Clinical Value of Vascular Endothelial Growth Factor Combined with Interferon-γ in Diagnosing Malignant Pleural Effusion and Tuberculous Pleural Effusion

In order to investigate the clinical value of vascular endothelial growth factor （VEGF） combined with interferon-γ （IFN-γ） in diagnosing malignant pleural effusion and tuberculous pleural effusion, 42 cases of malignant pleural effusion and 45 cases of tuberculous pleural effusion in Tongji Hospital, from March 2004 to May 2005, were included, The carcinoembryonic antigen （CEA）, VEGF and IFN-γ levels of pleural effusion were detected by using ELISA, and adenosine deaminase （ADA） activity was determined by using enzyme kinetic analytical method. The sensitivity, specificity, accuracy and area under the curve （AUCR^ROC） of CEA and VEGF, VEGF/IFN-γ ratio, ADA and IFN-γ were measured by receiver operating characteristic curve （ROC）, The results showed that CEA, VEGF levels and VEGF/IFN-γ ratio were significantly higher and the ADA and IFN-γ levels were significantly lower in malignant group than those in tuberculous group （P〈0,01）, The sensitivity, specificity, accuracy and AUCR^ROC of VEGF/IFN-γ ratio （88,7%, 99,8%, 94,4%, 0.96 respectively） were higher than those of CEA （67.8%, 96.1%, 82,4%, 0.78 respectively） and VEGF （81,5%, 84,3%, 82.9%, 0.79 respectively）. The sensitivity, specificity, accuracy and AUCR^ROC of IFN-γ （85.7%, 96,4%, 90.9%, 0.94 respectively） were higher than those of ADA （80,2%, 87,6%, 83.8%, 0,81 respectively）. It was concluded that VEGF/IFN-γ ratio and IFN-γ could be used as valuable parameters for the differential diagnosis of malignant pleural effusion and tuberculous pleural effusion.

Th17/Treg Imbalance in Malignant Pleural Effusion

Both T helper IL-17-producing cells （Thl7 cells） and regulatory T cells （Tregs） have been found to be increased in malignant pleural effusion （MPE）. However, the possible imbalance between Thl7 cells and Tregs, as well as the association of.Thl7/Treg and Thl/Th2 cells in MPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th 17 cells in relation to Tregs, as well as Thl/Th2 balance in MPE. The number ofThl7, Tregs, Thl, and Th2 cells in MPE and peripheral blood was determined by using flow cytometry. The relationship among the number of Thl7, Tregs, Thl, and Th2 cells was explored. It was found that the number of Thl7, Tregs, Thl, and Th2 cells was all increased in MPE as compared with the corresponding peripheral blood. The number of Thl7 cells was correlated negatively with Tregs in MPE, but not in blood. Thl7 cells and Thl7/Treg ratio were positively, and Tregs were negatively, correlated with Thl cells, but not with either Th2 cells or Th1/Th2 ratio in MPE. This study supports earlier data that both Thl7 cells and Treg are present at higher frequencies in MPE than in the autologous blood. For the first time, we show that Thl7/Treg imbalance exists in MPE.

Regional hyperthermia combined with intrapleural chemotherapy in patients with malignant pleural effusion

Objective: The aim of our study was to assess the efficacy of regional hyperthermia combined with intrapleural chemotherapy and to evaluate the effect on the immunologic cells and vascular endothelial growth factor (VEGF) in patients with malignant pleural effusion. Methods: The 102 patients with malignant pleural effusion were included in this study: 52 patients undergoing regional hyperthermia with intrapleural chemotherapy (HICT), and 50 patients treated with intrapleural chemotherapy (ICT). Chemotherapy was administered into the thoracic cavity weekly through a tube with CDDP (dose = 40 mg/m2), and hyperthermia was performed twice a week for 60 minutes following the ICT. We evaluated the response rates and side-effects after 4 weeks. Before and after the treatment, T cell subsets and NK cells were detected by flow cytometry and VEGF was measured with ELISA kits. Results: Compared HICT to ICT, the overall response rates of the whole group, breast cancers and lung cancers were 80.8% vs 54% (P < 0.01), 86.7% vs 56.3% (P > 0.05) and 78.4% vs 52.9% (P < 0.05) respectively. The ratios of CD4+, CD4+/CD8+ and NK cells increased and the concentration of VEGF decreased more significantly after HICT. Conclusion: We concluded that combined regional hyperthermia with intrapleural chemotherapy could control the malignant pleural effusion effectively with mild toxicity. The levels of the T cell subset, NK cells and VEGF in both blood and effusion changed obviously.

Study on the Correlation between Syndrome Differentiation of Malignant Pleural Effusion Treated by External Treatment of Traditional Chinese Medicine and Immunohistochemistry of Biopsy Tissue Based on Medical Video-assisted Thoracoscope

Objective:Guided by the theory of syndrome differentiation of yin and yang in traditional Chinese medicine surgery,through visual observation of internal medicine thoracoscope,comprehensive observation of pleural cavity and immunohistochemistry of biopsy tissue,to classify malignant pleural effusion according to syndrome differentiation,and to explore the scientific nature of its theory.Methods:From March 1,2014 to February 28,2015,40 cases of malignant pleural effusion were treated in Beijing Chaoyang Hospital affiliated to Capital Medical University.According to the proposed TCM diagnostic criteria for yin and yang syndrome differentiation,and collect age,gender,course of disease,clinical symptoms,tumor primary focus,histomorphological manifestations and immunohistochemical results and other related information,and carry out statistical data processing.Results:The positive syndrome was mainly metastatic lung adenocarcinoma,which accounted for the majority of all MPE cases,up to 75%.The immunohistochemical results of biopsy tissues were mainly CEA and TTF-1 positive;While pleural effusion caused by pleural mesothelioma was the main type of yin syndrome,and the results of immunohistochemistry combined with biopsy were mainly positive for D2-40,Calretinin,WT-1 and CK5/6.Conclusion:TCM syndrome differentiation of MPE based on internal thoracoscopy combined with biopsy immunohistochemical results has sufficient theoretical basis and certain scientific nature,and further clinical research is needed to verify its effectiveness and practicability in the future.

The diagnostic significance and the assessment of the value of vascular endothelial growth factor as a marker for success of chemical pleurodesis in malignant pleural effusion

Differential diagnosis of pleural effusion is an important issue, since the treatment modalities and prognosis strictly depend on early and correct diagnosis of the underlying etiology. We assessed the efficacy of vascular endothelial growth factor (VEGF) in the differential diagnosis of patients with malignant and non-malignant pleural diseases. And also is assessed of the VEGF as a marker for success of chemical pleurodesis in malignant pleural effusion. Pleural effusions of 40 patients with a mean age of 55 (range, 26 to 78 years) were examined. A total of 20 patients had malignant pleural effusion;malignant mesothelioma (n=7), lung cancer (n=5) and metastatic malignancies (n=8). Twenty patients had benign pleural effusion;fibrinous pleuritis (n=6), tuberculosis (n=3) empyema (n=5), congestive heart failure (n=3), and acute pancreatitis (n=3). Definitive diagnosis was obtained in all cases with blind or open pleural biopsy, and cytological examination. VEGF levels were determined by enzyme-linked immunosorbent assay. The VEGF level of pleural effusion was comparably higher in the malignant group. The mean level of VEGF in patients with malignant pleural effusions (21.7 ± 1.8 ng/ml) was significantly (P <0.001) higher than that of (13.2 ± 1.5 ng/ml) non-malignant effusions. No significant difference was found regarding the VEGF levels and histological types in malignant pleural effusions. Negative correlation was observed between success rate of pleurodesis and VEGF level of pleural effusion (p= 0.015). The measurement of VEGF levels in pleural effusion may be useful to differentiate malignant from nonmalignant pleural effusions. VEGF level may also be an important prognostic marker for effective treatment of the patients who had malignant pleural effusions with pleurodesis. It is important issue in here whether VEGF could be useful in prognostication of outcome of chemical pleurodesis or not.

Management of recurrent malignant pleural effusions with a tunneled indwelling pleural catheter

In this review, we report on the use of indwelling pleural catheters in the treatment of malignant pleural effusions. We describe the most commonly used catheter. Also, treatment with indwelling pleuralcatheters as compared to talc pleurodesis is reviewed. A comparison of efficacy, costs, effects on quality of life, and complications is made. Only one randomized controlled trial comparing the two is available up to date, but several are underway. We conclude that treatment for malignant pleural effusions with indwelling pleural catheters is a save, cost-effective, and patientfriendly method, with low complication rates.

Comparison of intra-pleural injection efficacy between Endostar and Bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor-/anaplastic lymphoma kinase-lung adenocarci

Objective To compare intra-pleural injection efficacy and safety between Endostar and bevacizumab combined with pemetrexed/cisplatin for the treatment of malignant pleural effusion in patients with epidermal growth factor receptor(EGFR)-/anaplastic lymphoma kinase(ALK)-lung adenocarcinoma. Methods Sixty-four pCVatients with EGFR-/ALK-lung adenocarcinoma with malignant pleural effusion(MPE) were admitted to the authors' hospital between January 2016 and June 2017. Patients were randomly divided into two groups: Endostar combined with pemetrexed/cisplatin(Endostar group); and bevacizumab plus pemetrexed/cisplatin(Bevacizumab group). They underwent thoracic puncture and catheterization, and MPE was drained as much as possible. Both groups were treated with pemetrexed 500 mg/m^2, intravenous drip(d1), cisplatin 37.5 mg/m^2 per time, intra-pleural injection(d1, d3). Patients in the Endostar group were treated with Endostar 30 mg per time, intra-pleural injection(d1, 3), and patients in the Bevacizumab group were treated with bevacizumab 5 mg/kg per time, intra-pleural injection(d1). Only one cycle of treatment was applied. MPE was extracted before treatment and on day 7 after treatment. The levels of vascular endothelial growth factor(VEGF) were determined using ELISA. Efficacy and side effects were evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1, and National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) version 3.0 criteria. Results The objective response rates in the Endostar and Bevacizumab groups were 50.0% and 56.3%, respectively; there was no statistical difference between the groups(P > 0.05). After one cycle of treatment, the mean VEGF levels in MPE in both groups decreased significantly, and there was no significant difference in the degree of decline between the two groups(P > 0.05). In both groups, pre-treatment VEGF levels for patients achieving complete response were significantly higher than those for patients achieving stable disease + progressive disease(P < 0.05). No specific side effects were recorded. Conclusion Endostar and Bevacizumab demonstrated similar efficacy in controlling MPE in patients with EGFR-/ALK-lung adenocarcinoma through an anti-angiogenesis pathway, with tolerable side effects. The levels of VEGF in MPE could predict the efficacy of intra-pleural injection of anti-angiogenesis drugs.

Effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion

Objective:To study the effect of intrapleural endostatin and mannatide infusion on malignant molecule expression in pleural fluid of malignant pleural effusion.Methods:Patients with lung cancer and malignant pleural effusion treated in our hospital between April 2013 and December 2015 were selected and randomly divided into two groups, the observation group received intrapleural endostatin and mannatide infusion treatment and control group accepted routine intrapleural infusion treatment. 4 weeks after treatment, the pleural fluid samples were collected to determine the levels of tumor markers, invasion-related molecules, VEGF-related molecules and anti-tumor cytokines.Results:4 weeks after treatment, CEA, CYFRA21-1, NSE, SCC-Ag, CXCL12, CXCR4, MMP2, MMP9, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2 and VEGF-R3 levels in pleural fluid of observation group were significantly lower than those of control group while LASS2/TMSG-1, IFN-γ, IL-2, TNF-α, IL-17 and IL-23 levels were significantly higher than those of control group.Conclusion:Intrapleural endostatin and mannatide infusion treatment of malignant pleural effusion can more effectively kill cancer cells, inhibit cell invasion, angiogenesis and lymphangiogenesis, and enhance antitumor immune response.

Correlation of RCAS1 and Claudin-18 expression with proliferation and invasion gene expression in malignant pleural effusion

Objective: To investigate the correlation of RCAS1 and Claudin-18 expression with proliferation and invasion gene expression in malignant pleural effusion. Methods: A total of 187 patients with primary non-small cell lung cancer complicated by malignant pleural effusion were selected as malignant pleural effusion group and 56 patients with tuberculous pleural effusion were selected as tuberculous pleural effusion group. The expression of RCAS1 and Claudin-18 gene as well as proliferation and invasion-related genes in the pleural effusion were compared between the two groups, and Pearson test was used to evaluate the correlation of RCAS1 and Claudin-18 expression with proliferation and invasion gene expression in malignant pleural effusion. Results: RCAS1 and Claudin-18 mRNA expression in pleural effusion of malignant pleural effusion group were greatly higher than those of tuberculous pleural effusion group. Proliferation genes LRRC3B and TCF21 mRNA expression in pleural effusion of malignant pleural effusion group were lower than those of tuberculous pleural effusion group whereas SIRT1 and EZH2 mRNA expression were higher than those of tuberculous pleural effusion group;invasion genes DDX17, Nectin4, Vav3, NGAL and Snail mRNA expression were higher than those of tuberculous pleural effusion group whereas EFEMP1 and MCPH1 mRNA expression were lower than those of tuberculous pleural effusion group. The Pearson test showed that the RCAS1 and Claudin-18 expression in malignant pleural effusion were directly correlated with the expression of proliferation-related genes and invasion-related genes. Conclusion: RCAS1 and Claudin-18 expression increase abnormally in malignant pleural effusion, the specific expression is directly correlated with tumor cell proliferation and invasion activity, and they can be used as the reliable indicators for the identification of benign or malignant pleural effusion.

Gastric Malrotation Relieved by Pleural Effusion Drainage

Mr M., 55-year-old, with metastatic adenocarcinoma of lung (stage IV) was admitted to the hospital after an earlier visit to oncology, where he presented with abdominal pain and distention suspected of having ascites for the first time. After performing abdominal CT and gastric passage film, it was hypothesized that clinical manifestation was related to gastric malrotation. The latter was forced by the huge left pleural effusion. Draining the pleural effusion may be complicated by a trapped lung, an adverse effect where the lung does not expand post drainage. After considering the palliative therapeutic options the effusion was drained, the stomach recoiled to its anatomical position, gastric malrotation was relieved, and the patient resumed oral nutrition. Though gastric malrotation due to a huge, malignant left pleural effusion is rare, it should be considered as more patients are being treated for lung cancer.

Malignant pleural mesothelioma:The disdained member of thoracic oncology!

Pleural mesothelioma is a very aggressive malignancy that arises from the pleural mesothelial cell lining and is linked strongly to prior asbestos exposure.The ban on asbestos has helped to lower the incidence,but in developing countries like India,it is expected to rise.It has an extended latency period usually progressing over decades and presents with nonspecific symptoms.It has a median survival ranging between 10-22 months.The diagnosis of malignant pleural mesothelioma is challenging and is done using computed tomography(CT),magnetic resonance imaging,or positron emission tomography-CT,with the last two predicting the resectability of the tumor better than CT alone.A pleural biopsy along with an array of immunohistochemical markers,such as p16,BRCA1 associated protein 1,and claudin-4,are required for a definitive diagnosis.Several genetic alterations have prognostic significance as well.The current histological subtype identification is indispensable for decision making because of the new therapeutic avenues being explored.The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes.However,the latter continues to be a robust treatment option for patients with the epithelioid subtype.Surgery is recommended for resectable cases with radiotherapy being indicated in neoadjuvant,adjuvant,and palliative settings along with systemic treatment.This review article provides an overview of epidemiology,etiology,clinical manifestations,diagnostic approaches(including immunohistochemical and genetic markers),staging,and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery,chemotherapy,immunotherapy,and radiotherapy.It also sheds light on some recent studies(EMPHACIS,CALGB30901,Checkmate-743,etc.)that have led to significant developments in recent years with clinically meaningful results.

Interleukin-17 inhibits development of malignant pleural effusion via interleukin-9-dependent mechanism

Th17 and Th9 cells have been demonstrated to possess immune regulatory functions in malignant pleural effusion （MPE）. However, whether IL-17 can affect differentiation and function of Th9 cells in MPE remains unknown. The objective of the present study was to explore the impact of IL-17 on the in vivo differentiation of Th9 cells in relation to Th2 cells in a murine model of MPE, and to explore whether IL-17 inhibits MPE formation via IL-9-dependent mechanism. It was found that Th9 and Th2 cells were decreased in MPE from 1L-17-/- mice as compared with wild type mice. IL-17 deficiency inhibited Th9 and Th2 cell differentiation via suppressing transcription faclLors IRF4 and GATA-3, respectively. IL-17 deficiency enhanced MPE formation by promoting angiogenesis and proliferation of pleurai tumors, and thus accelerated the death of mice bearing MPE. The in vivo administration of anti-IL-9 neutralizing mAb accelerated the death of WT mice; whereas administration of exoge- nous IL-9 improved the survival of IL-17-/- mice. Our data provide the first definitive evidence that IL-17 promotes the differ- entiation of Th9 and Th2 cells in MPE. Our findings also demonstrate that IL-17 inhibits the formation of MPE and improves the survival of mice bearing MPE via an IL-9-dependent mechanism.

Immune Regulation of Interleukin-27 in Malignant Pleural Effusion

Background： lnterlcukin （IL）-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion （MPE） remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon （IFN）-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE. Methods： The distribution ofl L-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions otcytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription （STAT） signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored. Results： The expression of IL-27 was increased in M PE when compared with blood （ 147.3 ± 25. 1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04）. IL-27 was noted to suppress both proliferation （18.33 ±0.21 vs. 27.77 ±0.88, P = 0.0005） and migration （1.82 ±0.44 vs. 3.13 ±0.07, P = 0.04） of A549 cells, but obviously prornoted apoptosis of A549 cells （9.47 ±1.14 vs. 4.96 ±0.17, P = 0.02） by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities ofA549 cells to pleural mesothelial cell monolayer by activating different STAT signalings. Conelusions： IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.

Clinical Observation on the Efficacy of Xiaoshui Decoction (消水方) Combined with Intrapleural Perfusion of Cisplatin in Treating Malignant Pleural Effusion

Objective： To observe the clinical efficacy of Xiaoshui decoction （XSD,消水方） combined with intrapleural perfusion of cisplatin in the treatment of malignant pleural effusion. Methods： Fifty-one patients with malignant pleural effusion were randomly assigned to two groups. The treated group patients） received oral administration of XSD combined with intrapleural perfusion of cisplatin, and control group （25 patients） was only treated with intrapleural perfusion of cisplatin. The effects of 26 he he short-term efficacy, quality of life scores and clinical symptom scores of malignant pleural effusion were evaluated. Results： The short-term efficacy in the treated group and the control group was 72.0% and 58.3%, respectively, and no significant difference was found （P〉0.05）. In contrast, the quality of life in the treated group was significantly improved compared to that of the control group （P〈0.05）, and so was the symptom remission （P〈0.05）. Conclusions： The combined therapy of XSD and intrapleural perfusion of cisplatin did not show obvious improvement in short-term efficacy, but the therapy remarkably alleviated the symptoms and improved the quality of life of patients.

Soluble CD40 in plasma and malignant pleural effusion with non-small cell lung cancer:A potential marker of prognosis

Objective: Soluble CD40 (sCD40) is a potential modulator for both antitumor responses and CD40-based immunotherapy;however the levels and significance of sCD40 in non-small cell lung cancer (NSCLC) patients with malignant pleural effusion are unknown. Methods: Forty-eight patients with lung cancer were treated in our institutions from January 2008 to January 2010. Peripheral blood and pleural effusion samples were collected from each subject. sCD40 levels in plasma and malignant pleural effusions supernatant were measured. The CD40L expression on CD3t T-cells was confirmed by flow cytometric direct immunofluorescence analysis. All patients were followed up after the study ended on January 1, 2010. Results: Patients with malignant pleural effusion of NSCLC had elevated circulating and pleural effusion levels of sCD40, and these elevated sCD40 levels were associated with advanced diseases and a poor prognosis. Conclusions: These findings indicate that elevated sCD40 may have a role in modulating antitumor responses and may also be a useful prognostic marker. Copyright ? 2015, Chinese Medical Association Production. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

A STUDY OF THE CYTOTOXICITY OF MALIGNANT PLEURAL EFFUSION LYMPHOCYTES AND LAK CELLS AGAINST AUTOLOGOUS TUMOR CELLS

The cytotoxicity of malignant pleural effusion lymphocytes (MPEL) against autologous tumor cells (ATC) were compared with that of peripheral blood lymphocytes (PBL). It was demonstracted that the cytotoxicity of PBL was higher than that of MPEL (P< 0.001), but the cytotoxicity and expansion of MPEL-activated by rIL-2 was much higher than that of PBL activated by rIL-2 (LAK cells) (P< 0.001). This shows that local immune reaction of the pleural cavity of patients with malignant pleural effusion was in the state of suppression. MPEL activated are better effector cells than LAK cells in tumor adoptive immunotherapy.

Meta Analysis of Lentinan Injection plus Cisplatin in Treatment of Malignant Pleural Effusion

Objective To evaluate the efficacy and safety of lentinan injection plus cisplatin(LIC)in the treatment of malignant pleural effusion(MPE).Methods We searched the database of Cochrane Library,PubMed,EMBASE, ISI Web of Knowledge,Chinese Biomedical Literature Database,Chinese Scientific Journals Full-text Database, Chinese Journal Full-text,and Google Scholar,etc.,up to February 28th,2011 to identify randomized controlled trials(RCTs)about lentinan injection(LI)for MPE,evaluate the quality of the included studies,and analyze the data by Cochrane Collaboration’s RevMan5.0 software.Results Twenty-nine RCTs involving 1831 patients were included.Meta analysis results suggested that there were some differences when comparing LIC with control groups suffering from MPE,for LIC could improve the near-term curative effect and the quality of life to some extent. Besides,compared with chemotherapy alone,LI plus chemotherapy had an advantage in relieving adverse reactions, such as gastrointestinal reactions,myelosuppression,chest pain,and general malaise.Conclusion The current evidence indicates that LI may have adjuvant therapeutic effects for MPE.

Low-Frequency Sonophoresis of Chinese Medicine Formula Improves Efficacy of Malignant Pleural Effusion Treatment

Objective:To evaluate whether low-frequency ultrasound-facilitated transdermal delivery of a Chinese medicine(CM)formula could improve the efficacy of intrapleural administration of interleukin?2(IL-2)in treatment of malignant pleural effusion(MPE).Methods:A total of 110 eligible participants were randomized into the low-frequency sonophoresis(LFS)of CM(LSF/CM)group(55 cases)and the control group(55 cases)by simple randomization using a random number table.The control group was treated with an intrapleural administration of IL-2;and the LFS/CM group was treated with LFS of a CM gel formulation,combined with the same IL-2 injection as in the control group.The CM formula consisted of Semen Lepidii,Semen Sinapis,Flamulus Cinnamomi,Poriacocos,Herba Lycopi,and Radix Paeoniae Rubra.After 2-week treatment,the therapeutic outcome was determined by the change of the amount of MPE,which was evaluated by B-scan ultrasound and/or chest X-ray,and the change of quality of life(QOL)scores,which were evaluated by the Eastern Cooperative Oncology Group(ECOG)performance status.Results:A significantly higher objective remission rate(ORR)was obtained with intrapleural IL-2 plus LFS/CM than IL-2 treatment alone(P=0.049).In addition,more patients in the LFS/CM group than in the control group had an improved QOL score(P=0.048),and no patients in the LFS/CM group had a reduced QOL.Conclusion:LFS of CM formulation could effectively alleviate MPE and improve the QOL of cancer patients.

Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels

Background:Malignant pleural effusion(MPE)is a complicated condition of patients with advanced tumors.Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression.Methods:The possible involvement of microRNAs(miRNAs)in malignant pleural fluid was investigated using small RNA sequencing.Regulatory T cell(Treg)markers(CD4,CD25,forkhead box P3),and Helios(also known as IKAROS Family Zinc Finger 2[IKZF2])were detected using flow cytometry.The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction.The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays.The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system.Correlation assays between miR-4772-3p and functional molecules of Tregs were performed.Results:Compared with non-malignant controls,patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells.The verified downregulation of miR-4772-3p was inversely related to the Helios*Tregs frequency and Helios expression in the MPE.Overexpression of miR-4772-3p could inhib让Helios expression in in vitro experiments.However,ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression.Additionally,miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA.Conclusion:Downregulation of miR-4772-3p,by targeting Helios,contributes to enhanced Tregs activities in the MPE microenvironment.

Clinical Value of Tumor Markers for Determining Cause of Pleural Effusion

Background： It is often challenging to distinguish tuberculous pleural effusion （TPE） from malignant pleural effusion （MPE）;thoracoscopy is among the techniques with the highest diagnostic ability in this regard.However, such invasive examinations cannot be performed on the elderly, or on those in poor physical condition.The aim of this study was to explore the differential diagnostic value of carbohydrate antigen 125 （CA 125）, carbohydrate antigen 199 （CA 199）, carcinoembryonic antigen （CEA）, neuron-specific enolase （NS E）, and squamous cell carcinoma （SCC） associated antigen in patients with TPE and MPE.Methods： Using electrochemiluminescence, we measured the concentration of tumor markers （TMs） in the pleural effusion and serum of patients with TPE （n =35） and MPE （n =95）.We used receiver operating characteristic （ROC） curve analysis to evaluate the TMs and differentiate between TPE and MPE.Results： The cut-offvalues for each TM in serum were： CA125, 151.55 U/ml;CA199, 9.88 U/ml;CEA, 3.50 ng/ml;NSE, 13.27 ng/ml;and SCC, 0.85 ng/ml.Those in pleural fluid were： CA125, 644.30 U/ml;CA199, 12.08 U/ml;CEA, 3.35 ng/ml;NSE, 9.71 ng/ml;and SCC, 1.35 ng/ml.The cut-offvalues for the ratio ofpleural fluid concentration to serum concentration （P/S ratio） of each TM were： CA125, 5.93;CA199, 0.80;CEA, 1.47;NSE, 0.76;and SCC, 0.90.The P/S ratio showed the highest specificity in the case of CEA （97.14%）.ROC curve analysis revealed that, for all TMs, the area under the curve in pleural fluid （0.95） was significantly different from that in serum （0.85;P 〈 0.001）.Conclusions： TMs in TPE differ significantly from those in MPE, especially when detected in pleural fluid.The combined detection of TMs can improve diagnostic sensitivity.