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Jamroziak, Krzysztof, Zofia Szemraj, Janusz Szemraj, Olga Grzybowska-Izydorczyk, Katarzyna Oszajca, Grazyna Janiszewska, Ewa Balcerczak, Marek Mirowski, Halina Urbanska-Rys, and Tadeusz Robak. "Polymorphisms in CD31/PECAM-1 and CD38 Genes Are Associated with Susceptibility to Multiple Myeloma." Blood 112, no. 11 (November 16, 2008): 5113. http://dx.doi.org/10.1182/blood.v112.11.5113.5113.
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Abstract Interactions with bone marrow microenvironment play a major role in the control of multiple myeloma (MM) growth and survival. MM clonal plasma cells co-express high levels of a signaling receptor CD38 and its ligand, the platelet endothelial adhesion molecule-1, CD31//PECAM-1. Homotypic and heterotypic interactions through these adhesion molecules (CD31/CD31, CD38/CD31 and CD38/hyaluronate interactions) may be involved in the pathogenesis of MM. The objective of this study was to investigate whether inherited variants in CD31/PECAM-1 and CD38 genes influence on susceptibility to MM. A total of 189 Caucasian patients with MM and 209 healthy controls were genotyped with the use of PCR-based methods. Genotyping was performed to assess allelic frequencies of three non-synonymous single nucleotide polymorphisms (SNPs) in CD31/PECAM1 gene including 373C>G (Leu 125Val), 1688G>A (Ser563Asn) and 2008A>G (Arg670Gly) as well as two SNPs in CD38 gene including 184C>G in intron 1 and non-synonymous 418C>T (Arg140Trp) in exon 3. Analyzing the prevalence of investigated genetic variants, we found that allelic frequencies of two SNPs in CD31/PECAM-1 gene and intron 1 184C>G SNP in CD38 gene differed significantly between MM patients and controls. Concerning CD31/PECAM-1 SNPs, the carriership of 373G allele was associated with the relative risk of MM of 4.5 (p=8×10−10), while in carriers of 1688A allele the relative risk of MM reached 3.0 (p=2×10−6). Regarding CD38 gene, compared to wild-type 184C-allele carriers, the carriers of variant 184G-allele had 3.4-fold increased risk of MM (p=1×1−9). In conclusion, the results of this study suggest that inherited variants in ligand-receptor CD31/PECAM1 - CD38 system contribute to the genetic susceptibility to MM in Caucasians.
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Cramer, EM, G. Berger, and MC Berndt. "Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1." Blood 84, no. 6 (September 15, 1994): 1722–30. http://dx.doi.org/10.1182/blood.v84.6.1722.1722.
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Abstract CD9 (p24) and PECAM1 (CD31) antigens are well-defined components of the platelet plasma membrane. Both are integral glycoproteins (GPs) implicated in the adhesive and aggregative properties of human platelets. In the present report, we have investigated their subcellular localization using immunoelectron microscopy. The monospecificity of the two polyclonal antibodies used was confirmed by immunoblotting. On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system. Some labeling was also consistently found on the alpha-granule limiting membrane. This was confirmed by double labeling experiments in which fibrinogen and von Willebrand factor (vWF) were used as alpha-granule markers. CD9 and PECAM-1 were found lining the membrane of the same granules that contained fibrinogen and vWF in their matrix. CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor. To rule out a cross-reactivity of the two polyclonal antibodies with GPIIb/IIIa, we studied PECAM1 and CD9 expression on the platelets from a patient with type I Glanzmann's thrombasthenia whose platelets are devoid of GPIIb/IIIa. The same pattern of labeling was observed for both antigens as for normal platelets. Normal platelets were further observed after stimulation by agonists that either fail to induce (ADP) or induce granule secretion (thrombin). After treatment with ADP, platelets changed shape and centralized their granules; the plasma membrane immunolabeling remained unchanged; and gold particles were still found decorating the periphery of the centralized alpha- granules. After thrombin treatment, alpha-granules fused with the platelet membrane and secretion occurred. A significant increase of labeling was then observed on the platelet surface. From these results we conclude that the alpha-granule membrane contains two additional receptors in common with the plasma membrane. This suggests that alpha- granule membrane receptors may originate from a dual mechanism: direct targeting from the Golgi complex in megakaryocytes (for alpha-granule- specific receptors such as P-selectin) or by endocytosis from the plasma membrane (for proteins distributed in the two compartments).
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Cramer, EM, G. Berger, and MC Berndt. "Platelet alpha-granule and plasma membrane share two new components: CD9 and PECAM-1." Blood 84, no. 6 (September 15, 1994): 1722–30. http://dx.doi.org/10.1182/blood.v84.6.1722.bloodjournal8461722.
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CD9 (p24) and PECAM1 (CD31) antigens are well-defined components of the platelet plasma membrane. Both are integral glycoproteins (GPs) implicated in the adhesive and aggregative properties of human platelets. In the present report, we have investigated their subcellular localization using immunoelectron microscopy. The monospecificity of the two polyclonal antibodies used was confirmed by immunoblotting. On normal resting platelets, immunolabeling for CD9 and PECAM1 was found lining the plasma membrane and the luminal face of the open canalicular system. Some labeling was also consistently found on the alpha-granule limiting membrane. This was confirmed by double labeling experiments in which fibrinogen and von Willebrand factor (vWF) were used as alpha-granule markers. CD9 and PECAM-1 were found lining the membrane of the same granules that contained fibrinogen and vWF in their matrix. CD9 and PECAM-1 thus appear to have an intracellular distribution identical to GPIIb-IIIa, a major aggregation platelet receptor. To rule out a cross-reactivity of the two polyclonal antibodies with GPIIb/IIIa, we studied PECAM1 and CD9 expression on the platelets from a patient with type I Glanzmann's thrombasthenia whose platelets are devoid of GPIIb/IIIa. The same pattern of labeling was observed for both antigens as for normal platelets. Normal platelets were further observed after stimulation by agonists that either fail to induce (ADP) or induce granule secretion (thrombin). After treatment with ADP, platelets changed shape and centralized their granules; the plasma membrane immunolabeling remained unchanged; and gold particles were still found decorating the periphery of the centralized alpha- granules. After thrombin treatment, alpha-granules fused with the platelet membrane and secretion occurred. A significant increase of labeling was then observed on the platelet surface. From these results we conclude that the alpha-granule membrane contains two additional receptors in common with the plasma membrane. This suggests that alpha- granule membrane receptors may originate from a dual mechanism: direct targeting from the Golgi complex in megakaryocytes (for alpha-granule- specific receptors such as P-selectin) or by endocytosis from the plasma membrane (for proteins distributed in the two compartments).
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Fei, Hongjun, Songchang Chen, and Chenming Xu. "Interactive Verification Analysis of Multiple Sequencing Data for Identifying Potential Biomarker of Lung Adenocarcinoma." BioMed Research International 2020 (October 1, 2020): 1–18. http://dx.doi.org/10.1155/2020/8931419.
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Background. Lung adenocarcinoma (LUAD) comprises around 40% of all lung cancers, and in about 70% of patients, it has spread locally or systemically when first detected leading to a worse prognosis. Methods. We filtered out differentially expressed genes (DEGs) based on the RNA sequencing data in the Gene Expression Omnibus database and verified and deeply analyzed screened DEGs using a combined bioinformatics approach. Results. Expressions of 11,143 genes in 694 nontumor lung tissues and LUAD cases from 8 independent laboratories were analyzed; 188 mRNAs were identified as differentially expressed genes (DEGs). A PPI network constructed with 188 DEGs screened out 8 hub DEGs (CDH5, PECAM1, VWF, CLDN5, COL1A1, MMP9, SPP1, and IL6) which highly interconnected with other nodes. The expression levels of 8 hub genes in LUAD and control were assessed in the Oncomine database, and the results were consistent. The survival curves of 8 hub genes showed that their expressions are significantly related to the prognosis of lung cancer and LUAD patients except for IL6. Since the expression of IL6 is nonspecific and highly sensitive, we choose the other 7 hub genes we had verified to do the next analysis. Mutual exclusivity or cooccurrence analysis of 7 hub genes identified a tendency towards cooccurrence between CDH5, PECAM1, and VWF in LUAD. The coexpression profiles of CDH5 in LUAD were identified, and we found that PECAM1 and VWF coexpressed with CDH5. Immunohistochemistry and RT-PCR analysis showed that higher levels of CDH5, PECAM1, and VWF were expressed in normal lung tissues but a low or undetectable level was found in LUAD tissues. Conclusions. Taken together, we speculate that CDH5, PECAM1, and VWF played an important role in LUAD.
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Chen, Zhengshan, Huimin Geng, Maike Buchner, Lars Klemm, Kaveh Hemati, Seyedmehdi Shojaee, Mak W. Tak, et al. "ITIM-Containing Inhibitory Receptors Are Required to Balance Oncogenic Signaling Strength in Ph+ ALL." Blood 120, no. 21 (November 16, 2012): 291. http://dx.doi.org/10.1182/blood.v120.21.291.291.
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Abstract Abstract 291 Background: ITIM (immunoreceptor tyrosine-based inhibition motifs) motifs in the cytoplasmic tail of inhibitory receptors recruit inhibitory phosphatases. Upon ligation, these phosphatases inhibit signal transduction from tyrosine kinases including BCR-ABL1. ITIM-receptors are critical in the control of immune responses of B and T cells. Surprisingly, we found that a number of inhibitory ITIM-receptors are expressed at very high levels on the surface of patient-derived Ph+ acute lymphoblastic leukemia (ALL) cells compared to normal pre-B cells. In this study, three central ITIM-receptors were identified and analyzed for their function in Ph+ALL: PECAM1 (platelet/endothelial cell adhesion molecule 1/CD31), CD300A and LAIR1 (leukocyte-associated immunoglobulin-like receptor 1). Results: Microarray data showed mRNA levels of PECAM1, CD300A and LAIR1 were about 5-fold higher (p<0.005) in Ph+ ALL (n=15) than normal human pre-B cells (n=8). We confirmed this difference at the protein level by flow cytometry studying patient-derived Ph+ALL (n=11) and pre-B cells from normal bone marrow samples (n=2). These findings seem counterintuitive because signaling from these receptors would attenuate the signaling strength downstream of BCR-ABL1. Importantly, we found that high expression levels of ITIM-receptors are predictive of poor outcome in two clinical trials. In the COG trial (P9906; n=207) for children with high-risk ALL, we found that mRNA levels of PECAM1, CD300A and LAIR1 at diagnosis positively correlated with early minimal residual disease (MRD) findings on day 29 (p<0.0005), and negatively correlated with overall survival (OS) rate (p<0.02) or relapse free survival (RFS) rate (p<0.05). In ECOG trial E2993 for adults with ALL (n=215), we found that PECAM1 mRNA level in ALL patients negatively correlated with OS rate (p=0.0285). These results collectively indicate that inhibitory ITIM-receptors contribute to the course of human ALL disease. To study the role of PECAM1, CD300A and LAIR1 in Ph+ ALL in genetic experiments, we transformed pre-B cells from Pecam1−/−, Cd300a−/− and wildtype mice with BCR-ABL1. Compared to wildtype ALL cells, Pecam1−/− or Cd300a−/− ALL cells showed increased ROS levels. Consistent with higher levels of ROS, the Pecam1−/− and Cd300a−/− ALL cells accumulate p53, p21 and p27 protein, are prone to G0/G1cell cycle arrest and cellular senescence. Colony forming assays revealed that Pecam1- and cd300-deficient leukemia cells also formed 10-fold fewer colonies in methyl cellulose compared to wildtype ALL cells (p<0.0001). For Lair1, we performed genetic loss-of-function experiments by inducible activation of Cre in Lair1fl/fl leukemia cells. Inducible deletion of Lair1 resulted in drastic upregulation of ROS, accumulation of Arf, p53 and p21, cellular senescence and subsequent leukemia cell death. Transplanting Lair1fl/fl ALL cells into NOD-SCID mice, we found that Lair1 deletion resulted in rapid leukemia regression and prolonged survival of recipient mice. Leukemia cell death caused by Lair1 deletion could be rescued by overexpression of the inhibitory phosphatase Ptpn6 (SHP1) indicating that the protective effect of the Lair1 is indeed mediated by ITIM-based recruitment of inhibitory phosphatases. To test whether these findings are also relevant to other subtypes of ALL, we used a model for NRASG12D-driven ALL. BCR-ABL1 (∼25%) and NRAS lesions (∼30%) account for more than half of cases of ALL. Consistent with our findings with BCR-ABL1, NRASG12D Pecam1−/−, Cd300a−/−leukemia cells were prone to G0/G1 cell cycle arrest and cellular senescence (p<0.01). Conclusion: These results indicated that inhibitory ITIM-receptors are critical regulators of oncogenic signaling strength in BCR-ABL1 and NRAS-driven ALL. Deficiency of ITIM-receptor signaling can be rescued by overexpression of the PTPN6 phosphatase. These findings are of particular relevance, because they identify ITIM-receptors and inhibitory phosphatases as members of a fundamentally novel class of therapeutic targets. The concept of pharmacological perturbance of oncogenic signaling equilibrium in leukemia cells by inhibition (e.g. TKI-treatment) or exaggeration of signaling strength (e.g. blockade of ITIM-receptors) may lead to the discovery of multiple additional therapeutic targets and broaden our repertoire of currently available pathways for therapeutic intervention. Disclosures: No relevant conflicts of interest to declare.
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Wang, Xinyu, Jiaojiao Yang, and Xueren Gao. "Identification of key genes associated with lung adenocarcinoma by bioinformatics analysis." Science Progress 104, no. 1 (January 2021): 003685042199727. http://dx.doi.org/10.1177/0036850421997276.
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Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.
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Minchenko, Dmytro O., D. O. Tsymbal, O. P. Yavorovsky, N. V. Solokha, and O. H. Minchenko. "Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles." Endocrine Regulations 51, no. 2 (April 25, 2017): 84–95. http://dx.doi.org/10.1515/enr-2017-0008.
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AbstractObjective. The aim of the present study was to examine the effect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic effects of these nanoparticles.Methods. Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. The expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction.Results. Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was significantly stronger as compared to titanium nitride nanoparticles.Conclusions. The results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable effects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may reflect the genotoxic activities of the studied nanoparticles.
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Gumina, Richard J., Nancy E. Kirschbaum, P. Nagesh Rao, Peter vanTuinen, and Peter J. Newman. "The Human PECAM1 Gene Maps to 17q23." Genomics 34, no. 2 (June 1996): 229–32. http://dx.doi.org/10.1006/geno.1996.0272.
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Leclerc, Michel. "Platelets, Pecam1 Gene, Thromboxane Genes, in Invertebrates." International Journal of Research Studies in Medical and Health Sciences 5, no. 4 (2020): 12–14. http://dx.doi.org/10.22259/ijrsmhs.0504004.
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Корытина, Г. Ф., Ю. Г. Азнабаева, М. Ю. Темнов, Ш. Р. Зулькарнеев, Л. З. Ахмадишина, О. В. Кочетова, Ш. З. Загидуллин, and Т. В. Викторова. "Molecular mechanisms of phenotypic heterogeneity of chronic obstructive pulmonary disease: the role of JAK / STAT-, NFKB1-signaling pathway and inflammatory response molecules." Nauchno-prakticheskii zhurnal «Medicinskaia genetika», no. 8(217) (August 31, 2020): 100–104. http://dx.doi.org/10.25557/2073-7998.2020.08.100-104.
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Хроническая обструктивная болезнь легких (ХОБЛ) - это многофакторное хроническое воспалительное заболевание респираторной системы. Одной из причин трудностей в идентификации маркеров ХОБЛ является фенотипическая гетерогенность. Цель - идентификация новых молекулярных маркеров патогенетических изменений, связанных с фенотипической гетерогеностью ХОБЛ на основе анализа профиля экспрессии генов вовлеченных в развитие иммунного ответа в мононуклеарных клетках периферической крови и анализа ассоциации полиморфных вариантов новых кандидатных генов с развитием ХОБЛ. Проведен сравнительный анализ профиля экспрессии панели 84 генов, кодирующих цитокины, хемокины в PBMC пациентов с различными фенотипами ХОБЛ: с частыми обострениями N=10 и редкими обострениями N=10 и контрольной группе N=10. Для анализа ассоциации использовали образцы ДНК больных ХОБЛ (N=601) и контроля (N=617), методом ПЦР в реальном времени проведен анализ 56 полиморфных локусов генов JAK/STAT-, NFKB1-сигнального путей, кодирующих белки, вовлеченные в реализацию реакций иммунного ответа и воспаления. Выявлены значимые изменения профиля экспрессии ряда генов в группе больных ХОБЛ с частыми обострениями. Впервые получены данные по вкладу полиморфных локусов генов JAK1, JAK3, STAT3, ICAM1, PECAM1, SAA1, NFKB1, IL17A, CCR2, CCR6, CCL8, CRP, CX3CL1, CXCR2, CXCR1, TNFRSF1A, IL20, IL19, в развитие данного заболевания. Выявлены специфические генетические маркеры развития фенотипа с частыми обострениями: CXCR2, TNFRSF1B, CCR6, TNF, IL1B, IL10, JAK3, PECAM1. Установлена ассоциация полиморфных вариантов генов TNFRSF1B, TNFRSF1A, CCL23, CXCR2, JAK1, NFKB1, PECAM1, ICAM1, STAT1, LTA, CD14, CXCL12, CCL20, ADIPOR1 и CX3CR1 с показателями функции внешнего дыхания. Определена взаимосвязь аллельных вариантов генов: IL17A, JAK1, JAK3, NFKB1, CCL5, CCL11, CCL17, CXCL8, TNFRSF1A, CX3CL1, CCL8, CCR6, CXCR2, IL19, IL20 с индексом курения. Chronic obstructive pulmonary disease (COPD) is a multifactorial heterogeneous chronic inflammatory disease of the respiratory system predominantly affecting the lower respiratory pathways and the lung parenchyma. One of the reason for difficulties in identifying of COPD markers is phenotypic heterogeneity. The goal of the study is the identification of new molecular markers of pathogenetic changes associated with phenotypic heterogeneity of COPD based on the analysis of the expression profile of genes involved in the development of the immune response in peripheral blood mononuclear cells and analysis of the association of polymorphic variants of new candidate genes with COPD. Methods: to identify differential gene expression in COPD we performed expression profiling of 84 cytokines and chemokines genes in peripheral blood samples from COPD (N=10 with frequent exacerbation phenotype, N=10 rare exacerbation phenotype) and N=10 smoking controls. RNA was isolated from PBMCs, and gene expression was assessed using RT2 Profiler PCR Arrays «Human Cytokines & Chemokines PCR Array»» (Qiagen, Valencia, CA, USA). 56 SNPs of JAK / STAT-, NFKB1-signaling pathway and inflammatory response molecules genes were genotyped by the real-time polymerase chain reaction (TaqMan assays) in a case-control study (601 COPD patients and 617 controls). Results. Significant changes were revealed in the expression profile of several genes in “frequent exacerbator» COPD phenotype. The results indicate a down-regulation of inflammatory molecules in “frequent exacerbator» COPD phenotype. For the first time, we indicated the contribution of JAK1, JAK3, STAT3, ICAM1, PECAM1, SAA1, NFKB1, IL17A, CCR2, CCR6, CCL8, CRP, CX3CL1, CXCR2, CXCR1, TNFRSF1A, IL20, IL19 genes polymorphisms to COPD. Specific genetic markers of “frequent exacerbator” COPD phenotype have been identified, which are modifiers of COPD progression, including polymorphic loci of the CXCR2, TNFRSF1B, CCR6, TNF, IL1B, IL10, JAK3, PECAM1 genes. A significant genotype-dependent variation of lung function parameters was observed for CXCR2, JAK1, NFKB1, PECAM1, ICAM1, STAT1, LTA, CD14, CXCL12, CCL20, ADIPOR1 and CX3CR1 genes. The relationship of IL17A, JAK1, JAK3, NFKB1, CCL5, CCL11, CCL17, CXCL8, TNFRSF1A, CX3CL1, CCL8, CCR6, CXCR2, IL19, IL20 genes with smoking pack-years was found.
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Chen, Zhengshan, Seyedmehdi Shojaee, Huimin Geng, Jaewoong Lee, Maike Buchner, Lars Klemm, Clifford A. Lowell, et al. "Inhibitory Receptors and Phosphatases Enable Oncogenic Tyrosine Kinase Signaling In B Cell Lineage Leukemia." Blood 122, no. 21 (November 15, 2013): 229. http://dx.doi.org/10.1182/blood.v122.21.229.229.
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Abstract Background B cells are selected at multiple developmental checkpoints for an intermediate level of (pre-) B cell receptor (BCR) signaling strength: either insufficient or hyperactive signaling (e.g. from an autoreactive BCR) results in cell death. Acute lymphoblastic leukemia (ALL) is the most frequent type of cancer in children and typically arises from pre-B cells, a large fraction of which are autoreactive. In ∼25% of patients, ALL is driven by an oncogenic tyrosine kinase (e.g. BCR-ABL1 in Ph+ ALL) and defines the ALL subgroup with the worst clinical outcome. Ph+ ALL cells invariably develop resistance against tyrosine kinase inhibitors (TKI). Here we tested the hypothesis that inherent mechanisms of negative selection to eliminate autoreactive clones with hyperactive pre-BCR signaling are still active in transformed pre-B cells and identified a potential therapeutic target for ALL patients. Results The BCR-ABL1 oncogene mimics a constitutively active pre-BCR and an incremental increase of pre-BCR downstream signaling (ITAM overexpression) was indeed sufficient to induce cell death in Ph+ ALL, but not in normal pre-B cells with low baseline signaling strength. TKI-treatment, while designed to kill leukemia cells, seemingly paradoxically rescued Ph+ ALL cells in this experimental setting. Patient-derived Ph+ ALL cells differ from normal pre-B cells by expression of high levels of ITIM containing inhibitory receptors including PECAM1, CD300A and LAIR1. However, ITAM containing activation receptors like CD79B was absent on the cell surface, and there was point or frame-shift mutation for both CD79A and CD79B. Importantly, high expression levels of ITIM-receptors are predictive of poor outcome in two clinical trials. In the COG trial (P9906; n=207) for children high-risk ALL, mRNA levels of PECAM1, CD300A and LAIR1 at diagnosis positively correlated with early minimal residual disease (MRD) findings on day 29 (p<0.0005), and negatively correlated with overall survival (OS) rate (p<0.02) or relapse free survival (RFS) rate (p<0.05). In the ECOG trial (E2993; n=215) for adults ALL, PECAM1 mRNA level negatively correlated with OS rate (p=0.0285). Genetic studies revealed that Pecam1, Cd300a and Lair1 receptors are critical to calibrate oncogenic signaling strength and prevent excessive tyrosine kinase activity through recruitment of the inhibitory phosphatases Ptpn6 (SHP1) and Inpp5d (SHIP1). Deletion of Pecam1, Cd300a or Lair1 in Ph+ ALL cells caused increased ROS levels, accumulation of p53, p21 and p27 protein, G0/G1cell cycle arrest and cellular senescence. P-STAT5 and p-ERK were increased after Lair1 deletion. Transplant experiments indicated that Lair1 deletion resulted in rapid leukemia regression and prolonged survival of recipient mice. Leukemia cell death caused by Lair1 deletion could be rescued by overexpression of the inhibitory phosphatase Ptpn6 (SHP1) or Inpp5d (SHIP1). Genetic deletion of Ptpn6 and Inpp5d caused cell death in BCR-ABL1 ALL cells but neither in normal pre-B cells with weak baseline signaling, nor myeloid cells (normal and BCR-ABL1-transformed), which -unlike B cells- are not subject to negative selection of auto-reactive clones. To test if these findings are also relevant to other subtypes of ALL, we used a model for NRASG12D-driven ALL. BCR-ABL1 (∼25%) and NRAS lesions (∼30%) account for more than half cases of ALL. Consistently, NRASG12D Pecam1-/-, Cd300a-/- leukemia cells were prone to G0/G1 cell cycle arrest and cellular senescence (p<0.01). Using chimeric PECAM1, CD300A and LAIR1 receptor decoys and a novel small molecule inhibitor of INPP5D (SHIP1), we demonstrate that inhibitory phosphatase signaling represents a potential novel class of therapeutic targets for tyrosine kinase-driven ALL. Conclusion These results indicated that inhibitory receptors and downstream phosphatases are critical regulators of oncogenic signaling strength in tyrosine kinase-driven ALL, and identified ITIM-receptors and phosphatases as members of a potential novel class of therapeutic targets. The concept of pharmacological perturbance of oncogenic signaling equilibrium in leukemia cells by inhibition (e.g. TKI-treatment) or exaggeration of signaling strength (e.g. blockade of ITIM-receptors) may lead to the discovery of multiple additional therapeutic targets and broaden our repertoire of currently available therapeutic intervention. Disclosures: No relevant conflicts of interest to declares.
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Xu, Suowen, Chang Hoon Ha, Weiye Wang, Xiangbin Xu, Meimei Yin, Felix Q. Jin, Michael Mastrangelo, Marina Koroleva, Keigi Fujiwara, and Zheng Gen Jin. "PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling." Cellular Signalling 28, no. 3 (March 2016): 117–24. http://dx.doi.org/10.1016/j.cellsig.2015.12.007.
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Chen, Zhengshan, Seyedmehdi Shojaee, Huimin Geng, Jae-Woong Lee, Maike Buchner, Lars Klemm, Clifford A. Lowell, et al. "Harnessing Negative B Cell Selection to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia." Blood 124, no. 21 (December 6, 2014): 792. http://dx.doi.org/10.1182/blood.v124.21.792.792.
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Abstract Background: B cells are selected for an intermediate level of (pre-) B cell receptor (BCR) signaling strength: attenuation below minimum (e.g. non-functional BCR) or hyperactivation above maximum (e.g. autoreactive BCR) thresholds of signaling strength causes negative selection and cell death. About 25% of B cell acute lymphoblastic leukemia (ALL) is driven by oncogenic tyrosine kinases (e.g. BCR-ABL1 in Ph+ ALL), which mimics constitutively active pre-BCR signaling and defines the ALL subgroup with the worst clinical outcome. Currently more potent tyrosine kinase inhibitors (TKI) are developed for Ph+ ALL to suppress oncogenic signaling below a minimum threshold for survival. However Ph+ ALL cells invariably develop resistance against TKI. Here, we tested the hypothesis that targeted hyperactivation of oncogenic signaling above a maximum threshold will trigger B cell-inherent mechanisms of negative selection and selectively kill Ph+ALL cells. Results: The Ph+ ALL cells don not express a functional pre-BCR and BCR-ABL1 oncogene mimics a constitutively active pre-BCR by phosphorylating SYK, LYN, BTK and PLCg2. An incremental increase of pre-BCR downstream signaling (ITAM or SYK overexpression) was indeed sufficient to induce cell death in Ph+ ALL. TKI-treatment, while designed to kill leukemia cells, seemingly paradoxically rescued Ph+ALL cells in this experimental setting. Ph + ALL cells differ from normal pre-B cells by expression of high levels of ITIM containing inhibitory receptors including PECAM1 (CD31), CD300A and LAIR1. Importantly, high expression levels of ITIM-receptors are predictive of poor outcome in two clinical trials. In the COG trial (P9906; n=207) for children high-risk ALL, mRNA levels of PECAM1, CD300A and LAIR1at diagnosis positively correlated with early minimal residual disease (MRD) findings on day 29 (p<0.0005), and negatively correlated with overall survival (OS) rate (p<0.02) or relapse free survival (RFS) rate (p<0.05). In the ECOG trial (E2993; n=215) for adults ALL, PECAM1 mRNA level negatively correlated with OS rate (p=0.0285). Genetic studies revealed that Pecam1, Cd300a and Lair1 receptors are critical to calibrate pre-BCR signaling strength through recruitment of the inhibitory phosphatases Ptpn6 (SHP1) and Inpp5d (SHIP1). Deletion of Pecam1, Cd300a or Lair1 in Ph+ ALL cells caused increased ROS levels, G0/G1cell cycle arrest, decreased colony formation capacity and cellular senescence. Phosphorylation of pre-BCR downstream molecules (SYK, LYN, BTK and PLCg2) was increased after Lair1 deletion and this hyper-signaling could not be tolerated by Ph+ ALL cells. Lair1 deletion resulted in rapid leukemia regression and prolonged survival of recipient mice in a transplant experiment. Leukemia cell death caused by Lair1-deletion could be rescued by overexpression of the active inhibitory phosphatase Ptpn6 (CD8-SHP1) or Inpp5d (CD8-SHIP1). Genetic deletion of Ptpn6 and Inpp5d caused increased pre-BCR signaling and cell death in BCR-ABL1 ALL cells but not myeloid cells (normal and BCR-ABL1-transformed), which -unlike B cells- are not subject to negative selection of auto-reactive clones. Decreasing pre-BCR signaling by SYK inhibition rescued cell death after Ptpn6- or Inpp5d- deletion. Blocking inhibitory receptors by using chimeric PECAM1, CD300A and LAIR1 receptor decoys inhibited proliferation and caused cell death in Ph+ ALL xenograft cells. More potently, a novel small molecule inhibitor of INPP5D (SHIP1) selectively killed Ph+ ALL xenograft cells through inducing hyper pre-BCR signaling, regardless of TKI resistance. We demonstrate that inhibitory phosphatase signaling represents a potential novel class of therapeutic targets for Ph+ALL. Conclusions: These results indicated that inhibitory receptors and downstream phosphatases are critical regulators of pre-BCR signaling strength in Ph+ ALL, and identified ITIM-receptors and phosphatases as members of a potential novel class of therapeutic targets. The concept of pharmacological perturbance of oncogenic signaling equilibrium in leukemia cells by inhibition (e.g. TKI-treatment) or exaggeration of signaling strength (e.g. blockade of ITIM-receptors) may lead to the discovery of multiple additional therapeutic targets and broaden our repertoire of currently available therapeutic intervention. Disclosures No relevant conflicts of interest to declare.
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Zhu, Zhidong, Yanyun Shen, Yunfeng Chen, Haiming Shi, and Yun Shi. "The exosome of platelet endothelial cell adhesion molecule-1 (PECAM1) protein." Medicine 100, no. 4 (January 29, 2021): e21370. http://dx.doi.org/10.1097/md.0000000000021370.
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Onitsuka, Izumi, Masaki Takeuchi, Tomoya Okabe, Yoshiko Kamiya, Ayami Hirata, Ichiro Yahara, and Atsushi Miyajima. "Two Distinct Precursors of Hematopoietic Stem Cells and Endothelial Progenitors Characterized by the PCLP1 Expression." Blood 106, no. 11 (November 16, 2005): 2274. http://dx.doi.org/10.1182/blood.v106.11.2274.2274.
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Abstract Blood cells and endothelia are believed to arise from their common progenitor hemangioblast. However, it still remains unknown how these lineages develop. Here we report the existence of two distinct precursors for hematopoietic stem cells (HSCs) and endothelial progenitors in murine fetal liver (FL). Podocalyxin-like protein 1 (PCLP1) is a member of the sialomucin family and was shown to be expressed in hemangioblasts in the aorta-gonad-mesonephros region in murine embryo. To further analyze the fates of hematopoietic/endothelial cells, we focused on embryonic day 14.5 (E14.5) FL, since it is a major hematopoietic organ during embryonic period. Based on the PCLP1 expression levels, E14.5 FL cells could be fractionated into four distinct populations. In vitro colony-forming assay and in vivo transplantation analysis revealed that lineage-committed progenitors with colony-forming activities and long-term repopulating hematopoietic stem cells (LTR-HSCs) were in PCLP1neg cells. PCLP1dull cells contained erythroid lineage-committed cells. Interestingly, while PCLP1med cells lacked colony-forming activities, they showed LTR-HSC activity in vivo. To further characterize these cell populations, we cultured them with OP9 stromal cells, since OP9 cells have been used to induce hematopoietic and endothelial lineages from embryonic stem cells. In co-culture with OP9 cells, PCLP1neg cells immediately generated blood cells with colony-forming activity but lacking in vivo hematopoietic activity, indicating that OP9 cells failed to support hematopoietic progenitor/HSCs. However, PCLP1med generated colony-forming hematopoietic progenitors with LTR-HSC activities in the presence of OP9 cells. These results indicated that PCLP1med cells contained stromal cell-dependent immature precursors for HSCs. PCLP1high cells did not express the hematopoietic markers or endothelial cell markers such as PECAM1 and VE-cadherin. However, they formed endothelia-like cell colonies which were highly proliferative and serially transferable in OP9 co-culture. Interestingly, the addition of vascular endothelial growth factor (VEGF) to the culture strongly induced the expression of PECAM1 and VE-cadherin in these colonies. PCLP1high cells contributed to PECAM1+ endothelium in several organs in vivo when transplanted to conditioned neonatal liver. Therefore, PCLP1high cells contained immature precursors for endothelial progenitors. These results indicate that PCLP1 expression levels distinguish previously unrecognized early precursors for HSCs and endothelial progenitors, which are distinct from hemangioblasts.
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Sinitsky, M. Yu, A. V. Tsepokina, A. G. Kutikhin, D. K. Shishkova, and A. V. Ponasenko. "The gene expression signature in endothelial cells exposed to mitomycin C." Biomeditsinskaya Khimiya 67, no. 2 (2021): 130–36. http://dx.doi.org/10.18097/pbmc20216702130.
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The expression of DNA repair (DDB1, ERCC4, ERCC5), leukocyte adhesion (VCAM1, ICAM1, SELE, SELP), endothelial mechanotransduction (KLF4), endothelial differentiation (PECAM1, CDH5, CD34, NOS3), endothelial-to-mesenchymal transition (SNAI1, SNAI2, TWIST1, GATA4, ZEB1, CDH2), scavenger receptors (LOX1, SCARF1, CD36, LDLR, VLDR), antioxidant system (PXDN, CAT, SOD1) and transcription factor (HEY2) genes in primary human coronary (HCAEC) and internal thoracic (HITAEC) arteries endothelial cells exposed to alkylating mutagen mitomycin C (MMC) was studied at two time points — after 6 h of incubation with MMC and after 6 h of the genotoxic load followed by 24 h of incubation in pure culture medium using the quantitative PCR. Immediately after MMC exposure, in the exposed HCAEC and HITAEC a decreased expression of almost all studied genes was noted excepted SNAI, which demonstrated a 4-told increase in its expression compared to the unexposed control. Elimination of MMC from the cultures, an increased expression of the VCAM1, ICAM1, SELE, SNAI2, KLF4 genes and a decreased the mRNA level of the PECAM1, CDH5, CD34, ZEB1, CAT, PXDN genes were observed in both cell lines. In addition, HITAEC cells were characterized by a decreased expression of the SOD1, SCARF1, CD36 genes and an increased expression of the SNAI1 and TWIST1 genes; in HCAEC, an increased mRNA level of the LDLR and VLDLR genes was noted. Thus, MMC-induced genotoxic stress is associated with the endothelial dysfunction.
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Mickael, Michel-Edwar, Norwin Kubick, Pavel Klimovich, Patrick Henckell Flournoy, Irmina Bieńkowska, and Mariusz Sacharczuk. "Paracellular and Transcellular Leukocytes Diapedesis Are Divergent but Interconnected Evolutionary Events." Genes 12, no. 2 (February 10, 2021): 254. http://dx.doi.org/10.3390/genes12020254.
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Infiltration of the endothelial layer of the blood-brain barrier by leukocytes plays a critical role in health and disease. When passing through the endothelial layer during the diapedesis process lymphocytes can either follow a paracellular route or a transcellular one. There is a debate whether these two processes constitute one mechanism, or they form two evolutionary distinct migration pathways. We used artificial intelligence, phylogenetic analysis, HH search, ancestor sequence reconstruction to investigate further this intriguing question. We found that the two systems share several ancient components, such as RhoA protein that plays a critical role in controlling actin movement in both mechanisms. However, some of the key components differ between these two transmigration processes. CAV1 genes emerged during Trichoplax adhaerens, and it was only reported in transcellular process. Paracellular process is dependent on PECAM1. PECAM1 emerged from FASL5 during Zebrafish divergence. Lastly, both systems employ late divergent genes such as ICAM1 and VECAM1. Taken together, our results suggest that these two systems constitute two different mechanical sensing mechanisms of immune cell infiltrations of the brain, yet these two systems are connected. We postulate that the mechanical properties of the cellular polarity is the main driving force determining the migration pathway. Our analysis indicates that both systems coevolved with immune cells, evolving to a higher level of complexity in association with the evolution of the immune system.
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Boissard, Frederic, Jean Jacques Fournie, Loic Ysebaert, and Mary Poupot. "Lymphocyte Function-Associated Antigen 3 (LFA-3): Key Factor of the Interactions Between Nurse-like-Cells and B Leukemic Cells from Chronic Lymphocytic Leukemia." Blood 124, no. 21 (December 6, 2014): 1955. http://dx.doi.org/10.1182/blood.v124.21.1955.1955.
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Abstract Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western Countries. This pathology is characterized by an accumulation of monoclonal, non-functional and mature CD5+ CD19+ leukemic B-cells (CLL cells) in lymph nodes, peripheral blood and bone marrow. Despite a high resistance to the in vivo apoptosis, CLL cells die spontaneously in vitro due to a lack in ex vivo conditions of sustaining cells and factors from their microenvironment such as stroma cells (Lagneaux L et al, Blood. 1998; 91:2387-2396), follicular dendritic cells or Nurse-Like-Cells (NLC) (Burger JA et al, Blood. 2000; 96:2655-2663). NLC are derived from CD14+ cells in contact with CLL cells in vitro (Tsukada N et al, Blood. 2002; 99:1030-1037) and were found in lymph nodes of CLL patients (Ysebaert L et al, Leuk Lymphoma. 2011; 52:1404-1406). NLC were shown to have a Tumour Associated Macrophages phenotype and gene expression profile. These cells have been first described to be essential for in vitro CLL cells survival partially through the production of soluble factors such as CXCL12 (Burger JA et al, Blood. 2000; 96:2655-2663), CCL3 and CCL4 (Burger JA et al, Blood. 2009; 113:3050-3058). Thus, other mechanisms are required for CLL cells survival. Indeed, we showed that contact of CLL cells with NLC was necessary to protect CLL cells from the in vitro apoptosis. We then investigated the mechanism of these interactions at a molecular level. We also determined their influences on the in vitro CLL cells survival and on the NLC-induced chemoresistance. We observed close and strong interactions evaluated by the measurement of trogocytosis from NLC to CLL cells. Trogocytosis is an active phenomenon with transfer of membrane fragments from one cell to another. We showed that NLC/CLL cells trogocytosis is dependant to actin polymerization and SRC phosphorylation. To find possible couples of molecules involved in this contact, we compared different transcriptomic data from NLC, monocyte, CLL cells and B lymphocytes. We highlighted potential couples of molecules and confirmed their expression on CLL cells and NLC by flow cytometry analysis. Finally, we obtained 3 couples probably implicated: Lymphocyte Function-Associated Antigen 3 (LFA-3)/CD2, Platelet/Endothelial Cell Adhesion Molecule 1 (PECAM1)/CD38 and Intercellular Adhesion Molecule 1 (ICAM-1)/LFA-1. Antibody blocking strategies revealed that LFA-3, which is up-regulated in CLL cells compared to healthy donors B lymphocytes, was necessary for the interaction between CLL cells/NLC when PECAM1, ICAM-1 and their co-partners were not essential (figure 1). Furthermore, this contact, through LFA-3, induced Akt phosphorylation but not ERK1/2 phosphorylation in CLL cells. Finally, we showed that LFA-3 and its receptor CD2 are necessary to the rescue of CLL cells by NLC (figure 2). To go further, we tested the chemoprotective effect of NLC on CLL cells. We showed that NLC slightly protect CLL cells against bendamustin but not against rituximab, dasatinib or ibrutinib. We hypothesized that the contact through LFA-3 could be involved in this chemoresistance. However, we did not observed a significant effect of the combination of bendamustin and LFA-3-blocking compared to bendamustin alone suggesting that this chemoprotection of CLL cells by NLC involved another pathway. Altogether, our results indicate that overexpression of LFA-3 by CLL cells and its critical implication in the interaction with NLC might be a new therapeutic target in CLL to disturb the interaction of CLL cells with their microenvironment. Figure 1: LFA-3 blocking but not ICAM-1 and PECAM1 decrease trogocytosis from NLC to CLL cells. a) Representative overlay of an experiment of trogocytosis from NLC to CLL cells treated or not by a blocking antibody anti-LFA-3. b) Representative overlay of an experiment of trogocytosis from NLC to CLL cells treated or not by a blocking antibody anti-ICAM-1. c) Representative overlay of an experiment of trogocytosis from NLC to CLL cells treated or not by a blocking antibody anti-PECAM1. Figure 1:. LFA-3 blocking but not ICAM-1 and PECAM1 decrease trogocytosis from NLC to CLL cells. a) Representative overlay of an experiment of trogocytosis from NLC to CLL cells treated or not by a blocking antibody anti-LFA-3. b) Representative overlay of an experiment of trogocytosis from NLC to CLL cells treated or not by a blocking antibody anti-ICAM-1. c) Representative overlay of an experiment of trogocytosis from NLC to CLL cells treated or not by a blocking antibody anti-PECAM1. Figure 2: LFA-3 is critical for the survival of CLL cells in contact with NLC. Figure 2:. LFA-3 is critical for the survival of CLL cells in contact with NLC. Disclosures No relevant conflicts of interest to declare.
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P.T, Adegun. "Mapping Angiogenic Cells CD31 (PECAM1) and CD45 in PCa and BPH Biopsies." Journal of Cancer Research and Experimental Oncology 5, no. 1 (November 30, 2013): 1–7. http://dx.doi.org/10.5897/jcreo2013.0101.
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Berger, Sanne S., Louise Turner, Christian W. Wang, Jens E. V. Petersen, Maria Kraft, John P. A. Lusingu, Bruno Mmbando, et al. "Plasmodium falciparum Expressing Domain Cassette 5 Type PfEMP1 (DC5-PfEMP1) Bind PECAM1." PLoS ONE 8, no. 7 (July 9, 2013): e69117. http://dx.doi.org/10.1371/journal.pone.0069117.
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Bianchi, María S., Stefanía Bianchi, Andrés Hernado-Insúa, Leandro M. Martinez, Néstor Lago, Carlos Libertun, Norma A. Chasseing, Alejandro D. Montaner, and Victoria A. Lux-Lantos. "Proposed mechanisms for oligonucleotide IMT504 induced diabetes reversion in a mouse model of immunodependent diabetes." American Journal of Physiology-Endocrinology and Metabolism 311, no. 2 (August 1, 2016): E380—E395. http://dx.doi.org/10.1152/ajpendo.00104.2016.
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Type 1 diabetes (T1D) originates from autoimmune β-cell destruction. IMT504 is an immunomodulatory oligonucleotide that increases mesenchymal stem cell cloning capacity and reverts toxic diabetes in rats. Here, we evaluated long-term (20 doses) and short-term (2–6 doses) effects of IMT504 (20 mg·kg−1·day−1 sc) in an immunodependent diabetes model: multiple low-dose streptozotocin-injected BALB/c mice (40 mg·kg−1·day−1 ip for 5 consecutive days). We determined blood glucose, glucose tolerance, serum insulin, islet morphology, islet infiltration, serum cytokines, progenitor cell markers, immunomodulatory proteins, proliferation, apoptosis, and islet gene expression. IMT504 reduced glycemia, induced β-cell recovery, and impaired islet infiltration. IMT504 induced early blood glucose decrease and infiltration inhibition, increased β-cell proliferation and decreased apoptosis, increased islet indoleamine 2,3-dioxygenase (IDO) expression, and increased serum tumor necrosis factor and interleukin-6 (IL-6). IMT504 affected islet gene expression; preproi nsulin-2, proglucagon, somatostatin, nestin, regenerating gene-1, and C-X-C motif ligand-1 cytokine ( Cxcl1) increased in islets from diabetic mice and were decreased by IMT504. IMT504 downregulated platelet endothelial cell adhesion molecule- 1 ( Pecam1) in islets from control and diabetic mice, whereas it increased regenerating gene-2 ( Reg2) in islets of diabetic mice. The IMT504-induced increase in IL-6 and islet IDO expression and decreased islet Pecam1 and Cxcl1 mRNA expression could participate in keeping leukocyte infiltration at bay, whereas upregulation of Reg2 may mediate β-cell regeneration. We conclude that IMT504 effectively reversed immunodependent diabetes in mice. Corroboration of these effects in a model of autoimmune diabetes more similar to human T1D could provide promising results for the treatment of this disease.
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Boc, Vinko, Mojca Božic Mijovski, Maja Pohar Perme, and Ales Blinc. "Diabetes and smoking are more important for prognosis of patients with peripheral arterial disease than some genetic polymorphisms." Vasa 48, no. 3 (May 1, 2019): 229–35. http://dx.doi.org/10.1024/0301-1526/a000766.
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Abstract. Background: The role of genetic polymorphisms in peripheral arterial disease (PAD) is incompletely understood. We tested whether selected single nucleotide polymorphisms (SNPs) were associated with PAD and with adverse events in an observational study cohort. Also, the role of diabetes and smoking was studied. Patients and methods: 742 patients with PAD and 713 age- and gender-matched control subjects were subjected to yearly physical and laboratory investigations and were managed for 5 years according to the European guidelines on cardiovascular disease prevention. The occurrence of all-cause death, cardiovascular death, non-fatal myocardial infarction, ischemic stroke or critical limb ischemia (major events) and revascularization procedures (minor events) was recorded. In 655 patients with PAD and 612 control subjects the following SNPs were determined: rs1466408, rs13428968 and rs12803 of NR4A2 gene, rs10499563 of IL6 gene, rs668 and rs12953 of PECAM1 gene, and rs10861032 of Chr12 locus. Results: The distribution of selected SNPs did not differ between patients with PAD and control subjects, and neither between subjects with or without major adverse events. In contrast, diabetes and smoking affected survival and event-free survival. Among patients with PAD, diabetes doubled the hazard ratio (HR) for cardiovascular death and smoking doubled the HR for death or major event. The 5-year survival of diabetics with PAD was 0.80 (CI 0.75–0.85) and of non-diabetics with PAD 0.87 (CI 0.84–0.90), p = 0.045. The 5-year survival of active smokers with PA D was 0.80 (CI 0.75–0.62), of former smokers 0.83 (CI 0.79–0.88), and of never-smokers 0.89 (CI 0.86–0.93), p = 0.024. Conclusions: SNPs of NR4A2, IL6, PECAM1 and Chr12 were not associated with PAD or with major adverse events. However, diabetes and smoking were associated with worse survival and event-free survival in patients with PAD.
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Sun, Xiaogang, Shuhong Huang, Xin Wang, Xiaohua Zhang, and Xin Wang. "CD300A promotes tumor progression by PECAM1, ADCY7 and AKT pathway in acute myeloid leukemia." Oncotarget 9, no. 44 (January 11, 2018): 27574–84. http://dx.doi.org/10.18632/oncotarget.24164.
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Xie, Y., and W. A. Muller. "Assignment of PECAM1 to human chromosome bands 17q22→q23 by in situ hybridization." Cytogenetic and Genome Research 74, no. 1-2 (1996): 156. http://dx.doi.org/10.1159/000134406.
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Etich, Julia, Vera Bergmeier, Christian Frie, Sandra Kreft, Lena Bengestrate, Sabine Eming, Cornelia Mauch, et al. "PECAM1+/Sca1+/CD38+ Vascular Cells Transform into Myofibroblast-Like Cells in Skin Wound Repair." PLoS ONE 8, no. 1 (January 4, 2013): e53262. http://dx.doi.org/10.1371/journal.pone.0053262.
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Leclerc, Michel. "Evidence of Cxcr4 Gene, Pecam1 Gene, Icam1 Gene, from Cells Showing the Antigen, in Invertebrates." International Journal of Research Studies in Medical and Health Sciences 5, no. 4 (2020): 29–30. http://dx.doi.org/10.22259/ijrsmhs.0504008.
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Terashima, Masanori, Wataru Ichikawa, Atsushi Ochiai, Koji Kitada, Issei Kurahashi, Sinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura, and Mitsuru Sasako. "Association of gene expressions of TOP2A, GGH, and PECAM1 with hematogenous, lymph-node, and peritoneal recurrence in patients with stage II/III gastric cancer enrolled in the ACTS-GC study." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 4019. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.4019.
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4019 Background: Exploratory biomarker analysis was conducted to identify factors related to relapse sites in the ACTS-GC study, a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients (pts) with stage II/III gastric cancer. Methods: Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 pts (78.3%), and 63 genes involved in pyrimidine metabolic pathway, growth factor signaling pathway, apoptosis, DNA repair, etc., were analyzed by quantitative RT-PCR after TaqMan assay-based pre-amplification. Gene expression levels were normalized to the geometric mean expressions of GAPDH, ACTB, and RPLP0, used as reference genes. The expression of each gene was categorized as lower or higher than the median value. The impact of gene expression on relapse site was analyzed using the 5-year relapse-free survival (RFS) data of the ACTS-GC. Results: Among the 829 pts, hematogenous, lymph-node, and peritoneal recurrence developed in 72, 105, and 138 pts, respectively. The hazard ratios (HR) (S-1 vs. surgery alone) were 0.79 (95%CI, 0.54-1.16) for hematogenous, 0.51 (95%CI, 0.31-0.82) for lymph-node, and 0.60 (95%CI, 0.42-0.84) for peritoneal recurrence. Among 63 screened genes, topoisomerase II alpha (TOP2A), gamma-glutamyl hydrolase (GGH), and platelet/endothelial cell adhesion molecule 1 (PECAM1) most strongly correlated with hematogenous, lymph-node, and peritoneal recurrence, respectively. Hematogenous RFS was significantly worse in TOP2A high pts than in low pts (HR, 2.35; 95% CI, 1.55-3.57). Lymph-node RFS was significantly worse in GGH high pts than in low pts (HR, 1.87; 95% CI, 1.13-3.08). Likewise, peritoneal RFS was significantly worse in PECAM1high pts than in low pts (HR, 2.37: 95% CI, 1.65-3.41). These factors were independent and stronger risk factors than tumor histological type on multivariate analysis. Conclusions: Expression levels of the TOP2A, GGH, and PECAM1 genes in primary tumors are respectively linked to high risks of hematogenous, lymph-node, and peritoneal recurrence in pts with stage II/III gastric cancer.
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Xu, Yingying, Deyang Kong, Zhongtang Li, Lingling Qian, Junchao Li, and Chunbo Zou. "Screening and identification of key biomarkers of papillary renal cell carcinoma by bioinformatic analysis." PLOS ONE 16, no. 8 (August 6, 2021): e0254868. http://dx.doi.org/10.1371/journal.pone.0254868.
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Background Papillary renal cell carcinoma (PRCC) is the most common type of renal cell carcinoma after clear cell renal cell carcinoma (ccRCC). Its pathological classification is controversial, and its molecular mechanism is poorly understood. Therefore, the identification of key genes and their biological pathways is of great significance to elucidate the molecular mechanisms of PRCC occurrence and progression. Methods The PRCC-related datasets GSE7023, GSE48352 and GSE15641 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Cytoscape and STRING were used to construct the protein-protein interaction network (PPI) and perform module analysis to identify hub genes and key pathways. A heatmap of hub genes was constructed using the UCSC cancer genomics browser. Overall survival and recurrence-free survival of patients stratified by the expression levels of hub genes were analysed using Kaplan-Meier Plotter. The online database UALCAN was applied to analyse gene expression based on tissue type, stage, subtype and race. Results A total of 214 DEGs, specifically, 205 downregulated genes and 9 upregulated genes, were identified. The DEGs were mainly enriched in angiogenesis, kidney development, oxidation-reduction process, metabolic pathways, etc. The 17 hub genes identified were mainly enriched in the biological processes of angiogenesis, cell adhesion, platelet degranulation, and leukocyte transendothelial migration. Survival analysis showed that EGF, KDR, CXCL12, REN, PECAM1, CDH5, THY1, WT1, PLAU and DCN might be related to the carcinogenesis, metastasis or recurrence of PRCC. UALCAN analysis showed that low expression of PECAM1 and PLAU in PRCC tissues was related to stage, subtype and race. Conclusions The DEGs and hub genes identified in the present study provide insight into the specific molecular mechanisms of PRCC occurrence and development and may be potential molecular markers and therapeutic targets for the accurate classification and efficient diagnosis and treatment of PRCC.
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Yatsula, B., C. Galvao, M. McCrann, and A. S. Perkins. "Assessment of F-MuLV-induced tumorigenesis reveals new candidate tumor genes including Pecam1, St7, and Prim2." Leukemia 20, no. 1 (November 24, 2005): 162–65. http://dx.doi.org/10.1038/sj.leu.2404034.
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Tanaka, Tetsuya S. "Transcriptional heterogeneity in mouse embryonic stem cells." Reproduction, Fertility and Development 21, no. 1 (2009): 67. http://dx.doi.org/10.1071/rd08219.
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The embryonic stem (ES) cell is a stem cell derived from early embryos that can indefinitely repeat self-renewing cell division cycles as an undifferentiated cell in vitro and give rise to all specialised cell types in the body. However, manipulating ES cell differentiation in vitro is a challenge due to, at least in part, heterogeneous gene induction. Recent experimental evidence has demonstrated that undifferentiated mouse ES cells maintained in culture exhibit heterogeneous expression of Dppa3, Nanog, Rex1, Pecam1 and Zscan4 as well as genes (Brachyury/T, Rhox6/9 and Twist2) normally expressed in specialised cell types. The Nanog-negative, Rex1-negative or T-positive ES cell subpopulation has a unique differentiation potential. Thus, studying the mechanism that generates ES cell subpopulations will improve manipulation of ES cell fate and help our understanding of the nature of embryonic development.
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Chen, Zhengshan, Huimin Geng, Clifford A. Lowell, Arthur Weiss, Stephen P. Hunger, Ari Melnick, and Markus Muschen. "Targeted Activation of B Cell Autoimmunity Checkpoints in Acute Lymphoblastic Leukemia." Blood 126, no. 23 (December 3, 2015): 3716. http://dx.doi.org/10.1182/blood.v126.23.3716.3716.
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Abstract Background: Unlike other cell types, B cells are selected for an intermediate level of signaling strength. Critical survival and proliferation signals emanate from the B cell receptor (BCR): If B-cells fail to express a functional BCR, signaling output is too weak, resulting in "death by neglect". If the BCR binds to ubiquitous self-antigen, BCR signals are exceedingly strong. Both attenuation below minimum (non-functional BCR; death by neglect) and hyperactivation above maximum (autoreactive BCR) thresholds of signaling strength trigger negative selection and cell death. Rationale: Unlike any other types of cancer, we recently discovered that pre-B acute lymphoblastic leukemia (ALL) cells are bound by the same rules that also govern normal B cell selection. The oncogenic BCR-ABL1 tyrosine kinase mimics active pre-BCR signaling in Ph+ acute lymphoblastic leukemia which defines the ALL subgroup with the worst clinical outcome. Current therapy approaches are largely focused on the development of more potent tyrosine kinase inhibitors (TKI) to suppress oncogenic signaling. However resistance to TKI is developed invariably. Here, we test the hypothesis that targeting hyperactivation above a maximum threshold will selectively kill Ph+ ALL cells through a mechanism that is functionally equivalent to removal of self-reactive B cells. Results: ALL typically originates from pre-B cells that critically depend on survival signals emanating from a functional pre-BCR. Despite their pre-B cell origin, Ph+ ALL cells lack expression of pre-BCR signaling chains Iga and Igb, indicating lack of a functional pre-BCR. Reconstitution of Iga and Igb was indeed sufficient to induce cell death in BCR-ABL1 ALL. TKI-treatment, while designed to kill leukemia cells, seemingly paradoxically rescued Ph+ ALL cells in this experimental setting. These findings suggest that Ph+ ALL are uniquely sensitive to even incremental increases of pre-BCR signaling. Consistent with this concept, patient-derived Ph+ ALL cells express high levels of inhibitory surface receptors PECAM1, CD300A and LAIR1 that recruit and activate phosphatases SHP1 and SHIP1, which terminate pre-BCR signaling. Importantly, high expression levels of these surface receptors were strong predictors of poor outcome of patients with ALL in two clinical trials, including both pediatric and adult ALL patients. Genetic studies revealed that Pecam1, Cd300a and Lair1 were critical to calibrate pre-BCR signaling strength through recruitment of the inhibitory phosphatases SHP1 and SHIP1. Genetic deletion of Lair1, Ptpn6 or Inpp5d in BCR-ABL1 transformed ALL caused cell death in vitro and in vivo through hyperactivation of pre-BCR signaling. Testing various components of proximal pre-BCR signaling, we found that an incremental increase of SYK tyrosine kinase activity was required and sufficient to induce cell death. Hyperactive SYK was functionally equivalent to acute activation of an autoreactive BCR on ALL cells. Despite oncogenic transformation, this basic mechanism of negative selection was still functional in Ph+ ALL cells. Using chimeric PECAM1, CD300A and LAIR1 receptor decoys and a novel small molecule inhibitor of SHIP1, we demonstrated that pharmacological hyperactivation of pre-BCR signaling and engagement of negative B cell selection represents a promising new strategy to overcome drug-resistance in human Ph+ ALL. Conclusion: These results indicated that inhibitory receptors and downstream phosphatases are critical regulators of pre-BCR signaling strength in Ph+ ALL, and identified targeting hyperactivation of pre-BCR signaling as a potential novel class of therapeutic strategy. Disclosures No relevant conflicts of interest to declare.
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Entin, Igor, Shmuel Yaccoby, Wen Zhining, John Shaughnessy, Bart Barlogie, and Joshua Epstein. "Myeloma Cell Interaction with Osteoclasts and Mesenchymal Stem Cells Reveals Genes Associated with Post Relapse Survival." Blood 116, no. 21 (November 19, 2010): 2957. http://dx.doi.org/10.1182/blood.v116.21.2957.2957.
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Abstract Abstract 2957 Myeloma is intimately associated with osteolytic bone disease, resulting from myeloma cells' interactions with osteoclasts and osteoblasts and their progenitors, and is dependent on the changes it induces in bone metabolism for progression. Myeloma cell dependence on the bone marrow microenvironment is also evident experimentally, where interaction of primary myeloma plasma cells (MMPC) with osteoclasts (OC) and with mesenchymal stem cells (MSC) support the survival of primary myeloma cells. To understand the molecular mechanisms associated with the survival of MMPC, we used Acuity 4 software to analyze Affymetrix U133 Plus2 chip data and identify changes in gene expression in induced MMPC freshly isolated from 8 patients by interaction with OC and from 8 additional patients with MSC. Expression by MMPC of 675 genes was changed following interaction with OC; 552 genes were upregulated and 123 down regulated. Expression of 296 genes was changed in MSC co cultures (161 upregulated, 135 down regulated). Comparison of the genes whose expression was similarly changed in both co culture systems identified 72 probesets, representing 58 genes, that were commonly changed; 33 were upregulated and 25 down regulated. Ingenuity Pathway Analysis assigned 54 of the 58 genes to 4 distinguished networks of interrelated genes with high probability scores. We next tested the hypothesis that the expression of genes whose expression was commonly changed in the co culture systems has clinical significance. To accomplish this, we used gene expression data available on 127 relapsed patients who had been uniformly treated on our Total Therapy 2 protocol, and for whom gene expression (GEP) data at first relapse (RL) were available. 71 of these patients also had pre treatment (BL) GEP data; for these 71 patients we calculated change in expression of the 72 probesets as the ratio of RL/BL expression signal. We identified 7 genes whose expression changes were significantly (p≤0.05) associated with survival after relapse: These genes were, in order of significance: CCNE2, PECAM1, KLHL21, ICAM1, PLAU, ANPEP, and DUSP1, with p-values ranging from 0.017 to 0.05. Up regulation of PECAM1, ANPEP, DUSP1, and down regulation of CCNE2, KLHL21, ICAM1, and PLAU were associated with longer survival. We further determined whether expression level of these 72 probesets at relapse, defined by signal intensity, correlated with post relapse survival of the 127 patients; 18 genes were significantly (p<0.05)associated with survival: of these, the top 6 genes, sorted in order of p-values of the univariate test were CCNE2 (p<1e-7, HR, defined as ratio of hazard for a twofold increased in signal) =1.83), PECAM1 (p=2e-7, HR=0.64), FOSB (p=2.3e-6, HR=0.76), HMOX1 (p=8.2e-5; HR=0.72), CISH (p<0.0002, HR=0.76), and JUN (p=0.0008, HR=0.78). Eleven other genes associated with survival had p values ranging from <0.002 to 0.047. Although not the purpose of this work, we also tested the ability of the 72 probesets to predict survival with each probeset dichotomized at the median. Using the BRB Array tool, we found that 17 genes predict post relapse survival with at p=0.01 based on log-rank tests in 100 permutations. The percent variability explained by the first 2 principal components = 42.5. Using co culture of myeloma cells with osteoclasts and MSC we identified MMPC genes whose expression is associated with the survival of patients after relapse. These genes define potential targets for improving the survival of relapsed myeloma patients. Disclosures: No relevant conflicts of interest to declare.
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Nelissen, Inge, Pierre Fiten, Koen Vandenbroeck, Jan Hillert, Tomas Olsson, Maria Giovanna Marrosu, and Ghislain Opdenakker. "PECAM1, MPO and PRKAR1A at chromosome 17q21-q24 and susceptibility for multiple sclerosis in Sweden and Sardinia." Journal of Neuroimmunology 108, no. 1-2 (August 2000): 153–59. http://dx.doi.org/10.1016/s0165-5728(00)00293-9.
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Qu, Y. Y., W. H. Xu, X. Tian, Y. Zhu, H. L. Zhang, D. Ye, and A. H. T. M. J. An Wai Er. "Screening, identification and validation of CCND1 and PECAM1/CD31 in predicting prognosis for renal cell carcinoma patients." European Urology Open Science 19 (July 2020): e1947-e1948. http://dx.doi.org/10.1016/s2666-1683(20)33911-2.
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Tai, Lung-kuo, Qinlei Zheng, Shi Pan, Zheng-Gen Jin, and Bradford C. Berk. "Flow Activates ERK1/2 and Endothelial Nitric Oxide Synthase via a Pathway Involving PECAM1, SHP2, and Tie2." Journal of Biological Chemistry 280, no. 33 (June 28, 2005): 29620–24. http://dx.doi.org/10.1074/jbc.m501243200.
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Guo, Feng, Chenchen Si, Mingjuan Zhou, Jingwen Wang, Dan Zhang, Peter C. K. Leung, Bufang Xu, and Aijun Zhang. "Decreased PECAM1-mediated TGF-β1 expression in the mid-secretory endometrium in women with recurrent implantation failure." Human Reproduction 33, no. 5 (March 30, 2018): 832–43. http://dx.doi.org/10.1093/humrep/dey022.
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Yang, Jian-Feng, Shen-Nan Shi, Wen-Hao Xu, Yun-Hua Qiu, Jin-Zhou Zheng, Kui Yu, Xiao-Yun Song, et al. "Screening, identification and validation of CCND1 and PECAM1/CD31 for predicting prognosis in renal cell carcinoma patients." Aging 11, no. 24 (December 18, 2019): 12057–79. http://dx.doi.org/10.18632/aging.102540.
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Qing, Zhu, Matyas Sandor, Zsuzsa Radvany, Diane Sewell, Andras Falus, Dan Potthoff, William A. Muller, and Zsuzsa Fabry. "Inhibition of Antigen-Specific T Cell Trafficking into the Central Nervous System via Blocking PECAM1/CD31 Molecule." Journal of Neuropathology & Experimental Neurology 60, no. 8 (August 2001): 798–807. http://dx.doi.org/10.1093/jnen/60.8.798.
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Sanfilippo, Cristina, Paola Castrogiovanni, Rosa Imbesi, and Michelino Di Rosa. "CHI3L2 Expression Levels Are Correlated with AIF1, PECAM1, and CALB1 in the Brains of Alzheimer’s Disease Patients." Journal of Molecular Neuroscience 70, no. 10 (July 23, 2020): 1598–610. http://dx.doi.org/10.1007/s12031-020-01667-9.
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Luo, Xuan, Lei Feng, WenBo Xu, XueJing Bai, and MengNa Wu. "Weighted gene co-expression network analysis of hub genes in lung adenocarcinoma." Evolutionary Bioinformatics 17 (January 2021): 117693432110098. http://dx.doi.org/10.1177/11769343211009898.
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Lung adenocarcinoma (LUAD) is a tumor with high incidence. This study aimed to identify the central genes of LUAD. LUAD were analyzed by weighted gene co-expression network (WGCNA), and differentially expressed genes (DEGs) were identified. Samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases and included 515 LUAD samples and 347 normal samples. The WGCNA algorithm generated a total of 10 modules. The top 2 modules (MEturquoise and MEblue) with the highest correlation to LUAD were selected. Ten Hub genes (IL6, CDH1, PECAM1, SPP1, THBS1, HGF, SNCA, CDH5, CAV1, and DLC1) were screened in the intersecting genes of DEGs and WGCNA (MEturquoise and MEblue). Only SPP1 was correlated with LUAD poor survival, indicating that SPP1 may be a key Hub gene for LUAD. The competing endogenous RNA (ceRNA) network was constructed to analyze the regulatory relationship of Hub genes, and SPP1 may be directly regulated by 4 microRNAs (miRNAs) and indirectly regulated by 49 long noncoding RNAs (lncRNAs).
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Guo, Feng, Chenchen Si, Mingjuan Zhou, Jingwen Wang, Dan Zhang, Peter C. K. Leung, Bufang Xu, and Aijun Zhang. "Corrigendum. Decreased PECAM1-mediated TGF-β1 expression in the mid-secretory endometrium in women with recurrent implantation failure." Human Reproduction 35, no. 1 (November 26, 2019): 253. http://dx.doi.org/10.1093/humrep/dez236.
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Moore, Eli D., Gary W. Williams, Marco A. Palma, and Leonardo Lombardini. "Effectiveness of State-level Pecan Promotion Programs: The Case of the Texas Pecan Checkoff Program." HortScience 44, no. 7 (December 2009): 1914–20. http://dx.doi.org/10.21273/hortsci.44.7.1914.
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The Texas Pecan Board was established in 1998 to administer the Texas Pecan Checkoff Program and is financed through a half cent per pound assessment on grower pecan sales. The Board spends the assessment collections on a variety of advertising campaigns in an attempt to expand demand for Texas pecans and to increase the welfare of Texas pecan growers. This article presents an evaluation of the economic effectiveness of the Texas Pecan Checkoff Program in expanding sales of Texas pecans. First, the effects of Texas Pecan Board promotion on sales of all Texas pecans are determined using the ordinary least squares estimator followed by a test for differential effects of Texas Pecan Board promotion activities on sales of improved and native Texas pecan varieties using the seemingly unrelated regression estimator. The analysis indicates that the Texas Pecan Checkoff Program has effectively increased sales of improved varieties of Texas pecans but has had no statistically measurable impact on sales of native varieties of Texas pecans. A benefit–cost analysis determines that $35.0 in additional sales revenues are generated for every dollar invested in promotion, indicating that the Texas pecan promotion program has been financially successful. The per unit return is large but on a very few dollars available for investment in promotion implying the need for more investment for more meaningful returns.
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Lillywhite, Jay M., Jennifer E. Simonsen, and Richard J. Heerema. "U.S. Consumer Purchases and Nutritional Knowledge of Pecans." HortTechnology 24, no. 2 (April 2014): 222–30. http://dx.doi.org/10.21273/horttech.24.2.222.
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The U.S. pecan (Carya illinoinensis) industry is important to the country in both economic and cultural terms. Although the industry has expanded its export markets considerably, domestic pecan consumption has remained relatively flat. Expanding a domestic market is an important risk management strategy. To diversify, industry stakeholders may need to focus effort on growing domestic demand for pecans and pecan products, yet relatively little is known about U.S. pecan consumers because the majority of available information is garnered from supply side (production) data. This study used a web-based panel survey of 1009 U.S. food consumers to explore the demographics of pecan consumers, gauge their current tree nut nutrition knowledge, and examine the preferences surrounding their pecan purchases. Almost three-quarters (74%) of survey respondents consume pecans; demographic differences were observed between respondents who consume pecans and those who do not. Respondents’ knowledge of general and tree nut nutrition concepts varied. Respondents most frequently purchase pecans from a grocery store, buy them shelled as a raw ingredient for baking/cooking, and consume pecans four to six times per year.
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Morin-Kensicki, Elizabeth M., Brian N. Boone, Michael Howell, Jaclyn R. Stonebraker, Jeremy Teed, James G. Alb, Terry R. Magnuson, Wanda O'Neal, and Sharon L. Milgram. "Defects in Yolk Sac Vasculogenesis, Chorioallantoic Fusion, and Embryonic Axis Elongation in Mice with Targeted Disruption of Yap65." Molecular and Cellular Biology 26, no. 1 (January 1, 2006): 77–87. http://dx.doi.org/10.1128/mcb.26.1.77-87.2006.
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ABSTRACT YAP is a multifunctional adapter protein and transcriptional coactivator with several binding partners well described in vitro and in cell culture. To explore in vivo requirements for YAP, we generated mice carrying a targeted disruption of the Yap gene. Homozygosity for the Yap tm1Smil allele (Yap −/− ) caused developmental arrest around E8.5. Phenotypic characterization revealed a requirement for YAP in yolk sac vasculogenesis. Yolk sac endothelial and erythrocyte precursors were specified as shown by histology, PECAM1 immunostaining, and alpha globin expression. Nonetheless, development of an organized yolk sac vascular plexus failed in Yap −/− embryos. In striking contrast, vasculogenesis proceeded in both the allantois and the embryo proper. Mutant embryos showed patterned gene expression domains along the anteroposterior neuraxis, midline, and streak/tailbud. Despite this evidence of proper patterning and tissue specification, Yap −/− embryos showed developmental perturbations that included a notably shortened body axis, convoluted anterior neuroepithelium, caudal dysgenesis, and failure of chorioallantoic fusion. These results reveal a vital requirement for YAP in the developmental processes of yolk sac vasculogenesis, chorioallantoic attachment, and embryonic axis elongation.
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Hansen, Marten, Sabrina Zeddies, Marjolein Meinders, Franca di Summa, Ewa Rollmann, Floris P. J. van Alphen, Arjan J. Hoogendijk, et al. "The RNA-Binding Protein ATXN2 is Expressed during Megakaryopoiesis and May Control Timing of Gene Expression." International Journal of Molecular Sciences 21, no. 3 (January 31, 2020): 967. http://dx.doi.org/10.3390/ijms21030967.
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Megakaryopoiesis is the process during which megakaryoblasts differentiate to polyploid megakaryocytes that can subsequently shed thousands of platelets in the circulation. Megakaryocytes accumulate mRNA during their maturation, which is required for the correct spatio-temporal production of cytoskeletal proteins, membranes and platelet-specific granules, and for the subsequent shedding of thousands of platelets per cell. Gene expression profiling identified the RNA binding protein ATAXIN2 (ATXN2) as a putative novel regulator of megakaryopoiesis. ATXN2 expression is high in CD34+/CD41+ megakaryoblasts and sharply decreases upon maturation to megakaryocytes. ATXN2 associates with DDX6 suggesting that it may mediate repression of mRNA translation during early megakaryopoiesis. Comparative transcriptome and proteome analysis on megakaryoid cells (MEG-01) with differential ATXN2 expression identified ATXN2 dependent gene expression of mRNA and protein involved in processes linked to hemostasis. Mice deficient for Atxn2 did not display differences in bleeding times, but the expression of key surface receptors on platelets, such as ITGB3 (carries the CD61 antigen) and CD31 (PECAM1), was deregulated and platelet aggregation upon specific triggers was reduced.
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Aneesh Kumar, A., G. S. Ajith Kumar, Gopika Satheesh, Arun Surendran, Mahesh Chandran, Chandrasekharan C. Kartha, and Abdul Jaleel. "Proteomics Analysis Reveals Diverse Molecular Characteristics between Endocardial and Aortic-Valvular Endothelium." Genes 12, no. 7 (June 30, 2021): 1005. http://dx.doi.org/10.3390/genes12071005.
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The variations in the protein profile of aortic-valvular (AVE) and endocardial endothelial (EE) cells are currently unknown. The current study’s objective is to identify differentially expressed proteins and associated pathways in both the endothelial cells. We used endothelial cells isolated from the porcine (Sus scrofa) aortic valve and endocardium for the profiling of proteins. Label-free proteomics was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Our proteomics analysis revealed that 29 proteins were highly expressed, and 25 proteins were less expressed in the valve than the endocardial endothelium. The cell surface markers, such as CD63, ICAM1, PECAM1, PROCR, and TFRC, were highly expressed in EE. In contrast, CD44 was highly expressed in AVE. The pathway analysis showed that metabolic process-related proteins and extracellular matrix-related proteins were enriched in valves. Differential enrichment of signaling pathways was observed in the endocardium. The hemostasis function-related proteins were increased in both endothelial cells. The proteins and pathways enriched in aortic-valvular and endocardial endothelial cells revealed the distinct phenotype of these two closely related cells.
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Miragliotta, Vincenzo, Zoë Ipiña, Josiane Lefebvre-Lavoie, Jacques G. Lussier, and Christine L. Theoret. "Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair." BMC Physiology 8, no. 1 (2008): 1. http://dx.doi.org/10.1186/1472-6793-8-1.
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Ricci, Gianna, and F. Bailey Norwood. "A Sensory Analysis of Raw Native, ‘Kanza’, and ‘Pawnee’ Pecans." HortTechnology 30, no. 6 (December 2020): 725–32. http://dx.doi.org/10.21273/horttech04639-20.
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The purpose of this study is to evaluate the appearance, texture, color, and taste of two popular pecan (Carya illinoinensis) clones relative to native pecans in a blind sensory analysis. Subjects tasted the raw pecans acquired from the same farm and evaluated them using hedonic scores. Results suggest consumers prefer the two clones to natives, and most of this preference seems to be related to the pecan size. A crossmodal effect was detected whereby the subjects reported an improved flavor in whole native pecans compared with clones that were cut in half and were thus less visually appealing. Consequently, although a previous study showed that consumers prefer pecans in a hypothetical (nontasting) situation when they are labeled as a “native” as opposed to clones, when the pecans are actually eaten and there are no labels designating the pecan type, they prefer the clones.
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Okunade, Albert A., and Mark J. Cochran. "Functional Forms and Farm-Level Demand for Pecans by Variety." Journal of Agricultural and Applied Economics 23, no. 2 (December 1991): 95–102. http://dx.doi.org/10.1017/s0081305200018215.
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AbstractRecent developments in the U.S. pecan industry appear to limit the utility of past research. The importance of pecan variety has emerged as an issue which could alter past results. The linear and double-log models previously fitted to all-pecans (averaged) data may be too restrictive and hence, are less useful for variety-specific analysis. Past research also analyzed price turning points using nominal data. This study investigated functional form and data-averaging problems by fitting separate flexible Box-Cox price-dependent models for all-pecans and each variety of pecans (1970/71-1988/89 deflated data). Results indicate: other nuts substitute for different pecan varieties, estimated all-pecans price flexibility is biased and clouds variety-specific flexibilities, and restrictive functional forms are inappropriate.
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Park, Timothy A., and Wojciech J. Florkowski. "Demand and Quality Uncertainty in Pecan Purchasing Decisions." Journal of Agricultural and Applied Economics 31, no. 1 (April 1999): 29–39. http://dx.doi.org/10.1017/s0081305200028752.
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AbstractA generalized Heckman model of purchase decisions incorporating perceived consumer quality attributes, ease of purchase, and familiarity with marketing outlets as factors influencing pecan purchases is estimated. Marketing efforts that encourage consumers to expand expenditures on nut products increase both the probability of pecan purchases and the amount purchased. Consumers who use all types of nuts in a wider variety of foods tend to purchase pecans more frequently. A diverse set of marketing outlets provides consumers with convenient sources for purchasing pecans and has a significant influence on the probability of pecan purchases but not the amount of pecans purchased.