In Vivo and In Vitro Human Brain Tumor Models for Improving the Therapeutic Ratio of Ionizing Radiation and DNA Repair Inhibitors

✓ Since the development of a specific monoclonal antibody against the thymidine analogue bromodeoxyuridine (BUdR), many investigators have used intravenous infusion of BUdR to estimate the proliferative potential of human brain tumors. However, side effects such as the induction of cell mutation, latent virus promotion, or inhibition of cytodifferentiation cannot be ignored, and thus many workers hesitate to use it in patients, especially those with hepatic disease or of reproductive age. Furthermore, if BUdR remains in the deoxyribonucleic acid of tumor cells after injection, analysis of the effect of chemical and radiation therapy may not be evaluated correctly. In this report, in vitro BUdR labeling with an anti-BUdR antibody is compared with the in vivo methods described by previous authors. This method appears to be useful for determining the S-phase fraction of human brain tumor. It was more rapid, and was simple, safe, and reproducible as compared to the intravenous infusion method.

Download Full-text

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue

Journal of Neuro-Oncology ◽

10.1007/s11060-016-2062-8 ◽

2016 ◽

Vol 127 (3) ◽

pp. 473-482 ◽

Cited By ~ 48

Author(s):

Sven R. Kantelhardt ◽

Darius Kalasauskas ◽

Karsten König ◽

Ella Kim ◽

Martin Weinigel ◽

...

Keyword(s):

Brain Tumor ◽

Human Brain ◽

Fluorescence Lifetime ◽

Tumor Tissue ◽

Fluorescence Lifetime Imaging ◽

Human Brain Tumor ◽

Lifetime Imaging ◽

Multiphoton Tomography

Download Full-text

Assessment of brain tumor cell motility in vivo and in vitro

Journal of Neurosurgery ◽

10.3171/jns.1995.82.4.0615 ◽

1995 ◽

Vol 82 (4) ◽

pp. 615-622 ◽

Cited By ~ 105

Author(s):

Michael R. Chicoine ◽

Daniel L. Silbergeld

Keyword(s):

Brain Tumor ◽

Cell Motility ◽

Human Brain Tumor ◽

Content Type ◽

Brain Tumor Cells ◽

Tumor Cell Motility ◽

Brain Tumor Cell ◽

Fine Print

✓ Brain tumor dispersal far from bulk tumor contributes to and, in some instances, dominates disease progression. Three methods were used to characterize brain tumor cell motility in vivo and in vitro: 1) 2 weeks after implantation in rat cerebral cortex, single C6 cells labeled with a fluorescent tag had migrated to brain sites greater than 16 mm distant from bulk tumor; 2) time-lapse videomicroscopy of human brain tumor cells revealed motility of 12.5 µm/hr. Ruffling leading edges and pseudopod formation were most elaborate in more malignant cells; 3) an in vitro assay was devised to quantitatively evaluate motility from a region of high cell density to one of lower cell density. Human brain tumor cells were plated in the center of a petri dish, washed, and refed, establishing a 2-cm circular zone of cells in the dish center. Motility was determined by counting cells daily at predetermined distances from the central zone perimeter. Cells were found 1 cm from the perimeter by 24 hours and 3 cm from the perimeter by 4 days. Increasing serum concentration increased motility; however, neither fibronectin nor arrest of cells in the G0 phase by hydroxyurea altered motility. The addition of cytochalasin B to block cytoskeletal assembly prevented cell motility. Motility increased with increased malignancy. Subpopulations of cells were created by clonal amplification of cells that had migrated most rapidly to the dish periphery. Although morphologically indistinguishable when compared to the original cell line from which they were derived, these subpopulations demonstrated significantly increased motility.

Download Full-text

In vitro screen of a small molecule inhibitor drug library identifies multiple compounds that synergize with oncolytic myxoma virus against human brain tumor-initiating cells

Neuro-Oncology ◽

10.1093/neuonc/nou359 ◽

2015 ◽

Vol 17 (8) ◽

pp. 1086-1094 ◽

Cited By ~ 22

Author(s):

Brienne A. McKenzie ◽

Franz J. Zemp ◽

Alexandra Pisklakova ◽

Aru Narendran ◽

Grant McFadden ◽

...

Keyword(s):

Brain Tumor ◽

Human Brain ◽

Small Molecule ◽

Myxoma Virus ◽

Tumor Initiating Cells ◽

Human Brain Tumor ◽

Molecule Inhibitor ◽

Brain Tumor Initiating Cells ◽

Inhibitor Drug

Download Full-text

PTEN inhibitor bpV(HOpic) confers protection against ionizing radiation

Scientific Reports ◽

10.1038/s41598-020-80754-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ankit Chauhan ◽

Dhananjay Kumar Sah ◽

Neeraj Kumari ◽

Namita Kalra ◽

Ravi Soni ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Repair ◽

Ionizing Radiation ◽

Antioxidant Defense ◽

Defense Mechanism ◽

Akt Signaling ◽

Proliferation Index ◽

Membrane Phospholipids

AbstractExposure to Ionizing radiation (IR) poses a severe threat to human health. Therefore, there is an urgent need to develop potent and safe radioprotective agents for radio-nuclear emergencies. Phosphatidylinositol-3-kinase (PI3K) mediates its cytoprotective signaling against IR by phosphorylating membrane phospholipids to phosphatidylinositol 3,4,5 triphosphate, PIP3, that serve as a docking site for AKT. Phosphatase and Tensin Homolog on chromosome 10 (PTEN) antagonizes PI3K activity by dephosphorylating PIP3, thus suppressing PI3K/AKT signaling that could prevent IR induced cytotoxicity. The current study was undertaken to investigate the radioprotective potential of PTEN inhibitor (PTENi), bpV(HOpic). The cell cytotoxicity, proliferation index, and clonogenic survival assays were performed for assessing the radioprotective potential of bpV(HOpic). A safe dose of bpV(HOpic) was shown to be radioprotective in three radiosensitive tissue origin cells. Further, bpV(HOpic) significantly reduced the IR-induced apoptosis and associated pro-death signaling. A faster and better DNA repair kinetics was also observed in bpV(HOpic) pretreated cells exposed to IR. Additionally, bpV(HOpic) decreased the IR-induced oxidative stress and significantly enhanced the antioxidant defense mechanism in cells. The radioprotective effect of bpV(HOpic) was found to be AKT dependant and primarily regulated by the enhanced glycolysis and associated signaling. Furthermore, this in-vitro observation was verified in-vivo, where administration of bpV(HOpic) in C57BL/6 mice resulted in AKT activation and conferred survival advantage against IR-induced mortality. These results imply that bpV(HOpic) ameliorates IR-induced oxidative stress and cell death by inducing AKT signaling mediated antioxidant defense system and DNA repair pathways, thus strengthening its potential to be used as a radiation countermeasure.

Download Full-text

ChemInform Abstract: Synthesis and in vitro Cytotoxic Activity of Novel Hexahydro-2H-pyrido[1,2-b]isoquinolines Against Human Brain Tumor Cell Lines.

ChemInform ◽

10.1002/chin.199812120 ◽

2010 ◽

Vol 29 (12) ◽

pp. no-no

Author(s):

A. MONSEES ◽

S. LASCHAT ◽

M. HOTFILDER ◽

J. WOLFF ◽

K. BERGANDER ◽

...

Keyword(s):

Brain Tumor ◽

Tumor Cell ◽

Human Brain ◽

Cytotoxic Activity ◽

Cell Lines ◽

Tumor Cell Lines ◽

Human Brain Tumor ◽

Brain Tumor Cell

Download Full-text

In vivo antitumor activity of S16020, a topoisomerase II inhibitor, and doxorubicin against human brain tumor xenografts

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-003-0584-1 ◽

2003 ◽

Vol 51 (5) ◽

pp. 385-394 ◽

Cited By ~ 14

Author(s):

Gilles Vassal ◽

Jean-Louis Merlin ◽

Marie-José Terrier-Lacombe ◽

Jacques Grill ◽

Fabrice Parker ◽

...

Keyword(s):

Brain Tumor ◽

Antitumor Activity ◽

Human Brain ◽

Topoisomerase Ii ◽

Human Brain Tumor ◽

Tumor Xenografts ◽

Topoisomerase Ii Inhibitor ◽

In Vivo Antitumor Activity

Download Full-text

Preclinical Models of Pediatric Brain Tumors—Forging Ahead

Bioengineering ◽

10.3390/bioengineering5040081 ◽

2018 ◽

Vol 5 (4) ◽

pp. 81 ◽

Cited By ~ 5

Author(s):

Tara Dobson ◽

Vidya Gopalakrishnan

Keyword(s):

Brain Tumor ◽

Cognitive Abilities ◽

Pediatric Brain Tumor ◽

Economic Incentives ◽

Molecular Heterogeneity ◽

Tumor Models ◽

Preclinical Research ◽

Pediatric Brain

Approximately five out of 100,000 children from 0 to 19 years old are diagnosed with a brain tumor. These children are treated with medication designed for adults that are highly toxic to a developing brain. Those that survive are at high risk for a lifetime of limited physical, psychological, and cognitive abilities. Despite much effort, not one drug exists that was designed specifically for pediatric patients. Stagnant government funding and the lack of economic incentives for the pharmaceutical industry greatly limits preclinical research and the development of clinically applicable pediatric brain tumor models. As more data are collected, the recognition of disease sub-groups based on molecular heterogeneity increases the need for designing specific models suitable for predictive drug screening. To overcome these challenges, preclinical approaches will need continual enhancement. In this review, we examine the advantages and shortcomings of in vitro and in vivo preclinical pediatric brain tumor models and explore potential solutions based on past, present, and future strategies for improving their clinical relevancy.

Download Full-text