Newly Developed Self-Assembling Antioxidants as Potential Therapeutics for the Cancers

Elevated reactive oxygen species (ROS) have been implicated as significant for cancer survival by functioning as oncogene activators and secondary messengers. Hence, the attenuation of ROS-signaling pathways in cancer by antioxidants seems a suitable therapeutic regime for targeting cancers. Low molecular weight (LMW) antioxidants such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO), although they are catalytically effective in vitro, exerts off-target effects in vivo due to their size, thus, limiting their clinical use. Here, we discuss the superior impacts of our TEMPO radical-conjugated self-assembling antioxidant nanoparticle (RNP) compared to the LMW counterpart in terms of pharmacokinetics, therapeutic effect, and adverse effects in various cancer models.

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The truncated somatostatin receptor sst5TMD4 stimulates the production of pro-angiogenic factors in in vitro and in vivo breast cancer models

Endocrine Abstracts ◽

10.1530/endoabs.35.p516 ◽

2014 ◽

Author(s):

Raul M Luque ◽

Mario Duran-Prado ◽

David Rincon-Fernandez ◽

Marta Hergueta-Redondo ◽

Michael D Culler ◽

...

Keyword(s):

Breast Cancer ◽

Somatostatin Receptor ◽

Angiogenic Factors ◽

Cancer Models

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The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽

10.3390/cancers13040930 ◽

2021 ◽

Vol 13 (4) ◽

pp. 930

Author(s):

Donatella Delle Cave ◽

Riccardo Rizzo ◽

Bruno Sainz ◽

Giuseppe Gigli ◽

Loretta L. del Mercato ◽

...

Keyword(s):

Pancreatic Cancer ◽

Therapeutic Response ◽

Three Dimensional ◽

Cellular Models ◽

Common Cancer ◽

Cancer Models ◽

Anti Cancer ◽

Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

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Meet me halfway: Are in vitro 3D cancer models on the way to replace in vivo models for nanomedicine development?

Advanced Drug Delivery Reviews ◽

10.1016/j.addr.2021.04.001 ◽

2021 ◽

Author(s):

Sabina Pozzi ◽

Anna Scomparin ◽

Sahar Israeli-Dangoor ◽

Daniel Rodriguez ◽

Paula Ofek ◽

...

Keyword(s):

In Vivo Models ◽

Cancer Models ◽

The Way

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An In Vitro and In Vivo Investigation of the Antimetastatic Effects of a Chinese Medicinal Decoction, Erxian Decoction, on Human Ovarian Cancer Models

Integrative Cancer Therapies ◽

10.1177/1534735412464519 ◽

2012 ◽

Vol 12 (4) ◽

pp. 336-346 ◽

Cited By ~ 9

Author(s):

Ellie S. M. Chu ◽

Stephen C. W. Sze ◽

Ho P. Cheung ◽

Qing Liu ◽

Tzi B. Ng ◽

...

Keyword(s):

Ovarian Cancer ◽

Human Ovarian Cancer ◽

Erxian Decoction ◽

Cancer Models

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De novo design of self-assembling helical protein filaments

Science ◽

10.1126/science.aau3775 ◽

2018 ◽

Vol 362 (6415) ◽

pp. 705-709 ◽

Cited By ~ 48

Author(s):

Hao Shen ◽

Jorge A. Fallas ◽

Eric Lynch ◽

William Sheffler ◽

Bradley Parry ◽

...

Keyword(s):

De Novo ◽

Computational Design ◽

Building Blocks ◽

Repeat Units ◽

Self Assembling ◽

Wide Range ◽

Helical Protein ◽

Monomeric Proteins

We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo–electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.

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Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers

Scientific Reports ◽

10.1038/s41598-021-99177-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Adam J. Davenport ◽

Ioana Neagoe ◽

Nico Bräuer ◽

Markus Koch ◽

Andrea Rotgeri ◽

...

Keyword(s):

Receptor Antagonist ◽

Underlying Disease ◽

Nerve Fibers ◽

P2x3 Receptor ◽

P2x3 Receptors ◽

Pain Pathways ◽

Pathological Pain ◽

Target Effects

AbstractATP-dependent P2X3 receptors play a crucial role in the sensitization of nerve fibers and pathological pain pathways. They are also involved in pathways triggering cough and may contribute to the pathophysiology of endometriosis and overactive bladder. However, despite the strong therapeutic rationale for targeting P2X3 receptors, preliminary antagonists have been hampered by off-target effects, including severe taste disturbances associated with blocking the P2X2/3 receptor heterotrimer. Here we present a P2X3 receptor antagonist, eliapixant (BAY 1817080), which is both highly potent and selective for P2X3 over other P2X subtypes in vitro, including P2X2/3. We show that eliapixant reduces inflammatory pain in relevant animal models. We also provide the first in vivo experimental evidence that P2X3 antagonism reduces neurogenic inflammation, a phenomenon hypothesised to contribute to several diseases, including endometriosis. To test whether eliapixant could help treat endometriosis, we confirmed P2X3 expression on nerve fibers innervating human endometriotic lesions. We then demonstrate that eliapixant reduces vaginal hyperalgesia in an animal model of endometriosis-associated dyspareunia, even beyond treatment cessation. Our findings indicate that P2X3 antagonism could alleviate pain, including non-menstrual pelvic pain, and modify the underlying disease pathophysiology in women with endometriosis. Eliapixant is currently under clinical development for the treatment of disorders associated with hypersensitive nerve fibers.

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A Novel Assay for Profiling GBM Cancer Model Heterogeneity and Drug Screening

Cells ◽

10.3390/cells8070702 ◽

2019 ◽

Vol 8 (7) ◽

pp. 702 ◽

Cited By ~ 4

Author(s):

Christian T. Stackhouse ◽

James R. Rowland ◽

Rachael S. Shevin ◽

Raj Singh ◽

G. Yancey Gillespie ◽

...

Keyword(s):

High Throughput Screening ◽

Therapeutic Response ◽

Specific Gene ◽

Cancer Model ◽

In Vivo Models ◽

Cancer Models ◽

Model Independent ◽

Orthotopic Xenografts

Accurate patient-derived models of cancer are needed for profiling the disease and for testing therapeutics. These models must not only be accurate, but also suitable for high-throughput screening and analysis. Here we compare two derivative cancer models, microtumors and spheroids, to the gold standard model of patient-derived orthotopic xenografts (PDX) in glioblastoma multiforme (GBM). To compare these models, we constructed a custom NanoString panel of 350 genes relevant to GBM biology. This custom assay includes 16 GBM-specific gene signatures including a novel GBM subtyping signature. We profiled 11 GBM-PDX with matched orthotopic cells, derived microtumors, and derived spheroids using the custom NanoString assay. In parallel, these derivative models underwent drug sensitivity screening. We found that expression of certain genes were dependent on the cancer model while others were model-independent. These model-independent genes can be used in profiling tumor-specific biology and in gauging therapeutic response. It remains to be seen whether or not cancer model-specific genes may be directly or indirectly, through changes to tumor microenvironment, manipulated to improve the concordance of in vitro derivative models with in vivo models yielding better prediction of therapeutic response.

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