scholarly journals Immunohistochemical analysis of NANOG expression and epithelial-mesenchymal transition in pulmonary sarcomatoid carcinoma

2017 ◽  
Vol 13 (5) ◽  
pp. 3695-3702 ◽  
Author(s):  
Takeshi Tamaki ◽  
Toshiki Shimizu ◽  
Maiko Niki ◽  
Michiomi Shimizu ◽  
Tohru Nishizawa ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Sarcomatoid Carcinoma ◽  
Immunohistochemical Analysis ◽  
Mesenchymal Transition ◽  
Nanog Expression ◽  
Pulmonary Sarcomatoid Carcinoma

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 Different macrophages equally induce EMT in endometria of adenomyosis and normal

Reproduction ◽  
2017 ◽  
Vol 154 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Min An ◽  
Dong Li ◽  
Ming Yuan ◽  
Qiuju Li ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Quantitative Polymerase Chain Reaction ◽  
Immunohistochemical Analysis ◽  
Secretory Phase ◽  
Normal Endometrium ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Endometrial Cells

Endometrial cells and microenvironment are two important factors in the pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can induce eutopic epithelial cells of adenomyosis to suffer from epithelial–mesenchymal transition (EMT). The aim of this study is to detect whether macrophages interacting with epithelial cells equally induce the EMT process in normal and eutopic endometria of healthy and adenomyotic patients; and whether macrophages parallelly polarize to M2. We investigated the expression levels of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7 (CK7), vimentin, transforming growth factor-β1 (TGFB1), SMAD3 and pSMAD3 using immunohistochemistry and western blot, and then estimated the genetic levels of CD163, IL10 and MMP12 using real-time quantitative polymerase chain reaction (RT-PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20 patients with adenomyosis and 11 control patients without adenomyosis, respectively. The immunohistochemical analysis shows distinct EMT in eutopic endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3 that indicate signal pathway of EMT were also higher in secretory phase. Macrophages can induce EMT process in primary endometrial epithelial cells derived from normal and eutopic endometria. After co-culturing, THP-1-derived macrophages polarized to M2. Compared with the eutopic endometrium group, further polarization to M2 was observed in the normal endometrium group. These results indicate that adenomyosis may be promoted by the pathologic EMT of epithelial cells, which is induced by macrophages that incapably polarize to M2.

scholarly journals Personalized approach to assessing mRNA expression of histidine-rich glycoprotein and immunohistochemical markers in diseases of the breast

2019 ◽  
Vol 484 (5) ◽  
pp. 624-628 ◽  
Author(s):  
A. I. Autenshlyus ◽  
A. V. Golovanova ◽  
A. A. Studenikina ◽  
I. I. Brusentsov ◽  
A. V. Proskura ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Breast Diseases ◽  
Biopsy Material ◽  
Mesenchymal Transition ◽  
Benign Breast Diseases ◽  
Immunohistochemical Markers ◽  
Atypical Cells ◽  
Personalized Approach

Biopsy material of patients with malignant and benign breast diseases was examined. HRG mRNA expression was detected in 70% of cases in biopsy material obtained from patients with nonspecific invasive carcinoma and in 66.7% of cases in biopsy material of patients with benign breast diseases. Immunohistochemical analysis revealed expression of collagen II, the beta-1 integrin, and E-cadherin – markers of epithelial–mesenchymal transition. The use of RT-qPCR combined with immunohistochemical study made it possible to identify atypical cells, which can be regarded as precancerous changes, in individual patients.

scholarly journals BMI1,ALDH1A1, andCD133Transcripts Connect Epithelial-Mesenchymal Transition to Cancer Stem Cells in Lung Carcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ana Koren ◽  
Matija Rijavec ◽  
Izidor Kern ◽  
Eva Sodja ◽  
Peter Korosec ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mrna Expression ◽  
Whole Blood ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Underlying Mechanism ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Cellular Models ◽  
Nsclc Patients

Epithelial-mesenchymal transition (EMT) is the underlying mechanism of tumor invasion and metastasis. Evidences from lung cancer cellular models show EMT can trigger conversion to a cancer stem cell (CSC) phenotype. In this study, we assessed mRNA expression levels of EMT-inducing transcription factors (BMI1,TWIST1), CSC (CD133,ALDH1A1), and epithelial (EpCAM) markers in primary tumor and whole blood samples obtained from 57 patients with operable non-small-cell lung cancer (NSCLC) as well as in circulating tumor cells (CTCs) of 13 patients with metastatic disease; then possible associations between marker expressions were evaluated. In primary tumors as well as in whole blood, correlations betweenBMI1andALDH1A1and betweenBMI1andCD133mRNA expressions were identified. No correlations betweenTWIST1and CSC markers were observed.BMI1mRNA expression in tumors positively correlated withBMI1mRNA expression in blood. The immunohistochemical analysis confirmed coexpression of BMI1 and CSC markers in tumors. Gene expression profiling in CTCs revealed upregulated expression of EMT/CSC markers in CTCs. Our results suggest CSCs are present in both, tumor tissue and blood of NSCLC patients, whereas Bmi1 may play an important role in initiation and maintenance of CSCs and might be involved in the blood-borne dissemination of NSCLC.

scholarly journals Epithelial-Mesenchymal Transition Markers in Breast Cancer and Pathological Responseafter Neoadjuvant Chemotherapy

2018 ◽  
Vol 12 ◽  
pp. 117822341878807 ◽  
Author(s):  
Shaimaa Elzamly ◽  
Nabeel Badri ◽  
Osvaldo Padilla ◽  
Alok Kumar Dwivedi ◽  
Luis A Alvarado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Mesenchymal Transition ◽  
Pathologic Complete Response ◽  
Inverse Correlation ◽  
Immunohistochemical Analysis ◽  
Wilcoxon Test ◽  
Fisher Exact Test ◽  
Mesenchymal Transition ◽  
E Cadherin

The association between pathologic complete response (pCR) following to neoadjuvant chemotherapy (NAC) and the improved survival in breast cancer has been previously reported. The aim of this study was is to explore the expression of several biomarkers described during epithelial-mesenchymal transition (EMT) and the achievement of pCR in different molecular subtypes of breast cancer. We identified archived pathology tissue from patients with breast cancer who received NAC during the year 2014. We performed immunohistochemical analysis of vimentin, nuclear factor κB (NF-κB), epidermal growth factor receptor (EGFR), E-cadherin, estrogen receptor (ER), progesterone receptor, and Her2neu and studied the association between the expression of these markers and pCR. A Fisher exact test for categorical cofactors, an unpaired t test and a nonparametric Wilcoxon test for continuous cofactors were used. The results showed a significant expression of vimentin in triple-negative breast cancer (TNBC; P = .023). An inverse correlation between vimentin and the ER expression ( P = .032) was observed. No significant association was noted for vimentin, NF-κB, EGFR, and E-cadherin was associated with pCR. This study suggests that the evaluated EMT related biomarkers are not associated with pCR after NAC chemotherapy in an unselected breast cancer population. Vimentin and NF-κB expressions were associated with TNBC and could be further explored as potential therapeutic targets in this subgroup. A prevalence of vimentin and NF-κB among Hispanic patients with breast cancer warrants further investigation as a possibly contributing to the prevalence of TNBC and adverse prognosis in this population.

scholarly journals SQSTM1/p62 in Intrahepatic Cholangiocarcinoma Promotes Tumor Progression Via Epithelial-Mesenchymal Transition and Mitochondrial Function Maintenance

2021 ◽  
Author(s):  
Jiafeng Chen ◽  
Zheng Gao ◽  
Xiaogang Li ◽  
Yinghong Shi ◽  
Zheng Tang ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Mitochondrial Function ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Vital Role ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Consumption Rates ◽  
Invasive Capacity

Abstract Background: SQSTM1/p62, as a selective autophagy receptor, regulates multiple signaling pathways participating in the initiation and progression of tumors. Since metastasis is still a main cause for intrahepatic cholangiocarcinoma (ICC)-associated mortality, this study aimed to explore the mechanism of p62 promoting progression of ICC.Methods: Western blotting and immunohistochemical analysis were conducted to detect the expression level of protein p62 in ICC tissues. Subsequently, loss of function experiments was applied to define the role of p62 in the progression of ICC in vitro and in vivo. Mitochondrial function and mitophagy was evaluated by measuring oxygen consumption rates (OCR) and immunofluorescence detection respectively.Results: Here we identified expression of p62 was significantly upregulated in ICC specimens compared to normal tissue. And we further illustrated that p62 expression was positively correlated with lymph-node metastasis and poor prognosis. Loss of function assays revealed that p62 not only promoted ICC cells proliferation, migration and invasive capacity in vitro, but also induced lung metastasis in xenograft mouse model. Mechanistically, high expression of p62 induced epithelial-mesenchymal transition (EMT) with upregulation of Snail1, Vimentin and down-regulation of E-Cadherin. Moreover, OCR assays and immunofluorescence cell staining demonstrated that the autophagy-dependent function of p62 may play a vital role in maintaining mitochondrial function of ICC by mitophagy.Conclusions: These data provide new evidence and feasible mechanism that abundant p62 expression promote ICC progression, suggesting a promising therapeutic target for anti-metastatic strategies in ICC patients.

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.

The role of miRNA-21 and epithelial mesenchymal transition (EMT) process in colorectal cancer

2016 ◽  
Vol 70 (4) ◽  
pp. 331-356 ◽  
Author(s):  
Anelisa Jaca ◽  
Padmini Govender ◽  
Michael Locketz ◽  
Richard Naidoo
Keyword(s):  
Colorectal Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Clinicopathological Features ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Sporadic Cases ◽  
E Cadherin

AimsThe study was conducted to assess the expression levels of epithelial mesenchymal transition (EMT) proteins (E-cadherin, N-cadherin, snail-1 and vimentin) and miRNA-21. In addition, we correlated these data with clinicopathological features in Colorectal cancer.MethodsH&E slides from a total of 59 formalin fixed paraffin embedded tissue blocks were examined by a pathologist to demarcate normal and tumour regions. Immunohistochemical analysis of mismatch repair proteins (MLH1, MSH2 and MSH6) and EMT markers (E-cadherin, N-cadherin, snail-1 and vimentin) was performed. The miRNA-21 expression levels were determined using qRT-PCR and the data was analysed using the relative quantification method. The Fisher's exact and Pearson's χ2 tests were used to correlate snail-1, E-cadherin, miRNA-21 and clinicopathological data.ResultsOur results showed a statistically significant correlation between high miRNA-21 expression levels and E-cadherin positive cases. There was also an association between high miRNA-21 expression levels and negative snail-1 expression. No significant correlation was seen between miRNA-21 expression levels and clinicopathological features. Moreover, high expression levels of miRNA-21 were significantly associated with the sporadic cases.ConclusionsOur data suggest that miRNA-21 in association with E-cadherin and snail-1 does not play a significant role in the development and progression of this disease.

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.

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