scholarly journals Extracellular matrix alterations in low-grade lung adenocarcinoma compared with normal lung tissue by imaging mass spectrometry

2020 ◽  
Vol 55 (4) ◽  
pp. e4450 ◽  
Author(s):  
Peggi M. Angel ◽  
Evelyn Bruner ◽  
Jennifer Bethard ◽  
Cassandra L. Clift ◽  
Lauren Ball ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Extracellular Matrix ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Imaging Mass Spectrometry ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Low Grade

Micro-RNA signature differences in lung adenocarcinoma with specific driver alterations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11066-11066
Author(s):  
Lorenza Landi ◽  
Pierluigi Gasparini ◽  
Stefania Carasi ◽  
Carmelo Tibaldi ◽  
Luciano Cascione ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Kras Mutation ◽  
Triple Negative ◽  
Egfr Mutation ◽  
Differential Expression Analysis ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Expression Levels

11066 Background: Oncogenic driving alterations define types of lung adenocarcinoma with different prognosis and sensitivity to targeted agents. MicroRNAs (miRNAs) are a new class of non-coding RNAs involved in gene expression regulation. How miRNAs are dysregulated in lung cancer with ALK translocation, EGFR or KRAS mutation is unknown. In this study we aimed to identify miRNA signatures according to the presence of specific driver and to correlate miRNAs deregulation with patient outcome. Methods: The study was conducted in a cohort of 70 lung cancer patients (pts) including 18 ALK+ tumors, 11 ALK-/EGFR mutation+, 15 ALK-/KRAS mutation+, 26 ALK-/EGFR and KRAS wild-type and defined as triple negative. Matched normal lung tissue from 18 cases representative of the entire cohort were also included onto the analysis. RNA was isolated from formalin-fixed paraffin-embedded tissue (FFPE), using the Recover ALL kit (Ambion). NanoString nCounter system platform was used to generate the miRNA profile. We used Limma to test for differential expression analysis of data. The miR-515 family expression between tissues was validated by RT-qPCRs, analyzed using the parametric t-test (unpaired, 2-tailed for validation). Results: miRNA expression profile clusters distinctly ALK+ pts from ALK- and normal lung tissue. Within the ALK- group we found specific miRNAs subsets able to sub-stratify KRAS versus EGFR careers clustering sharply triple negative versus EGFR mutation+ and triple negative versus KRAS mutation+. miRNAs belonging to the miR-515 family seems to be the most deregulated in the ALK+ versus ALK-. Although their expression is stably high in normal tissues and ALK+ class, they are highly downregulated in KRAS mutated versus EGFR mutated and versus triple negative (p-value <0.001 for all comparisons). Conclusions: miRNAs profile significantly differs in pts with ALK translocation, EGFR mutations and KRAS mutations. Analysis of miR-515 family members is ongoing in order to correlate their expression levels with pts’ outcome. In vitro modulation of miR-515 family expression levels, together with drugs treatment are ongoing in order to find possible chemo-resistance/chemo-sensitivity miRNA dependent, in ALK+ and ALK- model.

scholarly journals Intratumoural heterogeneity and immune modulation in lung adenocarcinoma of female smokers and never smokers

2021 ◽  
Author(s):  
Timo Benedikt Trefzer ◽  
Marc A. Schneider ◽  
Katharina Jechow ◽  
Lorenz Robert Chua ◽  
Thomas Muley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Significant Proportion ◽  
Cellular Heterogeneity ◽  
Tobacco Smoke Exposure ◽  
Smoking History ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Never Smokers

Lung cancer is still the leading cause of cancer death worldwide despite declining smoking prevalence in industrialised countries. Although lung cancer is highly associated with smoking status, a significant proportion of lung cancer cases develop in patients who never smoked, with an observable bias towards female never smokers. A better understanding of lung cancer heterogeneity and immune system involvement during tumour evolution and progression in never smokers is therefore highly warranted. We employed single nucleus transcriptomics of surgical lung adenocarcinoma (LADC) and normal lung tissue samples from patients with or without smoking history. Immune cells as well as fibroblasts and endothelial cells respond to tobacco smoke exposure by inducing a highly inflammatory state in normal lung tissue. In the presence of LADC, we identified differentially expressed transcriptional programmes in macrophages and cancer-associated fibroblasts, providing insight into how the niche favours tumour progression. Within tumours, we distinguished eight subpopulations of neoplastic cells in female smokers and never smokers. Through pseudotemporal ordering, we inferred a trajectory towards two differentiated tumour cell states implicated in cancer progression and invasiveness. A proliferating cell population sustaining tumour growth exhibits differential immune modulating signatures in both patient groups. Our results resolve cellular heterogeneity and immune interactions in LADC, with a special emphasis on female never smokers and implications for the design of therapeutic approaches.

scholarly journals The effect of miR-496 on eIF3h in lung invasive adenocarcinoma

2021 ◽  
Author(s):  
Ji-Chun
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Invasive Adenocarcinoma ◽  
Tissue Samples ◽  
Node Metastasis ◽  
Low Expression

This study explores the correlation between microRNA-496 (miR-496) expression and eukaryotic translation initiation factor 3H (eIF3h) expression in lung invasive adenocarcinoma. A total of 71 patients with lung adenocarcinoma were included in the study. The tumor tissue samples were collected together with the normal lung tissue samples that were acquired more than 2 cm away from the edge of the tumor). Expression of miR-496 was detected using real-time fluorescence quantitative PCR. Expression of Ki67 and Bcl-2 in lung adenocarcinoma was detected with Western blotting, and expression of eIF3hwas detected with immunohistochemistry. Expression of miR-496 was significantly lower in the tumor than in normal lung tissue (P<0.05). miR-496 expression was significantly decreased in the tumor samples from the patients with large tumor maximum diameter, pleural recidivism, lymph node metastasis, and TNM stage III + IV, compared to the samples from the patients with small tumor diameter, no pleural recidivism, no lymph node metastasis, and TNM stage I + II (P<0.05). No significant difference in miR-496 expression was identified among the groups of different sex, age, and tumor differentiation degree (P>0.05). Low expression of miR-496 correlated with a shorter survival time of the patients (P<0.05). Moreover, miR-496 expression was negatively correlated with Ki67, Bcl-2 and eIF3h expression. We speculate that and miR-496 has the potential to regulates eIF3h expression, and low expression of miR-496 in lung adenocarcinoma may be related to the occurrence and development of the tumor. Mir-496 may be an independent prognostic factor in lung adenocarcinoma.

Lactate dehydrogenase in human maxillary adenocarcinoma and in experimental adenocarcinoma in mice

1985 ◽  
Vol 99 (2) ◽  
pp. 171-175 ◽  
Author(s):  
Wiesław Gołabek ◽  
Leonard M. Franks
Keyword(s):  
Lactate Dehydrogenase ◽  
Lung Adenocarcinoma ◽  
Lung Tissue ◽  
Isoenzyme Pattern ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Ldh Activity ◽  
Ldh Isoenzyme ◽  
Human Tumours

Total lactate dehydrogenase (LDH) activity and isoenzyme pattern were studied in tumore tissue from eight patients with maxillary adenocarcinoma, chronic inflammatory mucosa from 12 patients, normal maxillary mucosa from 12 patients, and an experimental lung adenocarcinoma and normal lung tissue from 12 mice.An increase in the total LDH activity and cathodic shift in LDH isoenzyme pattern was found in human maxillary adenocarcinoma as compared to normal and inflammatory mucosa. The inflammatory mucosa showed an increase in the total LDH activity and a normal isoenzyme pattern. The LDH alterations in the total LDH activity and a normal isoenzyme pattern. The LDH alterations in the experimental lung adenocarcinoma in mice were similar to those in the human tumours but they were much more marked.

scholarly journals Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-β responsiveness

2012 ◽  
Vol 303 (3) ◽  
pp. L169-L180 ◽  
Author(s):  
Aleksandar Marinković ◽  
Justin D. Mih ◽  
Jin-Ah Park ◽  
Fei Liu ◽  
Daniel J. Tschumperlin
Keyword(s):  
Extracellular Matrix ◽  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Pivotal Role ◽  
Lung Fibroblasts ◽  
Normal Lung Tissue ◽  
Fluorescent Label ◽  
Normal Lung ◽  
Tgf Β1 ◽  
Traction Microscopy

Lung fibroblast functions such as matrix remodeling and activation of latent transforming growth factor-β1 (TGF-β1) are associated with expression of the myofibroblast phenotype and are directly linked to fibroblast capacity to generate force and deform the extracellular matrix. However, the study of fibroblast force-generating capacities through methods such as traction force microscopy is hindered by low throughput and time-consuming procedures. In this study, we improved at the detail level methods for higher-throughput traction measurements on polyacrylamide hydrogels using gel-surface-bound fluorescent beads to permit autofocusing and automated displacement mapping, and transduction of fibroblasts with a fluorescent label to streamline cell boundary identification. Together these advances substantially improve the throughput of traction microscopy and allow us to efficiently compute the forces exerted by lung fibroblasts on substrates spanning the stiffness range present in normal and fibrotic lung tissue. Our results reveal that lung fibroblasts dramatically alter the forces they transmit to the extracellular matrix as its stiffness changes, with very low forces generated on matrices as compliant as normal lung tissue. Moreover, exogenous TGF-β1 selectively accentuates tractions on stiff matrices, mimicking fibrotic lung, but not on physiological stiffness matrices, despite equivalent changes in Smad2/3 activation. Taken together, these results demonstrate a pivotal role for matrix mechanical properties in regulating baseline and TGF-β1-stimulated contraction of lung fibroblasts and suggest that stiff fibrotic lung tissue may promote myofibroblast activation through contractility-driven events, whereas normal lung tissue compliance may protect against such feedback amplification of fibroblast activation.

scholarly journals Analysis of the Expression and Clinical Significance of VIPR1 in Lung Adenocarcinoma Based on TCGA Database

2021 ◽  
Author(s):  
Xiaobo Li ◽  
Yunfei Wang ◽  
Xiaowan Wei ◽  
Guojun Zhang ◽  
Huaqi Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Clinical Significance ◽  
Lung Tissue ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Clinical Prognosis ◽  
Expression Levels

Abstract Background: The expression of VIPR1 is associated with the prognosis of many malignant tumors. To analyze the expression and clinical significance of vasoactive intestinal peptide Types I (VIPR1) in lung adenocarcinoma based on The Cancer Genome Atlas (TCGA)database. Methods and results：The RNASeq data, clinical data and prognosis data of lung adenocarcinoma and normal lung tissue were downloaded from TCGA database. The expression difference of VIPR1 mRNA in lung adenocarcinoma and normal lung tissue（p<0.05）, and the correlations of the expression levels of VIPR1 in lung adenocarcinoma with clinical pathological characteristics and prognosis were analyzed. The possible regulatory signaling pathways of VIPR1 were predicted by the gene set enrichment analysis (GSEA). CIBERSORT was used to analyze the expression of immune cells in tumor tissues and normal tissues. TIMER was used to analyze the relationship between VIPR1 and immune cell expression. The expression levels of VIPR1 mRNA in lung adenocarcinoma tissues were significantly lower than that in normal lung tissues. The expression levels of VIPR1 mRNA were significantly correlated with gender, T staging，N staging and pathological grade（p<0.05）but not with age, M staging and survival status. Survival analysis showed that the survival time of patients with low expression of VIPR1 was significantly lower than that of patients with high expression. In addition, the expression level of VIPR1 in lung adenocarcinoma was negatively correlated with the infiltration level of myeloid inhibitory cells (r = -0.448, p < 0.01). Through GSEA functional enrichment analysis, it was found that VIPR1 was mainly related to cell cycle pathway, p53 signal pathway, DNA replication pathway, RNA degradation pathway and so on.Conclusions：VIPR1 gene may be a new target for the clinical prognosis and targeted therapy of lung adenocarcinoma.

scholarly journals Metformin Protects against Radiation-Induced Acute Effects by Limiting Senescence of Bronchial-Epithelial Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7064
Author(s):  
Christine Hansel ◽  
Samantha Barr ◽  
Alina V. Schemann ◽  
Kirsten Lauber ◽  
Julia Hess ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lung Tissue ◽  
Cellular Stress ◽  
Lung Epithelial Cells ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Metformin Treatment ◽  
Acute Effects ◽  
Lung Epithelial ◽  
Radiation Induced

Radiation-induced damage to normal lung parenchyma remains a dose-limiting factor in thorax-associated radiotherapy (RT). Severe early and late complications with lungs can increase the risk of morbidity in cancer patients after RT. Herein, senescence of lung epithelial cells following RT-induced cellular stress, or more precisely the respective altered secretory profile, the senescence-associated secretory phenotype (SASP), was suggested as a central process for the initiation and progression of pneumonitis and pulmonary fibrosis. We previously reported that abrogation of certain aspects of the secretome of senescent lung cells, in particular, signaling inhibition of the SASP-factor Ccl2/Mcp1 mediated radioprotection especially by limiting endothelial dysfunction. Here, we investigated the therapeutic potential of a combined metformin treatment to protect normal lung tissue from RT-induced senescence and associated lung injury using a preclinical mouse model of radiation-induced pneumopathy. Metformin treatment efficiently limited RT-induced senescence and SASP expression levels, thereby limiting vascular dysfunctions, namely increased vascular permeability associated with increased extravasation of circulating immune and tumor cells early after irradiation (acute effects). Complementary in vitro studies using normal lung epithelial cell lines confirmed the senescence-limiting effect of metformin following RT finally resulting in radioprotection, while fostering RT-induced cellular stress of cultured malignant epithelial cells accounting for radiosensitization. The radioprotective action of metformin for normal lung tissue without simultaneous protection or preferable radiosensitization of tumor tissue might increase tumor control probabilities and survival because higher radiation doses could be used.

scholarly journals MO14-4 Machine learning-based clustering of scRNAseq data from normal lung tissue and application to lung cancer

2021 ◽  
Vol 32 ◽  
pp. S306
Author(s):  
Hiroaki Ikushima ◽  
Hidenori Kage ◽  
Takahide Nagase
Keyword(s):  
Machine Learning ◽  
Lung Cancer ◽  
Lung Tissue ◽  
Normal Lung Tissue ◽  
Normal Lung

PH-0480: Early repair mechanisms after Synchrotron Microbeam Radiation Therapy in normal lung tissue

2020 ◽  
Vol 152 ◽  
pp. S270
Author(s):  
V. Trappetti ◽  
C. Fernandez-Palomo ◽  
P. Pellicioli ◽  
V. Djonov
Keyword(s):  
Radiation Therapy ◽  
Lung Tissue ◽  
Normal Lung Tissue ◽  
Normal Lung ◽  
Early Repair ◽  
Microbeam Radiation Therapy ◽  
Repair Mechanisms
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