Voxel-Based Analysis of the Relation of 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET and Diffusion-Weighted (DW) MR Signals in Subcutaneous Tumor Xenografts Does Not Reveal a Direct Spatial Relation of These Two Parameters

Abstract Purpose Multimodal molecular imaging allows a direct coregistration of different images, facilitating analysis of the spatial relation of various imaging parameters. Here, we further explored the relation of proliferation, as measured by [18F]FLT PET, and water diffusion, as an indicator of cellular density and cell death, as measured by diffusion-weighted (DW) MRI, in preclinical tumor models. We expected these parameters to be negatively related, as highly proliferative tissue should have a higher density of cells, hampering free water diffusion. Procedures Nude mice subcutaneously inoculated with either lung cancer cells (n = 11 A549 tumors, n = 20 H1975 tumors) or colorectal cancer cells (n = 13 Colo205 tumors) were imaged with [18F]FLT PET and DW-MRI using a multimodal bed, which was transferred from one instrument to the other within the same imaging session. Fiducial markers allowed coregistration of the images. An automatic post-processing was developed in MATLAB handling the spatial registration of DW-MRI (measured as apparent diffusion coefficient, ADC) and [18F]FLT image data and subsequent voxel-wise analysis of regions of interest (ROIs) in the tumor. Results Analyses were conducted on a total of 76 datasets, comprising a median of 2890 data points (ranging from 81 to 13,597). Scatterplots showing [18F]FLT vs. ADC values displayed various grades of relations (Pearson correlation coefficient (PCC) varied from − 0.58 to 0.49, median: -0.07). When relating PCC to tumor volume (median: 46 mm3, range: 3 mm3 to 584 mm3), lung tumors tended to have a more pronounced negative spatial relation of [18F]FLT and ADC with increasing tumor size. However, due to the low number of large tumors (> ~ 200 mm3), this conclusion has to be treated with caution. Conclusions A spatial relation of water diffusion, as measured by DW-MRI, and cellular proliferation, as measured by [18F]FLT PET, cannot be detected in the experimental datasets investigated in this study.

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Supercritical Fluid Extraction of Citrus iyo Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model

Integrative Cancer Therapies ◽

10.1177/1534735416649659 ◽

2016 ◽

Vol 16 (2) ◽

pp. 227-243 ◽

Cited By ~ 2

Author(s):

Chulwon Kim ◽

Il Ho Lee ◽

Ho Bong Hyun ◽

Jong-Chan Kim ◽

Rajendra Gyawali ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Tumor Cells ◽

Cellular Proliferation ◽

Human Prostate ◽

Parp Cleavage ◽

G1 Arrest ◽

Gene Products ◽

Human Prostate Cancer ◽

Male Mice

Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan ( Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.

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Evidence and potential clinical significance of changes in gene network interactions in ovarian cancer

Journal of Biomedical Engineering and Informatics ◽

10.5430/jbei.v2n1p1 ◽

2015 ◽

Vol 2 (1) ◽

pp. 1

Author(s):

Christopher G. Hill ◽

John F. McDonald

Keyword(s):

Ovarian Cancer ◽

Epithelial Cells ◽

Cancer Cells ◽

Gene Network ◽

Pearson Correlation ◽

Regulatory Control ◽

Ovarian Cancer Cells ◽

New Class ◽

Regulatory Mutations ◽

Ovarian Surface Epithelial

The molecular basis of cancer is not merely the consequence of structural and/or regulatory mutations in genes, but additionally to disruptions in networks of regulatory interactions existing among these genes and other components of the genome. Disruptions in network relationships may manifest as the loss, gain or reversal of functionally significant interactive gene relationships in cancer cells. In this study, we first employ an unsupervised (Pearson correlation) approach to quantitatively estimate the overall change in network relationships between precursor (control) ovarian surface epithelial cells and ovarian cancer epithelial cells. We find that ovarian cancer cells display a significant overall reduction in correlated gene network interactions relative to normal precursor cells reflective of an overall loss of regulatory control. We next focus on gene relationships that qualitatively change between normal and cancer samples. We find that biological processes significantly over represented among differentially expressed genes are substantially different from those associated with genes involved in qualitatively disrupted network interactions. Our findings provide novel insights into the processes underlying ovarian cancer and identify a potential new class of genes for targeted therapy.

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932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

Gastroenterology ◽

10.1016/s0016-5085(13)60596-x ◽

2013 ◽

Vol 144 (5) ◽

pp. S-166-S-167

Author(s):

Karen Boland ◽

Caoimhin Concannon ◽

Niamh McCawley ◽

Elaine W. Kay ◽

Deborah McNamara ◽

...

Keyword(s):

Colon Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cellular Proliferation ◽

Colon Cancer Cells ◽

Proliferation In Vitro

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Identification of traffic accident risk-prone areas under low-light conditions

Natural Hazards and Earth System Science ◽

10.5194/nhess-15-2059-2015 ◽

2015 ◽

Vol 15 (9) ◽

pp. 2059-2068 ◽

Cited By ~ 9

Author(s):

K. Ivan ◽

I. Haidu ◽

J. Benedek ◽

S. M. Ciobanu

Keyword(s):

Traffic Accident ◽

Traffic Accidents ◽

Pearson Correlation ◽

Injury Rate ◽

Spatial Relation ◽

Accident Risk ◽

Light Conditions ◽

Low Light ◽

The Impact ◽

The City

Abstract. Besides other non-behavioural factors, low-light conditions significantly influence the frequency of traffic accidents in an urban environment. This paper intends to identify the impact of low-light conditions on traffic accidents in the city of Cluj-Napoca, Romania. The dependence degree between light and the number of traffic accidents was analysed using the Pearson correlation, and the relation between the spatial distribution of traffic accidents and the light conditions was determined by the frequency ratio model. The vulnerable areas within the city were identified based on the calculation of the injury rate for the 0.5 km2 areas uniformly distributed within the study area. The results show a strong linear correlation between the low-light conditions and the number of traffic accidents in terms of three seasonal variations and a high probability of traffic accident occurrence under the above-mentioned conditions at the city entrances/exits, which represent vulnerable areas within the study area. Knowing the linear dependence and the spatial relation between the low light and the number of traffic accidents, as well as the consequences induced by their occurrence, enabled us to identify the areas of high traffic accident risk in Cluj-Napoca.

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Tumor-suppressor function of Beclin 1 in breast cancer cells requires E-cadherin

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2020478118 ◽

2021 ◽

Vol 118 (5) ◽

pp. e2020478118

Author(s):

Tobias Wijshake ◽

Zhongju Zou ◽

Beibei Chen ◽

Lin Zhong ◽

Guanghua Xiao ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Target Genes ◽

Cellular Proliferation ◽

Beclin 1 ◽

Beta Catenin ◽

A Genome ◽

E Cadherin

Beclin 1, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown. To address this question, we performed a genome-wide CRISPR/Cas9 screen in MCF7 breast cancer cells to identify genes whose loss of function reverse Beclin 1-dependent inhibition of cellular proliferation. Small guide RNAs targeting CDH1 and CTNNA1, tumor-suppressor genes that encode cadherin/catenin complex members E-cadherin and alpha-catenin, respectively, were highly enriched in the screen. CRISPR/Cas9-mediated knockout of CDH1 or CTNNA1 reversed Beclin 1-dependent suppression of breast cancer cell proliferation and anchorage-independent growth. Moreover, deletion of CDH1 or CTNNA1 inhibited the tumor-suppressor effects of Beclin 1 in breast cancer xenografts. Enforced Beclin 1 expression in MCF7 cells and tumor xenografts increased cell surface localization of E-cadherin and decreased expression of mesenchymal markers and beta-catenin/Wnt target genes. Furthermore, CRISPR/Cas9-mediated knockout of BECN1 and the autophagy class III phosphatidylinositol kinase complex 2 (PI3KC3-C2) gene, UVRAG, but not PI3KC3-C1–specific ATG14 or other autophagy genes ATG13, ATG5, or ATG7, resulted in decreased E-cadherin plasma membrane and increased cytoplasmic E-cadherin localization. Taken together, these data reveal previously unrecognized cooperation between Beclin 1 and E-cadherin–mediated tumor suppression in breast cancer cells.

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Verification of multispectral data processing for the Sentinel-2A bands, field ASD FieldSpec® 3FR and UAV with the DJI STS-VIS

Ukrainian journal of remote sensing ◽

10.36023/ujrs.2019.21.147 ◽

2019 ◽

pp. 29-39 ◽

Cited By ~ 2

Author(s):

Stanislav Dugin ◽

Oksana Sybirtseva ◽

Stanislav Golubov ◽

Yelizaveta Dorofey

Keyword(s):

Pearson Correlation ◽

Plant Cover ◽

Satellite Image ◽

Vegetation Indices ◽

Image Data ◽

Multispectral Data ◽

Maximum Value ◽

Substantial Correlation ◽

Satellite Image Data ◽

Sentinel 2A

The study of plant cover have been performed by the hyperspectral remote sensing method using ASD FieldSpec® 3FR and DJI STS-VIS measurements. The orthophotoplans are compiled for the test plots of interest at the spatial resolution of 2.5 cm. The substantial correlation for the results of terrestrial verification for the satellite image data in the range of Sentinel-2A bands are confirmed. 15 vegetation indices for the Sentinel-2А wavelength bands were drawn at the Pearson correlation coefficient r > 0.97, with a maximum value of the correlation error of 0.07.

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miR-340 Restrains the Growth of Lung Cancer Cells Through Mitogen-Activated Protein Kinase (MAPK) Signaling

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2639 ◽

2021 ◽

Vol 11 (5) ◽

pp. 963-969

Author(s):

Wenhong Zheng ◽

Wenrui Xie ◽

Lijuan Fu ◽

Zhengqi Fu

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cellular Proliferation ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Lung Cancer Cells ◽

Luciferase Assay ◽

Knock Out ◽

Novel Target

The lung cancer was most deadly tumor in the world and the suvival rate needs to be improved clinically and urgently. The abnormal miR-340 expression is found in several solid tumors. Our study was aimed to explore miR-340’s role in lung cancer. 14 cases of patients with lung cancer was selected to measure miR-340 level by RT-PCR and analyze its correlation with clinical characteristics. The relation between the miR-340 and DICER1 was detected by dual luciferase assay and cell proliferation was measured by MTT assay along with analysis of cell migration and invasive by Scratch-Wound experiment. The miR-340 in lung cancer cells was reduced significantly and DICER1 was predicted to be a potential target of miR-340. DICER1 level was found to be negatively related with miR-340 level. The DICER1 as the direct target gene of miR-340 was conducive to improve miR-340 function through overexpression and knock-out experiment further. Abnormal miR-340 level affected lung cancer cell proliferation and migration as well as MAPK signaling. miR-340 could affect the biological morphology and transformation of physiological function of lung cancer cells mainly through restraining the expression of apoptosis and prompting the cellular proliferation, indicating that it might be a novel target to improve the treatment of lung cancer.

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Linking Cancer Metabolic Dysfunction and Genetic Instability through the Lens of Iron Metabolism

Cancers ◽

10.3390/cancers11081077 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1077 ◽

Cited By ~ 11

Author(s):

Michael S. Petronek ◽

Douglas R. Spitz ◽

Garry R. Buettner ◽

Bryan G. Allen

Keyword(s):

Dna Damage ◽

Steady State ◽

Cancer Cells ◽

Iron Metabolism ◽

Genetic Instability ◽

Cellular Proliferation ◽

Intracellular Iron ◽

Iron Regulatory Proteins ◽

Wide Range ◽

Labile Iron

Iron (Fe) is an essential element that plays a fundamental role in a wide range of cellular functions, including cellular proliferation, DNA synthesis, as well as DNA damage and repair. Because of these connections, iron has been strongly implicated in cancer development. Cancer cells frequently have changes in the expression of iron regulatory proteins. For example, cancer cells frequently upregulate transferrin (increasing uptake of iron) and down regulate ferroportin (decreasing efflux of intracellular iron). These changes increase the steady-state level of intracellular redox active iron, known as the labile iron pool (LIP). The LIP typically contains approximately 2% intracellular iron, which primarily exists as ferrous iron (Fe2+). The LIP can readily contribute to oxidative distress within the cell through Fe2+-dioxygen and Fenton chemistries, generating the highly reactive hydroxyl radical (HO•). Due to the reactive nature of the LIP, it can contribute to increased DNA damage. Mitochondrial dysfunction in cancer cells results in increased steady-state levels of hydrogen peroxide and superoxide along with other downstream reactive oxygen species. The increased presence of H2O2 and O2•− can increase the LIP, contributing to increased mitochondrial uptake of iron as well as genetic instability. Thus, iron metabolism and labile iron pools may play a central role connecting the genetic mutational theories of cancer to the metabolic theories of cancer.

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Disrupting Androgen Receptor Functionality with Xanthones from the Mangosteen (Garcinia mangostana) Fruit

Proceedings ◽

10.3390/proceedings2019040050 ◽

2020 ◽

Vol 40 (1) ◽

pp. 50

Author(s):

Jeremy J. Johnson

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Cancer Cells ◽

Cellular Proliferation ◽

Xenograft Model ◽

Pharmacokinetic Studies ◽

Garcinia Mangostana ◽

Optimal Dosing ◽

Anti Cancer

The Southeast Asian mangosteen (Garcinia mangostana) contains a class of phytochemicals known as xanthones that possess extensive biological activity. Applications of xanthones, including the most prominent, alpha-mangostin, have been shown to possess anti-cancer, anti-oxidant, and anti-proliferation properties. To confirm the anti-cancer activity of xanthones we have evaluated 9 xanthones for decreasing cellular proliferation of cancer cells. These xanthones include alpha-mangostin, gartanin, 9-hydroxycalabaxanthone, garcinone C, garcinone D, and others. Using this approach, we have focused on understanding the ability of xanthones to disrupt androgen receptor in prostate cancer cells with a combination of cell free and cell-based assays. In addition, we have performed pharmacokinetic studies in mice with alpha-mangostin to characterize the optimal dosing strategy. Taken together, we have identified individual xanthones as capable of disrupting kinases, including CDK4, using cell free biochemical models and cell-based animal models. These results have been further validated in an in vivo xenograft model. Taken together, we have begun to describe the anti-cancer potential of xanthones for prostate cancer.

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