scholarly journals Epithelial-Mesenchymal Transition with Malignant Transformation Leading Multiple Metastasis from Disseminated Peritoneal Leiomyomatosis

2018 ◽  
Vol 7 (8) ◽  
pp. 207 ◽  
Author(s):  
Hsiao-Chen Chiu ◽  
Meng-Yu Wu ◽  
Chao-Hsu Li ◽  
Su-Cheng Huang ◽  
Giou-Teng Yiang ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Hepatic Metastases ◽  
Imaging Study ◽  
Premenopausal Women ◽  
Rare Condition ◽  
Exploratory Laparotomy ◽  
Rapid Progression ◽  
Mesenchymal Transition ◽  
Disseminated Peritoneal Leiomyomatosis

Disseminated peritoneal leiomyomatosis (DPL) is a rare condition that is characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules of varying sizes on the omentum and peritoneal surfaces, grossly mimicking disseminated carcinoma. DPL usually develops in premenopausal women with a benign course, and it is often found incidentally during abdominal surgery. Malignant transformation is a rare clinical course of DPL. Only a few studies have focused on DPL transformation into a leiomyosarcoma. Herein, we describe the case of a 61-year-old woman with a history of recurrent leiomyoma of the uterus who presented with intermittent progressive abdominal pain. The imaging study revealed a huge heterogeneous density mass in the pelvic region with pulmonary and hepatic metastases. Exploratory laparotomy and debulking surgery were performed, and showed the coexistence of DPL and leiomyosarcoma. She died approximately one month after the diagnosis because of rapid progression of pleural effusion due to malignancy. This case highlights the clinical features of DPL and its malignant transformation and metastasis so physicians can make an early diagnosis and provide timely management.

scholarly journals Changing ALK-TKI-Resistance Mechanisms in Rebiopsies of ALK-Rearranged NSCLC: ALK- and BRAF-Mutations Followed by Epithelial-Mesenchymal Transition

2020 ◽  
Vol 21 (8) ◽  
pp. 2847 ◽  
Author(s):  
Edyta M. Urbanska ◽  
Jens B. Sørensen ◽  
Linea C. Melchior ◽  
Junia C. Costa ◽  
Eric Santoni-Rugiu
Keyword(s):  
Kinase Inhibitors ◽  
Epithelial Mesenchymal Transition ◽  
Hepatic Metastases ◽  
Resistance Mechanisms ◽  
Rapid Progression ◽  
Longitudinal Assessment ◽  
Mechanisms Of Resistance ◽  
Braf Mutations ◽  
Mesenchymal Transition ◽  
Anaplastic Lymphoma

Anaplastic lymphoma-kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) is prone to developing heterogeneous, only partly known mechanisms of resistance to ALK-tyrosine-kinase-inhibitors (ALK-TKIs). We present a case of a 38-year old male, who never smoked with disseminated ALK-rearranged (EML4 (20) – ALK (20) fusion variant 2) lung adenocarcinoma, who received four sequentially different ALK-TKIs and two lines of chemotherapy in-between. We observed significant clinical benefit by the first three ALK-TKIs (Crizotinib, Ceritinib, Alectinib) and chemotherapy with Pemetrexed, resulting in overall survival over 3 years. Longitudinal assessment of progressions by rebiopsies from hepatic metastases showed different mechanisms of resistance to each ALK-TKI, including secondary ALK-mutations and the downstream p.V600E BRAF-mutation that had not been linked to second-generation ALK-TKIs before. Ultimately, in connection with terminal rapid progression and resistance to Alectinib and Lorlatinib, we identified phenotypical epithelial-mesenchymal transition (EMT) of newly occurred metastatic cells, a phenomenon not previously related to these two ALK-TKIs. This resistance heterogeneity suggests a continuously changing disease state. Sequential use of different generation’s ALK-TKIs and combination therapies may yield prolonged responses with satisfactory quality of life in patients with advanced ALK-positive NSCLC. However, the development of EMT is a major hurdle and may explain rapid disease progression and lack of response to continued ALK-inhibition.

scholarly journals HIF-1α Promotes Hepatocellular Carcinoma Metastasis by Regulating Angiogenesis and Epithelial-Mesenchymal Transition

2020 ◽  
Author(s):  
Min Yao ◽  
Li Wang ◽  
Xiyu Chen ◽  
Ying Chen ◽  
Jie Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Medical Society ◽  
Mesenchymal Transition ◽  
Positive Correlations ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor ◽  
Hcc Cells

Abstract Background: Invasion and metastasis of hepatocellular carcinoma (HCC) still remain to be hard in medical society. However, little knowledge is known regarding the hypoxia impact in HCC with angiogenesis and epithelial-mesenchymal transition (EMT). The aims of this study were to explore the regulating roles of hypoxia-inducible factor-1α (HIF-1α) in angiogenesis and EMT of HCC. Method: The levels of HIF-1α, angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) expression in a cohort of chronic liver diseases were detected by enzyme- linked immunosorbent assays, and their dynamic up-regulations were confirmed in model of rat hepatocyte malignant transformation. After HIF-1α gene transfected with specific miRNA, biological behaviors of HCC cells were analyzed by transwell or invasion assay; angiogenesis and EMT were analyzed at protein level by Western blot or at mRNA by quantitative real-time PCR. Results: The levels of circulating HIF-1α, VEGF, and Ang-2 in the HCC group (145.6 ± 32.6 μg/L, 458.9 ± 125.3 μg/L, and 42.9 ± 5.1μg/L) were significantly higher (P < 0.001) than those in the LC (79.5 ± 8.4 μg/L, 206.8 ± 56.8 μg/L, and 26.2 ± 6.1 μg/L) or the CH (60.1 ± 18.8 μg/L, 178.1 ± 85.4 μg/L, and 21.8 ± 6.9 μg/L) group, respectively. Dynamic up-regulations of HIF-1α and angiogenic factors have been confirmed by rat model with hepatocyte malignant transformation. There were closely positive correlations (P < 0.001) between them of HIF-1α and VEGF or Ang-2. After HCC cells transfected with specific HIF-1α-miRNA, the levels of HIF-1α, VEGF and Ang-2 expression were significantly down-regulated, with inhibiting infiltration or migration, blockading EMT with increasing E-cadherin and decreasing of snail, twist and vimentin. Conclusions: HIF-1α over-expression could promote the metastasis or invasion of HCC via regulating neovascularization and EMT formation.

Abstract 3358: Acquired epithelial-mesenchymal transition synergizes with normal epithelial cells to induce hepatic metastases

2011 ◽  
Author(s):  
Idoia G. Zubeldia ◽  
Anne-Marie Bleau ◽  
Carmen Gil-Puig ◽  
Fernando Vidal-Vanaclocha ◽  
Alfonso Calvo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hepatic Metastases ◽  
Mesenchymal Transition

scholarly journals Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Caiqin Wang ◽  
Qing He ◽  
Yingxuan Yin ◽  
Yinjuan Wu ◽  
Xuerong Li
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Clonorchis Sinensis ◽  
Akt Signaling ◽  
Eukaryotic Expression ◽  
Cell Counting ◽  
Mesenchymal Transition

The biological functions of growth factor, such as granulins, have been explored in parasites, and we elucidated that Clonorchis sinensis granulin (CsGRN) promoted the metastasis of hepatocellular carcinoma in our previous study. However, it is still unclear for the malignant transformation role of CsGRN in normal human hepatocytes. In this study, by transfecting pEGFP-C1-CsGRN eukaryotic expression plasmid, a cell line with stable overexpression of CsGRN in normal hepatocyte (LO2-GRN cells) was constructed. The effects on cell proliferation were detected by carrying out cell counting kit-8 (CCK8) assay and colony formation assay. Additionally, we conducted flow cytometry analysis to determine whether the proliferation of CsGRN was due to cell cycle arrest. Subsequently, the migration ability and the invasion ability of LO2-GRN cells were evaluated through wound-healing assay and transwell assay. Meanwhile, the levels of the markers of RAS/MAPK/ERK and PI3K/Akt signaling pathways activation in LO2-GRN cells were assessed by quantitative RT-PCR and Western blot. Our results indicated that CsGRN promoted the proliferation of LO2 cells by regulating the expression of cell-cycle-related genes. Moreover, the overexpression of CsGRN regulates malignant metastasis of liver cells by inducing the upregulation of epithelial–mesenchymal transition (EMT) marker proteins. Furthermore, both mRNA and protein expression levels of p-EGFR, RAS, p-ERK, p-AKT, p-PI3K, and p-braf have been enhanced by CsGRN. These results showed that CsGRN promoted the malignant transformation of hepatocytes by regulating epidermal growth factor receptor (EGFR)-mediated RAS/MAPK/ERK and PI3K/Akt signaling pathways, which suggested that CsGRN could serve as a novel oncoprotein during Clonorchis sinensis–associated malignant transformation of hepatocytes.

scholarly journals RAC1B: A Rho GTPase with Versatile Functions in Malignant Transformation and Tumor Progression

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 21 ◽  
Author(s):  
Catharina Melzer ◽  
Ralf Hass ◽  
Hendrik Lehnert ◽  
Hendrik Ungefroren
Keyword(s):  
Tumor Progression ◽  
Malignant Transformation ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Rho Gtpase ◽  
Epithelial Mesenchymal Transition ◽  
Biochemical Properties ◽  
Apoptosis Resistance ◽  
Comprehensive Overview ◽  
Mesenchymal Transition

RAC1B is an alternatively spliced isoform of the monomeric GTPase RAC1. It differs from RAC1 by a 19 amino acid in frame insertion, termed exon 3b, resulting in an accelerated GDP/GTP-exchange and an impaired GTP-hydrolysis. Although RAC1B has been ascribed several protumorigenic functions such as cell cycle progression and apoptosis resistance, its role in malignant transformation, and other functions driving tumor progression like epithelial-mesenchymal transition, migration/invasion and metastasis are less clear. Insertion of exon 3b endows RAC1B with specific biochemical properties that, when compared to RAC1, encompass both loss-of-functions and gain-of-functions with respect to the type of upstream activators, downstream targets, and binding partners. In its extreme, this may result in RAC1B and RAC1 acting in an antagonistic fashion in regulating a specific cellular response with RAC1B behaving as an endogenous inhibitor of RAC1. In this review, we strive to provide the reader with a comprehensive overview, rather than critical discussions, on various aspects of RAC1B biology in eukaryotic cells.

scholarly journals MicroRNA-21 activation of Akt via PTEN is involved in the epithelial–mesenchymal transition and malignant transformation of human keratinocytes induced by arsenite

2016 ◽  
Vol 5 (4) ◽  
pp. 1140-1147 ◽  
Author(s):  
Xiaolin Lu ◽  
Yang Liu ◽  
Fei Luo ◽  
Aihua Zhang ◽  
Xinlu Liu ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Human Keratinocytes ◽  
Mesenchymal Transition

MicroRNAs are involved in the epithelial–mesenchymal transition (EMT) and malignant transformation of cells.

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