Abstract:
:Antibody drug conjugates (ADCs), consisting of a cancer-specific antibody and cytotoxic payload, are shown to be a potent class of anticancer therapeutics, with enhanced therapeutic efficacy and reduced "off-target" side effects. However, the therapeutic window of ADCs is narrowed by problems such as difficulty in site-specific conjugation of payload, changes in antibody stability due to payload conjugation, and difficulty in tissue penetration. In this respect, aptamers have advantages in drug-delivery, as they can be easily and stably conjugated with cytotoxic drugs. We previously reported that oligobody, an aptamer-antibody complex, is a novel delivery method for aptamer-based therapeutics. In the current study, we describe DOligobody, a drug-conjugated oligobody comprising an aptamer-drug conjugate and an antibody. A cotinine-conjugated anti-HER2 aptamer (cot-HER2apt) was specifically bound to HER2-positive NCI-N87 cells, and underwent receptor-mediated endocytosis. Further, HER2-DOligobody, a cot-HER2apt-conjugated monomethyl auristatin E (cot-HER2apt-MMAE) oligobody, inhibited the growth of HER2-positive NCI-N87 cells. Finally, systemic administration of HER2-DOligobody significantly reduced tumor growth in a xenograft mouse model. Taken together, these results suggest that our DOligobody strategy may be a powerful platform for rapid, low-cost and effective cancer therapy.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Kim HJ,Sung HJ,Lee YM,Choi SI,Kim YH,Heo K,Kim IHdoi
10.3390/ijms21093286subject
Has Abstractpub_date
2020-05-06 00:00:00issue
9issn
1422-0067pii
ijms21093286journal_volume
21pub_type
杂志文章abstract:BACKGROUND:Gadolinium chloride (GdCl3) has been reported to attenuate liver injury caused by a variety of toxicants. Gap junctional intercellular communication (GJIC) is thought to be essential in controlling liver homeostasis and pathology. Here we evaluate the effects of GdCl3 on functional GJIC and connexin expressi...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20153748
更新日期:2019-07-31 00:00:00
abstract::Carbamazepine (CBZ) binds adenosine receptors, but detailed effects of CBZ on astroglial transmission associated with adenosine receptor still need to be clarified. To clarify adenosinergic action of CBZ on astroglial transmission, primary cultured astrocytes were acutely or chronically treated with CBZ, proinflammato...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20153727
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abstract::Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells...
journal_title:International journal of molecular sciences
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更新日期:2020-04-08 00:00:00
abstract::Self-assembling peptides have been employed as biotemplates for biomineralization, as the morphologies and sizes of the inorganic materials can be easily controlled. We synthesized two types of highly ordered self-assembling peptides with different secondary structures and investigated the effects of secondary structu...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms20184650
更新日期:2019-09-19 00:00:00
abstract::Complex neuropsychiatric-cardiac syndromes can be genetically determined. For the first time, the authors present a syndromal form of short QT syndrome in a 34-year-old German male patient with extracardiac features with predominant psychiatric manifestation, namely a severe form of secondary high-functioning autism s...
journal_title:International journal of molecular sciences
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abstract::Yeast proteins Ntr1, Ntr2 and Prp43 function in spliceosome disassembly. An Ntr1-Ntr2 protein complex recruits Prp43 to allow the removal of the lariat-intron in late-stage RNA splicing activity. Based on amino-acid sequence similarities across species, TFIP11 and mDEAH9/Dhx15 have been identified as homologues of yea...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms9112105
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abstract::Impairment of mucociliary clearance with reduced airway fluid secretion leads to chronically inflamed airways. Cystic fibrosis transmembrane conductance regulator (CFTR) is crucially involved in airway fluid secretion and dexamethasone (dexa) has previously been shown to elevate CFTR activity in airway epithelial cell...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms18081807
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abstract::It has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. Hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. These studies show that, when i...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19082228
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abstract::Two-component systems (TCS) in plants have evolved into a more complicated multi-step phosphorelay (MSP) pathway, which employs histidine kinases (HKs), histidine-containing phosphotransfer proteins (HPts), and response regulators (RRs) to regulate various aspects of plant growth and development. How plants perceive t...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
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更新日期:2020-07-11 00:00:00
abstract::A k-nearest neighbor (k-NN) classification model was constructed for 118 RDT NEDO (Repeated Dose Toxicity New Energy and industrial technology Development Organization; currently known as the Hazard Evaluation Support System (HESS)) database chemicals, employing two acute toxicity (LD50)-based classes as a response an...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms160511659
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abstract::Collaterals are unique blood vessels present in the microcirculation of most tissues that, by cross-connecting a small fraction of the outer branches of adjacent arterial trees, provide alternate routes of perfusion. However, collaterals are especially susceptible to rarefaction caused by aging, other vascular risk fa...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20153608
更新日期:2019-07-24 00:00:00
abstract::In this study, we systematically investigated the process of sex reversal induced by 17-methyltestosterone (MT) feeding and MT-feeding withdrawal at the ovary differentiation stage in orange-spotted groupers, Epinephelus coioides. Gonadal histology showed that MT feeding induced a precocious sex reversal from immature...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19092828
更新日期:2018-09-19 00:00:00
abstract::Transcription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data have been widely used to infer cellular regulatory networks, existing methods mainly infer correlations rather than causality. We developed statist...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19113609
更新日期:2018-11-15 00:00:00
abstract::Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21176337
更新日期:2020-09-01 00:00:00
abstract::Obesity-related metabolic abnormalities, including adipokine imbalance and chronic inflammation, are involved in liver carcinogenesis. Chemerin, a novel adipokine, plays a critical role in adipogenesis, energy metabolism, and inflammation. We evaluated the impact of serum chemerin levels on liver functional reserves i...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms150711294
更新日期:2014-06-25 00:00:00
abstract::Spinal cord injury is a chronic and debilitating neurological condition that is currently being managed symptomatically with no real therapeutic strategies available. Even though there is no consensus on the best time to start interventions, the chronic phase is definitely the most stable target in order to determine ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19061776
更新日期:2018-06-15 00:00:00
abstract::Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-artic...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19082304
更新日期:2018-08-06 00:00:00
abstract::We aimed to validate the effect of non-canonical splice site variants in the RPGR gene in five patients from four families diagnosed with retinitis pigmentosa. Four variants located in intron 2 (c.154 + 3_154 + 6del), intron 3 (c.247 + 5G>A), intron 7 (c.779-5T>G), and intron 13 (c.1573-12A>G), respectively, were anal...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22020850
更新日期:2021-01-16 00:00:00
abstract::Laser printer-emitted nanoparticles (PEPs) generated from toners during printing represent one of the most common types of life cycle released particulate matter from nano-enabled products. Toxicological assessment of PEPs is therefore important for occupational and consumer health protection. Our group recently repor...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20246348
更新日期:2019-12-16 00:00:00
abstract::The incorporation of plant residues into soil can be considered a keystone sustainability factor in improving soil structure function. However, the effects of plant residue addition on the soil microbial communities involved in biochemical cycles and abiotic stress phenomena are poorly understood. In this study, exper...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20092125
更新日期:2019-04-29 00:00:00
abstract::Treatment with 1-methylcyclopropylene (1-MCP) is an effective technique to preserve fruits, but inappropriate treatment with 1-MCP causes a ripening disorder (rubbery texture) in papaya fruit. In this study, a combined metabolomic and transcriptomic analysis was conducted to reveal the possible mechanism of the ripeni...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms22020916
更新日期:2021-01-18 00:00:00
abstract::Natural killer (NK) cells play a significant and vital role in the first line of defense against infection through their ability to target cells without prior sensitization. They also contribute significantly to the activation and recruitment of both innate and adaptive immune cells through the production of a range o...
journal_title:International journal of molecular sciences
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更新日期:2020-11-23 00:00:00
abstract::Factor binding IST-1 (FBI-1) plays an important role in oncogenic transformation and tumorigenesis. As FBI-1 is over-expressed in multiple human cancers, the regulation of itself would provide new effective options for cancer intervention. In this work, we aimed to study the role that EPAS-1 plays in regulating FBI-1....
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms150915689
更新日期:2014-09-04 00:00:00
abstract::The Bromeliaceae family is one of the most morphologically diverse families with a pantropical distribution. To schedule an appropriate flowering time for bromeliads, ethylene is commonly used to initiate flower development in adult plants. However, the mechanism by which ethylene induces flowering in adult bromeliads...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17030303
更新日期:2016-02-27 00:00:00
abstract::DNA alkylating drugs have been used in clinics for more than seventy years. The diversity of their mechanism of action (major/minor groove; mono-/bis-alkylation; intra-/inter-strand crosslinks; DNA stabilization/destabilization, etc.) has undoubtedly major consequences on the cellular response to treatment. The aim of...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms161125971
更新日期:2015-11-05 00:00:00
abstract::To date, viruses are reported to be responsible for more than 15% of all tumors worldwide. The oncogenesis could be influenced directly by the activity of viral oncoproteins or by the chronic infection or inflammation. The group of human oncoviruses includes Epstein–Barr virus (EBV), human papillomavirus (HPV), ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19041217
更新日期:2018-04-17 00:00:00
abstract::Chromosomal rearrangements of the mixed lineage leukaemia (MLL, also known as KMT2A) gene on chromosome 11q23 are amongst the most common genetic abnormalities observed in human acute leukaemias. MLL rearrangements (MLLr) are the most common cytogenetic abnormalities in infant and childhood acute myeloid leukaemia (AM...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms21124266
更新日期:2020-06-15 00:00:00
abstract::This narrative review aims to summarize the current controversy on the balance between ethanol and phytochemicals in wine, focusing on light drinking and oral cancer. Extensive literature search included PUBMED and EMBASE databases to identify in human studies and systematic reviews (up to March 2015), which contribut...
journal_title:International journal of molecular sciences
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doi:10.3390/ijms160817029
更新日期:2015-07-27 00:00:00
abstract::Fingertip response to trauma represents a fascinating example of tissue regeneration. Regeneration derives from proliferative mesenchymal cells (blastema) that subsequently differentiate into soft and skeletal tissues. Clinically, conservative treatment of the amputated fingertip under occlusive dressing can shift the...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18051054
更新日期:2017-05-13 00:00:00
abstract::Cultured human primary cells have a limited lifespan undergoing dedifferentiation or senescence. Anterior cruciate ligaments (ACL) are hypocellular but tissue engineering (TE) requires high cell numbers. Simian virus (SV) 40 tumor (T) antigen expression could extend the lifespan of cells. This study aimed to identify ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21020593
更新日期:2020-01-16 00:00:00