Membrane-type metalloproteinases (including MMP-14 and MMP-15) are enzymes involved in the degradation of extracellular matrix components. In cancer, they are involved in processes such as cellular invasion, angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the expression, content and activity of MMP-14 and MMP-15 in human renal cell carcinoma. Samples of healthy kidney tissue (n = 20) and tissue from clear-cell kidney cancer (n = 20) were examined. The presence and contents of the MMPs were assessed using Western blot and ELISA techniques, respectively. Their activity-both actual and specific-was evaluated using fluorimetric analysis. Both control and cancer human kidney tissues contain MMP-14 and MMP-15 enzymes in the form of high-molecular-weight complexes. Moreover, these enzymes occur in both active and latent forms. Their content in cancer tissues is very similar, but with a noteworthy decrease in content with an increase in the kidney cancer grade for both membrane-type metalloproteinases. Even more notable is the highest content of the investigated enzymes represented by MMP-14 in the control tissues. Considering the actual and specific activity outcomes, MMP-14 dominates over MMP-15 in all of the investigated tissues. Nevertheless, we also noted a significant enhancement of the activity of both metalloproteinases with an increase in the grade of renal cancer. The expression and activity of both enzymes were detected in all examined renal cancer tissues. However, our findings suggest that transmembrane metalloproteinase 14 (MMP-14) plays a much more significant and essential role than MMP-15 in the studied renal carcinoma tissues. Therefore, it seems that MMP-14 could be a promising target in the diagnosis, prognosis and therapy of renal cell carcinoma.
- MeSH
- dospělí MeSH
- karcinom z renálních buněk * metabolismus patologie enzymologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 14 * metabolismus MeSH
- matrixová metaloproteinasa 15 * metabolismus genetika MeSH
- nádory ledvin * patologie metabolismus enzymologie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Renal cell carcinoma (RCC) is a common malignancy frequently diagnosed at the metastatic stage. We performed a comprehensive analysis of the tumor immune microenvironment (TIME) in RCC patients, including the peritumoral tissue microenvironment, to characterize the phenotypic patterns and functional characteristics of infiltrating immune cells. T cells from various compartments (peripheral blood, tumor, peritumoral area, and adjacent healthy renal tissue) were assessed using flow cytometry and Luminex analyses, both before and after T cell-specific stimulation, to evaluate activation status and migratory potential. Our findings demonstrated that tumor-infiltrating lymphocytes (TILs) exhibited heightened cytokine production compared to peritumoral T cells (pTILs), acting as the primary source of cytotoxic markers (IFN-γ, granzyme B, and FasL). CD8+ T cells primarily employed Fas Ligand for cytotoxicity, while CD4+ T cells relied on CD107a. In addition, a statistically significant negative correlation between patient mortality and the presence of CD4+CD107+ pTILs was demonstrated. The engagement with the PD-1/PD-L1 pathway was also more evident in CD4+ and CD8+ pTILs as opposed to TILs. PD-L1 expression in the non-leukocyte fraction of the tumor tissue was relatively lower than in their leukocytic counterparts and upon stimulation, peripheral blood T cells displayed much stronger responses to stimulation than TILs and pTILs. Our results suggest that tumor and peritumoral T cells exhibit limited responsiveness to additional activation signals, while peripheral T cells retain their capacity to respond to stimulatory signals.
- Publikační typ
- časopisecké články MeSH
Úvod: Sérový prostatický specifický antigen (PSA) je nenahraditelný marker v detekci i v dalším sledování pacientů s karcinomem prostaty. V naší analýze se věnujeme faktorům, které by mohly poukázat na pravděpodobnost recidivy časně po radikální prostatektomii. Zabýváme se především pozitivním chirurgickým okrajem (R1). Metody: Retrospektivní hodnocení a analýza databáze pacientů s karcinomem prostaty po radikální prostatektomii od roku 2001 do roku 2019. Celkem se studie účastnilo 1529 pacientů, střední doba sledování byla 48 měsíců, věk pacientů byl od 49 do 76 let. Využili jsme předoperační hodnoty PSA, sledování dynamiky vývoje PSA 3. generace (detekční limit 0,003 ng/ml) po operaci v intervalech 1. měsíc po operaci, 3. měsíc po operaci a dále v 3 měsíčních intervalech. Sledovali jsme pozitivitu chirurgického resekčního okraje (R0 negativní, R1 pozitivní) a Gleason skóre (GS) z histologického preparátu a analyzovali vztah k biochemické recidivě onemocnění. Výsledky: Hodnota PSA před operací neprokázala přímou souvislost s rizikem R1. Hodnoty pacientů skupiny R1 a R0 se lišily pouze o 1,159 ng/ml (p=NS). Hodnota PSA 3. generace 1. měsíc od operace byla u pacientů skupiny R1 o 50,82 % vyšší (p>0,001). 50 % pacientů s R1, kterých bylo celkem 29,5 %, po dobu sledování dosáhlo BCR, zatímco u pacientů s R0, kterých bylo celkem 70,5 %, bylo toto zastoupení 30 % (p>0,001). Skupina pacientů GS 6–7 dosáhla BCR z 47 %. Skupina s GS 8–10 recidivovala v 75 % případů (p>0,001). Závěr: Stadia biochemické recidivy dle naší analýzy dosáhlo 33 % pacientů. Riziko recidivy jsme prokázali v přímé závislosti závěrečného Gleason skóre. Přítomnost R1 by neměla být přímou indikací k adjuvantní radioterapii.
Introduction: Serum prostate specific antigen (PSA) is an irreplaceable marker in the detection and follow-up of patients with prostate cancer. In our analysis we addressed factors that could indicate the likelihood of biochemical recurrence (BCR) early after radical prostatectomy. We mainly focused on the positive surgical margin (R1). Methods: Retrospective evaluation and analysis of the database of patients with prostate cancer after radical prostatectomy from 2001 to 2019. In total 1529 patients were enrolled in the study. The median follow-up was 48 months. The age of the patients ranged from 49 to 76 years. We used pre-operative PSA values, and the monitoring of the dynamics of 3rd generation PSA progression (detection limit 0.003 ng/ml) at month 1 and month 3 after surgery and then in 3-month intervals. We monitored the surgical margin positivity (R0 negative, R1 positive) and the Gleason score (GS) based on histological samples and we analysed the relationship to biochemical recurrence of the disease. Results: The pre-operative PSA value did not show a direct relationship to the R1 risk. Patient values in the groups R1 and R0 differed only by 1.159 ng/ml (p=NS). The 3rd generation PSA value at month 1 after surgery was 50.82% higher in R1 patients (p>0.001). 50% of patients with R1 (29.5% patients of the total) did develop BCR during the follow-up period, while in patients with R0 (70.5% patients of the total) this proportion was 30% (p>0.001). Among those with GS 6−7, 47% developed BCR. The GS 8−10 group relapsed in 75% of the cases (p>0.001). Conclusion: According to our analysis 33% of the patients reached the stage of biochemical recurrence. We demonstrated a direct dependency between the risk of recurrence and the final Gleason score. The presence of R1 should not be viewed as a direct indication for adjuvant radiotherapy.
PURPOSE: To compare the ability of Prostate Health Index (PHI) to diagnose csPCa, with that of total PSA, PSA density (PSAD) and the multiparametric magnetic resonance (mpMRI) of the prostate. METHODS: We analysed a group of 395 men planned for a prostate biopsy who underwent a mpMRI of the prostate evaluated using the PIRADS v1 criteria. All patients had their PHI measured before prostate biopsy. In patients with an mpMRI suspicious lesions, an mpMRI/ultrasound software fusion-guided biopsy was performed first, with 12 core systematic biopsy performed in all patients. A ROC analysis was performed for PCa detection for total PSA, PSAD, PIRADS score and PHI; with an AUC curve calculated for all criteria and a combination of PIRADS score and PHI. Subsequent sub-analyses included patients undergoing first and repeat biopsy. RESULTS: The AUC for predicting the presence of csPCa in all patients was 59.5 for total PSA, 69.7 for PHI, 64.9 for PSAD and 62.5 for PIRADS. In biopsy naive patients it was 61.6 for total PSA, 68.9 for PHI, 64.6 for PSAD and 63.1 for PIRADS. In patients with previous negative biopsy the AUC for total PSA, PHI, PSAD and PIRADS was 55.4, 71.2, 64.4 and 69.3, respectively. Adding of PHI to PIRADS increased significantly (p = 0.007) the accuracy for prediction of csPCa. CONCLUSION: Prostate Health Index could serve as a tool in predicting csPCa. When compared to the mpMRI, it shows comparable results. The PHI cannot, however, help us guide prostate biopsies in any way, and its main use may, therefore, be in pre-MRI or pre-biopsy triage.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- multiparametrická magnetická rezonance * MeSH
- nádory prostaty diagnostické zobrazování patologie MeSH
- prediktivní hodnota testů MeSH
- retrospektivní studie MeSH
- senioři MeSH
- ultrazvukem navigovaná biopsie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- srovnávací studie MeSH
Purpose: Prostate-specific antigen (PSA) is a sensitive but unspecific marker for prostate cancer (PC) detection, which may result in harms including overdiagnosis and overtreatment. Therefore, the development of new markers is of absolute value. The urinary level of engrailed-2 (EN2) protein has been recently suggested as a promising PC biomarker, correlating with tumour volume and stage. This study evaluated EN2 and its potential use in clinical practice.Materials and methods: Urinary EN2 was assessed by different commercially available enzyme-linked immunosorbent assay kits. The study sample included 90 patients with clinically localized PC compared to 30 healthy controls, and a group of 40 patients indicated for prostate biopsy due to an elevated PSA level where both pre- and post-digital rectal examination urine samples were collected.Results: No statistical difference between the patient group and the control group was obtained in all measured variables. There was no significant correlation between urinary EN2 and serum PSA, tumour staging and grading. Attentive DRE did not lead to significant changes of urinary EN2 or impact on its predictive power.Conclusions: Our results show that EN2 as a PC biomarker brings no additional value to the current use of PSA in clinical practice.
- MeSH
- analýza moči MeSH
- biopsie MeSH
- dospělí MeSH
- ELISA MeSH
- homeodoménové proteiny moč MeSH
- kalikreiny krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev moč MeSH
- nádory prostaty krev diagnóza patologie moč MeSH
- prediktivní hodnota testů MeSH
- prostatický specifický antigen krev MeSH
- proteiny nervové tkáně moč MeSH
- senioři MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- stupeň nádoru MeSH
- tumor burden MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: We aimed to explore the utility of prostate specific antigen (PSA) isoform [- 2] proPSA and its derivatives for prediction of pathological outcome after radical prostatectomy (RP). METHODS: Preoperative blood samples were prospectively and consecutivelyanalyzed from 472 patients treated with RP for clinically localized prostate cancerat four medical centers. Measured parameters were PSA, free PSA (fPSA), fPSA/PSA ratio, [- 2] proPSA (p2PSA), p2PSA/fPSA ratio and Prostate Health Index (PHI)(p2PSA/fPSA)*√PSA]. Logistic regression models were fitted to determine the accuracy of markers for prediction of pathological Gleason score (GS) ≥7, Gleason score upgrading, extracapsular extension of the tumor (pT3) and the presence of positive surgical margin (PSM). The accuracy of predictive models was compared using area under the receiver operating curve (AUC). RESULTS: Of 472 patients undergoing RP, 339 (72%) were found to have pathologic GS ≥ 7, out of them 178 (53%) experienced an upgrade from their preoperative GS = 6. The findings of pT3 and PSM were present in 132 (28%) and 133 (28%) cases, respectively. At univariable analysis of all the preoperative parameters, PHI was the most accurate predictor of pathological GS ≥7 (OR 1.02, 95% CI 1.01-1.03, p<0.001), GS upgrading (OR 1.02, 95% CI 1.01-1.03, p<0.003), pT3 disease (OR 1.01, 95% CI 1.00-1.02, p<0.007) and the presence of PSM (OR 1.01, 95% CI 1.00-1.02, p<0.002). Adding of PHI into the base multivariable model increased significantly the accuracy for prediction of pathological GS by 4.4% to AUC = 66.6 (p = 0.015) and GS upgrading by 5.0% to AUC = 65.9 (p = 0.025), respectively. CONCLUSIONS: Preoperative PHI levels may contribute significantly to prediction of prostate cancer aggressiveness and expansion of the tumor detected at final pathology.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty krev patologie chirurgie MeSH
- prediktivní hodnota testů MeSH
- předoperační období MeSH
- prospektivní studie MeSH
- prostatektomie * metody MeSH
- prostatický specifický antigen krev MeSH
- senioři MeSH
- stupeň nádoru MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
