Effect of Expression of Multidrug Resistance Genes in Newly Diagnosed Multiple Myeloma on the Clinical Course of the Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5144-5144 ◽  
Author(s):  
Yulia Chernykh ◽  
Anatoly Golenkov ◽  
Lyudmila Vysotskaya ◽  
Sain Shushanov ◽  
Ekaterina Rybalkina
Keyword(s):  
Plasma Cells ◽  
Visual Assessment ◽  
Mean Value ◽  
Induction Treatment ◽  
Newly Diagnosed ◽  
Genes Expression ◽  
The Common ◽  
The Mean ◽  
Mdr 1 ◽  
Mdr Genes

Abstract Multidrug resistance (MDR) is the biological phenomenon, significantly reduces the survival of patients with multiple myeloma (MM) to the conventional chemotherapy. Overexpression of MDR gene (MDR1, MRP1, LRP, BCRP) by plasma cells may be clinically manifest of disease progression during therapy. Proteasome inhibitor Bortezomib for the treatment of MM in clinical practice has greatly improved the survival of patients with this malignant disease, but at the same time, there is a group of patients resistant to the treatment with Bortezomib. The common (total, summary) effect of the expression of 4 MDR genes on the development of drug resistance to the treatment of Bortezomib have not been studied earlier. Aim. Determination of the expression of mRNA genes MDR1, MRP1, LRP, BCRP, responsible for the development of MDR in bone marrow aspirates in patients with newly diagnosed MM before the Bortezomib-containing therapy on the clinical course of the disease and response to the treatment. Materials and methods. Was investigated a group of 15 patients with newly diagnosed stage III MM classification Durie-Salmon before the start of cytostatic therapy. The expression of MDR genes was studied in bone marrow mononuclear cells fraction containing plasma cells, by RT-PCR (polymerase chain reaction reverse transcription). The degree of expression was assessed by semi-quantitative visual assessment from 0 (no electrophoretic strips) to 4 points (bright glow of the transcript). Results. The expression of MDR gene was found in all patients with newly diagnosed MM before the start of cytostatic therapy: MDR 1 gene is expressed in 14 patients (93%), genes MRP 1 and LRP were detected in 11 patients (73%), the expression of BCRP gene was found in 15 patients (100%). The mean value of expression of MRP 1 and BCRP genes according to visual assessment was 1. The mean value of gene expression MDR 1 (M ± SE) is 1.5 ± 0.27 points and LRP gene is 1.47 ± 0.14 points. The common (summary) mean expression of 4 genes was 5.0 ± 0.76 points. According to the expression level - above or below the mean value, we have identified two subgroups of the patients: subgroup A - Patients with higher overall expression of 4 genes and subgroup B - Patients with lower overall MDR genes expression. In these subgroups was analyzed the clinical parameters of disease at the moment of diagnosis, such as the level of hemoglobin, red blood cells, paraprotein, creatinine, calcium, LDH and the effectiveness of the 6 courses of induction therapy with Bortezomib- containing treatment. No significant differences in clinical scores in the subgroups A and B were not found. After induction treatment, in the subgroup A with higher overall MDR genes expression is not detected significant reduction in the absolute value of paraprotein (32,0 ± 3,7 g / l before the treatment, and 19.34 ± 6.47 g /l after the treatment). Whereas, in the subgroup B with lower overall expression, in the same conditions of the treatment, registered a significant reduction of paraprotein value (41,9 ± 5,0 g /l before the treatment, and 14.85 ± 6.53 g / l after the treatment p <0.05). Conclusion. We the first time identified the group of patients with newly diagnosed MM associated with high common expression of MDR genes before to the cytostatic treatment. The common overexpression of 4 MDR genes not associated with such clinical parameters of the disease as the level of hemoglobin, red blood cells, paraprotein, creatinine, calcium, LDH, but it decreases the immediate response to the Bortezomib-containing induction treatment. Disclosures No relevant conflicts of interest to declare.

Cooperative Salvo Attack Using Guidance Law of Multiple Missiles

2015 ◽  
Vol 19 (2) ◽  
pp. 301-306 ◽  
Author(s):  
Jie Zeng ◽  
◽  
Lihua Dou ◽  
Bin Xin
Keyword(s):  
Mean Value ◽  
Stationary Target ◽  
Impact Time ◽  
State Variable ◽  
Guidance Law ◽  
Multiple Missiles ◽  
The Common ◽  
The Mean ◽  
Guidance Problem ◽  
Common Target

In this article, a guidance problem for cooperative salvo attack of multiple missiles against a single stationary target is investigated. The proposed guidance law combines the well-known PNG law and cooperative acceleration command, which is based on the feedback of state error between the current missile and the mean value of participant missiles. The state variable in this paper is used as the approximate calculation of time-to-go. The cooperative acceleration command is designed to adjust the flight path and impact time, which leads the multi-missiles to hit the common target simultaneously. During the engagement, the velocities of missiles are not changed and presetting impact time is not needed. Simulation results show the effectiveness of the proposed guidance law.

Apparent volume of the biliary tree in the dog

1979 ◽  
Vol 57 (5) ◽  
pp. 524-528 ◽  
Author(s):  
James L. Barnhart ◽  
Burton Combes
Keyword(s):  
Bile Flow ◽  
Bolus Injection ◽  
Common Duct ◽  
Biliary Tree ◽  
Apparent Volume ◽  
Mean Value ◽  
Maximal Concentration ◽  
A Value ◽  
The Common ◽  
The Mean

The apparent volume of the biliary tree (ABV) in the dog was determined by measuring the mean biliary transit time of injected [14C]taurocholate ([14C]TC). After bolus injection of [14C]TC, entry of bile salt into the lumen of the biliary tree is signaled by an increase in bile flow. The volume of bile collected at the common duct from onset of choleresis until maximal concentration of 14C radioactivity is reached in bile minus the calculated quantity of bile that contains radioactivity and the cannula volume yields a value for the volume of the biliary tree present just prior to injection of [14C]TC. The mean value for ABV in 19 dogs was 2.49 ± 0.65 μL/g liver (mean ± SD).

scholarly journals The Energy Sources in Ontogenesis

1935 ◽  
Vol 12 (1) ◽  
pp. 27-35 ◽  
Author(s):  
ERNEST BALDWIN
Keyword(s):  
Uric Acid ◽  
Oxygen Consumption ◽  
Respiratory Quotient ◽  
Mean Value ◽  
Energy Sources ◽  
Pond Snail ◽  
The Common ◽  
The Mean ◽  
Limnaea Stagnalis ◽  
Nitrogenous Metabolism

1. Experiments have been made upon the oxygen consumption, CO2 content, and respiratory quotient of the eggs of Limnaea stagnalis, the common pond snail. 2. Throughout the period of development, during which accurate determinations are possible, the mean value of the R.Q. was 1.05. The significance of the observations is discussed in the text, the main conclusion being that fat is synthesised in the course of development. This was confirmed by extraction of the ether-soluble substances. 3. Preliminary experiments upon the nitrogenous metabolism show that uric acid is synthesised by the embryo during the latter part of development, but suggest that protein does not constitute the source of the synthetic fat.

Clinical Significance of Circulating Plasma Cells in Myeloma: Multiparameter Flow Cytometric Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5352-5352 ◽  
Author(s):  
Manabu Fujisawa ◽  
Yasuhito Suehara ◽  
Kota Fukumoto ◽  
Kentaro Narita ◽  
Yoshiaki Usui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Partial Response ◽  
Light Chain ◽  
Plasma Cells ◽  
Tumor Burden ◽  
Light Chains ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Mean Values ◽  
The Mean

Abstract [Introduction] It has been reported that clonal circulating plasma cells (cPC) were detected in patients with multiple myeloma (MM) and other plasma cell dyscrasias (PCD), and their detection has been shown to be a risk in newly diagnosed MM and shortened progression free survival in patients smoldering MM (sMM). It is unclear that the detection of cPCs in peripheral blood may be a simple reflection of tumor burden of bone marrow plasma cells or may represent different. This study was performed to evaluate the clinical utility of quantifying clonal cPC using 6-color FCM in patients with MGUS, SMM, and symptomatic MM (symMM) at diagnosis (Dx). They were compared with bone marrow samples (BM PCs) simulatneously analyzed in the same way. Besides we evaluated the transition of quantification of clonal cPC of PB samples at various stages after treatment. [Materials and Methods] We analyzed 280 peripheral blood (PB) samples from 194 patients with PCD (MGUS, SMM, and symMM; n  = 34/39/121, respectively) diagnosed at the Department of Hematology/Oncology, Kameda Medical Center and Kanazawa University Hospital from January 2012 to July 2015. Similarly, we analyzed 30 PB samples from 30 healthy controls. Mononuclear cells (MNC) were isolated from PB by density gradient centrifugation and stained with antibodies to CD45, CD38, CD19, CD138, CD56, and cytoplasmic kappa and lambda immunoglobulin (Ig) light chains. The cells were collected using a Beckman-Coulter NAVIOS and analyzed using Kaluza software. The gating strategy employed was expression of CD38, CD45, CD138, and cytoplasmic Ig light chains. Clonal cPC was defined as the population of CD138+, CD38+ CD45-~±, and CD19-. To confirm the clonality of these cells, light chain restriction of cytoplasmic Ig was used (κ/λ>4 or <0.5) using the 2nd tube. Quantification was performed by acquiring > 2×106 total events. At least ≥ 20 clonal cPC were required for the analysis. [Results] We analyzed clonal cPC of 194 PB samples with MGUS, SMM, and symMM (n  = 34/39/121, respectively) at diagnosis (Dx). The mean values of clonal cPC were: MGUS, 2.67×10-5/MNC (range, 0 - 3.0×10-4); SMM, 2.43×10-4/MNC (range, 0 - 3.6×10-3); symMM, 6.99×10-3/MNC (range, 0 - 1.5×10-1). The number of clonal cPC was significantly higher in SMM than MGUS, and in symMM than SMM (P  < 0.001). In healthy controls, the mean value of cPC without CD19 expression was 3.84×10-6/MNC (range, 0 - 1.3×10-5). Although these cPC lacked the expression of CD19, none of the samples did not show the light chain restriction of cytoplasmic Ig. Next, we analyzed clonal cPC of 185 PB samples (Dx, n  = 85; partial response [PR], n  = 31; very good partial response [VGPR], n  = 25; complete response [CR], n  = 22; progressive disease [PD], n  = 23) in various treatment responses of symMM. The mean values of clonal cPC were: at Dx, 6.99×10-3/MNC (range, 0 - 1.5×10-1); at PR, 5.19×10-5/MNC (range, 0 - 3.5×10-4); at VGPR, 9.79×10-5/MNC (range, 0 - 9.7×10-4); at CR, 1.90×10-5/MNC (range, 0 - 1.2×10-4); at PD, 1.94×10-3/MNC (range, 0 - 3.9×10-2). The number of clonal cPC was significantly higher at Dx than from PR to CR, and significantly lower in CR than from PR to VGPR (P  < 0.01, P  = 0.23, respectively). However, the number of clonal cPC was not significantly different between PR and VGPR (P  = 0.61). When patients with PCD at Dx were divided into high and low clonal cPC groups (high cPC ≥ 1.0x10-4/MNC and low cPC < 1.0x10-3/MNC), the number of the high cPC group was as follows: (MGUS 2/35 (5.7%), SMM 9/38 (23.7%), symMM 35/85 (41.2%)) (P<0.01). In symMM patients, clinical characteristics were comparable between the two groups except for bone marrow PCs. A total of 133 bone marrow samples (BM PCs) were measured simultaneously with PB samples at Dx. The number of clonal cPC tended to be related to the percentage of clonal plasma cells/total plasma cells in BM in symMM (R = 0.579), but no such relation was observed in MGUS and SMM (R = 0.112, -0.03). [Conclusions] In conclusion, quantification of clonal cPC by 6-color FCM is feasible and appears to reflect the tumor burden in patients with newly diagnosed MM and sMM, but not in patients after treatment. Further studies using quantification of clonal cPC combined with other hematological parameters will identify patients at high risk of early progression and poor prognosis. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures No relevant conflicts of interest to declare.

scholarly journals High and Low Tumor Infiltration Affect the Differences Among the Detection of Plasma Cells Evaluated in Bone Marrow By Flow Cytometry, Aspirate and Biopsy(Grupo Interdisciplinario de Mieloma Multiple, Hospital Universitario Fundacion Santa Fe, Colombia)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5604-5604
Author(s):  
Diego Martinez ◽  
Maria Valencia ◽  
Juan Pablo Mayorga ◽  
Andres Melo ◽  
Carlos Saavedra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Bone Marrow Involvement ◽  
Tumor Infiltration ◽  
Newly Diagnosed ◽  
Santa Fe ◽  
Plasma Cell Neoplasms ◽  
The Mean

Abstract Background In plasma cell neoplasms, the percentage of plasma cells in bone marrow (PPCBM) is important for diagnosis and assessment of the treatment. This quantification is performed using bone marrow multiparameter flow cytometry (FC), aspirate smears (BMA) and biopsy. Differences among the percentage of infiltration detected by these techniques have been reported, which can be related to a heterogeneous pattern of infiltration of multiple myeloma (MM) or sample quality. However, a simultaneous evaluation of these three techniques has not been reported nor their ability to detect bone marrow involvement with high or low infiltration, associated with different stages of this disease. Purpose The aim of this study was to compare the results of PPCBM obtained by FC, BMA, and biopsy with CD138 immunohistochemistry (BMB) in different stages of the disease with high and low infiltration, and the ability of these techniques to correctly classify the disease. Methods Pathological studies of patients referred to Hospital Fundación Santa Fe, Colombia were reviewed between January 2015 and June 2018. The selection of patients was based on both, a diagnosis of plasma cell neoplasms, classified according to the International Myeloma Working Group criteria and the simultaneous use of FC by FACSCanto II flow cytometer (Infinicyt 2.0 software program), wright-stained aspirate smears and biopsy with CD138 immunohistochemistry in the detection. Descriptive analysis was performed and PPCBM was expressed as the mean± standard error of the mean (SEM). The Kruskal-Wallis test was used to compare the mean of PPCBM among the three methods. Lineal regression and Spearman´s coefficient were used to correlate the variables. Statistical association was considered significant for p values <0.05. Results A total of 130 patients with plasma cells neoplasms were included in this study, 57 with newly diagnosed MM (N), 58 following therapy MM (F) and 15 MGUS patients. In the N patients, the mean of infiltration was 12.3% ±1.8, 30.3% ±3.4 and 52.2% ±3.74 detected by FC, BMA and BMB, respectively. The PPCBM detected by this three analysis were significantly different (p<0.001). In F patients, the mean of infiltration was 0.37% ±0.05, 1.88 % ±0.16 and 2.61% ±0.21 while in MGUS-patients was 0.49% ±0.09, 2.067 % ±0.37 and 2.4% ±0.28 detected by FC, BMA and BMB, respectively. For F and MGUS patients, significant statistic differences between BMB and BMA versus FC (p<0.01) were observed, but not between BMB and BMA (Figure 1). In the comparative analysis of the three methods in all patients, the highest infiltration was always detected by BMB, followed by BMA and finally by FC (p<0.01) (Figure 2). Linear regression established that for each 1% of infiltration detected by FC or BMA, the BMB identified 2.11% and 1.4% of infiltration, respectively (Figure 2). However, each univariate model only explained 55% and 67% of the observed results. Notably, there was a high correlation among these three techniques (Spearman´s coefficient > 0.8). Finally, given that there are important PPCBM such as ≥10 that allows establishing the diagnosis of MM or ≥60%, considered an MM definitive event, we found that 21% and 52% of cases assessed by BMA and FC had PPCBM <10%, but all of them were reclassified as MM with BMB. None case had PCBM <10% using BMB. Finally, among all cases diagnosed as MM, there were identified 26 by FC and 35 cases by BMA with a PCBM percentage between 10 and 59%, of which 84% and 54% respectively had ≥60% of involvement detected by BMB Conclusion In the comparison of the PCBM was observed a high linear correlation between MFC, BMA, and BMB, although we found a differential behavior of these methods, depending on the level of tumor infiltration. High percentages of infiltration, such as newly diagnosed MM patients, the BMB detected significantly more PPCBM than the others two methods (1.7 to 4-fold compared to BMA and FC). This supports the systematic incorporation of BMB into the analysis of patients with suspected MM for allowing a proper classification of disease. With low percentages of infiltration, such as MGUS and following therapy patients, the difference of PPCBM between BMA and BMB was not significant. Although, FC detected the lowest percentage of infiltration, it known its high specificity to discriminate tumor and normal plasma cells, being in one of the most important analysis to monitor minimal residual. Disclosures No relevant conflicts of interest to declare.

Long-period modulated superstructures in Pd-12.5 at.%Ce and Pd-15 at.%Ce alloys

1990 ◽  
Vol 48 (4) ◽  
pp. 164-165
Author(s):  
Noriyuki Kuwano ◽  
Masaru Itakura ◽  
Kensuke Oki
Keyword(s):  
Electron Microscopy ◽  
Mean Value ◽  
Heavy Elements ◽  
Arc Furnace ◽  
X Ray ◽  
Long Period ◽  
Ultra High Purity ◽  
Heat Treated ◽  
Atomic Scattering ◽  
The Mean

Pd-Ce alloys exhibit various anomalies in physical properties due to mixed valences of Ce, and the anomalies are thought to be strongly related with the crystal structures. Since Pd and Ce are both heavy elements, relative magnitudes of (fcc-fpd) are so small compared with <f> that superlattice reflections, even if any, sometimes cannot be detected in conventional x-ray powder patterns, where fee and fpd are atomic scattering factors of Ce and Pd, and <f> the mean value in the crystal. However, superlattices in Pd-Ce alloys can be analyzed by electron microscopy, thanks to the high detectability of electron diffraction. In this work, we investigated modulated superstructures in alloys with 12.5 and 15.0 at.%Ce.Ingots of Pd-Ce alloys were prepared in an arc furnace under atmosphere of ultra high purity argon. The disc specimens cut out from the ingots were heat-treated in vacuum and electrothinned to electron transparency by a jet method.

Partition Coefficient Ratios and Tumour Perfusion Studied with 85mKr and 133Xe

1987 ◽  
Vol 26 (06) ◽  
pp. 253-257
Author(s):  
M. Mäntylä ◽  
J. Perkkiö ◽  
J. Heikkonen
Keyword(s):  
Partition Coefficient ◽  
Partition Coefficients ◽  
Regional Blood Flow ◽  
Blood Perfusion ◽  
Compartmental Analysis ◽  
Malignant Tumour ◽  
Mean Value ◽  
Perfusion Rate ◽  
Biological Variables ◽  
The Mean

The relative partition coefficients of krypton and xenon, and the regional blood flow in 27 superficial malignant tumour nodules in 22 patients with diagnosed tumours were measured using the 85mKr- and 133Xe-clearance method. In order to minimize the effect of biological variables on the measurements the radionuclides were injected simultaneously into the tumour. The distribution of the radiotracers was assumed to be in equilibrium at the beginning of the experiment. The blood perfusion was calculated by fitting a two-exponential function to the measuring points. The mean value of the perfusion rate calculated from the xenon results was 13 ± 10 ml/(100 g-min) [range 3 to 38 ml/(100 g-min)] and from the krypton results 19 ± 11 ml/(100 g-min) [range 5 to 45 ml/(100 g-min)]. These values were obtained, if the partition coefficients are equal to one. The equations obtained by using compartmental analysis were used for the calculation of the relative partition coefficient of krypton and xenon. The partition coefficient of krypton was found to be slightly smaller than that of xenon, which may be due to its smaller molecular weight.

Detection of Soluble Fibrin Monomer Complexes in Blood by Means of Protamine Sulphate Test

1968 ◽  
Vol 20 (01/02) ◽  
pp. 044-049 ◽  
Author(s):  
B Lipiński ◽  
K Worowski
Keyword(s):  
Human Subjects ◽  
Coronary Thrombosis ◽  
Mean Value ◽  
Healthy Human ◽  
Protamine Sulphate ◽  
Soluble Fibrin ◽  
Fibrin Monomer ◽  
Dog Plasma ◽  
The Mean ◽  
Precipitable Protein

SummaryIn the present paper described is a simple test for detecting soluble fibrin monomer complexes (SFMC) in blood. The test consists in mixing 1% protamine sulphate with diluted oxalated plasma or serum and reading the optical density at 6190 Å. In experiments with dog plasma, enriched with soluble fibrin complexes, it was shown that OD read in PS test is proportional to the amount of fibrin recovered from the precipitate. It was found that SFMC level in plasma increases in rabbits infused intravenously with thrombin and decreases after injection of plasmin with streptokinase. In both cases PS precipitable protein in serum is elevated indicating enhanced fibrinolysis. In healthy human subjects the mean value of OD readings in plasma and sera were found to be 0.30 and 0.11, while in patients with coronary thrombosis they are 0.64 and 0.05 respectively. The origin of SFMC in circulation under physiological and pathological conditions is discussed.

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.

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