The B-Cell Chemoattractant Factor CXCL13 Is Expressed in the Malignant Lymphocyte of the Sezary Syndrome.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2292-2292
Author(s):  
Maria Grazia Narducci ◽  
Maria Cristina Picchio ◽  
Cristina Lazzeri ◽  
Irene Angelucci ◽  
Enrico Scala ◽  
...  
Keyword(s):  
B Cell ◽  
Critical Role ◽  
Pcr Analysis ◽  
Low Grade ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Qrt Pcr ◽  
Cellular Recruitment ◽  
Skin Biopsies ◽  
Infiltrating Lymphocytes

Abstract Sézary Syndrome (SS) is a rare and aggressive form of Cutaneous T-Cell Lymphoma (CTCL) characterised by a distinct metastatic pattern mainly involving blood and skin. Our expression analyses performed by microarrays demonstrated that many chemokines resulted up-regulated in this type of lymphoma. Since these chemoattractant molecules play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors, we focused our attention on one of them named CXCL13, a lymphoid chemokine involved in B-cell compartmental homing within secondary lymphoid organs. Peripheral Blood Mononuclear cells (PBMCs) were isolated from blood obtained from SS patients and controls by Ficoll-Hypaque density gradient centrifugation (Sigma Aldrich). SS cells and healthy resting CD4+ lymphocytes were purified by positive selection using an anti-human-CD4 conjugated dynabeads (Oxoid). Total RNA was extracted using the Trizol reagent (Life Technologies). Quantitative-Real Time RT-PCR analysis was performed on CD4+ sorted from 14 SS patients and 3 controls. CXCL13 primers were designed by means of the Primer Express software package (Applied Biosystems). The qRT-PCR were performed with a SYBR Green I dye chemistry and AmpliTaq Gold DNA Polymerase on an ABI PRISM 7000 machine (Applied Biosystems). Immunohistochemistry analyses for CXCL13 were performed on formalin-fixed, paraffin-embedded skin biopsies from 15 SS, 15 MF, 6 MF-B cell rich patients using streptoavidin-biotin peroxidase labeling method (DAKO). Sections were counterstained with hematoxylin. Plasma CXCL13 levels were determined using a CXCL13 ELISA kit (BD Pharmingen). Results can be summarized as follow: qRT-PCR analysis revealed that 6 out 13 of SS patients showed an high mRNA levels of CXCL13; Immunohistochemistry analysis showed that CXCL13 is abundantly expressed by neoplastic skin-infiltrating lymphocytes of 9 out 15 SS skin biopsies. Conversely, CXCL13 is weakly expressed on scattered neoplastic skin-infiltrating lymphocytes of 1 out 15 MF and 1 out 6 MF-B cell rich biopsies. Plasma CXCL13 concentrations in SS patients (n = 10) were 1362 ± 134 pg/mL. Conversely, those in MF patients (n = 10) and healthy donors (n = 5) were 70 ± 43 and 13 ± 10 pg/mL, respectively. Compared with healthy controls, plasma CXCL13 levels were significantly higher in patients with SS (p<0.001) and with MF (p=0.04). In this study we report that both circulating and skin-infiltrating neoplastic lymphocytes of SS patients abundantly express CXCL13. Furthermore, this chemokine is also detectable at high level on plasma of SS patients. Conversely, CXCL13 is not observable in healthy controls as well as in Mycosis Fungoides, a variant of low grade of CTCL. These findings indicate that CXCL13 could play a role in pathobiology of Sézary Syndrome and that the expression of this chemokine could be used as diagnostic marker for this kind of tumor

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

ZAP-70 Expression in Human B cells: Analysis of Normal Cells and Acute Lymphoblastic Leukemia (ALL) Cells with Pro/Pre B Phenotype.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4443-4443
Author(s):  
Marta Crespo ◽  
Neus Villamor ◽  
Eva Gine ◽  
Dolors Colomer ◽  
Teresa Marafioti ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Protein Tyrosine Kinase ◽  
Lymphoblastic Leukemia ◽  
Human Lymphocytes ◽  
Critical Role ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Qrt Pcr ◽  
Human B Cells

Abstract ZAP-70 is a protein tyrosine kinase of the Syk/ZAP-70 family that plays a critical role in the signal transduction from the T-cell receptor. In human lymphocytes, ZAP-70 gene has been reported to be expressed in T and NK derived cells, and in IgVH unmutated B-chronic lymphocytic leukemia cells. More recently, ZAP-70 expression has been shown to be required for the development of pro-B cells to pre-B cells in mice. To ascertain the expression of ZAP-70 gene in human immature B-cell stages, we analyzed ZAP-70 protein and/or mRNA in normal human B cells at different stages of B cell maturation, including pro/pre-B cells and tumoral cells from 20 B-ALL. ZAP-70 expression was assessed by flow cytometry (FC), immunofluorescence (IF), and/or by quantitative real time RT-PCR (QRT-PCR). In normal bone marrow, ZAP-70 expression was found only in T and in immature B cells (CD19+/CD10+/CD20 −). Moreover, T cells -but no mature B cells- from normal tonsil expressed ZAP-70, as assessed by QRT-PCR and IF. In B-ALLs, a high ZAP-70 expression by FC was observed in 9/13 cases (mean, 82.6%, range 60–99%), whereas in 4 cases ZAP-70 was barely detectable (mean, 13%). By QRT-PCR, 10/16 B-ALLs showed levels of expression similar to ZAP-70 non-expressing cell lines and normal B-cells, whereas in the remaining cases ZAP-70 expression was 3–4 times higher than in normal mature B-cells. Taken together, a high expression of ZAP-70 was found in 11/21 (52%) B-ALLs. No relationship was observed between the level of ZAP-70 expression and the B-ALL maturation status. In conclusion, among normal B cell subsets ZAP-70 expression is restricted to B-cells with pro/pre phenotype. In addition, ZAP-70 is expressed in 52% of B-ALLs, probably as a reflection of their B-cell origin.

scholarly journals Analysis of Colorectal Carcinogenesis Paradigm between Cold Constitution and Heat Constitution: Earlier ECM Collagen Deposition

2021 ◽  
Vol 2021 ◽  
pp. 1-25
Author(s):  
Feifei Nong ◽  
Yuqi Liang ◽  
Shangping Xing ◽  
Huixuan Li ◽  
Xizheng Lin ◽  
...  
Keyword(s):  
Lysyl Oxidase ◽  
Critical Role ◽  
Polarized Light ◽  
Malignant Progression ◽  
Colorectal Carcinogenesis ◽  
Mrna Levels ◽  
Collagen Deposition ◽  
Colon Tissue ◽  
Qrt Pcr ◽  
Sirius Red

Colorectal cancer (CRC) is a common malignant tumor around the world. Studying the unique constitution of CRC patients is conducive to the application of personalized medical treatment for CRC. The most common types of constitution in CRC are cold and heat constitution. A previous study has suggested that the malignant progression in cold and heat constitution CRC are different; however, the mechanism remains unclear. The tumor microenvironment (TME) is likely to vary with each individual constitution, which may affect the tumor growth in different constitutions. The extracellular matrix (ECM), the most important component of TME, plays a critical role in disease progression and outcome in patients with CRC. Moreover, collagen, the major component of the ECM, determines the main functional characteristics of ECM and tissue fibrosis caused by collagen deposition, which is one of the signs of CRC malignant progression. This study aimed to explore the mechanisms leading to different colorectal carcinogenesis paradigms between the cold constitution and heat constitution within the context of ECM collagen deposition. We established the CRC rat models and enrolled 30 CRC patients with cold and heat constitution. The collagen-related parameters were detected by using Sirius red staining combined with polarized light microscope, and expressions of collagen (COL I and COL III) and lysyl oxidase (LOX and LOXL2) were determined using immunohistochemistry, while the mRNA levels of COL1A1, COL3A1, LOX, and LOXL2 were measured by qRT-PCR. We found that a higher degree of collagen deposition in the cold-constitution group. The results suggest cold and heat constitution may affect the colorectal carcinogenesis paradigm by influencing the early collagen deposition in colon tissue. The study may provide an effective idea for clinicians to improve the prognosis of CRC patients with different constitutions.

A blood-based gene expression signature of early-stage non-small cell lung cancer.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 69-69
Author(s):  
Melissa Rotunno ◽  
Nan Hu ◽  
Hua Su ◽  
Chaoyu Wang ◽  
Pier Alberto Bertazzi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Predictive Accuracy ◽  
Early Stage ◽  
Single Gene ◽  
Gene Expression Signature ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Expression Signature ◽  
Qrt Pcr

69 Background: Accurate blood-based biomarker for early cancer detection could be an easier and more convenient screening option than monitoring the target organ via tissue or imaging. We recently identified and validated eight genetic biomarkers of early-stage lung adenocarcinoma detectable in both peripheral whole blood (PWB) and lung tissue of smokers. Since biomarkers distinguishing benign disease versus lung malignancy across all cell types are needed in the diagnostic clinical setting, it is important to test the identified biomarkers in other lung cancer histologies, particularly in squamous cell carcinoma (SQCC), the second most common lung cancer histology after adenocarcinoma (AD). Methods: Using Real-Time Quantitative PCR (qRT-PCR), we measured mRNA levels for the eight candidate genes in PWB of 48 randomly sampled stage I SQCC cases, in addition to previously analyzed 82 AD cases and 130 age, sex, and smoking frequency matched healthy controls from the Environment And Genetics in Lung cancer Etiology (EAGLE) case-control study. The qRT-PCR data were analyzed using the 2-ΔΔCtmethod to compare SQCC cases with controls. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the candidate biomarkers in SQCC separately, and in SQCC and AD together. Results: Expression of TGFBR3, RUNX3, TRGC2, TRGV9, TARP, and TSTA3 genes, significantly differentiated SQCC cases versus controls, while ACP1 and VCAN gene expression did not. The eight genes combined discriminated patients with lung cancer from healthy controls with similarly high accuracy in SQCC and overall (AUC = 0.80 ± 0.1). RUNX3 showed the highest single gene accuracy for SQCC (AUC = 0.78). Conclusions: We showed that the previously identified gene expression signature of early-stage lung AD also differentiated early stage SQCC from healthy controls and demonstrated its sensitivity and specificity as a potential diagnostic lung cancer biomarker. Since lung cancer is the most common cause of cancer mortality worldwide and current smokers are at very high risk, our smoking-specific findings, if confirmed and translated into screening approaches, have the potential to impact public health.

Relapsed MALT Lymphomas Are Associated with a Restricted VH3-30.3 Immunoglobulin VH Gene Repertoire and Are Targeted by Aberrant Somatic Hypermutation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2830-2830
Author(s):  
Alexander JA Deutsch ◽  
Ruth I Brezinschek ◽  
Hans-Peter Brezinschek ◽  
Christine Beham-Schmid ◽  
Peter Neumeister
Keyword(s):  
Salivary Gland ◽  
B Cell ◽  
Salivary Glands ◽  
Malt Lymphoma ◽  
Somatic Hypermutation ◽  
Gene Segment ◽  
Low Grade ◽  
Gene Repertoire ◽  
Mrna Levels ◽  
Vh Gene

Abstract Mucosa associated lymphoid tissue (MALT) type lymphomas are B-cell neoplasms that develop out of a reactive infiltrate; Sjoegren syndrome, Hashimoto thyroiditis, and Helicobacter pylori gastritis provide the pathogenetic background. Direct antigen stimulation through surface immunoglobulin (Ig) molecules may be playing an important role in the development of MALT lymphomas. In rare cases MALT lymphomas may undergo transformation into extranodal diffuse large B-cell lymphomas (eDLBCL). Previous reports suggested salivary gland MALT lymphomas expressed a restricted Ig VH gene repertoire with over use of VH1-69 gene segments. Because knowledge about the VH gene used by MALT lymphoma of gastric and extragastric origin and by eDLBCL is limited, we sequenced the VH genes from 11 MALT lymphomas [5 of gastric and 6 of extragastric origin (3 salivary gland, 3 thyroid)] and from 10 eDLBCL, all arisen from MALT lymphoma and still exhibiting a low grade component [= so called “transformed MALT lymphoma”: 5 of gastric and 5 of extragastric origin (3 salivary gland and 2 thyroid)]. MALT lymphomas used gene segments of the VH1 (1–69: 2 salivary gland and 1 thyroid), VH3 (3–30.3: 1 thyroid), VH4 (4–34: 1 thyroid, 1 salivary gland and 2 gastric), VH5 (5–51: 2 gastric) and VH6 (6-1: 1 gastric) families. Extranodal DLBCLs used segments derived from VH1 (1–69: 1 gastric and 1 salivary gland), VH2 (2–70: 1 thyroid), VH3 (3–23: 1 gastric; 3–30: 1 gastric; 3–30.3: 1 gastric and 2 salivary glands) and VH4 (4–34: 1 gastric) families as shown in table 1. The VH1-69 gene segment was found in 3 of 6 extragastric MALT lymphomas (2 salivary glands and 1 thyroid), in one gastric and one salivary gland eDLBCL but in no gastric MALT lymphoma. Further, 4 of the 21 lymphomas relapsed, 3 eDLBCL and one MALT lymphoma – and remarkably, all of them used the VH3-30.3 gene segment. Comparing the frequency of somatic hypermutation (SHM) of the immunoglobuline locus and aberrant somatic hypermutation (ASHM) of the four proto-oncogenes PAX-5, PIM-1, Rho/TTF and c-MYC between the relapsed (n=4) and non relapsed lymphomas (n=17) a ~2.9 fold (5.8 vs 2.0 × 10−2/bp, p=0.017) and 2.1 fold (0.067 vs 0.032 × 10−2/bp, p=0.027) higher mutation rate for SHM and ASHM in relapsed lymphomas was observed. Also, the AID mRNA relative expression number was 1.7 fold higher in the group of relapsed lymphomas (4.66 vs 2.71, p=0.049). Performing immunohistochemical analysis for AID a significant positive correlation (p=0.01; correlation coefficient (Spearman rho) = 0.794) was observed when comparing protein expression with mRNA levels. These results are consistent with the model in which only certain B cells displaying specific patterns of VH immunoglobuline molecules binding to an as yet undefined antigen together with a highly aberrant somatic hypermutation process are preferentially selected for malignant transformation and determine the natural course of disease. Table1: VH gene sement used by MALT lymphomas and eDLBCL Case Type Origin V H gene Relapse GHM2 eDLBCL stomach 1–69 no GHM3 eDLBCL stomach 3–23 no GHM5 eDLBCL stomach 3-30-3 yes GHM7 eDLBCL stomach 4–34 no GHM8 eDLBCL stomach 3–30 no EHM12 eDLBCL thyroid 6–1 no EHM15 eDLBCL salivary gland 3-30-3 yes EHM16 eDLBCL salivary gland 3-30-3 yes EHM18 eDLBCL thyroid 2–70 no EHM19 eDLBCL salivary gland 1–69 no ENM14 MALT thyroid 3-30-3 yes ENM21 MALT salivary gland 1–69 no ENM29 MALT salivary gland 1–69 no ENM30 MALT salivary gland 4–34 no ENM33 MALT thyroid 1–69 no ENM35 MALT thyroid 4–34 no GNM36 MALT stomach 5–51 no GNM37 MALT stomach 4–34 no GNM38 MALT stomach 6–1 no GNM39 MALT stomach 5–51 no GNM41 MALT stomach 4–34 no

scholarly journals Immunological Aspects of Fulminant Type 1 Diabetes in Chinese

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Zhen Wang ◽  
Ying Zheng ◽  
Yiting Tu ◽  
Zhijie Dai ◽  
Jian Lin ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Rapid Onset ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Fulminant Type 1 Diabetes ◽  
C Peptide ◽  
Cell Responses ◽  
Qrt Pcr ◽  
Fulminant Type

Background.Fulminant type 1 diabetes (FT1D) is a novel subtype of type 1 diabetes characterized by extremely rapid onset and complete deficiency of insulin due to the destruction of pancreaticβcells. However, the precise mechanisms underlying the etiology of this disease remain unclear.Methods.A total of 22 patients with FT1D and 10 healthy subjects were recruited. Serum antibodies to GAD, IA2, and ZnT8 in patients were tested. And peripheral T cell responses to GAD65, insulin B9–23 peptide, or C peptide were determined in 10 FT1D patients and 10 healthy controls. The mRNA levels of several related cytokines and molecules, such as IFN-γ, IL-4, RORC, and IL-17 in PBMCs from FT1D patients were analyzed by qRT-PCR.Result.We found that a certain proportion of Chinese FT1D patients actually have developed islet-related autoantibodies after onset of the disease. The GAD, insulin, or C peptide-reactive T cells were found in some FT1D patients. We also detected a significant increase for IFN-γexpression in FT1D PBMCs as compared with that of healthy controls.Conclusion.Autoimmune responses might be involved in the pathogenesis of Chinese FT1D.

scholarly journals Diagnostic significance of serum lncRNA HOTAIR and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Huiyun Wang ◽  
Yu Xia ◽  
Yanxia Zhang
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Multivariate Analysis ◽  
Fasting Blood Glucose ◽  
Pcr Analysis ◽  
Healthy Controls ◽  
Chronic Complications ◽  
Qrt Pcr

Abstract Background Type 2 diabetes mellitus (T2DM) affects the social economy and quality of life, and has become a major threat to human health. This observation aimed to study the possibility of serum HOTAIR as a diagnostic index in patients with T2DM and to explore the prognostic potential of HOTAIR in the development of T2DM. Methods The expression of HOTAIR in serum of 96 patients with T2DM and 82 healthy controls was detected by the qRT-PCR technique. The related biochemical indexes of all participants were determined, such as total cholesterol (TC) and fasting blood glucose (FBG). The value of serum HOTAIR in the diagnosis of T2DM in the two groups was analyzed by the ROC curve. Moreover, the prognostic value of HOTAIR on T2DM was examined by the K-M curve and COX multivariate analysis. Results The results of the qRT-PCR analysis showed that the serum level of HOTAIR in patients with T2DM was significantly higher than that in healthy controls. ROC analysis showed that HOTAIR in serum was a diagnostic factor of T2DM. Further multivariate analysis showed that HOTAIR could be an independent biomarker in the prediction of chronic complications for T2DM patients, such as diabetic retinopathy and diabetic nephropathy. Conclusions We found the augment of HOTAIR expression was a character of T2DM. The high expression of serum HOTAIR was a potential non-invasive diagnostic marker and independent prognostic factor in patients with T2DM.

scholarly journals BZW1 Promotes Cell Proliferation in Prostate Cancer by Regulating TGF-β1/Smad Pathway

2020 ◽  
Author(s):  
Teng-Cheng Li ◽  
Zhuo-Lun Sun ◽  
Chu-Tian Xiao ◽  
Jie-Ying Wu ◽  
Ke Li
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Specific Antigen ◽  
High Expression ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Smad Pathway ◽  
Over Expression ◽  
Qrt Pcr ◽  
Tgf Β1

Abstract Background Recently, basic leucine zipper and the W2 domain-containing protein 1 (BZW1) is reported to be implicated in tumor progression. However, the role of BZW1 in prostate cancer remains unknown. This study is aimed to investigate the expression of BZW1 and its influence on cell proliferation in prostate cancer. Methods The expression levels of BZW1 were measured in 136 cases of prostate cancer and matched adjacent non-cancerous prostate tissues by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Then, the effect of BZW1 on cell proliferation was further explored. Results QRT-PCR analysis shown that the mRNA levels of BZW1 in prostate cancer were significantly greater compared with those in matched adjacent non-cancerous prostate tissues (P<0.001). IHC results shown the high-expression rate of BZW1 in prostate cancer and matched adjacent non-cancerous prostate tissues were 68.4% and 32.4%, and the difference was statistically significant (P<0.001). BZW1 high-expression significantly correlated with T stage, lymph node metastasis, prostate specific antigen (PSA) and Gleason score (P<0.05). Patients with BZW1 high-expression presented unfavorable prognosis compared with those with BZW1 low-expression (P=0.002). In addition, CCK-8 and Colony formation assays revealed that BZW1 over-expression significantly promoted cell proliferation in vitro. Tumor xenograft shown BZW1 knockdown significantly inhibited tumor growth in vivo. Moreover, BZW1 overexpression activated the TGF-β1/Smad1/Smad3 pathway. Conclusion BZW1 over-expression predicts poorer prognosis and promotes cell proliferation in prostate cancer by regulating TGF-β1/Smad pathway.

Regulation of Apoptosis and Oxidative Stress by LMP1 Oncoprotein of Epstein-Barr Virus in Patients with Low Grade B-Cell Leukemic Lymphomas

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5212-5212
Author(s):  
Panagiotis Theodorou Diamantopoulos ◽  
Katerina Polonyfi ◽  
Nikolaos Spanakis ◽  
Athanassios Galanopoulos ◽  
Georgia Diamantopoulou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
B Cell ◽  
Cell Lines ◽  
Peripheral Blood ◽  
Cell Aging ◽  
Control Group ◽  
Low Grade ◽  
Qrt Pcr ◽  
Epstein Barr

Abstract Abstract 5212 Background: In all Epstein-Barr (EBV)-associated malignancies, the virus displays a latency program of infection and a restricted pattern of gene expression. Among the products of these genes, latent membrane protein 1 (LMP1) is a potent transforming protein with several different roles. LMP1 has been shown in cell lines to stimulate apoptosis. Survivin, a member of the inhibitor of apoptosis (IAP) family, is an important regulator of the mitochondrial apoptotic pathway, while oxidative stress (OS) is a cellular condition particularly relevant to cell aging. In the present study we enrolled patients with non-EBV-related low grade B-cell lymphoproliferative diseases. The aim was to detect (1) the viral load of EBV-positive patients, (2) the expression of LMP1 oncoprotein, (3) the possible apoptotic properties of LMP1 by correlating the levels of survivin with LMP1 expression, and (4) the levels of oxidative stress in LMP1-positive and negative patients. Patients and Methods: Forty eight Greek patients with EBV-unrelated low grade B-cell leukemic lymphomas, were enrolled in the study (chronic lymphocytic leukemia: 27, marginal zone lymphoma: 12, mantle cell lymphoma: 4, hairy cell leukemia: 2, follicular lymphoma: 2, lymphoplasmacytic lymphoma: 1). The majority of patients (61.2%) were treatment-naïve, while the rest had not received any treatment for at least 6 months. DNA from peripheral blood was tested by quantitative real time (qRT) PCR for the EBV-R gene. RNA from EBV-positive patients was examined by RT-PCR and qRT PCR for LMP-1, while using qRT PCR we measured survivin expression in all patients. Densitometric analysis (DA) was used for semi-quantification of the survivin gene expression. The results were expressed relative to the expression of ABL housekeeping gene. The control group included 30 EBV-negative healthy adults. Oxidative stress was measured in the serum of all patients using the PerOx (TOS/TOC) Kit, by Immunodiagnostik. Non parametric methods (Mann-Whitney test) were used for statistical analysis of the results. Results: Twenty five (25) men and 23 women, with a median age of 74 (51–87 years old) were studied. EBV positivity was detected in 19/48 (39.6%) patients, and LMP1 was expressed in 13/19 (68.4%) EBV-positive patients. Survivin levels were lower in LMP1-positive patients vs LMP1-negative patients (2-tailed p=0.009). The oxidative stress was lower (261.4 μmol/L) in LMP1-positive patients vs LMP1-negative patients (372.3 μmol/L), (2-tailed p=0.014). Discussion: The literature lacks information about the expression of LMP1 in the peripheral blood of patients with non-EBV-related low grade B-cell leukemic lymphomas. Previous studies in LMP1-positive lymphoma cell lines have shown the apoptotic functions of LMP1 during type II latency. In this study LMP1-positive patients express statistically significant lower levels of survivin vs LMP1-negative patients. This finding is in accordance to the hypothesis that LMP1 oncoprotein can induce apoptosis. LMP1-positive patients had lower levels of oxidative stress compared to LMP1-negative patients. According to our findings, in non-EBV-related lymphomas, LMP1 may increase apoptosis and decrease the levels of oxidative stress. Disclosures: No relevant conflicts of interest to declare.

Ontogeny of the eotaxins in human lung

2008 ◽  
Vol 294 (2) ◽  
pp. L214-L224 ◽  
Author(s):  
Kathleen J. Haley ◽  
Mary E. Sunday ◽  
Yolanda Porrata ◽  
Colleen Kelley ◽  
Anne Twomey ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lung Tissue ◽  
Human Lung ◽  
Airway Epithelial Cells ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Human Lung Tissue ◽  
Qrt Pcr ◽  
Explant Cultures

The ontogeny of the C-C chemokines eotaxin-1, eotaxin-2, and eotaxin-3 has not been fully elucidated in human lung. We explored a possible role for eotaxin in developing lung by determining the ontogeny of eotaxin-1 (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), and the eotaxin receptor, CCR3. We tested discarded surgical samples of developing human lung tissue using quantitative RT-PCR (QRT-PCR) and immunostaining for expression of CCL11, CCL24, CCL26, and CCR3. We assessed possible functionality of the eotaxin-CCR3 system by treating lung explant cultures with exogenous CCL11 and analyzing the cultures for evidence of changes in proliferation and activation of ERK1/2, a signaling pathway associated with CCR3. QRT-PCR analyses of 22 developing lung tissue samples with gestational ages 10–23 wk demonstrated that eotaxin-1 mRNA is most abundant in developing lung, whereas mRNAs for eotaxin-2 and eotaxin-3 are minimally detectable. CCL11 mRNA levels correlated with gestational age ( P < 0.05), and immunoreactivity was localized predominantly to airway epithelial cells. QRT-PCR analysis detected CCR3 expression in 16 of 19 developing lung samples. Supporting functional capacity in the immature lung, CCL11 treatment of lung explant cultures resulted in significantly increased ( P < 0.05) cell proliferation and activation of the ERK signaling pathway, which is downstream from CCR3, suggesting that proliferation was due to activation of CCR3 receptors by CCL11. We conclude that developing lung expresses the eotaxins and functional CCR3 receptor. CCL11 may promote airway epithelial proliferation in the developing lung.

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