Discovery of a novel linc01125 isoform in serum exosomes as a promising biomarker for NSCLC diagnosis and survival assessment

2021 ◽  
Author(s):  
Jianfeng Xian ◽  
Yuyuan Zeng ◽  
Shizhen Chen ◽  
Liming Lu ◽  
Li Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Area Under The Curve ◽  
Lung Cancer Patients ◽  
Non Invasive ◽  
Invasive Method ◽  
Highly Correlated ◽  
Nsclc Patients ◽  
Serum Exosomes

Abstract A non-invasive method to distinguish potential lung cancer patients would improve lung cancer prevention. We employed the RNA-Seq analysis to profile serum exosomal long non-coding RNAs (lncRNAs) from non-small cell lung cancer (NSCLC) patients and pneumonia controls, and then determined the diagnostic and prognostic value of a promising lncRNA in four datasets. We identified 90 dysregulated lncRNAs for NSCLC and found the most significant lncRNA was a novel isoform of linc01125. Serum exosomal linc01125 could distinguish NSCLC cases from disease-free and tuberculosis controls, with the area under the curve (AUC) values as 0.662 (95% confidence interval [CI]= 0.614-0.711) and 0.624 (95%CI= 0.522–0.725), respectively. High expression of exosomal linc01125 was also correlated with an unfavorable overall survival of NSCLC (hazard ratio [HR] = 1.58, 95%CI = 1.01–2.49). Clinic treatment decreased serum exosomal linc01125 in NSCLC patients (P = 0.036). Linc01125 functions to inhibit cancer growth and metastasis via acting as a competing endogenous RNA to up-regulate TNFAIP3 expression by sponging miR-19b-3p. Notably, the oncogenic transformation of 16HBE leads to decreased linc01125 in cells but increased linc01125 in cell-derived exosomes. The expression of linc01125 in total exosomes was highly correlated with that in tumor-associated exosomes in serum. Moreover, lung cancer cells were capable of releasing linc01125 into exosomes in vitro and in vivo. Our analyses suggest serum exosomal linc01125 as a promising biomarker for non-invasively diagnosing NSCLC and predicting the prognosis of NSCLC.

scholarly journals Phosphorylation of CAP1 regulates lung cancer proliferation, migration, and invasion

2021 ◽  
Author(s):  
Jie Zeng ◽  
Xuan Li ◽  
Long Liang ◽  
Hongxia Duan ◽  
Shuanshuan Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Cancer Proliferation ◽  
Mesenchymal Transition ◽  
Lung Cancer Patients ◽  
Nsclc Patients

Abstract Purpose Cyclase-associated protein 1 (CAP1) is a ubiquitous protein which regulates actin dynamics. Previous studies have shown that S308 and S310 are the two major phosphorylated sites in human CAP1. In the present study, we aimed to investigate the role of CAP1 phosphorylation in lung cancer. Methods Massive bioinformatics analysis was applied to determine CAP1’s role in different cancers and especially in lung cancer. Lung cancer patients’ serum and tissue were collected and analyzed in consideration of clinical background. CAP1 shRNA-lentivirus and siRNA were applied to CAP1 gene knockdown, and plasmids were constructed for CAP1 phosphorylation and de-phosphorylation. Microarray analysis was used for CAP1-associated difference analysis. Both in vitro and in vivo experiments were performed to investigate the roles of CAP1 phosphorylation and de-phosphorylation in lung cancer A549 cells. Results CAP1 is a kind of cancer-related protein. Its mRNA was overexpressed in most types of cancer tissues when compared with normal tissues. CAP1 high expression correlated with poor prognosis. Our results showed that serum CAP1 protein concentrations were significantly upregulated in non-small cell lung cancer (NSCLC) patients when compared with the healthy control group, higher serum CAP1 protein concentration correlated with shorter overall survival (OS) in NSCLC patients, and higher pCAP1 and CAP1 protein level were observed in lung cancer patients’ tumor tissue compared with adjacent normal tissue. Knockdown CAP1 in A549 cells can inhibit proliferation and migration, and the effect is validated in H1975 cells. It can also lead to an increase ratio of F-actin/G-actin. In addition, phosphorylated S308 and S310 in CAP1 promoted lung cancer cell proliferation, migration, and metastasis both in vitro and in vivo. When de-phosphorylated, these two sites in CAP1 showed the opposite effect. Phosphorylation of CAP1 can promote epithelial–mesenchymal transition (EMT). Conclusion These findings indicated that CAP1 phosphorylation can promote lung cancer proliferation, migration, and invasion. Phosphorylation sites of CAP1 might be a novel target for lung cancer treatment.

scholarly journals USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription

2021 ◽  
Author(s):  
Xiaohua Jie ◽  
William Pat Fong ◽  
Rui Zhou ◽  
Ye Zhao ◽  
Yingchao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Affinity Purification ◽  
Smad Signaling ◽  
Lung Cancer Patients ◽  
Lysine Specific Demethylase ◽  
Underlying Mechanisms ◽  
H3k9me3 Level ◽  
Critical Binding

AbstractRadioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.

Effect of Octreotide on Neuroenolase Levels in Patients with Small Cell Lung Cancer

1994 ◽  
Vol 80 (5) ◽  
pp. 332-334 ◽  
Author(s):  
Enzo Soresi ◽  
Giovanni Invernizzi ◽  
Roberto Boffi ◽  
Umberto Borghini ◽  
Gianfranco Schiraldi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Serum Levels ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Octreotide Treatment

Aims and Background The somatostatin analog octreotide has an antiproliferative effect on small cell lung cancer lines in vitro and in experimental xenograft transplantation systems in vivo. Thus it is worth investigating octreotide activity in the clinical setting. Methods We studied the effect of octreotide (200 μg three times a day subcutaneously for seven days) on serum levels of the tumor marker neuroenolase in 13 patients with small cell lung cancer. Results A decrease in neuroenolase levels was observed at day 7 during octreotide treatment, with a mean ± SD of 32.6 ± 42.0 ng/ml compared to basal values of 44.4 ± 57.7 ng/ml and to washout values of 50.3 ± 65.7 ng/ml ( P < 0.03). Conclusions Our results indicate that octreotide is effective in reducing neuroenolase levels in small cell lung cancer patients. These data suggest a possible role for octreotide in the treatment of this kind of tumor.

Design of an Ingestible Capsule With Wireless Communication and Powering Function for Obesity Treating

2013 ◽  
Author(s):  
Liang Yan ◽  
Tianyi Wang ◽  
Zongxia Jiao ◽  
Juanjuan Peng
Keyword(s):  
Morbid Obesity ◽  
Wireless Communication ◽  
In Vitro Experiments ◽  
Non Invasive ◽  
Removal Process ◽  
Wireless Control ◽  
Invasive Method ◽  
Energy Shortage

Intra-gastric balloons have been and effective and non-invasive method for morbid obesity treating since it is proposed. However, traditional balloons lead to complications such as nausea and sickness caused by insertion and removal endoscopes. Despite free of endoscope-guide insertion and removal process, wireless controlled balloons still have to face the problem of energy shortage. This paper proposes a novel wireless controlled and powered endoscope capsule of edible size. The performance of wireless control and powering are tested respectively. In addition, in-vivo and in-vitro experiments are conducted for further evaluation and shows feasibility for treating morbid obesity. This study may contribute to the development of endoscopic devices and surgery as well.

scholarly journals Epigenetic control of INSL4 promotes cell growth and invasiveness in Non-Small-Cell Lung Cancer

2020 ◽  
Author(s):  
Damiano Scopetti ◽  
Danilo Piobbico ◽  
Cinzia Brunacci ◽  
Stefania Pieroni ◽  
Guido Bellezza ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Relaxin Family ◽  
Nsclc Patients

Abstract Background Non-Small Cell Lung Cancer accounts for 80–85% of all forms of Lung Cancer as leading cause of cancer-related death in human. Despite remarkable advances in the diagnosis and therapy of Lung Cancer, no significant improvements have thus far been achieved in terms of patients’ prognosis. Here, we investigated the role of INSL4 – a member of the relaxin family –in NSCLC.Methods We permanently overexpressed INSL4 in NSCLC cells in vitro to analyse the growth rate and the tumourigenic features. We further investigated the signalling pathways engaged in INSL4 overexpressing cells and the tumour growth ability by studying the tumour development in a patient derived tumour xenograft mouse model. Results We found a cell growth promoting effect by INSL4 overexpression in vitro in H1299 cells and in vivo in NOD/SCID mice. Surprisingly, in NSCLC-A549 cells, stable INSL4 overexpression has not showed similar effect, despite has an INSL4-mRNA expressed up to 22.000 fold more respect H1299. The INSL4-mRNA analysis of eight different NSCLC-derived cell lines, has revealed a great discrepancy between the amount of INSL4-mRNA and specific protein. Notably, similar result has been observed in studied NSCLC patients analysing and comparing INSL4 mRNA and protein expression. However, in a cohort of NSCLC patients, we found a significant inverse correlation between INSL4 expression and Overall Survival.Conclusions By combining the results from the in vitro and in vivo models and in silico analysis in patients whose NSCLCs adenocarcinoma spontaneously expressed high levels of INSL4 our results suggest that epigenetic modifications that affect INSL4 does not allow to assess precision therapy in selected patients without consider protein INSL4 amount.

scholarly journals High Level of Staufen1 Expression Confers Longer Recurrence Free Survival to Non-Small Cell Lung Cancer Patients by Promoting THBS1 mRNA Degradation

2021 ◽  
Vol 23 (1) ◽  
pp. 215
Author(s):  
Florence Bonnet-Magnaval ◽  
Leïla Halidou Diallo ◽  
Valérie Brunchault ◽  
Nathalie Laugero ◽  
Florent Morfoisse ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Adhesion ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Rna Binding ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Lung Cancer Patients

Stau1 is a pluripotent RNA-binding protein that is responsible for the post-transcriptional regulation of a multitude of transcripts. Here, we observed that lung cancer patients with a high Stau1 expression have a longer recurrence free survival. Strikingly, Stau1 did not impair cell proliferation in vitro, but rather cell migration and cell adhesion. In vivo, Stau1 depletion favored tumor progression and metastases development. In addition, Stau1 depletion strongly impaired vessel maturation. Among a panel of candidate genes, we specifically identified the mRNA encoding the cell adhesion molecule Thrombospondin 1 (THBS1) as a new target for Staufen-mediated mRNA decay. Altogether, our results suggest that regulation of THBS1 expression by Stau1 may be a key process involved in lung cancer progression.

In-Vivo Force Estimation of the Anterior Cruciate Ligament

2009 ◽  
Author(s):  
Ali Hosseini ◽  
Thomas J. Gill ◽  
Guoan Li
Keyword(s):  
Anterior Cruciate Ligament ◽  
Cruciate Ligament ◽  
Acl Injury ◽  
Force Estimation ◽  
Non Invasive ◽  
Injury Mechanisms ◽  
Invasive Method ◽  
Anterior Cruciate

The knowledge of in-vivo ACL forces is instrumental for understanding ACL injury mechanisms and for improving surgical ACL reconstruction techniques. Several in-vitro investigations have measured ACL forces in response to various loads applied to the knee. However, in-vivo ACL forces in response to controlled loading are still unknown. The objective of this study was to estimate the force of healthy ACL as well as the possible upper bound of ACL forces under an increasing axial tibial loading in living subjects using a non-invasive method.

Abstract 515: Non-invasive Method of Generating Human Induced-mesenchymal Stem Cells Derived From Urinary Epithelial Cells for Regenerative Therapy

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Narasimman Gurusamy ◽  
SHEEJA RAJASINGH ◽  
Vijay Selvam ◽  
Vinoth Sigamani ◽  
Jayavardini Vasanthan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Adult Stem Cells ◽  
Regenerative Therapy ◽  
Non Invasive ◽  
Proliferation Capacity ◽  
Invasive Method

Introduction: Mesenchymal stem cells (MSCs) are multipotent adult stem cells having an extensive proliferation capacity in vitro and in vivo. These MSCs can differentiate into various mesoderm-type cells such as osteoblasts, cardiomyocytes, etc. A subpopulation of urinary epithelial cells (UECs) have been identified in urine samples, is considered a promising cell resource for generating autologous induced-pluripotent stem cells (iPSCs). Hypothesis: We hypothesize that the production of high quality, autologous, induced-MSCs (iMSCs) with high replicative potential suitable for the regenerative therapy, using an easy, and the most non-invasive method of isolation, from human UECs. Methods and Results: Human urine was collected and centrifuged to obtain the UECs, which were characterized by the expression of CK19 and ZO1. These UECs were reprogrammed to iPSCs using a cocktail of mRNAs (OCT4, KLF4, SOX2, c-MYC, Nanog and Lin28) along with Lipofectamine for 11 days in culture. These iPSCs were characterized by the expression of the pluripotent markers such as OCT4, SOX2 and SSEA4. The iPSCs were subsequently differentiated into iMSCs using the mesenchymal specific medium for 21 days. iMSCs were harvested at the end of 21 days, and they were characterized by the high levels of mRNA and protein expressions of mesenchymal specific markers such as CD73, CD90 and CD105 (Fig. 1A). FACS analysis showed that more than 93% of the cells were positive for the markers of MSCs (Fig. 1B) . Moreover, the obtained iMSCs have high proliferation capacity compared with the adult stem cells. Conclusions: We have developed an easy, non-invasive method for obtaining autologous, non-immunogenic and highly-proliferating iMSCs suitable for various regenerative therapies including cardiac diseases, from urinary epithelial cells.

Diameter and Pulsatile Oscillations of the Femoral Artery Recorded by Ultrasound

1984 ◽  
Vol 25 (4) ◽  
pp. 313-316 ◽  
Author(s):  
T. Christensen ◽  
J. Jørgensen ◽  
B. Neubauer
Keyword(s):  
Arterial Wall ◽  
External Iliac Artery ◽  
Non Invasive ◽  
Time Motion ◽  
Invasive Method ◽  
Inner Diameter ◽  
In Vitro Examination

A new non-invasive method for in vivo investigations of the inner diameter and pulsatile oscillations of large muscular arteries by means of an ultrasound time-motion technique is presented. Each histologic layer of the arterial wall is identified at in vitro examination of the external iliac artery. The method has been used for in vivo investigations of 16 long term diabetics and of 16 non-diabetics. A reduction of the lumen and decrement in pulse deflections were found in the diabetics when compared with those of the normal group.

Evaluation of a Non-Invasive Method for the Measurement of Metabolic rate in Humans

1985 ◽  
Vol 69 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Charles Weissman ◽  
Michael C. Damask ◽  
Jeffrey Askanazi ◽  
Stanley H. Rosenbaum ◽  
John M. Kinney
Keyword(s):  
Carbon Dioxide Production ◽  
Nutritional Management ◽  
Clinical Measurement ◽  
Non Invasive ◽  
Pathological Conditions ◽  
Invasive Method ◽  
Metabolic Measurement ◽  
Predicted Values

1. Measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) can be used to calculate energy expenditure. Such data are useful in the nutritional management of a variety of pathological conditions. 2. This study is an evaluation in vitro and in vivo of the mating of a canopy and a Beckman metabolic measurement cart 1 (MMC). The canopy allows for the collection of expired gases without facial attachments. 3. Studies in vitro demonstrated the necessity of calibrating the CO2 analyser at the concentrations used in such a system (0.50-0.80% CO2). Measurements of Vo2 were within +12% to −8% of predicted values, and when calibrated at 0.50% and 0.75% CO2, measurements of Vco2 were within +2% and −7% of predicted values. 4. The studies in vivo revealed that VO2 and Vco2 were within ± 11% of the values obtained by using a canopy-spirometer-computer system. 5. The MMC plus canopy may provide an alternative method for the clinical measurement of Vo2 and Vco2, especially in subjects unable to tolerate a tight-fitting mask for prolonged periods.

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