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Sample records for advanced lung adenocarcinomas

  1. Vandetanib Treatment in Refractory Advanced Lung Adenocarcinoma Patients: 
Five Cases and Review of Literature

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    Lili GUO

    2012-02-01

    Full Text Available Background and objective Vandetanib is a once-daily oral multi-target inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET tyrosine kinases. The current study aimed to evaluate the effect and safety of vandetanib administered in refractory advanced lung adenocarcinoma patients. Methods Five patients who accepted chemotherapy and Tarceva therapy as first- and second-line treatments received vandetanib (300 mg, oral, once daily. Results The effects are stable disease on two patients (40% and progressive disease on three patients (60%. With a median follow-up of 36 months, one patient remained on follow-up. The median progression free survival (PFS is 2 months, and the mean overall survival is 22.6 months. The adverse events include rash (n=2, skin change (n=2, paronychia (n=2, asymptomatic QTc prolongation (n=2, ST-T change (n=1, diarrhea (n=1, and increased transaminase (n=1. Conclusion There were lower incidences of severe side effects with vandetanib therapy in refractory advanced lung adenocarcinoma patients. The results of effect and safety of vandetanib are similar with the related reviewed articles.

  2. Efficacy of Gefitinib for Young Patients with Unknown EGFR Gene Mutation 
in Advanced Lung Adenocarcinoma

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    Yutao LIU

    2014-05-01

    Full Text Available Background and objective Lung cancer in young patients (less or equal to 45 years is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the median age was 41 years. The objective response rate and disease control rate were 43.6% and 90.9%, respectively.. The median progression-free survival (PFS was 9.0 months. Among the factors analyzed, brain metastasis had significant effect on PFS (P=0.017. The median overall survival (OS was 24.0 months. The independent prognostic factors to significantly improve OS included non-smoking history (P=0.028 and receiving other anti-cancer treatment after Gefitinib therapy (P<0.001. Conclusion The median PFS and OS of the young patients with Unknown EGFR gene mutation in advanced lung adenocarcinoma were similar with general population.

  3. Achievement of Cure with Gefitinib in Advanced Lung Adenocarcinoma Harboring an Activating EGFR Mutation: A Case Report

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    Taiji Kuwata

    2016-10-01

    Full Text Available Tyrosine kinase inhibitors (TKIs of the epidermal growth factor receptor (EGFR may achieve long-term survival in selected cases with advanced non-small cell lung cancer harboring activating mutations in the EGFR gene, but a cured case has not been reported yet. Here, we present the first case of EGFR-mutated lung adenocarcinoma cured with an EGFR-TKI, as the 75-year-old Japanese man has achieved complete response with gefitinib treatment and has survived without tumor 10 years after termination of gefitinib treatment.

  4. Association between vascular-poor area of primary tumors and epidermal growth factor receptor gene status in advanced lung adenocarcinoma.

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    Togashi, Yosuke; Masago, Katsuhiro; Kubo, Takeshi; Fujimoto, Daichi; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Togashi, Kaori; Mishima, Michiaki

    2012-12-01

    Mutation of the epidermal growth factor receptor gene (EGFR mutation) is a very important marker in the treatment for non-small cell lung cancer. Since signaling from this receptor induces tumor-associated angiogenesis, we hypothesized that lung cancers with EGFR mutations tend to develop locally with increased angiogenesis. Thus, the association between vascular-poor area of primary tumors and EGFR status was retrospectively investigated in advanced lung adenocarcinomas. To assess vascular-poor area, contrast-enhanced computed tomography scans taken before initial treatment for lung cancer were analyzed, together with primary tumor location (peripheral or central) and size. We analyzed 178 patients with advanced lung adenocarcinoma. EGFR mutations were detected in 95 of the 178 patients (53.4 %). EGFR mutation was found to be significantly related to women (P = 0.0070), never-smokers (P area (P area (P = 0.0001), and tumor size >30 mm (P = 0.0080). EGFR mutations were found in 41 of 51 never-smokers without vascular-poor area (80.4 %), 19 of 36 never-smokers with vascular-poor area (52.8 %), 19 of 37 current or former-smokers without vascular-poor area (51.4 %), and 16 of 54 current or former-smokers with vascular-poor area (29.6 %). This study showed an association between vascular-poor area of primary tumors and EGFR status. As a consequence, evaluation using a combination of smoking status and vascular-poor area allows us to predict presence of EGFR mutations at a high frequency.

  5. Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma

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    Chien-Ming Liu

    2015-01-01

    Full Text Available Introduction. Epidermal growth factor receptor (EGFR mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells and A549 (EGFR wild type; Gefitinib-resistant cells cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.

  6. Transcriptomic Microenvironment of Lung Adenocarcinoma.

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    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  7. Primary adenocarcinoma of lung: A pictorial review of recent updates

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    Gaikwad, Anand, E-mail: anandgaik@yahoo.co.in [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gupta, Ashish, E-mail: ashgupta@toh.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Hare, Sam, E-mail: samanjeet@btinternet.com [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gomes, Marcio, E-mail: mgomes@toh.on.ca [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Sekhon, Harman, E-mail: hsekhon@toh.on.ca [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Souza, Carolina, E-mail: csouza@ottawahospital.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Inacio, Joao, E-mail: joao.r.inacio@gmail.com [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Lad, Shilpa, E-mail: slad@toh.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Seely, Jean, E-mail: jeseely@ottawahospital.on.ca [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada)

    2012-12-15

    Primary adenocarcinoma of lung has replaced squamous cell carcinoma as the commonest histological subtype of lung cancer and the incidence of primary lung adenocarcinoma appears to be rising. Although the main factors behind this ‘epidemic-like’ situation are largely undiscovered, filter cigarettes appear to significantly contribute to this shift in the histopathological spectrum. The new multidisciplinary classification of adenocarcinoma of lung was introduced to address advances in clinical, pathological, radiological and molecular sciences. The purpose of this essay is to discuss various classes of lung adenocarcinoma in the new classification with their classical imaging features on computed tomography and summarise the recent advances in the field of radiology and review radiology recommendations.

  8. Prognostic Value of Baseline 18F-FDG PET/CT Functional Parameters in Patients with Advanced Lung Adenocarcinoma Stratified by EGFR Mutation Status.

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    Dalong Wang

    Full Text Available The study objective was to retrospectively analyze the metabolic variables derived from 18 F-fluorodeoxyglucose (18F-FDG positron emission tomography/computed tomography (PET/CT as predictors of progression-free survival (PFS and overall survival (OS in advanced lung adenocarcinoma stratified by epidermal growth factor receptor (EGFR mutation status. A total of 176 patients (91, EGFR mutation; 85, wild-type EGFR who underwent 18F-FDG PET/CT before treatment were enrolled. The main 18F-FDG PET/CT-derived variables: primary tumor maximum standardized uptake value (SUVmaxT, primary tumor total lesion glycolysis (TLGT, the maximum SUVmax of all selected lesions in whole body determined using the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 criteria (SUVmaxWBR, and whole-body total TLG determined using the RECIST 1.1 criteria (TLGWBR were measured. Survival analysis regarding TLGWBR, and other factors in advanced lung adenocarcinoma patients stratified using EGFR mutation status, were evaluated. The results indicated that high TLGWBR (≥259.85, EGFR wild-type, and high serum LDH were independent predictors of worse PFS and OS in all patients with advanced lung adenocarcinoma. Among patients with wild-type EGFR, only TLGWBR retained significance as an independent predictor of both PFS and OS. Among patients with the EGFR mutation, high serum LDH level was an independent predictor of worse PFS and OS, and high TLGWBR (≥259.85 was an independent predictor of worse PFS but not worse OS. In conclusion, TLGWBR is a promising parameter for prognostic stratification of patients with advanced lung adenocarcinoma and EGFR status; however, it cannot be used to further stratify the risk of worse OS for patients with the EGFR mutation. Further prospective studies are needed to validate our findings.

  9. Prognostic potential of initial CT changes for progression-free survival in gefitinib-treated patients with advanced adenocarcinoma of the lung: a preliminary analysis

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    Wu, Yu-Cheng; Hsu, Hsian-He; Chang, Wei-Chou; Ko, Kai-Hsiung; Hsu, Yi-Chih [Tri-Service General Hospital, National Defense Medical Center, Department of Radiology, Taipei (China); Tung, Ho-Jui [Asia University, Department of Healthcare Administration, Taichung (China); Huang, Tsai-Wang; Chang, Hung [Tri-Service General Hospital, National Defense Medical Center, Division of Thoracic Surgery, Department of Surgery, Taipei (China); Ho, Ching-Liang [Tri-Service General Hospital, National Defense Medical Center, Division of hematology-oncology, Department of internal Medicine, Taipei (China)

    2015-06-01

    We aimed to determine whether initial tumour responses measured during short-term follow-up computed tomography (CT) examinations after baseline examinations would correlate with clinical outcomes in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR)-targeted therapy. A total of 86 gefitinib-treated patients with advanced adenocarcinoma of the lung were retrospectively reviewed. All patients underwent baseline and short-term follow-up CT examinations. The new response criteria (NRC) by Lee et al. were used for the response evaluations. A Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses were used to evaluate correlations between the initial tumour changes and progression-free and overall survival (PFS, OS). Better separation and smaller p values were observed for both PFS and OS when good and poor disease responses (as defined by NRC) were compared after excluding tumours with characteristic morphologies. Early tumour changes correlated with PFS in a size-dependent manner. Moreover, a stronger association was observed between size changes and PFS when characteristic morphology was also considered. Initial changes in tumour size during short-term post-treatment CT examinations could act as a potential prognostic imaging surrogate for PFS in gefitinib-treated patients with advanced adenocarcinoma of the lung. (orig.)

  10. Rare coexistence of sarcoidosis and lung adenocarcinoma

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    Amit Girish Kachalia

    2014-01-01

    Conclusion: While evidence is still lacking regarding association between sarcoidosis and lung adenocarcinoma, it is important for clinicians to exclude metastatic malignancy in patients exhibiting clinical and radiographic findings consistent with sarcoidosis.

  11. EGFR Mutation Status in Uighur Lung Adenocarcinoma Patients

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    Li SHAN

    2013-02-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR, a transmembrane protein, is a member of the tyrosine kinase family. Gefitinib, an EGFR tyrosine-kinase inhibitors, has shown a high response rate in the treatment of lung cancer in patients with EGFR mutation. However, significant differences in EGFR mutations exist among different ethnic groups. The aim of this study is to investigate the prevalence of EGFR mutations in Uighur lung adenocarcinoma patients by using a rapid and sensitive detection method and to analyze EGFR mutation differences compared with Han lung adenocarcinoma patients. Methods We examined lung adenocarcinoma tissues from 138 patients, including 68 Uighur lung adenocarcinoma patients and 70 Han lung adenocarcinoma patients, for EGFR mutations in exons 18, 19, 20, and 21 by using the amplification refractory mutation system (ARMS PCR method. The mutation differences between Uighur and Han lung adenocarcinoma were compared by using the chi-square test method. Results EGFR mutations were detected in 43 (31.2% of the 138 lung adenocarcinoma patients. EGFR mutations were detected in 11 (16.2% of the 68 Uighur lung adenocarcinoma patients and in 32 (45.7% of the 70 Han lung adenocarcinoma patients. Significant differences were observed in the EGFR mutations between Uighur lung adenocarcinoma patients and Han lung adenocarcinoma patients (P<0.001. Conclusion Our results indicate that the EGFR mutation in Uighur lung adenocarcinoma patients (16.2% is significantly lower than that in Han lung adenocarcinoma patients (45.7%.

  12. Imaging Characteristics of Driver Mutations in EGFR, KRAS, and ALK among Treatment-Naïve Patients with Advanced Lung Adenocarcinoma

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    Park, Jangchul; Kobayashi, Yoshihisa; Urayama, Kevin Y.; Yamaura, Hidekazu; Yatabe, Yasushi; Hida, Toyoaki

    2016-01-01

    This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB–IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups’ characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB–IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal

  13. Intermittent Chemotherapy and Erlotinib for Nonsmokers or Light Smokers with Advanced Adenocarcinoma of the Lung: A Phase II Clinical Trial

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    Matjaz Zwitter

    2011-01-01

    Full Text Available Background. Intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs. This hypothesis was tested in a Phase II clinical trial. Patients and Methods. Eligible patients were nonsmokers or light smokers, chemo-naïve, with metastatic adenocarcinoma of the lung. Treatment: 4 to 6 cycles of gemcitabine 1250 mg/m2 on days 1 and 4, cisplatin 75 mg/m2 on day 2, and erlotnib 150 mg daily on days 5–15, followed by erlotinib as maintenance. Results. 24 patients entered the trial. Four pts had grade 3 toxicity. Complete remission (CR and partial remission (PR were seen in 5 pts and 9 pts, respectively (response rate 58%. Median time to progression (TTP was 13.4 months and median overall survival (OS was 23 months. When compared to patients with negative or unknown status of EGFR mutations, 8 patients with EGFR gene activating mutations had significantly superior experience: 4 CR and 4 PR, with median TTP 21.5 months and OS 24.2 months (P  <  .05. Conclusions. Intermittent schedule with gemcitabine, cisplatin and erlotinib has mild toxicity. For patients who are positive for EGFR gene activating mutations, this treatment offers excellent response rate, time to progression and survival.

  14. Molecular heterogeneity assessment by next-generation sequencing and response to gefitinib of EGFR mutant advanced lung adenocarcinoma.

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    Bria, Emilio; Pilotto, Sara; Amato, Eliana; Fassan, Matteo; Novello, Silvia; Peretti, Umberto; Vavalà, Tiziana; Kinspergher, Stefania; Righi, Luisella; Santo, Antonio; Brunelli, Matteo; Corbo, Vincenzo; Giglioli, Eliana; Sperduti, Isabella; Milella, Michele; Chilosi, Marco; Scarpa, Aldo; Tortora, Giampaolo

    2015-05-20

    Cancer molecular heterogeneity might explain the variable response of EGFR mutant lung adenocarcinomas to tyrosine kinase inhibitors (TKIs). We assessed the mutational status of 22 cancer genes by next-generation sequencing (NGS) in poor, intermediate or good responders to first-line gefitinib. Clinical outcome was correlated with Additional Coexisting Mutations (ACMs) and the EGFR Proportion of Mutated Alleles (PMA). Thirteen ACMs were found in 10/17 patients: TP53 (n=6), KRAS (n=2), CTNNB1 (n=2), PIK3CA, SMAD4 and MET (n=1 each). TP53 mutations were exclusive of poor/intermediate responders (66.7% versus 0, p=0.009). Presence of ACMs significantly affected both PFS (median 3.0 versus 12.3 months, p=0.03) and survival (3.6 months versus not reached, p=0.03). TP53 mutation was the strongest negative modifier (median PFS 4.0 versus 14.0 months). Higher EGFR PMA was present in good versus poor/intermediate responders. Median PFS and survival were longer in patients with EGFR PMA ≥0.36 (12.0 versus 4.0 months, p=0.31; not reached versus 18.0 months, p=0.59). Patients with an EGFR PMA ≥0.36 and no ACMs fared significantly better (p=0.03), with a trend towards increased survival (p=0.06). Our exploratory data suggest that a quantitative (PMA) and qualitative (ACMs) molecular heterogeneity assessment using NGS might be useful for a better selection of patients.

  15. File list: Pol.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.05.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.05.AllAg.Lung_adenocarcinoma.bed ...

  16. File list: DNS.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.05.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma http://...dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.05.AllAg.Lung_adenocarcinoma.bed ...

  17. File list: Unc.Lng.20.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lng.20.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.20.AllAg.Lung_adenocarcinoma.bed ...

  18. File list: Unc.Lng.10.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lng.10.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.10.AllAg.Lung_adenocarcinoma.bed ...

  19. File list: Unc.Lng.50.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lng.50.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.50.AllAg.Lung_adenocarcinoma.bed ...

  20. File list: DNS.Lng.50.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.50.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma http://...dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.50.AllAg.Lung_adenocarcinoma.bed ...

  1. File list: Pol.Lng.50.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.50.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.50.AllAg.Lung_adenocarcinoma.bed ...

  2. File list: DNS.Lng.20.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.20.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma http://...dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.20.AllAg.Lung_adenocarcinoma.bed ...

  3. File list: Unc.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lng.05.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.05.AllAg.Lung_adenocarcinoma.bed ...

  4. File list: DNS.Lng.10.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.10.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma http://...dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.10.AllAg.Lung_adenocarcinoma.bed ...

  5. File list: Pol.Lng.20.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Pol.Lng.10.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.10.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.10.AllAg.Lung_adenocarcinoma.bed ...

  7. Follistatin is a novel biomarker for lung adenocarcinoma in humans.

    Directory of Open Access Journals (Sweden)

    Fangfang Chen

    Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

  8. [Pseudo-mesotheliomatous adenocarcinoma of the lung].

    Science.gov (United States)

    Aumann, K; Günter, J; Freudenberg, N

    2010-07-01

    Both pathologists and clinicians are challenged by the diagnosis of a particular variant of the peripheral adenocarcinoma with involvement of the pleura parietalis, the so-called pseudo-mesotheliomatous adenocarcinoma of the lung (PMAC), which is hard to differentiate from epithelioid mesothelioma on imaging and cytology, macroscopically as well as histologically. However, the exact diagnosis is not only crucial for the patient's therapy but also for insurance matters. Immunohistochemical evaluation represents a quick and a relatively cheap tool for which a few antibody panels have been proposed in recent years as being suitable to distinguish between these two entities. One of the positive markers for epithelioid mesothelioma most often suggested seems to be calretinin. We would like to report on a case of PMAC with the special feature of positive calretinin immunohistochemical staining. Using histochemistry and a few additional antibodies we were able to reliably characterize the tumor and provide the patient with appropriate therapy. This article gives a short overview of the possibilities available for distinguishing between these two entities in the context of a case report.

  9. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  10. Pediatric primary lung adenocarcinoma in the absence of congenital pulmonary airway malformation.

    Science.gov (United States)

    Guddati, Achuta K; Marak, Creticus P

    2012-12-01

    Primary lung adenocarcinoma is a rare entity in the pediatric population, especially in the absence of an underlying congenital pulmonary airway malformation. Primary lung malignancies in pediatric patients are rare and constitute 0.2% of all childhood malignancies. EGFR mutations and congenital airway malformations have been identified as etiological factors in the development of precancerous lesions that eventually progress to malignancy. The availability of genome sequencing and advanced imaging has made it possible to associate primary lung adenocarcinoma with mutations and structural malformations. Early diagnosis with the help of these techniques may result in surgical resection during early stages of the disease and possibly provide definitive treatment. Development of lung adenocarcinoma in pediatric patients in the absence of the above factors has been recorded anecdotally. It is possible that these patients may harbor a yet unknown set of mutations and recording this cases and preserving their tissues is of vital importance in the detection of these yet unknown etiologies.

  11. ATM protein is deficient in over 40% of lung adenocarcinomas.

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    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  12. File list: His.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  7. Dual surrogate markers for rapid prediction of epidermal growth factor receptor mutation status in advanced adenocarcinoma of the lung: A novel approach in resource-limited setting

    Directory of Open Access Journals (Sweden)

    K S Udupa

    2015-01-01

    Full Text Available Introduction: Tyrosine kinase inhibitors have revolutionized the treatment of metastatic lung cancer in patients with epidermal growth factor receptor (EGFR mutations. Amplified refractory mutation system (ARMS-reverse transcription-polymerase chain reaction (RT-PCR, the current standard for detecting EGFR mutation status is time-consuming and highly expensive. Consequently any surrogate test which are cheaper, faster and as accurate as the PCR method will help in early diagnosis and management of patients with lung cancer, especially in resource-limited settings. Materials and Methods: Eighty-five patients, all of South Indian origin, with adenocarcinoma of lung, registered between October 2009 and January 2013, were evaluated for EGFR mutation status by using scorpion probe based ARMS RT-PCR method. Immunohistochemical (IHC was performed using the phosphorylated AKT (P-AKT and thyroid transcription factor-1 (TTF-1 on above patient's sample, and the results were compared with EGFR mutation tests. Results: EGFR mutation was positive in 34 of 85 patients (40%. P-AKT and TTF-1 were positive in 50 (58.8% and 68 (80% patients respectively. Both P-AKT and TTF-1 had statistically significant correlation with EGFR mutation status. Positive and negative predictive value of P-AKT in diagnosing EGFR mutation was 58% and 85.5% and that for TTF-1 was 48.5% and 94.1%, respectively. The problem of low positive predictive value can partly be overcome by testing P-AKT and TTF-1 simultaneously. Conclusion: P-AKT and TTF-1 using IHC had statistically significant correlation with EGFR mutation with high negative predictive value. In the case of urgency of starting treatment, EGFR mutation testing may be avoided in those patients who are negative for these IHC markers and can be started on chemotherapy.

  8. CLINICAL OBSERVATION OF GEFITINIB IN TREATMENT OF PATIENTS WITH ADVANCED ADENOCARCINOMA OF LUNG CANCER%吉非替尼治疗晚期肺腺癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    江波; 赵金奇; 何文杰

    2011-01-01

    [Objective] To analyze the efficacy, median survival time, media progression-free survival and control of the related symptoms of SO advanced lung adenocarcinoma caaes treated with Gefitinib. [Methods] A total of 50 patients with advanced lung adenocarcinoma of stage IE B or IV confirmed by pathology or cytology took Gefitinib 2S0mg orally once a day, until death or tumor progression or withdrawal by intolerable reaction. CT scan was performed before treatment and after treatment once a month. [Results] Objective response rate was 24%, disease control rate was 76%, and symptom improving rate was 70%. Significant difference was found in the efficacy of gender and smoking history (P 0.05). Median progression-free survival time was 7.5 months. Median survival time was 16.8 months. Skin rash and diarrha were the most common complication. [Conclusion] Gefitinib is better choice for the patients with advanced lung adenocarcinoma.%[目的]分析吉非替尼治疗50例晚期肺腺癌的疗效、中位生存期、中位无进展生存期及对相关症状的控制.[方法]50例经病理学或细胞学证实的ⅢB期或Ⅳ期肺腺癌患者,口服吉非替尼250 mg/d,直至患者死亡或肿瘤进展或发生不可耐受的不良反应,服药前或服药后每月复查CT进行疗效评价.[结果]客观缓解率为24%,疾病控制率为76%,症状改善率为70%,性别及吸烟两亚组之间疗效对比有统计学差异(P<0.05);年龄、分期、PS评分及既往治疗等各亚组之间疗效对比均无统计学差异(P>0.05).中位无进展生存期7.5个月,中位生存期16.8个月,最常见的不良反应为皮疹和腹泻.[结论]吉非替尼是晚期肺腺癌治疗较好的选择.

  9. Hydronephrosis as a complication of adenocarcinoma of the lung.

    Science.gov (United States)

    Hiraki, Akio; Ueoka, Hiroshi; Gemba, Kenich; Kuyama, Syouich; Kishino, Daizo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune; Harada, Mine

    2003-01-01

    We describe a patient with adenocarcinoma of the lung who developed hydronephrosis secondary to compression by right common iliac lymph node metastases. The most common primary sites of cancers causing ureteral obstruction are the cervix, prostate, bladder and colo-rectum. To date, few reports of ureteral obstruction attributable to lung cancer have been published. Although rare, physicians should be aware that hydronephrosis can complicate the course of patients with non-small cell lung cancer.

  10. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

    DEFF Research Database (Denmark)

    Wu, Kui; Zhang, Xin; Li, Fuqiang

    2015-01-01

    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13...

  11. The distinctive nature of adenocarcinoma of the lung

    Directory of Open Access Journals (Sweden)

    Roviello G

    2015-09-01

    Full Text Available Giandomenico RovielloDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyAbstract: In recent years, many personalized treatments have been developed for NSCLC (non-small-cell lung cancer patients. Among these, gefitinib, erlotinib, and afatinib are selective epidermal growth factor receptor (EGFR tyrosine kinase inhibitors for patients with EGFR gene mutations, while crizotinib and ceritinib are two new tyrosine kinase inhibitors directed against the echinoderm microtubule-like protein 4-anaplastic lymphoma kinase translocation. The possibility of these new molecules being used to treat patients without adenocarcinoma histology is notably small. For example, EGFR mutations and anaplastic lymphoma kinase fusion gene rearrangement are rare in patients with squamous cell carcinoma (generally <1%. Additionally, the benefit of targeted treatment approaches in patients with small-cell lung cancer histology is limited. All of these findings highlight the distinctive nature of adenocarcinoma of the lung among all lung cancer subtypes. Unfortunately, to date, less than 15% of patients with adenocarcinoma of the lung are ideal candidates for these targeted therapies.Keywords: lung cancer, adenocarcinoma, EGFR, ALK

  12. Unusual synchronous lung tumors: mucoepidermoid carcinoma and mucinous adenocarcinoma.

    Science.gov (United States)

    Ponea, Ana M; Marak, Creticus P; Sun, Ying; Guddati, Achuta Kumar; Tibb, Amit S

    2014-01-01

    Primary mucoepidermoid tumors of the lung are rare entities. Synchronous primary malignancies of the lung involving mucoepidermoid carcinoma and mucinous adenocarcinoma are even rarer and constitute a unique set of patient population. The presentation, diagnosis and treatment strategies for this patient population are not well described. In most cases, the diagnosis of synchronous primary lung malignancy is made after pathological examination of the resected lung specimen. Molecular and genetic analysis is now being used to supplement the diagnosis of synchronous primary lung malignancies. In this work, we briefly discuss the current state of knowledge of this unique combination of primary lung malignancies and describe the clinical presentation and management of a patient with a rare combination of synchronous primary lung malignancies.

  13. Unusual Synchronous Lung Tumors: Mucoepidermoid Carcinoma and Mucinous Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ana M. Ponea

    2014-01-01

    Full Text Available Primary mucoepidermoid tumors of the lung are rare entities. Synchronous primary malignancies of the lung involving mucoepidermoid carcinoma and mucinous adenocarcinoma are even rarer and constitute a unique set of patient population. The presentation, diagnosis and treatment strategies for this patient population are not well described. In most cases, the diagnosis of synchronous primary lung malignancy is made after pathological examination of the resected lung specimen. Molecular and genetic analysis is now being used to supplement the diagnosis of synchronous primary lung malignancies. In this work, we briefly discuss the current state of knowledge of this unique combination of primary lung malignancies and describe the clinical presentation and management of a patient with a rare combination of synchronous primary lung malignancies.

  14. Cutaneous metastasis as a first presentation for lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Yazan Abdeen

    2016-01-01

    Full Text Available Context: According to the recent World Health Organization reports, lung cancer has become the most common type of malignancy and the leading cause of death from cancer. Lung cancer frequently metastasizes to hilar lymphnodes, brain, adrenal glands, bone, but rarely to skin. Case Report: We report a case of a 72-year-old male with a past medical history of pulmonary fibrosis and no prior history of smoking who presented to the emergency room for progressive dyspnea over three weeks. The patient reported having a rapidly growing scalp lesion as well. A computed tomography (CT scan of the chest showed diffuse fibrotic changes and multiple densities of different diameters; a CT guided biopsy of lung revealed a poorly differentiated adenocarcinoma. Excision of right scalp lesion was performed, and pathology revealed poorly differentiated malignant neoplasm favoring adenocarcinoma. Conclusion: We are presenting a rare case of lung adenocarcinoma presenting with skin metastasis, which was simultaneously diagnosed during the same hospitalization. Although cutaneous metastasis from the lung is rare, it must be ruled out in patients with suspicious skin lesions, smoking history, or lung cancer.

  15. Lung adenocarcinoma with GGO nodules:HRCT radiological and pathological correlation

    Institute of Scientific and Technical Information of China (English)

    ACHARYA Prashanta; PAUDEL Rasmita; XU Qiu-zhen

    2015-01-01

    Background:Lung cancer is the most common cancer related death in the world for the both male and female as well .Adenocarcinoma is the most common pathological type which is in increasing trend .With recent ad-vancement of screening of lung cancer with HRCT , GGO lesion has been noted frequently .GGO is a nonspecific finding that may be caused by various disorders , including inflammatory diseases , focal fibrosis , atypical adenoma-tous hyperplasia , bronchoalveolar carcinoma ( BAC) , and adenocarcinoma .This study intends to analyze the corre-lation between high resolutions computed tomography ( HRCT) findings and the pathological findings of lung adeno-carcinoma.Material and methods:Retrospective review of 16 cases of lung adenocarcinoma lesions after surgical resection.Tumors were defined as air containing type based on ratio of maximum dimension of the tumor on medias-tinal window to the maximum diameter of the tumor on lung window was≤50%and as solid density if the ratio was >50%.The correlation between CT findings ( homogenous/heterogeneous , airbronchogram , pleural tag , specula-tion, vascular involvement , pleural thickening , margin, shape ) and pathological findings were investigated .Re-sults:Of 3 air containing 2 were pre-invasive type and 1 was invasive .Among 13 solid density type all 13 were in-vasive type .Presence of speculation , heterogeneous appearance was found significantly associated with pathological invasion .Conclusion:Air containing type of small cells lung adenocarcinomas are preinvasive whereas solid densi-ties are invasive .Speculation and heterogeneous are significant factor in invasive adenocarcinoma .

  16. Prior EGFR tyrosine-kinase inhibitor therapy did not influence the efficacy of subsequent pemetrexed plus platinum in advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Tseng JS

    2014-05-01

    Full Text Available Jeng-Sen Tseng,1,2 Tsung-Ying Yang,2 Kun-Chieh Chen,1,2 Kuo-Hsuan Hsu,1,3 Chong-Jen Yu,4 Wei-Yu Liao,4 Chi-Ren Tsai,5,6 Meen-Hsin Tsai,2,7 Sung-Liang Yu,8–11 Kang-Yi Su,8,12 Jeremy JW Chen,1 Hsuan-Yu Chen,7 Gee-Chen Chang1,2,13–151Institute of Biomedical Sciences, National Chung-Hsing University, 2Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, 3Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, 4Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, 5Department of Pediatrics, Taichung Veterans General Hospital, 6Institute of Molecular Biology, National Chung-Hsing University, Taichung, 7Institute of Statistical Science, Academia Sinica, 8Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, 9Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, 10Graduate Institute of Pathology, College of Medicine, National Taiwan University, 11Department of Laboratory Medicine, National Taiwan University Hospital, 12Center of Genomic Medicine, National Taiwan University, Taipei, 13School of Medicine, China Medical University, 14Comprehensive Cancer Center, Taichung Veterans General Hospital, Taichung, 15Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, TaiwanBackground: Tumor cells before and after epidermal growth-factor receptor (EGFR tyrosine-kinase inhibitor (TKI therapy might display different characteristics. The aim of this study was to evaluate the influence of prior EGFR TKI therapy on the efficacy of subsequent pemetrexed plus platinum (PP in advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma.Materials and methods: Advanced chemonaïve patients with EGFR-mutant lung adenocarcinoma receiving PP as first

  17. Herceptin responsive lung adenocarcinoma in the setting of bilateral synchronous lung primaries and breast carcinoma

    Directory of Open Access Journals (Sweden)

    Gerard J Fitzmaurice

    2017-01-01

    Full Text Available The incidence of human epidermal growth factor receptor 2 (Her-2 mutations in lung adenocarcinoma is approximately 3%; however, its significance in the management of these lung cancers remains under investigation. We describe an incidental but unique opportunity to evaluate the response to treatment with herceptin in a patient with bilateral synchronous lung primaries in conjunction with breast carcinoma. Interval imaging following surgical resection of the squamous cell carcinoma while on herceptin treatment delineated the radiological regression of the Her-2 positive lung adenocarcinoma. We feel that this case highlights the potential role for herceptin treatment in Her-2 positive lung adenocarcinomas and demonstrates the importance of screening for these mutations.

  18. Clinical observation of pemetrexed alone in the treatment of advanced recurrent lung adenocarcinoma%培美曲塞单药治疗晚期复发肺腺癌患者的临床观察

    Institute of Scientific and Technical Information of China (English)

    张萍; 武晓楠; 聂鑫; 张子瑾; 李琳; 程刚

    2012-01-01

    Objective: To evaluate the efficacy and safety of domestic pemetrexed disodium injection in patients with advanced recurrent lung adenocarcinoma. Methods; Fifty-four patients with advanced recurrent lung adenocarcinoma diagnosed by histology or cytology who had failed to prior chemotherapy were assigned to pemetrexed 500 mg·rn alone every 3 weeks. The efficacy and side effects were assessed after two therapeutic cycles. In accordance with the labeling of pemetrexed disodium injection, patients also received oral dexamethascme, oral folic acid and intramuscular vitamin B12 to reduce toxicity. Results: All patients received more than two cycles of chemotherapy. Among the 54 patients, no one achieved complete response, 7 patients had partial response, 26 patients were stable, and 21 patients had progressed disease. The total response rate was 13.0% (7/54) , and disease control rate was 61. 1% (33/54). The median progression free survival was 3 months. The main adverse events were grade 1 and 2 hematologic toxicities,gastrointestinal toxicities and fatigue. No treatment-related deaths, or treatment interruption due to toxicities were observed. Conclusion; Domestic pemetrexed disodium is effective and well tolerated for monotherapy of patients with advanced recurrent lung adenocarcinoma.%目的:回顾性分析国产培美曲塞二钠单药治疗晚期复发肺腺癌患者的临床疗效及耐受性.方法:54例经组织学或细胞学确诊的晚期肺腺癌患者,均经既往治疗失败,采用国产培美曲塞单药化疗,方案为培美曲塞500 mg·m-2,d1,ivgtt,每3周重复,均按照说明书口服地塞米松、叶酸并肌内注射维生素B12以减轻不良反应,完成2个周期以上化疗后评价疗效和不良反应.结果:54例患者均接受2个周期以上的治疗,全组无完全缓解(CR)病例,部分缓解(PR)7例,疾病稳定(SD) 26例,疾病进展(PD)21例,有效率(CR+ PR)为13.0% (7/54),疾病控制率(DCR)为61.1% (33/54),

  19. Unusual presentation of metastatic adenocarcinoma of the lung

    Institute of Scientific and Technical Information of China (English)

    Blerina Resuli; Roberto Lisi; Daniela Musio; Vincenzo Tombolini

    2016-01-01

    On September 2013, a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand. The biopsy confirmed metastatic adenocarcinoma of the lung to the finger. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient's right hand. The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy. After magnetic resonance-guided focused ultrasound surgery, the clinical symptoms improved significantly. No serious adverse effects were reported and the patient compliance was very high. Our patient showed improvement of clinical symptoms after combined treatment. The patient remains in good health conditions.

  20. Unusual presentation of metastatic adenocarcinoma of the lung

    Institute of Scientific and Technical Information of China (English)

    Blerina Resuli; Roberto Lisi; Daniela Musio; Vincenzo Tombolini

    2016-01-01

    On September 2013, a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand. The biopsy confirmed metastatic adenocarcinoma of the lung to the finger. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient’s right hand. The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy. After magnetic resonance-guided focused ultrasound surgery, the clinical symptoms improved significantly. No serious adverse effects were reported and the patient compliance was very high. Our patient showed improvement of clinical symptoms after combined treatment. The patient remains in good health conditions.

  1. Clinical impacts of a micropapillary pattern in lung adenocarcinoma: a review

    Directory of Open Access Journals (Sweden)

    Cao Y

    2015-12-01

    Full Text Available Ying Cao, Li-Zhen Zhu, Meng-Jie Jiang, Ying Yuan Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China Abstract: Lung adenocarcinoma with a micropapillary pattern (MPPAC has recently drawn increased attention among researchers. Micropapillary-predominant adenocarcinoma (MPA, which is defined by micropapillary pattern (MPP, is the primary histological pattern observed semiquantitatively in 5% increments on resection specimens, and MPA was formally determined to be a new histological subtype according to the new multidisciplinary classification in 2011. According to published studies, MPPAC is most common in males and nonsmokers and is associated with lymphatic invasion, pleural invasion, and lymph node metastases. MPPAC often presents as part-solid and lobulated nodules in computed tomography scans. MPP tends to have a higher maximum standardized uptake value as determined by fluorodeoxyglucose positron emission tomography combined with computed tomography, indicating a high risk of recurrence. Molecular markers, including vimentin, napsin A, phosphorylated c-Met, cytoplasmic maspin, Notch-1, MUC1, and tumoral CD10, may have higher expression in MPPAC than other subtypes; conversely, markers such as MUC4 and surfactant apoprotein A have lower expression in MPPAC. MPPAC with EGFR mutations can benefit from treatment with EGFR tyrosine kinase inhibitors. Furthermore, a complete lobectomy may be more suitable than limited resection for MPPAC because of the low sensitivity of intraoperative frozen sections and the high risk of lymph node metastasis. MPA benefits more from adjuvant chemotherapy than do other histological subtypes, whereas MPA does not benefit from adjuvant radiotherapy. Of note, MPP is associated with poor prognosis in early-stage lung adenocarcinoma, but the prognostic value of MPP is controversial in advanced-stage lung adenocarcinoma. Keywords

  2. Targeting adhesion signaling in KRAS, LKB1 mutant lung adenocarcinoma

    Science.gov (United States)

    Konen, Jessica; Koo, Junghui; Robinson, Brian S.; Wiles, Walter Guy; Huang, Chunzi; Martin, W. David; Behera, Madhusmita; Smith, Geoffrey H.; Hill, Charles E.; Rossi, Michael R.; Sica, Gabriel L.; Rupji, Manali; Chen, Zhengjia; Kowalski, Jeanne; Kasinski, Andrea L.; Ramalingam, Suresh S.; Khuri, Fadlo R.; Marcus, Adam I.

    2017-01-01

    Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre–induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen. Modeling invasion in 3D, loss of Lkb1, but not p53, was sufficient to drive collective invasion and collagen alignment that was highly sensitive to FAK inhibition. Treatment of early, stage-matched KLLenti tumors with FAK inhibitor monotherapy resulted in a striking effect on tumor progression, invasion, and tumor-associated collagen. Chronic treatment extended survival and impeded local lymph node spread. Lastly, we identified focally upregulated FAK and collagen-associated collective invasion in KRAS and LKB1 comutated human lung adenocarcinoma patients. Our results suggest that patients with LKB1 mutant tumors should be stratified for early treatment with FAK inhibitors.

  3. Pemetrexed combined with cisplatin as first-line treatment of advanced lung adenocarcinoma%一线培美曲塞联合顺铂治疗晚期肺腺癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    高云; 何兴平; 杨胜利; 苏敏; 庞洁

    2011-01-01

    目的 比较一线培美曲塞联合顺铂与多烯紫杉醇联合顺铂方案治疗晚期肺腺癌患者的疗效、不良反应及生存质量.方法 经病理或细胞学确诊的晚期肺腺癌患者共87例,随机分为培美曲塞治疗组和多烯紫杉醇治疗组.培美曲塞治疗组45例:培美曲塞500 mg/m2,顺铂75 mg/m2,静脉滴注,均第1天给药,并口服地塞米松、叶酸和肌肉注射维生素B12治疗,21d为1周期.多烯紫杉醇治疗组42例:多烯紫杉醇75mg/m2,顺铂75 mg/m2,静脉滴注,均第1天给药,21d为1周期.完成治疗2个周期以上的患者进行临床疗效、不良反应及生存质量评估.结果 培美曲塞治疗组和多烯紫杉醇治疗组有效率(RR)分别为55.6%、42.9%,肿瘤控制率(TGCR)分别为80%、59.5%(P <0.05).培美曲塞治疗组骨髓抑制度消化道不良反应较轻,患者生存质量改善优于多烯紫杉醇治疗组(P<0.05).结论 培蔓曲塞联合顺铂一线治疗晚期肺腺癌与多烯紫杉醇联合顺铂方案相比,疗效较好,骨髓抑制及消化道不良反应较轻,患者生存质量改善更显著.晚期肺腺癌患者可从一线培美曲塞联合顺铂治疗中获益.%Objective To evaluate the clinical efficacy, adverse effect and life quality of pemetrexed combined with cispl-atin or docetaxel combined with cisplatin as first-line treatment of advanced lung adenocarcinoma. Methods Eighty-seven patients with advanced lung adenocarcinoma proved by pathology or cytology were divided randomly into group P ( pemetrexed combined with cisplatin) and group D (docetaxel combined with cisplatin) . 45 cases in group P received pemetrexed at a dose of 500 mg/m2 and cisplatin of 75 mg/m2 intravenousely on day 1, repeated every 21days for one cycle. Folic acid, vitamin B12 and oral dexamethasone were also given in group P. 42 cases in group D received docetaxel at a doae of 75mg/m3 and cisplatin intravenousely on day 1, repeated every 21days for one cycle. Tne clinical

  4. Choline Transporters in Human Lung Adenocarcinoma: Expression and Functional Implications

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Choline is an essential nutrient for cell survival and proliferation, however, the expression and function of choline transporters have not been well identified in cancer. In this study, we detected the mRNA and protein expression of organic cation transporter OCT3, carnitine/cation transporters OCTN 1 and OCTN2,and choline transporter-like protein CTL1 in human lung adenocarcinoma cell lines A549, H1299 and SPC-A-1.Their expression pattern was further confirmed in 25 human primary adenocarcinoma tissues. The choline uptake in these cell lines was significantly blocked by CTL1 inhibitor, but only partially inhibited by OCT or OCTN inhibitors. The efficacy of these inhibitors on cell proliferation is closely correlated with their abilities to block choline transport. Under the native expression of these transporters, the total choline uptake was notably blocked by specific PI3K/AKT inhibitors. These results describe the expression of choline transporters and their relevant function in cell proliferation of human lung adenocarcinoma, thus providing a potential"choline-starvation" strategy of cancer interference through targeting choline transporters, especially CTL1.

  5. File list: InP.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines hg19 Input control Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  6. File list: His.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines hg19 Histone Lung Lung adenocarcino...ma cell lines SRX1143598,SRX1143596,SRX1143599,SRX1143597 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  7. File list: Pol.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines hg19 RNA polymerase Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  8. File list: Unc.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: NoD.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: NoD.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: Pol.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: Oth.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines hg19 TFs and others Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  13. File list: DNS.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines hg19 DNase-seq Lung Lung adenocarci...noma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  14. File list: ALL.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Oth.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: Oth.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: Pol.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines hg19 RNA polymerase Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  18. File list: InP.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines hg19 Input control Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  19. File list: ALL.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: ALL.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: InP.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines hg19 Input control Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  2. File list: DNS.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines hg19 DNase-seq Lung Lung adenocarci...noma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  3. File list: Unc.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Unc.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: ALL.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines hg19 All antigens Lung Lung adenocar...cinoma cell lines SRX1143598,SRX1143596,SRX1143599,SRX1143597 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  6. File list: NoD.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines hg19 No description Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/NoD.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  7. File list: Pol.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines hg19 RNA polymerase Lung Lung adenocar...cinoma cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Lng.10.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  8. File list: His.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines hg19 Histone Lung Lung adenocarcino...ma cell lines SRX1143597,SRX1143599,SRX1143598,SRX1143596 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  9. File list: DNS.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines hg19 DNase-seq Lung Lung adenocarcinoma... cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  10. File list: DNS.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines hg19 DNase-seq Lung Lung adenocarcinoma... cell lines http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  11. File list: Unc.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines hg19 Unclassified Lung Lung adenocarcinoma cell line...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  12. File list: InP.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines hg19 Input control Lung Lung adenocarcinoma cell line...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Lng.05.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  13. File list: Oth.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines hg19 TFs and others Lung Lung adenocarcinoma cell line...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  14. File list: His.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines hg19 Histone Lung Lung adenocarcinoma cell line...s SRX1143596,SRX1143597,SRX1143598,SRX1143599 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Lng.20.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  15. File list: His.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines hg19 Histone Lung Lung adenocarcinoma cell line...s SRX1143596,SRX1143597,SRX1143598,SRX1143599 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Lng.50.AllAg.Lung_adenocarcinoma_cell_lines.bed ...

  16. EGFR-Mutant Lung Adenocarcinoma Mimicking a Pneumonia

    Directory of Open Access Journals (Sweden)

    Álvaro Taus

    2012-01-01

    Full Text Available PET-CT scan has demonstrated to be very effective in lung cancer diagnosis and staging, but lung cancer has multiple ways of presentation, which can lead to an error in diagnosis imaging and a delay on the beginning of specific treatment. We present a case of a 77-year-old man with an initial PET-CT scan showing high 18F-FDG intake, suggesting a bilateral pneumonia, who was finally diagnosed of an EGFR-mutant lung adenocarcinoma. EGFR-activating mutation allowed us to start treatment with the oral tyrosin kinase inhibitor Gefitinib, obtaining a rapid and sustained response. Histological confirmation of imaging findings is always necessary to avoid diagnostic errors.

  17. Adenocarcinoma of the lung presenting with atypical cystic brain lesions

    Science.gov (United States)

    Costa, Ricardo; Costa, Rubens B; Bacchi, Carlos; Sarinho, Filipe

    2014-01-01

    Brain metastases occur in up to 10–30% of patients with cancer. Metastatic lesions are usually diagnosed as multiple mass lesions at the junction of the grey and white matter with associated perilesional vasogenic oedema. Cysticercosis is an endemic disease in underdeveloped countries of Africa, Central and South America and is the most common parasitic infection of the central nervous system. The classical radiological finding of neurocysticercosis is cystic lesions showing the scolex in the brain parenchyma. We report a case of metastatic adenocarcinoma of the lung presenting with cystic brain lesions mimicking neurocysticercosis. PMID:24717598

  18. Superior Vena Cava Thrombosis in a Case of Lung Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Santanu Ghosh

    2013-01-01

    Full Text Available Superior vena cava syndrome is a common presentation of bronchogenic carcinoma. The mechanism of obstruction is by compression of superior vena cava by the bronchogenic tumor itself or enlarged mediastinal lymph nodes. However obstruction due to intravascular thrombosis is extremely uncommon. Here, we report a rare case of a 65-year-old male smoker who presented with superior vena cava syndrome and bilateral pleural and pericardial effusion with thrombotic occlusion of the superior vena cava in adenocarcinoma of the lung. He was given chemotherapy with carboplatin and gemcitabine with anticoagulant therapy.

  19. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Energy Technology Data Exchange (ETDEWEB)

    Bispo, Irving Gabriel Araujo; Nascimento, Diego Teixeira; Ferreira, Karina Oliveira; Fakhouri, Ricardo; Godinho, Atilano Salvador; Ferrao, Thiago de Oliveira, E-mail: irvingbispo@yahoo.com.br [Universidade Federal de Sergipe (HU-UFS), Aracaju, SE (Brazil). Hospital Universitario

    2013-09-15

    The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed. (author)

  20. Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells.

    Directory of Open Access Journals (Sweden)

    Michael S Mulvihill

    Full Text Available BACKGROUND: Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues. Here, we sought to quantify expression of Gremlin in cancers of the lung and performed in vitro experiments to check whether Gremlin promotes cell growth and proliferation. METHODOLOGY/PRINCIPAL FINDINGS: Expression of Gremlin in 161 matched tumor and normal lung cancer specimens is quantified by quantitative real-time PCR and protein level is measured by immunohistochemistry. GREM1 was transfected into lung fibroblast and epithelial cell lines to assess the impact of overexpression of Gremlin in vitro. RESULTS: Lung adenocarcinoma but not squamous cell carcinoma shows a significant increase in Gremlin expression by mRNA and protein level. Lung fibroblast and epithelial cell lines transfected with GREM1 show significantly increased cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could hold promise as a new diagnostic marker or potential therapeutic target in lung AD or general thoracic malignancies.

  1. Stromal micropapillary component as a novel unfavorable prognostic factor of lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ohe Miki

    2012-01-01

    Full Text Available Abstract Background Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC] rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]. We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases. Patients and Methods We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR and KRAS mutations. Results SMPC-positive (SMPC(+ tumors were observed in 19 cases (3.4%. The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+ tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035. SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases

  2. Surgery for lung adenocarcinoma with smokers’ polycythemia: a case report

    Directory of Open Access Journals (Sweden)

    Sugiura Yasoo

    2013-02-01

    Full Text Available Abstract Background Smoking is a cause of cancer and polycythemia. Therefore, surgeons who treat patients with cancer may also encounter patients with polycythemia. However, few cases of surgical patients with polycythemia have been reported; in particular, a surgical case involving smokers’ polycythemia has never been reported. We herein report a patient with lung cancer and smokers’ polycythemia who successfully underwent lobectomy with control of hematocrit based on a modified formula in the perioperative period. Case presentation A 67-year-old man underwent abdominoperineal resection for rectal carcinoma in June 2008. A ground glass opacity had been identified in the upper lobe of the right lung and was gradually enlarging. In March 2012, bronchoscopic cytology for investigation of the mass revealed non-small cell lung cancer, suggesting primary lung non-small cell carcinoma (T1bN0M0, Stage IA. When he was referred to our hospital for surgery, his complete blood count showed a red blood cell level of 6.50×106/μL, hemoglobin of 21.0 g/dL, and hematocrit of 60.1%. The hematologists’ diagnosis was secondary polycythemia due to heavy smoking (smokers’ polycythemia because the white blood cell and platelet counts were within normal limits and the erythropoietin was not increased. We calculated the appropriate phlebotomy and infusion volumes based on a formula that we modified. After 550 g of blood was phlebotomized to reduce the hematocrit to approximately 55%, video-assisted right lung upper lobectomy with lymph node dissection was performed in April 2012. The hematocrit was maintained at Conclusion We experienced a patient with smokers’ polycythemia who underwent right upper lobectomy for adenocarcinoma. The findings in this case report are meaningful for surgeons treating cancer patients because there are few reports discussing the perioperative care of surgical patients with polycythemia.

  3. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Casal, Roberto; Bhattacharya, Chitralekha [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Epperly, Michael W. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Basse, Per H. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Hong [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Biostatistics, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Xinhui [Harvard Medical School, Harvard University, 25 Shattuck Street, Boston, MA 02115 (United States); Proia, David A. [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States); Greenberger, Joel S. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Socinski, Mark A.; Levina, Vera, E-mail: levinav@upmc.edu [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-05-22

    The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors.

  4. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Kai, E-mail: gk161@163.com [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Department of Respiration, 161th Hospital, PLA, Wuhan 430015 (China); Jin, Faguang, E-mail: jinfag@fmmu.edu.cn [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

  5. Adenocarcinoma of lung masquerading as systemic auto-immune disease.

    Science.gov (United States)

    Naha, Kushal; Thakare, Sayali; Vivek, G; Prabhu, Mukhyaprana

    2012-06-14

    A 40-year-old previously healthy male presented with acute onset painless dimness of vision in both eyes since the past week and low-grade fever, anorexia and weight loss for the past 1 month. He had been evaluated at a local hospital and diagnosed to have a posterior cerebral artery territory infarct on the left side on the strength of cranial CT. Shortly after receiving antiplatelets and warfarin he had developed severe coagulopathy as evidenced by haematemesis, epistaxis and haematuria. Preliminary investigation revealed prolonged clotting parameters, renal failure and anaemia. Cerebral MRI showed multiple areas of cortical haemorrhage. In the course of his hospital stay, he developed further stigmata of auto-immunity including Coomb's positive haemolytic anaemia, recurrent venous thromboses and a palpable purpuric truncal rash. He was eventually diagnosed to have an adenocarcinoma of the lung, and was subsequently referred to an oncologist for further therapy.

  6. Genomic aberrations in lung adenocarcinoma in never smokers.

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    Bastien Job

    Full Text Available BACKGROUND: Lung cancer in never smokers would rank as the seventh most common cause of cancer death worldwide. METHODS AND FINDINGS: We performed high-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in sixty never smokers and identified fourteen new minimal common regions (MCR of gain or loss, of which five contained a single gene (MOCS2, NSUN3, KHDRBS2, SNTG1 and ST18. One larger MCR of gain contained NSD1. One focal amplification and nine gains contained FUS. NSD1 and FUS are oncogenes hitherto not known to be associated with lung cancer. FISH showed that the amplicon containing FUS was joined to the next telomeric amplicon at 16p11.2. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. Other cancer genes present in aberrations included ARNT, BCL9, CDK4, CDKN2B, EGFR, ERBB2, MDM2, MDM4, MET, MYC and KRAS. Unsupervised hierarchical clustering with adjustment for false-discovery rate revealed clusters differing by the level and pattern of aberrations and displaying particular tumor characteristics. One cluster was strongly associated with gain of MYC. Another cluster was characterized by extensive losses containing tumor suppressor genes of which RB1 and WRN. Tumors in that cluster frequently harbored a central scar-like fibrosis. A third cluster was associated with gains on 7p and 7q, containing ETV1 and BRAF, and displayed the highest rate of EGFR mutations. SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity. CONCLUSIONS: The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers.

  7. Lung Adenocarcinoma with Pulmonary Miliary Metastases and Complex Somatic Heterozygous EGFR Mutation

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    Alexandre Schaller

    2014-11-01

    Full Text Available The pretreatment detection of an activating mutation of EGFR is now routinely performed in metastatic nonsquamous non-small cell lung cancer (NSCLC. The therapeutic impact of such a detection is major, as patients with advanced NSCLC exhibiting a mutation of exon 19 or 21 will benefit from EGFR-tyrosine kinase inhibitors (TKI. The presence of an EGFR resistance mutation, such as T790M in EGFR-TKI-naïve patients, is seldom looked for and is related either to a germinal mutation or to somatically mutated subclones. It has a negative predictive impact. We present the case of a patient with a lung papillary adenocarcinoma and miliary intrapulmonary metastases whose tumor displays a somatic complex heterozygous EGFR mutation, combining L858R (exon 21 and a primary resistance mutation T790M (exon 20, both detected by direct sequencing.

  8. Prognostic factorsin inoperable adenocarcinoma of the lung: A multivariate regression analysis of 259 patiens

    DEFF Research Database (Denmark)

    Sørensen, Jens Benn; Badsberg, Jens Henrik; Olsen, Jens

    1989-01-01

    The prognostic factors for survival in advanced adenocarcinoma of the lung were investigated in a consecutive series of 259 patients treated with chemotherapy. Twenty-eight pretreatment variables were investigated by use of Cox's multivariate regression model, including histological subtypes...... and degree of differentiation, the new international staging system for lung cancer, and seven laboratory parameters. Staging of the patients included bone marrow examination but were otherwise nonextensive without routine bone, liver, and brain scans. Factors predicting poor survival were low performance...... status, stage IV disease, no prior nonradical resection, liver metastases, high values of white blood cell count, and lactate dehydrogenase, and low values of aspartate aminotransaminase. The nonradical resection may not be a prognostic factor because of the resection itself but may rather serve...

  9. Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma

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    Qing-Ping Deng

    2017-03-01

    Full Text Available Background: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2 in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. Methods: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα. The animal model was confirmed by the hematoxylin and eosin (H&E method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST, alanine amino transferase (ALT, urea and creatinine were carried out. Results: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS as well as proliferating cell nuclear antigen (PCNA, recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. Conclusions: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.

  10. EGFR Mutation Heterogeneity and the Mixed Response to EGFR Tyrosine Kinase Inhibitors of Lung Adenocarcinomas

    OpenAIRE

    Chen, Zhi-yong; Zhong, Wen-Zhao; Zhang, Xu-Chao; Su, Jian; Yang, Xue-Ning; Chen, Zhi-Hong; Yang, Jin-Ji; Zhou, Qing; Yan, Hong-Hong; An, She-Juan; Chen, Hua-Jun; JIANG, BEN-YUAN; Mok, Tony S.; Wu, Yi-Long

    2012-01-01

    Direct sequencing was used to identify EGFR mutations in 180 pairs of lung adenocarcinoma samples from the primary tumor and one metastatic site in 3,071 patients. Correlations between EGFR genetic heterogeneity and patient characteristics were examined.

  11. ADENOVIRUS-MEDIATED WILD-TYPE P53 EXPRESSION SUPPRESSES GROWTH OF LUNG ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Li Jian; Xia Yongjing; Jiang Lei; Li Hongxia; Hu Yajun; Yi Lin; Hu Shixue; Xu Hongji

    1998-01-01

    Objective: To study the growth suppression of lung adenocarcinoma cell by the introduction of wild-type P53gene and explore a gene therapy approach for lung adenocarcinoma. Methods: A replication-deficient adenovirus vector encoding a wild-type P53 was constructed and transfected into the cultured human lung adenocarcinoma cell line GLC-82. The efficiency of gene transfection and expression was detected by immunochemical staining and polymerase chain reaction. The cell growth rate and cell cycle were analysed by cell-counting and flow cytometry. Results: Wild-type P53 gene could be quickly and effectively transfected into the cells by adenovirus vector. Wild-type P53 expression could inhibit GLC-82 cell proliferation and induce apoptosis.Conclusion: The results indicated that recombinant adenovirus expressing wild-type P53 might be useful vector for gene therapy of human lung adenocarcinoma.

  12. Effects of the Spider Venom on proliferation of Human Lung Adenocarcinoma Cell A549

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    Zengxiang HU

    2010-10-01

    Full Text Available Background and objective The spider venom may inspire new drugs to treat cancer. The aim of this study is to investigate the effects and mechanisms of spider venom on lung adenocarcinoma cell A549. Methods The proliferation of lung adenocarcinoma A549 cells was detected by MTT. The apoptosis rate was observed with MTT assay and flow cytometer. The activity of catalase was detected by colorimetry. The malondialdehyde (MDA content was determined by improved thiobarbituric acid fluorometric method. The expression of P38MAPK protein was analyzed with Western blot. Results Spider venom can remarkably inhibite the proliferation of lung adenocarcinoma A549 cells, increased activity of catalase and MDA content, down-regulated expression of P38MAPK compared with the control group. Conclusion The reduced proliferation of lung adenocarcinoma A549 cells by spider venom is may be associated with the increased of activity of catalase and MDA content and decreased expression of P38MAPK.

  13. Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma

    OpenAIRE

    Gao, Feng; Liu, Qicai; Li, Guoping; Dong, Feng; Qiu, Minglian; Lv, Xiaoting; Zhang, Sheng; Guo, Zheng

    2016-01-01

    Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using ...

  14. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Directory of Open Access Journals (Sweden)

    Irving Gabriel Araujo Bispo

    2013-09-01

    Full Text Available The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed.

  15. Identification of serum biomarkers for diagnosing stage Ⅰ lung adenocarcinoma by MALDI-TOF mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To identify specific biomarkers that could improve early diagnosis of lung adenocarcinoma using matrix-assisted laser desorption/ionization (MALDI) technology. Methods Serum samples were isolated from 17 patients with stage Ⅰ lung adenocarcinoma and 17 age-and sex-matched healthy controls,and the serum proteomic profiles were obtained by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Results Compared with healthy control group,two highly expressed potenti...

  16. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion

    OpenAIRE

    Verma, Akash; Phua, Chee Kiang; Sim, Wen Yuan; Algoso, Reyes Elmer; Tee, Kuan Sen; Lew, Sennen J. W.; Lim, Albert Y.H.; Goh, Soon Keng; Tai, Dessmon Y. H.; Kor, Ai Ching; Ho, Benjamin; Abisheganaden, John

    2016-01-01

    Abstract To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis. Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012. Univariate analyses showed lower pleural fluid LDH 667 (313–967) versus 971 (214–3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 ...

  17. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Woloschak, G.E. [Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology

    1997-08-01

    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  18. Advances on Driver Oncogenes of Squamous Cell Lung Cancer

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    Wei HONG

    2014-05-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC of the lung is the most frequent histologic subtype in non-small cell lung cancer. Several molecular alterations have been defined as "driver oncogenes" responsible for both the initiation and maintenance of the malignancy. The squamous cell carcinoma of the lung has recently shown peculiar molecular characteristics which relate with both carcinogenesis and response to targeted drugs. So far, about 40% of lung squamous cell carcinoma has been found harbouring driver oncogenes, in which fibroblast growth factor receptor 1 (FGFR1 plays important roles. In this review, we will report the mainly advances on some latest driver mutations of squamous cell lung cancer.

  19. SIRT1 expression is associated with poor prognosis of lung adenocarcinoma

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    Li C

    2015-04-01

    Full Text Available Chong Li,1,2,* Lingling Wang,3,* Liang Zheng,4 Xianghong Zhan,4 Bin Xu,1,2 Jingting Jiang,1,2 Changping Wu1,2 1Department of Tumor Biological Treatment, the Third Affiliated Hospital, Soochow University, Changzhou, 2Cancer Immunotherapy Engineering Research Center of Jiangsu Province, Changzhou, 3Department of Medical Education, Jinling Hospital, Medical School of Nanjing University, Nanjing, 4Department of Thoracic Surgery, the Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Several studies have reported that the overexpression of Sirtuin 1 (SIRT1 was associated with poor prognosis in various human cancers. However, little is known regarding the prognostic value of SIRT1 in lung adenocarcinoma. Therefore, the aim of this study is to evaluate the role of SIRT1 in the prognosis of lung adenocarcinoma patients. Using a tissue microarray, we detected SIRT1 expression by immunohistochemistry in lung adenocarcinoma tissue, as well as in corresponding noncancerous tissues (NCTs. A high expression level of SIRT1 was observed in 74.7% (56/75 of patients with lung adenocarcinoma and 6.7% (5/75 of NCTs (P<0.001. SIRT1 expression was significantly associated with high pathological stage. Importantly, we found that SIRT1 expression was associated with worse overall survival in these lung adenocarcinoma patients (67.0 months vs 104.5 months; P=0.005. In addition, anaplastic lymphoma kinase, epidermal growth factor receptor, vascular endothelial growth factor (VEGF, and Survivin expression were evaluated by fluorescent in situ hybridization or immunohistochemistry, respectively. We found that VEGF and Survivin were both highly expressed in the lung adenocarcinoma tissues, as compared to NCTs. Moreover, the SIRT1 and VEGF expression statuses were significantly positively correlated (r=0.238, P=0.039, while SIRT1 and Survivin expression status were not

  20. The Study on Gene Amplification of EGFR in Bronchioloalveolar Carcinoma and Conventional Adenocarcinoma of the Lung

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    Xin SONG

    2009-08-01

    Full Text Available Background and objective Patients with adenocarcinoma of the lung have disproportionately response to the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI. The aim of this study is to analyze the difference of EGFR gene amplification in bronchioloalveolar carcinoma (BAC, adenocarcinma mixed subtype and conventional adenocarcinoma of the lung and provide some information to clinical therapies. Methods Lung cancer cases were collected and reviewed from the archives of the Department of Pathology, Chinese PLA General Hospital during the time period from 2004 to 2006. The definite diagnosis of BAC based on 2004 WHO classification of lung tumors was made by two pathologists. Fluorescence in situ hybridization (FISH was performed to detect EGFR gene amplification in pure BAC, adenocarcinma mixed subtype and conventional adenocarcinoma. Results Conventional adenocarcinoma had higher EGFR amplification compared with pure BAC and adenocarcinma mixed subtype (χ2=11.632, P<0.05. EGFR gene amplification was found in 45.45% of conventional adenocarcinoma, 14.81% in pure BACs, and 22.58% in adenocarcinma mixed subtype. EGFR gene amplification was observed as scattered signals in most cases. Conclusion EGFR gene amplification was seen more frequently in the invasive components than in BAC. EGFR gene amplification might be associated with the development of adenocarcinoma of the lung.

  1. 25-Hydroxycholesterol promotes migration and invasion of lung adenocarcinoma cells.

    Science.gov (United States)

    Chen, Li; Zhang, Lishan; Xian, Guozhe; Lv, Yinping; Lin, Yanliang; Wang, Yibing

    2017-03-18

    25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase in various organs and is involved in many processes, including lipid metabolism, inflammation and the immune response. However, the role of 25-HC in the migration and invasion of lung adenocarcinoma (ADC) cells remains largely unknown. In this study, we demonstrated that 0.1 μM 25-HC promoted ADC cell migration and invasion without affecting cell proliferation, especially after coculture with THP1-derived macrophages. Further investigation showed that 0.1 μM 25-HC significantly stimulated interleukin-1β (IL-1β) secretion in a coculture system and increased the expression of LXR and Snail. IL-1β also mimicked the effect of 25-HC. LXR knockdown notably blocked the 25-HC-induced Snail expression, migration and invasion in both the monoculture system and the coculture system, but it did not impact the effect of IL-1β, which suggested that IL-1β functioned in an LXR-independent manner. These results suggested that 25-HC promoted ADC cell migration and invasion in an LXR-dependent manner in the monoculture system but that in the coculture system, the 25-HC-induced IL-1β secretion enhanced the effect of 25-HC in an LXR-independent manner.

  2. Yes associated protein is a poor prognostic factor in well-differentiated lung adenocarcinoma.

    Science.gov (United States)

    Kim, Mi Hyun; Kim, Young Keum; Shin, Dong Hoon; Lee, Hyun Jeong; Shin, Nari; Kim, Arong; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Lee, Chang Hun; Sol, Mee Young

    2015-01-01

    The Hippo pathway is a highly conserved potent regulator of cell growth and apoptosis including large tumor suppressor (LATS) and Yes-associated protein (YAP). LATS has been regarded as a tumor suppressor gene and YAP as either of a tumor suppressor gene or an oncogene. We investigated their expression in lung adenocarcinoma. YAP and LATS protein expression was assessed in 167 surgically resected lung adenocarcinomas and compared with clinicopathologic factors. Disease free survival and overall survival were also evaluated. YAP expression was noted in cytoplasm (48 cases; 28.7%), nuclear (34; 20.4%) and both locations (4; 2.4%). The nuclear expression was typically observed in well differentiated adenocarcinoma. LATS was expressed in cytoplasm when its signal is weak. Perinuclear expression of LATS was observed when it is strongly expressed. While cytoplasmic and nuclear YAP expressions were inversely related. In well differentiated adenocarcinoma patients, YAP nuclear expression was related with more frequent relapse. Both of nuclear YAP and LATS expression were more frequently observed in well differentiated adenocarcinoma. Furthermore, YAP expression exhibited more frequent relapse in well differentiated adenocarcinoma group. We suggest that YAP may act as an oncogene and predict poorer prognosis in well differentiated lung adenocarcinoma.

  3. ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas.

    Science.gov (United States)

    Wright, Casey M; Larsen, Jill E; Hayward, Nicholas K; Martins, Maria U; Tan, Maxine E; Davidson, Morgan R; Savarimuthu, Santiyagu M; McLachlan, Rebecca E; Passmore, Linda H; Windsor, Morgan N; Clarke, Belinda E; Duhig, Edwina E; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M

    2010-08-01

    Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.

  4. Tumor lysis without syndrome in adenocarcinoma of the lung: Case report.

    Science.gov (United States)

    Chopra, Amit; Marak, Creticus; Alappan, Narendra Kumar; Alterman, Daniel; Shim, Chang

    2013-01-01

    Tumor lysis syndrome TLS is commonly seen during the treatment of rapidly proliferating. However TLS is rarely reported in Non-small cell Lung Cancer. This may because of low proliferative rate and chemo-resistant nature of NSCLC. We are reporting a case of tumor lysis without concomitant syndrome in a patient with adenocarcinoma of Lung.

  5. Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Cinegaglia, Naiara C; Andrade, Sonia Cristina S; Tokar, Tomas;

    2016-01-01

    of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma....

  6. EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report.

    Science.gov (United States)

    Dansin, Eric; Carnot, Aurélien; Servent, Véronique; Daussay, Dorothée; Robin, Yves-Marie; Surmei-Pintilie, Ecaterina; Lauridant, Géraldine; Descarpentries, Clothilde; Révillion, Françoise; Delattre, Claire

    2015-01-01

    Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same activating EGFR mutations were identified in both the primary lung carcinoma and the breast metastasis.

  7. EGFR-Mutated Breast Metastasis of Lung Adenocarcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Eric Dansin

    2015-03-01

    Full Text Available Breast metastasis from other primary carcinoma is very rare and could be difficult to identify despite immunohistochemistry analysis. Breast metastasis from lung adenocarcinoma can mimic triple-negative breast cancer. Given the prognosis and therapeutic challenges, a correct diagnosis appears essential, and molecular biomarkers could be useful. We report the case of a 52-year-old woman with a breast mass initially diagnosed as primary breast cancer and secondarily attached to breast metastasis from an EGFR-mutated lung adenocarcinoma. The same activating EGFR mutations were identified in both the primary lung carcinoma and the breast metastasis.

  8. Ion channel gene expression in lung adenocarcinoma: potential role in prognosis and diagnosis.

    Science.gov (United States)

    Ko, Jae-Hong; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Eun A; Zhou, Tong

    2014-01-01

    Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts.

  9. The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma.

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    Jau-Chung Hwang

    Full Text Available Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1 and RAD54B (RAD54 homolog B were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230. These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B.

  10. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  11. Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma

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    Hagen Jeffrey A

    2007-10-01

    Full Text Available Abstract Background Lung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients. Results We identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value Conclusion The identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.

  12. A robust prognostic gene expression signature for early stage lung adenocarcinoma

    DEFF Research Database (Denmark)

    Krzystanek, Marcin; Moldvay, Judit; Szüts, David;

    2016-01-01

    Stage I lung adenocarcinoma is usually not treated with adjuvant chemotherapy; however, around half of these patients do not survive 5 years. Therefore, a reliable prognostic biomarker for early stage patients would be critical to identify those most likely to benefit from early additional treatm...... not given adjuvant therapy. Seven genes consistently obtained statistical significance in Cox regression for overall survival. The combined signature has a weighted mean hazard ratio of 3.2 in all cohorts and 3.0 (C.I. 1.3-7.4, p ...... treatments. Several studies have searched for gene expression prognostic biomarkers for lung adenocarcinoma, but these have not yielded a widely accepted prognosticator. We analyzed gene expression from seven published lung adenocarcinoma cohorts for which we included only stage I and II patients who were...

  13. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

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    Mathieu Salaün

    Full Text Available Several matrix metalloproteinases (MMPs are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27, but in none of the non-invasive (0/4 (p=0.001.MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.

  14. Comparative analysis of the correlation between HRCT image features and histopathologic characteristics of cyst-like lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    张丽

    2014-01-01

    Objective To evaluate the high resolution CT(HRCT)features of cyst-like lung adenocarcinoma,explore the correlation between HRCT image features and histopathological characteristics,and observe the pathological basis of air-containing space.Methods HRCT and histopathologic findings of cyst-like lung adenocarcinoma in 86 patients were investigated retrospectively.

  15. A CASE OF CONCOMITANT ADENOCARCINOMA OF LUNG AND PULMONARY TUBERCULOSIS IN A YOUNG FEMALE

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    Pujari Vishwanath

    2014-07-01

    Full Text Available 28 year female presented to us with X-ray chest suggestive of right opaque hemithorax. She was on anti-tubercular treatment for the presence of Acid Fast Bacilli (AFB in pleural fluid. Clinical examination revealed bronchial breathing on right side. CT thorax showed large mass lesion in right hemi thorax with mild pleural effusion. Thoracocentesis and bronchoscopy showed no evidence of malignancy however AFB were detected in bronchial washing. Transthoracic biopsy was positive for malignancy. On Immunohistochemistry (IHC, Thyroid Transcription Factor 1(TTF1 and NAPSIN A were positive, confirming the diagnosis of adenocarcinoma lung. Final diagnosis of primary adenocarcinoma lung with concomitant tuberculosis was established.

  16. Detection and Analysis of EGFR and KRAS Mutation with Lung Adenocarcinoma

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    Hui ZHANG

    2015-11-01

    Full Text Available Background and objective Mutations in epidermal growth factor receptor (EGFR and KRAS are important markers in non-small cell lung cancer, which are closely related to the clinical therapeutic effect. To analysis the EGFR and KRAS gene mutation rate and its relationship with clinical features in patients with lung adenocarcinoma. Methods 395 patients with treatment naïve lung adenocarcinoma, tumor tissue samples were available for testing. Tumor sample EGFR and KRAS mutation status were detected using mutant enriched liquidchip. Results 395 cases of lung adenocarcinoma, EGFR mutations were detected in 192 cases (48.9%, KRAS mutations were detected in 29 cases (7.8%, and the presence of EGFR and KRAS mutation were detected in 1 case (0.3%. EGFR mutations were found to occur significantly more often in female than in male patients (62.0% vs 37.1%, P0.05 in each clinical factors, only occurred in the wild type EGFR gene in patients (13.5%, 27/200 was significantly higher than that of patients with EGFR mutation (1.0%, 2/192, the difference was statistically significant (P<0.001. Conclusion In lung adenocarcinomas, EGFR mutation was higher in female and non-smoking patients, KRAS mutation only in patients with wild-type EGFR gene was higher. Before using TKI targeted therapy, EGFR and KRAS mutations should be detected.

  17. The Role of DNA Methylation in the Development and Progression of Lung Adenocarcinoma

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    Keith M. Kerr

    2007-01-01

    Full Text Available Lung cancer, caused by smoking in ∼87% of cases, is the leading cause of cancer death in the United States and Western Europe. Adenocarcinoma is now the most common type of lung cancer in men and women in the United States, and the histological subtype most frequently seen in never-smokers and former smokers. The increasing frequency of adenocarcinoma, which occurs more peripherally in the lung, is thought to be at least partially related to modifications in cigarette manufacturing that have led to a change in the depth of smoke inhalation. The rising incidence of lung adenocarcinoma and its lethal nature underline the importance of understanding the development and progression of this disease. Alterations in DNA methylation are recognized as key epigenetic changes in cancer, contributing to chromosomal instability through global hypomethylation, and aberrant gene expression through alterations in the methylation levels at promoter CpG islands. The identification of sequential changes in DNA methylation during progression and metastasis of lung adenocarcinoma, and the elucidation of their interplay with genetic changes, will broaden our molecular understanding of this disease, providing insights that may be applicable to the development of targeted drugs, as well as powerful markers for early detection and patient classification.

  18. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas.

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    Campbell, Joshua D; Alexandrov, Anton; Kim, Jaegil; Wala, Jeremiah; Berger, Alice H; Pedamallu, Chandra Sekhar; Shukla, Sachet A; Guo, Guangwu; Brooks, Angela N; Murray, Bradley A; Imielinski, Marcin; Hu, Xin; Ling, Shiyun; Akbani, Rehan; Rosenberg, Mara; Cibulskis, Carrie; Ramachandran, Aruna; Collisson, Eric A; Kwiatkowski, David J; Lawrence, Michael S; Weinstein, John N; Verhaak, Roel G W; Wu, Catherine J; Hammerman, Peter S; Cherniack, Andrew D; Getz, Gad; Artyomov, Maxim N; Schreiber, Robert; Govindan, Ramaswamy; Meyerson, Matthew

    2016-06-01

    To compare lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SqCC) and to identify new drivers of lung carcinogenesis, we examined the exome sequences and copy number profiles of 660 lung ADC and 484 lung SqCC tumor-normal pairs. Recurrent alterations in lung SqCCs were more similar to those of other squamous carcinomas than to alterations in lung ADCs. New significantly mutated genes included PPP3CA, DOT1L, and FTSJD1 in lung ADC, RASA1 in lung SqCC, and KLF5, EP300, and CREBBP in both tumor types. New amplification peaks encompassed MIR21 in lung ADC, MIR205 in lung SqCC, and MAPK1 in both. Lung ADCs lacking receptor tyrosine kinase-Ras-Raf pathway alterations had mutations in SOS1, VAV1, RASA1, and ARHGAP35. Regarding neoantigens, 47% of the lung ADC and 53% of the lung SqCC tumors had at least five predicted neoepitopes. Although targeted therapies for lung ADC and SqCC are largely distinct, immunotherapies may aid in treatment for both subtypes.

  19. Hepatic Artery Chemotherapy for Advanced Adenocarcinoma of the Pancreas

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    Robert Levin

    2016-08-01

    Full Text Available Context Seventy patients with adenocarcinoma of the pancreas with liver metastases, received chemotherapy every four weeks and their outcomes are reported in this retrospective series. Objective Advanced adenocarcinoma of the pancreas has a poor prognosis with only 2% 5-year survival reported by SEER (Surveillance, Epidemiology and End Results of the NCI. Chemotherapy given as intra-arterial perfusions is more intense than intravenous chemotherapy. Responses in perfused tumor is expected to be better than that obtained with only intravenous chemotherapy. Design Hepatic artery therapy is given monthly as a 5 hour perfusion of the hepatic artery using DDP and MIC. Also given is monthy Intravenous (IV therapy with four hours of Leucovorin (LV, with an injection of FUDR during the last hour of LV, daily x 5 days. Setting all therapy was given at Midwestern Regional Medical Center. Patients Thirty seven patients had no prior chemotherapy, while 33 patients had progressed after prior IV chemotherapy. Intervention Hepatic artery therapy with IV LV-FUDR was given for up to six months depending upon marrow tolerance and response. At that point, if response was ongoing or improving, therapy was continued monthly with only IV LV-FUDR; all therapy was stopped whenever progressive disease was evident. Results of those without prior chemotherapy, the mean overall survival (OS was 17.3 ± 30.2 months (mean±SD, ranging up to 13 years. Six patients survived more than three years with four are living in continuing complete remission for more than five years. Conclusion This therapy offers the opportunity for long term survival in a subset of patients with metastatic adenocarcinoma of the pancreas who have liver metastases, and some patients can be cured.

  20. A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

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    Foroulis Christophoros N

    2008-12-01

    Full Text Available Abstract Background Coexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition. Case presentation A 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14. The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later. Conclusion This is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for

  1. Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion

    Science.gov (United States)

    2015-08-01

    AWARD NUMBER: W81XWH-14-1-0223 TITLE: Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion...COVERED 1Aug2014 - 31Jul2015 4. TITLE AND SUBTITLE Genetic and Epigenetic Determinants of Lung Cancer Subtype: 5a. CONTRACT NUMBER W81XWH-14-1-0223...same patient will provide substantial insight into the determinants of subtype specificity. Preliminary data on one such case demonstrates a

  2. Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma.

    Science.gov (United States)

    Cinegaglia, Naiara C; Andrade, Sonia Cristina S; Tokar, Tomas; Pinheiro, Maísa; Severino, Fábio E; Oliveira, Rogério A; Hasimoto, Erica N; Cataneo, Daniele C; Cataneo, Antônio J M; Defaveri, Júlio; Souza, Cristiano P; Marques, Márcia M C; Carvalho, Robson F; Coutinho, Luiz L; Gross, Jefferson L; Rogatto, Silvia R; Lam, Wan L; Jurisica, Igor; Reis, Patricia P

    2016-05-17

    Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma.

  3. Identification and characterization of SP cells in human lung adenocarcinoma SPC-A1 cells

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    Yanliang ZHU

    2008-10-01

    Full Text Available Background and objective Recently, eloquent studies from some solid tumors have provided proofs that cancers originate from cancer stem cells (CSC. The discovery of CSC has changed our view of carcinogenesis and chemotherapy. The aim of this study is to identify and characterize the CSC population that drives and maintains lung adenocarcinoma growth and metastasis. Methods Side population (SP cell analysis combined with serum-free media (SFM were applied to established human lung adenocarcinoma cell lines. Properties of SP cells were evaluated by their proliferative index, colony-forming efficiency and tumorigenic potential. Results Characteristic SP cells could be detected by FACS in lung adenocarcinoma cell lines. And the proportion of SP cells is greatly increased after serum-free culture.SP cells have a greater proliferative index, a higher colony-forming efficiency and a greater ability to form tumor in vivo .Conclusion SP cells exist in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.

  4. Frequency of epidermal growth factor receptor mutations in Jordanian lung adenocarcinoma patients at diagnosis

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    Natheir Obeidat

    2016-01-01

    Conclusion: The present study revealed that the EGFR mutations rate in Jordanian patients with adenocarcinoma of the lung was higher than in African-American, and some white Caucasian patients, and was lower than in patients in East Asia, and other countries of South Asia.

  5. Lipase member H is a novel secreted protein selectively upregulated in human lung adenocarcinomas and bronchioloalveolar carcinomas

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    Seki, Yasuhiro [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Yoshida, Yukihiro [Department of Surgery, Asahi General Hospital, Chiba (Japan); Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Ishimine, Hisako [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan); Shinozaki-Ushiku, Aya [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Ito, Yoshimasa [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Sumitomo, Kenya [Department of Internal Medicine, JA Kochi Hospital, Kochi (Japan); Nakajima, Jun [Department of Thoracic Surgery, The University of Tokyo, Graduate School of Medicine, Tokyo (Japan); Fukayama, Masashi [Department of Pathology, Graduate School of Medicine, The University of Tokyo, Hongo, Tokyo (Japan); Michiue, Tatsuo [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Asashima, Makoto, E-mail: asashi@bio.c.u-tokyo.ac.jp [Graduate School of Arts and Sciences, The University of Tokyo, Tokyo (Japan); Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Life Science Center of Tsukuba Advanced Research Alliance (TARA), The University of Tsukuba, Tsukuba, Ibaraki (Japan); Kurisaki, Akira, E-mail: akikuri@hotmail.com [Research Center for Stem Cell Engineering, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba (Japan); Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki (Japan)

    2014-01-24

    Highlights: • Most of the adenocarcinomas and bronchioloalveolar carcinomas were LIPH-positive. • LIPH is necessary for the proliferation of lung cancer cells in vitro. • A high level of LIPH in serum is correlated with better survival in early phase lung-cancer patients after surgery. - Abstract: Lung cancer is one of the most frequent causes of cancer-related death worldwide. However, molecular markers for lung cancer have not been well established. To identify novel genes related to lung cancer development, we surveyed publicly available DNA microarray data on lung cancer tissues. We identified lipase member H (LIPH, also known as mPA-PLA1) as one of the significantly upregulated genes in lung adenocarcinoma. LIPH was expressed in several adenocarcinoma cell lines when they were analyzed by quantitative real-time polymerase chain reaction (qPCR), western blotting, and sandwich enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis detected LIPH expression in most of the adenocarcinomas and bronchioloalveolar carcinomas tissue sections obtained from lung cancer patients. LIPH expression was also observed less frequently in the squamous lung cancer tissue samples. Furthermore, LIPH protein was upregulated in the serum of early- and late-phase lung cancer patients when they were analyzed by ELISA. Interestingly, high serum level of LIPH was correlated with better survival in early phase lung cancer patients after surgery. Thus, LIPH may be a novel molecular biomarker for lung cancer, especially for adenocarcinoma and bronchioloalveolar carcinoma.

  6. [Advances of molecular targeted therapy in squamous cell lung cancer].

    Science.gov (United States)

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  7. Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Wang Jianing

    2011-05-01

    Full Text Available Abstract Background The human coagulation trigger tissue factor (TF is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. Methods The specific small interfering RNA (siRNA designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. Results TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. Conclusions Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways.

  8. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma

    Science.gov (United States)

    Yu, Wendan; Li, Jinxiu; Tang, Zhipeng; Yu, Zhenlong; Zhao, Lei; Zhang, Yixiang; Wang, Ziyi; Wang, Peng; Li, Yechi; Li, Fengzhou; Sun, Zhe; Xuan, Yang; Tang, Ranran; Deng, Wu-guo; Guo, Wei; Gu, Chundong

    2016-01-01

    Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma. PMID:27384875

  9. [Adenocarcinoma of lung cancer with solitary metastasis to the stomach].

    Science.gov (United States)

    Koh, Sung Ae; Lee, Kyung Hee

    2014-09-25

    Although hematogenous metastasis of cancer to the gastrointestinal track is rare, it sometime has been reported in patients with malignant melanoma and breast cancer. However, it is extremely rare for lung cancer to metastasize to the stomach, not to mention solitary gastric metastasis. Herein, the authors report a case of a 69-year-old man who was initially diagnosed with lung cancer with synchronous primary gastric cancer which proved to be lung cancer with solitary gastric metastasis after the operation.

  10. Dynamic MR imaging: value of differentiating subtypes of peripheral small adenocarcinoma of the lung

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    Ohno, Yoshiharu E-mail: yosirad@kobe-u.ac.jpyosirad@med.kobe-u.ac.jpyoshiharuohno@aol.com; Hatabu, Hiroto; Takenaka, Daisuke; Uematsu, Hidemasa; Ohbayashi, Chiho; Higashino, Takanori; Nogami, Munenobu; Yoshimura, Masahiro; Fujii, Masahiko; Sugimura, Kazuro

    2004-11-01

    Purpose: To determine the utility of dynamic magnetic resonance imaging (MRI) in the differential subtyping of small adenocarcinomas of the lung. Materials and methods: Twenty-nine pathologically diagnosed peripheral adenocarcinomas (less than 20 mm in diameter) underwent dynamic contrast-enhanced MRI. Maximum relative enhancement ratio, slope of enhancement, and corrected start time of enhancement were calculated from signal intensity-time curve of pulmonary lesion for each subject, and were statistically compared among bronchioloalveolar carcinoma (BAC) group (7 cases), mixed BAC group (10 cases), and adenocarcinoma group (12 cases). Results: Maximum relative enhancement ratio (P<0.001) and slope of enhancement (P<0.001) of BAC group were significantly higher than those of mixed BAC and adenocarcinoma groups. Start times of BAC group were significantly earlier than those of mixed BAC (P=0.0001) and adenocarcinoma groups (P<0.0001). Adapting the thresholds values of MR indexes from the positive tests, sensitivity, specificity, positive predictive value, negative predictive value and accuracy for differentiating BAC from other subtypes were 85.7, 100.0, 100.0, 95.7, and 96.6%, respectively. Conclusions: Dynamic MRI is useful for differentiating subtypes of small peripheral adenocarcinoma.

  11. Identification of serum biomarkers for diagnosing stage I lung adenocarcinoma by MALDI-TOF mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Xin-ju Li; Da-lin He; Jun-ke Fu; Jing-ren Liang

    2009-01-01

    Objectire To identify specific biomarkers that could improve early diagnsis of lung adenuearcinoma using matrix-assisted laser desorptian/ionization (MALDI) technology. Methods Serum samples were isolated from 17 patients with stage I lung adenuearcinoma and 17 age- and sex-matched healthy controls, and the serum proteomic profiles were obtained by matrix-assistcd laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Results Compared with healthy control group, two highly expressed potential biomarkers were identified with the relative molecular weights of 6 631.64 Da and 4 964. 21 Da. The two best novel protein peaks were automatically chosen for the system training and the development of the constructed model. The constructed model was then used to test an independent set of masked serum samples from 15 lung adenocarcinoma patients and 22 healthy individuals. The analysis yielded a sensitivity of 93.3 %, and a specificity of 95.5 %. Conclusion These results suggest that MALDI-TOF-MS ProteinChip technology is a quick, convenient, and high-output analyzing method that is capable of selecting several relatively potential biomarkers from the serum of lung adenocarcinoma patients and may have a clinical value in the future, and will provide clues to identifying new serologic btomarkers of lung adenocarcinoma.

  12. [A case of poorly differentiated lung adenocarcinoma showing air-space consolidation caused by aerogenic metastasis].

    Science.gov (United States)

    Fujita, Kazue; Kurihara, Takeyuki; Ohba, Hideo; Nakamura, Junichi; Okimoto, Niro

    2004-05-01

    A 78-year-old woman was admitted to our hospital because of dyspnea. A chest radiograph and a computed tomogram on admission showed air-space consolidation in the left upper lung field, and so pneumonia was diagnosed. Although antibiotics were administered, the air-space consolidation did not improve. A transbronchial lung biopsy was performed, yielding a pathologic diagnosis of poorly differentiated lung adenocarcinoma. Despite combination chemotherapy with docetaxel and UFT, the air-space consolidation expanded, and the patient finally died of respiratory failure 3 months after diagnosis. Autopsy revealed air-space consolidation due to poorly differentiated lung adenocarcinoma, with large atypical cells diffusely floating in the alveolar spaces. It has been recognized that bronchiolo-alveolar carcinoma and well-differentiated lung adenocarcinoma present with air-space consolidation, reflecting the cancer cells lining the alveolar walls. However, in this case, the air-space consolidation was due to cancer cells diffusely floating in the alveolar spaces in aerogenic metastasis. It was considered that this is a rare case, which presented with a very interesting development pattern.

  13. Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Fumiaki; Toki; Atsushi; Takahashi; Ryusuke; Aihara; Kyoichi; Ogata; Hiroyuki; Ando; Tetsuro; Ohno; Erito; Mochiki; Hiroyuki; Kuwano

    2010-01-01

    AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RE...

  14. Progressive multiple cystic changes in both lungs in a patient treated with gefitinib for lung adenocarcinoma with multiple lung metastases

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    Ryu, Yon Ju; Chun, Eun Mi; Lee, Soon Nam; Shim, Sung Shin [Ewha Womans University School of Medicine, Seoul (Korea, Republic of)

    2014-04-15

    Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.

  15. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

    Science.gov (United States)

    Ikari, Akira; Watanabe, Ryo; Sato, Tomonari; Taga, Saeko; Shimobaba, Shun; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Endo, Satoshi; Matsunaga, Toshiyuki; Sugatani, Junko

    2014-09-01

    Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.

  16. Mammalian mediator 19 mediates H1299 lung adenocarcinoma cell clone conformation, growth, and metastasis.

    Science.gov (United States)

    Xu, Lu-Lu; Guo, Shu-Liang; Ma, Su-Ren; Luo, Yong-Ai

    2012-01-01

    Mammalian mediator (MED) is a multi-protein coactivator that has been identified by several research groups. The involvement of the MED complex subunit 19 (MED 19) in the metastasis of lung adenocarcinoma cell line (H1299), which expresses the MED 19 subunit, was here investigated. When MED 19 expression was decreased by RNA interference H1299 cells demonstrated reduced clone formation, arrest in the S phase of the cell cycle, and lowered metastatic capacity. Thus, MED 19 appears to play important roles in the biological behavior of non-small cell lung carcinoma cells. These findings may be important for the development of novel lung carcinoma treatments.

  17. Urinary bladder metastasis from lung adenocarcinoma: A rare cause of hematuria

    Directory of Open Access Journals (Sweden)

    Kan Wai Man Raymond

    2014-01-01

    Full Text Available We presented an unusual case of hematuria caused by a solitary bladder metastasis from lung adenocarcinoma. A confident diagnosis of secondary adenocarcinoma of the bladder was made by clinical suspicion based on patient′s past history, careful examination of tumor morphology, and a directed panel (cytokeratin [CK] 7/CK20/thyroid transcription factor 1 of immunohistochemistry. We sought, through sharing our experience in the investigative and diagnostic process, to contribute to the better understanding of this unusual cause of hematuria.

  18. Synchronous advanced gastric adenocarcinoma and advanced esophageal squamous cell carcinoma

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    Fernando Augusto Mardiros Herbella

    2002-01-01

    Full Text Available CONTEXT: Synchronous associations of esophageal and gastric cancers are not a common finding, especially with differing histological types and both tumors in advanced forms. A case with such an association is presented, in which an unusual therapy was proposed: palliative gastrectomy and esophageal intubation. CASE REPORT: A 75-year-old white man was referred to our service complaining of malaise and weight loss for one year and dysphagia and vomiting for 2 months. The patient had sought out medical consultation as a result of the latter two complaints.

  19. Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood

    Science.gov (United States)

    Zamay, Galina S; Kolovskaya, Olga S; Zamay, Tatiana N; Glazyrin, Yury E; Krat, Alexey V; Zubkova, Olga; Spivak, Ekaterina; Wehbe, Mohammed; Gargaun, Ana; Muharemagic, Darija; Komarova, Mariia; Grigorieva, Valentina; Savchenko, Andrey; Modestov, Andrey A; Berezovski, Maxim V; Zamay, Anna S

    2015-01-01

    Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics. PMID:26061649

  20. Clinical observation of pemetrexed plus carboplatin as the first-line chemotherapy in elderly patients with advanced lung adenocarcinoma%培美曲塞联合卡铂一线治疗老年晚期肺腺癌临床观察

    Institute of Scientific and Technical Information of China (English)

    吴标; 黄诚; 张晶; 蒋侃; 庄武; 朱凯

    2013-01-01

    Objective To evaluate the efficacy and toxicity of pemetrexed plus carboplatin in the chemotherapy of elderly patients with advanced lung adenocarcinoma. Methods 35 cases of elderly patients with advanced lung adenocarcinoma received pemetrexed 500mg/m2 administered as an intravenous infusion on day 1 plus carboplatin area under the curve (AUC =5) on day 2 every 21 days for up to six cycles. Dexamethasone, folic acid and vitamin B12 were applied to relieve pemetrexed toxicity. The efficacy was estimated by image every two cycle. Results 35 patients were enrolled in this study, 11 patients had a partial response (PR) , 17 patients had a stable disease (SD) , 7 patients had a progression disease (PD) , with an objective response rate of 31. 4% and a disease control rate of 80. 0%. The median progression free survival was 3. 5 months, the median overall survival time was 10. 5 months and 1 year survival was 31. 4% . The most commonly seen adverse events (AEs) was myelosuppression with grade I and grade II toxicity. Non-hematologic toxicity was mild and well tolerated by the patient. Conclusions It was effective and safety of pemetrexed plus carboplatin as the first-line chemotherapy in elderly patients with advanced lung adenocarcinoma.%目的 探讨培美曲塞联合卡铂治疗晚期老年肺腺癌的疗效和不良反应.方法 35例老年晚期肺腺癌患者,给予培美曲塞500mg/m2静脉滴注,第1天,并口服地塞米松、叶酸和肌内注射维生素B12以减轻毒副反应.卡铂(AUC =5)静脉滴注,第2天,每21天为1个周期,最多不超过6个周期.每2个化疗周期进行影像学检查以评价疗效.结果 35例患者中,部分缓解11例(31.4%),稳定17例(48.6%),进展7例(20.0%),客观有效率31.4%,疾病控制率80.0%.中位无进展生存时间为3.5个月,中位生存时间为10.5个月,1年生存率为31.4%.最常见的不良反应为骨髓抑制,多为Ⅰ-Ⅱ级.非血液学毒性反应较轻,病人耐受良好.结论 培

  1. Adverse Events of Afatinib as First-line Treatment for Five Cases of Advanced
Lung Adenocarcinoma and Review of Literature

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    Hong TAO

    2014-04-01

    Full Text Available Background and objective Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR mutations. The aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. Methods Patients with lung adenocarcinoma (stage IIIb or IV with EGFR mutations were first-line treated with an oral administration of afatinib (40 mg/d until disease progression. Adverse events, effects, and survival condition were observed. Results The most common adverse events were diarrhea (n=5, 100%, skin rash (n=4, 80%, and mucositis/stomatitis (n=4, 80%. Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. Three patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%, one with stable disease (25% and one with progressive disease (25%. Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. Conclusion Afatinib was approved as first-line treatment for patients with advanced lung adenocarcinoma. The most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for confirmation.

  2. Osteosclerotic lesions in patients treated with gefitinib for lung adenocarcinomas: a sign of favorable therapeutic response

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, Yoshiko; Aoki, Takatoshi; Korogi, Yukunori [University of Occupational and Environmental Health, School of Medicine, Department of Radiology, Kitakyushu (Japan); Hanagiri, Takeshi; Uramoto, Hidetaka [University of Occupational and Environmental Health, School of Medicine, Second Department of Surgery, Kitakyushu (Japan); Yoshii, Chiharu; Mukae, Hiroshi [University of Occupational and Environmental Health, School of Medicine, Department of Respiratory Disease, Kitakyushu (Japan)

    2012-04-15

    To assess the frequency of osteosclerotic changes on CT that appeared after treatment with gefitinib in patients with lung adenocarcinoma and the relationship between the osteosclerotic changes and the response to the therapy. Our study included 41 patients with lung adenocarcinoma who underwent chest CT both before (CTpre) and after (CTpost) starting treatment with gefitinib. The presence or absence of bone metastases was assessed on the CTpre, and the interval bony change after the therapy was classified as lytic, sclerotic, or no changes on the CTpost. The relationship between treatment results of primary lung cancer and interval bony changes was evaluated. Osteosclerotic lesions were identified in 11 patients (27%) on CTpost; in 6 of 11 patients osteosclerotic lesions newly appeared where the CTpre showed no bone metastasis before the gefitinib therapy. There were significant differences in the therapeutic response of the primary cancers (P < 0.001) and in the survival rate (P < 0.01) in patients with osteosclerotic changes versus those without osteosclerotic changes. Osteosclerotic changes on CT, observed after gefitinib treatment in patients with lung adenocarcinomas, may be an indicator of a good therapeutic response. (orig.)

  3. KRAS Mutations in Lung Adenocarcinoma: Molecular and Epidemiological Characteristics, Methods for Detection, and Therapeutic Strategy Perspectives.

    Science.gov (United States)

    Guibert, N; Ilie, M; Long, E; Hofman, V; Bouhlel, L; Brest, P; Mograbi, B; Marquette, C H; Didier, A; Mazieres, J; Hofman, P

    2015-01-01

    KRAS mutations are detected in over one third of lung adenocarcinomas, most frequently in Caucasian and smoker patients. The impact of KRAS mutations on lung adenocarcinoma prognosis is currently subject to debate, as is their impact on the response to chemotherapy and EGFR tyrosine kinase inhibitors. The different methods for KRAS status assessment, based on histological and cytological samples or biological fluids, offer varying sensitivities. Since no treatments are available in clinical routine for KRAS-mutated lung cancer patients, one of the current major challenges in thoracic oncology is developing new dedicated strategic therapies. Different molecules can be developed that act on a post-transcriptional KRAS protein level, blocking its cytoplasmic membrane recruitment. The efficacy of these molecules' targeting of the different signaling pathways activated by the KRAS mutation (such as the MEK and BRAF pathways) is related to the particular KRAS mutation subtype. New therapeutic strategies are currently focused on certain genes linked with KRAS inducing a synthetic lethal interaction. The purpose of this work is to provide an overview of i) the recent epidemiological and molecular findings concerning KRASmutated lung adenocarcinoma, ii) the prognostic impact of KRAS mutations, in particular during response to treatment, iii) the available methods for detecting this mutation, and iv) the current molecules under development for new therapeutic strategies and the clinical trials targeting this genomic alteration.

  4. Adenocarcinoma of the lung with scattered consolidation: Radiological–pathological correlation and prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Binghu, E-mail: mbhh@live.cn [Thoracic Medical Center and Department of Radiology, BenQ Hospital, Nanjing Medical University, 71 Hexi Street, Nanjing, Jiangsu 210019 (China); Department of Diagnostic Radiological Imaging, Division of Allied Health Sciences, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takashima, Shodayu; Hakucho, Tomoaki; Hodaka, Numasaki [Department of Diagnostic Radiological Imaging, Division of Allied Health Sciences, Osaka University Graduate School of Medicine, 1-7 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yasuhiko, Tomita; Masahiko, Higashiyama [Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka 537-0025 (Japan)

    2013-10-01

    Purpose: To investigate the clinicopathological features and prognosis in patients with adenocarcinoma of the lung with scattered consolidation (ALSC). Materials and methods: Between January 2006 and March 2010, 139 consecutive patients with lung adenocarcinoma of ≤3 cm, who underwent pulmonary resection for lung cancer, were investigated retrospectively. Radiologic classification was based on the findings of thin-section CT such as the presence of consolidation or ground-glass opacity (GGO). Type I (n = 15) and Type II (n = 14), showed a pure GGO and a mixed GGO with consolidation <50%, respectively. Type IV (n = 38) and Type V (n = 52) showed a mixed GGO with consolidation ≥50% and a pure consolidation, respectively. Type III (n = 20) was the adenocarcinoma of the lung with scattered consolidation (ALSC). The clinicopathological features and prognosis of ALSC was investigated with comparative analysis and survival analysis. Results: Because of the similar recurrence rate for Type I and Type II (P = 1.000), Type IV and Type V (P = 0.343), we merged Type I and Type II as Type I + II, Type IV and Type V as Type IV + V, respectively. In the 20 (14.4%) patients with ALSC, lymph node metastasis was not observed, and it was rare in lymphatic invasion and vascular invasion. On the basis of IASLC/ATS/ERS 2011 classification, 80% of the ALSC were preinvasive lesions. In Noguchi classification, there was no significant difference between Type I + II and ALSC (P = 0.260). The prognosis of ALSC was similar to Type I + II (P = 0.408), but better than Type IV + V (P = 0.040). Conclusion: Adenocarcinoma of the lung with scattered consolidation (ALSC) on thin-section CT was a relatively favorable prognostic factor.

  5. Overexpression of Aquaporin-1 in lung adenocarcinomas and pleural mesotheliomas

    OpenAIRE

    López-Campos, José Luis; Sánchez Silva, Rocío; Gómez Izquierdo, Lourdes; Márquez, Eduardo; Ortega Ruiz, Francisco; Cejudo, Pilar; Barrot Cortés, Emilia; Toledo Aral, Juan José; Echevarría, Miriam

    2011-01-01

    Aquaporin-1 (AQP1) is the main water channel responsible for water transport through many epithelia and endothelia. The latest evidence pointed toward an important role of this protein also in gas permeation, angiogenesis, cell proliferation and migration. In the present work we studied the expression of AQP1 by immunohistochemical staining of 92 lung biopsies from patients diagnosed with a pleuropulmonary tumor (71 lung and 21 pleural neoplasms). AQP1 expression wa...

  6. Synergistic effect of Kanglaite Injection combined with Pemetrexed and Cisplatin in the treatment of advanced lung adenocarcinoma%康莱特在培美曲塞联合顺铂治疗晚期肺腺癌中的协同作用

    Institute of Scientific and Technical Information of China (English)

    王红艳; 汤虹; 吴育锋; 王莉莉; 何振; 张哲; 王启鸣

    2016-01-01

    Objective To investigate the synergistic effect of Kanglaite Injection combined with Pemetrexed and Cisplatin in the treatment of advanced lung adenocarcinoma. Methods 52 patients with advanced lung adenocarcinoma treated in Tumor Hospital Affiliated to Zhengzhou University from March 2014 to July 2015 were selected. According to random number table method patients were divided into the observation group and control group, each group had 26 cases. Patients in the control group were given Pemetrexed and Cisplatin. Patients in the observation group were given Kanglaite Injection combined with Pemetrexed and Cisplatin. All patients were treated for 2 cycles of chemotherapy. The treatment effect, adverse reaction and patients′ quality of life between the two groups were compared. Results In the observation group, the effective alleviation rate was 41.6%, the disease control rate was 54.1%;in the control group, the effective alleviation rate was 32.0%, the disease control rate was 48.0%; the treatment effect between the two group had no significant difference (P > 0.05). Compared with the control group, the bone marrow suppression in the observation was slight, with statistically significant difference (P0.05). Compared with the control group, the quality of life (KPS score) in the observation improved significantly, with statistically significant difference (P0.05).与对照组相比,观察组骨髓抑制较轻,两组比较差异有统计学意义(P0.05).与对照组相比,观察组生活质量(KPS评分)明显改善,差异有统计学意义(P<0.05).结论 康莱特注射液联合培美曲塞与顺铂与培美曲塞与顺铂治疗晚期肺腺癌效果相当, 但是加用康莱特注射液骨髓抑制较轻,并且可提高患者的生活质量.

  7. Silenced Expression of NFKBIA in Lung Adenocarcinoma Patients with a Never-smoking History

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    Furukawa,Masashi

    2013-02-01

    Full Text Available Nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α (NFKBIA, which is a tumor suppressor gene, was found to be silenced in lung adenocarcinomas. We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. NFKBIA expression was evaluated using immunohistochemistry. NFKBIA expression was negative in 16 of the 101 samples (15.8%. EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%, 1 (1.0%, and 2 (2.0% of the 101 samples, respectively, in a completely mutually exclusive manner. Negative NFKBIA expression was observed significantly more frequently among the tumors with none of the three genetic alterations compared to those with such alterations (p=0.009. In addition, negative NFKBIA expression was significantly more frequent among the EGFR-wild type samples compared to the EGFR-mutant samples (p=0.013. In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion.

  8. Radiogenomic correlation in lung adenocarcinoma with epidermal growth factor receptor mutations: Imaging features and histological subtypes

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Su Jin [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Hanyang University, Department of Radiology, School of Medicine, Seoul (Korea, Republic of); Kim, Tae Jung [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Samsung Medical Center, Department of Radiology, Seoul (Korea, Republic of); Choi, Yo Won [Hanyang University, Department of Radiology, School of Medicine, Seoul (Korea, Republic of); Park, Jeong-Soo [Dankook Universicity, Department of Biochemistry, College of Medicine, Cheonan (Korea, Republic of); Chung, Jin-Haeng [Seoul National University Bundang Hospital, Department of Pathology, Seongnam-si, Gyeonggi-do (Korea, Republic of); Lee, Kyung Won [Seoul National University Bundang Hospital, Department of Radiology, Seongnam-si, Gyeonggi-do (Korea, Republic of)

    2016-10-15

    To correlate imaging features of resected lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutation and the IASLC/ATS/ERS classification histological subtypes. In 250 consecutive patients with resected lung adenocarcinoma, EGFR mutation status was correlated with demographics, imaging features including ground-glass opacity (GGO) proportion and the IASLC/ATS/ERS classification histological subtypes. EGFR mutations were significantly more frequent in women (54.5 % vs. 38.1 %, p = 0.011) and in never-smokers (54.7 % vs. 35.3 %, p = 0.003). GGO proportion was significantly higher in tumours with EGFR mutation than in those without (30.3 ± 33.8 % vs. 19.0 ± 29.3 %, p = 0.005). EGFR mutation was significantly more frequent in tumours with GGO ≥ 50 % and tumours with any GGO (p = 0.026 and 0.008, respectively). Adenocarcinomas with exon 19 or 21 mutation showed significantly higher GGO proportion than that in EGFR wild-type tumours (p = 0.009 and 0.029, respectively). Absence of GGO was an independent predictor of negative EGFR mutation (odds ratio, 1.81; 95 % confidence interval, 1.16-3.04; p = 0.018). GGO proportion in adenocarcinomas with EGFR mutation was significantly higher than that in EGFR wild-type tumours, and the absence of GGO on CT was an independent predictor of negative EGFR mutation. (orig.)

  9. [Innovation in Surgery for Advanced Lung Cancer].

    Science.gov (United States)

    Nakano, Tomoyuki; Yasunori, Sohara; Endo, Shunsuke

    2016-07-01

    Thoracoscopic surgery can be one of less invasive surgical interventions for early stage lung cancer. Locally advanced lung cancer, however, cannot avoid aggressive procedures including pneumonectomy and/or extended combined resection of chest wall, aorta, esophagus, etc. for complete resection. Surgical approach even for advanced lung cancer can be less invasive by benefit from new anti-cancer treatment, innovated manipulations of bronchoplasty and angioplasty, and bench surgery( lung autotransplantation technique). We herein reviewed the strategy to minimize invasive interventions for locally advanced lung cancer, introducing 2 successful cases with advanced lung cancer. The 1st patient is a 62-year old man with centrally advanced lung cancer invading to mediastinum. Right upper sleeve lobectomy with one-stoma carinoplasty following induction chemoradiation therapy was successful. The operation time was 241 minutes. The performance status is good with no recurrence for 60 months after surgery. The 2nd is a 79-year old man with advanced lung cancer invading to the distal aortic arch. Left upper segmentectomy following thoracic endovascular aortic repair with stentgraft was successful with no extracorporeal circulation. The operation time was 170 minutes. The performance status is good with no recurrence for 30 months after surgery. The invasiveness of surgical interventions for local advanced lung cancer can be minimized by innovated device and new anti-cancer drugs.

  10. Spectrum of oncogenic driver mutations in lung adenocarcinomas from East Asian never smokers.

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    Chenguang Li

    Full Text Available PURPOSE: We previously showed that 90% (47 of 52; 95% CI, 0.79 to 0.96 of lung adenocarcinomas from East Asian never-smokers harbored well-known oncogenic mutations in just four genes: EGFR, HER2, ALK, and KRAS. Here, we sought to extend these findings to more samples and identify driver alterations in tumors negative for these mutations. EXPERIMENTAL DESIGN: We have collected and analyzed 202 resected lung adenocarcinomas from never smokers seen at Fudan University Shanghai Cancer Center. Since mutations were mutually exclusive in the first 52 examined, we determined the status of EGFR, KRAS, HER2, ALK, and BRAF in stepwise fashion as previously described. Samples negative for mutations in these 5 genes were subsequently examined for known ROS1 fusions by RT-PCR and direct sequencing. RESULTS: 152 tumors (75.3% harbored EGFR mutations, 12 (6% had HER2 mutations, 10 (5% had ALK fusions all involving EML4 as the 5' partner, 4 (2% had KRAS mutations, and 2 (1% harbored ROS1 fusions. No BRAF mutation were detected. CONCLUSION: The vast majority (176 of 202; 87.1%, 95% CI: 0.82 to 0.91 of lung adenocarcinomas from never smokers harbor mutant kinases sensitive to available TKIs. Interestingly, patients with EGFR mutant patients tend to be older than those without EGFR mutations (58.3 Vs 54.3, P = 0.016 and patient without any known oncogenic driver tend to be diagnosed at a younger age (52.3 Vs 57.9, P = 0.013. Collectively, these data indicate that the majority of never smokers with lung adenocarcinoma could benefit from treatment with a specific tyrosine kinase inhibitor.

  11. Identification of Epigenetic Biomarkers of Lung Adenocarcinoma through Multi-Omics Data Analysis.

    Science.gov (United States)

    Kikutake, Chie; Yahara, Koji

    2016-01-01

    Epigenetic mechanisms such as DNA methylation or histone modifications are essential for the regulation of gene expression and development of tissues. Alteration of epigenetic modifications can be used as an epigenetic biomarker for diagnosis and as promising targets for epigenetic therapy. A recent study explored cancer-cell specific epigenetic biomarkers by examining different types of epigenetic modifications simultaneously. However, it was based on microarrays and reported biomarkers that were also present in normal cells at a low frequency. Here, we first analyzed multi-omics data (including ChIP-Seq data of six types of histone modifications: H3K27ac, H3K4me1, H3K9me3, H3K36me3, H3K27me3, and H3K4me3) obtained from 26 lung adenocarcinoma cell lines and a normal cell line. We identified six genes with both H3K27ac and H3K4me3 histone modifications in their promoter regions, which were not present in the normal cell line, but present in ≥85% (22 out of 26) and ≤96% (25 out of 26) of the lung adenocarcinoma cell lines. Of these genes, NUP210 (encoding a main component of the nuclear pore complex) was the only gene in which the two modifications were not detected in another normal cell line. RNA-Seq analysis revealed that NUP210 was aberrantly overexpressed among the 26 lung adenocarcinoma cell lines, although the frequency of NUP210 overexpression was lower (19.3%) in 57 lung adenocarcinoma tissue samples studied and stored in another database. This study provides a basis to discover epigenetic biomarkers highly specific to a certain cancer, based on multi-omics data at the cell population level.

  12. Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions.

    Directory of Open Access Journals (Sweden)

    Ning Zhao

    Full Text Available Changes in intermolecular interactions (differential interactions may influence the progression of cancer. Specific genes and their regulatory networks may be more closely associated with cancer when taking their transcriptional and post-transcriptional levels and dynamic and static interactions into account simultaneously. In this paper, a differential interaction analysis was performed to detect lung adenocarcinoma-related genes. Furthermore, a miRNA-TF (transcription factor synergistic regulation network was constructed to identify three kinds of co-regulated motifs, namely, triplet, crosstalk and joint. Not only were the known cancer-related miRNAs and TFs (let-7, miR-15a, miR-17, TP53, ETS1, and so on were detected in the motifs, but also the miR-15, let-7 and miR-17 families showed a tendency to regulate the triplet, crosstalk and joint motifs, respectively. Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma. Specifically, the two 4-node motifs (crosstalk and joint based on co-expression and interaction had a closer relationship to lung adenocarcinoma, and so further research was performed on them. A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1 was selected from the joint motif, and a survival analysis indicated its significant association with survival. Among the ten genes, JUN, NR3C1 and GRB2 are our newly detected candidate lung adenocarcinoma-related genes. The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

  13. The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

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    Zhang HB

    2016-04-01

    Full Text Available Huibiao Zhang,1 Chen Lu,2 Yingjie Lu,1 Bo Yu,2 Fanzhen Lv,1 Zhenghong Zhu1 1Department of Thoracic Surgery, 2Department of Pathology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China Background: The predictive and prognostic impact of factors associated with visceral pleural invasion (VPI on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined.Patients and methods: A total of 505 consecutive patients with stage Ia–IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed.Results: The incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001 and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively. VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564–3.504 and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665–2.89 in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS] and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence. Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS

  14. Fibulin-2 is a driver of malignant progression in lung adenocarcinoma.

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    Brandi N Baird

    Full Text Available The extracellular matrix of epithelial tumors undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How matrix integrity is maintained in the face of dynamic biophysical forces is largely undefined. Here we investigated the role of fibulin-2, a matrix glycoprotein that functions biomechanically as an inter-molecular clasp and thereby facilitates supra-molecular assembly. Fibulin-2 was abundant in the extracellular matrix of human lung adenocarcinomas and was highly expressed in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma from co-expression of mutant K-ras and p53. Loss-of-function experiments in tumor cells revealed that fibulin-2 was required for tumor cells to grow and metastasize in syngeneic mice, a surprising finding given that other intra-tumoral cell types are known to secrete fibulin-2. However, tumor cells grew and metastasized equally well in Fbln2-null and -wild-type littermates, implying that malignant progression was dependent specifically upon tumor cell-derived fibulin-2, which could not be offset by other cellular sources of fibulin-2. Fibulin-2 deficiency impaired the ability of tumor cells to migrate and invade in Boyden chambers, to create a stiff extracellular matrix in mice, to cross-link secreted collagen, and to adhere to collagen. We conclude that fibulin-2 is a driver of malignant progression in lung adenocarcinoma and plays an unexpected role in collagen cross-linking and tumor cell adherence to collagen.

  15. Multisystem Langerhans cell histiocytosis coexisting with metastasizing adenocarcinoma of the lung: A case report

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    Lovrenski Aleksandra

    2013-01-01

    Full Text Available Introduction. Langerhans cell histiocytosis (LCH is an uncommon disease of unknown etiology characterized by uncontrolled proliferation and infiltration of various organs by Langerhans cells. Case report. We presented a 54-year-old man, heavy smoker, with dyspnea, cough, hemoptysis, headache and ataxia, who died shortly after admission to our hospital. On the autopsy, tumor was found in the posterior segment of the right upper pulmonary lobe as well as a right-sided occipitoparietal lesion which penetrated into the right ventricle resulting in internal and external hematocephalus. Histologically and immunohistohemically, the diagnosis of primary lung adenocarcinoma with brain metastasis was made (tumor cells showed positivity for CK7 and TTF-1 which confirmed the diagnosis. In the lung parenchyma around the tumor, as well as in brain tissue around the metastatic adenocarcinoma histiocytic lesions were found. Light microscopic examination of the other organs also showed histiocytic lesions involving the pituitary gland, hypothalamus, spleen and mediastinal lymph nodes. Immunohistochemical studies revealed CD68, S-100 and CD1a immunoreactivity within the histiocytes upon which the diagnosis of Langerhans' cells histiocytosis was made. Conclusion. The multisystem form of LCH with extensive organ involvement was an incidental finding, while metastatic lung adenocarcinoma to the brain that led to hematocephalus was the cause of death.

  16. Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Olya Grove

    Full Text Available Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity and intratumor density variation (feature 2: entropy ratio in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47 of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically. Segmented tumor regions were further subdivided into core and boundary sub-regions, to quantify intensity variations across the tumor. Reproducibility of the features was evaluated in an independent test-retest dataset of 32 patients. The proposed metrics showed high degree of reproducibility in a repeated experiment (concordance, CCC≥0.897; dynamic range, DR≥0.92. Association with overall survival was evaluated by Cox proportional hazard regression, Kaplan-Meier survival curves, and the log-rank test. Both features were associated with overall survival (convexity: p = 0.008; entropy ratio: p = 0.04 in Cohort 1 but not in Cohort 2 (convexity: p = 0.7; entropy ratio: p = 0.8. In both cohorts, these features were found to be descriptive and demonstrated the link between imaging characteristics and patient survival in lung adenocarcinoma.

  17. Empirical studies about quercetin increasing chemosensitivity on human lung adenocarcinoma cell line A549

    Institute of Scientific and Technical Information of China (English)

    Xuejun Zhan; Runxiang Zhang; Yanping Xu; Shuhua Yang; Daze Xie; Liwei Tan

    2012-01-01

    Objective: The present study was designed to investigate whether quercetin exerts increasing chemosensitivity on human lung adenocarcinoma cells when quercetin combined with cisplatin (DDP) and vincristine (VCR) in vitro respectively and its possible antitumor mechanism. To provide experimental proof for clinical combination application. Methods: Using intermittent administration of high dose VCR, human lung adenocarcinoma sensitive cell line (A549/S) was induced to VCR-resistant human lung adenocarcinoma cell line (A549/VCR). MTT assay was adapted for examing the 50% inhibition (IC50) value of DDP and VCR on A549/S and A549/VCR when quercetin combined with DDP and VCR respectively. Results: IC50 of DDP on A549/S and A549/VCR was 10.18 and 12.35 mg/L, and the IC50 of VCR on the two cell lines was 1.21 and 12.77 mg/L, respectively. The resistance fold of A549/VCR on VCR and DDP was 10.55 and 1.21, respectively. When quercetin at concentration of 50, 100 and 200 μmol/L in combination with DDP and VCR respectively, the IC50 of DDP and VCR on A549/S and A549/VCR were obvious decreased (P < 0.05 – P < 0.01). Conclusion: The experiment results suggested that quercetin could increase the chemosensitivity and partly revise the resistance of A549/VCR.

  18. Analysis of Differential Gel Electrophoresis of Paclitaxol Resistant and Sensitive Lung Adenocarcinoma Cells' Secretome

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    Tianqing CHU

    2009-07-01

    Full Text Available Background and objective Paclitaxol (PTX resistance is one of main factors which affect the outcome of chemotherapy of lung adenocarcinoma. The aim of this study is to compare the secreted protein expression profiles between Paclitaxol (PTX resistant and sensitive lung adenocarcinoma cells by proteomic research method, so as to provide evidence of choosing individual chemotherapy drugs in clinical treatment. Methods Total secreted proteins extracted from a PTX sensitive cell line A549 and a PTX resistant cell line A549-Taxol were separated by fluorscent differential gel electrophoresis (DIGE. High quality 2-DE profiles were obtained and analyzed by Decyder 6.5 analysis software to screen differentially expressed protein spots. Those spots were identified by mass spectrometry. Results 2-DE patterns of lung adenocarcinoma cells with high-resolution and reproducibility were obtained. 76 significantly differentially expressed protein spots were screened, 19 proteins were identified by mass spectrometry. The identified proteins could be classified into different catogories: metabolic enzyme, extracellular matrix (ECM degradation enzyme, cytokine, signal transducer, cell adhesion, and so on. Conclusion Multiple secreted proteins related to chemoresistance of A549-Taxol cells were identified in this study for the first time. The results presented here would provide clues to identify new serologic chemoresistant biomarkers of NSCLC.

  19. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion.

    Science.gov (United States)

    Verma, Akash; Phua, Chee Kiang; Sim, Wen Yuan; Algoso, Reyes Elmer; Tee, Kuan Sen; Lew, Sennen J W; Lim, Albert Y H; Goh, Soon Keng; Tai, Dessmon Y H; Kor, Ai Ching; Ho, Benjamin; Abisheganaden, John

    2016-06-01

    To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis.Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012.Univariate analyses showed lower pleural fluid LDH 667 (313-967) versus 971 (214-3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 (100%) versus 36 (55.3%), P = 0.009, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy 8 (89%) versus 26 (40%), P = 0.009 to correlate with survival of more than 1.7 year versus less than 1.7 year. In multivariate analysis, low pleural fluid LDH and female gender maintained significance. The pleural LDH level of ≤1500 and >1500 U/L discriminated significantly (P = 0.009) between survival.High pleural LDH (>1500 IU/L) predicts shorter survival (less than a year) in patients with adenocarcinoma lung presenting with MPE at the time of initial diagnosis. This marker may be clinically applied for selecting therapeutic modality directed at prevention of reaccumulation of MPE. Patients with low pleural LDH may be considered suitable for measures that provide more sustained effect on prevention of reaccumulation such as chemical pleurodesis or tunneled pleural catheter.

  20. TWIST1 a new determinant of epithelial to mesenchymal transition in EGFR mutated lung adenocarcinoma.

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    Karine Pallier

    Full Text Available Metastasis is a multistep process and the main cause of mortality in lung cancer patients. We previously showed that EGFR mutations were associated with a copy number gain at a locus encompassing the TWIST1 gene on chromosome 7. TWIST1 is a highly conserved developmental gene involved in embryogenesis that may be reactivated in cancers promoting both malignant conversion and cancer progression through an epithelial to mesenchymal transition (EMT. The aim of this study was to investigate the possible implication of TWIST1 reactivation on the acquisition of a mesenchymal phenotype in EGFR mutated lung cancer. We studied a series of consecutive lung adenocarcinoma from Caucasian non-smokers for which surgical frozen samples were available (n = 33 and showed that TWIST1 expression was linked to EGFR mutations (P<0.001, to low CDH1 expression (P<0.05 and low disease free survival (P = 0.044. To validate that TWIST1 is a driver of EMT in EGFR mutated lung cancer, we used five human lung cancer cell lines and demonstrated that EMT and the associated cell mobility were dependent upon TWIST1 expression in cells with EGFR mutation. Moreover a decrease of EGFR pathway stimulation through EGF retrieval or an inhibition of TWIST1 expression by small RNA technology reversed the phenomenon. Collectively, our in vivo and in vitro findings support that TWIST1 collaborates with the EGF pathway in promoting EMT in EGFR mutated lung adenocarcinoma and that large series of EGFR mutated lung cancer patients are needed to further define the prognostic role of TWIST1 reactivation in this subgroup.

  1. Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma.

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    Jun-Chieh J Tsay

    Full Text Available Field of cancerization in the airway epithelium has been increasingly examined to understand early pathogenesis of non-small cell lung cancer. However, the extent of field of cancerization throughout the lung airways is unclear. Here we sought to determine the differential gene and microRNA expressions associated with field of cancerization in the peripheral airway epithelial cells of patients with lung adenocarcinoma. We obtained peripheral airway brushings from smoker controls (n=13 and from the lung contralateral to the tumor in cancer patients (n=17. We performed gene and microRNA expression profiling on these peripheral airway epithelial cells using Affymetrix GeneChip and TaqMan Array. Integrated gene and microRNA analysis was performed to identify significant molecular pathways. We identified 26 mRNAs and 5 miRNAs that were significantly (FDR <0.1 up-regulated and 38 mRNAs and 12 miRNAs that were significantly down-regulated in the cancer patients when compared to smoker controls. Functional analysis identified differential transcriptomic expressions related to tumorigenesis. Integration of miRNA-mRNA data into interaction network analysis showed modulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK pathway in the contralateral lung field of cancerization. In conclusion, patients with lung adenocarcinoma have tumor related molecules and pathways in histologically normal appearing peripheral airway epithelial cells, a substantial distance from the tumor itself. This finding can potentially provide new biomarkers for early detection of lung cancer and novel therapeutic targets.

  2. Molecular typing of lung adenocarcinoma on cytological samples using a multigene next generation sequencing panel.

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    Aldo Scarpa

    Full Text Available Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%. In 24/36 cases (67% at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16% and 10/36 (28% cases, were mutually exclusive. Nine samples (25% showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy.

  3. Molecular Typing of Lung Adenocarcinoma on Cytological Samples Using a Multigene Next Generation Sequencing Panel

    Science.gov (United States)

    Fassan, Matteo; Rachiglio, Anna Maria; Cappellesso, Rocco; Antonello, Davide; Amato, Eliana; Mafficini, Andrea; Lambiase, Matilde; Esposito, Claudia; Bria, Emilio; Simonato, Francesca; Scardoni, Maria; Turri, Giona; Chilosi, Marco; Tortora, Giampaolo; Fassina, Ambrogio; Normanno, Nicola

    2013-01-01

    Identification of driver mutations in lung adenocarcinoma has led to development of targeted agents that are already approved for clinical use or are in clinical trials. Therefore, the number of biomarkers that will be needed to assess is expected to rapidly increase. This calls for the implementation of methods probing the mutational status of multiple genes for inoperable cases, for which limited cytological or bioptic material is available. Cytology specimens from 38 lung adenocarcinomas were subjected to the simultaneous assessment of 504 mutational hotspots of 22 lung cancer-associated genes using 10 nanograms of DNA and Ion Torrent PGM next-generation sequencing. Thirty-six cases were successfully sequenced (95%). In 24/36 cases (67%) at least one mutated gene was observed, including EGFR, KRAS, PIK3CA, BRAF, TP53, PTEN, MET, SMAD4, FGFR3, STK11, MAP2K1. EGFR and KRAS mutations, respectively found in 6/36 (16%) and 10/36 (28%) cases, were mutually exclusive. Nine samples (25%) showed concurrent alterations in different genes. The next-generation sequencing test used is superior to current standard methodologies, as it interrogates multiple genes and requires limited amounts of DNA. Its applicability to routine cytology samples might allow a significant increase in the fraction of lung cancer patients eligible for personalized therapy. PMID:24236184

  4. Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Daugaard, Iben; Dominguez, Diana; Kjeldsen, Tina E;

    2016-01-01

    , HOXA5, Chr1(q21.1).A, and Chr6(p22.1). In particular the OSR1, SIM1 and HOXB3/HOXB4 regions demonstrated high potential as biomarkers in LAC. For OSR1, hypermethylation was detected in 47/48 LAC cases compared to 1/31 tumor-adjacent normal lung samples. Similarly, 45/49 and 36/48 LAC cases compared...... patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3...... to 3/31 and 0/31 tumor-adjacent normal lung samples showed hypermethylation of the SIM1 and HOXB3/HOXB4 regions, respectively. In conclusion, this study has identified and validated 15 DMRs that can be targeted as biomarkers in LAC....

  5. Epigenomic analysis of lung adenocarcinoma reveals novel DNA methylation patterns associated with smoking

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    Tan Q

    2013-10-01

    Full Text Available Qiang Tan,1,* Guan Wang,1,* Jia Huang,1 Zhengping Ding,1 Qingquan Luo,1 Tony Mok,2 Qian Tao,2 Shun Lu1 1Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 2Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong *These authors contributed equally to this paper Abstract: The importance of epigenetic regulation has been increasingly recognized in the development of cancer. In this study, we investigated the impact of smoking, a major risk factor of lung cancer, on DNA methylation by comparing the genome-wide DNA methylation patterns between lung adenocarcinoma samples from six smokers and six nonsmokers. We identified that smoking-induced DNA methylations were enriched in the calcium signaling and neuroactive ligand receptor signaling pathways, which are closely related to smoking-induced lung cancers. Interestingly, we discovered that two genes in the mitogen-activated protein kinase signaling pathway (RPS6KA3 and ARAF were hypomethylated in smokers but not in nonsmokers. In addition, we found that the smoking-induced lung cancer-specific DNA methylations were mostly enriched in nuclear activities, including regulation of gene expression and chromatin remodeling. Moreover, the smoking-induced hypermethylation could only be seen in lung adenocarcinoma tissue but not in adjacent normal lung tissue. We also used differentially methylated DNA loci to construct a diagnostic model to distinguish smoking-associated lung cancer from nonsmoking lung cancer with a sensitivity of 88.9% and specificity of 83.2%. Our results provided novel evidence to support that smoking can cause dramatic changes in the DNA methylation landscape of lung cancer, suggesting that epigenetic

  6. Comparable rate of EGFR kinase domain mutation in lung adenocarcinomas from Chinese male and female never-smokers

    Institute of Scientific and Technical Information of China (English)

    Yi-hua SUN; Rong FANG; Bin GAO; Xiang-kun HAN; Jun-hua ZHANG; William PAO; Hai-quan CHEN; Hong-bin JI

    2010-01-01

    @@ Lung cancer patients with the epidermal growth factor receptor (EGFR) kinase domain mutations frequently show good responses to small molecule tyrosine kinase inhibitors, including Iressa and Tarceva, in clinical studies[1-3]. Previous studies have demonstrated that EGFR kinase domain mutations are commonly observed in lung adenocarcinomas, never-smokers,East Asian, and females[4-8].

  7. Role of nicotine dependence on the relationship between variants in the nicotinic receptor genes and risk of lung adenocarcinoma.

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    Tung-Sung Tseng

    Full Text Available Several variations in the nicotinic receptor genes have been identified to be associated with both lung cancer risk and smoking in the genome-wide association (GWA studies. However, the relationships among these three factors (genetic variants, nicotine dependence, and lung cancer remain unclear. In an attempt to elucidate these relationships, we applied mediation analysis to quantify the impact of nicotine dependence on the association between the nicotinic receptor genetic variants and lung adenocarcinoma risk. We evaluated 23 single nucleotide polymorphisms (SNPs in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4 previously reported to be associated with lung cancer risk and smoking behavior and 14 SNPs in the four 'control' genes (TERT, CLPTM1L, CYP1A1, and TP53, which were not reported in the smoking GWA studies. A total of 661 lung adenocarcinoma cases and 1,347 controls with a smoking history, obtained from the Environment and Genetics in Lung Cancer Etiology case-control study, were included in the study. Results show that nicotine dependence is a mediator of the association between lung adenocarcinoma and gene variations in the regions of CHRNA5/A3/B4 and accounts for approximately 15% of this relationship. The top two CHRNA3 SNPs associated with the risk for lung adenocarcinoma were rs1051730 and rs12914385 (p-value = 1.9×10(-10 and 1.1×10(-10, respectively. Also, these two SNPs had significant indirect effects on lung adenocarcinoma risk through nicotine dependence (p = 0.003 and 0.007. Gene variations rs2736100 and rs2853676 in TERT and rs401681 and rs31489 in CLPTM1L had significant direct associations on lung adenocarcinoma without indirect effects through nicotine dependence. Our findings suggest that nicotine dependence plays an important role between genetic variants in the CHRNA5/A3/B4 region, especially CHRNA3, and lung adenocarcinoma. This may provide valuable information for

  8. Identification of cancer initiating cells in K-Ras driven lung adenocarcinoma.

    Science.gov (United States)

    Mainardi, Sara; Mijimolle, Nieves; Francoz, Sarah; Vicente-Dueñas, Carolina; Sánchez-García, Isidro; Barbacid, Mariano

    2014-01-07

    Ubiquitous expression of a resident K-Ras(G12V) oncogene in adult mice revealed that most tissues are resistant to K-Ras oncogenic signals. Indeed, K-Ras(G12V) expression only induced overt tumors in lungs. To identify these transformation-permissive cells, we induced K-Ras(G12V) expression in a very limited number of adult lung cells (0.2%) and monitored their fate by X-Gal staining, a surrogate marker coexpressed with the K-Ras(G12V) oncoprotein. Four weeks later, 30% of these cells had proliferated to form small clusters. However, only SPC(+) alveolar type II (ATII) cells were able to form hyperplastic lesions, some of which progressed to adenomas and adenocarcinomas. In contrast, induction of K-Ras(G12V) expression in lung cells by intratracheal infection with adenoviral-Cre particles generated hyperplasias in all regions except the proximal airways. Bronchiolar and bronchioalveolar duct junction hyperplasias were primarily made of CC10(+) Clara cells. Some of them progressed to form benign adenomas. However, only alveolar hyperplasias, exclusively made up of SPC(+) ATII cells, progressed to yield malignant adenocarcinomas. Adenoviral infection induced inflammatory infiltrates primarily made of T and B cells. This inflammatory response was essential for the development of K-Ras(G12V)-driven bronchiolar hyperplasias and adenomas, but not for the generation of SPC(+) ATII lesions. Finally, activation of K-Ras(G12V) during embryonic development under the control of a Sca1 promoter yielded CC10(+), but not SPC(+), hyperplasias, and adenomas. These results, taken together, illustrate that different types of lung cells can generate benign lesions in response to K-Ras oncogenic signals. However, in adult mice, only SPC(+) ATII cells were able to yield malignant adenocarcinomas.

  9. Differences in miRNA expression in early stage lung adenocarcinomas that did and did not relapse.

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    Mick D Edmonds

    Full Text Available Relapse of adenocarcinoma, the most common non-small cell lung cancer (NSCLC, is a major clinical challenge to improving survival. To gain insight into the early molecular events that contribute to lung adenocarcinoma relapse, and taking into consideration potential cell type specificity, we used stringent criteria for sample selection. We measured miRNA expression only from flash frozen stage I lung adenocarcinomas, excluding other NSCLC subtypes. We compared miRNA expression in lung adenocarcinomas that relapsed within two years to those that did not relapse within three years after surgical resection prior to adjuvant therapy. The most significant differences in mRNA expression for recurrent tumors compared to non-recurrent tumors were decreases in miR-106b*, -187, -205, -449b, -774* and increases in miR-151-3p, let-7b, miR-215, -520b, and -512-3p. A unique comparison between adjacent normal lung tissue from relapse and non-relapse groups revealed dramatically different miRNA expression, suggesting dysregulation of miRNA in the environment around the tumor. To assess patient-to-patient variability, miRNA levels in the tumors were normalized to levels in matched adjacent normal lung tissue. This analysis revealed a different set of significantly altered miRNA in tumors that recurred compared to tumors that did not. Together our analyses elucidated miRNA not previously linked to lung adenocarcinoma that likely have important roles in its development and progression. Our results also highlight the differences in miRNA expression in normal lung tissue in adenocarcinomas that do and do not recur. Most notably, our data identified those miRNA that distinguish early stage tumors likely to relapse prior to treatment and miRNA that could be further studied for use as biomarkers for prognosis, patient monitoring, and/or treatment decisions.

  10. MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells.

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    Yi-Jyun Liu

    Full Text Available Lung cancer is the leading cause of cancer-related mortality worldwide. Radiotherapy is often applied for treating lung cancer, but it often fails because of the relative non-susceptibility of lung cancer cells to radiation. MicroRNAs (miRNAs have been reported to modulate the radiosensitivity of lung cancer cells and have the potential to improve the efficacy of radiotherapy. The purpose of this study was to identify a miRNA that can adjust radiosensitivity in lung adenocarcinoma cells. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5 with different metastatic ability and radiosensitivity were used. In order to understand the regulatory mechanisms of differential radiosensitivity in these isogenic tumor cells, both CL1-0 and CL1-5 were treated with 10 Gy radiation, and were harvested respectively at 0, 1, 4, and 24 h after radiation exposure. The changes in expression of miRNA upon irradiation were examined using Illumina Human microRNA BeadChips. Twenty-six miRNAs were identified as having differential expression post-irradiation in CL1-0 or CL1-5 cells. Among these miRNAs, miR-449a, which was down-regulated in CL1-0 cells at 24 h after irradiation, was chosen for further investigation. Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation.

  11. Chromosomal and Genetic Analysis of a Human Lung Adenocarcinoma Cell Line OM

    Institute of Scientific and Technical Information of China (English)

    Yong-Wu Li; Lin Bai; Lyu-Xia Dai; Xu He; Xian-Ping Zhou

    2016-01-01

    Background: Lung cancer has become the leading cause of death in many regions.Carcinogenesis is caused by the stepwise accumulation of genetic and chromosomal changes.The aim of this study was to investigate the chromosome and gene alterations in the human lung adenocarcinoma cell line OM.Methods: We used Giemsa banding and multiplex fluorescence in situ hybridization focusing on the human lung adenocarcinoma cell line OM to analyze its chromosome alterations.In addition, the gains and losses in the specific chromosome regions were identified by comparative genomic hybridization (CGH) and the amplifications of cancer-related genes were also detected by polymerase chain reaction (PCR).Results: We identified a large number of chromosomal numerical alterations on all chromosomes except chromosome X and 19.Chromosome 10 is the most frequently involved in translocations with six different interchromosomal translocations.CGH revealed the gains on chromosome regions of 3q25.3-28, 5p13, 12q22-23.24, and the losses on 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33 and 17p 13.1-13.3.And PCR showed the amplification of genes: Membrane metalloendopeptidase (MME), sucrase-isomaltase (SI), butyrylcholinesterase (BCHE), and kininogen (KNG).Conclusions: The lung adenocarcinoma cell line OM exhibited multiple complex karyotypes, and chromosome 10 was frequently involved in chromosomal translocation, which may play key roles in tumorigenesis.We speculated that the oncogenes may be located at 3q25.3-28, 5p13, 12q22-23.24, while tumor suppressor genes may exist in 3p25-26, 6p25, 6q26-27, 7q34-36, 8p22-23, 9p21-24, 10q25-26.3, 12p 13.31-13.33, and 17p 13.1-13.3.Moreover, at least four genes (MME, SI, BCHE, and KNG) may be involved in the human lung adenocarcinoma cell line OM.

  12. Molecular testing guidelines for lung adenocarcinoma: Utility of cell blocks and concordance between fine-needle aspiration cytology and histology samples

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    Jonas J. Heymann

    2014-01-01

    Full Text Available Background: Lung cancer is a leading cause of mortality, and patients often present at a late stage. More recently, advances in screening, diagnosing, and treating lung cancer have been made. For instance, greater numbers of minimally invasive procedures are being performed, and identification of lung adenocarcinoma driver mutations has led to the implementation of targeted therapies. Advances in molecular techniques enable use of scant tissue, including cytology specimens. In addition, per recently published consensus guidelines, cytology-derived cell blocks (CBs are preferred over direct smears. Yet, limited comparison of molecular testing of fine-needle aspiration (FNA CBs and corresponding histology specimens has been performed. This study aimed to establish concordance of epidermal growth factor receptor (EGFR and Kirsten rat sarcoma (KRAS virus homolog testing between FNA CBs and histology samples from the same patients. Materials and Methods: Patients for whom molecular testing for EGFR or KRAS was performed on both FNA CBs and histology samples containing lung adenocarcinoma were identified retrospectively. Following microdissection, when necessary, concordance of EGFR and KRAS molecular testing results between FNA CBs and histology samples was evaluated. Results: EGFR and/or KRAS testing was performed on samples obtained from 26 patients. Concordant results were obtained for all EGFR (22/22 and KRAS (17/17 mutation analyses performed. Conclusions: Identification of mutations in lung adenocarcinomas affects clinical decision-making, and it is important that results from small samples be accurate. This study demonstrates that molecular testing on cytology CBs is as sensitive and specific as that on histology.

  13. Duodenal adenocarcinoma: Advances in diagnosis and surgical management

    Institute of Scientific and Technical Information of China (English)

    Jordan M Cloyd; Elizabeth George; Brendan C Visser

    2016-01-01

    Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma(DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multiinstitutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles.

  14. Genome-wide identification of bone metastasis-related microRNAs in lung adenocarcinoma by high-throughput sequencing.

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    Lin Xie

    Full Text Available BACKGROUND: MicroRNAs (miRNAs are a class of small noncoding RNAs that regulate gene expression at the post-transcriptional level. They participate in a wide variety of biological processes, including apoptosis, proliferation and metastasis. The aberrant expression of miRNAs has been found to play an important role in many cancers. RESULTS: To understand the roles of miRNAs in the bone metastasis of lung adenocarcinoma, we constructed two small RNA libraries from blood of lung adenocarcinoma patients with and without bone metastasis. High-throughput sequencing combined with differential expression analysis identified that 7 microRNAs were down-regulated and 21 microRNAs were up-regulated in lung adenocarcinoma with bone metastasis. A total of 797 target genes of the differentially expressed microRNAs were identified using a bioinformatics approach. Functional annotation analysis indicated that a number of pathways might be involved in bone metastasis, survival of the primary origin and metastatic angiogenesis of lung adenocarcinoma. These include the MAPK, Wnt, and NF-kappaB signaling pathways, as well as pathways involving the matrix metalloproteinase, cytoskeletal protein and angiogenesis factors. CONCLUSIONS: This study provides some insights into the molecular mechanisms that underlie lung adenocarcinoma development, thereby aiding the diagnosis and treatment of the disease.

  15. Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods.

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    Leilei Liu

    Full Text Available Anaplastic lymphoma kinase (ALK and echinoderm microtubule-associated protein-like 4 (EML4 gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC, leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib. Malignant pleural effusion occurs in most patients with advanced lung cancer, especially adenocarcinoma, and tissue samples are not always available from these patients. We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. We obtained 66 samples of pleural effusion from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were formalin fixed and paraffin embedded. The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH, reverse transcription-polymerase chain reaction (RT-PCR, and immunohistochemistry (IHC. EML4-ALK was detected in three of 66 patient samples (4.5% with RT-PCR. When the RT-PCR data were used as the standard, one false positive and one false negative samples were identified with IHC; and one false negative sample was identified with FISH. These results suggest that a block of pleural effusion cells can be used to detect the EML4-ALK fusion gene. IHC had good sensitivity, but low specificity. FISH had low sensitivity, but high specificity. RT-PCR is a good candidate method for detecting EML4-ALK in blocks of pleural effusion cells from lung cancer patients.

  16. Adverse Events of Afatinib as First-line Treatment for Five Cases of Advanced Lung Adenocarcinoma and Review of Literature%阿法替尼一线治疗5例晚期肺腺癌患者的不良反应分析及相关文献回顾

    Institute of Scientific and Technical Information of China (English)

    陶虹; 仝丽; 吴洪波; 史亮; 刘喆; 郭丽丽; 唐俊舫; 朱允中; 徐丽艳; 孟弃逸; 武玮; 李明智; 吴卫华

    2014-01-01

    Background and objective Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. hTe aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. Methods Patients with lung adenocarcinoma (stage IIIb or IV) with EGFR mutations were ifrst-line treated with an oral administration of afatinib (40 mg/d) until disease progression. Adverse events, effects, and survival condition were observed. Results hTe most common adverse events were diarrhea (n=5, 100%), skin rash (n=4, 80%), and mucositis/stomatitis (n=4, 80%). Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. hTree patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%), one with stable disease (25%) and one with progressive disease (25%). Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. Conclusion Afa-tinib was approved as ifrst-line treatment for patients with advanced lung adenocarcinoma. hTe most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for conifrmation.%背景与目的阿法替尼是一种新型的低分子量人类表皮生长因子受体(human epidermal growth factor receptor, HER)家族抑制剂,它属于第二代表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors, EGFR-TKIs),在临床前和临床研究中显示了该药对具有表皮生长因子受体(epidermal growth factor receptor, EGFR)活性突变

  17. Context-Dependent Effects of Amplified MAPK Signaling during Lung Adenocarcinoma Initiation and Progression

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    Michelle Cicchini

    2017-02-01

    Full Text Available Expression of oncogenic KrasG12D initiates lung adenomas in a mitogen-activated protein kinase (MAPK signal-dependent manner from only a subset of cell types in the adult mouse lung. Amplification of MAPK signaling is associated with progression to malignant adenocarcinomas, but whether this is a cause or a consequence of disease progression is not known. To better understand the effects of MAPK signaling downstream of KrasG12D expression, we capitalized on the ability of Braf inhibition to selectively amplify MAPK pathway signaling in KrasG12D-expressing epithelial cells. MAPK signal amplification indeed promoted the rapid progression of established adenomas to malignant adenocarcinomas. However, we observed, surprisingly, a greater number of overall tumor-initiating events after MAPK signal amplification, due to induced proliferation of cell types that are normally refractory to KrasG12D-induced transformation. Thus, MAPK signaling in the lung is thresholded not only during malignant progression but also at the moment of tumor initiation.

  18. PCAF-primed EZH2 acetylation regulates its stability and promotes lung adenocarcinoma progression

    Institute of Scientific and Technical Information of China (English)

    Wan Junhu; Chin Y Eugene; Zhang Hongquan; Zhan Jun; Li Shuai; Ma Ji; Xu Weizhi; Liu Chang; Xue Xiaowei; Xie Yuping; Fang Weigang

    2015-01-01

    Enhancer of zeste homolog 2 ( EZH2 ) is a key epigenetic regulator that catalyzes the trimethyla-tion of H3K27 and is modulated by post-translational modifications (PTMs). However, the precise regulation of EZH2 PTMs remains elusive. We, herein, report that EZH2 is acetylated by acetyltransferase P300/CBP-associat-ed factor (PCAF) and is deacetylated by deacetylase SIRT1. We identified that PCAF interacts with and acetylates EZH2 mainly at lysine 348 (K348). Mechanistically, K348 acetylation decreases EZH2 phosphorylation at T345 and T487 and increases EZH2 stability without disrupting the formation of polycomb repressive complex 2 ( PRC2 ) . Functionally, EZH2 K348 acetylation enhances its capacity in suppression of the target genes and promotes lung cancer cell migration and invasion. Further, elevated EZH2 K348 acetylation in lung adenocarcinoma patients pre-dicts a poor prognosis. Our findings define a new mechanism underlying EZH2 modulation by linking EZH2 acety-lation to its phosphorylation that stabilizes EZH2 and promotes lung adenocarcinoma progression.

  19. Prevalence and Clinicopathological Characteristics of HER2 and BRAF Mutation in Chinese Patients with Lung Adenocarcinoma.

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    Ling Shan

    Full Text Available To determine the prevalence and clinicopathological characteristics of BRAF V600E mutation and HER2 exon 20 insertions in Chinese lung adenocarcinoma (ADC patients.Given the fact that the driver mutations are mutually exclusive in lung ADCs, 204 EGFR/KRAS wild-type cases were enrolled in this study. Direct Sanger sequencing was performed to examine BRAF V600E and HER2 exon 20 mutations. The association of BRAF and HER2 mutations with clinicopathological characteristics was statistically analyzed.Among the 204 lung ADCs tested, 11 cases (5.4% carried HER2 exon 20 insertions and 4 cases (2.0% had BRAF V600E mutation. HER2 mutation status was identified to be associated with a non-smoking history (p<0.05. HER2 mutation occurs in 9.4% of never smokers (10/106, 8.7% of female (8/92 and 2.7% of male (3/112 in this selected cohort. All four BRAF mutated patients were women and three of them were never-smokers. No HER2 mutant patients harbor BRAF mutation.HER2 and BRAF mutations identify a distinct subset of lung ADCs. Given the high prevalence of lung cancer and the availability of targeted therapy, Chinese lung ADC patients without EGFR and KRAS mutations are recommended for HER2 and BRAF mutations detection, especially for those never smokers.

  20. Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series.

    Science.gov (United States)

    Li, Shih-Hong; Hsieh, Meng-Heng; Fang, Yueh-Fu

    2015-10-01

    Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain

  1. Ghrelin relieves cancer cachexia associated with the development of lung adenocarcinoma in mice.

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    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Matsumoto, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu

    2014-11-15

    Cancer cachexia is a multifactorial, critical illness syndrome characterized by an ongoing loss of skeletal muscle and adipose tissue. The reductions in body weight and skeletal muscle mass are important prognostic indicators for cancer patients that are refractory to current therapies. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced in the stomach, stimulates food intake and growth hormone secretion, suppresses inflammation, and prevents muscle catabolism. We investigated the pharmacological potential of ghrelin in the treatment of cancer cachexia by using urethane-treated, bronchioalveolar epithelium-specific Pten-deficient mice that developed lung adenocarcinomas. Ghrelin or phosphate-buffered saline was given to mice daily for four weeks beginning at five months after urethane injection, which corresponded to the time point of lung adenocarcinoma formation. Ghrelin inhibited the inductions of C-reactive protein, tumor necrosis factor-α, interleukin-1β, and interleukin-6, mitigated the reduction of food intake and fat mass, and consequently ameliorated body weight loss in the mouse model of lung adenocarcinoma. We also demonstrated that skeletal muscle mass and muscle contraction force in both fast-twitch muscle and slow-twitch muscle were retained in ghrelin-treated mice in conjunction with an upregulation of local insulin-like growth factor 1/Akt signaling. In addition, ghrelin administration reduced the expressions of phosphorylated-p38 mitogen-activated protein kinase, phosphorylated-nuclear factor-kappa B, Forkhead box protein O1, muscle RING-finger protein-1, and F-Box protein 32 in the lysates of skeletal muscle in the tumor-bearing state. Our results indicate that ghrelin administration exerts a protective effect against cancer cachexia by ameliorating skeletal muscle wasting and regulating systemic inflammation.

  2. F18-FDG PET-CT analyses of small peripheral adenocarcinoma of the lung

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    Takahashi, Yoshiyuki; Takashima, Shodayu [Osaka Univ. Graduate School of Medicine, Div. of Allied Health Sciences, Dept. of Diagnostic Radiological Imaging, Osaka (Japan)], e-mail: yoshi_seat_128@yahoo.co.jp; Watanabe, Shinichiro [Osaka University Graduate School of Medicine, Department of Nuclear Medicine and Tracer Kinetics, Osaka (Japan)

    2013-03-15

    Background: Radiological discrimination of histologic subtypes of small peripheral adenocarcinoma of the lung is clinically important. Although there are many articles in which CT findings were used for this purpose, there are only a few reports on the capability of FDG PET-CT findings for histologic classification of this tumor. Purpose: To investigate the correlation between visual assessment or maximum standard uptake values (SUVmax) on F18-FDG PET-CT and histology grading of small peripheral adenocarcinoma of the lung. Material and Methods: Proportions of positive PET-CT diagnoses and SUVmax were retrospectively reviewed on 96 solitary pulmonary nodules of {<=}2 cm in 90 consecutive patients. Tumors were classified into four groups according to Noguchi's classification (group 1 [n = 10], atypical adenomatous hyperplasia and type A tumors; group 2 [n = 12], type B tumors; group 3 [n = 42], type C tumors; group 4 [n = 32], types D, E, and F tumors). Proportions of positive PET-CT diagnoses and mean SUVmax of lesions among four groups were compared using trend tests to examine if there is a significant linear correlation with the progression of the histology grading of tumors. Then, an optimal threshold of SUVmax was proposed to best discriminate tumors of poor (groups 3 and 4) from good (groups 1 and 2) prognosis. Results: There was a significant linear trend for both visual assessment (P < 0.01) and SUVmax (P < 0.01). A SUVmax of 0.42 showed the highest accuracy of 84% with 95% sensitivity and 50% specificity for predicting tumors of poor prognosis. A SUVmax of 2.05 showed 100% specificity with 49% sensitivity, and 60% accuracy. Positive visual diagnoses showed accuracy of 83% with 90% sensitivity and 59% specificity. Conclusion: Visual assessment and SUVmax on PET-CT correlated well with the histology grading of small peripheral adenocarcinoma of the lung.

  3. Lung Adenocarcinomas and Lung Cancer Cell Lines Show Association of MMP-1 Expression With STAT3 Activation

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    Alexander Schütz

    2015-04-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 is constitutively activated in the majority of lung cancer. This study aims at defining connections between STAT3 function and the malignant properties of non–small cell lung carcinoma (NSCLC cells. To address possible mechanisms by which STAT3 influences invasiveness, the expression of matrix metalloproteinase-1 (MMP-1 was analyzed and correlated with the STAT3 activity status. Studies on both surgical biopsies and on lung cancer cell lines revealed a coincidence of STAT3 activation and strong expression of MMP-1. MMP-1 and tyrosine-phosphorylated activated STAT3 were found co-localized in cancer tissues, most pronounced in tumor fronts, and in particular in adenocarcinomas. STAT3 activity was constitutive, although to different degrees, in the lung cancer cell lines investigated. Three cell lines (BEN, KNS62, and A549 were identified in which STAT3 activitation was inducible by Interleukin-6 (IL-6. In A549 cells, STAT3 activity enhanced the level of MMP-1 mRNA and stimulated transcription from the MMP-1 promoter in IL-6–stimulated A549 cells. STAT3 specificity of this effect was confirmed by STAT3 knockdown through RNA interference. Our results link aberrant activity of STAT3 in lung cancer cells to malignant tumor progression through up-regulation of expression of invasiveness-associated MMPs.

  4. Advanced Gastric Neuroendocrine Carcinoma with an Adenocarcinoma Component

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    Masashi Miguchi

    2012-01-01

    Full Text Available In the present study, we observed that the adenocarcinoma component in the mucosa was continuous with neuroendocrine carcinoma (NEC in the deeper layers; this suggests the normal course of NEC carcinogenesis at the histological level. A 72-year-old man was admitted to our hospital with a chief complaint of tarry stools. Endoscopic examination of the upper gastrointestinal tract revealed a 2-cm tumor, with a deep central depression, surrounded by a smooth elevated area, in the middle of the stomach body. A biopsy showed that the tumor was a moderately differentiated gastric adenocarcinoma. The patient underwent total gastrectomy and standard lymph node dissection. The resected tumor was a 3.5 × 2.5 cm type 2 lesion. It comprised two elements at the histological level: (i a moderately differentiated adenocarcinoma in the superficial portion of the mucous membrane layer, and (ii NEC-like cells with dark, round nuclei and scant cytoplasm, presenting a solid and trabecular pattern, in the submucosal and muscularis propria layers. Immunohistochemical findings showed that the NEC-like cells were diffusely positive for chromogranin A, synaptophysin, neural cell adhesion molecule, and neuron-specific enolase, but were negative for carcinoembryonic antigen. The Ki-67 labeling index was 95%. The final pathological diagnosis was gastric NEC with an adenocarcinoma component and a high cellular proliferative potential.

  5. Successful treatment with pemetrexed, Carboplatin, and bevacizumab for platinum-resistant adenocarcinoma of the lung.

    Science.gov (United States)

    Wada, Sae; Fujimoto, Nobukazu; Gemba, Kenichi; Asano, Michiko; Fuchimoto, Yasuko; Ono, Katsuichiro; Ozaki, Shinji; Kishimoto, Takumi

    2012-01-01

    WE PRESENT TWO CASES OF RELAPSED ADENOCARCINOMA OF THE LUNG: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

  6. Successful Treatment with Pemetrexed, Carboplatin, and Bevacizumab for Platinum-Resistant Adenocarcinoma of the Lung

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    Sae Wada

    2012-01-01

    Full Text Available We present two cases of relapsed adenocarcinoma of the lung: a 50-year-old male and a 67-year-old male. Both patients had previously been treated with platinum-containing systemic chemotherapy. In both cases, significant clinical efficacy was demonstrated with combination chemotherapy consisting of pemetrexed, carboplatin, and bevacizumab as salvage treatment. Adverse events were mild. This regimen might be a viable therapeutic option even after heavy treatment such as platinum-containing chemotherapy, especially for patients with preserved organ function and good performance status.

  7. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia

    2011-01-01

    Objective: There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods: Side population(SP) cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting (FACS) was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results: Lung cancer cells could grow in a serum-free Medium(SFM) as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of

  8. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Institute of Scientific and Technical Information of China (English)

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia

    2010-01-01

    Objective:There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs)has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods:Side population(SP)cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS)was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results:Lung cancer cells could grow in a serum-free Medium(SFM)as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion:SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of cancer stem

  9. EGFR mutation detection in circulating cell-free DNA of lung adenocarcinoma patients: analysis of LUX-Lung 3 and 6

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    Wu, Yi-Long; Sequist, Lecia V; Hu, Cheng-Ping; Feng, Jifeng; Lu, Shun; Huang, Yunchao; Li, Wei; Hou, Mei; Schuler, Martin; Mok, Tony; Yamamoto, Nobuyuki; O'Byrne, Kenneth; Hirsh, Vera; Gibson, Neil; Massey, Dan; Kim, Miyoung; Yang, James Chih-Hsin

    2017-01-01

    Background: In the Phase III LUX-Lung 3/6 (LL3/LL6) trials in epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma patients, we evaluated feasibility of EGFR mutation detection using circulating cell-free DNA (cfDNA) and prognostic and predictive utility of cfDNA positivity (cfDNA+). Methods: Paired tumour and blood samples were prospectively collected from randomised patients. Mutations were detected using cfDNA from serum (LL3) or plasma (LL6) by a validated allele-specific quantitative real-time PCR kit. Results: EGFR mutation detection rates in cfDNA were 28.6% (serum) and 60.5% (plasma). Mutation detection in blood was associated with advanced disease characteristics, including higher performance score, number of metastatic sites and bone/liver metastases, and poorer prognosis. In patients with common EGFR mutations, afatinib improved progression-free survival vs chemotherapy in cfDNA+ (LL3: HR, 0.35; P=0.0009; LL6: HR, 0.25; Pafatinib was observed in cfDNA+ patients. Conclusions: Plasma cfDNA is a promising alternative to biopsy for EGFR testing. Detectable mutation in blood was associated with more advanced disease and poorer prognosis. Afatinib improved outcomes in EGFR mutation-positive patients regardless of blood mutation status. PMID:28006816

  10. Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma.

    Science.gov (United States)

    Yoneda, Mitsuhiro; Suzuki, Toru; Nakamura, Takahisa; Ajima, Rieko; Yoshida, Yutaka; Kakuta, Shigeru; Katsuko, Sudo; Iwakura, Yoichiro; Shibutani, Makoto; Mitsumori, Kunitoshi; Yokota, Jun; Yamamoto, Tadashi

    2009-02-01

    The abundant in neuroepithelium area (ana) gene was originally identified as a member of the tob/btg family of antiproliferative genes. Like the other family members, Ana inhibits growth of NIH3T3 cells when overexpressed. However, whether or not Ana is involved in tumor progression has been elusive. Here, we show that expression of ana is relatively high in the lung, the expression being restricted in type II alveolar epithelial cells. We further show that ana expression is reduced in 97% of the human lung cancer cell lines examined (61/63) and 86% of clinical samples from lung adenocarcinoma patients (36/42). Long-term observation of ana-deficient (ana−/–) mice reveals that 8% of them develop lung tumors (5/66) by 21 months after birth, while 0% of wild-type mice (0/35) develop the same type of tumors. We also show that exogenously expressed ana gene product suppresses the levels of matrix metalloproteinase-2 (MMP-2) and plasminogen activator inhibitor-1 (PAI-1) expression in lung cancer cells. Taken together, we propose that ana functions as a tumor suppressor and that its product inhibits tumor progression as well by suppressing angiogenesis, invasion, and metastasis.

  11. Comparison of EGFR Mutation Status in Paired Pre- and Post-chemotherapy Serum for Advanced Pulmonary Adenocarcinoma

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    Rubing HAN

    2011-02-01

    Full Text Available Background and objective Non-small cell lung cancer (NSCLC with mutations in the epidermal growth factor receptor (EGFR is a distinct subgroup of NSCLC, which is particularly responsive to EGFR tyrosine kinase inhibitors (TKIs. The aim of this study is to detect EGFR mutations in paired serum of pre- and post-chemotherapy from advanced pulmonary adenocarcinoma patients to evaluate impact of chemotherapy on EGFR mutation status. Methods Magnetic beads were used for DNA extraction from paired serum of pre- and post-chemotherapy of 33 advanced pulmonary adenocarcinoma patients. The EGFR exon 19 and 21 were amplified by mutant-enriched nested PCR and analyzed by direct sequencing. Results EGFR mutations were detected in 39.4% (13/33 and 54.5% (18/33 serum samples of pre- and postchemotherapy, respectively. The EGFR mutation status was consistent in 54.5% (18/33 patients. Among 15 discordant cases, 10 changed from pre-chemo wild-type to post-chemo mutant-type status, while 5 from pre-chemo mutant-type to post-chemo wild-type status. Conclusion Chemotherapy may have influence on serum EGFR mutation status in advanced adenocacinoma patients.

  12. Oleanolic acid-induced apoptosis and its relation with intracellular calcium in human lung adenocarcinoma A549 cells

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    Asmitanand; Thakur

    2010-01-01

    Objective To investigate the effect of oleanolic acid (OA) on apoptosis,correlation between apoptosis and intracellular calcium,and its mechanism in human lung adenocarcinoma cell line A549. Methods Human lung adenocarcinoma A549 cells were incubated in vitro and assigned with OA concentrations of 0,10,20 and 40μg/mL. The apoptosis status of A549 cell line was detected with Annexin V-FITC/PI by flow cytometry (FCM); fluorescence intensity (FI) of A549 cells was assessed and the level of intracellular calciu...

  13. Epidermal growth factor receptor mutations detected in tumors from Chinese "never smokers" with lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    REN Guo-ping; Theresa Y.WANG; PAN Qiu-lu; William PAO; HUAI Jing

    2005-01-01

    @@ Lung cancer is the leading cause of cancer-related death in the world as well as in China. It is estimated that approximately 429 000 Chinese individuals may die from lung cancer in 2005, and the mortality rate for lung cancer will double in the next century.1 Currently, chemotherapy is the a main treatment of advanced and recurrent lung cancer. However, the recent development of tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib may change the therapeutic approaches for this disease.

  14. The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations

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    Zheng DF

    2016-02-01

    Full Text Available Difan Zheng,1,2,* Rui Wang,1,2,* Yang Zhang,1,2 Yunjian Pan,1,2 Xinghua Cheng,3 Chao Cheng,1,2 Shanbo Zheng,1,2 Hang Li,1,2 Ranxia Gong,1,2 Yuan Li,2,4 Xuxia Shen,2,4 Yihua Sun,1,2 Haiquan Chen1–3,51Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, 3Shanghai Chest Hospital, Shanghai Jiao Tong University, 4Department of Pathology, Fudan University Shanghai Cancer Center, 5Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workBackground: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients.Patients and methods: Patients from 2007 to 2013 diagnosed with primary lung adenocarcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor–lymph node–metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed.Result: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations.Conclusion: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368 of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of

  15. Orbital metastasis as the initial presentation of lung adenocarcinoma: a case report

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    Sun LC

    2016-05-01

    Full Text Available Liangchao Sun,1,2,* Yali Qi,1,3,* Xindong Sun,2 Jinming Yu,2 Xue Meng2 1Medical College of Shandong University, 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, 3Department of Oncology, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Orbital metastasis as the initial presentation of lung adenocarcinoma is very rare, and so the lack of knowledge about this phenomenon can easily result in misdiagnosis, either as a orbital primary tumor or benign lesion. Here, we report a rare case in which the orbital symptom appeared first without any pulmonary manifestations. Our patient developed decreasing vision in his right eye over a 3-month duration. He then presented with proptosis and multiple aches from head to back. After systemic evaluation, our patient was diagnosed with Stage IV non-small-cell lung cancer and was managed with palliative chemoradiotherapy. The final result of treatment suggests that the therapeutic efficacy of chemotherapy on orbital metastasis is uncertain, and only some orbital metastatic masses may have a favorable response to radiation. Furthermore, we review the recent data and provide an in-depth discussion on the clinical features and course of ocular pulmonary metastases, and explain a new type of non-small-cell lung cancer metastatic pattern for ophthalmologists and oncologists to help them distinguish the orbital metastasis as the first manifestation. Keywords: orbital metastasis, skeletal metastasis, rare metastasis, initial presentation, lung adenocarcinoma

  16. Clinicopathological and immunohistochemical features of lung invasive mucinous adenocarcinoma based on computed tomography findings

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    Shimizu K

    2016-12-01

    Full Text Available Katsuhiko Shimizu, Riki Okita, Shinsuke Saisho, Ai Maeda, Yuji Nojima, Masao Nakata Department of General Thoracic Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan Background: We performed an analysis to clarify differences in clinicopathological and molecular features of lung invasive mucinous adenocarcinoma (IMA based on computed tomography (CT findings and their impact on prognosis.Patients and methods: On the basis of CT findings, we divided lung IMA into three subtypes: solid, bubbling, and pneumonic. We then investigated differences in clinicopathological characteristics, prognosis, and the expressions of well-identified biomarkers, including cyclooxygenase-2 (Cox-2, excision repair cross-complementation group 1 (ERCC1, ribonucleotide reductase M1 (RRM1, class III beta-tubulin, thymidylate synthase (TS, secreted protein acidic and rich in cysteine (SPARC, programmed cell death-1 ligand-1 (PD-L1, and epidermal growth factor receptor mutation, among the three subtypes.Results: A total of 29 patients with resected lung IMA were analyzed. Compared with the solid or bubbling type, the pneumonic type had a higher proportion of symptoms, a larger tumor size, a higher pathological stage, and a significantly worse prognosis. The immunohistochemical findings tended to show high expression of RRM1, class III beta-tubulin, and Cox-2 in the tumor and of SPARC in the stroma, but not of ERCC1, TS, and PD-L1 in the tumor. None of the biomarkers with high expression levels in the tumor were prognostic biomarkers, but the expression of SPARC in the stroma was correlated with a poor outcome.Conclusion: Clinical and pathological features, in conjunction with molecular data, indicate that IMA should be divided into different subgroups. In our results, the pneumonic type was correlated with a significantly worse outcome. Further studies should be performed to confirm our conclusion and to explore its molecular implications. Keywords: non-small cell

  17. Transcription Activity of Ectogenic Human Carcinoembryonic Antigen Promoter in Lung Adenocarcinoma Cells A549

    Institute of Scientific and Technical Information of China (English)

    XIONG Weining; FANG Huijuan; XU Yongjian; XIONG Shendao; CAO Yong; SONG Qingfeng; ZENG Daxiong; ZHANG Huilan

    2006-01-01

    The transcription activity of ectogenic human carcinoembryonic antigen (CEA) promoter in lung adenocarcinoma cells A549 was investigated for the further gene-targeting therapy. The reporter gene green fluorescent protein (GFP) driven by CEA promoter and human cytomegalovirus (CMV) promoter were relatively constructed and named plasmid pCEA-EGFP and pCMV-GFP respectively. The intensity of fluorescence was detected by fluorescence microscope and flow cytometry analysis after the pCEA-GFP and pSNAV-GFP plasmids were transfected into A549 cells through liposome respectively. The results showed (4.08±0.63) % of the A549 cells transfected with pCEA-AFP plasmid expressed, significantly lower than that of the A549 cells transfected with pCMV-GFP [(43.27±3.54) %]. It was suggested that ectogenic human CEA promoter in lung adenocarcinoma cells A549 was weakly expressed. The distinct specificity of CEA promoter in CEA high expression cells was regarded as a tool in selective gene therapy, but the transcription activity of ectogenic human CEA promoter was needed to increase in the future.

  18. Uncommon features of surgically resected ALK-positive cavitary lung adenocarcinoma: a case report.

    Science.gov (United States)

    Takamori, Shinkichi; Yamaguchi, Masafumi; Taguchi, Kenichi; Edagawa, Makoto; Shimamatsu, Shinichiro; Toyozawa, Ryo; Nosaki, Kaname; Hirai, Fumihiko; Seto, Takashi; Takenoyama, Mitsuhiro; Ichinose, Yukito

    2017-12-01

    Some features found on chest computed tomography (CT), such as central tumor location, large pleural effusion, and the absence of a pleural tail, and a patient age of less than 60 years, have been suggested to be useful in predicting anaplastic lymphoma kinase (ALK) rearrangement in patients with non-small cell lung cancer (NSCLC).A 68-year-old female patient with a history of gynecological treatment was found to have a cavitary mass in the right lower lobe on an annual chest roentgenogram. The tumor was located in the peripheral area with a pleural tail showing no pleural effusion. In addition, two pure ground-glass-opacity nodules (p-GGNs) in the right upper lobe of the lung were detected on consecutive chest CT scans. The patient underwent right lower lobectomy, partial resection of the right upper lobe, and hilar mediastinal lymph node dissection for complete resection of each tumor. The pathological diagnosis was invasive mucinous adenocarcinoma with signet-ring cells for the cavitary mass in the right lower lobe and invasive adenocarcinoma for the rest of the p-GGNs; subcarinal lymph node metastasis was also detected. The ALK rearrangement was detected by fluorescence in situ hybridization from the cavitary mass. The patient underwent four cycles of cisplatin and vinorelbine chemotherapy as standard adjuvant chemotherapy for pStage III NSCLC. The ALK fusion gene status of NSCLC with atypical CT features should also be investigated.

  19. THE ROLE OF RECOMBINANT Rb GENE ADENOVIRUS VECTOR IN THE GROWTH OF LUNG ADENOCARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    Li Jian; Jiang Lei; Xia Yongjing; Li Hongxia; Hu Yajun; Hu Shixue; Xu Hongji

    1998-01-01

    Objective:To study the role of the most extensively studied tumor suppressor gene, retinoblastoma (Rb) gene,on the growth of lung adenocarcinoma cell line GLC-82 and explore a gene therapy approach for lung adenocarcinoma. Methods: The recombinant Rb gene adenovirus vector was constructed, the control virus which carries LacZ gene was producted by the same method. Infection effects were detected by biochemical staining of β-gal and immunohistochemical analysis of Rb protein. The Rb cDNA of infected cells were determined by PCR. The cell growth rate and cell cycle were observed by cell-counting and flow cytometry. Results: The constructed recombinant adenovirus vector could infect effectively the cells with high level expression of Rb cDNA and Rb protein. The transfection of wild-type Rb gene could suppress GLC-82 cell proliferation and decrease the cellular DNA synthesis. Conclusions: These results showed the possibility of using recombinant Rb gene adenovirus vector in the gene therapy of cancer to inhibit the growth of cancer.

  20. Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, J.Y.; Zheng, J.; Chen, X.; Zhou, J.Y. [Zhejiang University, Department of Respiratory Disease, Thoracic Disease Center, First Affiliated Hospital, College of Medicine, Hangzhou (China); Yu, Z.F.; Xiao, W.B.; Jiang, L.N. [Zhejiang University, Department of Radiology, First Affiliated Hospital, College of Medicine, Hangzhou (China); Zhao, J.; Sun, K.; Wang, B.; Ding, W. [Zhejiang University, Department of Pathology, First Affiliated Hospital, College of Medicine, Hangzhou (China)

    2015-05-01

    To compare the clinicoradiologic features of tumours with echinoderm anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, or wild type (WT) for both genes in a cohort of patients with lung adenocarcinoma to identify useful characteristics of different gene statuses. In 346 lung adenocarcinoma patients, ALK rearrangements were confirmed with fluorescence in situ hybridisation, and EGFR mutations were determined by pyrosequencing assay. Patients were divided into three groups: ALK rearrangement (ALK+ group, n = 48), EGFR mutation (EGFR+ group, n = 166), and WT for both genes (WT group, n = 132). Chest computed tomography (CT) examinations were performed in all patients. The percentages of ground-glass opacity volume (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi-automated nodule assessment software. The pGGO was significantly lower in the ALK+ group (25.1 % ± 24.3) than in the EGFR+ group (37.2 % ± 25.7, p < 0.001) and the WT group (36.1 % ± 24.6, p = 0.001). The TDR in the ALK+ group (17.3 % ± 25.1) was significantly lower than in the EGFR+ group (26.8 % ± 24.9, p = 0.002) and the WT group (25.7 % ± 24.6, p = 0.003). Solid pattern with lower incidence of lobulated border, finely spiculated margins, pleural retraction, and bubble-like lucency on CT imaging are the main characteristics of ALK rearrangement tumours. (orig.)

  1. Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC.

    Science.gov (United States)

    Shi, Mu-mu; Xiong, Yan-lei; Jia, Xin-shan; Li, Xin; Zhang, Li; Li, Xiao-lei; Wang, En-Hua

    2013-06-01

    Most adult stem cells are in the G0 or quiescent phase of the cell cycle and account for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. This study sought to enrich cancer stem cells and explore cancer stem-like cell clones using 5-fluorouracil (5-FU) in the lung adenocarcinoma cell line, SPC. Proliferation inhibition was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, according to which half maximal inhibitory concentration values were calculated. Expression levels of stem cell markers after treatment with 5-FU were examined using immunofluorescence and Western blotting. Additionally, side population (SP) cells were sorted using FACS. Properties of SP cells were evaluated by using Transwell, colony-forming assays, and tumor formation experiments. 5-FU greatly inhibits proliferation, especially of cells in S phase. SP cells possess greater invasive potential, higher clone-forming potential, and greater tumor-forming ability than non-SP cells. Treatment with 5-FU enriches the SP cells with stem cell properties in human lung adenocarcinoma cell lines.

  2. Different maspin functions in the lung adenocarcinoma A549 and SPC-A1 cell lines.

    Science.gov (United States)

    Zhou, Jun; Hualong, Qin; Zhou, Peng; Guo, Feng

    2015-11-01

    Mammary serine protease inhibitor (maspin) is a tumor suppressor gene that is silenced in the majority of cancer cells during metastatic progression by transcriptional and epigenetic mechanisms. The function of maspin in non‑small cell lung cancer cells (NSCLC) has not been clearly defined. In the present study, the expression of maspin in NSCLC cell lines, in particular, the adenocarcinoma cell lines, was heterogeneous. While the expression levels of maspin in PC‑9 and H460 cell lines were intact, the expression of maspin in the A549 and SPC‑A1 cells was hardly detected. Ectopic expression of maspin in A549 cells carrying the K‑ras gene point mutation significantly inhibited cell migration and invasion abilities, which was associated with downregulated expression of matrix metalloproteinase‑2 and integrin β1. Ectopic expression of maspin in SPC‑A1 cells harboring the wild‑type K‑ras gene predominantly affected cell growth via targeting the AKT signaling molecules. Maspin functions differently in lung adenocarcinoma cells, possibly due to the varied molecular characteristics.

  3. Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose systematic administration

    Indian Academy of Sciences (India)

    Yan Shan; Chunting Wang; Li Yang; Li Juan Chen; Hong Xin Deng; Han Shuo Yang; Zhimian Li; Zhiyong Li; Li Pan; Fei Leng; Yuquan Wei

    2010-06-01

    Anti-apoptosis plays an important role in tumour formation and development. Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a target for anti-cancer drug exploitation was replaced as development. We investigated the role of the homo dominant-negative mutant Survivin-T34A in suppressing human lung adenocarcinomas (A549). The anti-tumour activity of HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing A549 subcutaneous tumours. Low-dose systemic administration was continuously used. The HSurvivinT34A plasmid (5 g/one) complexed with a cationic liposome (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed microvessel density degradation by CD31 immunohistochemistry and apoptotic cell increase by TUNEL assay, PI staining and flow cytometric analysis in the treated group. The present findings suggest that the HSurvivinT34A plasmid complexed with a cationic liposome may provide an effective approach to inhibit the growth of human lung adenocarcinomas in vitro and in vivo.

  4. Erlotinib Versus Radiation Therapy for Brain Metastases in Patients With EGFR-Mutant Lung Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Naamit K.; Yamada, Yoshiya; Rimner, Andreas [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Shi, Weiji [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Riely, Gregory J. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Beal, Kathryn [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yu, Helena A. [Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Wu, Abraham J., E-mail: wua@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2014-06-01

    Purpose/Objectives: Radiation therapy (RT) is the principal modality in the treatment of patients with brain metastases (BM). However, given the activity of EGFR tyrosine kinase inhibitors in the central nervous system, it is uncertain whether upfront brain RT is necessary for patients with EGFR-mutant lung adenocarcinoma with BM. Methods and Materials: Patients with EGFR-mutant lung adenocarcinoma and newly diagnosed BM were identified. Results: 222 patients were identified. Exclusion criteria included prior erlotinib use, presence of a de novo erlotinib resistance mutation, or incomplete data. Of the remaining 110 patients, 63 were treated with erlotinib, 32 with whole brain RT (WBRT), and 15 with stereotactic radiosurgery (SRS). The median overall survival (OS) for the whole cohort was 33 months. There was no significant difference in OS between the WBRT and erlotinib groups (median, 35 vs 26 months; P=.62), whereas patients treated with SRS had a longer OS than did those in the erlotinib group (median, 64 months; P=.004). The median time to intracranial progression was 17 months. There was a longer time to intracranial progression in patients who received WBRT than in those who received erlotinib upfront (median, 24 vs 16 months, P=.04). Patients in the erlotinib or SRS group were more likely to experience intracranial failure as a component of first failure, whereas WBRT patients were more likely to experience failure outside the brain (P=.004). Conclusions: The survival of patients with EGFR-mutant adenocarcinoma with BM is notably long, whether they receive upfront erlotinib or brain RT. We observed longer intracranial control with WBRT, even though the WBRT patients had a higher burden of intracranial disease. Despite the equivalent survival between the WBRT and erlotinib group, this study underscores the role of WBRT in producing durable intracranial control in comparison with a targeted biologic agent with known central nervous system activity.

  5. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: Prevalence and relation with different clinical variables

    Science.gov (United States)

    Kasana, Basharat Ahmad; Dar, Waseem Raja; Aziz, Sheikh Aijaz; Lone, Abdul Rashid; Sofi, Najeeb Ullah; Dar, Imtiyaz Ahmad; Latief, Muzamil; Arshad, Faheem; Hussain, Moomin; Hussain, Mir

    2016-01-01

    Introduction: Lung cancer is one of the most common causes of cancer deaths worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the predominant histological subtype. Several cytotoxic drugs are available for the treatment of lung cancer, but side effects limit their use. Recently, targeted therapies for cancers have come into clinical practice. Aims and Objectives: To determine the prevalence of epidermal growth factor receptor (EGFR) mutation in adenocarcinoma lung in a North Indian population and its relation with different clinical variables. Materials and Methods: A total of 57 patients who met inclusion criteria were recruited into the study. Relevant history, clinical examination and investigations were done. EGFR mutation was done in all patients. Results: A total of twenty patients tested positive for EGFR mutation. EGFR was more frequently detected in female patients (53.8%), while as only 19.4% of the male patients expressed EGFR mutation, which was statistically very significant (P = 0.007). EGFR mutation was more frequently detected in nonsmokers (52%) as compared to smokers (21.9%) which also was statistically significant (P value of 0.018). EGFR mutation was more common in Stage III and IV adenocarcinomas (48%) as compared to Stage I and II (21.4%) which was statistically significant (P value 0.034). Conclusion: EGFR mutation should be routinely done in all patients of adenocarcinoma lung particularly non-smoker females with Stage III and IV disease. PMID:27688613

  6. ADAM9 up-regulates N-cadherin via miR-218 suppression in lung adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Yuh-Pyng Sher

    Full Text Available Lung cancer is the leading cause of cancer death worldwide, and brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker of the epithelial-mesenchymal transition and ADAM9 (a type I transmembrane protein are related to lung cancer brain metastasis; however, it is unclear how they interact to mediate this metastasis. Because microRNAs regulate many biological functions and disease processes (e.g., cancer by down-regulating their target genes, microRNA microarrays were used to identify ADAM9-regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and western blot analysis showed that CDH2 is a target gene of miR-218. MiR-218 was generated from pri-mir-218-1, which is located in SLIT2, in non-invasive lung adenocarcinoma cells, whereas its expression was inhibited in aggressive lung adenocarcinoma. The down-regulation of ADAM9 up-regulated SLIT2 and miR-218, thus down-regulating CDH2 expression. This study revealed that ADAM9 activates CDH2 through the release of miR-218 inhibition on CDH2 in lung adenocarcinoma.

  7. Spheres derived from lung adenocarcinoma pleural effusions: molecular characterization and tumor engraftment.

    Directory of Open Access Journals (Sweden)

    Rita Mancini

    Full Text Available Malignant pleural effusions (MPEs could represent an excellent source to culture a wide variety of cancer cells from different donors. In this study, we set up culture conditions for cancer cells deriving from MPEs of several patients affected by the most frequent form of lung cancer, namely the subset of non small cell lung cancers (NSCLC classified as Lung Adenocarcinomas (AdenoCa which account for approximately 40% of lung cancer cases. AdenoCa malignant pleural effusions gave rise to in vitro cultures both in adherent and/or in spheroid conditions in almost all cases analyzed. We characterized in greater detail two samples which showed the most efficient propagation in vitro. In these samples we also compared gene profiles of spheroid vs adherent cultures and identified a set of differentially expressed genes. Finally we achieved efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells.

  8. Suppression subtractive hybridization identified differentially expressed genes in lung adenocarcinoma: ERGIC3 as a novel lung cancer-related gene

    Directory of Open Access Journals (Sweden)

    Wu Mingsong

    2013-02-01

    Full Text Available Abstract Background To understand the carcinogenesis caused by accumulated genetic and epigenetic alterations and seek novel biomarkers for various cancers, studying differentially expressed genes between cancerous and normal tissues is crucial. In the study, two cDNA libraries of lung cancer were constructed and screened for identification of differentially expressed genes. Methods Two cDNA libraries of differentially expressed genes were constructed using lung adenocarcinoma tissue and adjacent nonmalignant lung tissue by suppression subtractive hybridization. The data of the cDNA libraries were then analyzed and compared using bioinformatics analysis. Levels of mRNA and protein were measured by quantitative real-time polymerase chain reaction (q-RT-PCR and western blot respectively, as well as expression and localization of proteins were determined by immunostaining. Gene functions were investigated using proliferation and migration assays after gene silencing and gene over-expression. Results Two libraries of differentially expressed genes were obtained. The forward-subtracted library (FSL and the reverse-subtracted library (RSL contained 177 and 59 genes, respectively. Bioinformatic analysis demonstrated that these genes were involved in a wide range of cellular functions. The vast majority of these genes were newly identified to be abnormally expressed in lung cancer. In the first stage of the screening for 16 genes, we compared lung cancer tissues with their adjacent non-malignant tissues at the mRNA level, and found six genes (ERGIC3, DDR1, HSP90B1, SDC1, RPSA, and LPCAT1 from the FSL were significantly up-regulated while two genes (GPX3 and TIMP3 from the RSL were significantly down-regulated (P  Conclusions The two libraries of differentially expressed genes may provide the basis for new insights or clues for finding novel lung cancer-related genes; several genes were newly found in lung cancer with ERGIC3 seeming a novel lung cancer

  9. Lung Adenocarcinoma Staged as an Unknown Primary Presenting with Symptomatic Colon Metastases: Staging by 18F FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William [Brandon Regional Health Centre, Brandon (Canada); Ciarallo, Anthony [Royal Victoria Hospital, Montreal (Canada)

    2011-12-15

    A 66 year old man, who presented with bright red blood per rectum, was referred for an {sup 18F} FDG PET/CT after colonoscopy showed two suspicious colon masses, which were biopsied to reveal an adenocarcinoma of unknown origin. PET/CT showed two intensely FDG avid colon massed as well as an unsuspected FDG avid lung mass, which was biopsied to reveal a primary lung adenocarcinoma. Immunohistochemistry confirmed the two colon metastases were of pulmonary origin. It is extremely rare for lung carcinoma to present with symptomatic colon metastases, with only 11 cases described in the literature. We report the first case of the utility of {sup 18F} FDG PET/CT in staging a patient who presented with symptomatic colon metastases of an unknown primary lung malignancy.

  10. S-1 in combination with docetaxel and oxaliplatin in patients with advanced gastro-esophageal adenocarcinoma

    DEFF Research Database (Denmark)

    Pfeiffer, Per; Qvortrup, Camilla; Krogh, Merete

    2017-01-01

    BACKGROUND: Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended...

  11. Cigarette smoking and K-ras mutations in pancreas, lung and colorectal adenocarcinomas: Etiopathogenic similarities, differences and paradoxes

    NARCIS (Netherlands)

    Porta, M.; Crous-Bou, M.; Wark, P.A.; Vineis, P.; Real, F.X.; Malats, N.; Kampman, E.

    2009-01-01

    Surprisingly different frequencies and patterns of K-ras mutations are observed in human adenocarcinomas of the pancreas, colorectum and lung. Their respective relationships with smoking are apparently paradoxical. We evaluated all the available types of clinical and epidemiological studies on the r

  12. Cigarette smoking and K-ras mutations in pancreas, lung and colorectal adenocarcinomas: etiopathogenic similarities, differences and paradoxes.

    NARCIS (Netherlands)

    Porta, M.; Crous-Bou, M.; Wark, P.A.; Vineis, P.; Real, F.X.; Malats, N.; Kampman, E.

    2009-01-01

    Surprisingly different frequencies and patterns of K-ras mutations are observed in human adenocarcinomas of the pancreas, colorectum and lung. Their respective relationships with smoking are apparently paradoxical. We evaluated all the available types of clinical and epidemiological studies on the r

  13. Next-generation sequencing for molecular diagnosis of lung adenocarcinoma specimens obtained by fine needle aspiration cytology

    Science.gov (United States)

    Qiu, Tian; Guo, Huiqin; Zhao, Huan; Wang, Luhua; Zhang, Zhihui

    2015-06-01

    Identification of multi-gene variations has led to the development of new targeted therapies in lung adenocarcinoma patients, and identification of an appropriate patient population with a reliable screening method is the key to the overall success of tumor targeted therapies. In this study, we used the Ion Torrent next-generation sequencing (NGS) technique to screen for mutations in 89 cases of lung adenocarcinoma metastatic lymph node specimens obtained by fine-needle aspiration cytology (FNAC). Of the 89 specimens, 30 (34%) were found to harbor epidermal growth factor receptor (EGFR) kinase domain mutations. Seven (8%) samples harbored KRAS mutations, and three (3%) samples had BRAF mutations involving exon 11 (G469A) and exon 15 (V600E). Eight (9%) samples harbored PIK3CA mutations. One (1%) sample had a HRAS G12C mutation. Thirty-two (36%) samples (36%) harbored TP53 mutations. Other genes including APC, ATM, MET, PTPN11, GNAS, HRAS, RB1, SMAD4 and STK11 were found each in one case. Our study has demonstrated that NGS using the Ion Torrent technology is a useful tool for gene mutation screening in lung adenocarcinoma metastatic lymph node specimens obtained by FNAC, and may promote the development of new targeted therapies in lung adenocarcinoma patients.

  14. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

    Science.gov (United States)

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang

    2016-01-01

    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

  15. Lung adenocarcinoma as a solitary pulmonary nodule: prognostic determinants of CT, PET, and histopathologic findings.

    Science.gov (United States)

    Lee, Ho Yun; Han, Joungho; Lee, Kyung Soo; Koo, Ji Hyun; Jeong, Sun Young; Kim, Byung-Tae; Cho, Young-Seok; Shim, Young Mog; Kim, Jhingook; Kim, Kwanmien; Choi, Yong Soo

    2009-12-01

    We aimed to retrospectively compare CT, PET, and histopathologic (the extent of bronchioloalveolar carcinoma [BAC] components) findings of solitary pulmonary nodular (SPN) adenocarcinomas of the lung to determine their value as prognostic determinants. We reviewed CT and PET characteristics of tumors and pathologic specimens from 65 consecutive patients who underwent surgical resection for SPN adenocarcinomas. Nodule size and TDR (tumor shadow disappearance rate) were assessed from CT scans, and maximum standardized uptake value (SUVmax) of tumors was measured at PET. On pathologic examination, BAC, non-BAC, and central fibrous scar ratios were quantified. Prognosis was evaluated by noting disease recurrence during a minimum 12-month follow-up period after curative resection. The interrelationships between TDR, SUVmax, BAC, and non-BAC ratio were studied, and relationships between recurrence and various variables were analyzed. The median follow-up time was 33 months, and seven patients (11%) developed disease recurrence after surgical resection. TDR at CT and SUVmax at PET correlated well with pathologic BAC and non-BAC ratios. Between subgroups with and without recurrence, there were significant differences in SUVmax and BAC and non-BAC ratios. Based on univariate survival analyses, pathologic BAC and non-BAC ratios were risk factors significantly related to recurrence, but only high non-BAC ratio remained as an independent factor associated with recurrence in the multivariate analysis (hazard ratio [HR]=0.956, P=0.013). Among the factors examined, pathologic non-BAC ratio is the only independent risk factor for poor prognosis in patients with SPN adenocarcinomas.

  16. Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer

    Science.gov (United States)

    2016-08-25

    Extensive Stage Small Cell Lung Carcinoma; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Small Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

  17. Lung adenocarcinoma with Lambert–Eaton myasthenic syndrome indicated by voltage-gated calcium channel: a case report

    Directory of Open Access Journals (Sweden)

    Arai Hiromasa

    2012-09-01

    Full Text Available Abstract Introduction Lambert–Eaton myasthenic syndrome is a rare disorder and it is known as a paraneoplastic neurological syndrome. Small cell lung cancer often accompanies this syndrome. Lambert–Eaton myasthenic syndrome associated with lung adenocarcinoma is extremely rare; there are only a few reported cases worldwide. Case presentation A 75-year-old Japanese man with a past history of chronic rheumatoid arthritis and Sjögren syndrome was diagnosed with Lambert–Eaton myasthenic syndrome by electromyography and serum anti-P/Q-type voltage-gated calcium channel antibody level preceding the diagnosis of lung cancer. A chest computed tomography to screen for malignant lesions revealed an abnormal shadow in the lung. Although a histopathological examination by bronchoscopic study could not reveal the malignancy, lung cancer was mostly suspected after the results of a chest computed tomography and [18F]-fluorodeoxyglucose positron emission tomography. An intraoperative diagnosis based on the frozen section obtained by tumor biopsy was adenocarcinoma so the patient underwent a lobectomy of the right lower lobe and lymph node dissection with video-assisted thoracoscopic surgery. The permanent pathological examination was the same as the frozen diagnosis (pT2aN1M0: Stage IIa: TNM staging 7th edition. Immunohistochemistry revealed that most of the cancer cells were positive for P/Q-type voltage-gated calcium channel. Conclusions Our case is a rare combination of Lambert–Eaton myasthenic syndrome associated with lung adenocarcinoma, rheumatoid arthritis and Sjögren syndrome, and to the best of our knowledge it is the first report that indicates the presence of voltage-gated calcium channel in lung adenocarcinoma by immunostaining.

  18. Bax is not involved in the resveratrol-induced apoptosis in human lung adenocarcinoma cells

    Science.gov (United States)

    Zhang, Wei-wei; Wang, Zhi-ping; Chen, Tong-sheng

    2010-02-01

    Resveratrol (RV) is a natural plant polyphenol widely present in foods such as grapes, wine, and peanuts. Previous studies indicate that RV has an ability to inhibit various stages of carcinogenesis and eliminate preneoplastic cells in vitro and in vivo. However, little is known about the molecular mechanism of RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cell. In this report, we analyzed whether Bax translocation from cytoplasm to mitochondria during RV-induced apoptosis in single living cell using onfocal microscopey. Cells were transfected with GFP-Bax plasmid. Cell counting kit (CCK-8) assay was used to assess the inhibition of RV on the cells viability. Apoptotic activity of RV was detected by Hoechst 33258 and propidium iodide (PI) staining. Our results showed that RV induced a dose-dependent apoptosis in which Bax did not translocate to mitochondrias.

  19. Levels of PEDF in Pleural Effusions from Lung Adenocarcinoma and Benign Disease Patients

    Directory of Open Access Journals (Sweden)

    Nuria Sánchez-Otero

    2013-01-01

    Full Text Available Anti-tumor properties assigned to PEDF, beside its role as an inhibitor of angiogenesis, make it a promising candidate in the search of new biomarkers for malignancy. In this study levels of PEDF were investigated in pleural effusions from lung adenocarcinoma and benign inflammatory disease patients. The mean PEDF concentration in the malignant group was slightly superior to that in patients suffering benign diseases (4.59 μg/mL vs 3.97 μg/mL, although the difference did not reach statistical significance (P 0.166. Pleural effusion PEDF levels were not related to gender, age, smoking habit or pleural effusion size. We also investigated the possible relationship of PEDF levels in pleural effusion regarding clinicopathological features. Correlations were found for monocytes (P 0.010 and polymorphonuclear leukocytes (P 0.023 with PEDF levels in pleural effusion of malignant origin.

  20. RAI,one candidate gene associated with differentiation of human lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    王雪皎; 张睿; 刘芝华; 王秀琴; 丁芳; 郭明洲; 吴旻

    2000-01-01

    From all-trans retinoic acid (ATRA)-treated human lung adenocarcinoma GLC-82 cells and control, subtractive cDNA library has been constructed using subtractive hybridization technique in our laboratory. The screening of the cDNA subtractive library resulted in identification of a clone containing cDNA fragment of one ATRA-induced gene (RAI) in GLC-82 cells. The positive clone with full-length cDNA of RAI was identified by screening fetal brain cDNA library using colony hybridization technique, and then sequenced. RT-PCR results showed that RAI was expressed in many different human fetal tissues. These results suggest that RAI may be involved in cell differentiation and play an important role in vital activities of cells.

  1. RAI, one candidate gene associated with differentiation of human lung adenocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    From all-trans retinoic acid (ATRA)-treated human lung adenocarcinoma GLC-82 cells and control, subtractive cDNA library has been constructed using subtractive hybridization technique in our laboratory. The screening of the cDNA subtractive library resulted in identification of a clone containing cDNA fragment of one ATRA-induced gene (RAI) in GLC-82 cells. The positive clone with full-length cDNA of RAI was identified by screening fetal brain cDNA library using colony hybridization technique, and then sequenced. RT-PCR results showed that RAI was expressed in many different human fetal tissues. These results suggest that RAI may be involved in cell differentiation and play an important role in vital activities of cells.

  2. 4-Nitroquinoline-1-oxide effects human lung adenocarcinoma A549 cells by regulating the expression of POLD4

    OpenAIRE

    HUANG, QIN-MIAO; ZENG, YI-MING; ZHANG, HUA-PING; LV, LIANG-CHAO; YANG, DONG-YONG; LIN, HUI-HUANG

    2016-01-01

    The aim of the present study was to explore the expression of POLD4 in human lung adenocarcinoma A549 cells under 4-nitroquinoline-1-oxide (4NQO) stimulation to investigate the role of POLD4 in smoking-induced lung cancer. The lung cancer A549 cell line was treated with 4NQO, with or without MG132 (an inhibitor of proteasome activity), and subsequently the POLD4 level was determined by western blot analysis. Secondly, the cell sensitivity to 4NQO and Taxol was determined when the POLD4 expres...

  3. Smoking history and lung carcinoma: KRAS mutation is an early hit in lung adenocarcinoma development.

    NARCIS (Netherlands)

    Thunnissen, F.B.J.M.; Prinsen, C.; Hol, B.; Drift, M.A. van der; Vesin, A.; Brambilla, C.; Montuenga, L.; Field, J.K.

    2012-01-01

    BACKGROUND: In a European multicenter prospective study patients with lung cancer were interviewed for smoking history and biological samples centrally collected. The aim of this study was to compare KRAS mutation analysis with smoking status at the time of diagnosis. METHODS: A nested case-study wa

  4. Sulforaphane‐induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC‐05

    Science.gov (United States)

    Zhou, Lan; Yao, Qian; Huang, Yun‐chao; Jiang, Hua; Wang, Chuan‐qiong; Fan, Lei

    2016-01-01

    Background Xuanwei district in Yunnan Province has the highest incidence of lung cancer in China, especially among non‐smoking women. Cruciferous vegetables can reduce lung cancer risk by prompting a protective mechanism against respiratory tract inflammation caused by air pollution, and are rich in sulforaphane, which can induce changes in gene expression. We investigated the effect of sulforaphane‐induced apoptosis in Xuanwei lung adenocarcinoma cell line (XWCL‐05) to explore the value of sulforaphane in lung cancer prevention and treatment. Methods Cell growth inhibition was determined by methyl thiazolyl tetrazolium assay; cell morphology and apoptosis were observed under transmission electron microscope; cell cycle and apoptosis rates were detected using flow cytometry; B‐cell lymphoma 2 (Bcl‐2) and Bcl‐2‐like protein 4 (Bax) messenger RNA expression were determined by quantitative PCR; and p53, p73, p53 upregulated modulator of apoptosis (PUMA), Bax, Bcl‐2, and caspase‐9 protein expression were detected by Western blotting. Results Sulforaphane inhibited XWLC‐05 cell growth with inhibitory concentration (IC)50 of 4.04, 3.38, and 3.02 μg/mL at 24, 48, and 72 hours, respectively. Sulforaphane affected the XWLC‐05 cell cycle as cells accumulated in the G2/M phase. The proportion of apoptotic cells observed was 27.6%. Compared with the control, the sulforaphane group showed decreased Bcl‐2 and p53 expression, and significantly increased p73, PUMA, Bax, and caspase‐9 protein expression (P cancer cells, downregulation of the anti‐apoptotic gene B cl ‐2, and activation of caspase‐9. It may also involve downregulation of the mutant p53 protein. PMID:27878984

  5. Life expectancy with perioperative chemotherapy and chemoradiotherapy for locally advanced gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sadighi S

    2008-12-01

    Full Text Available "nBackground: Although postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach, curative surgery occurs in less than 50% of nonmetastatic gastric cancers. A regimen of docetaxel, cisplatin and infusional fluorouracil improves survival of patients with incurable locally-advanced gastric adenocarcinoma. So we assessed the perioperative regimen of docetaxel, cisplatin and infusions 5FU (TCF and postoperative chemoradiotherapy to improve outcomes in patients with potentially resectable gastric adenocarcinoma. "nMethods: Between March 2005 and March 2008, we 100 enrolled patients with stage II to IV (M0 adenocarcinoma of the stomach who had not been treated previously. Treatment consisted of three preoperative and one postoperative cycles of TCF followed by chemoradiotherapy. The primary end point was overall survival. The secondary end points were progression-free survival and toxicity of treatment. "nResults: A total of 100 patients participated, 83 of whom received neoadjuvant and 17 received adjuvant chemotherapy. Seventy-five patients underwent at least D0 gastrectomy. After chemotherapy, tumor stages were significantly lower than before beginning the protocol. Out of 100 patients, 44 had stage IV before chemotherapy versus 15 after the treatment. Three patients showed complete pathologic response. The median survival time was 25 months. "nConclusion: Docetaxel, cisplatin and 5FU combination chemotherapy is an active preoperative treatment in locally advanced gastric cancer. Perioperative chemoradio-therapy should be considered as an option to lengthen patient survival.

  6. Expression and Clinical Significance of CD147 and MMP-2 
in Squamous Cell Carcinoma and Adenocarcinoma of the Lungs

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    Siwen WANG

    2011-09-01

    Full Text Available Background and objective It has been proven that CD147 was an extracellular matrix metalloproteinase inducer reportedly involved in the invasion and metastasis of malignancies. The aim of this study is to investigate CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs and to analyze their clinical significance. Methods Tissue samples from 55 patients with squamous cell carcinoma and adenocarcinoma of the lungs and their corresponding non-cancerous tissues were examined for CD147 and MMP-2 expression using immunohistochemistry. Results The positive expression rates of CD147 and MMP-2 in the squamous cell carcinoma and adenocarcinoma among the lung tissues were significantly higher than those in the corresponding normal lung tissues. Moreover, the CD147 and MMP-2 expression in squamous cell carcinoma and adenocarcinoma of the lungs were related to lymph node metastasis and TNM stages (P<0.05, but not to age, gender and histologic type (P>0.05. MMP-2 expression was highly correlated with CD147 expression. Conclusion CD147 and MMP-2 expression is correlated with the invasion and metastasis of squamous cell carcinoma and adenocarcinoma of the lungs and may be used as objective markers for predicting the behavior of squamous cell carcinoma and adenocarcinoma of the lungs.

  7. Mechanism of arctigenin-mediated specific cytotoxicity against human lung adenocarcinoma cell lines.

    Science.gov (United States)

    Susanti, Siti; Iwasaki, Hironori; Inafuku, Masashi; Taira, Naoyuki; Oku, Hirosuke

    2013-12-15

    The lignan arctigenin (ARG) from the herb Arctium lappa L. possesses anti-cancer activity, however the mechanism of action of ARG has been found to vary among tissues and types of cancer cells. The current study aims to gain insight into the ARG mediated mechanism of action involved in inhibiting proliferation and inducing apoptosis in lung adenocarcinoma cells. This study also delineates the cancer cell specificity of ARG by comparison with its effects on various normal cell lines. ARG selectively arrested the proliferation of cancer cells at the G0/G1 phase through the down-regulation of NPAT protein expression. This down-regulation occurred via the suppression of either cyclin E/CDK2 or cyclin H/CDK7, while apoptosis was induced through the modulation of the Akt-1-related signaling pathway. Furthermore, a GSH synthase inhibitor specifically enhanced the cytotoxicity of ARG against cancer cells, suggesting that the intracellular GSH content was another factor influencing the susceptibility of cancer cells to ARG. These findings suggest that specific cytotoxicity of ARG against lung cancer cells was explained by its selective modulation of the expression of NPAT, which is involved in histone biosynthesis. The cytotoxicity of ARG appeared to be dependent on the intracellular GSH level.

  8. Deep Feature Transfer Learning in Combination with Traditional Features Predicts Survival Among Patients with Lung Adenocarcinoma.

    Science.gov (United States)

    Paul, Rahul; Hawkins, Samuel H; Balagurunathan, Yoganand; Schabath, Matthew B; Gillies, Robert J; Hall, Lawrence O; Goldgof, Dmitry B

    2016-12-01

    Lung cancer is the most common cause of cancer-related deaths in the USA. It can be detected and diagnosed using computed tomography images. For an automated classifier, identifying predictive features from medical images is a key concern. Deep feature extraction using pretrained convolutional neural networks (CNNs) has recently been successfully applied in some image domains. Here, we applied a pretrained CNN to extract deep features from 40 computed tomography images, with contrast, of non-small cell adenocarcinoma lung cancer, and combined deep features with traditional image features and trained classifiers to predict short- and long-term survivors. We experimented with several pretrained CNNs and several feature selection strategies. The best previously reported accuracy when using traditional quantitative features was 77.5% (area under the curve [AUC], 0.712), which was achieved by a decision tree classifier. The best reported accuracy from transfer learning and deep features was 77.5% (AUC, 0.713) using a decision tree classifier. When extracted deep neural network features were combined with traditional quantitative features, we obtained an accuracy of 90% (AUC, 0.935) with the 5 best post-rectified linear unit features extracted from a vgg-f pretrained CNN and the 5 best traditional features. The best results were achieved with the symmetric uncertainty feature ranking algorithm followed by a random forests classifier.

  9. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

    Directory of Open Access Journals (Sweden)

    Christopher M Bryant

    Full Text Available Lung adenocarcinoma (AD represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87 and Europe (N = 89 using the identical analytic procedures.

  10. Rab27A regulates exosome secretion from lung adenocarcinoma cells A549: involvement of EPI64.

    Science.gov (United States)

    Li, Wenhai; Hu, Yunsheng; Jiang, Tao; Han, Yong; Han, Guoliang; Chen, Jiakuan; Li, Xiaofei

    2014-11-01

    Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis. The unique composition of exosomes can be transported to other cells which allow cells to exert biological functions at distant sites. However, in lung cancer, the regulation of exosome secretion was poorly understood. In this study, we employed human lung adenocarcinoma A549 cells to determine the exosome secretion and involved regulation mechanism. We found that Rab27A was expressed in A549 cells and the reduction of Rab27A by Rab27A-specific shRNA could significantly decrease the secretion of exosome by A549 cells. EPI64, a candidate GAP that is specific for Rab27, was also detected in A549 cells. By pull-down assay, we found that EPI64 participated in the exosome secretion of A549 cells by acting as a specific GAP for Rab27A, not Rab27B. Overexpression of EPI64 enhanced exosome secretion. Taken together, in A549 cells, EPI64 could regulate the exosome secretion by functioning as a GAP specific for Rab27A.

  11. Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray.

    Science.gov (United States)

    Kikuchi, Takefumi; Daigo, Yataro; Ishikawa, Nobuhisa; Katagiri, Toyomasa; Tsunoda, Tatsuhiko; Yoshida, Seiichi; Nakamura, Yusuke

    2006-04-01

    Distant metastasis is one of the crucial parameters determining the type of treatment and prognosis of patients. Previous studies discovered important factors involved in multiple steps of metastasis, the precise mechanisms of metastasis still remain to be clarified. To identify genes associated with this complicated biological feature of cancer, we analyzed expression profiles of 16 metastatic brain tumors derived from primary lung adenocarcinoma (ADC) using cDNA microarray representing 23,040 genes. We applied bioinformatic algorithm to compare the expression data of these 16 brain metastatic loci with those of 37 primary NSCLCs including 22 ADCs, and found that metastatic tumor cells has very different characteristics of gene expression patterns from primary ones. Two hundred and forty-four genes that showed significantly different expression levels between the two groups included plasma membrane bounding proteins, cellular antigens, and cytoskeletal proteins that might play important roles in altering cell-cell communication, attachment, and cell motility, and enhance the metastatic ability of cancer cells. Our results provide valuable information for development of predictive markers as well as novel therapeutic target molecules for metastatic brain tumor of ADC of the lung.

  12. Trichostatin A suppresses lung adenocarcinoma development in Grg1 overexpressing transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ju, E-mail: ju.liu@sdu.edu.cn [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan (China); Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Li, Yan [Children' s Health Care Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014 (China); Dong, Fengyun; Li, Liqun [Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, 16766 Jingshi Road, Jinan (China); Masuda, Takahiro; Allen, Thaddeus D. [Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Lobe, Corrinne G. [Molecular and Cellular Biology Division, Sunnybrook Health Science Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5 (Canada); Miami Mice Research Corp., MaRS Centre, Heritage Bldg., 101 College Street, Toronto, Ontario M5G 1L7 (Canada)

    2015-08-07

    Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We found that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression. - Highlights: • TSA suppresses lung tumorigenesis in Grg1 overexpressing transgenic mice. • TSA does not affect overall Grg1 protein levels in the mice and in A549 cells. • TSA reduces ErbB1 and ErbB2 expression in the mice and in A549 cells. • Lapatinib masks TSA-induced inhibition of A549 cell proliferation and migration. • TSA inhibits VEGF signaling, but not basic FGF

  13. Surveillance of the remaining nodules after resection of the dominant lung adenocarcinoma is an appropriate follow-up strategy

    Directory of Open Access Journals (Sweden)

    Massimo eCastiglioni

    2015-01-01

    Full Text Available IntroductionAdenocarcinomas, commonly present as a dominant lesion (DL with additional nodules in the ipsilateral or contralateral lung. We sought to determine the fate and management of the secondary nodules and to assess the risk of these nodules using the Lung CT Screening Reporting and Data System (Lung-RADS criteria and the National Comprehensive Cancer Network (NCCN guidelines to determine if surveillance is an appropriate strategy.MethodsWe retrospectively evaluated patients with lepidic growth pattern adenocarcinoma and secondary nodules from 2000 to 2013. Risk assessment of the additional lesions was completed with a simplified model of Lung-RADS and NCCN-Guidelines. ResultsEighty-seven patients underwent resection of 87 DLs (Group 1 concurrently with 60 additional pulmonary nodules (Group 2 while 157 non-DLs were radiologically surveyed over a median follow-up time of 3.2 years (Group 3. Malignancy was found in 29/60 (48% nodules in Group 2. Whereas, only 9/157 (6% of the lesions in Group 3 enlarged, 4 of which (2.5% of total were found to be malignant, and then treated, while the remaining nodules continued surveillance. After applying the Lung-RADS and NCCN simplified models, nodules in Group 2 were at higher risk for lung cancer than those in Group 3. ConclusionsIn patients with lepidic growth pattern adenocarcinoma associated with multiple secondary nodules, surveillance of the remaining nodules, after resection of the DL, is a reasonable strategy since these nodules exhibited a slow rate of growth and minimal malignancy. In contrast, nodules resected from the ipsilateral lung at the time of the DL, harbor malignancy in 48%. Risk assessment models may provide a useful and standardized tool for clinical assessment of pulmonary nodules.

  14. The tumor suppressor gene RBM5 inhibits lung adenocarcinoma cell growth and induces apoptosis

    Directory of Open Access Journals (Sweden)

    Shao Chen

    2012-08-01

    Full Text Available Abstract Background The loss of tumor suppressor gene (TSG function is a critical step in the pathogenesis of human lung cancer. RBM5 (RNA-binding motif protein 5, also named H37/LUCA-15 gene from chromosome 3p21.3 demonstrated tumor suppressor activity. However, the role of RBM5 played in the occurrence and development of lung cancer is still not well understood. Method Paired non-tumor and tumor tissues were obtained from 30 adenocarcinomas. The expression of RBM5 mRNA and protein was examined by RT-PCR and Western blot. A549 cell line was used to determine the apoptotic function of RBM5 in vitro. A549 cells were transiently transfected with pcDNA3.1-RBM5. AnnexinV analysis was performed by flow cytometry. Expression of Bcl-2, cleaved caspase-3, caspase-9 and PAPP proteins in A549 lung cancer cells and the A549 xenograft BALB/c nude mice model was determined by Western blot. Tumor suppressor activity of RBM5 was also examined in the A549 xenograft model treated with pcDNA3.1-RBM5 plasmid carried by attenuated Salmonella typhi Ty21a. Result The expression of RBM5 mRNA and protein was decreased significantly in adenocarcinoma tissues compared to that in the non-tumor tissues. In addition, as compared to the vector control, a significant growth inhibition of A549 lung cancer cells was observed when transfected with pcDNA3.1-RBM5 as determined by cell proliferation assay. We also found that overexpression of RBM5 induced both early and late apoptosis in A549 cells using AnnexinV/PI staining as determined by flow cytometry. Furthermore, the expression of Bcl-2 protein was decreased, whereas the expression of cleaved caspase-3, caspase-9 and PARP proteins was significantly increased in the RBM5 transfected cells; similarly, expression of decreased Bcl-2 and increased cleaved caspase-3 proteins was also examined in the A549 xenograft model. More importantly, we showed that accumulative and stable overexpression of RBM5 in the A549 xenograft BALB

  15. Identification of crucial microRNAs and genes in hypoxia-induced human lung adenocarcinoma cells

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    Geng Y

    2016-07-01

    Full Text Available Ying Geng,1,* Lili Deng,2,* Dongju Su,1 Jinling Xiao,1 Dongjie Ge,3 Yongxia Bao,1 Hui Jing4 1Department of Respiratory, 2Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, 3Department of Respiratory, The First Hospital of Harbin, 4Department of Emergency, The Second Affiliated Hospital of Harbin Medical University Harbin, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Background: Variations of microRNA (miRNA expression profile in hypoxic lung cancer cells have not been studied so far. Therefore, using miRNA microarray technology, this study aimed to study the miRNA expression profile and investigate the potential crucial miRNAs and their target genes in hypoxia-induced human lung adenocarcinoma cells.Materials and methods: Based on miRNA microarray, miRNA expression profiling of hypoxia-induced lung adenocarcinoma A549 cells was obtained. After identification of differentially expressed miRNAs (DE-miRNAs in hypoxic cells, target genes of DE-miRNAs were predicted, and functional enrichment analysis of targets was conducted. Furthermore, the expression levels of DE-miRNAs and their target genes were validated by real-time quantitative polymerase chain reaction. In addition, using miRNA mimics, the effect of overexpressed DE-miRNAs on A549 cell behaviors (cell proliferation, cell cycle, and apoptosis was evaluated.Results: In total, 14 DE-miRNAs (nine upregulated miRNAs and five downregulated miRNAs were identified in hypoxic cells, compared with normoxic cells. Target genes of both upregulated and downregulated miRNAs were enriched in the functions such as chromatin modification, and pathways such as Wnt signaling pathway and transforming growth factor (TGF-β signaling pathway. The expression levels of several miRNAs and their target genes were confirmed, including hsa-miR-301b/FOXF2, hsa-miR-148b-3p/WNT10B, hsa-miR-769-5p/(SMAD2, ARID1A, and hsa-miR-622. Among them

  16. Effect of cisplatin alone or combined with monoclonal anti-programmed death ligand-1 anti-body on lung adenocarcinoma cell line SPCA-1 and T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    潘雪

    2014-01-01

    Objective To observe the effect of cisplatin alone or combined with anti-programmed death ligand 1 monoclonal antibody(anti-PD-L1 mA b)on the co-culture system of lung adenocarcinoma SPCA-1 cells and T lymphocytes,and therefore to study the immunotherapeutic effect of anti-PD-L1 mA b on lung cancer.Methods Human adenocarcinoma SPCA-1 cell line was selected by

  17. Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

    Directory of Open Access Journals (Sweden)

    He YY

    2016-04-01

    Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

  18. Activated Notch1 induces lung adenomas in mice and cooperates with Myc in the generation of lung adenocarcinoma.

    Science.gov (United States)

    Allen, Thaddeus D; Rodriguez, Elena M; Jones, Kirk D; Bishop, J Michael

    2011-09-15

    Notch1 encodes the canonical member of the mammalian Notch receptor family. Activating lesions frequently affect Notch1 in T-cell acute lymphoblastic leukemia (T-ALL) and, recently, have been found in non-small-cell lung cancer (NSCLC) as well. We explored the oncogenic potential of activated Notch1 in the lung by developing a transgenic mouse model in which activated Notch1 was overexpressed in the alveolar epithelium. The initial response to activated Notch1 was proliferation and the accumulation of alveolar hyperplasia, which was then promptly cleared by apoptosis. After an extended latency period, however, pulmonary adenomas appeared in the transgenic mice but failed to progress to become carcinomas. Interestingly, Myc and MycL1 were expressed in the adenomas, suggesting that selection for enhanced Myc activity may facilitate tumorigenesis. Using mice engineered to coexpress activated Notch1 and Myc, we found that supplementing Myc expression resulted in increased frequency of Notch1 intracellular domain (N1ICD)-induced adenoma formation and enabled progression to adenocarcinoma and metastases. Cooperation stemmed from synergistic activation of tumor cell cycling, a process that apparently countered any impedance to tumorigenesis posed by Myc and/or activated Notch1-induced apoptosis. Significantly, cooperation was independent of RAS activation. Taken together, the data suggest that activated Notch1 substitutes for RAS activation synergistically with Myc in the development of NSCLC. These tumor models should be valuable for exploring the role of activated Notch1 in the genesis of NSCLC and for testing therapies targeting either activated Notch1 or its downstream effectors.

  19. Selected flavonoids potentiate the toxicity of cisplatin in human lung adenocarcinoma cells: A role for glutathione depletion

    OpenAIRE

    Kachadourian, Remy; LEITNER, VHEATHER M.; Day, Brian J.

    2007-01-01

    Adjuvant therapies that enhance the anti-tumor effects of cisplatin are actively being pursued. Growing evidence supports the involvement of mitochondrial dysfunction in the anti-cancer effect of cis-diammineplatinum(II) dichloride (cisplatin, CDDP). We examined the potential of using selective flavonoids that are effective in depleting tumor cells of glu-tathione (GSH) to potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549) cells. We found that cisplatin (40 μM, 48-...

  20. Sequence-dependent Effect of Docetaxel with Gefitinib on the Proliferation 
and Apoptosis of Lung Adenocarcinoma Cell H1975

    Directory of Open Access Journals (Sweden)

    Xinyu ZHANG

    2012-03-01

    Full Text Available Background and objective Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs such as gefitinib and erlotinib show promising therapeutic effects in patients with advanced non-small cell lung cancer (NSCLC. However, despite an initial response to EGFR-TKIs treatment among responsive patients, most inevitably acquire resistance after a progression-free period of about 10 months. The percentage of T790M in TKI acquired-resistant patients in most studies is around 50%. The aim of this study is to assess the effects of the sequential administration of docetaxel and gefitinib on cell proliferation and apoptosis of lung adenocarcinoma cell H1975. Methods An MTT assay was used to measure cell proliferation. The potency of the sequential administration of docetaxel and gefitinib were determined by isobolograms and combination index (CI. Cell apoptosis and cycle distribution were determined by flow cytometry. The Hoechst 33258 method was used to observe the apoptotic morphology. Chemical colorimetric luminescence was used to measure the caspase activity. Results The isobolograms and CI showed that the sequential administration of docetaxel following gefitinib remarkably inhibits cell proliferation and cell apoptosis compared with other sequential administration models. The cycle distribution results indicate that sequential docetaxel administration following gefitinib blocked the cells in the G2/M phase but not in the G0/G1. The activation of the Caspase-8/Caspase-3 cascade is mainly involved in the apoptotic pathway of lung adenocarcinoma cell H1975 in all sequential administration models. Conclusion The docetaxel administration following gefitinib might be a new stratagy for lung cancer with T790M mutation after having EGFR-TKIs resistance.

  1. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations.

    LENUS (Irish Health Repository)

    Sequist, Lecia V

    2013-09-20

    The LUX-Lung 3 study investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR\\/ErbB1), human epidermal growth factor receptor 2 (HER2\\/ErbB2), and ErbB4 and has wide-spectrum preclinical activity against EGFR mutations. A phase II study of afatinib in EGFR mutation-positive lung adenocarcinoma demonstrated high response rates and progression-free survival (PFS).

  2. Ovine pulmonary adenocarcinoma as an animal model of progressive lung cancer and the impact of nutritional selenium supply.

    Science.gov (United States)

    Humann-Ziehank, Esther; Wolf, Petra; Renko, Kostja; Schomburg, Lutz; Ludwig Bruegmann, Michael; Andreae, Arnim; Brauer, Carsten; Ganter, Martin

    2011-01-01

    Jaagsiekte sheep retrovirus (JSRV) is known to induce ovine pulmonary adenocarcinoma (OPA). Several studies have suggested an influence of selenium (Se) status on cancer progression. Thus, combining OPA with a defined Se supply might serve as a suitable animal model to study the impact of Se on lung cancer progression. 16 naturally JSRV-infected sheep were divided into 2 treatment groups receiving (a) CT) was performed repeatedly and evaluated using a CT-OPA-score system. Liver biopsies were taken three-monthly, blood samples were collected biweekly to study treatment effects on Se concentrations and glutathione peroxidase (GPx) activity. Cell pellets from bronchoalveolar lavage fluid (BALF) were tested for JSRV by PCR to approve the infection. To date, four animals of the ongoing study have been euthanised. Autopsy and histopathology were performed and correlated to CT analysis. JSRV was detected in BALF cell pellets. Progression of lung tumours was monitored successfully by repeated CT examinations, enabling the detection of even small nodules or increased lung density. Histopathology revealed bronchioloalveolar adenocarcinoma in lung areas suspicious to be OPA from CT evaluation. Score-based analysis of CT images for quantifying tumour progression proved as a valuable tool. Se concentration and GPx activity increased in liver and serum of group b and verified the efficiency of different feeding regime. In conclusion, OPA along with CT, autopsy/histopathology, trace element and enzyme activity analysis provide a suitable large animal model to examine the impact of Se supply on lung tumourigenesis.

  3. Crizotinib Treatment in a Lung Adenocarcinoma Harboring ALK Fusion Gene with Bone Marrow Metastasis: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Xiaoyan LI

    2015-02-01

    Full Text Available Background and objective Distant metastasis was common in lung cancer, especially patients with bone marrow metastasis had poor prognosis and there were few effective methods. Crizotinib had been confirmed to be used in anaplastic lymphoma kinase (ALK positive lung adenocarcinoma, but the efficacy in lung cancer with bone marrow metastasis was unknown. In the present study, we reported one case of ALK-positive lung adenocarcinoma with bone marrow matastasis given crizotinib treatment, the safety and efficacy was summarized. Methods ALK fusion was tested by fluorescence in situ hybridization (FISH. Crizotinib was given with dose of 250 mg, bid. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST v1.1 and bone marrow response was evaluated by bone marrow puncture and biopsy. Adeverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE v4.0. Results The patient achieved partial response (PR after 6 weeks of crizotinib, especially the objective response of bone marrow metastasis was complete response (CR. The patient stopped crizotinib because of pneumonia. The progression free survival (PFS and overall survival (OS was 20 weeks and 22 weeks respectively. Conclusion Crizotinib could be an effective method for ALK-positive lung cancer with bone marrow metastasis and showed good tolerance.

  4. Distinct Afatinib Resistance Mechanisms Identified in Lung Adenocarcinoma Harboring an EGFR Mutation.

    Science.gov (United States)

    Yamaoka, Toshimitsu; Ohmori, Tohru; Ohba, Motoi; Arata, Satoru; Murata, Yasunori; Kusumoto, Sojiro; Ando, Koichi; Ishida, Hiroo; Ohnishi, Tsukasa; Sasaki, Yasutsuna

    2017-03-13

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are associated with significant responses in non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations. However, acquired resistance to reversible EGFR-TKIs remains a major obstacle. In particular, while the second-generation irreversible EGFR-TKI afatinib is currently used for treating NSCLC patients, the mechanisms underlying acquired afatinib resistance remain poorly understood. Here, heterogeneous mechanisms of acquired resistance were identified following long-term exposure to increasing doses of afatinib in EGFR mutant lung adenocarcinoma PC9 cells. Notably, three resistant cell lines, PC-9AFR1, PC-9AFR2, and PC-9AFR3 (AFR1, AFR2, and AFR3, respectively), employed distinct mechanisms for avoiding EGFR inhibition, with increased EGFR expression being detected in all resistant cell lines. Moreover, an activating EGFR mutation was partially lost in AFR1 and AFR2 cells. AFR1 cells exhibited afatinib resistance as a result of wild-type KRAS amplification and overexpression; however, these cells showed a progressive decrease and eventual loss of the acquired KRAS dependence, as well as resensitization to afatinib, following a drug holiday. Meanwhile, AFR2 cells exhibited increased expression of insulin-like growth factor-binding protein 3 (IGFBP3), which promoted insulin-like growth factor 1 receptor (IGF1R) activity and subsequent AKT phosphorylation, thereby indicating a potential bypass signaling pathway associated with IGFR1. Finally, AFR3 cells harbored the secondary EGFR mutation T790M. Our findings constitute the first report showing acquired wild-type KRAS overexpression and attenuation of afatinib resistance following a drug holiday.

  5. Novel monoclonal antibody against beta 1 integrin enhances cisplatin efficacy in human lung adenocarcinoma cells.

    Science.gov (United States)

    Kim, Min-Young; Cho, Woon-Dong; Hong, Kwon Pyo; Choi, Da Bin; Hong, Jeong Won; Kim, Soseul; Moon, Yoo Ri; Son, Seung-Myoung; Lee, Ok-Jun; Lee, Ho-Chang; Song, Hyung Geun

    2016-05-01

    The use of anti-beta 1 integrin monoclonal antibody in lung cancer treatment has proven beneficial. Here, we developed a novel monoclonal antibody (mAb), called P5, by immunizing mice with human peripheral blood mononuclear cells (PBMC). Its anti-tumor effect is now being tested, in a clinical phase III trial, in combinatorial treatments with various chemical drugs. To confirm that P5 indeed binds to beta 1 integrin, cell lysates were immunoprecipitated with commercial anti-beta 1 integrin mAb (TS2/16) and immunoblotted against P5 to reveal a 140 kDa molecular weight band, as expected. Immunoprecipitation with P5 followed by LC/MS protein sequence analysis further verified P5 antigen to be beta 1 integrin. Cisplatin treatment upregulated cell surface expression of beta 1 integrin in A549 cells, while causing inhibition of cell growth. When cells were co-treated with different concentrations of P5 mAb, the cisplatin-mediated inhibitory effect was enhanced in a dose-dependent manner. Our findings show that a combinatorial treatment of P5 mAb and cisplatin in A549 cells resulted in a 30% increase in apoptosis, compared to baseline, and significantly more when compared to either the cisplatin or P5 alone group. The entire peptide sequences in CDR from variable region of Ig heavy and light chain gene for P5 mAb are also disclosed. Together, these results provide evidence of the beneficial effect of P5 mAb in combinatorial treatment of human lung adenocarcinoma.

  6. Apoptosis signal-regulating kinase 1 mediates denbinobin-induced apoptosis in human lung adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Pan Shiow-Lin

    2009-05-01

    Full Text Available Abstract In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1 in denbinobin-induced apoptosis in human lung adenocarcinoma (A549 cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN, two antioxidants (N-acetyl-L-cysteine (NAC and glutathione (GSH, a c-Jun N-terminal kinase (JNK inhibitor (SP600125, and an activator protein-1 (AP-1 inhibitor (curcumin. Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

  7. DNA damage response signaling in lung adenocarcinoma A549 cells following gamma and carbon beam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Somnath [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Narang, Himanshi, E-mail: himinarang@gmail.com [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India); Sarma, Asitikantha [Radiation Biology Laboratory, Inter University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi 110 067 (India); Krishna, Malini [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400 085 (India)

    2011-11-01

    Carbon beams (5.16 MeV/u, LET = 290 keV/{mu}m) are high linear energy transfer (LET) radiation characterized by higher relative biological effectiveness than low LET radiation. The aim of the current study was to determine the signaling differences between {gamma}-rays and carbon ion-irradiation. A549 cells were irradiated with 1 Gy carbon or {gamma}-rays. Carbon beam was found to be three times more cytotoxic than {gamma}-rays despite the fact that the numbers of {gamma}-H2AX foci were same. Percentage of cells showing ATM/ATR foci were more with {gamma}-rays however number of foci per cell were more in case of carbon irradiation. Large BRCA1 foci were found in all carbon irradiated cells unlike {gamma}-rays irradiated cells and prosurvival ERK pathway was activated after {gamma}-rays irradiation but not carbon. The noteworthy finding of this study is the early phase apoptosis induction by carbon ions. In the present study in A549 lung adenocarcinoma, authors conclude that despite activation of same repair molecules such as ATM and BRCA1, differences in low and high LET damage responses might be due to their distinct macromolecular complexes rather than their individual activation and the activation of cytoplasmic pathways such as ERK, whether it applies to all the cell lines need to be further explored.

  8. Pneumatosis intestinalis and portal venous gas secondary to Gefitinib therapy for lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Lee Joo

    2012-03-01

    Full Text Available Abstract Background Pneumatosis intestinalis (PI, defined as the presence of gas in the bowel wall, and portal venous gas (PVG are relatively rare radiological findings. Although several chemotherapeutic agents and anti-vascular endothelial growth factor agents are reported to be associated with PI and PVG, an association with anti-epidermal growth factor receptor (EGFR agents has not been described previously. Case presentation The present report describes a case of PI and PVG secondary to treatment with an EGFR tyrosine kinase inhibitor. A 66-year-old woman who had been diagnosed with metastatic lung adenocarcinoma presented with nausea, vomiting and abdominal distension after commencing gefitinib. A computed tomography (CT scan of the abdomen revealed PI extending from the ascending colon to the rectum, hepatic PVG, and infarction of the liver. Gefitinib therapy was discontinued immediately and the patient was managed conservatively. A follow-up CT scan 2 weeks later revealed that the PI and hepatic PVG had completely resolved. Conclusion This is the first report of PI and PVG caused by EGFR tyrosine kinase inhibitor. Although these complications are extremely rare, clinicians should be aware of the risk of PI and PVG in patients undergoing targeted molecular therapy.

  9. Previous heat shock treatment inhibits Mayaro virus replication in human lung adenocarcinoma (A549) cells.

    Science.gov (United States)

    Virgilio, P L; Godinho-Netto, M C; Carvalho Mda, G

    1997-01-01

    Human lung adenocarcinoma cells (A549) were submitted to mild or severe heat shock (42 degrees C or 44 degrees C) for 1 h, while another group of cells was double-heat-shocked (submitted to 42 degrees C for 1 h, returned to 37 degrees C for 3 h, then exposed to 44 degrees C for 1 h). After each heat treatment, the cells were infected with Mayaro virus for 24 h and incubated at 37 degrees C. The results showed that the double-heat-shocked thermotolerant cells exhibited a 10(4)-fold virus titre inhibition, despite the recovery of protein synthesis and original morphology 24 h post-infection. In contrast, cells submitted to mild or severe heat shock exhibited weaker inhibition of Mayaro virus titre (10(2)-fold). The mildly heat-shocked cells also presented a full recovery in protein synthesis, which was not observed in severely heat-shocked cells. These results indicate that exposure of A549 cells to a mild or to a double heat shock treatment before Mayaro virus infection induces an antiviral state.

  10. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1994-05-01

    From 1971--1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF{sub 1} mice irradiated with {sup 60}Co {gamma}-rays or JANUS fission-spectrum neutrons. Polymerase chain reaction (PCR) technique was used to detect deletions in the mouse retinoblastoma (mRb) gene. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. Absence of any of these fragments on a Southern blot indicated a deletion of that portion of the mRb gene. Tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice were analyzed for mRb deletions. In all normal mouse tissues studies all six mRb exon fragments were present on Southern blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, 1 of 6 tumors from {gamma}-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice showed a deletion in one or both mRb alleles. All deletions detected were in the 5{prime} region of the mRb gene.

  11. Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy.

    Science.gov (United States)

    Saito, Motonobu; Suzuki, Hiroyuki; Kono, Koji; Takenoshita, Seiichi; Kohno, Takashi

    2017-03-09

    Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC. Interestingly, the frequency of driver gene aberrations differs according to ethnicity, sex, and smoking, which leads to differences in treatment efficacy. To date, several molecular-targeted drugs against driver genes have been developed, and several clinical trials have been conducted to evaluate the efficacy. However, targeted therapies against driver-gene-negative cases have not yet been well developed. Efforts to identify a new druggable target for such cases are currently underway. Furthermore, immune checkpoint blockade therapy might be effective for driver-negative cases, especially those with accumulated mutations.

  12. RESTRICTION ENDONUCLEASE ANALYSIS OF MITOCHONDRIAL DNA FROM HUMAN LUNG ADENOCARCINOMA CELL LINE SPC-A-1

    Institute of Scientific and Technical Information of China (English)

    HU Yide; QIAN Guisheng; CHEN Weizhong; LI Shuping; WANG Guansong; MAO Baoling

    1999-01-01

    Objective: To understand the role of mitochondrial DNA (mtDNA) in carcinogenesis. Methods: single-step method was used to isolate the mtDNA from human lung adenocarcinoma cell line SPC-A-1. The mtDNA was analyzed by restriction fragment length polymorphism (RFLP) with 11 kinds of restriction endonuclease, which were Pvu Ⅱ, Xho Ⅰ, Pst Ⅰ, EcoR Ⅰ,BstE Ⅱ, Hind Ⅲ, Hpa Ⅰ, Bcl Ⅰ, EcoR Ⅴ, Sca Ⅰ and Xba Ⅰ.Restriction map of mtDNA from SPC-A-1 cell was obtained by the single and double-digestion method.Results: It was found that no variation at 32 restrictionsites could be detected in the coding region of mtDNA from SPC-A-1 cell line. But a new site was found at nucleotide 16276 (EcoR Ⅴ) within the noncoding region.Conclusion: These results indicate that the primary structure of gene coding region of mtDNA isolated from SPC-A-1 cell is highly stable. While the major variation of nucleotide is probably located in the noncoding region.

  13. ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

    Science.gov (United States)

    Teixido, Cristina; Michels, Sebastian; Morales-Espinosa, Daniela; Viteri, Santiago; Hartmann, Wolfgang; Merkelbach-Bruse, Sabine; Fischer, Rieke; Schildhaus, Hans-Ulrich; Fassunke, Jana; Sebastian, Martin; Serke, Monika; Kaminsky, Britta; Randerath, Winfried; Gerigk, Ulrich; Ko, Yon-Dschun; Krüger, Stefan; Schnell, Roland; Rothe, Achim; Kropf-Sanchen, Cornelia; Heukamp, Lukas; Rosell, Rafael

    2015-01-01

    Background While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. Patients and Methods 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. Results 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. Conclusion ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC. PMID:25868855

  14. Mastic Oil Inhibits the Metastatic Phenotype of Mouse Lung Adenocarcinoma Cells

    Energy Technology Data Exchange (ETDEWEB)

    Loutrari, Heleni, E-mail: elloutrar@med.uoa.gr; Magkouta, Sophia [“G.P. Livanos and M. Simou Laboratories”, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, School of Medicine, University of Athens, 3 Ploutarchou Street, 10675 Athens (Greece); Papapetropoulos, Andreas [Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504 Patras (Greece); Roussos, Charis [“G.P. Livanos and M. Simou Laboratories”, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, School of Medicine, University of Athens, 3 Ploutarchou Street, 10675 Athens (Greece)

    2011-02-23

    Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC). However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01–0.04% v/v): (a) abrogated their Matrigel invasion and migration capabilities in transwell assays; (b) reduced the levels of secreted MMP-2; (c) restricted phorbol ester-induced actin remodeling and (d) limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis.

  15. Mastic Oil Inhibits the Metastatic Phenotype of Mouse Lung Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Heleni Loutrari

    2011-02-01

    Full Text Available Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC. However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01–0.04% v/v: (a abrogated their Matrigel invasion and migration capabilities in transwell assays; (b reduced the levels of secreted MMP-2; (c restricted phorbol ester-induced actin remodeling and (d limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis.

  16. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    Science.gov (United States)

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

  17. Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study

    Science.gov (United States)

    Zhu, Bin; Wang, Mingyi; Pariscenti, Gianluca; Jones, Kristine; Bouk, Aaron J.; Boland, Joseph; Luke, Brian T.; Song, Lei; Duan, Jubao; Liu, Pengyuan; Kohno, Takashi; Chen, Qingrong; Meerzaman, Daoud; Marconett, Crystal; Mills, Ian; Caporaso, Neil E.; Gail, Mitchell H.; Pesatori, Angela C.; Consonni, Dario; Bertazzi, Pier Alberto; Chanock, Stephen J.; Landi, Maria Teresa

    2016-01-01

    Background Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. Methods and Findings We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study. We detected driver genes by testing whether the nonsynonymous mutation rate was significantly higher than the background mutation rate and replicated our findings in public datasets with 724 samples. We performed subclonality analysis for mutations based on mutant allele data and copy number alteration data. We also tested the association between mutation signatures and clinical outcomes, including distant metastasis, survival, and tumor grade. We identified and replicated two novel candidate driver genes, POU class 4 homeobox 2 (POU4F2) (mutated in 9 [8.9%] samples) and ZKSCAN1 (mutated in 6 [5.9%] samples), and characterized their major deleterious mutations. ZKSCAN1 was part of a mutually exclusive gene set that included the RTK/RAS/RAF pathway genes BRAF, EGFR, KRAS, MET, and NF1, indicating an important driver role for this gene. Moreover, we observed strong associations between methylation in specific genomic regions and somatic mutation patterns. In the tumor evolution analysis, four driver genes had a significantly lower fraction of subclonal mutations (FSM), including TP53 (p = 0.007), KEAP1 (p = 0.012), STK11 (p = 0.0076), and EGFR (p = 0.0078), suggesting a tumor initiation role for these genes. Subclonal mutations were significantly enriched in APOBEC-related signatures (p < 2.5×10−50). The total number of somatic mutations (p = 0.0039) and the fraction of transitions (p = 5.5×10−4) were

  18. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Science.gov (United States)

    Islas-Vazquez, Lorenzo; Prado-Garcia, Heriberto; Aguilar-Cazares, Dolores; Meneses-Flores, Manuel; Galicia-Velasco, Miriam; Romero-Garcia, Susana; Camacho-Mendoza, Catalina; Lopez-Gonzalez, Jose Sullivan

    2015-01-01

    Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP) TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells. PMID:26582240

  19. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Lorenzo Islas-Vazquez

    2015-01-01

    Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

  20. Xanthohumol inhibits the extracellular signal regulated kinase (ERK) signalling pathway and suppresses cell growth of lung adenocarcinoma cells.

    Science.gov (United States)

    Sławińska-Brych, Adrianna; Zdzisińska, Barbara; Dmoszyńska-Graniczka, Magdalena; Jeleniewicz, Witold; Kurzepa, Jacek; Gagoś, Mariusz; Stepulak, Andrzej

    2016-05-16

    Aberrant activation of the Ras/MEK/ERK signaling pathway has been frequently observed in non-small-cell lung carcinoma (NSCLC) and its important role in cancer progression and malignant transformation has been documented. Hence, the ERK1/2 kinase cascade becomes a potential molecular target in cancer treatment. Xanthohumol (XN, a prenylated chalcone derived from hope cones) is known to possess a broad spectrum of chemopreventive and anticancer activities. In our studies, the MTT and BrdU assays revealed that XN demonstrated greater antiproliferative activity against A549 lung adenocarcinoma cells than against the lung adenocarcinoma H1563 cell line. We observed that XN was able to suppress the activities of ERK1/2 and p90RSK kinases, followed by inhibition of phosphorylation and activation of the CREB protein. Additionally, the XN treatment of the cancer cells caused upregulation of key cell cycle regulators p53 and p21 as well as downregulation of cyclin D1. As a result, the cytotoxic effect of XN was attributed to the cell cycle arrest at G1 phase and induction of apoptosis indicated by increased caspase-3 activity. Thus, XN might be a promising anticancer drug candidate against lung carcinomas.

  1. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  2. Advancements in radiotherapy for lung cancer in China

    Institute of Scientific and Technical Information of China (English)

    Lujun Zhao; Luhua Wang

    2015-01-01

    Lung cancer is the leading cause of death due to cancer in China. In recent years, great progress has been made in radiotherapy for lung cancer patients in China. The main advance-ments include the fol owing aspects:(1) stereotactic ablative radiotherapy for early stage non-smal cel lung cancer (NSCLC), (2) post-operative radiotherapy for NSCLC, (3) combined chemotherapy and radiotherapy for local y advanced NSCLC, (4) improved radiotherapy for advanced NSCLC, and 5) prediction of radiation-induced lung toxicity.

  3. Anaplastic lymphoma kinase-positive lung adenocarcinoma patient with development of sick sinus syndrome while on targeted treatment with crizotinib.

    Science.gov (United States)

    Jiang, Hao; Li, Mei-Mei; Jin, Shu-Xian

    2015-03-01

    The anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are younger and have never smoked, while pathologically are predominately adenocarcinomas. Crizotinib as an ALK inhibitor has been used in treating ALK positive NSCLC patients for several years and some adverse effects should be paid attention to. We now describe a case of ALK positive NSCLC patient with development of sick sinus syndrome (SSS) while on targeted treatment with crizotinib. A 46-year-old non-smoking woman with right hilar mass and underwent transesophageal endoscopic ultrasonography lymph node biopsy showed low differentiation adenocarcinoma, immunohistochemistry (IHC) of tumor samples revealed the ALK overexpression. The severe sinus bradycardia and RR interval prolongation were detected 3 months after crizotinib treatment, she underwent pacemaker implantation. Although the severe sinus bradycardia and RR interval prolongation were unusual adverse effects, physicians should be aware of these side effects when using crizotinib.

  4. Cell cycle progression score is a marker for five-year lung cancer-specific mortality risk in patients with resected stage I lung adenocarcinoma

    Science.gov (United States)

    Eguchi, Takashi; Kadota, Kyuichi; Chaft, Jamie; Evans, Brent; Kidd, John; Tan, Kay See; Dycoco, Joe; Kolquist, Kathryn; Davis, Thaylon; Hamilton, Stephanie A.; Yager, Kraig; Jones, Joshua T.; Travis, William D.; Jones, David R.; Hartman, Anne-Renee; Adusumilli, Prasad S.

    2016-01-01

    Purpose The goals of our study were (a) to validate a molecular expression signature (cell cycle progression [CCP] score and molecular prognostic score [mPS; combination of CCP and pathological stage {IA or IB}]) that identifies stage I lung adenocarcinoma (ADC) patients with a higher risk of cancer-specific death following curative-intent surgical resection, and (b) to determine whether mPS stratifies prognosis within stage I lung ADC histological subtypes. Methods Formalin-fixed, paraffin-embedded stage I lung ADC tumor samples from 1200 patients were analyzed for 31 proliferation genes by quantitative RT-PCR. Prognostic discrimination of CCP score and mPS was assessed by Cox proportional hazards regression, using 5-year lung cancer–specific mortality as the primary outcome. Results In multivariable analysis, CCP score was a prognostic marker for 5-year lung cancer–specific mortality (HR=1.6 per interquartile range; 95% CI, 1.14–2.24; P=0.006). In a multivariable model that included mPS instead of CCP, mPS was a significant prognostic marker for 5-year lung cancer–specific mortality (HR=1.77; 95% CI, 1.18–2.66; P=0.006). Five-year lung cancer–specific survival differed between low-risk and high-risk mPS groups (96% vs 81%; P<0.001). In patients with intermediate-grade lung ADC of acinar and papillary subtypes, high mPS was associated with worse 5-year lung cancer–specific survival (P<0.001 and 0.015, respectively), compared with low mPS. Conclusion This study validates CCP score and mPS as independent prognostic markers for lung cancer–specific mortality and provides quantitative risk assessment, independent of known high-risk features, for stage I lung ADC patients treated with surgery alone. PMID:27153551

  5. Phospholipid flippase associates with cisplatin resistance in plasma membrane of lung adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The fusion of the liposomes containing N-(7-nitro-2, 1, 3-benzoxadiazol-4-yl)-i ,2-hexadecanoylSn-glycero-3-1abeled phosphatidylethanolamine (NBD-PE) with A549 and A549/DDP cells was performed, and the activity of the phospholipid flippase in the plasma membrane of the cells was measured by fluorescence intensity change of NBDPE in the outer membrane. When A549 or A549/DDP cells containing N BD-PE were incubated at 37 C for 0, 30, 60 and 90 min, the fluorescence intensities in the outer membrane of the cells were 0%, 1.4%, 2.9% and 7.8% for A59cells, and 0%, 10.5 %, 15. 5 % and 18.3 % for A549/DDP cells respectively, demonstrating that the phospholipid flippase was distributed in the plasma membrane of As49 cells, but its activity in the drug-resistant A549/DDP cells was much higher than that in the A549 cells. When the A549/DDP cells were incubated with a multidrug resistance reverse agent, verapamil, for 60 min at 37C, the results showed that the NBD-PE in outer membrane decreased by 25.0% compared with the control's. Furthermore, when A549/DDP cells were incubated with 25 μmol/L cisplatin, which is a specific anticancer drug, the flippase activity decreased by 31.6%, and it further decreased with the increase of cisplatin concentration, suggesting that phospholipid flippase in the membrane might be related to the cisplatin-resistance of human lung adenocarcinoma cancer cells.

  6. Anti-tumor activity of CrTX in human lung adenocarcinoma cell line A549

    Institute of Scientific and Technical Information of China (English)

    Bin YE; Yan XIE; Zheng-hong QIN; Jun-chao WU; Rong HAN; Jing-kang HE

    2011-01-01

    Aim:To assess the cytotoxic effect of crotoxin (CrTX),a potent neurotoxin extracted from the venom of the pit viper Crotalus durissus terrificus,in human lung adenocarcinoma A549 cells and investigated the underlying mechanisms.Methods:A549 cells were treated with gradient concentrations of CrTX,and the cell cycle and apoptosis were analyzed using a flow cytometric assay.The changes of cellular effectors p53,caspase-3 and cleaved caspase-3,total P38MAPK and pP38MAPK were investigated using Western blot assays.A549 xenograft model was used to examine the inhibition of CrTX on tumor growth in vivo.Results:Treatment of A549 cells with CrTX (25-200 μg/mL) for 48 h significantly inhibited the cell growth in a dose-dependent manner (IC50=78 μg/mL).Treatment with CrTX (25 iJg/mL) for 24 h caused G1 arrest and induced cell apoptosis.CrTX (25 μg/mL) significantly increased the expression of wt p53,cleaved caspase-3 and phospho-P38MAPK.Pretreatment with the specific P38MAPK inhibitor SB203580 (5 μmol/L) significantly reduced CrTX-induced apoptosis and cleaved caspase-3 level,but G1 arrest remained unchanged and highly expressed p53 sustained.Intraperitoneal injection of CrTX (10 μg/kg,twice a week for 4 weeks) significantly inhibited A549 tumor xenograft growth,and decreased MVD and VEGF levels.Conclusion:CrTX produced significant anti-tumor effects by inducing cell apoptosis probably due to activation of P38MAPK and caspase-3,and by cell cycle arrest mediated by increased wt p53 expression.In addition,CrTX displayed anti-angiogenic effects in vivo.

  7. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-04-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF{sub 1} mice irradiated with {sup 60}Co {gamma} rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of {sup 60}Co {gamma} rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from {gamma}-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5{prime} region of the mRb gene.

  8. PCR detection of retinoblastoma gene deletions in radiation-induced mouse lung adenocarcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Churchill, M.E.; Gemmell, M.A.; Woloschak, G.E.

    1993-01-01

    From 1971 to 1986, Argonne National Laboratory conducted a series of large-scale studies of tumor incidence in 40,000 BCF[sub 1] mice irradiated with [sup 60]Co [gamma] rays or JANUS fission-spectrum neutrons; normal and tumor tissues from mice in these studies were preserved in paraffin blocks. A polymerase chain reaction (PCR) technique has been developed to detect deletions in the mouse retinoblastoma (mRb) gene in the paraffin-embedded tissues. Microtomed sections were used as the DNA source in PCR reaction mixtures. Six mRb gene exon fragments were amplified in a 40-cycle, 3-temperature PCR protocol. The absence of any of these fragments (relative to control PCR products) on a Southern blot indicated a deletion of that portion of the mRb gene. The tumors chosen for analysis were lung adenocarcinomas that were judged to be the cause of death in post-mortem analyses. Spontaneous tumors as well as those from irradiated mice (569 cGy of [sup 60]Co [gamma] rays or 60 cGy of JANUS neutrons, doses that have been found to have approximately equal biological effectiveness in the BCF, mouse) were analyzed for mRb deletions. In all normal mouse tissues studies, all six mRb exon fragments were present on Southem blots. Tumors in six neutron-irradiated mice also had no mRb deletions. However, I of 6 tumors from [gamma]-irradiated mice and 6 of 18 spontaneous tumors from unirradiated mice had a deletion in one or both mRb alleles. All deletions detected were in the 5[prime] region of the mRb gene.

  9. Expression of xeroderma pigmentosum complementation group C protein predicts cisplatin resistance in lung adenocarcinoma patients.

    Science.gov (United States)

    Lai, Tan-Chen; Chow, Kuan-Chih; Fang, Hsin-Yuan; Cho, Hsin-Ching; Chen, Chih-Yi; Lin, Tze-Yi; Chiang, I-Ping; Ho, Shu-Peng

    2011-05-01

    DNA repair has been suggested to be a major cause of spontaneous drug resistance in patients with lung adenocarcinomas (LADC). Among the DNA repair-related proteins, excision repair cross-complementation group 1 (ERCC1) has been shown to be essential for repairing cisplatin-induced interstrand cross-linkage. However, the role of other DNA repair-related proteins in drug resistance has not been clearly elucidated. In this study, we used suppression subtractive hybridization and microarray analysis to identify the DNA repair-related genes associated with cisplatin resistance. We focused on the association of XPC protein expression, which plays a pivotal role in the earliest response to global genomic repair, with the survival of LADC patients. Using suppression subtractive hybridization and a microarray analysis to identify drug resistance-associated DNA repair-related genes, we found that the mRNA levels of ERCC1, MSH-3, MSH-6 and XPC were significantly increased in LADC patients. Since the results of ERCC1 mRNA expression corresponded well with those in previous reports, in this study we focused on the clinical correlation between XPC expression and patient survival. The level of XPC protein was determined by immunohistochemical and immunoblotting analyses. We detected the XPC protein in 46 (43%) of 107 pathological LADC samples. XPC protein expression correlated with tumor stage, cigarette smoking and poor survival. In the in vitro experiments with LADC cell lines, increased XPC expression was associated with elevated drug resistance, and silencing of XPC expression reduced cisplatin resistance. Our results suggest that XPC expression predicts drug resistance in LADC.

  10. Kinase domain activation of FGFR2 yields high-grade lung adenocarcinoma sensitive to a Pan-FGFR inhibitor in a mouse model of NSCLC.

    Science.gov (United States)

    Tchaicha, Jeremy H; Akbay, Esra A; Altabef, Abigail; Mikse, Oliver R; Kikuchi, Eiki; Rhee, Kevin; Liao, Rachel G; Bronson, Roderick T; Sholl, Lynette M; Meyerson, Matthew; Hammerman, Peter S; Wong, Kwok-Kin

    2014-09-01

    Somatic mutations in FGFR2 are present in 4% to 5% of patients diagnosed with non-small cell lung cancer (NSCLC). Amplification and mutations in FGFR genes have been identified in patients with NSCLCs, and clinical trials are testing the efficacy of anti-FGFR therapies. FGFR2 and other FGFR kinase family gene alterations have been found in both lung squamous cell carcinoma and lung adenocarcinoma, although mouse models of FGFR-driven lung cancers have not been reported. Here, we generated a genetically engineered mouse model (GEMM) of NSCLC driven by a kinase domain mutation in FGFR2. Combined with p53 ablation, primary grade 3/4 adenocarcinoma was induced in the lung epithelial compartment exhibiting locally invasive and pleiotropic tendencies largely made up of multinucleated cells. Tumors were acutely sensitive to pan-FGFR inhibition. This is the first FGFR2-driven lung cancer GEMM, which can be applied across different cancer indications in a preclinical setting.

  11. Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology

    Institute of Scientific and Technical Information of China (English)

    BU Li-na; LIN Xiu-li; LIU Yan-feng; LIN Yu-rong; RONG Biao-xue; YANG Shuan-ying; LI Feng-tao; SHANG Wen-li; ZHANG Wei; HUO Shu-fen; NAN Yan-dong; TIAN Ying-xuan; DU Jie

    2010-01-01

    Background In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA.Methods We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal calls from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm.Results About 2.895x106 and 1.584x106 cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z)between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%.Conclusions Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a

  12. Selective gene therapy for human lung adenocarcinoma by tumor-specific expression of herpes simplex virus thymidine kinase gene

    Institute of Scientific and Technical Information of China (English)

    高振强; 高志萍; 张涛; 刘喜富

    1997-01-01

    According to the fact that CEA gene expressed only in lung adenocarcinoma but not in normal lung cells, a retroviral expression vector (pCEATK) of the herpes simplex virus thymidine kinase (HSV-TK) gene regulated by CEA promoter was constructed and introduced into CEA-producing human lung adenocarcinoma cells GL and non-CEA-producing HeLa cells. The expression of pCEATK and Ganciclovir (GCV) sensitivity of the transfected cells were tested in vitro and in vivo . pCEATK expressed only in CEA-producing GL cells but not in non-CEA-producing HeLa cells. The sensitivity to GCV of pCEATK-transfected GL was 992 times higher compared with that of the parental cell line and there was obvious "bystander effect" in vitro. HeLa cells transfected wtih pCEATK were still resistant to GCV. Injection of GCV resulted in significant regression of pCEATK-transfected GL tumors in nude mice. In addition, all mice with any fraction of GL cells expressing HSV-TK exhibited a significant reduction in tumor growth, including mice

  13. Usefulness of CDK5RAP3, CCNB2, and RAGE genes for the diagnosis of lung adenocarcinoma.

    Science.gov (United States)

    Stav, D; Bar, I; Sandbank, J

    2007-01-01

    We used oligonucleotide microarrays with probe sets to 22,283 genes to analyze the gene expression profile of lung adenocarcinoma. Cancerous and noncancerous tissue samples were obtained from 23 patients with stage I or II lung cancer; 18 tissue pairs and 5 cancerous tissues. A list of 2065 genes that differentiate between cancerous and noncancerous tissues was generated using Winsorized paired t-tests. We analyzed CDK5RAP3 and CCNB2, which are involved in cell cycle progression, and RAGE. The first 2 of these 3 genes proved to be overexpressed in tumor tissue, whereas the RAGE gene was suppressed in tumor tissue. When CDK5RAP3 and CCNB2 were examined in individual patients we found that in cases where one of these genes was only slightly overexpressed the other was highly overexpressed. The combined expression of the 2 cell cycle genes was found to be statistically significant for differentiating between cancerous and noncancerous tissues. Inclusion of the data for the RAGE gene made the differentiation more powerful. The gene expression ratio gave a clear result: when CDK5RAP3 was expressed more than RAGE, the tissue was carcinomatous, and vice versa. We therefore conclude that these 3 genes may be used as a very reliable biomarker of lung adenocarcinoma.

  14. Lung adenocarcinoma of never smokers and smokers harbor differential regions of genetic alteration and exhibit different levels of genomic instability.

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    Kelsie L Thu

    Full Text Available Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS. High resolution whole genome DNA copy number profiling of 69 lung adenocarcinomas from smokers (n = 39 and NS (n = 30 revealed both global and regional disparities in the tumor genomes of these two groups. We found that NS lung tumors had a greater proportion of their genomes altered than those of smokers. Moreover, copy number gains on chromosomes 5q, 7p, and 16p occurred more frequently in NS. We validated our findings in two independently generated public datasets. Our findings provide a novel line of evidence distinguishing genetic differences between smoker and NS lung tumors, namely, that the extent of segmental genomic alterations is greater in NS tumors. Collectively, our findings provide evidence that these lung tumors are globally and genetically different, which implies they are likely driven by distinct molecular mechanisms.

  15. Antitumor activity and systemic effects of PVM/MA-shelled selol nanocapsules in lung adenocarcinoma-bearing mice

    Science.gov (United States)

    de Souza, Ludmilla Regina; Alexandre Muehlmann, Luis; Carneiro Matos, Lívia; Simón-Vázquez, Rosana; Guerreiro Marques Lacava, Zulmira; Maurício Batista De-Paula, Alfredo; Mosiniewicz-Szablewska, Ewa; Suchocki, Piotr; César Morais, Paulo; González-Fernández, África; Nair Báo, Sônia; Bentes Azevedo, Ricardo

    2015-12-01

    Selol is a semi-synthetic compound containing selenite that is effective against cancerous cells and safer for clinical applications in comparison with other inorganic forms of selenite. Recently, we have developed a formulation of poly(methyl vinyl ether-co-maleic anhydride)-shelled selol nanocapsules (SPN), which reduced the proliferative activity of lung adenocarcinoma cells and presented little deleterious effects on normal cells in in vitro studies. In this study, we report on the antitumor activity and systemic effects induced by this formulation in chemically induced lung adenocarcinoma-bearing mice. The in vivo antitumor activity of the SPN was verified by macroscopic quantification, immunohistochemistry and morphological analyses. Toxicity analyses were performed by evaluations of the kidney, liver, and spleen; analyses of hemogram and plasma levels of alanine aminotransferase, aspartate transaminase, urea, and creatinine; and DNA fragmentation and cell cycle activity of the bone marrow cells. Furthermore, we investigated the potential of the SPN formulation to cause hemolysis, activate the complement system, provoke an inflammatory response and change the conformation of the plasma proteins. Our results showed that the SPN reduced the area of the surface tumor nodules but not the total number of tumor nodules. The biochemical and hematological findings were suggestive of the low systemic toxicity of the SPN formulation. The surface properties of the selol nanocapsules point to characteristics that are consistent with the treatment of the tumors in vivo: low hemolytic activity, weak inflammatory reaction with no activation of the complement system, and mild or absent conformational changes of the plasma proteins. In conclusion, this report suggests that the SPN formulation investigated herein exhibits anti-tumoral effects against lung adenocarcinoma in vivo and is associated with low systemic toxicity and high biocompatibility.

  16. Deoxyribonucleic acid (DNA) methyltransferase contributes to p16 promoter CpG island methylation in lung adenocarcinoma with smoking.

    Science.gov (United States)

    Sun, Rongju; Liu, Jiahong; Wang, Bo; Ma, Lingyun; Quan, Xiaojiao; Chu, Zhixiang; Li, Tanshi

    2015-01-01

    In this study, the relationship between CpG island methylation and smoking and DNA methyltransferase in the occurrence and development of lung adenocarcinoma was explored by detecting p16 promoter methylation status. Protein and mRNA levels of p16 were detected by immunohistochemistry and in situ hybridization assays. p16 gene promoter and exon 1 CpG island locus Hap II sites methylation status was analyzed with the methylation-specific PCR. Only 4 of 40 p16-positive cases were detected to methylate on CpG islands with 10% methylating rate whereas 18 of p16-negative cases were methylated up to 36.73% of methylating rate. The methylating rates of both p16-positive and p16-negative groups were significantly different. 17 of 50 cases with smoking from total 89 lung adenocarcinoma cases were detected to methylate on CpG islands while only 5 of the remaining 39 non-smokers to methylate. The difference of the methylating rates in both smokers and non-smokers was significant to suggest the closely association of CpG island methylation of p16 with smoking. Furthermore, p16 promoter CpG islands were detected to methylate in 15 of 35 cases with higher DNA methyltransferase activity whereas only 7 detected to methylate in the remaining 54 cases with lower DNA methyltransferase activity. p16 promoter CpG island methylation likely made p16 expressing silence thus contributed to the tumorigenesis of lung adenocarcinoma. Smoking is likely to promote p16 CpG island methylation or by its effect of the activity and metabolism of DNA methyltransferase 1 (DNMT) on CpG island methylation status.

  17. Evaluation of two preoparative chemotherapy regimens for complete operability of advanced gastric adenocarcinoma: a clinical trial

    Directory of Open Access Journals (Sweden)

    S. Sedighi

    2006-08-01

    Full Text Available Background: This prospective phase III study was designed to compare the activity of two combinations chemotherapy drugs in advanced gastric adenocarcinoma Methods: In a double blinded clinical trial, From Jan. 2002 to Jan. 2005, ninety patients with advanced gastric adenocarcinoma were randomly assigned to 1 Cisplatin and continuous infusion of 5FU and Epirubicin (ECF, and 2 Cisplatin and continuous infusion of 5FU with Docetaxel (TCF. Reduction in tumor mass, overall survival (OS, time to progression (TTP, and safety were measured outcome. Results: About 90% of patients had stage III or IV disease and the most common sites of tumor spread were peritoneal surfaces, liver and Paraaortic lymph nodes in either group. The objective clinical response rate (more than 50% decreases in tumor mass was 38% and 43% in ECF and TCF group respectively. Global quality of life increased (p=0 002 and symptoms of pain and insomnia decreased after chemotherapy. Patients in TCF had more grade one or two skin reactions, neuropathy and diarrhea. Fourteen patients underwent surgery. Complete microscopic (R0 resection had done in two of ECF and six of TCF tumors (p=0.015. Two cases in TCF group showed complete pathologic response. Median TTP was nine months and 10 months in ECF and TCF group respectively. Median OS was 12 months in both groups. Conclusion: Although there wasn’t statistically significant difference regarded to clinical response or survival between two groups, TCF showed more complete pathologic response.

  18. Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion.

    Science.gov (United States)

    Saintigny, Pierre; Peng, Shaohua; Zhang, Li; Sen, Banibrata; Wistuba, Ignacio I; Lippman, Scott M; Girard, Luc; Minna, John D; Heymach, John V; Johnson, Faye M

    2012-09-01

    The Eph family of receptors is the largest family of receptor tyrosine kinases, but it remains poorly studied in lung cancer. We aimed to systematically explore the human Eph receptors and their ligands, the ephrins, in lung adenocarcinoma. The prognostic impact of Eph receptor and ephrin gene expression was analyzed using 2 independent cohorts of lung adenocarcinoma. Gene expression profiles in lung adenocarcinoma compared with normal adjacent lung were studied in 3 independent cohorts and in cell lines. Gene expression profiles were validated with quantitative polymerase chain reaction (qPCR) and Western blotting in cell lines. Functional studies to assess the role of Eph receptor A4 (EphA4) were carried out in vitro. The biological effects of EphA4 in lung cancer cell lines were assayed following overexpression and knockdown. Of the 11 Eph receptors and 8 ephrins analyzed, only EphA4 and ephrin A1 gene expression were consistently associated with an improved outcome in patients with lung adenocarcinoma. Expression levels of EphA4 by microarray correlated well with expression levels measured by qPCR and Western blotting. EphA4 overexpression reduced cell migration and invasion but did not affect cell cycle, apoptosis, or drug sensitivity. Surprisingly, EphA4 was expressed at higher levels in cancer compared with non-cancer tissues and cell lines. EphA4 gene expression is associated with an improved outcome in patients with resected lung adenocarcinoma, possibly by affecting cancer cell migration and invasion.

  19. Advances in Lung Stem Cells and Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Huijing YIN

    2015-10-01

    Full Text Available Cancer stem cells (CSCs are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs, including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH and ATP-binding cassette sub-family G member 2 (ABCG2. Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR, signal transducer and activator of transcription 3 (STAT3 and phosphatidylinositol 3 kinase (PI3K pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  20. [Advances in Lung Stem Cells and Lung Cancer Stem Cells].

    Science.gov (United States)

    Yin, Huijing; Deng, Jiong

    2015-10-20

    Cancer stem cells (CSCs) are emerging as a hot topic for cancer research. Lung CSCs share many characteristics with normal lung stem cells (SCs), including self-renewal and multi-potency for differentiation. Many molecular markers expressed in various types of CSCs were also found in lung CSCs, such as CD133, CD44, aldehyde dehydrogenase (ALDH) and ATP-binding cassette sub-family G member 2 (ABCG2). Similarly, proliferation and expansion of lung CSCs are regulated not only by signal transduction pathways functioning in normal lung SCs, such as Notch, Hedgehog and Wnt pathways, but also by those acting in tumor cells, such as epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K) pathways. As CSC plays an critical role in tumor recurrence, metastasis and drug-resistance, understanding the difference between lung CSCs and normal lung SCs, identifying and targeting CSC markers or related signaling pathways may increase the efficacy of therapy on lung cancer and improved survival of lung cancer patients.

  1. CT Features and Pathology of Adenocarcinoma of Lung in Young Patients%青年肺腺癌患者CT影像特点及病理

    Institute of Scientific and Technical Information of China (English)

    景瑞; 赵绍宏; 蔡祖龙; 金鑫; 吴芳; 吴坚; 吴重重

    2014-01-01

    and 20 with low differentiation. Most of the cases were advanced stage when diagnosed, 44 presented with metastasis, 38 patients with chest metastasis, pleural effusion occurred in 14 patients. Conclusion Peripheral mass and nodule are the predominant CT features of lung adenocarcinoma in young patients. Poor-differentiated tumor with metastasis is common when diagnosed.

  2. Screening of the different TNM stage-associated genes in lung adenocarcinoma by genomewide gene expression profile analysis in the Chinese population

    Institute of Scientific and Technical Information of China (English)

    张晓莉

    2014-01-01

    Objective To screen for the differentially expressed genes associated with various TNM stages in lung adenocarcinoma of Chinese by comparing the expression profiles in tumor samples of different TNM stages.Methods This study was a case-case study.Lung adenocarcinoma specimens were collected from total of 240 patients receiving thoracic surgery in our hospital from May of 2008to October of 2011.There were 90 samples(30 each for stageⅠ,ⅡandⅢA)for the gene array,and 150 samples(50 and may

  3. The Inhibitory Effects of Rh-endostatin(YH-16) in Combination with Radiotherapy on Lung Adenocarcinoma A549 in Mice and the Underlying Mechanisms

    Institute of Scientific and Technical Information of China (English)

    吴辉塔; 邓洁; 于世英; 王馨; 陈元

    2010-01-01

    In order to investigate the inhibitory effects of Endostar(rh-endostatin,YH-16)in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy,the transplantation tumor models of A549 lung adenocarcinoma were established.When the largest diameter of tumor reached 1.0cm,all nude mice were randomly divided into 4 groups:Endostar group,radiotherapy group,radiotherapy plus Endostar(combined treatment)group,and control group(n=6 in each group).The largest d...

  4. Characterization of the cell of origin and propagation potential of the fibroblast growth factor 9-induced mouse model of lung adenocarcinoma.

    Science.gov (United States)

    Arai, Daisuke; Hegab, Ahmed E; Soejima, Kenzo; Kuroda, Aoi; Ishioka, Kota; Yasuda, Hiroyuki; Naoki, Katsuhiko; Kagawa, Shizuko; Hamamoto, Junko; Yin, Yongjun; Ornitz, David M; Betsuyaku, Tomoko

    2015-03-01

    Fibroblast growth factor 9 (FGF9) is essential for lung development and is highly expressed in a subset of human lung adenocarcinomas. We recently described a mouse model in which FGF9 expression in the lung epithelium caused proliferation of the airway epithelium at the terminal bronchioles and led to rapid development of adenocarcinoma. Here, we used this model to characterize the effects of prolonged FGF9 induction on the proximal and distal lung epithelia, and examined the propagation potential of FGF9-induced lung tumours. We showed that prolonged FGF9 over-expression in the lung resulted in the development of adenocarcinomas arising from both alveolar type II and airway secretory cells in the lung parenchyma and airways, respectively. We found that tumour cells harboured tumour-propagating cells that were able to form secondary tumours in recipient mice, regardless of FGF9 expression. However, the highest degree of tumour propagation was observed when unfractionated tumour cells were co-administered with autologous, tumour-associated mesenchymal cells. Although the initiation of lung adenocarcinomas was dependent on activation of the FGF9-FGF receptor 3 (FGFR3) signalling axis, maintenance and propagation of the tumour was independent of this signalling. Activation of an alternative FGF-FGFR axis and the interaction with tumour stromal cells is likely to be responsible for the development of this independence. This study demonstrates the complex role of FGF-FGFR signalling in the initiation, growth and propagation of lung cancer. Our findings suggest that analysing the expressions of FGF-FGFRs in human lung cancer will be a useful tool for guiding customized therapy.

  5. 4-cholesten-3-one suppresses lung adenocarcinoma metastasis by regulating translocation of HMGB1, HIF1α and Caveolin-1

    Science.gov (United States)

    Ma, Jinben; Fu, Guobin; Wu, Jing; Han, Shaoxian; Zhang, Lishan; Yang, Ming; Yu, Yong; Zhang, Mengyuan; Lin, Yanliang; Wang, Yibing

    2016-01-01

    Metastasis is a great challenge in lung adenocarcinoma (ADC) therapy. Cholesterol has been implicated in ADC metastasis. 4-cholesten-3-one, as cholesterol metabolite and analog, can substitute membrane cholesterol and increase membrane fluidity. In this study, we explored the possibility that 4-cholesten-3-one inhibited ADC metastasis. Low-dose 4-cholesten-3-one significantly restrained ADC cells migration and invasion with little effects on cells viabilities. Further investigation showed that 4-cholesten-3-one promoted ROS generation, which transiently activated AMPKα1, increased HIF1α expression, reduced Bcl-2 expression and caused autophagy. AMPKα1 knockdown partly suppressed 4-cholesten-3-one-induced autophagy but, neither prevented 4-cholesten-3-one-induced upregulation of HIF1α or downregulation of Bcl-2. 4-cholesten-3-one-induced autophagy facilitated the release of HMGB1 from nuclei to cytoplasm, blocking nuclear translocation of HIF1α and activation of MMP2 and MMP9. Also, 4-cholesten-3-one induced time-dependent phosphorylation of caveolin-1, Akt and NF-κB. With increasing treatment time, 4-cholesten-3-one accelerated caveolin-1 internalization, but reduced the phosphorylation of Akt and NF-κB, and inhibited the expression of snail and twist. These data suggested that 4-cholesten-3-one could be a potential candidate for anti-metastasis of lung adenocarcinoma. PMID:27899819

  6. A combination of preoperative CT findings and postoperative serum CEA levels improves recurrence prediction for stage I lung adenocarcinoma

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    Yamazaki, Motohiko, E-mail: xackey2001@gmail.com [Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences (Japan); Ishikawa, Hiroyuki [Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences (Japan); Kunii, Ryosuke [Division of Cellular and Molecular Pathology, Niigata University Graduate School of Medical and Dental Sciences (Japan); Tasaki, Akiko; Sato, Suguru; Ikeda, Yohei; Yoshimura, Norihiko [Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences (Japan); Hashimoto, Takehisa; Tsuchida, Masanori [Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences (Japan); Aoyama, Hidefumi [Department of Radiology, Niigata University Graduate School of Medical and Dental Sciences (Japan)

    2015-01-15

    Objectives: To assess the prognostic value of combined evaluation of preoperative CT findings and pre/postoperative serum carcinoembryonic antigen (CEA) levels for pathological stage I lung adenocarcinoma. Methods: This retrospective study included 250 consecutive patients who underwent complete resection for ≤3-cm pathological stage I (T1–2aN0M0) adenocarcinomas (132 men, 118 women; mean age, 67.8 years). Radiologists evaluated following CT findings: maximum tumor diameter, percentage of solid component (%solid), air bronchogram, spiculation, adjacency of bullae or interstitial pneumonia (IP) around the tumor, notch, and pleural indent. These CT findings, pre/postoperative CEA levels, age, gender, and Brinkman index were assessed by Cox proportional hazards model to determine the best prognostic model. Prognostic accuracy was examined using the area under the receiver operating characteristic curve (AUC). Results: Median follow-up period was 73.2 months. In multivariate analysis, high %solid, adjacency of bullae or IP around the tumor, and high postoperative CEA levels comprised the best combination for predicting recurrence (P < 0.05). A combination of these three findings had a greater accuracy in predicting 5-year disease-free survival than did %solid alone (AUC = 0.853 versus 0.792; P = 0.023), with a sensitivity of 85.7% and a specificity of 74.3% at the optimal threshold. The best cut-off values of %solid and postoperative CEA levels for predicting high-risk patients were ≥48% and ≥3.7 ng/mL, respectively. Conclusion: Compared to %solid alone, combined evaluation of %solid, adjacency of bullae or IP change around the tumor, and postoperative CEA levels improves recurrence prediction for stage I lung adenocarcinoma.

  7. Preoperative docetaxel/cisplatin/5-fluorouracil chemotherapy in patients with locally advanced gastro-esophageal adenocarcinoma.

    Science.gov (United States)

    Bayraktar, Ulas Darda; Bayraktar, Soley; Hosein, Peter; Chen, Emerson; Koniaris, Leonidas G; Rocha-Lima, Caio Max S; Montero, Alberto J

    2012-09-01

    Perioperative chemotherapy plus surgery improves survival compared to surgery alone in GE junctional (GEJ) and gastric adenocarcinomas. The docetaxel/cisplatin/5-fluorouracil (DCF) combination is superior to CF in patients with metastatic gastric cancer. We retrospectively evaluated the safety and efficacy of preoperative DCF chemotherapy in patients with locally advanced gastric and GEJ cancer. Twenty-one gastric and 10 gastroesophageal junctional (GEJ) cancer patients received 2-3 cycles of preoperative docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) on day 1, 5-FU 750 mg/m(2) (continuous infusion) on days 1-5 every 3 weeks. Clinical response was evaluated by comparing pre- and postchemotherapy CT scans. Overall survival (OS) and progression-free survival (PFS) were calculated from the initiation of chemotherapy. None of the patients achieved complete clinical remission while 11 (35%) patients achieved partial clinical remission. Ten patients with GEJ cancer (100%) and 13 with gastric cancer (62%) underwent curative surgery (P = 0.023). Seventeen (55%) patients experienced grade 3-4 chemotherapy-related adverse events. The most common adverse events were anemia, nausea/vomiting, diarrhea, and febrile neutropenia. At a median follow-up of 17.0 months, median OS and PFS were 26.1 months (95% CI: 22.7-29.5) and 18.8 months (95% CI: 9.9-27.7), respectively. The DCF regimen is active in patients with gastric and GEJ adenocarcinoma in the preoperative setting.

  8. Detection of soluble tumor-associated antigens in sera and effusions using novel monoclonal antibodies, KL-3 and KL-6, against lung adenocarcinoma.

    Science.gov (United States)

    Kohno, N; Akiyama, M; Kyoizumi, S; Hakoda, M; Kobuke, K; Yamakido, M

    1988-09-01

    Two novel monoclonal antibodies, KL-3 (IgM) and KL-6 (IgG1), which can detect soluble antigens in sera and effusions (molecular weights greater than 1,000 K) were produced against human pulmonary adenocarcinoma VMRC-LCR cells. KL-3 and KL-6 antibodies reacted with asialo- and sialo-carbohydrate antigenic determinants, respectively. Both carbohydrate epitopes appear, from competitive inhibition studies, to be different from Lex, Ley, sialyl Lea and sialyl Lexi which were recognized with FH2, AH6, NS19-9 and FH6 antibodies, respectively. Using an enzyme linked immunosorbent assay, elevated KL-6 antigen levels were frequently observed in the sera of patients with lung adenocarcinoma [52% (17/33)], pancreatic cancer [44% (4/9)] and breast cancer [40% (8/20)], but infrequently in the sera of patients with lung squamous cell carcinoma [18% (4/22)], lung small cell carcinoma [8% (1/13)], gastric cancer [0% (0/19)], colorectal cancer [0% (0/8)] and hepatocellular cancer [13% (1/8)]. The levels and positive rates of serum KL-6 antigen increased with the progression of clinical stage of lung adenocarcinoma. In pleural effusions, the prevalences of lung adenocarcinoma cases with elevated levels of KL-3 and KL-6 antigens were 76% (13/17) and 82% (14/17), respectively. These monoclonal antibodies can define novel soluble antigens in sera and effusions which could be useful in tumor diagnoses and for monitoring tumor progression.

  9. Anticancer function of α-solanine in lung adenocarcinoma cells by inducing microRNA-138 expression.

    Science.gov (United States)

    Zhang, Furui; Yang, Rui; Zhang, Guojun; Cheng, Ruirui; Bai, Yong; Zhao, Huasi; Lu, Xinhua; Li, Hui; Chen, Shanshan; Li, Juan; Wu, Shujun; Li, Ping; Chen, Xiaonan; Sun, Qianqian; Zhao, Guoqiang

    2016-05-01

    Currently, lung cancer is still a main cause of malignancy-associated death worldwide. Even though various methods for prevention and treatment of lung cancer have been improved in recent decades, the 5-year survival rate has remained very low. Insights into the anticancer function of small-molecule anticancer compounds have opened our visual field about cancer therapy. α-Solanine has been well studied for its antitumor properties, but its effect in lung cancer and associated molecular mechanisms have not yet been evaluated. To explore the anticancer function of α-solanine, we performed an MTT assay, Transwell arrays, colony-forming survival assay, quantitative reverse transcription PCR (qRT-PCR), Western blotting, and dual luciferase reporter assays in A549 and H1299 cells. We found that α-solanine not only inhibited cell migration and invasion ability but also enhanced the chemosensitivity and radiosensitivity of A549 and H1299 cells. Moreover, we discovered that α-solanine could affect the expression of miR-138 and focal adhesion kinase (FAK), both of which were also found to affect the chemosensitivity and radiosensitivity of A549 and H1299 cells. In conclusion, α-solanine could affect miR-138 and FAK expression to restrict cell migration and invasion and enhance the chemosensitivity and radiosensitivity of A549 and H1299 cells. The α-solanine/miR-138/FAK cascade can probably be a potential therapy target against lung adenocarcinoma.

  10. Construction and expression of recombinant prokaryotic vector PGEX-4T-1-BC006151 correlated with multidrug resistant of lung adenocarcinoma

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    Xuejun LI

    2008-06-01

    Full Text Available Background and objective The drug resistance to chemotherapeutics is one of the important causes of low survival rate of lung cancer patients. Our previous study has demonstrated that BC006151 is a gene correlated with multidrug resistance of adenocarcinoma of lung. The aim of this study is to clone the BC006151 gene, and to construct recombinant prokaryotic vector PGEX-4T-1-BC006151, and to express it in E. coli BL21. Methods The primer was designed with restriction endonuclease position, then amplified BC006151 by RT-PCR, cleaved BC006151 cDNA and PGEX-4T-1 by BamH and EcoR I. linked it with PGEX-4T-1. Then the two fragments were linked by T4DNA. The post-linked vector was transformed into E. coli. DH5 and then expressed. Transformed the recombinant plasmids containing the correct clone into E. coli BL21 and protein was highly effective expressed. The production of GST fusion protein was identifisd by SDS-PAGE and Western-Blotting. Results The sequence of BC006151 was amplified and identified with that published in GenBank. The prokaryotic expression plasmid PGEX-4T-1-BC006151 was constructed successfully. And a new fusion protein with relative molecular mass of 13 KD was highly effectively expressed in E. coli. Conclusion The BC006151 gene correlated with multidrug resistance of lung adenocarcinoma is successfully cloned and expressed, which is helpful for the preparation of monoclonal and polyclonal antibodies.

  11. Ly6/uPAR-related protein C4.4A as a marker of solid growth pattern and poor prognosis in lung adenocarcinoma

    DEFF Research Database (Denmark)

    Jacobsen, Benedikte; Muley, Thomas; Meister, Michael;

    2013-01-01

    We have recently shown that the protein C4.4A is induced in early precursor lesions of pulmonary adenocarcinomas and squamous cell carcinomas. In the present study, we aimed at analyzing the impact of C4.4A on the survival of non-small cell lung cancer patients and determining whether its unexpec...

  12. Crizotinib for Advanced Non-Small Cell Lung Cancer

    Science.gov (United States)

    A summary of results from an international phase III clinical trial that compared crizotinib versus chemotherapy in previously treated patients with advanced lung cancer whose tumors have an EML4-ALK fusion gene.

  13. CT characteristics and pathological implications of early stage (T1N0M0) lung adenocarcinoma with pure ground-glass opacity

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    Jin, Xin; Zhao, Shao-hong; Wu, Jian; Wu, Chong-chong; Chang, Rui-ping; Ju, Hai-yue [Chinese PLA General Hospital, Department of Radiology, Beijing (China); Gao, Jie; Wang, Dian-jun [Chinese PLA General Hospital, Department of Pathology, Beijing (China)

    2015-09-15

    To analyze the CT characteristics and pathological classification of early lung adenocarcinoma (T1N0M0) with pure ground-glass opacity (pGGO). Ninety-four lesions with pGGO on CT in 88 patients with T1N0M0 lung adenocarcinoma were selected from January 2010 to December 2012. All lesions were confirmed by pathology. CT appearances were analyzed including lesion location, size, density, uniformity, shape, margin, tumour-lung interface, internal and surrounding malignant signs. Lesion size and density were compared using analysis of variance, lesion size also assessed using ROC curves. Gender of patients, lesion location and CT appearances were compared using χ2-test. There were no significant differences in gender, lesion location and density with histological invasiveness (P > 0.05). The ROC curve showed that the possibility of invasive lesion was 88.73 % when diameter of lesion was more than 10.5 mm. There was a significant difference between lesion uniformity and histological invasiveness (P = 0.01). There were significant differences in margin, tumour-lung interface, air bronchogram with histological invasiveness (P = 0.02,P = 0.00,P = 0.048). The correlation index of lesion size and uniformity was r = 0.45 (P = 0.00). The lesion size and uniformity, tumour-lung interface and the air bronchogram can help predict invasive extent of early stage lung adenocarcinoma with pGGO. (orig.)

  14. Enhanced chemosensitivity of p73α gene transferred into H1299 cell line of human lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    HE Yong; FAN Shi-zhi; Kalkunte S Srivenugopal; JIANG Yao-guang; QIN Chuan

    2004-01-01

    Objective: To study the effects of transferred wild type p73α gene on the sensitivity to the chemotherapeutic agents and the growth of p53-null H1299 cells of human lung adenocarcinoma. Methods: The pcDNA3-HA-p73α plasmid was transferred into the cultured p53-null H1299 cells of human lung adenocarcinoma with the mediation of Dosper liposome;The cells resistant to G418 were selected. The expression of p73α gene in the cells was examined with Western blot. MTT assay was used to analyze the response of the transfected cells to cis-dichlorodiamine platinum (cDDP) and adriamycin (ADM). The rate of drug-induced apoptosis of the transfected cells was determined with flow cytometry and DNA fragmentation assay. The changes of the biological behaviors were observed with colony formation assay. Results: The transfected H1299 cells of human lung adenocarcinoma over-expressed p73α protein stably. MTT assay showed that the IC50 values of cDDP and ADM were reduced by approximately 7 fold and 130 fold respectively in the transfected cells as compared with the untransfected ones. Lower concentration of the chemotherapeutic agents ( 1.25 μmol/L of cDDP and 0.05 μmol/L of ADM)could be employed to suppress markedly the growth of the transfected H1299 cells. The apoptotic rate induced by cDDP was increased from 10.1% to 38.4% ( P < 0.01 ) and that of ADM from 12.1% to 49.3 % ( P < 0.01 ). The clonogenecity after the administration of chemotherapeutic agents was significantly lower in the transfected H1299 cells than in the parental cells (P < 0.01). The sensitive enhancement ratios were 1.8 and 2.6 for cDDP and ADM respectively. Conclusion: The transfection of H1299 cells with wild type p73α gene results in an increase of the sensitivity of the cells to chemotherapeutic agents.

  15. Chronic myelomonocytic leukemia blast crisis in a patient with advanced non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors.

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    Ogata, Hiroaki; Okamoto, Isamu; Yoshimoto, Goichi; Obara, Teppei; Ijichi, Kayo; Iwama, Eiji; Harada, Taishi; Akashi, Koichi; Nakanishi, Yoichi

    2017-03-01

    A 59-year-old woman with epidermal growth factor receptor gene (EGFR) mutation-positive advanced lung adenocarcinoma was treated with afatinib after a diagnosis of chronic myelomonocytic leukemia (CMML). Twenty-one weeks later, she developed agranulocytosis, and CMML subsequently progressed to blast crisis. After complete remission of CMML, gefitinib was initiated; however, agranulocytosis recurred. This is the first reported case of both EGFR mutation-positive advanced non-small cell lung cancer with CMML, and of CMML blast crisis. Physicians should be aware of such risks and monitor EGFR-TKI-treated patients with myeloid neoplasms accordingly.

  16. Lung Cancer Clinical Trials: Advances in Immunotherapy

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    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  17. Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Aiqin Gu; Chunlei Shi; Liwen Xiong; Tianqing Chu; Jun Pei; Baohui Han

    2013-01-01

    To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC).Methods:A total of 89 patients with stage ⅢB or Ⅳ NSCLC received icotinib at a dose of 125 mg admimstered 3 times a day.Icotinib treatment was continued until disease progression or development of unacceptable toxicity.Results:A total of 89 patients were assessable.In patients treated with icotinib,the overall response rate (RR) was 36.0% (32/89),and the disease control rate (DCR) was 69.7% (62/89).RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05).The symptom improvement rate was 57.3% (51/89),and the main symptoms improved were cough,pain,chest distress,dyspnea,and Eastern Cooperative Oncology Group performance status.The main toxic effects were rash [30/89 (33.7 %)] and diarrhea [15/89 (16.9%)].The level of toxicity was typically low.Conclusions:The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe,and its toxic effects are tolerable.

  18. Analysis of Prognostic Factors in 541 Female Patients with Advanced Non-small Cell Lung Cancer

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    Meina WU

    2011-03-01

    Full Text Available Background and objective As there is a sharp increase in the incidence of lung cancer in women in recent years, it has brought broad concerns with its unique clinical and epidemiological characteristics and better prognosis. The aim of this study is to analyze the clinical data of women with advanced non-small cell lung cancer (NSCLC retrospectively to explore the prognostic factors. Methods Clinical data of 541 female patients with advanced NSCLC were collected and followed up till death. The primary endpoint is overall survival (OS. SPSS 11.0 statistical analysis software was used for univariate and multivariate analysis. Results The mean age is 59 years (20 years-86 years, adenocarcinoma account for 80.2% (434/541. The median OS was 15 months (95%CI: 13.87-16.13, and 1, 2, 5-year survival rates were 58.8%, 23.7% and 3.20% respectively. Univariate analysis showed that clinical stage, ECOG score, weight loss, clinical symptoms, liver/bone/brain metastasis and received more than one chemotherapy regimen, good response to the first-line chemotherapy, EGFR-TKI targeted therapy and radiotherapy treatment were significantly correlated with the OS and survival rate (P < 0.05. Combined with multivariate analysis, weight loss before treatment, ECOG score, received EGFR-TKI targeted therapy and response to first-line chemotherapy were independent prognostic factor for survival (P < 0.05. Conclusion There is a higher percentage of adenocarcinoma in female NSCLC. Weight loss before treatment, ECOG score, EGFR-TKI targeted therapy and response to first-line chemotherapy may become independent prognostic factors for survival of female patients with advanced NSCLC.

  19. Soluble Human Epidermal Growth Factor Receptor 2 (sHER2 as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

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    Andre T. Baron

    2013-01-01

    Full Text Available Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2 for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81 and 7.93 (95% CI: 2.26, 27.82 greater for women and men with high sHER2 concentrations (≥6.60 ng/mL vs. low sHER2 concentrations (≤1.85 ng/mL, respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer.

  20. Production and radioimmunoimaging of novel fully human phage display recombinant antibodies and growth inhibition of lung adenocarcinoma cell line overexpressing Prx I.

    Science.gov (United States)

    Luo, Yi; Pang, Hua; Li, Shujie; Cao, Hui; Peng, Zhiping; Fan, Chunbo; Li, Shaolin

    2009-07-01

    The Peroxiredoxin I (Prx I) is a member of the Peroxiredoxin family, which is overexpressed in many diverse tumor types and is an anti-apoptosis protein for tumor cell proliferation and survival. Therapeutic strategies targeting the Prx I may therefore be effective broad-spectrum anticancer agents. We constructed a phage display single-chain variable fragment (scFv) antibody library and sieve out the fully human, lung adenocarcinoma-sepcific monoclonal antibodies. The selection on Prx I was performed using above-mentioned lung adenocarcinoma-sepcific monoclonal antibodies with high affinity to Prx I overexpressing lung adenocarcinoma cells. The candidate scFv sequences, based on enzyme-linked immunosorbent assay (ELISA) screening data, were chosen for soluble expression, and a 30 kDa band was observed on polyacrylamide gel electrophoresis as predicted. The purified antibodies were characterized by immunoblotting and showed high specificity to Prx I-overexpressing lung adenocarcinoma cells A549. Radioimmunoimaging was taken to evaluate specificity and distribution of antibodies in vivo. The radiolocalization index (RI) of tumor/serum and tumor/muscle gradually increased, reaching its peak (4.06 +/- 0.13 and 5.17 +/- 0.97, respectively) at 48 h postadministration. Single photon emission computed tomography (SPECT) imaging showed the radioactivity was aggregated in tumor locations and tumor imaging was clearly observed. The internalized scFv resulted in antibody-mediated cell apoptosis and downregulation of Prx I expression. These results demonstrate that the scFv possesses strong antitumor activity on lung adenocarcinoma and may therefore be an effective therapeutic candidate for the treatment of cancers that are dependent on Prx I for growth and survival.

  1. Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells by inducing cycle arrest and apoptosis.

    Science.gov (United States)

    Lv, Xue-Jiao; Zhao, Li-Jing; Hao, Yu-Qiu; Su, Zhen-Zhong; Li, Jun-Yao; Du, Yan-Wei; Zhang, Jie

    2015-01-01

    Lung cancer is the leading cause of cancer death in the world. Schizandrin B (Sch B) is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Sch B has multiple functions against cancer. The aim of this study was to determine the effect of Sch B on the proliferation, cell cycling, apoptosis and invasion of lung adenocarcinoma A549 cells by MTT, flow cytometry, wound healing and transwell invasion assays. Treatment with Sch B inhibited the proliferation of A549 cells in a dose-dependent manner. Sch B induced cell cycle arrest at G0/G1 phase by down-regulating the expression of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK6, but up-regulating p53 and p21 expression in A549 cells. Furthermore, Sch B triggered A549 cell apoptosis by increasing Bax, cleaved caspase-3, 9, Cyto C, but decreasing Bcl-2 and PCNA expression. In addition, Sch B inhibited the invasion and migration of A549 cells by down-regulating the expressions of HIF-1, VEGF, MMP-9 and MMP-2. Therefore, Sch B has potent anti-tumor activity and may be a promising traditional Chinese medicine for human lung carcinoma.

  2. Lineage analysis of early and advanced tubular adenocarcinomas of the stomach: continuous or discontinuous?

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    Mukaisho Ken-ichi

    2010-06-01

    Full Text Available Abstract Background Eradication of early gastric carcinoma (GC is thought to contribute to reduction in the mortality of GC, given that most of the early GCs progress to the advanced GCs. However, early GC is alternatively considered a dormant variant of GC, and it infrequently progresses to advanced GC. The aim of this study was to clarify the extent of overlap of genetic lineages between early and advanced tubular adenocarcinomas (TUBs of the stomach. Methods Immunohistochemical staining for p53 was performed using 28 surgically resected stomachs with 13 intramucosal and 15 invasive TUBs. By chromosome- and array-based comparative genomic hybridization (CGH, genomic copy number constitution was compared between the mucosal and invasive parts of the invasive TUBs and between the mucosal parts of the invasive and intramucosal TUBs, using 25 and 22 TUBs, respectively. TP53 mutation in exons 5-8 was examined in 20 TUBs. Results Chromosomal CGH revealed that 4q+ and 11q+ were more common in advanced and early TUBs, respectively, whereas copy number changes in 8q and 17p showed no significant differences between early and advanced TUBs. However, array CGH revealed that, of the 13 intramucosal TUBs examined, loss of MYC (MYC- and gain of TP53 (TP53+ was detected in 9 TUBs and MYC+ and/or TP53- was detected in 3 TUBs. Of the mucosal samples of 9 invasive TUBs, 7 showed MYC-/TP53+ and none showed MYC+ and/or TP53-. Of the 9 samples from the invasive parts, 1 (from submucosal cancers showed MYC-/TP53+ and 6 (1 from submucosal and 5 from advanced cancers showed MYC+ and/or TP53-. The latter 6 tumours commonly showed a mutant pattern (diffuse or null in p53 immunohistochemistry, and 4 of the 6 tumours assessable for TP53 sequence analysis revealed mutations. The overall array CGH pattern indicated that, between the mucosal and invasive parts, genetic lineage was found discontinuous in 5 advanced cancers and continuous in 3 submucosal cancers. Conclusions

  3. Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature

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    Demirci Ilhan

    2012-01-01

    Full Text Available Abstract Background Overdiagnosis of bronchopulmonary carcinoid tumors together with overtreatment can cause serious postoperative consequences for the patient. We report of a patient with a typical bronchopulmonary carcinoid tumor, which was initially misdiagnosed and treated as an adenocarcinoma of the lung. GnrH receptors and the associated Raf-1/MEK/ERK-1/2-pathway are potential targets for analogs in cancer treatment. We suspected a correlation between the lack of tumor growth, application of leuprolide and the Raf-1/MEK/ERK-1/2-pathway. Therefore, we examined GnrH receptor status in the examined specimen. Case presentation In 2010 a 77 year-old male patient was shown to have a tumor mass of about 1.7 cm diameter in the inferior lobe of the left lung. Since 2005, this tumor had hitherto been known and showed no progression in size. The patient suffered from prostate cancer 4 years ago and was treated with TUR-P, radiation therapy and the application of leuprolide. We conducted an explorative thoracotomy with atypical segment resection. The first histological diagnosis was a metastasis of prostate cancer with lymphangiosis carcinomatosa. After several immunohistochemical stainings, the diagnosis was changed to adenocarcinoma of the lung. We conducted a re-thoracotomy with lobectomy and systematic lymphadenectomy 12 days later. The tumor stage was pT1 N0 MX G2 L1 V0 R0. Further immunohistochemical studies were performed. We received the results 15 days after the last operation. The diagnosis was ultimately changed to typical carcinoid tumor without any signs of lymphatic vessel invasion. The patient recovered well from surgery, but still suffers from dyspnea and lack of physical performance. Lung function testing revealed no evidence of impairment. Conclusion The use of several immunohistochemical markers, careful evaluation of hematoxylin-eosin sections and the Ki-67 labelling index are important tools in discriminating between carcinoids

  4. Successful erlotinib rechallenge for leptomeningeal metastases of lung adenocarcinoma after erlotinib-induced interstitial lung disease: a case report and review of the literature.

    Science.gov (United States)

    Togashi, Yosuke; Masago, Katsuhiro; Hamatani, Yasuhiro; Sakamori, Yuichi; Nagai, Hiroki; Kim, Young Hak; Mishima, Michiaki

    2012-08-01

    The most serious adverse reaction associated with treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is drug-induced interstitial lung disease (ILD). Because EGFR-TKIs are key drugs for patients with non-small cell lung cancer who have somatic activating mutations of the epidermal growth factor receptor gene (EGFR mutations), several cases of retreatment with EGFR-TKIs after ILD induced by these drugs have been reported. Here, we present a 68-year-old man with lung adenocarcinoma and leptomeningeal metastases having an EGFR mutation who was retreated with erlotinib after erlotinib-induced ILD. He suffered no ILD recurrence and his leptomeningeal metastases dramatically improved. In addition to the present case, reports of nine patients who were retreated with EGFR-TKIs after ILD were found in the literature. Only one patient had recurrence of ILD (although seven were retreated at a reduced dose of EGFR-TKIs, including the patient with recurrence). In contrast, three patients had no recurrence of ILD even without dose-reduction. These reports suggest that dose-reduction plays a limited role in preventing recurrence. Many patients received corticosteroids during retreatment, but not the one with recurrence of ILD. This may suggest that corticosteroids can prevent recurrence due to their antiinflammatory properties.

  5. Subclavian thrombosis in a patient with advanced lung cancer: a case report

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    Mitrakas Alexandros

    2011-05-01

    Full Text Available Abstract Introduction Lung cancer is now considered the most common cause of death among cancer patients. Although target biological regimens have emerged in recent years for non-small cell lung carcinoma, the survival and quality of life of patients with this condition still remain low. The five-year survival rate for all stages of lung cancer is 17% or less. Case presentation We describe the case of a 53-year-old Caucasian woman who was diagnosed with advanced stage IIIa (T2aN2M0 non-small cell lung carcinoma (adenocarcinoma and underwent a complete left upper lobectomy three years ago. After two and a half years of follow-up, she suddenly presented with facial edema and venous distension and was immediately treated for superior vena cava syndrome. Because of a diagnostic check, a major clot was detected in the right subclavian vein. Our patient was informed about treatment options, and she was taken to the catheterization laboratory for percutaneous stenting of the superior vena cava to restore superior vena cava patency. Conclusion Lung cancer has a vast number of complications. Superior vena cava syndrome and thrombosis should be considered upon the presentation of a patient with obstructive symptoms. In this case report, even though we expected the clot to be on the side of the former lesion, it was present on the opposite side. Treatment should also start immediately in these patients with clinical suspicion of thrombosis to avoid further complications, even in cases with a differential diagnosis problem. Finally, although patients with non-small cell lung carcinoma have a high incidence of thromboembolic events, anticoagulant treatment is given only as maintenance therapy after a first event occurs.

  6. Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas

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    Jason M. Fritz

    2014-11-01

    Full Text Available Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2 had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression.

  7. The CD24/P-selectin binding pathway initiates lung arrest of human A125 adenocarcinoma cells.

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    Friederichs, J; Zeller, Y; Hafezi-Moghadam, A; Gröne, H J; Ley, K; Altevogt, P

    2000-12-01

    Carbohydrates on tumor cells have been shown to play an important role in tumor metastasis. We demonstrated before that CD24, a Mr 35,000-60,000 mucine-type glycosylphosphatidylinositol-linked cell surface molecule, can function as ligand for P-selectin and that the sialylLex carbohydrate is essential for CD24-mediated rolling of tumor cells on P-selectin. To investigate the role of both antigens more closely, we transfected human A125 adenocarcinoma cells with CD24 and/or fucosyltransferase VII (Fuc TVII) cDNAs. Stable transfectants expressed CD24 and/or sialylLex. Biochemical analysis confirmed that in A125-CD24/FucTVII double transfectants, CD24 was modified with sialylLex. Only double transfectants showed rolling on P-selectin in vivo. When injected into mice, double transfectants arrested in the lungs, and this step was P-selectin dependent because it was strongly enhanced in lipopolysaccharide (LPS) pretreated wild-type mice but not in P-selectin knockout mice. CD24 modified by sialylLex was required on the tumor cells because the LPS-induced lung arrest was abolished by removal of CD24 from the cell surface by phosphatidylinositol-specific phospholipase C. A125-FucTVII single transfectants expressing sialylLex but not CD24 did not show P-selectin-mediated lung arrest. The sialylLex epitope is abundantly expressed on human carcinomas, and significant correlations between sialylLex expression and clinical prognosis exist. Our data suggest an important role for sialylLex-modified CD24 in the lung colonization of human tumors.

  8. Poorer prognosis in Taiwanese female ever smokers with stage IV lung adenocarcinoma who were readministered a tyrosine kinase inhibitor

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    Yang CJ

    2016-03-01

    Full Text Available Chih-Jen Yang,1–4 Ming-Ju Tsai,2 Jen-Yu Hung,2,4 Ying-Ming Tsai,1–3 Jui-Ying Lee,5 Shah-Hwa Chou,5,6 Ta-Chih Liu,7,8 Mei-Chiou Shen,9 Ming-Shyan Huang,2,4,10 Inn-Wen Chong2,6 1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 3Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 4Department of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, 5Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 6Department of Respiratory Care, College of Medicine, Kaohsiung Medical University, 7Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 8Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, 9Department of Pharmacy, Kaohsiung Medical University Hospital, 10Division of Geriatric Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan Background: Readministering a second epidermal growth factor receptor (EGFR tyrosine kinase inhibitor (TKI in patients with lung adenocarcinoma with acquired resistance to an initial EGFR TKI is a common treatment strategy. However, the prognostic factors for the second EGFR TKI are still uncertain.  Patients and methods: In this retrospective study, we enrolled patients with stage IV lung adenocarcinoma diagnosed between June 2009 and October 2013 at two university-affiliated hospitals in Taiwan. Basic characteristics including age, sex, smoking status, performance status, EGFR mutation status, tumor response, and progression-free survival (PFS of the second

  9. Predicting adenocarcinoma recurrence using computational texture models of nodule components in lung CT

    Energy Technology Data Exchange (ETDEWEB)

    Depeursinge, Adrien, E-mail: adrien.depeursinge@hevs.ch [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Business Information Systems, University of Applied Sciences Western Switzerland (HES-SO), Sierre 3960 (Switzerland); Yanagawa, Masahiro [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 and Department of Radiology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871 (Japan); Leung, Ann N.; Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California 94305 (United States)

    2015-04-15

    Purpose: To investigate the importance of presurgical computed tomography (CT) intensity and texture information from ground-glass opacities (GGO) and solid nodule components for the prediction of adenocarcinoma recurrence. Methods: For this study, 101 patients with surgically resected stage I adenocarcinoma were selected. During the follow-up period, 17 patients had disease recurrence with six associated cancer-related deaths. GGO and solid tumor components were delineated on presurgical CT scans by a radiologist. Computational texture models of GGO and solid regions were built using linear combinations of steerable Riesz wavelets learned with linear support vector machines (SVMs). Unlike other traditional texture attributes, the proposed texture models are designed to encode local image scales and directions that are specific to GGO and solid tissue. The responses of the locally steered models were used as texture attributes and compared to the responses of unaligned Riesz wavelets. The texture attributes were combined with CT intensities to predict tumor recurrence and patient hazard according to disease-free survival (DFS) time. Two families of predictive models were compared: LASSO and SVMs, and their survival counterparts: Cox-LASSO and survival SVMs. Results: The best-performing predictive model of patient hazard was associated with a concordance index (C-index) of 0.81 ± 0.02 and was based on the combination of the steered models and CT intensities with survival SVMs. The same feature group and the LASSO model yielded the highest area under the receiver operating characteristic curve (AUC) of 0.8 ± 0.01 for predicting tumor recurrence, although no statistically significant difference was found when compared to using intensity features solely. For all models, the performance was found to be significantly higher when image attributes were based on the solid components solely versus using the entire tumors (p < 3.08 × 10{sup −5}). Conclusions: This study

  10. [Transcatheter Arterial Chemoembolization with Super absorbent Polymer Microspheres for a Large Lung Cystic Adenocarcinoma in the Left Pulmonary Cavity].

    Science.gov (United States)

    Kennoki, Norifumi; Hori, Shinichi; Yuki, Takeo; Sueyoshi, Satoshi; Hori, Atsushi

    2015-11-01

    A 57-year-old woman presented with lung adenocarcinoma and carcinomatous pleurisy in January 2013. The primary lesion had been treated with 60-Gy radiation therapy. She, however, showed a recurrence of the tumor in her pulmonary cavity. She received systemic chemotherapy for 1 year but did not show any improvement. She visited our clinic in March 2014. Her performance level was 3. Her hemoglobin level was 8.5 g/dL. The CT scan showed that the size of the cystic tumor was 200 × 144 × 143 mm. The tumor severely compressed her heart. We performed TACE using a spherical embolic agent. The microcatheter was guided through the left bronchial artery; left intercostal artery 9, 10, and 11; and the left inferior phrenic artery. The anticancer drugs selected were CDDP and 5-FU. The embolic material used was SAP-MS. After 3 therapy sessions, the CT scan showed shrinkage of the target lesion to 100 × 93 × 54 mm. Her hemoglobin level increased to 13.8 g/dL; furthermore, the severity of dyspnea decreased, and she showed a performance status of 0. TACE with SAP-MS was successfully performed for the large cystic tumor in the pulmonary cavity that metastasized from the lung cancer and was refractory to standard treatments. After the treatment, the tumor size decreased and the patient's symptoms alleviated.

  11. Visualization-aided classification ensembles discriminate lung adenocarcinoma and squamous cell carcinoma samples using their gene expression profiles.

    Directory of Open Access Journals (Sweden)

    Ao Zhang

    Full Text Available INTRODUCTION: The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC, there are two major histological types of NSCLC, adenocarcinoma (AC and squamous cell carcinoma (SCC. RESULTS: In this paper, we proposed to integrate a visualization method called Radial Coordinate Visualization (Radviz with a suitable classifier, aiming at discriminating two NSCLC subtypes using patients' gene expression profiles. Our analyses on simulated data and a real microarray dataset show that combining with a classification method, Radviz may play a role in selecting relevant features and ameliorating parsimony, while the final model suffers no or least loss of accuracy. Most importantly, a graphic representation is more easily understandable and implementable for a clinician than statistical methods and/or mathematic equations. CONCLUSION: To conclude, using the NSCLC microarray data presented here as a benchmark, the comprehensive understanding of the underlying mechanism associated with NSCLC and of the mechanisms with its subtypes and respective stages will become reality in the near future.

  12. Notch-1 Confers Chemoresistance in Lung Adenocarcinoma to Taxanes through AP-1/microRNA-451 Mediated Regulation of MDR-1.

    Science.gov (United States)

    Huang, Jiayuan; Chen, Yitian; Li, Junyang; Zhang, Kai; Chen, Jing; Chen, Dongqin; Feng, Bing; Song, Haizhu; Feng, Jifeng; Wang, Rui; Chen, Longbang

    2016-01-01

    We previously demonstrated that expression of Notch-1 is associated with poor prognosis in lung adenocarcinoma (LAD) patients. The aim of this study is to reveal whether Notch-1 was associated with Taxanes-resistant LAD and, the underlying mechanisms. We collected 39 patients of advanced LAD treated with Taxanes and found that positive Notch-1 expression is closely related to LAD lymph node metastasis, recurrence and poorer prognosis, and Notch-1 acts as an independent poor prognostic factor in LAD by multivariate analysis with Cox regression model. Then, by using the Docetaxel (DTX)-resistant LAD cell lines that we established previously, we found that Notch-1 contributes to resistance of LAD cells to DTX in vitro, and inhibition of Notch-1 sensitizes LAD to DTX in vivo. We further demonstrated that Notch-1 mediates chemoresistance response and strengthens proliferation capacity in LAD cells partially through negative regulation of miR-451 by transcription factor AP-1. Moreover, we found that MDR-1 is a direct target of miR-451 and influences chemoresistance of LAD cells. Taken together, our data revealed a novel Notch-1/AP-1/miR-451/MDR-1 signaling axis, and suggested a new therapeutic strategy of combining DTX with Notch inhibitors to treat DTX-resistant LAD.

  13. EGFR Mutation Status in Uighur Lung Adenocarcinoma Patients%维吾尔族肺腺癌患者的EGFR基因突变分析

    Institute of Scientific and Technical Information of China (English)

    单莉; 张琰; 赵峰; 郑立谋; 张国庆

    2013-01-01

    Background and objective Epidermal growth factor receptor (EGFR), a transmembrane protein, is a member of the tyrosine kinase family. Gefitinib, an EGFR tyrosine-kinase inhibitors, has shown a high response rate in the treatment of lung cancer in patients with EGFR mutation. However, significant differences in EGFR mutations exist among different ethnic groups. The aim of this study is to investigate the prevalence of EGFR mutations in Uighur lung adenocarcinoma patients by using a rapid and sensitive detection method and to analyze EGFR mutation differences compared with Han lung adenocarcinoma patients. Methods We examined lung adenocarcinoma tissues from 138 patients, including 68 Uighur lung adenocarcinoma patients and 70 Han lung adenocarcinoma patients, for EGFR mutations in exons 18, 19, 20, and 21 by using the amplification refractory mutation system (ARMS) PCR method. The mutation differences between Uighur and Han lung adenocarcinoma were compared by using the chi-square test method. Results EGFR mutations were detected in 43 (31.2%) of the 138 lung adenocarcinoma patients. EGFR mutations were detected in 11 (16.2%) of the 68 Uighur lung adenocarcinoma patients and in 32 (45.7%) of the 70 Han lung adenocarcinoma patients. Significant differences were observed in the EGFR mutations between Uighur lung adenocarcinoma patients and Han lung adenocarcinoma patients (P<0.00l). Conclusion Our results indicate that the EGFR mutation in Uighur lung adenocarcinoma patients (16.2%) is significantly lower than that in Han lung adenocarcinoma patients (45.7%).%背景与目的 表皮生长因子受体(epidermal growth factor receptor,EGFR)是一种跨细胞膜糖蛋白,属于受体型酪氨酸激酶家族.以吉非替尼为代表的EGFR酪氨酸激酶抑制剂对于EGFR突变的肺癌患者显示出良好的治疗效果,然而EGFR的突变率在不同民族和不同种族的人群中表现出较大差异.本研究旨在分析维吾尔族中肺腺癌患者肿瘤组织

  14. Correlations between EGFR Tyrosine Kinase Inhibitor and Serum Level of Tumor Marker in Lung Adenocarcinoma%EGFR-TKI治疗肺腺癌的疗效与血清肿瘤标志物的相关性

    Institute of Scientific and Technical Information of China (English)

    潘金兵; 侯宇虹; 钱皓瑜

    2012-01-01

    Objective To investigate the relationship between epidermal growth factor receptor tyrosine ki-nase inhibitorsC EGFR-TKI) treatment effects and serum tumor markers in lung adenocarcinoma. Methods Forty-eight patients with advanced lung adenocarcinoma were treated with EGFR-TKI. The clinical features, survival time and the level of serum tumor markers for the patients before and after treatment were retrospectively analyzed. Results After EGFR-TKI treatment,the RR was 58.2% and DCR was 65. 6% in lung adenocarcinoma; and median survival time was 13. 2 months. Responses correlated significantly with smoking history and level of CEA or CA19-9 in serum(P<0. 05). Patients with higher level of serum CEA and CA19-9 had higher disease control rate and longer survival (P<0. 05). Conclusion Serum CA19-9 or CEA level can predict the response of EGFR-TKI to lung adenocarcinoma.%目的 探讨表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKD对肺腺癌的疗效和血清肿瘤标志物间的关系.方法 回顾分析48例应用EGFR-TKI治疗的晚期肺腺癌患者的临床特征、生存时间和治疗前血清肿瘤标志物水平的相关性.结果 EGFR-TKI治疗后有效率为58.3%,控制率为65.6%;中位生存时间为13.2月.统计学分析显示:吸烟史、血清CEA和CA19-9水平与EGFR-TKI的疗效相关(P<0.05);治疗前血清CEA,CA19-9水平高者有着更高的治疗有效率、控制率和更长的生存期(P<0.05).结论 EGFR-TKI治疗前血清CA19-9和CEA的水平对预测EGFR-TRI对肺腺癌患者的疗效有参考价值.

  15. Activated NOTCH1 induces lung adenomas in mice and cooperates with MYC in the generation of lung adenocarcinoma

    OpenAIRE

    ALLEN, THADDEUS D.; Rodriguez, Elena M.; Jones, Kirk D.; Bishop, J. Michael

    2011-01-01

    NOTCH1 encodes the canonical member of the mammalian Notch receptor family. Activating lesions frequently affect NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL) and recently have been found in non-small cell lung cancer (NSCLC) as well. We explored the oncogenic potential of activated NOTCH1 in the lung by developing a transgenic mouse model in which activated NOTCH1 was overexpressed in the alveolar epithelium. The initial response to activated NOTCH1 was proliferation and the accumula...

  16. MicroRNA-650 was a prognostic factor in human lung adenocarcinoma and confers the docetaxel chemoresistance of lung adenocarcinoma cells via regulating Bcl-2/Bax expression.

    Directory of Open Access Journals (Sweden)

    Jia-Yuan Huang

    Full Text Available Increasing evidence shows that dysregulation of microRNAs (miRNAs is involved in malignant transformation. We investigated the clinical significance of miR-650 and its involvement in chemoresistance to docetaxel. Our results showed that the relative expression level of miR-650 was significantly higher in LAD tissues than in corresponding nontumor tissues and high level of miR-650 expression was found to be significantly associated with high incidence of lymph node metastasis, advanced clinical stage and poor prognosis of LAD patients. Univariate and multivariate analyses indicated that high miR-650 expression was an independent prognostic factor for survival. Also, we found that the level of miR-650 in LAD tissues was correlated with the response of patients to docetaxel-based chemotherapy. Silencing of miR-650 could increase the in vitro sensitivity of docetaxel-resistant LAD cells to docetaxel, while upregulation of miR-650 decreased the sensitivity of parental LAD cells to docetaxel both in vitro and in vivo. Additionally, silencing of miR-650 could enhance the caspase-3-dependent apoptosis, which might be correlated with the decreased ratio of Bcl-2/Bax. Further researches suggested that inhibitor of growth 4 (ING4 was a direct target of miR-650. Downregulated or upregulated ING4 expression could partially rescue the effects of miR-650 inhibitor or mimics in docetaxel-resistant or parental LAD cells. Furthermore, we found that ING4 was upregulated in docetaxel-responding LAD tissues, and its expression was inversely correlated with miR-650. Thus, miR-650 is a novel prognostic marker in LAD and its expression is a potential indicator of chemosensitivity to docetaxel-based chemotherapy regimen.

  17. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain.

    Directory of Open Access Journals (Sweden)

    William Pao

    2005-03-01

    Full Text Available BACKGROUND: Lung adenocarcinomas from patients who respond to the tyrosine kinase inhibitors gefitinib (Iressa or erlotinib (Tarceva usually harbor somatic gain-of-function mutations in exons encoding the kinase domain of the epidermal growth factor receptor (EGFR. Despite initial responses, patients eventually progress by unknown mechanisms of "acquired" resistance. METHODS AND FINDINGS: We show that in two of five patients with acquired resistance to gefitinib or erlotinib, progressing tumors contain, in addition to a primary drug-sensitive mutation in EGFR, a secondary mutation in exon 20, which leads to substitution of methionine for threonine at position 790 (T790M in the kinase domain. Tumor cells from a sixth patient with a drug-sensitive EGFR mutation whose tumor progressed on adjuvant gefitinib after complete resection also contained the T790M mutation. This mutation was not detected in untreated tumor samples. Moreover, no tumors with acquired resistance had KRAS mutations, which have been associated with primary resistance to these drugs. Biochemical analyses of transfected cells and growth inhibition studies with lung cancer cell lines demonstrate that the T790M mutation confers resistance to EGFR mutants usually sensitive to either gefitinib or erlotinib. Interestingly, a mutation analogous to T790M has been observed in other kinases with acquired resistance to another kinase inhibitor, imatinib (Gleevec. CONCLUSION: In patients with tumors bearing gefitinib- or erlotinib-sensitive EGFR mutations, resistant subclones containing an additional EGFR mutation emerge in the presence of drug. This observation should help guide the search for more effective therapy against a specific subset of lung cancers.

  18. Mutational analysis of EGFR and related signaling pathway genes in lung adenocarcinomas identifies a novel somatic kinase domain mutation in FGFR4.

    Directory of Open Access Journals (Sweden)

    Jenifer L Marks

    Full Text Available BACKGROUND: Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16 of FGFR4 (Glu681Lys, identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr in a lung adenocarcinoma cell line. CONCLUSIONS/SIGNIFICANCE: This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas.

  19. Could erlotinib treatment lead to acute cardiovascular events in patients with lung adenocarcinoma after chemotherapy failure?

    Directory of Open Access Journals (Sweden)

    Kus T

    2015-06-01

    Full Text Available Tulay Kus, Gokmen Aktas, Alper Sevinc, Mehmet Emin Kalender, Celaletdin Camci Department of Internal Medicine, Division of Medical Oncology, Gaziantep University, Gaziantep, Turkey Abstract: Erlotinib, an epidermal growth factor receptor and tyrosine kinase inhibitor, is a targeted drug that was approved for the treatment of non-small-cell lung cancers and pancreatic cancers. Targeted tyrosine kinase inhibitors are known to have cardiotoxic effects. However, erlotinib does not have a statistically proven effect of increasing acute cardiovascular event (ACE risk. Preclinical studies showed that beta agonist stimulation among rats that were administered erlotinib led to cardiovascular damage. Thus, there would be an aggregate effect of erlotinib on ACE, although it is not thought to be a cardiotoxic drug itself. In this paper, we present two non-small-cell lung cancer cases that developed ACE under erlotinib treatment. Keywords: erlotinib, lung cancer, myocardial infarction, EGFR

  20. Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling.

    Science.gov (United States)

    Sullivan, James P; Spinola, Monica; Dodge, Michael; Raso, Maria G; Behrens, Carmen; Gao, Boning; Schuster, Katja; Shao, Chunli; Larsen, Jill E; Sullivan, Laura A; Honorio, Sofia; Xie, Yang; Scaglioni, Pier P; DiMaio, J Michael; Gazdar, Adi F; Shay, Jerry W; Wistuba, Ignacio I; Minna, John D

    2010-12-01

    Aldehyde dehydrogenase (ALDH) is a candidate marker for lung cancer cells with stem cell-like properties. Immunohistochemical staining of a large panel of primary non-small cell lung cancer (NSCLC) samples for ALDH1A1, ALDH3A1, and CD133 revealed a significant correlation between ALDH1A1 (but not ALDH3A1 or CD133) expression and poor prognosis in patients including those with stage I and N0 disease. Flow cytometric analysis of a panel of lung cancer cell lines and patient tumors revealed that most NSCLCs contain a subpopulation of cells with elevated ALDH activity, and that this activity is associated with ALDH1A1 expression. Isolated ALDH(+) lung cancer cells were observed to be highly tumorigenic and clonogenic as well as capable of self-renewal compared with their ALDH(-) counterparts. Expression analysis of sorted cells revealed elevated Notch pathway transcript expression in ALDH(+) cells. Suppression of the Notch pathway by treatment with either a γ-secretase inhibitor or stable expression of shRNA against NOTCH3 resulted in a significant decrease in ALDH(+) lung cancer cells, commensurate with a reduction in tumor cell proliferation and clonogenicity. Taken together, these findings indicate that ALDH selects for a subpopulation of self-renewing NSCLC stem-like cells with increased tumorigenic potential, that NSCLCs harboring tumor cells with ALDH1A1 expression have inferior prognosis, and that ALDH1A1 and CD133 identify different tumor subpopulations. Therapeutic targeting of the Notch pathway reduces this ALDH(+) component, implicating Notch signaling in lung cancer stem cell maintenance.

  1. Up-regulation of the expression of S100A8 and S100A9 in lung adenocarcinoma and its correlation with inflammation and other clinical features

    Institute of Scientific and Technical Information of China (English)

    SU Yan-jun; XU Feng; YU Jin-pu; YUE Dong-sheng; REN Xiu-bao; WANG Chang-li

    2010-01-01

    Background S100A8 and S100A9 are two members of the S100 protein family characterized by the presence of two Ca2+-binding sites of the EF-hand type.Previous studies suggested that the whole S100 family displays significant functions in tumor growth, progression and invasion.This study aimed to determine the expression of the two indices of the family, S100A8 and S100A9, in lung cancer tissues and normal lung tissues and its correlation with clinical features.Methods A total of 60 cases with a variety of clinical data that were diagnosed with different histological subtypes of lung cancer were investigated.Semi-quantitative reverse transcriptase-PCR (Sq-Rt-PCR) and immunohistochemical staining of cancer, adjacent and peripheral lung tissues were executed to distinguish the expression patterns of S100A8and S100A9 and to further clarify their correlation with clinical features.Results Immunohistochemical staining of both proteins showed a significant up-regulation in lung cancer tissue (S100A8, S100A9, P<0.0001), and PCR revealed that the levels of S100A8 and S100A9 expression were significantly higher in lung cancer tissues (S100A8 P=0.002/0.004; S100A9 P=0.022/0.026).The higher expression was found to be correlated with the clinical characteristics of adenocarcinoma, inflammation and stage Ⅳ lesion.Conclusions S100A8, S100A9 up-regulation was found in the lung adenocarcinoma and end stage lung cancer tissue,the correlation of which with their higher expression in inflammatory lung tissues may indicate the collaborative effect of inflammation on the progression of cancer.

  2. Significance of FGFR4 expression in prognosis in lung adenocarcinoma%成纤维细胞生长因子受体4在肺腺癌组织中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    杨胜利; 何建行; 肖大凯; 黄丽燕; 何慧鸣; 潘辉

    2015-01-01

    Objective To investigate the expression of FGFR4 in lung adenocarcinoma tissue and its association with the prognosis of lung adenocarcinoma. Methods The expression FGFR4 in 128 lung adenocarcinoma tissue and the normal lung tissue was detected by the immunohistochemistry SP method.The relationship between the expression of FGFR4 in lung adenocarcinoma and the prognosis of lung adenocarcinoma was analyzed. Results The expression of FGFR4 protein in lung adenocarcinoma was significantly lower than that in the tumor-adjacent normal lung tissue (P 0.05), but was significantly and positively correlated with the degree of tumor differentiation and T stage, N stage and the clinical TNM stage of lung adenocarcinoma (P 0.05). FGFR4的表达与TNM分期以及肿瘤分化情况、T分期、N分期有显著的相关性 (P < 0.05). Kaplan-Meier生存分析法结果显示, 高表达FGFR4蛋白组的肺腺癌患者的手术后生存时间较肺癌患者的低表达组明显延长(P < 0.05). 结论:肺腺癌组织中FGFR4蛋白表达低于癌旁正常肺组织,FGFR4蛋白高表达组的肺腺癌患者术后生存时间较低表达组肺癌患者明显延长,FGFR4可能是肺癌的一个保护性因素.

  3. Selective reversal of drug resistance in drug-resistant lung adenocarcinoma cells by tumor-specific expression of MDR1 ribozyme gene mediated by retrovirus

    Institute of Scientific and Technical Information of China (English)

    高振强; 高志萍; 刘喜富; 张涛

    1997-01-01

    According to the fact that CEA gene expressed only in lung adenocarcinoma and not in normal lung cells, a retroviral vector (pCEAMR) was constructed which carried the CEA promoter coupled to MDR1 ribozyme gene. pCEAMR was introduced into drug-resistant lung adenocarcinoma cells GAOK with CEA expression and HeLaK without CEA expression; the expression of pCEAMR and drug resistance in the infected cells were analyzed in vitro and in vivo ; pCEAMR expressed only in CEA-producing GAOK cells and not in non-CEA-producing HeLa cells. The drug resistance to doxorubicin (DOX) decreased 91.5% in the infected GAOK cells and did not change in the infected HeLa cells. In nude mice, DOX could obviously inhibit the growth of the infected GAOK tumors, and had no effect on the growth of the infected HeLa cells. These results indicated that MDR1 ribozyme gene regulated by CEA promoter expressed only in human adenocarcinoma cells and reversed their drug resistance selectively. This gene-drug therapy might serve as an effe

  4. Exercise and relaxation intervention for patients with advanced lung cancer

    DEFF Research Database (Denmark)

    Adamsen, Lis; Stage, M; Laursen, J

    2012-01-01

    (NSCLC) (III-IV) and small cell lung cancer (SCLC) (ED), undergoing chemotherapy. The intervention consisted of a hospital-based, supervised, group exercise and relaxation program comprising resistance-, cardiovascular- and relaxation training 4 h weekly, 6 weeks, and a concurrent unsupervised home......Lung cancer patients experience loss of physical capacity, dyspnea, pain, reduced energy and psychological distress. The aim of this study was to explore feasibility, health benefits and barriers of exercise in former sedentary patients with advanced stage lung cancer, non-small cell lung cancer......-based exercise program. An explorative study using individual semi-structured interviews (n=15) and one focus group interview (n=8) was conducted among the participants. Throughout the intervention the patients experienced increased muscle strength, improvement in wellbeing, breathlessness and energy. The group...

  5. Afatinib: a review of its use in the treatment of advanced non-small cell lung cancer.

    Science.gov (United States)

    Keating, Gillian M

    2014-02-01

    Afatinib (Gilotrif™, Giotrif(®)) is an orally administered, irreversible inhibitor of the ErbB family of tyrosine kinases. Afatinib downregulates ErbB signalling by covalently binding to the kinase domains of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER) 2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation; it also inhibits transphosphorylation of HER3. Afatinib is approved as monotherapy for the treatment of EGFR tyrosine kinase inhibitor (TKI)-naïve adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating EGFR mutations in the EU, and for the first-line treatment of patients with metastatic NSCLC whose tumours have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a US FDA-approved test in the US. In two randomized, open-label, multinational phase III trials, progression-free survival was significantly prolonged with afatinib compared with pemetrexed plus cisplatin (LUX-Lung 3) or gemcitabine plus cisplatin (LUX-Lung 6) in treatment-naïve patients with advanced NSCLC with activating EGFR mutations. The objective response rate was significantly higher with afatinib than with pemetrexed plus cisplatin or gemcitabine plus cisplatin, and patient-reported outcomes for symptoms such as cough and dyspnoea and certain health-related quality of life measures significantly favoured afatinib versus pemetrexed plus cisplatin or gemcitabine plus cisplatin. Afatinib also showed efficacy in EGFR TKI-naïve patients with advanced lung adenocarcinoma and activating EGFR mutations who had received no more than one prior chemotherapy regimen for advanced disease, according to the results of the noncomparative, multinational, phase II LUX-Lung 2 trial. Oral afatinib had a manageable tolerability profile. EGFR-mediated adverse events (e.g. diarrhoea, rash/acne) were generally managed using dose reduction and delays. In conclusion, afatinib

  6. Clinical Observation of Erlotinib in the Treatment of Advanced and Previously Treated Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Liyan XU

    2009-12-01

    Full Text Available Background and objective Erlotinib is a small molecular inhibitor of tyrosine kinase. One study has confirmed that it can prolong the median progression-free survival time (PFS, and can improve the one-year survival rate of patients with advanced non-small cell lung cancer. The aim of this trial is to evaluate the response and adverse reaction of agent erlotinib in advanced and previously treated non-small-cell lung cancer. Methods The study was one part of the EAP (Expanded Access Programme study. Forty-five patients with advanced non-small cell lung cancer, which had been treated with 1-2 regimens containing platinum previously, were treated with erlotinib from Dec 2005. Erlotinib was prescribed at a dose of 150 mg daily. Results Forty-three patients were evaluated response and all patients were evaluated toxicity. Among these patients, CR 0 case, PR 19 cases (44.2%, RR (CR+PR 44.2% and SD 13 cases as their best response, disease control rate (DCR=CR+PR+SD 74.4%, PD 11cases (25.6%. The median progression-free survival time was 4.8 months; the median survival time was 15.0 months; the one-year survival rate was 68.8% (31/45. The median PFS of patients with adenocarcinoma and with non-adenocarcinoma was 7.6 months vs 2.6 months (P=0.018. The drug-related adverse reactions were skin rash (41 cases, 91.1%, billirubine increased (15 cases, 33.3%, ALT increased (9 cases, 20% and diarrhea (4 cases, 8.9%. For patients with and without skin rash, the median PFS was 7.5 months vs 1.1 months (P=0.001, and the median survival time was 15.6 months vs 5.2 months (P=0.002. Conclusion Erlotinib is effective in advanced and previously treated non-small cell lung cancer, and it is much more effective in adenocarcinoma and patients with skin rash. It is well tolerated, only with some minimal adverse reactions.

  7. Therapeutic Potential of Andrographolide Isolated from the Leaves of Andrographis paniculata Nees for Treating Lung Adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Yu-Tang Tung

    2013-01-01

    Full Text Available Andrographolide is one of the major diterpene lactones found in Andrographis paniculata Nees and exhibits remarkable inhibitory effects on various cancers. In this study, the antipulmonary cancer effects of andrographolide were studied in a lung tumor mouse model induced by human vascular endothelial growth factor A165 (hVEGF-A165. These results demonstrated that andrographolide significantly reduced the expression of hVEGF-A165 compared with a mock group in the Clara cells of the lungs. In addition, andrographolide also decreased tumor formation by reducing VEGF, EGFR, Cyclin A, and Cyclin B expression on the transcriptional and translational levels. These results indicated that andrographolide treatment on the overexpression of VEGF can arrest the cell cycle, which induced pulmonary tumors in transgenic mice. In conclusion, the antiangiogenesis and chemotherapeutic potential of andrographolide may provide a cure for pulmonary tumors in the future.

  8. Anticancer Effects of Sinulariolide-Conjugated Hyaluronan Nanoparticles on Lung Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Kuan Yin Hsiao

    2016-03-01

    Full Text Available Lung cancer is one of the most clinically challenging malignant diseases worldwide. Sinulariolide (SNL, extracted from the farmed coral species Sinularia flexibilis, has been used for suppressing malignant cells. For developing anticancer therapeutic agents, we aimed to find an alternative for non-small cell lung cancer treatment by using SNL as the target drug. We investigated the SNL bioactivity on A549 lung cancer cells by conjugating SNL with hyaluronan nanoparticles to form HA/SNL aggregates by using a high-voltage electrostatic field system. SNL was toxic on A549 cells with an IC50 of 75 µg/mL. The anticancer effects of HA/SNL aggregates were assessed through cell viability assay, apoptosis assays, cell cycle analyses, and western blotting. The size of HA/SNL aggregates was approximately 33–77 nm in diameter with a thin continuous layer after aggregating numerous HA nanoparticles. Flow cytometric analysis revealed that the HA/SNL aggregate-induced apoptosis was more effective at a lower SNL dose of 25 µg/mL than pure SNL. Western blotting indicated that caspases-3, -8, and -9 and Bcl-xL and Bax played crucial roles in the apoptotic signal transduction pathway. In summary, HA/SNL aggregates exerted stronger anticancer effects on A549 cells than did pure SNL via mitochondria-related pathways.

  9. Metastasis of Lung Adenocarcinoma to the Gingiva: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    M. Rajini Kanth

    2015-05-01

    Full Text Available Metastatic tumors account for 1% of all oral malignancies. Metastasis to jaw bones is common, particularly in the mandible, rare in the oral soft tissues, and account for only 0.1% of oral malignancies. The majority of metastatic cases (70% reported in the literature have primary tumors located in the lung, breast, kidney, and colon. Metastasis is a biological complex process that involves detachment from the surrounding cells, regulation of cell motility, invasion, survival, proliferation, and evasion of the immune system. Clinical presentation of metastatic tumors is variable, which may create diagnostic dilemma or may lead to erroneous diagnosis. Metastatic tumors clinically mimic as dental infections. Metastasis to the oral soft tissue from lung cancer, especially gingiva is a rare condition. Metastasis to the gingiva can affect the oral function, speech, and nutrition. Most of the cases in the literature reported that lesion presented in oral soft tissues before the diagnosis of primary tumors. Here we report a case of 62-year-old male patient with metastasis from lung to the gingiva, where the metastasis was detected before primary tumor.

  10. Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

    Science.gov (United States)

    Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

    2017-01-10

    In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

  11. Miliary brain metastases from adenocarcinoma of the lung: MR imaging findings with clinical and post-mortem histopathologic correlation

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    Iguchi, Yohei; Mano, Kazuo; Goto, Yoji; Nakano, Tomonobu [Japanese Red Cross Nagoya First Hospital, Department of Neurology Medicine, Nagoya, Aichi (Japan); Nomura, Fumio; Shimokata, Tomoya [Japanese Red Cross Nagoya First Hospital, Department of Respiratory Medicine, Nagoya, Aichi (Japan); Iwamizu-Watanabe, Sachiko [Nagoya University Graduate School of Medicine, Department of Pathology of Molecular Diagnosis, Nagoya (Japan); Hashizume, Yoshio [Aichi Medical University, Institute for Medical Science of Aging, Nagakute, Aichi (Japan)

    2007-01-15

    Miliary dissemination is a rare form of brain metastasis. The clinical and pathologic features of this form are unclear. We report a 66-year-old man with miliary brain metastases from adenocarcinoma of the lung, describing MRI and neuropathologic findings in the context of previously reported cases. Initial disorientation progressed to an apallic state within 6 months. Although, CT with administration of contrast agent failed to demonstrate any lesions, MRI with Gd-DTPA administration showed multiple enhancing miliary nodules in the cerebral cortex, basal ganglia, thalamus, cerebellum, and brainstem. Some of those nodules also could be seen on T2-weighted imaging without Gd-DTPA, but were difficult to identify conclusively. A histopathologic examination at autopsy disclosed diffusely distributed miliary tumor nodules in a perivascular distribution without surrounding focal edema or reactive gliosis. Notably, this patient with miliary brain metastases developed disorientation followed by unconsciousness, which overshadowed other focal neurologic signs at that time. We should consider this pattern of brain dissemination when a cancer is associated with unexplained disturbance of consciousness. (orig.)

  12. [Study on the cell apoptosis induced by intracellular hyperthermia in human lung adenocarcinoma SPC-A1 cells].

    Science.gov (United States)

    Ma, Yongjie; Li, Hong; Yan, Zhubing; Gu, Hongchen

    2007-12-01

    This is a comparative study on the efficacy of differential cell apoptosis induced by three methods (intracellular hyperthermia, with water bath hyperthermia and extracellular hyperthermia) in human lung adenocarcinoma SPC-A1 cells in vitro. The effects of hyperthermia on cell apoptosis were determined by Transmission electron microscopy(TEM), agarose gel electrophoresis and flow cytometry methods, respectively. The intracellular effect of particle heating was compared with that of water bath hyperthermia and extracellular hyperthermia; significant differences between these heating methods were detected, the rate of apoptosis being 36.59%, 5.66%, 7.78% respectively. When treated with intracellular hyperthermia, the SPC-A1 cells manifested typical morphological characters of apoptosis by TEM observation, and the SPC-A1 cell DNA was degraded into large fragments by agarose gel electrophoresis assay. Our results showed that amino-silane Fe3O4 induced intracellular hyperthermia was superior to water bath hyperthermia and extracellular hyperthermia. It is mainly the interaction between intracellular nanoparticles and cell that induced apoptosis. Therefore, the aminosilane-coated Fe3O4 may be used in hyperthermia or chemotherapeutics on cancer cells for further clinical application.

  13. Integrin {beta}1-dependent invasive migration of irradiation-tolerant human lung adenocarcinoma cells in 3D collagen matrix

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    Ishihara, Seiichiro [Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810 (Japan); Haga, Hisashi, E-mail: haga@sci.hokudai.ac.jp [Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810 (Japan); Yasuda, Motoaki [Department of Oral Pathobiological Science, Graduate School of Dental Medicine, Hokkaido University, N13-W7, Kita-ku, Sapporo 060-8586 (Japan); Mizutani, Takeomi; Kawabata, Kazushige [Transdisciplinary Life Science Course, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810 (Japan); Shirato, Hiroki [Department of Radiology, Hokkaido University Graduate School of Medicine, N15-W7, Kita-ku, Sapporo 060-8638 (Japan); Nishioka, Takeshi [Department of Biomedical Sciences and Engineering, Faculty of Health Sciences, Hokkaido University, N12-W5, Kita-ku, Sapporo 060-0812 (Japan)

    2010-06-04

    Radiotherapy is one of the effective therapies used for treating various malignant tumors. However, the emergence of tolerant cells after irradiation remains problematic due to their high metastatic ability, sometimes indicative of poor prognosis. In this study, we showed that subcloned human lung adenocarcinoma cells (A549P-3) that are irradiation-tolerant indicate high invasive activity in vitro, and exhibit an integrin {beta}1 activity-dependent migratory pattern. In collagen gel overlay assay, majority of the A549P-3 cells displayed round morphology and low migration activity, whereas a considerable number of A549P-3IR cells surviving irradiation displayed a spindle morphology and high migration rate. Blocking integrin {beta}1 activity reduced the migration rate of A549P-3IR cells and altered the cell morphology allowing them to assume a round shape. These results suggest that the A549P-3 cells surviving irradiation acquire a highly invasive integrin {beta}1-dependent phenotype, and integrin {beta}1 might be a potentially effective therapeutic target in combination with radiotherapy.

  14. Melatonin inhibits the migration of human lung adenocarcinoma A549 cell lines involving JNK/MAPK pathway.

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    Qiaoyun Zhou

    Full Text Available OBJECTIVE: Melatonin, an indolamine produced and secreted predominately by the pineal gland, exhibits a variety of physiological functions, possesses antioxidant and antitumor properties. But, the mechanisms for the anti-cancer effects are unknown. The present study explored the effects of melatonin on the migration of human lung adenocarcinoma A549 cells and its mechanism. METHODS: MTT assay was employed to measure the viability of A549 cells treated with different concentrations of melatonin. The effect of melatonin on the migration of A549 cells was analyzed by wound healing assay. Occludin location was observed by immunofluorescence. The expression of occludin, osteopontin (OPN, myosin light chain kinase (MLCK and phosphorylation of myosin light chain (MLC, JNK were detected by western blots. RESULTS: After A549 cells were treated with melatonin, the viability and migration of the cells were inhibited significantly. The relative migration rate of A549 cells treated with melatonin was only about 20% at 24 h. The expression level of OPN, MLCK and phosphorylation of MLC of A549 cells were reduced, while the expression of occludin was conversely elevated, and occludin located on the cell surface was obviously increased. The phosphorylation status of JNK in A549 cells was also reduced when cells were treated by melatonin. CONCLUSIONS: Melatonin significantly inhibits the migration of A549 cells, and this may be associated with the down-regulation of the expression of OPN, MLCK, phosphorylation of MLC, and up-regulation of the expression of occludin involving JNK/MAPK pathway.

  15. Advances in target therapy in lung cancer

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    Jean-Paul Sculier

    2015-03-01

    Full Text Available Herein, we have reviewed and analysed recent literature, published in 2013 and early 2014, in the context of pre-existing data. Considered target therapies were tyrosine kinase inhibitors of active epidermal growth factor receptor mutations (e.g. erlotinib, gefinitib and afatinib, anaplastic lymphoma kinase rearrangements (e.g. crizotinib or angiogenesis (drugs under development, or monoclonal antibodies against vascular endothelial growth factor (e.g. bevacizumab or epidermal growth factor receptors (e.g. cetuximab. The therapeutic project has to consider tyrosine kinase inhibitors in the case of nonsmall cell lung cancer with active epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangement. However, these drugs should not be used in the absence of the targeted genetic abnormalities.

  16. The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia.

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    Chao Agnes Hsiung

    2010-08-01

    Full Text Available Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10(-7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30 x 10(-11. This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38 x 10(-11. A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60 x 10(-20, allelic risk = 1.54, 95% Confidence Interval (CI 1.41-1.68. Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40-1.87, and 2.35 (95% CI: 1.95-2.83, respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma.

  17. Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

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    Petrović Marina

    2007-01-01

    Full Text Available Beckground/Aim. Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC. Methods. A clinical trial included 158 patients (74% males and 26% females, with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion or chemotherapy only in stage III (with pleural effusion and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion, the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. Results. A total of 53 patients (34% had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively. Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.5%, 34 (21.5% and 33 (20.1% patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (p < 0.001; a two - year survival time noted in 30% of the patients (p = 0

  18. Advances of Molecular Targeted Therapy in Squamous Cell Lung Cancer

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    Li MA

    2013-12-01

    Full Text Available Squamous cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR inhibitors or anaplastic lymphoma kinase (ALK inhibitors that show exquisite activity in lungadenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1 gene, the discoidin domain receptor 2 (DDR2 gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lungcancer assessing the value of novel therapeutics addressing these targets.

  19. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian, E-mail: zhangjian197011@yahoo.com [Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China); Zhang, Tao [Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Ti, Xinyu; Shi, Jieran; Wu, Changgui; Ren, Xinling [Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China); Yin, Hong, E-mail: yinnhong@yahoo.com [The Medical Image Center, Xijing Hospital, The Fourth Military Medical University, Xi' an 710032 (China)

    2010-08-13

    Research highlights: {yields} Curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells {yields} Curcumin promotes apoptosis in A549/DDP cells through a miRNA signaling pathway {yields} Curcumin induces A549/DDP cell apoptosis by downregulating miR-186* {yields} miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin -- Abstract: Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186* in A549/DDP. In addition, transfection of cells with a miR-186* inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186* significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.

  20. GalNAc-T14 promotes metastasis through Wnt dependent HOXB9 expression in lung adenocarcinoma.

    Science.gov (United States)

    Kwon, Ok-Seon; Oh, Ensel; Park, Jeong-Rak; Lee, Ji-Seon; Bae, Gab-Yong; Koo, Jae-Hyung; Kim, Hyongbum; Choi, Yoon L; Choi, Young Soo; Kim, Jhingook; Cha, Hyuk-Jin

    2015-12-01

    While metastasis, the main cause of lung cancer-related death, has been extensively studied, the underlying molecular mechanism remains unclear. A previous clinicogenomic study revealed that expression of N-acetylgalactosaminyltransferase (GalNAc-T14), is highly inversely correlated with recurrence-free survival in those with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism(s) has not been determined. Here, we showed that GalNAc-T14 expression was positively associated with the invasive phenotype. Microarray and biochemical analyses revealed that HOXB9, the expression of which was increased in a GalNAc-T14-dependent manner, played an important role in metastasis. GalNAc-T14 increased the sensitivity of the WNT response and increased the stability of the β-catenin protein, leading to induced expression of HOXB9 and acquisition of an invasive phenotype. Pharmacological inhibition of β-catenin in GalNAc-T14-expressing cancer cells suppressed HOXB9 expression and invasion. A meta-analysis of clinical genomics data revealed that expression of GalNAc-T14 or HOXB9 was strongly correlated with reduced recurrence-free survival and increased hazard risk, suggesting that targeting β-catenin within the GalNAc-T14/WNT/HOXB9 axis may be a novel therapeutic approach to inhibit metastasis in NSCLC.

  1. Establishment of A Novel Chinese Human Lung Adenocarcinoma Cell Line CPA-Yang3 and Its Real Bone Metastasis Clone CPA-Yang3BM in Immunodeficient Mice

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    Shunfang YANG

    2011-02-01

    Full Text Available Background and objective The recurrence and metastasis of lung cancer is a tough problem worldwide. The aim of this study is to establish a novel Chinese lung adenocarcinoma cell line and its real bone-seeking clone sub-line for exploring the molecular mechanism of lung cancer metastasis. Methods The cells came from the pleural effusion of a sixtyfive years old female patient with lung adenocarcinoma and supraclavicular lymph node metastases. The gene expression was detected by real-time quantitative PCR. Intracardiac injection of the cells into nude mice was performed and in vivo imaging was obtained by bone scintigraphy and conventional radiography. Bone metastases were determined on bone scintigraphy and then the lesions were resected under deep anesthesia for bone metastasis cancer cell culture. The process was repeated for four cycles to obtain a real bone-seeking clone. Results The tumorigenesis rate started at 4th passage in immunodeficient mice via subcutaneously and as well as later passages. Approximately 1×106 cancer cells were injected into left cardiac ventricle of immunodeficient mice resulted bone metastasis sites were successfully revealed by bone scintigraphy and pathological diagnosis, the mandible (100%, scapula (33%, humerus (50%, vertebral column (50%, femur (66.7% and accompanied invasion with other organs, the adrenal gland (17%, pulmonary (33%, liver (50%, submaxillary gland (33% in the mice after inoculation two-three weeks. The chromosome karyotype analysis of the cells was subdiploid. Quantitative real-time PCR was used to examined and compared with SPC-A-1 lung adenocarcinoma, ESM1, VEGF-C, IL-6, IL-8, AR, SVIL, FN1 genes were overexpress. The novel cell was named CPA-Yang3. The femur metastasis cell was repeated in vivo-in vitro-in vivo with three cycles and harvested a real bone metastasis clone. It was named CPA-Yang3BM. Conclusion Tne characteristics of novel strain CPAYang3 is a highly metastasis cell line of

  2. Ifosfamide in advanced adenocarcinoma of the oesophagus or oesophageal-gastric junction area

    NARCIS (Netherlands)

    T.C. Kok (Tjebbe); A. van der Gaast (Ate); T.A.W. Splinter (Ted); H.W. Tilanus (Hugo)

    1991-01-01

    markdownabstractAbstract 25 previously untreated patients with inoperable or metastatic adenocarcinoma of the oesophagus or oesophageal-gastric junction area were treated with ifosfamide 6 g/m2 over 48 hours, combined with mesna 6 g/m2. 1 complete response and 1 partial response were seen among 23

  3. Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers.

    Science.gov (United States)

    Schuller, Hildegard M; Porter, B; Riechert, A; Walker, K; Schmoyer, R

    2004-07-01

    Lung cancer continues to be the leading cause of cancer death in developed countries. With smoking the major etiological factor for lung cancer, there is a great need for the development of chemopreventive treatments that inhibit the progression of initiated cells and premalignant lesions into overt lung cancer in smokers who quit. Although the major focus of chemoprevention research has been on agents that inhibit the metabolic activation of genotoxic chemicals contained in tobacco products, some of these agents may additionally modulate growth-regulating signal transduction. In turn, the function of such signaling pathways is highly cell type-specific, with a given pathway inhibiting the growth of one cell type while stimulating the growth of others. The current experiment has tested the hypothesis that green tea and the methylxanthine theophylline contained in tea inhibit the progression of neuroendocrine lung carcinogenesis in hamsters with hyperoxic lung injury and initiated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) while promoting the development of Clara cell-derived pulmonary adenocarcinomas initiated by NNK in healthy hamsters. This hypothesis is based on published evidence that human small cell lung cancer as well as the neuroendocrine hamster tumors are regulated via autocrine signaling pathways that activate Raf-1 and the mitogen-activated (MAP) kinase pathway whereas human pulmonary adenocarcinomas of Clara cell lineage and the hamster model of this cancer type are regulated by a beta-adrenergic pathway involving the activation of cyclic adenosine 3',5'-monophosphate (cAMP) and the arachidonic acid (AA) cascade. In turn, it was hypothesized that theophylline would inhibit Raf-1-dependent tumor progression while promoting cAMP-dependent tumor progression due to its documented ability to inhibit the enzyme cAMP-phophodiesterase. The experimental design simulated chemoprevention in former smokers in that treatments

  4. [An autopsy case of sarcomatoid malignant mesothelioma mimicking adenocarcinoma with sarcomatoid elements of lung].

    Science.gov (United States)

    Tamiya, Motohiro; Yamane, Hiroyuki; Terada, Haruko; Matsuno, Osamu; Yamamoto, Suguru

    2008-11-01

    A 62-year-old man with pain in his hip joints and back was admitted to our hospital. His chest radiograph and CT showed a huge mass extending from the left upper pericardium to the left hilum, but no pleural effusion or other lesions. A contrast-enhanced abdominal CT showed multiple metastases to bones and both kidneys. Bronchoscopy revealed obstruction of the left B3 by a visible tumor. The biopsy specimens of the initial immunohistochemical staining were slightly positive for calretinin. However, we diagnosed the condition as sarcomatoid carcinoma of the lung on the basis of the clinical evaluation. Although radiotherapy was administered, his condition rapidly deteriorated and he died due to progression of the disease. Autopsy revealed extensive invasion, suggesting mesothelioma. Therefore, immunohistochemical staining was performed; the findings revealed sarcomatoid malignant mesothelioma. In conclusion, we encountered a rare case of sarcomatoid malignant mesothelioma (stage IV).

  5. Role of ATM in bystander signaling between human monocytes and lung adenocarcinoma cells.

    Science.gov (United States)

    Ghosh, Somnath; Ghosh, Anu; Krishna, Malini

    2015-12-01

    The response of a cell or tissue to ionizing radiation is mediated by direct damage to cellular components and indirect damage mediated by radiolysis of water. Radiation affects both irradiated cells and the surrounding cells and tissues. The radiation-induced bystander effect is defined by the presence of biological effects in cells that were not themselves in the field of irradiation. To establish the contribution of the bystander effect in the survival of the neighboring cells, lung carcinoma A549 cells were exposed to gamma-irradiation, 2Gy. The medium from the irradiated cells was transferred to non-irradiated A549 cells. Irradiated A549 cells as well as non-irradiated A549 cells cultured in the presence of medium from irradiated cells showed decrease in survival and increase in γ-H2AX and p-ATM foci, indicating a bystander effect. Bystander signaling was also observed between different cell types. Phorbol-12-myristate-13-acetate (PMA)-stimulated and gamma-irradiated U937 (human monocyte) cells induced a bystander response in non-irradiated A549 (lung carcinoma) cells as shown by decreased survival and increased γ-H2AX and p-ATM foci. Non-stimulated and/or irradiated U937 cells did not induce such effects in non-irradiated A549 cells. Since ATM protein was activated in irradiated cells as well as bystander cells, it was of interest to understand its role in bystander effect. Suppression of ATM with siRNA in A549 cells completely inhibited bystander effect in bystander A549 cells. On the other hand suppression of ATM with siRNA in PMA stimulated U937 cells caused only a partial inhibition of bystander effect in bystander A549 cells. These results indicate that apart from ATM, some additional factor may be involved in bystander effect between different cell types.

  6. Advances in lung ultrasound; Avancos na ultrassonografia pulmonar

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    Francisco Neto, Miguel Jose; Rahal Junior, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmao, E-mail: miguelneto@einstein.br [Hospital Israelita Albert Einstein, Sao Paulo, SP (Brazil)

    2016-11-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. (author)

  7. Clinical Response to Gefitinib Retreatment of Lung Adenocarcinoma Patients Who Benefited from An Initial Gefitinib Therapy: A Retrospective Analysis

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    Junling LI

    2012-01-01

    Full Text Available Background and objective Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI that has been widely used for the treatment of non-small cell lung cancer (NSCLC. It is most effective in women, as well as in patients who have never smoked, have pulmonary adenocarcinomas, or are of Asian origin. Several treatment options are available for NSCLC patients who responded to initial gefitinib therapy but demonstrated tumor progression, of which gefitinib readministration is the chosen therapeutic option. The present study aims to evaluate the efficacy and toxicity of gefitinib readministration. Methods The clinical data of 18 patients with NSCLC who had shown partial response (PR or achieved a stable disease (SD status after gefitinib administration and were retreated with gefitinib due to failure of the initial therapy were reviewed and retrospectively analyzed. Results Of the 18 patients studied, 1 (6% showed partial remission (PR, 11 (61% achieved SD, and 6 (33% experienced disease progression. The disease control rate was 67%, and the median progression-free survival was 5.16 months (range, 1 to 24.8 months. The median overall survival from the start of the gefitinib therapy was 39.4 months (range, 15.38 to 52.44 months. Moreover, the median overall survival from the beginning of the 2nd therapy was 12.41 months (range, 3.98 to 38.24 months. Mild toxicity was observed with the 2nd gefitinib therapy. Conclusion The results of the present study indicate that patients with NSCLC may still be expected to achieve prolonged survival through gefitinib readministration if they initially responded to gefitinib and underwent various subsequent treatments.

  8. Assessment of DDR2, BRAF, EGFR and KRAS mutations as therapeutic targets in non-adenocarcinoma lung cancer patients.

    Science.gov (United States)

    Yashima, Hideaki; Shimizu, Kimihiro; Araki, Takuya; Aomori, Tohru; Ohtaki, Yoichi; Nagashima, Toshiteru; Enokida, Yasuaki; Atsumi, Jun; Nakamura, Tomonori; Takeyoshi, Izumi; Yamamoto, Koujirou

    2014-09-01

    Molecular-targeted therapy has not been established in non-adenocarcinoma lung cancer (non-AdLC), as no targets that affect the clinical efficacy of molecular-targeted drugs have yet been identified. In this study, we investigated the frequency of genetic variations in discoidin domain receptor 2 (DDR2), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in non-AdLC patients, in order to evaluate the possibility of genetic mutations in these genes being used as therapeutic targets for the treatment of patients with non-AdLC. For this purpose, we enrolled 150 non-AdLC patients who had undergone surgery at the Gunma University Hospital between December, 2003 and December, 2012. Genetic mutations in the EGFR, KRAS, DDR2 and BRAF genes were detected by a sequencing method or probe assay using DNA derived from cancer tissues. No somatic mutations in DDR2 or BRAF were detected in non-AdLC patients. Conversely, genetic mutations in EGFR exon 19 were found in 3 squamous cell carcinoma (SCC) and 3 adenosquamous carcinoma patients, whereas KRAS codon 12 mutations were also found in 3 SCC patients and 1 large-cell neuroendocrine carcinoma patient. EGFR and KRAS mutations were mutually exclusive. This study indicated that, although DDR2 and BRAF mutations may only rarely be used as therapeutic targets, EGFR and KRAS mutations may represent candidate therapeutic targets, at least in the non-AdLC patients investigated.

  9. Synergistic effects of tea polyphenols and ascorbic acid on human lung adenocarcinoma SPC-A-1 cells.

    Science.gov (United States)

    Li, Wei; Wu, Jian-xiang; Tu, You-ying

    2010-06-01

    Tea polyphenols have been shown to have anticancer activity in many studies. In the present study, we investigated effects of theaflavin-3-3'-digallate (TF(3)), one of the major theaflavin monomers in black tea, in combination with ascorbic acid (AA), a reducing agent, and (-)-epigallocatechin-3-gallate (EGCG), the main polyphenol presented in green tea, in combination with AA on cellular viability and cell cycles of the human lung adenocarcinoma SPC-A-1 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that the 50% inhibition concentrations (IC(50)) of TF(3), EGCG, and AA on SPC-A-1 cells were 4.78, 4.90, and 30.62 micromol/L, respectively. The inhibitory rates of TF(3) combined with AA (TF(3)+AA) and EGCG combined with AA (EGCG+AA) at a molar ratio of 1:6 on SPC-A-1 cells were 54.4% and 45.5%, respectively. Flow cytometry analysis showed that TF(3)+AA and EGCG+AA obviously increased the cell population in the G(0)/G(1) phase of the SPC-A-1 cell cycle from 53.9% to 62.8% and 60.0%, respectively. TF(3)-treated cells exhibited 65.3% of the G(0)/G(1) phase at the concentration of its IC(50). Therefore, TF(3)+AA and EGCG+AA had synergistic inhibition effects on the proliferation of SPC-A-1 cells, and significantly held SPC-A-1 cells in G(0)/G(1) phase. The results suggest that the combination of TF(3) with AA or EGCG with AA enhances their anticancer activity.

  10. Afatinib treatment in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hurwitz JL

    2011-10-01

    Full Text Available Jane L Hurwitz, Paula Scullin, Lynn CampbellDepartment of Medical Oncology, Northern Ireland Cancer Centre, Belfast, UKAbstract: Despite some recent advances in the management of advanced non-small cell lung cancer (NSCLC, prognosis for these patients remains poor. Small molecule epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs have however provided a new therapeutic option in this disease setting and EGFR mutation testing is now routine practice for newly diagnosed NSCLC patients. A proportion of patients will not respond to first-generation EGFR-TKIs however, and those who do will ultimately develop resistance and disease relapse. Next-generation EGFR-TKIs which inhibit multiple members of the EGFR family are being developed in order to increase sensitivity and overcome resistance to existing agents. Afatinib (BIBW 2992 is an oral, irreversible inhibitor of EGFR and HER2 tyrosine kinases and is the most advanced of these agents in clinical development. Pre-clinical and early-phase clinical trials have demonstrated a favorable safety profile as a single agent and in combination with other anti-cancer agents, and provide evidence of clinical activity in advanced NSCLC. The LUX-Lung trials suggest that for selected patients, afatinib offers symptomatic improvement and prolonged progression-free survival, although this has not yet translated into improved overall survival. This article aims to review the use of EGFR-TKIs in the management of advanced NSCLC and the mechanisms underlying resistance to these agents. We will discuss the current pre-clinical and clinical data regarding afatinib, its potential to overcome resistance to first-generation TKIs, and its emerging role in advanced NSCLC treatment.Keywords: EGFR, tyrosine kinase inhibitor, mutation, LUX-lung

  11. Higher Incidence of Lung Adenocarcinomas Induced by DMBA in Connexin 43 Heterozygous Knockout Mice

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    Krishna Duro de Oliveira

    2013-01-01

    Full Text Available Gap junctions are communicating junctions which are important for tissue homeostasis, and their disruption is involved in carcinogenic processes. This study aimed to verify the influence of deletion of one allele of the Connexin 43 gene on cancer incidence in different organs. The 7, 12-dimethylbenzanthracene (DMBA carcinogenic model, using hebdomadary doses by gavage of 9 mg per animal, was used to induce tumors in Connexin 43 heterozygous or wild-type mice. The experiment began in the eighth week of the mice life, and all of them were euthanized when reaching inadequate physical condition, or at the end of 53 weeks. No statistical differences occurred for weight gain and cancer survival time (P=0.9853 between heterozygous and wild-type mice. Cx43+/− mice presented significantly higher susceptibility to lung cancer (P=0.0200 which was not evidenced for benign neoplasms (P=0.3449. In addition, incidence of ovarian neoplasms was 2.5-fold higher in Cx43+/− mice, although not statistically significant. Other organs showed a very similar cancer occurrence between Cx43 groups. The experiment strengthens the evidence of the relationship between Connexin 43 deficiency and carcinogenesis.

  12. Expression of Axl in Lung Adenocarcinoma and Correlation with Tumor Progression

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    Yi-Shing Shinh

    2005-12-01

    Full Text Available We used the Transwell system to select highly invasive cell lines from minimally invasive parent cells, and we compared gene expression in paired cell lines with high and low invasive potentials. Axl was relatively overexpressed in the highly invasive cell lines when compared with their minimally invasive counterparts. However, there is only limited information about the role of Axl in cancer invasion. The biologic function of Axl in tumor invasion was investigated by overexpression of full-length Axl in minimally invasive cells and by siRNA knockdown of Axl expression in highly invasive cells. Overexpression of Axl in minimally invasive cells increased their invasiveness. siRNA reduced cell invasiveness as Axl was downregulated in highly invasive cells. We further investigated the protein expression of Axl by immunohistochemistry and its correlation with clinicopathologic features. Data from a study of 58 patient specimens showed that Axl immunoreactivity was statistically significant with respect to lymph node status (P < .0001 and the patient's clinical stage (P < .0001. Our results demonstrate that Axl protein kinase seems to play an important role in the invasion and progression of lung cancer.

  13. Estrogen and insulin-like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice.

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    Tang, Hexiao; Liao, Yongde; Xu, Liqiang; Zhang, Chao; Liu, Zhaoguo; Deng, Yu; Jiang, Zhixiao; Fu, Shengling; Chen, Zhenguang; Zhou, Sheng

    2013-11-15

    Estrogen receptor (ER) and insulin-like growth factor-1 receptor (IGF-1R) signaling are implicated in lung cancer progression. Based on their previous findings, the authors sought to investigate whether estrogen and IGF-1 act synergistically to promote lung adenocarcinoma (LADE) development in mice. LADE was induced with urethane in ovariectomized Kunming mice. Tumor-bearing mice were divided into seven groups: 17β-estradiol (E2), E2+fulvestrant (Ful; estrogen inhibitor), IGF-1, IGF-1+AG1024 (IGF-1 inhibitor), E2+IGF-1, E2+IGF-1+Ful+AG1024 and control groups. After 14 weeks, the mice were sacrificed, and then the tumor growth was determined. The expression of ERα/ERβ, IGF-1, IGF-1R and Ki67 was examined using tissue-microarray-immunohistochemistry, and IGF-1, p-ERβ, p-IGF-1R, p-MAPK and p-AKT levels were determined based on Western blot analysis. Fluorescence-quantitative polymerase chain reaction was used to detect the mRNA expression of ERβ, ERβ2 and IGF-1R. Tumors were found in 93.88% (46/49) of urethane-treated mice, and pathologically proven LADE was noted in 75.51% (37/49). In the E2+IGF-1 group, tumor growth was significantly higher than in the E2 group (p < 0.05), the IGF-1 group (p < 0.05) and control group (p < 0.05). Similarly, the expression of ERβ, p-ERβ, ERβ2, IGF-1, IGF-1R, p-IGF-1R, p-MAPK, p-AKT and Ki67 at the protein and/or mRNA levels was markedly higher in the ligand group than in the ligand + inhibitor groups (all p < 0.05). This study demonstrated for the first time that estrogen and IGF-1 act to synergistically promote the development of LADE in mice, and this may be related to the activation of the MAPK and AKT signaling pathways in which ERβ1, ERβ2 and IGF-1R play important roles.

  14. Nanostructured delivery system for zinc phthalocyanine: preparation, characterization, and phototoxicity study against human lung adenocarcinoma A549 cells

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    Mariana da Volta Soares

    2011-01-01

    Full Text Available Mariana da Volta Soares1, Mainara Rangel Oliveira1, Elisabete Pereira dos Santos1, Lycia de Brito Gitirana2, Gleyce Moreno Barbosa3, Carla Holandino Quaresma3, Eduardo Ricci-Júnior11Department of Medicines, Laboratório de Desenvolvimento Galênico (LADEG, Faculty of Pharmacy, 2Laboratory of Animal and Comparative Histology, Glycobiology Research Program, Institute of Biomedical Science, 3Department of Medicines, Laboratório Multidisciplinar de Ciências Farmacêuticas, Faculty of Pharmacy, Federal University of Rio de Janeiro (UFRJ, Rio de Janeiro, BrazilAbstract: In this study, zinc phthalocyanine (ZnPc was loaded onto poly-ε-caprolactone (PCL nanoparticles (NPs using a solvent emulsification–evaporation method. The process yield and encapsulation efficiency were 74.2% ± 1.2% and 67.1% ± 0.9%, respectively. The NPs had a mean diameter of 187.4 ± 2.1 nm, narrow distribution size with a polydispersity index of 0.096 ± 0.004, zeta potential of -4.85 ± 0.21 mV, and spherical shape. ZnPc has sustained release, following Higuchi’s kinetics. The photobiological activity of the ZnPc-loaded NPs was evaluated on human lung adenocarcinoma A549 cells. Cells were incubated with free ZnPc or ZnPc-loaded NPs for 4 h and then washed with phosphate-buffered saline. Culture medium was added to the wells containing the cells. Finally, the cells were exposed to red light (660 nm with a light dose of 100 J/cm2. The cellular viability was determined after 24 h of incubation. ZnPc-loaded NPs and free photosensitizer eliminated about 95.9% ± 1.8% and 28.7% ± 2.2% of A549 cells, respectively. The phototoxicity was time dependent up to 4 h and concentration dependent at 0–5 µg ZnPc. The cells viability decreased with the increase of the light dose in the range of 10–100 J/cm2. Intense lysis was observed in the cells incubated with the ZnPc-loaded NPs and irradiated with red light. ZnPc-loaded PCL NPs are the release systems that promise photodynamic

  15. Adenocarcinoma pulmonar, dermatomiosite e síndrome miastênica de Lambert-Eaton: uma rara associação Lung adenocarcinoma, dermatomyositis, and Lambert-Eaton myasthenic syndrome: a rare combination

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    Fernanda Manente Milanez

    2008-05-01

    Full Text Available A incidência das neoplasias pulmonares vem aumentando no Brasil e no mundo, provavelmente como resultado do aumento do tabagismo. Com o maior número de casos, surgem as apresentações atípicas. Relatamos o caso de um paciente do sexo masculino, 66 anos, tabagista e hipertenso, que apresentava quadro de fraqueza muscular proximal progressiva e, em dois meses, evoluiu com disfagia para alimentos sólidos, disfonia e lesões cutâneas em forma de "V" no tórax. O radiograma de tórax mostrou um nódulo pulmonar espiculado no lobo superior direito. A análise bioquímica revelou aumento da creatinoquinase. Após exames complementares e biópsias, o paciente foi submetido à lobectomia superior direita. A histopatologia evidenciou um adenocarcinoma moderadamente diferenciado. A análise global do caso e a revisão de literatura permitem sugerir que o quadro clínico do paciente era resultante da sobreposição de duas síndromes paraneoplásicas, a saber, a dermatomiosite e a síndrome miastênica de Lambert-Eaton, secundárias a um adenocarcinoma pulmonar.The incidence of lung neoplasms is increasing in Brazil and in the world, probably as a result of the increase in smoking. Due to the greater number of cases, atypical presentations appear. We report the case of a 66-year-old hypertensive male smoker who presented progressive proximal muscular weakness and, in two months, evolved to dysphagia, dysphonia, and V-shaped skin lesions on the chest. A chest X-ray showed a spiculated pulmonary nodule in the right upper lobe. The biochemical analysis revealed elevated creatine kinase levels. After complementary tests and biopsies, the patient underwent right upper lobectomy. Histopathology showed a moderately differentiated adenocarcinoma. The overall analysis of the case and a review of the literature allow us to suggest that the clinical profile of the patient was a result of an overlap of two paraneoplastic syndromes (dermatomyositis and Lambert

  16. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression

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    Zhang Xuchao

    2010-07-01

    Full Text Available Abstract Background The anaplastic lymphoma kinase (ALK gene is frequently involved in translocations that lead to gene fusions in a variety of human malignancies, including lymphoma and lung cancer. Fusion partners of ALK include NPM, EML4, TPM3, ATIC, TFG, CARS, and CLTC. Characterization of ALK fusion patterns and their resulting clinicopathological profiles could be of great benefit in better understanding the biology of lung cancer. Results RACE-coupled PCR sequencing was used to assess ALK fusions in a cohort of 103 non-small cell lung carcinoma (NSCLC patients. Within this cohort, the EML4-ALK fusion gene was identified in 12 tumors (11.6%. Further analysis revealed that EML4-ALK was present at a frequency of 16.13% (10/62 in patients with adenocarcinomas, 19.23% (10/52 in never-smokers, and 42.80% (9/21 in patients with adenocarcinomas lacking EGFR and KRAS mutations. The EML4-ALK fusion was associated with non-smokers (P = 0.03, younger age of onset (P = 0.03, and adenocarcinomas without EGFR/KRAS mutations (P = 0.04. A trend towards improved survival was observed for patients with the EML4-ALK fusion, although it was not statistically significant (P = 0.20. Concurrent deletion in EGFR exon 19 and fusion of EML4-ALK was identified for the first time in a Chinese female patient with an adenocarcinoma. Analysis of ALK expression revealed that ALK mRNA levels were higher in tumors positive for the EML-ALK fusion than in negative tumors (normalized intensity of 21.99 vs. 0.45, respectively; P = 0.0018. However, expression of EML4 did not differ between the groups. Conclusions The EML4-ALK fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking EGFR/KRAS mutations. The EML4-ALK fusion appears to be tightly associated with ALK mRNA expression levels. RACE-coupled PCR sequencing is a highly sensitive method that could be used clinically for the identification of EML4-ALK

  17. Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21

    Institute of Scientific and Technical Information of China (English)

    Jiang-Yong Yu; Si-Fan Yu; Shu-Hang Wang; Hua Bai; Jun Zhao; Tong-Tong An; Jian-Chun Duan; Jie Wang

    2016-01-01

    Background: Epidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibi‑tor (EGFR‑TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R muta‑tions exhibit different responsiveness to EGFR‑TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR‑TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes. Methods: Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR‑TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high‑performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next‑generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations. Results: Of the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR‑TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression‑free survival (PFS) after first‑line EGFR‑TKI treatment (14.4 vs. 11.4 months,P= 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR‑TKI treatment and 134 after EGFR‑TKI treatment, and there was no significant difference in the co‑exist‑ence of T790M mutation with EGFR 19 del and L858R mutations

  18. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma.

    Science.gov (United States)

    Lee, Su-Min; Joshi, Jay; Wolfe, Konrad; Acher, Peter; Liyanage, Sidath H

    2016-06-01

    We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  19. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma

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    Su-Min Lee

    2016-06-01

    Full Text Available We present a case of nonspecific granulomatous prostatitis (GP, a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  20. Monitoring KRAS mutations in circulating DNA and tumor cells using digital droplet PCR during treatment of KRAS-mutated lung adenocarcinoma.

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    Guibert, Nicolas; Pradines, Anne; Farella, Magali; Casanova, Anne; Gouin, Sandrine; Keller, Laura; Favre, Gilles; Mazieres, Julien

    2016-10-01

    Liquid biopsies are a new non-invasive strategy to detect and monitor the biology of non-small-cell lung cancer (NSCLC) in the era of personalized medicine. KRAS is an oncogenic driver that is mutated in 30% of NSCLCs and is associated with a poor prognosis. 62 samples from 32 patients, treated for metastatic KRAS-mutated lung adenocarcinoma, had DNA extracted from plasma and circulating tumor cells (CTCs) prospectively tested for the presence of KRAS mutations using droplet digital PCR. A KRAS mutation was detected in 82% of patients. Sensitivity was 78% for circulating free DNA (cfDNA) and 34% for CTCs. The presence of a KRAS mutation in cfDNA was correlated with a poor response to chemotherapy or targeted therapy. When a KRAS-mutated-DNA was detected and then monitored in cfDNA, its variation during targeted or conventional therapy was correlated with response, according to RECIST criteria, in 87.5% of cases (n=14/16), whereas this correlation was observed in 37.5% of cases for CTCs (n=3/8). We report the usefulness of using digital droplet PCR on liquid biopsies to predict and monitor responses to treatment of KRAS-mutated lung adenocarcinoma. ctDNA was much more sensitive than CTCs in this context.

  1. Downregulation of peroxiredoxin-1 by β-elemene enhances the radiosensitivity of lung adenocarcinoma xenografts.

    Science.gov (United States)

    Li, Guoquan; Xie, Bingbing; Li, Xiaolong; Chen, Yinghai; Xu, Yinghui; Xu-Welliver, Meng; Zou, Lijuan

    2015-03-01

    β-elemene, the active component of elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane), is a naturally occurring compound isolated from the traditional Chinese medicinal herb Curcuma wenyujin. Studies have confirmed that β-elemene enhances the radiosensitivity of lung cancer cell lines such as A549, by multiple pathways; however, their underlying mechanisms and pathways are yet to be elucidated. In the present study, two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry were used to profile the different proteins in A549 cell xenograft models of both treatment groups. The protein/mRNA expression was assessed by reverse transcription-polymerase chain reaction and western blotting techniques in tumor samples from all treatment groups. As a critical player in redox regulation of cancer cells, inhibition of peroxiredoxin-1 (Prx-1) may be an effective option for enhancing the tumor response to radiation. We further verified Prx-1 expression at the transcription and translation levels. β-elemene at a dose of 45 mg/kg had little effect on the Prx-1 protein expression, which was correlated with a moderate antitumor effect. However, a 45 mg/kg dose of β-elemene significantly inhibited the Prx-1 mRNA expression, thereby suggesting a possible influence on the transcriptional process, and radiation significantly increased the Prx-1 mRNA/protein expression compared to the control group (p<0.01). Notably, Prx-1 mRNA/protein expression was significantly lower in the β-elemene/radiation co-treatment group compared to the baseline levels in the control group (p<0.01). These results suggest that radiation-induced Prx-1 expression is directly or indirectly suppressed by β-elemene, thus suggesting a new pathway by which to reverse radioresistance.

  2. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3......) has been shown of value in NSCLC, but evidence is not uniform. Accordingly, we explored the predictive role of TUBB3 in advanced NSCLC....

  3. NF-{kappa}B signaling is activated and confers resistance to apoptosis in three-dimensionally cultured EGFR-mutant lung adenocarcinoma cells

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    Sakuma, Yuji, E-mail: ysakuma@gancen.asahi.yokohama.jp [Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama (Japan); Yamazaki, Yukiko; Nakamura, Yoshiyasu; Yoshihara, Mitsuyo; Matsukuma, Shoichi; Koizume, Shiro; Miyagi, Yohei [Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama (Japan)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer EGFR-mutant cells in 3D culture resist EGFR inhibition compared with suspended cells. Black-Right-Pointing-Pointer Degradation of I{kappa}B and activation of NF-{kappa}B are observed in 3D-cultured cells. Black-Right-Pointing-Pointer Inhibiting NF-{kappa}B enhances the efficacy of the EGFR inhibitor in 3D-cultured cells. -- Abstract: Epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells in suspension undergo apoptosis to a greater extent than adherent cells in a monolayer when EGFR autophosphorylation is inhibited by EGFR tyrosine kinase inhibitors (TKIs). This suggests that cell adhesion to a culture dish may activate an anti-apoptotic signaling pathway other than the EGFR pathway. Since the microenvironment of cells cultured in a monolayer are substantially different to that of cells existing in three-dimension (3D) in vivo, we assessed whether two EGFR-mutant lung adenocarcinoma cell lines, HCC827 and H1975, were more resistant to EGFR TKI-induced apoptosis when cultured in a 3D extracellular matrix (ECM) as compared with in suspension. The ECM-adherent EGFR-mutant cells in 3D were significantly less sensitive to treatment with WZ4002, an EGFR TKI, than the suspended cells. Further, a marked degradation of I{kappa}B{alpha}, the inhibitor of nuclear factor (NF)-{kappa}B, was observed only in the 3D-cultured cells, leading to an increase in the activation of NF-{kappa}B. Moreover, the inhibition of NF-{kappa}B with pharmacological inhibitors enhanced EGFR TKI-induced apoptosis in 3D-cultured EGFR-mutant cells. These results suggest that inhibition of NF-{kappa}B signaling would render ECM-adherent EGFR-mutant lung adenocarcinoma cells in vivo more susceptible to EGFR TKI-induced cell death.

  4. Class III β-tubulin in advanced NSCLC of adenocarcinoma subtype predicts superior outcome in a randomized trial

    DEFF Research Database (Denmark)

    Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

    2011-01-01

    Platinum-based doublets are the cornerstone of treatment in advanced non-small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III ß-tubulin (TUBB3...

  5. Relationship between Insulin-Like Growth Factor Signaling Pathway and Drug Resistance of EGFR-TKI Therapy in Lung Adenocarcinoma%IGF信号通路与肺腺癌 EGFR-TKI治疗获得性耐药的关系

    Institute of Scientific and Technical Information of China (English)

    王永涛; 李波清

    2016-01-01

    目的:探究胰岛素样生长因子信号通路在肺腺癌EGFR-TKI治疗获得性耐药中的作用。方法采用免疫组织化学SP法检测64例肺腺癌组织和16例正常肺组织中IGF1R和EGFR的表达,ELISA法检测晚期肺腺癌患者血清中IGF1的含量。结果 IGF1R在肺腺癌组织中的表达与对照组无显著差异,IGF1R的表达与患者各临床病理参数无显著相关性(P>0.05)。 EGFR在肺腺癌组织中的表达显著高于对照组,且EGFR的表达受肿瘤分化程度、浸润深度、淋巴结转移及分期的影响(P<0.05)。 IGF1R与EGFR在肺腺癌患者中的表达显著相关(P<0.05);在晚期接受EGFR-TKI治疗的肺腺癌患者中,病情进展后血清中IGF1的含量较治疗前显著增高(P<0.05)。结论胰岛素样生长因子信号通路在肺腺癌患者EGFR-TKI治疗获得性耐药中起一定作用。%Objective To explore the relationship between insulin-like growth factor( IGF) signaling pathway drug re-sistance of EGFR-TKI therapy in lung adenocarcinoma.Methods The expression of IGF1R and EGFR were detected by strepta-vidin perotridase in 64 cases of lung adenocarcinoma tissues and 16 cases of normal lung tissues.The content of IGF1 in serum of patients with advanced lung adenocarcinoma were detected by ELISA.Results There were no significant differences in IGF1R expression between the 2 groups and the expression of IGF1R also had no significant correlation with clinicopathologic parameters (P>0.05).The expression of EGFR in the lung adenocarcinoma was significantly higher than that of the control group and was associated with degrees of differentiation,depth of invasion,lymph nodes metastasis and stages (P<0.05).The expression of IGF1R in patients with lung adenocarcinoma was significantly associated with EGFR (P<0.05).The serum level of IGF1 in pa-tients with advanced lung adenocarcinoma significantly increased after resistance to EGFR-TKI therapy (P<0

  6. Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine.

    Science.gov (United States)

    Lu, Gang; Liao, Jie; Yang, Guangyu; Reuhl, Kenneth R; Hao, Xingpei; Yang, Chung S

    2006-12-01

    The present study investigated the inhibitory effects of Polyphenon E [a standardized green tea polyphenol preparation containing 65% (-)-epigallocatechin-3-gallate] and caffeine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor progression from adenoma to adenocarcinoma. Female A/J mice were treated with a single dose of NNK (103 mg/kg body weight, i.p.) and kept for 20 weeks for the mice to develop lung adenomas. The mice were then given a solution of 0.5% Polyphenon E or 0.044% caffeine as the sole source of drinking fluid until week 52. Both treatments significantly decreased the number of visible lung tumors. Histopathologic analysis indicated that Polyphenon E administration significantly reduced the incidence (by 52%) and multiplicity (by 63%) of lung adenocarcinoma. Caffeine also showed marginal inhibitory effects in incidence and multiplicity of adenocarcinoma (by 48% and 49%, respectively). Markers of cell proliferation, apoptosis, and related cell signaling were studied by immunohistochemistry, and the labeling index and staining intensity were quantified by the Image-Pro system. Polyphenon E and caffeine treatment inhibited cell proliferation (by 57% and 50%, respectively) in adenocarcinomas, enhanced apoptosis in adenocarcinomas (by 2.6- and 4-fold, respectively) and adenomas (both by 2.5-fold), and lowered levels of c-Jun and extracellular signal-regulated kinase (Erk) 1/2 phosphorylation. In the normal lung tissues, neither agent had a significant effect on cell proliferation or apoptosis. The results show that tea polyphenols (and perhaps caffeine) inhibit the progression of NNK-induced lung adenoma to adenocarcinoma. This effect is closely associated with decreased cell proliferation, enhanced apoptosis, and lowered levels of c-Jun and Erk1/2 phosphorylation.

  7. Complete Response after Treatment with Neoadjuvant Chemoradiation with Prolonged Chemotherapy for Locally Advanced, Unresectable Adenocarcinoma of the Pancreas

    Directory of Open Access Journals (Sweden)

    Tiffany A. Pompa

    2017-01-01

    Full Text Available Surgery is the only chance for cure in pancreatic ductal adenocarcinoma. In unresectable, locally advanced pancreatic cancer (LAPC, the National Comprehensive Cancer Network (NCCN suggests chemotherapy and consideration for radiation in cases of unresectable LAPC. Here we present a rare case of unresectable LAPC with a complete histopathological response after chemoradiation followed by surgical resection. A 54-year-old female presented to our clinic in December 2013 with complaints of abdominal pain and 30-pound weight loss. An MRI demonstrated a mass in the pancreatic body measuring 6.2×3.2 cm; biopsy revealed proven ductal adenocarcinoma. Due to splenic vein/artery and contiguous celiac artery encasement, she was deemed surgically unresectable. She was started on FOLFIRINOX therapy (three cycles, intensity modulated radiation to a dose of 54 Gy in 30 fractions concurrent with capecitabine, followed by FOLFIRI, and finally XELIRI. After 8 cycles of ongoing XELIRI completed in March 2015, restaging showed a remarkable decrease in tumor size, along with PET-CT revealing no FDG-avid uptake. She was reevaluated by surgery and taken for definitive resection. Histopathological evaluation demonstrated a complete R0 resection and no residual tumor. Based on this patient and literature review, this strategy demonstrates potential efficacy of neoadjuvant chemoradiation with prolonged chemotherapy, followed by surgery, which may improve outcomes in patients deemed previously unresectable.

  8. Two-gene signature improves the discriminatory power of IASLC/ATS/ERS classification to predict the survival of patients with early-stage lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Sun Y

    2016-07-01

    Full Text Available Yifeng Sun,1,* Likun Hou,2,* Yu Yang,1 Huikang Xie,2 Yang Yang,1 Zhigang Li,1 Heng Zhao,1 Wen Gao,3 Bo Su4 1Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiaotong University, 2Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 3Department of Thoracic Surgery, Shanghai Huadong Hospital, Fudan University School of Medicine, Shanghai, 4Central Lab, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: In this study, we investigated the contribution of a gene expression–based signature (composed of BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, SH3BGR to survival prediction for early-stage lung adenocarcinoma categorized by the new International Association for the Study of Lung Cancer (IASLC/the American Thoracic Society (ATS/the European Respiratory Society (ERS classification. We also aimed to verify whether gene signature improves the risk discrimination of IASLC/ATS/ERS classification in early-stage lung adenocarcinoma. Patients and methods: Total RNA was extracted from 93 patients with pathologically confirmed TNM stage Ia and Ib lung adenocarcinoma. The mRNA expression levels of ten genes in the signature (BAG1, BRCA1, CDC6, CDK2AP1, ERBB3, FUT3, IL11, LCK, RND3, and SH3BGR were detected using real-time polymerase chain reaction. Each patient was categorized according to the new IASLC/ATS/ERS classification by accessing hematoxylin–eosin-stained slides. The corresponding Kaplan–Meier survival analysis by the log-rank statistic, multivariate Cox proportional hazards modeling, and c-index calculation were conducted using the programming language R (Version 2.15.1 with the “risksetROC” package. Results: The multivariate analysis demonstrated that the risk factor of the ten-gene expression signature can significantly improve the discriminatory

  9. Evaluating the significance of density, localization, and PD-1/PD-L1 immunopositivity of mononuclear cells in the clinical course of lung adenocarcinoma patients with brain metastasis

    DEFF Research Database (Denmark)

    Téglási, Vanda; Reiniger, Lilla; Fabian, Katalin

    2017-01-01

    therapeutic strategies with these agents. The aim of this study was to characterize the distribution of ICs and determine the expression of the checkpoint molecules programmed death protein 1 (PD-1) and its ligand, PD-L1, in brain metastasis of lung adenocarcinoma (LUAD) patients and to analyze......Background. Management of lung cancer patients who suffer from brain metastases represents a major challenge. Considering the promising results with immune checkpoint inhibitor treatment, evaluating the status of immune cell (IC) infiltrates in the prognosis of brain metastasis may lead to better...... their clinicopathological correlations. Methods. We determined the presence of peritumoral mononuclear cells (mononuclear ring) and the density of intratumoral stromal mononuclear cells on brain metastasis tissue sections of 208 LUAD patients. PD-L1/PD-1 expressions were analyzed by immunohistochemistry. Results...

  10. [A case of cardiac tamponade due to malignant pericarditis with lung adenocarcinoma, effectively treated with pericardial drainage and pemetrexed plus cisplatin chemotherapy].

    Science.gov (United States)

    Yoshida, Kazufumi; Teramoto, Shinji

    2015-01-01

    A 68-year-old man was diagnosed with non small cell lung cancer in May 2013. Although the patient was negative for EGFR mutation, he wished to undergo treatment with gefitinib and erlotinib as first-line therapy. However, one year later, he was admitted to our hospital because of cardiac tamponade due to malignant pericarditis. He received pericardial drainage, after which his condition was stabilized. He was diagnosed with lung adenocarcinoma by cytology of pericardial effusion and treated with pemetrexed plus cisplatin as second-line therapy. Thereafter, the malignant effusion was decreased and the primary lesion was regressed. He received six courses of chemotherapy, however, brain metastases and bone metastases appeared. The brain metastases were controlled with gamma knife radiosurgery and he received carboptatin-paclitaxel plus bevacizumab as third-line therapy. The patient is currently receiving chemotherapy without any recurrence of malignant pericarditis or cardiac tamponade.

  11. Curcumol induces apoptosis in SPC-A-1 human lung adenocarcinoma cells and displays anti-neoplastic effects in tumor bearing mice.

    Science.gov (United States)

    Tang, Qi-Ling; Guo, Ji-Quan; Wang, Qi-You; Lin, Hai-Shu; Yang, Zhou-Ping; Peng, Tong; Pan, Xue-Diao; Liu, Bing; Wang, Su-Jun; Zang, Lin-Quan

    2015-01-01

    Curcumol is a sesquiterpene originally isolated from curcuma rhizomes, a component of herbal remedies commonly used in oriental medicine. Its beneficial pharmacological activities have attract significant interest recently. In this study, anti-cancer activity of curcumol was examined with both in vitro and in vivo models. It was found that curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses. Interestingly, curcumol did not display growth inhibition in MRC-5 human embryonic lung fibroblasts, suggesting the anti-proliferative effects of curcumol were specific to cancer cells. Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity. In conclusion, curcumol appears a favorable anti-cancer candidate for further development.

  12. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Shang-Jyh [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Su, Jen-Liang [Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung, Taiwan (China); Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan (China); Department of Biotechnology, Asia University, Taichung, Taiwan (China); Chen, Chi-Kuan [Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua [Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Bien, Mauo-Ying [School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Yang, Shun-Fa [Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chien, Ming-Hsien, E-mail: mhchien1976@gmail.com [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2012-05-15

    The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. -- Highlights: ► Osthole treatment inhibits lung adenocarcinoma cells migration and invasion. ► Osthole reduces the expression and proteolytic activity of MMP-9. ► Osthole inhibits MMP-9 transcription via suppression of NF-κB binding activity. ► Osthole

  13. Evaluation of EGFR and RTK signaling in the electrotaxis of lung adenocarcinoma cells under direct-current electric field stimulation.

    Science.gov (United States)

    Tsai, Hsieh-Fu; Huang, Ching-Wen; Chang, Hui-Fang; Chen, Jeremy J W; Lee, Chau-Hwang; Cheng, Ji-Yen

    2013-01-01

    Physiological electric field (EF) plays a pivotal role in tissue development and regeneration. In vitro, cells under direct-current electric field (dcEF) stimulation may demonstrate directional migration (electrotaxis) and long axis reorientation (electro-alignment). Although the biophysical models and biochemical signaling pathways behind cell electrotaxis have been investigated in numerous normal cells and cancer cells, the molecular signaling mechanisms in CL1 lung adenocarcinoma cells have not been identified. Two subclones of CL1 cells, the low invasive CL1-0 cells and the highly invasive CL 1-5 cells, were investigated in the present study. CL1-0 cells are non-electrotactic while the CL 1-5 cells are anodally electrotactic and have high expression level of epidermal growth factor receptor (EGFR), in this study, we investigated the generally accepted hypothesis of receptor tyrosine kinase (RTK) activation in the two cell lines under dcEF stimulation. Erbitux, a therapeutic drug containing an anti-EGFR monoclonal antibody, cetuximab, was used to investigate the EGFR signaling in the electrotaxis of CL 1-5 cells. To investigate RTK phosphorylation and intracellular signaling in the CL1 cells, large amount of cellular proteins were collected in an airtight dcEF stimulation device, which has advantages of large culture area, uniform EF distribution, easy operation, easy cell collection, no contamination, and no medium evaporation. Commercial antibody arrays and Western blotting were used to study the phosphorylation profiles of major proteins in CL1 cells under dcEF stimulation. We found that electrotaxis of CL 1-5 cells is serum independent and EGFR independent. Moreover, the phosphorylation of Akt and S6 ribosomal protein (rpS6) in dcEF-stimulated CL1 cells are different from that in EGF-stimulated cells. This result suggests that CL1 cells' response to dcEF stimulation is not through EGFR-triggered pathways. The new large-scale dcEF stimulation device developed

  14. KRAS mutation-positive bronchial surface epithelium (BSE)-type lung adenocarcinoma with strong expression of TTF-1: a case providing a further insight as for the role of TTF-1 in the oncogenesis.

    Science.gov (United States)

    Takanashi, Yusuke; Tajima, Shogo; Hayakawa, Takamitsu; Neyatani, Hiroshi; Funai, Kazuhito

    2015-01-01

    Bronchial surface epithelium (BSE)-type lung adenocarcinoma is a subtype of non-terminal respiratory unit (TRU)-type lung adenocarcinoma originating in the bronchial surface epithelium. However, there are few known cases of BSE-type adenocarcinoma with marked expression of thyroid transcription factor-1 (TTF-1). This paper describes a very rare case of KRAS mutation-positive BSE-type adenocarcinoma that exhibited strong expression of TTF-1 that was putatively involved in oncogenesis. An 84-year-old woman, a never smoker, was referred to our hospital because of an abnormal chest radiograph. Chest computed tomography (CT) showed a solid mass lesion, 15 mm × 10 mm, with a relatively smooth margin in the left upper lobe. The patient underwent partial resection of the left upper lobe for strongly suspected lung cancer with a clinical stage of cT1aN0M0. Histopathological findings showed continuous migration of papillary, hyperplastic, atypical columnar tumor cells originating from normal bronchial surface epithelium, leading to a diagnosis of BSE-type adenocarcinoma. TTF-1 was strongly expressed in almost 100% of the tumor cells, which tested positive for the KRAS mutation. TTF-1 has recently attracted attention as an oncogene, and it is purportedly involved in the carcinogenesis and survival of lung adenocarcinoma cells. There is typically an inverse correlation between the respective expressions of KRAS and TTF-1, but in the present study, they appeared simultaneously and were both putatively involved as oncogenic driver alterations. This case is important in that it sheds some light on the largely unknown pathogenic mechanism of BSE-type adenocarcinoma.

  15. Prognostic impact of nomogram based on whole tumour size, tumour disappearance ratio on CT and SUVmax on PET in lung adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Song, So Hee; Lee, Ho Yun; Kim, Eun Young; Lee, Kyung Soo [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Gangnam-Gu, Seoul (Korea, Republic of); Ahn, Joong Hyun [Samsung Biomedical Research Institute, Biostatistics Team, Seoul (Korea, Republic of); Lee, Geewon [Pusan National University Hospital, Pusan National University School of Medicine, Department of Radiology and Medical Research Institute, Busan (Korea, Republic of); Choi, Joon Young [Sungkyunkwan University School of Medicine, Departments of Nuclear Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kang, Jun [Catholic University of Korea, Department of Pathology, Inchun St. Mary' s Hospital, College of Medicine, Inchun (Korea, Republic of); Han, Joungho [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea, Republic of); Kwon, O.J. [Sungkyunkwan University School of Medicine, Division of Respiratory and Critical Medicine of the Department of Internal Medicine, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Hong Kwan; Choi, Yong Soo; Kim, Jhingook; Shim, Young Mog [Sungkyunkwan University School of Medicine, Department of Thoracic and Cardiovascular Surgery, Samsung Medical Center, Seoul (Korea, Republic of)

    2016-06-15

    Lung adenocarcinoma frequently manifests as subsolid nodules, and the solid portion and ground-glass-opacity (GGO) portion on CT have different prognostic significance. Therefore, current T descriptor, defined as the whole tumour diameter without discrimination between solid and GGO, is insufficient. We aimed to determine the prognostic significance of solid tumour size and attempt to include prognostic factors such as tumour disappearance rate (TDR) on CT and SUVmax on PET/CT. Five hundred and ninety-five patients with completely resected lung adenocarcinoma were analyzed. We developed a nomogram using whole tumour size, TDR, and SUVmax. External validation was performed in another 102 patients. In patients with tumours measuring ≤2 cm and >2 to 3 cm, disease free survival (DFS) was significantly associated with solid tumour size (P < 0.001), but not with whole tumour size (P = 0.052). Developed nomogram was significantly superior to the conventional T stage (area under the curve of survival ROC; P = 0.013 by net reclassification improvement) in stratification of patient survival. In the external validation group, significant difference was noted in DFS according to proposed T stage (P = 0.009). Nomogram-based T descriptors provide better prediction of survival and assessment of individual risks than conventional T descriptors. (orig.)

  16. MiR-100 resensitizes docetaxel-resistant human lung adenocarcinoma cells (SPC-A1) to docetaxel by targeting Plk1.

    Science.gov (United States)

    Feng, Bing; Wang, Rui; Chen, Long-Bang

    2012-04-28

    MicroRNAs (miRNAs) expression correlates with biological characteristics of both normal cells and cancer cells, but their roles in cancer chemoresistance remain unclear. By microarray analysis, miR-100 was found significantly down-regulated in docetaxel-resistant SPC-A1/DTX cells compared with parental SPC-A1 cells. Ectopic miR-100 expression resensitized SPC-A1/DTX cells to docetaxel by suppression of cell proliferation and induction of cell arrest in G(2)/M phase and apoptosis. Knock-down of Plk1, which was a direct target of miR-100, yielded similar effects as that of ectopic miR-100 expression. The inverse correlation between miR-100 and Plk1 expression was also detected in nude mice SPC-A1/DTX tumor xenografts and clinical lung adenocarcinoma tissues and was proved to be related with the in vivo response to docetaxel. Thus, our results suggested that down-regulation of miR-100 could lead to Plk1 over-expression and eventually to docetaxel chemoresistance of human lung adenocarcinoma.

  17. Apoptotic activity of genistein on human lung adenocarcinoma SPC-A-1 cells and preliminary exploration of its mechanisms using microarray.

    Science.gov (United States)

    Zou, Huafei; Zhan, Shuxuan; Cao, Kaiming

    2008-11-01

    Soy isoflavone genistein is active against certain solid malignancies, but its direct effect on lung adenocarcinoma and its mechanisms of action remain to be elucidated. In the present study, using the human lung adenocarcinoma cell line SPC-A-1, we found that genistein decreased SPC-A-1 cell viability in both a dose and time dependent manner. Flow cytometry analysis revealed that genistein significantly induced arrest of SPC-A-1 cells at the G2/M phase of the cell cycle. Furthermore, through DNA fragmentation and TUNEL assays, we demonstrated that the addition of genistein led to SPC-A-1 apoptosis in both a dose and time dependent manner. Finally, the apoptosis pathway-related gene expression profile affected by genistein was investigated using the oligonucleotide microarray method. The result showed that the expression profile of 20 genes (ratio of genistein group/control group >2 or <0.5) related to the apoptotic pathways changed. These genes, mainly consisting of the Bcl-2 family and TNF ligand and receptor family, are involved in regulation of the apoptosis process.

  18. [Inhibition Function of Dominant-negative Mutant Gene Survivin-D53A to SPC-A1 Lung Adenocarcinoma Xenograft in Nude Mice Models].

    Science.gov (United States)

    Yu, Min; Peng, Xingchen; Lu, You; Huang, Meijuan

    2015-06-01

    Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i. v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.

  19. Engagement of overexpressed Her2 with GEP100 induces autonomous invasive activities and provides a biomarker for metastases of lung adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Toshi Menju

    Full Text Available Overexpression of Her2/ErbB2/Neu in cancer is often correlated with recurrent distant metastasis, although the mechanism still remains largely elusive. We have previously shown that EGFR, when tyrosine-phosphorylated, binds to GEP100/BRAG2 to activate Arf6, which induces cancer invasion and metastasis. We now show that overexpressed Her2 in lung adenocarcinoma cells also employs GEP100. Like EGFR-GEP100 binding, this association is primarily mediated by the pleckstrin homology (PH domain of GEP100 and Tyr1139/Tyr1196 of Her2. Tyr1139/Tyr1196 are autonomously phosphorylated, when Her2 is overexpressed. Accordingly, invasive activities mediated by the Her2-GEP100 pathway are not dependent on external factors. Blocking Her2-GEP100 binding, as well as its signaling pathway all inhibit cancer invasive activities. Moreover, our clinical study indicates that co-overexpression of Her2 with GEP100 in primary lung adenocarcinomas of patients is correlated with the presence of their node-metastasis with a statistical significance. Since the GEP100 PH domain interacts with both Her2 and EGFR, targeting this domain may provide novel cancer therapeutics.

  20. Radio(chemotherapy in locally advanced nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Markus Glatzer

    2016-03-01

    Full Text Available Definitive radiochemotherapy is the standard treatment for many patients with locally advanced nonsmall cell lung cancer (NSCLC. Treatment outcomes have improved over the last decades. Several treatment regimens have been shown effective and safe. This review summarises the results of significant studies between 1996 and 2015 on concomitant and sequential radiochemotherapy regimens and radiation dose per fraction. Beside therapy regimens, optimised radiotherapy planning is indispensable to improve outcome and minimise radiation-induced toxicity. An insight into the rationale of radiotherapy planning for stage III NSCLC is also provided.

  1. 人肺腺癌多西他赛耐药机制的研究%Research on the mechanisms of docetaxel-resistant human lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    陈龙邦

    2012-01-01

    深入研究肺腺癌对多西他赛(docetaxel,DTX)耐药的分子机制,不仅有助于筛选出可用于临床指导DTX个体化用药的分子靶标,也可为耐药的干预策略研究提供研究方向.笔者课题组采用体外逐步提高DTX浓度的方法诱导建立了稳定传代的人肺腺癌SPC-A1耐DTX细胞系SPC-A1/DTX,并从细胞形态、化疗敏感性、增殖、凋亡、细胞周期、药物转运等方面比较了亲本细胞与耐药细胞间的差异.进一步通过基因芯片及miRNA芯片分析,筛选出耐药细胞中差异表达显著的基因(如ING4)以及miRNA(如miR-200b、miR-100),在体内、外模型中进行功能获得性和(或)缺失性研究,证实ING4表达下调、miR-200b/E2F3及miR-100/Plk-1通路的异常参与了肺腺癌细胞DTX耐药表型的形成.%In-depth study of the molecular mechanisms of lung adenocarcinoma resistance to docetaxel ( DTX ) not only offers us the new promising targets of individualized treatment for lung adenocarcinoma patients, but also provides new insights into clinical intervention strategies. In this study, the docetaxel-resistant human lung adenocarcinoma cell line SPC-Al/DTX was derived from parental SPC-A1 cell line by continuous exposure to increasing concentration of DTX in vitro. Differences in biological characteristics, such as cell morphology, chemosensitivity, cell proliferation, apoptosis, cell cycle, and drug transportation were compared between SPC-A1 and SPC-A1/DTX cell lines. Based on gene expression-and miRNA-microarray analysis, differentially expressed genes, such as ING4 and miRNAs ( e. G. miR-200b and miR-100) were screened out from SPC-A1/DTX cells. With further gain-of-function and (or) loss-of-function studies of these molecules in both in vitro and in vivo models, we provided potential mechanistic explanations for DTX resistance of human lung adenocarcinoma. It was found that down-regulation of ING4 gene and abnormalities of crosstalk between miR-200b and E2F3 gene

  2. [Peripheral lung adenocarcinoma versus squamous cell carcinoma: evaluation with first-pass perfusion imaging using 64-detector row CT].

    Science.gov (United States)

    Li, Yuan; Yang, Zhigang; Chen, Tianwu; Yu, Jianqun; Deng, Yuping; Li, Zhenlin

    2009-04-01

    The aim of this study was to elucidate the characteristics of time attenuation curve and CT perfusion parameters for pulmonary adenocarcinomas and squamous cell carcinomas. 58 cases of pulmonary adenocarcinomas and 27 cases of squamous cell carcinomas underwent first pass CT perfusion imaging with 64-row MDCT. Data were analyzed using commercial software to generate time attenuation curve (TAC) and CT perfusion parameters, including perfusion, peak enhanced (PE), time to peak (TTP), and blood volume (BV). For TAC, there were 36.2% of type I and 63.8% of type II in adenocarcinomas, while there were 22.2% of type I and 77.8% of type II in squamous cell carcinomas. There was not significant difference (P>0.05). Perfusion, PE, TTP and BV of adenocarcinomas were 63.2 +/- 45.4 ml x min(-1) x ml(-1), 60.2 +/- 46.6 Hu, 34.8 +/- 10.2 s and 34.3 +/- 23.6 ml x 100 g(-1), respectively, while 54.3 +/- 50.2 ml x min(-1) x ml(-1), 48.5 +/- 34.9 Hu, 36.1 +/- 11.2 s and 27.6 +/- 21.7 ml x 100 g(-1), for squamous cell carcinoma, respectively. No significant differences were found between groups (P>0.05). No significant differences in TAC and CT perfusion parameters were found between adenocarcinomas and squamous cell carcinomas.

  3. Establishment of an experimental human lung adenocarcinoma cell line SPC-A-1BM with high bone metastases potency by {sup 99m}Tc-MDP bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Yang Shunfang [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China)], E-mail: yzyg@sh163.net; Dong Qianggang [Laboratory of Mol-diagnosis, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Yao Ming [Laboratory of Pathology, Shanghai Cancer Institute of Shanghai Jiaotong University, Shanghai 200032 (China); Shi Meiping [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Ye Jianding [Department of Radiology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Zhao Langxiang [Department of Pathology, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Su Jianzhong; Gu Weiyong [Shanghai Thoracic Tumor Institute, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Xie Wenhui [Department of Nuclear Medicine, Shanghai Chest Hospital of Shanghai Jiaotong University, Shanghai 200030 (China); Wang Kankan; Du Yanzhi [State Key Laboratory of Medical Genomics, Ruijin Hospital of Shanghai Jiaotong University, Shanghai 200025 (China); Li Yao [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China); Huang Yan [State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433 (China)], E-mail: huangyan@fudan.edu.cn

    2009-04-15

    Background: Bone metastasis is one of the most common clinical phenomena of late stage lung cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal and cell model. This study aims to establish human lung adenocarcinoma cell line with highly bone metastases potency with {sup 99m}Tc-MDP bone scintigraphy. Methods: The human lung adenocarcinoma cancer cells SPC-A-1 were injected into the left cardiac ventricle of NIH-Beige-Nude-XID (NIH-BNX) immunodeficient mice. The metastatic lesions of tumor-bearing mice were imaged with {sup 99m}Tc-MDP bone scintigraphy on a Siemens multi-single photon emission computed tomography. Pinhole images were acquired on a GZ-B conventional gamma camera with a self-designed pinhole collimator. The mice with bone metastasis were sacrificed under deep anesthesia, and the lesions were resected. Bone metastatic cancer cells in the resected lesions were subjected for culture and then reinoculated into the NIH-BNX mice through left cardiac ventricle. The process was repeated for eight cycles to obtain a novel cell subline SPC-A-1BM. Real-time polymerase chain reaction (PCR) was used to compare the gene expression differences in the parental and SPC-A-1BM cells. Results: The bone metastasis sites were successfully revealed by bone scintigraphy. The established bone metastasis cell line SPC-A-1BM had a high potential to metastasize in bone, including mandible, humerus, thoracic vertebra, lumbar, femur, patella, ilium and cartilage rib. The expression level of vascular endothelial growth factor gene family, Bcl-2 and cell adhesion-related genes ECM1, ESM1, AF1Q, SERPINE2 and FN1 were examined. Gene expression difference was found between parental and bone-seeking metastasis cell SPC-A-1BM, which indicates SPC-A-1BM has metastatic capacity vs. its parental cells. Conclusion: SPC-A-1BM is a bone-seeking metastasis human lung adenocarcinoma cell line. Bone scintigraphy may be used as

  4. Claudin-18 inhibits cell proliferation and motility mediated by inhibition of phosphorylation of PDK1 and Akt in human lung adenocarcinoma A549 cells.

    Science.gov (United States)

    Shimobaba, Shun; Taga, Saeko; Akizuki, Risa; Hichino, Asami; Endo, Satoshi; Matsunaga, Toshiyuki; Watanabe, Ryo; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Sugatani, Junko; Ikari, Akira

    2016-06-01

    Abnormal expression of claudin subtypes has been reported in various cancers. However, the pathological role of each claudin has not been clarified in detail. Claudin-18 was absent in human non-small cell and small cell lung cancers, although it is expressed in normal lung tissues. Here, we examined the effect of claudin-18 expression on the expression of junctional proteins, cell proliferation, and cell motility using human lung adenocarcinoma A549 cells. Real-time PCR and western blotting showed that exogenous expression of claudin-18 had no effect on the expression of junctional proteins including claudin-1, zonula occludens-1 (ZO-1), occludin, and E-cadherin. Claudin-18 was mainly distributed in cell-cell contact areas concomitant with ZO-1. Cell proliferation was significantly decreased at 48 and 72h after seeding of claudin 18-expressing cells. Claudin-18 suppressed cell motility, whereas it increased cell death in anoikis. Claudin-18 decreased phosphorylated (p)-3-phosphoinositide-dependent protein kinase-1 (PDK1) and p-Akt levels without affecting p-epidermal growth factor receptor and p-phosphatidylinositol-3 kinase (PI3K) levels. Furthermore, claudin-18 was bound with PDK1 and suppressed the nuclear localization of PDK1. We suggest that claudin-18 suppresses the abnormal proliferation and motility of lung epithelial cells mediated by inhibition of the PI3K/PDK1/Akt signaling pathway.

  5. Low cost biological lung volume reduction therapy for advanced emphysema

    Directory of Open Access Journals (Sweden)

    Bakeer M

    2016-08-01

    Full Text Available Mostafa Bakeer,1 Taha Taha Abdelgawad,1 Raed El-Metwaly,1 Ahmed El-Morsi,1 Mohammad Khairy El-Badrawy,1 Solafa El-Sharawy2 1Chest Medicine Department, 2Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt Background: Bronchoscopic lung volume reduction (BLVR, using biological agents, is one of the new alternatives to lung volume reduction surgery.Objectives: To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue.Methods: Enrolled patients were divided into two groups: group A (seven patients in which autologous blood was used and group B (eight patients in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications.Results: In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted (P-value: <0.001 and 0.038, respectively. In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted (P-value: 0.005 and 0.004, respectively. All patients tolerated the procedure with no mortality.Conclusion: BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. Keywords: BLVR, bronchoscopy, COPD, interventional pulmonology

  6. Pulmonary Rehabilitation in Advanced Lung Cancer Patients During Chemotherapy.

    Science.gov (United States)

    Jastrzębski, D; Maksymiak, M; Kostorz, S; Bezubka, B; Osmanska, I; Młynczak, T; Rutkowska, A; Baczek, Z; Ziora, D; Kozielski, J

    2015-01-01

    The aim of this study was to investigate the utility of pulmonary rehabilitation for improving of exercises efficiency, dyspnea, and quality of life of patients with lung cancer during chemotherapy. After the enrollment selection, the study included 20 patients with newly diagnosed advanced lung cancer and performance status 0-2. There were 12 patients randomly allocated to the pulmonary rehabilitation group and another 8 constituted the control group that did not undergo physical rehabilitation. Both groups of patients had continual cycles of chemotherapy. Data were analyzed before and after 8 weeks of physical rehabilitation, and before and after 8 weeks of observation without rehabilitation in controls. The inpatient rehabilitation program was based on exercise training with ski poles and respiratory muscle training. We found a tendency for enhanced mobility (6 Minute Walk Test: 527.3 ± 107.4 vs. 563.9 ±64.6 m; p > 0.05) and a significant increase in forced expired volume in 1 s (66.9 ± 13.2 vs. 78.4 ± 17.7 %predicted; p = 0.016), less dyspnea (p = 0.05), and a tendency for improvement in the general quality of life questionnaire after completion of pulmonary rehabilitation as compared with the control group. This report suggests that pulmonary rehabilitation in advanced lung cancer patients during chemotherapy is a beneficial intervention to reduce dyspnea and enhance the quality of life and mobility.

  7. Deep sequence analysis of non-small cell lung cancer: Integrated analysis of gene expression, alternative splicing, and single nucleotide variations in lung adenocarcinomas with and without oncogenic KRAS mutations

    Directory of Open Access Journals (Sweden)

    Krishna R Kalari

    2012-02-01

    Full Text Available KRAS mutations are highly prevalent in non-small cell lung cancer (NSCLC, and tumors harboring these mutations tend to be aggressive and resistant to chemotherapy. We used next-generation sequencing technology to identify pathways that are specifically altered in lung tumors harboring a KRAS mutation. Paired-end RNA-sequencing of 15 primary lung adenocarcinoma tumors (8 harboring mutant KRAS and 7 with wild-type KRAS were performed. Sequences were mapped to the human genome, and genomic features, including differentially expressed genes, alternate splicing isoforms and single nucleotide variants, were determined for tumors with and without KRAS mutation using a variety of computational methods. Network analysis was carried out on genes showing differential expression (374 genes, alternate splicing (259 genes and SNV-related changes (65 genes in NSCLC tumors harboring a KRAS mutation. Genes exhibiting two or more connections from the lung adenocarcinoma network were used to carry out integrated pathway analysis. The most significant signaling pathways identified through this analysis were the NFkB, ERK1/2 and AKT pathways. A 27 gene mutant KRAS-specific sub network was extracted based on gene-gene connections within the integrated network, and interrogated for druggable targets. Our results confirm previous evidence that mutant KRAS tumors exhibit activated NFkB, ERK1/2 and AKT pathways and may be preferentially sensitive to target therapeutics toward these pathways. In addition, our analysis indicates novel, previously unappreciated links between mutant KRAS and the TNFR and PPARγ signaling pathways, suggesting that targeted PPARγ antagonists and TNFR inhibitors may be useful therapeutic strategies for treatment of mutant KRAS lung tumors. Our study is the first to integrate genomic features from RNA-Seq data from NSCLC and to define a first draft genomic landscape model that is unique to tumors with oncogenic KRAS mutations.

  8. A complete response to S-1 plus cis-diamminedichloroplatinum in advanced-stage esophageal and gastric adenocarcinoma: a case report

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    Matsuno Yoritaka

    2012-07-01

    Full Text Available Abstract Background Complete remission from advanced-stage synchronous double primary (SDP esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP. Case presentation The patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22 months after the disappearance of the original tumor and metastatic lesions without surgical treatment. Conclusion These results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.

  9. Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer

    OpenAIRE

    Hall, Z.; Ament, Z; Wilson, CH; Burkhart, DL; Ashmore, T; Koulman, A.; Littlewood, T; Evan, GI; Griffin, JL

    2016-01-01

    MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We fo...

  10. Establishment of a Multidrug Resistance Cell Line A549/cDDP of Human Lung Adenocarcinoma and Expression Analysis of Multidrug Resistance-Associated Genes

    Directory of Open Access Journals (Sweden)

    Yongcheng PAN

    2009-03-01

    Full Text Available Background and objective It has been proven that chemotherapy failure caused by multidrug resistance in lung tumor cells is the main cause for the patient's survival rate. The aim of this study is to establish a multidrug resistance cell line of human lung adenocarcinoma and study the mechanism of multidrug resistance. Methods Human lung adenocarcinoma cell line A549 was induced to multidrug resistance cell line A549/cDDP by intermittentadministration of high dose of cisplatin (cDDP. The multidrug resistance was detected by using MTT assay. The levels of expression of MDR-1 gene-coded P-glycoportein (P-gp, multidrug resistance-associated protein (MRP, and GSH/GST were examined by flow cytometric assay. The levels of expression of MDR and MRP gene were also detected by RTPCR in both A549/cDDP and A549 cell lines. Results A549/cDDP was resistant to many anti-tumor agents. The IC50 of A549/cDDP was 16.87 times higher than that of A549. The expressions of P-gp and MRP in A549/cDDP were increased significantly to (70.5±4.9% and (29.4±2.9%, respectively, vs (42.4±5.6% and (21.4±3.5% in A549. There was no difference of the GSH/GST expression between A549/cDDPand A549 cells. Conclusion A549/cDDP is a model with multidrug resistance and the levels of MDR and MRP mRNA expressions are remarkably higher in A549/cDDP than those in A549.

  11. Clinical characteristics and outcomes of patients with primary lung adenocarcinoma harboring ALK rearrangements detected by FISH, IHC, and RT-PCR.

    Science.gov (United States)

    Wang, Jinghui; Cai, Yiran; Dong, Yujie; Nong, Jingying; Zhou, Lijuan; Liu, Guimei; Su, Dan; Li, Xi; Wu, Shafei; Chen, Xuejing; Qin, Na; Zeng, Xuan; Zhang, Haiqing; Zhang, Zongde; Zhang, Shucai

    2014-01-01

    EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib. The objectives of this study were to determine the frequency of ALK rearrangements in a large cohort of patients with primary lung adenocarcinoma and to analyze the association of ALK rearrangements with clinicopathological characteristics and clinical outcomes. The roles of fluorescence in situ hybridization (FISH), Ventana immunohistochemistry (IHC), and reverse transcriptase polymerase chain reaction (RT-PCR) in the detection of ALK rearrangements were evaluated. The ALK rearrangement was detected in 430 specimens from individual patients with primary lung adenocarcinoma using FISH and Ventana IHC based on tissue microarrays. The EGFR status was detected in all of the specimens through DNA sequencing. An RT-PCR was performed on 200 of the specimens and confirmed by sequencing. Of the 430 patients, 46 (10.7%) harbored ALK rearrangements. The ALK rearrangements were associated with a younger age and the EGFR wild type in comparison with ALK-negative patients. The sensitivity and specificity of the Ventana IHC were 100% and 98.2%, respectively, and the concordance rate between the FISH and the Ventana IHC was 98.4%. The sensitivity and specificity of RT-PCR were 95.5% and 87.0%, respectively, and the concordance rate between the FISH and the RT-PCR was 89.0%. The Cox analysis indicated that an early stage and EGFR-activating mutations were independently associated with a longer OS. This study demonstrated that ALK rearrangements are associated with a younger age and the EGFR wild type rather than with other clinicopathological factors. Although the FISH and Ventana IHC have better concordance, and RT-PCR is a more sensitive method and can identify different variants or partners, the IHC and RT-PCR need to be further evaluated in clinical trials to identify their roles in guiding patients' targeted therapy using crizotinib.

  12. Clinical characteristics and outcomes of patients with primary lung adenocarcinoma harboring ALK rearrangements detected by FISH, IHC, and RT-PCR.

    Directory of Open Access Journals (Sweden)

    Jinghui Wang

    Full Text Available EML4-ALK is a new driver gene of non-small cell lung cancer and a target of crizotinib. The objectives of this study were to determine the frequency of ALK rearrangements in a large cohort of patients with primary lung adenocarcinoma and to analyze the association of ALK rearrangements with clinicopathological characteristics and clinical outcomes. The roles of fluorescence in situ hybridization (FISH, Ventana immunohistochemistry (IHC, and reverse transcriptase polymerase chain reaction (RT-PCR in the detection of ALK rearrangements were evaluated. The ALK rearrangement was detected in 430 specimens from individual patients with primary lung adenocarcinoma using FISH and Ventana IHC based on tissue microarrays. The EGFR status was detected in all of the specimens through DNA sequencing. An RT-PCR was performed on 200 of the specimens and confirmed by sequencing. Of the 430 patients, 46 (10.7% harbored ALK rearrangements. The ALK rearrangements were associated with a younger age and the EGFR wild type in comparison with ALK-negative patients. The sensitivity and specificity of the Ventana IHC were 100% and 98.2%, respectively, and the concordance rate between the FISH and the Ventana IHC was 98.4%. The sensitivity and specificity of RT-PCR were 95.5% and 87.0%, respectively, and the concordance rate between the FISH and the RT-PCR was 89.0%. The Cox analysis indicated that an early stage and EGFR-activating mutations were independently associated with a longer OS. This study demonstrated that ALK rearrangements are associated with a younger age and the EGFR wild type rather than with other clinicopathological factors. Although the FISH and Ventana IHC have better concordance, and RT-PCR is a more sensitive method and can identify different variants or partners, the IHC and RT-PCR need to be further evaluated in clinical trials to identify their roles in guiding patients' targeted therapy using crizotinib.

  13. Cytogenetic findings in lung cancer that illuminate its biological history from adenomatous hyperplasia to bronchioalveolar carcinoma to adenocarcinoma: A case report.

    Science.gov (United States)

    Bettio, Daniela; Cariboni, Umberto; Venci, Anna; Valente, Marialuisa; Spaggiari, Paola; Alloisio, Marco

    2012-12-01

    The biological and chronological evolution of lung cancer remain to be fully elucidated. A multi-step carcinogenesis hypothesis suggests a progression from atypical adenomatous hyperplasia (AAH) through bronchioalveolar carcinoma (BAC) to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated. We report a case of a patient diagnosed by computed tomography (CT) with lung cancer in the superior right lobe who also presented with a pure ground-glass opacity (GGO) in the inferior lobe, while the middle lobe appeared normal. Following pneumonectomy, cytogenetic analysis successfully performed on spontaneous metaphases obtained by the direct method from samples of the three lung lobes showed the presence of three clonal cell populations, each progressively having increased karyotype complexity. Fluorescence in situ hybridization (FISH), performed using ALK (2p23) break probe and ALK/EML4 t(2;2);inv(2) fusion probe, showed a normal pattern for all specimens. Histological evaluation confirmed the presence of AC in the superior right lobe and classified the GGO lesion as BAC and the normal tissue of the middle lobe as AAH. To the best of our knowledge, this is the first case in which the cytogenetic study of spontaneous metaphases showed a clear clonal relationship among AC, BAC and AAH present simultaneously in different lobes of the same lung. This case appears to indicate that the entire lung was somehow predisposed to a neoplastic transformation starting with a diffuse AAH characterized by high proliferative activity. Moreover, the 5q13 region involved in the translocation shared by BAC and AC contains at least 4 genes encoding important regulators of the cell cycle that may be considered new molecular markers of lung cancer.

  14. VINDESINE WITH CYCLOPHOSPHAMIDE-EPIRUBICIN-CISPLATIN IN THE TREATMENT LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    HU Yan-ping; KE Yu-hua; FU Xiao-yu

    1999-01-01

    Objective: To evaluate the addition of vindesine to a cyclophosphamide-epirubicin-cisplatin (CAP) regimen for treating the patients with locally advanced non-small cell lung cancer (NSCLC). Methods: From May 1994to August 1998, 59 previously untreated patients with stage Ⅲa and Ⅲb non-small cell lung cancer were enrolled into this trial. Patients characteristics were the following: the median age was 52 years; the median performance status was 1; there were 19 stage Ⅲa and 40 stage Ⅲb; there were 47 adenocarcinoma, 10squamous cell carcinoma and 2 large cell carcinoma. All patients were treated with vindesine (2 mg/m2, on day 1and day 8), cyclophosphamide (0.6/m2, on day 1),epirubicin (40 mg/m2, on day 1) and cisplatin (60 mg/m2,on day 1) every 3 or 4 weeks. Results: Four achieved a complete response (6.8%), 29 achieved a partial response (49.2%), 15 had stable disease, and 10 had progressive disease. A clinical improvement was in 45 of 59 patients (76.3%). The most frequent major toxic effects were myelosuppression, nausea and vomiting.Conclusion: The vindesine with CAP regimen was active combination chemotherapy in patients with locally advanced NSCLC accompanied by the limited side effects.

  15. EGFR mutations in patients with lung adenocarcinoma in southwest China: are G719S/A and L861Q more likely detected in tumors derived from smokers?

    Directory of Open Access Journals (Sweden)

    Wang QS

    2013-07-01

    Full Text Available Qiushi Wang,1 Jianghong Mou,1 Xin Yang,1 Yong He,2 Zengpeng Li,1 Qingya Luo,1 Yanqing Li,1 Li Lin,1 Yu Ma,1 Hualiang Xiao11Department of Pathology, 2Department of Respiration, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing, People’s Republic of ChinaBackground: The clinical characteristics of epidermal growth factor receptor (EGFR hotspot mutations, such as deletions in exon 19, substitution of L858R in exon 21, and mutations in exon 20, have been widely reported in nonsmall cell lung cancer. However, the clinical features of other low frequency EGFR mutations in these four exons (especially the relationship with smoking history, eg, substitutions of G719S/A/C in exon 18 and L861Q in exon 21, remain unclear. This study investigated the relationship between G719S/A/C and L861Q mutations (in exon 18 and 21 and smoking history.Methods: Specimens from 194 patients with lung adenocarcinoma were analyzed for EGFR mutations in exons 18–21 by high-resolution melting curve analysis and amplification refractory mutation technology to establish the relationship between G719S/A/C and L861Q mutations and smoking history.Results: Ninety-six of 194 tumors (49.5% were confirmed to be EGFR mutation-positive. Among these mutations, 71 of 104 (68.3% were from never smokers, six of 17 (35.3% were from former smokers, and 19 of 73 (26.0% were from current smokers (P < 0.001. The mutation rate in heavy smokers (5/23, 21.7% was significantly lower than in light smokers (20/67, 29.9% and never smokers (71/104, 68.3%, P < 0.001. Seven low frequency EGFR mutations (four substitutions of G719S, and G719 A, respectively, and three of L861Q in exon 21 were identified. Five of these mutations were derived from smokers (one former light smoker, one current heavy smoker, and three current light smokers. Four of these patients had been treated with tyrosine kinase inhibitors and all had a partial response, with median overall

  16. TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Kung-Chu [National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei (China); Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Taoyuan (China); Fang, Yu-Hua Dean [National Cheng Kung University, Department of Biomedical Engineering, Tainan (China); Chung, Hsiao-Wen [National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei (China); Liu, Yuan-Chang [Chang Gung Memorial Hospital and Chang Gung University, Department of Medical Imaging and Intervention, Taoyuan (China); Chang, John Wen-Cheng; Hou, Ming-Mo [Chang Gung Memorial Hospital and Chang Gung University, Division of Hematology-Oncology, Department of Internal Medicine, Taoyuan (China); Yang, Cheng-Ta [Chang Gung Memorial Hospital and Chang Gung University, Department of Thoracic Medicine, Taoyuan (China); Cheng, Nai-Ming; Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Department of Nuclear Medicine and Center for Advanced Molecular Imaging and Translation, Taoyuan (China); Su, Tzu-Pei [Chang Gung Memorial Hospital, Department of Nuclear Medicine, Keelung (China)

    2016-11-15

    In this retrospective review of prospectively collected data, we sought to investigate whether early FDG-PET assessment of treatment response based on total lesion glycolysis measured using a systemic approach (TLG-S) would be superior to either local assessment with EORTC (European Organization for Research and Treatment of Cancer) criteria or single-lesion assessment with PERCIST (PET Response Criteria in Solid Tumors) for predicting clinical outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib. We also examined the effect of bone flares on tumor response evaluation by single-lesion assessment with PERCIST in patients with metastatic bone lesions. We performed a retrospective review of prospectively collected data from 23 patients with metastatic lung adenocarcinoma treated with erlotinib. All participants underwent FDG-PET imaging at baseline and on days 14 and 56 after completion of erlotinib treatment. In addition, diagnostic CT scans were performed at baseline and on day 56. FDG-PET response was assessed with TLG-S, EORTC, and PERCIST criteria. Response assessment based on RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) from diagnostic CT imaging was used as the reference standard. Two-year progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. We identified 13 patients with bone metastases. Of these, four (31 %) with persistent bone uptake due to bone flares on day 14 were erroneously classified as non-responders according to the PERCIST criteria, but they were correctly classified as responders according to both the EORTC and TLG-S criteria. Patients who were classified as responders on day 14 based on TLG-S criteria had higher rates of 2-year PFS (26.7 % vs. 0 %, P = 0.007) and OS (40.0 % vs. 7.7 %, P = 0.018). Similar rates were observed in patients who showed a response on day 56 based on CT imaging according to the RECIST criteria. Patients classified as responders on day 14

  17. Advances and perspectives in lung cancer imaging using multidetector row computed tomography.

    Science.gov (United States)

    Coche, Emmanuel

    2012-10-01

    The introduction of multidetector row computed tomography (CT) into clinical practice has revolutionized many aspects of the clinical work-up. Lung cancer imaging has benefited from various breakthroughs in computing technology, with advances in the field of lung cancer detection, tissue characterization, lung cancer staging and response to therapy. Our paper discusses the problems of radiation, image visualization and CT examination comparison. It also reviews the most significant advances in lung cancer imaging and highlights the emerging clinical applications that use state of the art CT technology in the field of lung cancer diagnosis and follow-up.

  18. Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection; Adenocarcinomes pancreatiques localement evolues. Chimioradiotherapie, reevaluation et resection secondaire?

    Energy Technology Data Exchange (ETDEWEB)

    Delpero, J.R.; Turrini, O. [Institut Paoli-Calmettes, Dept. de chirurgie, 13 - Marseille (France)

    2006-11-15

    Induction chemoradiotherapy (CRT) may down-stage locally advanced pancreatic tumors but secondary resections are unfrequent. However some responders' patients may benefit of a RO resection. Patients and methods. We report 18 resections among 29 locally advanced pancreatic cancers; 15 patients were treated with neo-adjuvant 5-FU-cisplatin based (13) or taxotere based (2 patients) chemoradiotherapy (45 Gy), and 3 patients without histologically proven adenocarcinoma were resected without any preoperative treatment. Results. The morbidity rate was 28% and the mortality rate was 7%; one patient died after resection (5.5%) and one died after exploration (9%). The RO resection rate was 50%. The median survival for the resected patients was not reached and the actuarial survival at 3 years was 59%. Two specimens showed no residual tumor and the two patients were alive at 15 and 46 months without recurrence; one specimen showed less than 10% viable tumoral cells and the patient was alive at 36 months without recurrence. A mesenteric infarction was the cause of a late death at 3 years in a disease free patient (radiation induced injury of the superior mesenteric artery). The median survival of the 11 non-resected patients was 21 months and the actuarial survival at 2 years was 0%. When the number of the resected patients (18) was reported to the entire cohort of the patients with locally advanced pancreatic cancer treated during the same period in our institution, the secondary resectability rate was 9%. Conclusion. Preoperative chemoradiotherapy identifies poor surgical candidates through observation and may enhance the margin status of patients undergoing secondary resection for locally advanced tumors. However it remains difficult to evaluate the results in the literature because of the variations in the definitions of resectability. The best therapeutic strategy remains to be defined, because the majority of patients ultimately succumb with distant metastatic

  19. 三种缝线材料对人肺腺癌细胞A549增殖和细胞周期的影响%Effect of three suture lines on the proliferation and cell cycle of lung adenocarcinoma cell A549 in vitro

    Institute of Scientific and Technical Information of China (English)

    Lianhua Ye; Yunchao Huang; Qilin Jin; Feng Hua; Guangqiang Zhao

    2011-01-01

    Objective: The interaction of cell and medical biomaterial is one of the significant factors to affect clinical application of medical biomaterial. This research is to investigate three of suture lines how to affect the proliferation and cell cycle of lung adenocarcinoma cell A549 in vitro. Methods: Three of suture lines were respectively cultivated with lung adenocarcinoma cell A549, after of 72 hours, we detected absorptions of each group by MTT method in order to reflect the proliferation of lung adenocarcinoma cell A549, and also examined percentage of G1 period cells and S period cells of each group by flow cytometry. Results: Different of suture lines had different effects on the proliferation and cell cycle of lung adenocarcinoma cell A549 (P < 0.05). The effect of absorbent suture line was the strongest on the proliferation and cell cycle of lung adenocarcinoma cell A549, the effect of chorda serica chirurgicalis was medium, and the effect of slide wire was poor. Different length of each suture line had different effects on the proliferation and cell cycle of lung adenocarcinoma cell A549 (P < 0.05).Conclusion: Three of suture line materials have different effects on the proliferation and cell cycle of lung adenocarcinoma cell A549, with dose-effect relationship.

  20. Growth-inhibiting and apoptosis-inducing activities of Myricanol from the bark of Myrica rubra in human lung adenocarcinoma A549 cells.

    Science.gov (United States)

    Dai, G H; Meng, G M; Tong, Y L; Chen, X; Ren, Z M; Wang, K; Yang, F

    2014-09-25

    Myrica rubra (Lour.) Sieb. Et Zucc. is a myricaceae Myrica plant. It is a subtropical fruit tree in China and other Asian countries. The bark of M. rubra is used in Chinese folk medicine because of its antibacterial, antioxidant, anti-inflammatory, and anticancer activities. However, the mechanisms underlying such activities remain unclear. This study investigated whether or not Myricanol extracted from M. rubra bark elicits anti-cancer effects on human lung adenocarcinoma A549 cells by inducing apoptosis in vivo. Myricanol was extracted from M. rubra bark through system solvent extraction and silica gel layer column separation. The results of tritiated thymidine assay, colony formation assay, and flow cytometry indicated that Myricanol inhibited the growth of A549 cells. The effects of Myricanol on the expression of key apoptosis-related genes in A549 cells were evaluated by quantitative PCR and Western blot analyses. Myricanol significantly inhibited the growth of A549 cells in a dose-dependent manner, with a half maximal inhibitory concentration of 4.85 μg/ml. Myricanol significantly decreased colony formation and induced A549 cell apoptosis. Myricanol upregulated the expression of Caspase-3, Caspase-9, Bax, and p21 and downregulated the expression of Bcl-2 at the mRNA and protein levels. These changes were associated with apoptosis. Based on these results, we propose that Myricanol elicits growth inhibitory and cytotoxic effects on lung cancer cells. Therefore, Myricanol may be a clinical candidate for the prevention and treatment of lung cancer.

  1. Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Liu, J; Yang, X Y; Shi, W J

    2014-01-08

    Non-small cell lung carcinoma, NSCLC, accounts for 80-85% of lung cancers. NSCLC can be mainly divided into two types: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The purpose of our study was to identify and differentiate the pathogenesis of ADC and SCC at the molecular level. The gene expression profiles of ADC and SCC were downloaded from Gene Expression Omnibus under accession No. GSE10245. Accordingly, differentially expressed genes (DEGs) were identified by the limma package in R language. In addition, DEGs were functionally analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. A total of 4124 DEGs were identified, including CDK1, CDK2, CDK4, and SKP2. The DEGs were mainly involved in 16 pathways related to cell proliferation, cell signal transduction and metabolism. We conclude that the molecular mechanisms of ADC and SCC are considerably different, and that they are involved in immune response, cell signal transduction, metabolism, cell division, and cell proliferation. Therefore, the two diseases should be treated differently. This study offers new insight into the diagnosis and therapy of these two types of lung cancer.

  2. 某市蒙古族与汉族肺腺癌EGFR基因突变的分析%Mongolian and Han Nationality EGFR Gene Mutations in Lung Adenocarcinoma in A City

    Institute of Scientific and Technical Information of China (English)

    孟令茹; 袁晓荣; 曹坤; 杨雪洁; 金娜

    2015-01-01

    目的:研究内蒙古包头市蒙古族肺腺癌EGFR突变与汉族肺腺癌EGFR突变表达是否存在差异。方法收集临床肺腺癌患者石蜡包埋组织标本108例,包括53例蒙古族和55例汉族肺腺癌的样本,采用ARMS(amplification refractory mutation system, ARMS)PCR扩增方法检测非小细胞肺癌EGFR基因外显子18、19、20及21的突变,χ2析对比内蒙古地区蒙古族和汉族肺腺癌EGFR基因突变差异。结果108例肺腺癌患者中有46例EGFR基因突变,总突变率为42.59%,其中蒙古族突变22例,突变率为41.51%,汉族突变24例,突变率为43.64%,内蒙古包头市蒙古族肺腺癌EGFR突变率与汉族肺腺癌EGFR突变率比较无明显差异(P<0.001),突变以外显子19核苷酸缺失起始位2235为主要突变点。结论内蒙古包头市蒙古族中肺腺癌EGFR基因突变率为41.51%,汉族中EGFR基因突变率为43.64%,内蒙古包头市蒙古族肺腺癌EGFR突变率与汉族肺腺癌EGFR突变率比较无明显差异,都适宜靶向药物治疗。%ObjectiveTo investigate ethnic difference and correlation of EGFR of non-small cell lung cancer in the Mongolian and Han patients in Baotou city of Inner Mongolia Mongolian.MethodsCollect the clinical patients with adenocarcinoma of the lung parafifn-embedded tissue specimens from 108 patients, including 53 cases in Inner Mongolia baotou city Mongolia group and 55 cases of Han lung adenocarcinoma samples, using ARMS (ampliifcation refractory mutation system, ARMS) PCR ampliifcation method for detection of non-small cell lung cancer EGFR gene exon 18, 19, 20 and 21 differences between the mutant gene mutation, Mongolia and Han nationality in lung adenocarcinoma EGFR,χ2 comparative analysis of Baotou city of Inner Mongolia Results108 cases of patients with lung adenocarcinoma in 46 cases of EGFR gene mutation, the total mutation rate was 42.59%, of which Mongolia in 22 cases, the mutation rate was 41.51%, the Han

  3. Monitoring of TGF-β 1-Induced Human Lung Adenocarcinoma A549 Cells Epithelial-Mesenchymal Transformation Process by Measuring Cell Adhesion Force with a Microfluidic Device.

    Science.gov (United States)

    Li, Yuan; Gao, AnXiu; Yu, Ling

    2016-01-01

    The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. It is believed that EMT is associated with initiation and completion of the invasion-metastasis cascade. In this study, an economic approach was developed to fabricate a microfluidic device with less instrumentation requirement for the investigation of EMT by quantifying cell adhesion force. Fluid shear force was precisely controlled by a homemade microfluidic perfusion apparatus and interface. The adhesion capability of the human lung adenocarcinoma cell line A549 on different types of extracellular matrix protein was studied. In addition, effects of transforming growth factor-β (TGF-β) on EMT in A549 cells were investigated by characterizing the adhesion force changes and on-chip fluorescent staining. The results demonstrate that the microfluidic device is a potential tool to characterize the epithelial-mesenchymal transition process by measuring cell adhesion force.

  4. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung.

    Science.gov (United States)

    Chang, Alex; Amin, Ali; Gabrielson, Edward; Illei, Peter; Roden, Richard B; Sharma, Rajni; Epstein, Jonathan I

    2012-10-01

    Distinguishing invasive high-grade urothelial carcinoma (UC) from other carcinomas occurring in the genitourinary tract may be difficult. The differential diagnosis includes high-grade prostatic adenocarcinoma, spread from an anal squamous cell carcinoma (SCC), or spread from a uterine cervical SCC. In terms of metastatic UC, the most common problem is differentiating spread of UC to the lung from a primary pulmonary SCC. Immunohistochemical analysis (IHC) for GATA binding protein 3 (GATA3), thrombomodulin (THROMBO), and uroplakin III was performed on a tissue microarray (TMA) containing 35 cases of invasive high-grade UC. GATA3 IHC was also performed on TMAs containing 38 high-grade (Gleason score ≥8) prostatic adenocarcinomas, representative tissue sections from 15 invasive anal SCCs, representative tissue sections from 19 invasive cervical SCCs, and TMAs with 12 invasive cervical carcinomas of the cervix [SCC (n=10), SCC with neuroendocrine features (n=1), and adenosquamous carcinoma (n=1)]. In addition, GATA3 IHC was performed on representative tissue sections from 15 pulmonary UC metastases and a TMA with 25 SCCs of the lung and 5 pulmonary non-small cell carcinomas with squamous features. GATA3, THROMBO, and uroplakin III were positive in 28 (80%), 22 (63%), and 21 (60%) cases of high-grade UC, respectively. All cases of GATA3-positive staining were nonfocal; 25 (89%) cases demonstrated moderate to strong staining, and 3 (11%) demonstrated weak staining. Of the 7 cases that failed to express GATA3, 5 were positive for THROMBO and/or uroplakin III, whereas 2 were negative for all 3 markers. None of the 38 high-grade prostatic adenocarcinomas was positive for GATA3. Weak GATA3 staining was present in occasional basal cells of benign prostate glands, in a few benign atrophic glands, and in urothelial metaplasia. Of the 15 cases of anal SCCs, 2 (7%) cases showed focal weak staining, and 1 (3%) showed focal moderate staining. Weak staining was also rarely

  5. Long-term Survival of A Patient with Advanced Non-small Cell Lung Cancer 
on Bevacizumab Therapy: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Wei WU

    2013-06-01

    Full Text Available We report an advanced stage Chinese female lung adenocarcinoma patient who was negative for epidermal growth factor receptor (EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS gene mutations, also negative for chinodem microtubule-associated protein-like 4/anaplastic lymphoma kinase (EML4-ALK gene rearrangement and treated with bevacizumab (15 mg/kg in combination with 6 cycles of conventional doses of paclitaxel and carboplatin chemotherapy. She was then treated with maintenance bevacizumab for a total of 42 cycles, the total dose of bevacizumab is 44,730 mg. The progression-free survival was 39 months. Our findings suggest that maintenance bevacizumab for the treatment of non-small cell lung cancer (NSCLC is safe and its benefit for long-term survival overwhelms its side effects.

  6. Destaining of Diff-Quik stained cytologic smears is not necessary for the detection of anaplastic lymphoma kinase gene rearrangement in lung adenocarcinoma by fluorescence in situ hybridization

    Directory of Open Access Journals (Sweden)

    Weisheng Xu

    2016-01-01

    Full Text Available Background: Anaplastic lymphoma kinase (ALK gene rearrangement analysis by fluorescence in situ hybridization (FISH is one of the standard molecular tests for targeted therapy of lung adenocarcinoma. However, insufficient cell block cellularity may impede molecular testing. A recent study showed that Diff-Quik (DQ stained cytology smear is suitable for ALK by FISH. Aims: The aim of our study was to observe the impact of destaining intervals on the quality of FISH signals and determine if DQ smears without destaining would allow FISH analysis. Materials and Methods: Thirty-five DQ smears from 27 cases of lung adenocarcinoma were analyzed for ALK gene rearrangement by FISH. Twenty three DQ smears were destained for different intervals, including 30 s (13 cases, 1 min (6 cases, or 2 min (4 cases. Twelve DQ smears were not subjected to destaining. For further validation, FISH signals in 8 smears and 6 cell blocks were compared with the paired destained DQ smears. The signal quality was semi-quantified and analyzed with Chi-squared test. Results: Of the total 27 selected cases, three (11% were positive for ALK gene rearrangement, whereas 24 (89% were negative. FISH signal was satisfactory in all DQ smears. There was no significant difference in the quality of signal among smears with different destaining intervals (P = 0.55 or between smears with and without destaining (P = 0.41. DQ smears without destaining showed identical FISH results and similar or better signals as compared with paired destained smears and cell blocks in all cases. Conclusions: Duration of destaining intervals does not impact the quality of FISH signal on DQ smears. Destaining of DQ smears is not necessary for ALK by FISH.

  7. A case of EGFR mutant lung adenocarcinoma that acquired resistance to EGFR-tyrosine kinase inhibitors with MET amplification and epithelial-to-mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Miyoshi S

    2015-04-01

    Full Text Available Seigo Miyoshi,1 Takahide Kato,1 Hitoshi Katayama,1 Ryoji Ito,1 Yosuke Mizuno,2 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Ehime, Japan; 2Department of Molecular Pathology, Ehime University Graduate School of Medicine, Ehime, Japan Abstract: EGFR mutant lung cancer responds to EGFR tyrosine kinase inhibitors (TKIs, but all patients eventually develop resistance to EGFR-TKIs. Herein we report a case of EGFR mutant lung adenocarcinoma that acquired resistance to EGFR-TKI with MET amplification and epithelial-to-mesenchymal transition (EMT. A 73-year-old woman was diagnosed with adenocarcinoma harboring an EGFR exon 19 deletion. She received gefitinib as second-line therapy. Tumors were reduced 1 month after gefitinib therapy. However, only a few months later, chest computed tomography results indicated cancer progression. Gefitinib therapy was stopped and docetaxel therapy started. However, she died 13 days after admission. Microscopic examination of postmortem specimens revealed a diffuse proliferation of atypical giant cells in primary and metastatic lesions, but no adenocarcinomatous components as in the antemortem specimens. Immunohistochemical analyses showed that antemortem tumor specimens were positive for CDH1 but negative for VIM. In contrast, postmortem tumor specimens were positive for VIM but negative for CDH1. Genetic analyses revealed MET amplification. We concluded that resistance to EGFR-TKI might be caused by MET amplification and EMT. To our knowledge, no clinical studies have reported that MET amplification and EMT together may be associated with acquired resistance to EGFR-TKI. Second biopsy after the development of EGFR-TKI resistance may be recommended to determine the best therapeutic strategy. Keywords: epidermal growth factor receptor tyrosine kinase inhibitor, MET amplification, epithelial-to-mesenchymal transition

  8. EXPRESSION AND REVERSION OF DRUG RESISTANCE-AND APOPTOSIS-RELATED GENES OF A DDP-RESISTANT LUNG ADENOCARCINOMA CELL LINE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the co-expression of drug resistance- and apoptosis-related genes of cisplatin (CDDP)-selected lung adenocarcinoma cell line A549DDP for compared to the parental cell line A549, and reverse of drug resistance by antisense s-oligodeoxynucleotides (S-ODNs) of differentially expressed genes. Methods: Sense and antisense S-ODN were transferred into A549DDP cells by lipofectin. The expression of drug resistance and apoptosis related genes was examined by RT-PCR, immunocytochemistry and flow cytometry, respectively. Apoptostic cells were identified by DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT)-mediated biotin dUTP nick end-labeling(TUNEL). Drug resistance of tumor cells was detected by a cell viability (MTT) assay. Results: The expression of bc1-2 was positive and that of multidrug resistance-associated protein (MRP) at mRNA and protein level was increased in A549DDP compared to A549 cells. MDR1, c-myc and topoisomeras II (TOPO II) were similarly co-expressed in two cell lines. Both cell lines were negative for c-erbB-2 expression. In A549DDP cells, the expression of bc1-2 and MRP was significantly inhibited by their respective antisense S-ODNs. Antisense S-ODNs could also decrease significantly drug resistance of A549DDP cells to CDDP by promoting cell apoptosis. Conclusion: Both intrinsic and acquired drug resistance were involved in co-expression of multiple MDR-related genes in lung adenocarcinoma. Co- operation of bc1-2 and MRP genes appeared to play an important action to confer the resistance of A549DDP cells to CDDP. Their antisense S-ODNs are responsible for the decrease of drug resistance of this cell line by promoting apoptosis.

  9. [Mucosecretor adenocarcinoma of the lung with pleural involvement presenting as a pneumothorax. Presentation of a clinical case].

    Science.gov (United States)

    Hermida Pérez, J A; Hernández Guerra, J S; Bermejo Hernandez, Á; Sobenes Gutierrez, R J

    2013-10-01

    The combination of a pneumothorax and lung cancer is rare and diagnosis is complex. Clinical suspicion of cancer must be based on radiological findings and the existence of risk factors. We discuss the mechanisms involved in the development of pneumothorax in patients with lung cancer, as well as the clinical significance, the recommended diagnostic approach, and therapeutic guidelines.

  10. Umbelliprenin is cytotoxic against QU-DB large cell lung cancer cell line but anti-proliferative against A549 adenocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Khaghanzadeh Narges

    2012-10-01

    Full Text Available Abstract Background Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins. Recently, umbelliprenin has attracted the researchers' attention for its antitumor activities against skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer. Methods The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells, and propidium iodide (for necrotic cells dyes were employed. Results Data from three independent MTT experiments in triplicate revealed that IC50 values for QU-DB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells, but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and less concentrations of umbelliprenin, no suppressive effect was observed. Conclusions We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

  11. Umbelliprenin is Cytotoxic against QU-DB Large Cell Lung Cancer Cell Line but Anti-Proliferative against A549 Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Abbas Ghaderi

    2012-10-01

    Full Text Available Background:Umbelliprenin is a natural compound, belonging to the class of sesquiterpene coumarins.Recently, umbelliprenin has attracted the researchers' attention for its antitumor activitiesagainst skin tumors. Its effect on lung cancer is largely unknown. The aim of our study was to investigate the effects of this natural compound, which is expected to have low adverse effects, on lung cancer.Methods:The QU-DB large cell and A549 adenocarcinoma lung cancer cell lines were treated with umbelliprenin. IC50 values were estimated using methyl thiazolely diphenyl-tetrazolium bromide (MTT assay, in which a decrease in MTT reduction can occur as a result of cell death or cell proliferation inhibition. To quantify the rate of cell death at IC50 values, flow cytometry using Annexin V-FITC (for apoptotic cells, and propidium iodide (for necrotic cells dyes were employed.Results:Data from three independent MTT experiments in triplicate revealed that IC50 values for QUDB and A549 were 47 ± 5.3 μM and 52 ± 1.97 μM, respectively. Annexin V/PI staining demonstrated that umbelliprenin treatment at IC50 induced 50% cell death in QU-DB cells,but produced no significant death in A549 cells until increasing the umbelliprenin concentration to IC80. The pattern of cell death was predominantly apoptosis in both cell lines. When peripheral blood mononuclear cells were treated with 50 μM and lessconcentrations of umbelliprenin, no suppressive effect was observed.Conclusions:We found cytotoxic/anti-proliferative effects of umbelliprenin against two different types of lung cancer cell lines.

  12. A novel sulindac derivative inhibits lung adenocarcinoma cell growth through suppression of Akt/mTOR signaling and induction of autophagy.

    Science.gov (United States)

    Gurpinar, Evrim; Grizzle, William E; Shacka, John J; Mader, Burton J; Li, Nan; Piazza, Nicholas A; Russo, Suzanne; Keeton, Adam B; Piazza, Gary A

    2013-05-01

    Nonsteroidal anti-inflammatory drugs such as sulindac sulfide have shown promising antineoplastic activity in multiple tumor types, but toxicities resulting from COX inhibition limit their use in cancer therapy. We recently described a N,N-dimethylethyl amine derivative of sulindac sulfide, sulindac sulfide amide (SSA), that does not inhibit COX-1 or -2, yet displays potent tumor cell growth-inhibitory activity. Here, we studied the basis for the growth-inhibitory effects of SSA on human lung adenocarcinoma cell lines. SSA potently inhibited the growth of lung tumor cells with IC50 values of 2 to 5 μmol/L compared with 44 to 52 μmol/L for sulindac sulfide. SSA also suppressed DNA synthesis and caused a G0-G1 cell-cycle arrest. SSA-induced cell death was associated with characteristics of autophagy, but significant caspase activation or PARP cleavage was not observed after treatment at its IC50 value. siRNA knockdown of Atg7 attenuated SSA-induced autophagy and cell death, whereas pan-caspase inhibitor ZVAD was not able to rescue viability. SSA treatment also inhibited Akt/mTOR signaling and the expression of downstream proteins that are regulated by this pathway. Overexpression of a constitutively active form of Akt was able to reduce autophagy markers and confer resistance to SSA-induced cell death. Our findings provide evidence that SSA inhibits lung tumor cell growth by a mechanism involving autophagy induction through the suppression of Akt/mTOR signaling. This unique mechanism of action, along with its increased potency and lack of COX inhibition, supports the development of SSA or related analogs for the prevention and/or treatment of lung cancer.

  13. An unusual presentation of tumor lysis syndrome in a patient with advanced gastric adenocarcinoma: case report and literature review.

    Science.gov (United States)

    Vodopivec, Danica Maria; Rubio, Jose Enrique; Fornoni, Alessia; Lenz, Oliver

    2012-01-01

    Tumor lysis syndrome (TLS) is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications) identified through these searches were reviewed and included.

  14. An Unusual Presentation of Tumor Lysis Syndrome in a Patient with Advanced Gastric Adenocarcinoma: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Danica Maria Vodopivec

    2012-01-01

    Full Text Available Tumor lysis syndrome (TLS is characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia in patients with a malignancy. When these laboratory abnormalities develop rapidly, clinical complications such as cardiac arrhythmias, acute renal failure, seizures, or death may occur. TLS is caused by rapid release of intracellular contents by dying tumor cells, a condition that is expected to be common in hematologic malignancies. However, TLS rarely occurs with solid tumors, and here we present the second chemotherapy-induced TLS in a patient with advanced gastric adenocarcinoma to be reported in the literature. We also provide information regarding the total cases of TLS in solid tumors reported from 1977 to present day. Our methodology involved identifying key articles from existing reviews of the literature and then using search terms from these citations in MEDLINE to find additional publications. We relied on a literature review published in 2003 by Baeksgaard et al., where they gathered all total 45 cases reported from 1977 to 2003. Then, we looked for new reported cases from 2004 to present day. All reports (case reports, brief reports, letters to editor, correspondence, reviews, journals, and short communications identified through these searches were reviewed and included.

  15. Use of CT-guided fine needle aspiration biopsy in epidermal growth factor receptor mutation analysis in patients with advanced lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhuang, Yi-Ping; Wang, Hai-Yan; Zhang, Jin; Feng, Yong (Dept. of Radiology, Jiangsu Cancer Inst. and Hospital, Nanjing, Jiangsu (China)), email: yipingzhuang2010@sina.com; Shi, Mei-Qi (Dept. of Chemotherapy, Jiangsu Cancer Inst. and Hospital, Nanjing, Jiangsu (China))

    2011-12-15

    Background. The safety of using a cutting needle when performing a core-needle biopsy is of major concern, in particular for small lung tumors or tumors near the hilum. Purpose. To investigate the usefulness of CT-guided fine needle aspiration biopsy (FNAB) of the lung in obtaining tumor tissue for epidermal growth factor receptor (EGFR) mutation analysis in advanced lung cancer patients. Material and Methods. Forty-three patients with stage IIIB-IV lung cancer were enrolled. In all patients, CT-guided FNAB was performed using an 18-gauge or 20-gauge Chiba aspiration needle for histology diagnosis and EGFR mutation analysis. Complications associated with CT-guided FNAB were observed, and the specimen mutational assessments were recorded. Results. The obtained tumor samples ranged from 0.5-1.5 cm in length and were adequate for histological and DNA analyses in all patients. No patient had a pneumothorax or hemoptysis. Minor needle tract bleeding appeared in eight patients. Mutation analysis was satisfactorily demonstrated in 23 mutations and 20 non-mutations. Ten and 13 mutations were identified by 18-gauge and 20-gauge needle biopsies, respectively. EFGR mutations, including 12 cases of EGFR exon 19 deletion and 11 cases of exon 21 point mutation, were present in 21 patients with adenocarcinomas, one with squamous cell carcinoma, and one with undifferentiated carcinoma. Conclusion. CT-guided FNAB is a feasible and safe technique for obtaining lung tumor tissues for EGFR gene mutation analysis

  16. Lung cancer in women

    Directory of Open Access Journals (Sweden)

    Barrera-Rodriguez R

    2012-12-01

    Full Text Available Raúl Barrera-Rodriguez,1 Jorge Morales-Fuentes2 1Biochemistry and Environmental Medicine Laboratory, National Institute of Respiratory Disease, 2Lung Cancer Medical Service, National Institute of Respiratory Disease, Tlalpan, Mexico City, Distrito Federal, Mexico Both authors contributed equally to this workAbstract: Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer.Keywords: lung cancer, adenocarcinoma, women, genetic susceptibility, genetic differences, tobacco

  17. First- and second-line treatment of advanced metastatic non-small-cell lung cancer: a global view

    Directory of Open Access Journals (Sweden)

    Thatcher Nicholas

    2008-09-01

    Full Text Available Abstract Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses therapeutic options for first- and second-line treatment in patients with advanced non-small-cell lung cancer. According to current data, the combination of two cytotoxic agents is the optimum first-line treatment for patients with non-small-cell lung cancer and performance status of 0–1. Addition of bevacizumab has shown to provide an even longer survival and to increase response rate. Within the first-line setting, erlotinib appears to be effective in the treatment of elderly patients who would not derive a benefit from standard chemotherapy or those refusing standard chemotherapy. The administration of erlotinib as first-line maintenance therapy is being assessed. There are currently three drugs approved for second-line treatment of patients with advanced non-small-cell lung cancer after failure of first-line chemotherapy. These drugs have proven to be effective in phase III trials. In the phase III trial BR.21 study, the response rate was 8.9% in the erlonitib group, and less than 1% in placebo; median response duration was 7.9 months and 3.7 months, respectively; and the median survival was 6.7 months and 4.7 with erlotinib and placebo, respectively. One-year survival was 31% and 21% with erlotinib and placebo, respectively. In addition, the BR.21 trial revealed that significantly greater improvements in overall quality of life and in both physical and emotional functioning were observed in the erlotinib arm as compared with the placebo arm. Erlotinib is not significantly associated with hematologic adverse effects. Erlotinib is administered orally, and does not require concomitant administration of other drugs, thus causing patients less inconvenience. Analysis of data from different

  18. Effects of matrine on the growth inhibition, c-myc and hTERT protein expression in human adenocarcinoma lung cancer cell line A549

    Directory of Open Access Journals (Sweden)

    Qiong CHEN

    2008-08-01

    Full Text Available Background and objective It was reported that telomerase was associated with the oncogenesis and progression of cancer, and to be the common targets of cancer therapy. The mechanism of matrine on lung cancer in vitro is not clear. We studied the effect of matrine on growth of human lung adenocarcinoma A549 cells and the mechanism related with telomerase. Methods MTT was used for measuring A549 cells viability, Hoechst 33342-propidium iodide fluorescent staining for observing apoptotic cells, flow cytometry (FCM for analyzing cell cycle and apoptosis, and immunocytochemistry for measuring the protein expressions of c-myc and hTERT in A549 cells. Results Matrine inhibited the proliferation of A549 cells with a time-dose-dependent manner (P<0.05. Hoechst 33342-propidium iodide staining showed apoptotic cells with chromatin condensation and fragmentation of nuclei. FCM analysis indicated elevating rate of cells in G0/G1 phase, lowering rate of that in S phase and the highering apoptotic rate. The levels of c-myc and hTERT protein expression in the matrine group was lower than that in the control group (P<0.05, and AOD of c-myc showed positive correlation with AOD of hTERT (r=0.633, P<0.01 Conclusion The inhibitory effect of matrine on A549 cells may be related to the lower expression of c-myc and hTERT.

  19. Impact of siRNA targeting pirh2 on proliferation and cell cycle control of the lung adenocarcinoma cell line A549

    Institute of Scientific and Technical Information of China (English)

    SU Yuan; ZHU Liping; JIN Yang; ZHANG Xiaoju; ZHOU Qiong; BAI Ming

    2007-01-01

    The aim of this study was to investigate the role of pirh2(p53-induced RING-H2)protein in the proliferation,apoptosis and cell cycle control of the lung cancer cell line A549.Pirh2 expression was detected by immunofluorescence,Western blot analysis and real-time polymerase chain reaction(PCR).Cell proliferation was assessed by cell counting kit-8(CCK-8).Cell cycle control and apoptosis were analyzed by flow cytometry.The results showed that pirh2 was expressed in the cytoplasm ofA549 cells.The inhibition of pirh2 expression by siRNA(psiRNA-pirh2)resulted in reduced cell proliferation and increased apoptosis.In addition,the number of G0/G1 phase cells was increased but G2/M cells were not affected significantly.Taken together,the inhibition of pirh2 expression in the lung adenocarcinoma cell line A549 resulted in reduced tumor cell growth via the inhibition of cell proliferation,the activation of apoptosis and the interruption of cell cycle transition.

  20. CT findings of minimally invasive adenocarcinoma (MIA) of the lung and comparison of solid portion measurement methods at CT in 52 patients

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Min; Lee, Kyung Hee; Park, Chang Min [Seoul National University Medical Research Center, Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Goo, Jin Mo [Seoul National University Medical Research Center, Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Seoul National University College of Medicine, Cancer Research Institute, Seoul (Korea, Republic of); Chung, Doo Hyun; Koh, Jaemoon [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of)

    2015-08-15

    We aimed to retrospectively investigate CT findings of minimally invasive adenocarcinoma (MIA) and to determine the appropriate method for measurement of solid portions in MIAs at CT. From May 2012 to April 2014, 55 pulmonary nodules in 52 patients were pathologically confirmed as MIAs and were included in this study. CT findings of MIAs and measurements of solid portions at CT were evaluated by two independent radiologists. Mean size of MIAs was 10.5 mm ± 4.8 (range, 4-28 mm). Fifty-two MIAs manifested as 28 pure ground glass nodules (GGNs) (53.8 % %), 22 part-solid GGNs (42.3 % %), and 2 two solid nodules (3.8 % %) at CT. Lobulated border, bubble lucency, and pleural retraction were frequently found in both observers (26.9-42.3 % %). Differences according to window settings between solid portion size and invasive component size were not significantly different in both observers (p > 0.05). As for interobserver agreement, 95 % CIs for solid portion size in the mediastinal window setting (-2.2 to 3.4; mean, 0.6) were slightly narrower than those in the lung window setting (-2.6 to 3.1; mean, 0.3). Nearly all MIAs appear as pure and part-solid GGNs. Mediastinal and lung window settings can be applied for measurement of solid portions at CT without a significant difference. (orig.)

  1. Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray.

    Science.gov (United States)

    Wu, Ying; Yu, Dan-Dan; Hu, Yong; Yan, Dali; Chen, Xiu; Cao, Hai-Xia; Yu, Shao-Rong; Wang, Zhuo; Feng, Ji-Feng

    2016-06-01

    Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis and the development of EGFR-TKI resistance in lung cancer. To gain insight into the molecular mechanisms of EGFR-TKI resistance, we generated an EGFR-TKI-resistant HCC827-8-1 cell line and analyzed expression patterns by lncRNA microarray and compared it with its parental HCC827 cell line. A total of 1,476 lncRNA transcripts and 1,026 mRNA transcripts were dysregulated in the HCC827‑8-1 cells. The expression levels of 7 chosen lncRNAs were validated by real-time quantitative PCR. As indicated by functional analysis, several groups of lncRNAs may be involved in the bio-pathways associated with EGFR-TKI resistance through their cis- and/or trans‑regulation of protein-coding genes. Thus, lncRNAs may be used as novel candidate biomarkers and potential targets in EGFR-TKI therapy in the future.

  2. Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer

    Science.gov (United States)

    2015-09-01

    Recurrent Large Cell Lung Carcinoma; Recurrent Lung Adenocarcinoma; Recurrent Squamous Cell Lung Carcinoma; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Squamous Cell Lung Carcinoma

  3. Síndrome de Fournier secundária a adenocarcinoma de próstata avançado: relato de caso Fournier's syndrome secondary to advanced prostatic adenocarcinoma: case report

    Directory of Open Access Journals (Sweden)

    Rodrigo Rocha Batista

    2010-06-01

    Full Text Available A Síndrome de Fournier é uma fasciite necrotizante rapidamente progressiva que acomete a genitália e região perineal. Mesmo com os avanços na terapêutica, a morbidade e a mortalidade desta afecção permanecem elevadas. É relatado caso de paciente masculino, 70 anos, com diagnóstico de adenocarcinoma de próstata avançado. Há um dia com dor e aumento de volume escrotal associado a febre. Ao exame físico, paciente séptico com gangrena gasosa do pênis e escroto; ao toque retal, lesão ulcero-vegetante em parede anterior do reto estendendo-se de 3 a 7 cm da borda anal. Realizado desbridamento cirúrgico, com identificação de fístula reto-escrotal transtumoral. Estudo histo-patológico da lesão retal confirmou infiltração por adenocarcinoma de próstata. Recebeu alta hospitalar no vigésimo dia de internação, atualmente em acompanhamento oncológico ambulatorial.Fournier's syndrome is a rapidly progressive necrotizing fasciitis affecting the genitalia and perineal region. Even with the advances in therapy, morbidity and mortality of this disease remain high. We report the case of male patient, 70 years old, diagnosed with advanced adenocarcinoma of the prostate. A day with pain and swelling near scrotum associated with fever. The physical examination revealed septic patient with gas gangrene of the penis and scrotum; on digital rectal examination, a vegetative and ulcerated lesion on the anterior wall of the rectum extending from 3 to 7 cm from the anal edge. Performed surgical debridement, with identification of scrotal-rectal fistula transtumoral. Histo-pathological study of the lesion confirmed rectal infiltration by adenocarcinoma of prostate. Was discharged from the hospital on the twentieth day of hospitalization, outpatient cancer currently monitoring.

  4. Advanced Research of Fibroblast Growth Factor Receptor 
in Non-small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Dan PU

    2013-11-01

    Full Text Available Lung cancer is severely threatening human health. In recent years, the treatment for lung adenocarcinoma has made a great progress, targeted therapy has been widely applied in clinic, and benefits amount of patients. However, in squamous cell lung cancer, the incidence of epidermal growth factor receptor (EGFR gene mutant and ALK fusion gene are low,and targeted therapy like Tarceva and crizotinib, can hardly work. Since the fibroblast growth factors (fibroblast growth factor, FGF pathway is considered to be related to tumor cell proliferation, metastasis and angiogenesis, more and more researches proved the amplification of fibroblast growth factor receptor (FGFR in squamous cell lung cancer. Experiments in vivo and in vitro found that blocking FGF pathway could reduce the proliferation of tumor cells and inhibit metastasis. The FGF pathway might be a new target for treatment of squamous cell lung cancer. This article reviews the effect of FGFR in tumorigenesis,as well as the prospect as a therapeutic target in non-small cell lung cancer.

  5. 培美曲塞联合洛铂治疗肺腺癌的近期疗效和安全性研究%Efficacy and safty of pemetrexed combined with lobaplatin treating patients with lung adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    包明红; 章俊强; 梅晓冬

    2012-01-01

    OBJECTIVE: To evaluate the efficacy and safety of domestic pemetrexed and domestic luoplatin in the treatment of the patients with mid-advanced lung adenocarcinoma in the first line. METHODS: A total of 40 patients with pathologically confirmed adenocarcinoma, received pemetrexed 500 mg/m2 and lobaplatin 30 mg/m2 , d] , iv drip, 21 days per cycle. The patients received oral dexamethasonet oralfolic acid and im vitamin Bi2 supplementation to alleviate toxici-ty. The anti-tumor effect, response rate and toxicity of the drugs were measured by the WHO criteria published in 1981. RESULTS: In 40 patients, 2 cases CR(5. 0%) ,16 cases PR(40. 0%), 13 cases SD(32. 5%) and 9 cases PD(22. 5%) ;The objective response rate was 45. 0%(18/40). The disease control rates was 77. 5% (31/40). The median progression free survival time(mPFS) was 5. 6 months. No differences of response was found as compared stage DIB with IVpatients. The drug-related adverse reactions were mainly grade I / II marrow toxicity and gastrointestinal response (The grade HI/ IV incidence of toxicity were 2 cases(5. 0%) ;hair lose, kidney toxicity and neurotoxicity were 0. CONCLUSIONS; The regiment of pemetrexed combined with lobaplatin is effective and safe in the treatment of mid-advanced patients with lung adenocarcinoma in the first line.%目的:评价国产培美曲塞联合国产洛铂一线治疗中晚期肺腺癌的近期疗效和毒副作用.方法:对40例经病理确诊为中晚期肺腺癌患者,国产培美曲塞500 mg/m2,静脉滴入,d1;国产洛铂30 mg/m2,静脉滴入,d1,21 d为1个周期,并口服地塞米松、叶酸和肌肉注射维生素B12以减轻毒副作用.按照1981年WHO实体瘤疗效评定标准评价有效率、无进展生存期和毒副作用.结果:40例患者中,完全缓解2例(5.0%),部分缓解16例(40.0%),稳定13例(32.5%),疾病进展9例(22.5%),总有效率为45.0%(18/40),疾病控制率为77.5%(31/40),中位无进展生存期5.6个月.ⅢB和Ⅳ期患者

  6. Gene identification for risk of relapse in stage I lung adenocarcinoma patients: a combined methodology of gene expression profiling and computational gene network analysis.

    Science.gov (United States)

    Ludovini, Vienna; Bianconi, Fortunato; Siggillino, Annamaria; Piobbico, Danilo; Vannucci, Jacopo; Metro, Giulio; Chiari, Rita; Bellezza, Guido; Puma, Francesco; Della Fazia, Maria Agnese; Servillo, Giuseppe; Crinò, Lucio

    2016-05-24

    Risk assessment and treatment choice remains a challenge in early non-small-cell lung cancer (NSCLC). The aim of this study was to identify novel genes involved in the risk of early relapse (ER) compared to no relapse (NR) in resected lung adenocarcinoma (AD) patients using a combination of high throughput technology and computational analysis. We identified 18 patients (n.13 NR and n.5 ER) with stage I AD. Frozen samples of patients in ER, NR and corresponding normal lung (NL) were subjected to Microarray technology and quantitative-PCR (Q-PCR). A gene network computational analysis was performed to select predictive genes. An independent set of 79 ADs stage I samples was used to validate selected genes by Q-PCR.From microarray analysis we selected 50 genes, using the fold change ratio of ER versus NR. They were validated both in pool and individually in patient samples (ER and NR) by Q-PCR. Fourteen increased and 25 decreased genes showed a concordance between two methods. They were used to perform a computational gene network analysis that identified 4 increased (HOXA10, CLCA2, AKR1B10, FABP3) and 6 decreased (SCGB1A1, PGC, TFF1, PSCA, SPRR1B and PRSS1) genes. Moreover, in an independent dataset of ADs samples, we showed that both high FABP3 expression and low SCGB1A1 expression was associated with a worse disease-free survival (DFS).Our results indicate that it is possible to define, through gene expression and computational analysis, a characteristic gene profiling of patients with an increased risk of relapse that may become a tool for patient selection for adjuvant therapy.

  7. Prognostic impact of initial maximum standardized uptake value of 18F-FDG PET/CT on treatment response in patients with metastatic lung adenocarcinoma treated with erlotinib

    Directory of Open Access Journals (Sweden)

    Kus T

    2015-12-01

    Full Text Available Tulay Kus,1 Gokmen Aktas,1 Alper Sevinc,1 Mehmet Emin Kalender,1 Mustafa Yilmaz,2 Seval Kul,3 Serdar Oztuzcu,4 Cemil Oktay,5 Celaletdin Camci1 1Department of Internal Medicine, Division of Medical Oncology, Gaziantep Oncology Hospital, 2Department of Nuclear Medicine, 3Department of Biostatistics, Faculty of Medicine, 4Department of Medical Biology, Faculty of Medicine, University of Gaziantep, Gaziantep, 5Department of Radiology, Faculty of Medicine, University of Akdeniz, Antalya, Turkey Purpose: To investigate whether the initial maximum standardized uptake value (SUVmax on fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT has a prognostic significance in metastatic lung adenocarcinoma.Patients and methods: Sixty patients (24 females, mean age: 57.9±12 years with metastatic stage lung adenocarcinoma who used erlotinib and underwent 18F-FDG PET/CT at the time of diagnosis between May 2010 and May 2014 were enrolled in this retrospective study. The patients were stratified according to the median SUVmax value, which was found as 11. Progression-free survival (PFS rates for 3, 6, and 12 months were examined for SUVmax values and epidermal growth factor receptor (EGFR mutation status.Results: The number of EGFR-sensitizing mutation positive/negative/unknown was 26/17/17, respectively, and the number of patients using erlotinib at first-line, second-line, and third-line therapy was 15, 31, and 14 consecutively. The PFS rates of EGFR mutation positive, negative, and unknown patients for 3 months were 73.1%, 35.3%, and 41.2% (P=0.026, odds ratio [OR]=4.39; 95% confidence interval [CI]: 1.45–13.26, respectively. The PFS rates of EGFR positive, negative, and unknown patients for 6 months were 50%, 29.4%, and 29.4% (P=0.267, OR: 2.4; 95% CI: 0.82–6.96, respectively. The PFS rates of EGFR positive, negative, and unknown patients for 12 months were 42.3%, 29.4%, 23.5% (P=0.408, OR: 2.0; 95% CI: 0.42

  8. Medical treatment of advanced non-small cell lung cancer: progress in 2014

    Directory of Open Access Journals (Sweden)

    Yong SONG

    2015-04-01

    Full Text Available Non-small cell lung cancer is the most common pathological type of lung cancer. Along with the rising incidence in recent years, lung cancer has been the leading cause of death due to malignancies both in our country and worldwide. Due to simplistic therapeutic approach for lung cancer decades ago, those patients suffering from advanced lung cancer had short lifetime, and it was difficult to ensure their life quality. In recent years, many molecular targeted drugs, such as Gefitinib, Erlotinib and Crizotinib etc., have been successively applied in clinical use, and they bring about a substantial prolongation of survival life and improvement in life quality of those patients with advanced lung cancer. In 2014, there was a number of important reports concerning the diagnosis and treatment of non-small cell lung cancer in the annual meetings of either American Society of Clinical Oncology or European Society for Medical Oncology. On the basis of the relevant reports delivered in the conferences, it is our attempt to summarize the recent advances in regard to chemotherapy, molecular targeted therapy, measures to treat TKI therapy resistant cases, and immune therapy, followed by a comment regarding recent advances in the treatment of non-small cell lung cancer in 2014. DOI: 10.11855/j.issn.0577-7402.2015.01.03

  9. Many with Advanced Lung Cancer Don't Get Treatments That Might Help

    Science.gov (United States)

    ... gov/news/fullstory_163162.html Many With Advanced Lung Cancer Don't Get Treatments That Might Help Study found 21 percent went ... Health News Related MedlinePlus Health Topics Cancer Chemotherapy Lung Cancer Radiation Therapy About MedlinePlus Site Map FAQs Customer Support Get ...

  10. Ressecção alargada para o adenocarcinoma colorretal localmente invasivo: relato de caso e revisão da literatura Enlarged resection for locally advanced colorectal adenocarcinoma: case report and literature review

    Directory of Open Access Journals (Sweden)

    Sergio Henrique Couto Horta

    2009-03-01

    Full Text Available O câncer colorretal localmente invasivo, que acomete por contiguidade estruturas adjacentes e sem metástases à distância, ocorre de 5 a 18% dos casos. São adequadamente tratados com ressecção do tumor e órgãos comprometidos em monobloco e margens livres. É relatado o caso de paciente de 27 anos, masculino, portador de adenocarcinoma de retossigmóide com extensa invasão para bexiga e ceco. Tratado com colectomia total, cistectomia radical em monobloco e ileostomia. O trânsito urinário foi reconstituído com reservatório ileal e anastomose com a uretra prostática. O estudo anátomo-patológico da peça cirúrgica revelou adenocarcinoma moderadamente diferenciado, invasão perineural e invasão da parede da bexiga (T4, N0. Realizou no pós-operatório quimioterapia adjuvante, 6 ciclos, com 5-Fluorouracil e ácido folínico. Após 36 meses de seguimento, o paciente encontra-se livre de doença neoplásica, função urinária preservada, porém com ejaculação retrógrada.The locally advanced colorectal cancer compromises adjacent structures and do not disseminate distant metastasis, occur in 5 to 18% of patients. It is properly treated with tumour resection as well as other compromised organs in an "en bloc" resection with free margins. We report a 27 year old, male patient with colorectal adenocarcinoma invading the urinary bladder and cecum. He was treated with total colectomy associated with radical cistectomy and ileostomy. The urinary transit was established building an ileal reservatory anastomosed to the urethra. The tumour histopathologic study showed adenocarcinoma moderate differentiated, invading urinary bladder (T4N0. Postoperative treatment was 5-fluorouracil and folinic acid chemotherapy. After 36 months of outcome, patient is improving and preserves urinary function but has ejaculatory dysfunction.

  11. Gene-targeted radiation therapy mediated by radiation-sensitive promoter in lung adenocarcinoma and the feasibility of micro-PET / CT in evaluation of therapeutic effectiveness in small animals

    Institute of Scientific and Technical Information of China (English)

    徐昊平

    2014-01-01

    Objective To explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo,and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness.Methods Thirty5-6 week old male BALB/c nude mice were used in this study.The mouse models of xenotransplanted human

  12. Antitumor effect of a copper (II) complex of a coumarin derivative and phenanthroline on lung adenocarcinoma cells and the mechanism of action.

    Science.gov (United States)

    Zhu, Taofeng; Chen, Ruhua; Yu, Hao; Feng, Yan; Chen, Jianqiang; Lu, Qin; Xie, Jing; Ding, Weiliang; Ma, Tieliang

    2014-11-01

    In order to investigate the effect of a copper (II) complexes of a coumarin derivative and phenanthroline (hereinafter referred to as the coumarin-copper drug) on lung adenocarcinoma cells in vivo and in vitro, along with the mechanism of action, LA795 lung adenocarcinoma cells were treated with different concentrations of coumarin-copper drug. An MTT assay was performed to determine the cell proliferation ratio, cell apoptosis was detected by Annexin V/propidium iodide staining with flow cytometric analysis and western blot analysis was employed to evaluate the expression levels of apoptosis-associated proteins. In addition, an LA795 cell xenograft tumor model was established in nude mice, with mice receiving intraperitoneal injection once a week for three weeks of either 2 or 4 mg/kg in three divided doses coumarin‑copper drug, or phosphate‑buffered saline. The tumor growth curves were drawn and the tumor growth inhibition rates were calculated. The apoptotic index of subcutaneously transplanted tumor cells was determined by terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end‑labeling assay. The coumarin-copper drug effectively inhibited the proliferation of LA795 cells in a dose‑ and time‑dependent manner, with the half maximal inhibitory concentration equaling 2.0 µmol/l. The coumarin-copper drug also significantly induced LA795 cell apoptosis in a time-dependent manner (P<0.05), which was accompanied by upregulation p35 and B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax), and downregulation of Bcl-2. Furthermore, the coumarin‑copper drug significantly inhibited the growth of LA795 tumors in a dose dependent manner (P<0.05), in accordance with the apoptotic index. In conclusion, the coumarin-copper drug may inhibit the proliferation of LA795 cells through the induction of cell apoptosis, which may be associated with the upregulation of p53 and Bax, with concurrent downregulation of Bcl-2.

  13. Crizotinib Treatment Combined with Resection and Whole-brain Radiation Therapy 
in A ROS1 Rearranged Lung Adenocarcinoma with Brain Metastasis: 
Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Min ZHANG

    2016-08-01

    Full Text Available Background and objective Lung cancer with brain metastasis had poor prognosis. Crizotinib had been confirmed to be used in ROS1 (C-ros oncogene 1 receptor tyrosine kinase rearranged lung adenocarcinoma, but its efficacy in lung cancer with brain metastasis was poor due to the blood brain barrier. In the present study, we reported one case of ROS1 fusion lung adenocarcinoma with symptomatic brain matastasis, who was treated with brain metastases resection, crizotinib, and whole brain radiotherapy plus boost to residual brain metastasis. The safety and efficacy was summarized. Methods At first, surgical resection was used to relive mass effect and to biopsy. Then crizotinib (250 mg, bid was chosen for the existence of ROS1 fusion gene. Whole brain radiotherapy plus boost to residual brain metastasis were used after surgery. Objective response was evaluated by Response Evaluation Criteriation in Solid Tumours (RECIST v1.1 and brain metastasis were evaluated by computer tomography (CT/magnetic resonance imaging (MRI image. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTC AE v4.0. Results After taking crizotinib for 3 months, the lung lesions were close to complete response (CR, the brain metastasis were partial response (PR, the abdomen metastasis were CR and the symptom of blurred vision relieved. Conclusion Crizotinib combined with palliative operation and radiation therapy (WBRT plus boost to residual brain metastasis in the treatment of ROS1 fusion gene positive lung adenocarcinoma with symptomatic brain metastases, can effectively control intracranial lesions with good tolerance.

  14. [An unusual secondary localization of bronchial adenocarcinoma].

    Science.gov (United States)

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J

    1993-01-01

    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  15. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    Science.gov (United States)

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  16. Pyrosequencing Analysis of EGFR and KRAS Mutations in EUS and EBUS-Derived Cytologic Samples of Adenocarcinomas of the Lung

    NARCIS (Netherlands)

    Stigt, Jos A.; 't Hart, Nils A.; Knol, Ageeth J.; Uil, Steven M.; Groen, Harry J. M.

    2013-01-01

    Introduction: Patients with stage IV non-small-cell lung cancer harboring an activating epidermal growth factor receptor (EGFR) mutation are eligible for treatment with EGFR tyrosine kinase inhibitors. With pyrosequencing, low-frequency mutations may be detected more easily even in small diagnostic

  17. Remote multiple intracranial hemorrhage in multiple metastatic lung adenocarcinoma following decompression of posterior fossa lesion: Unknown cause

    Directory of Open Access Journals (Sweden)

    Subhas Konar

    2015-01-01

    Full Text Available Cerebral metastasis can present with hemorrhage. However, multiple hemorrhages in metastatic lesions following surgical decompression of a single lesion are never reported. We report a case of cerebral metastasis from lung cancer that developed multiple hemorrhages in supratentorial metastatic lesions following surgical resection of an infratentorial lesion.

  18. Can EGFR mutation status be reliably determined in pre-operative needle biopsies from adenocarcinomas of the lung?

    DEFF Research Database (Denmark)

    Lindahl, Kim Hein; Sørensen, Flemming Brandt; Jonstrup, Søren Peter;

    2015-01-01

    The identification of EGFR mutations in non-small-cell lung cancer is important for selecting patients, who may benefit from treatment with EGFR tyrosine kinase inhibitors. The analysis is usually performed on cytological aspirates and/or histological needle biopsies, representing a small fraction...

  19. The Relationship between EGFR Mutations and Response and Prognosis of Tyrosine Kinase Inhibitors in Advanced Non-small-cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xuebing LI

    2008-04-01

    Full Text Available Background and objectives It has been proven that epigermal growth factor receptor (EGFR signal pathway plaied an important role in the oncogenesis and development of non-small cell lung cancer (NSCLC. EGFR tyrosine kinase inhibitors (EGFR-TKIs are currently investigated in the treatment of NSCLC. It was suggested in previous studies that the EGFR gene mutations were correlated with the response to EGFR-TKIs therapy and prognosis of NSCLC. We studied the role of EGFR gene mutations in response to two kinds of TKIs therapy and prognosis of NSCLC in this study. Methods The tissue samples of 59 advanced NSCLC patients (34 patients receiving Gefitinib monotherapy and 25 patients receiving Erlotinib monotherapy were collected, and patient charts were reviewed. The mutations in exons 19 and 21 of EGFR gene were detected by PCR-PAGE and PCR-RFLP respectively. The sequences of interested fragments were verified by direct sequencing. Relationship between EGFR mutation and response to TKIs therapy was analyzed with X^2 test. Results EGFR gene mutations were identified in 22 of 59 samples (37.3%. EGFR gene mutation rate was significantly higher in female, non-smoker and patients with adenocarcinoma than in others (50% vs 18.9%, P0.05. Conclusions EGFR gene mutation occurs more frequently in female, non-smoker and patients with adenocarcinoma. In patients with advanced NSCLC, EGFR mutation is associated with good response to EGFR-TKIs therapy.

  20. Apoptotic induction of lung adenocarcinoma A549 cells infected by recombinant RVG Newcastle disease virus (rL-RVG) in vitro.

    Science.gov (United States)

    Yan, Yulan; Liang, Bing; Zhang, Jin; Liu, Yang; Bu, Xuefeng

    2015-01-01

    Newcastle disease virus (NDV) is a member of the genus Avulavirus in the Paramyxoviridae family and its antitumor properties depend on its ability to kill malignant cells while not affecting normal cells. The present study investigated a recombinant avirulent NDV LaSota strain (wild-type NDV strain) expressing the rabies virus glycoprotein (rL-RVG), examined its oncolytic effect on the lung adenocarcinoma A549 cell line and evaluated its potential to serve as a vaccine against lung cancer. A549 cells were infected with the rL-RVG virus and analyzed by MTT, western blot, polymerase chain reaction (PCR), immunofluorescence, terminal deoxynucleotidyl transferase dUTP nick end labeling and flow-cytometric analyses. PCR, western blot and immunofluorescence showed that the RVG gene and protein were stably expressed in A549 cells following infection with rL-RVG. The growth of A549 cells in the rL-RVG group was inhibited more effectively compared to those infected with the wild-type NDV strain. MTT results showed that cell growth inhibition rates in the rL-RVG group were significantly higher than those in the NDV group (PrL-RVG group was also more evident, with the apoptotic index being increased in rL-RVG group. The expression of the pro-apoptotic proteins caspase-3, -8 and -9 increased. The expression of caspase-3 decreased following application of the broad-specificity caspase inhibitor Z-VAD-FMK. However, the expression of the inhibitory apoptosis protein B-cell lymphoma 2 (bcl-2) did not change, but bcl-2-associated X/bcl-2 ratio was higher in the rL-RVG group than that in the NDV group. The rL-RVG strain was able to suppress lung cancer cell growth and promote lung cancer cell apoptosis to a greater extent than the wild-type NDV strain. Therefore, the rL-RVG strain is a potent antitumor agent.

  1. Effect of antisense transfecting of monocarboxylate transporter gene on biological characteristics of lung adenocarcinoma A549 cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Gui-zhi; HUANG Gui-jun; GUO Xian-jian; QIAN Gui-sheng

    2002-01-01

    Objective: To study the influence of transfecting antisense expression vector of the first subtype of the monocarboxylate transporter (MCT1) gene into lung cancer cells on pHi regulation, lactate transportation and cell growth, Methods: MCT1 antisense gene recombinant vector was introduced into human lung cancer cell line A549 by electroporation. The transfected A549 cells resistant to G418 were selected. Positive clones were examined by using PCR. The changes of intracellular pH and lactate were examined with spectrophotometric method. Cell growth was studied with cell growth curve. Results: Intracellular pH and lactate were remarkably decreased in the cells transfected pLXSN-MCT1 in comparison with A549 cells without transfection (P<0. 001). The growth of A549 cells transfected pLXSN-MCT1 was also inhibited remarkably. Conclusion: MCT1 gene may play an important role in pHi regulation, lactate transportation and cell growth in tumor cells.

  2. Cyto- and genotoxicity assessment of Gold nanoparticles obtained by laser ablation in A549 lung adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Bucchianico, Sebastiano Di [Karolinska Institutet, Institute of Environmental Medicine (Sweden); Migliore, Lucia [University of Pisa, Department of Translational Research and New Technologies in Medicine and Surgery, Division of Medical Genetics (Italy); Marsili, Paolo [Institute of Complex Systems (ISC-CNR) (Italy); Vergari, Chiara [Plasma Diagnostics and Technologies s.r.l. (Italy); Giammanco, Francesco [University of Pisa, Department of Physics “E. Fermi” (Italy); Giorgetti, Emilia, E-mail: emilia.giorgetti@fi.isc.cnr.it [Institute of Complex Systems (ISC-CNR) (Italy)

    2015-05-15

    Gold nanoparticles have attracted enormous interest in biomedical applications, based on their unique optical properties. However, their toxicity on human tissues is still an open issue. Beyond the potential intrinsic toxicity of nanostructured gold, a non-negligible contribution of stabilizers or reaction by-products related to current wet chemical synthesis procedures can be expected. Aimed at isolating gold contribution from that of any other contaminant, we produced colloidal suspensions of Gold nanoparticles having average size <10 nm in deionized water or acetone by pulsed laser ablation, that permits preparation of uncoated and highly stable Gold nanoparticles in pure solvents. Subsequently, we investigated the role of surface chemistry, size, and dispersivity of synthesized Gold nanoparticles in exerting toxicity in a cell model system of deep respiratory tract, representing the main route of exposure to NPs, namely adenocarcinoma epithelial A549 cells. Gold nanoparticles prepared in water showed no particular signs of cytotoxicity, cytostasis, and/or genotoxicity as assessed by MTT colorimetric viability test and Cytokinesis-block micronucleus cytome assay up to concentrations of the order of 5 μg/mL. In contrast, Gold nanoparticles produced in pure acetone and then transferred into deionized water showed impaired cell viability, apoptosis responses, micronuclei, and dicentric chromosomes induction as well as nuclear budding, as a function of the amount of surface contaminants like amorphous carbon and enolate ions.

  3. Cytotoxic Activities of Physalis minima L. Chloroform Extract on Human Lung Adenocarcinoma NCI-H23 Cell Lines by Induction of Apoptosis

    Directory of Open Access Journals (Sweden)

    Ooi Kheng Leong

    2011-01-01

    Full Text Available Physalis minima L. is reputed for having anticancer property. In this study, the chloroform extract of this plant exhibited remarkable cytotoxic activities on NCI-H23 (human lung adenocarcinoma cell line at dose- and time-dependent manners (after 24, 48 and 72 h of incubation. Analysis of cell-death mechanism demonstrated that the extract exerted apoptotic programed cell death in NCI-H23 cells with typical DNA fragmentation, which is a biochemical hallmark of apoptosis. Morphological observation using transmission electron microscope (TEM also displayed apoptotic characteristics in the treated cells, including clumping and margination of chromatins, followed by convolution of the nuclear and budding of the cells to produce membrane-bound apoptotic bodies. Different stages of apoptotic programed cell death as well as phosphatidylserine externalization were confirmed using annexin V and propidium iodide staining. Furthermore, acute exposure to the extract produced a significant regulation of c-myc, caspase-3 and p53 mRNA expression in this cell line. Due to its apoptotic effect on NCI-H23 cells, it is strongly suggested that the extract could be further developed as an anticancer drug.

  4. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1

    Directory of Open Access Journals (Sweden)

    Valentina Pirazzoli

    2014-05-01

    Full Text Available Patients with EGFR-mutant lung adenocarcinomas (LUADs who initially respond to first-generation tyrosine kinase inhibitors (TKIs develop resistance to these drugs. A combination of the irreversible TKI afatinib and the EGFR antibody cetuximab can be used to overcome resistance to first-generation TKIs; however, resistance to this drug combination eventually emerges. We identified activation of the mTORC1 signaling pathway as a mechanism of resistance to dual inhibition of EGFR in mouse models. The addition of rapamycin reversed resistance in vivo. Analysis of afatinib-plus-cetuximab-resistant biopsy specimens revealed the presence of genomic alterations in genes that modulate mTORC1 signaling, including NF2 and TSC1. These findings pinpoint enhanced mTORC1 activation as a mechanism of resistance to afatinib plus cetuximab and identify genomic mechanisms that lead to activation of this pathway, revealing a potential therapeutic strategy for treating patients with resistance to these drugs.

  5. A novel combination of multiple primary carcinomas: Urinary bladder transitional cell carcinoma, prostate adenocarcinoma and small cell lung carcinoma- report of a case and review of the literature

    Directory of Open Access Journals (Sweden)

    Giannikaki Elpida

    2005-07-01

    Full Text Available Abstract Background The incidence of multiple primary malignant neoplasms increases with age and they are encountered more frequently nowadays than before, the phenomenon is still considered to be rare. Case presentation We report a case of a man in whom urinary bladder transitional cell carcinoma, metachronous prostate adenocarcinoma and small cell lung carcinoma were diagnosed within an eighteen-month period. The only known predisposing factor was that he was heavy smoker (90–100 packets per year. The literature on the phenomenon of multiple primary malignancies in a single patient is reviewed and the data is summarized. Conclusion It is important for the clinicians to keep in mind the possibility of a metachronous (successive or a synchronous (simultaneous malignancy in a cancer patient. It is worthy mentioning this case because clustering of three primary malignancies (synchronous and metachronous is of rare occurrence in a single patient, and, to our knowledge, this is the first report this combination of three carcinomas appearing in the same patient.

  6. Artemisinin induces caspase-8/9-mediated and Bax/Bak-independent apoptosis in human lung adenocarcinoma (ASTC-a-1) cells.

    Science.gov (United States)

    Xiao, Feng-Lian; Gao, Wei-Jie; Liu, Cheng-Yi; Wang, Xiao-Ping; Chen, Tong-Sheng

    2011-01-01

    Artemisinin (ARTE), an antimalarial phytochemical component from the sweet wormwood plant, has been shown a potential anticancer activity by inducing cell apoptosis. The aim of this report is to explore the mechanism of ARTE-induced human lung adenocarcinoma (ASTC-a-1) cell apoptosis. Cell counting kit (CCK-8) assay showed that ARTE induced cytotoxcity in a dose- and time-dependent manner. Confocal microscopy fluorescence imaging of cells stained with Hoechst 33258 and flow cytometry (FCM) analysis of cells stained with Annexin V-FITC/propidium iodide (PI) showed that ARTE induced reactive oxygen species (ROS)-dependent apoptosis. Confocal fluorescence resonance energy transfer (FRET) imaging of single living cells expressing SCAT3, SCAT9 or CFP-Bid-YFP and fluorometic substrate assay showed that ARTE induced the activation of caspase-3, -8 and -9. Moreover, inhibition of caspase-8 or -9 completely blocked ARTE-induced apoptosis which was only partially attenuated by caspase-3 inhibitor. Interestingly, silencing Bax and Bak by RNA interference (RNAi) did not attenuate ARTE-induced apoptosis. Collectively, ARTE induces caspase-dependent but Bax/Bak-independent apoptosis in ASTC-a-1 cells.

  7. Identification of Subtype-Specific Prognostic Genes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma Patients Using an Embedded Feature Selection Algorithm.

    Directory of Open Access Journals (Sweden)

    Suyan Tian

    Full Text Available The existence of fundamental differences between lung adenocarcinoma (AC and squamous cell carcinoma (SCC in their underlying mechanisms motivated us to postulate that specific genes might exist relevant to prognosis of each histology subtype. To test on this research hypothesis, we previously proposed a simple Cox-regression model based feature selection algorithm and identified successfully some subtype-specific prognostic genes when applying this method to real-world data. In this article, we continue our effort on identification of subtype-specific prognostic genes for AC and SCC, and propose a novel embedded feature selection method by extending Threshold Gradient Descent Regularization (TGDR algorithm and minimizing on a corresponding negative partial likelihood function. Using real-world datasets and simulated ones, we show these two proposed methods have comparable performance whereas the new proposal is superior in terms of model parsimony. Our analysis provides some evidence on the existence of such subtype-specific prognostic genes, more investigation is warranted.

  8. Expression of the CXCR4 ligand SDF-1/CXCL12 is prognostically important for adenocarcinoma and large cell carcinoma of the lung.

    Science.gov (United States)

    Sterlacci, William; Saker, Shereen; Huber, Bettina; Fiegl, Michael; Tzankov, Alexandar

    2016-04-01

    The SDF-1/CXCR4 axis is associated with tumor progression and has been reported as a prognostic parameter, although with conflicting data for non-small cell lung cancer (NSCLC). This study examines a large cohort of clinically and pathologically well-characterized NSCLC patients and includes the activated form of CXCR4 (pCXCR4), which has not been studied in this context so far. SDF-1, CXCR4, and pCXCR4 were assessed immunohistochemically in 371 surgically resected NSCLC using a standardized tissue microarray platform. Extensive clinical and pathological data and a postoperative follow-up period of 17 years enabled detailed correlations. CXCR4 and pCXCR4 were frequently expressed on squamous cell carcinoma. Membranous expression of SDF-1 was a marker of poor prognosis and proved to be an independent prognostic parameter for the entire cohort and for patients with adenocarcinoma (ACA) and large cell carcinoma (LCC). Targeted cancer therapies blocking SDF-1/CXCR4 interaction already exist, and our data suggest that expression of SDF-1, especially on poorer prognosis subgroups of LCC and ACA, indicates patients that might benefit more than others. This should be taken into account when assessing the effectiveness of such targeted approaches for NSCLC patients and could lead to important implications.

  9. Green tea induces annexin-I expression in human lung adenocarcinoma A549 cells: involvement of annexin-I in actin remodeling.

    Science.gov (United States)

    Lu, Qing-Yi; Jin, Yu Sheng; Zhang, Zuo-Feng; Le, Anh D; Heber, David; Li, Frederick P; Dubinett, Steven M; Rao, Jian Yu

    2007-05-01

    Green tea polyphenols exhibit multiple antitumor activities in various in vitro and in vivo tumor models, and the mechanisms of action are not clear. Previously, we found that green tea extract (GTE) regulates actin remodeling in different cell culture systems. Actin remodeling plays an important role in cancer cell morphology, cell adhesion, motility, and invasion. Using proteomic approaches, we found GTE-induced expression of annexin-I, a multifunctional actin binding protein, in these cell lines. In this study, we aimed to further define the functional role of GTE-induced annexin-I expression in actin remodeling, cell adhesion, and motility in lung adenocarcinoma A549 cells. We found that GTE stimulates the expression of annexin-I in a dose-dependent fashion. The GTE-induced annexin-I expression appears to be at the transcription level, and the increased annexin-I expression mediates actin polymerization, resulting in enhanced cell adhesion and decreased motility. Annexin-I specific interference resulted in loss of GTE-induced actin polymerization and cell adhesion, but not motility. In fact, annexin-I specific interference itself inhibited motility even without GTE. Together, annexin-I plays an important role in GTE-induced actin remodeling, and it may serve as a potential molecular target associated with the anticancer activities of green tea.

  10. S-1 plus cisplatin versus fluorouracil plus cisplatin in advanced gastric or gastro-esophageal junction adenocarcinoma patients: a pilot study.

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    Li, Yu Hong; Qiu, Miao Zhen; Xu, Jian Ming; Sun, Guo Ping; Lu, Hui Shan; Liu, Yun Peng; Zhong, Mei Zuo; Zhang, He Long; Yu, Shi Ying; Li, Wei; Hu, Xiao Hua; Wang, Jie Jun; Cheng, Ying; Zhou, Jun Tian; Guo, Zeng Qing; Guan, Zhon Gzhen; Xu, Rui Hua

    2015-10-27

    The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

  11. Advanced Research on Circulating Tumor Cells in Lung Cancer

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    Hui LI

    2012-11-01

    Full Text Available Lung cancer is the malignant disease with the highest rate in terms of incidence and mortality in China. Early diagnosis and timely monitoring tumor recurrence and metastasis are extremely important for improving 5-year survival rate of lung cancer patients. Circulating tumor cells (CTCs, as a "liquid biopsy specimens” for the primary tumor, provide the possibility to perform real-time, non-invasive histological identification for lung cancer patients. The detection of CTCs contributes to early diagnosis, surveillance of tumor recurrence and metastasis, and prediction of therapeutic efficacy and prognosis. Furthermore, CTCs-dependent detection emerges as a new approach for molecularly pathologic examination, study of molecular mechanisms involved in drug resistance, and resolution for tumor heterogeneity. This study reviewed the recent progress of CTCs in lung cancer research field.

  12. The influence of anthracosis and p16ink4a gene abberant methylation to the oncogenesis and progression of small pulmonary adenocarcinoma

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    Daye WANG

    2008-08-01

    Full Text Available Background and objective Anthracosis is black dust matter deposition in the pulmonary parenchyma, which can cause bronchial deformity and destruction. Previously reported, anthracosis is closely correlated to the oncogenesis and progression of small pulmonary adenocarcinoma and p16ink4a gene aberrant methylation was closely associated with lung carcinogenesis. In this study, we want to characterize the influence of anthracosis and p16ink4a gene aberrant methylation on small adenocarcinoma. Methods DNA was bisulfite modified and then Methylation Specific PCR was used to detect p16ink4a gene aberrant methylation, and black dust matter was extracted from lung tissues, the absolute absorbance (A detected by densitometry was defined as anthracotic index (AI. The histopathologic diagnosis was according to Noguchi's classification for small pulmonary adenocarcinoma. Results For heavy smokers, the mean AI was significantly higher than that of nonsmokers (P=0.005 and the frequency of p16ink4a gene aberrant methylation was also significantly higher than that of nonsmokers (P=0.023. The frequency of p16ink4a gene aberrant methylation of early stage small adenocarcinoma was lower than that of advanced and poor differentiated small adenocarcinoma, otherwise p16ink4a protein expression of early stage small adenocarcinoma was significantly higher than that of poor differentiated small adenocarcinoma (P=0.032. Conclusion AI and p16ink4a gene aberrant methylation detection could be used as a combined potential biomarker of small adenocarcinoma.  

  13. The Systemic Evaluation and Clinical Significance of Immunological Function for Advanced Lung Cancer Patients

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    Jialing WANG

    2010-04-01

    Full Text Available Background and objective The actual evaluation of immunological function is significant for studing the tumor development and devising a treatment in time. The aim of this study is to evaluate the immunological function of advanced lung cancer patients systematically, and to discuss the clinical significance. Methods The nucleated cell amounts of advanced lung cancer patients and the healthy individuals were counted. The immune cell subsets and the levels of IL-4, INF-γ, perforin and granzyme in CD8+T cells by the flow cytometry were measured. The proliferation activity and the inhibition ratio of immune cells to several tumor cell lines were evaluated by MTT assay. Results The absolute amounts and subsets of T, B, NK cells of advanced lung cancer patients were lower than the healthy individuals (P < 0.05; However, the proportion of regulatory T cells of advanced lung cancer patients (4.00±1.84% was lower than the healthy individuals (1.27±0.78% (P < 0.05. The positive rates of IFN-γ perforin, granzyme in CD8+T cells decreased while them in IL-4 did not in the advanced lung cancer patients compared to the healthy control group (P < 0.05. The proliferation activity of immune cells, the positive rate of PPD masculine and the inhibition ratio to tumor cells in the advanced lung cancer patients was lower than the healthy subsets obviously (P < 0.05. Conclusion There was a significant immune depression in the advanced lung cancer patients compared to the healthy individuals.

  14. Poor response to gefitinib in lung adenocarcinoma with concomitant epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.

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    Zhou, Jianya; Zheng, Jing; Zhao, Jing; Sheng, Yihong; Ding, Wei; Zhou, Jianying

    2015-03-01

    A patient presenting with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation is rare. We report a non-small cell lung cancer (NSCLC) patient with concomitant ALK rearrangement and exon 19 (E746-A750del) EGFR mutation. The ALK rearrangement was confirmed not only in the primary tumor biopsy specimen, but also in the pleural effusion cell block by reverse transcriptase-polymerase chain reaction (RT-PCR), Ventana ALK immunohistochemistry assay, and fluorescence in situ hybridization. No clinical benefit using chemotherapy or EGFR tyrosine kinase inhibitor gefitinib was obtained in this case.