Investigation of Tumor Growth Based on Phase Field Model

2011 ◽  
Author(s):  
Zhi Zhu He ◽  
Jing Liu
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Phase Field ◽  
Classical Model ◽  
Phase Field Method ◽  
Phase Method ◽  
Hilliard Equation ◽  
Cahn Hilliard Equation

This paper presents and investigates the tumor growth based on a phase model. The tumor core is necrotic and inhibitor chemical species are considered. The interface of tumor and health tissue is tracked using a phase field equation. The reformulation of a classical model, accounting for cell-proliferation, apoptosis, cell-to-cell and cell-to-matrix adhesion, is derived. The advantages of the finite difference methodology employed are generality and relative simplicity implication. We present simulations of the nonlinear evolution of growing tumors morphology and discuss the effects of tumor microenvironment. Mechanisms reflecting the tumor growth and development behavior was preliminarily interpreted. Recently numerous mathematical have been developed to investigate the growth dynamics of tumor [1–8]. One of most significant model developed by Wise [8] is based on Cahn-Hilliard equation, which is conservation phase field method. Allen-Chan nonconservation phase field has been developed to track the moving interface for multiphase simulation by Sun [9]. Allen-Chan equation is second order, while Cahn-Hilliard equation is fourth order in space. Thus, we introduce the Allen-Chan phase method [9–10] to simulate the tumor growth, which is very simple for numerical simulation The computation domain is illustrated in Fig. 1, where ΩH denotes host tissue, the tumor domains is comprised of viable tumor cell ΩV and dead tumor cell ΩD. The numerical results are presented at Fig. (2–4). One can find that the growth of tumor strongly depend on the nutrients and nonlinear unstable growth may lead to finger shaped pattern, which is in agreement with recent experimental observations [7] of in vivo tumor. In summary, a phase method has been developed to study diffusion and consumption of the nutrients and tumor cell proliferation, necrosis and migration, which discloses the evolution of complex shape of tumor.

scholarly journals Tumor quiescence: elevating SOX2 in diverse tumor cell types downregulates a broad spectrum of the cell cycle machinery and inhibits tumor growth

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ethan P. Metz ◽  
Erin L. Wuebben ◽  
Phillip J. Wilder ◽  
Jesse L. Cox ◽  
Kaustubh Datta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cell Cycle Machinery

Abstract Background Quiescent tumor cells pose a major clinical challenge due to their ability to resist conventional chemotherapies and to drive tumor recurrence. Understanding the molecular mechanisms that promote quiescence of tumor cells could help identify therapies to eliminate these cells. Significantly, recent studies have determined that the function of SOX2 in cancer cells is highly dose dependent. Specifically, SOX2 levels in tumor cells are optimized to promote tumor growth: knocking down or elevating SOX2 inhibits proliferation. Furthermore, recent studies have shown that quiescent tumor cells express higher levels of SOX2 compared to adjacent proliferating cells. Currently, the mechanisms through which elevated levels of SOX2 restrict tumor cell proliferation have not been characterized. Methods To understand how elevated levels of SOX2 restrict the proliferation of tumor cells, we engineered diverse types of tumor cells for inducible overexpression of SOX2. Using these cells, we examined the effects of elevating SOX2 on their proliferation, both in vitro and in vivo. In addition, we examined how elevating SOX2 influences their expression of cyclins, cyclin-dependent kinases (CDKs), and p27Kip1. Results Elevating SOX2 in diverse tumor cell types led to growth inhibition in vitro. Significantly, elevating SOX2 in vivo in pancreatic ductal adenocarcinoma, medulloblastoma, and prostate cancer cells induced a reversible state of tumor growth arrest. In all three tumor types, elevation of SOX2 in vivo quickly halted tumor growth. Remarkably, tumor growth resumed rapidly when SOX2 returned to endogenous levels. We also determined that elevation of SOX2 in six tumor cell lines decreased the levels of cyclins and CDKs that control each phase of the cell cycle, while upregulating p27Kip1. Conclusions Our findings indicate that elevating SOX2 above endogenous levels in a diverse set of tumor cell types leads to growth inhibition both in vitro and in vivo. Moreover, our findings indicate that SOX2 can function as a master regulator by controlling the expression of a broad spectrum of cell cycle machinery. Importantly, our SOX2-inducible tumor studies provide a novel model system for investigating the molecular mechanisms by which elevated levels of SOX2 restrict cell proliferation and tumor growth.

scholarly journals BAP31 Promotes Tumor Cell Proliferation by Stabilizing SERPINE2 in Hepatocellular Carcinoma

2020 ◽  
Vol 8 ◽  
Author(s):  
Xiyang Zhang ◽  
Dongbo Jiang ◽  
Shuya Yang ◽  
Yuanjie Sun ◽  
Yang Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Colony Formation ◽  
Clinical Stage ◽  
Tumor Cell Proliferation ◽  
Ki 67 ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) patients are mostly diagnosed at an advanced stage, resulting in systemic therapy and poor prognosis. Therefore, the identification of a novel treatment target for HCC is important. B-cell receptor-associated protein 31 (BAP31) has been identified as a cancer/testis antigen; however, BAP31 function and mechanism of action in HCC remain unclear. In this study, BAP31 was demonstrated to be upregulated in HCC and correlated with the clinical stage. BAP31 overexpression promoted HCC cell proliferation and colony formation in vitro and tumor growth in vivo. RNA-sequence (RNA-seq) analysis demonstrated that serpin family E member 2 (SERPINE2) was downregulated in BAP31-knockdown HCC cells. Coimmunoprecipitation and immunofluorescence assays demonstrated that BAP31 directly binds to SERPINE2. The inhibition of SERPINE2 significantly decreased the BAP31-induced cell proliferation and colony formation of HCC cells and phosphorylation of Erk1/2 and p38. Moreover, multiplex immunohistochemistry staining of the HCC tissue microarray showed positive associations between the expression levels of BAP31, SERPINE2, its downstream gene LRP1, and a tumor proliferation marker, Ki-67. The administration of anti-BAP31 antibody significantly inhibited HCC cell xenograft tumor growth in vivo. Thus, these findings suggest that BAP31 promotes tumor cell proliferation by stabilizing SERPINE2 and can serve as a promising candidate therapeutic target for HCC.

scholarly journals Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

2020 ◽  
Vol 117 (12) ◽  
pp. 6640-6650 ◽  
Author(s):  
Xiaodong Wang ◽  
Xiaohui Yang ◽  
Chang Zhang ◽  
Yang Wang ◽  
Tianyou Cheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Colony Formation ◽  
Immune Escape ◽  
Potential Biomarker

The programmed cell death 1 (PD-1) receptor on the surface of immune cells is an immune checkpoint molecule that mediates the immune escape of tumor cells. Consequently, antibodies targeting PD-1 have shown efficacy in enhancing the antitumor activity of T cells in some types of cancers. However, the potential effects of PD-1 on tumor cells remain largely unknown. Here, we show that PD-1 is expressed across a broad range of tumor cells. The silencing of PD-1 or its ligand, PD-1 ligand 1 (PD-L1), promotes cell proliferation and colony formation in vitro and tumor growth in vivo. Conversely, overexpression of PD-1 or PD-L1 inhibits tumor cell proliferation and colony formation. Moreover, blocking antibodies targeting PD-1 or PD-L1 promote tumor growth in cell cultures and xenografts. Mechanistically, the coordination of PD-1 and PD-L1 activates its major downstream signaling pathways including the AKT and ERK1/2 pathways, thus enhancing tumor cell growth. This study demonstrates that PD-1/PD-L1 is a potential tumor suppressor and potentially regulates the response to anti-PD-1/PD-L1 treatments, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.

scholarly journals Depleting RhoA/Stress Fiber-Organized Fibronectin Matrices on Tumor Cells Non-Autonomously Aggravates Fibroblast-Driven Tumor Cell Growth

2020 ◽  
Vol 21 (21) ◽  
pp. 8272
Author(s):  
Li-Tzu Huang ◽  
Chen-Lung Tsai ◽  
Shin-Huei Huang ◽  
Ming-Min Chang ◽  
Wen-Tsan Chang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Stress Fiber ◽  
Tumor Cell Growth ◽  
Primary Tumor Growth

Fibronectin (FN) expressed by tumor cells has been known to be tumor suppressive but the pericellular FN (periFN) assembled on circulating tumor cells appears to evidently promote distant metastasis. Whereas the regulation of periFN assembly in suspended cells has currently been under investigation, how it is regulated in adherent tumor cells and the role of periFN in primary tumor growth remain elusive. Techniques of RNAi, plasmid transfections, immunoblotting, fluorescence/immunohistochemistry staining, cell proliferation assays, and primary tumor growth in C57BL6 mice and Fischer 344 rats were employed in this study. We found that endogenously synthesized FN in adherent tumor cells was required for periFN assembly which was aligned by RhoA-organized actin stress fiber (SF). Depleting periFN on adherent tumor cells congruently promoted in vivo tumor growth but surprisingly did not autonomously impact on in vitro tumor cell proliferation and apoptosis, suggestive of a non-autonomous role of periFN in in vivo tumor growth. We showed that the proliferative ability of shFN-expressing tumor cells was higher than shScramble cells did in the presence of fibroblasts. Altogether, these results suggested that depriving RhoA/SF-regulated periFN matrices non-autonomously promotes fibroblast-mediated tumor cell growth.

scholarly journals A comprehensive in vivo and mathematic modeling-based kinetic characterization for aspirin-induced chemoprevention in colorectal cancer

2020 ◽  
Vol 41 (6) ◽  
pp. 751-760 ◽  
Author(s):  
Tadanobu Shimura ◽  
Shusuke Toden ◽  
Natalia L Komarova ◽  
Crichard Boland ◽  
Dominik Wodarz ◽  
...  
Keyword(s):  
Mathematical Modeling ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Proliferation ◽  
Death Rates ◽  
Kinetics Of

Abstract Accumulating evidence suggests that aspirin has anti-tumorigenic properties in colorectal cancer (CRC). Herein, we undertook a comprehensive and systematic series of in vivo animal experiments followed by 3D-mathematical modeling to determine the kinetics of aspirin’s anti-cancer effects on CRC growth. In this study, CRC xenografts were generated using four CRC cell lines with and without PIK3CA mutations and microsatellite instability, and the animals were administered with various aspirin doses (0, 15, 50, and 100 mg/kg) for 2 weeks. Cell proliferation, apoptosis and protein expression were evaluated, followed by 3D-mathematical modeling analysis to estimate cellular division and death rates and their impact on aspirin-mediated changes on tumor growth. We observed that aspirin resulted in a dose-dependent decrease in the cell division rate, and a concomitant increase in the cell death rates in xenografts from all cell lines. Aspirin significantly inhibited cell proliferation as measured by Ki67 staining (P < 0.05–0.01). The negative effect of aspirin on the rate of tumor cell proliferation was more significant in xenograft tumors derived from PIK3CA mutant versus wild-type cells. A computational model of 3D-tumor growth suggests that the growth inhibitory effect of aspirin on the tumor growth kinetics is due to a reduction of tumor colony formation, and that this effect is sufficiently strong to be an important contributor to the reduction of CRC incidence in aspirin-treated patients. In conclusion, we provide a detailed kinetics of aspirin-mediated inhibition of tumor cell proliferation, which support the epidemiological data for the observed protective effect of aspirin in CRC patients.

Use of PG545, a heparanase inhibitor, to inhibit pancreatic cancer tumor cell proliferation and migration in vitro and in vivo.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 234-234
Author(s):  
Katherine Ostapoff ◽  
Niranjan Awasthi ◽  
Roderich Schwarz ◽  
Rolf A. Brekken
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

234 Background: Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy, as result there is an ongoing search to find novel effective strategies. Resistance is due in part to the high proportion of stromal tissue within the primary tumor. This intricate ECM (extracellular matrix) includes heparan-sulfate glycosaminoglycans which participate in tumor progression, angiogenesis and metastasis. PG545 is a heparanase inhibitor developed to target these pathways. Methods: In vitro cell viability assays were performed using WST-1 reagent and migration was evaluated using T- scratch assay. Animal survival experiments were performed by intraperitoneal injection of AsPC-1 (0.75 x 10^6) cells. In vivo tumor growth experiments were performed by orthotopic injection of PanO2-HY (5x10^5) cells. Results: PG545 significantly inhibited proliferation of tumor cells (AsPC-1 and PanO2) and fibroblasts (WI-38). PG545 caused only a modest inhibition in endothelial cell (HUVECs) proliferation. Migration was significantly inhibited by 1 µM PG545 in AsPC-1 and PanO2 after 12 hours. In a metastatic model of pancreatic cancer, treatment with PG545 (10 mg/kg 1st week, 5 mg/kg 2nd week) improved survival (35 days) compared to saline (22 days) and gemcitabine (28 days). In an immunocompetent orthotopic model, mice treated with PG545 (5 mg/kg twice weekly) had significantly decreased tumor weights after 3 weeks of therapy (p=0.002). Total metastatic events were also reduced in PG545 compared to gemcitabine and control treatment in the PanO2 model. Conclusions: PG545 inhibits tumor cell proliferation and migration in vitro and prolongs survival and inhibits tumor growth in vivo. Additionally it inhibits metastasis in vivo. Further studies are underway to elucidate the mechanism of inhibition and changes to pancreatic tumor microenvironment.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

Increased expression of MAP2 inhibits melanoma cell proliferation, invasion and tumor growth in vitro and in vivo

2010 ◽  
Vol 19 (11) ◽  
pp. 958-964 ◽  
Author(s):  
Zhiqi Song ◽  
Chun-Di He ◽  
Changkai Sun ◽  
Yanni Xu ◽  
Xin Jin ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Melanoma Cell ◽  
Melanoma Cell Proliferation

Hsa_circ_0023990 Promotes Tumor Growth and Glycolysis in Dedifferentiated TC via Targeting miR-485-5p/FOXM1 Axis

Endocrinology ◽  
2021 ◽  
Vol 162 (12) ◽  
Author(s):  
Qing Zhang ◽  
Lian Wu ◽  
Shao-Zheng Liu ◽  
Qing-Jie Chen ◽  
Ling-Peng Zeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Radioactive Iodine ◽  
Lactate Production ◽  
Luciferase Reporter ◽  
Current Therapy ◽  
Biological Processes ◽  
Reporter Assay ◽  
Potential Therapeutic Target

Abstract Background During the transformation to dedifferentiated thyroid cancer (TC) types, the ability of papillary thyroid carcinomas (PTCs) to concentrate radioactive iodine might be lost, raising difficulty for the current therapy. circRNAs were proved to be implicated in the progression of various cancers. In this study, we aimed to investigate the functional role and mechanism of hsa_circ_0023990 in dedifferentiated TC. Methods The expression pattern of genes were detected using quantitative PCR or western blot assays. Cell proliferation was determined by CCK8, colony formation, EdU, and cell-cycle assays. Glycolysis was assessed using glucose uptake and lactate production assays. Luciferase reporter assay was performed to examine the interactions between miR-485-5p and hsa_circ_0023990 or FOXM1. Xenograft assay was allowed for observation of tumor growth in vivo. Results Hsa_circ_0023990 and FOXM1 were upregulated in dedifferentiated TC tissues and cell lines. The higher level of hsa_circ_0023900 could stimulate the proliferation and glycolysis of dedifferentiated TC cells via positively regulating FOXM1. Mechanistically, miR-485-5p was demonstrated to interact with hsa_circ_0023990 and FOXM1 and involved in the regulation of has_circ_0023990 and FOXM1 in TC biological processes. Conclusion Our results discovered the functional network of hsa_circ_0023990 in dedifferentiated TC development by facilitating cell proliferation and glycolysis via miR-485-5p/FOXM1 axis, implying that hsa_circ_0023990 might be a potential therapeutic target for the dedifferentiated TC treatment.

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