Correction: HDAC6 inhibitor WT161 downregulates growth factor receptors in breast cancer.

[This corrects the article DOI: 10.18632/oncotarget.19019.

Effect of stent crimping on calcification of transcatheter aortic valves.

Objectives: Although many challenges related to the acute implantation of transcatheter aortic valves have been resolved, durability and early degeneration are currently the main concerns. Recent reports indicate the potential for early valve degeneration and calcification. However, only little is known about the underlying mechanisms behind the early degeneration of these valves.

Multimodal imaging guides surgical management in a preclinical spinal implant infection model.

Spine implant infections portend disastrous outcomes, as diagnosis is challenging and surgical eradication is at odds with mechanical spinal stability. Current imaging modalities can detect anatomical alterations and anomalies but cannot differentiate between infection and aseptic loosening, diagnose specific pathogens, or delineate the extent of an infection. Herein, a fully human monoclonal antibody 1D9, recognizing the immunodominant staphylococcal antigen A on the surface of Staphylococcus aureus, was assessed as a nuclear and fluorescent imaging probe in a preclinical model of S.

HDAC6 inhibitor WT161 downregulates growth factor receptors in breast cancer.

We have shown that WT-161, a histone deacetylase 6 (HDAC6) inhibitor, shows remarkable anti-tumor activity in multiple myeloma (MM) in preclinical models. However, its activity in other type of cancers has not yet been shown. In this study, we further evaluated the biologic sequelae of WT161 in breast cancer cell lines.

Fluorescence imaging of bombesin and transferrin receptor expression is comparable to 18F-FDG PET in early detection of sorafenib-induced changes in tumor metabolism.

Physical measurement of tumor volume reduction is the most commonly used approach to assess tumor progression and treatment efficacy in mouse tumor models. However, it is relatively insensitive, and often requires long treatment courses to achieve gross physical tumor destruction. As alternatives, several non-invasive imaging methods such as bioluminescence imaging (BLI), fluorescence imaging (FLI) and positron emission tomography (PET) have been developed for more accurate measurement.

In vivo imaging of endogenous enzyme activities using luminescent 1,2-dioxetane compounds.

Background: Here we present a non-invasive imaging method for visualizing endogenous enzyme activities in living animals. This optical imaging method is based on an energy transfer principle termed chemically initiated electron exchange luminescence (CIEEL). The light energy is provided by enzymatic activation of metastable 1,2-dioxetane substrates, whose protective groups are removed by hydrolytic enzymes such as β-galactosidase and alkaline phosphatase.

A twist tale of cancer metastasis and tumor angiogenesis.

Twist1 is an evolutionally conserved transcription factor. Originally identified in Drosophila as a key regulator for mesoderm development, it was later implicated in many human diseases, including Saethre-Chotzen syndrome and cancer. Twist1's involvement in cancer has been well recognized.

Noninvasive imaging of tumor burden and molecular pathways in mouse models of cancer.

Imaging plays a central role in the diagnosis of cancer and the evaluation of therapeutic efficacy in patients with cancer. Because macroscopic imaging is noninvasive and quantitative, the development of specialized instruments for small animals has spurred increasing utilization in preclinical cancer studies. Some small-animal imaging devices are miniaturized derivatives of clinical imaging modalities, including computed tomography, magnetic resonance imaging, positron-emission tomography, single-photon emission computed tomography, and ultrasonography.

Quantitative bioluminescence imaging of mouse tumor models.

Bioluminescence imaging (BLI) has become an essential technique for preclinical evaluation of anticancer therapeutics and provides sensitive and quantitative measurements of tumor burden in experimental cancer models. For light generation, a vector encoding firefly luciferase is introduced into human cancer cells that are grown as tumor xenografts in immunocompromised hosts, and the enzyme substrate luciferin is injected into the host. Alternatively, the reporter gene can be expressed in genetically engineered mouse models to determine the onset and progression of disease.

Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia.

Activating mutations of the interleukin-7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T-ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand-independent activation of STAT5. We hypothesized that the reducing agent N-acetylcysteine (NAC), a well-tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R-mediated oncogenic signalling.

Enhanced efficacy of CKD-516 in combination with doxorubicin: pre-clinical evaluation using a hepatocellular carcinoma xenograft model.

Aim: To evaluate the anticancer efficacy of CKD-516, a novel vascular-disrupting agent, alone and in combination with doxorubicin in the treatment of hepatocellular carcinoma (HCC).

Materials And Methods: In mice bearing luciferized HCC cells, therapeutic efficacy was assessed for seven days after single administration of CKD-516, doxorubicin, or combination of CKD-516 and doxorubicin.

Results: Bioluminescence-imaging (BLI) signals in the CKD-516 group abruptly decreased initially, but recovered at seven days after treatment.

Using glow stick chemistry for biological imaging.

Purpose: This study describes an imaging strategy based on glow stick chemistry to non-invasively image oxidative stress and reactive oxygen species (ROS) production in living animals.

Procedures: Upon stimulation, phagocytes produce toxic levels of ROS to kill engulfed microorganisms. The mitochondrial respiratory chain continually generates low levels of superoxide (O2·(-)) that serve as a source for generation of downstream ROS, which function as regulatory signaling intermediaries.

In vivo imaging method to distinguish acute and chronic inflammation.

Inflammation is a fundamental aspect of many human diseases. In this video report, we demonstrate non-invasive bioluminescence imaging techniques that distinguish acute and chronic inflammation in mouse models. With tissue damage or pathogen invasion, neutrophils are the first line of defense, playing a major role in mediating the acute inflammatory response.

In Vivo Fluorescent Labeling of Tumor Cells with the HaloTag® Technology.

Many fluorescent sensors are currently available for in vitro bio-physiological microscopic imaging. The ability to label cells in living animals with these fluorescent sensors would help translate some of these assays into in vivo applications. To achieve this goal, the first step is to establish a method for selectively labeling target cells with exogenous fluorophores.

In vivo imaging of inflammatory phagocytes.

Inflammation contributes to the pathophysiology of many diseases. In this report, we present noninvasive bioluminescence imaging methods that distinguish acute and chronic inflammation in mouse models. Systemic delivery of luminol (5-amino-2,3-dihydro-1,4-phthalazinedione) enables detection of acute inflammation largely mediated by tissue-infiltrating neutrophils, whose myeloperoxidase (MPO) activity is required for luminol bioluminescence.

Incongruity of imaging using fluorescent 2-DG conjugates compared to 18F-FDG in preclinical cancer models.

Purpose: We compared the use of near-infrared conjugates of 2-deoxyglucose (NIR 2-DG) to 2-deoxy-2-[18F]fluoro-d-glucose (18F-FDG) for the purposes of imaging tumors, as well as response to therapy.

Procedures: Uptake of both 18F-FDG and NIR 2-DG within gastrointestinal stromal tumor xenografts were imaged before and after nilotinib treatment. Confocal microscopy was performed to determine NIR 2-DG distribution in tumors.

Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma.

Histone deacetylase (HDAC) enzymatic activity has been linked to the transcription of DNA in cancers including multiple myeloma (MM). Therefore, HDAC inhibitors used alone and in combination are being actively studied as novel therapies in MM. In the present study, we investigated the preclinical activity of ACY-1215, an HDAC6-selective inhibitor, alone and in combination with bortezomib in MM.

High-level IGF1R expression is required for leukemia-initiating cell activity in T-ALL and is supported by Notch signaling.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer of immature T cells that often shows aberrant activation of Notch1 and PI3K-Akt pathways. Although mutations that activate PI3K-Akt signaling have previously been identified, the relative contribution of growth factor-dependent activation is unclear. We show here that pharmacologic inhibition or genetic deletion of insulin-like growth factor 1 receptor (IGF1R) blocks the growth and viability of T-ALL cells, whereas moderate diminution of IGF1R signaling compromises leukemia-initiating cell (LIC) activity as defined by transplantability in syngeneic/congenic secondary recipients.

A class of human proteins that deliver functional proteins into mammalian cells in vitro and in vivo.

We discovered a class of naturally occurring human proteins with unusually high net positive charge that can potently deliver proteins in functional form into mammalian cells both in vitro and also in murine retina, pancreas, and white adipose tissues in vivo. These findings represent diverse macromolecule delivery agents for in vivo applications, and also raise the possibility that some of these human proteins may penetrate cells as part of their native biological functions.

Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor.

Mislocated enzymatic activity of DOT1L has been proposed as a driver of leukemogenesis in mixed lineage leukemia (MLL). The characterization of EPZ004777, a potent, selective inhibitor of DOT1L is reported. Treatment of MLL cells with the compound selectively inhibits H3K79 methylation and blocks expression of leukemogenic genes.

Activation of cytotoxic and regulatory functions of NK cells by Sindbis viral vectors.

Oncolytic viruses (OVs) represent a relatively novel anti-cancer modality. Like other new cancer treatments, effective OV therapy will likely require combination with conventional treatments. In order to design combinatorial treatments that work well together, a greater scrutiny of the mechanisms behind the individual treatments is needed.

Multiple functions of the 37/67-kd laminin receptor make it a suitable target for novel cancer gene therapy.

The 37/67-kd laminin receptor, LAMR, is a multifunctional protein that associates with the 40S ribosomal subunit and also localizes to the cell membrane to interact with the extracellular matrix. LAMR is overexpressed in many types of cancer, playing important roles in tumor-cell migration and invasion. Here, we show that LAMR is also vital for tumor-cell proliferation, survival, and protein translation.

CCR7 signalling as an essential regulator of CNS infiltration in T-cell leukaemia.

T-cell acute lymphoblastic leukaemia (T-ALL) is a blood malignancy afflicting mainly children and adolescents. T-ALL patients present at diagnosis with increased white cell counts and hepatosplenomegaly, and are at an increased risk of central nervous system (CNS) relapse. For that reason, T-ALL patients usually receive cranial irradiation in addition to intensified intrathecal chemotherapy.

Tumor-specific in vivo transfection with HSV-1 thymidine kinase gene using a Sindbis viral vector as a basis for prodrug ganciclovir activation and PET.

Unlabelled: One type of gene therapy of tumors, gene-directed enzyme-prodrug therapy (GDEPT), holds considerable promise, although practical considerations limit its clinical applicability. These include the lack of acceptable noninvasive methods that are adaptable to humans for selective tumor targeting of the therapeutic genetic material. Sindbis virus is an oncolytic, alpha-virus that selectively targets tumors through the 67-kDa laminin receptor (LAMR).