The Clinical Significance of Serum Free Light Chains in Bladder Cancer.

This research aimed to assess the clinical usefulness of serum kappa (κ) and lambda (λ) free light chains (FLCs) in patients with bladder cancer (BC). One hundred samples were collected and analysed from healthy volunteers (C) and bladder cancer patients. Cancer patients were divided into two subgroups: low-grade (LG) and high-grade cancer (HG). Concentrations of FLCs, CEA, CA19-9, creatinine and urea were measured per manufacturers' guidelines. The concentrations of κ and λ FLCs and CEA were significantly higher in BC patients in comparison to the control group. Moreover, the concentrations of κ and λ FLCs and CEA were significantly higher in both low-grade as well as high-grade cancer in comparison to the controls. The levels of κ and λ FLCs differed between tumour grades, with patients presenting higher concentrations in high-grade compared to low-grade cancer. In the total study group, κFLC correlated with λFLC, the κ:λ ratio, CRP, CEA, CA19-9, creatinine and urea. There was also a correlation between λFLC and κFLC, CRP, CEA, creatinine and urea. The λFLC showed a higher ability (sensitivity and PPV) to detect bladder cancer in comparison to κFLC and CEA. In addition, λFLC had a higher ability to exclude BC (specificity and NPV) than κFLC and CEA. λFLC also showed the highest accuracy in the detection of bladder cancer. In conclusion, the revealed differences in the concentrations of both κ and λ FLCs suggest their potential participation in bladder cancer development. Increased concentrations of free light chains in bladder cancer patients and the association with the tumour grade suggest that κ and λ FLC measurements may be useful in the diagnosis and prognosis of bladder cancer. This is the first research that evaluates the concentration of FLCs in bladder cancer, so further studies are necessary to confirm their usefulness as tumour markers of this malignancy.

The Significance of Matrix Metalloproteinase 9 (MMP-9) and Metalloproteinase 2 (MMP-2) in Urinary Bladder Cancer.

INTRODUCTION: Urinary bladder cancer is a serious oncological problem that is the cause of many deaths worldwide. The processes of metastasis and origination of local tumor invasion depend on the extracellular matrix (ECM) degradation. The cancer microenvironment, particularly the ECM, may be considered a key factor in cancer progression. Matrix metalloproteinases (MMPs) are classified as the main factors responsible for the degradation of ECM components. Therefore, the aim of the study was to evaluate the expression and activity of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) in urinary bladder cancer according to different stages. MATERIAL AND METHODS: Urinary bladder tissue samples were analyzed. Cancer patients were divided into two groups: low-grade tumors (LG; Group I) and high-grade tumors (HG; Group II). Control tissue was obtained from the opposite site to the tumor. MMPs content and activity (actual and specific) were evaluated using ELISA and Western blot methods, respectively. RESULTS: Both MMPs are present in high and low molecular complexes in healthy or bladder cancer tissues. The content of MMP-9 is enhanced in comparison with MMP-2, particularly in HG cancer tissue. The actual activity of MMP-2 was highest in LG cancer tissue whereas the actual activity of MMP-9 was highest in HG cancer. Specific activity of both MMPs was highest in LG cancer, but the activity of MMP-9 was higher in comparison with MMP-2. CONCLUSIONS: In conclusion, the content and specific activity of MMP-9 were increased in comparison with MMP-2. The revealed differences in content and activity of both MMPs demonstrate their different participation in ECM remodeling at different stages of cancer development. Moreover, it seems that MMP-9 has higher clinical utility than MMP-2 as a potential therapeutic option and a diagnostic biomarker of urinary bladder cancer.

Higher Content but Not Activity of Stromelysin-2 (MMP-10) in Comparison to Stromelysin-1 (MMP-3) in Human Renal Carcinoma.

Stromelysin-1 and stromelysin-2 (matrix metalloproteinase 3; MMP-3 and matrix metalloproteinase 10; MMP-10, respectively) are enzymes that activate other metalloproteinases. Apart from collagen, they also degrade elastin, fibronectin, gelatin and laminin. In carcinogenic processes, they are involved in angiogenesis and metastasis. Therefore, the aim of this study was to evaluate the DNA content, expression and activity of both stromelysines in cancers of human kidney. Renal carcinoma tissue samples were analyzed. Low- and high-grade cancer tissues were collected. Control material was collected from part of the kidney opposite to the tumor. DNA content, stromelysines content and stromelysin-1 and stromelysin-2 activity were measured using ELISA and Western blot methods. A higher content of deoxyribonucleic acid in low- and high-grade cancer tissues in comparison to the respective control tissue was observed. Both stromelysines were presented in control and cancer tissues in high-molecular-weight complexes. The content of MMP-10 was significantly higher in comparison to MMP-3 in all investigated tissues. Moreover, the content of stromelysin-2 was significantly higher in high-grade (G3) tissues compared to grade 2 (G2) kidney cancer. A significant decrease in the actual and specific activities of both stromelysines was observed with the increase in renal cancer grade. The presented results may indicate that the degradation of extracellular matrix increases with a higher grade of cancer. Moreover, the elevated content and decreased specific activity of stromelysin-2 in cancer tissue indicate that MMP-10 is mainly present in an inactive form in renal carcinoma. Detailed knowledge of the mechanism and participation of stromelysines in extracellular matrix degradation may be important in understanding the pathomechanism of renal cancer development. Therefore, the potential application of stromelysines in the monitoring or prognosis of kidney cancer should be discussed.

Enhanced Expression but Decreased Specific Activity of Matrix Metalloproteinase 10 (MMP-10) in Comparison with Matrix Metalloproteinase 3 (MMP-3) in Human Urinary Bladder Carcinoma.

Human urinary bladder cancer is a huge worldwide oncological problem causing many deaths every year. The degradation of extracellular matrix (ECM) induced by molecules such as matrix metalloproteinases (MMPs) is one of the main factors influencing the process of metastasis origination. The MMP expression is tied to tumor aggressiveness, stage, and patient prognosis. The cleavage of constituent proteins is initiated and prolonged by matrix metalloproteinases, such as MMP-3 and MMP-10. The aim of this study was to evaluate the expression and activity of both MMPs in human urinary bladder cancer occurring at various stages of the disease. Tissue samples from patients with urinary bladder cancer were analyzed. Samples were collected from patients with a low- and high-grade cancer. Control tissue was collected from the site opposite to the tumor. DNA content, MMPs content, and activity of MMP-3 and MMP-10 were measured using ELISA and Western blot techniques. MMP-3 and MMP-10 occur in high molecular complexes in human urinary bladder in healthy and cancerous tissues. Particularly, in high-grade tumors, the content of MMP-10 prevails over MMP-3. The actual and specific activities vary in both grades of urinary bladder cancer; however, the highest activity for MMP-3 and MMP-10 was found in low-grade tissues. In conclusion, MMP-10 had a higher content, but a lower activity in all investigated tissues compared to MMP-3. Generally, obtained results demonstrated a contrary participation of MMP-3 and MMP-10 in ECM remodeling what may be crucial in the pathogenesis of human urinary bladder carcinoma.

The Role of Chemokine Receptor CXCR3 and Its Ligands in Renal Cell Carcinoma.

The major invasive subtype of kidney cancer is renal cell carcinoma (RCC). The essential components of cancer development are chronic inflammation and neoangiogenesis. It has been suggested that the chemokine ligand 9, -10, -11 (CXCL9-11) and chemokine receptor 3 (CXCR3) chemokines receptor expressed on monocytes, T and NK cells may be involved in the inhibition of angiogenesis. However, to date, little is known about the potential clinical significance of these chemokines and their receptor in renal cell carcinoma. Therefore, in this review, we described the role of CXCR3 and its ligands in pathogenesis of RCC. We performed an extensive search of the current literature in our investigation, using the MEDLINE/PubMed database. The changes of chemokines and their specific receptor in renal cell carcinoma were observed. Published studies revealed an increased expression of CXCR3 and elevated concentration of its ligands in RCC. The association between treatment of RCC and CXCL9-11/CXCR3 concentration and expression was also observed. Moreover, CXCR3 and its ligands levels were related to patient's prognosis, risk of metastasis and tumor growth. This review describes the potential role of CXCR3 and its ligands in pathogenesis of RCC, as well as their potential immune-therapeutic significance. However, future studies should aim to confirm the clinical and prognostic role of CXCL9-11/CXCR3 in renal cell carcinoma.

Dominative role of MMP-14 over MMP-15 in human urinary bladder carcinoma on the basis of its enhanced specific activity.

BACKGROUND: Human urinary bladder cancer is one of the most common cancers worldwide with the mortality rate of approximately 165,000 people annually. The modulation of extracellular matrix is a crucial event in the metastatic spread, among others in angiogenesis. It is initiated and prolonged by the cascade of matrix metalloproteinases. MMP-14 and MMP-15 are associated with a high degree of malignancy, aggressiveness, and survival prognosis by the activation of other matrix metalloproteinases (MMPs). This study was aimed at evaluating the expression and the activity of selected transmembrane metalloproteinases at different stages of human urinary bladder cancer. METHODS: Western blot and enzyme linked immunosorbent assay (ELISA) method were used to evaluate the expression and content of MMPs and TIMP-1. The activity of studied enzymes was determined with fluorometric method. RESULTS: Both transmembrane metalloproteinases are found in healthy or cancerous tissue in high molecular complexes of human urinary bladder. MMP-14 dominates over MMP-15, particularly in high-grade urinary bladder cancer. Their contents significantly change with the grade of bladder tumor. The amount of MMP-14 increases with increasing grade of tumor. MMP-15 content decreases in high-grade bladder cancer. With increasing grade of urinary bladder cancer their actual activity (per kg of total protein content) is varying in different ways. In all examined tissues, the specific activity of MMP-15 (per kg of the enzyme content) is much higher in comparison to MMP-14. Human urinary bladder cancer contains higher TIMP-1 amounts than control tissue but with the decrease with an increase in tumor grade. CONCLUSION: Comparison of investigated enzymes' activity and the inhibitor content suggests it opposite effects, higher suppression of MMP-14 than MMP-15 activity in low-grade bladder cancer and reverse TIMP-1 action in high-grade cancer. The MMP-14 activity determination in urinary bladder cancer tissue may be used as a predictor of a risk of metastasis.

Suppressed Expression but Not Activity of Collagenases MMP-1 and MMP-13 in Human Renal Carcinoma.

BACKGROUND: Collagenases are enzymes starting collagen degradation. The role of collagenases in renal carcinoma development is not well understood. OBJECTIVE: Evaluation of collagen content and collagenase expression and activity in human kidney cancers. METHODS: Collagen content was measured by the hydroxyproline assay. The expression and the content of collagenases were evaluated by Western blotting and ELISA. Fluorogenic substrate was used to measure enzyme activity. RESULTS: Collagen content significantly decreases with the progression of kidney cancer. Both collagenases are first present in high molecular complexes in both control and cancer tissue. The healthy part of the kidney contains similar amounts of both collagenases. Collagenase content decreased significantly in tumor tissue with increasing cancer stage. MMP-13 activity is much higher than that of MMP-1 in all tissues investigated. We observed increasing collagenase activity (MMP-1 and MMP-13) with increasing renal cancer grade. CONCLUSIONS: The lower content and higher activity of the collagenases investigated in cancer tissue indicate that most of these enzymes are in active form in renal carcinoma. The lower collagen content in cancer tissue can be explained at least in part by increased collagenase activity.

Chromium in urothelial carcinoma of the bladder.

INTRODUCTION AND OBJECTIVES: Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, the involvement of heavy metals in tumourigenesis of urothelial carcinoma of the bladder has been poorly investigated. Therefore, the aim of this study was to examine the relationship between chromium (Cr) and bladder cancer. MATERIAL AND METHODS: Chromium concentration in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of a control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. RESULTS: While the median chromium concentration levels reached statistically higher values in the bladder cancer tissue, compared with the non-cancer tissue (99.632ng/g and 33.144ng/g, respectively; p<0.001), the median Cr levels in the sera of the patients with this carcinoma showed no statistical difference when compared to those of the control group (0.511µg/l and 0.710µg/l, respectively; p=0.408). The median levels of Cr in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p<0.001 and p<0.01, respectively). CONCLUSIONS: This study shows that patients with urothelial carcinoma of the bladder had higher tissue Cr levels than people without tumour, while no difference was found in the Cr serum levels between the two groups of patients under investigation.

Cadmium in urothelial carcinoma of the bladder.

The aim of this study was to examine the relationship between cadmium (Cd) and bladder cancer (urothelial carcinoma of the bladder). Cadmium concentrations in two 36-sample series of bladder cancer tissue and blood, from patients with the neoplasm, were matched with those of the control group. The amount of heavy metal in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumour stage. While the median cadmium concentration levels reached statistically lower values in the bladder cancer tissue, as compared with the non-cancer one (11.695 ng/g and 56.32 ng/g respectively, p < 0.001), the median Cd levels in the blood of the patients with this carcinoma showed no statistical difference when compared to those of the control group (8.237 µg/l and 7.556 µg/l respectively, p = 0.121). The median levels of cadmium in the bladder tissue, depending on the stage of the tumour, compared with the tissue without the neoplasm, observed the same relationship for both non-muscle invasive and muscle-invasive tumours (p < 0.002 and p < 0.02 respectively). This study has shown that patients with urothelial carcinoma of the bladder had lower tissue cadmium levels than people without tumour while no difference in the Cd blood levels between the two groups of patients under investigation was found.

Phospholipid composition and electric charge in healthy and cancerous parts of human kidneys.

Phospholipids are ubiquitous in nature and are essential for the lipid bilayer of cell membranes. Their structural and functional properties are pivotal for the survival of the cell. In this study the phospholipids of healthy and cancerous human renal tissues from the same patients are compared with special reference to the electric charge of the membrane. A simple and highly effective normal-phase method is described for analyzing phospholipids content. This work is focused on changes of phospholipids content (PtdIns, phosphatidylinositol; PtdSer, phosphatidylserine; PtdEtn, phosphatidylethanoloamine; PtdCho, phosphatidylcholine) in cell membranes of renal cancer of pT1 stage, G2 grade, without metastasis. Surface charge density of healthy and cancerous human renal tissues was measured by electrophoresis. The measurements were carried out at various pH of solution. Depending on the surface charge density as a function of pH, acidic (C(TA)) and basic (C(TB)) functional group concentrations and their average association constants with hydrogen (K(AH)) or hydroxyl (K(BOH)) ions were evaluated. The process of cancer transformation was accompanied by an increase in total amount of phospholipids as well as an increase in C(TA) and K(BOH), whereas K(AH) and C(TB) were decreased compared with unchanged tumor cells.

Copper, zinc, and Cu/Zn ratio in transitional cell carcinoma of the bladder.

INTRODUCTION: Many epidemiological and experimental studies report a strong role of chemical carcinogens in the etiology of bladder cancer. However, involvement of trace elements in the tumorigenesis of transitional cell carcinoma of the bladder has been poorly investigated. The aim of this study was to examine the relationship between zinc, copper and bladder cancer. MATERIALS AND METHODS: Zinc and copper concentration and Cu/Zn ratio in two 36-sample series of bladder cancer tissue and sera from patients with this neoplasm were matched with those of the control group. The amount of trace elements in every tissue sample was determined using atomic absorption spectrometry. This was correlated with tumor stage. RESULTS: While the copper concentrations reached statistically higher values in the bladder cancer tissue, the zinc levels in the sera and bladder tissue of the patients with this carcinoma were substantially lower as compared to those of the control group. The serum Cu/Zn ratio was significantly higher in the bladder cancer group and this increase was greater in the patients with muscle-invasive neoplasm. CONCLUSIONS: The results obtained suggest a relationship between trace elements and the bladder cancer.

Lead concentration in the bladder tissue and blood of patients with bladder cancer.

OBJECTIVE: To investigate the relationship between lead and bladder cancer. MATERIAL AND METHODS: The levels of lead concentration in blood and bladder cancer tissue from a sample set of 36 bladder cancer patients were measured and then compared with those of a normal group. The levels of lead obtained in the bladder cancer tissue were evaluated depending on the stage of the tumour. The level of lead concentration in each tissue sample was determined by atomic absorption spectrometry. RESULTS: The lead concentration reached statistically higher values in both the bladder cancer tissue and the blood of patients with this carcinoma compared with those of the control group. No relationship between lead concentration levels in the bladder cancer tissue and blood of patients with this neoplasm on stage of tumour was demonstrated. CONCLUSION: The results suggest that there is a relationship between exposure to lead and the initialization and development of bladder cancer.

[Assessment of the efficacy of cancer procoagulant (CP) activity evaluation in the oncological diagnosis of the urinary system]. / Ocena przydatnosci badania aktywnosci nowotworowego prokoagulanta (CP) w diagnostyce onkologicznej ukladu moczowego.

Many studies have been carried out to develop unfailing diagnostic methods that could improve cancer detection. There are available cancer markers of relatively low sensitivity and specificity, which makes a reason why they not always let detect neoplasm at their earliest stage. There is a new protease cysteine enzyme named cancer procoagulant (CP) isolated from rabbit V2 Ca neoplasm and characterized by Gordon et al in 1975. Because of its exclusive presentation in the cancer tissues and blood serum of the patients with tumor, this neoplasm-cell-originated protein seems to be a new biochemical cancer disease marker. The elevated activity of CP was found in the cancers of pancreatic, breast, lung, alimentary and urinary system. The blood serum CP activity levels in the patients with renal, bladder, and prostate cancers were determined statistically higher as compared to controls but the difference varied depending on the mentioned organ of the urinary system. The CP highest activity levels was determined in the patients with prostate cancer, lower ones in bladder carcinoma ones and the lowest ones in individuals with renal tumours. That is why it appears to be justifiable to apply the determination of the CP in the oncological diagnosis in the urinary system.

[Cancer procoagulant (CP)]. / Nowotworowy prokoagulant (CP).

Epidemiological studies point out steady increase of the incidence of cancer disease in Poland and all over the world. Neoplasms are associated with blood coagulation disorders very frequently. The investigations concentrate on searching for the substance producing malignant cells and causing activation of blood coagulation in neoplasm disease patients. Gordon and co-workers were the first who published results of their investigation in searching for such a substance in 1975. It was isolated from the rabbit's neoplasm type V2 Ca and then characterized and named as cancer procoagulant (CP). Cancer procoagulant is responsible for blood coagulation disorders in neoplasm disease patients, incorrect metabolism of fibrin and its concentration around malignant tissues. This enzyme (in vitro) is a direct activator of the factor X, without contribution of factor VII or any other cofactors. CF differs in physical, chemical and enzymatic activity from others procoagulants. The main aim of the paper is a review of the literature for structure, chemical characteristic, occurrence and clinical relevance of the cancer procoagulant (CP) and its clinical use in current oncological diagnostics.

[Cancer procoagulant and cathepsin D activity in blood serum in patients with bladder cancer]. / Aktywnosc nowotworowego prokoagulanta i katepsyny D w surowicy chorych na raka pecherza moczowego.

The increasing morbidity and mortality rates of bladder cancer forced the scientists to search for new unfailing diagnostic and therapeutic methods that will improve treatment effects. There are biochemical cancer markers as cancer procoagulant (CP) and cathepsin D which may be used to this end. The aim of the study was to evaluate the activity of the cancer procoagulant and cathepsin D in the blood serum in patients with superficial bladder cancer. The venous blood samples were from 15 patients with microscopically proved superficial bladder carcinoma (i.e. study group) and 15 normal volunteers as a control group. The serum blood CP activity was determined by the Gordon-Benson's coagulation method and expressed by the clotting time in seconds (s) while the cathepsin D activity was determined by the Folin-Ciocalteau's method and expressed by a quantity of released tyrosine in nmol/ml per 4 hours. The CP activity in serum of patients with superficial bladder cancer was increased in statistically way as compared to the non-cancer controls (p<0.0001). The cathepsin D activity in blood serum of the study group was also enhanced as compared to the control group and the said values differed statistically (p<0.0351). It appears to be justifiable to apply the determination of the CP and cathepsin D activity in blood serum for the diagnostics of superficial bladder cancer.