Letteratura scientifica selezionata sul tema "CXCR2 receptors"
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Articoli di riviste sul tema "CXCR2 receptors"
1
Hou, Zhi-Shuai, Hong-Kui Zhao, Pedro Perdiguero, Meng-Qun Liu, Kai-Wen Xiang, Chu Zeng, Zhao Li et al. "Pleiotropic Role of Rainbow Trout CXCRs in Response to Disease and Environment: Insights from Transcriptional Signatures and Structure Analysis". Biomolecules 14, n. 3 (12 marzo 2024): 337. http://dx.doi.org/10.3390/biom14030337.
Testo completoAbstract (sommario):
Chemokines are cytokines with chemoattractant capacities that exert their physiological functions through the binding of chemokine receptors. Thus, chemokine and receptor complexes exert important roles in regulating development and homeostasis during routine immune surveillance and inflammation. Compared to mammals, the physiology and structure of chemokine receptors in fish have not been systematically studied. Furthermore, the salmonid-specific whole genome duplication has significantly increased the number of functional paralogs of chemokine receptors. In this context, in the current study, trout exhibited 17 cxcr genes, including 12 newly identified and 5 previously identified receptors. Interestingly, gene expression of brain cxcr1 and cxcr4, kidney cxcr3 and cxcr4, and spleen cxcr3, cxcr4, and cxcr5 subtypes were altered by bacterial infection, whereas brain cxcr1, kidney cxcr1 and cxcr7, and liver cxcr2, cxcr3, and cxcr4 subtypes were changed in response to environmental changes. Based on protein structures predicted by ColabFold, the conserved amino acids in binding pockets between trout CXCR4.1 subtypes and human CXCR4 were also analyzed. Our study is valuable from a comparative point of view, providing new insights into the identification and physiology of salmonid chemokine receptors.
2
Korbecki, Jan, Klaudyna Kojder, Patrycja Kapczuk, Patrycja Kupnicka, Barbara Gawrońska-Szklarz, Izabela Gutowska, Dariusz Chlubek e Irena Baranowska-Bosiacka. "The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature". International Journal of Molecular Sciences 22, n. 2 (15 gennaio 2021): 843. http://dx.doi.org/10.3390/ijms22020843.
Testo completoAbstract (sommario):
Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (Tregs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.
3
Doroshenko, Tatyana, Yuri Chaly, Valery Savitskiy, Olga Maslakova, Anna Portyanko, Irina Gorudko e Nikolai N. Voitenok. "Phagocytosing neutrophils down-regulate the expression of chemokine receptors CXCR1 and CXCR2". Blood 100, n. 7 (1 ottobre 2002): 2668–71. http://dx.doi.org/10.1182/blood.100.7.2668.
Testo completoAbstract (sommario):
CXC chemokines play a central role in regulation of neutrophil activation and chemotaxis. Because the chemotactic responses of neutrophils are impaired after phagocytosis, we explored the effect of phagocytic stimuli on the expression of interleukin-8 (IL-8) receptors, CXCR1 and CXCR2, in human neutrophils. After phagocytosis of opsonized yeast, the expression of CXCR1 and CXCR2 was substantially down-regulated and was accompanied by reduced Ca++responses to corresponding ligands, IL-8 and neutrophil-activating peptide–2 (NAP-2). The levels of CXCR1 and CXCR2 mRNA were constant during phagocytic stimulation of neutrophils. Confocal microscopy revealed that CXCR reduction was not via internalization. Metalloproteinase inhibitor, 1,10-phenantroline, prevented the reduction of CXCRs induced by phagocytosis, indicating that proteolytic degradation may be responsible for down-regulation. These observations suggest that down-regulation of CXCR expression may substantially reduce the responsiveness of phagocytosing neutrophils to CXC chemokines.
4
Lepsenyi, Mattias, Nader Algethami, Amr A. Al-Haidari, Anwar Algaber, Ingvar Syk, Milladur Rahman e Henrik Thorlacius. "CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells". Clinical & Experimental Metastasis 38, n. 4 (11 giugno 2021): 401–10. http://dx.doi.org/10.1007/s10585-021-10103-0.
Testo completoAbstract (sommario):
AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.
5
Konrad, F. M., e J. Reutershan. "CXCR2 in Acute Lung Injury". Mediators of Inflammation 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/740987.
Testo completoAbstract (sommario):
In pulmonary inflammation, recruitment of circulating polymorphonuclear leukocytes is essential for host defense and initiates the following specific immune response. One pathological hallmark of acute lung injury and acute respiratory distress syndrome is the uncontrolled transmigration of neutrophils into the lung interstitium and alveolar space. Thereby, the extravasation of leukocytes from the vascular system into the tissue is induced by chemokines that are released from the site of inflammation. The most relevant chemokine receptors of neutrophils are CXC chemokine receptor (CXCR) 1 and CXCR2. CXCR2 is of particular interest since several studies implicate a pivotal role of this receptor in development and promotion of numerous inflammatory disorders. CXCR2 gets activated by ELR+chemokines, including MIP-2, KC (rodents) and IL-8 (human). Since multiple ELR+CXC chemokines act on both receptors—CXCR1 and CXCR2—a pharmacologic agent blocking both receptors seems to be advantageous. So far, several CXCR1/2 antagonists have been developed and have been tested successfully in experimental studies. A newly designed CXCR1 and CXCR2 antagonist can be orally administered and was for the first time found efficient in humans. This review highlights the role of CXCR2 in acute lung injury and discusses its potential as a therapeutic target.
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Uhl, Barbara, Katharina T. Prochazka, Katrin Pansy, Kerstin Wenzl, Johanna Strobl, Claudia Baumgartner, Marta M. Szmyra et al. "Distinct Chemokine Receptor Expression Profiles in De Novo DLBCL, Transformed Follicular Lymphoma, Richter’s Trans-Formed DLBCL and Germinal Center B-Cells". International Journal of Molecular Sciences 23, n. 14 (17 luglio 2022): 7874. http://dx.doi.org/10.3390/ijms23147874.
Testo completoAbstract (sommario):
Chemokine receptors and their ligands have been identified as playing an important role in the development of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and Richter syndrome (RS). Our aim was to investigate the different expression profiles in de novo DLBCL, transformed follicular lymphoma (tFL), and RS. Here, we profiled the mRNA expression levels of 18 chemokine receptors (CCR1–CCR9, CXCR1–CXCR7, CX3CR1 and XCR1) using RQ-PCR, as well as immunohistochemistry of seven chemokine receptors (CCR1, CCR4–CCR8 and CXCR2) in RS, de novo DLBCL, and tFL biopsy-derived tissues. Tonsil-derived germinal center B-cells (GC-B) served as non-neoplastic controls. The chemokine receptor expression profiles of de novo DLBCL and tFL substantially differed from those of GC-B, with at least 5-fold higher expression of 15 out of the 18 investigated chemokine receptors (CCR1–CCR9, CXCR1, CXCR2, CXCR6, CXCR7, CX3CR1 and XCR1) in these lymphoma subtypes. Interestingly, the de novo DLBCL and tFL exhibited at least 22-fold higher expression of CCR1, CCR5, CCR8, and CXCR6 compared with RS, whereas no significant difference in chemokine receptor expression profile was detected when comparing de novo DLBCL with tFL. Furthermore, in de novo DLBCL and tFLs, a high expression of CCR7 was associated with a poor overall survival in our study cohort, as well as in an independent patient cohort. Our data indicate that the chemokine receptor expression profile of RS differs substantially from that of de novo DLBCL and tFL. Thus, these multiple dysregulated chemokine receptors could represent novel clinical markers as diagnostic and prognostic tools. Moreover, this study highlights the relevance of chemokine signaling crosstalk in the tumor microenvironment of aggressive lymphomas.
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Coperchini, Francesca, Laura Croce, Michele Marinò, Luca Chiovato e Mario Rotondi. "Role of chemokine receptors in thyroid cancer and immunotherapy". Endocrine-Related Cancer 26, n. 8 (agosto 2019): R465—R478. http://dx.doi.org/10.1530/erc-19-0163.
Testo completoAbstract (sommario):
Inflammation is currently regarded as an essential component of malignancies. It is now known that the tumor microenvironment may profoundly influence the biological behavior of cancer cells and ultimately the patient’s outcome. Chemokine and their receptor play a major role in determining the immune phenotype of the cells infiltrating the thyroid tumor microenvironment. Experimental evidence shows that both normal and cancer thyroid cells express specific chemokine receptors. The expression of at least some of these receptors exerts several biological effects, which influence the course of the disease. The present review article will take into account the role of the most studied chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, DARC, CCR3, CCR6 and CCR7) in the context of thyroid cancer. This review will focus on current knowledge provided by in vitro and in vivo studies specifically performed on thyroid cancer including (i) expression of chemokine receptors in normal and cancer thyroid cells; (ii) role of chemokine receptors in affecting the biological behavior of thyroid tumors including the metastatic process; (iii) current knowledge about immunotherapies through targeting of chemokine receptors in thyroid cancer.
8
Daniele, Simona, Simona Saporiti, Stefano Capaldi, Deborah Pietrobono, Lara Russo, Uliano Guerrini, Tommaso Laurenzi et al. "Functional Heterodimerization between the G Protein-Coupled Receptor GPR17 and the Chemokine Receptors 2 and 4: New Evidence". International Journal of Molecular Sciences 24, n. 1 (23 dicembre 2022): 261. http://dx.doi.org/10.3390/ijms24010261.
Testo completoAbstract (sommario):
GPR17, a G protein-coupled receptor, is a pivotal regulator of myelination. Its endogenous ligands trigger receptor desensitization and downregulation allowing oligodendrocyte terminal maturation. In addition to its endogenous agonists, GPR17 could be promiscuously activated by pro-inflammatory oxysterols and chemokines released at demyelinating lesions. Herein, the chemokine receptors CXCR2 and CXCR4 were selected to perform both in silico modelling and in vitro experiments to establish their structural and functional interactions with GPR17. The relative propensity of GPR17 and CXCR2 or CXCR4 to form homo- and hetero-dimers was assessed by homology modelling and molecular dynamics (MD) simulations, and co-immunoprecipitation and immunoenzymatic assay. The interaction between chemokine receptors and GPR17 was investigated by determining receptor-mediated modulation of intracellular cyclic adenosine monophosphate (cAMP). Our data show the GPR17 association with CXCR2 or CXCR4 and the negative regulation of these interactions by CXCR agonists or antagonists. Moreover, GPR17 and CXCR2 heterodimers can functionally influence each other. In contrast, CXCR4 can influence GPR17 functionality, but not vice versa. According to MD simulations, all the dimers reached conformational stability and negative formation energy, confirming the experimental observations. The cross-talk between these receptors could play a role in the development of the neuroinflammatory milieu associated with demyelinating events.
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Zhang, Jing, Shouguo Huang, Lini Quan, Qiu Meng, Haiyan Wang, Jie Wang e Jin Chen. "Determination of Potential Therapeutic Targets and Prognostic Markers of Ovarian Cancer by Bioinformatics Analysis". BioMed Research International 2021 (19 marzo 2021): 1–13. http://dx.doi.org/10.1155/2021/8883800.
Testo completoAbstract (sommario):
This study is to study the expression of CXCRs in ovarian cancer tissues and their value in prognosis. The expressions of CXCR1-CXCR7 mRNA between ovarian tumor tissues and normal tissues and in different pathological types of ovarian tumor tissues were compared by ONCOMINE online tool. The relationship between the expression of CXCRs and clinical pathological staging was studied by GEPIA. Kaplan-Meier plotter online tool was used to analyze prognosis. Finally, GO and KEGG analyses and protein interaction network analysis were performed for CXCRs by the DAVID software to predict their function, and cBioPortal was used to identify the key functional genes. The expression of CXCR3/4/7 mRNA in ovarian cancer tissues was higher than that in normal ovarian tissues, and the expression of CXCR4 was the highest ( fold change = 306.413 , P < 0.05 ). The expression of CXCR1/2/3/4/7 mRNA in different pathological types of ovarian tumors was significantly different ( P < 0.05 ). Only CXCR5 expression level was associated with tumor staging. Survival analysis showed that high CXCR7 mRNA expression and low CXCR5/6 expression were associated with the shortening of overall survival. High CXCR4/7 expression and low CXCR5/6 expression were associated with the shortening of progression-free survival. High CXCR2/4 expression and low CXCR5/6 expression were closely related to the shortening of postprogressing survival. Protein interaction network analysis showed that GNB1, PTK2, MAPK1, PIK3CA, GNB4, GNA11, KNG1, and ARNT proteins were closely related to the CXC receptor family. CXCR3/4/7 are potential therapeutic targets, and CXCR2/4/5/6/7 are new markers for the prognosis of ovarian cancer.
10
Inngjerdingen, Marit, Bassam Damaj e Azzam A. Maghazachi. "Expression and regulation of chemokine receptors in human natural killer cells". Blood 97, n. 2 (15 gennaio 2001): 367–75. http://dx.doi.org/10.1182/blood.v97.2.367.
Testo completoAbstract (sommario):
Abstract Using flow cytometric and RNase protection assays, this study examined the expression of chemokine receptors in nonactivated natural killer (NK) cells and compared this expression with NK cells activated with interleukin (IL)-2, which either adhered to plastic flasks (AD) or did not adhere (NA). None of the NK cell subsets expressed CXCR2, CXCR5, or CCR5. The major differences between these cells include increased expression of CXCR1, CCR1, CCR2, CCR4, CCR8, and CX3CR1 in AD when compared to NA or nonactivated NK cells. The chemotactic response to the CXC and CC chemokines correlated with the receptor expression except that all 3 populations responded to GRO-α, despite their lack of CXCR2 expression. Pretreatment of these cells with anti-CXCR2 did not inhibit the chemotactic response to GRO-α. In addition, nonactivated and NA cells responded to fractalkine, although they lack the expression of CX3CR1. This activity was not inhibited by anti-CX3CR1. Viral macrophage inflammatory protein (vMIP)-I, I-309, and TARC competed with the binding of 125I-309 to AD cells with varying affinities. Transforming growth factor (TGF)-β1 but not any other cytokine or chemokine examined including interferon (IFN)-γ, MIP-3β, macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC) or I-309, up-regulated the expression of CXCR3 and CXCR4 on NK cell surface. This is correlated with increased chemotaxis of NK cells treated with TGF-β1 toward stromal cell–derived factor (SDF)-1α and interferon-inducible protein-10 (IP-10). Messenger RNA for lymphotactin, RANTES, MIP-1α, and MIP-1β, but not IP-10, monocyte chemotactic protein (MCP)-1, IL-8, or I-309 was expressed in all 3 NK cell subsets. Our results may have implications for the dissemination of NK cells at the sites of tumor growth or viral replication.
Tesi sul tema "CXCR2 receptors"
1
Wilson, Shirley Risk. "Oligomerisation of chemokine receptors CXCR1 and CXCR2". Thesis, University of Glasgow, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418346.
Testo completo
2
Khurram, Syed Ali. "The chemokine receptors XCR1, CXCR1 and CXCR2 regulate oral epithelial cell behaviour". Thesis, University of Sheffield, 2008. http://etheses.whiterose.ac.uk/10311/.
Testo completoAbstract (sommario):
Chemokines are chemoattractant cytokines which act on specific receptors and play an important role in tumour biology. The aim of this project was to determine whether the chemokine receptors XCRl, CXCRl and CXCR2 and their respective ligands lymphotactin, IL-8 (CXCRl&2) and GRO-a regulate the behaviour of normal and malignant oral epithelial cells. XCRl, CXCRl and CXCR2 mRNA and surface protein expression was detected in normal and oral cancer cell lines. Lymphotactin, IL-8 and GRO-a facilitated intracellular activation of ERK1/2 signaling pathway and stimulated migration, invasion and proliferation of all cells. These effects were mediated through XCRl for lymphotactin, CXCRl and CXCR2 for IL-8 and CXCR2 for GRO-a. The cancer cells showed a greater response than normal cells and a direct relationship between receptor expression and migration, invasion and proliferation was observed. XCRl but not lymphotactin was expressed by epithelial cells in normal oral mucosa in vivo and both were expressed and upregulated in inflammation and cancer. Constitutive expression of both XCRl and lymphotactin was found in regional lymph nodes and on metastatic tumours. Lymphotactin mRNA al}d constitutive intracellular protein was detected in normal and cancerous oral cells. Exposure of normal cells to lymphotactin resulted in increased adhesion to fibronectin but not collagen and stimulated MMP-2 and -9 release whereas exposure of cancer cells resulted in increased adhesion to both collagen and fibronectin and stimulated MMP-2, 9 and MMP-7 release. These findings show for the first time that XCRl and its ligand lymphotactin are expressed by epithelial cells in a range of oral conditions and strongly suggest that they play an important role in regulating the behaviour of normal and malignant epithelial cells. Similarly CXCRl and CXCR2 are upregulated on malignant oral cells in vitro and may be important in the biology of oral cancer.
3
Filho, Décio Abdo. ""Avaliação da expressão dos receptores de interleucina-8, CXCR1 e CXCR2, e da atividade proliferativa em fibroblastos de quelóide e de pele normal"". Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5132/tde-16102006-171640/.
Testo completoAbstract (sommario):
O quelóide é um tumor fibroso benigno que ocorre durante a cicatrização da pele em indivíduos geneticamente predispostos. A cicatrização é um processo biológico complexo e depende da interação de diferentes estruturas teciduais e de um grande número de tipos celulares residentes e infiltrativos, que produzem citocinas. A interleucina 8 (IL-8), citocina pró-inflamatória, é super-expressa pelos fibroblastos durante o desenvolvimento do tecido de granulação, acelerando o processo de cicatrização. Como o quelóide resulta de uma reparação tecidual anormal após lesão da pele, o presente estudo teve por objetivo determinar a expressão dos receptores da IL-8, CXCR1 e CXCR2, e a capacidade proliferativa, pelo ciclo celular, dos fibroblastos queloideanos cultivados e extraídos ex vivo, por citometria de fluxo. Fibroblastos de cicatriz queloideana e de pele normal foram obtidos de 21 pacientes da raça negra, com idade variando entre 10 e 40 anos, de lesões com até 2 anos de evolução. Em nosso estudo constatamos expressão reduzida dos receptores para a IL-8, CXCR1(35,7%±11,2) e CXCR2 (27,8%±11,3), em fibroblastos de cicatriz queloideana cultivados, comparando com a pele normal (44,1±16,2 e 46,3±27,1 respectivamente). Entretanto, essa diferença só foi significante para o receptor CXCR2. A baixa expressão desses receptores poderia ser decorrente da atividade de metaloproteinases, que regulam a expressão de proteínas da superfície celular, através de clivagem enzimática, ou a capacidade reduzida de internalização e a reciclagem de receptores, mantida por filamentos de actina do citoesqueleto, que nos fibroblastos do quelóide estão diminuídos. Em relação ao ciclo celular de fibroblastos cultivados do quelóide e da pele normal, verificamos diferenças não significantes da capacidade de replicação (fase S do ciclo celular) e de apoptose. No quelóide observamos significante aumento de células na fase G2/M, indicando aumento da velocidade de divisão celular. Para confirmar esses achados estudamos o ciclo celular de fibroblastos extraídos ex vivo, da porção periférica e central do quelóide e da pele normal. Os fibroblastos da porção periférica apresentaram porcentagem significantemente maior de células com capacidade replicativa, fase S do ciclo (22,9% ± 11,6), em relação à porção central (4,7% ± 2,9) e à pele normal (6,8% ± 4,9), e maior velocidade de divisão celular, fase G2/M (18,6 ± 12,0), em relação à porção central (35,6 ± 7,0) e pele normal (32,3 ± 6,9). Verificamos que a porção central apresentou maior porcentagem de células em apoptose (7,0% ± 2,1), comparado à porção periférica (4,9% ± 1,9) e pele normal (2,0% ± 0,86). Esses dados indicam que as células da porção periférica do quelóide parecem ser responsáveis pela elevada taxa de proliferação, justificando o crescimento expansivo a partir das margens da cicatriz queloideana, com desenvolvimento de lesão semelhante a tumor, bem como a porção central ser responsável pela fibrose, contendo células quiescentes e apoptóticas. Esses resultados sugerem modulação diferencial das reações celulares através das vias de sinalização para proliferação ou morte celular programada. Neste sentido, a baixa expressão dos receptores da IL-8, CXCR1 e principalmente de CXCR2, nos fibroblastos do quelóide sugere capacidade reduzida da IL-8 em promover cicatrização acelerada. A baixa atividade da IL-8 sobre os fibroblastos queloideanos estaria promovendo desregulação da resposta inflamatória e com isso atraindo novas células inflamatórias para o local e produzindo sinais alterados, como grande produção da citocina TGFβ. Essa desregulação do processo de cicatrização, com alteração de citocinas e da matriz extracelular, poderia ser responsável pelas duas populações de fibroblastos, uma proliferativa na periferia e outra quiescente e apoptótica na porção central. Finalizando, podemos concluir que nossos resultados correspondem às alterações histológicas e clínicas do quelóide que se expande nos limites da lesão.A keloid is a benign fibrous tumor that occurs during wound healing in genetically predisposed individuals. Healing is a complex biological process and depends on the interaction of different tissue structures and a great number of resident and infiltrative cell types. The interleukin-8 (IL-8), a proinflammatory chemokine, showed higher expression in fibroblasts during the development of the granulation tissue, promoting more rapid tissue maturation. Since keloids result from abnormal wound healing, the objective of the present study was to determine the expression of CXCR1 and CXCR2, IL-8 receptors, and the proliferation capacity, throughout the cell cycle, of the keloid fibroblasts extracted ex vivo and those submitted to in vitro cultivation. Normal skin and keloid scar fibroblasts were obtained from 21 African-Brazilian patients, aged from 10 to 40 years, whose lesions had evolved for no longer than 2 years. Expression of receptors and the cell cycle was assessed by flow cytometry. We showed lower expression of the CXCR1 (35,7% ± 11,2) and CXCR2 (27,8%±11,3) in keloid fibroblasts, when compared with normal skin (44,1 ± 16,2 e 46,3 ± 27,1 respectively), but the difference was not significant for the CXCR1 receptor. This lower expression of IL-8 receptors in keloid fibroblasts could be due to the action of metalloproteinases, which regulate the surface protein enzymatically, or fibroblastic cytoskeleton conditions, which influence receptor internalization and recycling. The distribution assessment of cell cycle phases of fibroblasts cultivated from keloid scars and normal skin did not show significant difference in replication capacity and apoptosis. The keloid fibroblasts presented a significantly higher proportion of cells in the G2/M phase, suggesting higher rate of cell division. To confirm these results we studied the cell cycle of fibroblasts extracted ex vivo, now separated by central and peripheral portions of keloid and normal skin. The peripheral fibroblasts showed significant high cell proportions in phase S (22,9% ± 11,6), compared with the central portion (4,7% ± 2,9) and normal skin (6,8% ± 4,9), and higher cells in division phase G2/M (18,6% ± 12,0), compared with the central portion (35,6% ± 7,0) and normal skin (32,3% ± 6,9). The central portion showed higher proportion of apoptosis (7,0% ± 2,1), compared with the peripheral portion (4,9% ± 1,9) and normal skin (2,0% ± 0,86). These results suggest that the keloid peripheral cells could be responsible for the proliferation rate, justifying the expansive keloid growth at the borders of the keloid scar, in a similar fashion to tumor development and the central portion being responsible for fibrosis, with quiescent and apoptotic cells. These results suggest a differentiated modulation of cell reactions by signal pathways for programmed cellular proliferation or death. In this sense, the low expression of the IL-8 receptors CXCR1 and CXCR2 in keloid fibroblasts suggests a diminished capacity of IL-8 to promote accelerated healing. This low expression of IL-8 receptors in keloid fibroblasts could promote the dysregulation of the inflammatory response and thus attract more inflammatory cells to the site, producing different signals, such as a high production of the TGFβ cytokine. This dysregulation of the healing process, with changed cytokine and extracellular matrix expression, could be responsible for two different cell populations of fibroblasts, one proliferation at the periphery and the other fibrotic at the center of the lesion, with apoptotic and quiescent cells. Finally, we conclude that our results correspond to the histological and clinical changes of keloids that grow beyond the wound boundaries.
4
Le, Du Julie. "Développement d'antagonistes des récepteurs CXCR2 contre les pathologies angiogéniques oculaires et le cancer". Electronic Thesis or Diss., Université Côte d'Azur, 2024. http://www.theses.fr/2024COAZ5067.
Testo completoAbstract (sommario):
L'angiogenèse, ou processus de formation de nouveaux vaisseaux sanguins, joue un rôle majeur dans la progression de nombreux cancers et diverses pathologies oculaires. Les récepteurs aux chimiokines CXCR2 sont impliqués dans ces processus en médiant la prolifération cellulaire, l'inflammation et la formation de nouveaux vaisseaux sanguins. Le but de cette thèse a donc été de développer des antagonistes des récepteurs CXCR2 pour inhiber ces mécanismes pathologiques, et en particulier l'angiogenèse pathologique tumorale et oculaire. Sur la base de recherches antérieures, nous avons étudié de nouveaux analogues de N,N'-diarylurée comme inhibiteurs de la voie ELR+CXCL-CXCR2, pour le traitement du cancer. Deux séries d'analogues ont été synthétisées afin d'étudier la relation structure-activité et d'optimiser un composé lead. Des évaluations sur des lignées cellulaires de cancer du rein, de la tête et du cou et de mélanomes uvéaux, ainsi que sur des cultures sphéroïdes 3D ont identifié un composé lead optimisé, montrant une inhibition significative de l'invasion, de la migration et de la néo-angiogenèse. De plus, des études de pharmacologie, de pharmacodynamie et de polymorphisme ont été réalisées. Dans le cadre des pathologies oculaires angiogéniques, le développement d'une seconde famille de composés a été poursuivi, avec notamment l'étude de nouvelles voies de synthèse en vue d'une montée en échelle pour une future production industrielle et des études de formulation afin de réaliser des préparations de principes actifs sous forme de collyre. Enfin, une nouvelle série de composés à visée anticancéreuse a été conçue et une voie de synthèse a été développée pour obtenir une première série d'analogues. L'évaluation des activités biologiques de ces composés a permis de dégager une relation de structure-activité préliminaireAngiogenesis, the process of forming new blood vessels, plays a crucial role in the progression of various cancers and ocular diseases. CXCR2 chemokine receptors are implicated in these processes by mediating cell proliferation, inflammation, and the formation of new blood vessels. This thesis aims to develop CXCR2 receptor antagonists to inhibit these pathological mechanisms, particularly pathological tumor and ocular angiogenesis. Based on previous research, we investigated new N,N'-diarylurea analogues as inhibitors of the ELR+CXCL-CXCR2 pathway for cancer treatment. Two series of analogues were synthesized to study the structure-activity relationship and to optimize a lead compound. Evaluations on renal, head and neck cancer, and uveal melanoma cell lines, as well as on 3D spheroid cultures, identified an optimized lead compound showing significant inhibition of invasion, migration, and neo-angiogenesis. Additionally, pharmacology, pharmacodynamics, and polymorphism studies were conducted.In the context of ocular angiogenic diseases, the development of a second family of compounds was pursued, including the study of new synthetic routes for scaling up for future industrial production and formulation studies to create active ingredient preparations in the form of eye drops.Finally, a new series of anticancer compounds was designed, and a synthetic route was developed to obtain a first series of analogues. The evaluation of the biological activities of these compounds allowed the establishment of a preliminary structure-activity relationship
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Desurmont, Thibault. "Etude de l'implication des chimiokines et de leurs récepteurs dans la survenue d'une rechute métastatique chez des patients atteints d'un cancer du côlon métastatique et traités par chirurgie hépatique avec ou sans chimiothérapie néoadjuvante". Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S042/document.
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Notre objectif était d’analyser l’implication potentielle des voies associées aux récepteurs de chimiokines CXCR2 et CXCR4 dans le cancer colorectal métastatique au foie. Les niveaux d’expression de CXCR2, CXCR4 et de leurs chimiokines étaient évalués dans les métastases hépatiques de cancers colorectaux dans le but d’étudier leurs corrélations avec la survie globale et la survie sans récidive de patients ayant reçu, ou non, une chimiothérapie néoadjuvante. Des analyses d’expression pour RT-PCR quantitative et immunohistochimie étaient réalisées en utilisant des prélèvements humains de métastases hépatiques de cancers colorectaux. Les niveaux d’expression de CXCR2, CXCR4 et de leurs ligands étaient statistiquement analysés en fonction des traitements par chimiothérapie néoadjuvante administrés ou non, et en fonction du suivi des patients. Des modèles murins de xénogreffes sous-cutanées et orthotopiques intracaecales ont été mis au point et utilisés pour étudier l’expression de CXCR2, CXCR4 et CXCL7 en relation avec le traitement des souris par chimiothérapie.Nous avons montré que la surexpression de CXCR2 et CXCL7 était corrélée à de plus courtes survies globales et sans récidive de nos patients. En analyse multivariée, l’expression de CXCR2 et de CXCL7 étaient des facteurs indépendants de survie globale et sans récidive. La chimiothérapie néoadjuvante augmentait significativement l’expression de CXCR2, et de CXCL7 de façon proche de la significativité. Les résultats de nos modèles murins ont montré une tendance à la surexpression de nos gènes d’intérêts dans les tissus tumoraux des souris traités. En conclusion, ces résultats suggèrent l’implication de la voie de signalisation CXCL7/CXCR2 comme facteur prédictif de mauvais pronostic dans le cancer colorectal métastatique. Les chimiothérapies à base de 5 Fluoro-uracile augmentent l’expression de ces gènes dans les métastases hépatiques, fournissant une explication sur l’agressivité des tumeurs métastatiques en échappement thérapeutique. Un blocage sélectif de l’axe CXCR2/CXL7 pourrait fournir de nouvelles opportunités thérapeutiquesOur aim was to analyze the potential role of chemokine receptors CXCR2 and CXCR4 signalling pathways in liver metastatic colorectal cancer (CRC) relapse. Expression levels of CXCR2, CXCR4, and their chemokine ligands were evaluated in liver metastases of colorectal cancer in order to study their correlation with overall and disease-free survival of patients having received, or not received, a neoadjuvant chemotherapy regimen.Quantitative RT-PCR and CXCR2 immunohistochemical staining were carried out using human CRC liver metastasis samples. Expression levels of CXCR2, CXCR4, and their ligands were statistically analyzed according to treatment with neoadjuvant chemotherapy and patients ' outcome. Murine models of subcutaneous and orthotopic intracaecal xenografts have been developed and used to study the expression of CXCR2, CXCR4 and CXCL7 in connection with the treatment of mice with chemotherapy.We showed that CXCR2 and CXCL7 overexpression are correlated to patient’s shorter overall and disease-free survival. By multivariate analysis, CXCR2 and CXCL7 expressions are independent factors of overall and disease-free survival. Neoadjuvant chemotherapy increases significantly the expression of CXCR2 and CXCL7 was overexpressed close to significance. Results of our mouse models have shown a trend over-expression of our interest genes in tumor tissues of the treated mice.In conclusion, we show the involvement of CXCL7/CXCR2 signalling pathways as a predictive factor of poor outcome in metastatic CRC. 5-Fluorouracil-based chemotherapy regimens increase the expression of these genes in liver metastasis, providing one explanation for aggressiveness of relapsed drug-resistant tumors. Selective blockage of CXCR2/CXCL7 signalling pathways could provide new potential therapeutic opportunities
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Franz, Juliana Pires Marafon. "Estudo de polimorfismos dos genes CXCR2 e IL-8 em pacientes com câncer de próstata e grupo controle". reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/139982.
Testo completoAbstract (sommario):
A Interleucina 8 (IL-8) é uma quimiocina CXC angiogênica que tem papel importante no desenvolvimento e progressão de vários tumores malignos, incluindo o câncer de próstata (CaP). O polimorfismo de nucleotídeo único (SNP) -251 T/A da região promotora do gene da IL-8, relativo ao local de início da transcrição deste gene, está associado com a produção desta citocina. O efeito da IL-8 é mediado através de dois receptores de alta afinidade, CXCR1 e CXCR2. O presente estudo investigou a influência da variação dos genes IL-8 e CXCR2 na susceptibilidade e nas características clinicopatológicas do CaP em um grupo de brasileiros. Duzentos e um pacientes e 185 controles saudáveis foram selecionados neste estudo casocontrole. Amostras de sangue foram coletadas para extração de DNA; a tipagem da IL-8 -251 T/A e CXCR2 +1208 C/T foi realizada através da reação em cadeia da polimerase com sequência específica de primers (PCR-SSP), seguida pela eletroforese em gel de agarose. O risco associado entre os genótipos, a susceptibilidade do CaP e as características do tumor, foi estimado pelo odds ratio (OR), com intervalo de confiança de 95%, usando análise de regressão logística e ajustando para idade ao diagnóstico. Encontramos uma associação estatisticamente significativa entre o genótipo heterozigoto CT do gene CXCR2 +1208 e CaP. Este genótipo foi significativamente menos frequente em pacientes com estádio clínico T3-T4 comparado com T1-T2 (56.7% versus 80.5%). Nossos achados sugerem que os portadores do genótipo CT CXCR2 +1208 tiveram um efeito protetor para estádio avançado de CaP (CT versus CC: OR ajustado = 0.25; P = 0.02). Não foi encontrada associação significativa entre o polimorfismo -251 T/A da IL-8 e os parâmetros clinicopatológicos do CaP. Estes resultados indicam que o genótipo CT do CXCR2 +1208 é menos frequente em estádios avançado de CaP, sugerindo que este receptor de quimiocina tenha um papel na patogênese desta doença.Interleukin-8 (IL-8) is an angiogenic CXC chemokine that plays an important role in both the development and progression of several human malignancies including prostate cancer (PC). A single nucleotide polymorphism (SNP) at -251 upstream of the transcriptional start site of the IL-8 gene has been shown to influence its production. The effects of IL-8 are mediated by two highly related chemokine receptors, CXCR1 and CXCR2. The present study investigated the influence of the IL-8 and CXCR2 gene variation on susceptibility and clinicopathological characteristics of PC in a group of Brazilian subjects. Two hundred and one patients and 185 healthy controls were enrolled in a case-control study. Blood was collected for DNA extraction; typing of IL-8 -251 T/A and CXCR2 +1208 C/T genes was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP), followed by agarose gel electrophoresis. Risk association between the genotypes, PC susceptibility and tumor characteristics was estimated by odds ratio (OR) and 95% confidence intervals (95% CI) using logistic regression analysis, after adjusting for age at diagnosis. A significant association was found between the heterozygous CXCR2 +1208 CT genotype and PC. The CXCR2 +1208 CT genotype was significantly less frequent in patients with clinical stage T3-T4 compared to T1-T2 (56.7 versus 80.5%). Our findings suggest that carriers of the CXCR2 +1208 CT genotype had a protective effect for advanced PC (CT versus CC: adjusted OR = 0.25; P = 0.02). No association was observed between the SNP for IL-8 -251 T/A and clinicopathological parameters of PC. These results indicated that the CXCR2 +1208 CT genotype is less frequent in advanced stages of PC, suggesting that this chemokine receptor plays a role in the pathogenesis of this disease.
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Kiss, Debra Lois. "Regulation of the Chemokine Receptors CXCR4, CXCR7 , and the Androgen Receptor in Prostate Cancer". Thesis, Griffith University, 2013. http://hdl.handle.net/10072/367690.
Testo completoAbstract (sommario):
The chemokine receptor CXCR4 contributes to tumour cell migration and invasion during the progression of prostate cancer. In particular, this pathway is central to the metastasis of prostate cancer to the bone marrow. Limited therapeutic options exist for prostate cancer patients who have progressed to advanced metastatic disease, and pharmacological interference of the chemokine network may serve to control tumour cell dissemination and the establishment of metastasis. A more detailed knowledge of the mechanisms regulating chemokine receptors is required, in order to further characterise and explore the capacity and effectiveness of targeting these pathways for therapeutic intervention in prostate cancer.
Here, the regulation of CXCR4 protein expression and function was investigated in relation to androgens and the extracellular matrix. Accumulating evidence of CXCR4 regulation by androgens and the androgen receptor have indicated that androgens not only promote the growth and development of prostate cancer, but may actively contribute to the metastatic progression of prostate through modulation of the chemokine network. In the current study, the endogenous protein expression and functionality of the androgen receptor were firstly characterised in the androgen-insensitive prostate cancer cell lines DU145 and PC3, using the androgen-sensitive LNCaP cells as a basis for comparison. Investigations were performed using two-dimensional culture in conjunction with the more physiologically relevant three-dimensional in vitro culture model.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Eskitis Institute for Cell and Molecular Therapies
Science, Environment, Engineering and Technology
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McDonagh, Ellen Mary. "The molecular mechanisms governing the regulation of chemokine receptors CXCR3 and CXCR6". Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523747.
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Melo, Rita de Cássia Carvalho 1988. "Expressão e função de CXCR7 em sídromes mielodisplásicas e leucemias". [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311982.
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Orientadores: Sara Teresinha Olalla Saad, Carolina Louzão BigarellaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A medula óssea é constituída por microambientes específicos denominados "nichos". O fator SDF-1 (Stromal derived factor-1) foi identificado como um importante fator quimioatrativo produzido por células estromais da medula óssea. Sua ação sobre seu receptor CXCR4 desempenha função primordial na migração, retenção e desenvolvimento dos progenitores hematopoiéticos na medula óssea. Células leucêmicas mielóides e linfóides expressam CXCR4 e aproveitam-se disso para acessar nichos medulares normalmente restritos ás células progenitoras, passando a residir em microambientes que propiciam sobrevivência e proliferação. Recentemente foi descoberto que o receptor CXCR7 é capaz de se ligar ao SDF-1. Ele é expresso em várias linhagens tumorais, mas em células hematopoiéticas seu papel é ainda pouco explorado. Em vista da escassez de dados na literatura o objetivo deste trabalho foi investigar a expressão e função de CXCR7 em síndromes mielodisplásicas e leucemias agudas. Neste estudo, foi mostrado que a expressão gênica de CXCR7 foi significativamente maior em leucemia linfoblástica aguda (LLA) em comparação com sindrome mielodisplásica (SMD), leucemia mielóide aguda (LMA) e indivíduos controles (p<0.0001, Mann-Whitney). A proteína CXCR7 também foi mais expressa em linhagens celulares linfoblástica T (Molt-4 e Jurkat) em comparação com linhagens mielóides. Em células linfoblásticas T, a localização subcelular de CXCR7 e CXCR4 por microscopia confocal e citometria de fluxo evidenciou CXCR7 mais próximo à membrana das células Molt-4 e mais frequentemente no citoplasma de células Jurkat enquanto CXCR4 está na membrana de ambas as linhas celulares. Curiosamente, notamos também que, depois da indução de SDF-1, células Molt-4 têm maior capacidade migratória comparada com Jurkat (mediana Molt 4 = 52,0 ± 5 vs Jurkat = 24,1 ± 3, p = 0,0079, teste de Mann-Whitney), que pode estar relacionado com a disponibilidade de membrana de CXCR7. Além disso, a inibição da CXCR7 ou CXCR4 resultou em mudanças significativas na resposta migratória de Molt4 e Jurkat (p<0,05 Mann-Whitney), no entanto, a inibição de ambos, CXCR7 e CXCR4 resultou em uma redução mais significativa na migração celular (p = 0.0079/Molt-4; p = 0.0043/Jurkat, Mann-Whitney). Uma vez que é bem estabelecido que células CD34+ de pacientes com SMD não são atraídas pelo gradiente de SDF-1, apesar de terem expressão normal de CXCR4, nos interessou investigar qual a localização de CXCR4 nas células SMD e se esta irresponsividade estava associada a CXCR7. Linhagens mielóides P39 e U937 foram usadas como modelo de SMD e LMA, respectivamente. Foram encontrados níveis similares de expressão de CXCR4 e CXCR7 em ambas as linhagens celulares, no entanto encontramos que CXCR4 está localizado no citoplasma de células P39 enquanto ele está na membrana das células U937. Uma vez que a proteína quinase C isotipo zeta (PKC'dzeta' está relacionada com a sinalização SDF-1/CXCR4 aumentando a expressão de CXCR4 e sua disponibilidade na membrana, resolvemos trabalhar também com células P39 hiperexpressando PKC'dzeta' (PKC'dzeta'wt). Este procedimento resultou na translocação de CXCR4 para a membrana de células P39, mas não alterou a localização subcelular de CXCR7. Ensaios de migração por tranwell mostraram que células P39 PKC'dzeta'wt apresentam maior capacidade de migração em relação a SDF-1 em comparação com células P39 controle (aumento de 35 vezes pcDNA3 PKC-'dzeta'-HA vs pcDNA3 transfectadas células P39, p = 0,0032, Mann-Whitney), sugerindo que a PKC'dzeta' restaura a capacidade quimiotática de células P39. Aumento da expressão de CXCR7, como aqui observado em células leucemicas linfoblásticas, é um fenômeno já descrito em uma variedade de linhagens de células tumorais sólidas, tais como cérebro, próstata e pulmão. Em tumores sólidos, CXCR7 principalmente aumenta a proliferação de células malignas. Estes resultados sugerem que a função biológica de CXCR7 depende tecido e órgãos que ele está localizado e que, na leucemia linfoblástica aguda pode ter um papel na migração de células, potencializando a resposta de CXCR4 a SDF-1 e, portanto, poderia contribuir para o recrutamente de células leucêmicas para nichos uma vez já ocupados por células-tronco hematopoéticas normais. Além disso, nossos resultados levam a crer que um defeito na via PKC'dzeta'/CXCR4 está envolvido com a irresponsividade de células SMD a SDF-1, gerando uma hematopoese ineficaz. E confirma dados que sugerem que PKC'dzeta' é uma proteína central na via de sinalização SDF-1/CXCR4, muito importante para a migração de células hematopoéticas malignas
Abstract: Bone marrow is constituted of specific microenvironments called "niches". The factor SDF-1 (stromal derived factor-1) was identified as an important chemoattractant factor produced by bone marrow cells. SDF-1 acts on its receptor CXCR4 and plays primordial function in migration, retention and development of hematopoietic progenitors in bone marrow. CXCR4 is expressed in leukemic cells and enables them to access marrow niches that normally are restricted to quiescent stem cells, thereby ensuring its protection from cell death resulting in a worse prognosis. Recently, CXCR7 was identified as another SDF-1-binding receptor, but its contribution to SDF-1 - mediated effects in hematopoietic cells is still poorly explored, even though the CXCR7 relationship with tumor progression in non-hematopoietic malignancies is well established. Given that there is little information regarding CXCR7 we investigated its function and expression in MDS and acute leukemias. This work, was showed that CXCR7 is significantly higher expressed in ALL compared to MDS, AML and control subjects (p<0.0001, Mann-Whitney test). CXCR7 protein is also higher expressed in lymphoblastic cell lines (Molt-4 and Jurkat) compared with myeloid cells. In lymphoblastic cell lines, the subcellular location of CXCR7 and CXCR4 by confocal microscopy and flow cytometry evidenced CXCR7 closer in the membrane of Molt-4 cells and more frequently in the cytoplasm of Jurkat cells whereas CXCR4 was in the membrane of both cell lines. Interestingly, we also noticed that, after SDF-1 induction, Molt-4 cells have higher chemotactic ability compared with Jurkat (median Molt 4=52.0 ± 5 vs Jurkat=24.1 ± 3, p=0.0079, Mann-Whitney test) which may be related with the membrane availability of CXCR7. In addition, the inhibition of CXCR7 or CXCR4 resulted in significant changes in Molt4 and Jurkat chemotactic response (p<0,05, Mann-Whitney test), however, the inhibition of both CXCR7 and CXCR4 resulted in a more significant reduction in cell migration (p=0.0079/Molt-4; p=0.0043/Jurkat, Mann-Whitney test). Since it is well established that CD34 + progenitor cells from patients with myelodysplastic syndromes (MDS) are not attracted by gradient of SDF-1 despite of having CXCR4 normal expression, we addressed if MDS cells have an abnormal localization of CXCR4 or association with CXCR7. P39 and U937 cell line were used as a model of MDS and AML, respectively. Similar expression levels of CXCR4 and CXCR7 in both cell lines however we found, by confocal microscopy and flow cytometry, that CXCR4 was localized in the cytoplasm of P39 cells while it was in the membrane of U937 cells. Since the protein quinase C (PKC'dzeta') is related to the SDF-1/CXCR4 signaling by increasing CXCR4 expression and its membrane availability, we decided to work with cells P39 overexpressing PKC'dzeta' (PKC'dzeta'wt). This procedure resulted in translocation of CXCR4 to the membrane of P39 cells but did not change the CXCR7 subcellular localization. Transwell chemotaxis assay showed that P39 cells overexpressing PKC'dzeta' displayed higher chemotactic ability upon SDF-1 treatment compared with control P39 (35 fold increase pcDNA3-PKC'dzeta'-HA vs pcDNA3-HA transfected P39 cells, p=0.0032; Mann-Whitney), suggesting that PKC'dzeta' restored the chemotactic capacity of P39 cells. Increased expression of CXCR7, as here observed in lymphoblastic leukemia cells, is a phenomenon already described in a variety of solid tumor cell lines such as brain, prostate and lung. In solid tumors, CXCR7 mainly increases the proliferation of malignant cells. These results suggest that the biological function of CXCR7 depends on its tissue and organ localization and that, in acute lymphoblastic leukemia may have a role in cell chemotaxis, potentiating CXCR4 response to SDF-1 and thus, could contribute for leukemia initiating cell recruitment to niches once occupied by normal hematopoietic stem cells. Furthermore, our results lead us to believe that a defect in the PKC'dzeta'/CXCR4 pathway is involved with the unresponsiveness of MDS cells to SDF-1, generating an ineffective hematopoiesis. It confirms data that suggest that PKC'dzeta' is a central protein in the SDF-1/CXCR4 signaling pathway, important for the migration of malignant hematoietic cells
Mestrado
Fisiopatologia Médica
Mestre em Ciências
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Danilucci, Taís Marolato [UNESP]. "CXCL12 estimula fibroblastos pulmonares a produzir CCL3, CXCL2, LTB4 e LTC4 via p38, MEK1/2, PI-3K e JNK". Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/108908.
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000749985.pdf: 1413898 bytes, checksum: 7421bc33cc6d75478dcb676de29021bd (MD5)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
A quimiocina C-X-X motif ligand 12 (CXCL12) e seu receptor de quimiocina 4 (CXCR4) desenvolvem um papel crítico na inflamação das vias aéreas. No entanto, os efeitos da ativação da via CXCL12/CXCR4 sobre fibroblastos pulmonares ainda são desconhecidos. Neste estudo, investigamos o efeito da via CXCL12/CXCR4 sobre a quimiocina (C-C motif) ligante 3 (CCL3) e (C-X-C motif) ligante 2 (CXCL2) e sobre os mediadores lipídicos leucotrienos B4 (LTB4) e C4 (LTC4) por fibroblastos pulmonares e a sinalização intracelular envolvida neste processo. CXCL12 foi capaz de induzir a produção de CCL3, CXCL2, LTB4 e LTC4; a produção de CCL3 não é dependente da produção de CXCL2, mas a produção de CXCL2 é dependente da produção de CCL3. A produção de LTB4 pode ser parcialmente regulada por CXCL2 e CCL3 e a produção de LTC4 é dependente da produção de CCL3 e CXCL2. Fibroblastos pulmonares constitutivamente expressam CXCR4 e a estimulação com CXCL12 induz sua expressão. Análises de Western blot mostraram que CXCL12 aumenta a expressão proteica de CXCR4 e induz a fosforilação da S339 do CXCR4. A expressão gênica constitutiva e induzida de CXCR4 foram inibidas pelo anticorpo anti-CXCL2. No entanto, o anticorpo anti-CCL3 e o inibidor farmacológico MK886 foram capazes de diminuir a expressão gênica induzida de CXCR4. Os fibroblastos pulmonares foram pré-tratados com MK886, dexametasona (Dexa) e/ou loratadina (Lor). MK886 e Lor promoveram a diminuição da produção de LTC4 e LTB4, mas não a de CCL3 e CXCL2. Dexa diminuiu níveis de CCL3, CXCL2, LTB4 e LTC4, e quando associado com Lor esta diminuição foi mais eficaz. Identificamos...
C-X-X motif ligand 12 (CXCL12) and its specific receptor Chemokine receptor 4 (CXCR4) play a critical role in airway inflammation. However, the effects of CXCL12/CXCR4 axis on pulmonary fibroblast activation are unknown. In this study, we investigated the effect of CXCL12/CXCR4 axis on chemokine (C-C motif) ligand 3 (CCL3), chemokine (C-X-C motif) ligand 2 (CXCL2), leukotrienes B4 (LTB4) and C4 (LTC4) production by pulmonary fibroblasts and the intracellular signaling involved in the process. CXCL12 induced CCL3, CXCL2, LTB4 and LTC4 production, and CCL3 production is not dependent on CXCL2; but CXCL2 production is dependent on CCL3 production. LTB4 production can be partially down-regulated by CXCL2 and CCL3 production and LTC4 production is dependent on CCL3 and CXCL2 production. Pulmonary fibroblasts constitutively expressed CXCR4, and CXCL12 stimulation up-regulated its expression. Western blot analysis showed that CXCL12 increased protein expression of CXCR4 and induced phosphorylation at S339 of CXCR4. Constitutive CXCR4 expression was decreased by anti-CCL3 antibody or MK 886. Inducible CXCR4 was inhibited by anti-CXCL2 antibody. Indeed pulmonary fibroblasts were pretreated with MK886, dexamethasone (Dexa) and loratadine (Lor). MK886 and loratadine was able to reduced LTB4 and LTC4 production but not CCL3 and CXCL2. Dexa decreased CCL3, CXCL2, LTB4 and LTC4 production, and when associated with Lor this decrease was more effective. We found that PI-3K and JNK intracellular signaling play a role in CCL3 production; p38, MEK1/2, PI-3K and JNK are involved in CXCL2 production and p38 and MEK1/2 pathways are involved in LTB4 production by...
Libri sul tema "CXCR2 receptors"
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Livingston, Schuyler, Benjamin Young, Martin Markowitz, Poonam Mathur e Bruce L. Gilliam. HIV Virology. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0017.
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HIV is a member of the lentivirus subfamily of retroviruses. Two distinct groups of viruses are pathogenic in humans: HIV-1 and HIV-2. Both are transmitted sexually and known to cause immunodeficiency disease. HIV enters the cell through use of the CD4 receptor and chemokine co-receptors, primarily CCR5 and CXCR4. The viral genome is transcribed from RNA to DNA by reverse transcriptase and integrated into the host genome by integrase. The HIV genome encodes 15 proteins, comprising three categories: structural, regulatory, and accessory. After budding from the host cell, the virus matures into its infectious form through cleavage of viral precursor proteins by protease.
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Fruehauf, Stefan, W. Jens Zeller e Gary Calandra. Novel Developments in Stem Cell Mobilization: Focus on CXCR4. Springer, 2014.
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Fruehauf, Stefan, W. Jens Zeller e Gary Calandra. Novel Developments in Stem Cell Mobilization: Focus on CXCR4. Springer, 2012.
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Noels, Heidi, e Jürgen Bernhagen, a cura di. The CXCR4 Ligand/Receptor Family and the DPP4 Protease in High-Risk Cardiovascular Patients. Frontiers Media SA, 2016. http://dx.doi.org/10.3389/978-2-88919-858-0.
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Novel Developments In Stem Cell Mobilization Focus On Cxcr4. Springer, 2012.
Cerca il testo completoCapitoli di libri sul tema "CXCR2 receptors"
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Furusato, Bungo, e Johng S. Rhim. "CXCR4 and Cancer". In Chemokine Receptors in Cancer, 31–45. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-60327-267-4_2.
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Blay, Jonathan. "Chemokine Receptor CXCR4". In Encyclopedia of Cancer, 1–5. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-642-27841-9_1067-3.
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Blay, Jonathan. "Chemokine Receptor CXCR4". In Encyclopedia of Cancer, 932–36. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/978-3-662-46875-3_1067.
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Baljinder, Singh, Watts Ankit, Amit Singh Shekhawat, Singh Ashwin, Pankaj Malhotra, Abdul Waheed, Kaur Harneet et al. "CXCR4 Theranostics: A Potential Game Changer in Solid Tumors and Hematological Malignancies". In Beyond Becquerel and Biology to Precision Radiomolecular Oncology: Festschrift in Honor of Richard P. Baum, 309–20. Cham: Springer International Publishing, 2024. http://dx.doi.org/10.1007/978-3-031-33533-4_31.
Testo completoAbstract (sommario):
AbstractAn overexpression of CXCR4 receptors is reported in at least 30 different human solid tumors and hematological malignancies. This overexpression is often associated with tumor aggressiveness, increased risk of metastasis, and a higher probability of recurrence, which in turn leads to a poor prognosis. No in vivo method suitable for whole-body CXCR4 disease quantification has been described and this unmet clinical need or the scientific question has been reported recently. 68Ga-Pentixafor which is a CXCR4 targeting high-affinity PET imaging probe and the tracer has been evaluated in multiple myeloma, lymphoproliferative disorders, and in lung carcinoma, and the imaging results are extremely promising. Human dosimetry studies demonstrated excellent pharmacokinetics and low radiation burden to patients. The clinical applications of 68Ga-Pentixafor/177Lu/213Bi-Pentixather as a “theranostics pair” for the diagnosis and treatment of CXCR4-expressing cancers are emerging. CXCR4-based theranostics, which had not been investigated in clinical practice till now (except few preliminary proof-of-concept studies), may be a potential game changer both in the diagnosis and treatment of CXCR4 overexpressing solid tumors and hematological malignancies in which all other available treatment options have eventually failed.
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Sarau, Henry M., Katherine L. Widdowson, Michael R. Palovich, John R. White, David C. Underwood/surname e Don E. Griswold. "Interleukin-8 Receptor (CXCR2) Antagonists". In New Drugs for Asthma, Allergy and COPD, 293–96. Basel: KARGER, 2001. http://dx.doi.org/10.1159/000062157.
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Li, Yanchun, e Amy M. Fulton. "The CXCR3/CXCL3 Axis in Cancer". In Chemokine Receptors in Cancer, 79–91. Totowa, NJ: Humana Press, 2009. http://dx.doi.org/10.1007/978-1-60327-267-4_5.
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Wijtmans, Maikel, Iwan J. P. de Esch e Rob Leurs. "Therapeutic Targeting of the CXCR3 Receptor". In Methods and Principles in Medicinal Chemistry, 301–22. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2011. http://dx.doi.org/10.1002/9783527631995.ch13.
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Calì, Corrado, Julie Marchaland, Osvaldo Mirante e Paola Bezzi. "Chemokines as Neuromodulators: Regulation of Glutamatergic Transmission by CXCR4-Mediated Glutamate Release From Astrocytes". In Chemokine Receptors and NeuroAIDS, 271–300. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-1-4419-0793-6_12.
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Lam, Clarissa, Mahmud Arif Pavel, Parul Kashyap, Zahra Salehi-Najafabadi, Victoria Valentino e Yong Yu. "Detection of CXCR2 Cytokine Receptor Surface Expression Using Immunofluorescence". In Cytokine Bioassays, 193–200. New York, NY: Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4939-0928-5_17.
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Sengupta, Rajarshi, e Olimpia Meucci. "Regulation of Neuronal Chemokine Receptor CXCR4 by μ-Opioid Agonists and Its Involvement in NeuroAIDS". In Chemokine Receptors and NeuroAIDS, 379–97. New York, NY: Springer New York, 2009. http://dx.doi.org/10.1007/978-1-4419-0793-6_17.
Testo completoAtti di convegni sul tema "CXCR2 receptors"
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Adekoya, Timothy O., Nikia Smith, Parag Kothari e Ricardo M. Richardson. "Abstract PO-134: Differential effects of CXCR1 and CXCR2 receptors on prostate tumorigenesis". In Abstracts: AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; October 6-8, 2021. American Association for Cancer Research, 2022. http://dx.doi.org/10.1158/1538-7755.disp21-po-134.
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Pham, Kien, Che Liu, Defang Luo, Brent A. Reynolds e Jeffrey K. Harrison. "Abstract 5194: Heterogenous expression of chemokine receptors in primary patient-derived GBM lines; association of CXCR3, CXCR4, and CXCR7 with a slow cycling sub-population". In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-5194.
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Silva, Mariane Ricciardi da, Nádia Calvo Martins Okuyama e Karen Brajão De Oliveira. "PAPEL DAS VARIANTES GENÉTICAS DE CXCL12 (RS1801157) E DE CXCR4 (RS2228014) NA EXPRESSÃO PROTEICA DO RECEPTOR E EM PARÂMETROS CLINICOPATOLÓGICOS DO CÂNCER DE COLO DE ÚTERO". In II Congresso Brasileiro de Saúde On-line. Revista Multidisciplinar em Saúde, 2021. http://dx.doi.org/10.51161/rems/1519.
Testo completoAbstract (sommario):
Introdução: O câncer cervical é o terceiro câncer mais comum em mulheres no mundo e a inflamação é um componente crucial na progressão do tumor, mas outros cofatores devem estar presentes para o desenvolvimento da malignidade, como fatores genéticos individuais. Nesse contexto, os genes CXCL12 e CXCR4 podem ter uma variação de nucleotídeo único (SNV) rs1801157 e rs2228014, respectivamente, que estão envolvidas na sobrevivência, angiogênese e invasão de células malignas. Objetivos: O objetivo do presente estudo foi verificar uma possível associação entre SNVs de CXCL12 e CXCR4 e sua influência na expressão de CXCR4 em tecido tumoral de câncer cervical, analisar associação entre as variantes de nucleotídeo único de CXCL12 e CXCR4 com parâmetros clinicopatológicos (tumor, grau da histologia e estágio) e a expressão de CXCR4 em tecido tumoral. Material e métodos: CXCL12 e CXCR4 foram avaliados por PCR, seguida de digestão enzimática para 90 pacientes, e imuno-histoquímica foi realizada em 35 amostras de tumor cervical fixado em formalina e incluso em parafina. Resultados: Não foi encontrada diferença na distribuição genotípica entre os grupos para cada variável. Nem o efeito principal dos SNVs, nem as interações (GA + AA por CT +TT) foram associadas com as características clinicopatológicas analisadas. Em relação a marcação proteica de CXCR4, não houve relação significativa com os parâmetros clinicopatológicos analisados. A avaliação de rs1801157 de CXCL12 e rs2228014 de CXCR4 e a imunocoloração não demonstraram relação significativa entre os graus de imunocoloração de CXCR4 e cada modelo de SNVs de CXCL12 e CXCR4. Conclusão: Os resultados demonstram que não foi comprovada associação entre os SNVs e os parâmetros analisados. Essa é a primeira vez que os SNVs de CXCL12 e CXCR4 foram analisados com o objetivo de verificar a possibilidade de associação com a imunocoloração de CXCR4 e parâmetros clinicopatológicos.
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Miekus, Katarzyna, Danuta Jarocha, Elzbieta Trzyna e Marcin Majka. "Abstract B113: Role of I‐TAC‐binding receptors CXCR3 and CXCR7 in biology of various tumor cell lines". In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-b113.
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Costa, Leonardo, Jürgen Haas, Henriette Rudolph, Saskia Libicher, Sven Jarius, Tobias Tenenbaum, Horst Schroten e Brigitte Brigitte Wildemann. "The Choroid Plexus Is Permissive for a Preactivated Antigen-Experienced Memory B Cell Subset in Multiple Sclerosis". In Building Bridges in Medical Science 2021. Cambridge Medicine Journal, 2021. http://dx.doi.org/10.7244/cmj.2021.03.001.2.
Testo completoAbstract (sommario):
Background: The role of B cells in multiple sclerosis (MS) is increasingly recognized. B cells undergo compartmentalized redistribution in blood and cerebrospinal fluid (CSF) during active MS, whereby memory B cells accumulate in the CSF. While B-cell trafficking across the blood– brain barrier has been intensely investigated, cellular diapedesis through the blood–CSF barrier (BCSFB) is incompletely understood. Objectives: To investigate how B cells interact with the choroid plexus to transmigrate into the CSF, we isolated circulating B cells from healthy donors (HC) and MS patients, utilized an inverted cell culture filter system of human choroid plexus papilloma (HIBCPP) cells to determine transmigration rates of B-cell subsets, immunofluorescence, and electron microscopy to analyze migration routes, and qRT-PCR to determine cytokines/chemokines mediating B-cell diapedesis. We also screened the transcriptome of intrathecal B cells from MS patients. Results: We found that spontaneous transmigration of HC- and MS-derived B cells was scant yet increased significantly in response to B-cell specific chemokines CXCL-12/CXCL-13, was further boosted upon pre-activation and occurred via paracellular and transcellular pathways. Migrating cells exhibited upregulation of several genes involved in B-cell activation/migration and enhanced expression of chemokine receptors CXCR4/CXCR5 and were predominantly of isotype class switched memory phenotype. This antigen-experienced migratory subset displayed more pronounced chemotactic activities in MS than in HC and was retrieved in intrathecal B cells from patients with active MS. Trafficking of class-switched memory B cells was downscaled in a small cohort of natalizumab-exposed MS patients and the proportions of these phenotypes were reduced in peripheral blood yet were enriched intrathecally in patients who experienced recurrence of disease activity after withdrawal of natalizumab. Conclusion: Our findings highlight the relevance of the BCSFB as an important gate for the entry of potentially harmful activated B cells into the CSF.
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Miller, Eric J., Petra Gregorova, Carrie Q. Sun, Leon Jacobs, Zafer Sahin, Yesim Altas Tahirovic, Samantha L. Burton et al. "Tetrahydroisoquinoline-Based Small Molecule Inhibitors of the Chemokine Receptor CXCR4". In ASPET 2024 Annual Meeting Abstract. American Society for Pharmacology and Experimental Therapeutics, 2024. http://dx.doi.org/10.1124/jpet.291.127096.
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Sharma, Bhawna, Dhananjay M. Nawandar, Michelle L. Varney e Rakesh K. Singh. "Abstract 693: Evaluating the role of CXCR2 receptor and its ligand in breast cancer therapy resistance". In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-693.
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Wade, R. C., D. Xing, V. Lin, Y. Wu, C. Song, X. Xu, N. Harris, J. M. Wells e G. A. Payne. "Inflammatory Ligands of CXC Chemokine Receptor 2 (CXCR2) Are Associated with Coronary Artery Calcification in COPD". In American Thoracic Society 2022 International Conference, May 13-18, 2022 - San Francisco, CA. American Thoracic Society, 2022. http://dx.doi.org/10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2401.
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Wei, Xiao-Lan, Jing Zhang e Zhi-Hong Mo. "Regulation of chemokine receptor CXCR4 in HepG2 cell adhesion sensing by QCM". In 2011 International Conference on Human Health and Biomedical Engineering (HHBE). IEEE, 2011. http://dx.doi.org/10.1109/hhbe.2011.6029075.
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Mona, Christine, Marilou Lefrançois, Philip E. Boulais, Élie Besserer-Offroy, Richard Leduc, Nikolaus Heveker, Éric Marsault e Emanuel Escher. "Synthetic Agonists for the CXCR4 Receptor: SAR, Signaling Pathways and Peptidomimetic Transition". In The Twenty-Third American and the Sixth International Peptide Symposium. Prompt Scientific Publishing, 2013. http://dx.doi.org/10.17952/23aps.2013.198.
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