scholarly journals Pleomorphic carcinoma of the trachea after chemoradiotherapy for laryngeal cancer

2020 ◽  
Vol 13 (10) ◽  
pp. e236819
Author(s):  
Hirotaka Saikawa ◽  
Noriyuki Uesugi ◽  
Tamotsu Sugai ◽  
Makoto Maemondo
Keyword(s):  
Radiation Therapy ◽  
Ct Scan ◽  
Tracheal Tube ◽  
Laryngeal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Sarcomatoid Carcinoma ◽  
Pleomorphic Carcinoma ◽  
Histopathological Diagnosis ◽  
Mesenchymal Transition ◽  
Local Doctor

A 66-year-old male patient who had received chemoradiotherapy (CRT) for laryngeal cancer 2 years ago visited a local doctor complaining of dyspnoea and wheezing. CT scan showed narrowing of the trachea caused by a tumour. We intubated the trachea over the tumour using a bronchoscope. A week later, the truncated tracheal tumour obstructed the tracheal tube, compromising the patient’s breathing. We removed the obstructed tube and inserted a new one. We submitted the tissue from the tube to a pathologist. Histopathological diagnosis was pleomorphic carcinoma, a subtype of sarcomatoid carcinoma. The mechanism of epithelial–mesenchymal transition (EMT) occurring after CRT was detected in the tumour. Because he had undergone CRT for laryngeal cancer, surgery was not indicated, and we started radiation therapy. Sarcomatoid carcinomas including pleomorphic carcinoma of the trachea are extremely rare, with few reported cases, and EMT is associated with this histological type and CRT.

MicroRNA-21 inhibitor potentiates anti-tumor effect of radiation therapy in vitro and in vivo

2014 ◽  
Vol 2 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Bong Jun Cho ◽  
Hans H. Kim ◽  
David J Lee ◽  
Eun Jung Choi ◽  
Yeo Hyun Hwang ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Combined Treatment ◽  
A549 Cells ◽  
Specific Inhibitor ◽  
Tumor Burden ◽  
Mesenchymal Transition ◽  
Human Cancer Cells

AbstractMicroRNA-21 (miR-21) plays important roles in carcinogenesis and is highly expressed in diverse human cancers. We evaluated the potential of targeting miRNA-21 to overcome the radioresistance of human cancer cells having an activated EGFR2-associated signaling and also aimed to elucidate the mechanisms of radiosensitization, and the effect on epithelial- mesenchymal transition (EMT). Ectopic overexpression of miR-21 up-regulated EGFR/HER2-associated signaling and increased radioresistance of a panel of human cancer cells (U251, U87, and A549 cells). In contrast, a specific inhibitor of miR-21 attenuated this signaling and radiosensitized a panel of human cancer cells. Inhibition of miR-21 was associated with persistent γH2AX foci formation. Inhibition of miR-21 decreased the typical features of EMT, such as invasion and migration and vascular tube formation. Treatment with anti-miR-21 decreased tumor burden in nude mice bearing intracranial U251 xenografts compared to controls. Combined treatment of anti-miR-21 and radiation further decreased tumor burden compared to each treatment alone. In summary, miR-21 is an important onco-miR, which confers radioresistance and diverse features of EMT. Inhibition of miR-21 could be a potential strategy for improving the efficacy of radiation therapy via unique modulation of pro-survival signaling implicated in radiation response and EMT.

Sarcomatoid carcinoma represents a complete phenotype with various pathways of epithelial mesenchymal transition

2013 ◽  
Vol 66 (7) ◽  
pp. 601-606 ◽  
Author(s):  
Chang Ohk Sung ◽  
Hannah Choi ◽  
Keun-Woo Lee ◽  
Seok-Hyung Kim
Keyword(s):  
Transcription Factors ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Smooth Muscle Actin ◽  
Expression Patterns ◽  
Sarcomatoid Carcinoma ◽  
Phenotypic Markers ◽  
Mesenchymal Transition ◽  
Related Phenotype ◽  
Phenotype Markers

AimsSarcomatoid carcinoma (SC) is considered to be a result of the sarcomatoid change of epithelial carcinoma. However, epithelial–mesenchymal transition (EMT) in SC has been insufficiently studied.MethodsWe evaluated the expression patterns of EMT-related phenotypic markers with transcription factors in 27 SCs originating from various organs, and we investigated the phenotypic characteristics of SCs classified as complete, incomplete or wild-type. We further analysed correlations between EMT-related phenotype markers and transcription factors.ResultsEpithelial markers (E-cadherin, claudin-3 and claudin-4) were consistently down-regulated, whereas mesenchymal markers (S100A4, α-smooth muscle actin (SMA), vimentin, PDGFRα and β-catenin) were variously expressed except for vimentin. EMT-related transcription factors (SIP1, Snail1, Slug, Twist1, ZEP1 and Oct-4) also showed various expression patterns. The expression patterns of phenotypic markers showed that most SCs (22/27, 81.5%, 95% CI 65.8 to 97.1%) had complete EMT phenotypes, whereas the remaining 5 (18.5%, 95% CI 2.8 to 24.1%) were of incomplete type. Unsupervised hierarchical clustering analysis revealed that SCs were clustered into several subgroups by EMT-related protein expression pattern. Twist1 positivity was significantly concordant with α-SMA positivity (κ value: 0.908; 95% CI 0.73 to 1.00, p<0.001, adjusted p<0.001). The EMT phenotypes of SC were simple, with complete phenotype being the predominant form, and the morphological changes of the SCs were also relevant in terms of EMT.ConclusionsSC seems to be an irreversible, permanent change in the EMT phenomenon, with complete EMT phenotypes and various EMT-related pathways being involved in SC.

scholarly journals Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ren-Bo Ding ◽  
Ping Chen ◽  
Barani Kumar Rajendran ◽  
Xueying Lyu ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Specific Treatment ◽  
Sarcomatoid Carcinoma ◽  
Radiation Sensitivity ◽  
High Morbidity ◽  
Precision Oncology ◽  
Cancer Type ◽  
Mesenchymal Transition ◽  
Molecular Features

AbstractNasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.

scholarly journals Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhenlin Yang ◽  
Jiachen Xu ◽  
Lin Li ◽  
Renda Li ◽  
Yalong Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Sarcomatoid Carcinoma ◽  
Molecular Classification ◽  
Therapeutic Strategies ◽  
Molecular Characteristics ◽  
Mesenchymal Transition ◽  
Mutation Burden ◽  
Entry Points ◽  
Pulmonary Sarcomatoid Carcinoma

Abstract Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of lung cancer with poor prognosis. Here, we perform multi-omics analysis of 56 PSC samples, 14 of which are microdissected to analyze intratumoral heterogeneity. We report the mutational landscape of PSC. The epithelial and sarcomatoid components share numerous genomic alterations, indicating a common progenitor. We find that epithelial-mesenchymal transition (EMT) plays important roles in the carcinogenesis of PSC. The pan-cancer analysis reveals high tumor mutation burden and leukocyte fraction of PSC. Integrated molecular classification shows three subgroups with distinct biology, prognosis and potential therapeutic strategies. Actionable mutations are enriched in C1 and C2, patients in C3 have a significantly longer overall survival, and C1 and C2 exhibit T-cell inflamed microenvironments. The three subgroups show molecular similarities to specific subtypes of conventional lung cancer. In conclusion, our study reveals the molecular characteristics and provides entry points for the treatment of PSC.

scholarly journals A case of pulmonary pleomorphic carcinoma with malignant phenotypes induced by ZEB1-associated epithelial-mesenchymal transition

2018 ◽  
Vol 25 ◽  
pp. 119-121 ◽  
Author(s):  
Mayo Kondo ◽  
Hirokazu Ogino ◽  
Hirohisa Ogawa ◽  
Tania Afroj ◽  
Yuko Toyoda ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Pleomorphic Carcinoma ◽  
Mesenchymal Transition
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