scholarly journals Endothelin-1 Induces Mesothelial Mesenchymal Transition and Correlates with Pleural Fibrosis in Tuberculous Pleural Effusions

2019 ◽  
Vol 8 (4) ◽  
pp. 426 ◽  
Author(s):  
Zhung-Han Wu ◽  
Jie-Heng Tsai ◽  
Cheng-Ying Hsieh ◽  
Wei-Lin Chen ◽  
Chi-Li Chung
Keyword(s):  
Pleural Effusion ◽  
Smooth Muscle Actin ◽  
Mesenchymal Transition ◽  
Pleural Diseases ◽  
Pleural Thickening ◽  
Pleural Fibrosis ◽  
Parapneumonic Pleural Effusion ◽  
Insight Into

Endothelin (ET)-1 is involved in various fibrotic diseases. However, its implication in pleural fibrosis remains unknown. We aimed to study the profibrotic role of ET-1 in tuberculous pleural effusion (TBPE). The pleural effusion ET-1 levels were measured among 68 patients including transudative pleural effusion (TPE, n = 12), parapneumonic pleural effusion (PPE, n = 20), and TBPE (n = 36) groups. Pleural fibrosis, defined as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Additionally, the effect of ET-1 on mesothelial mesenchymal transition (MMT) and extracellular matrix (ECM) producion in human pleural mesothelial cells (PMCs) was assessed. Our findings revealed that effusion ET-1 levels were significantly higher in TBPE than in TPE and PPE, and were markedly higher in TBPE patients with RPT >10 mm than those with RPT ≤10 mm. ET-1 levels correlated substantially with residual pleural shadowing and independently predicted RPT >10 mm in TBPE. In PMCs, ET-1 time-dependently induced MMT with upregulation of α-smooth muscle actin and downregulation of E-cadherin, and stimulated ECM production; furthermore, ET receptor antagonists effectively abrogated these effects. In conclusion, ET-1 induces MMT and ECM synthesis in human PMCs and correlates with pleural fibrosis in TBPE. This study confers a novel insight into the pathogenesis and potential therapies for fibrotic pleural diseases.

scholarly journals Thrombin Upregulates PAI-1 and Mesothelial–Mesenchymal Transition Through PAR-1 and Contributes to Tuberculous Pleural Fibrosis

2019 ◽  
Vol 20 (20) ◽  
pp. 5076
Author(s):  
Cheng-Ying Hsieh ◽  
Joen-Rong Sheu ◽  
Chih-Hao Yang ◽  
Wei-Lin Chen ◽  
Jie-Heng Tsai ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Smooth Muscle Actin ◽  
Plasminogen Activator Inhibitor ◽  
Plasminogen Activator Inhibitor 1 ◽  
Mesenchymal Transition ◽  
Pleural Thickening ◽  
Pleural Fibrosis ◽  
Pai 1

Thrombin is an essential procoagulant and profibrotic mediator. However, its implication in tuberculous pleural effusion (TBPE) remains unknown. The effusion thrombin and plasminogen activator inhibitor-1 (PAI-1) levels were measured among transudative pleural effusion (TPE, n = 22) and TBPE (n = 24) patients. Pleural fibrosis, identified as radiological residual pleural thickening (RPT) and shadowing, was measured at 12-month follow-up. Moreover, in vivo and in vitro effects of thrombin on PAI-1 expression and mesothelial–mesenchymal transition (MMT) were assessed. We demonstrated the effusion thrombin levels were significantly higher in TBPE than TPE, especially greater in TBPE patients with RPT > 10mm than those without, and correlated positively with PAI-1 and pleural fibrosis area. In carbon black/bleomycin-treated mice, knockdown of protease-activated receptor-1 (PAR-1) markedly downregulated α-smooth muscle actin (α-SMA) and fibronectin, and attenuated pleural fibrosis. In pleural mesothelial cells (PMCs), thrombin concentration-dependently increased PAI-1, α-SMA, and collagen I expression. Specifically, Mycobacterium tuberculosis H37Ra (MTBRa) induced thrombin production by PMCs via upregulating tissue factor and prothrombin, and PAR-1 silencing considerably abrogated MTBRa−stimulated PAI-1 expression and MMT. Consistently, prothrombin/PAR-1 expression was evident in the pleural mesothelium of TBPE patients. Conclusively, thrombin upregulates PAI-1 and MMT and may contribute to tuberculous pleural fibrosis. Thrombin/PAR-1 inhibition may confer potential therapy for pleural fibrosis.

scholarly journals Mesomesenchymal transition of pleural mesothelial cells is PI3K and NF-κB dependent

2015 ◽  
Vol 308 (12) ◽  
pp. L1265-L1273 ◽  
Author(s):  
Shuzi Owens ◽  
Ann Jeffers ◽  
Jake Boren ◽  
Yoshikazu Tsukasaki ◽  
Kathleen Koenig ◽  
...  
Keyword(s):  
Smooth Muscle Actin ◽  
Akt Signaling ◽  
Mesothelial Cells ◽  
Acute Injury ◽  
Phosphatidylinositol 3 Kinase ◽  
Mesenchymal Transition ◽  
Pleural Diseases ◽  
Pleural Mesothelial Cells ◽  
Pleural Fibrosis

Pleural organization follows acute injury and is characterized by pleural fibrosis, which may involve the visceral and parietal pleural surfaces. This process affects patients with complicated parapneumonic pleural effusions, empyema, and other pleural diseases prone to pleural fibrosis and loculation. Pleural mesothelial cells (PMCs) undergo a process called mesothelial mesenchymal transition (MesoMT), by which PMCs acquire a profibrotic phenotype characterized by cellular enlargement and elongation, increased expression of α-smooth muscle actin (α-SMA), and matrix proteins including collagen-1. Although MesoMT contributes to pleural fibrosis and lung restriction in mice with carbon black/bleomycin-induced pleural injury and procoagulants and fibrinolytic proteases strongly induce MesoMT in vitro, the mechanism by which this transition occurs remains unclear. We found that thrombin and plasmin potently induce MesoMT in vitro as does TGF-β. Furthermore, these mediators of MesoMT activate phosphatidylinositol-3-kinase (PI3K)/Akt and NF-κB signaling pathways. Inhibition of PI3K/Akt signaling prevented TGF-β-, thrombin-, and plasmin-mediated induction of the MesoMT phenotype exhibited by primary human PMCs. Similar effects were demonstrated through blockade of the NF-κB signaling cascade using two distinctly different NF-κB inhibitors, SN50 and Bay-11 7085. Conversely, expression of constitutively active Akt-induced mesenchymal transition in human PMCs whereas the process was blocked by PX866 and AKT8. Furthermore, thrombin-mediated MesoMT is dependent on PAR-1 expression, which is linked to PI3K/Akt signaling downstream. These are the first studies to demonstrate that PI3K/Akt and/or NF-κB signaling is critical for induction of MesoMT.

Treatment of Antidepressant-Resistant Bulimia with Naltrexone

1987 ◽  
Vol 16 (4) ◽  
pp. 305-309 ◽  
Author(s):  
Jeffrey M. Jonas ◽  
Mark S. Gold
Keyword(s):  
Eating Disorders ◽  
Preliminary Data ◽  
Endogenous Opioids ◽  
Opiate Antagonist ◽  
Percent Reduction ◽  
Bulimic Symptoms ◽  
Long Acting ◽  
Insight Into

Ten individuals with antidepressant-resistant bulimia were treated with the long-acting opiate antagonist naltrexone. Seven of the ten experienced at least a 75 percent reduction of their bulimic symptoms, and have maintained their improvment on three to five month follow-up. These preliminary data suggest that naltrexone may be of use in bulimia unresponsive to standard antidepressant therapy, and may provide insight into the role of endogenous opioids in the etiology of eating disorders.

scholarly journals β-Arrestin-1 expression and epithelial-to-mesenchymal transition in laryngeal carcinoma

2019 ◽  
Vol 34 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Gino Marioni ◽  
Lorenzo Nicolè ◽  
Rocco Cappellesso ◽  
Rosario Marchese-Ragona ◽  
Elena Fasanaro ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Disease Free Survival ◽  
The Novel ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
End Point ◽  
Zeb2 Expression ◽  
E Cadherin

Aim: The novel primary end-point of the present study was to ascertain β-arrestin-1 expression in a cohort of consecutive patients with laryngeal squamous cell carcinoma (LSCC) with information available on their cigarette-smoking habits. A secondary end-point was to conduct a preliminary clinical and pathological investigation into the possible role of β-arrestin-1 in the epithelial-to-mesenchymal transition (EMT), identified by testing for E-cadherin, Zeb1, and Zeb2 expression, in the setting of LSCC. Methods: The expression of β-arrestin-1, E-cadherin, zeb1, and zeb2 was ascertained in 20 consecutive LSCCs. Results: Statistical analysis showed no significant associations between β-arrestin-1 and EMT (based on the expression of E-cadherin, Zeb1, and Zeb2). The combined effect of nicotine and β-arrestin-1 was significantly associated with a shorter disease-free survival ( P=0.01) in our series of LSCC. This latter result was also confirmed in an independent, publicly available LSCC cohort ( P=0.047). Conclusions: Further investigations on larger series (ideally in prospective settings) are needed before we can consider closer follow-up protocols and/or more aggressive treatments for patients with LSCC and a combination of nicotine exposure and β-arrestin-1 positivity in tumor cells at the time of their diagnosis. Further studies on how β-arrestin functions in cancer via different signaling pathways might reveal potential targets for the treatment of even advanced laryngeal malignancies.

scholarly journals Complications and residual pleural thickening after intrapleural instillation of streptokinase with pigtail catheter drainage of tuberculous pleural effusion

2019 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Sandeepa H. S. ◽  
Narendra U. ◽  
Gajanan S. Gaude ◽  
Supriya Sandeepa
Keyword(s):  
Pleural Effusion ◽  
Total Duration ◽  
Control Group ◽  
Study Group ◽  
Pigtail Catheter ◽  
Catheter Drainage ◽  
Female Ratio ◽  
Tuberculous Pleural Effusion ◽  
Pleural Thickening

Background: Tuberculosis is the most common cause of exudative lymphocytic pleural effusion in India. Residual pleural thickening (RPT) is observed in about 50 percent of patients even after proper treatment with ATT. Pleural fluid drainage either with simple aspiration or with intercostal drainage and addition of corticosteroids along with antitubercular drugs have not shown to influence the incidence of RPT. The present study was undertaken to study the complications and residual effects of tubercular pleural effusion on the patients during the follow up period following intrapleural streptokinase instillation.Methods: Clinical profile, hospital course and outcome of tuberculous pleural effusion patients at the end of six months of anti-tubercular treatment of 50 patients from January 2009 to June 2010 were analyzed. These patients were randomly divided into two groups. One group (n=25) received intrapleural streptokinase via pigtail catheter and the other group (n=25) received intercostal drainage without intrapleural streptokinase instillation. All the patients received standard daily anti TB regimen of 2HERZ/4HR for a total duration of six months. All the patients were followed up for a total duration of 1 year for evidence of any residual pleural thickening.Results: Majority of the patients were above 40 years of age (60%). The male to female ratio was 2.3:1. The major symptoms of the patients were, fever in 44 patients (88%), cough in 42 patients (84%), breathlessness in 33 patients (66%), loss of appetite in 25 patients (50%) and chest pain in 25 patients (50%). Most of the patients had ADA levels between 40-70IU/L (48%) and only 6% had ADA levels below 40IU/L. The incidence of residual pleural thickening in the study group was less as compared to the control group (2.36±0.49mm vs 9.28±1.50mm) (p <0.0001).Conclusion: Intrapleural streptokinase instillation with pigtail catheter drainage less number of complications associated with study group and is successful with the decreased incidence of residual pleural thickening during the follow up period.

scholarly journals Exosomes in Lung Cancer: Actors and Heralds of Tumor Development

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4330
Author(s):  
Amaia Sandúa ◽  
Estibaliz Alegre ◽  
Álvaro González
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Epithelial Mesenchymal Transition ◽  
Biological Fluids ◽  
Tumor Development ◽  
Mesenchymal Transition ◽  
Cargo Proteins ◽  
New Biomarkers

Lung cancer is a leading cause of cancer-related death worldwide and in most cases, diagnosis is reached when the tumor has already spread and prognosis is quite poor. For that reason, the research for new biomarkers that could improve early diagnosis and its management is essential. Exosomes are microvesicles actively secreted by cells, especially by tumor cells, hauling molecules that mimic molecules of the producing cells. There are multiple methods for exosome isolation and analysis, although not standardized, and cancer exosomes from biological fluids are especially difficult to study. Exosomes’ cargo proteins, RNA, and DNA participate in the communication between cells, favoring lung cancer development by delivering signals for growth, metastasis, epithelial mesenchymal transition, angiogenesis, immunosuppression and even drug resistance. Exosome analysis can be useful as a type of liquid biopsy in the diagnosis, prognosis and follow-up of lung cancer. In this review, we will discuss recent advances in the role of exosomes in lung cancer and their utility as liquid biopsy, with special attention to isolating methods.

STUDY OF HISTOPATHOLOGICAL SPECTRUM OF LESIONS IN PLUERAL BIOPSY.

2021 ◽  
pp. 12-13
Author(s):  
Siva Chaithanya Bangi ◽  
Vivek Krishna ◽  
Triveni B
Keyword(s):  
Pleural Effusion ◽  
Lung Tumor ◽  
Correct Diagnosis ◽  
Cost Effective ◽  
Limiting Factors ◽  
Pleural Biopsy ◽  
Pleural Diseases ◽  
Pleural Thickening ◽  
Neoplastic Lesions ◽  
A Prospective Study

Pleural diseases, both neoplastic (primary and metastatic) and non-neoplastic, exhibit similar clinical, radiographic and gross features, including pleural pain, pleural-based masses or pleural thickening, and pleural effusions. However, the treatments and prognoses of these diverse conditions vary greatly. As such, accurate diagnosis of pleural disease is critical, and histological interpretation of pleural biopsies is extremely important for correct diagnosis. Methods: A prospective study was conducted in Department of Pathology, Government Chest hospital, Osmania Medical college, Telangana, during March 2019 to March 2020 that evaluated 65 patients with history of pleural effusion, mass involving pleura and pleural thickening. Detailed history, clinical examination, Radiological Imaging along with pleural biopsy with Abram needle was performed in all the 65 Patients. The biopsy specimens were formalin xed and the sections were stained with Hematoxylin and Eosin. Result: The patients aged from 15 to 90 years, average age at presentation was 46.2 yrs. Of total 65 cases 20 were female (31%) and 45(69%) were male. The commonest clinical presentation was shortness of breath with cough. In 65 cases pleural effusion in 58 cases (89%), mass lesion in the lung 6 cases (9%) and pleural thickening 1 case (2%) was preliminary nding on radiology. Histo-pathological evaluation revealed 46 cases (69%) were inammatory lesions. 8cases (12%) were neoplastic lesions and 11(19%) cases were inadequate sampling. Of 46 inammatory lesions 12 cases (26%) were granulomatous lesions. Of 8 neoplastic lesions 1 case (12%) was malignant mesothelioma with calretinin and WT1 positive on Immunohistochemistry. Conclusion: A Pleural Biopsy is a safe, cost effective modality of investigation which not only guides us to diagnosis but also helps in nding out metastatic involvement in a primary Lung tumor. In inammatory lesions it at times aids in differentiating between granulomatous versus non granulomatous when correlated along with the ndings of pleural uid analysis. But lack of expertise in performing the blind procedure and sample inadequacy are some of the limiting factors in having good satisfactory Pleural Biopsy.

scholarly journals Evaluation of Malignant Mesothelioma in Central Anatolia: A Study of 67 Cases

2004 ◽  
Vol 11 (4) ◽  
pp. 287-290 ◽  
Author(s):  
Inci Gulmez ◽  
Levent Kart ◽  
Hakan Buyukoglan ◽  
Ozlem Er ◽  
Suleyman Balkanli ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Malignant Mesothelioma ◽  
Environmental Control ◽  
Public Health Problem ◽  
Central Anatolia ◽  
Major Public Health Problem ◽  
Pleural Thickening ◽  
Chest X Ray ◽  
Fibrous Mineral

BACKROUND:Malignant mesothelioma (MM) is a fatal neoplasm which frequently results from exposure to asbestos or erionite.METHOD:Sixty-seven patients with MM were seen between 1990 and 2001. Their clinical and radiological features, as well as the therapy, were retrospectively evaluated.RESULTS:In 51 patients (76.1%), the MM was confined to the pleura, in 14 patients it was exclusively peritoneal and in two patients, it involved both areas. Of the 67 cases, 35 (52.2%) were women. The mean (± SD) age for all cases was 57.6±11.5 years. Dyspnea (67.2%), cough (55.2%) and chest pain (50.7%) were the most frequent symptoms of onset. Pleural effusion (92.4%) was the most common chest x-ray finding, whereas pleural effusion (60.8%), pleural nodules (34.7%) and pleural thickening (34.7%) were the most common computed tomography findings in pleural MM patients. The histological subtypes of MM were determined as epithelial in 60 patients (89.5%), sarcomatous in four patients (5.9%) and mixed in three patients (4.4%). Although 50.7% and 25.4% of the cases were exposed to erionite and asbestos, respectively, 23.9% of the cases recalled no exposure to asbestos or erionite. Exposures were environmental as opposed to occupational. Thirty-five patients (52.2%) were administered chemotherapy, and follow-up data were available for 22 patients. For these patients, the two-year survival rate was 22% and the two-year progression-free interval was 15.7%. There were no differences between patients with asbestos and erionite exposure.CONCLUSION:MM should be considered when exudative pleural effusion is detected in a patient who has been exposed to asbestos or erionite. MM is a major public health problem in parts of Turkey and compulsory environmental control of fibrous mineral should be considered.

The Role of Pleural Fluid Procalcitonin Level in the Diagnosis of Parapneumonic Pleural Effusion

2012 ◽  
Vol 13 (3) ◽  
pp. 117-121
Author(s):  
Burcu Cirit Kocer ◽  
Aydin Ciledag ◽  
Merda Erdemir Isik ◽  
Aydin Yilmaz ◽  
Selma Firat Guven ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Pleural Fluid ◽  
Procalcitonin Level ◽  
Parapneumonic Pleural Effusion
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