Abstract:
:Immune checkpoint inhibitors (ICI) have revolutionised cancer therapy. However, they have been effective in only a small subset of patients and a principal mechanism underlying immune-refractoriness is a 'cold' tumour microenvironment, that is, lack of a T-cell-rich, spontaneously inflamed phenotype. As such, there is a demand to develop strategies to transform the tumour milieu of non-responsive patients to one supporting T-cell-based inflammation. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway is a fundamental regulator of innate immune sensing of cancer, with potential to enhance tumour rejection through the induction of a pro-inflammatory response dominated by Type I interferons. Recognition of these positive immune-modulatory properties has rapidly elevated the STING pathway as a putative target for immunotherapy, leading to a myriad of preclinical and clinical studies assessing natural and synthetic cyclic dinucleotides and non-nucleotidyl STING agonists. Despite pre-clinical evidence of efficacy, clinical translation has resulted into disappointingly modest efficacy. Poor pharmacokinetic and physiochemical properties of cyclic dinucleotides are key barriers to the development of STING agonists, most of which require intra-tumoral dosing. Development of systemically administered non-nucleotidyl STING agonists, or conjugation with liposomes, polymers and hydrogels may overcome pharmacokinetic limitations and improve drug delivery. In this review, we summarise the body of evidence supporting a synergistic role of STING agonists with currently approved ICI therapies and discuss whether, despite the numerous obstacles encountered to date, the clinical development of STING agonist as novel anti-cancer therapeutics may still hold the promise of broadening the reach of cancer immunotherapy.
journal_name
J Clin Medjournal_title
Journal of clinical medicineauthors
Motedayen Aval L,Pease JE,Sharma R,Pinato DJdoi
10.3390/jcm9103323subject
Has Abstractpub_date
2020-10-16 00:00:00issue
10issn
2077-0383pii
jcm9103323journal_volume
9pub_type
杂志文章,评审abstract::Hemorrhagic strokes account for half of all strokes seen in children, and the etiologies of these hemorrhagic strokes differ greatly from those seen in adult patients. This review gives an overview about incidence and etiologies as well as presentation of children with intracerebral hemorrhage and with differential di...
journal_title:Journal of clinical medicine
pub_type: 杂志文章,评审
doi:10.3390/jcm9051518
更新日期:2020-05-18 00:00:00
abstract::Hypothermic machine perfusion (HMP) has been introduced as an alternative to static cold storage (SCS) in kidney transplantation, but its true benefit in the clinical routine remains incompletely understood. The aim of this study was to assess the effect of HMP vs. SCS in kidney transplantation. All kidney transplants...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9072311
更新日期:2020-07-21 00:00:00
abstract::The limited number of available studies that examined the pathology of alcohol hangover focused on biomarkers of alcohol metabolism, oxidative stress and the inflammatory response to alcohol as potentially important determinants of hangover severity. The available literature on alcohol metabolism and oxidative stress ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章,评审
doi:10.3390/jcm9113421
更新日期:2020-10-25 00:00:00
abstract::The aim of this study was to compare surgical and refractive outcomes between phacotrabeculectomy (P-Trab) and phaco with Ex-PRESS (P-Ex-PRESS) for glaucoma at a 6-month follow-up. This prospective randomized controlled trial included 81 eyes; 43 eyes (53%) and 38 eyes (47%) were assigned to the P-Ex-PRESS and P-Trab ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm10030424
更新日期:2021-01-22 00:00:00
abstract::Central serous chorioretinopathy (CSC) is a complex and not entirely understood retinal disease. The aim of our research was to describe a novel optical coherence tomography (OCT) finding named "choroidal rift", which may be identified in the choroid of eyes with CSC. We collected data from 357 patients (488 eyes) wit...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9072260
更新日期:2020-07-16 00:00:00
abstract:BACKGROUND:The assessment of ovarian reserve in the case of endometrioma is of pivotal importance for planning a tailored management. However, both the antral follicle count (AFC) and the antimüllerian hormone (AMH) dosage are subject to a fair degree of variability in ovarian endometriosis. This study aimed to identif...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9124076
更新日期:2020-12-17 00:00:00
abstract::The investigation of the potential association between ischemic stroke and subclinical atrial fibrillation (SCAF) is important for secondary prevention. We aimed to determine whether SCAF can be predicted by atrial substrate measurement with P wave signal-averaged electrocardiography (SAECG). We recruited 125 consecut...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9041134
更新日期:2020-04-15 00:00:00
abstract::Paragangliomas and pheochromytomas (PPGLs) exhibit variable malignancy, advanced/hormonally active/progressive need therapy. PRRT (Peptide Receptor Radionuclide Therapy) could be an option for these patients. To evaluate the effectiveness of PRRT (90Y DOTATATE), based on overall survival (OS) and progression-free surv...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8070952
更新日期:2019-06-30 00:00:00
abstract::Patients with chronic lymphocytic leukemia (CLL) have defects in both humoral and cellular immunity as a result of their underlying malignancy, as well as chemotherapy-related immune suppression. Upper respiratory tract (URT) colonization can be regarded as a major contributor to infection, so the relationship between...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8060861
更新日期:2019-06-16 00:00:00
abstract::Nitric oxide (NO) synthesis markers, comprising L-homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are significantly associated with cardiovascular events and mortality. Being involved in NO pathways, they may be of high importance regulating vascular tone and arterial hypertensi...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9123895
更新日期:2020-11-30 00:00:00
abstract:PURPOSE:Multidisciplinary approach is widely advised for an effective care of patients with neuroendocrine neoplasia (NEN). Since data on efficacy of multidisciplinary management of NENs patients in referral centers are scanty, this study aimed at analyzing the modality of presentation and clinical outcome of patients ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8060910
更新日期:2019-06-25 00:00:00
abstract:BACKGROUND:In-depth knowledge about potential predictors of mortality in transcatheter aortic valve replacement (TAVR) is still warranted. Currently used risk stratification models for TAVR often fail to reach a holistic approach. We, therefore, aimed to create a new staged risk model for 1-year mortality including sev...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8101642
更新日期:2019-10-08 00:00:00
abstract:BACKGROUND AND AIMS:Data from clinical trials suggest that biological drugs may improve the outcomes in Crohn's disease (CD) by reducing the need for surgery or hospitalization. The aim of this study is to evaluate the time-trends of the use of biological drugs and other treatments for CD, and its relationship with out...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9092896
更新日期:2020-09-08 00:00:00
abstract::(1) Background: Omega-3 fatty acids (ω3FAs) are known to improve protein anabolism, increase the sensitivity to anabolic stimuli, decrease lipogenesis, and stimulate lipid oxidation. We aim to investigate whether ω3FAs are associated with the prevalence of sarcopenic obesity (SO). (2) Methods: Data were obtained from ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9123856
更新日期:2020-11-27 00:00:00
abstract::Tuberculosis (TB) remains a major health issue worldwide. In order to contain TB infections, improved vaccines as well as accurate and reliable diagnostic tools are desirable. Exosomes are employed for the diagnosis of various diseases. At present, research on exosomes in TB is still at the preliminary stage. Recent s...
journal_title:Journal of clinical medicine
pub_type: 杂志文章,评审
doi:10.3390/jcm10010145
更新日期:2021-01-04 00:00:00
abstract::C-peptide measurement may represent a better index of pancreatic β-cell function compared to insulin. While insulin is mainly cleared by liver, C-peptide is mainly metabolized by kidneys. The aim of our study was to evaluate the association between baseline plasma C-peptide level and the development of type 2 diabetes...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9093001
更新日期:2020-09-17 00:00:00
abstract::In addition to its regulatory function in the formation of red blood cells (erythropoiesis) in vertebrates, Erythropoietin (Epo) contributes to beneficial functions in a variety of non-hematopoietic tissues including the nervous system. Epo protects cells from apoptosis, reduces inflammatory responses and supports re-...
journal_title:Journal of clinical medicine
pub_type: 杂志文章,评审
doi:10.3390/jcm7020024
更新日期:2018-02-02 00:00:00
abstract::T-cell-depleted (TCD) human leukocyte antigen (HLA) haploidentical (haplo) hematopoietic stem cell transplantation (HSCT) (TCD-haplo-HSCT) has had a huge impact on the treatment of many haematological diseases. The adoptive transfer of a titrated number of T cells genetically modified with a gene suicide can improve i...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8111904
更新日期:2019-11-07 00:00:00
abstract::Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of...
journal_title:Journal of clinical medicine
pub_type: 杂志文章,评审
doi:10.3390/jcm9061753
更新日期:2020-06-05 00:00:00
abstract::Objectives/Hypothesis: Stenosis of the middle meatus antrostomy (MMA) represents a major cause of recurrent disease following endoscopic sinus surgery (ESS). Various strategies have been developed to prevent the occurrence of MMA stenosis. The aim of the present study was to evaluate the effects of spray cryotherapy (...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9010088
更新日期:2019-12-29 00:00:00
abstract::The purpose of this study is to describe the Minimally Invasive Intraoral Approach (MIIA) performed on selected cases of abscesses and neck phlegmons of odontogenic origin when the infection has not spread beyond the inferior mandibular margin. This technique allows us to avoid cervicotomy by a direct approach to the ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9092971
更新日期:2020-09-14 00:00:00
abstract::Differing beliefs about the acceptability of living-donor kidney transplants (LDKTs) have been proposed as explaining age, ethnic and socioeconomic disparities in their uptake. We investigated whether certain patient groups hold beliefs incompatible with LDKTs. This questionnaire-based case-control study was based at ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9010031
更新日期:2019-12-21 00:00:00
abstract::The 14-3-3 protein family are molecular chaperones involved in several biological functions and neurological diseases. We previously pinpointed YWHAZ (encoding 14-3-3ζ) as a candidate gene for autism spectrum disorder (ASD) through a whole-exome sequencing study, which identified a frameshift variant within the gene (...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm9061851
更新日期:2020-06-13 00:00:00
abstract::An improvement in negative symptoms and a reduction in the number of visits to the emergency department have been reported in a problem solving based psychoeducational group intervention (PE) for adolescents with psychosis relative to a nonstructured group (NS). One of the factors that may play a role on the response ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8122108
更新日期:2019-12-02 00:00:00
abstract::Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint sc...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8040461
更新日期:2019-04-05 00:00:00
abstract::Antiretroviral therapy (ART) has significantly improved life expectancy of infected subjects, generating a new epidemiological setting of people aging withHuman Immunodeficiency Virus (HIV). People living with HIV (PLWH), having longer life expectancy, now face several age-related conditions as well as side effects of...
journal_title:Journal of clinical medicine
pub_type: 杂志文章,评审
doi:10.3390/jcm8081254
更新日期:2019-08-19 00:00:00
abstract::Secretogranin III (SCG3) plays a crucial role in the biogenesis of secretory granules in endocrine cells, and thus affects glucose homeostasis by regulating insulin secretion by pancreatic beta cells. Insulin resistance and compensatory hyperinsulinemia are hallmarks of metabolic syndrome (MetS). However, the role of ...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8091436
更新日期:2019-09-11 00:00:00
abstract::We examined the association between self-rated health (SRH), a subjective measure of an individual's health status, and the incidence of metabolic abnormalities, as well as the effect of obesity on this association in metabolically healthy individuals. The cohort study included 85,377 metabolically healthy men and wom...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm8010034
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Spironolactone, a non-selective mineralocorticoid receptor antagonist, can protect against cardiac fibrosis and left ventricular dysfunction, and improve endothelial dysfunction and proteinuria. However, the safety and effects of spironolactone on patient-centered cardiovascular and renal endpoints remain un...
journal_title:Journal of clinical medicine
pub_type: 杂志文章
doi:10.3390/jcm7110459
更新日期:2018-11-21 00:00:00
abstract::Ocular surgery is one of the most performed medical procedures in the world. Its limitation or suspension, recursively extended over time, could be associated with a significant increase in the number of blind people worldwide. Indeed, cataract causes more than half of all cases of visual impairment in those countries...
journal_title:Journal of clinical medicine
pub_type: 社论
doi:10.3390/jcm9051403
更新日期:2020-05-09 00:00:00