Search results for "Inhibition"
showing 10 items of 590 documents
Innovative therapy, monoclonal antibodies, and beyond: Highlights from the eighth annual meeting
2018
The eighth annual conference of “Innovative therapy, monoclonal antibodies, and beyond” was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS–Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies. Presentations in the first session addressed the issue of cancer immunotherapy activity with respect to tumor heterogeneity, with key topics addressing: 1) tumor heterogeneit…
Cardiovascular Issues in Tyrosine Kinase Inhibitors Treatments for Chronic Myeloid Leukemia: A Review
2021
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo wh…
Pain-Induced Negative Affect Is Mediated via Recruitment of The Nucleus Accumbens Kappa Opioid System.
2019
Negative affective states affect quality of life for patients suffering from pain. These maladaptive emotional states can lead to involuntary opioid overdose and many neuropsychiatric comorbidities. Uncovering the mechanisms responsible for pain-induced negative affect is critical in addressing these comorbid outcomes. The nucleus accumbens (NAc) shell, which integrates the aversive and rewarding valence of stimuli, exhibits plastic adaptations in the presence of pain. In discrete regions of the NAc, activation of the kappa opioid receptor (KOR) decreases the reinforcing properties of rewards and induces aversive behaviors. Using complementary techniques, we report that in vivo recruitment …
Bacterial Biofilm Inhibition in the Development of Effective Anti-Virulence Strategy
2018
There is an urgent need for new therapeutic strategies to counteract the global threat of antibiotic resistance, which has become, in recent years, one of the major public health concern. An important contribution to the microbial survival in hostile environments has been given by the capability of pathogens to form sessile communities able to adhere to biotic or abiotic surfaces, known as biofilms.
Substrate Specificity of Aglaia loheri Active Isolate towards P-glycoprotein in Multidrug-Resistant Cancer Cells
2016
Multidrug resistance (MDR) is a major contributory factor in the failure of chemotherapy. Concrete interpretation of P-glycoprotein (P-gp) substrate specificity, whether a substance is a substrate or an inhibitor, represents an important feature of a compound's pharmaceutical profiling in drug design and development. In this work, the P-gp substrate specificity of Maldi 531.2[M+H]+, a phenol ester from Aglaia loheri Blanco leaves was investigated. This study focuses on the effect of Maldi 531.2[M+H]+ on P-gp ATPase activity, which was examined by measuring the amount of inorganic phosphates (Pi) released as a result of ATP hydrolysis. To test the effects of Maldi 531.2[M+H]+ on MDR activit…
Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake
2017
The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Here, we report the design, chemical synthesis, and biological profiling of natural product-derived N-substituted 2,4-dodecadienamides as a selective endocannabinoid uptake inhibitor. The highly potent (IC50 = 10 nM) inhibitor N-(3,4-dimethoxyphenyl)ethyl amide (WOBE437) exerted pronounced canna…
Wharton’s Jelly Mesenchymal Stromal Cells from Human Umbilical Cord: a Close-up on Immunomodulatory Molecules Featured In Situ and In Vitro
2019
Therapeutic options for end-stage organ failure are often limited to whole organ transplantation. The tolerance or rejection of the transplanted organ is driven by both early non-specific innate and specific adaptive responses. The use of mesenchymal stromal cells (MSCs) is considered a promising tool in regenerative medicine. Human umbilical cord (HUC) is an easily available source of MSCs, without relevant ethical issues. Moreover, Wharton's jelly-derived MSCs (WJ-MSCs), showed consistent immunomodulatory features that may be useful to promote immune tolerance in the host after transplantation. Few data are available on the phenotype of WJ-MSCs in situ. We investigated the expression of i…
PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study.
2019
Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradatio…
Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G-Quadruplex: a Joint ESI MS and XRD Investi…
2016
International audience; The dicarbene gold(I) complex [Au(9-methylcaffein-8-ylidene)(2)]BF4 is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines invitro and behaves as a selective G-quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X-ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9-methylcaffein-8-ylidene)(2)]…
On the Antibacterial Activity of Azacarboxylate Ligands: Lowered Metal Ion Affinities for Bis-amide Derivatives of EDTA do not mean Reduced Activity.
2018
EDTA is widely used as an inhibitor of bacterial growth, affecting the uptake and control of metal ions by microorganisms. We describe the synthesis and characterisation of two symmetrical bis-amide derivatives of EDTA, featuring glycyl or pyridyl substituents: AmGly2 and AmPy2 . Metal ion affinities (logK) have been evaluated for a range of metals (Mg2+ , Ca2+ , Fe3+ , Mn2+ , Zn2+ ), revealing less avid binding compared to EDTA. The solid-state structures of AmGly2 and of its Mg2+ complex have been determined crystallographically. The latter shows an unusual 7-coordinate, capped octahedral Mg2+ centre. The antibacterial activities of the two ligands and of EDTA have been evaluated against …