scholarly journals CD16A and CD16B mRNA levels as a potential immunological marker in prostate cancer

2021 ◽  
Author(s):  
Khalil Arioua
Keyword(s):  
Prostate Cancer ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Mrna Levels ◽  
Relative Level ◽  
Immunological Markers ◽  
Healthy Donors ◽  
Genes Encoding ◽  
Degree Of Differentiation ◽  
Prostate Antigen

Introduction and purpose Understanding the movement of immune cells in prostate cancer is the best solution for development antitumor therapy. In our study, we will evaluate level mRNA CD16А (FCGR3A) and mRNA CD16B (FCGR3B) in patients diagnosing benign hyperplasia and patients diagnosing prostate cancer (Pc). Materials and methods In the study, we analyzed 240 samples of mRNA, 49 was the blood of healthy donors, 37 was the blood of prostate cancer patients and 62 tumors of prostate, 37 were blood of hyperplasia and 55 was tissue of hyperplasia, all patients treated in the Hospital 33 (Niznhy Novgord, Russia). The relative level of mRNA in peripheral blood and tumors was determined by the method of reverse transcription-polymerase chain reaction in real time. Results In the peripheral blood of patients with prostate cancer and patients with hyperplasia, the level of mRNA FCGR3A and FCGR3B was statistically significantly lower than in healthy individuals. The normalization of the CD16 level in the blood of healthy donors was higher The relative level of mRNA FCGR3A, FCGR3B was the highest in patients with Prostate antigen specific (PSA) from 10Ng/ml to 20Ng/ml. The higher level mRNA FCGR3A and FCGR3B was for patients with higher testosterone ≥8mmol/L. also a higher level of FCGR3A, FCGR3B was found in patients diagnosed with an adenopathy:, a higher size prostate and a higher Gleason Scores. The results of Classification based on the degree of differentiation shows that the level of mRNA FCGR3A and FCGR3B in patients with medium differentiation was higher and statistically significant than in patient with lower differentiation. Conclusion. The Changes in the mRNA level of genes encoding CD16A (FCGR3A) and CD16B (FCGR3A) was detected in blood and tumor samples. The results indicate the potential use of these indicators as monitoring immunological markers in hyperplasia and prostate cancer.

scholarly journals The CD16A and CD16B mRNA level as potential immunological marker in colorectal cancer

2019 ◽  
Vol 18 (1) ◽  
pp. 220-227
Author(s):  
N. V. Krasnogorova ◽  
D. V. Novikov ◽  
S. G. Fomina ◽  
A. V. Alyasova ◽  
M. A. Magomedov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Tumor Development ◽  
Moderate Degree ◽  
Mrna Levels ◽  
Healthy Individuals ◽  
Immunological Markers ◽  
Genes Encoding ◽  
Colorectal Cancer Patients

The purpose of this study is to evaluate mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3B) in peripheral blood and tumors of colorectal cancer patients (CRC).Materials and methods. The study included 66 CRC patients from Nizhny Novgorod Regional Clinical Oncology Center and 111 people without cancer as a comparison group from Nizhny Novgorod Regional Blood Center named after N.Ya. Klimova. The mRNA relative levels in peripheral blood and tumor was detected by reverse transcription real-time polymerase chain reaction. The mRNA levels correlation and association with CRC clinical characteristics were assessed by statistic methods.Results. The study suggests that in the peripheral blood of CRC patients the levels of mRNA FCGR3A and FCGR3B were statistically significantly lower than in healthy individuals. The mRNA levels remained low at 7–10 days after surgery. The FCGR3A mRNA normalized level in the blood and tumors of CRC patients, as well as in the blood of healthy individuals, was several times higher than the FCGR3B mRNA level. At the II stage of tumor development in CRC patients, the FCGR3A and FCGR3B mRNA levels were statistically significantly decreased, but as the tumor progressed is normalized. Moderate degree of tumor differentiation was also characterized by a drop in mRNA levels of the tested genes. Reduced FCGR3A and FCGR3B mRNA levels in the blood of patients were observed in the absence of metastases. In tumor samples, FCGR3A mRNA was tested in 95.5% of cases, FCGR3B mRNA in 68.2% of cases. Progression of CRC was accompanied by an increase in FCGR3A mRNA level in tumors, the FCGR3B mRNA level did not change. Positive correlation of FCGR3A mRNA level with TNF and FOXP3 mRNA levels was found, which indicates the possible involvement of FCGR3A in the regulation of chronic inflammation in tumors of CRC patients.Conclusion. Changes in mRNA levels of genes encoding CD16A (FCGR3A) and CD16B (FCGR3A) molecules were detected in blood and tumor samples. The results indicate the potential for their use as monitoring immunological markers in CRC.

scholarly journals Comparative analysis of expression of genes encoding enzymes of catecholamine catabolism and renalase in tissues of normotensive and hypertensive rats

2017 ◽  
Vol 63 (4) ◽  
pp. 312-315 ◽  
Author(s):  
V.I. Fedchenko ◽  
A.E. Medvedev
Keyword(s):  
Comparative Analysis ◽  
Mrna Level ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Relative Level ◽  
Mao B ◽  
Wky Rats ◽  
Expression Of Genes ◽  
Mao A ◽  
Genes Encoding

Comparative analysis of expression of genes encoding enzymes of catecholamine catabolism (monoaminbe oxidases A and B (MAO A and MAO B) and catechol-O-methyl transferase (COMT)) and renalase has been carried out in tissues of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Among investigated tissues the highest level of mRNA of genes encoding key enzymes of catecholamine catabolism (MAO A, MAO B, COMT) was found in the heart of WKY rats. In SHR the mRNA levels of these genes were lower (p<0.05-0.01), however, no similar changes were observed in the tissues studied in dependence of hypertension. The relative mRNA levels of the studied genes normalized versus actin mRNA significantly varied. In heart and kidney the relative level of COMT mRNA significantly exceeded the relative levels of both MAO A mRNA and MAO B mRNA. In the brain differences in mRNAs of MAOA, MAOB, and COMT were less pronounced. However, in all examined tissue the renalase mRNA level was much (at least 10-20-fold) lower than any other mRNA studied. Taking into consideration known correlations between mRNAs and corresponding protein products reported in the literature for many genes these results suggest that in the case of any catalytic scenarios proposed or even proved for renalase this protein cannot contribute to catecholamine degradation. It is also unlikely that the products of renalase reaction, b-NAD(P)+ and hydrogen peroxide, can exhibit a hypotensive effect due to low expression of the renalase encoding gene.

scholarly journals Akt Inhibitors Induce Apoptosis in Chronic Lymphocytic Leukemia Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1731-1731
Author(s):  
Mercè de Frias ◽  
Daniel Iglesias-Serret ◽  
Ana M Cosialls ◽  
Llorenç Coll-Mulet ◽  
Antonio F Santidrián ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Therapeutic Option ◽  
Mrna Level ◽  
Lymphocytic Leukemia ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Healthy Donors ◽  
Induced Apoptosis

Abstract Abstract 1731 Poster Board I-757 Phosphatidylinositol-3-kinase (PI3K)/Akt pathway has been described to be critical in the survival of chronic lymphocytic leukemia (CLL) cells. Here, we have analyzed the effect of two selective chemical inhibitors of Akt (Akti-1/2 and A-443654) in the survival of CLL cells. We studied by cytometric analysis the cytotoxic effects of Akt inhibitors on peripheral B and T lymphocytes from patients with CLL and from healthy donors. Both inhibitors induced apoptosis in CLL cells in a dose-dependent manner. Moreover, B cells from CLL samples were more sensitive to Akt inhibitors than T cells from CLL samples, and B or T cells from healthy donors. Survival factors for CLL cells, such as IL-4 and SDF-1a, were not able to block the apoptosis induced by both Akt inhibitors. We studied the changes induced by Akti-1/2 and A-443654 at mRNA level by performing reverse transcriptase multiplex ligation–dependent probe amplification (RT-MLPA). Akti-1/2 did not induce any change in the mRNA expression profile of genes involved in apoptosis, while A-443654 induced some changes, including an increase in NOXA and PUMA mRNA levels, suggesting the existence of additional targets for A-443654. We also studied the changes induced by both Akt inhibitors in some BCL-2 protein family members on CLL cells by Western blot. Both inhibitors induced an increase in PUMA and NOXA protein levels, and a decrease in MCL-1 protein level. Moreover, Akti-1/2 and A-443654 induced apoptosis irrespective of TP53 status. These results demonstrate that Akt inhibitors induce apoptosis of CLL cells and might be a new therapeutic option for the treatment of CLL. Disclosures No relevant conflicts of interest to declare.

Prognostic Impact of the Detection of the WT1 Gene mRNA with Peripheral Blood in Adult Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3289-3289
Author(s):  
Shuichi Miyawaki ◽  
Nahoko Hatsumi ◽  
Toshiharu Tamaki ◽  
Tomoki Naoe ◽  
Keiya Ozawa ◽  
...  
Keyword(s):  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Relapse Rate ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Prognostic Impact ◽  
Mrna Levels ◽  
Consolidation Therapy

Abstract Background: Approximately 70–80% of all newly diagnosed patients with adult AML achieve a complete remission (CR). However, only about one third of those pts remain free of disease for more than 5 years. It is therefore important to predict which pts are most likely to suffer a relapse and thus perform alternative treatments such as stem cell transplantation in order to improve the prognosis of AML. We evaluated the impact of the detection of Wilms’ tumor gene1 (WT1) mRNA in the peripheral blood on the prognosis of AML pts. Patients and Methods: From June 1, 2001 to October 30, 2003 a study was performed on 191 pts with AML which evaluated the clinical usefulness of a WT1 mRNA assay kit for the early detection of relapse in AML pts (submitted in Rinsho Ketsueki). From these 191 pts, we selected the subjects for this study. All selected subjects achieved a complete remission, and also had their WT1 expression analyzed after consolidation therapy. The pts were excluded if they had received a stem cell transplantation before relapse. The WT1 mRNA levels were determined using the WT1 mRNA assay kit (Otsuka Pharmaceutical Co. Ltd) in accordance with the standard operating procedures using peripheral blood. The lower limit of detection was 50 copy/μgRNA. Therefore, less than 50 copy/μgRNA was judged as negative. All induction, consolidation and maintenance therapies were performed according to institutional standards. Results: Of 118 pts who achieved a complete remission, 50 pts (median age: 56 yrs 22–86) were evaluable. Their median WT1 mRNA levels before induction therapy was 48327 copy/μgRNA (137–329185). The WT1 mRNA levels at diagnosis did not correlate with either the relapse rate, DFS or OS, respectively. After CR, the WT1 mRNA level ranged from &lt;50 copy/μg to 30732 copy/μgRNA. Thirty-four (69.4%) pts were positive and 15 pts (30.6%) were negative for the WT1 mRNA. The relapse rate of the positive pts and of the negative pts was 73.5% and 40.0% (P=0.0248 sensitivity=80.6 % specificity=50.0%), respectively. The OS rate at 3 years was 53.1% in the positive pts and 79.0% in the negative pts (P=0.1227), respectively. The DFS rate at 3 years was 30.0% in the positive pts and 60.0 % in the negative pts (P=0.0906), respectively. After consolidation therapy, the WT1 mRNA level ranged from &lt;50 copy/μgRNA to 49174 copy/μgRNA. The WT1 positive pts numbered only 15 pts (32.6%) and the negative pts numbered 31 (67.4%). The relapse rate of the positive pts and the negative pts was 80.0% and 54.8% (P=0.0974), respectively. The OS of rate at 3 years was 42.8% in the positive pts and 69.8% in the negative pts (P=0.0381), respectively. The DFS rate at 3 years was 20.0% in the positive pts and 50.0% in the negative pts (P=0.0116). The rate of relapse within 1 year was 73.3% in the positive pts and only 33.3% in the negative pts (P= 0.0116). Conclusion: This study shows that the detection of the WT1 mRNA in the peripheral blood after treatment closely correlated with the prognosis in AML.

Prognostic Significance of WT1 mRNA and Anti-WT1 Antibody Levels in Peripheral Blood in Patients with Myelodysplastic Syndromes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3821-3821
Author(s):  
Hideto Tamura ◽  
Kazuo Dan ◽  
Norio Yokose ◽  
Rika Iwakiri ◽  
Masatsugu Ohta ◽  
...  
Keyword(s):  
Immune Response ◽  
Mrna Expression ◽  
Myelodysplastic Syndromes ◽  
Peripheral Blood ◽  
Quantitative Polymerase Chain Reaction ◽  
Mrna Level ◽  
Prognostic Significance ◽  
Refractory Anemia ◽  
Mrna Levels ◽  
Disease Subtype

Abstract Abstract 3821 Poster Board III-757 (INTRODUCTION) The Wilms tumor gene (WT1) message is overexpressed in tumor cells from various solid cancers as well as hematologic malignancies including myelodysplastic syndromes (MDS). We reported previously that WT1 mRNA expression in peripheral blood mononuclear cells (PBMCs) as well as bone marrow (BM) cells increased with the aggressiveness of MDS disease subtype as defined by the French-American-British (FAB) classification and that a humoral immune response, IgG- or IgM-type anti-WT1 antibody (Ab) expression, was detected in sera from most MDS patients. In this study, we investigated whether WT1 mRNA expression and anti-WT1 Ab titers in PB were associated with prognosis in MDS patients by examining their long-term follow-up data. (METHODS AND RESULTS) (1) WT1 mRNA expression in PBMCs was examined in 80 patients: 35 with refractory anemia (RA); 5 with RA with ringed sideroblasts (RARS); 24 with RA with excess blasts (RAEB); 5 with RAEB in transformation (RAEB-t); and 11 with acute myeloid leukemia transformed from MDS (AML-MDS). Levels of WT1 mRNA expression were assessed using the real-time quantitative polymerase chain reaction [Tamaki H, et al, Leukemia 1999]. WT1 mRNA levels increased with the aggressiveness of disease subtype (mean: RA, 220.9; RARS, 129.4; RAEB, 5,554.3; RAEB-t, 14,284.0; AML-MDS, 56,272.7 copies/μg) and with the aggressiveness of the International Prognostic Scoring System (IPSS) category (mean: low, 114.5; intermediate-1, 360.8; intermediate-2, 12,041.6; high, 7,357.9 copies/μg) in these patients. (2) IgG- and IgM-type anti-WT1 Ab titers were determined using the dot-blot assay [Elisseeva OA, Blood 2002] in sera from 45 of the 80 patients: 15 RA; 3 RARS; 18 RAEB; 3 RAEB-t; and 6 AML-MDS. IgM and IgG WT1 Abs were detected in 31 (79.5%) and 34 (87.2%) MDS patients, and 5 (83.3%) and 6 (100%) AML-MDS patients, respectively. WT1 Abs levels were not correlated with FAB subtype, IPSS, or WT1 mRNA expression in PBMCs. (3) When patients were divided into three groups based on the WT1 mRNA level (fewer than 100 copies/μg, 100 to 10,000 copies/μg, and more than 10,000 copies/μg), their survival rates differed significantly (P = 0.0186): survival was worse in those with increased WT1 mRNA levels. Specifically, a high WT1 mRNA level was a strong predictor of rapid AML transformation even if adjusted by the IPSS (P = 0.0005). Furthermore, patients with high levels of either IgM or IgG WT1 Abs had significantly better survival compared with those whose IgM and IgG WT1 Abs values were both low (P = 0.0007) even when adjusted by the IPSS (P = 0.0019). (CONCLUSIONS) This study showed for the first time that high WT1 mRNA expression and high WT1 Ab titers in PB affected the prognosis of MDS patients negatively and positively, respectively, suggesting that an optimal immune response against WT1 may beneficial. Recently, clinical trials of WT1 peptide-based immunotherapy have been conducted for various malignancies including MDS. Our data presented here may provide a rationale for anti-WT1 immunotherapy in MDS. Disclosures: No relevant conflicts of interest to declare.

Quantitative Expression Analysis of WT1 Main Isoforms in AML

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1469-1469
Author(s):  
Irene Luna ◽  
Esperanza Such ◽  
Jose Cervera ◽  
Eva Barragan ◽  
Marta Llop ◽  
...  
Keyword(s):  
Cord Blood ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Wilms Tumor ◽  
Mrna Level ◽  
Prognostic Impact ◽  
Cell Selection ◽  
Healthy Donors ◽  
Cd34 Cells ◽  
Cord Blood Cd34

Abstract Abstract 1469 The Wilms Tumor 1 (WT1) gene was first described as a tumour suppressor gene, but its accurate role in leukemia development has not been completely elucidated. Some authors support the role of WT1 as a prognostic marker in acute myeloid leukemia (AML) based on the assessment of its expression at the mRNA level. However, the prognostic value of the main isoforms of WT1 has been less studied. The aim of this study was to develop a specific quantitative assay to estimate the ratio of expression of the four major WT1 isoforms (A, 5-/KTS-; B, 5+/KTS-; C, 5-/KTS+; D, 5+/KTS+) and to evaluate their prognostic impact. WT1 expression was analyzed in bone marrow samples from 108 patients with AML at diagnosis (65 male/46 female, median age: 61 yr, range: 17 – 91). Likewise, peripheral blood samples of 20 healthy donors and 6 samples of cord blood CD34+ cell selection were analyzed as normal controls. We performed a new method to quantify the ratios of the four major isoforms of WT1. Briefly, to amplify all isoforms within a PCR reaction, specific WT1 primers flanking exon 4 to exon 10 were used in cDNA samples, followed by capillary electrophoresis with laser-induced fluorescence analysis on an ABIPRISM 310 DNA Analyzer (Applied Biosystems, Foster City, CA) and lastly analyzed with the Gene Mapper 4.2 software (Applied Biosystems). The amount of each isoform was calculated by the area under the curve. Subsequent comparisons of isoform ratios were made by standardized calculation of percentage. All values are given as the mean of duplicate PCRs. In parallel, RQ-PCR for total WT1 detection was performed as previously described by Barragan et al. (Haematologica 2004; 89: 926–933). GUS gene was used as housekeeping gene. Eighteen patients (17%) did not express WT1, while 90 patients (83%) overexpressed WT1 above background levels. The median value of each WT1 isoform was: 18% (range: 2 – 73) for A isoform; 16% (range: 7 – 63) for B isoform; 24% (range: 2 – 52) for C isoform; and 33% (range: 3 – 55) for D isoform. None of healthy donors had detectable WT1 levels in peripheral blood. All samples of CD34+ cells expressed the four isoforms of WT1: 21% (range: 2 – 26) for A isoform; 16% (range: 1 – 64) for B isoform; 24% (range: 1 – 47) for C isoform; and 36% (range: 25 – 44) for D isoform. These data reveal that, in our series, the most predominant isoform was +5/+KTS, both in AML and in cord blood CD34+ cell selection samples. There were no significant differences when comparing the proportion of each isoform between the cord blood CD34+ cell selection samples and the cohort of AML patients. There was not significant correlation between the overexpression of total WT1 with the ratio of each isoform, and we were unable to demonstrate that the overexpression of WT1 is due to a particular isoform overexpression. A significant lower event-free survival (EFS) was observed in those patients overexpressing total WT1, taking a cut-off value of 3000 WT1 copies/ GUS copies × 104 (75th percentile, P =.001). However, when the same cut-off as well as the median value for each one of the isoforms was used, we found no significant differences in EFS and in overall survival. To sum up, none of the isoforms were correlated with overexpression of total WT1 or survival. We were unable to find differences between the expression of each isoform of WT1 in CD34+ cells from normal cord blood and in AML patients. Further studies including larger controls need to be carried out. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Modulation of Cholesterol Metabolism Improves Response to Enzalutamide Treatment in Prostate Cancer

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 269-269
Author(s):  
Sora Kim ◽  
Kee-Hong Kim
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Cholesterol Metabolism ◽  
Mrna Level ◽  
Mrna Levels ◽  
Index Method ◽  
Cell Counts ◽  
Potential Biomarker ◽  
Ester Formation ◽  
Short Period

Abstract Objectives Prostate cancer (PCa) growth is mediated by androgens via activation of androgen receptor (AR). Accordingly, androgen deprivation therapy (ADT) is the gold standard for the treatment of advanced PCa, but progression to castration-resistant PCa (CRPC) follows. Enzalutamide (ENZ) is an AR antagonist used for the management of CRPC. However, patients acquire resistance to the drug in a short period. As cholesterol metabolism is dysregulated in PCa and lipogenesis is upregulated by AR signaling, we hypothesized that inhibition of cholesteryl ester formation and suppression of lipogenesis by blockage of sterol-O-acyltransferase 1 (SOAT1) could enhance the response to ENZ. Methods The mRNA expression of SOAT1 in PCa patients was analyzed using Oncomine and TCGA database. Survival analysis of TCGA PCa patients data was executed using cBioPortal. 22RV1 cells inherently resistant to ENZ, were challenged to avasimibe (AVA), a pharmacological inhibitor of SOAT1, with or without ENZ. Results We found SOAT1 mRNA is significantly overexpressed in prostate carcinoma compared to the normal tissue in separate datasets (Taylor 3; Grasso; Liu). Analysis of the TCGA PCa dataset among patients who had undergone ADT showed longer disease-free status (P = 0.039) and a trend toward better overall survival status (P = 0.066) in low SOAT1 mRNA expressing patients. Moreover, SOAT1 mRNA expression positively correlated with AR mRNA expression with Pearson coefficient of 0.5 (P = 7.475e-6). We also found that combination of 20 μM ENZ and 2 μM AVA reduced 52% of cell counts after 5 days and 53% of colony formation after 2 weeks, whereas AVA resulted in 20% and 28% reduction, respectively, with no effect from ENZ. Synergism of these two drugs was observed based on MTT assay with Chou-Talalay's combination index method. 4 μM AVA treatment for 24h downregulated AR downstream nkx3.1 mRNA level with no difference in AR or ARV7 mRNA levels. AVA treatment also downregulated lipogenic SCD1 mRNA level, inhibition of which was previously reported to enhance response to ENZ. Conclusions SOAT1 is a potential biomarker predictive of the success of ENZ treatment in PCa according to TCGA data. Our in vitro study further supports that SOAT1-regulated cholesterol metabolism is an important factor for the ENZ response. Funding Sources Purdue Research Foundation, Ralph W. and Grace M. Showalter Research Trust.

Increased Endothelin-1 Mrna Expression in Peripheral Blood Monocytes of Dialysis Patients

1997 ◽  
Vol 17 (6) ◽  
pp. 595-601 ◽  
Author(s):  
Isao Ebihara ◽  
Tsukasa Nakamura ◽  
Toshimasa Takahashi ◽  
Yasuhiko Tomino ◽  
Noriaki Shimada ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Blood Monocytes ◽  
Dialysis Patients ◽  
Peripheral Blood Monocytes ◽  
Different Types

Objective To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Design Endothelin-1 mRNA level in peripheral blood monocytes and plasma ET -1 level were studied in 30 HD patients, 15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20 normal healthy controls. Hemodialysis patients were dialyzed three times per week with a bicarbonate dialysate. Different types of dialyzer membrane, viz., cellulose triacetate, cuprophane, poly-sulfone, polyacrylonitrile, and ethylenevinylalcohol were used in 8,6,6,5, and 5 patients, respectively. Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to 2.5%. Results Higher levels of ET -1 mRNA in monocytes were observed in HD patients than in CAPD patients (p < 0.01), chronic renal failure patients (p < 0.01), or normal healthy controls (p < 0.001). The level of ET -1 mRNA in monocytes at the end of HD was not significantly higher than that at the start of HD. ln addition, these mRNA levels in HD patients showed littledifference with different types of dialysis membrane. Plasma ET -1 level in HD patients (10.2 ± 2.4 pg/mL) was also higher than that in CAPD patients (7.8 ± 1.6 pg/mL, p < 0.01), in chronic renal failure patients (4.8 ± 1.2 pg/mL, p < 0.01), or in normal controls (2.6 ± 0.8 pg/mL, p < 0.001). Conclusion Dialysis itself did not significantly affect ET -1 mRNA levels in monocytes. Chronic stimulation of peripheral blood monocytes may be associated with higher levels of ET -1 mRNA and plasma ET -1 in HD patients than in CAPD patients.

Alterations in the Expression of Amyloid Precursor Protein Cleaving Enzymes mRNA in Alzheimer Peripheral Blood

2018 ◽  
Vol 16 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Prapimpun Wongchitrat ◽  
Nattaporn Pakpian ◽  
Kuntida Kitidee ◽  
Kamonrat Phopin ◽  
Pornpatr A. Dharmasaroja ◽  
...  
Keyword(s):  
Amyloid Precursor Protein ◽  
Cognitive Performance ◽  
Peripheral Blood ◽  
Mrna Level ◽  
Precursor Protein ◽  
Mrna Levels ◽  
App Processing ◽  
Chain Reactions ◽  
Expression Of Genes ◽  
A Disintegrin And Metalloproteinase

Background: Alzheimer’s disease (AD) is the most common cause of dementia in elderly populations. Changes in the expression of the Amyloid Precursor Protein (APP)-cleaving enzymes directly affect the formation of Amyloid Beta (Aβ) plaques, a neuropathological hallmark of AD. Objective: We used peripheral blood from AD patients to investigate the expression of genes related to APP-processing [(β-site APP-cleaving enzyme 1 (BACE1), presenilin1 (PSEN1), and a disintegrin and metalloproteinase family 10 (ADAM10) and 17 (ADAM17)] and the epigenetic genes sirtuin (SIRT)1-3, which regulate Aβ production. Method: Real-time polymerase chain reactions were performed to determine the specific mRNA levels in plasma. The mRNA levels in AD patients were compared to those in healthy persons and assessed in relation to the subjects’ cognitive performance. Results: BACE1 mRNA level in AD subjects was significantly higher than those of healthy controls, whereas ADAM10 level was significantly lower in the AD subjects. The SIRT1 level was significantly decreased, while that of SIRT2 was increased in AD subjects and elderly controls compared to levels in healthy young control. In addition, correlations were found between the expression levels of BACE1, ADAM10 and SIRT1 and cognitive performance scores. Total Aβ (Aβ40+Aβ42) levels and the Aβ40/Aβ42 ratio were significantly increased in the AD subjects, whereas decrease in plasma Aβ42 was found in AD subjects. There was a negative correlation between Aβ40 or total Aβ and Thai Mental State Examination (TMSE) while there was no correlation between Aβ40/Aβ42 ratio or Aβ42 and TMSE. Conclusion: The present findings provide evidence and support for the potential roles of these enzymes that drive Aβ synthesis and for epigenetic regulation in AD progression and development, which can possibly be considered peripheral markers of AD.

scholarly journals Estrogen Receptors β1 and β2 Have Opposing Roles in Regulating Proliferation and Bone Metastasis Genes in the Prostate Cancer Cell Line PC3

2012 ◽  
Vol 26 (12) ◽  
pp. 1991-2003 ◽  
Author(s):  
Prasenjit Dey ◽  
Philip Jonsson ◽  
Johan Hartman ◽  
Cecilia Williams ◽  
Anders Ström ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Mrna Level ◽  
Gleason Grade ◽  
Mrna Levels ◽  
Proliferation Markers ◽  
Pc3 Cells

Abstract The estrogen receptor (ER)β1 is successively lost during cancer progression, whereas its splice variant, ERβ2, is expressed in advanced prostate cancer. The latter form of cancer often metastasizes to bone, and we wanted to investigate whether the loss of ERβ1 and/or the expression of ERβ2 affect such signaling pathways in prostate cancer. Using PC3 and 22Rv1 prostate cancer cell lines that stably express ERβ1 or ERβ2, we found that the ERβ variants differentially regulate genes known to affect tumor behavior. We found that ERβ1 repressed the expression of the bone metastasis regulator Runx2 in PC3 cells. By contrast, RUNX2 expression was up-regulated at the mRNA level by ERβ2 in PC3 cells, whereas Slug was up-regulated by ERβ2 in both PC3 and 22Rv1 cells. In addition, the expression of Twist1, a factor whose expression strongly correlates with high Gleason grade prostate carcinoma, was increased by ERβ2. In agreement with the increased Twist1 expression, we found increased expression of Dickkopf homolog 1; Dickkopf homolog 1 is a factor that has been shown to increase the RANK ligand/osteoprotegerin ratio and enhance osteoclastogenesis, indicating that the expression of ERβ2 can cause osteolytic cancer. Furthermore, we found that only ERβ1 inhibited proliferation, whereas ERβ2 increased proliferation. The expression of the proliferation markers Cyclin E, c-Myc, and p45Skp2 was differentially affected by ERβ1 and ERβ2 expression. In addition, nuclear β-catenin protein and its mRNA levels were reduced by ERβ1 expression. In conclusion, we found that ERβ1 inhibited proliferation and factors known to be involved in bone metastasis, whereas ERβ2 increased proliferation and up-regulated factors involved in bone metastasis. Thus, in prostate cancer cells, ERβ2 has oncogenic abilities that are in strong contrast to the tumor-suppressing effects of ERβ1.

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