Data from Fer Protein-Tyrosine Kinase Promotes Lung Adenocarcinoma Cell Invasion and Tumor Metastasis
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<div>Abstract<p>Epidermal growth factor receptor (EGFR) is frequently amplified or mutated in non–small cell lung cancer (NSCLC). Although Fer protein-tyrosine kinase signals downstream of EGFR, its role in NSCLC tumor progression has not been reported. Here, Fer kinase was elevated in NSCLC tumors compared to normal lung epithelium. EGFR signaling in NSCLC cells fosters rapid Fer activation and increased localization to lamellipodia. Stable silencing of Fer in H1299 lung adenocarcinoma cells (Fer KD) caused impaired EGFR-induced lamellipodia formation compared to control cells. Fer KD NSCLC cells showed reduced Vav2 tyrosine phosphorylation that was correlated with direct Fer-mediated phosphorylation of Vav2 on tyrosine-172, which was previously reported to increase the guanine nucleotide exchange factor activity of Vav2. Indeed, Fer KD cells displayed defects in Rac-GTP localization to lamellipodia, cell migration, and cell invasion <i>in vitro</i>. To test the role of Fer in NSCLC progression and metastasis, control and Fer KD cells were grown as subcutaneous tumors in mice. Although Fer was not required for tumor growth, Fer KD tumor-bearing mice had significantly fewer numbers of spontaneous metastases. Combined, these data demonstrate that Fer kinase is elevated in NSCLC tumors and is important for cellular invasion and metastasis.</p><p><b>Implications:</b> Fer protein-tyrosine kinase is a potential therapeutic target in metastatic lung cancer. <i>Mol Cancer Res; 11(8); 952–63. ©2013 AACR</i>.</p></div>Mean nuclear areas (MNA) were calculated morphometrically in ten cases of well-differentiated adenocarcinoma, ten cases of atypical alveolar cuboidal cell hyperplasia (AAH), and five cases of alveolar cuboidal cell hyperplasia (AH) and were compared with each other. In cases of adenocarcinoma, the MNA were significantly larger than those of AAH and AH, and the standard deviation (SD) of nuclear area was greater in adenocarcinoma than that in AAH and AH, thus implying greater "scatter" of the nuclear areas in the former than the latter two. The MNA and the SD of nuclear area in AH were smallest in these three groups. In one case each of AAH and adenocarcinoma, there were two different populations of nuclear size in the same lesions, that is, histograms showed both adenocarcinoma and AAH in the same tumor. Through the use of the morphometric method, many cases of AAH were easily distinguishable from adenocarcinoma cases, and there were two cases in which foci of adenocarcinoma and AAH coexisted.
Atypical adenomatous hyperplasia
Cuboidal Cell
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Background: The high mortality rate in pulmonary carcinoma is a problem encountered in various countries, including Indonesia. According to WHO, there are 2.09 million people affected by lung cancer and 1.76 million deaths due to lung cancer worldwide. This study was aimed to determine the profile of lung adenocarcinoma patients with positive EGFR mutation.
Methods: The study was descriptive study with cross-sectional approach using secondary data obtained from medical records of lung adenocarcinoma patients.
Results: The present study revealed that lung adenocarcinoma was found higher in patients with age >40 years old (93.9%) compared to those with age <40 years old. It was also higher in male (66.7%) than in female patients. Most patient with lung adenocarcinoma were at the IIIB stage (42.4%). It was also reported that higher cases was found in patients with history of smoking more than 15 years (42.4%). Hemoptoe was the most reported clinical symptoms in patients with lung adenocarcinoma (87.9%). Lung adenocarcinoma was also observed higher in patients without family history of pulmonary adenocarcinoma (81.8%). Seventeen of 33 EGFR mutations (51.5%) were observed in exon 19 and fourteen (48.5%) were in exon 21.
Conclusion: The most common EGFR mutation lung adenocarcinoma was observed in exon 19.
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Hepatoid adenocarcinoma of the lung is a special type of primary origin in the lung with obvious pathological features and short survival time. However, standard treatment guidelines have not yet been established. Herein, we report a case of hepatoid adenocarcinoma with the primary lesion located in the left upper lung. The tumour size was reduced after four cycles of combined therapy. Subsequent postoperative pathology confirmed complete remission.
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On the basis of clinical investigations of 1,000 resected lung cancer patients we comment on the prognostic implications of histological type and tumour localisation with special regard to adenocarcinoma. 1. 198 patients, resected for primary adenocarcinoma of the lung, had 5- and 10-year survival rates of 42% and 25.3% respectively, similar to the survival rate of patients who had been operated on for squamous cell carcinoma. 2. Of 6 patients suffering from central adenocarcinoma according to WHO classification of 1967, or 10 patients according to WHO classification of 1981, not a single patient survived for more than 3 years. In patients with peripheral adenocarcinoma the survival rates after 5 and 10 years amounted to 42.4% and 26.6%. The 5-year survival rates of all patients with peripheral cancers were significantly better than those of central tumour patients. 3. The survival rates after 5 and 10 years among patients resected for primary adenocarcinoma dropped steeply in relation to tumour stage. While adenocarcinoma patients in stage I had the highest survival chances in comparison to other types, the survival curve of stage III patients with this type fell below that of small-cell and large-cell cancer patients. 4. The prognosis of patients resected for adenocarcinoma whose x-ray pictures showed a large infiltration, had a bad prognosis. Patients with peripheral coin lesions had good survival chances. 5. It was impossible to demonstrate a correlation between survival rate and grade of differentiation in adenocarcinoma patients. There were also no prognostic differences between papillary and acinar subtype. Patients with bronchiolo-alveolar carcinoma had the significantly highest survival rates.
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Objective To evaluate the expression patterns of TTF-1,CK7,CK5/6,P63 and CK20 in mucin producing lung cancer,and investigate the utility of immunohistochemical markers in differential diagnosis.Methods 15 mucin producing carcinoma of lung,including 5 signet ring cell adenocarcinoma,4 intestinal type adenocarcinoma. 3 mucinous bronchioloalveolar carcinoma,2 solid adenocarcinoma with mucin production,and 1 mucinous (colloid) adenocarcinoma,50 conventional lung adenocarcinoma(13 non-mucinous bronchioloalveolar carcinoma) were Studied with a panel of immunoslains.Results TTF-1 were expressed in 60.0%(9/15) of mucin producing carcinoma of lung and 94.0%(47/50) in lung adenocarcinoma;Mucin producing carcinoma of lung and lung adenocarcinoma exhibit a high frequency of CK7 expression with 100%(15/15) and 96.0%(48/50) respectively;CK5/ 6 expression was 0 and 2.0%(1/50) respectively;P63 was 13.3%(2/15) and 12.0%(6/50);CK20 expression was 6.7%(1/15) and 0,while negative immunohistochemical reactivity was seen in all lung adenocarcinoma.Conclusion Compared with lung adenocarcinoma,mucin producing carcinoma of lung often exhibit lower frequency of TTF- 1 and CK20 positive expression;CK7 positive expression was useful for confirming origin of lung cancer.
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Abstract Background The purpose of this study was to explore the reason for guanine nucleotide binding‐protein gamma subunit‐4 (GNG4) overexpression and the relationship between GNG4 overexpression and the poor prognosis of lung adenocarcinoma (LUAD) patients. Methods The genes and phenotypes related to GNG4 expression in patients with lung adenocarcinoma were analyzed by bioinformatics. The phenotype indicated by bioinformatic analysis was confirmed by experiments. Results GNG4 expression is elevated in lung adenocarcinoma, and overexpressed GNG4 is related to the poor prognosis of patients with lung adenocarcinoma. The hypoxic microenvironment of lung adenocarcinoma can promote GNG4 expression and GNG4 promotes the migration and proliferation of lung adenocarcinoma cells. Conclusions GNG4 expression in lung adenocarcinoma was significantly higher than in paired adjacent tissues. GNG4 overexpression is associated with a variety of malignant phenotypes of lung adenocarcinoma. Increased GNG4 expression is related to the hypoxic microenvironment in lung adenocarcinoma.
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This paper aims to determine the expression and clinical significance of DDX43 in lung adenocarcinoma. Expression of DDX43 gene and protein of lung adenocarcinoma tissue and para-carcinoma tissues was observed in 27 cases by RT-PCR and immunohistochemistry. These patients were diagnosed as lung adenocarcinoma in the Huaihe Hospital of Henan University from February 2015 to December 2015. The relative ratio of DDX43 mRNA expression in lung adenocarcinoma and para-carcinoma tissues was 0.87±0.62 versus 0.21±0.77 and the difference between the two groups was statistically significant (P<0.01). The expression of DDX43 in normal lung tissues and lung adenocarcinoma tissues was different. The positive rate of DDX43 expression in lung adenocarcinoma tissues was significantly higher than that in normal lung tissues, and the difference was statistically significant (P<0.05). The analysis of clinical pathological characteristics showed that the increase of protein expression was related to the stage and metastasis of lung adenocarcinoma. DDX43 is highly expressed in lung adenocarcinoma, and the expression level is related to the stage and metastasis of lung adenocarcinoma, suggesting that DDX43 is closely related to the occurrence and development of lung adenocarcinoma, and may be a molecular marker for early diagnosis of lung adenocarcinoma.
Clinical Significance
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Review of the histology of 219 lung cancers initially diagnosed at Lutheran General Hospital, Park Ridge, Illinois, in 1963-1967 and 1974-1976, confirms the increasing incidence of adenocarcinoma. This is due to an increase of adenocarcinoma in men. In women, the incidence of adenocarcinoma was higher than squamous carcinoma in the earliest period (44% adeno, 18% squamous). The percentage of women with lung cancer has also significantly increased from 19% to 31%, which increases the overall incidence of adenocarcinoma of the lung. As the number of women with lung carcinoma has increased, there has been no change in the percentage of adenocarcinoma in women.
Squamous carcinoma
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