Effect of Low-Dose Rapamycin on Tumor Growth in Two Human Hepatocellular Cancer Cell Lines

DNA methylation is an epigenetic event that involves adding a methyl group to the cytosine (C) site, especially the one that pairs with a guanine (G) site (ie, CG or CpG site), in a human genome. This event plays an important role in both cancerous and normal cell development. Previous studies often assume symmetric methylation on both DNA strands. However, asymmetric methylation, or hemimethylation (methylation that occurs only on 1 DNA strand), does exist and has been reported in several studies. Due to the limitation of previous DNA methylation sequencing technologies, researchers could only study hemimethylation on specific genes, but the overall genomic hemimethylation landscape remains relatively unexplored. With the development of advanced next-generation sequencing techniques, it is now possible to measure methylation levels on both forward and reverse strands at all CpG sites in an entire genome. Analyzing hemimethylation patterns may potentially reveal regions related to undergoing tumor growth. For our research, we first identify hemimethylated CpG sites in breast cancer cell lines using Wilcoxon signed rank tests. We then identify hemimethylation patterns by grouping consecutive hemimethylated CpG sites based on their methylation states, methylation “M” or unmethylation “U.” These patterns include regular (or consecutive) hemimethylation clusters (eg, “MMM” on one strand and “UUU” on another strand) and polarity (or reverse) clusters (eg, “MU” on one strand and “UM” on another strand). Our results reveal that most hemimethylation clusters are the polarity type, and hemimethylation does occur across the entire genome with notably higher numbers in the breast cancer cell lines. The lengths or sizes of most hemimethylation clusters are very short, often less than 50 base pairs. After mapping hemimethylation clusters and sites to corresponding genes, we study the functions of these genes and find that several of the highly hemimethylated genes may influence tumor growth or suppression. These genes may also indicate a progressing transition to a new tumor stage.

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Quercetin conjugated with silica nanoparticles inhibits tumor growth in MCF-7 breast cancer cell lines

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.04.174 ◽

2018 ◽

Vol 500 (4) ◽

pp. 860-865 ◽

Cited By ~ 22

Author(s):

Fahimeh Aghapour ◽

Ali Akbar Moghadamnia ◽

Andrea Nicolini ◽

Seydeh Narges Mousavi Kani ◽

Ladan Barari ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Growth ◽

Silica Nanoparticles ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Mcf 7

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PTU-042 DNA-PK or ATM inhibition inhibits non-homologous end joining and enhances chemo- and radio sensitivity in hepatocellular cancer cell lines

Gut ◽

10.1136/gutjnl-2012-302514c.42 ◽

2012 ◽

Vol 61 (Suppl 2) ◽

pp. A201.1-A201 ◽

Cited By ~ 1

Author(s):

L Cornell ◽

J Munck ◽

N Curtin ◽

H Reeves

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Hepatocellular Cancer ◽

Cancer Cell Lines ◽

End Joining ◽

Non Homologous End Joining ◽

Radio Sensitivity

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Inhibition of cMET in an experimental model of pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.185 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 185-185

Author(s):

Sven A. Lang ◽

Franziska Brandes ◽

Edward K. Geissler

Keyword(s):

Pancreatic Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Cancer Cell Lines ◽

Human Pancreatic Cancer ◽

Oncogenic Signaling

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P<0.05). Regarding oncogenic signaling, INC280 led to inhibition of HGF-induced phosphorylation of AKT, ERK and FAK. In addition, c-Myc expression was diminished in cancer cells. Interestingly, gemcitabine resistant cell line MiaPaCa2(G500) showed higher cMET expression levels compared to the normal MiaPaCa2. Stimulation of MiaPaCa2(G500) with HGF led to strong induction of oncogenic signaling and tumor cell motility, an effect that was significantly diminished by INC280. Moreover, results from in vivo experiments show that therapy with INC280 (10 mg/kg/d) significantly reduces tumor growth as determined by final tumor weight (P<0.05). Conclusions: In pancreatic cancer cell lines, targeting cMET with INC280 abrogates oncogenic signaling in vitro and impairs tumor growth in vivo. Therefore, the concept of cMET inhibition warrants further preclinical evaluation.

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Phase transitions in tumor growth: II prostate cancer cell lines

Physica A Statistical Mechanics and its Applications ◽

10.1016/j.physa.2015.01.038 ◽

2015 ◽

Vol 426 ◽

pp. 88-92 ◽

Cited By ~ 6

Author(s):

J.A. Llanos-Pérez ◽

A. Betancourt-Mar ◽

M.P. De Miguel ◽

E. Izquierdo-Kulich ◽

M. Royuela-García ◽

...

Keyword(s):

Prostate Cancer ◽

Phase Transitions ◽

Tumor Growth ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Lines ◽

Prostate Cancer Cell Lines

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1065 INFLUENCE OF RESISTANCE TO GEMCITABINE AND CISPLATIN ON TUMOR GROWTH, ADHESIVE AND INVASIVE PROPERTIES IN CHEMORESISTANT BLADDER CANCER CELL LINES

The Journal of Urology ◽

10.1016/j.juro.2012.02.1171 ◽

2012 ◽

Vol 187 (4S) ◽

Author(s):

Stefan Vallo ◽

Roman Blaheta ◽

Martin Michaelis ◽

Kilian M. Gust ◽

Peter C. Black ◽

...

Keyword(s):

Bladder Cancer ◽

Tumor Growth ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Bladder Cancer Cell ◽

Gemcitabine And Cisplatin

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A cell-based platform to potentiate oncolytic virus: Potential approach for cancer therapies.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.5_suppl.21 ◽

2020 ◽

Vol 38 (5_suppl) ◽

pp. 21-21

Author(s):

Duong Nguyen ◽

Alberto Gomez ◽

Ashley Alamillo ◽

Forrest Neuharth ◽

Ivelina Minev ◽

...

Keyword(s):

Tumor Growth ◽

Vaccinia Virus ◽

Cell Lines ◽

Cancer Cell ◽

Therapeutic Potential ◽

Cancer Cell Lines ◽

Oncolytic Viruses ◽

Oncolytic Virotherapy ◽

Adaptive Immune ◽

Immune Barriers

21 Background: Oncolytic virotherapy has been pursued by multiple companies and institutions with few candidates reaching the clinic and demonstrating limited efficacy. The therapeutic potential of oncolytic viruses can be severely restricted by innate and adaptive immune barriers. To overcome this obstacle, we load and protect tumor selective CAL1 oncolytic vaccinia virus into adipose-derived stem cells (AD-MSC) to generate a new therapeutic agent called SNV1(SuperNova1). Methods: SNV1s were generated by incubating AD-MSC with CAL1 virus. SNV1 was analyzed for its ability to kill cancer cell lines and protect virus in the presence of active neutralizing antibodies and complement. In animals, SNV1 was intratumorally injected in various xenograft and syngeneic models. Viral biodistribution was also evaluated by PCR. Immune infiltration were analyzed using flow cytometry. Results: Compared to the naked virus, SNV1 showed improved protection against the humoral barriers and efficient eradication of various human cancer cell lines in vitro. Intratumoral SNV1 treatment showed statistically significant and potentiated tumor growth inhibition compared to control or CAL1 naked virus treatment in all tested models (prostate, breast, melanoma, colon, and prostate cancers). Importantly, local administration of SNV1 induced systemic therapeutic effects. Five days after SNV1 administration, tumor infiltrating lymphocytes (TILs) from both treated and untreated tumors showed increased CD4 and CD8 T-cell populations. As well as decreased frequency of Tregs, and improved effector to Treg ratios, which was associated with inhibition of tumor growth at the treated tumor site and also at distant untreated sites. Ongoing and persistent virus infection could be detected in the treated tumor as late as 15 days after administration. Conclusions: This study demonstrates the ability of our cell-based platform to protect and potentiate oncolytic vaccinia virus by circumventing the innate and adaptive immune barriers, resulting in enhanced oncolytic virotherapy. These findings provide fundamental rationale for the development of cell-based platforms to maximize the therapeutic potential of various oncolytic viruses.

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