Search results for "CXC"
showing 10 items of 159 documents
Anti-Metastatic Activities of Heparins
2009
Heparins are commonly administered to cancer patients for the treatment and prophylaxis of thromboembolic events. Importantly, apart from the anti-thrombotic action of these drugs, several clinical trials have demonstrated an improved survival of cancer patients who were administered low-molecular-weight heparins (LMWHs). This improved survival was independent of the anti-thrombotic efficacy, since vitamin K antagonists did not improve clinical prognosis. Moreover, this protective effect was not the result of an inhibition of the growth of primary tumors, but rather the prevention of the spreading of cancer through metastases. This has been also shown in some animal experiments. The protect…
Interleukin-30 feeds breast cancer stem cells via CXCL10 and IL23 autocrine loops and shapes immune contexture and host outcome
2021
BackgroundBreast cancer (BC) progression to metastatic disease is the leading cause of death in women worldwide. Metastasis is driven by cancer stem cells (CSCs) and signals from their microenvironment. Interleukin (IL) 30 promotes BC progression, and its expression correlates with disease recurrence and mortality. Whether it acts by regulating BCSCs is unknown and could have significant therapeutic implications.MethodsHuman (h) and murine (m) BCSCs were tested for their production of and response to IL30 by using flow cytometry, confocal microscopy, proliferation and sphere-formation assays, and PCR array. Immunocompetent mice were used to investigate the role of BCSC-derived IL30 on tumor…
Expression of chemokine receptor CXCR4 correlates with progression of pancreatic cancer
2006
14018 Background: Despite many pathophysiological analyses, the process of tumor dissemination of pancreatic cancer remains vague. In diverse other tumor entities, expression of the chemokine receptor CXCR4 has been linked to tumor dissemination and poor prognosis. Therefore, we evaluated, if the expression of this chemokine receptor exerts similar effects in human pancreatic cancer. Methods: Expression of CXCR4 was evaluated in 120 patients with histologically confirmed pancreatic cancer and eight different pancreatic cancer cell lines. Expression intensities of tumor samples were correlated with both, tumor and patients characteristics. Results: Human pancreatic cancer samples and cell l…
Balixafortide (a CXCR4 antagonist) + eribulin in HER2-negative metastatic breast cancer (MBC): Survival outcomes of the phase I trial.
2019
2606 Background: Balixafortide (B) is a potent antagonist of the chemokine receptor CXCR4. Preclinical evidence suggests that disrupting CXCR4 dependent pathways prevents development of breast cancer metastases, enhances the cytotoxic effect of chemotherapy and immunotherapy, and counteracts tumor cell evasion of the immune system. Encouraging safety and efficacy data were published recently from the ongoing Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC (Pernas S. et al. Lancet Oncol. 2018; 19: 812−24). The objective response rate, median progression free survival and median overall survival (OS) for the expanded cohort (EC) and the overall efficacy popula…
Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransp…
2014
Abstract Background Chemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival. Methods In this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and…
IL1β Induces Mesenchymal Stem Cells Migration and Leucocyte Chemotaxis Through NF-κB
2012
Mesenchymal stem cells are often transplanted into inflammatory environments where they are able to survive and modulate host immune responses through a poorly understood mechanism. In this paper we analyzed the responses of MSC to IL-1β: a representative inflammatory mediator. Microarray analysis of MSC treated with IL-1β revealed that this cytokine activateds a set of genes related to biological processes such as cell survival, cell migration, cell adhesion, chemokine production, induction of angiogenesis and modulation of the immune response. Further more detailed analysis by real-time PCR and functional assays revealed that IL-1β mainly increaseds the production of chemokines such as CC…
Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells.
2014
BACKGROUND: Recent findings indicate that exosomes released from cancer cells contain microRNAs (miRNAs) that may be delivered to cells of tumor microenvironment. RESULTS: To elucidate whether miRNAs secreted from chronic myelogenous leukemia cells (CML) are shuttled into endothelial cells thus affecting their phenotype, we first analysed miRNAs content in LAMA84 exosomes. Among the 124 miRNAs identified in LAMA84 exosomes, we focused our attention on miR-126 which was found to be over-overexpressed in exosomes compared with producing parental cells. Transfection of LAMA84 with Cy3-labelled miR-126 and co-culture of leukemia cells with endothelial cells (EC) confirmed that miR-126 is shuttl…
Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic proge…
2001
Stromal cell-derived factor-1alpha (SDF-1alpha) is a potent chemoattractant for hematopoietic progenitor cells (HPC), suggesting that it could play an important role during their migration within or to the bone marrow (BM). The integrin VLA-4 mediates HPC adhesion to BM stroma by interacting with CS-1/fibronectin and VCAM-1. It is required during hematopoiesis and homing of HPC to the BM. As HPC migration in response to SDF-1alpha might require dynamic regulation of integrin function, we investigated if SDF-1alpha could modulate VLA-4 function on BM CD34(hi) cells.CD34(hi) BM cells and hematopoietic cell lines were tested for the effect of SDF-1alpha on VLA-4-dependent adhesion to CS-1/fibr…
Balixafortide (a CXCR4 antagonist) plus eribulin in HER2 negative metastatic breast cancer: Dose-response analysis of efficacy from phase I single-ar…
2020
e15209 Background: Balixafortide (B) is a potent, selective antagonist of the chemokine receptor CXCR4. High CXCR4 levels correlate with aggressive metastatic phenotypes and poor prognosis in metastatic breast cancer (MBC). Efficacy and safety data were published recently from the Phase 1 trial investigating B + eribulin (E) in patients with HER2 negative MBC1. We report the final efficacy analyses from this trial, including assessment of dose-response. Methods: In this single-arm, dose escalation trial, patients (pts) received E + increasing doses of B using a 3+3 design in 3 parts: Part I (cohorts received low E doses); Part II (dose-escalation cohort for B [1−5.5mg/kg] + 1.4mg/m2 E); Ex…
Cytogenetic analysis and metabolic profiling reveal a subgroup of benign meningiomas with chromosomal instabilities and aggressive metabolism
2010
Meningiomas add up to 30% of Central Nervous System (CNS) tumours. Atypical meningiomas show a high index of recurrence 5 years after complete resection. Sometimes, meningiomas with histological diagnosis of benign meningioma show genetics characteristics of atypical meningioma. Aberrations of chromosomes 1, 14, and 22 are the most frequently reported abnormalities in meningiomas. In this communication we used cytogenetic, FISH, and NMR metabolic profiling for a molecular characterization of a series of 46 meningiomas. Tumor samples were obtained from 46 patients with meningioma (36 benign and 12 atypical) from the Clinic Hospital of Valencia. Cytogenetic analyses were performed by short-te…