scholarly journals Plasma Level of MMP-10 May Be a Prognostic Marker in Early Stages of Breast Cancer

2020 ◽  
Vol 9 (12) ◽  
pp. 4122
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  

Background: Stromelysins are potential breast cancer biomarkers. The aim of the study was to evaluate if plasma levels of selected metalloproteinases (MMPs) (stromelysin-1 (MMP-3) and stromelysin-10 (MMP-10)) and cancer antigen 15-3 (CA 15-3) used separately and in combination demonstrated diagnostic usefulness in breast cancer (BC). Methods: The study group consisted of 120 patients with BC, while the control group included 40 patients with benign breast cancer and 40 healthy individuals. Concentrations of MMP-3 and MMP-10 were determined by enzyme-linked immunosorbent assay; CA 15-3 was determined by chemiluminescent microparticle immunoassay. Results: In the group of patients with BC, the area under the curve (AUC) was significantly higher for all markers (except MMP-3) and all sets of markers. At the earliest disease stage, only MMP-10 had a significantly higher AUC (AUC = 0.8692, p < 0.001). Moreover, MMP-10 had the highest AUC (0.9166) among parameters tested separately. The highest AUC was observed for the combination of MMP-10 + CA 15-3 and MMP-3 + MMP-10 + CA 15-3 in line with disease progression (stage I 0.8884 and 0.8906, stage II 0.9244 and 0.9308, stages III + IV 0.9919 and 0.9944, respectively, p < 0.001 in all cases). Conclusions: The results suggest that MMP-10 could be a potential marker in early stages of BC. Moreover, plasma concentration of MMP-10 and MMP-3 in combination with CA 15-3 may improve diagnosis of this type of cancer.

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Emilia Lubowicka ◽  
Andrzej Przylipiak ◽  
Monika Zajkowska ◽  
Barbara Maria Piskór ◽  
Paweł Malinowski ◽  
...  

The aim of this study was to investigate plasma levels and applicability of CCL2, CCR2, and tumor marker CA 15-3 in breast cancer (BC) patients and in relation to the control groups: patients with benign breast tumor and healthy subjects. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay (ELISA) and CA 15-3 by Chemiluminescent Microparticle Immunoassay (CMIA). The median levels of CCL2 in entire group of BC were significantly higher compared to the control groups, similarly as median levels of CA 15-3. CCR2 is a negative marker whose levels were significantly lower in BC group compared to healthy women. The concentration of CCL2 in BC increases with advancing tumor stage, while a median level of CCR2 decreases with advancing stage. CCL2 showed the highest value of sensitivity (SE) (64.95%) in entire BC group and also in early stages of disease. The highest specificity (SP) was obtained by CA 15-3 (85.71%). The area under the ROC curve (AUC) of CCR2 (0.7304) was the largest of all the tested parameters (slightly lower than CA 15-3) in the entire BC group, but a maximum range was obtained for the combination of all tested parameters with CA 15-3 (0.8271). In early stages of BC the highest AUC of all tested parameters was observed in CCL2 or CCR2 (stage I: 0.6604 and 0.6564; respectively; stage II: 0.7768, respectively, for CCR2). The findings of this study suggest that there may be applicability of CCL2, CCR2 in diagnosis of BC patients, particularly in conjunction with CA 15-3.


2019 ◽  
Vol 65 (6) ◽  
pp. 825-831
Author(s):  
Lyudmila Belskaya ◽  
Viktor Kosenok

Currently, the urgent task is to search for new biomarkers as a promising tool for early detection and monitoring of breast cancer. The aim of the study was to study the level of cytokines in the saliva of patients with breast cancer. In the case-control study volunteers participated, which were divided into 3 groups: the main (breast cancer, n = 43), the comparison group (fibroadenoma, n = 32) and the control group (conditionally healthy, n = 39). All participants were questioned; biochemical examination of saliva, histological verification of the diagnosis was carried out. Intergroup differences are estimated by a nonparametric criterion. It is shown that in the context of breast cancer, the level of cytokines (IL-2, IL-4, IL-6, IL-10 and IL-18) is increasing, except for IL-8, the content of which decreases compared to the control group. When the disease progresses by the nature of the dynamics, the parameters are divided into two groups: IL-2, IL-4, IL-18 and IL-6, IL-8, IL-10. For the first group of cytokines, there was a decrease in content during the transition from the early stages to the more common ones. For the second group, when passing from stages T1-2N0M0 to T1-2NjM0, the level of cytokines remains practically constant. In the future, the level of cytokines is observed for stage T3_4N0_2M0, and for IL-2, IL-4 and IL-10, the level of cytokines reaches values corresponding to early stages, whereas for IL-6, IL-8 and IL-18 in the same direction, a significant increase in indicators was noted. Additionally, the IL-6/IL-8 ratio was calculated depending on the tumor size, as well as the presence / absence of metastasis. It is shown that this ratio is statistically significantly increased in the advanced stages of the disease. Particularly interesting is the increase in this ratio in saliva at the initial stages of the disease.


2014 ◽  
Author(s):  
Γεώργιος Γεωργίου

Βackground: angiogenesis is seen during the multiple stages of carcinogenesis, aswell as during the process of surgical wound healing, a fact which has led tosubstantial debate over the last decades about the potential impact of surgery upon thefinal outcome of ceratin patients treated for breast cancer.Aim: the present research aims at investigating the potential effect of surgery on theprocess of angiogenesis, by studying a number of factors that are related to the latter,in patients suffering from breast cancer before and after the time of the procedure,whilst comparing these results with those of patients that were operated on their breastfor non-malignant disease.Material-Methods: blood from 10 female patients with breast adenocarcinoma(Study Group) was collected via venipuncture before surgery (labeled as PRO), aswell as on post-operative day 3 (labeled as D3) and day 7 (labeled as D7). Moreover,blood samples were also taken from 6 female patients with fibroadenoma (ControlGroup) before surgery (PRO) and on day 3 afetr surgery (D3). These samples weremeasured for detection of circulating levels of three established angiogenesisbiomarkers using ELISA (Enzyme-Linked ImmunoSorbent Assay): VascularEndothelial Growth Factor-A (VEFG-A), Interleukin-8 (IL-8) and basic FibroblastGrowth factor (bFGF or FGF-2). In addition, circulating transcripts of 84 agiogenesirelatedgenes were determined using RT-PCR (Real Time Polymerase ChainReaction). The two groups of patients were firstly compared to each other regardingtheir results. Also, patients belonging to the Study Group were analized at differenttime points regarding surgery. Finally, the results were investigated againstclinicopathological data and patient outcome.Results: using ELISA we were able to detect increased levels of circulating VEGF-Aand IL-8 in the Study Group patients compared to the Control Group patientspreoperatively (p=0,0381 and p=0,0218 respectively), while for bFGF there was nostatistically significant difference documented. Surgery resulted in a significantincrease in VEGF-A levels on D3 (p=0,0389) and D7 (p=0,0172) as compared toPRO levels. Perioperative kinetics of IL-8 showed a mild trend towards increase,which, however, was not statistically significant. Postoperative levels of bFGF wereslightly increased on D3, but on D7 they were even lower than preoperative values(p=0,0205). Using RT-PCR certain differences between the Study Group and theControl Group were recorded regarding the circulating transcripts of a great numberof angiogenesis-related genes preoperatively: upregulation of VEGF-C, EGF, IL-8,FGF-1, SPHK1, NRP1, LAMA5, COL4A3, TEK, EFNA3, EFNB2. AKT1, ITGB3,THBS1, CCL11, TIMP3 and downregulation of CXCL10. Moreover, mastectomyinduced an altered expression in several key-genes in breast cancer patients:upregulation of THBS1, COL4A3, BAI1, ITGB3 and downregulation of EREG,SERPIFN1, CXCL9, CXCL10, IL1B, CCL2, CXCL1, HIF1A, NOTCH4. Conclusions: patients suffering from breast cancer have a different angiogenic profilein comparison to patients with fibroadenoma, as documented through their differencesin circulating levels of angiogenic factors. These levels are greatly changed after thesurgical procedure. VEGF showed a transient increase, while bFGF initially increasedbut only to finally decrease to levels that were even lower than the preoperative ones.Moreover, mastectomy promoted a shift in the expression pattern of a broad panel ofangiogenesis-related gene transcripts.


Author(s):  
Т.Н. Жевак ◽  
Н.П. Чеснокова ◽  
Т.В. Шелехова ◽  
О.Е. Царева ◽  
И.А. Будник ◽  
...  

Цель. Изучить закономерности изменения экспрессии интерлейкина-10 и интерлейкина-24, обладающих иммуномодулирующим эффектом, при развитии B-клеточного хронического лимфолейкоза. С учетом этого выявить информативные прогностические критерии развития гемобластоза и/или нового подхода к терапии заболевания. Методы. У 120 больных с разными стадиями В-клеточного хронического лимфолейкоза методом твердофазного иммуноферментного анализа исследована динамика уровней интерлейкина-10 и интерлейкина-24 в сыворотке крови. Результаты. Обнаружено закономерное повышение содержания интерлейкина-10 и интерлейкина-24 в сыворотке крови пациентов уже на начальной стадии B-клеточного хронического лимфолейкоза и сохранение их достоверно высоких уровней на последующих стадиях заболевания. Заключение. Обнаруженный нами факт повышения содержания интерлейкина-10 в сыворотке крови пациентов с В-клеточным хроническим лимфолейкозом является фактором риска снижения противоопухолевой защиты организма вследствие подавления им механизмов клеточного иммунитета и способности ингибировать апоптоз малигнизированных клеток. Напротив, повышение экспрессии интерлейкина-24, обладающего проапоптотической активностью и стимулирующего дифференцировку клеток, может способствовать повышению эффективности механизмов противоопухолевой резистентности организма. Устранение дисбаланса продукции и/или содержания указанных цитокинов в сыворотке крови может создать условия повышения эффективности терапии пациентов с В-клеточным хроническим лимфолейкозом. Aim. To study serum levels of immunosuppressive cytokines (interleukin (IL)-10 and IL-24) in patients with B-cell chronic lymphocytic leukemia for assessment of the disease progression and elaboration of a new treatment strategy. Methods. 120 patients with B-cell chronic lymphocytic leukemia were enrolled in the study and divided into four groups according to the disease stage (Rai stage I-IV). Control group included 30 healthy volunteers. Concentrations of IL-10 and IL-24 were measured in serum using the enzyme-linked immunosorbent assay (ELISA). Results. Serum levels of IL-10 and IL-24 levels were significantly increased in all patient groups compared to the control. No difference in the cytokines levels between the patient groups was observed. Conclusion. In patients with B-cell chronic lymphocytic leukemia, the increased serum level of IL-10 might impair the antitumor defence by inhibiting the cell immune response and preventing apoptosis of malignant lymphocytes. On the other hand, the increased serum level of IL-24 might oppose these effects by promoting cellular differentiation and inducing apoptosis in malignant cells. Therefore, correction of IL-10/IL-24 imbalance may be a beneficial therapeutic strategy for patients with B-cell chronic lymphocytic leukemia.


2021 ◽  
Vol 10 (7) ◽  
pp. 1436
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  

Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are members of the MMPs group that show promise as potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the diagnostic utility of studied matrilysins in patients with BC. The study group consisted of 120 patients with BC, and the control group consisted of 40 subjects with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by enzyme-linked immunosorbent assay, and CA 15-3 by chemiluminescent microparticle immunoassay. Plasma levels of MMP-7 were significantly higher in the BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were highest in stages II and IV of the disease. The highest diagnostic sensitivity was observed in stages III and IV BC for the combination of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters combined in the BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) for the combination of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in stages III and IV. Individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of the disease. Study results indicate that MMP-7 could be used as an additional marker that would improve the diagnostic utility of CA 15-3 in early stages of BC. Therefore, the combined assessment of MMP-7 and MMP-26 with CA 15-3 might be useful in determining disease progression. Further studies are needed to evaluate whether matrilysins show promise as potential markers for improving the diagnosis of BC.


2020 ◽  
Author(s):  
Barbara Maria Piskór ◽  
Andrzej Przylipiak ◽  
Emilia Dąbrowska ◽  
Iwona Sidorkiewicz ◽  
Marek Niczyporuk ◽  
...  

Abstract Background: Metalloproteinases (MMPs) are a group of proteolytic enzymes involved in the maintenance of a proper structure of extracellular matrix (ECM). Matrilysins (MMP-7 and MMP-26) are the one of the group of MMPs that could represent potential breast cancer (BC) markers. The aim of the study was to evaluate plasma levels of MMP-7, MMP-26 and CA 15-3 individually and in combination and assess the a diagnostic utility of studied matrilysins in BC patients. Methods: The study group consisted of 120 patients with BC, the control group consisted of 40 patients with benign breast cancer and 40 healthy women. Concentrations of MMP-7 and MMP-26 were determined by Enzyme-Linked Immunosorbent Assay, CA 15-3 by Chemiluminescent Microparticle Immunoassay.Results: The plasma levels of MMP-7 were significantly higher in the entire BC group than in the control group. Concentrations of MMP-26 and CA 15-3 were the highest in the III and IV stage of disease. The highest diagnostic sensitivity was observed in the III and IV stage of cancer for set of all tested markers (92.5%). The highest diagnostic specificity was noted for all tested parameters in all studied BC group (95.0%). The area under the receiver operating characteristic (ROC) curve (AUC) set of markers (MMP-7+MMP-26+CA 15-3) was the largest (0.9138) in III and IV stage. Also individual marker analysis showed that MMP-7 had the highest AUC (0.8894) in advanced stages of disease. Conclusions: Data suggested that MMP-7 can be considered as additional marker improving diagnostic utility of CA 15-3 in early stages of BC patients. Therefore, combined analysis of MMP-7 and MMP-26 with CA 15-3 might be useful in detection of disease progression. Future investigation is needed to evaluate whether matrilysins might be a potential markers improving diagnosis of BC.


Author(s):  
Adnan M. Ismail ◽  
Eman S Saleh

Breast cancer is a disease in which cells in the breast grow out of control. CD200 is a cell surface glycoprotein expressed on many cells, it belongs to the immunoglobulin family (Ig) and have a great role in the regulation of inflammation in autoimmunity. CD200 is the ligand for CD200R1 receptor. To determine if serum level of CD200 and its receptor CD200R1 can be used as a diagnostic and prognostic marker in patients with breast cancer.This case control study was carried out at Oncology Teaching Hospital – Medical city in Baghdad. Six groups were enrolled, four groups were confirmed with breast cancer stage (I, II, III and IV), fifth group (benign) and sixth group was control (healthy individual). Serum is divided to measure CD200 and CD200R1 by utilizing quantitative sandwich enzyme-linked immunosorbent assay (ELISA) Kits. Serum level of CD200 was significantly different (P=0.000088) between breast cancer patients and control only, serum level of CD200 increases with disease stage and there is a significant positive correlation. Serum level of CD200R1 was different with stage, although the differences were not significant but the level of CD200R1 is lower in stage 4 patients than other stages. Serum CD200 level can be used as a diagnostic marker for breast cancer. Serum level of CD200R1 can be used as a prognostic marker


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4518-4518
Author(s):  
Jolanta Oleksiuk ◽  
Janusz Kloczko ◽  
Ewa Luksza ◽  
Marzenna Galar

Abstract Background Patients with multiple myeloma (MM) are relatively high risk of developing thromboembolic events. The pathogenesis of prothrombotic coagulation abnormalities in MM is not clear and probably of multifactorial origin. The deficiency of natural anticoagulant mechanisms, acquired resistance to protein C and reduced protein S function, has been described as one of the possible reason of hypercoagulable state in MM patients. Protein Z/Z-dependent protease inhibitor (PZ/ZPI) is a new anticoagulant system has been recently describe. PZ is a vitamin K-dependent protein which serves as cofactor for the ZPI that inactivates activated factor X, XI and IX by different mechanisms. Some reports suggest that protein Z deficiency might imbalance the haemostatic system with thrombotic consequences. However, to the best of our knowledge, no data are available regarding the potential role of protein Z in prothrombotic coagulation abnormalities in MM. Aim: The aim of our study was to evaluate the plasma concentration of protein Z in relation to disease stage, type and levels monoclonal protein in patients with newly diagnosed untreated multiple myeloma. Methods: The study population consisted of 41 patients (25 male, 16 female; median age: 63 years) with newly diagnosed untreated multiple myeloma. The presence of monoclonal serum immunoglobulin was found in 33 patients (25 and 8 with IgG and IgA paraprotein, respectively). The disease stage was evaluated according to Durie and Salmon criteria: 4 patients-stage I, 28 patients-stage II and 19 patients-stage III; in 8 of them abnormal renal function (serum creatinine value ≥2.0 mg/dl) was observed. The control group was formed by 19 healhty individuals with age and sex comparable with the patients. Protein Z plasma levels were measured using a commercial enzyme-linked immunosorbent assay (Asserachrom Protein Z; Diagnostica Stago, Asnieres) following the manufacturer’s instruction. Results: The median protein Z plasma levels in patients with multiple myeloma and control subjects were similar. Median PZ levels were 1.45 ug/ml (range 0.27–3.17 ug/ml) in patients and 1.37ug/ml (range 0.34–1.96 ug/ml) in controls (p≥0.05). No significant correlation was found between protein Z plasma levels and disease stage, monoclonal serum immunoglobulin concentration, and renal function as well. Conclusions: Our results suggest that protein Z is not an independent risk factor for thrombosis and does not play a significant role in the mechanism of thrombotic complication in patients with multiple myeloma.


1999 ◽  
Vol 45 (10) ◽  
pp. 1813-1820 ◽  
Author(s):  
Nil Dizdar ◽  
Anita Kullman ◽  
Björn Norlander ◽  
Jan-Edvin Olsson ◽  
Bertil Kågedal

Abstract Background: Intravenous and subcutaneous microdialysis was performed to compare the free concentrations and pharmacokinetics of l-3,4-dihyroxyphenylalanine (l-dopa) in blood and tissue in healthy subjects and in patients with Parkinson disease. Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of l-dopa and 25 mg of benserazide), and the microdialysis was continued for another 210 min. Blood samples were obtained at 30-min intervals. Results: The serum samples gave a significantly higher mean area under the curve (AUC; 491 ± 139 μmol · min/L) than that for intravenous dialysates (235 ± 55.3 μmol · min/L), suggesting a protein binding of 50%. The l-dopa concentrations from the subcutaneous dialysates matched those from the intravenous dialysates, indicating rapid distribution of l-dopa to the tissues. Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free l-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Gheyath Al Gawwam ◽  
Inas K. Sharquie

One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was1.318±0.543 nmol/ml and that of the controls was0.873±0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (pvalue = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.


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