Abstract:
BACKGROUND AND PURPOSE:Inflammation associated with the tumour microenvironment (TME) plays a critical role in the cancer development, and immunotherapeutic strategies that aim to modulate the immune response in cancer have been crucial. In this study, a Methotrexate-loaded (MTX) poly (lactic-co-glycolic acid)-based (PLGA) drug nanocarrier covered with polyethyleneimine (Pei) and hyaluronic acid (HA) was developed and combined with anti-PD-L1 immune checkpoint inhibitor to investigate the anti-cancer and immunomodulatory performance in the breast cancer TME. EXPERIMENTAL APPROACH:From the allographic model of orthotopic tumour growth, the tumours were evaluated by qRT-PCR and immunohistochemistry. Complementary analysis of cell death profile, cell migration and macrophage polarization were evaluated in vitro. KEY RESULTS:Naked or HA-coated PeiPLGA-MTX nanoparticles (NPs) used alone or combined with anti-PD-L1 promoted tumorigenic course modification as well as TME immunomodulation with significant reduction of primary tumour and metastasis. For the first time, we reported the involvement of M2 macrophages as major orchestrator of this response via NPs-mediated IL-10/STAT3/NF-κB downregulation. The suppression of this signalling axis seems to have disrupted the crosstalk between immune and malignant cells, reducing critical pro-tumour events such as: immune escape; cell survival; drug and apoptosis resistance, as well as some key mechanisms in the epithelial-mesenchymal transition. CONCLUSION AND IMPLICATIONS:These results contribute to our understanding of the immunological mechanisms that underlie the anti-tumorigenic effects of an effective and promising drug nanocarrier capable of satisfactorily immunomodulating the TME and providing a favourable outcome in breast cancer.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Cavalcante RS,Ishikawa U,Silva ES,Silva Júnior AA,Araújo AA,Cruz LJ,Chan AB,Araújo Júnior RFdoi
10.1111/bph.15373subject
Has Abstractpub_date
2021-01-12 00:00:00eissn
0007-1188issn
1476-5381pub_type
杂志文章abstract::By implanting a Teflon chamber subcutaneously into a sheep a mild aseptic inflammatory lesion was produced from which wound fluid could be sampled daily. The prostaglandin content of this wound fluid was examined. Prostaglandin E2 activity was found in all samples, and a peak was apparent on the fourth or fifth day af...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07363.x
更新日期:1975-02-01 00:00:00
abstract::Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Her...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.12217
更新日期:2013-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The aim of the current study was to investigate the role of arachidonic acid (AA) metabolism via cyclooxygenase (COX) in the endothelial dysfunction of penile arteries from pre-diabetic, obese Zucker rats (OZR). EXPERIMENTAL APPROACH:Penile arteries from OZR and from lean Zucker rats (LZR) were ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00553.x
更新日期:2010-02-01 00:00:00
abstract::1 The effects of piribedil on contractile responses and noradrenaline release evoked by sympathetic nerve stimulation have been studied in the isolated kidney of the rabbit. These effects were compared to those of apomorphine.2 Electrical stimulation (2, 5 and 10 Hz) of sympathetic renal nerves produced frequency-depe...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10965.x
更新日期:1980-01-01 00:00:00
abstract::1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0700885
更新日期:1997-01-01 00:00:00
abstract::1. The possible mechanisms of action of the inhibitory effect of gomisin C on the respiratory burst of rat neutrophils in vitro was investigated. 2. The peptide formyl-Met-Leu-Phe (FMLP) induced superoxide anion (O2-) formation and O2 consumption, which was inhibited by gomisin C in a concentration-dependent manner (I...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17084.x
更新日期:1994-11-01 00:00:00
abstract::1 The present study examined effects of agonist enzymes and receptor-activating peptides for protease-activated receptors (PARs) on duodenal motility in the rat, and also investigated possible mechanisms underlying the evoked responses. 2 Thrombin at 0.03-0.1 microM and the PAR-1-activating peptide SFLLR-NH2 at 3-100 ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702755
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Excitation-transcriptional coupling involves communication between plasma membrane ion channels and gene expression in the nucleus. Calcium influx through L-type Ca(2+) channels induces phosphorylation of the transcription factor, cyclic-AMP response element binding protein (CREB) and downstream ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00599.x
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The human kinome consists of roughly 500 kinases, including 150 that have been proposed as therapeutic targets. Protein kinases regulate an array of signalling pathways that control metabolism, cell cycle progression, cell death, differentiation and survival. It is not surprising, then, that new ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14062
更新日期:2017-12-01 00:00:00
abstract::1. We studied the inhibitory effect of pituitary adenylate cyclase activating polypeptide (PACAP 1-27) on the increase in total pulmonary resistance (RL) caused either by allergen or histamine in anaesthetized, ventilated guinea-pigs. 2. PACAP 1-27 given via i.v. infusion (0.045-4.5 nmol kg-1 min-1) dose-dependently r...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15897.x
更新日期:1995-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Normal pregnancy is associated with decreased vascular resistance and increased release of vasodilators. Endothelin-1 (ET-1) causes vasoconstriction via endothelin receptor type A (ET(A)R), but could activate ET(B)R in the endothelium and release vasodilator substances. However, the roles of ET(B...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12225
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:The human, rat, and mouse P2X(7) receptors have been previously characterized, and in this study we report the cloning and pharmacological properties of the guinea pig orthologue. EXPERIMENTAL APPROACH:A cDNA encoding for the guinea pig P2X(7) receptor was isolated from a guinea pig brain librar...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707596
更新日期:2008-02-01 00:00:00
abstract::1. The effects of a series of nine GABAB receptor antagonists of widely varying potencies on electrically stimulated release from cortical slices of [3H]-GABA in the absence or presence of 10 microM of the GABAB agonist, (-)-baclofen and of endogenous glutamate in the presence of (-)-baclofen were compared. 2. The con...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1994.tb17168.x
更新日期:1994-12-01 00:00:00
abstract::1. Flexor withdrawal reflexes to noxious mechanical pinch stimuli were recorded as single motor unit activity in alpha-chloralose anaesthetized rats, by means of tungsten bipolar electrodes inserted percutaneously into hindlimb flexor muscles. The relative spinal and supraspinal contributions to mu- and kappa-opioid a...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12402.x
更新日期:1991-09-01 00:00:00
abstract::1. Sabcomeline (SB-202026, 0.03 mg kg(-1), p.o.), a potent and functionally selective M1 receptor partial agonist, caused a statistically significant improvement in the performance of a visual object discrimination task by marmosets. No such improvement was seen after RS86 (0.1 mg kg(-1), p.o.). 2. Initial learning, w...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701844
更新日期:1998-05-01 00:00:00
abstract::1. Des-Arg9 bradykinin (DAB), a classical B1-kinin receptor agonist was without effect when applied to the basolateral surface of rat isolated colon epithelium. Three hours after tissues were isolated DAB caused, after a delay of up to 2 min, a maintained increase of short circuit current (SCC). 2. The SCC increase in...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701225
更新日期:1997-07-01 00:00:00
abstract::1. Vasorelaxant properties of three nitric oxide (NO) donor drugs (glyceryl trinitrate, sodium nitroprusside and spermine NONOate) in mouse aorta (phenylephrine pre-contracted) were compared with those of endothelium-derived NO (generated with acetylcholine), NO free radical (NO*; NO gas solution) and nitroxyl ion (NO...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704269
更新日期:2001-10-01 00:00:00
abstract::Osteoarthritis (OA) is the most common disease of joints, which are complex organs where cartilage, bone and synovium cooperate to allow a range of movements. During progression of the disease, the function of all three main components is jeopardized. Nevertheless, the involvement of each tissue in OA development is s...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.14204
更新日期:2019-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Lithocholic acid (LCA), the most toxic bile acid, induces cholestatic liver injury in rodents. We previously showed that LCA activates the oxidative stress-responsive nuclear factor (erythroid-2 like), factor 2 (Nrf2) in cultured liver cells, triggering adaptive responses that reduce cell injury....
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00953.x
更新日期:2010-11-01 00:00:00
abstract::1. In the neuronally isolated cortex of the cat, local application of bemegride, picrotoxin, nikethamide, caffeine and strychnine facilitated the surface positive response of the isolated cortex and lowered the stimulus threshold for this response. Excepting nikethamide, they all produced convulsive discharge in the i...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1970.tb09897.x
更新日期:1970-08-01 00:00:00
abstract::1. The electrical activity of guinea-pig pelvic ganglion cells following iontophoretically applied cholinergic drugs, alone and during orthodromic nerve stimulation via the hypogastric nerve, has been recorded intracellularly.2. Iontophoretic application of nicotine (Nic) and acetylcholine (ACh) reduced membrane resis...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb09932.x
更新日期:1971-01-01 00:00:00
abstract::A dispersed rat anterior pituitary cell system has been used to investigate the effects of cyproheptadine and metergoline on prolactin secretion. Both drugs were potent inhibitors of prolactin secretion. However, the inhibition was not antagonized by either 5-hydroxytryptamine or a variety of dopamine antagonists. We ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10896.x
更新日期:1980-09-01 00:00:00
abstract::1. The modulation of 4-aminopyridine sensitive transient outward potassium current (4-AP I(to)) by neuropeptide Y (NPY) (100 nM) in rat ventricular myocytes was examined using the whole cell voltage-clamp technique. 2. Continuous exposure to NPY (100 nM) for 3 - 6 h significantly increased 4-AP I(to) density. The stim...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704643
更新日期:2002-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Erectile dysfunction is highly prevalent in diabetic patients and PDE V inhibitors are effective and safe for the treatment of erectile dysfunction in men with diabetes. Therefore, in this study we investigated whether a pharmacokinetic interaction occurs between DA-8159 and metformin, as both dr...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707680
更新日期:2008-04-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentrat...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12194
更新日期:2013-07-01 00:00:00
abstract::1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of aut...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb10507.x
更新日期:1983-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Lysophosphatidylinositol (LPI), a lipid signalling molecule, activates GPR55 and elevates intracellular Ca(2+). Here, we examine the actions of LPI in the rat resistance mesenteric artery and Ca(2+) responses in endothelial cells isolated from the artery. EXPERIMENTAL APPROACH:Vascular responses...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.13107
更新日期:2015-06-01 00:00:00
abstract::1. An investigation into the effects of cholecystokinin octapeptide (CCK-8S) and its pentapeptide analogue, pentagastrin, on neurones located in ventromedial nuclei of rat hypothalamic slices maintained in vitro has been undertaken. 2. CCK-8S (0.01-1.0 microM) applied in the perfusion medium produced a concentration-d...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11521.x
更新日期:1988-05-01 00:00:00
abstract::The processes underpinning post-developmental neurogenesis in the mammalian brain continue to be defined. Such processes involve the proliferation of neural stem cells and neural progenitor cells (NPCs), neuronal migration, differentiation and integration into a network of functional synapses within the brain. Both in...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13186
更新日期:2015-08-01 00:00:00
abstract::1 The spasmogenic and spasmolytic effects of beta-lipotropin (LPH) fragments and one analogue were investigated on different parts of the gastro-intestinal tract of guinea-pig and rat in vitro.2 Changes in muscle tone were observed in colon and rectum and to a lesser extent in jejunum and ileum of both species. Rat co...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb10849.x
更新日期:1980-04-01 00:00:00