The alteration of progenitor/stem cells present in the airway epithelium has been observed in patients with COPD. Smoking exposure induces remodeling patterns in bronchial progenitor cells (BPCs), encompassing squamous metaplasia, hyperplasia of basal and of mucus-secreting cells, and the depletion of ciliated and non-mucous secretory cells. Our aim was to assess the expression of p63 and vimentin as potential markers of airway remodeling and the regulation of stem cell populations in obstructive and neoplastic lung disease patients. A retrospective single-center observational study was conducted, including patients undergoing bronchoscopy with bronchial biopsies for suspected lung cancer. p63 and vimentin expression were evaluated via immunohistochemical analysis. There were 25 patients, of which 21 with COPD were included, and 17 were diagnosed with lung cancer. We observed that FEV1% was negatively correlated with p63+ basal cell number (r = -0.614, p = 0.019) and positively correlated with vimentin expression (r = 0.670; p = 0.008). p63 was significantly higher in biopsies from the trachea and main bronchi compared to more distal areas (p = 0.040), whereas vimentin was prevalent in the more distal areas (p = 0.042). Our preliminary data suggest the initial evidence of structural changes in BPCs among patients with COPD and lung cancer. Further research efforts are warranted to investigate additional morphologic and functional respiratory parameters in these patients.

UNASSIGNED: Laparoscopic surgery for malignant tumours occasionally results in recurrence at the trocar insertion site or port-site metastasis (PSM). We report on a patient requiring emergency laparoscopic surgery for an ovarian tumour with a review of the relevant literature.
UNASSIGNED: A 42-year-old woman developed sudden abdominal pain and underwent laparoscopic right adnexectomy because of a suspected ovarian cystic tumour rupture. The postoperative histological diagnosis was a mucinous borderline ovarian tumour; however, an undifferentiated carcinoma was detected at the port site eight months after the initial surgery. The histopathological diagnosis of the abdominal wall tumour at the port site differed from intraoperative pathological findings, which was contradictory to PSM definition. Postoperatively, she received three systemic chemotherapy courses but died consequent to tumour metastasis.
UNASSIGNED: This is an atypical PSM case with histopathological differences from the initial tumour. Careful preoperative diagnosis and intraoperative attention are essential in such cases.

It has been proposed that epithelial-mesenchymal transition (EMT) is responsible for the pathogenesis of several diseases. However, the relationship between the EMT process and the severity of periodontitis has not been previously investigated.
This study aimed to localize and quantitatively assess the expression of transforming growth factor-beta 1 (TGF-β1), vimentin and E-cadherin in correlation with the EMT process in human gingiva of periodontally diseased patients in comparison with halthy individuals.
Gingival tissue samples from 36 participants were divided into 2 groups: the healthy (control) group (n = 9); and the periodontitis group (n = 27). The periodontitis group was further subclassified into mild, moderate and severe periodontitis subgroups (9 patients in each subgroup). The samples were subjected to histological staining, the histomorphometric analysis and the quantitative real-time polymerase chain reaction (RT‑PCR) analysis for TGF-β, vimentin and E-catherin. Statistical and correlation analyses were performed.
The hematoxylin and eosin (H&E) stain sections from both the moderate and severe periodontitis subgroups showed epithelial hyperplasia, perinuclear haloing and a marked increase in the inflammatory cell count as compared to the control group. The highest mean TGF-β1 and vimentin expression values were recorded in the severe periodontitis subgroup, whereas the lowest mean values were recorded in the control gingiva. On the contrary, the expression of E-catherin had the highest mean value in the control gingiva, whereas the lowest mean value was recorded in the severe periodontitis subgroup. All results were found to be statistically significant. The correlation analysis revealed a statistically significant positive correlation between the severity of periodontitis and the expression of TGF-β and vimentin, while a statistically significant inverse correlation was found between the expression of E-catherin and the severity of periodontitis.
There is a direct correlation between the severity of periodontitis and the expression of the EMT process markers (TGF-β and vimentin). This correlation indicates that EMT plays an important role in the pathogenesis and prognosis of periodontal disease. The data presented in this study could open the door for using anti-EMT agents in treating periodontal disease.

BACKGROUND: Taxane based conventional chemotherapy serves as the standard treatment regimen for triple-negative breast cancer (TNBC). However, the efficacy is plateaued due to toxicities, chemoresistance and metastasis. Hence, the development of new therapies that provide long-term cover is needed. Brusatol, a natural quassinoid, has been implicated to inhibit the migration and proliferation of metastatic cells in lung and liver carcinoma, but its efficacy in TNBC has not been explored.
METHODS: The growth inhibitory activity on TNBC cells was measured using MTT assay and flow cytometry. Epithelial to mesenchymal transition (EMT) and apoptotic markers were quantified using western blotting. The caspases using Calorimetric assay.
RESULTS: Brusatol along with paclitaxel showed an enhanced growth inhibitory activity and a combined synergistic effect. In addition, brusatol was also observed to inhibit the invasion, migratory potential of TNBC cells. Mechanistically, brusatol and its combination were observed to decrease the matrix metalloproteinase (MMP) and a modest increase in the reactive oxygen species (ROS) production. Furthermore, brusatol treatment activated both intrinsic and extrinsic pathways with morphological changes of apoptosis in TNBC cells.
CONCLUSIONS: This is the first in vitro report demonstrating antineoplastic, anti-EMT and synergistic activity of brusatol and in combination with paclitaxel in TNBC cell. Further in-vivo studies are needed to substantiate the above findings.

Endometriosis is common in reproductive-age women and its pathology is to increase proliferation and migration to enhance epithelial-to-mesenchymal transition progression (EMT). However, treatments are currently limited, so it is important to explore new therapeutic drugs. Hence, in this study, we investigate the therapeutic effect of fucoidan (FC) on the progression and mechanisms of endometriosis. The cell viability of endometrial cell lines End1/E6E7 and Vk2/E6E7 treated with different concentrations of FC were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell counting. Cell migration was evaluated using wound-healing assay. In an in vivo experiment, female Balb/c mice received surgically induced endometriosis followed by different concentrations of fucoidan for 6 weeks. High-frequency ultrasound imaging was applied to detect subsequent lesion growth. The results demonstrated that fucoidan inhibited the viability and migration ability of End1/E6E7 and Vk2/E6E7 cells. Additionally, the administration of fucoidan reduced the volume and weight of endometriotic lesions, decreased inflammatory cytokines and vascular endothelial growth factor (VEGF) of serum and lesions, and improved EMT proliferation and apoptosis-related protein expression. For the first time, fucoidan indicated anti-proliferative and anti-inflammatory effects as well as inhibited EMT progression and induced apoptosis, improving endometriosis.

Machine learning is increasingly being applied to the classification of microscopic data. In order to detect some complex and dynamic cellular processes, time-resolved live-cell imaging might be necessary. Incorporating the temporal information into the classification process may allow for a better and more specific classification.
We propose a methodology for cell classification based on the time-lapse quantitative phase images (QPIs) gained by digital holographic microscopy (DHM) with the goal of increasing performance of classification of dynamic cellular processes.
The methodology was demonstrated by studying epithelial-mesenchymal transition (EMT) which entails major and distinct time-dependent morphological changes. The time-lapse QPIs of EMT were obtained over a 48-h period and specific novel features representing the dynamic cell behavior were extracted. The two distinct end-state phenotypes were classified by several supervised machine learning algorithms and the results were compared with the classification performed on single-time-point images.
In comparison to the single-time-point approach, our data suggest the incorporation of temporal information into the classification of cell phenotypes during EMT improves performance by nearly 9% in terms of accuracy, and further indicate the potential of DHM to monitor cellular morphological changes.
Proposed approach based on the time-lapse images gained by DHM could improve the monitoring of live cell behavior in an automated fashion and could be further developed into a tool for high-throughput automated analysis of unique cell behavior.

UNASSIGNED: Conventional oral squamous cell carcinoma (OSCC) is relatively easy to diagnose on histopathology, as it comprises dysplastic epithelial cells with variable degrees of squamous differentiation. Different grading systems have been employed in grading OSCC based on its dysplastic features and host response. Some unusual features such as clear cell change, epithelial-mesenchymal transition (EMT), stromal hyalinization, stromal desmoplasia, perineural invasion, vascular invasion, tissue eosinophilia, giant cells, and tertiary lymphoid follicle formation are evident in OSCC histologically but have not yet been accounted in any grading systems of OSCC except perineural and vascular invasion.
UNASSIGNED: The aim of the present study was to identify these uncommon features and to correlate them with different grades of OSCC.Materials and Methods:This study was conducted on 100 histopathologically confirmed OSCC cases retrieved from the archives of our department. They were graded on the basis of Broder\'s grading system and were reviewed for the features mentioned above. Data collected were subjected to statistical analysis.
UNASSIGNED: Clear cell change, EMT, foreign body giant cells, and tumor giant cells were observed in 13%, 20%, 1%, and 3% of cases, respectively. We found stromal desmoplasia in 15% and stromal hyalinization in 9% of cases. Tissue eosinophilia, tertiary lymphoid follicle formation, and perineural invasion were observed in 12%, 3%, and 2% of cases, respectively. Vascular invasion was not evident in any of the cases examined.
UNASSIGNED: The incidence of the unusual features was 7.8% in our study.

BACKGROUND: Accumulating studies have shown that pseudogenes could become key regulators in human cancers. Misato family member 2, pseudogene (MSTO2P) is overexpressed in lung and gastric cancer and affects the biological functions of tumor cells. However, the role of MSTO2P in hepatocellular carcinoma (HCC) is unreported.
OBJECTIVE: This study aimed to examine the diagnostic and prognostic value of MSTO2P in HCC, to investigate the effects of MSTO2P on the biological functions of HCC cells, and to explore the potential mechanisms of MSTO2P in HCC.
METHODS: Relevant data on HCC were downloaded from the Gene Expression Omnibus database and the Cancer Genome Atlas database and used to analyze MSTO2P expression and the role of MSTO2P in HCC prognosis. MSTO2P in HCC cell lines was knocked down by shRNA to study the effects of MSTO2P on cell proliferation, apoptosis, metastasis and invasion in HCC. Expressions of the main proteins involved in epithelial-mesenchymal transition and the PI3K/AKT/mTOR signaling pathway in HCC were examined via Western blot analysis.
RESULTS: MSTO2P had significant diagnostic and prognostic value in HCC. MSTO2P was highly expressed in HCC tissues and cells, and MSTO2P increased HCC cell proliferation, invasion and metastasis. MSTO2P knockdown also increased E-cadherin expression and decreased N-cadherin and Vimentin expression. Additionally, MSTO2P increased the expressions of proteins in the PI3K/AKT/mTOR pathway, including PI3K, p-AKT and p-mTOR.
CONCLUSIONS: MSTO2P might be used as a potential target for diagnosing and curing HCC. MSTO2P may affect HCC cell proliferation, apoptosis, metastasis and invasion through the PI3K/AKT/mTOR pathway.

OBJECTIVE: Cancer stem cells (CSC) and epithelial-mesenchymal transition (EMT) pathways are crucial for cancer progression. However, synergistic interactions between CSC and EMT are not clear in non-small cell lung cancer (NSCLC). The objective of this study was to investigate CSC markers such as CD44, NANOG, and ALDH1 expression and its correlation with EMT markers in NSCLC patients. Its association with survival was also determined.
METHODS: CD44, NANOG, and ALDH1 protein expression was evaluated in 267 resected NSCLC and its correlation with e-cadherin, β-catenin, p120 catenin, vimentin, SNAIL, and TWIST expressions was determined based on immunohistochemical and mRNA expression data from The Cancer Genome Atlas (TCGA) database. Survival analyses also were performed based on immunohistochemistry and mRNA expression data from Gene Expression Omnibus dataset.
RESULTS: ALDH1 expression in lung adenocarcinoma was positively correlated with the epithelial-like phenotype, low vimentin and low TWIST in immunohistochemical and mRNA expression data. NANOG and ALDH1 expressions measured by immunohistochemical and mRNA expression profiling data of adenocarcinomas were associated with a favorable prognosis. ALDH1 was an independent favorable prognostic marker for overall survival or recurrence-free survival in adenocarcinoma (P = 0.026 and P = 0.033, respectively). The epithelial-like phenotype expressing P120-catenin and beta-catenin was associated with a favorable prognosis; however, the TWIST-expressing mesenchymal-like phenotype was correlated with an unfavorable prognosis.
CONCLUSIONS: NANOG and ALDH1 protein or mRNA expression showed improved prognosis in adenocarcinoma alone. ALDH1 expression correlated with an epithelial-like phenotype.

The epithelial-mesenchymal transition (EMT) plays an important role in development and cancer progression. Upon EMT, epithelial cells lose stable cell-cell adhesions and reorganize their cytoskeleton to acquire migratory activity. Recent data demonstrated that EMT drives cancer cells from the epithelial state to a hybrid epithelial/mesenchymal phenotype with retention of some epithelial markers (in particular, E-cadherin), which is important for cancer cell dissemination. In vitro studies of the effect of growth factors (in particular, epidermal growth factor (EGF)) on cultured cells can be highly advantageous for understanding the details of the early stages of EMT. The methods described in this chapter are intended for studying intermediate phenotypes of EMT. Time-lapse DIC microscopy is used for visualization of changes in morphology and motility of the cells stimulated with EGF. The transwell migration assay allows the evaluation of the migratory activity of the cells. Studying of dynamics of a fluorescently labeled actin-binding protein F-tractin-tdTomato using confocal microscopy allows detection of EGF-induced changes in the organization of the actin cytoskeleton. Live-cell imaging of cells stably expressing GFP-E-cadherin visualizes reorganization of stable tangential E-cadherin-based adherens junctions (AJs) into unstable radial AJs during the early stages of EMT.