Blastema cell cycle in vitro and attempted restimulation of blastema cell cycling in denervated blastemata of the adult newt,Notophthalmus viridescens

1984 ◽  
Vol 232 (2) ◽  
pp. 249-258 ◽  
Author(s):  
Bruce L. Tomlinson ◽  
Morton Globus ◽  
Swani Vethamany-Globus
Keyword(s):  
Cell Cycle ◽  
Notophthalmus Viridescens ◽  
Blastema Cell ◽  
Adult Newt ◽  
Cell Cycling

The Novel Vascular Disrupting Agent ANG501 Induces Cell Cycle Arrest and Enhances Endothelial Cell Sensitivity to Radiation

2009 ◽  
Vol 2 ◽  
pp. CGM.S2596 ◽  
Author(s):  
Shona T. Dougherty ◽  
Sean E. Walker ◽  
Peter D. Davis ◽  
Graeme J. Dougherty
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Stress Proteins ◽  
Vascular Disrupting Agent ◽  
Heat Shock Stress ◽  
Cell Cycling ◽  
Vascular Disrupting

The efficacy of approaches in which vascular disrupting agents (VDA) are used in combination with conventional chemotherapy and/or radiation therapy in the treatment of cancer might be improved if there were a better understanding of the cellular and molecular changes induced in normal and malignant cells as a result of VD A exposure. Toward this goal, murine endothelial cells were treated in vitro with ANG501, a novel stilbene VDA developed in our laboratory, and alterations in gene expression determined by genome-wide microarray analysis and subsequently confirmed by Western blot analysis. Among the genes that were shown to be induced upon brief exposure to non-cytotoxic doses of ANG501 were several involved in the control of cell cycle progression and apoptosis, including p21Wafl and the heat shock/stress proteins hsp25, hsp70 and anti-B-crystallin. Reflecting such induction, functional studies confirmed that normal cell cycling is temporarily inhibited following treatment with ANG501 such that the majority of cells accumulate at the radiation-sensitive G2/M phase of the cell cycle at 6 hr. The effects were transient and by 24 hr normal cell cycling had largely resumed. Combination experiments confirmed that endothelial cells treated 6 hr previously with ANG501 were more readily killed by radiation. Importantly, significant effects were evident at clinically relevant radiation doses. Taken together these findings emphasize the need to consider the radiosensitizing activity of VD As when developing therapies in which these promising compounds are used in combination with radiation.

Dorsal root ganglia grafts stimulate regeneration of denervated urodele forelimbs: timing of graft implantation with respect to denervation

Development ◽  
1987 ◽  
Vol 99 (2) ◽  
pp. 173-186
Author(s):  
B.L. Tomlinson ◽  
R.A. Tassava
Keyword(s):  
Cell Cycle ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Relative Number ◽  
Blastema Cell ◽  
Neurotrophic Activity ◽  
Adult Newt ◽  
Timing Strategies ◽  
Graft Implantation ◽  
Stimulation Of

Amphibian forelimb regeneration is a nerve-dependent process; nerves presumably release one or more neurotrophic factors that stimulate blastema cell division. To date several candidate molecules/factors have been shown to stimulate macromolecular synthesis and/or mitosis but sustained cell cycle activity and blastema development have not been achieved. Because dorsal root ganglia (DRG) implants are capable of promoting regeneration of denervated adult newt limbs (Kamrin & Singer, 1959), we have evaluated the DRG stimulation of regeneration in denervated limbs of adult newts and larval axolotls; two alternative timing strategies were tested as a step toward defining bioassay parameters that best reflect neurotrophic activity. The frequency of regeneration in denervated adult newt limbs was compared after providing DRG before or at the time of denervation (to maintain neurotrophic and cell cycle activity) versus DRG implantation at various postdenervation times (to resupply neurotrophic activity and restimulate suppressed cell cycle activity). The results show that denervated adult newt limbs regenerated most frequently using the maintenance strategy, but as the denervation interval was extended in the restimulation strategy, the frequency of regeneration declined. Larval axolotl limbs responded positively in both maintenance and restimulation DRG-grafting protocols. These results suggest that the efficacy of DRG stimulation of regeneration in adult newts was related to the relative number of blastema cells present at the time of denervation and the proliferative status of the blastema cells; bioassays with denervated adult newt limbs should be designed with these constraints in mind. Because such constraints are not as problematic with the larval axolotl, this species may provide the best opportunity for further defining bioassay parameters related to the neurotrophic stimulation of regeneration.

scholarly journals Cytogenetic Studies on Goat Blood Lymphocytes:Cell Cycling

2009 ◽  
Vol 3 (1) ◽  
pp. 3-14
Author(s):  
E. K. Shubber ◽  
Z. MT Jaffer ◽  
A. Abdul-Kareem ◽  
M. I. AL-Tememi
Keyword(s):  
Cell Cycle ◽  
Genetic Markers ◽  
Cell Cycle Progression ◽  
Peripheral Blood Lymphocytes ◽  
Nuclear Transplantation ◽  
Cycle Duration ◽  
Blood Lymphocytes ◽  
Growing Period ◽  
Cell Cycling

Peripheral blood lymphocytes from goats (local breed) were cultivated in RPMI-1640 medium containing 15µg/ml of BudR 20 µg/ml of PHA for different times (12, 24, 36, 48, 60, 72 and 96( hrs. to determination the cell cycle duration. Blastogenesis was appeared post first 12hr of cultivation followed by first mitoses post 24 hrs. of culture initiation. The second and third cell cycling lasted 22 and 21 hrs, respectively. Effects of 6-thioguanine, methotrexate , colchicine and tamoxifen on cell cycle progression were investigated. Goat cells were found to be resistant to tamoxifen and MTX and sensitive to 6 TG and colchicine, which could be use as genetic markers to chick cellular genome integrity. Priming of goat blood lymphocytes was achieved by treating the blood with PHA for 24hr. Such treatment increased the in vitro growing period of derived lymphoblasts with short cycling time. However, PHA was found to be a promoting factor for initiation of blastogenesis and cell divisions in goat blood lymphoblasts. These techniques: Genetic markers, cytogenetic analysis cell cycling and lymphoblast explantation are crucial processes for nuclear transplantation processes.

An analysis of proliferative activity in innervated and denervated forelimb regenerates of the newt, Notophthalmus viridescens

Development ◽  
1987 ◽  
Vol 100 (4) ◽  
pp. 619-628 ◽  
Author(s):  
D.J. Goldhamer ◽  
R.A. Tassava
Keyword(s):  
Cell Cycle ◽  
Mitotic Index ◽  
Proliferative Activity ◽  
Thymidine Incorporation ◽  
Labelling Index ◽  
Notophthalmus Viridescens ◽  
Pulse Labelling ◽  
Adult Newt ◽  
Kinetics Of ◽  
Continuous Labelling

Pulse and continuous labelling with [3H]thymidine combined with mitotic index determinations provided data on the kinetics of cell cycling in innervated and denervated early and mid-bud forelimb blastemas of the adult newt, Notophthalmus viridescens. Most or all blastema cells cycle during regeneration and are thus part of the proliferative fraction. At any given moment, however, only 26% of the blastema cells are actively progressing through the cell cycle, with the remainder being in a state of transient quiescence (TQ). The small size of the actively cycling (AC) population may in part explain the relatively slow rate of regeneration exhibited by the adult newt. The pulse-labelling index and mitotic index of denervated blastemas paralleled control values for 48h following nerve withdrawal, but both parameters were significantly reduced by 72h. By 5 days postdenervation, cell cycle activity was essentially zero. The combined pulse and continuous labelling data suggest that nerves may be primarily involved in the entry of TQ cells into the AC population, with subsequent progression through the cell cycle being less dependent on innervation. Relative to controls, no early postdenervation increases in TCA-precipitable [3H]thymidine incorporation, pulse-labelling index or mitotic index were observed.

scholarly journals Accelerated cell-cycling of hematopoietic progenitor cells by growth factors

Blood ◽  
1995 ◽  
Vol 86 (1) ◽  
pp. 73-79 ◽  
Author(s):  
R Tanaka ◽  
N Katayama ◽  
K Ohishi ◽  
N Mahmud ◽  
R Itoh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Progenitor Cells ◽  
Early Stage ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Progenitor ◽  
Cell Cycle Time ◽  
Cell Cycling

Recent advances in molecular biology have led to the identification of hematopoietic growth factors that support and influence the proliferation of hematopoietic progenitor cells in vitro and in vivo. Although these factors have been extensively studied, little is known of their role in the regulation of cell-cycling of hematopoietic progenitors, especially in the early stage of hematopoiesis. In the present study, we examined the effects of early acting growth factors on proliferative kinetics of hematopoietic progenitors by monitoring the number of cells in individual developing colonies, using an in vitro clonal assay. Interleukin-11 (IL-11) or steel factor (SF), alone or in combination, shortened the time for the size of IL-3-dependent colonies to double. Consecutive replating experiments provided evidence for direct action of growth factors on the growth rate of hematopoietic progenitor cells. Shortening of the time for the total cell number in the colonies to double was due to a reduction in time for each single cell within the respective colonies to become two daughter cells, and there was no alteration in the incidence of cells with a proliferative capacity. Cell-cycle analysis demonstrated that IL-11 has the potential to induce a shortened time for cell-cycle of hematopoietic progenitor cells without affecting distribution of each fraction of the cell- cycle, whereas SF has the potential to reduce cell-cycle time mainly by decreasing the time required for hematopoietic progenitor cells to go through the G1 phase. These results suggest that growth factors may modulate cell-cycling of hematopoietic progenitor cells.

The effects of partial and complete denervation on adult newt forelimb blastema cell-cycle parameters

1985 ◽  
Vol 29 (2) ◽  
pp. 121-126 ◽  
Author(s):  
Roy A. Tassava ◽  
Dale L. Laux ◽  
David P. Treece
Keyword(s):  
Cell Cycle ◽  
Blastema Cell ◽  
Adult Newt

Maytansine-Induced Mitotic Arrest in Human Lymphoblasts

1977 ◽  
Vol 35 ◽  
pp. 460-461
Author(s):  
Tai-Te Chao ◽  
John Sullivan ◽  
Awtar Krishan
Keyword(s):  
Electron Microscopy ◽  
Cell Cycle ◽  
Transmission Electron Microscopy ◽  
Tubulin Polymerization ◽  
Vinca Alkaloids ◽  
Antimitotic Activity ◽  
Transmission Electron ◽  
Flow Microfluorometry ◽  
Brain Tubulin

Maytansine, a novel ansa macrolide (1), has potent anti-tumor and antimitotic activity (2, 3). It blocks cell cycle traverse in mitosis with resultant accumulation of metaphase cells (4). Inhibition of brain tubulin polymerization in vitro by maytansine has also been reported (3). The C-mitotic effect of this drug is similar to that of the well known Vinca- alkaloids, vinblastine and vincristine. This study was carried out to examine the effects of maytansine on the cell cycle traverse and the fine struc- I ture of human lymphoblasts.Log-phase cultures of CCRF-CEM human lymphoblasts were exposed to maytansine concentrations from 10-6 M to 10-10 M for 18 hrs. Aliquots of cells were removed for cell cycle analysis by flow microfluorometry (FMF) (5) and also processed for transmission electron microscopy (TEM). FMF analysis of cells treated with 10-8 M maytansine showed a reduction in the number of G1 cells and a corresponding build-up of cells with G2/M DNA content.

OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

2020 ◽  
Vol 20 ◽  
Author(s):  
En Xu ◽  
Hao Zhu ◽  
Feng Wang ◽  
Ji Miao ◽  
Shangce Du ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Cell Counting ◽  
Gastric Cancer Cells ◽  
Ags Cells ◽  
Dual Inhibitor ◽  
Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

5-Nitro-Thiophene-Thiosemicarbazone Derivatives Present Antitumor Activity Mediated by Apoptosis and DNA Intercalation

2019 ◽  
Vol 19 (13) ◽  
pp. 1075-1091 ◽  
Author(s):  
Karla Mirella Roque Marques ◽  
Maria Rodrigues do Desterro ◽  
Sandrine Maria de Arruda ◽  
Luiz Nascimento de Araújo Neto ◽  
Maria do Carmo Alves de Lima ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Cell Line ◽  
Mitochondrial Membrane ◽  
In Vitro Cytotoxicity ◽  
Dna Intercalation ◽  
Phase Cell ◽  
Fluorescence Studies ◽  
In Silico Studies

Background: Considering the need for the development of new antitumor drugs, associated with the great antitumor potential of thiophene and thiosemicarbazonic derivatives, in this work we promote molecular hybridization approach to synthesize new compounds with increased anticancer activity. Objective: Investigate the antitumor activity and their likely mechanisms of action of a series of N-substituted 2-(5-nitro-thiophene)-thiosemicarbazone derivatives. Methods: Methods were performed in vitro (cytotoxicity, cell cycle progression, morphological analysis, mitochondrial membrane potential evaluation and topoisomerase assay), spectroscopic (DNA interaction studies), and in silico studies (docking and molecular modelling). Results: Most of the compounds presented significant inhibitory activity; the NCIH-292 cell line was the most resistant, and the HL-60 cell line was the most sensitive. The most promising compound was LNN-05 with IC50 values ranging from 0.5 to 1.9 µg.mL-1. The in vitro studies revealed that LNN-05 was able to depolarize (dose-dependently) the mitochondrial membrane, induceG1 phase cell cycle arrest noticeably, promote morphological cell changes associated with apoptosis in chronic human myelocytic leukaemia (K-562) cells, and presented no topoisomerase II inhibition. Spectroscopic UV-vis and molecular fluorescence studies showed that LNN compounds interact with ctDNA forming supramolecular complexes. Intercalation between nitrogenous bases was revealed through KI quenching and competitive ethidium bromide assays. Docking and Molecular Dynamics suggested that 5-nitro-thiophene-thiosemicarbazone compounds interact against the larger DNA groove, and corroborating the spectroscopic results, may assume an intercalating interaction mode. Conclusion: Our findings highlight 5-nitro-thiophene-thiosemicarbazone derivatives, especially LNN-05, as a promising new class of compounds for further studies to provide new anticancer therapies.

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