Photoacoustic lifetime based oxygen imaging with G2 polyacrylamide nanosonophores for in vivo tumor models

2021 ◽  
Author(s):  
Janggun Jo ◽  
Chang Lee ◽  
Raoul Kopelman ◽  
Xueding Wang
Keyword(s):  
Tumor Models ◽  
Oxygen Imaging

Evaluation of Potent Isoquinoline-Based Thiosemicarbazone Antiproliferatives Against Solid Tumor Models

2019 ◽  
Author(s):  
Daniel Sun ◽  
Soumya Poddar ◽  
Roy D. Pan ◽  
Juno Van Valkenburgh ◽  
Ethan Rosser ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Small Cell Lung Carcinoma ◽  
Single Agent ◽  
Resistance Mechanisms ◽  
Tumor Models ◽  
Cell Lung Carcinoma ◽  
Adaptive Resistance ◽  
Cancer Models ◽  
Nanomolar Range

The lead compound, an ⍺-N-heterocyclic carboxaldehyde thiosemicarbazone <b>HCT-13</b>, was highly potent against a panel of pancreatic, small cell lung carcinoma, and prostate cancer models, with IC<sub>90</sub> values in the low-to-mid nanomolar range.<b> </b>We show that the cytotoxicity of <b>HCT-13</b> is copper-dependent, that it acts as a copper ionophore, induces production of reactive oxygen species (ROS), and promotes mitochondrial dysfunction and S-phase arrest. Lastly, DNA damage response/replication stress response (DDR/RSR) pathways, specifically Ataxia-Telangiectasia Mutated (ATM) and Rad3-related protein kinase (ATR), were identified as actionable adaptive resistance mechanisms following <b>HCT-13 </b>treatment. Taken together, <b>HCT-13 </b>is potent against solid tumor models and warrants <i>in vivo</i> evaluation against aggressive tumor models, either as a single agent or as part of a combination therapy.

scholarly journals Therapeutic Application of Brain-Specific Angiogenesis Inhibitor 1 for Cancer Therapy

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3562
Author(s):  
Mitra Nair ◽  
Chelsea Bolyard ◽  
Tae Jin Lee ◽  
Balveen Kaur ◽  
Ji Young Yoo
Keyword(s):  
Angiogenesis Inhibitor ◽  
Suppressor Gene ◽  
Chemotherapeutic Agents ◽  
Tumor Models ◽  
In Vivo Models ◽  
Herpes Simplex Viruses ◽  
Multiple Tumor ◽  
And Function

Brain-specific angiogenesis inhibitor 1 (BAI1/ADGRB1) is an adhesion G protein-coupled receptor that has been found to play key roles in phagocytosis, inflammation, synaptogenesis, the inhibition of angiogenesis, and myoblast fusion. As the name suggests, it is primarily expressed in the brain, with a high expression in the normal adult and developing brain. Additionally, its expression is reduced in brain cancers, such as glioblastoma (GBM) and peripheral cancers, suggesting that BAI1 is a tumor suppressor gene. Several investigators have demonstrated that the restoration of BAI1 expression in cancer cells results in reduced tumor growth and angiogenesis. Its expression has also been shown to be inversely correlated with tumor progression, neovascularization, and peri-tumoral brain edema. One method of restoring BAI1 expression is by using oncolytic virus (OV) therapy, a strategy which has been tested in various tumor models. Oncolytic herpes simplex viruses engineered to express the secreted fragment of BAI1, called Vasculostatin (Vstat120), have shown potent anti-tumor and anti-angiogenic effects in multiple tumor models. Combining Vstat120-expressing oHSVs with other chemotherapeutic agents has also shown to increase the overall anti-tumor efficacy in both in vitro and in vivo models. In the current review, we describe the structure and function of BAI1 and summarize its application in the context of cancer treatment.

scholarly journals Endoglin based in vivo near-infrared fluorescence imaging of tumor models in mice using activatable liposomes

2018 ◽  
Vol 1862 (6) ◽  
pp. 1389-1400 ◽  
Author(s):  
Felista L. Tansi ◽  
Ronny Rüger ◽  
Ansgar M. Kollmeier ◽  
Markus Rabenhold ◽  
Frank Steiniger ◽  
...  
Keyword(s):  
Fluorescence Imaging ◽  
Near Infrared ◽  
Tumor Models ◽  
Near Infrared Fluorescence ◽  
Near Infrared Fluorescence Imaging

Effects of progestagens and Org OD14 in in vitro and in vivo tumor models

1994 ◽  
Vol 49 (4-6) ◽  
pp. 311-318 ◽  
Author(s):  
H.J. Kloosterboer ◽  
W.G.E.J. Schoonen ◽  
G.H. Deckers ◽  
J.G.M. Klijn
Keyword(s):  
Tumor Models

scholarly journals Investigation of the In Vitro and In Vivo efficiency of RM-532-105, a 17β-hydroxysteroid dehydrogenase type 3 inhibitor, in LAPC-4 prostate cancer cell and tumor models

PLoS ONE ◽  
2017 ◽  
Vol 12 (2) ◽  
pp. e0171871 ◽  
Author(s):  
Lucie Carolle Kenmogne ◽  
Jenny Roy ◽  
René Maltais ◽  
Mélanie Rouleau ◽  
Bertrand Neveu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Hydroxysteroid Dehydrogenase ◽  
Tumor Models ◽  
Type 3

scholarly journals Solvolysis of the Tumor-Inhibiting Ru(III)-Complex trans-Tetrachlorobis(Indazole)Ruthenate(III)

2000 ◽  
Vol 7 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Thomas Pieper ◽  
Wolfgang Peti ◽  
Bernhard K. Keppler
Keyword(s):  
Sodium Salt ◽  
Buffer System ◽  
Spectroscopic Techniques ◽  
Tumor Models ◽  
Solubility In Water ◽  
Aqueous Acetonitrile ◽  
Hydrolysis Of

The ruthenium(III) complex Hlnd trans-[RuCl4,(ind)2], with two trans-standing indazole (ind) ligands bound to ruthenium via nitrogen, shows remarkable activity in different tumor models in vitro and in vivo. The solvolysis of the complex trans-[RuCl4,(ind)2]- has been investigated by means of spectroscopic techniques (UV/vis, NMR)in different solvents. We investigated the indazolium as well as the sodium salt, the latter showing improved solubility in water. In aqueous acetonitrile and ethanol the solvolysis results in one main solvento complex. The hydrolysis of the complex is more complicated and depends on the pH of the solution as well as on the buffer system.

scholarly journals Using Spheroids as Building Blocks Towards 3D Bioprinting of Tumor Microenvironment

2021 ◽  
Vol 7 (4) ◽  
pp. 444
Author(s):  
Pei Zhuang ◽  
Yi-Hua Chiang ◽  
Maria Serafim Fernanda ◽  
Mei He
Keyword(s):  
Tumor Microenvironment ◽  
Prediction Models ◽  
Three Dimensional ◽  
3D Culture ◽  
Building Blocks ◽  
3D Bioprinting ◽  
Multicellular Spheroids ◽  
Tumor Models ◽  
3D Printed

Cancer still ranks as a leading cause of mortality worldwide. Although considerable efforts have been dedicated to anticancer therapeutics, progress is still slow, partially due to the absence of robust prediction models. Multicellular tumor spheroids, as a major three-dimensional (3D) culture model exhibiting features of avascular tumors, gained great popularity in pathophysiological studies and high throughput drug screening. However, limited control over cellular and structural organization is still the key challenge in achieving in vivo like tissue microenvironment. 3D bioprinting has made great strides toward tissue/organ mimicry, due to its outstanding spatial control through combining both cells and materials, scalability, and reproducibility. Prospectively, harnessing the power from both 3D bioprinting and multicellular spheroids would likely generate more faithful tumor models and advance our understanding on the mechanism of tumor progression. In this review, the emerging concept on using spheroids as a building block in 3D bioprinting for tumor modeling is illustrated. We begin by describing the context of the tumor microenvironment, followed by an introduction of various methodologies for tumor spheroid formation, with their specific merits and drawbacks. Thereafter, we present an overview of existing 3D printed tumor models using spheroids as a focus. We provide a compilation of the contemporary literature sources and summarize the overall advancements in technology and possibilities of using spheroids as building blocks in 3D printed tissue modeling, with a particular emphasis on tumor models. Future outlooks about the wonderous advancements of integrated 3D spheroidal printing conclude this review.

Bispecific anti-PD-1/PD-L1 antibody CTX-8371 to promote cellular clustering and PD-1 shedding, antitumor activity and tolerability.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15056-e15056
Author(s):  
Diana I. Albu ◽  
Yan Qin ◽  
Xianzhe Wang ◽  
Vivian Li ◽  
Taeg Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Activation ◽  
Cell Activation ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Cynomolgus Monkeys ◽  
Range Finding

e15056 Background: Checkpoint blockade therapies targeting PD-1 and PD-L1 have shown great success for the treatment of various malignancies. However, a substantial fraction of patients with PD-L1-positive tumors remain unresponsive to these therapies. Novel therapy with significantly greater activity than the leading PD-1/PD-L1 inhibitors is expected to bring additional clinical benefit to patients. Here we describe the preclinical evaluation of CTX-8371, which combines anti-PD-1 and anti-PD-L1 monoclonal antibodies in one bispecific tetravalent molecule. Methods: The immune-enhancing activity of CTX-8371 was tested in vitro in T cell activation assays and tumor cell killing assay. CTX-8371 anti-tumor efficacy in vivo was assessed using mouse tumor cells expressing human PD-L1 implanted in transgenic mice humanized at the PD-1 and PD-L1 loci. CTX-8371 anti-tumor activity was also tested in xenograft tumor models. The mechanism of action of CTX-8371 was investigated in vitro using Jurkat cells expressing PD-1 or PD-L1, human PBMCs, and in vivo in tumor-bearing, chimeric PD-1/PD-L1 transgenic mice. CTX-8371 PK was determined in mice using an MSD ELISA-based assay and in cynomolgus monkeys using a qualified ELISA method. Dose range finding and toxicokinetic studies were performed in cynomolgus monkeys. Results: CTX-8371 potently enhanced T cell activation and function in vitro and showed curative efficacy as monotherapy in multiple solid tumor models, isografts or xenografts. Furthermore, CTX-8371 demonstrated superior anti-tumor efficacy compared to Keytruda or atezolizumab in checkpoint inhibitors-sensitive and resistant syngeneic mouse tumor models. Mechanistically, in addition to blocking PD-1 interaction with PD-L1, CTX-8371 bispecific antibody facilitated cell to cell bridging between cells expressing PD-1 and cells expressing PD-L1. Furthermore, we show that simultaneous binding of CTX-8371 to both PD-1 and PD-L1 resulted in long term PD-1 shedding. This suggests that CTX-8371 may prevent or overcome T cell exhaustion within the tumor microenvironment, thus providing additional advantage over existing therapies. Lastly, excellent tolerability was observed in non-human primates given 2 weekly drug infusions at up to 50 mg/kg dose. Conclusions: CTX-8371 displays multiple mechanisms of action over monoclonal PD1/PD-L1 blockade. These unique pharmacological properties of CTX-8371 could explain the enhanced T cell responses to tumor antigens and superior efficacy over current monoclonal antibody therapies. With favorable PK/PD and toxicology profiles in mice and cynomolgus monkeys, CTX-8371 warrants further advancement to clinical testing.

CHAPTER 4. Hydrophilic Ir(iii) Complexes for In vitro and In vivo Oxygen Imaging

2018 ◽  
pp. 71-90
Author(s):  
Toshitada Yoshihara ◽  
Yosuke Hirakawa ◽  
Masaomi Nangaku ◽  
Seiji Tobita
Keyword(s):  
Oxygen Imaging
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