Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: could the combination with other drugs improve its antitumoral effect?

Abstract Background Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS). Methods In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D) spheroid cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity. Results Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest, for the first time, a synergistic effect with ifosfamide in all models, and with pazopanib in LMS as well as in myxoid and pleomorphic LPS. Conclusions Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.

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Eribulin activity in soft tissue sarcoma monolayer and three-dimensional cell line models: Could the combination with other drugs improve its antitumoral effect?

10.21203/rs.3.rs-754226/v1 ◽

2021 ◽

Author(s):

Javier Escudero ◽

Victoria Heredia-Soto ◽

Yiyin Wang ◽

Patricia Ruiz ◽

Alejandro Gallego ◽

...

Keyword(s):

Soft Tissue ◽

Cell Line ◽

Antitumour Activity ◽

Three Dimensional ◽

Soft Tissue Sarcomas ◽

Migration And Invasion ◽

2D And 3D ◽

First Time ◽

Dimensional Cell

Abstract Background Eribulin has shown antitumour activity in some soft tissue sarcomas (STSs), but it has only been approved for advanced liposarcoma (LPS). Methods In this study, we evaluated the effect of eribulin on proliferation, migration and invasion capabilities in LPS, leiomyosarcoma (LMS) and fibrosarcoma (FS) models, using both monolayer (2D) and three-dimensional (3D spheroid) cell cultures. Additionally, we explored combinations of eribulin with other drugs commonly used in the treatment of STS with the aim of increasing its antitumour activity. Results Eribulin showed activity inhibiting proliferation, 2D and 3D migration and invasion in most of the cell line models. Furthermore, we provide data that suggest for the first time a synergistic effect with ifosfamide in all models and with pazopanib in LMS as well as in myxoid and pleomorphic LPS. Conclusions Our results support the effect of eribulin on LPS, LMS and FS cell line models. The combination of eribulin with ifosfamide or pazopanib has shown in vitro synergy, which warrants further clinical research.

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Abstract A104: Development of pathophysiologically relevant in vitro tumor models: Cytotoxicity of anticancer drugs in two dimensional and three dimensional cell line cultures versus primary colorectal tumor cells

10.1158/1535-7163.targ-15-a104 ◽

2015 ◽

Author(s):

Viswanath Das ◽

Marta Zbozinkova ◽

Martin Holoubek ◽

Petr Dzubak ◽

Marian Hajduch

Keyword(s):

Cell Line ◽

Tumor Cells ◽

Anticancer Drugs ◽

Three Dimensional ◽

Colorectal Tumor ◽

Two Dimensional ◽

Tumor Models ◽

Primary Colorectal Tumor ◽

Dimensional Cell

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lncRNA CASC19 Contributes to Radioresistance of Nasopharyngeal Carcinoma by Promoting Autophagy via AMPK-mTOR Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22031407 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1407

Author(s):

Hongxia Liu ◽

Wang Zheng ◽

Qianping Chen ◽

Yuchuan Zhou ◽

Yan Pan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Line ◽

Malignant Tumors ◽

Underlying Mechanism ◽

Mtor Pathway ◽

Rna Seq ◽

Cellular Autophagy ◽

First Time

Nasopharyngeal carcinoma (NPC) is one of the most frequent head and neck malignant tumors and is majorly treated by radiotherapy. However, radiation resistance remains a serious obstacle to the successful treatment of NPC. The aim of this study was to discover the underlying mechanism of radioresistance and to elucidate novel genes that may play important roles in the regulation of NPC radiosensitivity. By using RNA-seq analysis of NPC cell line CNE2 and its radioresistant cell line CNE2R, lncRNA CASC19 was screened out as a candidate radioresistance marker. Both in vitro and in vivo data demonstrated that a high expression level of CASC19 was positively correlated with the radioresistance of NPC, and the radiosensitivity of NPC cells was considerably enhanced by knockdown of CASC19. The incidence of autophagy was enhanced in CNE2R in comparison with CNE2 and another NPC cell line HONE1, and silencing autophagy with LC3 siRNA (siLC3) sensitized NPC cells to irradiation. Furthermore, CASC19 siRNA (siCASC19) suppressed cellular autophagy by inhibiting the AMPK/mTOR pathway and promoted apoptosis through the PARP1 pathway. Our results revealed for the first time that lncRNA CASC19 contributed to the radioresistance of NPC by regulating autophagy. In significance, CASC19 might be a potential molecular biomarker and a new therapeutic target in NPC.

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Analysis of a Preliminary microRNA Expression Signature in a Human Telangiectatic Osteogenic Sarcoma Cancer Cell Line

International Journal of Molecular Sciences ◽

10.3390/ijms22031163 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1163

Author(s):

Gaia Palmini ◽

Cecilia Romagnoli ◽

Simone Donati ◽

Roberto Zonefrati ◽

Gianna Galli ◽

...

Keyword(s):

Cell Line ◽

Molecular Mechanisms ◽

Osteogenic Sarcoma ◽

Cancer Cell Line ◽

Microscopic Features ◽

In Vitro Establishment ◽

Profile Characteristic ◽

First Time

Telangiectatic osteosarcoma (TOS) is an aggressive variant of osteosarcoma (OS) with distinctive radiographic, gross, microscopic features, and prognostic implications. Despite several studies on OS, we are still far from understanding the molecular mechanisms of TOS. In recent years, many studies have demonstrated not only that microRNAs (miRNAs) are involved in OS tumorigenesis, development, and metastasis, but also that the presence in high-grade types of OS of cancer stem cells (CSCs) plays an important role in tumor progression. Despite these findings, nothing has been described previously about the expression of miRNAs and the presence of CSCs in human TOS. Therefore, we have isolated/characterized a putative CSC cell line from human TOS (TOS-CSCs) and evaluated the expression levels of several miRNAs in TOS-CSCs using real-time quantitative assays. We show, for the first time, the existence of CSCs in human TOS, highlighting the in vitro establishment of this unique stabilized cell line and an identification of a preliminary expression of the miRNA profile, characteristic of TOS-CSCs. These findings represent an important step in the study of the biology of one of the most aggressive variants of OS and the role of miRNAs in TOS-CSC behavior.

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Oncogenic UBE3C promotes breast cancer progression by activating Wnt/β-catenin signaling

Cancer Cell International ◽

10.1186/s12935-020-01733-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chen Hang ◽

Shanojie Zhao ◽

Tiejun Wang ◽

Yan Zhang

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Nuclear Accumulation ◽

Migration And Invasion ◽

Ubiquitin Protein Ligase ◽

Novel Target ◽

First Time ◽

Breast Tissues

Abstract Background Breast cancer (BrCa) is the most common female malignancy worldwide and has the highest morbidity among all cancers in females. Unfortunately, the mechanisms of BrCa growth and metastasis, which lead to a poor prognosis in BrCa patients, have not been well characterized. Methods Immunohistochemistry (IHC) was performed on a BrCa tissue microarray (TMA) containing 80 samples to evaluate ubiquitin protein ligase E3C (UBE3C) expression. In addition, a series of cellular experiments were conducted to reveal the role of UBE3C in BrCa. Results In this research, we identified UBE3C as an oncogenic factor in BrCa growth and metastasis for the first time. UBE3C expression was upregulated in BrCa tissues compared with adjacent breast tissues. BrCa patients with high nuclear UBE3C expression in tumors showed remarkably worse overall survival (OS) than those with low nuclear expression. Knockdown of UBE3C expression in MCF-7 and MDA-MB-453 BrCa cells inhibited cell proliferation, migration and invasion in vitro, while overexpression of UBE3C in these cells exerted the opposite effects. Moreover, UBE3C promoted β-catenin nuclear accumulation, leading to the activation of the Wnt/β-catenin signaling pathway in BrCa cells. Conclusion Collectively, these results imply that UBE3C plays crucial roles in BrCa development and progression and that UBE3C may be a novel target for the prevention and treatment of BrCa.

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Three-dimensional computational analysis of optical coherence tomography images for the detection of soft tissue sarcomas

Journal of Biomedical Optics ◽

10.1117/1.jbo.19.2.021102 ◽

2013 ◽

Vol 19 (2) ◽

pp. 021102 ◽

Cited By ~ 22

Author(s):

Shang Wang ◽

Chih-Hao Liu ◽

Valery P. Zakharov ◽

Alexander J. Lazar ◽

Raphael E. Pollock ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Soft Tissue ◽

Computational Analysis ◽

Three Dimensional ◽

Soft Tissue Sarcomas ◽

Optical Coherence

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Advanced in vitro management of three-dimensional cell cultures and explanted tissue

Cytotherapy ◽

10.1016/s1465324921005156 ◽

2021 ◽

Vol 23 (5) ◽

pp. S145

Author(s):

S. Kress ◽

D. Egger ◽

C. Kasper

Keyword(s):

Cell Cultures ◽

Three Dimensional ◽

Dimensional Cell

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A three-dimensional cell biology model of human hepatocellular carcinoma in vitro

Tumor Biology ◽

10.1007/s13277-010-0140-7 ◽

2010 ◽

Vol 32 (3) ◽

pp. 469-479 ◽

Cited By ~ 15

Author(s):

Jianhua Tang ◽

Jiefeng Cui ◽

Rongxin Chen ◽

Kun Guo ◽

Xiaonan Kang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Biology ◽

Three Dimensional ◽

Human Hepatocellular Carcinoma ◽

Dimensional Cell

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Decoction of heat-clearing, detoxifying and blood stasis removing relieves acute soft tissue injury via modulating miR-26b-5p/COX2 axis to inhibit inflammation

Bioscience Reports ◽

10.1042/bsr20201981 ◽

2020 ◽

Vol 40 (12) ◽

Author(s):

Shunwan Jiang ◽

Zhi Chen ◽

Wenqiang Lai ◽

Qingchun Mai ◽

Dayu Chen ◽

...

Keyword(s):

Soft Tissue ◽

Cell Line ◽

Tissue Injury ◽

Blood Stasis ◽

Soft Tissue Injury ◽

Enzyme Linked Immunosorbent Assay ◽

Microvascular Endothelium ◽

In Vivo Models ◽

Tnf Α

Abstract Traditional Chinese medicine (TCM), such as Huanglian-Jie-Du-Tang, a heat-clearing and detoxifying decoction is beneficial for alleviation of inflammation-related diseases. The objective of the present study is to uncover the effect and mechanism of heat-clearing, detoxifying and blood stasis removing decoction (HDBD) on the treatment of acute soft tissue injury (STI) which is characterized with excessive inflammatory cascade at the onset. Male Sprague–Dawley (SD) rats with hammer beating served as the in vivo models of acute STI. Hematoxylin–Eosin (HE) staining was used for histopathology assessment. The levels of inflammatory factors, including prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1t and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Human dermal microvascular endothelium cell line HMEC-1 and rat vascular endothelium cell line RAOEC were used to explore the mechanism in vitro. Luciferase gene reporter assay was applied to determine the relationship between miR-26b-5p and Cyclo-oxygenase 2 (COX2). The results showed that HDBD intervention significantly reduced the temperature difference between the healthy side and affected side of rats with hammer beating, together with the decreased levels of COX2, PGE2, TNF-α, IL-6 and IL-1β, and the increased level of miR-26b-5p. In mechanism, miR-26b-5p targeted COX2 and decreased its expression, leading to significant decreases in the levels of PGE2, TNF-α and IL-6 in RAOEC and HMEC-1 cells. In addition, miR-26b-5p inhibition impaired the effects of HDBD on the suppression of PGE2, TNF-α, IL-6 and IL-1β in vitro. In conclusion, the present study revealed that HDBD relieved acute STI via modulating miR-26b-5p/COX2 axis to inhibit inflammation.

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