Abstract:
:Talazoparib, a potent PARP inhibitor, has shown promising clinical and pre-clinical activity by inducing synthetic lethality in cancers with germline Brca1/2 mutations. Conventional oral delivery of Talazoparib is associated with significant off-target effects, therefore we sought to develop new delivery systems in the form of an implant loaded with Talazoparib for localized, slow and sustained release of the drug at the tumor site in Brca1-deficient breast cancer. Poly(lactic-co-glycolic acid) (PLGA) implants (0.8 mm diameter) loaded with subclinical dose (25 or 50 µg) Talazoparib were fabricated and characterized. In vitro studies with Brca1-deficient W780 and W0069 breast cancer cells were conducted to test sensitivity to PARP inhibition. The in vivo therapeutic efficacy of Talazoparib implants was assessed following a one-time intratumoral injection in Brca1Co/Co;MMTV-Cre;p53+/- mice and compared to drug-free implants and oral gavage. Immunohistochemistry studies were performed on tumor sections using PCNA and γ-H2AX staining. Sustained release of Talazoparib was observed over 28 days in vitro. Mice treated with Talazoparib implants showed statistically significant tumor growth inhibition compared to those receiving drug-free implants or free Talazoparib orally. Talazoparib implants were well-tolerated at both drug doses and resulted in less weight loss than oral gavage. PARP inhibition in mice treated with Talazoparib implants significantly increased double-stranded DNA damage and decreased tumor cell proliferation as shown by PCNA and γ-H2AX staining as compared to controls. These results demonstrate that localized and sustained delivery of Talazoparib via implants has potential to provide superior treatment outcomes at sub-clinical doses with minimal toxicity in patients with BRCA1 deficient tumors.
journal_name
Theranosticsjournal_title
Theranosticsauthors
Belz JE,Kumar R,Baldwin P,Ojo NC,Leal AS,Royce DB,Zhang D,van de Ven AL,Liby KT,Sridhar Sdoi
10.7150/thno.18563subject
Has Abstractpub_date
2017-09-26 00:00:00pages
4340-4349issue
17issn
1838-7640pii
thnov07p4340journal_volume
7pub_type
杂志文章相关文献
Theranostics文献大全abstract::Molecular photoacoustic imaging (PA) is a promising technology to understand tumor pathology and guide precision therapeutics. Despite the capability of activatable PA probes to image tumor-specific biomarkers, limitations in their molecular structure hamper them from effective drug delivery and the drug release monit...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.30779
更新日期:2019-01-01 00:00:00
abstract::Rationale: The evaluation of early treatment response is critical for patient prognosis and treatment planning. When the current methods rely on invasive protocols that evaluate the expression of DNA damage markers on patient biopsy samples, we aim to evaluate a non-invasive PET imaging approach to monitor the early e...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.44772
更新日期:2020-04-27 00:00:00
abstract::Norepinephrine modulates cognitive processes such as working and episodic memory. Pathological changes in norepinephrine and norepinephrine transporter (NET) function and degeneration of the locus coeruleus produce irreversible impairments within the whole norepinephrine system, disrupting cognitive processes. Monitor...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.29740
更新日期:2019-01-01 00:00:00
abstract::Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nano...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.7688
更新日期:2014-03-11 00:00:00
abstract::Long non-coding RNAs (lncRNAs) have emerged as integral components of E2F1-regulated gene regulatory networks (GRNs), but their implication in advanced or treatment-refractory malignancy is unknown. Methods: We combined high-throughput transcriptomic approaches with bioinformatics and structure modeling to search for ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.44176
更新日期:2020-07-29 00:00:00
abstract::Iron oxide nanoparticles are a useful diagnostic contrast agent and have great potential for therapeutic applications. Multiple emerging diagnostic and therapeutic applications and the numerous versatile parameters of the nanoparticle platform require a robust biological model for characterization and assessment. Here...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.3568
更新日期:2012-01-01 00:00:00
abstract::CUB-domain containing protein 1 (CDCP1) is a cancer associated cell surface protein that amplifies pro-tumorigenic signalling by other receptors including EGFR and HER2. Its potential as a cancer target is supported by studies showing that anti-CDCP1 antibodies inhibit cell migration and survival in vitro, and tumor g...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.30736
更新日期:2020-01-12 00:00:00
abstract::Background: Tobacco smoke (TS) critically contributes to the development of lung cancer; however, the underlying molecular mechanisms remain unclear. The induction of cancer stem cells (CSCs) by TS represents an early event in tumor initiation. The lung cancer-related gene ΔNp63α is highly expressed in epithelial tiss...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.33812
更新日期:2019-07-09 00:00:00
abstract::To enhance effective drug accumulation in drug-resistant tumors, a site-specific drug-releasing polypeptide system (PEG-Phis/Pasp-DOX/CA4) was exploited in response to tumor extracellular and intracellular pH. This system could firstly release the embedded tumor vascular inhibitor (CA4) to transiently 'normalize' vasc...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.11821
更新日期:2015-04-28 00:00:00
abstract::Background: Colorectal cancer (CRC) progression and related mortality are highly associated with metabolic disorders. However, the molecular mechanism involved in the regulation of hyperlipidemia-associated CRC metastasis remains unclear. This study aimed to investigate the effects of angiopoietin-like 4 (ANGPTL4) on ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.44744
更新日期:2020-05-30 00:00:00
abstract::Zinc-finger proteins (ZFPs) are the largest transcription factor family in mammals, involved in the regulation of multiple physiologic processes including cell differentiation, proliferation, apoptosis and neoplastic transformation. Approximately one-third of ZFPs are Krüppel-associated box domain (KRAB)-ZFPs. Methods...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.35861
更新日期:2020-01-12 00:00:00
abstract::Aims: Pathological cardiac fibrosis and hypertrophy are common features of left ventricular remodeling that often progress to heart failure (HF). Endothelial cells (ECs) are the most abundant non-myocyte cells in adult mouse heart. Simvastatin, a strong inducer of Krüppel-like Factor 2 (Klf2) in ECs, ameliorates press...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.48153
更新日期:2021-01-01 00:00:00
abstract::Mitochondria in cancer cells maintain a more negative membrane potential than normal cells. Mitochondria are the primary source of cellular reactive oxygen species (ROS), which are necessary for photodynamic therapy. Thus, the strategy of targeting mitochondria can maximize the photodynamic therapeutic efficiency for ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.15433
更新日期:2016-10-01 00:00:00
abstract::Histone deacetylase 3 (HDAC3) plays a pivotal role in the repression of cartilage-specific gene expression in human chondrocytes. The aim of this study was to determine whether microRNA-193b-3p (miR-193b-3p) regulates the expression of HDAC3 during chondrogenesis and chondrocyte metabolism. Methods: miR-193b-3p expres...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.23547
更新日期:2018-04-15 00:00:00
abstract::Periodontitis is a widespread oral disease that results in the loss of alveolar bone. Low-intensity pulsed ultrasound (LIPUS), which is a new therapeutic option, promotes alveolar bone regeneration in periodontal bone injury models. This study investigated the protective effect of LIPUS on oxidative stress in periodon...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.42508
更新日期:2020-08-01 00:00:00
abstract::In advanced atherosclerotic plaques, defective efferocytosis of apoptotic foam cells and decreased cholesterol efflux contribute to lesion progression. In our previous study, we demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (SDT) could induce foam cells apoptosis via the mitochondrial-casp...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.26193
更新日期:2018-09-29 00:00:00
abstract::Many drug controlled release methods have been integrated in multifunctional nanoparticles, such as pH-, redox-, temperature-, enzyme-, and light-responsive release. However, few report is associated with the ROS responsive drug controlled release. Herein, a thioketal linker-based ROS responsive drug (camptothecin con...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.14101
更新日期:2016-02-05 00:00:00
abstract::This work reports that when PEG-lipid-shelled microbubbles with fluorocarbon interior (C4F10, C5F12, or C6F14) are subjected to ultrasound pulses, they produce metastable, fluid-filled nanoparticles that can be re-imaged upon administration of HIFU. The nanoparticles produced by destruction of the microbubbles (MBNPs)...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.17522
更新日期:2017-01-15 00:00:00
abstract::SIRT6, NAD+-dependent deacetylase sirtuin 6, has recently shown to suppress tumor growth in several types of cancer. Colon cancer is a challenging carcinoma associated with high morbidity and death. However, whether SIRT6 play a direct role in colon tumorigenesis and the underlying mechanism are not understood. Method...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.29724
更新日期:2019-04-13 00:00:00
abstract::Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibri...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.12494
更新日期:2015-09-13 00:00:00
abstract::Cancer theranostics is one of the most important approaches for detecting and treating patients at an early stage. To develop such a technique, accurate detection, specific targeting, and controlled delivery are the key components. Various kinds of nanoparticles have been proposed and demonstrated as potential nanoveh...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.27828
更新日期:2018-11-29 00:00:00
abstract::The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC). Despite many efforts PDAC has still a dismal prognosis. Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing. Novel blood-based markers may help to overcome this...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.29247
更新日期:2019-02-12 00:00:00
abstract::This article aims at alerting scientists working with nanoparticles or microparticles about the specific adverse reactions due to the intravascular pulmonary macrophages present in pigs and other cloven-hoof animals, but not in humans. The history of a 25-year old study of an ultrasound contrast agent is used to illus...
journal_title:Theranostics
pub_type: 评论,杂志文章
doi:10.7150/thno.22420
更新日期:2017-10-23 00:00:00
abstract::Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection dat...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.5130
更新日期:2013-11-20 00:00:00
abstract::Arachidonic acid (AA) is a polyunsaturated fatty acid present at high concentrations in the ovarian cancer (OC) microenvironment and associated with a poor clinical outcome. In the present study, we have unraveled a potential link between AA and macrophage functions. Methods: AA-triggered signal transduction was studi...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.52442
更新日期:2021-01-01 00:00:00
abstract::Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. β-arrestin (βarr)-biased β-adrenergic receptor (βAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte ...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.26619
更新日期:2018-09-09 00:00:00
abstract::The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy. Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS2 (MS) flakes and Fe3O4 (IO) nanoparticles (NPs), where MoS2 converted near-infrared (NIR) light into heat an...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.11802
更新日期:2015-05-20 00:00:00
abstract::In the past decade, iron oxide nanoparticles (IONPs) have attracted more and more attention for their excellent physicochemical properties and promising biomedical applications. In this review, we summarize and highlight recent progress in the design, synthesis, biocompatibility evaluation and magnetic theranostic app...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.25220
更新日期:2018-05-11 00:00:00
abstract::The development of nanomedicine is expected to provide an innovative direction for addressing challenges associated with multidrug-resistant (MDR) bacteria. In the past decades, although nanotechnology-based phototherapy has been developed for antimicrobial treatment since it rarely causes bacterial resistance, the cl...
journal_title:Theranostics
pub_type: 杂志文章,评审
doi:10.7150/thno.52729
更新日期:2020-10-30 00:00:00
abstract::Topical administration permits targeted, sustained delivery of therapeutics to human skin. Delivery to the skin, however, is typically limited to lipophilic molecules with molecular weight of < 500 Da, capable of crossing the stratum corneum. Nevertheless, there are indications protein delivery may be possible in barr...
journal_title:Theranostics
pub_type: 杂志文章
doi:10.7150/thno.21668
更新日期:2018-01-01 00:00:00