scholarly journals Different Chromatin Organization in Benign and Malignant Cells Revealed by Unequal Nuclease Sensitivity between Tumor and Normal Cell Genomes

2007 ◽  
Vol 170 (2) ◽  
pp. 787-789 ◽  
Author(s):  
Manuel Rieber ◽  
Mary Strasberg-Rieber ◽  
Andrew J. Maniotis ◽  
Robert Folberg
Keyword(s):  
Normal Cell ◽  
Chromatin Organization ◽  
Malignant Cells ◽  
Nuclease Sensitivity

scholarly journals A Two-Stage Mutation Stochastic Model of Carcinogenesis Driven by a Three Level Environmental Process

2020 ◽  
Vol 5 (6) ◽  
pp. 1468-1487
Author(s):  
V. S. S. Yadavalli ◽  
S. Udayabaskaran ◽  
C. T. Dora Pravina ◽  
S. Sreelakshmi
Keyword(s):  
Random Environment ◽  
Normal Cell ◽  
Malignant Cell ◽  
Intermediate Cell ◽  
Malignant Cells ◽  
Level 3 ◽  
Environmental Process ◽  
The Mean ◽  
Intermediate Cells ◽  
Level 2

A two-mutation model of carcinogenesis which evolves under the influence of three level random environment on the production process is formulated and analyzed. A random environment occupies one of the levels 1, 2 and 3 at any time t according to a Markov process. When the environment is in level 1, a normal cell either divides into two normal cells or dies; and an intermediate cell divides into two intermediate cells or dies. When the environment is in level 2, a normal cell either divides into one normal cell and one intermediate cell or dies and an intermediate cell either divides into one intermediate cell and one malignant cell or dies. When the environment is in level 3, a normal cell either divides into two intermediate cells or dies and an intermediate cell either divides into two malignant cells or dies. It is assumed that, once a malignant cell is produced, it generates a malignant tumor with probability 1. We obtain the mean numbers of normal, intermediate and malignant cells at any time t.

scholarly journals CELL CONTACT DEPENDENCE OF SURFACE GALACTOSYLTRANSFERASE ACTIVITY AS A FUNCTION OF THE CELL CYCLE

1974 ◽  
Vol 63 (3) ◽  
pp. 796-805 ◽  
Author(s):  
Glenda C. Webb ◽  
Stephen Roth
Keyword(s):  
Cell Cycle ◽  
Normal Cell ◽  
Spatial Arrangement ◽  
The Other ◽  
Cell Contact ◽  
Transferase Activity ◽  
Intercellular Contact ◽  
Malignant Cells ◽  
Cell Type ◽  
3T3 Cells

Mitotic, nonmalignant Balb/c 3T3 cells exhibit endogenous, surface galactosyltransferase activity that does not require intercellular contact throughout the assay period. In this respect, mitotic 3T3 cells resemble malignant Balb/c 3T12 cells which similarly show no contact requirement for optimum transferase activity in any phase of their cell cycle. Previously, it was shown that randomly growing populations of 3T3 cells have lower galactosyltransferase activity when assayed under conditions which decreased cell contact. This led to the conclusion that these normal (3T3) and malignant (3T12) cells differed in that intercellular contact is required for optimum activity of surface galactosyltransferases on the normal cell type. The present data indicate that mitotic 3T3 cells may be capable of expressing enzyme activities exhibited at all times by malignant cells. That is, mitotic 3T3 cells and randomly growing 3T12 cells may readily catalyze galactosyltransferase reactions between enzymes and acceptors on the same cell. Interphase 3T3 cells, on the other hand, might require that enzymes glycosylate acceptors on adjacent cells. A model is proposed that suggests that changes in the spatial arrangement of surface enzymes and acceptors or variations in the fluidity of the cell membrane can account for this contact-related glycosylation.

scholarly journals The anticancer agent PB-100, selectively active on malignant cells, inhibits multiplication of sixteen malignant cell lines, even multidrug resistant

2000 ◽  
Vol 23 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Mirko Beljanski
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Plant Extract ◽  
Normal Cell ◽  
Anticancer Agent ◽  
Malignant Cell ◽  
Multidrug Resistant ◽  
Cell Multiplication ◽  
Malignant Cells

The plant-derived anticancer agent PB-100 selectively destroys cancer cells, even when multidrug resistant; yet, it does not inhibit normal (non-malignant) cell multiplication. Testing of PB-100 on sixteen malignant cell lines, several multidrug resistant, as well as on five normal cell lines, confirmed our previous results. Flavopereirine and dihydroflavopereirine, the active principles of PB-100, were chemically synthesized and displayed the same selectivity for tumor cells as the purified plant extract, being active at even lower concentrations.

scholarly journals A Two-Stage Mutation Stochastic Model of Carcinogenesis Driven by a Two Level Random Environment

2020 ◽  
Vol 5 (6) ◽  
pp. 1392-1408 ◽  
Author(s):  
V. S. S. Yadavalli ◽  
S. Udayabaskaran ◽  
C. T. Dora Pravina ◽  
S. Sreelakshmi
Keyword(s):  
Stochastic Model ◽  
Random Environment ◽  
Normal Cell ◽  
Malignant Cell ◽  
Intermediate Cell ◽  
Malignant Cells ◽  
Two Stage ◽  
Normal Cells ◽  
The Mean ◽  
Intermediate Cells

In this paper, we present a two-stage stochastic model of carcinogenesis in a two level random environment. The random environment switches between two levels, say, 1 and 2 alternately. When the environment is in level 1, a normal cell either divides into two normal cells or dies; and an intermediate cell divides into two intermediate cells or dies. When the environment is in level 2, a normal cell either divides into two intermediate cells or divides into one normal cell and one intermediate cell or divides into two normal cells or dies; and an intermediate cell either divides into two malignant cells or divides into one intermediate cell and one malignant cell or divides into two intermediate cells or dies. It is assumed that, once a malignant cell is produced, it generates a malignant tumor with probability 1. We obtain the mean numbers of normal, intermediate and malignant cells.

scholarly journals Integrative Analysis of Single-Cell RNA-Seq and ATAC-Seq Data across Treatment Time Points in Pediatric AML

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-29
Author(s):  
Lisa Wei ◽  
Diane Trinh ◽  
Rhonda E. Ries ◽  
Dan Jin ◽  
Richard D. Corbett ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Single Cell ◽  
Normal Cell ◽  
Cell Types ◽  
Malignant Cells ◽  
Rna Seq ◽  
Expression Of Genes ◽  
Transcriptional Changes ◽  
Cell Subpopulations ◽  
Pediatric Aml

Pediatric AML is a heterogeneous disease in which treatment resistance remains an unsolved problem that is responsible for most deaths (Yeung and Radich 2017). Recently we have come to learn that resistance may be driven by mechanisms that extend beyond somatic mutations and DNA methylation changes (Ghasemi et al. 2020; van Galen et al. 2019; Bell et al. 2019). Transcriptional changes within specific primitive and committed cell types in AML tumours, which may be accompanied by alterations in chromatin structure and topology, can also contribute to disease progression (Ghasemi et al. 2020). To study such changes at the single-cell level, we analyzed single-cell RNA-seq (scRNA-seq) and matched scATAC-seq data from primary, remission and/or relapse samples obtained from three pediatric AML patients enrolled in the AAML1031 clinical trial (Alpenc et al. 2016) (Figure 1). Using the 10X Genomics single-cell platforms, we profiled a total of 39,738 cells using scRNA-seq (~4,826 cells per sample, 1,571 genes per cell), and 46,580 cells and 197,128 peaks using scATAC-seq (~6,718 cells per sample, 5,628 unique reads per cell). We then integrated these data types to determine the extent to which these two modalities corroborated and/or complemented each other in analyses of these longitudinally-obtained samples. Cell subpopulations detected in scRNA-seq through Leiden clustering on a k-nearest neighbor graph were generally consistent with recent observations of malignant and normal cell types detected in the bone marrow and peripheral blood compartments (van Galen et al. 2019; Hay et al. 2018). Malignant-like subpopulations at primary and relapse stages exhibited similar levels of cell type diversity along the myeloid lineage. These included hematopoietic stem-like cells, progenitors, granulocyte-monocyte progenitors, monocytes and dendritic cell-like subpopulations. Remission samples appeared to contain normal blood cell types including natural killers (NK), B and T cells, platelets and erythrocytes, consistent with the clearance of blasts. However, we also observed putative malignant-like conventional dendritic cell subpopulations at remission (50% and 16% in the respective samples), noting that these cells displayed increased expression of genes involved in antigen presentation and lysosomal protein processing. To integrate scATAC-seq with scRNA-seq data we performed clustering of transformed and reduced scATAC-seq data through iterative latent semantic indexing (Granja et al. 2020), and aligned cells in scATAC-seq to cells from scRNA-seq data using canonical correlation analysis (Stuart et al. 2019). We observed similar patterns of T cell expansion, presence of monocyte-like populations and NK cells at remission in the scATAC-seq data. However, scRNA-seq subpopulations dominated by malignant-like cells showed variability in mapping to distinctive chromatin states, with a few notable exceptions (Figures 2 and 3). One such exception is a subpopulation in scRNA-seq, found mostly at relapse, marked by high expression of genes involved in proliferation and growth factor-mediated cellular processes such as YBX3 (binds to GM-CSF promoter), CYTL1, and EGFL7 (regulator of vasculogenesis) (Figures 3 and 4). Cells within this subpopulation mapped to two scATAC-seq clusters whose significantly more highly accessible regions were enriched for functional processes such as blood vessel remodeling and neutrophil/granulocyte activation (Figure 4). These observations are consistent with recent evidence that AML tumour cells can activate the immune system to acquire resistance (Melgar et al. 2020). The scRNA-seq subpopulation, however, did not display high expression of myeloid/granulocyte factors such as CD15, ELANE, and MPO (Figure 4), perhaps consistent with the notion that such transcriptional programs may be primed but not yet activated within these malignant cells. We thus evaluated the potential of scATAC-seq to complement scRNA-seq in understanding transcriptional changes within cell types in AML tumours. We observed that normal cell types and specific malignant cell states could occupy distinctive chromatin states. Through integrative analyses, we conclude that scATAC-seq results can add additional information to complement scRNA-seq data, including identifying nascent transcriptional programs that may be poised for activation within malignant cells. Disclosures No relevant conflicts of interest to declare.

Stimulated Virus Production in Vinblastine and Cytochalasin-Induced Multinucleate Cells

1970 ◽  
Vol 28 ◽  
pp. 186-187
Author(s):  
Krishan Awtar
Keyword(s):  
Cell Division ◽  
Normal Cell ◽  
Virus Production ◽  
Multinucleate Cells ◽  
Daughter Cells ◽  
Cell Divisions ◽  
Nuclear Membranes ◽  
Division 2 ◽  
Vinblastine Sulfate

Exposure of cells to low sublethal but mitosis-arresting doses of vinblastine sulfate (Velban) results in the initial arrest of cells in mitosis followed by their subsequent return to an “interphase“-like stage. A large number of these cells reform their nuclear membranes and form large multimicronucleated cells, some containing as many as 25 or more micronuclei (1). Formation of large multinucleate cells is also caused by cytochalasin, by causing the fusion of daughter cells at the end of an otherwise .normal cell division (2). By the repetition of this process through subsequent cell divisions, large cells with 6 or more nuclei are formed.

Electron Microscopy and image analysis of nucleo-protein complexes

1994 ◽  
Vol 52 ◽  
pp. 88-89
Author(s):  
E. H. Egelman ◽  
X. Yu
Keyword(s):  
Electron Microscopy ◽  
Image Analysis ◽  
Normal Cell ◽  
Genetic Recombination ◽  
Protein Complexes ◽  
Chromosomal Rearrangements ◽  
Reca Protein ◽  
E Coli ◽  
Helical Polymer ◽  
Specific Protease

The RecA protein of E. coli has been shown to mediate genetic recombination, regulate its own synthesis, control the expression of other genes, act as a specific protease, form a helical polymer and have an ATPase activity, among other observed properties. The unusual filament formed by the RecA protein on DNA has not previously been shown to exist outside of bacteria. Within this filament, the 36 Å pitch of B-form DNA is extended to about 95 Å, the pitch of the RecA helix. We have now establishedthat similar nucleo-protein complexes are formed by bacteriophage and yeast proteins, and availableevidence suggests that this structure is universal across all of biology, including humans. Thus, understanding the function of the RecA protein will reveal basic mechanisms, in existence inall organisms, that are at the foundation of general genetic recombination and repair.Recombination at this moment is assuming an importance far greater than just pure biology. The association between chromosomal rearrangements and neoplasms has become stronger and stronger, and these rearrangements are most likely products of the recombinatory apparatus of the normal cell. Further, damage to DNA appears to be a major cause of cancer.

Nuclear coiled bodies and the nucleolus

1994 ◽  
Vol 52 ◽  
pp. 20-21
Author(s):  
K. Brasch ◽  
J. Williams ◽  
D. Gallo ◽  
T. Lee ◽  
R. L. Ochs
Keyword(s):  
Mouse Liver ◽  
Nuclear Body ◽  
Nuclear Bodies ◽  
Model Systems ◽  
Coiled Body ◽  
Rrna Processing ◽  
Malignant Cells ◽  
Sm Proteins ◽  
Coiled Bodies ◽  
Unique Protein

Though first described in 1903 by Ramon-y-Cajal as silver-staining “accessory bodies” to nucleoli, nuclear bodies were subsequently rediscovered by electron microscopy about 30 years ago. Nuclear bodies are ubiquitous, but seem most abundant in hyperactive and malignant cells. The best studied type of nuclear body is the coiled body (CB), so termed due to characteristic morphology and content of a unique protein, p80-coilin (Fig.1). While no specific functions have as yet been assigned to CBs, they contain spliceosome snRNAs and proteins, and also the nucleolar protein fibrillarin. In addition, there is mounting evidence that CBs arise from or are generated near the nucleolus and then migrate into the nucleoplasm. This suggests that as yet undefined links may exist, between nucleolar pre-rRNA processing events and the spliceosome-associated Sm proteins in CBs.We are examining CB and nucleolar changes in three diverse model systems: (1) estrogen stimulated chick liver, (2) normal and neoplastic cells, and (3) polyploid mouse liver.

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