scholarly journals An Integrative Framework for Detecting Structural Variations in Cancer Genomes

2017 ◽  
Author(s):  
Jesse R. Dixon ◽  
Jie Xu ◽  
Vishnu Dileep ◽  
Ye Zhan ◽  
Fan Song ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Structural Variation ◽  
Cancer Cell Lines ◽  
Regulatory Sequences ◽  
Structural Variants ◽  
Structural Variations ◽  
Integrative Framework ◽  
Cancer Genomes ◽  
The Impact

AbstractStructural variants can contribute to oncogenesis through a variety of mechanisms, yet, despite their importance, the identification of structural variants in cancer genomes remains challenging. Here, we present an integrative framework for comprehensively identifying structural variation in cancer genomes. For the first time, we apply next-generation optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole genome sequencing to systematically detect SVs in a variety of cancer cells.Using this approach, we identify and characterize structural variants in up to 29 commonly used normal and cancer cell lines. We find that each method has unique strengths in identifying different classes of structural variants and at different scales, suggesting that integrative approaches are likely the only way to comprehensively identify structural variants in the genome. Studying the impact of the structural variants in cancer cell lines, we identify widespread structural variation events affecting the functions of non-coding sequences in the genome, including the deletion of distal regulatory sequences, alteration of DNA replication timing, and the creation of novel 3D chromatin structural domains.These results underscore the importance of comprehensive structural variant identification and indicate that non-coding structural variation may be an underappreciated mutational process in cancer genomes.

scholarly journals Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression

2019 ◽  
Vol 32 (3) ◽  
pp. 175-186 ◽  
Author(s):  
Hiraku Endo ◽  
Naoki Hama ◽  
Muhammad Baghdadi ◽  
Kozo Ishikawa ◽  
Ryo Otsuka ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Disease Progression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Lines ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Tissues ◽  
The Impact

Abstract Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.

scholarly journals ANTIPROLIFERATIVE ACTIVITY OF ELEPHANTOPUS SCABER MEDIATED SILVER NANOPARTICLES AGAINST MCF-7, A-549, SCC-40, AND COLO-205 HUMAN CANCER CELL LINES

2019 ◽  
pp. 163-167
Author(s):  
ASHWINI S SHINDE ◽  
VIJAY D MENDHULKAR
Keyword(s):  
Silver Nanoparticles ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Cancer Cell Lines ◽  
Synergistic Activity ◽  
Standard Drug ◽  
Elephantopus Scaber ◽  
The Impact ◽  
Mcf 7

Objective: To unearth the applications of nanotechnology in medicine has become imperative with all the advancements in the technique. In the current study, we have attempted to exploit the anticancer ability of the green synthesized silver nanoparticles (AgNPs). Methods: The AgNPs were synthesized using 60% methanol (H-MeOH) Elephantopus scaber leaf extract, characterized, and discussed priorly. The effect of AgNPs was studied on the human breast (MCF-7), lung (A-549), oral (SCC-40), and colon (COLO-205) cancer cell lines through sulforhodamine B assay. We also carried out the synergistic activity with standard drug adriamycin (ADR). Results: According to the results obtained, AgNPs showed good antiproliferative activity with GI50 <10 μg/ml on MCF-7, A-549, and SCC-40 cell lines when compared with the standard drug ADR. However, for COLO-205 cell line, the impact was 17.4 μg/ml and thus the treatment was less effective. Conclusion: The synergistic effect of AgNPs+ADR was even better for all the four cell lines than that of the AgNPs alone.

scholarly journals Cell-in-cell phenomenon: leukocyte engulfment by non-tumorigenic cells and cancer cell lines

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mareike F. Bauer ◽  
Michael Hader ◽  
Markus Hecht ◽  
Maike Büttner-Herold ◽  
Rainer Fietkau ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Mononuclear Cells ◽  
Cancer Cell Lines ◽  
Host Cells ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
The Impact ◽  
Microwave Hyperthermia

Abstract Background Research on cell-in-cell (CIC) phenomena, including entosis, emperipolesis and cannibalism, and their biological implications has increased in recent years. Homotypic and heterotypic engulfment of various target cells by numerous types of host cells has been studied in vitro and in tissue sections. This work has identified proteins involved in the mechanism and uncovered evidence for CIC as a potential histopathologic predictive and prognostic marker in cancer. Our experimental study focused on non-professional phagocytosis of leukocytes. Results We studied the engulfment of peripheral blood mononuclear cells isolated from healthy donors by counting CIC structures. Two non-tumorigenic cell lines (BEAS-2B, SBLF-9) and two tumour cell lines (BxPC3, ICNI) served as host cells. Immune cells were live-stained and either directly co-incubated or treated with irradiation or with conventional or microwave hyperthermia. Prior to co-incubation, we determined leukocyte viability for each batch via Annexin V-FITC/propidium iodide staining. All host cells engulfed their targets, with uptake rates ranging from 1.0% ± 0.5% in BxPC3 to 8.1% ± 5.0% in BEAS-2B. Engulfment rates of the cancer cell lines BxPC3 and ICNI (1.6% ± 0.2%) were similar to those of the primary fibroblasts SBLF-9 (1.4% ± 0.2%). We found a significant negative correlation between leukocyte viability and cell-in-cell formation rates. The engulfment rate rose when we increased the dose of radiotherapy and prolonged the impact time. Further, microwave hyperthermia induced higher leukocyte uptake than conventional hyperthermia. Using fluorescent immunocytochemistry to descriptively study the proteins involved, we detected ring-like formations of diverse proteins around the leukocytes, consisting, among others, of α-tubulin, integrin, myosin, F-actin, and vinculin. These results suggest the involvement of actomyosin contraction, cell-cell adhesion, and the α-tubulin cytoskeleton in the engulfment process. Conclusions Both non-tumorigenic and cancer cells can form heterotypic CIC structures by engulfing leukocytes. Decreased viability and changes caused by microwave and X-ray irradiation trigger non-professional phagocytosis.

scholarly journals Downregulation of 15-hydroxyprostaglandin dehydrogenase during acquired tamoxifen resistance and association with poor prognosis in ERα-positive breast cancer

2020 ◽  
Vol 1 (5) ◽  
Author(s):  
Milene Volpato ◽  
Michele Cummings ◽  
Abeer M. Shaaban ◽  
Balkees Abderrahman ◽  
Mark A. Hull ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Tamoxifen Resistance ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
The Impact ◽  
Mcf 7 ◽  
Positive Breast Cancer

Aim: Tamoxifen (TAM) resistance remains a clinical issue in breast cancer. The authors previously reported that 15-hydroxyprostaglandin dehydrogenase (HPGD) was significantly downregulated in tamoxifen-resistant (TAMr) breast cancer cell lines. Here, the authors investigated the relationship between HPGD expression, TAM resistance and prediction of outcome in breast cancer. Methods: HPGD overexpression and silencing studies were performed in isogenic TAMr and parental human breast cancer cell lines to establish the impact of HPGD expression on TAM resistance. HPGD expression and clinical outcome relationships were explored using immunohistochemistry and in silico analysis. Results: Restoration of HPGD expression and activity sensitised TAMr MCF-7 cells to TAM and 17β-oestradiol, whilst HPGD silencing in parental MCF-7 cells reduced TAM sensitivity. TAMr cells released more prostaglandin E2 (PGE2) than controls, which was reduced in TAMr cells stably transfected with HPGD. Exogenous PGE2 signalled through the EP4 receptor to reduce breast cancer cell sensitivity to TAM. Decreased HPGD expression was associated with decreased overall survival in ERα-positive breast cancer patients. Conclusions: HPGD downregulation in breast cancer is associated with reduced response to TAM therapy via PGE2-EP4 signalling and decreases patient survival. The data offer a potential target to develop combination therapies that may overcome acquired tamoxifen resistance.

scholarly journals In Vitro Evaluation of Sulforaphane and a Natural Analog as Potent Inducers of 5-Fluorouracil Anticancer Activity

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3040 ◽  
Author(s):  
Małgorzata Milczarek ◽  
Lidia Mielczarek ◽  
Katarzyna Lubelska ◽  
Aleksandra Dąbrowska ◽  
Zdzisław Chilmonczyk ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Natural Analog ◽  
Colon Cancer Cell Lines ◽  
The Impact

Isothiocyanates (R-NCS) are sulphur-containing phytochemicals. The main source are plants of the Brassicaceae family. The best known plant-derived isothiocyanate is sulforaphane that has exhibited anticancer activity in both in vivo and in vitro studies. Recent attempts to expand their use in cancer therapy involve combining them with standard chemotherapeutics in order to increase their therapeutic efficacy. The aim of this paper is to determine the impact of sulforaphane and its natural analog alyssin on the anticancer activity of the well-known anticancer drug 5-fluorouracil. The type of drug-drug interactions was determined in prostate and colon cancer cell lines. Confocal microscopy, western blot and flow cytometry methods were employed to determine the mechanism of cytotoxic and cytostatic action of the combinations. The study revealed that additive or synergistic interactions were observed between 5-fluorouracil and both isothiocyanates, which enhanced the anticancer activity of 5-fluorouracil, particularly in colon cancer cell lines. An increased cytostatic effect was observed in case of alyssin while for sulforaphane the synergistic interaction with 5-fluorouracil involved an intensification of apoptotic cell death.

scholarly journals Iranian propolis efficiently inhibits growth of oral streptococci and cancer cell lines

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Fariba Asgharpour ◽  
Ali Akbar Moghadamnia ◽  
Ebrahim Zabihi ◽  
Sohrab Kazemi ◽  
Amirmorteza Ebrahimzadeh Namvar ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Cell Lines ◽  
Cancer Cell ◽  
Biofilm Formation ◽  
Cytotoxic Effect ◽  
Cancer Cell Lines ◽  
Oral Streptococci ◽  
Cariogenic Bacteria ◽  
Wide Range ◽  
The Impact

Abstract Background Propolis is a natural bee product with a wide range of biological activities that are related to its chemical composition. The present study investigated the quantification of quercetin (Q) in Ardabil ethanol extract of propolis (AEEP), and then compared its anti-bacterial, anti- biofilm and cytotoxic effects on cancer and normal cell lines. Method In the present study, the chemical composition of AEEP was determined through the high-performance liquid chromatography (HPLC). The AEEP and its main component, quercetin (Q), were evaluated in vitro against 57 oral streptococci by a broth micro-dilution method. The biofilm formation was assessed through the crystal violet staining and MTT assays. The impact of AEEP and Q anti-proliferative effect were evaluated on the fibroblast as normal and cancer cell lines (KB and A431). Results The Q concentration in the composition of AEEP was 6.9% of all its components. The findings indicated that the AEEP and Q were efficient against the cariogenic bacteria and were able to inhibit the S.mutans biofilm adherence at a sub-MIC concentration. Moreover, electron micrographs indicated the inhibition of biofilms compared to control biofilms. In addition, the AEEP and Q indicated a dose-dependent cytotoxic effect on A431 and KB cell lines. On the contrary, they had no cytotoxic effect on fibroblast cells. Conclusion The results indicated that the synergistic impact of main components of AEEP was related to the inhibition of the cancer cell proliferation, cariogenic bacteria and oral biofilm formation. It may play a promising role in the complementary medicine and, it is suggested to be used as food additives.

scholarly journals The Impact of HIF1α on the Per2 Circadian Rhythm in Renal Cancer Cell Lines

PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e109693 ◽  
Author(s):  
Takashi Okabe ◽  
Megumi Kumagai ◽  
Yoshihiro Nakajima ◽  
Suguru Shirotake ◽  
Kiichiro Kodaira ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Cell Lines ◽  
Cancer Cell ◽  
Renal Cancer ◽  
Cancer Cell Lines ◽  
Renal Cancer Cell ◽  
The Impact
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