Therapeutic Effects of Adenovirus-Mediated Gene Transfer of TGF-β Signal Antagonists on Undesirable Epithelial-Mesenchymal Transition and Neovascularization

2008 ◽  
pp. 367-381 ◽  
Author(s):  
Shizuya Saika
Keyword(s):  
Gene Transfer ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Effects ◽  
Mesenchymal Transition

scholarly journals Role of the ABL tyrosine kinases in the epithelial–mesenchymal transition and the metastatic cascade

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jillian Hattaway Luttman ◽  
Ashley Colemon ◽  
Benjamin Mayro ◽  
Ann Marie Pendergast
Keyword(s):  
Solid Tumors ◽  
Tyrosine Kinases ◽  
Epithelial To Mesenchymal Transition ◽  
Kinase Inhibitors ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Metastatic Cascade ◽  
Abl Kinases ◽  
Treatment Paradigm

AbstractThe ABL kinases, ABL1 and ABL2, promote tumor progression and metastasis in various solid tumors. Recent reports have shown that ABL kinases have increased expression and/or activity in solid tumors and that ABL inactivation impairs metastasis. The therapeutic effects of ABL inactivation are due in part to ABL-dependent regulation of diverse cellular processes related to the epithelial to mesenchymal transition and subsequent steps in the metastatic cascade. ABL kinases target multiple signaling pathways required for promoting one or more steps in the metastatic cascade. These findings highlight the potential utility of specific ABL kinase inhibitors as a novel treatment paradigm for patients with advanced metastatic disease.

scholarly journals Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Xuehua Chen ◽  
Yongquan Huang ◽  
Hui Chen ◽  
Ziman Chen ◽  
Jiaxin Chen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Residual Tumor ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
New Paradigm ◽  
Zeolitic Imidazolate Framework ◽  
Mesenchymal Transition ◽  
Epr Effect

Abstract Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract

scholarly journals Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Jia-Rong Huang ◽  
Sheng-Te Wang ◽  
Meng-Ning Wei ◽  
Kun Liu ◽  
Jing-Wen Fu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Epithelial Mesenchymal Transition ◽  
Colonic Neoplasms ◽  
Causative Factor ◽  
Therapeutic Effects ◽  
Acute Colitis ◽  
Related Factors ◽  
Mesenchymal Transition

Colorectal cancer is one of the most common and lethal cancers in the world. An important causative factor of colorectal cancer is ulcerative colitis. In this study, we investigated the therapeutic effects of piperlongumine (PL) on the dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colorectal cancer mouse models. Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter >2 mm) of AOM/DSS-induced mouse colorectal cancer by downregulation of proinflammatory cytokines cyclooxygenase-2 and interleukin-6 and epithelial-mesenchymal transition-related factors, β-catenin, and snail expressions, but fail to improve the colitis symptoms and to decrease the incidence of colonic neoplasms and the number of small neoplasms (diameter <2 mm). These data suggested that PL might be an effective agent in treating colitis and colorectal cancer.

scholarly journals The Synergistic Anti-Cancer Effects of NVP-BEZ235 and Regorafenib in Hepatocellular Carcinoma

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2454
Author(s):  
Cheng-Chan Yu ◽  
Sung-Ying Huang ◽  
Shu-Fang Chang ◽  
Kuan-Fu Liao ◽  
Sheng-Chun Chiu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Kinase Inhibitor ◽  
Epithelial Mesenchymal Transition ◽  
Combined Treatment ◽  
Gelatin Zymography ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual PI3K/mTOR inhibitor BEZ235 in the human HCC cell lines (n = 3). The combined treatment with BEZ235 and regorafenib enhanced the inhibition of cell proliferation and increased the expression of cleaved caspase-3 and cleaved PARP in HCC cells. Moreover, the combined treatment suppressed HCC cell migration and invasion in the transwell assay. Further, the Western blot analyses confirmed the involvement of epithelial-mesenchymal transition (EMT)-related genes such as slug, vimentin, and matrix metalloproteinase (MMP)-9/-2. Additionally, the proteinase activity of MMP-9/-2 was analyzed using gelatin zymography. Furthermore, the inhibition of phosphorylation of the Akt, mTOR, p70S6K, and 4EBP1 after combined treatment was validated using Western blot analysis. Therefore, these results suggest that the combined treatment with BEZ235 and regorafenib benefits patients with HCC.

scholarly journals P11.16 The stemness andinvasiveness of glioblastoma tumorspheres were suppressed by combined treatment with2’-hydroxycinnamaldehyde andtemozolomide

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii45-iii46
Author(s):  
W Kim
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Expression Profiles ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Orthotopic Xenograft ◽  
Orthotopic Xenograft Model

Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive human primary brain malignancy. The key properties of GBM, stemness and invasiveness, are known to be associated with a highly unfavorable prognosis. Notably, the process of epithelial-mesenchymal transition (EMT) is closely related to the progression of GBM. On the basis of reports that 2′-hydroxycinnamaldehyde (HCA) and its derivative, 2′-benzoyloxycinnamaldehyde (BCA), suppresses EMT in several human cancer cells, we sought to evaluate the therapeutic efficacy of HCA and BCA, alone and in combination with temozolomide (TMZ), on GBM tumorspheres (TSs). MATERIAL AND METHODS Two human GBM TSs were treated with HCA, BCA, or TMZ. Therapeutic effects were evaluated by measuring ATP levels, neurosphere formation, 3D-invasion in collagen matrix, and viability. Protein expression profiles after drug treatment were evaluated by western blotting. In vivo anticancer efficacy of drugs was examined in a mouse orthotopic xenograft model. RESULTS Combined treatment of GBM TSs with HCA or BCA and TMZ significantly reduced cell viability, stemness, and invasiveness. Expression levels of stemness-, invasiveness-, and mesenchymal transition-associated markers, Zeb1, N-cadherin, and β-catenin, were also substantially decreased by the combined treatment. The combined treatment also reduced tumor growth in a mouse orthotopic xenograft model. CONCLUSION Our findings suggest that HCA and BCA, combined with TMZ, are potential therapeutic agents in the treatment of GBM.

scholarly journals A potent CBP/p300-Snail interaction inhibitor suppresses tumor growth and metastasis in wild-type p53-expressing cancer

2020 ◽  
Vol 6 (17) ◽  
pp. eaaw8500
Author(s):  
Hong-Mei Li ◽  
Yan-Ran Bi ◽  
Yang Li ◽  
Rong Fu ◽  
Wen-Cong Lv ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Effects ◽  
Creb Binding Protein ◽  
Wild Type ◽  
Mesenchymal Transition ◽  
Patients With Cancer ◽  
Wild Type P53

The zinc finger transcription factor Snail is aberrantly activated in many human cancers and associated with poor prognosis. Therefore, targeting Snail is expected to exert therapeutic benefit in patients with cancer. However, Snail has traditionally been considered “undruggable,” and no effective pharmacological inhibitors have been identified. Here, we found a small-molecule compound CYD19 that forms a high-affinity interaction with the evolutionarily conserved arginine-174 pocket of Snail protein. In aggressive cancer cells, CYD19 binds to Snail and thus disrupts Snail’s interaction with CREB-binding protein (CBP)/p300, which consequently impairs CBP/p300-mediated Snail acetylation and then promotes its degradation through the ubiquitin-proteasome pathway. Moreover, CYD19 restores Snail-dependent repression of wild-type p53, thus reducing tumor growth and survival in vitro and in vivo. In addition, CYD19 reverses Snail-mediated epithelial-mesenchymal transition (EMT) and impairs EMT-associated tumor invasion and metastasis. Our findings demonstrate that pharmacologically targeting Snail by CYD19 may exert potent therapeutic effects in patients with cancer.

Tepotinib inhibits the epithelial-mesenchymal transition and tumor growth of gastric cancers via increasing GSK3β, ECAD, MUC5AC, and MUC6.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16562-e16562
Author(s):  
Dae Young Zang ◽  
Sung-Hwa Sohn ◽  
Bohyun Kim ◽  
Hee Jung Sul ◽  
Jinhui Jeong ◽  
...  
Keyword(s):  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Apoptotic Cell ◽  
Xenograft Model ◽  
Control Group ◽  
Therapeutic Effects ◽  
Human Gastric Cancer ◽  
Beta Catenin ◽  
Aberrant Expression ◽  
Mesenchymal Transition

e16562 Background: Aberrant expression of mucins can promote the epithelial-mesenchymal transition (EMT), which leads to enhanced tumorigenesis. Carcinogenesis-related pathways involving c-MET and beta-catenin involve mucins. This study characterized expressions of MET, MUC5AC, MUC5B, and MUC6 EMT signaling in human gastric cancer (GC) cell lines, and further characterized the differential susceptibility of these cell lines to tepotinib. Methods: We assessed the antitumor activity of tepotinib in GC cell lines. The effect of tepotinib on cell viability (IC50), apoptotic cell death, the EMT, and c-MET and beta-catenin signaling were evaluated by MTS assay, flow cytometry, western blotting, and qRT-PCR. Antitumor efficacy was assessed in MKN45 xenograft mice. Results: Tepotinib treatment showed dose-dependent growth inhibition of c-MET-amplified SNU620, MKN45, and KATO III cells with concomitant induction of apoptosis, but tepotinib treatment did not have an effect on c-MET-reduced MKN28 and AGS cells. Tepotinib treatment also significantly reduced expressions of phospho-c-MET, total c-MET, phospho-ERK, total ERK, beta-catenin, and c-Myc protein in SNU620 and MKN45 cells. In contrast, this drug was only slightly active against KATO III cells. Notably, tepotinib significantly reduced the expressions of EMT promotion genes such as MMP7, COX-2, WNT1, MUC5B, and c-Myc in c-MET-expressed GC cells, and increased expressions of EMT suppression genes such as MUC5AC, MUC6, GSK3beta, and ECAD. In a murine xenograft model, tumor volumes were significantly reduced in the tepotinib-treated group, when administered by daily oral gavage at a dose of 10mg/kg/day. Histologically, tepotinib induced more necrosis than in the control group. Conclusions: These data show the possibility that tepotinib may have therapeutic effects in c-MET-amplified GC, suggesting that clinical studies need to confirm the therapeutic effect.

scholarly journals Transient adenoviral gene transfer of Smad7 prevents injury-induced epithelial–mesenchymal transition of lens epithelium in mice

2004 ◽  
Vol 84 (10) ◽  
pp. 1259-1270 ◽  
Author(s):  
Shizuya Saika ◽  
Kazuo Ikeda ◽  
Osamu Yamanaka ◽  
Misako Sato ◽  
Yasuteru Muragaki ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Epithelial Mesenchymal Transition ◽  
Lens Epithelium ◽  
Mesenchymal Transition ◽  
Adenoviral Gene Transfer

scholarly journals Kurarinone Attenuates BLM-Induced Pulmonary Fibrosis via Inhibiting TGF-β Signaling Pathways

2021 ◽  
Vol 22 (16) ◽  
pp. 8388
Author(s):  
Soo-Jin Park ◽  
Tae-hyoun Kim ◽  
Kiram Lee ◽  
Min-Ah Kang ◽  
Hyun-Jae Jang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Lung Epithelial Cells ◽  
Drug Candidate ◽  
Therapeutic Effects ◽  
Mesenchymal Transition ◽  
Lung Epithelial ◽  
Novel Drug

Idiopathic pulmonary fibrosis (IPF) is a refractory interstitial lung disease for which there is no effective treatment. Although the pathogenesis of IPF is not fully understood, TGF-β and epithelial–mesenchymal transition (EMT) have been shown to be involved in the fibrotic changes of lung tissues. Kurarinone is a prenylated flavonoid isolated from Sophora Flavescens with antioxidant and anti-inflammatory properties. In this study, we investigated the effect of kurarinone on pulmonary fibrosis. Kurarinone suppressed the TGF-β-induced EMT of lung epithelial cells. To assess the therapeutic effects of kurarinone in bleomycin (BLM)-induced pulmonary fibrosis, mice were treated with kurarinone daily for 2 weeks starting 7 days after BLM instillation. Oral administration of kurarinone attenuated the fibrotic changes of lung tissues, including accumulation of collagen and improved mechanical pulmonary functions. Mechanistically, kurarinone suppressed phosphorylation of Smad2/3 and AKT induced by TGF-β1 in lung epithelial cells, as well as in lung tissues treated with BLM. Taken together, these results suggest that kurarinone has a therapeutic effect on pulmonary fibrosis via suppressing TGF-β signaling pathways and may be a novel drug candidate for pulmonary fibrosis.

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