with shear wave elastography in prostate cancer detection by comparing data gained during elastography with histological analysis after prostatectomy. Thirty patients with prostate cancer qualified for radical prostatectomy were enrolled into the study. All patients underwent transrectal strain elastography and shear wave elastography during pre-surgical evaluation. In each prostate, 36 regions were evaluated separately whether there was a suspicious prostate cancer lesion or not. Subsequently, the same regions were analyzed during histological analysis of the resected gland. Strain elastography and shear wave elastography (overall stiffness cutoff value = 35 kPa) in our study were characterized by overall sensitivities of 58.9% and 65.3% and specificities of 71.8% and 70.2%, respectively. Cutoff values specific to the zones in the shear wave elastography examination (peripheral zone: 35 kPa, transitional zone: 45 kPa) were characterized by an overall prostate cancer detection sensitivity and specificity of 63.4% and 73% respectively. Shear wave elastography examination revealed a higher sensitivity versus strain elastography, 63.4% versus 58.9% (p = 0.038, p < 0.05), and comparable specificity, 73.0% versus 71.8% (p = 0.547, p > 0.05), respectively. Sensitivity in prostate cancer detection for both methods is higher for larger lesions (except Gleason score 5 massive lesions in strain elastography). Controversially we observed a decrease in sensitivity for strain elastography in the detection of lesions with a large diameter and a Gleason score of 5 near the prostate capsule. Overall sensitivity in the diagnosis of prostate cancer is more significant for shear wave elastography versus strain elastography.


Subject(s)
Elasticity Imaging Techniques , Prostatic Neoplasms , Male , Humans , Prostate/diagnostic imaging , Prostate/pathology , Elasticity Imaging Techniques/methods , Prostatic Neoplasms/pathology , Prostate-Specific Antigen , Prostatectomy , Sensitivity and Specificity
11.
Arch Med Sadowej Kryminol ; 73(2): 168-175, 2023.
Article in English, Polish | MEDLINE | ID: mdl-38186042

ABSTRACT

The most common complications of percutaneous coronary interventions and other endovascular procedures include minor hemorrhage, hematoma, or infection at the insertion site [1]. Much more serious ones include damage to the vessel wall, dissection, shock from contrast administration, acute kidney injury, myocardial infarction [2] and ischemic stroke [3]. Ischemic complications can be caused by an embolic incident due to a thrombus formation or detachment of atherosclerotic plaque fragments [3]. A rarely diagnosed complication is ischemia caused by microembolisms from the material covering the equipment inserted into the vessel - hydrophilic polymer coating (HPC)[4]. We present an interesting case of HPC revealed in coronary vessels within myocardial preparations taken in forensic post-mortem examination conducted at the Department of Forensic Medicine in Bydgoszcz (L.dz. 676/19). This article raises the issue of clinical implications and forensic aspects.


Subject(s)
Acute Kidney Injury , Embolism , Humans , Cause of Death , Embolism/etiology , Autopsy
12.
Int J Mol Sci ; 23(23)2022 Nov 25.
Article in English | MEDLINE | ID: mdl-36499030

ABSTRACT

Resistance to systemic therapy is one of the hallmarks of renal cell carcinoma (RCC). Recently, TOLLIP has emerged as a possible driver of autophagy and chemoresistance. We explored the relationship between primary and metastatic RCC tumor characteristics, patient survival, and TOLLIP expression. The tissue microarrays cohort contained 95 cores of the primary tumor, matched metastases, and matched adjacent tissues derived from 32 RCC patients. TOLLIP expression in tumor samples was evaluated using the H-score. All examined samples showed cytoplasmic TOLLIP expression, with a median value of 100 in primary tumors, 107.5 in metastases, and 220 in the control group. The expression was significantly higher in the normal adjacent tissues compared to primary or metastatic RCC (p < 0.05). We found a positive correlation between expressions of TOLLIP in the primary tumor and its metastases (p < 0.05; k = 0.48). TOLLIP expression significantly correlates with a lower overall survival rate (p = 0.047). TOLLIP functions as a ubiquitin-LC3 adaptor in the intracellular pathway associated with autophagy. Relative TOLLIP overexpression may augment autophagy-related signaling, limiting susceptibility to therapy. The blockade of TOLLIP physiological function seems to be a promising approach to overcoming resistance to systemic therapy.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Autophagy/genetics , Signal Transduction , Protein Processing, Post-Translational , Kidney Neoplasms/metabolism , Intracellular Signaling Peptides and Proteins/metabolism
13.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 02.
Article in English | MEDLINE | ID: mdl-36355527

ABSTRACT

BACKGROUND: The face is the area most exposed to the normal course of skin aging, both intrinsically and extrinsically. The aim of the study was to evaluate the cellular and clinical response of a therapeutic protocol aimed at countering facial skin aging. MATERIALS AND METHODS: Twenty female patients with facial skin laxity and photodamage underwent combined therapy including mesotherapy using non-cross-linked hyaluronic acid with calcium hydroxyapatite and an infrared energy-based device treatment with subsequent implementation of PEG-cross-linked hyaluronic acid soft tissue fillers. To evaluate the benefits, patients underwent histological, immunological, and biomechanical evaluations before the treatment and at 21 and 150 days after the treatment. RESULTS: The histological results at 21 days and 150 days after the procedure showed an increase in the number of fibroblasts and angiogenesis. As for the immunological aspect, it was shown that the treatment has an immunomodulating action, avoiding the activation of CD4 and CD8 cells. Biomechanical data showed that, at 150 days after treatment, the average changes in skin elasticity increased by 72% and the skin hydration increased by 49%. CONCLUSIONS: A combination of an infrared energy-based device treatment with both non-cross-linked hyaluronic acid and novel PEG-cross-linked hyaluronic acid leads to numerous positive cutaneous changes after histological, immunological, and biomechanical evaluations.

14.
Discov Oncol ; 13(1): 106, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-36242708

ABSTRACT

The present study aimed to investigate expression levels and prognostic significance of RUVBL1 and HNRNPU in stage I and II non-small-cell lung cancer (NSCLC) patients. Therefore, we evaluated immunohistochemical staining of RUVBL1 and HNRNPU, as well as RNA-seq data from public sources, and the results were evaluated concerning overall survival (OS) and clinicopathological features. We found that RUVBL1 and HNRNPU proteins and mRNA levels were higher in tumor tissues as compared to adjacent/normal tissues. RUVBL1 (p = 0.013) and HNRNPU (p = 0.021) high protein levels were independent prognostic factors for poor OS. Also, the multivariate analysis in the TCGA dataset revealed that high RUVBL1 (p = 0.064) and HNRNPU (p = 0.181) mRNA levels were not significantly associated with prognosis. However, the co-expression status of these markers (R + H +) was independently associated with poor OS both in the TCGA dataset (p = 0.027) and in our cohort (p = 0.001). In conclusion, combined and individual expression of RUVBL1 and HNRNPU proteins, as well as R + H + mRNA status, may serve as potential prognostic biomarkers for NSCLC. This study adds to the previous observations that RUVBL1 and HNRNPU might be novel and promising therapeutic targets and markers for prognostic evaluation.

15.
Pol J Pathol ; 73(2): 82-87, 2022.
Article in English | MEDLINE | ID: mdl-35979754

ABSTRACT

INTRODUCTION: Unresectable renal cell carcinoma continues to be a great challenge due to our limited understanding of its underlying pathophysiology. We explored the relationship between KIF11 protein expression and the clinical courses of clear cell renal cell carcinoma (ccRCC) using a tissue microarray. MATERIAL AND METHODS: The tissue microarray contained specimens derived from 90 patients, cancer and matched adjacent non-cancerous tissue (2 cores per case), followed up for 7 years. Tumour samples were evaluated for KIF11 expression using the H-score, and their correlations with clinicopathological data and survival data were analysed. RESULTS: 72.7% of ccRCC tissues presented KIF11 cytoplasmic expression with a median value of 20 (interquartile range 0-200). The nuclear staining was positive in 36.36% of ccRCC tissues. Among controls, nuclear KIF11 expression was absent, but cytoplasmic expression was identified in all cases, with a median value of 230 (interquartile range 45-290). Cytoplasmic KIF11 expression in ccRCC tissues was lower than in the control tissues and was positively correlated with tumour grade and mortality (p < 0.05). KIF11 nuclear expression did not correlate with overall survival. CONCLUSIONS: Elevated expression of KIF11 predicts poor clinical outcome in ccRCC patients. Downregulation of KIF11 may provide a new therapeutic strategy for ccRCC.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/pathology , Prognosis , Biomarkers, Tumor/analysis , Kinesins
16.
Front Oncol ; 12: 909767, 2022.
Article in English | MEDLINE | ID: mdl-35814405

ABSTRACT

Tumor cells have the ability to induce platelet activation and aggregation. This has been documented to be involved in tumor progression in several types of cancers, such as lung, colon, breast, pancreatic, ovarian, and brain. During the process, platelets protect circulating tumor cells from the deleterious effects of shear forces, shield tumor cells from the immune system, and provide growth factors, facilitating metastatic spread and tumor growth at the original site as well as at the site of metastasis. Herein, we present a wider view on the induction of platelet aggregation by specific factors primarily developed by cancer, including coagulation factors, adhesion receptors, growth factors, cysteine proteases, matrix metalloproteinases, glycoproteins, soluble mediators, and selectins. These factors may be presented on the surface of tumor cells as well as in their microenvironment, and some may trigger more than just one simple receptor-ligand mechanism. For a better understanding, we briefly discuss the physiological role of the factors in the platelet activation process, and subsequently, we provide scientific evidence and discuss their potential role in the progression of specific cancers. Targeting tumor cell-induced platelet aggregation (TCIPA) by antiplatelet drugs may open ways to develop new treatment modalities. On the one hand, it may affect patients' prognosis by enhancing known therapies in advanced-stage tumors. On the other hand, the use of drugs that are mostly easily accessible and widely used in general practice may be an opportunity to propose an unparalleled antitumor prophylaxis. In this review, we present the recent discoveries of mechanisms by which cancer cells activate platelets, and discuss new platelet-targeted therapeutic strategies.

17.
iScience ; 25(7): 104594, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35756892

ABSTRACT

Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic ß-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors in vitro. Moreover, we investigated mechanisms by which SARS-CoV-2 enters pancreatic cells, and found that ACE2 mediates the entry, while NRP1 and TMPRSS2 do not. Surprisingly, we found that in pancreatic progenitors, SARS-CoV-2 enters cells via cathepsin-dependent endocytosis, which is a different route than in respiratory tract. Therefore, pancreatic spheroids might serve as a model to study candidate drugs for endocytosis-mediated viral entry inhibition and to investigate whether SARS-CoV-2 infection may affect pancreas development, possibly causing lifelong health consequences.

18.
J Cancer Res Clin Oncol ; 148(12): 3313-3322, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35723727

ABSTRACT

PURPOSE: Matrin 3 (MATR3) is a nuclear matrix protein involved in mRNA stabilization, nuclear retention of hyper-edited RNAs, and RNA splicing. The role of MATR3 in cancer is still unclear. The present study aimed to investigate expression levels and prognostic significance of MATR3 in stage I and II non-small cell lung cancer (NSCLC) patients. METHODS: We examined MATR3 protein immunohistochemically in tumoral and non-tumoral tissue sections from n = 67 NSCLC patients treated at hospital, and MATR3 mRNA from The Cancer Genome Atlas (TCGA) cohort with respect to valid prognostic and predictive features, as well as treatment outcome. RESULTS: Significantly higher immunohistochemical levels of MATR3 protein were found in tumor-adjacent tissue compared to cancer (p = 0.049). A decrease in MATR3 protein expression was found to be a significant independent adverse prognostic factor for patients overall survival (p = 0.007). By contrast, we observed higher MATR3 mRNA levels in tumoral tissue compared to control lung tissues (p < 0.001). Based on the TCGA dataset, we reported that high MATR3 mRNA level was significantly associated with worse OS of NSCLC patients (p < 0.001); however, it was not an independent prognostic marker (p = 0.156). The discrepancies in prognostic significance of MATR3 gene mRNA and protein levels imply a need for further investigation. CONCLUSION: In conclusion, the present study warrants further investigation into the biological and prognostic value of MATR3 as a potential prognostic marker in early-stage NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Prognosis , Lung Neoplasms/metabolism , Nuclear Matrix-Associated Proteins/genetics , Nuclear Matrix-Associated Proteins/metabolism , RNA, Messenger/genetics , RNA-Binding Proteins
19.
Basic Clin Androl ; 32(1): 7, 2022 May 19.
Article in English | MEDLINE | ID: mdl-35590251

ABSTRACT

BACKGROUND: Sarcoidosis is a multi-system disease characterized by the formation of non-caseating granulomas in various organs. The lungs remain the most frequently affected organ, whereas lesions in the genitourinary system affect around 0.2% of patients. The primary site found in the spermatic cord is extremely rare. CASE PRESENTATION: We present a patient's case where the spermatic cord involvement was the first manifestation of sarcoidosis. For several months, a number of tests had been performed, which showed, among others, non-caseating granulomas in pathomorphological material, bilateral hilar lymphadenopathy, and leukopenia with lymphopenia. Tumor markers were normal. Infection with urogenital pathogens (including Chlamydia Trachomatis, Neisseria gonorrhea, Mycoplasma hominis) was excluded. The patient did not report any general symptoms such as fever, excessive fatigue, weight loss. He denied swelling, shortness of breath. At the same time, a complete differential diagnosis was carried out, and the extent of the disease was assessed. Due to interdisciplinary management, the patient's quality of life and fertility is preserved. In the discussion, we present the diagnosis, treatment, and prognosis of such patients. CONCLUSION: Sarcoidosis is a multi-system disease, which should not be omitted in the differential diagnosis. Selective excision of the lesion with intraoperative examination plays a significant role while establishing a diagnosis. However, in the primary site in the genitourinary system, the diagnosis is challenging.


RéSUMé: CONTEXTE: La sarcoïdose est une maladie multisystémique caractérisée par la formation de granulomes non caséeux dans divers organes. Les poumons restent l'organe le plus fréquemment touché, alors que les lésions du système génito-urinaire affectent environ 0,2% des patients. La découverte d'un site principal dans le cordon spermatique est extrêmement rare. PRéSENTATION DU CAS: Nous présentons le cas d'un patient où l'atteinte du cordon spermatique a été la première manifestation d'une sarcoïdose. Pendant plusieurs mois, un certain nombre de tests ont été effectués, qui montraient, entre autres, des granulomes non caséeux dans le matériel pathomorphologique, une lymphadénopathie hilaire bilatérale, et une leucopénie avec lymphopénie. Les marqueurs tumoraux étaient normaux. Une infection par des agents pathogènes urogénitaux (y compris Chlamydia Trachomatis, Neisseria gonorrhea, Mycoplasma hominis) a été exclue. Le patient n'a signalé aucun symptôme général tel que fièvre, fatigue excessive, ou perte de poids. Il a nié toute œdème ou essoufflement. Dans le même temps, un diagnostic différentiel complet a été effectué et l'étendue de la maladie a été évaluée. Grâce à la prise en charge interdisciplinaire, la qualité de vie et la fertilité du patient ont été préservées. Dans la discussion, nous présentons le diagnostic, le traitement et le pronostic de ces patients. CONCLUSION: La sarcoïdose est une maladie multisystémique, qui ne doit pas être omise dans le diagnostic différentiel. L'excision sélective de la lésion, avec examen peropératoire, joue un rôle important lors de l'établissement d'un diagnostic. Cependant, en cas de localisation du site primaire dans le système génito-urinaire, le diagnostic est difficile.

20.
J Clin Med ; 11(6)2022 Mar 13.
Article in English | MEDLINE | ID: mdl-35329898

ABSTRACT

Tendinopathy is a process of chaotic extracellular matrix remodeling followed by increased secretion of enzymes and mediators of inflammation. The histopathological assessment of tendinous tissue is crucial to formulate the diagnosis and establish the severity of tendon degeneration. Nevertheless, the microscopic analysis of tendinous tissue features is often challenging. In this review, we aimed to compare the most popular scales used in tendon pathology assessment and reevaluate the role of the neovascularization process. The following scores were evaluated: the Bonar score, the Movin score, the Astrom and Rausing Score, and the Soslowsky score. Moreover, the role of neovascularization in tendon degeneration was reassessed. The Bonar system is the most commonly used in tendon pathology. According to the literature, hematoxylin and eosin with additional Alcian Blue staining seems to provide satisfactory results. Furthermore, two observers experienced in musculoskeletal pathology are sufficient for tendinopathy microscopic evaluation. The control, due to similar and typical alterations in tendinous tissue, is not necessary. Neovascularization plays an ambiguous role in tendon disorders. The neovascularization process is crucial in the tendon healing process. On the other hand, it is also an important component of the degeneration of tendinous tissue when the regeneration is incomplete and insufficient. The microscopic analysis of tendinous tissue features is often challenging. The assessment of tendinous tissue using the Bonar system is the most universal. The neovascularization variable in tendinopathy scoring systems should be reconsidered due to discrepancies in studies.

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