scholarly journals Measuring single cell divisions in human cancers from multi-region sequencing data

2019 ◽  
Author(s):  
Benjamin Werner ◽  
Jack Case ◽  
Marc J. Williams ◽  
Kate Chkhaidze ◽  
Daniel Temko ◽  
...  
Keyword(s):  
Cell Division ◽  
Survival Rate ◽  
Cell Survival ◽  
Single Cell ◽  
Evolutionary Dynamics ◽  
Human Cancer ◽  
Cell Divisions ◽  
Human Cancers ◽  
Cell Survival Rate

AbstractCancer is driven by complex evolutionary dynamics involving billions of cells. Increasing effort has been dedicated to sequence single tumour cells, but obtaining robust measurements remains challenging. Here we show that multi-region sequencing of bulk tumour samples contains quantitative information on single-cell divisions that is accessible if combined with evolutionary theory. Using high-throughput data from 16 human cancers, we measured the in vivo per-cell point mutation rate (mean: 1.69×10−8 bp per cell division) and per-cell survival rate (mean: 0.57) in individual patient tumours from colon, lung and renal cancers. Per-cell mutation rates varied 50-fold between individuals, and per-cell survival rates were between nearly-homeostatic and almost perfect cell doublings, equating to tumour ages between 1 and 19 years. Furthermore, reanalysing a recent dataset of 89 whole-genome sequenced healthy haematopoietic stem cells, we find 1.14 mutations per genome per cell division and near perfect cell doublings (per-cell survival rate: 0.96) during early haematopoietic development. Our analysis measures in vivo the most fundamental properties of human cancer and healthy somatic evolution at single-cell resolution within single individuals.

A naphthalimide derivative can release COS and form H2S in a light-controlled manner and protect cells against ROS with real-time monitoring ability

The Analyst ◽  
2020 ◽  
Vol 145 (11) ◽  
pp. 3878-3884
Author(s):  
Wuyang Hua ◽  
Jian Zhao ◽  
Shaohua Gou
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Real Time ◽  
Uv Light ◽  
Real Time Monitoring ◽  
Cell Survival Rate

Triggered by UV light, the donor could release H2S to protect cells against the damage of ROS and prompt the cell survival rate, meanwhile turning on its fluorescence to be monitored in real time.

scholarly journals Survival Rate of Cells Sent by a Low Mechanical Load Tube Pump: The “Ring Pump”

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 447 ◽  
Author(s):  
Kaoru Uesugi ◽  
Keizo Nishiyama ◽  
Koki Hirai ◽  
Hiroaki Inoue ◽  
Yoichi Sakurai ◽  
...  
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Saline Solution ◽  
Mechanical Load ◽  
Survival Rates ◽  
Cell Culture System ◽  
Large Size ◽  
Cell Survival Rate ◽  
Peristaltic Pumps ◽  
Phosphate Buffered Saline

A ring pump (RP) is a useful tool for microchannels and automated cell culturing. We have been developing RPs (a full-press ring pump, FRP; and a mid-press ring pump, MRP). However, damage to cells which were sent by the RP and the MRP was not investigated, and no other studies have compared the damage to cells between RPs and peristaltic pumps (PPs). Therefore, first, we evaluated the damage to cells that were sent by a small size FRP (s-FRP) and small size MRPs (s-MRPs; gap = 25 or 50 μm, respectively). “Small size” means that the s-FRP and the s-MRPs are suitable for microchannel-scale applications. The survival rate of cells sent by the s-MRPs was higher than those sent by the s-FRP, and less damage caused by the former. Second, we compared the survival rate of cells that were sent by a large size FRP (l-FRP), a large size MRP (l-MRP) (gap = 50 μm) and a PP. “Large size” means that the l-FRP and the l-MRP are suitable for automated cell culture system applications. We could not confirm any differences among the cell survival rates. On the other hand, when cells suspended in Dulbecco’s phosphate-buffered saline solution were circulated with the l-MRP (gap = 50 μm) and the PP, we confirmed a difference in cell survival rate, and less damage caused by the former.

scholarly journals Chemically induced mutations in a MutaMouse reporter gene inform mechanisms underlying human cancer mutational signatures

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Marc A. Beal ◽  
Matthew J. Meier ◽  
Danielle P. LeBlanc ◽  
Clotilde Maurice ◽  
Jason M. O’Brien ◽  
...  
Keyword(s):  
Human Cancer ◽  
Published Data ◽  
Induced Mutations ◽  
Lung Cancers ◽  
Human Cancers ◽  
Chemically Induced ◽  
Mutation Pattern ◽  
Environmental Causes ◽  
Next Generation Sequencing Ngs

AbstractTransgenic rodent (TGR) models use bacterial reporter genes to quantify in vivo mutagenesis. Pairing TGR assays with next-generation sequencing (NGS) enables comprehensive mutation pattern analysis to inform mutational mechanisms. We used this approach to identify 2751 independent lacZ mutations in the bone marrow of MutaMouse animals exposed to four chemical mutagens: benzo[a]pyrene, N-ethyl-N-nitrosourea, procarbazine, and triethylenemelamine. We also collected published data for 706 lacZ mutations from eight additional environmental mutagens. We report that lacZ gene sequencing generates chemical-specific mutation signatures observed in human cancers with established environmental causes. For example, the mutation signature of benzo[a]pyrene, a carcinogen present in tobacco smoke, matched the signature associated with tobacco-induced lung cancers. Our results suggest that the analysis of chemically induced mutations in the lacZ gene shortly after exposure provides an effective approach to characterize human-relevant mechanisms of carcinogenesis and propose novel environmental causes of mutation signatures observed in human cancers.

Comparison of Effects of Curcumin and Nano-curcumin on the Survival of Human-Derived Mesenchymal Stem Cells: An Experimental Study

2020 ◽  
Vol 11 (2) ◽  
pp. 148-155
Author(s):  
Pinjari Hameeda ◽  
Sandeep Katti ◽  
Rajkishore Jammalamadugu ◽  
Kishore Bhatt ◽  
Malleswara Rao Peram ◽  
...  
Keyword(s):  
Stem Cells ◽  
Experimental Study ◽  
Mesenchymal Stem Cells ◽  
Survival Rate ◽  
Cell Viability ◽  
Cell Survival ◽  
Dependent Manner ◽  
Cell Survival Rate ◽  
Post Hoc ◽  
Dose Dependent

Aim: To evaluate and compare the effect of curcumin (CUR) and Nano-curcumin (N-CUR) on human-derived mesenchymal stem cells (MSCs) in a dose-dependent manner. Materials and Methods: An experimental study performed with putative MSCs from a total of five systemically healthy subjects with chronic periodontitis. These putative MSCs were isolated by cell culture and were further characterized and identified by colony-forming unit assay and immunocytochemical analysis using cell surface markers CD105, CD146, CD45 and CD73. The identified MSCs were treated with different doses of CUR and N-CUR, and compared with α-minimum essential medium (α -MEM) for its cell viability by performing MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay for 48 and 72 hr. The statistically analysis was performed using one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test and Bonferroni’s post hoc test. Results: Compared to the α-MEM group, both CUR and N-CUR treated cells have shown significantly ( P = .029) higher survival rate at lower concentration (0.1 and 0.5 µM/L), at 48 hr incubation. However, there was no statistically significant difference between the CUR and N-CUR groups on cell survival rate at both 48 and 72 hr incubation. When compared between the concentrations of the same group, significantly higher cell viability ( P = .001) was observed at lower concentrations (0.1, 0.5 µM/L) in both test groups after incubation for 48 and 72 hr. Conclusion: Both CUR and N-CUR have a dose-dependent effect on human derived MSCs survival when incubated for 48 hr, whereas N-CUR shows increased cell survival rate even at 72 hr of incubation. Although, the cautious use of CUR and N-CUR at higher concentrations is recommended.

scholarly journals Biocompatible Parylene Neurocages for Action Potential Recording and Stimulation

2006 ◽  
Vol 926 ◽  
Author(s):  
Angela Tooker ◽  
Jon Erickson ◽  
Yu-Chong Tai ◽  
Jerry Pine
Keyword(s):  
Neural Networks ◽  
Survival Rate ◽  
Cell Survival ◽  
Action Potentials ◽  
Fabrication Process ◽  
Glass Substrates ◽  
Cell Survival Rate ◽  
Potential Recording

ABSTRACTParylene neurocages are biocompatible and very robust, making them ideally suited for studying neural networks. We present a design and fabrication process for building parylene neurocages for in vitro studies of neural networks. The fabrication process, on either silicon or glass substrates, incorporates electrodes into the neurocages to allow for stimulation and recording of action potentials. The resulting neurocages have a long-term cell survival rate of ∼50% and have proven to be 99% effective in trapping neurons.

213: Radiosensitizing effect of a RasGAP derived peptide on cell survival in human cancer cells in vitro and in vivo

2014 ◽  
Vol 110 ◽  
pp. S104
Author(s):  
D. Viertl ◽  
A. Annibaldi ◽  
O. Matzinger ◽  
M.-C. Vozenin ◽  
C. Widmann ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cells ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Radiosensitizing Effect

Synergistic Suppression of Human Multiple Myeloma Cell Growth by the Natural Product TBL-12 in Combination with Low Doses of Velcade: Insight Into Mechanisms

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5109-5109
Author(s):  
Bhagavathi A Narayanan ◽  
Amitabha Mazumder
Keyword(s):  
Multiple Myeloma ◽  
Survival Rate ◽  
Side Effects ◽  
Cell Growth ◽  
Cell Survival ◽  
Treatment Efficacy ◽  
Low Doses ◽  
Myeloma Cells ◽  
Cell Survival Rate ◽  
Isobologram Analysis

Abstract Abstract 5109 Targeting Multiple Myeloma (MM) cells with potential natural agents could overcome the side effects of current treatment drugs while increasing the efficacy at very low doses. In this study we tested the efficacy of proteasome inhibitor Velcade (Bortezomib) with TBL-12, (an extract from Sea Cucumber, Unicorn Pacific Corporation) in human myeloma cells. Based on the findings from cell survival and proliferation assays we believe that as a single agent TBL-12 is effective in inducing cell growth inhibition with a dose of 100ug/ml in myeloma cells MM1, U266 and ARP1 cells and 200ug/ml in KMSI cells. We further examined the combined effect of Velcade with TBL-12 to test the hypothesis that a natural agent in combination with a pharmaceutical drug at low doses (but with different modes of action) can reduce toxicity while enhancing the treatment efficacy that may increase the survival rate. In this study we report the in vitro effect of low doses of Velcade in combination with TBL-12. We performed cell survival assays in MM1 and U266 cells using very low doses of Valcade ranging from 1–10ngs/ml in combination with an already established dose for TBL-12 (100ugs/ml) showed a time and dose dependent inhibitory effect on cell growth. We observed a cell survival rate that was reduced from 100 % to 30% at 48h and 20% at 72h (p<0.001) in both MM1 and U266 cells. These findings suggest the possibility of using very low doses of Velcade in combination with TBL-12 to be more effective and reduce the toxicity. Mechanistically, stimulation of MM cells with TNFa could trigger the activation of IL-6 and vasculendothelial growth factor (VEGF) and its receptors which will lead to progressive angiogenesis in preclinical models for myeloma. To address the effect of TBL-12 on angiogenesis, we conducted several independent assays by stimulating MM and U266 cells with TNFa or IL-6 for duration of 8h. First we determined the rate of cell survival in MM1 and U266 cells at different time points of 24, 48 and 72h in cells stimulated with TNFa (5ng/ml) followed by treatment with TBL-12 (100ug/ml) alone and in combination with Velcade. Although our data showed a 50% decrease in the cell survival rate by TBL-12 alone, we observed a significant decrease (70–80%, p<0.001)) in the cell survival rate in combination with Velcade in TNFa stimulated cells compared to the control. Co-culturing of myeloma cells MM1 and U266 with human umbilical vein endothelial cells (HUVEC) followed by treatment with an already established dose of TBL-12 showed a significant decrease (45%) in cells adhering to the surface of HUVEC determined by phase contrast and immunofluorescence microscopic observations. These findings suggest that TBL-12 may have potential to inhibit angiogenesis by targeting VEGF receptors in combination with Velcade at low doses (determined by isobologram analysis). Evidence from Western blot analysis of the MM1 and U266 cells treated with TBL-12 indicates a significant accumulation of caspase -3 and caspase -9 indicating the underlying targets of TBL-12 in mediating apoptosis. Findings on the isobologram analysis indicating synergistic effects exerted by TBL-12 in combination with Velcade on VEGFR1 receptor, and modulation of Bcl2 and Bax that is associated with apoptosis will be discussed during presentation. Overall findings from this study suggest the potential use of TBL-12 in combination with Velcade could improve treatment efficacy with reduced side effects related to high dose toxicity. Currently we are doing trials with TBL-12 at NYUCI and this data could form the basis for future trials. Disclosures: No relevant conflicts of interest to declare.

scholarly journals How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers

2011 ◽  
Vol 29 (16) ◽  
pp. 2273-2281 ◽  
Author(s):  
Katerina Politi ◽  
William Pao
Keyword(s):  
Mouse Models ◽  
Cancer Biology ◽  
Human Cancer ◽  
Genetically Engineered ◽  
Mouse Tumor ◽  
Tumor Models ◽  
Genetically Engineered Mouse Models ◽  
Human Cancers ◽  
Chemically Induced

Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review.

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