Search results for "M2"
showing 10 items of 256 documents
Novel Opportunities for Cathepsin S Inhibitors in Cancer Immunotherapy by Nanocarrier-Mediated Delivery
2020
Cathepsin S (CatS) is a secreted cysteine protease that cleaves certain extracellular matrix proteins, regulates antigen presentation in antigen-presenting cells (APC), and promotes M2-type macrophage and dendritic cell polarization. CatS is overexpressed in many solid cancers, and overall, it appears to promote an immune-suppressive and tumor-promoting microenvironment. While most data suggest that CatS inhibition or knockdown promotes anti-cancer immunity, cell-specific inhibition, especially in myeloid cells, appears to be important for therapeutic efficacy. This makes the design of CatS selective inhibitors and their targeting to tumor-associated M2-type macrophages (TAM) and DC an attr…
Genetics and Pathogenetic Role of Inflammasomes in Philadelphia Negative Chronic Myeloproliferative Neoplasms: A Narrative Review
2021
The last decade has been very important for the quantity of preclinical information obtained regarding chronic myeloproliferative neoplasms (MPNs) and the following will be dedicated to the translational implications of the new biological acquisitions. The overcoming of the mechanistic model of clonal evolution and the entry of chronic inflammation and dysimmunity into the new model are the elements on which to base a part of future therapeutic strategies. The innate immune system plays a major role in this context. Protagonists of the initiation and regulation of many pathological aspects, from cytokine storms to fibrosis, the NLRP3 and AIM2 inflammasomes guide and condition the natural hi…
The Role of p53 Signaling in Colorectal Cancer.
2021
Simple Summary The transcription factor p53 is a crucial tumor suppressor that regulates diverse cellular responses to protect against cancer development. Deactivating p53 signaling either by altering p53 regulators or by p53 mutations occurs frequently in human colorectal carcinoma (CRC). Forty-three percent of CRCs harbor p53 mutations that reduce wild-type p53 tumor suppressor activity and often provide neo-morphic functions, which contribute to tumorigenesis. In this review, we summarize wild-type p53 signaling, how it can be deregulated in CRC, and the functional and phenotypical effects of p53 mutations. We also discuss current therapeutic strategies of targeting p53. Abstract The tra…
The proof of Birman’s conjecture on singular braid monoids
2003
Let B_n be the Artin braid group on n strings with standard generators sigma_1, ..., sigma_{n-1}, and let SB_n be the singular braid monoid with generators sigma_1^{+-1}, ..., sigma_{n-1}^{+-1}, tau_1, ..., tau_{n-1}. The desingularization map is the multiplicative homomorphism eta: SB_n --> Z[B_n] defined by eta(sigma_i^{+-1}) =_i^{+-1} and eta(tau_i) = sigma_i - sigma_i^{-1}, for 1 <= i <= n-1. The purpose of the present paper is to prove Birman's conjecture, namely, that the desingularization map eta is injective.
Controlled polyhedral sweeping processes: existence, stability, and optimality conditions
2021
This paper is mainly devoted to the study of controlled sweeping processes with polyhedral moving sets in Hilbert spaces. Based on a detailed analysis of truncated Hausdorff distances between moving polyhedra, we derive new existence and uniqueness theorems for sweeping trajectories corresponding to various classes of control functions acting in moving sets. Then we establish quantitative stability results, which provide efficient estimates on the sweeping trajectory dependence on controls and initial values. Our final topic, accomplished in finite-dimensional state spaces, is deriving new necessary optimality and suboptimality conditions for sweeping control systems with endpoint constrain…
Existence de points fixes enlacés à une orbite périodique d'un homéomorphisme du plan
1992
Let f be an orientation-preserving homeomorphism of the plane such that f-Id is contracting. Under these hypotheses, we establish the existence, for every periodic orbit, of a fixed point which has nonzero linking number with this periodic orbit.
Identificación de TRIM29 localizado en la región cromosómica 11q23.3 como biomarcador de resistencia a Doxorubicina y proliferación celular en cáncer…
2018
El cáncer de mama es una enfermedad compleja y heterogénea en la que los pacientes pueden presentar síntomas similares y padecer la misma enfermedad por razones genéticas completamente diferentes. Los factores que contribuyen a esta heterogeneidad incluyen la variación en el genoma de cada paciente, las diferencias en el origen y la naturaleza de la célula tumoral y los eventos genéticos que contribuyen a la progresión del tumor. La recaída en cáncer de mama es una de las mayores causas de morbilidad en pacientes que desarrollan la enfermedad y, entre ellas, entre un 15-20% poseerán tumores de mama triple negativo (TN). La mortalidad de pacientes con cáncer de mama TN es considerablemente m…
Central functional response to the novel peptide cannabinoid, hemopressin.
2013
Hemopressin is the first peptide ligand to be described for the CB₁ cannabinoid receptor. Hemopressin acts as an inverse agonist in vivo and can cross the blood-brain barrier to both inhibit appetite and induce antinociception. Despite being highly effective, synthetic CB₁ inverse agonists are limited therapeutically due to unwanted, over dampening of central reward pathways. However, hemopressin appears to have its effect on appetite by affecting satiety rather than reward, suggesting an alternative mode of action which might avoid adverse side effects. Here, to resolve the neuronal circuitry mediating hemopressin's actions, we have combined blood-oxygen-level-dependent, pharmacological-ch…
Cannabinoid type 1 receptor modulates intestinal propulsion by an attenuation of intestinal motor responses within the myenteric part of the peristal…
2007
Cannabinoid-1 (CB1) receptor activation affects gastrointestinal propulsion in vivo. It was our aim to further characterize the involved myenteric mechanisms in vivo and in vitro. In CB1(-/-) mice and wild-type littermates we performed in vivo transit experiments by charcoal feeding and in vitro electrophysiological recordings in mouse small intestinal smooth muscle. Ascending neuronal contraction (ANC) following electrical field stimulation was studied in rat ileum in a partitioned organ bath separating the aboral stimulation site from the oral recording site. The knockout animals displayed an accelerated upper gastrointestinal transit compared to control animals. The CB1 receptor antagoni…
Differential effects of CB1 neutral antagonists and inverse agonists on gastrointestinal motility in mice
2010
Background Cannabinoid type 1 (CB1) receptors are involved in the regulation of gastrointestinal (GI) motility and secretion. Our aim was to characterize the roles of the CB1 receptor on GI motility and secretion in vitro and in vivo by using different classes of CB1 receptor antagonists. Methods Immunohistochemistry was used to examine the localization of CB1 receptor in the mouse ileum and colon. Organ bath experiments on mouse ileum and in vivo motility testing comprising upper GI transit, colonic expulsion, and whole gut transit were performed to characterize the effects of the inverse agonist/antagonist AM251 and the neutral antagonist AM4113. As a marker of secretory function we mea…