Abstract:
:Immune checkpoint blockade therapy has become a first-line treatment in various cancers. But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy. How to increase their treatment efficacy is an urgent and clinically unmet need. It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity. Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor, compared with monotherapy. Here, we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1, and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1. P-Lipo increases intratumoral drug accumulation and promotes DC maturation, and thereby facilitates adaptive immune responses against tumor growth. The remodeling tumor immune microenvironment was reflected by the increased amount of CD8+ T cells and the release of IFN-γ, and the reduced CD4+Foxp3+ regulatory T cells (Tregs). Collectively, the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
He ZD,Zhang M,Wang YH,He Y,Wang HR,Chen BF,Tu B,Zhu SQ,Huang YZdoi
10.1038/s41401-020-00570-8subject
Has Abstractpub_date
2020-12-11 00:00:00eissn
1671-4083issn
1745-7254pii
10.1038/s41401-020-00570-8pub_type
杂志文章abstract:AIM:Localized delivery of growth factors has significant potential as a future therapeutic strategy in tissue engineering and regenerative medicine. A nanoparticle vehicle was created and evaluated in this study with the intent to deliver growth factors for periodontal regeneration. METHODS:Novel composite nanoparticl...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.15
更新日期:2009-04-01 00:00:00
abstract:AIM:To study the influence of angiotensin (Ang) II receptor antagonist (AT1) valsartan and angiotensin-converting enzyme (ACE) inhibitor fosinopril on the cardiac hypertrophy induced by catecholamine. METHODS:A cardiac hypertrophy model was produced by i.p. norepinephrine (NE) 1.5 mg.kg-1.d-1 x 15 d. The animals were ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
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abstract:AIM:Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP w...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.20
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abstract:AIM:Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2-targeted compounds have been reported. In this study, we identified a novel Pim-2 in...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.60
更新日期:2016-09-01 00:00:00
abstract:AIM:In order to elucidate the molecular mechanism underlying the cardioprotection afforded by schisandrin B (Sch B), the effect of Sch B treatment on the sensitivity of mitochondria to Ca2+-stimulated permeability transition (PT) was investigated in rat hearts under normal and ischemia-reperfusion (I-R) conditions. RE...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00614.x
更新日期:2007-10-01 00:00:00
abstract:AIM:To study the synaptic mechanisms involved in the 5-hydroxytryptamine1A/7 (5-HT1A/7) receptor-mediated reflex control of cardiac vagal preganglionic neurons (CVPN). METHODS:CVPN were retrogradely labeled and identified in brain stem slices of newborn rats, and their synaptic activity was examined using whole-cell p...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00745.x
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abstract:AIM:To investigate the ultrastructural localization of atrial natriuretic peptide (ANP)-synthesizing cells and the relationship between ANP-synthesizing cells and microvessels in rat gastric mucosa. METHODS:Immunohistochemistry techniques and postembedding immunoelectron microscopy techniques were used to validate the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00226.x
更新日期:2006-02-01 00:00:00
abstract::Excessive and abnormal vessel growth plays a critical role in the pathogenesis of many diseases, such as cancer. Angiogenesis is one of the hallmarks of cancer growth, invasion, and metastasis. Discovery of novel antiangiogenic agents would provide new insights into the mechanisms of angiogenesis, as well as potential...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/s41401-019-0224-x
更新日期:2019-11-01 00:00:00
abstract:AIM:Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF). METHODS:P...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2008.00905.x
更新日期:2008-12-01 00:00:00
abstract:AIM:To investigate the mechanism of action of a potent analgesic, (+/-)-meptazinol. METHODS:The structures of meptazinol enantiomers were compared with opioid pharmacophore and tramadol. RESULTS:Neither enantiomer of meptazinol fitted any patterns among the opioid pharmacophore and tramadol, although they did share s...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00045.x
更新日期:2005-03-01 00:00:00
abstract:AIM:To evaluate the pharmacokinetics of L-threonate after single or multiple oral administrations and its safety profile in healthy Chinese volunteers. METHODS:This was an open-label, single- and multiple-dose study. The subjects were assigned to receive a single dose, 675, 2025, or 4050 mg, of calcium L-threonate (n=...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.138
更新日期:2011-12-01 00:00:00
abstract:AIM:Cathepsin L is a lysosomal cysteine protease that plays important roles in cancer tumorigenesis, proliferation and chemotherapy resistance. The aim of this study was to determine how cathepsin L regulated the radiosensitivity of human glioma cells in vitro. METHODS:Human glioma U251 cells (harboring the mutant typ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2015.36
更新日期:2015-09-01 00:00:00
abstract:AIM:To investigate the mechanism of brain interleukin-1 beta (IL-1 beta) in reserpine-induced behavioral depression in rats. METHODS:Porsult swim test was used in the measurement of depressive behavior and ELISA was used in measurement of brain IL-1 beta. RESULTS:Intraperitoneal injection of reserpine (0, 4, 6, and 8...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::Recent evidence shows that dopamine D2-like receptor (D2DR) antagonists, such as trifluoperazine and thioridazine, are effective for cancer therapy and inhibition of cancer stem-like cells (CSCs). In this study, we investigated the anti-cancer effects of combination therapy of dexamethasone (DEX) and sulpiride (SUL), ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.24
更新日期:2017-09-01 00:00:00
abstract:AIM:To investigate whether atorvastatin can promote formation of neurites in cultured cortical neurons and the signaling mechanisms responsible for this effect. METHODS:Cultured rat cerebral cortical neurons were incubated with atorvastatin (0.05-10 μmol/L) for various lengths of time. For pharmacological experiments,...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.59
更新日期:2012-07-01 00:00:00
abstract::Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/s41401-020-0429-z
更新日期:2020-07-01 00:00:00
abstract::Contact inhibition and its disruption of vascular smooth muscle cells (VSMCs) are important cellular events in vascular diseases. But the underlying molecular mechanisms are unclear. In this study we investigated the roles of microRNAs (miRNAs) in the contact inhibition and its disruption of VSMCs and the molecular me...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2018.6
更新日期:2018-05-01 00:00:00
abstract:AIM:To study the association between APOE polymorphisms and cerebral infarction through a case-control study among the Chinese Han population. METHODS:First-ever cerebral infarction patients (n=226) whose ages ranged from 40 to 60 years old were recruited from Department of Neurology, Zhongshan Hospital, Shanghai, and...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
abstract::A variety of Ca2+ signals, in the form of intercellular pulses and waves, have been reported to be associated with the various sequential stages of somitogenesis: from convergent extension and the formation of the paraxial mesoderm; during the patterning of the paraxial mesoderm to establish segmental units; throughou...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1111/j.1745-7254.2006.00401.x
更新日期:2006-07-01 00:00:00
abstract:AIM:To investigate the effects of small interfering RNA of cyclooxygenase-2 (COX-2) on the proliferation and apoptosis of human multiple myeloma RPMI8226 cells and its relation with the Bcl-2 family in vitro. METHODS:Transcription and expression of COX-2 in human myeloma RPMI8226 cells were checked by RT-PCR and Weste...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00550.x
更新日期:2007-07-01 00:00:00
abstract:AIM:To study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in freely moving rats. METHODS:Rats were assigned randomly to four treatment groups that received a single iv dose of 50, 100, 200 mg/kg of NFLX and 0.9 % saline, respectively. Electroencephalogram (EEG) was continuously recorded with a computeriz...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract:AIM:To study the expressions of vascular endothelial growth factor (VEG F), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Tie-1, and Tie-2 in C57BL/6 mouse brain after permanent focal cerebral ischemia. METHODS:The mRNA levels of VEGF, Ang-1, Ang-2, Tie-1, and Tie-2 were measured by semiquantitative reverse transcri...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
abstract:AIM:To examine the anti-cancer effects of chamaejasmenin B and neochamaejasmin C, two biflavonones isolated from the root of Stellera chamaejasme L (known as the traditional Chinese herb Rui Xiang Lang Du) in vitro. METHODS:Human liver carcinoma cell lines (HepG2 and SMMC-7721), a human non-small cell lung cancer cell...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.158
更新日期:2013-02-01 00:00:00
abstract:AIM:Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS:Two hundred epileptic children, whose VPA serum concentrations were collected,...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-12-01 00:00:00
abstract:AIM:To investigate the prevalence of hepatitis B virus (HBV) genotype mixtures among patients with chronic hepatitis B (CHB) in Eastern China. METHODS:A total of 4908 chronic HBV patients from Eastern China were enrolled. HBV genotypes and subgenotypes were determined using a multiplex PCR technique. Serum viral loads...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2012.78
更新日期:2012-10-01 00:00:00
abstract:AIM:To investigate the anticancer mechanism of a methoxyflavanone derivative, WJ9708012, highlighting its role on a crosstalk between endoplasmic reticulum (ER) and mitochondrial stress. METHODS:Cell proliferation was examined using sulforhodamine B assay. Cell-cycle progression, Ca(2+) mobilization and mitochondrial ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.173
更新日期:2011-01-01 00:00:00
abstract:AIM:To investigate the effect of tricyclodecane-9-yl-xanthogenate (D609) on cell differentiation in vascular endothelial cells (VECs) and marrow stromal cells (MSCs). METHODS:Morphological changes were observed under phase contrast microscope. Electron microscope and immunostaining were used for VECs identification. T...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-04-01 00:00:00
abstract:AIM:To investigate whether IL-12p40 plays a crucial role in regulating islet allograft rejection in a streptozotocin (STZ)-induced diabetes mouse model. METHODS:C57BL/6 and IL-12p40 gene knockout mice were selected as recipient mice, to which the diabetes was induced with a treatment of STZ (150-200 mg/kg) by a single...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00341.x
更新日期:2006-08-01 00:00:00
abstract::Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservati...
journal_title:Acta pharmacologica Sinica
pub_type: 历史文章,杂志文章,评审
doi:10.1038/aps.2017.182
更新日期:2018-05-01 00:00:00
abstract:AIM:To study the effect of adenovirus5-mediated human hepatocyte growth factor (Ad(5)-HGF) transfer on post-infarct heart failure in a swine model. METHODS:Twelve young Suzhong swine were randomly divided into 2 groups: the Ad(5)-HGF group (n=6) and the null-Ad(5) group (n=6). Four weeks after left anterior descending...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00306.x
更新日期:2006-05-01 00:00:00