Evaluation of pentavalent Tc-99m DMSA scintigraphy in small cell and nonsmall cell lung cancers

International Nuclear Information System (INIS)

Atasever, T.; Guendogdu, C.; Vural, G.; Kapucu, L.Oe.; Karalezli, A.; Uenlue, M.

1997-01-01

Aim: The purpose of this study was to evaluate the clinical usefulness of Tc-99m (V) DMSA in patients suspected of lung cancer and determine whether this agent may have value in differentiation between small cell (SCLC) and non-small cell (NSCLC) lung carcinoma. Methods: Thirty-six patients with clinical and radiological suspicion of primary lung carcinoma were injected 450-600 MBq of Tc-99m (V) DMSA intravenously. Whole body and planar anterior, posterior thorax images were obtained 4-5 h after injection of the radioactive complex. Results: Histopathological results confirmed 23 NSCLC, 10 SCLC and 1 metastatic lung carcinoma and 2 lung abscess. Nineteen of the 23 (82%) NSCLC and all of the 10 (100%) SCLC cases showed Tc-99m (V) DMSA uptake. Single metastatic lung cancer also accumulated radiotracer. Lung abscess did not show uptake. Lesion/Nonlesion (L/N) ratio of SCLC (1.59±0.32) and NSCLC (1.43±0.19) tumour types did not show statistical difference (p>0.05). Tc-99m (V) DMSA whole body imaging also showed bone metastases. Conclusion: Tc-99m (V) DMSA is a noninvasive and cheap imaging method to detect malignant lung cancers and their bone metastases but, differentiation of SCLC and NSCLC is not possible. (orig.) [de

[Optimization of radiotherapy planning for non-small cell lung cancer (NSCLC) using 18FDG-PET].

Science.gov (United States)

Schmidt, S; Nestle, U; Walter, K; Licht, N; Ukena, D; Schnabel, K; Kirsch, C M

2002-10-01

In recent years, FDG-PET examinations have become more important for problems in oncology, especially in staging of bronchogenic carcinoma. In the retrospective study presented here, the influence of PET on the planning of radiotherapy for patients with non-small-cell lung cancer (NSCLC) was investigated. The study involved 39 patients with NSCLC who had been examined by PET for staging. They received radiotherapy on the basis of the anterior/posterior portals including the primary tumour and the mediastinum planned according to CT- and bronchoscopic findings. The results of the PET examination were not considered in initial radiotherapy planning. The portals were retrospectively redefined on the basis of FDG uptake considering the size and localization of the primary tumour; and FDG activities outside the mediastinal part of the portals. In 15 out of 39 patients, the CT/PET-planned portals differed from the CT-planned ones. In most causes (n = 12) the CT/PET field was smaller than the CT field. The median geometric field size of the portals was 179 cm2, after redefinition using PET 166 cm2. In 20 patients with disturbed ventilation caused by the tumour (atelectasis, dystelectosis), a correction of the portal was suggested significantly more frequently than in the other patients (p = 0.03). Our results demonstrate the synergism of topographical (CT) and metabolic (FDG-PET) information, which could be helpful in planning radiotherapy of bronchial carcinoma, especially for patients with disturbed ventilation.

Dynamic FDG-PET Imaging to Differentiate Malignancies from Inflammation in Subcutaneous and In Situ Mouse Model for Non-Small Cell Lung Carcinoma (NSCLC).

Science.gov (United States)

Yang, Zhen; Zan, Yunlong; Zheng, Xiujuan; Hai, Wangxi; Chen, Kewei; Huang, Qiu; Xu, Yuhong; Peng, Jinliang

2015-01-01

[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been widely used in oncologic procedures such as tumor diagnosis and staging. However, false-positive rates have been high, unacceptable and mainly caused by inflammatory lesions. Misinterpretations take place especially when non-subcutaneous inflammations appear at the tumor site, for instance in the lung. The aim of the current study is to evaluate the use of dynamic PET imaging procedure to differentiate in situ and subcutaneous non-small cell lung carcinoma (NSCLC) from inflammation, and estimate the kinetics of inflammations in various locations. Dynamic FDG-PET was performed on 33 female mice inoculated with tumor and/or inflammation subcutaneously or inside the lung. Standardized Uptake Values (SUVs) from static imaging (SUVmax) as well as values of influx rate constant (Ki) of compartmental modeling from dynamic imaging were obtained. Static and kinetic data from different lesions (tumor and inflammations) or different locations (subcutaneous, in situ and spontaneous group) were compared. Values of SUVmax showed significant difference in subcutaneous tumor and inflammation (pPET based SUVmax, both subcutaneous and in situ inflammations and malignancies can be differentiated via dynamic FDG-PET based Ki. Moreover, Values of influx rate constant Ki from compartmental modeling can offer an assessment for inflammations at different locations of the body, which also implies further validation is necessary before the replacement of in situ inflammation with its subcutaneous counterpart in animal experiments.

[Pulmonary sarcomatoid carcinoma].

Science.gov (United States)

Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

2016-01-01

Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics. Copyright © 2016. Published by Elsevier Masson SAS.

Cytology-based treatment decision in primary lung cancer: is it accurate enough?

Science.gov (United States)

Sakr, Lama; Roll, Patrice; Payan, Marie-José; Liprandi, Agnès; Dutau, Hervé; Astoul, Philippe; Robaglia-Schlupp, Andrée; Loundou, Anderson; Barlesi, Fabrice

2012-03-01

Accurate distinction of lung cancer types has become increasingly important as recent trials have shown differential response to chemotherapy among non-small cell lung carcinoma (NSCLC) subtypes. Cytological procedures are frequently used but their diagnostic accuracy has been previously questioned. However, new endoscopic and cytological techniques might have improved cytological accuracy in comparison with prior findings. The aim of this study was to reassess cytological accuracy for diagnosis of lung cancer subtypes. A retrospective chart review of subjects who underwent fiberoptic bronchoscopy (FOB) for suspicion of lung cancer in 2007-2008, was undertaken. Reports of bronchoscopically derived cytological specimens were compared to those of histological material. Endoscopic findings and specific investigational techniques were taken into account. A total of 467 FOB with both cytological and histological diagnostic techniques were performed in 449 subjects. Patients consisted of 345 men and 104 women (median age, 65 yrs). Cytology proved malignancy in 157 patients. Cytologically diagnosed carcinomas were classified into squamous cell carcinoma (SqCC) in 56, adenocarcinoma (ADC) in 6, small cell lung carcinoma (SCLC) in 12, non-small cell lung carcinoma not otherwise specified (NSCLC-NOS) in 71, and unclassified carcinoma in 12. Cytology correlated fairly with biopsy specimens, as agreement was observed in 83% of SCLC, 100% of ADC, 74% of SqCC and 8% of NSCLC-NOS. Interestingly, 61% of cytologically identified NSCLC-NOS were classified as ADC by histology. Cytological accuracy improved in case of an endobronchial lesion, mainly for SqCC. These results indicate that cytological accuracy remains fair with regard to diagnosis of squamous and non-squamous lung cancer subtypes. Improvement of cytological accuracy is expected however with novel diagnostic strategies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Unravelling the Long Non-Coding RNA Profile of Undifferentiated Large Cell Lung Carcinoma.

Science.gov (United States)

Shukla, Sudhanshu

2018-02-05

Undifferentiated large cell lung carcinoma (LCLC) accounts for 2.9-9% of total lung cancers. Recently, RNA-seq based studies have revealed major genomic aberrations in LCLC. In this study, we aim to identify long non-coding RNAs (LncRNAs) expression pattern specific to LCLC. The RNA-seq profile of LCLC and other non-small cell lung carcinoma (NSCLC) was downloaded from Gene Expression Omnibus (GEO) and analyzed. Using 10 LCLC samples, we found that 18% of all the annotated LncRNAs are expressed in LCLC samples. Among 1794 expressed LncRNAs, 11 were overexpressed and 14 were downregulated in LCLC compared to normal samples. Based on receiver operating characteristic (ROC) analysis, we showed that the top five differentially expressed LncRNAs were able to differentiate between LCLC and normal samples with high sensitivity and specificity. Guilt by association analysis using genes correlating with differentially expressed LncRNAs identified several cancer-associated pathways, suggesting the role of these deregulated LncRNA in LCLC biology. We also identified the LncRNA differentially expressed in LCLC compared to lung squamous carcinoma (LUSC) and Lung-adenocarcinoma (LUAD). We found that LCLC sample showed more deregulated LncRNA in LUSC than LUAD. Interestingly, LCLC had more downregulated LncRNA compared to LUAD and LUSC. Our study provides novel insight into LncRNA deregulation in LCLC. This study also finds tools to diagnose LCLC and differentiate LCLC with other Non-Small Cell Lung Cancer.

Construction of a T7 Human Lung Cancer cDNA Library

Directory of Open Access Journals (Sweden)

Wentao YUE

2008-10-01

Full Text Available Background and objective Currently, only a limited numbers of tumor markers for non small lung cancer (NSCLC diagnosis, new biomarker, such as serum autoantibody may improve the early detection of lung cancer. Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients. Methods mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas, and then mRNA was reverse transcribed into double stranded cDNA. After digestion, the cDNA was inserted into T7Select 10-3 vector. The phage display cDNA library was constructed by package reaction in vitro and plate proliferation. Plaque assay and PCR were used to evaluate the library.Results Two T7 phage display cDNA library were established. Plaque assay show the titer of lung squamas carcinoma library was 1.8×106 pfu, and the adenocarcinoma library was 5×106 pfu. The phage titer of the amplified library were 3.2×1010 pfu/mL and 2.5×1010 pfu/mL. PCR amplification of random plaque show insert ratio were 100% (24/24 in adenocarcinoma library and 95.8% in human lung squamas carcinoma library (23/24. Insert range from 300 bp to 1 500 bp. Conclusion Two phage display cDNA library from NSCLC were constructed.

Time evolution of regional CT density changes in normal lung after IMRT for NSCLC

International Nuclear Information System (INIS)

Bernchou, Uffe; Schytte, Tine; Bertelsen, Anders; Bentzen, Søren M.; Hansen, Olfred; Brink, Carsten

2013-01-01

Purpose: This study investigates the clinical radiobiology of radiation induced lung disease in terms of regional computed tomography (CT) density changes following intensity modulated radiotherapy (IMRT) for non-small-cell lung cancer (NSCLC). Methods: A total of 387 follow-up CT scans in 131 NSCLC patients receiving IMRT to a prescribed dose of 60 or 66 Gy in 2 Gy fractions were analyzed. The dose-dependent temporal evolution of the density change was analyzed using a two-component model, a superposition of an early, transient component and a late, persistent component. Results: The CT density of healthy lung tissue was observed to increase significantly (p 12 months. Conclusions: The radiobiology of lung injury may be analyzed in terms of CT density change. The initial transient change in density is consistent with radiation pneumonitis, while the subsequent stabilization of the density is consistent with pulmonary fibrosis

Quality of life of inoperable non-small cell lung carcinoma

International Nuclear Information System (INIS)

Minet, P.; Chevalier, P.; Gras, A.; Dejardin-Closon, M.T.; Bartsch, P.; Raets, D.; Lennes, G.

1987-01-01

Eighty one patients with inoperable non-small cell lung carcinoma (NSCLC) were entered in a randomized phase II trial comparing split-dose irradiation alone to combined treatment radiotherapy and polychemotherapy (C.A.P. + V.D.S.). The quality of life and the survival of the patients were studied. The authors have defined three classes of quality of life responses based on the time elapsed before the performance status index drops. A higher quality of life failure rate was observed in the combined treatment group (p non-significant) but the time elapsed before the Karnofsky index drops is longer in the combined treatment group for the quality of life 'no change' subgroup (p = 0.15). Survival and quality adjusted survival are similar in both treatment groups. The same conclusion holds for retrospective stratified treatment groups. The authors conclude that as far as the quality of life is concerned, polychemotherapy combined with the particular split-dose irradiation schedule used is an effective treatment of inoperable NSCLC. (Auth.)

Personalizing Therapy in Advanced Non–Small Cell Lung Cancer

Science.gov (United States)

Villaruz, Liza C.; Burns, Timothy F.; Ramfidis, Vasilis S.; Socinski, Mark A.

2016-01-01

The recognition that non–small cell lung cancer (NSCLC) is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms, has permanently shifted the therapeutic landscape of NSCLC to a personalized approach. This personalization of NSCLC therapy is typified by the dramatic response rates seen in EGFR mutant NSCLC when treated with targeted tyrosine kinase inhibitor therapy and in ALK translocation–driven NSCLC when treated with ALK inhibitors. Targeted therapeutic approaches in NSCLC necessitate consideration of more invasive biopsy techniques aimed at providing sufficient tissue for both histological determination and molecular profiling in all patients with stage IV disease both at the time of diagnosis and at the time of disease progression. Comprehensive genotyping efforts have identified oncogenic drivers in 62% lung adenocarcinomas and an increasing proportion of squamous cell carcinomas of the lung. The identification of these oncogenic drivers and the triage of patients to clinical trials evaluating novel targeted therapeutic approaches will increasingly mold a landscape of personalized lung cancer therapy where each genotype has an associated targeted therapy. This review outlines the state of personalized lung cancer therapy as it pertains to individual NSCLC genotypes. PMID:24258572

CAFET algorithm reveals Wnt/PCP signature in lung squamous cell carcinoma.

Directory of Open Access Journals (Sweden)

Yue Hu

Full Text Available We analyzed the gene expression patterns of 138 Non-Small Cell Lung Cancer (NSCLC samples and developed a new algorithm called Coverage Analysis with Fisher's Exact Test (CAFET to identify molecular pathways that are differentially activated in squamous cell carcinoma (SCC and adenocarcinoma (AC subtypes. Analysis of the lung cancer samples demonstrated hierarchical clustering according to the histological subtype and revealed a strong enrichment for the Wnt signaling pathway components in the cluster consisting predominantly of SCC samples. The specific gene expression pattern observed correlated with enhanced activation of the Wnt Planar Cell Polarity (PCP pathway and inhibition of the canonical Wnt signaling branch. Further real time RT-PCR follow-up with additional primary tumor samples and lung cancer cell lines confirmed enrichment of Wnt/PCP pathway associated genes in the SCC subtype. Dysregulation of the canonical Wnt pathway, characterized by increased levels of β-catenin and epigenetic silencing of negative regulators, has been reported in adenocarcinoma of the lung. Our results suggest that SCC and AC utilize different branches of the Wnt pathway during oncogenesis.

Interaction between hypoxia, AKT and HIF-1 signaling in HNSCC and NSCLC: implications for future treatment strategies

NARCIS (Netherlands)

Stegeman, H.; Span, P.N.; Peeters, W.J.M.; Verheijen, M.M.; Grenman, R.; Meijer, T.W.H.; Kaanders, J.H.A.M.; Bussink, J.

2016-01-01

BACKGROUND: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). RESULTS/METHODOLOGY: pAKT was induced by

The option value of innovative treatments for non-small cell lung cancer and renal cell carcinoma.

Science.gov (United States)

Thornton Snider, Julia; Batt, Katharine; Wu, Yanyu; Tebeka, Mahlet Gizaw; Seabury, Seth

2017-10-01

To develop a model of the option value a therapy provides by enabling patients to live to see subsequent innovations and to apply the model to the case of nivolumab in renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC). A model of the option value of nivolumab in RCC and NSCLC was developed and estimated. Data from the Surveillance, Epidemiology, and End Results (SEER) cancer registry and published clinical trial results were used to estimate survival curves for metastatic cancer patients with RCC, squamous NSCLC, or nonsquamous NSCLC. To estimate the conventional value of nivolumab, survival with the pre-nivolumab standard of care was compared with survival with nivolumab assuming no future innovation. To estimate the option value of nivolumab, long-term survival trends in RCC and squamous and nonsquamous NSCLC were measured in SEER to forecast mortality improvements that nivolumab patients may live to see. Compared with the previous standard of care, nivolumab extended life expectancy by 6.3 months in RCC, 7.5 months in squamous NSCLC, and 4.5 months in nonsquamous NSCLC, according to conventional methods. Accounting for expected future mortality trends, nivolumab patients are likely to gain an additional 1.2 months in RCC, 0.4 months in squamous NSCLC, and 0.5 months in nonsquamous NSCLC. These option values correspond to 18%, 5%, and 10% of the conventional value of nivolumab, respectively. Option value is important when valuing therapies like nivolumab that extend life in a rapidly evolving area of care.

Adenylyl cyclase-associated protein 1 in metastasis of squamous cell carcinoma of the head and neck and non-small cell lung cancer

Science.gov (United States)

Kakurina, G. V.; Kolegova, E. S.; Cheremisina, O. V.; Zavyalov, A. A.; Shishkin, D. A.; Kondakova, I. V.; Choinzonov, E. L.

2016-08-01

Progression of tumors and metastasis in particular is one of the main reasons of the high mortality rate among cancer patients. The primary role in developing metastases plays cell locomotion which requires remodeling of the actin cytoskeleton. Form, dynamics, localization and mechanical properties of the actin cytoskeleton are regulated by a variety of actin-binding proteins, which include the adenylyl cyclase-associated protein 1 (CAP1). The study is devoted to the investigation of CAP1 level depending on the presence or absence of metastases in patients with squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). The results show the contribution of CAP1 to SCCHN and NSCLC progression. We detected the connection between the tissue protein CAP1 level and the stage of NSCLC and SCCHN disease. Also the levels of the CAP1 protein in tissues of primary tumors and metastases in lung cancer were different. Our data showed that CAP is important in the development of metastases, which suggests further perspectives in the study of this protein for projecting metastasis of NSCLC and SCCHN.

Loss of lung function after chemo-radiotherapy for NSCLC measured by perfusion SPECT/CT: Correlation with radiation dose and clinical morbidity

DEFF Research Database (Denmark)

Farr, Katherina P; Møller, Ditte S; Khalil, Azza A

2015-01-01

BACKGROUND: The purpose of the study was to assess dose and time dependence of radiotherapy (RT)-induced changes in regional lung function measured with single photon emission computed tomography (SPECT) of the lung and relate these changes to the symptomatic endpoint of radiation pneumonitis (RP......) in patients treated for non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: NSCLC patients scheduled to receive curative RT of minimum 60 Gy were included prospectively in the study. Lung perfusion SPECT/CT was performed before and three months after RT. Reconstructed SPECT/CT data were registered...

SU-F-T-112: Long-Term Follow-Up of NSCLC Patients Treated with Lung SBRT Using the Modified Conformal Arc (MDCA) Planning Technique

Energy Technology Data Exchange (ETDEWEB)

Ku, E; Desai, A [Frank H Netter, MD, School of Medicine, North Haven, CT (United States); Fang, D; Lawrence, C; Iannuzzi, C; Shi, C [St. Vincent’s Medical Center, Bridgeport, CT (United States)

2016-06-15

Purpose: To assess long-term toxicity and primary tumor changes for Stage I/II non-small cell lung carcinoma (NSCLC) patients after treatment with lung SBRT using the modified dynamic conformal arc (MDCA) planning technique. Methods: Clinical and radiograph data from electronic health records of 15 NSCLC patients treated with lung SBRT utilizing the MDCA technique between October 2011 and July 2014 were retrospectively reviewed. MDCA uses a coplanar beam arrangement, patient body center for the beam isocenter, and six partial rotation conformal arcs to target the tumor. Radiation Therapy Oncology Group (RTOG) guidelines for treatment parameters were followed. Most patients received 5 radiation fractions (Range: 3 to 7 fractions) with 48 hours between each fraction. Median total dose was 60 Gy (range: 45 to 70 Gy). Results: Median follow-up was 18 months (range: 6–51 months). Median age was 72.5 years (range: 48–90 years). Post-treatment findings included fatigue (n = 5) and chronic chest wall pain (n=1). Seven patients reported respiratory symptoms, which included: cough (n = 4), dyspnea (n = 5), and hemoptysis (n = 1). No patients deaths or grade ≥4 toxicity were recorded. Radiographic scarring was seen on computed tomography (CT) imaging in 6 patients. Local control rate was 93.3% (n = 14) and 1 patient had local recurrence. Conclusion: Our results were very similar to RTOG 0236 findings reported by Timmerman et al. – our local control rate was 93.3% compared to their 3-year primary tumor control rate of 97.6%. Toxicity rates were also similar – RTOG 0236 constitutional symptoms and pulmonary/upper respiratory symptoms rates were 36.4% and 60.0%, respectively, while ours were 33.3% and 46.7%, respectively. We were limited by a small sample size and relatively short follow-up but our findings support the use of the MDCA technique for lung SBRT treatment of Stage I/II NSCLC.

Treatment paradigms for patients with metastatic non small cell lung cancer (NSCLC, squamous lung cancer: first, second and third-line

Directory of Open Access Journals (Sweden)

Abdulaziz eAl Farsi

2014-06-01

Full Text Available Historically, the treatment algorithm applied to non small cell lung cancer (NSCLC was the same for all histologic subtypes. However, recent advances in our understanding of the molecular profiles of squamous and non-squamous NSCLC have changed this perspective. Histologic subtype and the presence of specific molecular abnormalities have predictive value for response to and toxicity from therapy, as well as overall survival. For patients with squamous NSCLC, a platinum agent plus gemcitabine, or paclitaxel is recommended as first-line therapy. The role of EGFR monoclonal antibodies is uncertain. Maintenance therapy is not widely recommended, although data exist for the use of erlotinib. The standard recommendation for second-line therapy is docetaxel and erlotinib should be considered as second or third-line therapy. There is ongoing research identifying molecular targets in squamous NSCLC and many agents are in early phase clinical trials. Immunotherapeutic approaches targeting programmed death 1 receptor (PD-1 and its ligand (PD-L1 appear promising.

An Immunohistochemical Study of Anaplastic Lymphoma Kinase and Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Carcinoma.

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Verma, Sonal; Kumar, Madhu; Kumari, Malti; Mehrotra, Raj; Kushwaha, R A S; Goel, Madhumati; Kumar, Ashutosh; Kant, Surya

2017-07-01

Lung cancer is one of the leading causes of cancer related death. Targeted treatment for specific markers may help in reducing the cancer related morbidity and mortality. To study expression of Anaplastic Lymphoma Kinase (ALK)and Epidermal Growth Factor Receptor (EGFR) mutations in patients of Non-Small Cell Lung Cancer NSCLC, that are the targets for specific ALK inhibitors and EGFR tyrosine kinase inhibitors. Total 69 cases of histologically diagnosed NSCLC were examined retrospectively for immunohistochemical expression of EGFR and ALK, along with positive control of normal placental tissue and anaplastic large cell lymphoma respectively. Of the NSCLC, Squamous Cell Carcinoma (SCC) accounted for 71.0% and adenocarcinoma was 26.1%. ALK expression was seen in single case of 60-year-old female, non-smoker with adenocarcinoma histology. EGFR expression was seen in both SCC (59.18%) and adenocarcinoma in (77.78%) accounting for 63.77% of all cases. Both ALK and EGFR mutation were mutually exclusive. EGFR expression was seen in 63.77% of cases, highlighting the importance of its use in routine analysis, for targeted therapy and better treatment results. Although, ALK expression was seen in 1.45% of all cases, it is an important biomarker in targeted cancer therapy. Also, the mutually exclusive expression of these two markers need further studies to develop a diagnostic algorithm for NSCLC patients.

WE-FG-206-08: Pulmonary Functional Imaging Biomarkers of NSCLC to Guide and Optimize Functional Lung Avoidance Radiotherapy

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Sheikh, Khadija; Capaldi, Dante PI; Parraga, Grace [Robarts Research Institute (Canada); Hoover, Douglas A; Palma, David A [Department of Medical Biophysics, Department of Oncology, The University of Western Ontario, London (Canada); Yaremko, Brian P [Department of Oncology, The University of Western Ontario, London (Canada)

2016-06-15

Purpose: Functional lung avoidance radiotherapy promises optimized therapy planning by minimizing dose to well-functioning lung and maximizing dose to the rest of the lung. Patients with NSCLC commonly present with co-morbid COPD and heterogeneously distributed ventilation abnormalities stemming from emphysema, airways disease, and tumour burden. We hypothesized that pulmonary functional imaging methods may be used to optimize radiotherapy plans to avoid regions of well-functioning lung and significantly improve outcomes like quality-of-life and survival. To ascertain the utility of functional lung avoidance therapy in clinical practice, we measured COPD phenotypes in NSCLC patients enrolled in a randomized-controlled-clinical-trial prior to curative intent therapy. Methods: Thirty stage IIIA/IIIB NSCLC patients provided written informed consent to a randomized-controlled-clinical-trial ( http://clinicaltrials.gov/ct2/show/NCT02002052 ) comparing outcomes in patients randomized to standard or image-guided radiotherapy. Hyperpolarized noble gas MRI ventilation-defect-percent (VDP) (Kirby et al, Acad Radiol, 2012) as well as CT-emphysema measurements were determined. Patients were stratified based on quantitative imaging evidence of ventilation-defects and emphysema into two subgroups: 1) tumour-specific ventilation defects only (TSD), and, 2) tumour-specific and other ventilation defects with and without emphysema (TSD{sub VE}). Receiver-operating-characteristic (ROC) curves were used to characterize the performance of clinical measures as predictors of the presence of non-tumour specific ventilation defects. Results: Twenty-one out of thirty subjects (70%) had non-tumour specific ventilation defects (TSD{sub VE}) and nine subjects had ONLY tumour-specific defects (TSD). Subjects in the TSD{sub VE} group had significantly greater smoking-history (p=.006) and airflow obstruction (FEV{sub 1}/FVC) (p=.001). ROC analysis demonstrated an 87% classification rate for

Breviscapine suppresses the growth of non-small cell lung cancer

Indian Academy of Sciences (India)

Breviscapine (BVP) has previously been shown to inhibit the proliferation of hepatocellular carcinoma cells.However, little is known about the effects of BVP on non-small cell lung cancer (NSCLC) growth. Here, we aimedto study the effects of BVP on human NSCLC growth. We employed A549, NCL-H460 and A549 cells ...

Lung Radiofrequency Ablation: Potential as a Therapy to Oligometastasis and Oligo-Recurrence

OpenAIRE

Hiraki, Takao; Kanazawa, Susumu

2012-01-01

The early results (e.g., patient survival) of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligo-recurrence or oligometastasis of lung cancer. The usefulness of RFA for oligo-recurrence or oligometastasis of lung cancer should be clarified by pro...

Lung radiofrequency ablation: potential as a therapy to oligometastasis and oligorecurrence.

Science.gov (United States)

Hiraki, Takao; Kanazawa, Susumu

2012-01-01

The early results (e.g., patient survival) of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligorecurrence or oligometastasis of lung cancer. The usefulness of RFA for oligorecurrence or oligometastasis of lung cancer should be clarified by prospective studies in the future.

Optimization of radiotherapy planning for Non-Small Cell Lung Cancer (NSCLC) by {sup 18}FDG-PET; Optimierung der Bestrahlungsplanung beim nicht-kleinzelligen bronchialkarzinom (NSCLC) mit Hilfe von {sup 18}FDG-PET

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Schmidt, S.; Nestle, U.; Kirsch, C.M. [Abt. fuer Nuklearmedizin, Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Walter, K. [Abt. fuer Strahlentherapie, Marienkrankenhaus Amberg (Germany); Licht, N.; Schnabel, K. [Abt. fuer Strahlentherapie, Universitaetskliniken des Saarlandes, Homburg/Saar (Germany); Ukena, D. [Innere Medizin V, Universitaetskliniken des Saarlandes, Homburg/Saar (Germany)

2002-10-01

Aim: In recent years, FDG-PET examinations have become more important for problems in oncology, especially in staging of bronchogenic carcinoma. In the retrospective study presented here, the influence of PET on the planning of radiotherapy for patients with non-small-cell lung cancer (NSCLC) was investigated. Methods: The study involved 39 patients with NSCLC who had been examined by PET for staging. They received radiotherapy on the basis of the anterior/posterior portals including the primary tumour and the mediastinum planned according to CT- and bronchoscopic findings. The results of the PET examination were not considered in initial radiotherapy planning. The portals were retrospectively redefined on the basis of FDG uptake considering the size and localization of the primary tumour; and FDG activities outside the mediastinal part of the portals. Results: In 15 out of 39 patients, the CT/PET-planned portals differed from the CT-planned ones. In most cases (n = 12) the CT/PET field was smaller than the CT field. The median geometric field size of the portals was 179 cm{sup 2}, after redefinition using PET 166 cm{sup 2}. In 20 patients with disturbed ventilation caused by the tumour (atelectosis, dystelectosis), a correction of the portal was suggested significantly more frequently than in the other patients (p = 0.03). Conclusions: Our results demonstrate the synergism of topographical (CT) and metabolic (FDG-PET) information, which could be helpful in planning radiotherapy of bronchial carcinoma, especially for patients with disturbed ventilation. (orig.) [German] Ziel: Die FDG-PET-Untersuchung hat in den vergangenen Jahren bei onkologischen Fragestellungen insbesondere beim Staging des Bronchialkarzinoms wachsende Bedeutung erlangt. In der vorliegenden retrospektiven Untersuchung wurde der Einfluss der PET auf die Strahlentherapieplanung bei Patienten mit non-small-cell lung cancer (NSCLC) untersucht. Methoden: Die Untersuchung umfasste 39 Patienten mit

Potential targets for lung squamous cell carcinoma

Science.gov (United States)

Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes

OpenAIRE

Zhou, Dongbo; Xie, Mingxuan; He, Baimei; Gao, Ying; Yu, Qiao; He, Bixiu; Chen, Qiong

2017-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. The most common subtypes of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). However, the pathophysiological mechanisms contributing to AC and SCC are still largely unknown, especially the roles of long non-coding RNAs (lncRNAs). The present study identified differentially expressed lncRNAs between lung AC and SCC by re-annotation of NSCLC microarray data analysis profiling. The potential func...

Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

Directory of Open Access Journals (Sweden)

Jing Lin

2017-12-01

Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

[Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma].

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Ren, Hongliang; Xu, Wengui; You, Jian; Song, Xiuyu; Huang, Hui; Zhao, Ning; Ren, Xiubao; Zhang, Xinwei

2016-04-20

Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022). There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (Pdifference by

Metastatic squamous cell non-small-cell lung cancer (NSCLC: disrupting the drug treatment paradigm with immunotherapies

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Sarah L Scarpace

2015-10-01

Full Text Available Lung cancer is the third most commonly diagnosed cancer and the leading cause of cancer-related death in the United States. Unlike non-squamous NSCLC, squamous NSCLC rarely harbor epidermal growth factor receptor (EGFR and anaplastic lymphoma kinase (ALK mutations for which there are directed therapies, and until the recent approval of immunotherapies for squamous NSCLC, a limited number of traditional cytotoxic chemotherapy drugs have been FDA-approved for use in the treatment of advanced and metastatic squamous NSCLC. Immunotherapies directed at the programmed cell death-1 receptor (PD-1 or its ligand (PD-L1 (nivolumab and pembrolizumab have demonstrated efficacy in both nonsquamous and squamous cell NSCLC. Because of their similar mechanism of action against the PD-L1/PD-1 pathway, both drugs have similar toxicity profiles related to immune-mediated adverse reactions that can generally be monitored and managed with oral corticosteroids. This paper provides an overview of drug therapy options for squamous cell NSCLC with a focus on the evidence and clinical application of the anti-PD1 therapies. A comparison of the dosing, administration, indications, and differences in the measurement of PD-L1 expression in the clinical trials of nivolumab and pembrolizumab is also provided.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) Signaling Capacity and the Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC): Implications for Use of 1,25(OH)2D3 in NSCLC Treatment

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Upadhyay, Santosh Kumar; Verone, Alissa; Shoemaker, Suzanne; Qin, Maochun; Liu, Song; Campbell, Moray; Hershberger, Pamela A.

2013-01-01

1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) exerts anti-proliferative activity by binding to the vitamin D receptor (VDR) and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC) cells which harbor epidermal growth factor receptor (EGFR) mutations display elevated VDR expression (VDR high ) and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDR low and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT). Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH) 2 D 3 sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH) 2 D 3 induces E-cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH) 2 D 3 -mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH) 2 D 3 opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH) 2 D 3 may prevent lung cancer progression in a molecularly defined subset of NSCLC patients

Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC

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Schytte, Tine; Hansen, Olfred; Stohlberg-Rohr, Thomine

2010-01-01

    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity   Backgro......    Cardiac Toxicity after definitive Radiotherapy of locally advanced NSCLC Tine Schytte, Olfred Hansen, Thomine Stolberg-Rohr* and Carsten Brink*. Dept. Oncology and Radiophysic Lab.* Odense University Hospital, Denmark   Keyword: Radiotherapy, Locally advanced NSCLC, Cardiac toxicity......   Background: Lung and oesophageal toxicity have been regarded as main toxicity in definitive radiotherapy (RT) of non-small cell lung cancer (NSCLC), whereas cardiac toxicity has not been offered much concern. This is probably due to the poor prognosis for patients with unresectable NSCLC. In this study we...

Lung Radiofrequency Ablation: Potential as a Therapy to Oligometastasis and Oligo-Recurrence

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Takao Hiraki

2012-01-01

Full Text Available The early results (e.g., patient survival of RFA for the treatment of patients with NSCLC and pulmonary metastasis from various primary lesions including colorectal cancer, lung cancer, hepatocellular carcinoma, renal cell carcinoma, and sarcoma appear encouraging and suggest the potential to offer long-term survival for the patients with oligo-recurrence or oligometastasis of lung cancer. The usefulness of RFA for oligo-recurrence or oligometastasis of lung cancer should be clarified by prospective studies in the future.

Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

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Lee, Ra H; Jeon, Young-Joo; Cho, Jin H; Jang, Jeong-Yun; Kong, Il-Keun; Kim, Seok-Ho; Kim, MinSeok S; Chung, Hak-Jae; Oh, Keon B; Park, Seon-Min; Shin, Jae-Cheon; Seo, Jae-Min; Ko, Sungho; Shim, Jung-Hyun; Chae, Jung-Il

2017-01-01

Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC.

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Anna Durrans

Full Text Available Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor "activated/reprogrammed" stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN, chemokine (C-C motif ligand 7 (CCL7 and thrombospondin 1 (TSP1 were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.

Incidence and survival from lung cancer in Greenland is comparable to survival in the Nordic countries

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Gelvan, Allan; Risum, Signe; Langer, Seppo W

2015-01-01

INTRODUCTION: Oncological treatment of lung cancer has been available in Greenland since 2004. We evaluated patient characteristics and survival rates for the first six years of local lung cancer treatment. METHODS: From September 2004 to August 2010, a total of 173 patients with lung cancer were...... referred to treatment at Queen Ingrid's Hospital. On 1 February 2014, treatment results, survival, and prognostic variables were analysed. RESULTS: The mean age at diagnosis was 63 years. Non-small cell lung cancer (NSCLC) was diagnosed in 145 patients (84%); 56% had squamous cell carcinoma, 34% had...... adenocarcinoma, 2% had large cell carcinoma and 8% had NSCLC not otherwise specified (NOS). In all, 28 (16%) had small cell lung cancer. A total of 142 patients (82%) received treatment; 20 underwent surgery (ten stage Ib, one stage IIa, five stage IIb, four stage IIIa); palliative chemotherapy was given to 122...

Loss of Bad expression confers poor prognosis in non-small cell lung cancer.

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Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin

2012-09-01

Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.

Rectal Metastases from Squamous Cell Carcinoma: A Case Report and Review of the Literature

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S. Cedrés

2012-01-01

Full Text Available Non-small-cell lung cancer (NSCLC represents 85% of lung cancer. The most frequent sites of distant metastasis are the liver, adrenal glands, bones and brain. Gastrointestinal metastases are uncommon and rectal metastases are extremely rare. Here we report a case of squamous cell carcinoma of the lung with rectal metastases.

Effective avoidance of a functional spect-perfused lung using intensity modulated radiotherapy (IMRT) for non-small cell lung cancer (NSCLC): An update of a planning study

International Nuclear Information System (INIS)

Lavrenkov, Konstantin; Singh, Shalini; Christian, Judith A.; Partridge, Mike; Nioutsikou, Elena; Cook, Gary; Bedford, James L.; Brada, Michael

2009-01-01

IMRT and 3-dimensional conformal radiotherapy (3-DCRT) plans of 25 patients with non-small cell lung (NSCLC) were compared in terms of planning target volume (PTV) coverage and sparing of functional lung (FL) defined by a SPECT perfusion scan. IMRT resulted in significant reduction of functional V 20 and mean lung dose in stage III patients with inhomogeneous hypoperfusion. If the dose to FL is shown to be the determinant of lung toxicity, IMRT would allow for effective dose escalation by specific avoidance of functional lung.

The CT Findings and the Peak SUV on PET/CT according to the Levels of Cyfra 21-1 and CEA in Patients with Non-Small Cell Lung Carcinoma

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Jou, Sung Shick; Kim, Young Tong; Han, Jong Kyu; Kim, Hyung Hwan; Park, Jeong Mi; Park, Jai Soung; Hwang, Jung Hwa

2009-01-01

We wanted to evaluate the CT findings and the peak SUV according to the levels of cyfra 21-1 and CEA in patients with non-small cell lung carcinoma (NSCLC). We evaluated the TNM staging, cell types, the CT findings and peak SUV of the NSCLC in 234 patients with NSCLC according to the tumor marker levels. The correlations of the CT findings and the peak SUV with the tumor markers were evaluated in 35 patients with stage I disease. The sensitivities of the combined tumor markers cyfra 21-1 and CEA in the NSCLC for each TNM staging (I-IV) were 48.5%, 66.7%, 78.3% and 84.3%, respectively (p<0.05). Cyfra 21-1 was more sensitive for squamous cell carcinoma and CEA was more sensitive for adenocarcinoma. The tumor size, tumor necrosis and peak SUV were greater in the NSCLC with an elevated cyfra 21-1 level than that in the NSCLC without an elevated cyfra 21-1 level (p<0.05). For stage I disease, the level of cyfra 21-1 was linearly correlated with the tumor size (r=0.54) and the peak SUV (r=0.46), and the level of CEA was high in the spiculated masses (p<0.05). The NSCLC with an elevated cyfra 21-1 level shows larger, more frequently necrosis and a higher peak SUV than the NSCLC without an elevated Cyfra 21-1 level. For stage 1 disease, the tumor size and peak SUV correlate with the level of cyfra 21-1, and spiculated masses show an elevated level of CEA

The CT Findings and the Peak SUV on PET/CT according to the Levels of Cyfra 21-1 and CEA in Patients with Non-Small Cell Lung Carcinoma

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Jou, Sung Shick; Kim, Young Tong; Han, Jong Kyu; Kim, Hyung Hwan [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of); Park, Jeong Mi; Park, Jai Soung [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Hwang, Jung Hwa [Soonchunhyang University Hospital, Seoul (Korea, Republic of)

2009-10-15

We wanted to evaluate the CT findings and the peak SUV according to the levels of cyfra 21-1 and CEA in patients with non-small cell lung carcinoma (NSCLC). We evaluated the TNM staging, cell types, the CT findings and peak SUV of the NSCLC in 234 patients with NSCLC according to the tumor marker levels. The correlations of the CT findings and the peak SUV with the tumor markers were evaluated in 35 patients with stage I disease. The sensitivities of the combined tumor markers cyfra 21-1 and CEA in the NSCLC for each TNM staging (I-IV) were 48.5%, 66.7%, 78.3% and 84.3%, respectively (p<0.05). Cyfra 21-1 was more sensitive for squamous cell carcinoma and CEA was more sensitive for adenocarcinoma. The tumor size, tumor necrosis and peak SUV were greater in the NSCLC with an elevated cyfra 21-1 level than that in the NSCLC without an elevated cyfra 21-1 level (p<0.05). For stage I disease, the level of cyfra 21-1 was linearly correlated with the tumor size (r=0.54) and the peak SUV (r=0.46), and the level of CEA was high in the spiculated masses (p<0.05). The NSCLC with an elevated cyfra 21-1 level shows larger, more frequently necrosis and a higher peak SUV than the NSCLC without an elevated Cyfra 21-1 level. For stage 1 disease, the tumor size and peak SUV correlate with the level of cyfra 21-1, and spiculated masses show an elevated level of CEA.

Prognostic value of plasma EGFR ctDNA in NSCLC patients treated with EGFR-TKIs.

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Chengjuan Zhang

Full Text Available Epidermal growth factor receptor (EGFR specific mutations have been known to improve survival of patients with non-small-cell lung carcinoma (NSCLC. However, whether there are any changes of EGFR mutations after targeted therapy and its clinical significance is unclear. This study was to identify the status of EGFR mutations after targeted therapy and predict the prognostic significance for NSCLC patients.A total of forty-five (45 NSCLC patients who received EGFR-TKI therapy were enrolled. We identified the changes of EGFR mutations in plasma ctDNA by Amplification Refractory Mutation System (ARMS PCR technology.In the 45 cases of NSCLC with EGFR mutations, the EGFR mutation status changed in 26 cases, in which, 12 cases (26.7% from positive to negative, and 14 cases (31.1% from T790M mutation negative to positive after TKI targeted therapy. The T790M occurance group had a shorter Progression -Free-Survival (PFS than the groups of EGFR mutation undetected and EGFR mutation turned out to have no change after EGFR-TKI therapy (p < 0.05.According to this study, it's necessary to closely monitor EGFR mutations during follow-up to predict the prognosis of NSCLC patients who are to receive the TKI targeted therapy.

Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences

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Blanco, Rancés; Domínguez, Elizabeth; Morales, Orlando; Blanco, Damián; Martínez, Darel; Rengifo, Charles E.; Viada, Carmen; Cedeño, Mercedes; Rengifo, Enrique; Carr, Adriana

2015-01-01

The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p = 0.006) and proliferation index (p = 0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p = 0.020) and multivariate (p = 0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended. PMID:26634172

Spotlight on necitumumab in the treatment of non-small-cell lung carcinoma

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Thakur MK

2017-02-01

Full Text Available Manish K Thakur, Antoinette J Wozniak, Department of Oncology, Karmanos Cancer Center, Detroit, MI, USA Abstract: The treatment options for metastatic non-small-cell lung cancer (NSCLC have expanded dramatically in the last 10 years with the discovery of newer drugs and targeted therapy. Epidermal growth factor receptor (EGFR, when aberrantly activated, promotes cell growth and contributes in various ways to the malignant process. EGFR has become an important therapeutic target in a variety of malignancies. Small-molecule tyrosine kinase inhibitors (TKIs of EGFR are being used to treat advanced NSCLC and are particularly effective in the presence of EGFR mutations. Monoclonal antibodies have also been developed that block the EGFR at the cell surface and work in conjunction with chemotherapy. Necitumumab is a second-generation fully human IgG1 monoclonal antibody that has shown promise in metastatic NSCLC. The benefit has mostly been restricted to squamous cell lung cancer in the frontline setting. Considering that the survival advantage for these patients was modest, there is a need to discover biomarkers that will predict which patients will likely have the best outcomes. This review focuses on the development and clinical trial experience with necitumumab in NSCLC. Keywords: lung cancer, squamous cell, necitumumab, EGFR

Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma

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Hongliang REN

2016-04-01

Full Text Available Background and objective Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC and small cell lung carcinoma (SCLC. Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%, squamous cell carcinoma (SCC (20%-30%, and large cell carcinoma (10%. Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET/computed tomography (CT has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. Methods One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. Results The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022. There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM stage

Chromogenic in situ hybridisation (CISH) is a powerful method to detect ALK-positive non-small cell lung carcinomas.

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Wagner, F; Streubel, A; Roth, A; Stephan-Falkenau, S; Mairinger, T

2014-05-01

We assessed the potential of a chromogenic in situ hybridisation (CISH) assay in comparison with quantitative reverse transcription (RT)-PCR (qPCR) to detect anaplastic lymphoma kinase (ALK) break apart-positive lung carcinomas. Dual-colour CISH using a break apart probe for the ALK gene on 2p23 was performed with 181 formalin-fixed, paraffin-embedded tissue and agar block sections from 175 cases of non-small cell lung carcinomas (NSCLC). Stained slides were analysed with a standard bright-field microscope at 1000× magnification by counting signals from 60 non-overlapping nuclei from three different tumour areas. Samples with ≥15% of positive nuclei were judged as ALK break apart-positive. All samples were simultaneously analysed by qPCR for EML4-ALK to validate CISH results, and positive samples were subject to Sanger sequencing. CISH was successful with 173 of 181 hybridised samples (96%), and seven ALK break apart-positive cases were detected. CISH signals were specific and distinct for both colours. All positive cases were confirmed by qPCR and Sanger sequencing, and concordance between CISH and qPCR was 100%. Nearly all samples (9/10) which failed by qPCR were accessible to CISH analysis. CISH is a very reliable, convenient and inexpensive method to detect ALK-positive NSCLC. CISH success rate is comparably high as with qPCR, and it detects all ALK break apart events in a single assay. It is of special value when RNA quality is poor, or when small biopsies with a very limited amount of tumour cells have to be analysed.

Semi-Nested Real-Time Reverse Transcription Polymerase Chain Reaction Methods for the Successful Quantitation of Cytokeratin mRNA Expression Levels for the Subtyping of Non-Small-Cell Lung Carcinoma Using Paraffin-Embedded and Microdissected Lung Biopsy Specimens

International Nuclear Information System (INIS)

Nakanishi, Yoko; Shimizu, Tetsuo; Tsujino, Ichiro; Obana, Yukari; Seki, Toshimi; Fuchinoue, Fumi; Ohni, Sumie; Oinuma, Toshinori; Kusumi, Yoshiaki; Yamada, Tsutomu; Takahashi, Noriaki; Hashimoto, Shu; Nemoto, Norimichi

2013-01-01

In patients with inoperable advanced non-small cell lung carcinomas (NSCLCs), histological subtyping using small-mount biopsy specimens was often required to decide the indications for drug treatment. The aim of this study was to assess the utility of highly sensitive mRNA quantitation for the subtyping of advanced NSCLC using small formalin fixing and paraffin embedding (FFPE) biopsy samples. Cytokeratin (CK) 6, CK7, CK14, CK18, and thyroid transcription factor (TTF)-1 mRNA expression levels were measured using semi-nested real-time quantitative (snq) reverse-transcribed polymerase chain reaction (RT-PCR) in microdissected tumor cells collected from 52 lung biopsies. Our results using the present snqRT-PCR method showed an improvement in mRNA quantitation from small FFPE samples, and the mRNA expression level using snqRT-PCR was correlated with the immunohistochemical protein expression level. CK7, CK18, and TTF-1 mRNA were expressed at significantly higher levels (P<0.05) in adenocarcinoma (AD) than in squamous cell carcinoma (SQ), while CK6 and CK14 mRNA expression was significantly higher (P<0.05) in SQ than in AD. Each histology-specific CK, particularly CK18 in AD and CK6 in SQ, were shown to be correlated with a poor prognosis (P=0.02, 0.02, respectively). Our results demonstrated that a quantitative CK subtype mRNA analysis from lung biopsy samples can be useful for predicting the histology subtype and prognosis of advanced NSCLC

Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

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Pranshu eBansal

2016-05-01

Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

Promoter methylation of APC and RAR-β genes as prognostic markers in non-small cell lung cancer (NSCLC).

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Feng, Hongxiang; Zhang, Zhenrong; Qing, Xin; Wang, Xiaowei; Liang, Chaoyang; Liu, Deruo

2016-02-01

Aberrant promoter hypermethylations of tumor suppressor genes are promising markers for lung cancer diagnosis and prognosis. The purpose of this study was to determine methylation status at APC and RAR-β promoters in primary NSCLC, and whether they have any relationship with survival. APC and RAR-β promoter methylation status were determined in 41 NSCLC patients using methylation specific PCR. APC promoter methylation was detectable in 9 (22.0%) tumor samples and 6 (14.6%) corresponding non-tumor samples (P=0.391). RAR-β promoter methylation was detectable in 13 (31.7%) tumor samples and 4 (9.8%) corresponding non-tumor samples (P=0.049) in the NSCLC patients. APC promoter methylation was found to be associated with T stage (P=0.046) and nodal status (P=0.019) in non-tumor samples, and with smoking (P=0.004) in tumor samples. RAR-β promoter methylation was found associated with age (P=0.031) in non-tumor samples and with primary tumor site in tumor samples. Patients with APC promoter methylation in tumor samples showed significantly longer survival than patients without it (Log-rank P=0.014). In a multivariate analysis of prognostic factors, APC methylation in tumor samples was an independent prognostic factor (P=0.012), as were N1 positive lymph node number (P=0.025) and N2 positive lymph node number (P=0.06). Our study shows that RAR-β methylation detected in lung tissue may be used as a predictive marker for NSCLC diagnosis and that APC methylation in tumor sample may be a useful marker for superior survival in NSCLC patients. Copyright © 2015. Published by Elsevier Inc.

The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer

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Linjie Liu

2017-01-01

Full Text Available Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125 in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p<0.05, and the levels of ProGRP and NSE were significantly higher in SCLC (p<0.05. According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

Radiation protective nursing intervene of 125I seed implantation in non-small cell lung carcinoma guided by CT

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Fu Li; Zhang Zuncheng; Yu Zhaochen; Zheng Guangjun; Tian Meirong

2009-01-01

Objective: To research radiation protective nursing intervene and important notice of 125 I seeds minimally invasive implantation in non-small cell lung carcinoma (NSCLC) by CT. Methods: Under the system of therapy planning system (TPS) and posologic validation, 125 I seeds were implanted in 89 cases of NSCLC patients. The consistent radiation protective nursing intervene was used in perioperative period management. The operative successful rate, therapeutic effect and complication rate, therapeutic effect and complication rate was observed. Results: The scientific radiation protective nursing intervene can ensure that the radioactive dose distribution of 125 I seed implantation brachytherapy is consistent with the principles of effective and minimally invasive. The operative successful rate was 100%. The local control rate and 1 year survival rate respectively was 97.4% and 92.2%. But the early and later incidence rate of radioactive damaging effect was 14.6% and 1.1% respectively. Leakage of radioactive contamination has not occurred. Conclusion: The consistent TPS and posologic validation 125 I seeds implantation integrated scientific radiation protective nursing intervene. It is very important to improve the therapeutic effect of NSCLC and reduce the incidence of complications. (authors)

Dendrimer-Based Selective Proteostasis-Inhibition Strategy to Control NSCLC Growth and Progression.

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Kyla Walworth

Full Text Available Elevated valosin containing protein (VCP/p97 levels promote the progression of non-small cell lung carcinoma (NSCLC. Although many VCP inhibitors are available, most of these therapeutic compounds have low specificity for targeted tumor cell delivery. Hence, the primary aim of this study was to evaluate the in vitro efficacy of dendrimer-encapsulated potent VCP-inhibitor drug in controlling non-small cell lung carcinoma (NSCLC progression. The VCP inhibitor(s (either in their pure form or encapsulated in generation-4 PAMAM-dendrimer with hydroxyl surface were tested for their in vitro efficacy in modulating H1299 (NSCLC cells proliferation, migration, invasion, apoptosis and cell cycle progression. Our results show that VCP inhibition by DBeQ was significantly more potent than NMS-873 as evident by decreased cell proliferation (p<0.0001, MTT-assay and migration (p<0.05; scratch-assay, and increased apoptosis (p<0.05; caspase-3/7-assay as compared to untreated control cells. Next, we found that dendrimer-encapsulated DBeQ (DDNDBeQ treatment increased ubiquitinated-protein accumulation in soluble protein-fraction (immunoblotting of H1299 cells as compared to DDN-control, implying the effectiveness of DBeQ in proteostasis-inhibition. We verified by immunostaining that DDNDBeQ treatment increases accumulation of ubiquitinated-proteins that co-localizes with an ER-marker, KDEL. We observed that proteostasis-inhibition with DDNDBeQ, significantly decreased cell migration rate (scratch-assay and transwell-invasion as compared to the control-DDN treatment (p<0.05. Moreover, DDNDBeQ treatment showed a significant decrease in cell proliferation (p<0.01, MTT-assay and increased caspase-3/7 mediated apoptotic cell death (p<0.05 as compared to DDN-control. This was further verified by cell cycle analysis (propidium-iodide-staining that demonstrated significant cell cycle arrest in the G2/M-phase (p<0.001 by DDNDBeQ treatment as compared to control

Src mediates cigarette smoke-induced resistance to tyrosine kinase inhibitors in NSCLC cells.

Science.gov (United States)

Filosto, Simone; Baston, David S; Chung, Samuel; Becker, Cathleen R; Goldkorn, Tzipora

2013-08-01

The EGF receptor (EGFR) is a proto-oncogene commonly dysregulated in several cancers including non-small cell lung carcinoma (NSCLC) and, thus, is targeted for treatment using tyrosine kinase inhibitors (TKI) such as erlotinib. However, despite the efficacy observed in patients with NSCLC harboring oncogenic variants of the EGFR, general ineffectiveness of TKIs in patients with NSCLC who are current and former smokers necessitates identification of novel mechanisms to overcome this phenomenon. Previously, we showed that NSCLC cells harboring either wild-type (WT) EGFR or oncogenic mutant (MT) L858R EGFR become resistant to the effects of TKIs when exposed to cigarette smoke, evidenced by their autophosphorylation and prolonged downstream signaling. Here, we present Src as a target mediating cigarette smoke-induced resistance to TKIs in both WT EGFR- and L858R MT EGFR-expressing NSCLC cells. First, we show that cigarette smoke exposure of A549 cells leads to time-dependent activation of Src, which then abnormally binds to the WT EGFR causing TKI resistance, contrasting previous observations of constitutive binding between inactive Src and TKI-sensitive L858R MT EGFR. Next, we show that Src inhibition restores TKI sensitivity in cigarette smoke-exposed NSCLC cells, preventing EGFR autophosphorylation in the presence of erlotinib. Furthermore, we show that overexpression of a dominant-negative Src (Y527F/K295R) restores TKI sensitivity to A549 exposed to cigarette smoke. Importantly, the TKI resistance that emerges even in cigarette smoke-exposed L858R EGFR-expressing NSCLC cells could be eliminated with Src inhibition. Together, these findings offer new rationale for using Src inhibitors for treating TKI-resistant NSCLC commonly observed in smokers.

Favorable prognosis of operable non-small cell lung cancer (NSCLC) patients harboring an increased expression of tumor endothelial markers (TEMs).

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Pircher, Andreas; Fiegl, Michael; Untergasser, Gerold; Heidegger, Isabel; Medinger, Michael; Kern, Johann; Hilbe, Wolfgang

2013-08-01

Genome analyses of endothelial cells identified genes specifically expressed by tumor endothelial cells, called tumor endothelial markers (TEMs). Currently there are no data available concerning the role of TEMs in non-small cell lung cancer (NSCLC). Therefore, the aim of this study was to investigate the role of TEMs in NSCLC in vitro and in vivo. First we evaluated the expression of various TEMs (Robo4, Clec14 and ECSCR) by qRT-PCR and Western blot analyses in three NSCLC cell lines (A549, Calu1, Colo699) and compared them to human umbilical vein endothelial cells (HUVECs), endothelial colony forming cells (ECFCs) and human bronchial epithelial cells (HBEpCs). Next the expression of TEMs was measured in resected tumor tissue of NSCLC patients (n = 63) by qRT-PCR and compared to adjacent non-cancerous lung tissue (n = 52). Further, immunohistochemical analysis of Robo4 expression in tumor tissue (n = 33) and adjacent non-cancerous tissue (n = 27) was performed. We found that NSCLC cell lines and HBEpC did not express TEMs on the mRNA level compared to HUVECs (p = 0.001). In the contrary, a significant up-regulation of Robo4 and Clec14 was found in tumor samples (Robo4 p = 0.03, Clec14 p = 0.002). Both facts clearly indicate that these proteins are allocated to the tumor stromal department. Correlation with clinical data showed that increased TEM expression correlated with prolonged overall survival of operated NSCLC patients (Robo4 high 120.5 vs. Robo4 low 47.6 months, Clec14 high 108.1 vs. Clec14 low 54.5 months and ECSCR high 120.5 vs. ECSCR low 42.2 months). In summary, we found that TEMs are overexpressed in NSCLC stromal tissue and that an increased TEM expression correlated with an increased overall survival in early stage NSCLC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An unusual metastasis of lung adenocarcinoma: Biceps brachii muscle

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Muzaffer Sariaydin

2016-01-01

Full Text Available Skeletal muscle metastasis of nonsmall cell lung carcinoma (NSCLC is a rare occurrence, and the most effective treatment modality is currently unknown. In this case presentation, we report a patient with NSCLC who underwent palliative radiotherapy for biceps muscle metastasis of NSLCS. Our case was a 49-year-old woman who had lung adenocarcinoma with biceps muscle metastasis. She had been followed up for 2 years due to Stage IV lung adenocarcinoma from whom a biopsy was taken from a painful mass in right arm that was found to be compatible with metastasis of lung adenocarcinoma. She had palliative radiotherapy for her painful mass and systemic chemotherapy was planned. After palliative radiotherapy, the pain originating from the metastatic mass in right biceps muscle alleviated. Palliative radiotherapy can be a valuable treatment option for cases with skeletal muscle metastasis.

Mucoepidermoid carcinoma of lung masquerading as urothelial carcinoma of bladder

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Graham, Donna M.; O’Connor, Kate M.; Hinchion, John; Coate, Linda E.; Burke, Louise; Power, Derek G.

2013-01-01

Background Mucoepidermoid carcinoma (MEC) of the lung is a rare subtype of non-small cell lung cancer. There is no consensus regarding optimal management for this disease. Case report We present a case of MEC of the lung in a 75 year-old female with a history of superficial urothelial carcinoma of the bladder. The patient was found to have an asymptomatic lung mass. Initial biopsy suggested metastatic recurrence of urothelial carcinoma and therefore, cisplatin and gemcitabine chemotherapy was administered prior to surgical resection. Pathological analysis of the resected specimen confirmed a diagnosis of stage IIIA MEC with focal high-grade features including transitional cell-like areas. Adjuvant radiotherapy was administered due to a positive microscopic resection margin. No chemotherapy was given due to lack of supporting data. The patient developed widespread metastatic disease 3 months following completion of radiotherapy and died 1 month later. Conclusion This case demonstrates the possibility of dual pathology in cases where metastatic disease is suspected. The use of small tissue samples may complicate diagnosis due to the heterogeneity of malignant tumours. PMID:24936321

Global gene expression profiling reveals a suppressed immune response pathway associated with 3q amplification in squamous carcinoma of the lung

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Jun Qian

2015-09-01

Full Text Available Chromosome 3q26–28 is a critical region of genomic amplification in non-small cell lung cancer (NSCLC, particularly lung squamous cell carcinomas (SCCs. No molecular therapeutic target has shown clinical utility for SCC, in contrast with adenocarcinomas of the lung. To identify novel candidate drivers in this region, we performed both Array Comparative Genomic Hybridization (array CGH, Agilent Human Genome CGH 244A oligo-microarrays and Gene Expression Microarray (Agilent Human Gene Expression 4 × 44 K microarray on 24 untreated lung SCC specimens. Using our previously published integrative genomics approach, we identified 12 top amplified driver genes within this region that are highly correlated and overexpressed in lung SCC. We further demonstrated one of the 12 top amplified driver Fragile X mental retardation-related protein 1 (FXR1 as a novel cancer gene in NSCLC and FXR1 executes its regulatory function by forming a novel complex with two other oncogenes, protein kinase C, iota ( PRKCI and epithelial cell transforming 2 (ECT2 within the same amplicon in lung cancer cell. Here we report that immune response pathways are significantly suppressed in lung SCC and negatively associated with 3q driver gene expression, implying a potential role of 3q drivers in cancer immune-surveillance. In light of the attractive immunotherapy strategy using blockade of negative regulators of T cell function for multiple human cancer including lung SCC, our findings may provide a rationale for targeting 3q drivers in combination of immunotherapies for human tumors harboring the 3q amplicon. The data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE40089.

Induction of apoptosis in non-small cell lung carcinoma A549 cells by PGD₂ metabolite, 15d-PGJ₂.

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Wang, Jun-Jie; Mak, Oi-Tong

2011-11-01

PGD2 (prostaglandin D2) is a mediator in various pathophysiological processes, including inflammation and tumorigenesis. PGD2 can be converted into active metabolites and is known to activate two distinct receptors, DP (PGD2 receptor) and CRTH2/DP2 (chemoattractant receptor-homologous molecule expressed on Th2 cells). In the past, PGD2 was thought to be involved principally in the process of inflammation. However, in recent years, several studies have shown that PGD2 has anti-proliferative ability against tumorigenesis and can induce cellular apoptosis via activation of the caspase-dependent pathway in human colorectal cancer cells, leukaemia cells and eosinophils. In the lung, where PGD2 is highly released when sensitized mast cells are challenged with allergen, the mechanism of PGD2-induced apoptosis is unclear. In the present study, A549 cells, a type of NSCLC (non-small cell lung carcinoma), were treated with PGD2 under various conditions, including while blocking DP and CRTH2/DP2 with the selective antagonists BWA868C and ramatroban respectively. We report here that PGD2 induces A549 cell death through the intrinsic apoptotic pathway, although the process does not appear to involve either DP or CRTH2/DP2. Similar results were also found with H2199 cells, another type of NSCLC. We found that PGD2 metabolites induce apoptosis effectively and that 15d-PGJ2 (15-deoxy-Δ12,14-prostaglandin J2) is a likely candidate for the principal apoptotic inducer in PGD2-induced apoptosis in NSCLC A549 cells.

1,25-Dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) Signaling Capacity and the Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer (NSCLC): Implications for Use of 1,25(OH){sub 2}D{sub 3} in NSCLC Treatment

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Upadhyay, Santosh Kumar; Verone, Alissa; Shoemaker, Suzanne [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Qin, Maochun; Liu, Song [Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States); Campbell, Moray; Hershberger, Pamela A., E-mail: pamela.hershberger@roswellpark.org [Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263 (United States)

2013-11-08

1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) exerts anti-proliferative activity by binding to the vitamin D receptor (VDR) and regulating gene expression. We previously reported that non-small cell lung cancer (NSCLC) cells which harbor epidermal growth factor receptor (EGFR) mutations display elevated VDR expression (VDR{sup high}) and are vitamin D-sensitive. Conversely, those with K-ras mutations are VDR{sup low} and vitamin D-refractory. Because EGFR mutations are found predominately in NSCLC cells with an epithelial phenotype and K-ras mutations are more common in cells with a mesenchymal phenotype, we investigated the relationship between vitamin D signaling capacity and the epithelial mesenchymal transition (EMT). Using NSCLC cell lines and publically available lung cancer cell line microarray data, we identified a relationship between VDR expression, 1,25(OH){sub 2}D{sub 3} sensitivity, and EMT phenotype. Further, we discovered that 1,25(OH){sub 2}D{sub 3} induces E-cadherin and decreases EMT-related molecules SNAIL, ZEB1, and vimentin in NSCLC cells. 1,25(OH){sub 2}D{sub 3}-mediated changes in gene expression are associated with a significant decrease in cell migration and maintenance of epithelial morphology. These data indicate that 1,25(OH){sub 2}D{sub 3} opposes EMT in NSCLC cells. Because EMT is associated with increased migration, invasion, and chemoresistance, our data imply that 1,25(OH){sub 2}D{sub 3} may prevent lung cancer progression in a molecularly defined subset of NSCLC patients.

Combination of paclitaxel and bevacizumab in heavily pre-treated non-small-cell lung cancer (NSCLC) patients: a case series study on 15 patients.

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Le Moulec, Sylvestre; Hadoux, Julien; Gontier, Eric; Chargari, Cyrus; Helissey, Carole; Lamand, Virginie; Tanz, Rachid; Farace, Françoise; Vedrine, Lionel; Bonardel, Gérald; Soria, Jean-Charles; Besse, Benjamin

2013-12-01

The combination of paclitaxel and bevacizumab was EMA-approved as first-line therapy in metastatic breast cancer. Moreover, in vitro studies showed a potential antiangiogenic synergistic effect of paclitaxel and bevacizumab. Between November 2008 and March 2010, this case series study included 15 patients with metastatic non squamous-cell lung carcinoma (NSCLC). Those were bevacizumab eligible and received the same regimen used in metastatic breast cancer with weekly paclitaxel (80 mg/m(2), days 1, 8 and 15) and bevacizumab (10 mg/kg at days 1 and 15) after at least one prior line of chemotherapy. Efficacy was evaluated by CT-scan and PET-FDG every two months. Circulating endothelial progenitor cells (CEP) and circulating endothelial cells (CEC) levels were explored in a subset of patients. Median age 56 (36-75), female: 47%, never smokers: 27%, adenocarcinoma: 100%, PS 0-1: 87% and PS 3: 13%. All patients were treated with a first-line platinum-based doublet with or without bevacizumab and 70% of them with erlotinib in the second-line. No major toxicity was observed. Partial response (PR) rate was 44% (31-63%) using RECIST criteria on CT-scan, and 65% (29-88%) with PET FDG. PS improved in 33% of the cases. Median progression free survival was 4.6 months. An increase of CEC and CEP was observed in patients with NSCLC treated with paclitaxel and bevacizumab. In this retrospective series, our results suggest efficacy signal in pre-treated metastatic NSCLC and warrant further assessment in a randomized clinical trial.

Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

Differences in practice patterns and costs between small cell and non-small cell lung cancer patients in Japan

International Nuclear Information System (INIS)

Kuwabara, Kazuaki; Matsuda, Shinya; Fushimi, Kiyohide; Anan, Makoto; Ishikawa, Koichi B.; Horiguchi, Hiromasa; Hayashida, Kenshi; Fujimori, Kenji

2009-01-01

Many reports exist regarding the economic evaluation of evolving chemotherapeutic regimens or diagnostic images for lung cancer (LC) patients. However, it is not clear whether clinical information, such as pathological diagnosis or cancer stage, should be considered as a risk adjustment in lung cancer. This study compared the cost and practice patterns between small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC) patients. 6,060 LC patients treated at 58 academic hospitals and 14,507 at 257 community hospitals were analyzed. Study variables included demographic variables, comorbid status, cancer stage, use of imaging and surgical procedures, type of adjuvant therapy (chemotherapy, radiation or chemoradiation), use of ten chemotherapeutic agents, length of stay (LOS), and total charges (TC; US$1=100 yen) in SCLC and NSCLC patients. The impact of pathological diagnosis on LOS and TC was investigated using multivariate analysis. We identified 3,571 SCLC and 16,996 NSCLC patients. The proportion of demographic and practice-process variables differed significantly between SCLC and NSCLC patients, including diagnostic imaging, adjuvant therapy and surgical procedures. Median LOS and TC were 20 days and US$6,015 for SCLC and 18 days and US$6,993 for NSCLC patients, respectively (p<0.001 for each variable). Regression analysis revealed that pathological diagnosis was not correlated with TC. Physicians should acknowledge that pathological diagnosis dose not accounts for any variation in cost of LC patients but that should remain as an indicator of appropriate care like selection of chemotherapeutic agents. (author)

Fasting blood glucose level and prognosis in non-small cell lung cancer (NSCLC) patients.

Science.gov (United States)

Luo, Juhua; Chen, Yea-Jyh; Chang, Li-Jung

2012-05-01

Diabetes has been consistently linked to many forms of cancers, such as liver, colorectal, pancreatic, and breast cancer, however, the role of diabetes in outcome among cancer patients remains unclear. In this study, we retrospectively reviewed electronic medical records of 342 inpatients newly diagnosed with NSCLC referred by a teaching hospital cancer center in southern Taiwan between 2005 and 2007 to examine the effects of fasting glucose levels at time of cancer diagnosis on overall survival in patients with non-small cell lung cancer (NSCLC). All patients were followed up until the end of 2010. The Kaplan-Meier method was used to compare survival curves for patients with and without diabetes. The Cox proportional hazards model was used to estimate hazard ratios for the association between diabetes, other prognostic factors and patient survival. We observed that significant prognostic factors for poor overall survival in patients with NSCLC included older age, smoking, poor performance status, advanced stage (stage IIIB or IV), and no cancer-directed surgery treatment. Particularly, we identified that diabetic state defined by fasting blood glucose level ≥126 mg/dl was another independent prognostic factor for these patients. Compared with those who had normal range of fasting glucose level (70-99 mg/dl), patients with high fasting glucose level (≥126 mg/dl) had 69% excess risk of all-cause mortality in patients with NSCLC. Diabetes as indicated by elevated fasting blood glucose was independently associated with a significantly higher risk of all-cause mortality in patients with NSCLC, indicating that diabetes or hyperglycemia effectively controlled may present an opportunity for improving prognosis in NSCLS patients with abnormal glucose level. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Evaluation of pentavalent Tc-99m DMSA scintigraphy in small cell and nonsmall cell lung cancers

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Atasever, T.; Guendogdu, C.; Vural, G.; Kapucu, L.Oe.; Karalezli, A.; Uenlue, M. [Gazi Univ., Faculty of Medicine, Nuclear Medicine Department and Atatuerk Chest Diseases and Surgery Center, Ankara (Turkey)

1997-10-01

Aim: The purpose of this study was to evaluate the clinical usefulness of Tc-99m (V) DMSA in patients suspected of lung cancer and determine whether this agent may have value in differentiation between small cell (SCLC) and non-small cell (NSCLC) lung carcinoma. Methods: Thirty-six patients with clinical and radiological suspicion of primary lung carcinoma were injected 450-600 MBq of Tc-99m (V) DMSA intravenously. Whole body and planar anterior, posterior thorax images were obtained 4-5 h after injection of the radioactive complex. Results: Histopathological results confirmed 23 NSCLC, 10 SCLC and 1 metastatic lung carcinoma and 2 lung abscess. Nineteen of the 23 (82%) NSCLC and all of the 10 (100%) SCLC cases showed Tc-99m (V) DMSA uptake. Single metastatic lung cancer also accumulated radiotracer. Lung abscess did not show uptake. Lesion/Nonlesion (L/N) ratio of SCLC (1.59{+-}0.32) and NSCLC (1.43{+-}0.19) tumour types did not show statistical difference (p>0.05). Tc-99m (V) DMSA whole body imaging also showed bone metastases. Conclusion: Tc-99m (V) DMSA is a noninvasive and cheap imaging method to detect malignant lung cancers and their bone metastases but, differentiation of SCLC and NSCLC is not possible. (orig.) [Deutsch] Ziel: Pruefung der klinischen Brauchbarkeit von {sup 99m}Tc-(V) DMSA bei Patienten mit Verdacht auf Bronchialkarzinom im Hinblick auf die Moeglichkeit einer Differenzierung zwischen Kleinzeller (KLZ) und Nichtkleinzeller (NKLZ). Methoden: Bei 36 Patienten mit klinischem und radiologischem Hinweis auf Bronchialkarzinom wurden 450 bis 600 MBq {sup 99m}Tc-(V) DMSA i.v. appliziert. 4-5 h spaeter wurden Ganzkoerper- und planare Szintigramme des Thorax durchgefuehrt. Ergebnisse: Feingewebliche Untersuchungen bestaetigten in 23 Faellen NKLZ, zehnmal KLZ, einmal ein metastasierendes Bronchialkarzinom und zwei Lungenabszesse. 19 der 23 NKLZ- (82%) und 100% der KLZ-Faelle zeigten eine {sup 99m}Tc-(V) DMSA-Speicherung ebenso wie das metastasierende

Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients

Science.gov (United States)

Yin, Ji-Ye; Huang, Qiong; Zhao, Ying-Chun; Zhou, Hong-Hao; Liu, Zhao-Qian

2012-01-01

Aim To determine the pharmacogenetics of platinum-based chemotherapy in Non Small Cell Lung Cancer (NSCLC) patients. Methods Publications were selected from PubMed, Cochrane Library and ISI Web of Knowledge. A meta-analysis was conducted to determine the association between genetic polymorphisms and platinum-based chemotherapy by checking odds ratio (OR) and 95% confidence interval (CI). Results Data were extracted from 24 publications, which included 11 polymorphisms in 8 genes for meta-analysis. MDR1 C3435T (OR = 1.97, 95% CI: 1.11–3.50, P = 0.02), G2677A/T (OR = 2.61, 95% CI: 1.44–4.74, P = 0.002) and GSTP1 A313G (OR = 0.32, 95% CI: 0.17–0.58, P = 0.0002) were significantly correlated with platinum-based chemotherapy in Asian NSCLC patients. Conclusion Attention should be paid to MDR1 C3435T, G2677A/T and GSTP1 A313G for personalized chemotherapy treatment for NSCLC patients in Asian population in the future. PMID:22761669

miR-151a induces partial EMT by regulating E-cadherin in NSCLC cells

DEFF Research Database (Denmark)

Daugaard, Iben; Sanders, K J; Idica, A

2017-01-01

mortality. Here, we demonstrate that miR-151a is overexpressed in non-small cell lung cancer (NSCLC) patient specimens, as compared to healthy lung. In addition, miR-151a overexpression promotes proliferation, epithelial-to-mesenchymal transition (EMT) and induces tumor cell migration and invasion of NSCLC......-cadherin in miR-151a NSCLC cell lines potently repressed miR-151a-induced partial EMT and cell migration of NSCLC cells. In conclusion, our findings suggest that miR-151a functions as an oncomiR in NSCLC by targeting E-cadherin mRNA and inducing proliferation, migration and partial EMT....

Predictive significance of standardized uptake value parameters of FDG-PET in patients with non-small cell lung carcinoma

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Duan, X-Y.; Wang, W.; Li, M.; Li, Y.; Guo, Y-M. [PET-CT Center, The First Affiliated Hospital of Xi' an, Jiaotong University, Xi' an, Shaanxi (China)

2015-02-03

{sup 18}F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is widely used to diagnose and stage non-small cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the predictive ability of different FDG standardized uptake values (SUVs) in 74 patients with newly diagnosed NSCLC. {sup 18}F-FDG PET/CT scans were performed and different SUV parameters (SUV{sub max}, SUV{sub avg}, SUV{sub T/L}, and SUV{sub T/A}) obtained, and their relationship with clinical characteristics were investigated. Meanwhile, correlation and multiple stepwise regression analyses were performed to determine the primary predictor of SUVs for NSCLC. Age, gender, and tumor size significantly affected SUV parameters. The mean SUVs of squamous cell carcinoma were higher than those of adenocarcinoma. Poorly differentiated tumors exhibited higher SUVs than well-differentiated ones. Further analyses based on the pathologic type revealed that the SUV{sub max}, SUV{sub avg}, and SUV{sub T/L} of poorly differentiated adenocarcinoma tumors were higher than those of moderately or well-differentiated tumors. Among these four SUV parameters, SUV{sub T/L} was the primary predictor for tumor differentiation. However, in adenocarcinoma, SUV{sub max} was the determining factor for tumor differentiation. Our results showed that these four SUV parameters had predictive significance related to NSCLC tumor differentiation; SUV{sub T/L} appeared to be most useful overall, but SUV{sub max} was the best index for adenocarcinoma tumor differentiation.

Should mediastinoscopy actually be incorporated into the FDG PET strategy for patients with non-small cell lung carcinoma?

International Nuclear Information System (INIS)

Hayashi, Katsumi; Abe, Katsumi; Yano, Fuzuki; Watanabe, Sadahiro; Iwasaki, Yoshie; Kosuda, Shigeru

2005-01-01

Incorporating mediastinoscopy (MS) into the PET-based strategy for non-small cell lung carcinoma (NSCLC) patients might be cost-effective because MS can allow unnecessary thoracotomies to be avoided. The objective of our study was to assess the cost-effectiveness of incorporating MS into a PET strategy for NSCLC patients. To determine life expectancy (LE), quality adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER), a decision-tree sensitivity analysis was designed for histopathologically confirmed NSCLC patients with M0 disease, based on the three competing strategies of chest CT only vs. PET+CT vs. PET+CT+MS. A simulation of 1,000 NSCLC patients was created using baselines of other relevant variables in regard to sensitivity, specificity, mortality, LE, utilities and cost from published data. One-way sensitivity analyses were performed to determine the influences of mediastinal metastasis prevalence on LE, QALY and ICER. The LE and QALY per patient in the CT only strategy, PET+CT strategy and PET+CT+MS strategy were 4.79 and 4.35, 5.33 and 4.93 and 5.68 and 5.33 years, respectively, with a 20% prevalence of mediastinal metastasis. The ICERs were 906.6 yen x 10 3 (US$7,555)/QALY/patient at a 20% mediastinal metastasis prevalence, and 2,194 yen x 10 3 (US$18,282)/QALY/patient at a 50% prevalence, but exceeded 5,280 yen x 10 3 (US$44,000)/QALY/patient at 80%. Our study quantitatively showed the CT+PET+MS strategy in place of the PET+CT strategy in managing NSCLC patients to be cost-effective. MS should be incorporated into the PET+CT strategy for NSCLC patients except in those highly suspected of having mediastinal disease on chest CT or PET. (author)

Expression of PAM50 Genes in Lung Cancer: Evidence that Interactions between Hormone Receptors and HER2/HER3 Contribute to Poor Outcome

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Jill M. Siegfried

2015-11-01

Full Text Available Non–small cell lung cancers (NSCLCs frequently express estrogen receptor (ER β, and estrogen signaling is active in many lung tumors. We investigated the ability of genes contained in the prediction analysis of microarray 50 (PAM50 breast cancer risk predictor gene signature to provide prognostic information in NSCLC. Supervised principal component analysis of mRNA expression data was used to evaluate the ability of the PAM50 panel to provide prognostic information in a stage I NSCLC cohort, in an all-stage NSCLC cohort, and in The Cancer Genome Atlas data. Immunohistochemistry was used to determine status of ERβ and other proteins in lung tumor tissue. Associations with prognosis were observed in the stage I cohort. Cross-validation identified seven genes that, when analyzed together, consistently showed survival associations. In pathway analysis, the seven-gene panel described one network containing the ER and progesterone receptor, as well as human epidermal growth factor receptor (HER2/HER3 and neuregulin-1. NSCLC cases also showed a significant association between ERβ and HER2 protein expression. Cases positive for HER2 expression were more likely to express HER3, and ERβ-positive cases were less likely to be both HER2 and HER3 negative. Prognostic ability of genes in the PAM50 panel was verified in an ERβ-positive cohort representing all NSCLC stages. In The Cancer Genome Atlas data sets, the PAM50 gene set was prognostic in both adenocarcinoma and squamous cell carcinoma, whereas the seven-gene panel was prognostic only in squamous cell carcinoma. Genes in the PAM50 panel, including those linking ER and HER2, identify lung cancer patients at risk for poor outcome, especially among ERβ-positive cases and squamous cell carcinoma.

Induction of Activating Transcription Factor 3 Is Associated with Cisplatin Responsiveness in Non–Small Cell Lung Carcinoma Cells

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Jair Bar

2016-09-01

Full Text Available Non–small cell lung carcinoma (NSCLC is the most common cause of cancer deaths, with platin-based combination chemotherapy the most efficacious therapies. Gains in overall survival are modest, highlighting the need for novel therapeutic approaches including the development of next-generation platin combination regimens. The goal of this study was to identify novel regulators of platin-induced cytotoxicity as potential therapeutic targets to further enhance platin cytotoxicity. Employing RNA-seq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their cisplatin-resistant sublines, Calu6cisR1 and H23cisR1, activating transcription factor 3 (ATF3 was robustly induced in cisplatin-treated parental sensitive cell lines but not their resistant sublines, and in three of six tumors evaluated, but not in their corresponding normal adjacent lung tissue (0/6. Cisplatin-induced JNK activation was a key regulator of this ATF3 induction. Interestingly, in both resistant sublines, this JNK induction was abrogated, and the expression of an activated JNK construct in these cells enhanced both cisplatin-induced cytotoxicity and ATF3 induction. An FDA-approved drug compound screen was employed to identify enhancers of cisplatin cytotoxicity that were dependent on ATF3 gene expression. Vorinostat, a histone deacetylase inhibitor, was identified in this screen and demonstrated synergistic cytotoxicity with cisplatin in both the parental Calu6 and H23 cell lines and importantly in their resistant sublines as well that was dependent on ATF3 expression. Thus, we have identified ATF3 as an important regulator of cisplatin cytotoxicity and that ATF3 inducers in combination with platins are a potential novel therapeutic approach for NSCLC.

File list: Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung mm9 Unclassified Lung Carcinoma, Lewis Lung ...http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Lng.20.AllAg.Carcinoma,_Lewis_Lung.bed ...

Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): Predictors for radiation pneumonitis and fibrosis

International Nuclear Information System (INIS)

Kong, F.-M.; Hayman, James A.; Griffith, Kent A.; Kalemkerian, Gregory P.; Arenberg, Douglas; Lyons, Susan; Turrisi, Andrew; Lichter, Allen; Fraass, Benedick; Eisbruch, Avraham; Lawrence, Theodore S.; Haken, Randall K. ten

2006-01-01

Purpose: We aimed to report the final toxicity results on a radiation-dose escalation trial designed to test a hypothesis that very high doses of radiation could be safely administered to patients with non-small-cell lung cancer (NSCLC) by quantifying the dose-volume toxicity relationship of the lung. Methods and Materials: A total of 109 patients with unresectable or medically inoperable NSCLC were enrolled and treated with radiation-dose escalation (on the basis of predicted normal-lung toxicity) either alone or with neoadjuvant chemotherapy by use of 3D conformal techniques. Eighty-four patients (77%) received more than 69 Gy, the trial was stopped after the dose reached 103 Gy. Estimated median follow-up was 110 months. Results: There were 17 (14.6%) Grade 2 to 3 pneumonitis and 15 (13.8%) Grade 2 to 3 fibrosis and no Grade 4 to 5 lung toxicity. Multivariate analyses showed them to be (1) not associated with the dose prescribed to the tumor, and (2) significantly (p < 0.001) associated with lung-dosimetric parameters such as the mean lung dose (MLD), volume of lung that received at least 20 Gy (V20), and the normal-tissue complication probability (NTCP) of the lung. If cutoffs are 30% for V20, 20 Gy for MLD, and 10% for NTCP, these factors have positive predictive values of 50% to 71% and negative predictive value of 85% to 89%. Conclusions: With long-term follow-up for toxicity, we have demonstrated that much higher doses of radiation than are traditionally administered can be safely delivered to a majority of patients with NSCLC. Quantitative lung dose-volume toxicity-based dose escalation can form the basis for individualized high-dose radiation treatment to maximize the therapeutic ratio in these patients

File list: DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.10.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 RNA polymerase Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung mm9 RNA polymerase Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.05.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung mm9 RNA polymerase Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Lng.10.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung mm9 DNase-seq Lung Carcinoma, Lewis Lung htt...p://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Lng.20.AllAg.Carcinoma,_Lewis_Lung.bed ...

EGFR Mutations in Surgically Resected Fresh Specimens from 697 Consecutive Chinese Patients with Non-Small Cell Lung Cancer and Their Relationships with Clinical Features

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Yuanyang Lai

2013-12-01

Full Text Available We aimed to reveal the true status of epidermal growth factor receptor (EGFR mutations in Chinese patients with non-small cell lung cancer (NSCLC after lung resections. EGFR mutations of surgically resected fresh tumor samples from 697 Chinese NSCLC patients were analyzed by Amplification Refractory Mutation System (ARMS. Correlations between EGFR mutation hotspots and clinical features were also explored. Of the 697 NSCLC patients, 235 (33.7% patients had tyrosine kinase inhibitor (TKIs sensitive EGFR mutations in 41 (14.5% of the 282 squamous carcinomas, 155 (52.9% of the 293 adenocarcinomas, 34 (39.5% of the 86 adenosquamous carcinomas, one (9.1% of the 11 large-cell carcinomas, 2 (11.1% of the 18 sarcomatoid carcinomas, and 2 (28.6% of the 7 mucoepidermoid carcinomas. TKIs sensitive EGFR mutations were more frequently found in female patients (p < 0.001, non-smokers (p = 0.047 and adenocarcinomas (p < 0.001. The rates of exon 19 deletion mutation (19-del, exon 21 L858R point mutation (L858R, exon 21 L861Q point mutation (L861Q, exon 18 G719X point mutations (G719X, including G719C, G719S, G719A were 43.4%, 48.1%, 1.7% and 6.8%, respectively. Exon 20 T790M point mutation (T790M was detected in 3 squamous carcinomas and 3 adenocarcinomas and exon 20 insertion mutation (20-ins was detected in 2 patients with adenocarcinoma. Our results show the rates of EGFR mutations are higher in all types of NSCLC in Chinese patients. 19-del and L858R are two of the more frequent mutations. EGFR mutation detection should be performed as a routine postoperative examination in Chinese NSCLC patients.

File list: Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung mm9 TFs and others Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Lng.05.AllAg.Carcinoma,_Lewis_Lung.bed ...

Expression of Rab25 in non-small cell lung cancer and its clinical significance

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Pu ZHOU

2014-03-01

Full Text Available Objective　To assess the expression of Rab25 protein in non-small cell lung cancer (NSCLC, and explore the correlation of its expression with tumor proliferation and metastasis. Methods　Sixty-one cases of NSCLC specimens (31 cases of squamous cell carcinoma, 26 cases of adenocarcinoma, and 4 cases of adenosquamous carcinoma undergone surgical treatment, and 40 specimens of adjacent normal lung tissues were obtained from Jan. 2009 to Jun. 2010 at Xingqiao Hospital of Third Military Medical University. Immunochemistry method of MaxVision was used to detect the expression of Rab25 in the specimens, and then the correlation of the expression with the clinicopathological parameters (patients' sex, age, smoking history, tumor type, differentiation, volume, TNM stage, lymph metastasis, etc. was analyzed using statistical software SPSS 21.0. Results 　Rab25 protein was mainly expressed in cytoplasm and cell membrane. The positive rate of Rab25 in NSCLC was 93.4%, which was significantly higher than that in adjacent normal tissues (27.5%, P＜0.01. The expression of Rab25 protein was significantly associated with the TNM stage and tumor size (P＜0.05. Conclusions　The expression of Rab25 is obviously higher in NSCLC than in the adjacent normal tissues, and the expression is associated with TNM stage and tumor size. Moreover, the later of the NSCLC stage, the larger of tumor size, and the higher of Rab25 expression will be in the NSCLC tissue. DOI: 10.11855/j.issn.0577-7402.2014.02.16

FOCUS ON NIVOLUMAB IN NSCLC

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Diego Luigi Cortinovis

2016-12-01

Full Text Available Immunotherapy is changing the treatment of non-small cell lung cancer (NSCLC. The PD-1 inhibitor nivolumab has demonstrated meaningful results in terms of efficacy with a good safety profile. The novel approach of treating NSCLC using immunotherapy has still unsolved questions and challenging issues in regard to the optimal selection of the patient, its role in first line of treatment, the individualization of the correct methodology of radiologic assessment and efficacy analysis, the best management of immunomediated adverse events, and how to overcome the immunoresistance.

Y-chromosome status identification suggests a recipient origin of posttransplant non-small cell lung carcinomas: chromogenic in situ hybridization analysis.

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Chen, Wei; Brodsky, Sergey V; Zhao, Weiqiang; Otterson, Gregory A; Villalona-Calero, Miguel; Satoskar, Anjali A; Hasan, Ayesha; Pelletier, Ronald; Ivanov, Iouri; Ross, Patrick; Nadasdy, Tibor; Shilo, Konstantin

2014-05-01

Owing to the need of lifelong immunosuppression, solid-organ transplant recipients are known to have an increased risk of posttransplant malignancies including lung cancer. Posttransplant neoplastic transformation of donor-derived cells giving rise to hematopoietic malignancies, Kaposi sarcoma, and basal cell carcinoma in nongraft tissues has been reported. The goal of this study was to assess the cell origin (donor versus recipient derived) of posttransplant non-small cell lung carcinomas (NSCLCs) in kidney and heart transplant recipients. An institutional database search identified 2557 kidney and heart transplant recipients in 8 consecutive years. Among this cohort, 20 (0.8%) renal and 18 (0.7%) heart transplant recipients developed NSCLC. The study cohort comprised 6 of 38 NSCLCs arising in donor-recipient sex-mismatched transplant patients. The tumor cell origin was evaluated by chromogenic in situ hybridization with Y-chromosome probe on formalin-fixed, paraffin-embedded tissues. Y-chromosome was identified in 97% ± 1% (range from 92% to 99%) of all types of nucleated cells in male control tissues. In all 5 NSCLCs from male recipients of female donor organ, Y-chromosome was identified in 97% ± 2% (range from 92% to 100%) of tumor cells, statistically equivalent to normal control (P recipient of male kidney. These findings suggest a recipient derivation of NSCLC arising in kidney and heart transplant recipients. A combination of histologic evaluation and chromogenic in situ hybridization with Y-chromosome analysis allows reliable determination of tissue origin in sex-mismatched solid-organ transplant recipients and may aid in management of posttransplant malignancy in such cases. Copyright © 2014 Elsevier Inc. All rights reserved.

Phase II trial of second-line erlotinib and digoxin for nonsmall cell lung cancer (NSCLC

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Fadi Kayali

2011-02-01

Full Text Available Fadi Kayali, Muhamad A Janjua, Damian A Laber, Donald Miller, Goetz H KloeckerUniversity of Louisville, James Graham Brown Cancer Center, Louisville, KY, USABackground: In vitro digoxin sensitizes cancer cells to the induction of apoptosis by chemotherapy. Inhibition of the Na/K-ATPase enzyme by ouabain disturbs the intracellular ion composition of cancer cells, altering cellular homeostasis. This suggests that inhibition of the Na/K pump results in cellular sensitization of malignant but not benign cells to the induction of apoptosis. Epidemiologic studies have also shown beneficial effects of digitalis in breast cancer incidence. At ASCO (American Society of Clinical Oncology 2007 our group presented a Phase II study showing encouraging results by adding digoxin to biochemotherapy for melanoma. Erlotinib is one of the standard second-line treatments for nonsmall cell lung cancer (NSCLC, with a response rate (RR of 10%. This study's hypothesis was that adding digoxin to erlotinib will improve the RR and time to progression (TTP in NSCLC.Methods: Patients with progressive disease (PD after chemotherapy were enrolled if they had an ECOG (Eastern Cooperative Oncology Group score from 0 to 2 and good organ function. Daily erlotinib 150 mg and digoxin 0.25 mg were taken by mouth. The digoxin dose was adjusted to keep levels between 1 and 2 ng/mL. Computed tomography scans were done every 6 weeks. Treatment continued until PD or significant toxicity occurred.Results: Patient accrual lasted from March 2006 until August 2008 and was stopped early at the time of interim analysis. Twenty-eight patients were enrolled, and 24 who completed at least 6 weeks of therapy are presented here. All patients had unresectable NSCLC stage III/IV at diagnosis. Median age was 61 (34–78, 14 were female, 17 had prior radiation (not involving the target lesions, 23 had one prior chemotherapy, and one subject had two. Only one patient was a never-smoker. Histologies were

An Evidence-Based Approach to the Use of Predictive Biomarkers in the Treatment of Non- Small Cell Lung Cancer (NSCLC)

International Nuclear Information System (INIS)

Quinton, Cindy; Ellis, Peter M.

2011-01-01

Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research

The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

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Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

2010-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival.

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Marsit, Carmen J; Liu, Mei; Nelson, Heather H; Posner, Marshall; Suzuki, Makoto; Kelsey, Karl T

2004-01-29

Inactivation of the FANC-BRCA pathway via promoter methylation of the FANCF gene renders cells sensitive to DNA crosslinking agents, and has been identified in ovarian cancer cell lines and sporadic primary tumor tissues. We investigated epigenetic alterations in the FANC-BRCA pathway in head and neck squamous cell carcinomas (HNSCC) and non-small-cell lung cancers (NSCLC) using methylation-specific PCR. Promoter methylation of FANCF occurred in 15% (13/89) of HNSCCs and 14% (22/158) of NSCLCs. Methylation of BRCA1 occurred only in 6/158 NSCLC, and was limited to adenocarcinomas and large-cell carcinomas of the lung. No methylation of BRCA2 was detected. FANCF methylation was associated with a shorter duration of tobacco use (P=0.03) and a younger age of starting smoking (P=0.06) in NSCLC, and with a greater number of years of alcohol drinking (P=0.02) in HNSCC. In adenocarcinomas of the lung, FANCF promoter methylation was a significant predictor of poor survival with a hazard ratio of 3.1 (95% CI 1.2-7.9). This study demonstrates that inactivation of the FANC-BRCA pathway is relatively common in solid tumors and may be related to tobacco and alcohol exposure and survival of these patients.

Distribution and mRNA Expression of BAMBI in Non-small-cell Lung Cancer

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Shen MIAO

2009-03-01

Full Text Available Background and objective BAMBI structure is similar with that of the receptor Ⅰof TGF-β, it broadly participates in the control of TGF-β signaling. The aim of this study is to investigate the expression and its significance of BAMBI in non-small cell lung cancer (NSCLC and explore the relation between BAMBI and clinical and pathological factors of NSCLC. Methods Sixty-three cases with NSCLC and adjacent normal tissue specimens were used for immunohistochemical assay. Thirty-one fresh lung cancer tissue specimens and surrounding normal lung tissue specimens was preserved for RT-PCR in -70 ℃ after quick-frozen in liquid nitrogen immediately. Results The level of BAMBI mRNA in cancer tissues was higher than that in the corresponding adjacent tissues (0.358±0.135 vs 0.249±0.129, with the difference being statistically significant (P =0.003. BAMBI protein expressed mainly in the membrane and the cytoplasm close to the membrane, its expression in the cancer tissue was higher than that in the adjacent tissues, the difference was significant (P <0.01. Expression of BAMBI in the cancer tissue was higher than that in the adjacent tissues, and the expression of BAMBI in adenocarcinoma of lung is higher than that in squamous carcinoma. Conclusion The expressions of BAMBI significantly increase in NSCLC. It might be a common affair in carcinogenesis of NSCLC.

Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

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Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

2010-11-01

Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. Copyright © 2010 Elsevier Ltd. All rights reserved.

File list: His.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Lng.05.AllAg.Carcinoma,_Lewis_Lung mm9 Histone Lung Carcinoma, Lewis Lung SRX10...91778,SRX1091782,SRX1091783,SRX1091781,SRX1091784,SRX1091779,SRX1091785,SRX1091780 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Lng.05.AllAg.Carcinoma,_Lewis_Lung.bed ...

Stat3 is a positive regulator of gap junctional intercellular communication in cultured, human lung carcinoma cells

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Geletu Mulu

2012-12-01

Full Text Available Abstract Background Neoplastic transformation of cultured cells by a number of oncogenes such as src suppresses gap junctional, intercellular communication (GJIC; however, the role of Src and its effector Signal transducer and activator of transcription-3 (Stat3 upon GJIC in non small cell lung cancer (NSCLC has not been defined. Immunohistochemical analysis revealed high Src activity in NSCLC biopsy samples compared to normal tissues. Here we explored the potential effect of Src and Stat3 upon GJIC, by assessing the levels of tyr418-phosphorylated Src and tyr705-phosphorylated Stat3, respectively, in a panel of NSCLC cell lines. Methods Gap junctional communication was examined by electroporating the fluorescent dye Lucifer yellow into cells grown on a transparent electrode, followed by observation of the migration of the dye to the adjacent, non-electroporated cells under fluorescence illumination. Results An inverse relationship between Src activity levels and GJIC was noted; in five lines with high Src activity GJIC was absent, while two lines with extensive GJIC (QU-DB and SK-LuCi6 had low Src levels, similar to a non-transformed, immortalised lung epithelial cell line. Interestingly, examination of the mechanism indicated that Stat3 inhibition in any of the NSCLC lines expressing high endogenous Src activity levels, or in cells where Src was exogenously transduced, did not restore GJIC. On the contrary, Stat3 downregulation in immortalised lung epithelial cells or in the NSCLC lines displaying extensive GJIC actually suppressed junctional permeability. Conclusions Our findings demonstrate that although Stat3 is generally growth promoting and in an activated form it can act as an oncogene, it is actually required for gap junctional communication both in nontransformed lung epithelial cells and in certain lung cancer lines that retain extensive GJIC.

File list: InP.Lng.50.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available InP.Lng.50.AllAg.Carcinoma,_Lewis_Lung mm9 Input control Lung Carcinoma, Lewis Lung... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Lng.50.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: NoD.Lng.05.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Lng.05.AllAg.Carcinoma,_Lewis_Lung mm9 No description Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Lng.05.AllAg.Carcinoma,_Lewis_Lung.bed ...

File list: NoD.Lng.10.AllAg.Carcinoma,_Lewis_Lung [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available NoD.Lng.10.AllAg.Carcinoma,_Lewis_Lung mm9 No description Lung Carcinoma, Lewis Lun...g http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Lng.10.AllAg.Carcinoma,_Lewis_Lung.bed ...

EGFR mutation is a better predictor of response to tyrosine kinase inhibitors in non-small cell lung carcinoma than FISH, CISH, and immunohistochemistry.

Science.gov (United States)

Sholl, Lynette M; Xiao, Yun; Joshi, Victoria; Yeap, Beow Y; Cioffredi, Leigh-Anne; Jackman, David M; Lee, Charles; Jänne, Pasi A; Lindeman, Neal I

2010-06-01

About 10% of patients with non-small cell lung carcinoma (NSCLC) respond to epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors (TKIs). More than 75% of "responders" have activating mutations in EGFR. However, mutation analysis is not widely available, and proposed alternatives (in situ hybridization and immunohistochemical analysis) have shown inconsistent associations with outcome. Fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), immunohistochemical analysis, and DNA sequencing were compared in this study of 40 NSCLC samples from TKI-treated patients. Response rates were 12 of 19 in EGFR-mutant vs 1 of 20 EGFR wild-type tumors (P = .0001), 7 of 19 FISH+ vs 4 of 17 FISH- tumors (not significant [NS]), 5 of 16 CISH+ vs 6 of 21 CISH- tumors (NS), and 3 of 9 immunohistochemically positive vs 7 of 22 immunohistochemically negative tumors (NS). EGFR mutation was associated with improved progression-free survival (P = .0004). Increased copy number (FISH or CISH) and protein expression (immunohistochemical) did not independently predict outcome. Thus, EGFR sequence analysis was the only method useful for predicting response and progression-free survival following TKI therapy in NSCLC.

Role of PAX8 in the regulation of MET and RON receptor tyrosine kinases in non-small cell lung cancer

International Nuclear Information System (INIS)

Kanteti, Rajani; El-Hashani, Essam; Dhanasingh, Immanuel; Tretiakova, Maria; Husain, Aliya N; Sharma, Sherven; Sharma, Jay; Vokes, Everett E; Salgia, Ravi

2014-01-01

Non-small cell lung cancers (NSCLC) are highly heterogeneous at the molecular level and comprise 75% of all lung tumors. We have previously shown that the receptor tyrosine kinase (RTK) MET frequently suffers gain-of-function mutations that significantly promote lung tumorigenesis. Subsequent studies from our lab also revealed that PAX5 transcription factor is preferentially expressed in small cell lung cancer (SCLC) and promotes MET transcription. PAX8, however, is also expressed in NSCLC cell lines. We therefore investigated the role of PAX8 in NSCLC. Using IHC analysis, PAX8 protein expression was determined in archival NSCLC tumor tissues (n = 254). In order to study the effects of PAX8 knockdown on NSCLC cellular functions such as apoptosis and motility, siRNA against PAX8 was used. Confocal fluorescence microscopy was used to monitor the localization of MET, RON and PAX8. The combinatorial effect of PAX8 knockdown and MET inhibition using SU11274 was investigated in NSCLC cell viability assay. Relative levels of PAX8 protein were elevated (≥ + 2 on a scale of 0–3) in adenocarcinoma (58/94), large cell carcinoma (50/85), squamous cell carcinoma (28/47), and metastatic NSCLC (17/28; lymph node). Utilizing early progenitors isolated from NSCLC cell lines and fresh tumor tissues, we observed robust overexpression of PAX8, MET, and RON. PAX8 knockdown A549 cells revealed abrogated PAX8 expression with a concomitant loss in MET and the related RON kinase expression. A dramatic colocalization between the active form of MET (also RON) and PAX8 upon challenging A549 cells with HGF was visualized. A similar colocalization of MET and EGL5 (PAX8 ortholog) proteins was found in embryos of C. elegans. Most importantly, knockdown of PAX8 in A549 cells resulted in enhanced apoptosis (~6 fold) and decreased cell motility (~45%), thereby making PAX8 a potential therapeutic target. However, the combinatorial approach of PAX8 knockdown and treatment with MET inhibitor, SU

Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis

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Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

2015-01-01

Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly-differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemistry for p40, p63, thyroid transcription factor-1 (TTF-1; clone SPT24 and 8G7G3/1), Napsin A, Chromogranin A, Synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma since they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly-differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly-differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

Chromosome 5p Region SNPs Are Associated with Risk of NSCLC among Women

International Nuclear Information System (INIS)

Dyke, A. L. V.

2009-01-01

In a population-based case-control study, we explored the associations between 42 polymorphisms in seven genes in this region and non-small cell lung cancer (NSCLC) risk among Caucasian (364 cases; 380 controls) and African American (95 cases; 103 controls) women. Two TERT region SNPs, rs2075786 and rs2853677, conferred an increased risk of developing NSCLC, especially among African American women, and TERT-rs2735940 was associated with a decreased risk of lung cancer among African Americans. Five of the 20 GHR polymorphisms and SEPP1-rs6413428 were associated with a marginally increased risk of NSCLC among Caucasians. Random forest analysis reinforced the importance of GHR among Caucasians and identified AMACR, TERT, and GHR among African Americans, which were also significant using gene-based risk scores. Smoking-SNP interactions were explored, and haplotype in TERT and GHR associated with NSCLC risk were identified. The roles of TERT, GHR, AMACR and SEPP1 genes in lung carcinogenesis warrant further exploration

A single-arm, multicenter, safety-monitoring, phase IV study of icotinib in treating advanced non-small cell lung cancer (NSCLC).

Science.gov (United States)

Hu, Xingsheng; Han, Baohui; Gu, Aiqin; Zhang, Yiping; Jiao, Shun Chang; Wang, Chang-Li; He, Jintao; Jia, Xueke; Zhang, Li; Peng, Jiewen; Wu, Meina; Ying, Kejing; Wang, Junye; Ma, Kewei; Zhang, Shucai; You, Changxuan; Tan, Fenlai; Wang, Yinxiang; Ding, Lieming; Sun, Yan

2014-11-01

The phase 3 ICOGEN trial established the non-inferiority of icotinib to gefitinib in terms of progression-free survival (PFS) in non-small cell lung cancer (NSCLC) patients, and this led to the approval of icotinib for NSCLC by the China Food and Drug Administration. A phase 4 study was conducted to assess the safety and efficacy of icotinib in a broad range of patients with advanced NSCLC across China. This study retrospectively analyzed data from unresectable, recurrent, and/or advanced NSCLC patients who received oral icotinib 125 mg three times per day. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR) and disease control rate (DCR), which were investigated overall and in subgroups such as patients with an EGFR mutation and elderly patients. Between August, 2011 and August, 2012, a total of 6087 advanced NSCLC patients were registered in this study, of which 5549 were evaluable for safety and tumor response. The median age was 63 years (range 21-95 years), and 1571 (28.3%) patients were over the age of 70. The majority of patients were non-smokers, and had adenocarcinoma and stage IV disease. The overall incidence of adverse drug reactions (ADRs) of any grade was 31.5%. The most common ADRs included rash (17.4%) and diarrhea (8.5%), and three patients experienced interstitial lung disease (ILD). The ORR and DCR were 30.0% and 80.6%, respectively, for the overall population, and 33.4% and 81.2%, 30.3% and 80.3%, and 30.4% and 89.3%, for first-line, second-line, and third-line or multiple line subsets, respectively. In 665 EGFR-mutated patients who were evaluable for tumor response, the ORR and DCR were 49.2% (327/665) and 92.3% (614/665), respectively. The data from over 6000 patients was consistent with the results of the ICOGEN study. Icotinib demonstrated a favorable toxicity profile and efficacy in the routine clinical setting. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Cost-Utility Analysis of PET-Scan in Diagnosis and Treatment of Non-Small Cell Lung Carcinoma in Iran

International Nuclear Information System (INIS)

Akbari Sari, Ali; Ravaghi, Hamid; Mobinizadeh, Mohammadreza; Sarvari, Sima

2013-01-01

PET scan is a non-invasive, complex and expensive medical imaging technology that is normally used for the diagnosis and treatment of various diseases including lung cancer. The purpose of this study is to assess the cost effectiveness of this technology in the diagnosis and treatment of non- small cell lung carcinoma (NSCLC) in Iran. The main electronic databases including The Cochrane Library and Medline were searched to identify available evidence about the performance and effectiveness of technology. A standard decision tree model with seven strategies was used to perform the economic evaluation. Retrieved studies and expert opinion were used to estimate the cost of each treatment strategy in Iran. The costs were divided into three categories including capital costs (depreciation costs of buildings and equipment), staff costs and other expenses (including cost of consumables, running and maintenance costs). The costs were estimated in both IR-Rials and US-Dollars with an exchange rate of 10.000 IR Rials per one US Dollar according to the exchange rate in 2008. The total annual running cost of a PET scan was about 8850 to 13000 million Rials, (0.9 to 1.3 million US$). The average cost of performing a PET scan varied between 3 and 4.5 million Rials (300 to 450US$). The strategies 3 (mediastinoscopy alone) and 7 (mediastinoscopy after PET scan) were more cost-effective than other strategies, especially when the result of the CT-scan performed before PET scan was negative. The technical performance of PET scan is significantly higher than similar technologies for staging and treatment of NSCLC. In addition, it might slightly improve the treatment process and lead to a small level of increase in the quality adjusted life year (QALY) gained by these patients making it cost-effective for the treatment of NSCLC

The Cost-Utility Analysis of PET-Scan in Diagnosis and Treatment of Non-Small Cell Lung Carcinoma in Iran.

Science.gov (United States)

Akbari Sari, Ali; Ravaghi, Hamid; Mobinizadeh, Mohammadreza; Sarvari, Sima

2013-06-01

PET scan is a non-invasive, complex and expensive medical imaging technology that is normally used for the diagnosis and treatment of various diseases including lung cancer. The purpose of this study is to assess the cost effectiveness of this technology in the diagnosis and treatment of non- small cell lung carcinoma (NSCLC) in Iran. The main electronic databases including The Cochrane Library and Medline were searched to identify available evidence about the performance and effectiveness of technology. A standard decision tree model with seven strategies was used to perform the economic evaluation. Retrieved studies and expert opinion were used to estimate the cost of each treatment strategy in Iran. The costs were divided into three categories including capital costs (depreciation costs of buildings and equipment), staff costs and other expenses (including cost of consumables, running and maintenance costs). The costs were estimated in both IR-Rials and US-Dollars with an exchange rate of 10.000 IR Rials per one US Dollar according to the exchange rate in 2008. The total annual running cost of a PET scan was about 8850 to 13000 million Rials, (0.9 to 1.3 million US$). The average cost of performing a PET scan varied between 3 and 4.5 million Rials (300 to 450US$). The strategies 3 (mediastinoscopy alone) and 7 (mediastinoscopy after PET scan) were more cost-effective than other strategies, especially when the result of the CT-scan performed before PET scan was negative. The technical performance of PET scan is significantly higher than similar technologies for staging and treatment of NSCLC. In addition, it might slightly improve the treatment process and lead to a small level of increase in the quality adjusted life year (QALY) gained by these patients making it cost-effective for the treatment of NSCLC.

Increasing the accuracy of 18F-FDG PET/CT interpretation of "mildly positive" mediastinal nodes in the staging of non-small cell lung cancer.

LENUS (Irish Health Repository)

Moloney, F

2014-05-01

The aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC).

Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells.

Directory of Open Access Journals (Sweden)

Reenu Punia

Full Text Available Anthracyclines are efficient and potent agents to treat broad range of cancers but cytotoxicity induced by them limits their use in therapeutics. Use of plant-derived agents help to prevent or delay the process of cancer progression and their combination increases the anti-cancer potential of mainstream compound. However, multidrug resistance is major cause of treatment failure in cancer patients.In this study, combination treatments of fisetin or acacetin with doxorubicin were explored for their potential synergistic effect on non-small-cell lung carcinoma (NSCLC cells.During this study, NSCLC model cell lines A549 and H1299 were used to determine the combinatorial effect of phytochemicals namly acacetin and fisetin with doxorubicin.The effects of individual compounds and their combination on cell viability, clonogenic potential and cell cycle progression were studied. Efflux of doxorubicin was measured by spectrofluorophotometer, whereas accumulation inside the cells was analyzed by flow cytometry and confocal microscopy. Expression of MDR1 was checked by semi-quantitative PCR.The results showed that the cell viability of A549 and H1299 cells were significantly decreased in time- and dose-dependent manner, although A549 cells showed more sensitivity toward doxorubicin than H1299 cells. Mostly, combination of doxorubicin showed good synergy with acacetin in both the cell lines whereas, fisetin exerted synergistic effect only at 72 h of treatment in H1299 cells. Acacetin with doxorubicin caused G2/M arrest by downregulating CDK-cyclin complex in A549 cells. Acacetin-doxorubicin combination decreased the clonogenic potential of A549 and H1299 cells upto 82% and 59%, respectively, as compared to control. Acacetin also decreased efflux of doxorubicin by 59% after 30 mins of exposure to A549 cells and further increased accumulation of doxorubicin inside the cells upto 55% in 2 h. The modulatory effect of acacetin-doxorubicin combination on

Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8)

DEFF Research Database (Denmark)

Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel

2015-01-01

BACKGROUND: There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced...... squamous cell carcinoma of the lung. METHODS: We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum...... be an additional option for the treatment of patients with squamous cell carcinoma of the lung. FUNDING: Boehringer Ingelheim....

Genomic profiling toward precision medicine in non-small cell lung cancer: getting beyond EGFR

Directory of Open Access Journals (Sweden)

Richer AL

2015-02-01

Full Text Available Amanda L Richer,1 Jacqueline M Friel,1 Vashti M Carson,2 Landon J Inge,1 Timothy G Whitsett2 1Norton Thoracic Institute, St Joseph’s Hospital and Medical Center, 2Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Lung cancer remains the leading cause of cancer-related mortality worldwide. The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of non-small cell lung cancer (NSCLC. A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR have been identified in NSCLC. While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomic events. This review looks at the current treatment paradigms for lung adenocarcinomas and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS, TP53, and LKB1 which, to date, have been considered “undruggable”. A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality rate observed in lung cancer. Keywords: non-small cell lung cancer, precision medicine, epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine kinase 11, tumor protein p53

Diagnostic utility of neuron specific enolase (NSE) in serum and pleural fluids from patients with lung cancer and tuberculosis

International Nuclear Information System (INIS)

Alam, J.M.; Baig, J.A.; Asghar, S.S.; Mahmood, S.R.; Ansari, M.A.; Jamil, S.

2010-01-01

Several past and recent investigations have focused on the determination of tumor markers in pleural fluids to assess their Usefulness as less invasive replacement method of diagnosis. In this regard, few studies have dealt with the determination of the tumor marker, neuron specific enolase (NSE), in pleural fluids of patients suffering from both benign and malignant diseases such as non small cell lung carcinoma( NSCLC), small cell lung carcinoma( SCLC) and tuberculosis. Therefore, the present study was undertaken to establish the diagnostic utility of NSE in malignant condition by assessing levels in serum and pleural fluids of patients with lung cancer and by comparing it with a benign pulmonary disease of tuberculosis. Pleural fluids were obtained from 22 patients with carcinomatous pleurisy due to SCLC, 11 patients with carcinomatous pleurisy due to non-small cell lung cancer, and 30 patients with tuberculosis pleurisy for comparison purpose. Determination of NSE levels was performed by ECL technology according to the manufacturer's instructions. NSE levels of pleural fluids from SCLC patients were significantly elevated( P<0.0001) when compared with pleural fluids from NSCLC and tuberculosis patients. Moreover, pleural fluids of all 30 tuberculosis patients and 11 NSCLC patients showed moderate significance ( P< O.05 and P < 0.01, respectively) when compared with each other. In addition, cumulative results of NSE levels from SCLC and NSCLC combined also showed high significance (P<0.001) as compared to pleural fluids of tuberculosis patients and moderate significance (P<0.01) when compared with serum levels of both malignant and benign groups. It is concluded that determination of NSE levels in pleural fluids of lung cancer patients noted to be an effective diagnostic tool to differentiate carcinomatous pleurisy due to SCLC from those occurring due to NSCLC and tuberculosis. Further studies with larger group of patients are under progress to further establish

GrB TWEAK: A Potential Novel Biologic for NSCLC Therapy

Science.gov (United States)

2017-07-01

granzyme B, lung cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT...cost extension period we were able to test whether our therapeutic construct GrB-Fc-IT4 could inhibit NSCLC tumor growth in vivo using the NSCLC patient ...derived Fn14-positive cell line M2010-1005. The M2010-1005 line was established from a NSCLC patient with a tumor harboring the EGFRdel747-752

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

Directory of Open Access Journals (Sweden)

Ahmet Yilmaz

2014-09-01

Full Text Available Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor-targeted therapy has been used in the treatment of LC (lung cancer, mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(PH:quinone oxidoreductase, also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin in 108 patients with non-small cell lung carcinoma (NSCLC. NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1 oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2 selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3 since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke.

Expression of TMPRSS4 in non-small cell lung cancer and its modulation by hypoxia

Science.gov (United States)

NGUYEN, TRI-HUNG; WEBER, WILLIAM; HAVARI, EVIS; CONNORS, TIMOTHY; BAGLEY, REBECCA G.; McLAREN, RAJASHREE; NAMBIAR, PRASHANT R.; MADDEN, STEPHEN L.; TEICHER, BEVERLY A.; ROBERTS, BRUCE; KAPLAN, JOHANNE; SHANKARA, SRINIVAS

2012-01-01

Overexpression of TMPRSS4, a cell surface-associated transmembrane serine protease, has been reported in pancreatic, colorectal and thyroid cancers, and has been implicated in tumor cell migration and metastasis. Few reports have investigated both TMPRSS4 gene expression levels and the protein products. In this study, quantitative RT-PCR and protein staining were used to assess TMPRSS4 expression in primary non-small cell lung carcinoma (NSCLC) tissues and in lung tumor cell lines. At the transcriptional level, TMPRSS4 message was significantly elevated in the majority of human squamous cell and adenocarcinomas compared with normal lung tissues. Staining of over 100 NSCLC primary tumor and normal specimens with rabbit polyclonal anti-TMPRSS4 antibodies confirmed expression at the protein level in both squamous cell and adenocarcinomas with little or no staining in normal lung tissues. Human lung tumor cell lines expressed varying levels of TMPRSS4 mRNA in vitro. Interestingly, tumor cell lines with high levels of TMPRSS4 mRNA failed to show detectable TMPRSS4 protein by either immunoblotting or flow cytometry. However, protein levels were increased under hypoxic culture conditions suggesting that hypoxia within the tumor microenvironment may upregulate TMPRSS4 protein expression in vivo. This was supported by the observation of TMPRSS4 protein in xenograft tumors derived from the cell lines. In addition, staining of human squamous cell carcinoma samples for carbonic anhydrase IX (CAIX), a hypoxia marker, showed TMPRSS4 positive cells adjacent to CAIX positive cells. Overall, these results indicate that the cancer-associated TMPRSS4 protein is overexpressed in NSCLC and may represent a potential therapeutic target. PMID:22692880

Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Glaysher, Sharon; Modi, Paul; Rahamim, Joe; Smith, Mark E; Amer, Khalid; Addis, Bruce; Poole, Matthew; Narayanan, Ajit; Gulliford, Tim J; Andreotti, Peter E; Cree, Ian A; Yiannakis, Dennis; Gabriel, Francis G; Johnson, Penny; Polak, Marta E; Knight, Louise A; Goldthorpe, Zoe; Peregrin, Katharine; Gyi, Mya

2009-01-01

NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA) and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissue. There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer

Carcinoembryonic antigen (CEA) as tumor marker in lung cancer.

Science.gov (United States)

Grunnet, M; Sorensen, J B

2012-05-01

The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA serum level as a prognostic marker in NSCLC was investigated in 23 studies and the use of CEA plasma level in two. In 18 (17 serum, 1 plasma) of these studies CEA was found to be a useful prognostic marker for either OS, recurrence after surgery or/and progression free survival (PFS) in NSCLC patients. Interestingly, an overweight of low stage (stage I-II) disease and adenocarcinoma (AC) patients were observed in this group. The remaining 7 studies (6 serum, 1 plasma) contained an overweight of patients with squamous carcinoma (SQ). One study found evidence for that a tumor marker index (TMI), based on preoperative CEA and CYFRA21-1 serum levels, is useful as a prognostic marker for OS in NSCLC. Six studies evaluated the use of CEA as a predictive marker for risk of recurrence and risk of death in NSCLC patients. Four of these studies found, that CEA was useful as a predictive marker for risk of recurrence and risk of death measured over time. No studies found CEA levels useful as a diagnostic marker for lung cancer. With regard to NSCLC the level of CEA measured in tumor tissue in

Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy

NARCIS (Netherlands)

Wink, Krista C. J.; Belderbos, José S. A.; Dieleman, Edith M. T.; Rossi, Maddalena; Rasch, Coen R. N.; Damhuis, Ronald A. M.; Houben, Ruud M. A.; Troost, Esther G. C.

2016-01-01

The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients).

Overexpression of the duffy antigen receptor for chemokines (DARC) by NSCLC tumor cells results in increased tumor necrosis

International Nuclear Information System (INIS)

Addison, Christina L; Belperio, John A; Burdick, Marie D; Strieter, Robert M

2004-01-01

The Duffy antigen receptor for chemokines (DARC) is known to be a promiscuous chemokine receptor that binds a variety of CXC and CC chemokines in the absence of any detectable signal transduction events. Within the CXC group of chemokines, DARC binds the angiogenic CXC chemokines including IL-8 (CXCL8), GROα (CXCL1) and ENA-78 (CXCL5), all of which have previously been shown to be important in non-small cell lung carcinoma (NSCLC) tumor growth. We hypothesized that overexpression of DARC by a NSCLC tumor cell line would result in the binding of the angiogenic ELR+ CXC chemokines by the tumor cells themselves, and thus interfere with the stimulation of endothelial cells and induction of angiogenesis by the tumor cell-derived angiogenic chemokines. NSCLC tumor cells that constitutively expressed DARC were generated and their growth characteristics were compared to control transfected cells in vitro and in vivo in SCID animals. We found that tumors derived from DARC-expressing cells were significantly larger in size than tumors derived from control-transfected cells. However, upon histological examination we found that DARC-expressing tumors had significantly more necrosis and decreased tumor cellularity, as compared to control tumors. Expression of DARC by NSCLC cells was also associated with a decrease in tumor-associated vasculature and a reduction in metastatic potential. The expression of DARC in the context of NSCLC tumors may act as a chemokine decoy receptor and interferes with normal tumor growth and chemokine-induced tumor neovascularization

Blood group antigen A type 3 expression is a favorable prognostic factor in advanced NSCLC.

Science.gov (United States)

Schmidt, L H; Kuemmel, A; Schliemann, C; Schulze, A; Humberg, J; Mohr, M; Görlich, D; Hartmann, W; Bröckling, S; Marra, A; Hillejan, L; Goletz, S; Karsten, U; Berdel, W E; Spieker, T; Wiewrodt, R

2016-02-01

Several blood group-related carbohydrate antigens are prognosis-relevant markers of tumor tissues. A type 3 (repetitive A) is a blood group antigen specific for A1 erythrocytes. Its potential expression in tumor tissues has so far not been examined. We have evaluated its expression in normal lung and in lung cancer using a novel antibody (A69-A/E8). For comparison an anti-A antibody specific to A types 1 and 2 was used, because its expression on lung cancer tissue has been previously reported to be of prognostic relevance. Resected tissue samples of 398 NSCLC patients were analyzed in immunohistochemistry using tissue microarrays. Expression of A type 3 was not observed in non-malignant lung tissues. A type 3 was expressed on tumor cells of around half of NSCLC patients of blood group A1 (ptype 1/2 antigen was observed (p=0.562), the expression of A type 3 by tumor cells indicated a highly significant favorable prognosis among advanced NSCLC patients (p=0.011) and in NSCLC patients with lymphatic spread (p=0.014). Univariate prognostic results were confirmed in a Cox proportional hazards model. In this study we present for the first time prognostic data for A type 3 antigen expression in lung cancer patients. Prospective studies should be performed to confirm the prognostic value of A type 3 expression for an improved risk stratification in NSCLC patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mucoepidermoid Lung Carcinoma in Child

African Journals Online (AJOL)

usually includes asthma, pneumonia, atelectasis, middle lobe syndrome and pleural effusion. Recurrent pneumonia in the same region of the lung should raise clinical suspicion of an endobronchial lesion or mass, such as mucoepidermoid carcinoma.[1] Because MECs are most commonly found in the segmental or lobar ...

1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference...

1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer

DEFF Research Database (Denmark)

Stahel, R; Thatcher, N; Früh, M

2011-01-01

The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21st and 22nd May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics and medical, surgical and radiation oncology. Before the conference......, the expert panel prepared clinically relevant questions concerning five areas as follows: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer (SCLC) to be addressed through...

Decision-tree sensitivity analysis for cost-effectiveness of whole-body FDG PET in the management of patients with non-small-cell lung carcinoma in Japan

International Nuclear Information System (INIS)

Kosuda, Shigeru; Kobayashi, Hideo; Kusano, Shoichi; Ichihara, Kiyoshi; Watanabe, Masazumi

2002-01-01

Whole-body 2-fluoro-2-D-[ 18 F]deoxyglucose[FDG] positron emission tomography (WB-PET) may be more cost-effective than chest PET because WB-PET does not require conventional imaging (CI) for extrathoracic staging. The cost-effectiveness of WB-PET for the management of Japanese patients with non-small-cell lung carcinoma (NSCLC) was assessed. Decision-tree sensitivity analysis was designed, based on the two competing strategies of WB-PET vs. CI. WB-PET was assumed to have a sensitivity and specificity for detecting metastases, of 90% to 100% and CI of 80% to 90%. The prevalences of M1 disease were 34% and 20%. On thousand patients suspected of having NSCLC were simulated in each strategy. We surveyed the relevant literature for the choice of variables. Expected cost saving (CS) and expected life expectancy (LE) for NSCLC patients were calculated. The WB-PET strategy yielded an expected CS of $951 US to $1,493 US per patient and an expected LE of minus 0.0246 years to minus 0.0136 years per patient for the 71.4% NSCLC and 34% M1 disease prevalence at our hospital. PET avoided unnecessary bronchoscopies and thoracotomies for incurable and benign disease. Overall, the CS for each patient was $833 US to $2,010 US at NSCLC prevalences ranging from 10% to 90%. The LE of the WB-PET strategy was similar to that of the CI strategy. The CS and LE minimally varied in the two situations of 34% and 20% M1 disease prevalence. The introduction of a WB-PET strategy in place of CI for managing NSCLC patients is potentially cost-effective in Japan. (author)

Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib.

Science.gov (United States)

Zhu, Zhouyu; Chai, Ying

2016-11-01

A 65-year-old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

International Nuclear Information System (INIS)

Regier, M.; Derlin, T.; Schwarz, D.; Laqmani, A.; Henes, F.O.; Groth, M.; Buhk, J.-H.; Kooijman, H.; Adam, G.

2012-01-01

Introduction: To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). Materials and methods: 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm 2 ) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV mean ) and maximum (SUV max ) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC mean ) and minimum ADC (ADC min ) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed. Results: Data analysis revealed a significant inverse correlation of the ADC min and SUV max (r = −0.46; p = 0.032). Testing the correlation of the ADC min and SUV max for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADC min and SUV mean (r = −0.29; p = 0.27), ADC mean vs. SUV mean (r = −0.28; p = 0.31) or ADC mean vs. SUV max (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers. Conclusion: This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC

PKC 412 sensitizes U1810 non-small cell lung cancer cells to DNA damage

International Nuclear Information System (INIS)

Hemstroem, Therese H.; Joseph, Bertrand; Schulte, Gunnar; Lewensohn, Rolf; Zhivotovsky, Boris

2005-01-01

Non-small cell lung carcinoma (NSCLC) is characterized by resistance to drug-induced apoptosis, which might explain the survival of lung cancer cells following treatment. Recently we have shown that the broad-range kinase inhibitor staurosporine (STS) reactivates the apoptotic machinery in U1810 NSCLC cells [Joseph et al., Oncogene 21 (2002) 65]. Lately, several STS analogs that are more specific in kinase inhibition have been suggested for tumor treatment. In this study the apoptosis-inducing ability of the STS analogs PKC 412 and Ro 31-8220 used alone or in combination with DNA-damaging agents in U1810 cells was investigated. In these cells Ro 31-8220 neither induced apoptosis when used alone, nor sensitized cells to etoposide treatment. PKC 412 as a single agent induced death of a small number of U1810 cells, whereas it efficiently triggered a dose- and time-dependent apoptosis in U1285 small cell lung carcinoma cells. In both cell types PKC 412 triggered release of mitochondrial proteins followed by caspase activation. However, concomitant activation of a caspase-independent pathway was essential to kill NSCLC cells. Importantly, PKC 412 was able to sensitize etoposide- and radiation-induced death of U1810 cells. The best sensitization was achieved when PKC 412 was administered 24 h after treatments. In U1810 cells, Ro 31-8220 decreased PMA-induced ERK phosphorylation as efficiently as PKC 412, indicating that the failure of Ro 31-8220 to induce apoptosis was not due to weaker inhibition of conventional and novel PKC isoforms. However, Ro 31-8220 increased the basal level of ERK and Akt phosphorylation in both cell lines, whereas Akt phosphorylation was suppressed in the U1810 cells, which might influence apoptosis. These results suggest that PKC 412 could be a useful tool in increasing the efficiency of therapy of NSCLC

Induction chemotherapy for locoregional lung cancer using paclitaxel combination. A preliminary report

International Nuclear Information System (INIS)

Takita, H.; Pitoniak, R.F.

2000-01-01

Induction chemotherapy has been reported to be effective in treatment of locally advanced, borderline resectable, (Stage III), non small cell lung carcinoma (NSCLC). A logical extension of the indication for the induction chemotherapy may be to treat earlier stage resectable lung cancers (stages I and II) because the cure rate of the resectable lung cancers still remains poor and is below 60% except for stage I A. Thirty eight patients with a diagnosis of loco-regional NSCLC were treated with paclitaxel combination chemotherapy. Following two courses of induction chemotherapy, patients underwent surgical therapy whenever possible. There ten patients with stage I disease, four patients with stage II, 13 with stage IIIA, nine had stage IIIB, and two with stage IV. An overall response rate of 74% was observed. The response rate for 14 resectable patients (stage I and II) was 86%. The chemotherapy regimen was well tolerated and apart from one instance of anaphylaxis, no serious side effects were observed

Enhanced expression of G-protein coupled estrogen receptor (GPER/GPR30) in lung cancer

International Nuclear Information System (INIS)

Jala, Venkatakrishna Rao; Radde, Brandie N; Haribabu, Bodduluri; Klinge, Carolyn M

2012-01-01

G-protein-coupled estrogen receptor (GPER/GPR30) was reported to bind 17β-estradiol (E 2 ), tamoxifen, and ICI 182,780 (fulvestrant) and promotes activation of epidermal growth factor receptor (EGFR)-mediated signaling in breast, endometrial and thyroid cancer cells. Although lung adenocarcinomas express estrogen receptors α and β (ERα and ERβ), the expression of GPER in lung cancer has not been investigated. The purpose of this study was to examine the expression of GPER in lung cancer. The expression patterns of GPER in various lung cancer lines and lung tumors were investigated using standard quantitative real time PCR (at mRNA levels), Western blot and immunohistochemistry (IHC) methods (at protein levels). The expression of GPER was scored and the pairwise comparisons (cancer vs adjacent tissues as well as cancer vs normal lung tissues) were performed. Analysis by real-time PCR and Western blotting revealed a significantly higher expression of GPER at both mRNA and protein levels in human non small cell lung cancer cell (NSCLC) lines relative to immortalized normal lung bronchial epithelial cells (HBECs). The virally immortalized human small airway epithelial cell line HPL1D showed higher expression than HBECs and similar expression to NSCLC cells. Immunohistochemical analysis of tissue sections of murine lung adenomas as well as human lung adenocarcinomas, squamous cell carcinomas and non-small cell lung carcinomas showed consistently higher expression of GPER in the tumor relative to the surrounding non-tumor tissue. The results from this study demonstrate increased GPER expression in lung cancer cells and tumors compared to normal lung. Further evaluation of the function and regulation of GPER will be necessary to determine if GPER is a marker of lung cancer progression

Cooperative regulation of non-small cell lung carcinoma by nicotinic and beta-adrenergic receptors: a novel target for intervention.

Directory of Open Access Journals (Sweden)

Hussein A N Al-Wadei

Full Text Available Lung cancer is the leading cause of cancer death; 80-85% of lung cancer cases are non-small cell lung cancer (NSCLC. Smoking is a documented risk factor for the development of this cancer. Although nicotine does not have the ability to initiate carcinogenic events, recent studies have implicated nicotine in growth stimulation of NSCLC. Using three NSCLC cell lines (NCI-H322, NCI-H441 and NCI-H1299, we identified the cooperation of nicotinic acetylcholine receptors (nAChRs and β-adrenergic receptors (β-ARs as principal regulators of these effects. Proliferation was measured by thymidine incorporation and MTT assays, and Western blots were used to monitor the upregulation of the nAChRs and activation of signaling molecules. Noradrenaline and GABA were measured by immunoassays. Nicotine-treated NSCLC cells showed significant induction of the α7nAChR and α4nAChR, along with significant inductions of p-CREB and p-ERK1/2 accompanied by increases in the stress neurotransmitter noradrenaline, which in turn led to the observed increase in DNA synthesis and cell proliferation. Effects on cell proliferation and signaling proteins were reversed by the α7nAChR antagonist α-BTX or the β-blocker propranolol. Nicotine treatment also down-regulated expression of the GABA synthesizing enzyme GAD 65 and the level of endogenous GABA, while treatment of NSCLC cells with GABA inhibited cell proliferation. Interestingly, GABA acts by reducing β-adrenergic activated cAMP signaling. Our findings suggest that nicotine-induced activation of this autocrine noradrenaline-initiated signaling cascade and concomitant deficiency in inhibitory GABA, similar to modulation of these neurotransmitters in the nicotine-addicted brain, may contribute to the development of NSCLC in smokers. Our data suggest that exposure to nicotine either by tobacco smoke or nicotine supplements facilitates growth and progression of NSCLC and that pharmacological intervention by β blocker may

Resistance gene expression determines the in vitro chemosensitivity of non-small cell lung cancer (NSCLC

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Amer Khalid

2009-08-01

Full Text Available Abstract Background NSCLC exhibits considerable heterogeneity in its sensitivity to chemotherapy and similar heterogeneity is noted in vitro in a variety of model systems. This study has tested the hypothesis that the molecular basis of the observed in vitro chemosensitivity of NSCLC lies within the known resistance mechanisms inherent to these patients' tumors. Methods The chemosensitivity of a series of 49 NSCLC tumors was assessed using the ATP-based tumor chemosensitivity assay (ATP-TCA and compared with quantitative expression of resistance genes measured by RT-PCR in a Taqman Array™ following extraction of RNA from formalin-fixed paraffin-embedded (FFPE tissue. Results There was considerable heterogeneity between tumors within the ATP-TCA, and while this showed no direct correlation with individual gene expression, there was strong correlation of multi-gene signatures for many of the single agents and combinations tested. For instance, docetaxel activity showed some dependence on the expression of drug pumps, while cisplatin activity showed some dependence on DNA repair enzyme expression. Activity of both drugs was influenced more strongly still by the expression of anti- and pro-apoptotic genes by the tumor for both docetaxel and cisplatin. The doublet combinations of cisplatin with gemcitabine and cisplatin with docetaxel showed gene expression signatures incorporating resistance mechanisms for both agents. Conclusion Genes predicted to be involved in known mechanisms drug sensitivity and resistance correlate well with in vitro chemosensitivity and may allow the definition of predictive signatures to guide individualized chemotherapy in lung cancer.

Cost-effective analysis of PET application in NSCLC

International Nuclear Information System (INIS)

Gu Aichun; Liu Jianjun; Sun Xiaoguang; Shi Yiping; Huang Gang

2006-01-01

Objective: To evaluate the cost-effectiveness of PET and CT application for diagnosis of non-small cell lung cancer (NSCLC) in China. Methods: Using decision analysis method the diagnostic efficiency of PET and CT for diagnosis of NSCLC in china was analysed. And also the value of cost for accurate diagnosis (CAD), cost for accurate staging (CAS) and cost for effective therapy (CAT) was calculated. Results: (1) For the accurate diagnosis, CT was much more cost-effective than PET. (2) For the accurate staging, CT was still more cost-effective than PET. (3) For the all over diagnostic and therapeutic cost, PET was more cost-effective than CT. (4) The priority of PET to CT was for the diagnosis of stage I NSCLC. Conclusion: For the management of NSCLC patient in China, CT is more cost-effective for screening, whereas PET for clinical staging and monitoring therapeutic effect. (authors)

Neuroendocrine carcinomas of the lung

International Nuclear Information System (INIS)

Forster, B.B.; Muller, N.L.; Miller, R.R.; Nelems, B.; Evans, K.G.

1988-01-01

Neuroendocrine lung carcinomas may be classified as Kulchitzky cell carcinoma (KCC) I (classic carcinoids), II (atypical carcinoids), and III (small cell carcinomas). The authors reviewed the clinical, CT, and pathologic findings in 31 patients with KCC. KCC I occurred mainly in younger nonsmoking women, and on CT were small (1.8 cm average diameter) and showed lymphadenopathy in one of ten patients. KCC II were found mainly in older smoking men and were larger (3.9 cm, P < .001), and four of ten patients had lymphadenopathy. KCC III occurred in older smoking men and were large (4.2 cm), and 11 of 11 patients had lymphadenopathy. Sputum cytology and percutaneous and bronchoscopic biopsy were often nondiagnostic or misleading. The authors conclude that chest CT provides additional discriminating information in the preoperative diagnosis of KCC

Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas.

Science.gov (United States)

Brock, Stephanie E; Rendon, Beatriz E; Yaddanapudi, Kavitha; Mitchell, Robert A

2012-11-02

AMP-activated protein kinase (AMPK) is a nutrient- and metabolic stress-sensing enzyme activated by the tumor suppressor kinase, LKB1. Because macrophage migration inhibitory factor (MIF) and its functional homolog, d-dopachrome tautomerase (d-DT), have protumorigenic functions in non-small cell lung carcinomas (NSCLCs) but have AMPK-activating properties in nonmalignant cell types, we set out to investigate this apparent paradox. Our data now suggest that, in contrast to MIF and d-DTs AMPK-activating properties in nontransformed cells, MIF and d-DT act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant human NSCLC cell lines. Our data further indicate that MIF and d-DT, acting through their shared cell surface receptor, CD74, antagonize NSCLC AMPK activation by maintaining glucose uptake, ATP production, and redox balance, resulting in reduced Ca(2+)/calmodulin-dependent kinase kinase β-dependent AMPK activation. Combined, these studies indicate that MIF and d-DT cooperate to inhibit AMPK activation in an LKB1-independent manner.

Accelerated hypofractionated three-dimensional conformal radiation therapy in the treatment of non-small cell lung cancer

International Nuclear Information System (INIS)

Yu Jinming; Zheng Aiqing; Yu Yonghua; Wang Xuetao; Yuan Shuanghu; Han Dali; Li Kunhai

2005-01-01

Objective: To evaluate the effect and complication of non-small-cell lung cancer (NSCLC) treated with accelerated hypofractionated three dimensional conforms] radiation therapy (3DCRT). Methods: There were squamous carcinoma 21, adenocarcinoma 7, squamous-adenocarcinoma 4 and other cancer 3. There were 17 stage I and 18 stage II. Thirty-five patients of NSCLC were treated with a dose of 30-48 Gy in 6 or 8 Gy per fraction, 3 times a week. The outcome of these patients Was analyzed. Results: The overall 1-, 2- and 3- Year survival rate was 78.2%, 46.9% and 36.3%, respectively. The 1- and 2-year recurrence-free survival rate was 64.6 % and 39.7 %, respectively. The acute radiation pneumonitis and late lung fibrosis rates were high. Univariate analysis showed that Vm was a significant predictor of acute radiation pneumonitis. Conclusion: Compared with accelerated hypofractionated irradiation, the routine conventional fractionated radiation therapy may be preferred for more patients of NSCLC. (authors)

Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

International Nuclear Information System (INIS)

Brodin, O.; Lennartsson, L.; Nilsson, S.

1991-01-01

Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

Placenta-specific protein 1 promotes cell proliferation and invasion in non-small cell lung cancer

Science.gov (United States)

Yang, Li; Zha, Tian-Qi; He, Xiang; Chen, Liang; Zhu, Quan; Wu, Wei-Bing; Nie, Feng-Qi; Wang, Qian; Zang, Chong-Shuang; Zhang, Mei-Ling; He, Jing; Li, Wei; Jiang, Wen; Lu, Kai-Hua

2018-01-01

Pulmonary carcinoma-associated proteins have emerged as crucial players in governing fundamental biological processes such as cell proliferation, apoptosis and metastasis in human cancers. Placenta-specific protein 1 (PLAC1) is a cancer-related protein, which is activated and upregulated in a variety of malignant tissues, including prostate cancer, gastric adenocarcinoma, colorectal, epithelial ovarian and breast cancer. However, its biological role and clinical significance in non-small cell lung cancer (NSCLC) development and progression are still unknown. In the present study, we found that PLAC1 was significantly upregulated in NSCLC tissues, and its expression level was associated with advanced pathological stage and it was also correlated with shorter progression-free survival of lung cancer patients. Furthermore, knockdown of PLAC1 expression by siRNA inhibited cell proliferation, induced apoptosis and impaired invasive ability in NSCLC cells partly via regulation of epithelial-mesenchymal transition (EMT)-related protein expression. Our findings present that increased PLAC1 could be identified as a negative prognostic biomarker in NSCLC and regulate cell proliferation and invasion. Thus, we conclusively demonstrated that PLAC1 plays a key role in NSCLC development and progression, which may provide novel insights on the function of tumor-related gene-driven tumorigenesis. PMID:29138842

Stereotactic radiotherapy using tomotherapy for early-stage non-small cell lung carcinoma: analysis of intrafaction tumour motion

International Nuclear Information System (INIS)

Boggs, Drexell Hunter; Feigenberg, Steven; Walter, Robert; Wissing, Dennis; Patel, Bijal; Wu, Terry; Rosen, Lane

2014-01-01

Intrafraction tumour motion in helical tomotherapy was investigated by comparing pre- and mid-fraction CT scans in patients with early non-small cell lung carcinoma (NSCLC) to assess the efficacy of a 7-mm margin around gross tumour volumes (GTVs) in stereotactic body radiation therapy (SBRT). Thirty patients with early-stage NSCLC received SBRT in four or five fractions for a total of 141 treatments. A slow positron emission tomography/CT scan was fused with the simulation CT to determine the GTV. A planning target volume was created by placing an isotropic margin of 7mm around the GTV. Data were retrospectively analyzed to assess translational tumour positional changes along the x, y and z axes and vector changes in millimeters from the pretreatment megavoltage (MV)-CT to the mid-fraction MV-CT. Average movements for all 141 treatment days along the x, y and z axes were 0.5±2.3, −0.3±3.0 and 0.9±3.0mm, respectively. Average movements for each patient along the x, y and z axes were 0.5±1.5, −0.2±2.0 and 0.9±1.9mm, respectively. Average vector displacement was 4.3±2.4mm for all treatment days and 4.2±1.7mm for each patient. Of 141 treatments, 137 (97.2%) fell within 7.0mm in all axes. The addition of a 7-mm margin to the GTV for patients receiving SBRT for NSCLC using tomotherapy is adequate to account for tumour movement. Mid-fraction CT scans proved to be valuable in assessing intrafraction tumour motion.

NSCLC and HER2: between lights and shadows.

Science.gov (United States)

Ricciardi, Giuseppina Rosaria Rita; Russo, Alessandro; Franchina, Tindara; Ferraro, Giuseppa; Zanghì, Mariangela; Picone, Antonio; Scimone, Antonino; Adamo, Vincenzo

2014-12-01

The therapeutic landscape of non-small-cell lung cancer (NSCLC) has dramatically changed in the last few years with the introduction of molecularly targeted agents, leading to unprecedented results in lung tumors with a paradigmatic shift from a "one size fits all" approach to an histologic and molecular-based approach. The discovery of epidermal growth factor receptor (EGFR) mutations in NSCLC in 2004 and the marked response to the EGFR tyrosine kinase inhibitor gefitinib, in a small subset of patients harboring these genetic abnormalities, stimulated the study of other kinase mutants involvement in NSCLC. The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors. The identification of these oncogenic drivers has dramatically changed the genetic landscape of NSCLC moving away from the old concept of a large indistinct histological entity to a combination of rare clinically relevant molecular subsets. Recently, a renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Genetic aberrations of this signaling pathway have been reported over time to be associated in NSCLC with different sensitivity to the EGFR tyrosine kinase inhibitors, to have a possible prognostic role and more recently HER2 amplification has been emerged as a possible mechanism in EGFR-mutated tumors of acquired resistance to the EGFR tyrosine kinase inhibitors. In addition, dysregulation of the HER2 pathway, in particular HER2 mutations (mostly, in-frame exon 20 insertions), may represent a possible novel therapeutic target in NSCLC, paving the way for a new generation of targeted agents in NSCLC. Since anecdotal case reports of clinical activity of anti-HER2 agents in NSCLC

Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base

Directory of Open Access Journals (Sweden)

A. Murinello

2010-07-01

Full Text Available Based on a case of gastric antral vascular ectasia (watermelon stomach that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma. Resumo: Baseados num caso de gastropatia antral com ectasia vascular (estômago em melancia associado a pericardite hemorrágica e a um carcinoma de pequenas células do pulmão com metástases ganglionares ao longo do mediastino e a um carcinoma pavimentocelular síncrono da base da língua, os autores fazem uma revisão dos aspectos clínicos, endoscópicos e histopatológicos deste tipo de gastropatia, da sua associação a outras doenças e das possibilidades terapêuticas actuais por via endoscópica. Referem-se igualmente as causas mais frequentes de pericardite hemorrágica, salientando-se a necessidade de esclarecer se o derrame é ou não de origem neoplásica. Não está referida na literatura a associação deste tipo de gastropatia ao carcinoma de pequenas células do pulmão nem ao carcinoma pavimento-celular da base da língua. A invasão extensa dos gânglios mediastínicos pelo carcinoma de pequenas células do pulmão é ocorrência frequente. Key-words: Gastric antral vascular ectasia, watermelon stomach, small cell lung carcinoma, oat cell lung carcinoma, squamous cell carcinoma of the base

Survival of localized NSCLC patients without active treatment or treated with SBRT

DEFF Research Database (Denmark)

Jeppesen, S S; Hansen, N C G; Schytte, T

2018-01-01

BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for pati......BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment...... for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival. MATERIAL AND METHODS: From 2007 to 2013, 136 patients treated...... with SBRT at Odense University Hospital were prospectively recorded. The thoracic SBRT consisted of three fractions of 15-22 Gy delivered in 9 days. For comparison, a national group of 73 untreated patients in the same time period was extracted from the Danish Lung Cancer Registry. All patients had...

Impact of lymph node micrometastasis for the UICC stage in non-small cell lung carcinoma

International Nuclear Information System (INIS)

Ouyang Weiwei; Lu Bing; He Chang; Long Yiguo; Wang Ping

2007-01-01

Objective: To detect cytokeratin in routine pathology negative regional lymph nodes postoperatively in non-small cell lung carcinoma (NSCLC). To investigate the relationship of lymph node micrometastasis in P-TNM stages NSCLC and survival rates. Methods: From Jan. 1996 to Dec. 2003, 107 paraffin-embedded specimens of T1-T4N0-N1M0 NSCLC patients were collected. Anti-cytokeratin(CK) antibody AE1/AE3 was applied to detect cytokeratin with Envision TM method in routine pathological negative region lymph nodes in NSCLC, and selected negative control, positive control and blank control. The pulmo- nary hilar lymph node micrometastasis was upward regulated with stage pCK-N1, mediastinal lymph node mi- crometastatsis was upward regulated with stage pCK-N2. The result applied to SPSS11.0 software to process. Results: The CK positive rate was 29.9% in all the patients. The CK positive rate was 27% (21/78), 30% (7/23), 67%(4/6)in stage p- I, p-II and p-III, respectively. All these data showed the tendency by which detectable rate increased and was accompanied by disease progress. Comparing the annual survival rate and median survival time of the non-micrometastasis group with the micrometastasis group in two groups, the survival rate difference was statistically significant. Comparing the armnal survival rate and median sur- vival time in pCK-III A stage with p- I -II stage, pCK-III A stage annual survival rate and median survival time was significantly different(P=0.020). Similarly, comparing the survival rate in pCK-II B stage with p- I B stage, pCK- II B stage survival rate was significantly different( P = 0. 059). Comparing the survival time of pCK-IIIA stage with p-III stage, pCK-II B stage, with p-II B stage, euther survival time difference was statistically significant (P=0.838, 0.518). Conclusions: The rate of positive cytokeratin increase is accompanied by the disease progress in NSCLC. Positive cytokeratin has disadvantageous prognosis. It is showed that pCK-N1 may

Reliability of chromogenic in situ hybridization for epidermal growth factor receptor gene copy number detection in non-small-cell lung carcinomas: a comparison with fluorescence in situ hybridization study.

Science.gov (United States)

Yoo, Seol Bong; Lee, Hyun Ju; Park, Jung Ok; Choe, Gheeyoung; Chung, Doo Hyun; Seo, Jeong-Wook; Chung, Jin-Haeng

2010-03-01

Fluorescence in situ hybridization (FISH) has been known to be the most representative and standardized test for assessing gene amplification. However, FISH requires a fluorescence microscope, the signals are labile and rapidly fade over time. Recently, chromogenic in situ hybridization (CISH) has emerged as a potential alternative to FISH. The aim of this study is to test the reliability of CISH technique for the detection of epidermal growth factor receptor (EGFR) gene amplification in non-small-cell lung carcinomas (NSCLC), to compare CISH results with FISH. A total of 277 formalin-fixed and paraffin embedded NSCLC tissue samples were retrieved from the surgical pathology archives at Seoul National University Bundang Hospital. CISH and FISH examinations were performed to test EGFR gene amplification status. There was high concordance in the assessment of EGFR gene copy number between CISH and FISH tests (Kappa coefficient=0.83). Excellent concordance was shown between two observers on the interpretation of the CISH results (Kappa coefficient=0.90). In conclusion, CISH result is highly reproducible, accurate and practical method to determine EGFR gene amplification in NSCLC. In addition, CISH allows a concurrent analysis of histological features of the tumors and gene copy numbers.

Correlation between Podoplanin-positive Lymphatic Microvessel Density 
and CT Characteristics of Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Hui ZHOU

2012-01-01

Full Text Available Background and objective It has been proven that ymphatic microvessel density (LMVD was closely correlated with the lymphatic metastasis of non-small cell lung cancer (NSCLC. The aim of the present study is to explore the relationship between podoplanin-LMVD and multi-slice spiral computed tomography (MSCT characteristics of NSCLC. Methods MSCT scanning was performed on 34 cases of NSCLC (squamous carcinoma, 15 cases; adenocarcinoma, 15 cases; and adenosquamous carcinoma, 4 cases prior to operation. Clinical pathology results, including lymph node metastasis, were obtained. CT characteristics, such as shape of the edge, internal structure, and adjacent structures, were described. LMVD in the central and peripheral areas examined respectively using SP immunohistochemical technique were analyzed. Results Lymph node metastasis was found to be associated with LMVD in the peripheral areas. LMVD in the peripheral areas of the resected lesions, the MSCT findings of which included spinous process, pleural indentation, and carcinomatous lymphangitis, was higher than that of the lesions without these MSCT characteristics (P<0.05. Conclusion MSCT findings of spinous process, pleural indentation, or carcinomatous lymphangitis of NSCLC may suggest a higher level of tumor lymphangiogenesis with a higher risk of lymph node metastasis.

Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiotherapy response prediction

Science.gov (United States)

Jeong, Youngtae; Hoang, Ngoc T.; Lovejoy, Alexander; Stehr, Henning; Newman, Aaron M.; Gentles, Andrew J.; Kong, William; Truong, Diana; Martin, Shanique; Chaudhuri, Aadel; Heiser, Diane; Zhou, Li; Say, Carmen; Carter, Justin N.; Hiniker, Susan M.; Loo, Billy W.; West, Robert B.; Beachy, Philip; Alizadeh, Ash A.; Diehn, Maximilian

2016-01-01

Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. PMID:27663899

Genomic Characterization of Non–Small-Cell Lung Cancer in African Americans by Targeted Massively Parallel Sequencing

Science.gov (United States)

Araujo, Luiz H.; Timmers, Cynthia; Bell, Erica Hlavin; Shilo, Konstantin; Lammers, Philip E.; Zhao, Weiqiang; Natarajan, Thanemozhi G.; Miller, Clinton J.; Zhang, Jianying; Yilmaz, Ayse S.; Liu, Tom; Coombes, Kevin; Amann, Joseph; Carbone, David P.

2015-01-01

Purpose Technologic advances have enabled the comprehensive analysis of genetic perturbations in non–small-cell lung cancer (NSCLC); however, African Americans have often been underrepresented in these studies. This ethnic group has higher lung cancer incidence and mortality rates, and some studies have suggested a lower incidence of epidermal growth factor receptor mutations. Herein, we report the most in-depth molecular profile of NSCLC in African Americans to date. Methods A custom panel was designed to cover the coding regions of 81 NSCLC-related genes and 40 ancestry-informative markers. Clinical samples were sequenced on a massively parallel sequencing instrument, and anaplastic lymphoma kinase translocation was evaluated by fluorescent in situ hybridization. Results The study cohort included 99 patients (61% males, 94% smokers) comprising 31 squamous and 68 nonsquamous cell carcinomas. We detected 227 nonsilent variants in the coding sequence, including 24 samples with nonoverlapping, classic driver alterations. The frequency of driver mutations was not significantly different from that of whites, and no association was found between genetic ancestry and the presence of somatic mutations. Copy number alteration analysis disclosed distinguishable amplifications in the 3q chromosome arm in squamous cell carcinomas and pointed toward a handful of targetable alterations. We also found frequent SMARCA4 mutations and protein loss, mostly in driver-negative tumors. Conclusion Our data suggest that African American ancestry may not be significantly different from European/white background for the presence of somatic driver mutations in NSCLC. Furthermore, we demonstrated that using a comprehensive genotyping approach could identify numerous targetable alterations, with potential impact on therapeutic decisions. PMID:25918285

Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

LENUS (Irish Health Repository)

Cathcart, Mary Clare

2011-06-01

Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng\\/ml) and cell survival\\/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation\\/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis\\/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor\\/potential target in

Detection of EGFR somatic mutations in non-small cell lung cancer (NSCLC) using a novel mutant-enriched liquidchip (MEL) technology.

Science.gov (United States)

Zhang, Li; Yang, Huiyi; Zhao, Yanwei; Liu, Wenchao; Wu, Shiyang; He, Jiaying; Luo, Xiaodi; Zhu, Zeyao; Xu, Jiasen; Zhou, Qinghua; Ren-Heidenreich, Lifen

2012-09-01

We have developed and standardized a novel technology, mutant-enriched liquidchip (MEL), for clinical detection of EGFR mutations. The MEL integrates a mutant-enriched PCR procedure with liquidchip technology for detections of EGFR exon 19 deletions and L858R mutation on both formalin-fixed and paraffin-embedded (FFPE) slides and plasma samples from patients with non-small cell lung cancer (NSCLC). The detection sensitivity was 0.1% of mutant DNA in the presence of its wild-type DNA. The cross-reaction rate was lower than 5%. To evaluate the MEL platform, the EGFR mutation status of 59 patients with advanced NSCLC treated with EGFRTKIs (Tyrosine Kinase Inhibitors) were tested on their FFPE samples. EGFR exon 19 deletions and L858R were detected in 21 patients (21/59) and 76.2% (16/21) of them had partial response to the EGFR-TKIs, while by sequencing method, only 4 (4/59) mutations were detected. Plasma samples from 627 patients with various stages of NSCLC were examined with the MEL and 22% of EGFR exon 19 deletions and L858R were detected. Furthermore, in patients with advanced disease there are more mutations detected in plasma samples than in patients with less advanced disease. In conclusion, the MEL is a sensitive, stable, and robust technology for detecting EGFR DNA mutations from both FFPE and plasma samples from patients with NSCLC and is now routinely used for clinical diagnosis.

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

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Lopci, Egesta; Olivari, Laura [Humanitas Clinical and Research Hospital, Nuclear Medicine Department, Rozzano, MI (Italy); Toschi, Luca; Marchetti, Silvia; Pistillo, Daniela [Humanitas Clinical and Research Hospital, Oncology, Rozzano, Milan (Italy); Grizzi, Fabio; Castino, Giovanni Francesco; Cortese, Nina; Qehajaj, Dorina [Humanitas Clinical and Research Hospital, Department of Immunology and Inflammation, Rozzano, Milan (Italy); Rahal, Daoud [Humanitas Clinical and Research Hospital, Department of Pathology, Rozzano, Milan (Italy); Alloisio, Marco [Humanitas Clinical and Research Hospital, Thoracic Surgery, Rozzano, Milan (Italy); Roncalli, Massimo [Humanitas Clinical and Research Hospital, Department of Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Allavena, Paola [Humanitas University, Rozzano, Milan (Italy); Santoro, Armando [Humanitas Clinical and Research Hospital, Oncology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Marchesi, Federica [Humanitas Clinical and Research Hospital, Department of Immunology and Inflammation, Rozzano, Milan (Italy); University of Milan, Department of Medical Biotechnologies and Translational Medicine, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine Department, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

2016-10-15

Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months. Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

International Nuclear Information System (INIS)

Lopci, Egesta; Olivari, Laura; Toschi, Luca; Marchetti, Silvia; Pistillo, Daniela; Grizzi, Fabio; Castino, Giovanni Francesco; Cortese, Nina; Qehajaj, Dorina; Rahal, Daoud; Alloisio, Marco; Roncalli, Massimo; Allavena, Paola; Santoro, Armando; Marchesi, Federica; Chiti, Arturo

2016-01-01

Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients. All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months. Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3-32.5) and SUVmean 6.4 (range: 1.5-13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84-14.01 %), CD8-TILs of 2.9 % (range: 0.11-11.92 %), PD-1 of 0.65 % (range: 0.02-5.87 %), and PD-L1 of 0.7 % (range: 0.03-10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1

Cetuximab and biomarkers in non-small-cell lung carcinoma

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Patil N

2012-07-01

Full Text Available Nitin Patil, Mohammed Abba, Heike AllgayerDepartment of Experimental Surgery, Medical Faculty Mannheim, University of Heidelberg and Molecular Oncology of Solid Tumors Unit, German Cancer Research Center (DKFZ, Heidelberg, GermanyAbstract: Cancer progression is a highly complex process that is driven by a constellation of deregulated signaling pathways and key molecular events. In non-small-cell lung cancer (NSCLC, as in several other cancer types, the epidermal growth factor receptor (EGFR and its downstream signaling components represent a key axis that has been found not only to trigger cancer progression but also to support advanced disease leading to metastasis. Two major therapeutic approaches comprising monoclonal antibodies and small molecule tyrosine kinase inhibitors have so far been used to target this pathway, with a combination of positive, negative, and inconsequential results, as judged by patient survival indices. Since these drugs are expensive and not all patients derive benefits from taking them, it has become both pertinent and paramount to identify biomarkers that can predict not only beneficial response but also resistance. This review focuses on the chimeric monoclonal antibody, cetuximab, its application in the treatment of NSCLC, and the biomarkers that may guide its use in the clinical setting. A special emphasis is placed on the EGFR, including its structural and mechanistic attributes.Keywords: NSCLC, cetuximab, biomarker, cancer progression

Overexpression of matrix metalloproteinase-7 and -9 in NSCLC tumor and stromal cells: correlation with a favorable clinical outcome.

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Stenvold, Helge; Donnem, Tom; Andersen, Sigve; Al-Saad, Samer; Al-Shibli, Khalid; Busund, Lill-Tove; Bremnes, Roy M

2012-02-01

Matrix metalloproteinases (MMPs) are considered important players in angiogenesis and cancer progression. Several drugs developed for targeting MMPs have until now been without clinical efficacy. As both malignant cells and cells of the surrounding stroma contribute to tumor growth, we have explored the impact of MMP-2, -7 and -9 expression in both the tumor and stromal compartment of non-small-cell lung cancers (NSCLC). From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarrays (TMAs). Immunohistochemistry was used to detect the expression of MMP-2, -7 and -9 in tumor and stromal cells. In univariate analyses, high tumor cell MMP-7 expression (P=0.029) and high stromal MMP-9 expression (P=0.001) were positive prognostic factors. In the multivariate analysis, high tumor cell MMP-7 expression (HR 1.58, CI 1.08-2.32, P=0.020) and high stromal MMP-9 expression (HR 1.92, CI 1.25-2.96, P=0.003) were independent positive prognostic factors for disease-specific survival. High levels of MMP-7 in tumor cells and high levels of MMP-9 in tumor associated stroma were independent positive prognostic factors in NSCLC patients. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Relationship between tuberculous scar and carcinomas of the lung

International Nuclear Information System (INIS)

Richardson, S.; Hirsch, A.; Bickel, M.

1987-01-01

Results of a transversal case-control study are reported which shows that there is a statistically significant association between tuberculous scars and carcinoma of the lung. Accordingly the possibility of malignancy has to be kept in mind when radiological or scintigraphic scanning reveal the presence of lung scars. (orig.)

EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10

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Vázquez S

2016-02-01

Full Text Available Sergio Vázquez,1 Joaquín Casal,2 Francisco Javier Afonso Afonso,3 José Luis Fírvida,4 Lucía Santomé,5 Francisco Barón,6 Martín Lázaro,7 Carolina Pena,7 Margarita Amenedo,8 Ihab Abdulkader,9 Carmen González-Arenas,10 Laura Fachal,11 Ana Vega11 On behalf of the Galician Lung Cancer Group (GGCP1Medical Oncology Department, Lucus Augusti University Hospital, Lugo, 2Medical Oncology Department, University Hospital Complex of Vigo, Pontevedra, 3Medical Oncology Department, University Hospital Complex of Ferrol, Ferrol, 4Medical Oncology Department, University Hospital Complex of Ourense, Ourense, 5Medical Oncology Department Povisa Hospital, Vigo, 6Medical Oncology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 7Medical Oncology Department, Hospital Complex of Pontevedra, Pontevedra, 8Medical Oncology Department, Oncology Center of Galicia, A Coruña, 9Anatomical Pathology Department, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, 10AstraZeneca, Madrid, 11Galician Public Foundation of Genomic Medicine-SERGAS, Santiago de Compostela Clinic Hospital, Santiago de Compostela, Spain Purpose: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR gene in non-small-cell lung cancer (NSCLC patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. Patients and methods: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens and serum samples. Results: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6% had EGFR mutations (84% sensitizing mutations. EGFR mutation was found in serum in 14 (8.1% patients (of 174 evaluable. Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52

Clinical value of 99Tcm-octreotide SPECT/CT in diagnostics of lung cancer

International Nuclear Information System (INIS)

Liu Xiaofang; Li Mei; Liu Yong; Li Ran; Xu Jie; Sun yongchang; Dai Haojie

2012-01-01

Objective: To evaluate the clinical value of 99 Tc m -Octreotide SPECT-CT in the diagnosis of lung cancer. Methods: Sixty-five consecutive patients with suspected lung cancer received intravenous injection of 740 MBq 99 Tc m -Octreotide and additional SPECT images of the chest were performed at 4h post injection. The SPECT/CT images were interpreted separately. The tumor uptake of 99 Tc m -Octreotide was visually determined and then measured and expressed as the activity ratio of tumor to normal tissues (T/N). The differences between lung cancer and benign lung lesion and between SCLC and NSCLC, and between adenocarcinoma and squamous carcinoma were studied by statistical analysis. Moreover, the receiver operating characteristic ROC curves were plotted and the predicted probabilities and areas under the curve were calculated. Results: Fifty-one patients and fourteen patients in 65 cases were diagnosed as lung cancer and benign lung lesion by histopathological analysis, respectively. The sensitivity, specificity, positive predictive value and negative predictive value of 99 Tc m -Octreotide SPECT/CT in diagnosis of lung cancer were 92.2%, 85.7%, 95.9% and 75%, respectively. The area under ROC curve was 0.889 (P 99 Tc m -Octreotide SPECT/CT could play an important role in the diagnosis of lung cancer, and it may be useful for identifying SCLC and NSCLC. (authors)

Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal F-18-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC)

OpenAIRE

Kerner, Gerald S. M. A.; Fischer, Alexander; Koole, Michel J. B.; Pruim, Jan; Groen, Harry J. M.

2015-01-01

Background: Deformable image registration allows volume of interest (VOI)- and voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates the performance of the elastix toolbox deformable image registration algorithm for VOI and voxel-wise assessment of longitudinal variations in FDG tumor uptake in NSCLC patients. Methods: Evaluation of the elastix toolbox was performed using F-18-FDG PET/CT ...

Molecular analysis of p53 and K-ras in lung carcinomas of coal miners

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Sarkar, F.H.; Li, Y.W.; Vallyathan, V. [Wayne State University, Detroit, MI (United States). School of Medicine, Dept. of Pathology

2001-10-01

Thirty-three cases of non-small cell lung cancers (NSCLC) from the archives of National Coal Workers' Autopsy Study were studied for mutational alterations in p53 and K-ras using PCR-SSCP, DNA sequencing and PCR-oligonucleotide probe hybridization techniques. Mutations of the p53 were observed in 4 smokers (19%) and one in a never smoker (8%). Two polymorphisms in smokers were detected at codon 213, a common site for sequence variation. Among the smokers the p53 mutations were in the heavy smokers. In never smokers there was only a single p53 mutation and two K-ras mutations. In never smokers the frequency of K-ras mutations was similar (17%) in smokers, but one never smoker had two K-ras mutations. Mutations of p53 were more frequent in adenocarcinomas (27%) and they were AT-GC transitions. There were two large cell undifferentiated carcinomas with p53 mutation and one with a K-ras mutation. Two of the 16 squamous cell carcinomas were positive for p53 mutation, while no K-ras mutations were found in this group. The results of these preliminary studies indicate a moderately different mutational spectrum of p53 and K-ras in coal miners independent of cigarette smoking. The mutational spectrum observed in this study of coal miners with heavy cigarette smoking history suggest a protective effect of coal mine dust in preventing abnormal mutations induced by chemical carcinogens in cigarette smoke or reactive oxygen species.

The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis

International Nuclear Information System (INIS)

Chen, Wen-Liang; Kuo, Kuang-Tai; Chou, Teh-Ying; Chen, Chien-Lung; Wang, Chih-Hao; Wei, Yau-Huei; Wang, Liang-Shun

2012-01-01

Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells. We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0

Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

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Ilie, M; Hofman, P

2012-01-01

New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

TP53 Mutations in Nonsmall Cell Lung Cancer

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Akira Mogi

2011-01-01

Full Text Available The tumor suppressor gene TP53 is frequently mutated in human cancers. Abnormality of the TP53 gene is one of the most significant events in lung cancers and plays an important role in the tumorigenesis of lung epithelial cells. Human lung cancers are classified into two major types, small cell lung cancer (SCLC and nonsmall cell lung cancer (NSCLC. The latter accounts for approximately 80% of all primary lung cancers, and the incidence of NSCLC is increasing yearly. Most clinical studies suggest that NSCLC with TP53 alterations carries a worse prognosis and may be relatively more resistant to chemotherapy and radiation. A deep understanding of the role of TP53 in lung carcinogenesis may lead to a more reasonably targeted clinical approach, which should be exploited to enhance the survival rates of patients with lung cancer. This paper will focus on the role of TP53 in the molecular pathogenesis, epidemiology, and therapeutic strategies of TP53 mutation in NSCLC.

Lung carcinoma mimicking malignant lymphoma: report of three cases.

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Matsui, K; Kitagawa, M; Wakaki, K; Masuda, S

1993-10-01

Three cases of lung carcinomas with unusual histologic appearances that have received little or no comment in the literature are presented. They were initially confused with malignant lymphoma because of a diffuse proliferation of relatively monotonous cells simulating large-cell immunoblastic lymphoma. In each case, the possibility of malignant lymphoma was excluded with confidence after the immunohistochemical study (leucocyte common antigen negative and cytokeratins positive), although with conventional microscopy several foci of cohesive groups of tumor cells were observed. The tumors were ranked at the clinical stage II or III when they were initially discovered, but all patients died of disease within 1 year. The present three tumors show an aggressive behavior and could be classified into a peculiar variant of 'large cell' carcinoma. It is necessary for surgical pathologists to have an idea of these variants of lung carcinoma in order to avoid erroneous diagnosis.

FDG PET in monitoring response to neoadjuvant chemoradiotherapy in patients with locally advanced non-small lung carcinoma

International Nuclear Information System (INIS)

Berlangieri, S. U.; Lee, S. T.; Chan, A. M.; Mitchell, P. L.; Knight, S. R.; Feigen, M. M.; Scott, A. M.

2009-01-01

Full text:Aim: The aim of our study was to correlate 18F-FDG PET response to neoadjuvant chemoradiotherapy with histopathology in patients with locally advanced non-small cell lung carcinoma. Methods: All patients with stage III NSCLC planned for surgery following induction chemotherpay and/or radiotherapy who underwent pre- and post-treatment FDG-PET between 2004 and 2007 were retrospectively reviewed. The PET scans were performed according to standard protocol. The clinical FDG-PET TNM stage was correlated with the histopathology of the surgical specimens. Results: There were 9 patients (6 M :3 F ), median age 59.7 years (range 49 to 73 years). Post-treatment FDG-PET correctly predicted mediastinal pathological N stage in 8/9 patients, with one patient having microsopic disease in two nodes. The post-treatment FDG-PET correctly predicted pathological T stage in 7/9 patients, with 2 patients having small volume T4 disease not detected by PET. Post-treatment FDG-PET correctly downstaged 4 patients. Of the 5 patients, incorrectly staged on the post-treatment FDG-PET, one patient had microscopic pN 2 disease, 2 had pN 1 disease, and 2 had pT 4 disease. Conclusion: Post-treatment FDG-PET is predictive of pathological nodal stage within the mediastinum in patients with locally advanced NSCLC treated with neoadjuvant chemoradiotherapy. FDG-PET does not detect microscopic or small volume disease, nor is it able to define the boundaries of mediastinal tissue invasion.

Mucoepidermoid carcinoma of the conjunctiva with lung metastasis

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Pukhraj Rishi

2015-01-01

Full Text Available A 36-year-old lady presented with redness and decreased vision in right eye since 6 months. She was earlier diagnosed of cavitary lung lesion, presumed secondary to tuberculosis and treated with anti-tubercular treatment for 4 months. Examination of affected right eye revealed nil light perception, conjunctival congestion with an exuberant mass in the inferotemporal bulbar conjunctiva, proptosis, iris neovascularization, 360° closed angles, intraocular pressure of 48 mm Hg, exudative retinal detachment, uveal mass and orbital extension. A diagnostic needle biopsy of uveal mass revealed malignant cells. Computed tomography-guided lung biopsy revealed squamous cell carcinoma (SCC, indicating metastatic spread from the orbit. She underwent lid-sparing exenteration of the right eye. Histopathological examination of the orbital tissue revealed mucoepidermoid carcinoma arising from the conjunctiva with extensive invasion into the orbital tissue, muscle fibers, sclera, choroid and optic nerve. Multiple tumor emboli were seen in the lumen of orbital blood vessels. In conclusion, mucoepidermoid carcinoma of the conjunctiva is a rare, aggressive variant of SCC. Early intervention is essential to prevent intraocular invasion and systemic metastasis.

Lifetime risk of urothelial carcinoma and lung cancer in the arseniasis-endemic area of Northeastern Taiwan

Science.gov (United States)

Yang, Tse-Yen; Hsu, Ling-I.; Chen, Hui-Chi; Chiou, Hung-Yi; Hsueh, Yu-Mei; Wu, Meei-Maan; Chen, Chi-Ling; Wang, Yuan-Hung; Liao, Ya-Tang; Chen, Chien-Jen

2013-11-01

Arsenic in drinking water has been shown to increase the risk of urothelial carcinoma and lung cancer. However, the lifetime risk of developing urothelial carcinoma and lung cancer caused by exposure to arsenic in drinking water has not been reported. This study aimed to assess the lifetime risk of urothelial carcinoma and lung cancer caused by arsenic exposure from drinking water and cigarette smoking habit for residents living in the arseniasis-endemic area in Northeastern Taiwan. We recruited 8086 residents in 1991-1994 and monitored them for their newly developed types of cancers, identified by computerized linkage with the national cancer registry profile. There were 37 newly diagnosed urothelial carcinoma cases and 223 new lung cancer cases during the follow-up period (until 2007). The lifetime (35-85 years old) cumulative risk of developing urothelial carcinoma from an arsenic concentration in the drinking water of smoking was associated with an increased risk of urothelial carcinoma and lung cancer, showing the hazard ratio (95% confidence interval) of 2.48 (1.27-4.82) and 3.44 (2.00-5.90) after adjusting for the arsenic concentration in drinking water. After adjusting for cigarette smoking, the hazard ratio (95% confidence interval) of developing urothelial carcinoma caused by the arsenic concentration in drinking water of smoking. It is suggested that people who have had a high exposure to arsenic in drinking water should stop smoking cigarettes to lower their lifetime risk of urothelial carcinoma and lung cancer.

Analysis of gene expression data from non-small cell lung carcinoma cell lines reveals distinct sub-classes from those identified at the phenotype level.

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Andrew R Dalby

Full Text Available Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that sub-classes were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC.

The 18F-FDG uptake in non small cell lung carcinoma correlates with the DNA-grading of malignancy

International Nuclear Information System (INIS)

Wu Jinchang

2002-01-01

In order to evaluate correlation of glucose metabolism and DNA ploidity of tumors, the uptake of 18 F-Deoxyglucose (FDG) by PET prior to surgery and the DNA content and DNA-grading of malignancy (DNA-MG) of Schiff-stained nuclei obtained from fresh tumor fragments by means of image cytometry were studied, and thereafter the correlation between standardized uptake value (SUV) and (DNA-MG) was analysed in forty-nine patients with histologically proven non-small cell lung carcinoma (NSCLC). As a result of the DNA histograms of these 49 patients, 46(93.88%) were aneuploidy and only 3(6.12%) were tetraploid. A linear correlation of the SUV versus the (DNA-MG) (r=0.336, p=0.024) was found, demonstrating that 18 F-FDG PET as a non-invasive metabolic imaging technique, may also provide information correlated to malignant DNA patterns which may be valuable in malignant differentiation and prognostic prediction

Utility evaluations for Markov states of lung cancer for PET-based disease management

International Nuclear Information System (INIS)

Papatheofanis, F.J.

2000-01-01

Utilities for the health outcomes states (Markov states) of non-small cell lung carcinoma (NSCLCL) should be measured to evaluate management options for patients because patients are key participants in the process of care, and their assessment of diagnostic and therapeutic value in the options presented to them ultimately impacts their net health outcomes. This investigation sought to measure utilities for stage-dependent outcomes states of NSCLC. Persons (n=23) with suspected NSCLC based on physical findings and computed tomography completed a short utilities survey. Utility valuations were obtained according to severity of morbidity and varied considerably. Respondents rated these health states according to accuracy measures for 18 flurodeoxyglucose ( 18 FDG) positron emission tomography (PET) imaging and mediastinoscopy. The results demonstrate that stage-dependent morbidity is an important consideration for patients with NSCLC and should be included in any decision analysis regarding the evaluation or treatment of NSCLC. Respondents valued the quality of information obtained from non-invasive mediastinoscopy comparably. The utilities obtained from this investigation are useful in clinical decision-making based on Markov processes because they provide an initial estimation of utility assessment for 18 FDG-based diagnostic evaluation of lung cancer. Consequently, these utilities will be useful in future decision analyses that require patient preference in the assignment of the evaluation of decision options (branches)

of lung metastases carcinoma of the cervix Surgical excision from ...

African Journals Online (AJOL)

of lung metastases carcinoma of the cervix. Surgical excision from squamous. A report of 2 cases. N. G. DE MOOR, A. V. BERRY, M. M. NISSENBAUM. These2casereportsservetoemphasizetwoimpor- tant points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; ...

Stereotactic hypofractionated radiotherapy in stage I (T1-2 N0 M0) non-small-cell lung cancer (NSCLC)

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Zimmermann, Frank B.; Geinitz, Hans; Schill, Sabine; Thamm, Reinhard; Nieder, Carsten; Schratzenstaller, Ulrich; Molls, Michael [Technical Univ., Klinikum rechts der Isar, Munich (Germany). Dept. of Radiation Oncology

2006-09-15

Stereotactic Radiotherapy has the potential to produce high local control rates with low risk of severe lung toxicity. From December 2000 to January 2006, 68 inoperable patients (median age 76 years) with stage I NSCLC received definitive hSRT. A mean total dose of 37.5 Gy (24-40 Gy; 60%-isodose) in 3-5 fractions was applied. Immobilisation was carried out by means of a vacuum couch and low pressure foil (Medical Intelligence, Schwab Muenchen, Germany). Staging procedures were thoracic and abdominal CT-scan, FDG-PET and CT or MRI of the brain in all patients. Clinical target volume was the tumor as seen in lung windowing of CT and in FDG-PET. Organ movements (6-22 mm) and patient positioning in the couch (3-12 mm) were added as safety margin for the definition of the planning target volume (PTV), that was enclosed by the 60%-isodose. We observed four (6%) local tumor recurrences, resulting in an actuarial local tumor control rate of 96%, 88% and 88% after 1, 2 and 3 year follow-up. Nineteen patients died, with eight patients due to cancer (12%), two to local tumor progression alone. Cancer-specific survival is 96%, 82% and 73% at 1, 2 and 3 years. Eleven patients died from comorbidities, making a 53% overall 3-year survival. Fifty five percent of the patients were affected by mild acute and subacute side effects, with only 3% experiencing pneumonitis III. Late effects were pneumonitis III in 1%, rib fractures in 3%, and benign pleural effusion in 2 patients. Hypofractionated SRT is safe even in elderly patients with stage I NSCLC and significantly reduced lung capacity. It leads to high local control rates and should be offered to patients not amenable for curative resection.

Percutaneous microwave ablation for early-stage non-small cell lung cancer (NSCLC) in the elderly: a promising outlook

International Nuclear Information System (INIS)

Acksteiner, Christian; Steinke, Karin

2015-01-01

Microwave ablation (MWA) is a relatively new minimally invasive treatment option for lung cancer with substantially lower morbidity and mortality than surgery. This retrospective study was performed to evaluate the safety, effectiveness and follow-up imaging of MWA in the elderly aged 75 years and above. Eleven percutaneous computed tomography (CT)-guided MWA of early-stage non-small cell lung cancer (NSCLC) were performed in 10 patients aged 75 years and older. All but one patient were treated with a high-powered MWA system delivering maximally 140 W. Follow-up with CT and fluorodeoxyglucose-positron emission tomography (FDG-PET) was carried out over a maximum period of 30 months and a median period of 12 months. There were no peri-procedural deaths or major complications. Seven patients were disease free at the time of manuscript submission. Three patients showed growth of the treated lesions, one patient aged 90 years deceased due to unknown cause after approximately 18 months. One patient presented with local progression and disseminated metastatic disease at 12 months; he is still alive. One patient showed increasing soft tissue at the ablation site 15 months post-treatment. Three consecutive core biopsies over 2 months failed to confirm tumour recurrence. MWA therapy is a promising option of treating early-stage NSCLC in the elderly with good treatment outcome and negligible morbidity. Determining successful treatment outcome may be challenging at times as local tissue increase and PET-CT positivity do not seem to necessarily correlate with recurrence of malignancy.

Emerging treatments and combinations in the management of NSCLC

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Reck, Martin; Mellemgaard, Anders

2015-01-01

There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast...

Immunoreactivity of the 14F7 Mab (Raised against N-Glycolyl GM3 Ganglioside as a Positive Prognostic Factor in Non-Small-Cell Lung Cancer

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Rancés Blanco

2012-01-01

Full Text Available Lung carcinoma is the leading cause of cancer-related mortality worldwide. Therefore, numerous studies are focusing on the assessment of other biological and molecular prognostic factors in these tumors. We evaluated the relationship between 14F7 Mab reactivity, pathological features, DNA-content and S-phase fraction (SPF, and their impact in the survival of NSCLC patients. Hematoxylin and eosin staining and immunohistochemistry optical microscopy assays as well as DNA content and SPF measuring using flow cytometry were performed. The 14F7 reactivity was widely observed in NSCLC sections, no depending of the clinicopathological characteristics. We also obtained differences in the intensity of reaction with 14F7 as well as in the SPF between diploid and aneuploid carcinomas. Patients with diploid tumors showing higher SPF and 14F7 reaction joint to a low mitotic index displayed higher survival rates. Our results are in agreement with the assumption of the possible positive prognostic value of 14F7 staining in NSCLC.

Immunoreactivity of the 14F7 Mab (Raised against N-Glycolyl GM3 Ganglioside) as a Positive Prognostic Factor in Non-Small-Cell Lung Cancer

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Blanco, Rancés; Rengifo, Charles E.; Cedeño, Mercedes; Frómeta, Milagros; Rengifo, Enrique; Carr, Adriana

2012-01-01

Lung carcinoma is the leading cause of cancer-related mortality worldwide. Therefore, numerous studies are focusing on the assessment of other biological and molecular prognostic factors in these tumors. We evaluated the relationship between 14F7 Mab reactivity, pathological features, DNA-content and S-phase fraction (SPF), and their impact in the survival of NSCLC patients. Hematoxylin and eosin staining and immunohistochemistry optical microscopy assays as well as DNA content and SPF measuring using flow cytometry were performed. The 14F7 reactivity was widely observed in NSCLC sections, no depending of the clinicopathological characteristics. We also obtained differences in the intensity of reaction with 14F7 as well as in the SPF between diploid and aneuploid carcinomas. Patients with diploid tumors showing higher SPF and 14F7 reaction joint to a low mitotic index displayed higher survival rates. Our results are in agreement with the assumption of the possible positive prognostic value of 14F7 staining in NSCLC. PMID:22482082

Stereotactic body radiotherapy for centrally located early-stage non-small cell lung cancer or lung metastases from the RSSearch® patient registry

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Davis, Joanne N.; Medbery, Clinton; Sharma, Sanjeev; Pablo, John; Kimsey, Frank; Perry, David; Muacevic, Alexander; Mahadevan, Anand

2015-01-01

The purpose of this study was to evaluate treatment patterns and outcomes of stereotactic body radiotherapy (SBRT) for centrally located primary non-small cell lung cancer (NSCLC) or lung metastases from the RSSearch ® Patient Registry, an international, multi-center patient registry dedicated to radiosurgery and SBRT. Eligible patients included those with centrally located lung tumors clinically staged T1-T2 N0, M0, biopsy-confirmed NSCLC or lung metastases treated with SBRT between November 2004 and January 2014. Descriptive analysis was used to report patient demographics and treatment patterns. Overall survival (OS) and local control (LC) were determined using Kaplan-Meier method. Toxicity was reported using the Common Terminology Criteria for Adverse Events version 3.0. In total, 111 patients with 114 centrally located lung tumors (48 T1-T2,N0,M0 NSCLC and 66 lung metastases) were treated with SBRT at 19 academic and community-based radiotherapy centers in the US and Germany. Median follow-up was 17 months (range, 1–72). Median age was 74 years for primary NSCLC patients and 65 years for lung metastases patients (p < 0.001). SBRT dose varied from 16 – 60 Gy (median 48 Gy) delivered in 1–5 fractions (median 4 fractions). Median dose to centrally located primary NSCLC was 48 Gy compared to 37.5 Gy for lung metastases (p = 0.0001) and median BED 10 was 105.6 Gy for primary NSCLC and 93.6 Gy for lung metastases (p = 0.0005). Two-year OS for T1N0M0 and T2N0M0 NSCLC was 79 and 32.1 %, respectively (p = 0.009) and 2-year OS for lung metastases was 49.6 %. Two-year LC was 76.4 and 69.8 % for primary NSCLC and lung metastases, respectively. Toxicity was low with no Grade 3 or higher acute or late toxicities. Overall, patients with centrally located primary NSCLC were older and received higher doses of SBRT than those with lung metastases. Despite these differences, LC and OS was favorable for patients with central lung tumors treated with SBRT. Reported toxicity

PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells.

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Bazzani, Lorenzo; Donnini, Sandra; Giachetti, Antonio; Christofori, Gerhard; Ziche, Marina

2018-03-13

Prostaglandin E 2 (PGE 2 ) contributes to tumor progression by promoting cancer cell growth, invasion and by creating a favorable pro-tumor microenvironment. PGE 2 has been reported to transactivate and internalize into the nucleus receptor tyrosine kinases such as Epidermal growth factor receptor (EGFR), thereby supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, PGE 2 induces EGFR nuclear translocation via different dynamin-dependent endocytic pathways, promotes the formation of an EGFR-STAT3 complex, affects nuclear EGFR target gene expression and mediates tumor cell proliferation. Indeed, we find that PGE 2 induces EGFR internalization and consequent nuclear import through Clathrin- and Caveolin-mediated endocytosis and through the interaction of EGFR with Importin β1. Within the nucleus, EGFR forms a complex with STAT3, an event blocked by ablation of Clathrin Heavy Chain or Caveolin-1. The combination of EGF and PGE 2 prolongs nuclear EGFR transcriptional activity manifested by the upregulation of CCND1 , PTGS2 , MYC and NOS2 mRNA levels and potentiates nuclear EGFR-induced NSCLC cell proliferation. Additionally, NSCLC patients with high expression of a nuclear EGFR gene signature display shorter survival times than those with low expression, thus showing a putative correlation between nuclear EGFR and poor prognosis in NSCLC. Together, our findings indicate a complex mechanism underlying PGE 2 -induced EGF/EGFR signaling and transcriptional control, which plays a key role in cancer progression.

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

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Fassan, Matteo; Indraccolo, Stefano; Calabrese, Fiorella; Favaretto, Adolfo; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Lunardi, Francesca; Attili, Ilaria; Pavan, Alberto; Rugge, Massimo; Guarneri, Valentina; Conte, PierFranco; Pasello, Giulia

2017-01-01

Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified. PMID:28427238

Knockdown of human serine/threonine kinase 33 suppresses human small cell lung carcinoma by blocking RPS6/BAD signaling transduction.

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Sun, E L; Liu, C X; Ma, Z X; Mou, X Y; Mu, X A; Ni, Y H; Li, X L; Zhang, D; Ju, Y R

2017-01-01

Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells. The expression of STK33 in human SCLC cell lines NCI-H466 and DMS153 was inhibited by specific shRNA. The cell proliferation, cell apoptosis, and cell invasion of the cells were assessed with a series of in vitro assays. To explore the mechanism through which STK33 gene exerted its function in the carcinogenesis of SCLC cells, the effect of STK33 knockdown on the activity of S6K1/RPS6/BAD signaling was detected. Then the results were further confirmed with STK33 inhibitor ML281 and in vivo assays. The results demonstrated that inhibition of STK33 in SCLC cells suppressed the cell proliferation and invasion while induced cell apoptosis. Associated with the change in the phenotypic features, knockdown of STK33 also decreased the phosphorylation of RPS6 and BAD while increased the expression of cleaved caspase 9, indicating that apoptosis induced by STK33 suppression was mediated via mitochondrial pathway. Similar to the results of STK33 knockdown, incubating NCI-H466 cells with STK33 inhibitor also reduced the cell viability by suppressing RPS6/BAD pathways. Additionally, STK33 knockdown also inhibited tumor growth and RPS6/BAD activity in mice models. Findings outlined in our study were different from that in NSCLC to some extent: knockdown of STK33 in SCLC cells induced the apoptosis through mitochondrial pathway but independent of S6K1 function, inferring that the function of STK33 might be cancer type specific.

Clinical Analysis of stereotactic body radiation therapy using extracranial gamma knife for patients with mainly bulky inoperable early stage non-small cell lung carcinoma

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Tang Hanjun

2011-07-01

Full Text Available Abstract Purpose To evaluate the clinical efficacy and toxicity of stereotactic body radiation therapy (SBRT using extracranial gamma knife in patients with mainly bulky inoperable early stage non-small cell lung carcinoma (NSCLC. Materials and methods A total of 43 medically inoperable patients with mainly bulky Stage I/II NSCLC received SBRT using gamma knife were reviewed. The fraction dose and the total dose were determined by the radiation oncologist according to patients' general status, tumor location, tumor size and the relationship between tumor and nearby organ at risk (OAR. The total dose of 34~47.5 Gy was prescribed in 4~12 fractions, 3.5~10 Gy per fraction, one fraction per day or every other day. The therapeutic efficacy and toxicity were evaluated. Results The median follow-up was 22 months (range, 3-102 months. The local tumor response rate was 95.35%, with CR 18.60% (8/43 and PR 76.74% (33/43, respectively. The local control rates at 1, 2, 3, 5 years were 77.54%, 53.02%, 39.77%, and 15.46%, respectively, while the 1- and 2-year local control rates were 75% and 60% for tumor ≤3 cm; 84% and 71% for tumor sized 3~5 cm; 55% and 14.6% for tumor sized 5~7 cm; and 45%, 21% in those with tumor size of >7 cm. The overall survival rate at 1, 2, 3, 5 years were 92.04%, 78.04%, 62.76%, 42.61%, respectively. The toxicity of stereotactic radiation therapy was grade 1-2. Clinical stages were significantly important factor in local control of lung tumors (P = 0.000. Both clinical stages (P = 0.015 and chemotherapy (P = 0.042 were significantly important factors in overall survival of lung tumors. Conclusion SBRT is an effective and safe therapy for medically inoperable patients with early stage NSCLC. Clinical stage was the significant prognostic factors for both local tumor control and overall survival. The toxicity is mild. The overall local control for bulky tumors is poor. Tumor size is a poor prognostic factor, and the patients for

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

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Mi, Shanwei; Xiang, Gang; Yuwen, Daolu; Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang; Su, Yongqian; Shen, Yan; Xu, Qiang

2016-01-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

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Mi, Shanwei; Xiang, Gang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Yuwen, Daolu [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Su, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

2016-11-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Aptamer-miRNA-212 Conjugate Sensitizes NSCLC Cells to TRAIL

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Margherita Iaboni

2016-01-01

Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is a promising antitumor agent for its remarkable ability to selectively induce apoptosis in cancer cells, without affecting the viability of healthy bystander cells. The TRAIL tumor suppressor pathway is deregulated in many human malignancies including lung cancer. In human non-small cell lung cancer (NSCLC cells, sensitization to TRAIL therapy can be restored by increasing the expression levels of the tumor suppressor microRNA-212 (miR-212 leading to inhibition of the anti-apoptotic protein PED/PEA-15 implicated in treatment resistance. In this study, we exploited a previously described RNA aptamer inhibitor of the tyrosine kinase receptor Axl (GL21.T expressed on lung cancer cells, as a means to deliver miR-212 into human NSCLC cells expressing Axl. We demonstrate efficient delivery of miR-212 following conjugation of the miR to GL21.T (GL21.T-miR212 chimera. We show that the chimera downregulates PED and restores TRAIL-mediate cytotoxicity in cancer cells. Importantly, treatment of Axl+ lung cancer cells with the chimera resulted in (i an increase in caspase activation and (ii a reduction of cell viability in combination with TRAIL therapy. In conclusion, we demonstrate that the GL21.T-miR212 chimera can be employed as an adjuvant to TRAIL therapy for the treatment of lung cancer.

KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer

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Jun Ma

2015-08-01

Full Text Available Background/Aims: Non-small cell lung carcinoma (NSCLC is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers. Methods: Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research. Results: We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27, inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells. Conclusions: These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.

High resolution CT for localization of early hilar lung carcinoma

International Nuclear Information System (INIS)

Minami, Yuko; Ishikawa, Shigemi; Saida, Yukihisa; Kajitani, Motomasa; Yamamoto, Tatsuo; Sato, Yukio; Onizuka, Masataka; Sakakibara, Yuzuru; Noguchi, Masayuki

2002-01-01

The purpose of this study was to analyse the usefulness of high resolution CT (HRCT) for the diagnosis and localization of roentgenographically occult lung cancer. HRCT was performed prospectively on chest X-ray negative patients with bloody sputum or suspicious or positive cells on sputum cytology between 1998 and 2000. After the HRCT scan, white light bronchoscopy and autofluorescence bronchoscopy were performed. HRCT depicted 19 hilar bronchial lesions in 13 cases out of 19 patients, of which 9 lesions were confirmed by white light broncoscope. Of 8 hilar squamous cell carcinomas diagnosed in this study, 7 lesions (87.5%) were depicted by HRCT. One CT-negative case (12.5%) was an in situ carcinoma in left B 1+2 . Four out of 20 lesions which showed bronchoscopic abnormality, could not be depicted by HRCT. HRCT could prospectively detect 80% of the bronchoscopic abnormalities and 87.5% of the hilar squamous cell carcinomas of the tracheobronchial lesions of the lung. Therefore, HRCT can be an effective supplemental means for screening for hilar squamous cell carcinoma. (author)

The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue

International Nuclear Information System (INIS)

Yue-Hua Wang; De-jie Chen; Tie-Nan Yi

2010-01-01

To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma.This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma (Author).

Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

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Fei Long

2015-01-01

Full Text Available Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC and non-small-cell lung cancer (NSCLC that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

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

International Nuclear Information System (INIS)

Ryu, Yon Ju; Chun, Eun Mi; Lee, Soon Nam; Shim, Sung Shin

2014-01-01

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.

Treatment of stage III non-small cell lung cancer and limited-disease small-cell lung cancer

NARCIS (Netherlands)

El Sharouni, S.Y.

2009-01-01

This thesis concerns the treatment of stage III non-small cell lung cancer (NSCLC) and limited disease small-cell lung cancer (SCLC). We described a systematic review on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCLC stage III with the aim to define the

Validations of SCT Methylation as a Hallmark Biomarker for Lung Cancers

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Fujimoto, Junya; Wistuba, Ignacio; Lam, Stephen; Yatabe, Yasushi; Wang, Yi-Wei; Stastny, Victor; Gao, Boning; Larsen, Jill E; Girard, Luc; Liu, Xiaoyun; Song, Kai; Behrens, Carmen; Kalhor, Neda; Xie, Yang; Zhang, Michael Q; Minna, John D; Gazdar, Adi F

2016-01-01

Background The human secretin (SCT) gene encodes secretin, a hormone with limited tissue distribution. Analysis of The Cancer Genome Atlas (TCGA) 450K methylation array data indicated that the SCT promoter region is differentially hypermethylated in lung cancer. Our purpose was to validate SCT methylation as a potential cancer biomarker for lung cancer. Methods We analyzed TCGA data, and developed and applied SCT-specific bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP) assays. Results The analyses of TCGA 450K data of 801 samples showed that SCT hypermethylation has an area under curve (AUC) value >0.98 to distinguish lung adenocarcinomas or squamous cell carcinomas from non-malignant lung. We confirmed the highly discriminative SCT methylation by bisulfite sequencing of lung cancer cell lines and normal blood cells. By applying qMSP, we found that SCT hypermethylation was frequently detected in all major subtypes of malignant NSCLC (AUC=0.92, n=108) and SCLC cancers (AUC=0.93, n=40) but less frequently present in lung carcinoids (AUC=0.54, n=20). SCT hypermethylation appeared in lung carcinoma in situ samples during multistage pathogenesis and increased in invasive samples. Further analyses of TCGA 450K data showed that SCT hypermethylation is highly discriminative in most types of other malignant tumors but less frequently present in low-grade malignant tumors. The only normal tissue with high methylation was the placenta. Conclusions Our findings demonstrated that SCT methylation is a highly discriminative biomarker for lung and other malignant tumors, and less frequently present in low-grade malignant tumors including lung carcinoids, and appears at the carcinoma in situ stage. PMID:26725182

Stage IV pleomorphic carcinoma of the lung without recurrence for 6 years: a case report.

Science.gov (United States)

Miura, Naoko; Mori, Ryo; Takenaka, Tomoyoshi; Yamazaki, Koji; Momosaki, Seiya; Takeo, Sadanori

2017-12-01

Pleomorphic carcinoma is a rare primary lung carcinoma that occurs at a rate of about 0.3%. Even with complete resection, the tumor usually recurs aggressively, resulting in a poor prognosis. Herein, we report a case of advanced pleomorphic carcinoma of the lung who had a long survival time after resection of the primary and metastatic sites. A 48-year-old man was admitted to our hospital due to abdominal pain. Systemic examination revealed a lung mass on the right and a tumor in the jejunum. Surgical resection of both tumors revealed pleomorphic carcinoma of the lung with metastasis to the jejunum. Follow-up after 6 years showed that the patient remained recurrence-free, without the need for additional postoperative treatment. A vigorous treatment strategy that included surgery had the potential to offer long-term survival, despite an advanced pleomorphic carcinoma with distant metastasis to other organs. Reports on more similar cases are needed to evaluate the value of this treatment option.

An experimental two-stage rat model of lung carcinoma initiated by radon exposure

International Nuclear Information System (INIS)

Poncy, J.L.; Laroque, P.; Fritsch, P.; Monchaux, G.; Masse, R.; Chameaud, J.

1992-01-01

We present the results of a two-stage biological model of lung carcinogenesis in rats. The histogenesis of these tumors was examined, and DNA content of lung cells was measured by flow cytometry during the evolving neoplastic stage. Tumors were induced in rat lungs after radon inhalation (1600 WLM) followed by a promoter treatment; six intramuscular injections of 5,6-benzoflavone (25 mg/kg of body weight/injection) every 2 wk. Less than 3 mo after the first injection of benzoflavone, squamous cell carcinoma was observed in the lungs of all rats exposed to radon. The preneoplastic lesions gradually developed as follows: hyperplastic bronchiolar-type cells migrated to the alveoli from cells that proliferated in bronchioles and alveolar ducts; initial lesions were observed in almost all respiratory bronchioles. From some hyperplasias, epidermoid metaplasias arose distally, forming nodular epidermoid lesions in alveoli, which progressed to form squamous papilloma and, finally, epidermoid carcinomas. The histogenesis of these experimentally induced epidermoid carcinomas showed the bronchioloalveolar origin of the tumor. This factor must be considered when comparing these with human lesions; in humans, lung epidermoid carcinomas are thought to arise mainly in the first bronchial generations. The labeling index of pulmonary tissue after incorporation of 3 H-thymidine by the cells was 0.2% in control rats. This index reached a value of 1 to 2% in the hyperplastic area of the bronchioles and 10 to 15% in epidermoid nodules and epidermoid tumors, respectively. DNA cytometric analysis was performed on cell suspensions obtained after enzymatic treatment of paraffin sections of lungs from rats sacrificed during different stags of neoplastic transformations. Data showed the early appearance of a triploid cell population that grew during the evolution of nodular epidermoid lesions to epidermoid carcinomas

Long-term survival in inoperable squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Ono, Ryosuke; Egawa, Sunao

1988-01-01

Radiotherapy is the first treatment of choice in cases of inoperable lung cancer. This paper reported the indications and limitations of radiotherapy for squamous cell carcinoma of the lung, based on the results of long-term survivors among non-resected squamous cell carcinoma. Materials consisted of 372 cases of squamous cell carcinoma of the lung treated with radiotherapy at the National Cancer Center Hospital between May 1962 and December 1980. Histopathological diagnosis was confirmed by biopsy in all cases. Among the 372 cases, 8 survived more than 5 years. Analyzing these 8 cases according to the TNM classification of the UICC, 7 were stage I, 1 was stage II, and there were no long-term survivors with stage III or IV. Of the 8 cases only one is alive. Analyzing 7 the fatal cases, 2 succumbed due to hepatic or brain metatasis following local recurrence and one had double primary cancer of the pancreas. The remaining 4 cases did not show recurrence or metastasis and succumbed due to pneumonia or myocardial infarct. (author)

Salinomycin enhances cisplatin-induced cytotoxicity in human lung cancer cells via down-regulation of AKT-dependent thymidylate synthase expression.

Science.gov (United States)

Ko, Jen-Chung; Zheng, Hao-Yu; Chen, Wen-Ching; Peng, Yi-Shuan; Wu, Chia-Hung; Wei, Chia-Li; Chen, Jyh-Cheng; Lin, Yun-Wei

2016-12-15

Salinomycin, a polyether antibiotic, acts as a highly selective potassium ionophore and has anticancer activity on various cancer cell lines. Cisplatin has been proved as chemotherapy drug for advanced human non-small cell lung cancer (NSCLC). Thymidylate synthase (TS) is a key enzyme in the pyrimidine salvage pathway, and increased expression of TS is thought to be associated with resistance to cisplatin. In this study, we showed that salinomycin (0.5-2μg/mL) treatment down-regulating of TS expression in an AKT inactivation manner in two NSCLC cell lines, human lung adenocarcinoma A549 and squamous cell carcinoma H1703 cells. Knockdown of TS using small interfering RNA (siRNA) or inhibiting AKT activity with PI3K inhibitor LY294002 enhanced the cytotoxicity and cell growth inhibition of salinomycin. A combination of cisplatin and salinomycin resulted in synergistic enhancement of cytotoxicity and cell growth inhibition in NSCLC cells, accompanied with reduced activation of phospho-AKT, and TS expression. Overexpression of a constitutive active AKT (AKT-CA) expression vector reversed the salinomycin and cisplatin-induced synergistic cytotoxicity. In contrast, pretreatment with LY294002 further decreased the cell viability in salinomycin and cisplatin cotreated cells. Our findings suggested that the down-regulation of AKT-mediated TS expression by salinomycin enhanced the cisplatin-induced cytotoxicity in NSCLC cells. These results may provide a rationale to combine salinomycin with cisplatin for lung cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer

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Shu Yong-Qian

2010-09-01

Full Text Available Abstract Background Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK inhibitor of epidermal growth factor receptor (EGFR, displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC in Chinese population are not sufficient. Purpose To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC, a study of single agent treatment with gefitinib in Chinese patients was conducted. Methods 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily until the disease progression or intolerable toxicity. Results Among the 45 patients, 15 patients achieved partial response (PR, 17 patients experienced stable disease (SD, and 13 patients developed progression disease (PD. None of the patients achieved complete response (CR. The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively. The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively. In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively. Conclusions Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.

Human papillomavirus-16 presence and physical status in lung carcinomas from Asia

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Morewaya Jacob

2010-11-01

Full Text Available Abstract Background Although human papillomavirus (HPV genome has been detected in lung cancer, its prevalence is highly variable around the world. Higher frequencies have been reported in far-east Asian countries, when compared with European countries. The present study analysed the HPV-16 presence in 60 lung carcinomas from the Asian countries China, Pakistan and Papua New Guinea. Results HPV-16 was present in 8/59 (13% samples. According to histological type, HPV-16 was detected in 8/18 (44% squamous cell carcinomas (SQCs, which were mainly from Pakistan; 0/38 (0% adenocarcinomas (ACs, which were mainly from China; and in 0/4 (0% small cell carcinomas (SCLCs. The observed histological difference was statistically significant (p Conclusion These results support the notion that HPV-16 infection is highly associated with SQCs in Pakistan. Our results show a frequent HPV-16 integration in SQCs, although the low viral load casts doubt respect a direct etiological role of HPV in lung carcinomas from Asia. Additional HPV-16 characterization is necessary to establish a direct or indirect etiological role of HPV in this malignancy.

Invasive ductal carcinoma within fibroadenoma and lung metastases

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Abu-Rahmeh, Zuhair; Nseir, William; Naroditzky, Inna

2012-01-01

Fibroadenomas are one of the most common benign tumors of the breast. Malignant transformation from fibroadenoma to cancer is rare. We present a case of an invasive ductal carcinoma within an otherwise benign fibroadenoma with lung metastasis in a 69-year-old woman. PMID:22259257

Medical economics of whole-body FDG PET in patients suspected of having non-small cell lung carcinoma. Reassessment based on the revised Japanese national insurance reimbursement system

International Nuclear Information System (INIS)

Abe, Katsumi; Kosuda, Shigeru; Kusano, Shoichi

2003-01-01

Focusing on the savings expected from the revised Japanese national insurance reimbursement system in the management of patients suspected of having non-small cell lung carcinoma (NSCLC), cost-effectiveness was assessed using decision tree sensitivity analysis on the basis of the 2 competing strategies of whole-body FDG PET (WB-PET) and conventional imaging (CI). A WB-PET strategy that models dependence upon chest FDG PET scan, WB-PET scan, and brain MR imaging with contrast was designed. The cost of a FDG PET examination was updated and determined to be US$625.00. The CI strategy involves a combination of conventional examinations, such as abdominal CT with contrast, brain MR imaging with contrast, and a whole-body bone scan. A simulation of 1,000 patients suspected of having NSCLC (Stages I to IV) was created for each strategy using a decision tree and baselines of other relevant variables cited from published data. By using the WB-PET strategy in place of the CI strategy for the management of patients suspected of having NSCLC in hospitals with an NSCLC prevalence of 75%, the cost saving (CS) for each patient would be US$697.69 for an M1 prevalence of 20% and US$683.52 for an M1 prevalence of 40%, but the CS gradually decreases as the NSCLC prevalence increases. The break-even point requires less than an 80% prevalence in order for the WB-PET strategy to gain life expectancy (LE) per patient. By using the WB-PET strategy in place of the CI strategy for the management of patients suspected of having NSCLC in hospitals with an NSCLC prevalence of 75%, the gain in LE for each patient would be 0.04 years (11.06 vs. 11.02 years) for an M1 prevalence of 20% and 0.10 years (10.13 vs. 10.03 years) for an M1 prevalence of 40%. The maximum cost of a PET study without losing LE would be US$1322.68 per patient for prevalences of 75% NSCLC and 20% M1 disease. The present study quantitatively showed WB-PET, employed in place of CI for managing NSCLC patients, to be cost

Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

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Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

2016-03-01

The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.

WIF-1 and Ihh Expression and Clinical Significance in Patients With Lung Squamous Cell Carcinoma and Adenocarcinoma.

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Zhang, Yue; Hu, Chunhong

2016-10-31

This study investigated the expression of wingless-type inhibitory factor-1 (WIF-1) and Ihh protein in tumor tissues and their clinical significance in patients with lung squamous cell carcinoma and adenocarcinoma. The expression of WIF-1 and Ihh protein in 74 squamous cell carcinomas and 76 adenocarcinomas was measured by immunohistochemistry. The percentage of positive WIF-1 protein expression was significantly higher, while positive Ihh protein expression was significantly lower in patients with well-differentiated lung squamous cell carcinoma and adenocarcinoma, tumor node metastasis (TNM) stage I disease, and lymph node metastasis than that in patients with poorly differentiated tumor, TNM stage III disease, and lymph node metastasis (PIhh protein expression survived significantly shorter than patients with negative Ihh protein expression. In contrast, no significant difference in mean survival was observed in patients with lung squamous cell carcinoma and adenocarcinoma with positive and negative WIF-1 protein expression (P>0.05). Ihh is a marker for poor prognosis in patients with lung squamous cell carcinoma and adenocarcinoma. WIF-1 is not a predictive marker for lung cancer.

Classification of Non-Small Cell Lung Cancer Using Significance Analysis of Microarray-Gene Set Reduction Algorithm

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Lei Zhang

2016-01-01

Full Text Available Among non-small cell lung cancer (NSCLC, adenocarcinoma (AC, and squamous cell carcinoma (SCC are two major histology subtypes, accounting for roughly 40% and 30% of all lung cancer cases, respectively. Since AC and SCC differ in their cell of origin, location within the lung, and growth pattern, they are considered as distinct diseases. Gene expression signatures have been demonstrated to be an effective tool for distinguishing AC and SCC. Gene set analysis is regarded as irrelevant to the identification of gene expression signatures. Nevertheless, we found that one specific gene set analysis method, significance analysis of microarray-gene set reduction (SAMGSR, can be adopted directly to select relevant features and to construct gene expression signatures. In this study, we applied SAMGSR to a NSCLC gene expression dataset. When compared with several novel feature selection algorithms, for example, LASSO, SAMGSR has equivalent or better performance in terms of predictive ability and model parsimony. Therefore, SAMGSR is a feature selection algorithm, indeed. Additionally, we applied SAMGSR to AC and SCC subtypes separately to discriminate their respective stages, that is, stage II versus stage I. Few overlaps between these two resulting gene signatures illustrate that AC and SCC are technically distinct diseases. Therefore, stratified analyses on subtypes are recommended when diagnostic or prognostic signatures of these two NSCLC subtypes are constructed.

ERCC1, toxicity and quality of life in advanced NSCLC patients randomized in a large multicentre phase III trial

DEFF Research Database (Denmark)

Vilmar, Adam Christian; Santoni-Rugiu, Eric; Sørensen, Jens Benn

2010-01-01

Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited.......Excision repair cross complementation group 1 (ERCC1) is a promising biomarker in advanced non-small cell lung cancer (NSCLC). However, current evidence regarding the impact of ERCC1 on toxicity and quality of life (QOL) is limited....

Evaluation of elastix-based propagated align algorithm for VOI- and voxel-based analysis of longitudinal F-18-FDG PET/CT data from patients with non-small cell lung cancer (NSCLC)

NARCIS (Netherlands)

Kerner, Gerald S. M. A.; Fischer, Alexander; Koole, Michel J. B.; Pruim, Jan; Groen, Harry J. M.

2015-01-01

Background: Deformable image registration allows volume of interest (VOI)- and voxel-based analysis of longitudinal changes in fluorodeoxyglucose (FDG) tumor uptake in patients with non-small cell lung cancer (NSCLC). This study evaluates the performance of the elastix toolbox deformable image

Trehalose Liposomes Suppress the Growth of Tumors on Human Lung Carcinoma-bearing Mice by Induction of Apoptosis In Vivo.

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Ichihara, Hideaki; Kuwabara, Keiji; Matsumoto, Yoko

2017-11-01

Previous evidence demonstrates that trehalose liposomes (DMTreC14) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and α-D-glycopyranosyl-α-D-glucopyranoside monomyristate (TreC14) inhibit proliferation and invasion on lung carcinoma (A549 cells) in vitro. Here, we aimed to investigate suppressive effects of DMTreC14 on the growth of tumor on human lung carcinoma bearing mice. DMTreC14 composed of 30 mol% DMPC and 70 mol% TreC14 were prepared by the sonication method. Anti-tumor activities of DMTreC14 using the subcutaneous and orthotopic graft-bearing mice of A549 cells were investigated in vivo. The remarkable reduction of volume and weight in subcutaneous tumors on subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were obtained. Apoptotic-positive cells in the subcutaneous tumor slice of subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were observed using TUNEL staining. Lung weights on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 were markedly decreased compared to those of the control group. Remarkable decrease in dimensions of tumor area of lung on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 was obtained in histological analysis using the hematoxylin and eosin staining. Remarkably high anti-tumor activities of DMTreC14 for the subcutaneous and orthotopic graft-bearing mice of lung carcinoma accompanied with apoptosis were revealed for the first time in vivo. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Relationship between genetic polymorphisms in MCP-1, CCR-2, and non-small-cell lung cancer in the Han nationality of Northern China.

Science.gov (United States)

Yang, L; Wang, J; Li, F-G; Han, M; Chang, X-J; Wang, Z-T

2015-04-22

Lung cancer is a common malignant tumor worldwide and is now the leading cause of cancer-related deaths. Monocyte chemoattractant protein 1 (MCP-1) and its receptor chemokine receptor 2 (CCR-2) are important chemokines. We examined the polymorphisms of 338 unrelated patients with non-small cell lung carcinoma (NSCLC) and 200 unrelated healthy controls of Han nationality in Northern China using polymerase chain reaction-restriction fragment length polymorphism. We found a significant increase in the frequency of the MCP-1 AA genotype [0.293 vs 0.195, odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.60] and a significant decrease in the frequency of the GG genotype (0.290 vs 0.41, OR = 0.64, 95%CI = 0.47-0.87) in NSCLC patients compared to controls. The frequencies of AA-ww (0.151 vs 0.090, P = 0.041, OR = 1.80, 95%CI = 1.33-2.43) and AA-wm (0.136 vs 0.080, P = 0.049, OR = 1.81, 95%CI = 1.01-3.27) were higher in lung cancer patients than in healthy controls; the frequency of GG-wm (0.121 vs 0.190, P = 0.030, OR = 0.60, 95%CI = 0.38-0.95) was lower in lung cancer patients than in healthy controls. Based on these results, the polymorphism in MCP-1 may be correlated with the development of NSCLC in the Han nationality of Northern China. However, the polymorphism in CCR-2 is not involved in NSCLC.

P13.10 Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases

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Yust-Katz, S.; Dudnik, E.; Perlov, E.; Zer, A.; Flex, D.; Peled, N.; Siegal, T.

2016-01-01

Abstract Background: Central nervous system (CNS) metastases occur in about 30% of patients (pts) with advanced non-small cell lung cancer (NSCLC). Local treatment strategies (e.g., radiotherapy or surgery) result in delays in systemic therapy administration and are frequently associated with neurocognitive impairment. Nivolumab is an anti-PD1 immune check-point inhibitor which has been recently approved by the FDA as a second line treatment of NSCLC. Data regarding its intracranial activity is lacking. Methods: We retrospectively reviewed efficacy and safety of nivolumab administered intravenously at a dose of 3mg/kg q2 weeks in five pts with advanced NSCLC and new or progressing intracranial metastases which were diagnosed before or within 1 month after starting the treatment. Results: Pt baseline characteristics were as follows: median age 78y (range, 52–84); 2 males; 4 smokers; ECOG PS 0/1/2 - 2 pts/1 pt/2 pts; histological subtype: adenocarcinoma/ squamous-cell carcinoma/NSCLC NOS 3 pts /1 pt/1 pt; EGFR WT/ALK neg/KRAS M all/all/2 pts. Four pts had parenchymal brain metastases, three pts had leptomeningeal disease. All pts were asymptomatic and did not require corticosteroids or immediate brain irradiation. Dramatic response in the brain was observed in two pts (including 1 pt with leptomeningeal spread demonstrating a complete response in the CNS); time-to-response comprised 5 weeks and 9 weeks; all responses are still ongoing at the time of the report (18+ weeks, 19+ weeks). In one pt stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved. Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS-metastases related grade ≥ 3 adverse events were observed. Conclusions: Nivolumab has a promising intracranial activity and favorable safety profile in pts with NSCLC and untreated/progressing CNS metastases. Nivolumab CNS activity warrants further evaluation.

Cerebral metastases from lung carcinoma: neurological and CT correlation: work in progress

International Nuclear Information System (INIS)

Tarver, R.D.; Richmond, B.D.; Klatte, E.C.

1984-01-01

To determine the role of brain CT in neurologically asymptomatic lung cancer patients a review was made of the CT and clinical findings in 279 patients. Brain metastases were found in 94.5% of patients with specific abnormal neurological findings, 26.6% of patients with vague neurological signs and symptoms, 11% of patients with oat cell carcinoma and a normal neurological examination, and 40% of patients with adenocarcinoma and a normal neurological examination. Brain metastasis was not seen on CT in the 29 patients with squamous cell carcinoma and a normal neurological examination. It is concluded that brain CT is useful for the detection of occult brain metastases, particularly oat cell carcinoma and adenocarcinoma, in neurologically asymptomatic lung cancer patients

Primary pulmonary non-small cell carcinomas: the College of American Pathologists Interlaboratory Comparison Program confirms a significant trend toward subcategorization based upon fine-needle aspiration cytomorphology alone.

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Yildiz-Aktas, Isil Z; Sturgis, Charles D; Barkan, Guliz A; Souers, Rhona J; Fraig, Mostafa M; Laucirica, Rodolfo; Khalbuss, Walid E; Moriarty, Ann T

2014-01-01

Context.-Subtyping of non-small cell lung carcinomas (NSCLCs) is necessary for optimal patient management with specific diagnoses triggering specific molecular tests and affecting therapy. Objective.-To assess the accuracy of the participants of the College of American Pathologists Interlaboratory Comparison Program in diagnosing and subtyping NSCLC fine-needle aspiration (FNA) slides, based on morphology alone, considering preparation and participant type and trends over time. Design.-The performance of program participants was reviewed for the 5-year period spanning 2007-2011. Lung FNA challenges with reference diagnoses of adenocarcinoma and squamous cell carcinoma (SCC) were evaluated for diagnostic concordance by using a nonlinear mixed model analysis. Results.-There were 10 493 pathologist and 6378 cytotechnologist responses with concordance rates of 97.4% and 97.9% for malignancy, respectively. Overall concordance rates for subcategorization were 54.6% for adenocarcinoma and 74.9% for SCC. For the exact reference diagnoses, pathologists performed better for adenocarcinoma and cytotechnologists performed better for SCC. Accurate subcategorization of adenocarcinomas significantly increased over time with 31.5% of adenocarcinomas classified as NSCLC in 2007 and 25.5% of adenocarcinomas classified as NSCLC in 2011 (P alone. During the study period, a statistically significant trend was confirmed toward greater accuracy of subcategorization of adenocarcinomas, suggesting that participants are cognizant of the impact that more specific cytomorphologic interpretations have in directing molecular triage and therapy.

Oestrogen receptor beta over expression in males with non-small cell lung cancer is associated with better survival

DEFF Research Database (Denmark)

Skov, Birgit Guldhammer; Sode, Birgitte M Fischer; Pappot, H.

2008-01-01

BACKGROUND: Adenocarcinoma of the lung is more frequent in females than in males and the association with smoking is less pronounced than for the other histological subtypes of lung cancer. Oestrogen induction of cell proliferation has been found in breast adenocarcinomas, and since oestrogen...... the results to gender and survival. METHODS: Paraffin embedded, histological material was collected from 104 patients (71 men and 33 women), operated in the period 1989-1992 for NSCLC (56 squamous cell carcinomas, 40 adenocarcinomas and 8 large cell carcinomas). ERalpha, ERbeta and progesterone were...... and progesterone expression for the prognosis. RESULTS: ERbeta positivity was demonstrated in 69% (72 of 104) of the tumours. There was no statistically significant correlation between ERbeta positivity and age, gender, stage, or histology. After adjusting for gender, age, stage at diagnosis and histology...

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC

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Nikaedo Sueli M

2004-09-01

Full Text Available Abstract Background Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC can be achieved with cisplatin-based chemotherapy (CT, its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. Methods In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m2, on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years, younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m2 or 90 mg/m2, and older patients were allocated to lower cisplatin doses (60 mg/m2 or 70 mg/m2. We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Results Analysis was by intention to treat. Main toxicities (grade 3–4 was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP and overall survival (OS were 27.0 (95% CI: 10.1 to 43.7 weeks and 30.1 (95% CI: 24.4 to 35.8 weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%, with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Conclusion Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions.

Chemotherapy with cisplatin and vinorelbine for elderly patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)

International Nuclear Information System (INIS)

Pereira, José Rodrigues; Martins, Sandro J; Nikaedo, Sueli M; Ikari, Flora K

2004-01-01

Although modest improvements in the survival of patients with non-small cell lung cancer (NSCLC) can be achieved with cisplatin-based chemotherapy (CT), its value is disputed in the geriatric setting. In this study, we evaluate the feasibility of vinorelbine/cisplatin CT for elderly NSCLC patients. In this pilot phase I/II trial, all patients received CT with vinorelbine 25 mg/m 2 , on day 1 and 8, and cisplatin on day 1, in 28 days-cycles. After stratification for age (up to 75 years), younger patients were sequentially allocated to moderate cisplatin doses (80 mg/m 2 or 90 mg/m 2 ), and older patients were allocated to lower cisplatin doses (60 mg/m 2 or 70 mg/m 2 ). We recruited patients aged over 70 years with newly diagnosed NSCLC, clinical stage III or IV, Karnofsky performance status ≥ 70%, normal serum creatinine, peripheral neuropathy ≤ grade 1, and no prior cancer therapy. Analysis was by intention to treat. Main toxicities (grade 3–4) was as follows: neutropenia, 20%; anemia, 11%; and thrombocytopenia, 2%; alopecia, 55%; fatigue, 11%; and peripheral neurotoxicity, 2%. No grade 3–4 emesis or renal toxicity occurred. Global median time to progression (TTP) and overall survival (OS) were 27.0 (95% CI: 10.1 to 43.7) weeks and 30.1 (95% CI: 24.4 to 35.8) weeks; 1- and 2-year survival rates were 36.3% and 13.2%, respectively. Overall response rate was 50.0% (95% CI: 35.4% to 64.5%), with 1 complete response; no difference on response rate was noticed according to cisplatin dose. Median overall survival was 30.1 weeks, with 1- and 2-year survival rates of 36.3% and 13.2%, respectively. Age does not preclude assessment on the role of cisplatin-vinorelbine CT for elderly NSCLC patients with good performance status and adequate bodily functions

Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)

International Nuclear Information System (INIS)

Higashi, Kotaro; Takase, Shuko; Ohguchi, Manabu; Seki, Hiroyasu; Okimura, Tetsuro; Miyamura, Toshio; Yamamoto, Itaru; Rikimaru, Shigeho.

1992-01-01

This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r=-0.701, p<0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy. (author)

Exploration of Postoperative Follow-up Strategies for Early Staged NSCLC Patients on the Basis of Follow-up Result of 416 Stage I NSCLC Patients after Lobectomy

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Liang DAI

2018-03-01

Full Text Available Background and objective Currently, there is no consensus on the follow-up strategy (follow-up time interval and content of non-small cell lung cancer (NSCLC in the world, and the relevant clinical evidence is also very limited. In this study, we aimed to summarize the recurrence/metastasis sites and timings of stage I NSCLC patients based on their follow-up data, aiming to provide a basis of follow-up time interval and content for this group of patients. Methods We retrospectively analyzed the 416 stage I NSCLC patients that underwent continuous anatomic lobectomy between Jan. 2000 to Oct. 2013 in our prospective lung cancer database. According to the recurrence/metastasis sites and timings, the long term follow-up time interval and content were explored. Results The 5-yr disease free survival (DFS and overall survival (OS in the whole group were 82.4% and 85.4%, respectively. There were 76 cases (18.3% had recurrence/metastasis during follow-up, among which the most frequent site was pulmonary metastasis (21 cases, 5.0%, followed by brain metastasis (20 cases, 4.8%, bone metastasis (12 cases, 2.9%, and mediastinal lymph node metastasis (12 cases, 2.9%. Among the factors that could influence recurrence/metastasis, patients with pT2a suffered from a higher recurrence/metastasis rate compared to patients with pT1 (P=0.006, with 5-yr DFS being 73.8% and 87.3%, respectively (P=0.002, and the 5-yr OS being 77.7% and 90.3%, respectively (P=0.011. Conclusion The commonest recurrence/metastasis sites of stage I NSCLC after anatomic lobectomy are lung, brain and mediastinal lymph nodes, the risk of recurrence/metastasis within 2 years were equal to that between 3 years and 5 years. The follow-up frequencies and content within 2 years could be adjusted according to T stages.

Detection of cytoskeletal proteins in small cell lung carcinoma

Czech Academy of Sciences Publication Activity Database

Hložánková, M.; Lukáš, Z.; Viklický, Vladimír

1999-01-01

Roč. 18, - (1999), s. 47-49 ISSN 0231-5882 Grant - others:MŠk1(CZ) OE10a/EU1450 Keywords : cytoskeletal proteins * small cell lung carcinoma Subject RIV: EI - Biotechnology ; Bionics Impact factor: 0.400, year: 1999

Levels of plasminogen activator inhibitor type 1 and urokinase plasminogen activator receptor in non-small cell lung cancer as measured by quantitative ELISA and semiquantitative immunohistochemistry

DEFF Research Database (Denmark)

Pappot, Helle; Skov, Birgit Guldhammer; Pyke, Charles

1997-01-01

The components of the plasminogen activation system have been reported to have prognostic impact in several cancer types, e.g. breast-, colon-, gastric- and lung cancer. Most of these studies have used quantification by enzyme-linked immunosorbent assay (ELISA) on tumour tissue extracts. However......, results in non-small cell lung cancer (NSCLC) studies obtained by quantitative ELISA and semiquantitative immunohistochemistry differ. If the prognostic value of the components of the plasminogen activation system is to be exploited clinically in the future, it is important to choose an easy and valid...... methodology. In the present study we investigated levels of plasminogen activator inhibitor type 1 (PAI-I) and urokinase plasminogen activator receptor (uPAR), as quantitated by ELISA in tumour extracts from 64 NSCLC patients (38 squamous cell carcinomas, 26 adenocarcinomas), and compared them to staining...

The Effect of Consolidation Chemotherapy for LA-NSCLC Patients Receiving Concurrent Chemoradiotherapy

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Yelda Varol

2016-09-01

Full Text Available Aim: The efficacy and safety of consolidation chemotherapy (CCT following concurrent chemoradiotherapy are not adequately established for patients with locally advanced non-small-cell lung cancer (LA-NSCLC. In this context, the present study aims to evaluate the efficacy and toxicity of CCT.Material and Method: We retrospectively analyzed the overall survival (OS and progression-free survival (PFS of 83 LA-NSCLC patients treated with concurrent CRT as an initial treatment with (n:20 or without CCT (n:63. All patients were cytohistologically proven to have NSCLC and diagnosed with clinical Stage III (n:48 for IIIA and n:35 for IIIB according to the staging system published by the American Joint Committee on Cancer (AJCC in 2009. All patients received curative thoracic radiotherapy with concurrent platinum doublet chemotherapy. Results: The mean age of the lung cancer patients was 59 (±7.3; 89.2% were male (n:74,and there were only 9 female patients (10.8%.When we compared the outcome of LA-NSCLC patients treated with CCT (median 10.4 months to the patients treated without CCT (median 13.8 months, the log-rank analysis demonstrated a statistically significant difference for an inferior progression-free survival (p=0.046 in patients receiving CCT. However, no significant association was observed for overall survival (17.4, 21 months, respectively (p>0.05. Patients with CCT presented higher levels of hematological side effects compared with the patients without CCT (p

Bevacizumab in the treatment of NSCLC: patient selection and perspectives

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Russo AE

2017-12-01

Full Text Available Alessia E Russo,1 Domenico Priolo,1 Giovanna Antonelli,1 Massimo Libra,2 James A McCubrey,3 Francesco Ferraù1 1Medical Oncology Department, San Vincenzo Hospital, Taormina (Messina, Italy; 2Laboratory of Translational Oncology & Functional Genomics, Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy; 3Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, NC, USA Abstract: Non-small-cell lung cancer (NSCLC represents about 85% of all lung cancers, and more than half of NSCLCs are diagnosed at an advanced stage. Chemotherapy has reached a plateau in the overall survival curve of about 10 months. Therefore, in last decade novel targeted approaches have been developed to extend survival of these patients, including antiangiogenic treatment. Vascular endothelial growth factor (VEGF signaling pathway plays a dominant role in stimulating angiogenesis, which is the main process promoting tumor growth and metastasis. Bevacizumab (bev; Avastin® is a recombinant humanized monoclonal antibody that neutralizes VEGF’s biologic activity through a steric blocking of its binding with VEGF receptor. Currently, bev is the only antiangiogenic agent approved for the first-line treatment of advanced or recurrent nonsquamous NSCLC in “bev-eligible” patients. The ineligibility to receive bev is related to its toxicity. In the pivotal trials of bev in NSCLC, fatal bleeding events including pulmonary hemorrhage were observed with rates higher in the chemotherapy-plus-bev group. Therefore, in order to reduce the incidence of severe pulmonary hemorrhage, numerous exclusion criteria have been characteristically applied for bev such as central tumor localization or tumor cavitation, use of anticoagulant therapy, presence of brain metastases, age of patients (elderly. Subsequent studies designed to evaluate the safety of bev have demonstrated that this agent is safe and

Genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC

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Liu Xiaolan; Wang Weili; Zhang Xueying; Hao Ming; Liu Linlin; Wu Zhenfeng; Jiang Hongwei

2008-01-01

Objective: To investigate the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of non-small cell lung cancer (NSCLC). Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was used to identify mdm2 genotypes. The Pearson Chi square test and Woolf statistic method were used to analyze the relative risk and 95% confidence interval (CI) in order to find the genetic association between polymorphism of mdm2 gene and symptoms and pathological types of NSCLC. Results: In the SNP rs1196337 (a G to A base change) AA genotype showed association with cough of NSCLC (P<0.05). Conclusion: The polymorphism of mdm2 gene may be associated with symptom as cough of NSCLC. (authors)

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?].

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Gómez, Ana M; Jarabo, José Ramón; Fernandez, Cristina; Calatayud, Joaquín; Fernández, Elena; Torres, Antonio J; Balibrea, José L; Hernando, Florentino

2014-04-01

Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Primary Lung Signet Ring Cell Carcinoma Presenting as a Cavitary Pancoast Tumor in a 32-Year-Old Man.

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Corvini, Michael; Koorji, Alysha; Sgroe, Erica; Nguyen, Uyen

2018-06-01

Signet ring cell carcinoma, a subtype of adenocarcinoma, is a rare cause of primary lung cancer. The authors report a case of primary lung signet ring cell carcinoma presenting as a cavitary Pancoast tumor in a 32-year-old male smoker. Beyond the rarity of primary lung signet ring cell carcinoma itself, the youth of the patient, his smoking status, the presence of cavitation, and the location of the tumor in the superior sulcus make it especially atypical.

Efficiency of lipofection combined with hyperthermia in Lewis lung carcinoma cells and a rodent pleural dissemination model of lung carcinoma.

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Okita, Atsushi; Mushiake, Hiroyuki; Tsukuda, Kazunori; Aoe, Motoi; Murakami, Masakazu; Andou, Akio; Shimizu, Nobuyoshi

2004-06-01

We have previously reported that hyperthermia at 41 degrees C enhanced lipofection-mediated gene transduction into cultured cells. In this study, we adapted hyperthermia technique to novel cationic liposome (Lipofectamine 2000) mediated gene transfection into Lewis lung carcinoma cells in vitro and in vivo. In vitro, transfection efficiencies were 38.9+/-3.3% by lipofection alone and 52.1+/-2.6% by lipofection with hyperthermia for 30 min, and 62.5+/-5.5% and 81.4+/-3.2% for 1 h, respectively. Hyperthermia significantly enhanced gene transfection efficiency 1.2-1.4 times more than that with lipofection only. We also evaluated the effect of hyperthermia with a pleural dissemination model of lung carcinoma of mice. We developed a model which was well-tolerated with hyperthermia with lipofection by the mice. In spite of repeated treatments, transfection efficiencies were very low and we could not show the augmentation of gene transfection by hyperthermia. Though Lipofectamine 2000 showed strong gene transduction effect and hyperthermia augmented its effect in vitro, further evaluation is needed to adapt both techniques in vivo.

Biologic Evaluation of Diabetes and Local Recurrence in Non-Small Cell Lung Cancer.

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Yang, Xuebin; Liu, Yongjun; Mani, Haresh; Olson, Jeffrey; Clawson, Gary; Caruso, Carla; Bruggeman, Richard; Varlotto, John M; Zander, Dani S; Rassaei, Negar

2017-01-01

A recent multicenter study led by our institution demonstrated that local recurrence of non-small cell lung cancer (NSCLC) was significantly more frequent in patients with diabetes, raising the possibility of different tumor biology in diabetics. Epithelial-to-mesenchymal transition (EMT) plays a key role in local tumor recurrence and metastasis. In the present study, we investigated differences of tumor microenvironment between patients with and without diabetes by examining expression of EMT markers. Seventy-nine NSCLC patients were selected from the cohort of our early multicenter study. These patients were classified into 4 groups: 39 with adenocarcinoma with (n = 19) and without (n = 20) diabetes, and 40 with squamous cell carcinoma with (n = 20) and without (n = 20) diabetes. Immunohistochemical expression of eight EMT markers was analyzed, including transforming growth factor-beta (TGF-β), epidermal growth factor receptor (EGFR), insulin-like growth factor 1 receptor (IGF-1R), vimentin, E-cadherin, N-cadherin, HtrA1, and beta-catenin. Five markers (E-cadherin, HtrA1, TGF-β, IGF-1R and vimentin) demonstrated significantly higher expression in diabetics than in non-diabetics in both histology types. N-cadherin had higher expression in diabetics, though the difference did not reach statistical significance. EGFR showed a higher expression in diabetics in squamous cell carcinoma only. Beta-catenin was the only marker with no difference in expression between diabetics versus non-diabetics. Our findings suggest that diabetes is associated with enhanced EMT in NSCLC, which may contribute to growth and invasiveness of NSCLC.

The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth.

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Chiappetta, Gennaro; Basile, Anna; Barbieri, Antonio; Falco, Antonia; Rosati, Alessandra; Festa, Michelina; Pasquinelli, Rosa; Califano, Daniela; Palma, Giuseppe; Costanzo, Raffaele; Barcaroli, Daniela; Capunzo, Mario; Franco, Renato; Rocco, Gaetano; Pascale, Maria; Turco, Maria Caterina; De Laurenzi, Vincenzo; Arra, Claudio

2014-08-30

BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy.

Hypofractionated High-Dose Proton Beam Therapy for Stage I Non-Small-Cell Lung Cancer: Preliminary Results of A Phase I/II Clinical Study

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Hata, Masaharu; Tokuuye, Koichi; Kagei, Kenji; Sugahara, Shinji; Nakayama, Hidetsugu; Fukumitsu, Nobuyoshi; Hashimoto, Takayuki; Mizumoto, Masashi; Ohara, Kiyoshi; Akine, Yasuyuki

2007-01-01

Purpose: To present treatment outcomes of hypofractionated high-dose proton beam therapy for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Twenty-one patients with Stage I NSCLC (11 with Stage IA and 10 with Stage IB) underwent hypofractionated high-dose proton beam therapy. At the time of irradiation, patient age ranged from 51 to 85 years (median, 74 years). Nine patients were medically inoperable because of comorbidities, and 12 patients refused surgical resection. Histology was squamous cell carcinoma in 6 patients, adenocarcinoma in 14, and large cell carcinoma in 1. Tumor size ranged from 10 to 42 mm (median, 25 mm) in maximum diameter. Three and 18 patients received proton beam irradiation with total doses of 50 Gy and 60 Gy in 10 fractions, respectively, to primary tumor sites. Results: Of 21 patients, 2 died of cancer and 2 died of pneumonia at a median follow-up period of 25 months. The 2-year overall and cause-specific survival rates were 74% and 86%, respectively. All but one of the irradiated tumors were controlled during the follow-up period. Five patients showed recurrences 6-29 months after treatment, including local progression and new lung lesions outside of the irradiated volume in 1 and 4 patients, respectively. The local progression-free and disease-free rates were 95% and 79% at 2 years, respectively. No therapy-related toxicity of Grade ≥3 was observed. Conclusions: Hypofractionated high-dose proton beam therapy seems feasible and effective for Stage I NSCLC. Proton beams may contribute to enhanced efficacy and lower toxicity in the treatment of patients with Stage I NSCLC

Sarcoma pleomórfico primário do pulmão Primary pleomorphic sarcoma of the lung

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Marcus da Matta Abreu

2008-07-01

Full Text Available A classificação recente da Organização Mundial da Saúde (OMS para os tumores pulmonares unificou o heterogéneo grupo do carcinoma de não pequenas células (CPNPC, que engloba os sarcomas e os tumores com componentes sarcomatosos, sob a denominação “carcinoma com elementos pleomórficos, sarcomatóides ou sarcomatosos”. Este grupo inclui diferentes entidades, como o carcinoma pleomórfico (CP, o carcinoma de células fusiformes (CCF, carcinoma de células gigantes (CCG, os carcinossarcomas (CS e o blastoma pulmonar (BP. De uma forma geral, estes tumores são raros e representam 0,1% a 0,4% de todas as neoplasias pulmonares. Ocorrem mais comummente em homens fumadores, com alta carga tabágica, e acomete-os em torno dos 60 anos e comummente tem evolução clínica muito agressiva. Os autores relatam o caso de um doente portador de sarcoma pleomórfico primário pulmonar e revêem a literatura sobre o assunto.The World Health Organization (WHO classification of lung cancers ranks the heterogeneous nonsmall cell lung cancer (N-SCLC group, encompassing sarcoma or sarcoma-containing tumours under one heading: “carcinomas with pleomorphic, sarcomatoid or sarcomatous elements”. This group contains entities such as pleomorphic carcinoma (PC, spindle cell carcinoma (SCC, giant cell carcinoma (GCC, carcinosarcoma (CS and pulmonary blastoma (PB. These tumors are rare overall, making up approx. 0.1-0.4% of all lung malignancies. They are more commonly found in males who are heavy smokers, diagnosed at the age of 60 on average and follow an aggressive clinical course. The authors describe the case of a male patient with primary pleomorphic lung sarcoma and also include a review of the literature.

Cyclopamine tartrate, an inhibitor of Hedgehog signaling, strongly interferes with mitochondrial function and suppresses aerobic respiration in lung cancer cells

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Alam, Md Maksudul; Sohoni, Sagar; Kalainayakan, Sarada Preeta; Garrossian, Massoud; Zhang, Li

2016-01-01

Aberrant Hedgehog (Hh) signaling is associated with the development of many cancers including prostate cancer, gastrointestinal cancer, lung cancer, pancreatic cancer, ovarian cancer, and basal cell carcinoma. The Hh signaling pathway has been one of the most intensely investigated targets for cancer therapy, and a number of compounds inhibiting Hh signaling are being tested clinically for treating many cancers. Lung cancer causes more deaths than the next three most common cancers (colon, breast, and prostate) combined. Cyclopamine was the first compound found to inhibit Hh signaling and has been invaluable for understanding the function of Hh signaling in development and cancer. To find novel strategies for combating lung cancer, we decided to characterize the effect of cyclopamine tartrate (CycT), an improved analogue of cyclopamine, on lung cancer cells and its mechanism of action. The effect of CycT on oxygen consumption and proliferation of non-small-cell lung cancer (NSCLC) cell lines was quantified by using an Oxygraph system and live cell counting, respectively. Apoptosis was detected by using Annexin V and Propidium Iodide staining. CycT’s impact on ROS generation, mitochondrial membrane potential, and mitochondrial morphology in NSCLC cells was monitored by using fluorometry and fluorescent microscopy. Western blotting and fluorescent microscopy were used to detect the levels and localization of Hh signaling targets, mitochondrial fission protein Drp1, and heme-related proteins in various NSCLC cells. Our findings identified a novel function of CycT, as well as another Hh inhibitor SANT1, to disrupt mitochondrial function and aerobic respiration. Our results showed that CycT, like glutamine depletion, caused a substantial decrease in oxygen consumption in a number of NSCLC cell lines, suppressed NSCLC cell proliferation, and induced apoptosis. Further, we found that CycT increased ROS generation, mitochondrial membrane hyperpolarization, and

Elective brain irradiation in patients with small-cell carcinoma of the lung: preliminary report

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Katsenis, A.T.; Karpasitis, N.; Giannakakis, D.; Maragoudakis, N.; Kiparissiadis, P.

1982-01-01

The brain is a common site of metastases in small-cell carcinoma of the lung. Prophylactic brain irradiation with doses of 4000-4500 rads in 3-4 weeks appears to decrease the occurrence of brain metastases although it does not prevent this completely. In a group of patients with small-cell carcinoma of the lung and without evidence of brain metastases, the authors review the site and extent of the primary, the methods of treatment, the techniques of brain irradiation, and the relapses rate in relation to the status of the primary and the rate of brain metastases in another group without prophylactic brain irradiation. They further attempt to investigate combined modalities of treatment which would prolong life and prevent neurological complications in the small number of long survivors with small-cell carcinoma of the lung. (Auth.)

Mucoepidermoid carcinoma of the lung with initial presentation of microangiopathic hemolytic anemia and thrombocytopenia

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Yuan-Chun Huang

2017-12-01

Full Text Available Mucoepidermoid carcinoma is a rare entity of lung malignancy that is subclassified into high-grade or low-grade types according to its histological features. High-grade mucoepidermoid carcinoma is a more aggressive form of malignancy, with a tendency towards lymph node involvement and distant metastasis. Cancer-related microangiopathic hemolytic anemia as a less common situation of paraneoplastic syndrome may be encountered with metastatic malignancy, but has not been reported previously in mucoepidermoid carcinoma of the lung. Herein, we report a 78-year-old male patient who presented with hemoptysis for one day. Laboratory tests showed microangiopathic hemolytic anemia and thrombocytopenia. A chest X-ray demonstrated consolidation in the left lung field. Chest computed tomography revealed a mass in the left upper lobe, and a subsequent bronchoscopic biopsy was performed. The histopathological results indicated a high-grade mucoepidermoid carcinoma. Magnetic resonance imaging of the brain demonstrated leptomeningeal carcinomatosis. The patient refused systemic chemotherapy, and palliative radiation therapy only was conducted for local disease control. The patient has performed well for 12 months to date since diagnosis of the tumor.

Prognostic value of lncRNAs in lung carcinoma: a meta-analysis.

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Fan, Fan; Zhu, Zhengqiu; Gao, Chao; Liu, Yun; Wang, Baoqing; Wang, Ziquan; Feng, Jifeng

2017-10-10

Many different long non-coding RNAs (lncRNAs) have been reported to be abnormally expressed in lung carcinoma and may thus serve as prognostic biomarkers for this disease. We conducted this meta-analysis, which included a total of 30 studies identified via searches of PubMed, Embase, Medline, and Web of Science and included 2912 patients from China (28), Germany (1), and Japan (1), to investigate the prognostic value of different lncRNAs in lung carcinoma. The results revealed that lncRNA transcription levels were significantly associated with overall survival in lung cancer patients (HR:1.46, 95% CI: 1.16-1.83, P = 0.000). However, lncRNA transcription levels were not associated with progression-free survival (PFS) (HR: 1.55, 95% CI: 0.50-4.80, P = 0.449). Further analysis showed that high lncRNA transcription levels were significantly associated with tumour-node-metastasis (TNM) stage (III/IV vs I/II: RR = 1.339, 95% CI: 1.046-1.716, P = 0.012), lymph node metastasis (positive vs negative: RR = 1.442, 95% CI: 1.103-1.885, P = 0.007), and distant metastasis (yes vs no: RR = 3.187,95% CI: 1.393-7.294, P = 0.006). Taken together, the results of our present meta-analysis revealed that lncRNAs may be useful prognostic markers for lung carcinoma and may also have value as biomarkers for TNM stage, lymph node metastasis and distant metastasis.

MHC class II expression in lung cancer.

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He, Yayi; Rozeboom, Leslie; Rivard, Christopher J; Ellison, Kim; Dziadziuszko, Rafal; Yu, Hui; Zhou, Caicun; Hirsch, Fred R

2017-10-01

Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). Seven (12.7%) NSCLC cell lines were positive for MHC Class II. No SCLC cell lines were found to be MHC Class II positive. We assessed 139 lung cancer samples available in the Hirsch Lab for MHC Class II. There was no positive MHC Class II staining on SCLC tumor cells. MHC Class II expression on TILs in SCLC was significantly lower than that on TILs in NSCLC (P＜0.001). MHC Class II was also assessed in an additional 139 NSCLC tumor tissues from Medical University of Gdansk, Poland. Patients with positive staining of MHC Class II on TILs had longer regression-free survival (RFS) and overall survival (OS) than those whose TILs were MHC Class II negative (2.980 years, 95% CI 1.628-4.332 vs. 1.050 years, 95% CI 0.556-1.554, P=0.028) (3.230 years, 95% CI 2.617-3.843 vs. 1.390 years, 95% CI 0.629-2.151, P=0.014). MHC Class II was expressed both in NSCLC cell lines and tissues. However, MHC Class II was not detected in SCLC cell lines or tissue tumor cells. MHC Class II expression was lower on SCLC TILs than on NSCLC TILs. Loss of expression of MHC Class II on SCLC tumor cells and reduced expression on SCLC TILs may be a means of escaping anti-cancer immunity. Higher MHC Class II expression on TILs was correlated with better prognosis in patients with NSCLC. Copyright © 2017. Published by Elsevier B.V.

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.

Mutation and Expression of the DCC Gene in Human Lung Cancer

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Takashi Kohno

2000-07-01

Full Text Available Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs and 32 non-small cell lung carcinomas (NSCLCs, to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24% of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50% than in NSCLCs (4/32, 13% (P = .01, Fisher's exact test. Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE feature.

Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

LENUS (Irish Health Repository)

Canney, A

2012-02-01

Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

Nimesulide has a role of radio-sensitizer against lung carcinoma A549 cells

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Won, Joo Yoon; Park, Jong Kuk; Hong, Sung Hee

2006-01-01

Cyclooxygenases (COX) are key enzymes in the prostaglandin synthesis. There are two isoforms of the COX enzyme, COX-1 and COX-2. COX-2 expression is associated with carcinogenesis in variety of cancers and to render cells resistant to apoptotic stimuli. Increased expression of COX-2 is shown in non-small cell lung cancer (NSCLC), specifically in adenocarcinomas. Radiotherapy has been the important treatment for NSCLC. In recent studies, newer molecules that target specific pathophysiology or molecular pathways have been tested for the radiation sensitizers. COX-2 inhibitors are shown to enhanced radioresponse of cultured human cancer cell lines and immunodeficient mice. However, little is known about the molecular and biochemical mechanisms how NSAIDs enhance radioresponse of tumor cells. Nimesulide (methanesulfonamide, N-(4-nitro-2- phenoxyphenyl)), selective COX-2 inhibitors, is a drug with anti-inflammatory, anti-pyretic and analgesic properties. Nimesulide has the specific affinity to inhibit the inducible form of cyclooxygenase (COX-2) rather than the constitutive form (COX-1), and is well tolerated by adult, elderly and pediatric patients. Nimesulide was found also to have a chemopreventive activity against colon, urinary bladder, breast, tongue, and liver carcinogenesis. In this study, we examined whether nimesulide can increase radiation induced cell death and its mechanism in NSCLC cells A549

Anti-tumor effect of bisphosphonate (YM529 on non-small cell lung cancer cell lines

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Date Hiroshi

2007-01-01

Full Text Available Abstract Background YM529 is a newly developed nitrogen-containing bisphosphonate (BP classified as a third-generation BP that shows a 100-fold greater potency against bone resorption than pamidronate, a second-generation BP. This agent is, therefore expected to be extremely useful clinically for the treatment of osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation BPs have also been shown to exert anti-tumor effects against various types of cancer cells both in vitro or/and in vivo. In this study, we investigate the anti-tumor effect of YM529 on non-small cell lung cancer (NSCLC. Methods Direct anti-tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI-H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous cell carcinoma: NCI-H157 were measured by MTS assay and calculated inhibition concentration 50 % (IC50 values. YM529 induced apoptosis of NCI-H1819 was examined by DNA fragmentation of 2 % agarose gel electrophoresis and flowcytometric analysis (sub-G1 method. We examined where YM529 given effect to apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by western blotting analysis. Results We found that there was direct anti-tumor effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50 values were 2.1 to 7.9 μM and YM529 induced apoptosis and G1 arrest cell cycle with dose-dependent manner and YM529 caused down regulation of phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819. Conclusion Our study demonstrate that YM529 showed direct anti-tumor effect on NSCLC cell lines in vitro, which supports the possibility that third-generation BPs including YM529 can be one of therapeutic options for NSCLC.

A Meta-Analysis of Platinum Plus Gemcitabine or Vinorelbine for Advanced Non-small Cell Lung Cancer

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Guanghui GAO

2009-01-01

Full Text Available Background and objective Platinum plus the third-generation agent doublet chemotherapy is the standard regimens and first line chemotherapy for advanced non-small cell lung cancer (NSCLC. The aim of this study is to determine the benefits and harms of platinum plus gemcitabine or vinorelbine for advanced NSCLC. Methods Thedatabases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words "non small cell lung cancer" or "Carcinoma, Non Small Cell Lung" so as to search the studies about the randomized controlled clinical trials (RCT that had compared the gemcitabine plus platinum versus vinorelbine plus platinum for advanced NSCLC. A meta-analysis was conducted. Results Nine randomized controlled trials, with total 2 186 patients,were included. The overall response rate and one-year survival rate of the gemcitabine group were not significantly different from that of vinorelbine regimen (RR=0.91, 95%CI: 0.81-1.03, P =0.15; RR=1.06, 95%CI: 0.96-1.18, P =0.27, respectively. The incidence rate of grade 3-4 netropenia, constipation, phlebitis and grade 1-4 neuropathy were higher in vinorelbine group, just like higher incidence rate of grade 3-4 thrombocytopenia in the gemcitabine group. Conclusion The curative effects of the gemcitabine or vinorelbine plus platinum regimens are similar. The choice of gemcitabine or vinorelbine depends on the toxicity of the drugs and patients' tolerance.

Detection and Analysis of EGFR and KRAS Mutations 
in the Patients with Lung Squamous Cell Carcinomas

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Hui ZHANG

2015-10-01

Full Text Available Background and objective Activating mutations in epidermal growth factor receptor (EGFR and KRAS are important markers in non-small cell lung cancer. However, EGFR and KRAS gene mutations in lung squamous cell carcinoma are rarely reported. The aim of this study was to analyze EGFR and KRAS gene mutation rate and their relationship with clinical features in patients with lung squamous cell carcinomas. Methods A total of 139 patients undergoing treatment for naïve lung squamous cell carcinomas with tumor tissue samples available for testing were recruited. EGFR and KRAS mutation statuses of the tumor samples were detected using a mutant enriched liquid chip. Results Of the 139 cases of lung squamous cell carcinoma, EGFR mutations were detected in 25 cases (18%, KRAS mutations were detected in 7 cases (5%, and the presence of both EGFR and KRAS mutations was detected in 1 case (0.7%. EGFR mutations occurred more often in females than in males (33.3% vs 16.5% and in patients that never smoked than in those who smoke (29.6% vs 16.1%. However, the difference did not reach statistical significance (P>0.05. No significant differences were observed in age, stage, and different biopsy type. KRAS mutations occurred more often in males than in females (5.5% vs 0%, but the difference did not reach statistical significance (P>0.05. No significant differences were observed in age, stage, different biopsy type, and smoking status (P>0.05. Conclusion EGFR and KRAS mutations were low in lung squamous cell carcinomas, and had no significant correlation with clinical features. Before using tyrosine kinase inhibitor targeted therapy, EGFR and KRAS mutations should be detected in patients with lung squamous cell carcinomas.

Role of Radiotherapy in Metastatic Non-small Cell Lung Cancer (NSCLC

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Sergio L. Faria

2014-10-01

Full Text Available Radiotherapy has had important role in the palliation of NSCLC. Randomized trials tend to suggest that, in general, short regimens give similar palliation and toxicity compared to longer regimens. The benefit of combining chemotherapy to radiosensitize the palliative radiation treatment is an open question, but so far it has not been proved to be very useful in NSCLC. The addition of molecular targeted drugs to radiotherapy outside of approved regimens or clinical trials warrants careful consideration for every single case and probably should not be used as a routine management.Stereotactic radiosurgery (SRS and stereotactic body radiation therapy (SBRT are modern techniques being used each time more frequently in the treatment of single or oligometastases. In general, they offer good tumour control with little toxicity (with a more expensive cost compared to the traditionally fractionated radiotherapy regimens.

Anti-CEA monoclonal antibody in the diagnosis of colorectal, lung and ovarian carcinoma

International Nuclear Information System (INIS)

Jiang, N.; Lu, B.; Lu, X.; Sha, X.; Yue, D.

2000-01-01

This study evaluated the diagnostic value of radioimmnoimaging (RII) with 99 Tc labeled monoclonal antibody C50, raised originally against carcinoembryonic antigen (anti-CEA) in various tumors. 152 pathologically confirmed patients with a tumor were imaged prior to surgery with an anti-CEA monoclonal antibody labeled with 99 Tc. There were 115 patients with ovarian carcinoma, 26 patients with colorectal carcinoma and 11 patients with lung carcinoma. Images were acquired at 3-6 h post injection and were analyzed by the double blind method. Images of patients with ovarian cancer were compared with B-ultrasound images. Immunohistochemical staining was performed on all cases of colorectal cancer. All RII images demonstrated excellent contrast, clear lesions, and no serious toxic or other side reactions occurred. Transient chills and fever were observed in 3 cases. This study showed a sensitivity=88.2%, specificity=83.2%, and an accuracy=4.0%. The smallest lesion size detected was 2 x 2 cm. The total combined lesion detection rate for primary, metastatic, and recurrence lesions was 84.4%. We conclude that 99 Tc labeled anti-CEA MoAb C50 can be used in the diagnosis of colorectal carcinoma, ovarian carcinoma, and lung carcinoma

Radiographic findings of oat cell carcinoma of the lung

International Nuclear Information System (INIS)

Park, Y. H.; Yoon, Y.; Kim, S. Y.

1984-01-01

Growth of oat cell carcinoma tends to be invasive and extends rapidly through the bronchial lymphatics to the hilus and mediastinum, where bulky mass of tumor develop. Authors have analysed roentgenologic manifestations of 22 cases of histologically proven oat cell carcinoma of the lung seen during the period of 3 years from Jan, 1980 to May. 1983. The results 18 males and 4 females. Incidence was the most common in 7th decade as 45%. 2. Chief complaints are cough, sputum and dyspnea. Metastatic symptoms are hoarseness, SVC syndrome and back pain. 3. The radiographic findings of oat cell carcinoma were as follows. 1) hilar and perihilar mass 73% 2) Mediastinal mass 64% 3) Bronchial obstruction sign 55% 4) Peripheral mass 18% 5) Pleural effusion 18%

Preparation of 99Tcm-CLP imaging probe of lung carcinoma

International Nuclear Information System (INIS)

Qiang Yonggang; Liao Yonghua

2004-01-01

The process of preparing an imaging micro-probe 99 Tc m -CLP from bovine nose cartilage is described in detail. Both labeled rate and radiochemical purity of 99 Tc m -CLP are greater than 90%, and KA is 1.12 x 10 9 L/mol in vitro. After the Balb/c nu/nu mice with lung cancer were intravenously injected by the 99 Tc m -CLP, the radioactivity was found to be well concentrated at the lung-cancer region, which suggests that the 99 Tc m -CLP micro-probe can be used in imaging study of lung carcinoma. (authors)

Feasibility of Using Real-time Cine-MRI for Treating Moving & Deforming Tumors

Science.gov (United States)

2012-12-05

Pancreatic Cancer; Liver Cancer; Lung Cancer; Lung Cancer Non-Small Cell Cancer (NSCLC); Lung Cancer Small Cell Lung Cancer (SCLC); Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Hepatobiliary Cancers Hepatocellular Carcinoma (Hepatoma); Hepatobiliary Cancers Gallbladder; Hepatobiliary Cancers Bile Duct

Prostacyclin synthase expression and epigenetic regulation in nonsmall cell lung cancer.

LENUS (Irish Health Repository)

Cathcart, Mary-Clare

2012-02-01

BACKGROUND: Prostacyclin synthase (PGIS) metabolizes prostaglandin H(2), into prostacyclin. This study aimed to determine the expression profile of PGIS in nonsmall cell lung cancer (NSCLC) and examine potential mechanisms involved in PGIS regulation. METHODS: PGIS expression was examined in human NSCLC and matched controls by reverse transcriptase polymerase chain reaction (RT-PCR), Western analysis, and immunohistochemistry. A 204-patient NSCLC tissue microarray was stained for PGIS and cyclooxygenase 2 (COX2) expression. Staining intensity was correlated with clinical parameters. Epigenetic mechanisms underpinning PGIS promoter expression were examined using RT-PCR, methylation-specific PCR, and chromatin immunoprecipitation analysis. RESULTS: PGIS expression was reduced\\/absent in human NSCLC protein samples (P < .0001), but not mRNA relative to matched controls. PGIS tissue expression was higher in squamous cell carcinoma (P = .004) and in male patients (P < .05). No significant correlation of PGIS or COX2 expression with overall patient survival was observed, although COX2 was prognostic for short-term (2-year) survival (P < .001). PGIS mRNA expression was regulated by DNA CpG methylation and histone acetylation in NSCLC cell lines, with chromatin remodeling taking place directly at the PGIS gene. PGIS mRNA expression was increased by both demethylation agents and histone deacetylase inhibitors. Protein levels were unaffected by demethylation agents, whereas PGIS protein stability was negatively affected by histone deacetylase inhibitors. CONCLUSIONS: PGIS protein expression is reduced in NSCLC, and does not correlate with overall patient survival. PGIS expression is regulated through epigenetic mechanisms. Differences in expression patterns between mRNA and protein levels suggest that PGIS expression and protein stability are regulated post-translationally. PGIS protein stability may have an important therapeutic role in NSCLC.

A Safety and Tolerability Study of INCAGN02385 in Select Advanced Malignancies

Science.gov (United States)

2018-05-15

Cervical Cancer; Microsatellite Instability (MSI)-High Endometrial Cancer; Gastric Cancer (Including Stomach and Gastroesophageal Junction [GEJ]); Esophageal Cancer; Hepatocellular Carcinoma; Melanoma (Uveal Melanoma Excluded); Merkel Cell Carcinoma; Mesothelioma; MSI-high Colorectal Cancer; Non-small Cell Lung Cancer (NSCLC); Ovarian Cancer; Squamous Cell Carcinoma of the Head and Neck (SCCHN); Small Cell Lung Cancer (SCLC); Renal Cell Carcinoma (RCC); Triple-negative Breast Cancer; Urothelial Carcinoma; Diffuse Large B-cell Lymphoma

Squamous cell lung carcinoma presenting as melena: a case report and review of the literature

Directory of Open Access Journals (Sweden)

Ibrahim Azar

2017-10-01

Full Text Available Lung cancer has a predilection to widely metastasize to the liver, bone, brain and adrenal glands. Metastasis of primary lung tumors to the stomach is infrequent, with only sporadic cases reported. Most cases are asymptomatic and diagnosed post-mortem on autopsy. The incidence of symptomatic gastrointestinal metastases is extremely rare. Herein, we describe a case of gastric metastasis by squamous cell lung carcinoma, presenting as melena and diagnosed by esophagogastroduodenoscopy. To the best of our knowledge, only twenty other cases in the English literature have reported symptomatic gastric metastasis of lung cancer diagnosed by endoscopic biopsy. A brief review of the literature shows gastric metastasis of lung cancer to have a predilection to occur most frequently in male smokers with the most common type of tumor likely to be squamous cell carcinoma.

Surgical excision of lung metastases from squamous carcinoma of ...

African Journals Online (AJOL)

These 2 case reports serveto emphasizetwo important points concerning carcinoma of the cervix: (i) blood-borne metastases are now frequently encountered in this disease; and (ii). in selected cases surgical excision of a secondary deposit in the lung is the treatment of choice and may even result -in cure.

Loss of expression of BAP1 is very rare in non-small cell lung carcinoma.

Science.gov (United States)

Andrici, Juliana; Parkhill, Thomas R; Jung, Jason; Wardell, Kathryn L; Verdonk, Brandon; Singh, Arjun; Sioson, Loretta; Clarkson, Adele; Watson, Nicole; Sheen, Amy; Farzin, Mahtab; Toon, Christopher W; Gill, Anthony J

2016-06-01

Germline mutations of the BAP1 gene have been implicated in a cancer predisposition syndrome which includes mesothelioma, uveal melanoma, cutaneous melanocytic lesions, renal cell carcinoma, and possibly other malignancies. Double hit inactivation of BAP1 with subsequent loss of expression of the BAP1 protein also occurs in approximately 50% of mesotheliomas. The link between BAP1 mutation and lung cancer is yet to be fully explored. We sought to assess BAP1 expression in a large cohort of lung cancers undergoing surgery with curative intent. We searched the Anatomical Pathology database of our institution for lung cancer patients undergoing surgery with curative intent between 2000 and 2010. Immunohistochemistry for BAP1 was then performed in tissue microarray format. Our cohort included 257 lung cancer patients, of which 155 (60%) were adenocarcinomas and 72 (28%) were squamous cell carcinomas, with no other subtype comprising more than 3%. BAP1 loss of expression was found in only one lung cancer. We conclude that BAP1 mutation occurs very infrequently (0.4%) in non-small cell lung cancer. Given that the pathological differential diagnosis between lung carcinoma and mesothelioma may sometimes be difficult, this finding increases the specificity of loss of expression for BAP1 for the diagnosis of mesothelioma. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Aquamous cell carcinomas of the lung which presented as numerous polypoid nodules in the tracheobronchial tree: A case report

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Lee, Hyun Gyu; Choi, Yo Won; Yoon, Hyun Jung; Paik, Seung Sam [Hanyang University Hospital, Hanyang University College of Medicine, Seoul (Korea, Republic of)

2017-03-15

We report a case of squamous cell carcinomas of the lung, which presented as numerous polypoid nodules in the tracheobronchial tree. They occurred at two years and 7 months after resection of squamous cell carcinoma, which presented as a lung nodule in the left lower lobe, and at 7 months after resection of tracheal squamous cell carcinoma.

Aquamous cell carcinomas of the lung which presented as numerous polypoid nodules in the tracheobronchial tree: A case report

International Nuclear Information System (INIS)

Lee, Hyun Gyu; Choi, Yo Won; Yoon, Hyun Jung; Paik, Seung Sam

2017-01-01

We report a case of squamous cell carcinomas of the lung, which presented as numerous polypoid nodules in the tracheobronchial tree. They occurred at two years and 7 months after resection of squamous cell carcinoma, which presented as a lung nodule in the left lower lobe, and at 7 months after resection of tracheal squamous cell carcinoma

An active treatment of lung adenocarcinoma cancer with brain metastases: icotinib

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Zhang Y

2015-06-01

Full Text Available Ying Zhang, Huaping Tang, Jun Li, Meng Li Department of Respiration Medicine, Municipal Hospital, Qingdao, People’s Republic of China Abstract: Lung cancer has the highest mortality rate of all cancers world­wide. A total of 70%–75% of all lung cancers are non-small cell lung cancer (NSCLC with two-thirds presenting with locally advanced or metastatic disease at diagnosis. Brain metastasis is one of the most common problems in the management of NSCLC, worsening the prognosis and quality of life of NSCLC patients. The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs gefitinib and erlotinib have been tested in patients with NSCLC and brain metastasis. Icotinib is a new type of oral EGFR-TKI. In this report, we describe a patient with lung adenocarcinoma cancer with brain metastases who received icotinib treatment and kept satisfactory health-related quality of life for 1 year. Keywords: EGFR, non-small cell lung cancer, tyrosine kinase inhibitor

Texture analysis of advanced non-small cell lung cancer (NSCLC) on contrast-enhanced computed tomography: prediction of the response to the first-line chemotherapy

International Nuclear Information System (INIS)

Farina, Davide; Morassi, Mauro; Maroldi, Roberto; Roca, Elisa; Tassi, Gianfranco; Cavalleri, Giuseppe

2013-01-01

To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n = 31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n = 22). GL*U did not correlate with overall survival. TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. (orig.)

High frequency of p 16 promoter methylation in non-small cell lung carcinomas from Chile

Directory of Open Access Journals (Sweden)

LEDA M GUZMAN

2007-01-01

Full Text Available The inactivation of tumour suppressor genes by aberrant methylation of promoter regions has been described as a frequent event in neoplasia development, including lung cancer. The p16 gene is a tumour suppressor gene involved in the regulation of cell cycle progression that has been reported to be inactivated by promoter methylation in lung carcinomas at variable frequencies around the world in a smoking habit dependent manner. The purpose of this study was to investigate the methylation status of the promoter region of the p16 gene in 74 non-small cell lung carcinomas from Chile. The frequency of p16 gene inactivation by promoter methylation was determined as 79.7% (59/74. When we considered histological type, we observed that p16 promoter methylation was significantly higher in squamous cell carcinomas (30/33, 91% compared with adenocarcinomas (21/30, 70% (p=0.029. In addition, no association between p16 promoter methylation and gender, age or smoking habit was found (p=0.202, 0.202 and 0.147 respectively. Our results suggest that p16 promoter hypermethylation is a very frequent event in non-small cell lung carcinomas from Chile and could be smoking habit-independent

CyberKnife with tumor tracking: An effective alternative to wedge resection for high-risk surgical patients with stage I non-small cell lung cancer (NSCLC

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Sean eCollins

2012-02-01

Full Text Available Published data suggests that wedge resection for stage I NSCLC results in improved overall survival compared to stereotactic body radiation therapy (SBRT. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV. Treatment plans were designed using hundreds of pencil beams. Doses delivered to the PTV ranged from 42-60 Gy in 3 fractions. The 30-Gy isodose contour extended at least 1cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3-month follow-up intervals. Forty patients (median age 76 with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm and a mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1 of 57% (range, 21 - 111% were treated. A mean dose of 50 Gy was delivered to the PTV over 3 to 13 days (median, 7 days. The 30-Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12 -72 months follow-up, the 3-year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91% and 75% , respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1 to 2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

Science.gov (United States)

In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to

Subcarinal lymph node in upper lobe non-small cell lung cancer patients: is selective lymph node dissection valid?

Science.gov (United States)

Aokage, Keiju; Yoshida, Junji; Ishii, Genichiro; Hishida, Tomoyuki; Nishimura, Mitsuyo; Nagai, Kanji

2010-11-01

Little is known about selective lymph node dissection in non-small cell lung cancer (NSCLC) patients. We sought to gain insight into subcarinal node involvement for its frequency and impact on outcome to evaluate whether it is valid to omit subcarinal lymph node dissection in upper lobe NSCLC patients. We reviewed node metastases distribution according to node region, tumor location, and histology among 1099 patients with upper lobe NSCLC. We paid special attention to subcarinal metastases patients without superior mediastinal node metastases, because their pathological stages would have been underdiagnosed if subcarinal node dissection had been omitted. We also assessed the outcome and the pattern of failure among subcarinal metastases patients. To identify subcarinal node involvement predictors, we analyzed 7 clinical factors. Subcarinal node metastases were found in 20 patients and were least frequent among squamous cell carcinoma patients (0.5%). Two of them were free from superior mediastinal metastases but died of the disease at 1 month and due to an unknown cause at 18 months, respectively. Seventeen of the 20 patients developed multi-site recurrence within 37 months. The 5-year survival rate of the 20 patients with subcarinal metastases was 9.0%, which was significantly lower than 32.0% of patients with only superior mediastinal metastases. Clinical diagnosis of node metastases was significantly predictive of subcarinal metastases. Subcarinal node metastases from upper lobe NSCLC were rare and predicted an extremely poor outcome. It appears valid to omit subcarinal node dissection in upper lobe NSCLC patients, especially in clinical N0 squamous cell carcinoma patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

'Dancing eyes, dancing feet syndrome' in small cell lung carcinoma.

Science.gov (United States)

Sharma, Chandramohan; Acharya, Mihir; Kumawat, Bansi Lal; Kochar, Abhishek

2014-04-23

A 60-year-old man presented with a 25-day history of acute onset instability of gait, tremulousness of limbs and involuntary eye movements. Examination revealed presence of opsoclonus, myoclonus and ataxia, without any loss of motor power in the limbs. Prompt investigations were directed towards identifying an underlying malignancy which is often associated with this type of clinical scenario. CT of the brain was normal and cerebrospinal fluid examination showed lymphocytic pleocytosis. A cavitatory lesion was found in the right lung base on the high-resolution CT of the chest and histopathological examination of this lung mass showed small cell lung carcinoma. The patient was managed symptomatically with levetiracetam and baclofen and referred to oncology department for resection of the lung mass.

Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

International Nuclear Information System (INIS)

Scholten, Ernst T.; Horeweg, Nanda; Koning, Harry J. de; Vliegenthart, Rozemarijn; Oudkerk, Matthijs; Mali, Willem P.T.M.; Jong, Pim A. de

2015-01-01

To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

Computed tomographic characteristics of interval and post screen carcinomas in lung cancer screening

Energy Technology Data Exchange (ETDEWEB)

Scholten, Ernst T. [University Medical Centre, Department of Radiology, Utrecht (Netherlands); Kennemer Gasthuis, Department of Radiology, Haarlem (Netherlands); Horeweg, Nanda [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Erasmus University Medical Centre, Department of Pulmonary Medicine, Rotterdam (Netherlands); Koning, Harry J. de [Erasmus University Medical Centre, Department of Public Health, Rotterdam (Netherlands); Vliegenthart, Rozemarijn [University of Groningen, University Medical Centre Groningen, Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Oudkerk, Matthijs [University of Groningen, University Medical Centre Groningen, Center for Medical Imaging-North East Netherlands, Groningen (Netherlands); Mali, Willem P.T.M.; Jong, Pim A. de [University Medical Centre, Department of Radiology, Utrecht (Netherlands)

2015-01-15

To analyse computed tomography (CT) findings of interval and post-screen carcinomas in lung cancer screening. Consecutive interval and post-screen carcinomas from the Dutch-Belgium lung cancer screening trial were included. The prior screening and the diagnostic chest CT were reviewed by two experienced radiologists in consensus with knowledge of the tumour location on the diagnostic CT. Sixty-one participants (53 men) were diagnosed with an interval or post-screen carcinoma. Twenty-two (36 %) were in retrospect visible on the prior screening CT. Detection error occurred in 20 cancers and interpretation error in two cancers. Errors involved intrabronchial tumour (n = 5), bulla with wall thickening (n = 5), lymphadenopathy (n = 3), pleural effusion (n = 1) and intraparenchymal solid nodules (n = 8). These were missed because of a broad pleural attachment (n = 4), extensive reticulation surrounding a nodule (n = 1) and extensive scarring (n = 1). No definite explanation other than human error was found in two cases. None of the interval or post-screen carcinomas involved a subsolid nodule. Interval or post-screen carcinomas that were visible in retrospect were mostly due to detection errors of solid nodules, bulla wall thickening or endobronchial lesions. Interval or post-screen carcinomas without explanation other than human errors are rare. (orig.)

Metastatic non-small-cell lung cancer: consensus on pathology and molecular tests, first-line, second-line, and third-line therapy: 1st ESMO Consensus Conference in Lung Cancer; Lugano 2010

DEFF Research Database (Denmark)

Felip, E; Gridelli, C; Baas, P

2011-01-01

the conference, the expert panel prepared clinically relevant questions concerning five areas: early and locally advanced non-small-cell lung cancer (NSCLC), first-line metastatic NSCLC, second-/third-line NSCLC, NSCLC pathology and molecular testing, and small-cell lung cancer to be addressed through discussion......The 1st ESMO Consensus Conference on lung cancer was held in Lugano, Switzerland on 21 and 22 May 2010 with the participation of a multidisciplinary panel of leading professionals in pathology and molecular diagnostics, medical oncology, surgical oncology and radiation oncology. Before...... at the Consensus Conference. All relevant scientific literature for each question was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The consensus agreement on three of these areas: NSCLC pathology and molecular testing, the treatment of first-line...

Microarray data re-annotation reveals specific lncRNAs and their potential functions in non-small cell lung cancer subtypes.

Science.gov (United States)

Zhou, Dongbo; Xie, Mingxuan; He, Baimei; Gao, Ying; Yu, Qiao; He, Bixiu; Chen, Qiong

2017-10-01

Non‑small‑cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide. The most common subtypes of NSCLC are adenocarcinoma (AC) and squamous cell carcinoma (SCC). However, the pathophysiological mechanisms contributing to AC and SCC are still largely unknown, especially the roles of long non‑coding RNAs (lncRNAs). The present study identified differentially expressed lncRNAs between lung AC and SCC by re‑annotation of NSCLC microarray data analysis profiling. The potential functions of lncRNAs were predicted by using coding‑non‑coding gene co‑expressing network. Reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) was used to investigate lncRNA expression levels in AC cell lines (A549 and L78), SCC cell lines (H226 and H520) and normal cells (NL‑20). Western blotting analysis was used to investigate the protein expression levels in these cell lines. A total of 65 lncRNAs were differentially expressed between AC and SCC including 28 lncRNAs that were downregulated in SCC subtypes compared with those in AC ones, and 37 upregulated lncRNAs in SCC subtypes compared with AC subtypes. Three lncRNAs, sex determining region Y‑box 2 overlapping transcript (SOX2‑OT), NCBP2 antisense RNA 2 (NCBP2‑AS2) and ubiquitin like with PHD and ring finger domains 1 (UHRF1), were predicted to be associated with lung cancer; RT‑qPCR confirmed that SOX2‑OT and NCBP2‑AS2 were associated with lung cancer. Finally, western blot assays demonstrated that there was no difference in β‑catenin and glycogen synthase kinase 3β (GSK‑3β) expression in cancer cells compared with NL‑20, but increased phosphorylated (p‑)β‑catenin and p‑GSK‑3β was detected in lung cancer cell lines compared with NL‑20, particularly in A549 cells. Although these results require further experimental verification, the analysis of lncRNA signatures between AC and SCC has provided insights into the regulatory mechanism of NSCLC development.

[Expression and clinical significance of Pokemon in non-small cell lung cancer].

Science.gov (United States)

Zhao, Zhihong; Wang, Shengfa; Zhang, Tiewa

2007-12-20

Proto-oncogene Pokemon is the special transcription inhibitor of ARF,which can regulate cell growth and differentiation by ARF-P53 path.It may be the important monitoring target of tumor because of being upstream region of many tumor suppressor genes and proto-oncogenes.The aim of this study is to explore the clinical significance of Pokemon gene in non-small cell lung cancer(NSCLC). Immunohistochemistry was applied to detect the expression of Pokemon protein in 92 cases of NSCLC and 20 cases of paracancerous lung tissues.Correlation between abnormal expression of Pokemon with pathologic characteristics and prognosis of NSCLC was analyzed. Pokemon was not expressed in paracancerous lung tissues and was found in 66 of 92(71.7%) cases of lung cancer tissues.Expression of Pokemon was closely related to TNM stages(P=0.011).Survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression(P=0.0015).Pokemon expression was demonstrated as independent prognostic factor of NSCLC. Pokemon is expressed in NSCLC and it may be identified as a new diagnostic marker.High expression of Pokemon may indicate poor prognosis of patients with NSCLC.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

Seki, Yasuhiro; Yoshida, Yukihiro; Ishimine, Hisako; Shinozaki-Ushiku, Aya; Ito, Yoshimasa; Sumitomo, Kenya; Nakajima, Jun; Fukayama, Masashi; Michiue, Tatsuo; Asashima, Makoto; Kurisaki, Akira

2014-01-01

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

Retinoides (RARβ y CRBP1 en carcinoma de pulmón a células no pequeñas Retinoid expression (RARβ and CRBP1 in non-small-cell lung carcinoma

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Laura V. Mauro

2008-06-01

Full Text Available Aunque los pacientes con cáncer de pulmón a células no pequeñas en estadios tempranos (NSCLC tienen buen pronóstico, el 20-30% recae, siendo relevante la identificación de biomarcadores pronósticos. Los retinoides regulan crecimiento y diferenciación, y pueden antagonizar la progresión tumoral. Su efecto depende del transporte citosólico mediado por moléculas como CRBP1, y de la unión a receptores específicos (RARβ. Alteraciones en esta vía se asociaron con cáncer. Nuestro objetivo fue estudiar la expresión, mediante inmunohistoquímica, de RARβ y CRBP1 en el tejido tumoral de 49 pacientes NSCLC Estadio I/II, obtenido durante la cirugía. La supervivencia se analizó mediante los test Log Rank y multivariado de Cox. El 44.9% de los tumores fueron positivos para RARβ con expresión a nivel citoplasmático, mientras que el 34.7% lo expresó a nivel nuclear. La tinción para CRBP1 se observó en el 61.2% de los tumores. No se encontró asociación entre la expresión de ambas moléculas y las características clinicopatológicas (sexo, tamaño tumoral, nódulos línfáticos comprometidos, histopatología y p53. Tampoco se encontró asociación con el hábito de fu-mar. La presencia de células tumorales en el lavado pleural se asoció significativamente con la expresión de CRBP1. Por otro lado, se demostró asociación entre la expresión elevada de RARβ citoplasmático y menor supervivencia global (LR 4.17, p=0.0412. El análisis multivariado no mostró asociación con otras variables de pronóstico en NSCLC. En conclusión, en este grupo de pacientes NSCLC Estadio I/II, RARβ pareciera predecir la supervivencia global en forma independiente.Although early-stage non-small-cell lung carcinoma (NSCLC patients have a relative by favorable prognosis, the risk of a bad outcome remains substantial. Identification of reliable prognostic markers for disease recurrence and death has meaningful clinical application. Retinoids are

Discovery of 2',4'-dimethoxychalcone as a Hsp90 inhibitor and its effect on iressa-resistant non-small cell lung cancer (NSCLC).

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Seo, Young Ho

2015-10-01

Heat shock protein 90 (Hsp90) is a ATP dependent molecular chaperone and has emerged as an attractive therapeutic target in the war on cancer due to its role in regulating maturation and stabilization of numerous oncogenic proteins. In this study, we discovered that 2',4'-dimethoxychalcone (1b) disrupted Hsp90 chaperoning function and inhibited the growth of iressa-resistant non-small cell lung cancer (NSCLC, H1975). The result suggested that 2',4'-dimethoxychalcone (1b) could serve as a potential therapeutic lead to circumvent the drug resistance acquired by EGFR mutation and Met amplification.

Complete resection of the primary lesion improves survival of certain patients with stage IV non-small cell lung cancer.

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Chikaishi, Yasuhiro; Shinohara, Shinji; Kuwata, Taiji; Takenaka, Masaru; Oka, Soichi; Hirai, Ayako; Yoneda, Kazue; Kuroda, Kouji; Imanishi, Naoko; Ichiki, Yoshinobu; Tanaka, Fumihiro

2017-12-01

The standard treatment for patients with stage IV non-small cell lung cancer (NSCLC) is systemic chemotherapy. However, certain patients, such as those with oligometastasis or M1a disease undergo resection of the primary lesion. We conducted a retrospective review of the records of 1,471 consecutive patients with NSCLC who underwent resection of the primary lesion for between June 2005 and May 2016. The present study included 38 patients with stage IV NSCLC who underwent complete resection of the primary lesion as first-line treatment. The median follow-up duration for the 38 patients (27 men) was 17.7 months (range, 1-82.3 months). The T factors were T1/T2/T3/T4 in 4/16/12/6 patients, respectively. The N factors were N0/N1/N2/N3 in 16/8/12/2 patients, respectively. The M factors were M1a/M1b/M1c in 19/13/6 patients, respectively. Of the 19 M1a patients, 11 were classified as cM0. We introduced the novel classification M-better/M-worse. M-better includes cM0 patients and M1b and M1c patients in whom all lesions have been locally controlled. M-worse includes cM1a patients and M1b and M1c patients in whom lesions cannot be locally controlled. The new M-better/M-worse statuses were 24/14 patients, respectively. The histology of NSCLC was adenocarcinoma/squamous cell carcinoma/others in 30/5/3 patients, respectively. The 5-year overall survival rate was 29%, and the median survival time was 725 days. Squamous cell carcinoma and M-worse were significant factors predicting poor outcomes (P=0.0017, P=0.0007, respectively). Even for stage IV NSCLC patients, resection of the primary lesion may be beneficial, especially for those with M-better status and those not diagnosed with squamous-cell carcinoma (SCC).

Contributions of cytology examination and methods in lung cancer diagnostic

International Nuclear Information System (INIS)

Jerse, M.; Tercelj, M.

2006-01-01

Background. Lung cancer (LC) is still the leading cause of cancer death according to published data worldwide and confirmed also by the data obtained from the central Cancer Registry of Slovenia. Early detection of LC has an important impact on the long-term survival rate of the patients. In spite of a great advance in imaging technology for a better visualization and early detection of the neoplasms and a variety of screening tests, only cytopathology examination finally define the neoplastic lesion. Methods. To evaluate the contribution of cytology examination in the diagnosis of LC we studied the cytology diagnoses, comparing them with histology reports in patients, who underwent the diagnostic procedure under suspicion of the LC during last 2 years. Results. Of a total 772 patients, in 241 patients cancer was microscopically confirmed. The most frequent diagnoses were adenocarcinoma (36.9%), squamous cell carcinoma (26.6%), and small cell carcinoma (SCLC) (12.9%). There were 22% of neoplasms classified as non-small cell carcinomas (NSCLC). From the clinician point of view considering the therapy it is very important to distinguish NSCLC from SCLC. And in our study the cytology-histology correlation between these two major types of carcinoma was almost 100%. Based only on cytology, 68 (28.2%) patients received microscopic diagnosis of malignoma, and the specimens for this group of patients were obtained mostly from transbronchial or transthoracic fine needle aspiration biopsies. Conclusions. Cytology is of great diagnostic value, a reliable and relatively non-invasive method for patients. Cytology specimens should be taken in cases where it is not possible to obtain samples for histology. (author)

NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma

OpenAIRE

Rocha, CM; Barros, AS; Goodfellow, BJ; Carreira, IM; Gomes, AA; Sousa, V; Bernardo, J; Carvalho, L; Gil, AM; Duarte, IF

2015-01-01

Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissue...

Fully automated VMAT treatment planning for advanced-stage NSCLC patients

International Nuclear Information System (INIS)

Della Gala, Giuseppe; Dirkx, Maarten L.P.; Hoekstra, Nienke; Fransen, Dennie; Pol, Marjan van de; Heijmen, Ben J.M.; Lanconelli, Nico; Petit, Steven F.

2017-01-01

To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored. Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V_9_5_% increased by 1.1% ± 1.1%), higher dose conformity (R_5_0 reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p [de

Partial response to carboplatin in an RRx-001 pretreated patient with EGFR-inhibitor-resistance and T790M-negative NSCLC.

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Carter, Corey A; Oronsky, Bryan; Caroen, Scott; Scicinski, Jan; Cabrales, Pedro; Degesys, Aiste; Brzezniak, Christina

2016-01-01

Few therapeutic options are available for T790M-negative non-small cell lung cancer (NSCLC) after failure of primary epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy. This report presents the case of a 71-year-old Asian female never smoker with EGFR mutated T790M negative non squamous cell lung cancer (NSCLC) pre-treated with the experimental epi-immunotherapeutic agent, RRx-001, that re-responded to single agent carboplatin after failure of platinum doublets, TKIs, pemetrexed and nivolumab. The management of advanced EGFR mutation-positive NSCLC is briefly reviewed herein and the emerging paradigm of episensitization, which contradicts the long-standing and widely accepted tenet about the immutability of resistance and the futility of therapeutic rechallenge, is introduced as a strategy to avert treatment failure and thereby stave off deterioration and death.

Impact of tumor extent and location on treatment outcome in patients with stage III non-small cell lung cancer treated with radiation therapy

International Nuclear Information System (INIS)

Hayakawa, Kazushige; Mitsuhashi, Norio; Saito, Yoshihiro

1996-01-01

The results of treatment of 141 patients with stage III non-small cell lung cancer (NSCLC) who received definitive radiation therapy at Gunma University Hospital between 1976 and 1989 were retrospectively analyzed. Radiation was given with standard fractionation for a planned prophylactic dose of 40 Gy over 4 weeks and a definitive dose of 60 Gy over 6 weeks or more. The two- and five-year survival rates were 27% and 12% for stage IIIA, and 18% and 8% for stage IIIB, respectively (P=0.052). By univariate analysis, a primary tumor less than 5 cm in diameter was also an important predictor of survival (P=0.008). As for tumor location, the patients with primary tumors in the upper lobes or the superior segment of the lower lobes of the lung lived longer than those with primary tumors at any other site (P=0.032). Patients with epidermoid carcinoma had a higher survival rate at 5 years than those with other histologic types (14% vs 3%, P=0.074). Multivariate analysis showed that among tumor characteristics, the site of the primary tumor, the pattern of tumor spread and N stage were significantly associated with overall survival. Among the patients with stage III NSCLC, those with stage IIIA epidermoid carcinoma in the upper lobe or the superior segment of the lower lobe of the lung were considered to be the most favorable candidates for definitive radiation therapy. (author)

Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2–q29 in squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Kang, Ji Un; Koo, Sun Hoe; Kwon, Kye Chul; Park, Jong Woo; Kim, Jin Man

2009-01-01

The underlying genetic alterations for squamous cell carcinoma (SCC) and adenocarcinoma (AC) carcinogenesis are largely unknown. High-resolution array- CGH was performed to identify the differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2–q29, 12p13.2–p13.33, and 19p13.3, as well as losses at 3p26.2–p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2–q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at the 3q26.2–q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Many significant genes at the 3q26.2–q29 regions previously linked to a specific histology, such as EVI1,MDS1, PIK3CA and TP73L, were observed in SCC (P < 0.05). In addition, we identified the following possible target genes (> 30% of patients) at 3q26.2–q29: LOC389174 (3q26.2),KCNMB3 (3q26.32),EPHB3 (3q27.1), MASP1 and SST (3q27.3), LPP and FGF12 (3q28), and OPA1,KIAA022,LOC220729, LOC440996,LOC440997, and LOC440998 (3q29), all of which were significantly targeted in SCC (P < 0.05). Among these same genes, high-level amplifications were detected for the gene, EPHB3, at 3q27.1, and MASP1 and SST, at 3q27.3 (18, 18, and 14%, respectively). Quantitative real time PCR demonstrated array CGH detected potential candidate genes that were over expressed in SCCs. Using whole-genome array CGH, we have successfully identified significant differences and unique information of chromosomal signatures prevalent between the SCC and AC subtypes of NSCLC. The newly identified candidate target genes may prove to be highly attractive candidate molecular markers for the classification of NSCLC histologic subtypes, and could potentially contribute to the

Smoking and Lung Cancer: A Geo-Regional Perspective.

Science.gov (United States)

Rahal, Zahraa; El Nemr, Shaza; Sinjab, Ansam; Chami, Hassan; Tfayli, Arafat; Kadara, Humam

2017-01-01

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) represents the most frequently diagnosed subtype of this morbid malignancy. NSCLC is causally linked to tobacco consumption with more than 500 million smokers worldwide at high risk for this fatal malignancy. We are currently lagging in our knowledge of the early molecular (e.g., genomic) effects of smoking in NSCLC pathogenesis that would constitute ideal markers for early detection. This limitation is further amplified when considering the variable etiologic factors in NSCLC pathogenesis among different regions around the globe. In this review, we present our current knowledge of genomic alterations arising during early stages of smoking-induced lung cancer initiation and progression, including discussing the premalignant airway field of injury induced by smoking. The review also underscores the wider spectra and higher age-adjusted rates of tobacco (e.g., water-pipe smoke) consumption, along with elevated environmental carcinogenic exposures and relatively poorer socioeconomic status, in low-middle income countries (LMICs), with Lebanon as an exemplar. This "cocktail" of carcinogenic exposures warrants the pressing need to understand the complex etiology of lung malignancies developing in LMICs such as Lebanon.

Smoking and Lung Cancer: A Geo-Regional Perspective

Directory of Open Access Journals (Sweden)

Zahraa Rahal

2017-09-01

Full Text Available Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC represents the most frequently diagnosed subtype of this morbid malignancy. NSCLC is causally linked to tobacco consumption with more than 500 million smokers worldwide at high risk for this fatal malignancy. We are currently lagging in our knowledge of the early molecular (e.g., genomic effects of smoking in NSCLC pathogenesis that would constitute ideal markers for early detection. This limitation is further amplified when considering the variable etiologic factors in NSCLC pathogenesis among different regions around the globe. In this review, we present our current knowledge of genomic alterations arising during early stages of smoking-induced lung cancer initiation and progression, including discussing the premalignant airway field of injury induced by smoking. The review also underscores the wider spectra and higher age-adjusted rates of tobacco (e.g., water-pipe smoke consumption, along with elevated environmental carcinogenic exposures and relatively poorer socioeconomic status, in low-middle income countries (LMICs, with Lebanon as an exemplar. This “cocktail” of carcinogenic exposures warrants the pressing need to understand the complex etiology of lung malignancies developing in LMICs such as Lebanon.

Chimeric Antigen Receptor-Modified T Cells Redirected to EphA2 for the Immunotherapy of Non-Small Cell Lung Cancer

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Ning Li

2018-02-01

Full Text Available Erythropoietin-producing hepatocellular carcinoma A2 (EphA2 is overexpressed in more than 90% of non-small cell lung cancer (NSCLC but not significantly in normal lung tissue. It is therefore an important tumor antigen target for chimeric antigen receptors (CAR-T-based therapy in NSCLC. Here, we developed a specific CAR targeted to EphA2, and the anti-tumor effects of this CAR were investigated. A second generation CAR with co-stimulatory receptor 4-1BB targeted to EphA2 was developed. The functionality of EphA2-specific T cells in vitro was tested with flow cytometry and real-time cell electronic sensing system assays. The effect in vivo was evaluated in xenograft SCID Beige mouse model of EphA2 positive NSCLC. These EphA2-specifc T cells can cause tumor cell lysis by producing the cytokines IFN-γ when cocultured with EphA2-positive targets, and the cytotoxicity effects was specific in vitro. In vivo, the tumor signals of mice treated with EphA2-specifc T cells presented the tendency of decrease, and was much lower than the mice treated with non-transduced T cells. The anti-tumor effects of this CAR-T technology in vivo and vitro had been confirmed. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive NSCLC.

Lectin enhancement of the lipofection efficiency in human lung carcinoma cells.

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Yanagihara, K; Cheng, P W

1999-10-18

Poor transfection efficiency of human lung carcinoma cells by lipofection begs further development of more efficient gene delivery strategies. The purpose of this study was to determine whether lectins can improve the lipofection efficiency in lung carcinoma cells. A549, Calu3, and H292 cells grown to 90% confluence were transfected for 18 h with a plasmid DNA containing a beta-galactosidase reporter gene (pCMVlacZ) using lipofectin plus a lectin as the vector. Ten different lectins, which exhibit a wide range of carbohydrate-binding specificities, were examined for their abilities to enhance the efficiency of lipofection. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (units/microg protein) and % blue cells following X-Gal stain. Lipofectin supplemented with Griffonia simplicifolia-I (GS-I) yields largest enhancement of the lipofection efficiency in A549 and Calu3 cells (5.3- and 28-fold, respectively). Maackia amurensis gives the largest enhancement (6.5-fold) of lipofection efficiency in H292 cells. The transfection efficiency correlates with the amounts of DNA delivered to the nucleus. Binding of FITC-labeled GS-I and the enhancement of the lipofection efficiency by GS-I were inhibited by alpha-methyl-D-galactopyranoside, indicating an alpha-galactoside-mediated gene transfer to lung carcinoma cells. We conclude that lectin-facilitated lipofection is an efficient gene delivery strategy. Employment of cell type-specific lectins may allow for efficient cell type-specific gene targeting.

Prognostic significance of blood coagulation tests in carcinoma of the lung and colon.

Science.gov (United States)

Wojtukiewicz, M Z; Zacharski, L R; Moritz, T E; Hur, K; Edwards, R L; Rickles, F R

1992-08-01

Blood coagulation test results were collected prospectively in patients with previously untreated, advanced lung or colon cancer who entered into a clinical trial. In patients with colon cancer, reduced survival was associated (in univariate analysis) with higher values obtained at entry to the study for fibrinogen, fibrin(ogen) split products, antiplasmin, and fibrinopeptide A and accelerated euglobulin lysis times. In patients with non-small cell lung cancer, reduced survival was associated (in univariate analysis) with higher fibrinogen and fibrin(ogen) split products, platelet counts and activated partial thromboplastin times. In patients with small cell carcinoma of the lung, only higher activated partial thromboplastin times were associated (in univariate analysis) with reduced survival in patients with disseminated disease. In multivariate analysis, higher activated partial thromboplastin times were a significant independent predictor of survival for patients with non-small cell lung cancer limited to one hemithorax and with disseminated small cell carcinoma of the lung. Fibrin(ogen) split product levels were an independent predictor of survival for patients with disseminated non-small cell lung cancer as were both the fibrinogen and fibrinopeptide A levels for patients with disseminated colon cancer. These results suggest that certain tests of blood coagulation may be indicative of prognosis in lung and colon cancer. The heterogeneity of these results suggests that the mechanism(s), intensity, and pathophysiological significance of coagulation activation in cancer may differ between tumour types.

Not traditional regimes of radiotherapeutic dose fractionation as modifier of radiotherapy for carcinoma of lungs

International Nuclear Information System (INIS)

Artemova, N.A.

2008-01-01

The efficiency of applying various of radiotherapeutic dose fractionation was analyzed. The results of the own studies performed at the Scientific and Research Institute of Oncology and Medical Radiology for elaborating not traditional regimes of radiotherapeutic dose fractionation (a dynamic fractionation applying enlarged regimes at the first stage and the classic ones at the second stage) were presented. Appliance of the modified radiotherapy for the epidermoid carcinoma of the lungs allowed to increase the objective response from 45,3+-3% to 80+-5% the tumor disappearing completely in 40+-6% of patients as compared with 10+-2%. Appliance of the intensive not traditional variant of the radiotherapy dynamic fractionation in case of a small cell carcinoma of the lungs resulted in the therapy duration reduction from 6 to 4 weeks. Thus the not traditional dose fractionation might become a mechanism for the improving the radiotherapy of persons suffering from the carcinoma of the lungs. (authors)

Protein signature of lung cancer tissues.

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Michael R Mehan

Full Text Available Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan to compare protein expression signatures of non small-cell lung cancer (NSCLC tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment.

Transforming growth factor β signaling overcomes dasatinib resistance in lung cancer.

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Edna Gordian

Full Text Available Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Despite recent advances in the development of targeted therapies, patients with advanced disease remain incurable, mostly because metastatic non-small cell lung carcinomas (NSCLC eventually become resistant to tyrosine kinase inhibitors (TKIs. Kinase inhibitors have the potential for target promiscuity because the kinase super family is the largest family of druggable genes that binds to a common substrate (ATP. As a result, TKIs often developed for a specific purpose have been found to act on other targets. Drug affinity chromatography has been used to show that dasatinib interacts with the TGFβ type I receptor (TβR-I, a serine-threonine kinase. To determine the potential biological relevance of this association, we studied the combined effects of dasatinib and TGFβ on lung cancer cell lines. We found that dasatinib treatment alone had very little effect; however, when NSCLC cell lines were treated with a combination of TGFβ and dasatinib, apoptosis was induced. Combined TGFβ-1 + dasatinib treatment had no effect on the activity of Smad2 or other non-canonical TGFβ intracellular mediators. Interestingly, combined TGFβ and dasatinib treatment resulted in a transient increase in p-Smad3 (seen after 3 hours. In addition, when NSCLC cells were treated with this combination, the pro-apoptotic protein BIM was up-regulated. Knockdown of the expression of Smad3 using Smad3 siRNA also resulted in a decrease in BIM protein, suggesting that TGFβ-1 + dasatinib-induced apoptosis is mediated by Smad3 regulation of BIM. Dasatinib is only effective in killing EGFR mutant cells, which is shown in only 10% of NSCLCs. Therefore, the observation that wild-type EGFR lung cancers can be manipulated to render them sensitive to killing by dasatinib could have important implications for devising innovative and potentially more efficacious treatment strategies for this

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Li, Zanhua [Medical School of Nanchang University (China); The Chest Hospital of Jiangxi Province Department of Respiration (China); Jiang, Xunsheng [Department of Respiration, Medical School of Nanchang University (China); Zhang, Wei, E-mail: weizhangncu@gmail.com [Department of Respiration, The First Affiliated Hospital of Nanchang University (China)

2016-01-29

Recent studies suggest that the human trophoblast cell-surface antigen TROP2 is highly expressed in a number of tumours and is correlated with poor prognosis. However, its role in non-small cell lung carcinoma (NSCLC) remains largely unknown. Here we examined TROP2 expression by immunohistochemistry in a series of 68 patients with adenocarcinoma (ADC). We found significantly elevated TROP2 expression in ADC tissues compared with normal lung tissues (P < 0.05), and TROP2 overexpression was significantly associated with TNM (tumour, node, metastasis) stage (P = 0.012), lymph node metastasis (P = 0.038), and histologic grade (P = 0.013). Kaplan–Meier survival analysis revealed that high TROP2 expression correlated with poor prognosis (P = 0.046). Multivariate analysis revealed that TROP2 expression was an independent prognostic marker for overall survival of ADC patients. Moreover, TROP2 overexpression enhanced cell proliferation, migration, and invasion in the NSCLC cell line A549, whereas knockdown of TROP2 induced apoptosis and impaired proliferation, migration, and invasion in the PC-9 cells. Altogether, our data suggest that TROP2 plays an important role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease.

XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

2015-08-21

Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival

International Nuclear Information System (INIS)

Ganeshan, Balaji; Miles, Ken; Panayiotou, Elleny; Burnand, Kate; Dizdarevic, Sabina

2012-01-01

To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing 18 F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. (orig.)

A clinical study on carcinoembryonic antigens in patients with squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Moriya, Hiroshi; Satoh, Toshihiko; Kimura, Kazuei; Togawa, Takafumi; Higuchi, Yoshisuke

1986-01-01

The serum levels of carcinoembryonic antigens (CEA) were determined in 57 patients with squamous cell carcinoma of the lung. The overall positive ratio was 45.6 %. The patients were classified into 2 groups, a peripheral type and a central type, according to bronchoscopic findings. The positive ratio in patients with peripheral type was 66.7 %. And the ratio with central type was 26.7 %. There was a significant difference (p < 0.005) between peripheral type and central type of squamous cell carcinoma of the lung. (author)

small cell lung cancer in a Chinese population

African Journals Online (AJOL)

clinical significance in patients with non-small cell lung cancer (NSCLC) in Hubei province ... diagnosis, tumor stage, treatment, progression .... Table 4: Association between EGFR mutation, gender and histologic type in 138 NSCLC patients.

Investigations of (99m)Tc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism.

Science.gov (United States)

Meng, Lanfang; Xiu, Yan; Li, Yanli; Xu, Xiaobo; Li, Shanqun; Li, Xiao; Pak, Koon Y; Shi, Hongcheng; Cheng, Dengfeng

2015-07-01

This study attempted to evaluate the feasibility of (99m)Tc-labeled glucarate ((99m)Tc-GLA) imaging in non-small cell lung cancer (NSCLC) and the potential tumor uptake mechanism. Cell lysates from two NSCLC cell lines, H292 and H1975, were immunoblotted with anti-glucose transporter 5 (GLUT5) antibody for Western blotting. Thereafter, the two cell lines were used to examine cellular uptake of (99m)Tc-GLA with or without fructose. SPECT/CT imaging studies were performed on small animals bearing H292 and H1975 tumors. Biodistribution studies were also conducted to achieve accurate tissue uptake of this tracer in two tumor models. Hematoxylin & eosin (H&E) staining and GLUT5, Ki67 and cytokeratin-7 (CK-7) immunohistochemistry (IHC) analysis were further investigated on tumor tissues. In Western blotting, H292 cells showed higher levels of GLUT5 compared to the H1975 cells. Meanwhile, the in vitro cell assays indicated GLUT5-dependent uptake of (99m)Tc-GLA in H292 and H1975 cells. The fructose competition assays showed a significant decrease in (99m)Tc-GLA uptake by H292 and H1975 cells when fructose was added. The (99m)Tc-GLA accumulation was as much as two-fold higher in H292 implanted tumors than in H1975 implanted tumors. (99m)Tc-GLA exhibited rapid clearance pharmacokinetics and reasonable uptake in human NSCLC H292 (1.69±0.37 ID%/g) and H1975 (0.89±0.06 ID%/g) implanted tumors at 30min post injection. Finally, the expression of GLUT5, Ki67 and CK-7 on tumor tissues also exhibited positive correlation with the in vitro cell test results and in vivo SPECT/CT imaging results in xenograft tumors. Both in vitro and ex vivo studies demonstrated that the uptake of (99m)Tc-GLA in NSCLC is highly related to GLUT5 expression. Imaging and further IHC results support that (99m)Tc-GLA could be a promising SPECT imaging agent for NSCLC diagnosis and prognosis evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of siRNA Silencing of TUG1 and LCAL6 Long Non-coding RNAs on Patient-derived Xenograft of Non-small Cell Lung Cancer.

Science.gov (United States)

Fang, Tian; Huang, Hairong; Li, Xiaoyou; Liao, Jing; Yang, Zhijian; Hoffman, Robert M; Cheng, X I; Liang, Lei; Hu, Wenjuan; Yun, Shifeng

2018-01-01

The aim of the present study was to establish a patient-derived xenograft (PDX) mouse model of non-small cell lung cancer (NSCLC) and investigate the anti-tumor efficacy of silencing of TUG1 and LCAL6 long non-coding RNA in the PDX model. PDXs were established by subcutaneously implanting NSCLC surgical tumor fragments into immunodeficient mice. PDX characterization was performed by histopathological, immunohistochemical and real-time polymerase chain reaction (RT-PCR) analyses for NSCLC subtype-specific markers and expression of LCAL6 and TUG1. Anti-tumor efficacy of siRNA silencing of TUG1 and LCAL6 was also investigated in the PDX model. The effect of TUG1 and LCAL6 silencing on protein expression of proliferation marker Ki67 and HOX-gene family HOXB7 in the tumors was assessed by immunohistochemical staining and Western blotting. Establishment of NSCLC PDX models resulted in 9 of 26 cases (34.6%). Lung squamous cell carcinomas (SCC) had a higher engraftment rate (58.3%) than lung adenocarcinomas (ADC) (18.2%) (pTUG1. The tumor volume and weight were significantly reduced in the TUG1-silenced group as compared to the control group (p0.05). Expression of both TUG1and LCAL6 was reduced by siRNA treatment. Expression of Ki67 and HOXB7 was significantly suppressed in both the TUG1- and LCAL6-silenced groups compared to the control group (pTUG1-silenced group showed more reduced Ki67 expression than the LCAL6-silenced group (pTUG1 and LCAL6. Silencing of TUG1 inhibited both tumor growth and expression of the proliferation marker Ki67 and HOX-gene family HOXB7 in the PDX model of NSCLC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Exosomes derived from mesenchymal non-small cell lung cancer cells promote chemoresistance.

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Lobb, Richard J; van Amerongen, Rosa; Wiegmans, Adrian; Ham, Sunyoung; Larsen, Jill E; Möller, Andreas

2017-08-01

Non-small cell lung cancer (NSCLC) is the most common lung cancer type and the most common cause of mortality in lung cancer patients. NSCLC is often associated with resistance to chemotherapeutics and together with rapid metastatic spread, results in limited treatment options and poor patient survival. NSCLCs are heterogeneous, and consist of epithelial and mesenchymal NSCLC cells. Mesenchymal NSCLC cells are thought to be responsible for the chemoresistance phenotype, but if and how this phenotype can be transferred to other NSCLC cells is currently not known. We hypothesised that small extracellular vesicles, exosomes, secreted by mesenchymal NSCLC cells could potentially transfer the chemoresistance phenotype to surrounding epithelial NSCLC cells. To explore this possibility, we used a unique human bronchial epithelial cell (HBEC) model in which the parental cells were transformed from an epithelial to mesenchymal phenotype by introducing oncogenic alterations common in NSCLC. We found that exosomes derived from the oncogenically transformed, mesenchymal HBECs could transfer chemoresistance to the parental, epithelial HBECs and increase ZEB1 mRNA, a master EMT transcription factor, in the recipient cells. Additionally, we demonstrate that exosomes from mesenchymal, but not epithelial HBECs contain the ZEB1 mRNA, thereby providing a potential mechanism for the induction of a mesenchymal phenotype in recipient cells. Together, this work demonstrates for the first time that exosomes derived from mesenchymal, oncogenically transformed lung cells can transfer chemoresistance and mesenchymal phenotypes to recipient cells, likely via the transfer of ZEB1 mRNA in exosomes. © 2017 UICC.

Second-Line Therapy for Advanced NSCLC.

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Weiss, Jared M; Stinchcombe, Thomas E

2013-01-01

Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.

Prognostic significance of CD44s expression in resected non-small cell lung cancer

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Ko Yoon

2011-08-01

Full Text Available Abstract Background CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC. Methods Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82 and squamous cell carcinoma (SCC; n = 77. Additionally, the immunoreactivity of cyclooxygenase (COX-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. Results High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7% than in those with AC histology (P 0.001. Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021. In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P P = 0.046, and high CD44s expression (P = 0.014. For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015. No significant association was found between CD44s and clinical outcome (P = 0.311. Conclusions High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

Prognostic significance of CD44s expression in resected non-small cell lung cancer

International Nuclear Information System (INIS)

Ko, Yoon Ho; Won, Hye Sung; Jeon, Eun Kyoung; Hong, Sook Hee; Roh, Sang Young; Hong, Young Seon; Byun, Jae Ho; Jung, Chan-Kwon; Kang, Jin Hyoung

2011-01-01

CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n = 82) and squamous cell carcinoma (SCC; n = 77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P <0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P = 0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P < 0.001), high-grade tumor differentiation (P = 0.046), and high CD44s expression (P = 0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P = 0.015). No significant association was found between CD44s and clinical outcome (P = 0.311). High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage

Identification of Logic Relationships between Genes and Subtypes of Non-Small Cell Lung Cancer

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Su, Yansen; Pan, Linqiang

2014-01-01

Non-small cell lung cancer (NSCLC) has two major subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). The diagnosis and treatment of NSCLC are hindered by the limited knowledge about the pathogenesis mechanisms of subtypes of NSCLC. It is necessary to research the molecular mechanisms related with AC and SCC. In this work, we improved the logic analysis algorithm to mine the sufficient and necessary conditions for the presence states (presence or absence) of phenotypes. We applied our method to AC and SCC specimens, and identified lower and higher logic relationships between genes and two subtypes of NSCLC. The discovered relationships were independent of specimens selected, and their significance was validated by statistic test. Compared with the two earlier methods (the non-negative matrix factorization method and the relevance analysis method), the current method outperformed these methods in the recall rate and classification accuracy on NSCLC and normal specimens. We obtained biomarkers. Among biomarkers, genes have been used to distinguish AC from SCC in practice, and other six genes were newly discovered biomarkers for distinguishing subtypes. Furthermore, NKX2-1 has been considered as a molecular target for the targeted therapy of AC, and other genes may be novel molecular targets. By gene ontology analysis, we found that two biological processes (‘epidermis development’ and ‘cell adhesion’) were closely related with the tumorigenesis of subtypes of NSCLC. More generally, the current method could be extended to other complex diseases for distinguishing subtypes and detecting the molecular targets for targeted therapy. PMID:24743794

Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma

DEFF Research Database (Denmark)

Jakobsen, Kristine Raaby; Paulsen, Birgitte Sandfeld; Bæk, Rikke

2015-01-01

Background: Lung cancer is one of the leading causes of cancer-related death. At the time of diagnosis, more than half of the patients will have disseminated disease and, yet, diagnosing can be challenging. New methods are desired to improve the diagnostic work-up. Exosomes are cell...... control subjects based on the differential display of exosomal protein markers. Methods: Plasma was isolated from 109 NSCLC patients with advanced stage (IIIa–IV) disease and 110 matched control subjects initially suspected of having cancer, but diagnosed to be cancer free. The Extracellular Vesicle Array...... (EV Array) was used to phenotype exosomes directly from the plasma samples. The array contained 37 antibodies targeting lung cancer-related proteins and was used to capture exosomes, which were visualised with a cocktail of biotin-conjugated CD9, CD63 and CD81 antibodies. Results: The EV Array...

Targeting apoptosis pathways in lung cancer

NARCIS (Netherlands)

Pore, Milind M.; Hiltermann, T. Jeroen N.; Kruyt, Frank A. E.

2013-01-01

Lung cancer is a devastating disease with a poor prognosis. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) represent different forms of lung cancer that are associated with distinct genetic causes and display different responses to therapy in the clinic. Whereas SCLC is often

MiR-124 Inhibits Growth and Enhances Radiation-Induced Apoptosis in Non-Small Cell Lung Cancer by Inhibiting STAT3

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Mengjie Wang

2017-12-01

Full Text Available Background/Aims: A growing body of evidence indicates that the abnormal expression of microRNAs (miRNAs play an important role in sensitizing the cellular response to ionizing radiation (IR. The aim of this study was to investigate whether the expression of miR-124 correlated with radiosensitivity in the context of non-small-cell lung carcinoma (NSCLC. Methods: Quantitative reverse transcription polymerase chain reaction (RT-PCR was used to quantify miR-124 expression in NSCLC tissues and cell lines. The role of miR-124 in NSCLC proliferation and radiosensitivity was analyzed using CCK-8 and flow cytometry apoptosis assays. Luciferase activity assays, RT-PCR, and Western blot assays were performed to confirm the target gene of miR-124. Results: In this study, we found that miR-124 was downregulated both in clinical NSCLC samples and in cell lines. miR-124 inhibited the proliferation of NSCLC cells and enhanced the apoptosis of NSCLC cells exposed to ionizing radiation. We identified signal transducer and activator of transcription 3 (STAT3 as a direct target of miR-124 by using target prediction algorithms and luciferase assays. Overexpression of STAT3 in A549 cell lines restored the enhanced radiosensitivity induced by miR-124. Conclusion: Taking these observations into consideration, we illustrated that miR-124 is a potential target for enhancing the radiosensitivity of NSCLC cells by targeting STAT3.

Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC).

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Cedrés, Susana; Nuñez, Isaac; Longo, Marina; Martinez, Pablo; Checa, Eva; Torrejón, Davis; Felip, Enriqueta

2011-05-01

Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases. Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Superior sulcus non-small cell lung carcinoma: A comparison of IMRT and 3D-RT dosimetry.

Science.gov (United States)

Truntzer, Pierre; Antoni, Delphine; Santelmo, Nicola; Schumacher, Catherine; Falcoz, Pierre-Emmanuel; Quoix, Elisabeth; Massard, Gilbert; Noël, Georges

2016-01-01

A dosimetric study comparing intensity modulated radiotherapy (IMRT) by TomoTherapy to conformational 3D radiotherapy (3D-RT) in patients with superior sulcus non-small cell lung cancer (NSCLC). IMRT became the main technique in modern radiotherapy. However it was not currently used for lung cancers. Because of the need to increase the dose to control lung cancers but because of the critical organs surrounding the tumors, the gains obtainable with IMRT is not still demonstrated. A dosimetric comparison of the planned target and organs at risk parameters between IMRT and 3D-RT in eight patients who received preoperative or curative intent irradiation. In the patients who received at least 66 Gy, the mean V95% was significantly better with IMRT than 3D-RT (p = 0.043). IMRT delivered a lower D2% compared to 3D-RT (p = 0.043). The IH was significantly better with IMRT (p = 0.043). The lung V 5 Gy and V 13 Gy were significantly higher in IMRT than 3D-RT (p = 0.043), while the maximal dose (D max) to the spinal cord was significantly lower in IMRT (p = 0.043). The brachial plexus D max was significantly lower in IMRT than 3D-RT (p = 0.048). For patients treated with 46 Gy, no significant differences were found. Our study showed that IMRT is relevant for SS-NSCLC. In patients treated with a curative dose, it led to a reduction of the exposure of critical organs, allowing a better dose distribution in the tumor. For the patients treated with a preoperative schedule, our results provide a basis for future controlled trials to improve the histological complete response by increasing the radiation dose.

Inhibitory effect and molecular mechanism of mesenchymal stem cells on NSCLC cells.

Science.gov (United States)

Pan, Mengwu; Hou, Lingling; Zhang, Jingsi; Zhao, Diandian; Hua, Jilei; Wang, Ziling; He, Jinsheng; Jiang, Hong; Hu, Honggang; Zhang, Lishu

2018-04-01

Non-small-cell lung cancer (NSCLC) is still the main threat of cancer-associated death. Current treatment of NSCLC has limited effectiveness, and unfortunately, the prognosis of NSCLC remains poor. Therefore, a novel strategy for cancer therapy is urgently needed. Stem cell therapy has significant potential for cancer treatment. Mesenchymal stem cells (MSCs) with capacity for self-renewal and differentiation into various cells types exhibit the feature of homing to tumor site and immunosuppression, have been explored as a new treatment for various cancers. Studies revealed that the broad repertoire of trophic factors secreted by MSCs extensively involved in the interplay between MSCs and tumor cells. In this study, we confirmed that MSCs do have the paracrine effect on proliferation and migration of NSCLC cells (A549, NCI-H460, and SK-MES-1). Co-culture system and conditioned medium experiments results showed that soluble factors secreted by MSCs inhibited the proliferation of NSCLC cells in vitro. The scratch assay showed that conditioned medium of MSCs could suppress the migration of NSCLC cells in vitro. Western blot results showed that the expression of proteins relevant to cell proliferation, anti-apoptosis, and migration was remarkably decreased via MAPK/eIF4E signaling pathway. We speculated that soluble factors secreted by MSCs might be responsible for inhibitory mechanism of NSCLC cells. By Human Gene Expression Microarray Assay and recombinant Vascular Endothelial Growth Factor 165 (VEGF165) neutralizing experiment, we verified that VEGF might be responsible for the down-regulation of proteins related to cell proliferation, anti-apoptosis, and migration by suppressing translation initiation factor eIF4E via MAPK signaling pathway. Taken together, our study demonstrated that a possible trophic factor secreted by MSCs could manipulate translation initiation of NSCLC cells via MAPK signaling pathway, and significantly affect the fate of tumor cells, which

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.

Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

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Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

2014-01-17

Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

International Nuclear Information System (INIS)

Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

2014-01-01

Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC

Late Lung Metastasis of a Primary Eccrine Sweat Gland Carcinoma 10 Years after Initial Surgical Treatment: The First Clinical Documentation

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R. F. Falkenstern-Ge

2013-01-01

Full Text Available Background. Sweat gland carcinoma is a rare malignancy with a high metastatic potential seen more commonly in elderly patients. The scalp is the most common site of occurrence and it usually spreads to regional lymph nodes. Liver, lungs, and bones are the most common sites of distant metastasis. Late lung metastasis of sweat gland adenocarcinoma after a time span of 5 years is extremely rare. Aim. We report a patient with late lung metastasis of a primary sweat gland carcinoma 10 years after initial surgical resection. Conclusion. Sweat gland carcinomas are rare cancers with a poor prognosis. Surgery in the form of wide local excision and lymph node dissection is the mainstay of treatment. Late pulmonary metastases with a latency of 10 years have never been reported in the literature. This is the first clinical documentation of late lung metastasis from sweat gland carcinoma with a latency period of 10 years.

Morphometrical analysis of pathomorphosis of squamous cell lung carcinoma after radiotherapy combined with hyperglycemia

International Nuclear Information System (INIS)

Furmanchuk, A.V.; Demidchik, Yu.E.; Khodina, T.V.

1987-01-01

Morphological changes are analysed and morphological assessment of the parenchyma, stroma, vessels and necrosis are provided in the squamous cell lung carcinoma tissue of 40 patients without preliminary irradiation, 40 patients after γ-beam therapy and 49 patients after radiotherapy combined with induced hyperglycemia (IH). The total focal dosage was 20 Gy (5 fractions during a week). In 25 patients IH was followed by irradiation and in 24 patients it followed irradiation. Operation was performed on the 7-8th day after therapy was initiated. It was concluded that preoperative γ-beam therapy followed by IH produced the most noticeable damaging effect on squamous cell lung carcinoma

Radiation sensitivity of human lung cancer cell lines

International Nuclear Information System (INIS)

Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

1989-01-01

X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

Peptide hormones and lung cancer.

Science.gov (United States)

Moody, T W

2006-03-01

Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.

FDG PET evaluation of therapeutic response and toxicity after radiotherapy for NSCLC

International Nuclear Information System (INIS)

Hicks, R.J.; MacManus, M.P.; Matthews, J.P.; Rischin, D.; Binns, D.; McKenzie, A.F.; Ball, D.L.

2002-01-01

Full text: Positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is recognised for staging and therapeutic planning of patients with non-small cell carcinoma of the lung (NSCLC). The potential for this technique to be used in the assessment of therapeutic response has also been highlighted but may be limited by false positive results due to inflammatory response, particularly early after radiotherapy (RT). To evaluate the utility of FEX PET for therapeutic monitoring early (<12 weeks) after completion of radical RT we prospectively evaluated metabolic response and radiation toxicity using a standardised scoring system in 73 consecutive patients. All 73 had evaluable PET scans but 6 of the CT scan results were considered non-evaluable for therapeutic response using WHO criteria. PET therapeutic response category differed from that by CT in 40/67 (60%) cases and in 80% of such cases suggested a more marked response than suggested by CT (p 0.0002). Multifactor analysis including PET response, CT response, performance status, weight loss and stage revealed that PET response was the only significant predictor of survival (p 0.0001). Radiation toxicity scores were inversely related to therapeutic response on both PET (p = 0.022) and CT (p =0.029). In particular, more severe (grade 2 or 3) radiotoxicity scores on PET were associated with a greater proportion of partial or complete responses on both PET and CT than were lower (grade 0 and 1) scores (p =0.0044 and 0.041 respectively) consistent with the known relationship between the radiosensitivity of normal host and tumoral tissues. Early after completion of radiotherapy for NSCLC, PET response provides better prognostic stratification than CT response. PET can also identify typical radiation toxicity changes which are associated with response to treatment. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Usefulness of SCC-antigen for diagnosis and monitoring recurrence and effectiveness of therapies of squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Mino, Naoko; Iio, Atsushi; Ata, Mariko; Murase, Kenya; Kataoka, Masaaki; Ito, Hisao; Ishine, Masahiro; Kawamura, Masashi; Hamamoto, Ken

1987-01-01

The serum levels of SCC antigen (squamous cell carcinoma related antigen) were measured in 111 patients with primary lung cancer to assess its clinical usefulness for diagnosis of squamous cell carcinoma and for monitoring recurrence and effectiveness of therapies. Serum SCC antigen level in patients with squamous cell carcinoma of the lung was 5.9 ± 10.4 ng/ml, which was high (p < 0.05) compared with those in normal controls (1.6 ± 0.5 ng/ml), patients with other types of lung cancer (2.4 ± 2.9 ng/ml) or benign disease (1.8 ± 1.1 ng/ml). Studies at various clinical stages of squamous cell carcinoma of the lung showed, however, that the SCC antigen levels were high only in the advanced stages (III and IV), whereas not so high in the earlier stages. These results confirmed that SCC antigen is a relatively specific marker to squamous cell carcinoma in the lung, as reported in the uterine cervix and the esophagus. The SCC antigen levels decreased after operation and more markedly after radiotherapy in dose-dependent manner, corresponding to the reduction of the tumor size. On the other hand, the SCC antigen levels were extremely high in the recurrence. It was concluded that SCC antigen is a useful marker for monitoring recurrence or effectiveness of the therapies of SCC of the lung, although not so for its early diagnosis. (author)

Fully automated VMAT treatment planning for advanced-stage NSCLC patients

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Della Gala, Giuseppe [Erasmus MC Cancer Institute, Department of Radiation Oncology, Rotterdam (Netherlands); Universita di Bologna, Scuola di Scienze, Alma Mater Studiorum, Bologna (Italy); Dirkx, Maarten L.P.; Hoekstra, Nienke; Fransen, Dennie; Pol, Marjan van de; Heijmen, Ben J.M. [Erasmus MC Cancer Institute, Department of Radiation Oncology, Rotterdam (Netherlands); Lanconelli, Nico [Universita di Bologna, Scuola di Scienze, Alma Mater Studiorum, Bologna (Italy); Petit, Steven F. [Erasmus MC Cancer Institute, Department of Radiation Oncology, Rotterdam (Netherlands); Massachusetts General Hospital - Harvard Medical School, Department of Radiation Oncology, Boston, MA (United States)

2017-05-15

To develop a fully automated procedure for multicriterial volumetric modulated arc therapy (VMAT) treatment planning (autoVMAT) for stage III/IV non-small cell lung cancer (NSCLC) patients treated with curative intent. After configuring the developed autoVMAT system for NSCLC, autoVMAT plans were compared with manually generated clinically delivered intensity-modulated radiotherapy (IMRT) plans for 41 patients. AutoVMAT plans were also compared to manually generated VMAT plans in the absence of time pressure. For 16 patients with reduced planning target volume (PTV) dose prescription in the clinical IMRT plan (to avoid violation of organs at risk tolerances), the potential for dose escalation with autoVMAT was explored. Two physicians evaluated 35/41 autoVMAT plans (85%) as clinically acceptable. Compared to the manually generated IMRT plans, autoVMAT plans showed statistically significant improved PTV coverage (V{sub 95%} increased by 1.1% ± 1.1%), higher dose conformity (R{sub 50} reduced by 12.2% ± 12.7%), and reduced mean lung, heart, and esophagus doses (reductions of 0.9 Gy ± 1.0 Gy, 1.5 Gy ± 1.8 Gy, 3.6 Gy ± 2.8 Gy, respectively, all p < 0.001). To render the six remaining autoVMAT plans clinically acceptable, a dosimetrist needed less than 10 min hands-on time for fine-tuning. AutoVMAT plans were also considered equivalent or better than manually optimized VMAT plans. For 6/16 patients, autoVMAT allowed tumor dose escalation of 5-10 Gy. Clinically deliverable, high-quality autoVMAT plans can be generated fully automatically for the vast majority of advanced-stage NSCLC patients. For a subset of patients, autoVMAT allowed for tumor dose escalation. (orig.) [German] Entwicklung einer vollautomatisierten, auf multiplen Kriterien basierenden volumenmodulierten Arc-Therapie-(VMAT-)Behandlungsplanung (autoVMAT) fuer kurativ behandelte Patienten mit nicht-kleinzelligem Bronchialkarzinom (NSCLC) im Stadium III/IV. Nach Konfiguration unseres auto

International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.

Science.gov (United States)

Travis, William D; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G; Geisinger, Kim R; Yatabe, Yasushi; Beer, David G; Powell, Charles A; Riely, Gregory J; Van Schil, Paul E; Garg, Kavita; Austin, John H M; Asamura, Hisao; Rusch, Valerie W; Hirsch, Fred R; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

2011-02-01

% disease-specific survival, respectively. AIS and MIA are usually nonmucinous but rarely may be mucinous. Invasive adenocarcinomas are classified by predominant pattern after using comprehensive histologic subtyping with lepidic (formerly most mixed subtype tumors with nonmucinous BAC), acinar, papillary, and solid patterns; micropapillary is added as a new histologic subtype. Variants include invasive mucinous adenocarcinoma (formerly mucinous BAC), colloid, fetal, and enteric adenocarcinoma. This classification provides guidance for small biopsies and cytology specimens, as approximately 70% of lung cancers are diagnosed in such samples. Non-small cell lung carcinomas (NSCLCs), in patients with advanced-stage disease, are to be classified into more specific types such as adenocarcinoma or squamous cell carcinoma, whenever possible for several reasons: (1) adenocarcinoma or NSCLC not otherwise specified should be tested for epidermal growth factor receptor (EGFR) mutations as the presence of these mutations is predictive of responsiveness to EGFR tyrosine kinase inhibitors, (2) adenocarcinoma histology is a strong predictor for improved outcome with pemetrexed therapy compared with squamous cell carcinoma, and (3) potential life-threatening hemorrhage may occur in patients with squamous cell carcinoma who receive bevacizumab. If the tumor cannot be classified based on light microscopy alone, special studies such as immunohistochemistry and/or mucin stains should be applied to classify the tumor further. Use of the term NSCLC not otherwise specified should be minimized. This new classification strategy is based on a multidisciplinary approach to diagnosis of lung adenocarcinoma that incorporates clinical, molecular, radiologic, and surgical issues, but it is primarily based on histology. This classification is intended to support clinical practice, and research investigation and clinical trials. As EGFR mutation is a validated predictive marker for response and progression

Impact of Neuro-Psychological Factors on Smoking-Associated Lung Cancer

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Schuller, Hildegard M. [Experimental Oncology Laboratory, Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, 2407 River Drive, Knoxville, TN 37996 (United States)

2014-03-13

Smoking has been extensively documented as a risk factor for all histological types of lung cancer and tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons reproducibly cause lung cancer in laboratory rodents. However, the most common lung cancer, non-small cell lung cancer (NSCLC), frequently develops in never smokers and is particularly common in women and African Americans, suggesting that factors unrelated to smoking significantly impact this cancer. Recent experimental investigations in vitro and in animal models have shown that chronic psychological stress and the associated hyperactive signaling of stress neurotransmitters via β-adrenergic receptors significantly promote the growth and metastatic potential of NSCLC. These responses were caused by modulation in the expression and sensitization state of nicotinic acetylcholine receptors (nAChRs) that regulate the production of stress neurotransmitters and the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Similar changes in nAChR-mediated neurotransmitter production were identified as the cause of NSCLC stimulation in vitro and in xenograft models by chronic nicotine. Collectively, these data suggest that hyperactivity of the sympathetic branch of the autonomic nervous system caused by chronic psychological stress or chronic exposure to nicotinic agonists in cigarette smoke significantly contribute to the development and progression of NSCLC. A recent clinical study that reported improved survival outcomes with the incidental use of β-blockers among patients with NSCLC supports this interpretation.

Impact of Neuro-Psychological Factors on Smoking-Associated Lung Cancer

International Nuclear Information System (INIS)

Schuller, Hildegard M.

2014-01-01

Smoking has been extensively documented as a risk factor for all histological types of lung cancer and tobacco-specific nitrosamines and polycyclic aromatic hydrocarbons reproducibly cause lung cancer in laboratory rodents. However, the most common lung cancer, non-small cell lung cancer (NSCLC), frequently develops in never smokers and is particularly common in women and African Americans, suggesting that factors unrelated to smoking significantly impact this cancer. Recent experimental investigations in vitro and in animal models have shown that chronic psychological stress and the associated hyperactive signaling of stress neurotransmitters via β-adrenergic receptors significantly promote the growth and metastatic potential of NSCLC. These responses were caused by modulation in the expression and sensitization state of nicotinic acetylcholine receptors (nAChRs) that regulate the production of stress neurotransmitters and the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Similar changes in nAChR-mediated neurotransmitter production were identified as the cause of NSCLC stimulation in vitro and in xenograft models by chronic nicotine. Collectively, these data suggest that hyperactivity of the sympathetic branch of the autonomic nervous system caused by chronic psychological stress or chronic exposure to nicotinic agonists in cigarette smoke significantly contribute to the development and progression of NSCLC. A recent clinical study that reported improved survival outcomes with the incidental use of β-blockers among patients with NSCLC supports this interpretation

Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer

Science.gov (United States)

Liu, Guangbo; Pei, Fen; Yang, Fengqing; Li, Lingxiao; Amin, Amit Dipak; Liu, Songnian; Buchan, J. Ross; Cho, William C.

2017-01-01

Non-small-cell lung cancer (NSCLC) constitutes 85% of all lung cancers, and is the leading cause of cancer-related death worldwide. The poor prognosis and resistance to both radiation and chemotherapy warrant further investigation into the molecular mechanisms of NSCLC and the development of new, more efficacious therapeutics. The processes of autophagy and apoptosis, which induce degradation of proteins and organelles or cell death upon cellular stress, are crucial in the pathophysiology of NSCLC. The close interplay between autophagy and apoptosis through shared signaling pathways complicates our understanding of how NSCLC pathophysiology is regulated. The apoptotic effect of autophagy is controversial as both inhibitory and stimulatory effects have been reported in NSCLC. In addition, crosstalk of proteins regulating both autophagy and apoptosis exists. Here, we review the recent advances of the relationship between autophagy and apoptosis in NSCLC, aiming to provide few insights into the discovery of novel pathogenic factors and the development of new cancer therapeutics. PMID:28208579

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

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Han, Jing; Wang, Dongjin; Di, Shouyin; Hu, Wei; Liu, Dong; Li, Xiaofei; Reiter, Russel J.; Yan, Xiaolong

2016-01-01

Non-small-cell lung cancer (NSCLC) is a leading cause of death from cancer worldwide. Melatonin, an indoleamine discovered in the pineal gland, exerts pleiotropic anticancer effects against a variety of cancer types. In particular, melatonin may be an important anticancer drug in the treatment of NSCLC. Herein, we review the correlation between the disruption of the melatonin rhythm and NSCLC incidence; we also evaluate the evidence related to the effects of melatonin in inhibiting lung carcinogenesis. Special focus is placed on the oncostatic effects of melatonin, including anti-proliferation, induction of apoptosis, inhibition of invasion and metastasis, and enhancement of immunomodulation. We suggest the drug synergy of melatonin with radio- or chemotherapy for NSCLC could prove to be useful. Taken together, the information complied herein may serve as a comprehensive reference for the anticancer mechanisms of melatonin against NSCLC, and may be helpful for the design of future experimental research and for advancing melatonin as a therapeutic agent for NSCLC. PMID:27102150

Therapeutic value of EGFR inhibition in CRC and NSCLC: 15 years of clinical evidence.

Science.gov (United States)

Troiani, Teresa; Napolitano, Stefania; Della Corte, Carminia Maria; Martini, Giulia; Martinelli, Erika; Morgillo, Floriana; Ciardiello, Fortunato

2016-01-01

Epidermal growth factor receptor (EGFR) plays a key role in tumour evolution, proliferation and immune evasion, and is one of the most important targets for biological therapy, especially for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). In the past 15 years, several EGFR antagonists have been approved for the treatment of NSCLC and metastatic CRC (mCRC). To optimise the use of anti-EGFR agents in clinical practice, various clinical and molecular biomarkers have been investigated, thus moving their indication from unselected to selected populations. Nowadays, anti-EGFR drugs represent a gold-standard therapy for metastatic NSCLC harbouring EGFR activating mutation and for RAS wild-type mCRC. Their clinical efficacy is limited by the presence of intrinsic resistance or the onset of acquired resistance. In this review, we provide an overview of the antitumour activity of EGFR inhibitors in NSCLC and CRC and of mechanisms of resistance, focusing on the development of a personalised approach through 15 years of preclinical and clinical research.

Clinical and prognostic significance of plasma fibrinogen in lung cancer

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Chen YS

2014-01-01

Full Text Available Objectives: Hyperfibrinogenemia is a common problem associated with various carcinomas. The recent studies have shown that high plasma fibrinogen concentration is associated with invasion, growth and metastases of cancer. Furthermore, the recent studies focus on the prognostic significance of fibrinogen in the patients with advanced NSCLC (stage IIIB -IV. However, the prognostic significance of the plasma fibrinogen levels in early stage NSCLC patients (stage I -IIIA still remains unclear. In addition, it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to the prognosis. The aims of this study were to 1 further explore the relationship between the plasma fibrinogen concentration and the stage and metastases of lung cancer 2 evaluate the prognostic significance of the basal plasma fibrinogen level in patients with lung cancer 3 explore the prognostic value of the change in fibrinogen levels between pre and post-chemotherapy. Methods: In this retrospective study, the data from 370 patients with lung cancer were enrolled into this study. The plasma fibrinogen levels were compared with the clinical and prognostic significance of lung cancer. The association between the plasma fibrinogen level and clinical-prognostic characteristics were analyzed using SPSS 17.0 software. Results: 1 The median pre-treatment plasma fibrinogen levels were 4.20g/L. Pre-treatment plasma fibrinogen levels correlated significantly with gender (p = 0.013. A higher plasma fibrinogen concentration was associated with squamous cell carcinoma versus adenocarcinoma (4.83±1.50 g/L versus 4.15±1.30 g/L; P<0.001, there was a significant association between plasma fibrinogen level and metastases of lung cancer, pointing a higher plasma fibrinogen level in lymph nodes or distant organ metastases (p < 0.001. 2 Patients with low plasma fibrinogen concentration demonstrates higher overall survival compared with those with high plasma fibrinogen

Improvement of Radiation-Mediated Immunosuppression of Human NSCLC Tumour Xenografts in a Nude Rat Model

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Sergey V. Tokalov

2010-01-01

Full Text Available Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour. To improve irradiation-mediated immunosuppression of human non-small cell lung cancer (NSCLC xenografts in a nude rat model irradiation (2 + 2 Gy from opposite sides of animals has been performed using a conventional X-ray tube. The described modification of whole body irradiation improves growth properties of human NSCLC xenografts in a nude rat model. The design of the whole body irradiation mediated immunosuppression described here for NSCLC xenografts may be useful for research applications involving other types of human tumours.

Genetic polymorphism rs3760396 of the chemokine (C-C motif) ligand 2 gene (CCL2) associated with the susceptibility of lung cancer in a pathological subtype-specific manner in Han-ancestry Chinese: a case control study

International Nuclear Information System (INIS)

Li, Xu; Lin, Fangcai; Zhou, Hong

2016-01-01

Chemokines are well known inflammatory factors critical for tumor development in diverse tissues, including lung cancer. Chemokine (C-C motif) Ligand 2 (CCL2) was one of such chemokines important for both primary tumor development and metastasis of various cancers. Polymorphism at rs3760396 of CCL2 genes is associated with the prognosis of non-small cell lung cancer (NSCLC). The goal of our study was to examine the relationship of genetic polymorphisms rs3760396 with the susceptibility of lung cancer and its pathological subtypes in Han-ancestry Chinese population. rs3760396 G/C polymorphism of CCL2 was genotyped using PCR in 394 patients with lung cancer and 545 cancer-free controls from the same Northeast region of China. After controlling for gender, age and smoking status, no significant association was observed between rs3760396 polymorphism and overall lung cancer. However, minor allele G of rs3760396 polymorphism was significantly associated with increased risk of adenosquamous lung carcinoma with either allelic genetic model (OR = 5.29, P < 0.001), or dominant genetic model (OR = 9.88, P < 0.001), or genotypic model (GC genotype vs. CC genotype, OR = 10.73, P < 0.001). Although rs3760396 polymorphism was not significantly associated with increased risk of adenocarcinoma subtype, it was nominally associated with the pooled outcome of either adenocarcinoma or adenosquamous carcinoma under allelic genetic model (OR = 1.54, P = 0.023) or dominant genetic model (OR = 1.57, P = 0.031). Our study suggested rs3760396 polymorphism of CCL2 is associated not only with prognosis of NSCLC, but also with risk of lung cancer in a subtype-specific manner. Our results further supported previous evidence of the important role of CCL2 in lung cancer development

Comparison of the effects of inhaled 239PuO2 and β- emitting radionuclides on the incidence of lung carcinomas in laboratory animals

International Nuclear Information System (INIS)

Hahn, F.F.; Griffith, W.C.; Boecker, B.B.; Muggenburg, B.A.; Lundgren, D.L.

1991-01-01

The health effects of inhaling radioactive particles when the lung is the primary organ irradiated were studied in rats and Beagle dogs. The animals were exposed to aerosols of 239 PuO 2 or fission-product radionuclides in insoluble forms and observed for their life span. Lung carcinomas were the primary late-occuring effect. The incidence rate for lung carcinomas was modeled using a proportional hazard rate model. Linear functions predominated below 5 Gy to the lung. The life-time risk for lung carcinomas per 10 4 Gy for beta emitters was 60 for rats and 65 for dogs, and for 239 PuO 2 it was 1500 for rats and 2300 for dogs

Comparison of the effects of inhaled 239PuO2 and β-emitting radionuclides of the incidence of lung carcinomas in laboratory animals

International Nuclear Information System (INIS)

Hahn, F.F.; Griffith, W.C.; Boecker, B.B.; Muggenburg, B.A.; Lundgren, D.L.

1992-01-01

The health effects of inhaling radioactive particles when the lung is the primary organ irradiated were studied in rats and dogs. The animals were exposed to aerosols of 239 PuO 2 or fission-product radionuclides in insoluble forms and observed for their life span. Lung carcinomas were the primary late-occurring effect. The incidence rate for lung carcinomas was modeled using a proportional hazard rate model. Linear functions predominated below 5 Gy to the lung. The life-time risk for lung carcinomas per 10 4 Gy for beta emitters was 60 for rats and 65 for dogs, and for 239 PuO 2 it was 1500 for rats and 2300 for dogs. (author)

Result of radiation therapy for non-resectable lung cancer

International Nuclear Information System (INIS)

Kataoka, Masaaki; Kawamura, Masashi; Kimura, Makoto; Mogami, Hiroshi; Kimura, Yoshiko; Hamamoto, Ken

1988-01-01

A total of 122 patients with non-resectable lung cancer, comprising 98 with non-small cell lung cancer (NSCLC) and 24 with small cell lung cancer (SCLC), who were treated from November 1976 through December 1985 with definitive radiation therapy (RT), were retrospectively analyzed for the outcome of RT. Overall, the 5-year survival rate was 6 %: it was 8 % for SCLC and 4 % for NSCLC. For NSCLC, survival was significantly better in stages I-III patients than stage IV patients (p < 0.01), although it was independent of histology, the combination of chemotherapy, and fractionation schedule. Local recurrence and distant metastasis were found to be the cause of death in 42 % and 13 %, respectively, in the stages I-II NSCLC group; and in 19 % and 52 %, respectively, in the SCLC group. The SCLC patients tended to have better survival when given chemotherapy before RT. Ten patients surviving for three years or more were characterized by having early stage of NSCLC, less than 100 cm of irradiated field, and a total dose of 60 Gy or more. Twelve patients (10 %) had severe radiation pneumonitis that resulted in death. Acute and fetal pneumonitis tended to be frequent when chemotherapy was combined with RT. (Namekawa, K.)

Economic impact of tissue testing and treatments of metastatic NSCLC in the era of personalized medicine.

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Donna Marie Graham

2014-09-01

Full Text Available A paradigm-shift in the management of non-small cell lung cancer (NSCLC has resulted in many new therapies becoming available for patients with advanced disease. Stratification of treatment by histologic and molecular subtype is recommended in order to obtain the greatest clinical benefit for patients while minimizing adverse effects of treatment. However, these advances in diagnosis and treatment of NSCLC have come at a financial cost. This review highlights the economic impact of screening for molecular abnormalities and targeted treatment for advanced NSCLC. Major determinants of cost are drug acquisition and molecular testing. As technologies advance, molecular testing costs may reduce. However, we must collaborate with payers and manufacturers to ensure that high drug costs do not limit patient accessibility to potentially beneficial treatment.

Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC. A phase III randomised controlled trial by the Norwegian Lung Cancer Study Group

DEFF Research Database (Denmark)

Fløtten, Ø; Grønberg, B H; Bremnes, R

2012-01-01

BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare...... a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin...... was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P

The Notch ligand delta-like 3 promotes tumor growth and inhibits Notch signaling in lung cancer cells in mice

International Nuclear Information System (INIS)

Deng, San-Ming; Yan, Xian-Chun; Liang, Liang; Wang, Li; Liu, Yuan; Duan, Juan-Li; Yang, Zi-Yan; Chang, Tian-Fang; Ruan, Bai; Zheng, Qi-Jun; Han, Hua

2017-01-01

Although it has been suggested that Dll3, one of the Notch ligands, promotes the proliferation and inhibits the apoptosis of cancer cells, the role of Dll3 in cancers remains unclear. In this study, we found that in the murine Lewis lung carcinoma (LLC) cells, the level of Dll3 mRNA changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with tumor necrosis factor (TNF)-α. Dll3 was also expressed at higher level in human lung carcinoma tissues than in the para-carcinoma tissues. Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro, and enhanced tumor growth when inoculated in vivo in mice. The Dll3-mediated proliferation could be due to increased Akt phosphorylation in LLC cells, because an Akt inhibitor counteracted Dll3-induced proliferation. Moreover, Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling. - Highlights: • The level of Dll3 in Lewis lung carcinoma changed upon tumor microenvironment (TME) stimulation, namely, decreased under hypoxia or stimulated with TNF-α. • The Dll3 was rarely detectable in the para-carcinoma tissues, but positive in 82.1% of NSCLC tissues from 84 patients. • Overexpression of Dll3 in LLC cells promoted tumor growth but did not remarkably alter TME after inoculated in mice. • Overexpression of Dll3 in LLC cells promoted cell proliferation and reduced apoptosis in vitro in an Akt-dependent way. • Dll3 overexpression promoted PI3K/Akt signaling through inhibiting Notch signaling.

Bmi-1 expression modulates non-small cell lung cancer progression

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Xiong, Dan; Ye, Yunlin; Fu, Yujie; Wang, Jinglong; Kuang, Bohua; Wang, Hongbo; Wang, Xiumin; Zu, Lidong; Xiao, Gang; Hao, Mingang; Wang, Jianhua

2015-01-01

Previous studies indicate that the role of B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is responsible for multiple cancer progression. However, Bmi-1 in controlling gene expression in non-small cell lung cancer (NSCLC) development is not well explored. Here we report that the Bmi-1 level is highly increased in primary NSCLC tissues compared to matched adjacent non-cancerous tissues and required for lung tumor growth in xenograft model. Furthermore, we also demonstrate that Bmi-1 level is lower in matched involved lymph node cancerous tissues than the respective primary NSCLC tissues. We find that Bmi-1 does not affect cell cycle and apoptosis in lung cancer cell lines as it does not affect the expression of p16/p19, Pten, AKT and P-AKT. Mechanistic analyses note that reduction of Bmi-1 expression inversely regulates invasion and metastasis of NSCLC cells in vitro and in vivo, followed by induction of epithelial-mesenchymal transition (EMT). Using genome microarray assays, we find that RNAi-mediated silence of Bmi-1 modulates some important molecular genetics or signaling pathways, potentially associated with NSCLC development. Taken together, our findings disclose for the first time that Bmi-1 level accumulates strongly in early stage and then declines in late stage, which is potentially important for NSCLC cell invasion and metastasis during progression. PMID:25880371

Quality-of-care indicators for non-small cell lung cancer.

Science.gov (United States)

Tanvetyanon, Tawee

2009-10-01

Quality-of-care indicators are measurable elements of practice performance that can be used to assess the quality or change in quality of the care provided. To date, the literature on quality-of-care indicators for non-small cell lung cancer (NSCLC) has not been reviewed. A search was performed to identify articles reporting on quality-of-care indicators specific for NSCLC published from January 2003 to May 2009 (using MEDLINE and American Society of Clinical Oncology abstract databases). Web sites of major quality care organizations were also searched. The identified indicators were then classified by their aspect of care provision (structure-of-care, process-of-care, or outcome-of-care indicator). For structure-of-care quality indicators, the most cited indicators were related to the quality of lung surgery. These included being National Cancer Institute-designated cancer centers or high-volume hospitals. For process-of-care quality indicators, the most common indicators were the receipt of surgery for early-stage NSCLC and the administration of chemotherapy for advanced-stage NSCLC. For outcome-of-care quality indicators, the most cited indicators were related to postoperative morbidity or mortality after lung surgery. Several quality-of-care indicators for NSCLC are available. Process-of-care indicators are the most studied. The use of these indicators to measure practice performance holds the promise of improving outcomes of patients with NSCLC.

Personalized medicine and treatment approaches in non-small-cell lung carcinoma

Directory of Open Access Journals (Sweden)

Vadakara J

2012-09-01

Full Text Available Joseph Vadakara, Hossein BorghaeiFox Chase Cancer Center, Philadelphia, PA, USAAbstract: Chemotherapy has been the traditional backbone for the management of metastatic lung cancer. Multiple trials have shown the benefits of treatment with platinum doublets in lung cancer. This “one treatment fits all” approach was further refined by the introduction of targeted agents and discovery of subpopulations of patients who benefited from treatment with these agents. It has also become evident that certain histologic subtypes of non-small-cell lung cancer respond better to one cytotoxic chemotherapy versus others. This has led to the concept of using histology to guide therapy. With the introduction of epidermal growth factor receptor (EGFR tyrosine kinase inhibitors and the discovery of activating mutations in the EGFR gene, further personalization of treatment for subgroups of patients has become a reality. More recently, the presence of a fusion gene, echinoderm microtubule-associated protein-like 4 – anaplastic lymphoma kinase (EML4-ALK, was identified as the driver mutation in yet another subgroup of patients, and subsequent studies have led to approval of crizotinib in this group of patients. In this article, efforts in personalizing delivery of care based on the histological subtypes of lung cancer and the role of K-RAS and EGFR mutations, EML4/ALK translocation, and ERCC1 (excision repair cross-complementing 1 and EGFR expression in choosing appropriate treatments for patients with advanced lung cancer are discussed. This article also reviews the problem of resistance to EGFR tyrosine kinase inhibitors and the ongoing trials that target novel pathways and mechanisms that are implicated in resistance.Keywords: NSCLC, EGFR, cancer treatment

An unusual presentation of multiple cavitated lung metastases from colon carcinoma

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Iannace Alessandro

2011-05-01

Full Text Available Abstract Background Consolidation with or without ground-glass opacity is the typical radiologic finding of lung metastases of adenocarcinoma from the gastrointestinal tract. Lung excavated metastases from gastrointestinal carcinoma are very rare. Case presentation The authors describe an unusual presentation of multiple cavitated lung metastases from colon adenocarcinoma and discuss the outcome of a patient. The absence both of symptoms and other disease localizations, the investigations related to different diagnostic hypotheses and the empirical treatments caused a delay in correct diagnosis. Only a transparietal biopsy revealed the neoplastic origin of nodules. Conclusions This report demonstrates that although lung excavated metastases are described in literature, initial failure to reach a diagnosis is common. We would like to alert clinicians and radiologists to the possibility of unusual atypical features of pulmonary metastases from colon adenocarcinoma.

Diagnostic Value of Early-Phase-Enhanced Computed Tomography for the Differentiation of Pulmonary Metastases from Hepatocellular Carcinoma and Primary Lung Cancer

International Nuclear Information System (INIS)

Choi, Joon-Il; Jung, Dae Chul; Kim, Min-Ju; Hong, Eun Kyung; Park, Joong-Won; Kim, Chang-Min; Choi, Hyuck Jae; Jang, Yun-Jin

2009-01-01

Background: The lung is the most common site of distant metastases from hepatocellular carcinoma. Correct differentiation between metastatic hepatocellular carcinoma of the lung and primary lung cancer is sometimes difficult without biopsy. Purpose: To evaluate the usefulness of measuring the attenuations of pulmonary nodules on early-phase contrast-enhanced computed tomography (CT) for the differentiation of pulmonary metastases from hepatocellular carcinoma and primary lung cancer. Material and Methods: Thirteen patients with pulmonary metastases from hepatocellular carcinoma (nine men, four women; age 53.9±14.2 years, range 16-70 years) and 25 patients with primary lung cancer (14 men, 11 women; age 62.2±9.4 years, range 43-72 years) were retrospectively evaluated. Contrast-enhanced scans were obtained 35 s after commencing intravenous injection of contrast medium. Attenuation values and the size of the pulmonary nodules were measured on contrast-enhanced CT scans. CT and clinical features were analyzed with regard to age, sex, body surface area of the patients, the attenuation values and size of the nodules, and CT machines using univariate analysis (Fisher's exact test for binary data sets and the Mann-Whitney U test for continuous data sets). Multiple linear regression analysis was used to eliminate confounding factors. Results: The mean attenuation value of metastatic pulmonary nodules from hepatocellular carcinoma (75.7±24.9 HU) was higher than that of primary lung cancer nodules (45.8±14.4 HU) (P<0.01). Other variables such as age, sex, body surface area of the patients, CT device, and nodule size were not significant variables on multiple regression analysis. When a cut-off value of 75 HU was applied, the positive predictive value for diagnosing metastatic nodules from hepatocellular carcinoma was 100%. Conclusion: Pending confirmation in a large study, our findings suggest that there is a difference in contrast enhancement between pulmonary

Influence of Vitamins on Secondary Reactive Oxygen Species Production in Sera of Patients with Resectable NSCLC

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Thierry Patrice

2016-07-01

Full Text Available Background: Singlet oxygen (1O2 oxidizes targets through the production of secondary reactive oxygen species (SOS. Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was to determine the oxidative status of patients with resectable Non-Small cell lung cancers (NSCLC and the potential influence of antioxidants, compared to sera from healthy donors. Materials and Methods: Serum samples from 10 women and 28 men, 19 adenocarcinomas (ADK, 15 patients N1 or M1 were submitted to a photoreaction producing 1O2. Then, samples were supplemented with vitamins (Vit C, Vit E, or glutathione (GSH. Results: Squamous cell carcinomas (SCC and metastatic SCCs induced a lower SOS rate. While Vit C increased SOS in controls as in patients with metastases, Vit E or the combination of Vit E and C strongly reduced SOS. GSH alone lightly decreased SOS in controls but had no effect in patients either alone or combined with Vit C. Conclusion: In “early” lung cancers, SOS are comparable or lower than for healthy persons. The role of Vitamins varies with gender, cancer type, and metastases. This suggests that an eventual supplementation should be performed on a per-patient basis to evidence any effect.

Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling.

Science.gov (United States)

Sun, Xiang; Xu, Yang; Wang, Yi; Chen, Qian; Liu, Liu; Bao, Yangyi

2018-05-15

BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC. MATERIAL AND METHODS Humanized NSCLC cell lines PC9 and A549 were co-cultured with thalidomide and/or icotinib to test for anti-tumor efficiency. Cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry and cell migration by wound healing assay. Western blot was performed to determine the expression of caspase-3, -8, -9, Bax, EGFR, VEGF-R, AKT, ERK, MMP2, MMP9, and NF-κB. The xenograft mouse model was used to explore the effects of thalidomide and icotinib in vivo. Immunohistochemical testing was used to determine the expression of Ki-67 and TUNEL staining in tumor tissues. RESULTS Treatments of thalidomide and/or icotinib reduced cell viability, induced apoptosis, and suppressed migration. Attenuation of pEGFR and pVEGF-R resulted in deactivation of ERK and AKT pathways, which eventually increased the anti-proliferative response. In PC9 xenograft model, combined administration of thalidomide and icotinib restrained tumor growth with remarkable reduced Ki-67 index and increased TUNEL positive cells. CONCLUSIONS Thalidomide sensitizes icotinib to increase apoptosis and prevent migration, and it may be a potentially promising anti-tumor drug in lung cancer multi-modality therapy.

Preserving Functional Lung Using Perfusion Imaging and Intensity-Modulated Radiation Therapy for Advanced-Stage Non-Small Cell Lung Cancer

International Nuclear Information System (INIS)

Shioyama, Yoshiyuki; Jang, Si Young; Liu, H. Helen; Guerrero, Thomas; Wang, Xuanmin; Gayed, Isis W.; Erwin, William D.; Liao, Zhongxing; Chang, Joe Y.; Jeter, Melenda; Yaremko, Brian P.; Borghero, Yerko O.; Cox, James D.; Komaki, Ritsuko; Mohan, Radhe

2007-01-01

Purpose: To assess quantitatively the impact of incorporating functional lung imaging into intensity-modulated radiation therapy planning for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Sixteen patients with advanced-stage NSCLC who underwent radiotherapy were included in this study. Before radiotherapy, each patient underwent lung perfusion imaging with single-photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The SPECT-CT was registered with simulation CT and was used to segment the 50- and 90-percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were designed and compared in each patient: an anatomic plan using simulation CT alone and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric parameters of the two types of plans were compared in terms of tumor coverage and avoidance of normal tissues. Results: In incorporating perfusion information in IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the anatomic plans. The median reductions in the percentage of volume irradiated with >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%, respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90 lung. A greater degree of sparing of the functional lung was achieved for patients with large perfusion defects compared with those with relatively uniform perfusion distribution. Conclusion: Function-guided IMRT planning appears to be effective in preserving functional lung in locally advanced-stage NSCLC patients

Carcinoma lung: Clinical presentation, diagnosis, and its surgical management

Directory of Open Access Journals (Sweden)

Farooq Ahmad Ganie

2013-01-01

Full Text Available The aim of this article is to review the surgical management of lung carcinoma. Lung cancer is the most common cancer in the world, and a leading cause of death in men and women. By any conventional measure, the enormity of this global problem is immense. In some countries incidence and mortality rates have peaked and are beginning to decline. In many developing nations, the burden of disease is rising and will continue to rise because of aggressive tobacco industry marketing which is leading to a growing prevalence of cigarette smoking. This is also one of the major causes of cancer deaths in our Kashmir valley. The method of literature search was from articles published in PubMed and Google Scholar.

The effect of dose protraction on the incidence of lung carcinomas in beagle dogs with internally deposited β-emitting radionuclides

International Nuclear Information System (INIS)

Griffith, W.C.; Boecker, B.B.; Hahn, F.F.; Muggenburg, B.A.; Snipes, M.B.

1992-01-01

Studies using Beagle dogs were conducted to understand health effects when lung is the primary organ irradiated after inhaling insoluble radioactive particles containing one of four β-emitting radionuclides, 90 Y, 91 Y, 144 Ce, or 90 Sr. The low-LET β irradiation was delivered over a wide range of total doses and dose rate patterns that protracted the dose to lung from about 1 wk to several years. The tumor incidence rates for lung carcinomas were estimated using a proportional hazard rate model. These studies suggest that dose protraction only affects production of lung carcinomas at doses above 50 Gy

Occipital condyle metastasis: an unusual clinical presentation in carcinoma of the lung

International Nuclear Information System (INIS)

Pasricha, R.; Mohanty, P.P.; Madan, R.C.; Datta, N.R.

2005-01-01

Metastases to the base of the skull and occipital condyle metastases are uncommon as a presenting feature of malignancy. Lung cancers are known for their metastatic potential to various sites, some of which could be the only presenting feature of the underlying malignancy. However, occipital condyle metastases are very rare and to the best of our knowledge, metastases to this site from carcinoma of the lung, as a presenting feature, have never been reported in the literature. The present case report describes the clinical, radiological and the therapeutic interventions that were undertaken in a patient presenting with lung cancer who had solely the features of occipital condyle metastasis

MicroRNA-429 induces tumorigenesis of human non-small cell lung cancer cells and targets multiple tumor suppressor genes

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Lang, Yaoguo; Xu, Shidong; Ma, Jianqun; Wu, Jun [Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Jin, Shi; Cao, Shoubo [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China); Yu, Yan, E-mail: yuyan@hrbmu.edu.cn [Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang 150081 (China)

2014-07-18

Highlights: • MiR-429 expression is upregulated in non-small cell lung cancer (NSCLC). • MiR-429 inhibits PTEN, RASSF8 and TIMP2 expression. • MiR-429 promotes metastasis and proliferation. • We report important regulatory mechanisms involved in NSCLC progression. • MiR-429 is a potential therapeutic target and diagnostic marker. - Abstract: Lung cancer is the major cause of cancer death globally. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression. Aberrant expression of microRNA (miRNA) has been implicated in cancer initiation and progression. In this study, we demonstrated that the expression of miR-429 are often upregulated in non-small cell lung cancer (NSCLC) compared with normal lung tissues, and its expression level is also increased in NSCLC cell lines compared with normal lung cells. Overexpression of miR-429 in A549 NSCLC cells significantly promoted cell proliferation, migration and invasion, whereas inhibition of miR-429 inhibits these effects. Furthermore, we demonstrated that miR-429 down-regulates PTEN, RASSF8 and TIMP2 expression by directly targeting the 3′-untranslated region of these target genes. Taken together, our results suggest that miR-429 plays an important role in promoting the proliferation and metastasis of NSCLC cells and is a potential target for NSCLC therapy.

Squamous cell carcinomas of the lung and of the head and neck: new insights on molecular characterization

Science.gov (United States)

Polo, Valentina; Pasello, Giulia; Frega, Stefano; Favaretto, Adolfo; Koussis, Haralabos; Conte, Pierfranco; Bonanno, Laura

2016-01-01

Squamous cell carcinomas of the lung and of the head and neck district share strong association with smoking habits and are characterized by smoke-related genetic alterations. Driver mutations have been identified in small percentage of lung squamous cell carcinoma. In parallel, squamous head and neck tumors are classified according to the HPV positivity, thus identifying two different clinical and molecular subgroups of disease. This review depicts different molecular portraits and potential clinical application in the field of targeted therapy, immunotherapy and chemotherapy personalization. PMID:26933818

Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients

DEFF Research Database (Denmark)

Bernchou, Uffe; Hansen, Olfred; Schytte, Tine

2015-01-01

BACKGROUND AND PURPOSE: This study investigates the ability of pre-treatment factors and response markers extracted from standard cone-beam computed tomography (CBCT) images to predict the lung density changes induced by radiotherapy for non-small cell lung cancer (NSCLC) patients. METHODS...... AND MATERIALS: Density changes in follow-up computed tomography scans were evaluated for 135 NSCLC patients treated with radiotherapy. Early response markers were obtained by analysing changes in lung density in CBCT images acquired during the treatment course. The ability of pre-treatment factors and CBCT...

ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial

DEFF Research Database (Denmark)

Vilmar, Adam Christian; Santoni-Rugiu, E; Sørensen, J B

2010-01-01

Customized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participa...

Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

International Nuclear Information System (INIS)

Li, Yuexia; Li, Xiaohui; Liu, Gang; Sun, Rongqing; Wang, Lirui; Wang, Jing; Wang, Hongmin

2015-01-01

Highlights: • TIPE2 is down-regulated in NSCLC tissues. • TIPE2 inhibits NSCLC cell proliferation, colony formation and invasion. • TIPE2 reduces the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. - Abstract: The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P = 0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression

Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

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Li, Yuexia [Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China); Li, Xiaohui [Department of Cardiovascular Surgery, Henan Provincial People’s Hospital, Zhengzhou, Henan 450003 (China); Liu, Gang; Sun, Rongqing; Wang, Lirui [Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China); Wang, Jing, E-mail: jing_wang1980@163.com [Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China); Wang, Hongmin, E-mail: hmwangzz@126.com [Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052 (China)

2015-01-30

Highlights: • TIPE2 is down-regulated in NSCLC tissues. • TIPE2 inhibits NSCLC cell proliferation, colony formation and invasion. • TIPE2 reduces the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. - Abstract: The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P < 0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P = 0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression.

Hot spot mutations in Finnish non-small cell lung cancers.

Science.gov (United States)

Mäki-Nevala, Satu; Sarhadi, Virinder Kaur; Rönty, Mikko; Kettunen, Eeva; Husgafvel-Pursiainen, Kirsti; Wolff, Henrik; Knuuttila, Aija; Knuutila, Sakari

2016-09-01

Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features. Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM). Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PIK3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure. Finnish NSCLC patients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells.

Science.gov (United States)

Sun, Bing; Bai, Yuxin; Zhang, Liyuan; Gong, Linlin; Qi, Xiaoyu; Li, Huizhen; Wang, Faming; Chi, Xinming; Jiang, Yulin; Shao, Shujuan

Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5) is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.

Quantitative Proteomic Profiling the Molecular Signatures of Annexin A5 in Lung Squamous Carcinoma Cells.

Directory of Open Access Journals (Sweden)

Bing Sun

Full Text Available Lung cancer remains the leading cancer killer around the world. It's crucial to identify newer mechanism-based targets to effectively manage lung cancer. Annexin A5 (ANXA5 is a protein kinase C inhibitory protein and calcium dependent phospholipid-binding protein, which may act as an endogenous regulator of various pathophysiological processes. However, its molecular mechanism in lung cancer remains poorly understood. This study was designed to determine the mechanism of ANXA5 in lung cancer with a hope to obtain useful information to provide a new therapeutic target. We used a stable isotope dimethyl labeling based quantitative proteomic method to identify differentially expressed proteins in NSCLC cell lines after ANXA5 transfection. Out of 314 proteins, we identified 26 and 44 proteins that were down- and up-regulated upon ANXA5 modulation, respectively. The IPA analysis revealed that glycolysis and gluconeogenesis were the predominant pathways modulated by ANXA5. Multiple central nodes, namely HSPA5, FN1, PDIA6, ENO1, ALDOA, JUP and KRT6A appeared to occupy regulatory nodes in the protein-protein networks upon ANXA5 modulation. Taken together, ANXA5 appears to have pleotropic effects, as it modulates multiple key signaling pathways, supporting the potential usefulness of ANXA5 as a potential target in lung cancer. This study might provide a new insight into the mechanism of ANXA5 in lung cancer.

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

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Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Cardarella, Stephanie [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Dahlberg, Suzanne E. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215 (United States); Araki, Tetsuro [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Lydon, Christine; Jackman, David M.; Rabin, Michael S. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States); Hatabu, Hiroto [Department of Radiology, Brigham and Women' s Hospital, 75 Francis St., Boston, MA 02115 (United States); Johnson, Bruce E. [Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, (United States)

2015-05-15

Highlights: • Interstitial lung abnormalities were present in 14% of stage IV NSCLC patients. • ILA was more common in older patients with heavier smoking history. • ILA was associated with shorter survival after adjusting for smoking and therapy. • ILA could be an additional independent marker for survival in advanced NSCLC. - Abstract: Objective: Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and method: The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0 = no evidence of ILA, 1 = equivocal for ILA, 2 = suspicious for ILA, 3 = ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results: ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3: n = 2, score2: n = 15). These 17 patients were significantly older (median age: 69 vs. 63, p = 0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p = 0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p = 0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9–9.4] compared to 14.8 months [95%CI: 11.1–18.4] in patients with ILA score 0 or 1 (p = 0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR = 2.09, p = 0.028) after adjusting for first-line systemic therapy (chemotherapy, p < 0.001; TKI, p < 0.001; each compared to no therapy) and pack years of smoking (p = 0.40). Conclusion: Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

High glucose contributes to the proliferation and migration of non-small cell lung cancer cells via GAS5-TRIB3 axis.

Science.gov (United States)

Ding, Cheng-Zhi; Guo, Xu-Feng; Wang, Guo-Lei; Wang, Hong-Tao; Xu, Guang-Hui; Liu, Yuan-Yuan; Wu, Zhen-Jiang; Chen, Yu-Hang; Wang, Jiao; Wang, Wen-Guang

2018-01-24

Despite the growing number of studies exhibited an association of diabetes mellitus (DM) and lung cancer progression, the concrete mechanism of DM aggravating lung cancer has not been elucidated. This study was to investigate whether and how high glucose (HG) contribute to the proliferation and migration of non-small cell lung cancer (NSCLC) cells in vitro. In the present study, we confirmed that HG promoted the proliferation and migration of NSCLC cells, and also induced an anti-apoptosis effect on NSCLC cells. Moreover, HG inhibited the expression of GAS5 in NSCLC cells but elevated the protein level of TRIB3. GAS5 overexpression promoted the degradation of TRIB3 protein by ubiquitination and inhibited the HG induced-proliferation, anti-apoptosis and migration of NSCLC cells. Importantly, TRIB3 overexpression reversed the effects of GAS5 on the HG-treated NSCLC cells. Taken together, down-regulated GAS5 by HG significantly enhanced the proliferation, anti-apoptosis and migration in NSCLC cells through TRIB3, thus promoting the carcinogenesis of NSCLC. ©2018 The Author(s).

EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.

Science.gov (United States)

Dong, Y U; Ren, Weihong; Qi, Jun; Jin, B O; Li, Ying; Tao, Huiqing; Xu, Ren; Li, Yanqing; Zhang, Qinxian; Han, Baohui

2016-04-01

Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies

Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset.

Science.gov (United States)

Guo, Yongjun; Ma, Jie; Lyu, Xiaodong; Liu, Hai; Wei, Bing; Zhao, Jiuzhou; Fu, Shuang; Ding, Lu; Zhang, Jihong

2014-11-18

The translocations of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene on chromosome 2p have been identified in non-small-cell lung cancers (NSCLCs) as oncogenic driver mutations. It has been suggested that EML4-ALK fusion is associated with the resistance in NSCLCs to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), such as gefitinib and erlotinib. In contrast, ALK tyrosine kinase inhibitor (ALK TKI) crizotinib has shown superior effects in combating NSCLCs with EML4-ALK. Thus, characterization of EML4-ALK fusion genes and clinical features of resulting carcinomas would be a great benefit to disease diagnosis and designing customized treatment plans. Studies have suggested that EML4-ALK translocation occurs more frequently in never-smokers with NSCLC, especially in female patients. However, it is not clear whether this is the case in male patients, too. In this study, we have determined the frequency of EML4-ALK translocation in male never-smokers with NSCLC in a cohort of Chinese patients. The clinical features associated with EML4-ALK translocation were also investigated. A cohort of 95 Chinese male never-smokers with NSCLC was enrolled in this study. EML4-ALK fusion genes were detected using one-step real time RT-PCR and DNA sequencing. We further determined the expression levels of ALK mRNA by RT-PCR and ALK protein by immunohistochemistry in these specimens. The clinical features of EML4-ALK-positive carcinomas were also determined. We have identified EML4-ALK fusion genes in 8 out of 95 carcinoma cases, accounting for 8.42% in Chinese male never-smokers with NSCLC. It is significantly higher than that in all Chinese male patients (3.44%) regardless smoking habit. It is also significantly higher than that in all Chinese smokers (8/356 or 2.25%) or in smokers worldwide (2.9%) by comparing to published data. Interestingly, EML4-ALK fusion genes are more frequently found in

Primary epithelial myoepithelial carcinoma of lung, reporting of a rare entity, its molecular histogenesis and review of the literature.

Science.gov (United States)

Arif, Farzana; Wu, Susan; Andaz, Shahriyour; Fox, Stewart

2012-01-01

Primary epithelial myoepithelial carcinoma of lung is a rare entity and is thought to arise from the submucosal bronchial glands distributed throughout the lower respiratory tract. Because of the rarity of this tumor, we describe one case of epithelial myoepithelial carcinoma arising in the bronchus intermedius and presenting as an endobronchial mass. A 57-year-old male patient presented with an incidental finding of an endobronchial mass located in the lumen of the right lower lobe bronchus and caused near total luminal occlusion of the bronchus. An endobronchial carcinoid tumor was entertained clinically. Subsequently the patient underwent an uneventful videothoracoscopic lobectomy of lower and middle lobes of the right lung. Morphologically and immunohistochemically the tumor was characterized by two cell populations with epithelial and myoepithelial cells forming duct-like structure. The final diagnosis of epithelial myoepithelial carcinoma of lung was rendered.

Contemporary review on the inequities in the management of lung cancer among the African-American population.

Science.gov (United States)

Kim, Anthony W; Liptay, Michael J; Higgins, Robert S D

2008-06-01

Lung cancer is the leading cause of cancer-related mortality. Nonsmall-cell lung cancer (NSCLC) constitutes approximately 80% of all the lung cancers observed. Despite the aggressive nature of this disease, totally adequate and fully comprehensive treatment yielding outstanding outcomes and survival has yet to be discovered. A uniform means by which to manage NSCLC is only in evolution. Without a universally accepted algorithm upon which clinical decisions can be referenced or compared, differences in the treatment of this disease process can and will exist. Racial bias in the management of NSCLC is being realized as a cause of a substandard delivery of adequate care. Whether this is a newly emerging phenomenon or simply one that is being exposed is unclear. Nevertheless, this inequity in management ranges from the early-to-late stages of NSCLC. The purpose of this manuscript is to explore the reasons behind the differences in the receipt of care for NSCLC that exists between the African-American and Caucasian population.

Polysomy and amplification of chromosome 7 defined for EGFR gene in squamous cell carcinoma of the lung together with exons 19 and 21 wild type Carcinoma epidermóide do pulmão: Polissomia e amplificação do cromossoma 7 e do gene EGRF com forma wild type nos exões 19 e 21

Directory of Open Access Journals (Sweden)

Patrícia Couceiro

2010-06-01

Full Text Available Purpose: The epidermal growth factor receptor (EGFR is overexpressed in the majority of nonsmall-cell lung cancers (NSCLC and is a major target specific EGFR tyrosine kinase inhibitors (TKIs developed and used for the treatment of advanced NSCLC. A number of biological factors are also associated with EGFR-TKIs responsiveness. This study was focused on EGFR somatic mutations and amplifications in squamous cell lung cancer. Material and methods: Representative sections of squamous cell carcinoma were selected from 54 surgical specimens from formalin-fixed paraffin-embedded tissues and submitted to TMA construction. Determination of EGFR protein expression was done by immunohistochemistry( IHC (Zymed, Laboratories. Fluorescence in situ hybridization (FISH was performed with LSI EGFR/CEP 7 (Vysis; Abbott Molecular, USA. Genomic DNA was extracted from 48 cases and exon 19 was amplified by polymerase chain reaction (PCR for search deletions and point mutations for exon 21. All cases expressed high weigh cytokeratin and were observed negativity for CK7, CD56 and chromogranin. Results: EGFR protein overexpression was identified in 49 cases, by the application of Hirsh’s scoring system. The chromosome 7 and EGFR gene were analyzed by FISH and scored according to Cappuzzo’s method that showed high polysomy in 31 cases and amplification in 7 cases. Deletion in exon 19 of EGFR was detected in 3 cases of 48 samples; the exon 21 of EGFR was expressed in its wild type by RFLP in all cases. Conclusions: Detection of common EGFR deletion and mutation showed to be a rare event in Squamous cell carcinoma of the lung. While EGFR mutation is the most effective molecular predictor or sensitivity in patients with advanced NSCLC submitted to EGFR-TKIs treatment, amplification and polysomy is the most effective molecular predictor for EGFR-TKIs responsiveness in squamous cell carcinoma, when valida ted isolated from the group of NSCLC.Objectivo: O receptor do

Effect of induced hyperglycemia on metastatic spreading in Lewis lung carcinoma

International Nuclear Information System (INIS)

Shmakova, N.L.; Fomenkova, T.E.; Fadeeva, T.A.

1991-01-01

The effect of induced hyperglycemia on the intensity of metastatic dissemination of Lewis lung carcinoma was investigated in experiments on mice. Neither long-, nor short-term hyperglycemia, induced at different phases of dissemination, influenced the intensity of metastatic spreading, primary tumor growth, the time of appearance of metastases, and the average life duration of tumor-bearing animals

A phase II study of cisplatin, oral administration of etoposide, OK-432 and radiation therapy for inoperable stage III non-small cell lung cancer

International Nuclear Information System (INIS)

Abe, Yoshinao; Takahashi, Jutaro; Fukuda, Hiroshi

1998-01-01

This study was designed to evaluate the feasibility and efficiency of giving cisplatin, etoposide, and OK-432 concurrently with conventional radiotherapy (RTx) for patient's with inoperable stage III, based on the TNM classification according to the International Union against Cancer staging system for lung cancer (1987) non-small cell lung cancer (NSCLC). From January 1992 to December 1994, 31 patients with cytologically or histologically confirmed stage III NSCLC were treated with RTx, to a total dose of 56-64 Gy, with concurrent daily oral administration of etoposide (25 mg) and cisplatin (20 mg) for 5 days during the third or fourth week from the start of RTx. The subcutaneous injection of 1 or 2 KE of OK-432, three times a week, for the duration of radiotherapy also started from the beginning of RTx. The number of eligible patients was 29 (26 men and 3 women). Their mean age was 66 years (range, 55-77 years). Six patients had an Eastern Cooperative Oncology Group performance status (PS) of 0; 15, 1; 8; 2. Three were stage IIIA, and 26, stage IIIB. Histologically, 2 had adenocarcinoma, 23, squamous cell carcinoma, and 4, large cell carcinoma. In 27 of the 29 patients, the RTx schedule was completed. There were no treatment-related deaths. Grade 4 toxicity (according to World Health Organisation criteria) leukopenia (700/μl) was observed in 1 patient. The response rate was 79% and the median survival was 17 months. Survival rates at 1, 2 and 3 years were 62%, 31%, and 21%, respectively. The local failure rate was 51%. The combination of cisplatin, etoposide, and OK-432, given concurrently with conventional RTx is feasible and effective for inoperable stage III NSCLC. (author)

Expression profiles and clinical value of plasma exosomal Tim-3 and Galectin-9 in non-small cell lung cancer.

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Gao, Jianwei; Qiu, Xiangyu; Li, Xinying; Fan, Hang; Zhang, Fang; Lv, Tangfeng; Song, Yong

2018-04-06

Exosomes are membrane-bound, virus-sized vesicles present in circulating blood. Tumor cells are avid producers of exosomes, which are thought to mimic molecular features of parent tumor cells. T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) is a the next-generation immune checkpoint that can be activated by its ligand Galectin-9 to negatively regulate the anti-tumor immune response. However, the characteristics of plasma exosomal Tim-3 and Galectin-9 (Exo-T/G) in cancer remained unknown. This study was conducted to investigate the expression patterns and clinical value of plasma exosomal total protein (Exo-pro) and Exo-T/G in non-small cell lung cancer (NSCLC). Plasma was collected from 103 NSCLC patients including 60 early stages and 43 advanced stages disease samples as well as 56 healthy subjects. Exosomes were isolated from plasma by commercial exosome precipitation solution and identified by western blotting of CD63 and transmission electron microscopy. Exo-pro concentration was measured by the BCA assay. Enzyme-linked immunosorbent assay was used to quantify Exo-T/G. Additionally, 34 NSCLC samples were applied to directly detect plasma TIM-3 (Plas-T) and Galectin-9 (Plas-G). Our results showed that Exo-pro, Exo-T, and Exo-G were significantly increased in NSCLC plasma compared to that in the healthy samples. High levels of Exo-T and Exo-G were all positively correlated with several malignant parameters, including larger tumor size, advanced stages, and more distant metastasis. High levels of Exo-pro and Exo-T were also correlated with more lymph node metastasis. Additionally, plasma from lung squamous cell carcinoma showed higher Exo-T and Exo-G compared with that from lung adenocarcinoma. ALK-positive patients showed to have decreased Exo-T and Exo-G levels. Pearson's correlation analysis revealed a significant correlation between Exo-pro and Exo-T/G, Exo-T and Exo-G, Exo-T and Plas-T, Exo-G and Plas-G, and Plas-T and Plas-G. Together

Tracking Genomic Cancer Evolution for Precision Medicine: The Lung TRACERx Study

DEFF Research Database (Denmark)

Jamal-Hanjani, Mariam; Hackshaw, Alan; Ngai, Yenting

2014-01-01

. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic...... analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve...

Abnormal A-type lamin organization in a human lung carcinoma cell line

NARCIS (Netherlands)

Machiels, BM; Broers, JL; Raymond, Y; de Leij, Louis; Kuijpers, HJH; Caberg, NEH; Ramaekers, Frans C. S.

We have studied the expression of lamins A and C (A-type lamins) in a lung carcinoma cell line using type-specific monoclonal antibodies, Using immunofluorescence and immunoblotting studies it was noted that several irregularities in lamin expression exist in the cell line GLC-A1, derived from an

Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

Directory of Open Access Journals (Sweden)

Cheng-Yuan Wang

2010-02-01

Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

Studies on mRNA expression of the somatostatin receptor family in lung cancer

International Nuclear Information System (INIS)

Wang Jing; Deng Jinglan; Wu Shengxi; Qiao Hongqing

2000-01-01

Objective: To investigate the characteristics of expression and distribution of 5 subtypes of somatostatin receptors (SSTR1∼5) in lung cancer. Methods: With [α- 35 S]dATP labelled oligonucleotides of the 5 SSTR subtypes as probes, using in situ hybridization, patterns of mRNA expression were detected in lung cancer tissue sections of 21 cases which fell in varied pathologic types. Additionally, Leica Q-500 image analyzing device was employed to semi-quantitatively analyze density of the expression. Results: Patterns of SSTR1∼5 expression in lung cancer were as follows: SSTR2 expression was dominant in small cell lung cancer (SCLC) while in non-small cell lung cancer (NSCLC) such as adenous and squamous, SSTR1 expression was stronger than that of the other 4 subtypes, In density of SSTR1∼5 expression in lung cancer, NSCLC was higher than SCLC (P<0.01). Conclusions: even though patterns and density of expression of SSTR subtypes in the lung cancer showed heterogeneity in different histopathologic types, as in SCLC and in NSCLC. Therefore, it has positive prospects for somatostatin analog-oriented agents to be used in treatment of both types of the lung cancers

Metagenes Associated with Survival in Non-Small Cell Lung Cancer

Science.gov (United States)

Urgard, Egon; Vooder, Tõnu; Võsa, Urmo; Välk, Kristjan; Liu, Mingming; Luo, Cheng; Hoti, Fabian; Roosipuu, Retlav; Annilo, Tarmo; Laine, Jukka; Frenz, Christopher M.; Zhang, Liqing; Metspalu, Andres

2011-01-01

NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%–55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies. A previously published dataset was used to evaluate gene expression profiles of different NSCLC subtypes. A moderated two-sample t-test was used to identify differentially expressed genes between all tumor samples and cancer-free control tissue, between SCC samples and AC/BC samples and between stage I tumor samples and all other tumor samples. Gene expression microarray measurements were validated using qRT-PCR. Bayesian regression analysis and Kaplan-Meier survival analysis were performed to determine metagenes associated with survival. We identified 599 genes which were down-regulated and 402 genes which were up-regulated in NSCLC compared to the normal lung tissue and 112 genes which were up-regulated and 101 genes which were down-regulated in AC/BC compared to the SCC. Further, for stage Ib patients the metagenes potentially associated with survival were identified. Genes that expressed differently between normal lung tissue and cancer showed enrichment in gene ontology terms which were associated with mitosis and proliferation. Bayesian regression and Kaplan-Meier analysis showed that gene-expression patterns and metagene profiles can be applied to predict the probability of different survival outcomes in NSCLC patients. PMID:21695068

Clinical Evaluation of Tumor Markers for Diagnosis in Patients with Non-small Cell Lung Cancer in China.

Science.gov (United States)

Ma, Li; Xie, Xiao-Wei; Wang, Hai-Yan; Ma, Ling-Yun; Wen, Zhong-Guang

2015-01-01

To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of non- small cell lung cancer (NSCLC). Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (PCEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA+CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (PCEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (PCEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA+CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.

Co-activation of STAT3 and YES-Associated Protein 1 (YAP1) Pathway in EGFR-Mutant NSCLC

DEFF Research Database (Denmark)

Chaib, Imane; Karachaliou, Niki; Pilotto, Sara

2017-01-01

Background: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) ...

FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

Institute of Scientific and Technical Information of China (English)

Matthijs; H; van; Gool; Tjeerd; S; Aukema; Koen; J; Hartemink; Renato; A; Valdés; Olmos; Houke; M; Klomp; Harm; van; Tinteren

2014-01-01

Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

Inhibition of PDGFR by CP-673451 induces apoptosis and increases cisplatin cytotoxicity in NSCLC cells via inhibiting the Nrf2-mediated defense mechanism.

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Yang, Yang; Deng, Yanchao; Chen, Xiangcui; Zhang, Jiahao; Chen, Yueming; Li, Huachao; Wu, Qipeng; Yang, Zhicheng; Zhang, Luyong; Liu, Bing

2018-05-29

Platelet-derived growth factor receptors (PDGFRs) are abundantly expressed by stromal cells in the non-small cell lung cancer (NSCLC) microenvironment, and in a subset of cancer cells, usually with their overexpression and/or activating mutation. However, the effect of PDGFR inhibition on lung cancer cells themselves has been largely neglected. In this study, we investigated the anticancer activity of CP-673451, a potent and selective inhibitor of PDGFRβ, on NSCLC cell lines (A549 and H358) and the potential mechanism. The results showed that inhibition of PDGFRβ by CP-673451 induced a significant increase in cell apoptosis, accompanied by ROS accumulation. However, CP-673451 exerted less cytotoxicity in normal lung epithelial cell line BEAS-2B cells determined by MTT and apoptosis assay. Elimination of ROS by NAC reversed the CP-673451-induced apoptosis in NSCLC cells. Furthermore, CP-673451 down-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) probably through inhibition of PI3K/Akt pathway. Rescue of Nrf2 activity counteracted the effects of CP-673451 on cell apoptosis and ROS accumulation. Silencing PDGFRβ expression by PDGFRβ siRNA exerted similar effects with CP-673451 in A549 cells, and when PDGFRβ was knockdowned by PDGFRβ siRNA, CP-673451 produced no additional effects on cell viability, ROS and GSH production, Nrf2 expression as well as PI3K/Akt pathway activity. Specifically, Nrf2 plays an indispensable role in NSCLC cell sensitivity to platinum-based treatments and we found that combination of CP-673451 and cisplatin produced a synergistic anticancer effect and substantial ROS production in vitro. Therefore, these results clearly demonstrate the effectiveness of inhibition of PDGFRβ against NSCLC cells and strongly suggest that CP-673451 may be a promising adjuvant chemotherapeutic drug. Copyright © 2018 Elsevier B.V. All rights reserved.

Synchronous Oligometastatic Non-Small Cell Lung Cancer and Isolated Renal Cell Carcinoma: A Case Report and Literature Review.

Science.gov (United States)

Nguyen, Timothy K; Louie, Alexander V

2015-10-27

A 58-year-old gentleman presenting with a progressive headache, visual disturbance, decreased appetite, and weight loss was found to have a localized clear cell carcinoma of the kidney and synchronous Stage IV non-small cell lung cancer with a solitary brain metastasis. This case illustrates the challenges in distinguishing between primary and metastatic disease in a patient with both renal cell carcinoma and lung cancer. We highlight the uncertainties in the diagnosis and management of this unique clinical scenario and the potential implications on prognosis.

Immunohistochemical expression of HER-2/neu in patients with lung carcinoma and its prognostic significance

International Nuclear Information System (INIS)

Petrusevska, G.; Banev, S.; Ilievska-Poposka, B.; Smickova, S.; Spirovski, Z.

2004-01-01

Background. The HER-2 protein or p185her2 is a membrane receptor with tyrosine kinase activity encoded by HER-2/neu gene. Overexpression of HER-2/neu has been observed in many human cancers, including lung cancer. In the study, the expression of HER-2 protein is determined in the spectrum of lung cancer (adenocarcinoma, squamous cell carcinoma and small cell carcinoma). Patients and methods. The study population consisted of two groups: 19 patients that had undergone surgical treatment and 10 patients that had undergone fiber-optic bronchoscopy and biopsy for primary diagnosis only. Tissue specimens were neutral formaldehyde-fixed and paraffin-embedded. Standard histochemical and immunohistochemical staining were used for diagnosis. Expression of HER-2/neu protein was determined by immunohistochemical staining with Hercep Test (DAKO). The results were graded 0-1 as negative and 2-3 as positive. Results. Overall incidence of HER-2/neu overexpression was 34.4% (10 of 29). Higher incidence was found in the patients with adenocarcinoma 45.4% (5 of 11). In squamous cell carcinoma and small cell carcinoma, the overexpression incidence was 30.7% (4 of 13) and 20% (1 of 5), respectively. No statistically significant difference was seen given the age and gender. HER-2/neu overexpression was more pronounced in the patients with advanced tumour: all patients with squamous cell carcinoma and HER-2/neu overexpression had stage IIIB and stage IV disease, while 80 % of adenocarcinoma patients with HER-2/neu overexpression had stage IIIA and IIIB disease. Conclusions. These results are satisfactory and encourage us to continue this work in the follow-up study to evaluate HER-2/neu role as predictive and prognostic factor for the patients with lung cancer. (author)

Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)—validation in two independent cohorts

DEFF Research Database (Denmark)

Buhl, Ida Kappel; Santoni Rugiu, Eric; Ravn, Jesper

2018-01-01

Introduction Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented....... Methods The profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel. An applied clinical samples filter focused the profiles to clinically relevant genes. The profiles were tested on 1......) univariate HR of 0.37 (95% CI:0.12–1.15, p = 0.09) in the ACV cohort and 2) univariate HR of 0.14 (95% CI:0.03–0.59, p = 0.0076) to three years. Functional analysis on the cisplatin profile revealed a group of upregulated genes related to RNA splicing as a part of DNA damage repair and apoptosis. Conclusions...

Expression of the somatostatin receptor family mRNAs in lung cancer

International Nuclear Information System (INIS)

Wang Jing; Wang Liangang; Deng Jinglan; Wu Shengxi

2000-01-01

To investigate the characteristics of expression and distribution of 5 subtypes of somatostatin receptors (SSTR1-5) in lung cancer, in situ hybridization was used to examine the expression patterns of SSTR mRNAs in 21 cases of different pathologic types of lung cancer tissues with [α- 35 S]dATP labelled oligonucleotides of the 5 SSTR subtypes as probes. Additionally, Leica Q-500 image analysis processing system was employed for the semi-quantitatively analysis of the hybridization signals. Patterns of SSTR1-5 expression in lung cancer tissues were found as follows. SSTR2 was prominent in small cell lung cancer (SCLC), whereas in non-small cell lung cancer (NSCLC) including the adenous cancer (Ad) and the squamous cancer (Sq), the expression of SSTR1 mRNA was stronger than that of the other 4 types. the expression density of SSTR1-5 in the NSCLC was higher that the SCLC (p < 0.01). The expression patterns and densities of the SSTR subtypes showed heterogeneity in different pathologic types of lung cancer. The expressions of the SSTR mRNAs in both SCLC and NSCLC indicated the positive prospects for somatostatin analog (SSA)-oriented agents in the treatment of both types of the lung cancer

Globo H expression is associated with driver mutations and PD-L1 expressions in stage I non-small cell lung cancer.

Science.gov (United States)

Yang, Ching-Yao; Lin, Mong-Wei; Chang, Yih-Leong; Wu, Chen-Tu

2017-12-12

Globo H is a tumor-associated carbohydrate antigen exclusively expressed in cancer cells rather than normal tissue. Globo H has been found on many cancers of epithelial origins, and become an attractive target for cancer vaccine. We aimed to study the expression of Globo H in non-small cell lung cancer (NSCLC) patients, and correlated its expression with common driver mutations, clinical outcomes, and status of immune checkpoint, programmed death-ligand 1 (PD-L1). The study enrolled 228 patients with surgically resected stage I NSCLC, including 139 patients with adenocarcinoma (ADC) and 89 patients with squamous cell carcinoma (SqCC). Using immunohistochemistry, tumors with moderate to strong membranous staining in ⩾ 1% tumor cells per section were scored as positive Globo H expression. Driver mutations including EGFR, KRAS, BRAF were detected by direct sequencing, while ALK, PI3KCA, FGFR1 and PD-L1 expression was detected by immunohistochemical (IHC) staining. Positive Globo H expression was detected in 88 of the 228 (38.6%) patients. These included 51 of 139 (36.7%) patients with ADC and 37 of 89 (41.6%) patients with SqCC. Positive Globo H expression was significantly associated with EGFR mutation and PD-L1 expression in the ADC group, and PI3KCA overexpression in the SqCC group. The survival analysis showed that Globo H expression was not an independent prognostic factor in stage I NSCLC. Globo H expression was correlated with specific driver mutations in ADC and SqCC NSCLC tumors, as well as PD-L1 status. Immunotherapy targeting Globo H may have potential application in lung cancer treatment.

Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).

Science.gov (United States)

Joerger, M; von Pawel, J; Kraff, S; Fischer, J R; Eberhardt, W; Gauler, T C; Mueller, L; Reinmuth, N; Reck, M; Kimmich, M; Mayer, F; Kopp, H-G; Behringer, D M; Ko, Y-D; Hilger, R A; Roessler, M; Kloft, C; Henrich, A; Moritz, B; Miller, M C; Salamone, S J; Jaehde, U

2016-10-01

Variable chemotherapy exposure may cause toxicity or lack of efficacy. This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure. Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B). In arm B, initial paclitaxel dose was adjusted to body surface area, age, sex, and subsequent doses were guided by neutropenia and previous-cycle paclitaxel exposure [time above a plasma concentration of 0.05 µM (Tc>0.05)] determined from a single blood sample on day 2. The primary end point was grade 4 neutropenia; secondary end points included neuropathy, radiological response, progression-free survival (PFS) and overall survival (OS). Among 365 patients randomly assigned, grade 4 neutropenia was similar in both arms (19% versus 16%; P = 0.10). Neuropathy grade ≥2 (38% versus 23%, P PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC. NCT01326767 (https://clinicaltrials.gov/ct2/show/NCT01326767). © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Lung cancer stage at diagnosis: Individual associations in the prospective VITamins and lifestyle (VITAL cohort

Directory of Open Access Journals (Sweden)

Au David H

2011-06-01

Full Text Available Abstract Background Lung cancer is the leading cause of cancer death in the United States. Identifying factors associated with stage of diagnosis can improve our understanding of biologic and behavioral pathways of lung cancer development and detection. We used data from a prospective cohort study to evaluate associations of demographic, health history, and health behaviors with early versus late stage at diagnosis of non-small cell lung cancer (NSCLC. Methods We calculated odds ratios (ORs for the association of patient-level characteristics with advanced stage of diagnosis for NSCLC. The OR's were then adjusted for age, gender, race/ethnicity, smoking status, income, education, chronic obstructive pulmonary disease, and a comorbidity index. Results We identified 612 cases of NSCLC among 77,719 adults, aged 50 to 76 years from Washington State recruited in 2000-2002, with followup through December 2007. In univariate analyses, subjects who quit smoking Conclusions Smoking status, education, and a screening activity were associated with stage at diagnosis of NSCLC. These results may guide future studies of the underlying mechanisms that influence how NSCLC is detected and diagnosed.

Quantum dots immunofluorescence histochemical detection of EGFR gene mutations in the non-small cell lung cancers using mutation-specific antibodies

Directory of Open Access Journals (Sweden)

Qu YG

2014-12-01

Full Text Available Yan-Gang Qu,1 Qian Zhang,2 Qi Pan,3 Xian-Da Zhao,4 Yan-Hua Huang,2 Fu-Chun Chen,3 Hong-Lei Chen41Department of Pathology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, 2Department of Molecular Pathology, Wuhan Nano Tumor Diagnosis Engineering Research Center, Wuhan, Hubei, People’s Republic of China; 3Department of Thoracosurgery, Traditional Chinese Medical Hospital of Wenling, Wenling, Zhejiang, People’s Republic of China; 4Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei, People’s Republic of ChinaBackground: Epidermal growth factor receptor (EGFR mutation status plays an important role in therapeutic decision making for non-small cell lung cancer (NSCLC patients. Since EGFR mutation-specific antibodies (E746-A750del and L858R have been developed, EGFR mutation detection by immunohistochemistry (IHC is a suitable screening test. On this basis, we want to establish a new screening test, quantum dots immunofluorescence histochemistry (QDs-IHC, to assess EGFR gene mutation in NSCLC tissues, and we compared it to traditional IHC and amplification refractory mutation system (ARMS.Materials and methods: EGFR gene mutations were detected by QDs-IHC, IHC, and ADx-ARMS in 65 cases of NSCLC composed of 55 formalin-fixed, paraffin-embedded specimens and ten pleural effusion cell blocks, including 13 squamous cell carcinomas, two adenosquamous carcinomas, and 50 adenocarcinomas.Results: Positive rates of EGFR gene mutations detected by QDs-IHC, IHC, and ADx-ARMS were 40.0%, 36.9%, and 46.2%, respectively, in 65 cases of NSCLC patients. The sensitivity of QDs-IHC when detecting EGFR mutations, as compared to ADx-ARMS, was 86.7% (26/30; the specificity for both antibodies was 100.0% (26/26. IHC sensitivity was 80.0% (24/30 and the specificity was 92.31% (24/26. When detecting EGFR mutations, QDs-IHC and ADx-ARMS had perfect consistency (κ=0.882; P<0.01. Excellent agreement was observed

The clinical evaluation of double intervention therapy for advanced lung carcinoma by bronchial and pulmonary arterial approach

International Nuclear Information System (INIS)

Shi Yue; Gao Congjing

2002-01-01

Objective: Seeking a better way of PAI and BAI double intervention therapy for mid and advanced lung carcinoma, to observe the clinical effect. Methods: 60 patients with double intervention therapy through bronchial and pulmonary arterial (BAI and PAI) approaches were analyzed. Results: The effective rates of BAI and PAI as CR, PR and NC were 9 cases (15%), 45% cases (75%), 6 cases (10%) with mean survival spans of 10.8 and 12.4 months respectively. Conclusions: The combined treatment effects of BAI and PAI were better than BAI alone in advanced lung carcinoma with operation

Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

Science.gov (United States)

Hynds, Robert E; Janes, Sam M

2017-09-01

Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer.

Science.gov (United States)

Takenaka, Tomoyoshi; Furuya, Kiyomi; Yamazaki, Koji; Miura, Naoko; Tsutsui, Kana; Takeo, Sadanori

2018-02-01

We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

Role of interim {sup 18}F-FDG-PET/CT for the early prediction of clinical outcomes of Non-Small Cell Lung Cancer (NSCLC) during radiotherapy or chemo-radiotherapy. A systematic review

Energy Technology Data Exchange (ETDEWEB)

Cremonesi, Marta; Garibaldi, Cristina [European Institute of Oncology, Radiation Research Unit, Milano (Italy); Gilardi, Laura; Travaini, Laura Lavinia; Grana, Chiara Maria [European Institute of Oncology, Division of Nuclear Medicine, Milano (Italy); Ferrari, Mahila Esmeralda; Botta, Francesca [Medical Physics Unit, European Institute of Oncology, Milano (Italy); Piperno, Gaia; Ronchi, Sara; Ciardo, Delia [European Institute of Oncology, Division of Radiation Oncology, Milano (Italy); Timmerman, Robert [University of Texas Southwestern Medical Center, Department of Radiation Oncology, Dallas, TX (United States); Baroni, Guido [Politecnico di Milano University, Department of Electronics, Information and Bioengineering, Milano (Italy); Jereczek-Fossa, Barbara Alicja [European Institute of Oncology, Division of Radiation Oncology, Milano (Italy); University of Milan, Department of Oncology and Hemato-Oncology, Milano (Italy); Orecchia, Roberto [University of Milan, Department of Oncology and Hemato-Oncology, Milano (Italy); European Institute of Oncology, Department of Medical Imaging and Radiation Sciences, Milano (Italy)

2017-10-15

Non-Small Cell Lung Cancer (NSCLC) is characterized by aggressiveness and includes the majority of thorax malignancies. The possibility of early stratification of patients as responsive and non-responsive to radiotherapy with a non-invasive method is extremely appealing. The distribution of the Fluorodeoxyglucose ({sup 18}F-FDG) in tumours, provided by Positron-Emission-Tomography (PET) images, has been proved to be useful to assess the initial staging of the disease, recurrence, and response to chemotherapy and chemo-radiotherapy (CRT). In the last years, particular efforts have been focused on the possibility of using ad interim {sup 18}F-FDG PET (FDG{sub int}) to evaluate response already in the course of radiotherapy. However, controversial findings have been reported for various malignancies, although several results would support the use of FDG{sub int} for individual therapeutic decisions, at least in some pathologies. The objective of the present review is to assemble comprehensively the literature concerning NSCLC, to evaluate where and whether FDG{sub int} may offer predictive potential. Several searches were completed on Medline and the Embase database, combining different keywords. Original papers published in the English language from 2005 to 2016 with studies involving FDG{sub int} in patients affected by NSCLC and treated with radiation therapy or chemo-radiotherapy only were chosen. Twenty-one studies out of 970 in Pubmed and 1256 in Embase were selected, reporting on 627 patients. Certainly, the lack of univocal PET parameters was identified as a major drawback, while standardization would be required for best practice. In any case, all these papers denoted FDG{sub int} as promising and a challenging examination for early assessment of outcomes during CRT, sustaining its predictivity in lung cancer. (orig.)

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

Science.gov (United States)

Wei, Shenhai; Tian, Jintao; Song, Xiaoping; Wu, Bingqun; Liu, Limin

2018-01-01

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Next-Generation Sequencing Workflow for NSCLC Critical Samples Using a Targeted Sequencing Approach by Ion Torrent PGM™ Platform.

Science.gov (United States)

Vanni, Irene; Coco, Simona; Truini, Anna; Rusmini, Marta; Dal Bello, Maria Giovanna; Alama, Angela; Banelli, Barbara; Mora, Marco; Rijavec, Erika; Barletta, Giulia; Genova, Carlo; Biello, Federica; Maggioni, Claudia; Grossi, Francesco

2015-12-03

Next-generation sequencing (NGS) is a cost-effective technology capable of screening several genes simultaneously; however, its application in a clinical context requires an established workflow to acquire reliable sequencing results. Here, we report an optimized NGS workflow analyzing 22 lung cancer-related genes to sequence critical samples such as DNA from formalin-fixed paraffin-embedded (FFPE) blocks and circulating free DNA (cfDNA). Snap frozen and matched FFPE gDNA from 12 non-small cell lung cancer (NSCLC) patients, whose gDNA fragmentation status was previously evaluated using a multiplex PCR-based quality control, were successfully sequenced with Ion Torrent PGM™. The robust bioinformatic pipeline allowed us to correctly call both Single Nucleotide Variants (SNVs) and indels with a detection limit of 5%, achieving 100% specificity and 96% sensitivity. This workflow was also validated in 13 FFPE NSCLC biopsies. Furthermore, a specific protocol for low input gDNA capable of producing good sequencing data with high coverage, high uniformity, and a low error rate was also optimized. In conclusion, we demonstrate the feasibility of obtaining gDNA from FFPE samples suitable for NGS by performing appropriate quality controls. The optimized workflow, capable of screening low input gDNA, highlights NGS as a potential tool in the detection, disease monitoring, and treatment of NSCLC.

Erlotinib no controlo tumoral prolongado do carcinoma do pulmão de não pequenas células avançado (CPNPC

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Teresa Guimarães

2008-10-01

Full Text Available Resumo: Os autores apresentam um caso clínico de um doente de raça caucasiana, sexo masculino, de 59 anos, não fumador, com um carcinoma do pulmão de não pequenas células (CPNPC, avançado, com 3 anos de follow-up, que se encontra actualmente a realizar tratamento com erlotinib, desde há 18 meses, após falência de mais de uma linha de quimioterapia, sem evidência de progressão oncológica. O doente evidencia excelente qualidade de vida, sintomatologia controlada, recuperação da capacidade de tolerância ao esforço e mantém a sua actividade profissional. O tratamento com erlotinib tem sido globalmente bem tolerado, embora exibindo toxicidade cutânea grau 1.Rev Port Pneumol 2008; XIV (Supl 3: S9-S15 Abstract: The authors present a clinical case of a caucasian male patient, 59 years-old, non-smoker, with an advanced non-small cell lung carcinoma (NSCLC, with 3 years of follow-up, received erlotinib for 18 months, after failure of more than one chemotherapy schedule, without evidence of oncologic progression. The patient evidences excellent quality of life, controlled sintomatology, recovery of the capacity of tolerance to the effort and it maintains his professional activities. The treatment with erlotinib has been well tolerated, although exhibiting grade 1 cutaneous toxicity.Rev Port Pneumol 2008; XIV (Supl 3: S9-S15 Palavras-chave: Carcinoma do pulmão de não pequenas células avançado ou metastático, CPNPC, erlotinib, inibi-dores da tirosina quinase (HER1/EGFR, quimioterapia, Key-words: Locally advanced or metastatic non-small cell lung cancer, NSCLC, erlotinib, thyrosine kinase epidermal growth factor receptor inhibitor (HER1/ EGFR, chemotherapy

Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

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Mariëlle I Gallegos Ruiz

Full Text Available BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC is essential to improve early diagnosis and treatment for this disease. METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%, which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008, survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04. Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS: We suggest that targeting HSP90 will have clinical impact for NSCLC patients.

Palatine Tonsillar Metastasis of Small-Cell Neuroendocrine Carcinoma from the Lung Detected by FDG-PET/CT After Tonsillectomy: A Case Report

International Nuclear Information System (INIS)

Chen, Xiao-Hong; Bao, Yang-Yang; Zhou, Shui-Hong; Wang, Qin-Ying; Zhao, Kui

2013-01-01

Metastasis from a malignant tumor to the palatine tonsils is rare, accounting for only 0.8% of all tonsillar tumors, with only 100 cases reported in the English-language literature. Various malignant lung carcinomas may metastasize to the tonsils. A few cases of tonsillar metastasis from neuroendocrine lung carcinoma have been reported. A 67-year-old female underwent a right tonsillectomy because of a sore throat and an enlarged right tonsil. The postoperative pathology showed right tonsillar small cell neuroendocrine carcinoma (SCNC). Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrated metabolic activity in the lower lobe of the right lung. In addition, hypermetabolic foci were noted in the lymph nodes of the right neck and mediastinum. A needle biopsy of the pulmonary mass showed SCNC. The patient received chemotherapy and died of multiple distant metastases after 6 months. This is the first report using PET/CT to evaluate tonsillar metastasis from lung SCNC

Expressions and Significances of CRABPII and E-FABP 
in Non-small Cell Lung Cancer

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Qian LIU

2013-01-01

Full Text Available Background and objective The cellular retinoic acid-binding protein II (CRABPII and epidermal fatty acid-binding protein (E-FABP both serving as the transport protein of retinoic acid (RA, through RA signal transduction pathway, commit the cell to opposite fate, apoptosis or survival. The aim of this study is to investigate the expression of CRABPII and E-FABP and significance in non-small cell lung cancer (NSCLC and their lymph node metastases with tissue microarray technique. Methods CRABPII and E-FABP proteins were detected in 54 normal lung tissues, 287 primary NSCLC tissues and 112 lymph node metastatic tissues by SP method of immunohistochemical staining. Results The expression level of CRABPII in the primary lesions was relevant to the gender of NSCLC patients, the metastasis and TNM staging of NSCLC (P<0.05, while the expression level of E-FABP was related to the grading and metastasis of NSCLC (P<0.05. The positive expression rate of E-FABP in NSCLC primary lesion was remarkably higher than that in adjacent normal lung tissues and lymph node metastases, respectively (P<0.05. The expression level of E-FABP had a recognizable advantage over that of CRABPII in NSCLC primary lesions (P<0.05. The differential expressions between CRABPII and E-FABP was correlated with the tumor size, grading, metastasis, TNM staging of NSCLC (P<0.05. The larger the tumor was and the later the TNM staging was, along with cancer metastasis, the more likely the expression of E-FABP would dominate. The expression of CRABPII and difference expression between CRABPII and E-FABP were closely related to the prognosis of NSCLC patients based on Kaplan-Meier survival analysis. Conclusion E-FABP showed high exp ression in NSCLC, and the increased E-FABP expression may involved in the occurrence and development of NSCLC. CRABPII might have a negative effect in NSCLC progression, and its expression was negatively related to the prognosis of NSCLC patients.

Concomitant active tuberculosis prolongs survival in non-small cell lung cancer: a study in a tuberculosis-endemic country.

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Chih-Hsi Kuo

Full Text Available BACKGROUND: Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. METHODS: Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. RESULTS: A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01. Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48 ~ 0.97. Squamous cell carcinoma (SCC (55.8 vs. 31.7%, p<0.01 is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05. Active tuberculosis in SCC increases the expression of CD3 (46.4 ± 24.8 vs. 24.0 ± 16.0, p<0.05, CXCR3 (35.1 ± 16.4 vs. 19.2 ± 13.3, p<0.01 and IP-10 (63.5 ± 21.9 vs. 35.5 ± 21.0, p<0.01, while expression of FOXP3 is decreased (3.5 ± 0.5 vs. 13.3 ± 3.7 p<0.05, p<0.05. Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05 and CXCR3 (12.1 vs. 4.4 month, p<0.05 is longer than that with low expression. CONCLUSIONS: Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches.

Radiotherapeutic management of non-small cell lung cancer (NSCLC). An overview based on the clinical trials of the radiation therapy oncology group (RTOG)

International Nuclear Information System (INIS)

Wilson, J.F.; Byhardt, R.W.

1995-01-01

Recent clinical trials clarified the role of radiation therapy (RT) in the treatment of non-small cell lung cancer (NSCLC). The evolution of this research is illustrated by a systemic succession of studies conducted during the last twenty years by the Radiation Therapy Oncology Group (RTOG). This article reviews past and present RTOG research efforts in NSCLC. For unresectable NSCLS, major research themes have included radiation dose intensification using both standard and altered fractionation (hyperfractionation or accelerated fraction RT), treatment intensification using combined modality RT and chemotherapy (CT), as well as noncytotoxic adjuvants to RT. These trials have shown that treatment intensification can yield improved survival with acceptable toxicity. Local control and survival was improved with induction CT followed by standard RT to 60 Gy. Current studies will evaluate the timing and sequencing of CT and RT and the combination of CT with altered fractionation RT. Hypoxic cell sensitizers and nonspecific immune stimulants, two noncytotoxic adjuvants to RT, have shown no survival benefit. Biologic response modifiers, including recombinant interferon-beta, will also be evaluated as adjuvants to standard RT, based on interferon-beta radiosensitization observed in the laboratory and clinical investigations suggesting improved survival. Overall, RTOG studies have demonstrated small, but definite, incremental improvements in treatment outcome in NSCLS and provide a solid foundation on which to develop future investigations. (N.K.) 51 refs

Inter-heterogeneity and intra-heterogeneity of α{sub v}β{sub 3} in non-small cell lung cancer and small cell lung cancer patients as revealed by {sup 68}Ga-RGD{sub 2} PET imaging

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Kang, Fei; Li, Guoquan; Wang, Shengjun; Liu, Daliang; Zhang, Mingru; Zhao, Mingxuan; Yang, Weidong; Wang, Jing [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Wang, Zhe [Fourth Military Medical University, Department of Nuclear Medicine, Xijing Hospital, Xi' an (China); Fourth Military Medical University, Department of Pathology, Xijing Hospital, Xi' an (China)

2017-08-15

Integrin α{sub v}β{sub 3} is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare α{sub v}β{sub 3} levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer {sup 68}Ga-labeled dimerized-RGD ({sup 68}Ga-RGD{sub 2}). Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using {sup 68}Ga-RGD{sub 2}.{sup 18}F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker α{sub v}β{sub 3} in NSCLC and SCLC lesions was analyzed by immunohistochemistry. The {sup 18}F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The {sup 68}Ga-RGD{sub 2} uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of {sup 68}Ga-RGD{sub 2} SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that α{sub v}β{sub 3} integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression. The uptake of {sup 68}Ga-RGD{sub 2} in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower α{sub v}β{sub 3} target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of α{sub v}β{sub 3} also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of α{sub v}β{sub 3} may potentially improve current applications of α{sub v}β{sub 3}-targeted therapy

CT-guided percutaneous conformal cryoablation for lung carcinoma

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Yueyong, Xiao; Bin, Wu; Xiao, Zhang; Hongjun, Li; Da, Yu; Jie, Li; Jun, Li [Department of Radiology, PLA General Hospital, Beijing (China)

2010-02-15

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

CT-guided percutaneous conformal cryoablation for lung carcinoma

International Nuclear Information System (INIS)

Xiao Yueyong; Wu Bin; Zhang Xiao; Li Hongjun; Yu Da; Li Jie; Li Jun

2010-01-01

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

[Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)].

Science.gov (United States)

Ma, Sheng-lin; Feng, Jian-guo; Gu, Lin-hui; Ling, Yu-tian

2003-03-01

To establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied. Intermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST. 1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable. D6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.

Combined effects of EGFR tyrosine kinase inhibitors and vATPase inhibitors in NSCLC cells

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Jin, Hyeon-Ok [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Hong, Sung-Eun [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Kim, Chang Soon [Department of Microbiological Engineering, Kon-Kuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 143–701 (Korea, Republic of); Park, Jin-Ah; Kim, Jin-Hee; Kim, Ji-Young; Kim, Bora [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Chang, Yoon Hwan; Hong, Seok-Il; Hong, Young Jun [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Park, In-Chul, E-mail: parkic@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Lee, Jin Kyung, E-mail: jklee@kirams.re.kr [KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of); Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 75 Nowon-ro, Nowon-gu, Seoul, 139–706 (Korea, Republic of)

2015-08-15

Despite excellent initial clinical responses of non-small cell lung cancer (NSCLC) patients to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), many patients eventually develop resistance. According to a recent report, vacuolar H + ATPase (vATPase) is overexpressed and is associated with chemotherapy drug resistance in NSCLC. We investigated the combined effects of EGFR TKIs and vATPase inhibitors and their underlying mechanisms in the regulation of NSCLC cell death. We found that combined treatment with EGFR TKIs (erlotinib, gefitinib, or lapatinib) and vATPase inhibitors (bafilomycin A1 or concanamycin A) enhanced synergistic cell death compared to treatments with each drug alone. Treatment with bafilomycin A1 or concanamycin A led to the induction of Bnip3 expression in an Hif-1α dependent manner. Knock-down of Hif-1α or Bnip3 by siRNA further enhanced cell death induced by bafilomycin A1, suggesting that Hif-1α/Bnip3 induction promoted resistance to cell death induced by the vATPase inhibitors. EGFR TKIs suppressed Hif-1α and Bnip3 expression induced by the vATPase inhibitors, suggesting that they enhanced the sensitivity of the cells to these inhibitors by decreasing Hif-1α/Bnip3 expression. Taken together, we conclude that EGFR TKIs enhance the sensitivity of NSCLC cells to vATPase inhibitors by decreasing Hif-1α/Bnip3 expression. We suggest that combined treatment with EGFR TKIs and vATPase inhibitors is potentially effective for the treatment of NSCLC. - Highlights: • Co-treatment with EGFR TKIs and vATPase inhibitors induces synergistic cell death • EGFR TKIs enhance cell sensitivity to vATPase inhibitors via Hif-1α downregulation • Co-treatment of these inhibitors is potentially effective for the treatment of NSCLC.

Prophylactic cranial irradiation for squamous cell carcinoma, large cell carcinoma, and adenocarcinoma of the lung: Indications and techniques

International Nuclear Information System (INIS)

Cox, J.D.; Komaki, R.

1986-01-01

Intracranial metastasis is one of the most morbid manifestations of cancer of the lung. The resulting seizures, headaches, and motor loss severely compromise the individual in the remaining days of his life. The median survival of patients with brain metastasis is only three to four months. Symptoms and signs resulting from brain metastasis are reversible to some degree with cranial irradiation in most patients. Headaches and seizures are most frequently controlled, but motor loss and impaired mentation are less reversible. The high frequency with which small cell carcinoma spreads to the brain has been recognized for many years. For the past decade, prophylactic cranial irradiation has been used widely in conjunction with combination chemotherapy for small cell carcinoma

Approach for oligometastasis in non-small cell lung cancer.

Science.gov (United States)

Suzuki, Hidemi; Yoshino, Ichiro

2016-04-01

Non-small cell lung cancer (NSCLC) harboring a limited number of distant metastases, referred to as the oligometastatic state, has been indicated for surgery for the past several decades. However, whether the strategy of surgical treatment results in a survival benefit for such patients remains controversial. Experientially, however, thoracic surgeons often encounter long-term survivors among surgically resected oligometastatic NSCLC patients. In this article, the current situation of surgical approach and potential future perspective for oligometastatic NSCLC are reviewed.

Lung Cancer—Health Professional Version

Science.gov (United States)

Lung cancer appears in two main types. Non-small cell (squamous cell carcinoma, large cell carcinoma, and adenocarcinoma), and small cell lung cancer (oat cell cancer and combined small cell carcinoma). Find evidence-based information on lung cancer treatment, causes and prevention, research, screening, and statistics.

Preoperative staging of lung cancer with combined PET-CT

DEFF Research Database (Denmark)

Fischer, Barbara; Lassen, Ulrik; Mortensen, Jann

2009-01-01

BACKGROUND: Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC...... one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause...

Clinical and experimental studies regarding the expression and diagnostic value of carcinoembryonic antigen-related cell adhesion molecule 1 in non-small-cell lung cancer

International Nuclear Information System (INIS)

Zhou, Mu-qing; Du, Yan; Liu, Yi-wen; Wang, Ying-zhi; He, Yi-qing; Yang, Cui-xia; Wang, Wen-juan; Gao, Feng

2013-01-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC. The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR. Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05). Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative

Preclinical evaluation of racotumomab, an anti-idiotype monoclonal antibody to N-glycolyl-containing gangliosides, with or without chemotherapy in a mouse model of non-small cell lung cancer