scholarly journals Comparative analysis of IL-1β blood serum concentration, neutrophil-to-lymphocytes ratio in peripheral blood, and the levels of PD-L1 expression in malignant tissues of the patients with various solid tumors

2021 ◽  
Vol 23 (5) ◽  
pp. 1105-1114
Author(s):  
R. V. Orlova ◽  
N. V. Zhukova ◽  
A. M. Malkova ◽  
E. A. Kaledina ◽  
A. R. Gubal ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Peripheral Blood ◽  
Tumor Tissue ◽  
Checkpoint Inhibitors ◽  
Interleukin 1 ◽  
Mean Value ◽  
Interleukin 1 Beta ◽  
The Mean

The action of checkpoint inhibitors is based on activation of T cell antitumor immunity, and, therefore, the search for markers of lymphocyte functional activity before starting the therapy is highly relevant. Determination of the PD-L1 expression in tumor tissues reflects immunosuppressive activity of malignant cells, and it is used as a predictive marker in clinical practice. The ratio of neutrophils to lymphocytes in tumor tissue and in peripheral blood can also indicate the activity of adaptive immunity and correlates with the efficacy of therapy. It has been shown that a high level of interleukin 1 beta in the tumor microenvironment is associated with immunosuppression of lymphocytes and, possibly, reflects the activity of the tumor microenvironment. The aim of this work is to study the relationship between tumor expression of PD-L1, the concentration of serum interleukin-1 beta and the ratio of neutrophils and lymphocytes in peripheral blood.Before starting therapy with checkpoint inhibitors in patients with various solid tumors (n = 50), the serum level of interleukin-1 beta was determined by ELISA (ELISA-Best, Novosibirsk, Russia), expression of PD-L1 in the tumor by immunohistochemical method, complete blood count was performed using cytometry. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using the statistical methods of Fisher, Mann-Whitney, and Spearman.The average value of the index of the ratio of neutrophils and lymphocytes (NLR) in peripheral blood was 2.65± 0.21 (95% CI 2.22-3.07). The index value of more than 3.5 was found in 18% (9/50) of patients. The mean value of the PD-L1 expression level was 23.02±4.52% (95% CI 13.86-32.18). Expression of PD-L1 in tumor tissue was detected in 60.1% (25/40) of patients, among whom an increased expression of more than 50% was detected in 20.0% (5/25) of cases. A positive weak correlation was found between the concentration of interleukin 1 beta and the number of leukocytes (r = 0.34; p = 0.019) and index (r = 0.32; p = 0.029). The level of PD-L1 expression in tumor tissue also had a weak positive correlation with the serum interleukin 1 beta concentration (r = 0.33; p = 0.037) and the neutrophil-lymphocyte ratio (r = 0.33; p = 0.034). In the group of patients with PD-L1 expression > 5%, the mean value of the concentration of interleukin 1 beta was 1.65±0.62 pg/ml, and the mean value of the index was 4.26±0.94 х 10 9/l, which exceeds the values groups with undetectable PD-L1, but the differences were not statistically significant.The obtained result may indicate the influence of the immunosuppressive properties of the tumor on the state of the patient's immunity. Comprehensive determination of tumor PD-L1 expression, serum interleukin 1 beta concentration and the ratio of neutrophils and lymphocytes in peripheral blood can be used as an assessment of the patient's immune status before starting treatment with checkpoint inhibitors.

Interleukin-1-beta concentration and neutrophil-lymphocyte ratio as possible predicting biomarkers of response to therapy with checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3024-3024
Author(s):  
Rashida Orlova ◽  
Natalia V. Zhukova ◽  
Anna Malkova ◽  
Ekaterina Kaledina ◽  
Anna Gubal ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Interleukin 1 ◽  
Anticancer Therapy ◽  
Response To Therapy ◽  
Interleukin 1 Beta ◽  
Group I ◽  
Significant Difference ◽  
The Mean ◽  
Group Ii

3024 Background: One of the discussed predictive markers of the immune therapy efficacy is the index of neutrophils to lymphocytes ratio in peripheral blood (NLr), which reflects the activity of adaptive immunity and correlates with the level of tumor-infiltrating lymphocytes (TILs). High NLr and low TILs are associated with disease progression. Interleukin-1-beta (IL-1β) is one of the main cytokines produced by the tumor microenvironment (TMO). Overexpression of the cytokine leads to a local immunosuppression. For some tumors, elevated serum IL-1β levels have been associated with a poor prognosis. The aim of this work is to analyze the serum IL-1β level as a marker of TMO activity and the NLr as a marker of adaptive immunity activity in relation to the response to therapy with checkpoint inhibitors in patients with various solid tumors. Methods: The study involved 63 patients with various solid tumors who were treated at the City Oncological Dispensary and were prescribed checkpoint inhibitors (nivolumab (n = 33), pembrolizumab (n = 23), ipilimumab + nivolumab (n = 7)). The determination of the level of IL-1β was performed using the ELISA method ("Interleukin-1-beta, ELISA-best", Novosibirsk), a clinical blood test was performed in a dispensary. The response to treatment was assessed 3-6 months after the start of therapy. Statistical analysis was carried out in GraphPad Prism. Results: Among the examined patients 49.21% (31/63) achieved partial regression or stabilization of the process (group I), and 50.79% (32/63) progressed (group II). The mean concentration of IL-1β before treatment in group I was 2.21±0.3 pg/ml, in group II - 0.98±0.2 pg/ml. NLr was increased in 7 patients from group I and in 9 patients from group II, with the mean index level being 2.9±0.39 and 3.2±0.5, respectively. There was no statistically significant difference in the concentration of IL-1β and the NLr between the studied groups. In group II, the number of patients undergoing systemic anticancer therapy before immune therapy (n = 18) was statistically significantly higher than in group I (n = 8), p = 0.033. There was no statistically significant difference in IL-1β concentration and NLr relative to previous treatment. Conclusions: Our study showed that the level of IL-1β corresponds to that of healthy donors and its isolated determination has no prognostic value. The NLr in most patients from the progression group was higher than normal, in contrast to group I, which is confirmed in the literature. The presence of previous systemic anticancer therapy was found to be associated with disease progression. The described feature can be explained by the fact that patients who received therapy before, already have a longer period of illness, a more severe clinical condition. The presence of systemic anticancer therapy does not affect the level of IL-1β and NLr.

Detection of Circulating Tissue Factor and Factor VII in a Normal Population

1996 ◽  
Vol 75 (05) ◽  
pp. 772-777 ◽  
Author(s):  
Sybille Albrecht ◽  
Matthias Kotzsch ◽  
Gabriele Siegert ◽  
Thomas Luther ◽  
Heinz Großmann ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Normal Population ◽  
Mean Value ◽  
Factor Vii ◽  
Significant Difference ◽  
Age Dependent ◽  
The Mean ◽  
Highly Correlated ◽  
And Gender

SummaryThe plasma tissue factor (TF) concentration was correlated to factor VII concentration (FVIIag) and factor VII activity (FVIIc) in 498 healthy volunteers ranging in age from 17 to 64 years. Immunoassays using monoclonal antibodies (mAbs) were developed for the determination of TF and FVIIag in plasma. The mAbs and the test systems were characterized. The mean value of the TF concentration was 172 ± 135 pg/ml. TF showed no age- and gender-related differences. For the total population, FVIIc, determined by a clotting test, was 110 ± 15% and the factor VIlag was 0.77 ± 0.19 μg/ml. FVII activity was significantly increased with age, whereas the concentration demonstrated no correlation to age in this population. FVII concentration is highly correlated with the activity as measured by clotting assay using rabbit thromboplastin. The ratio between FVIIc and FVIIag was not age-dependent, but demonstrated a significant difference between men and women. Between TF and FVII we could not detect a correlation.

Determination of Plasminogen in Clots and Thrombi

1966 ◽  
Vol 16 (01/02) ◽  
pp. 038-050 ◽  
Author(s):  
Ulla Hedner ◽  
Inga Marie Nilsson ◽  
B Robertson
Keyword(s):  
Mean Value ◽  
Main Mechanism ◽  
Clot Lysis ◽  
Post Mortem ◽  
Digestion Time ◽  
Normal Volunteers ◽  
Casein Solution ◽  
The Mean

SummaryThe plasminogen content was determined by a casein method in plasma and serum from 20 normal volunteers. The mean plasminogen content was found to be 10.1 ACU (the arbitrary caseinolytic unit defined in such a way that using a 3% casein solution and a digestion time of 20 min. at 37°C, 10 ACU gave an extinction of 0.300). No difference between serum and plasma regarding the plasminogen content was found.Plasminogen was determined in drained and drained plus washed clots prepared from 2 ml plasma. The highest values found in the drained clots were 0.9 ACU/clot and 0.2 ACU/clot in the drained plus washed clots.Plasminogen was also determined in drained and drained plus washed clots prepared from plasma with added purified plasminogen. The plasminogen was recovered in the washing fluid. According to these tests, then, purified added plasminogen is washed out of the clots.The plasminogen content of 20 thrombi obtained post mortem was also determined. The mean value was found to be 0.7 ACU/cm thrombus. Judging from our results, the “intrinsic clot lysis theory” is not the main mechanism of clot dissolution.

Determination of the Probability Distribution of the Mean Sound Level

2010 ◽  
Vol 35 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Wojciech Batko ◽  
Bartosz Przysucha
Keyword(s):  
Probability Distribution ◽  
Probability Distribution Function ◽  
Mean Value ◽  
Sound Level ◽  
Function Form ◽  
Noise Levels ◽  
Logarithmic Mean ◽  
The Mean ◽  
Estimation Of Uncertainty

AbstractAssessment of several noise indicators are determined by the logarithmic mean <img src="/fulltext-image.asp?format=htmlnonpaginated&src=P42524002G141TV8_html\05_paper.gif" alt=""/>, from the sum of independent random resultsL1;L2; : : : ;Lnof the sound level, being under testing. The estimation of uncertainty of such averaging requires knowledge of probability distribution of the function form of their calculations. The developed solution, leading to the recurrent determination of the probability distribution function for the estimation of the mean value of noise levels and its variance, is shown in this paper.

ENZYMATISCH-FLUOROMETRISCHE BESTIMMUNG DER CORTISOLBINDUNGSKAPAZITÄT DES PLASMA

1967 ◽  
Vol 56 (1) ◽  
pp. 99-106 ◽  
Author(s):  
K. Leybold ◽  
J. Rieper ◽  
L. Weissbecker
Keyword(s):  
Binding Capacity ◽  
Liver Microsomes ◽  
Mean Value ◽  
Female Rats ◽  
Plasma Samples ◽  
Simple Method ◽  
Adult Men ◽  
The Mean ◽  
Precision And Accuracy

ABSTRACT A simple method for the determination of cortisol-binding capacity is described. For saturation of the cortisol-binding proteins, plasma samples are incubated with an excess of cortisol. In the next step NADPH and liver microsomes of female rats are added. The microsomal Δ4-3-ketosteroid hydrogenase only reduces non protein-bound cortisol to tetrahydrocortisol-5α. Then the steroids are extracted by dichloromethane, and after some purification steps analyzed by fluorometry. Tetrahydrocortisol gives practically no fluorescence. The cortisol determined by this method corresponds to protein-bound cortisol and indicates the extent of cortisolbinding capacity. Precision and accuracy of the method were found to be good. The values of cortisol-binding capacity obtained by our method are compared with the results of other authors. The mean value of adult men was 25.5 ± 3.4 μg/100 ml, that of pregnant women, mens IX-X, 42.3 ± 4.2 μg/100 ml.

scholarly journals Transrenal passage of nitrates and nitrites in calves (short communication)

1999 ◽  
Vol 42 (3) ◽  
pp. 235-240
Author(s):  
A. Jacková ◽  
P. Siklenka ◽  
J. Pleva
Keyword(s):  
Short Communication ◽  
Clinical Signs ◽  
Potassium Nitrate ◽  
Mean Value ◽  
Significant Elevation ◽  
Total Hemoglobin ◽  
The Mean ◽  
Nitrate And Nitrite ◽  
Nitrite Content

Abstract. In a study with 12 calves on milk nutrition, the course of methemoglobinemia as well as ttansrenal passage of nitrates and nitrites after single per os administrations of 4 g NaNO2 per animal and 30 g KNO3 per animal in the form of water Solutions has been observed. The response of the organism of calves to per os administered doses of sodium nitrite and potassium nitrate was observed by the determination of tlie methemoglobin percentage in blood and the nitrate and nitrite content in urine before the administration ofthe respective dose and after h 1, 2, 3 and 4 after the administration. A significant elevation in the values of methemoglobin was recorded after h 2 after the administration of 4g NaNO3 per animal. The mean value of methemoglobin in blood was 18.84% of total hemoglobin. A slight decline in the values occurred as early as after h 3 after the administration. Of clinical signs, cyanosis of visible mucosae was observed. The highest nitrite and nitrate values in urine were determined after h 2 after per os administration of 4g NaNO2, With the administration of 30g KNO3 per animal, the most pronounced elevation in methemoglobinemia was observed after h 3, when the means values of methemoglobin was 11,75%. Of clinical signs, only slight cyanosis of mucosae was detectable. Maximum values of nitrates in urine of experimental calves after h 3 after the administration of 30 g KNO3 per animal, with the mean value of 29,9 mM NO3−1 clearly demonstrate a good transrenal passage of nitrates in calves on milk nutrition.

Is the Success of Cefazolin plus Ertapenem in Methicillin-Susceptible Staphylococcus aureus Bacteremia Based on Release of Interleukin 1-beta?

2022 ◽  
Author(s):  
Dan Smelter ◽  
Mary Hayney ◽  
George Sakoulas ◽  
Warren Rose
Keyword(s):  
Staphylococcus Aureus ◽  
Peripheral Blood ◽  
Interleukin 1 ◽  
Interleukin 1 Beta ◽  
Blood Monocytes ◽  
Salvage Regimen ◽  
Peripheral Blood Monocytes ◽  
Staphylococcus Aureus Bacteremia

Cefazolin and ertapenem has been shown to be an effective salvage regimen for refractory methicillin-susceptible Staphylococcus aureus bacteremia. Our findings suggest cefazolin plus ertapenem in vitro stimulates interleukin-1β release from peripheral blood monocytes both with and without S. aureus presence. This IL-1β augmentation was primarily driven by ertapenem. These findings support further exploration of cefazolin plus ertapenem in MSSA bacteremia and may partially explain its marked potency in vivo despite modest synergy in vitro .

Determination of high-density lipoprotein phospholipids in serum.

1980 ◽  
Vol 26 (9) ◽  
pp. 1275-1277 ◽  
Author(s):  
Y Yamaguchi
Keyword(s):  
High Density Lipoprotein ◽  
Density Lipoprotein ◽  
Mean Value ◽  
High Density ◽  
High Density Lipoproteins ◽  
Low Density ◽  
Very Low Density Lipoproteins ◽  
Color Development ◽  
The Mean

Abstract I describe a method for measuring high-density lipoprotein phospholipids. Magnesium chloride and dextran sulfate are used to precipitate all low-density and very-low-density lipoproteins. The supernate contains only high-density lipoproteins, the phospholipid concentration of which is determined by an enzymic method. The precision of the method (CV) is 2.35% (10 repeated assays), and the mean value for HDL-phospholipids was 1006 (SD 248) mg/L for 30 apparently healthy subjects. I used electrophoresis and enzymic color development to confirm the presence of HDL-phospholipids. Results are compared with those obtained by an ultracentrifugation method.

Determination of oxygenated, mixed venous blood CO2 tension by a breath-holding method

1960 ◽  
Vol 15 (2) ◽  
pp. 225-228 ◽  
Author(s):  
John H. Knowles ◽  
William Newman ◽  
Wallace O. Fenn
Keyword(s):  
Venous Blood ◽  
Mean Value ◽  
Rate Of Change ◽  
Breath Holding ◽  
Mixed Venous Blood ◽  
Clinical Method ◽  
Straight Line ◽  
Zero Rate ◽  
The Mean

At the end of a normal expiration the subject inhaled a given volume of gas mixtures containing different concentrations of CO2 in O2 from 5 to 17%. These were held in the lung for 3 and then again for 12 seconds and were then expired and analyzed. Analyses were made with an infrared analyzer and times were obtained from the graphical record. If the rate of change of CO2 tension is plotted against the mean CO2 tension a straight line results which passes through zero rate at the tension which equals the tension of CO2 in the mixed oxygenated venous blood. From the slope of this straight line it is possible to calculate the cardiac output if the lung volume and slope of the CO2 dissociation curve of the blood are known. Data are presented from 37 experiments on 10 subjects. The method is believed to be theoretically sound but has not been validated as a practical clinical method. Occasional erratic points were obtained, especially in untrained subjects. The standard error of the mean value for venous CO2 tension was 1.9 mm Hg. Submitted on July 13, 1959

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