Search results for "CX"

Estudio de nuevos mecanismos angiogénicos e inflamatorios asociados a la obesidad

2023

La obesidad es una enfermedad metabólica que se caracteriza por la acumulación excesiva de grasa acompañada de una inflamación crónica, leve y sistémica, debido a la elevada ingesta calórica, entre otros factores. Esta patología tiene varios grados y se diagnostica cuando los sujetos tienen un índice de masa corporal (IMC) mayor o igual a 30 kg/m2. Su prevalencia se ha triplicado a nivel mundial en los últimos 50 años y se ve afectada, aproximadamente, el 40% de la población mundial. Los mayores problemas de la obesidad son su alta mortalidad y el riesgo alto de desarrollar otras patologías asociadas como el síndrome metabólico y la diabetes mellitus tipo 2. El tejido adiposo se ha reconoci…

Abstract PO-46: Mechanisms of resistance to the PI3K inhibitor copanlisib in marginal zone lymphoma

2020

Abstract Background: PI3Kδ is expressed in B cells and has a central role in the B-cell receptor signaling. Copanlisib is a highly selective PI3Kδ and PI3Kα inhibitor, and it is currently under clinical development in indolent lymphomas including marginal zone lymphoma (MZL). Copanlisib is Food and Drug Administration (FDA) approved for the treatment of patients with relapsed or refractory follicular lymphoma. Nevertheless, a subset of patients can eventually relapse due to acquired resistance. A better understanding of resistance mechanisms could help to design improved therapies; hence, we generated MZL cell lines resistant to copanlisib. Materials and Methods: Cells were kept on copanlis…

Synthesis and studies of new optimised chelating agents for targeting chemokine receptor CXCR4

2012

The objective of this thesis work was to develop CXCR4-targeted tools to localize and treat cancer at an early stage. In this line, we investigated the synthesis of new target-specific radiopharmaceuticals. The work focused on two main axes, i.e. the chelating agent and the carrier, by using the know-how and the expertise of our group in polyazacycloalkanes synthesis and functionalization. In the first part, we were interested in developing new macrocyclic scaffolds of high potential for copper and gallium chelation. We first focused on the development of a new powerful route towards selectively functionalized constrained homocyclens. The second part was based on C-functionalized 1,4,7-tria…

GPCR Inhibition in Treating Lymphoma

2022

G protein-coupled receptors (GPCRs) are important classes of cell surface receptors involved in multiple physiological functions. Aberrant expression, upregulation, and mutation of GPCR signaling pathways are frequent in many types of cancers, promoting hyperproliferation, angiogenesis, and metastasis. Recent studies showed that alterations of GPCRs are involved in different lymphoma types. Herein, we review the synthetic strategies to obtain GPCR inhibitors, focusing on CXCR4 inhibitors which represent most of the GPCR inhibitors available in the market or under preclinical investigations for these diseases.

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…

CXL epi-on: esperienza personale

2013

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…