scholarly journals Phenotypic differences in murine chondrocyte cell lines derived from mature articular cartilage

2002 ◽  
Vol 10 (12) ◽  
pp. 977-986 ◽  
Author(s):  
H.M. van Beuningen ◽  
R. Stoop ◽  
P. Buma ◽  
N. Takahashi ◽  
P.M. van der Kraan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cell Lines ◽  
Phenotypic Differences

Development of Immortalized Human Articular Cartilage Cell Lines

1993 ◽  
pp. 267-272 ◽  
Author(s):  
G. Verbruggen ◽  
A. M. Malfait ◽  
K. F. Almgvist ◽  
E. M. Veys ◽  
S. Thenet ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cell Lines ◽  
Human Articular Cartilage ◽  
Cartilage Cell ◽  
Articular Cartilage Cell

Phenotypic differences in subclones and long-term cultures of clonally derived rat bone cell lines

1986 ◽  
Vol 31 (2) ◽  
pp. 153-169 ◽  
Author(s):  
Carlton G. Bellows ◽  
Jaro Sodek ◽  
Kam-Ling Yao ◽  
Jane E. Aubin
Keyword(s):  
Cell Lines ◽  
Bone Cell ◽  
Phenotypic Differences ◽  
Rat Bone

scholarly journals Molecular and cellular phenotypic differences distinguish murine syngeneic models from human tumors

2019 ◽  
Author(s):  
Wenyan Zhong ◽  
Jeremy S. Myers ◽  
Fang Wang ◽  
Kai Wang ◽  
Justin Lucas ◽  
...  
Keyword(s):  
Cell Lines ◽  
T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Human Tumors ◽  
Mouse Tumor ◽  
Phenotypic Differences ◽  
Human Cancers ◽  
Syngeneic Tumors

AbstractThe clinical success of immune checkpoint inhibitors that target cytotoxic T-lymphocyte associated protein 4 (CTLA4) and programmed cell death protein 1 (PD-1) or programmed death ligand-1 (PD-L1) demonstrates that reactivation of the human immune system delivers durable responses for some patients and represents an exciting approach for cancer treatment. The combination of multiple immunotherapies as well as the combination of immunotherapy with targeted therapy is being pursued vigorously to increase the rate and extend the duration of response. Preclinical in vivo models for immuno-oncology (IO) typically require immunocompetent mice bearing murine syngeneic tumors. To facilitate translation of preclinical studies into human, we characterized the genomic, transcriptomic, and protein expression of a panel of mouse tumor cell lines grown in vitro culture as well as in vivo tumor samples. Our studies identified many genetic and cellular phenotypic differences that distinguish murine syngeneic models from human cancers. For example, only a small fraction of the somatic single nucleotide variants (SNVs) in mouse cell lines directly match SNVs from human actionable cancer genes. At the cellular level, some epithelial tumor models have a more mesenchymal phenotype with relatively low T-lymphocyte infiltration compared to the corresponding human cancers. Furthermore, in contrast to what has been reported for human tumors, we did not observe a correlation between neoantigen load and cytolytic activity in syngeneic models. Finally, the relative immunogenicity of syngeneic tumors does not typically resemble that of human tumors of the same tissue origin. CT26, a colon tumor model, had the highest immunogenicity and was the most responsive model to CTLA4 inhibitor treatment, by contrast to the relatively low immunogenicity and response rate to checkpoint inhibitor therapies in human colon cancers. These differences highlight limitations of syngeneic models for evaluating novel immune therapies and rationalize some of the challenges associated with translating preclinical findings to clinical studies.

scholarly journals Dengue type 1 viruses circulating in humans are highly infectious and poorly neutralized by human antibodies

2018 ◽  
Vol 116 (1) ◽  
pp. 227-232 ◽  
Author(s):  
Rajendra Raut ◽  
Kizzmekia S. Corbett ◽  
Rashika N. Tennekoon ◽  
Sunil Premawansa ◽  
Ananda Wijewickrama ◽  
...  
Keyword(s):  
Cell Culture ◽  
Human Plasma ◽  
Cell Lines ◽  
Vaccine Development ◽  
Severe Disease ◽  
Clinical Samples ◽  
Denv Serotypes ◽  
Phenotypic Differences ◽  
Human Antibodies

The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses of humans. The interactions between DENVs and the human host that lead to asymptomatic, mild, or severe disease are poorly understood, in part, because laboratory models are poor surrogates for human DENV disease. Virologists are interested in how the properties of DENVs replicating in people compare with virions propagated on laboratory cell lines, which are widely used for research and vaccine development. Using clinical samples from a DENV type 1 epidemic in Sri Lanka and new ultrasensitive assays, we compared the properties of DENVs in human plasma and after one passage on laboratory cell lines. DENVs in plasma were 50- to 700-fold more infectious than cell culture-grown viruses. DENVs produced by laboratory cell lines were structurally immature and hypersensitive to neutralization by human antibodies compared with DENVs circulating in people. Human plasma and cell culture-derived virions had identical genome sequences, indicating that these phenotypic differences were due to the mature state of plasma virions. Several dengue vaccines are under development. Recent studies indicate that vaccine-induced antibodies that neutralized DENVs in cell culture assays were not sufficient for protecting people from DENV infections. Our results about structural differences between DENVs produced in humans versus cell lines may be key to understanding vaccine failure and developing better models for vaccine evaluation.

scholarly journals Assessing Candidate Gene nsSNPs for Phenotypic Differences in Double-Strand Break Repair Using Radiation-InducedγH2A.X Foci

2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Christina A. Markunas ◽  
David M. Umbach ◽  
Zongli Xu ◽  
Jack A. Taylor
Keyword(s):  
Cell Lines ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Screening Criteria ◽  
Phenotypic Differences ◽  
Dna Double Strand Break ◽  
Significant Difference ◽  
Break Repair ◽  
Repair Genes

Nonsynonymous SNPs (nsSNPs) in DNA repair genes may be important determinants of DNA damage and cancer risk. We applied a set of screening criteria to a large number of nsSNPs and selected a subset of SNPs that were likely candidates for phenotypic effects on DNA double-strand break repair (DSBR). In order to induce and follow DSBR, we exposed panels of cell lines to gamma irradiation and followed the formation and disappearance ofγH2A.X foci over time. All panels of cell lines showed significant increases in number, intensity, and area of foci at both the 1-hour and 3-hour time points. Twenty four hours following exposure, the number of foci returned to preexposure levels in all cell lines, whereas the size and intensity of foci remained significantly elevated. We saw no significant difference inγH2A.X foci between controls and any of the panels of cell lines representing the different nsSNPs.

scholarly journals Attachment of Coxsackievirus B3 Variants to Various Cell Lines: Mapping of Phenotypic Differences to Capsid Protein VP1

Virology ◽  
2000 ◽  
Vol 275 (1) ◽  
pp. 77-88 ◽  
Author(s):  
M. Schmidtke ◽  
H.-C. Selinka ◽  
A. Heim ◽  
B. Jahn ◽  
M. Tonew ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Cell Lines ◽  
Coxsackievirus B3 ◽  
Phenotypic Differences ◽  
Capsid Protein Vp1

scholarly journals Phenotypic Profiling of Raf Inhibitors and Mitochondrial Toxicity in 3D Tissue Using Biodynamic Imaging

2013 ◽  
Vol 19 (4) ◽  
pp. 526-537 ◽  
Author(s):  
Ran An ◽  
Dan Merrill ◽  
Larisa Avramova ◽  
Jennifer Sturgis ◽  
Maria Tsiper ◽  
...  
Keyword(s):  
Cell Culture ◽  
Cell Lines ◽  
Kinase Inhibitors ◽  
Colon Adenocarcinoma ◽  
Phenotypic Differences ◽  
Raf Kinase ◽  
Morphological Image Analysis ◽  
High Content Analysis ◽  
Phenotypic Clustering ◽  
Morphological Image

The existence of phenotypic differences in the drug responses of 3D tissue relative to 2D cell culture is a concern in high-content drug screening. Biodynamic imaging is an emerging technology that probes 3D tissue using short-coherence dynamic light scattering to measure the intracellular motions inside tissues in their natural microenvironments. The information content of biodynamic imaging is displayed through tissue dynamics spectroscopy (TDS) but has not previously been correlated against morphological image analysis of 2D cell culture. In this article, a set of mitochondria-affecting compounds (FCCP, valinomycin, nicardipine, ionomycin) and Raf kinase inhibitors (PLX4032, PLX4720, GDC, and sorafenib) are applied to multicellular tumor spheroids from two colon adenocarcinoma cell lines (HT-29 and DLD-1). These were screened by TDS and then compared against conventional image-based high-content analysis (HCA). The responses to the Raf inhibitors PLX4032 and PLX4720 are grouped separately by cell line, reflecting the Braf/Kras difference in these cell lines. There is a correlation between TDS and HCA phenotypic clustering for most cases, which demonstrates the ability of dynamic measurements to capture phenotypic responses to drugs. However, there are significant 2D versus 3D phenotypic differences exhibited by several of the drugs/cell lines.

scholarly journals Comparison of poliovirus recombinants: accumulation of point mutations provides further advantages

2009 ◽  
Vol 90 (8) ◽  
pp. 1859-1868 ◽  
Author(s):  
Carita Savolainen-Kopra ◽  
Elena Samoilovich ◽  
Heidi Kahelin ◽  
Anna-Kaisa Hiekka ◽  
Tapani Hovi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Lines ◽  
Temperature Sensitivity ◽  
Colorectal Adenocarcinoma ◽  
Point Mutations ◽  
Vaccine Recipient ◽  
Phenotypic Differences ◽  
Main Observation ◽  
Stool Specimens ◽  
Similar Growth

The roles of recombination and accumulation of point mutations in the origin of new poliovirus (PV) characteristics have been hypothesized, but it is not known which are essential to evolution. We studied phenotypic differences between recombinant PV strains isolated from successive stool specimens of an oral PV vaccine recipient. The studied strains included three PV2/PV1 recombinants with increasing numbers of mutations in the VP1 gene, two of the three with an amino acid change I→T in the DE-loop of VP1, their putative PV1 parent and strains Sabin 1 and 2. Growth of these viruses was examined in three cell lines: colorectal adenocarcinoma, neuroblastoma and HeLa. The main observation was a higher growth rate between 4 and 6 h post-infection of the two recombinants with the I→T substitution. All recombinants grew at a higher rate than parental strains in the exponential phase of the replication cycle. In a temperature sensitivity test, the I→T-substituted recombinants replicated equally well at an elevated temperature. Complete genome sequencing of the three recombinants revealed 12 (3), 19 (3) and 27 (3) nucleotide (amino acid) differences from Sabin. Mutations were located in regions defining attenuation, temperature sensitivity, antigenicity and the cis-acting replicating element. The recombination site was in the 5′ end of 3D. In a competition assay, the most mutated recombinant beat parental Sabin in all three cell lines, strongly suggesting that this virus has an advantage. Two independent intertypic recombinants, PV3/PV1 and PV3/PV2, also showed similar growth advantages, but they also contained several point mutations. Thus, our data defend the hypothesis that accumulation of certain advantageous mutations plays a key role in gaining increased fitness.

Immortalized mouse articular cartilage cell lines retain chondrocyte phenotype and respond to both anabolic factor BMP-2 and pro-inflammatory factor IL-1

2008 ◽  
Vol 215 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Manas K. Majumdar ◽  
Priya S. Chockalingam ◽  
Ramesh A. Bhat ◽  
Richard Sheldon ◽  
Cristin Keohan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Cell Lines ◽  
Inflammatory Factor ◽  
Cartilage Cell ◽  
Chondrocyte Phenotype ◽  
Articular Cartilage Cell

Human chondrocyte cell lines from articular cartilage of metatarsal phalangeal joints

1999 ◽  
Vol 31 (6) ◽  
pp. 550-554 ◽  
Author(s):  
A.M. Patti ◽  
A. Gabriele ◽  
C.Della Rocca
Keyword(s):  
Articular Cartilage ◽  
Cell Lines ◽  
Human Chondrocyte
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