scholarly journals THE REPLICATION TIME AND PATTERN OF CARCINOGEN-INDUCED HEPATOMA CELLS

1964 ◽  
Vol 22 (2) ◽  
pp. 341-350 ◽  
Author(s):  
Joseph Post ◽  
Joseph Hoffman
Keyword(s):  
Tumor Cell ◽  
Dna Synthesis ◽  
Tumor Cells ◽  
Cell Population ◽  
Tritiated Thymidine ◽  
Normal Liver ◽  
Hepatoma Cells ◽  
Male Rats ◽  
Time Intervals ◽  
Replication Time

The replication time and pattern have been investigated in hepatoma cells induced by feeding 3'Me-DAB to male rats for 5 months. With the use of tritiated thymidine as a DNA label along with autoradiography, mitotic nuclear labeling has been studied 0.5 to 72 hours after the administration of the label. The following time intervals have been estimated: replication time, 31 hours; DNA synthesis, 17 hours; G2 plus Mitosis, 2 hours; G1, 12 hours. Only about 8 per cent of the tumor cell (interphase) population is "flash" labeled, following a single dose of 50 µC of H3TDR. This group of cells has been followed through three cycles of division. The repeated rhythmic passage of tumor cells through cell division is similar to that previously reported for normal liver cells in the growing rat. However, tumor cells have longer replication and DNA synthesis times. In addition, the several time intervals studied vary more in the tumor cell population than they do in the growing normal cell population.

scholarly journals THE REPLICATION TIME AND PATTERN OF THE LIVER CELL IN THE GROWING RAT

1963 ◽  
Vol 18 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Joseph Post ◽  
Cheng-Ya Huang ◽  
Joseph Hoffman
Keyword(s):  
Dna Synthesis ◽  
Liver Cell ◽  
Tritiated Thymidine ◽  
Liver Cells ◽  
Male Rats ◽  
Interphase Nuclei ◽  
Replication Time ◽  
Wistar Strain ◽  
Growing Rat ◽  
Liver Cell Population

Three-week-old male rats of the Wistar strain were given tritiated thymidine, 1 µc/gm body weight, intraperitoneally and were killed at intervals from 0.25 to 72 hours later. Autoradiographs were made from 5 µ sections, stained by the Feulgen method. The replication time and its component intervals were determined from the scoring of the labeling of interphase nuclei as well as of prophase, metaphase, anaphase, and telophase nuclei. Absorption of the intraperitoneally injected label is rapid and is attended by "flash" labeling during interphase. The results show that at any one time about 4 per cent of the liver cells are synthesizing DNA preliminary to cell division. These cells alternate with waves of other cells and it is estimated that about 10 per cent of the liver cell population is engaged in cell duplication. The replication time is about 21.5 hours, and its component intervals occupy the following times: DNA synthesis, 9 hours; post-DNA synthesis gap, 0.50 hour; prophase, 1.3 hours; metaphase, 1.0 hour; anaphase, 0.4 hour; telophase, 0.3 hour; postmitosis gap, 9.0 hours. A group of liver cells has been recorded in at least 3 successive replication cycles.

scholarly journals Relevance of Circulating Hybrid Cells as a Non-Invasive Biomarker for Myriad Solid Tumors

2021 ◽  
Author(s):  
Matthew S. Dietz ◽  
Thomas L. Sutton ◽  
Brett S. Walker ◽  
Charles E. Gast ◽  
Luai Zarour ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cell Population ◽  
Cancer Biology ◽  
Cell Populations ◽  
Hybrid Cells ◽  
Neoplastic Cells

AbstractMetastatic progression defines the final stages of tumor evolution and underlies the majority of cancer-related deaths. The heterogeneity in disseminated tumor cell populations capable of seeding and growing in distant organ sites contributes to the development of treatment resistant disease. We recently reported the identification of a novel tumor-derived cell population, circulating hybrid cells (CHCs), harboring attributes from both macrophages and neoplastic cells, including functional characteristics important to metastatic spread. These disseminated hybrids outnumber conventionally defined circulating tumor cells (CTCs) in cancer patients. It is unknown if CHCs represent a generalized cancer mechanism for cell dissemination, or if this population is relevant to the metastatic cascade. Herein, we detect CHCs in the peripheral blood of patients with cancer in myriad disease sites encompassing epithelial and non-epithelial malignancies. Further, we demonstrate that in vivo-derived hybrid cells harbor tumor-initiating capacity in murine cancer models and that CHCs from human breast cancer patients express stem cell antigens, features consistent with the ability to seed and grow at metastatic sites. Finally, we reveal heterogeneity of CHC phenotypes reflect key tumor features, including oncogenic mutations and functional protein expression. Importantly, this novel population of disseminated neoplastic cells opens a new area in cancer biology and renewed opportunity for battling metastatic disease.Simple SummaryThere is an incomplete understanding of circulating neoplastic cell populations and the fundamental mechanisms that drive dissemination, immune evasion, and growth —all critical information to more effectively prevent and treat cancer progression. A novel disseminated tumor cell population, circulating hybrid cells, are detected across many cancer types and carry functional tumor-initiating properties. Additionally, circulating hybrid cells are found at significantly higher levels than conventionally defined circulating tumor cells. Our study demonstrates that neoplastic hybrid cells harbor phenotypic and genetic characteristics of tumor and immune cells, display stem features, and are a generalizable phenomenon in solid tumors. Circulating hybrid cells therefore have relevance as a novel biomarker and open a new field of study in malignancy.

scholarly journals Some Characteristics of DNA Synthesis and the Mitotic Cycle in Ehrlich Ascites Tumor Cells

1960 ◽  
Vol 7 (2) ◽  
pp. 273-282 ◽  
Author(s):  
Joshua L. Edwards ◽  
Arthur L. Koch ◽  
Pauline Youcis ◽  
Herbert L. Freese ◽  
Melville B. Laite ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Tumor Cells ◽  
Mitotic Cycle ◽  
Average Rate ◽  
Tritiated Thymidine ◽  
Ehrlich Ascites Tumor ◽  
In Vivo Studies ◽  
Ehrlich Ascites Tumor Cells ◽  
Ascites Tumor ◽  
Ehrlich Ascites

In vivo studies of Ehrlich ascites tumor cells during the first 5 days of growth in peritoneal cavities of mice consisted of the following: 1. Determination of growth curves by direct enumeration of cells. 2. Estimation of the duration of each phase of the mitotic cycle based on incidence of cells in different phases. 3. Radioautographic studies to determine the proportion of cells in different phases of the mitotic cycle that incorporate tritiated thymidine during a single brief exposure to this precursor of DNA. 4. Estimation of the rate of incorporation of tritiated thymidine at different times during the period of DNA synthesis by comparison of mean grain counts over nuclei in radioautographs at different times following exposure to tritiated thymidine. The assumptions underlying these experiments and our observations concerning the duration of the period of DNA synthesis and its relation to the mitotic cycle are discussed. It is concluded that DNA synthesis is continuous, occupying a period of 8.5 hours during the interphase and that the average rate of synthesis is approximately constant.

scholarly journals Tumorigenicity of Ascites-Derived Tumor Cells: Insights Into the Molecular Mechanisms of Ovarian Cancer Progression and Therapy Resistance

2020 ◽  
Author(s):  
Yi Ding ◽  
Vera Labitzky ◽  
Karen Legler ◽  
Minyue Qi ◽  
Udo Schumacher ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Population ◽  
Adherent Cell ◽  
Cell Aggregates ◽  
Tumorigenic Potential ◽  
Extracellular Matrix Components

Abstract Background: Ovarian cancer (OvCa) cells disseminate primarily intraperitoneally. Here, detached tumor cell aggregates (spheroids) from the primary tumor are generally regarded as “metastatic units”, which exhibit a survival benefit, probably due to the protective microenvironment and their unique molecular characteristics. Hence, current therapeutic concepts such as classical chemotherapy are not sufficient preventing growth and spread of OvCa spheroids. Methods: In the current study we analyzed the cellular composition of ascites from ovarian cancer patients using flow cytometry and the tumorigenic potential of the different subpopulations in an intraperitoneal mouse model. Comparative transcriptome analyses (RNAseq) from ascites-derived tumor cells spheroids (n=10) vs. tumor samples from different metastatic sites (n=30) were further performed in order to identify key molecular players responsible for the special cellular characteristics of OvCa spheroids. Results: In vitro culture of ascites-derived cells gave rise to two different subpopulations: an adherent cell population (ADs) including mainly CD90+ cells with highly proliferative rates in vitro but no tumorigenic potential in vivo, and a non-adherent cell population (NADs) containing principally EpCAM+/CD24+ cells with low proliferative potential in vitro. NADs included cell aggregates and single cells, the first showing a high content (> 80%) of tumor cells (EpCAM+/CD24+). Enriched tumor cell spheroids from the ascites using cell strainers showed higher tumorigenic potential in vivo in comparison to the original ascites-derived cell population. Interestingly, the different metastatic spread patterns observed in the mice resembled the tumor dissemination pattern found in the corresponding patients. RNAseq analyses from tumor-spheroids revealed up-regulation of genes involved in chemoresistance (TGM1, HSPAs, MT1s), cell-adhesion and cell barrier (PKP3, CLDNs, PPL) and the oxidative phosphorylation (OXPHOS) process compared to the solid tumor tissue samples. Additionally, down-regulation of extracellular matrix components and angiogenesis-related genes could be observed. Targeting OXPHOS by metformin treatment led to reduced viability of ascites-derived spheroids from OvCa patients, showing to some extent a synergistic effect with cisplatin treatment. Conclusions: the actual study contributes to a better understanding of the biology of ovarian cancer spheroids and to the identification of new treatment opportunities in advanced ovarian cancer.

scholarly journals Modulation of gold nanoparticle mediated radiation dose enhancement through synchronization of breast tumor cell population

2019 ◽  
Vol 92 (1100) ◽  
pp. 20190283 ◽  
Author(s):  
Kristy Rieck ◽  
Kyle Bromma ◽  
Wonmo Sung ◽  
Aaron Bannister ◽  
Jan Schuemann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Radiation Dose ◽  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cells ◽  
Cell Population ◽  
Triple Combination ◽  
Tumor Cell Death ◽  
Tumor Cell Population

Objective: The incorporation of high atomic number materials such as gold nanoparticles (GNPs) into tumor cells is being tested to enhance the local radiotherapy (RT) dose. It is also known that the radiosensitivity of tumor cells depends on the phase of their cell cycle. Triple combination of GNPs, phase of tumor cell population, and RT for improved outcomes in cancer treatment. Methods: We used a double-thymidine block method for synchronization of the tumor cell population. GNPs of diameters 17 and 46 nm were used to capture the size dependent effects. A radiation dose of 2 Gy with 6 MV linear accelerator was used to assess the efficacy of this proposed combined treatment. A triple negative breast cancer cell line, MDA-MB-231 was chosen as the model cell line. Monte Carlo (MC) calculations were done to predict the GNP-mediated cell death using the experimental GNP uptake data. Results: There was a 1.5- and 2- fold increase in uptake of 17 and 46 nm GNPs in the synchronized cell population, respectively. A radiation dose of 2 Gy with clinically relevant 6 MV photons resulted in a 62 and 38 % enhancement in cell death in the synchronized cell population with the incorporation of 17 and 46 nm GNPs, respectively. MC data supported the experimental data, but to a lesser extent. Conclusion: A triple combination of GNPs, cell cycle synchronization, and RT could pave the way to enhance the local radiation dose while minimizing side effects to the surrounding healthy tissue. Advances in knowledge: This is the first study to show that the combined use of GNPs, phase of tumor cell population, and RT could enhance tumor cell death.

A short-term in vitro drug-screening assay for cancer chemotherapy.

1982 ◽  
Vol 28 (9) ◽  
pp. 1852-1856 ◽  
Author(s):  
S L Chen ◽  
J R Snoga ◽  
H Croft
Keyword(s):  
Tumor Cell ◽  
Dna Synthesis ◽  
Tumor Cells ◽  
Soft Agar ◽  
Cell Renewal ◽  
Short Term ◽  
Screening Assay ◽  
Vitro Assay ◽  
Drug Screening Assay

Abstract In this short-term in vitro assay for detection of tumor cell sensitivity to drugs, we have replaced the traditional soft-agar colony-forming assay with the measurement of DNA synthesis, to determine the cell renewal capability of the tumor cell population. The tumor cells are treated with drugs and cultured for five days. During the last 12--18 h of culture the cells are pulsed with [3H]thymidine, then harvested for scintillation counting. The effects of drugs are expressed as the percentage of DNA synthesis as compared with that of the control. When the % DNA synthesis is less than 40%, the drug is considered to be effective. So far we have studied tumor cells from multiple myeloma, non-Hodgkin's lymphoma, and carcinoma of lung, breast, ovary, stomach, and bladder. The overall negative predictive value is 1.0. The results are available within five days, compared with 21--28 days for completion of soft-agar assays; fewer cells are required; and the process is semiautomated.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

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